Journal articles: 'Zhan shi fu' – Grafiati (2024)

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Abstract Shandong province is the leading peanut-producing province in China which in turn is the leading peanut-producing country in the world. Shandong Peanut Research Institute (SPRI), an institute of the Shandong Academy of Agricultural Science, has had an ongoing breeding program for more than 40 yr and is the source of the peanut cultivars that dominate production in Shandong province and northern China. About 75 peanut cultivars and breeding lines have been released in Shandong by SPRI and other institutions. The genetic base of Shandong peanut cultivars has been described as narrow. The objective of this study was to (a) determine the genetic contribution of main ancestors to the genetic base of Shandong peanut cultivars and (b) study the genetic relationships among the peanut cultivars released in Shandong province during 1950-1999. Twentysix ancestors were identified in the pedigrees of 69 improved lines, 24 ancestors of Chinese origin contributed 96.1% of the Shandong peanut genetic base, and two exotic introductions contributed only 3.6%. The four most important ancestors based on average coancestry with the 69 improved lines are Fu Hua Sheng (PI 436545), Shi Tou Qi (PI 430227 and PI 461435), Jianggezhuang Ban Man (PI 433351), and Shuyang Da Zhan Yang from which 67, 28, 27 and 19 lines were derived, respectively. Among the 20 dominant cultivars of Shandong province, recently released cultivars Lu Hua 14 and Lu Hua 15 have the lowest average coancestry with the others which means those two new cultivars' have the high genetic divergence. In contrast, the very popular cultivars Fu Hua Sheng, Baisha 1016, Xuzhou 68-4, Lu Hua 9, and the new cultivar 8130 were closely related to the other cultivars. The results suggest that the genetic base of Shandong peanut cultivars released before 1990 is narrow, but that cultivars released after 1990 have broadened the genetic base due to introduction and use of new germplasm in the pedigrees. This information will be used as a guide for peanut breeders in choosing parents and avoiding genetic vulnerability to pests. For new cross combinations, parents with low coefficients of coancestry should be chosen in order to keep enlarging the gene pool of the new cultivars.

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Background:TCZ is a monoclonal antibody against Interleukin-6 receptor (IL-6R) which is used for relieving inflammation and reducing mortality in COVID-19 patients. Safety and efficacy of Tocilizumab (TCZ) in Covid-19 pneumonia is uncertain yet. In this study, we aimed to determine clinical outcomes in patients treated with TCZ.Objectives:In this study we aimed to share our retrospective results which we had obtained from patients with COVID-19 diagnosis received TCZ.Methods:We performed a retrospective case control study between May and August 2020 in Turkey. We compared outcomes in patients who received TCZ with those who did not. Death in hospital and intensive care unit (ICU) requirements were evaluated as endpoints. Demographic data, comorbidities, additional treatment, treatment side effects, laboratory and clinical results were retrospectively assessed. There are no significant differences between groups according to age, gender and Charlson Comorbidity Index (CCI).Results:12 (27.3%) patients died in standard group and eight (18.6%) patients died in TCZ group (p=0.150).Days of staying in the hospital were eight days in standard treatment group and 12 days in TCZ group (p=0.03). 10 of 43 patients in TCZ group were admitted to ICU. MV support was needed in 8 of these patients. 18 of 44 patients (40.9%) within the standard group were admitted to ICU and 12 patients (27.3%) were intubated (p=0.125,p=0.480). Significant IL-6 decrease was not observed post treatment in TCZ group according to pretreatment period (p=0.60). Significant decreases were examined in CRP and ferritin values through TCZ treatment. However, D-dimer and thrombocyte values increased.Conclusion:TCZ may not be an effective treatment for reducing ICU requirement, to prevent intubation or death, for shortening period for staying in hospital. The patients should be followed up closely for possible thrombosis because of increased D-dimer and thrombocytes with TCZ treatment.References:[1]Sharma A, Tiwari S, Deb MK, Marty JL. Severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2): A global pandemic and treatment strategies. IntJ Antimicrob Agents. 2020 Aug; 56(2):106054.[2]Singhal T. A rewiev of coronavirus Disease-2019(COVID-19). Indian J Pediatr. 2020 Apr;87(4):281-286.[3]Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall R.S, Manson J.J. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-[4]Teijaro J.R. Cytokine storms in infectious diseases. SeminImmunopathol. 2017;39:501–503.[5]Zhang Y, Li J, Zhan Y, Wu L, Yu X, Zhang W et al. Analysis of Serum Cytokines in Patients with Severe Acute Respiratory Syndrome. Infect Immun 2004 Aug;72(8):4410-4415.[6]Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020 May; 55(5):105954.[7]Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–2[8]Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med 18,164 (2020).[9]Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol. 2020 Aug;2(8):e474-e484.[10]Gupta S, Wang W, Hayek S.S, Chan L, MathewsK.S, Melamed M.L et al. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Intern Med. 2021 Jan1;181(1):41-51.[11]Campochiaro C, Della-Torre E, Cavalli G, De Luca G, Ripa M, Boffini N et al Efficacy and safety of tocilizumab in severe COVID- 19 patients: a single-centre retrospective cohort study. Eur J Intern Med. 2020 Jun;76:43-49.Disclosure of Interests:None declared

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ABSTRACT(N.B. A version of this paper has now been published in Kaogu 1983.6:537-41.)Fu Hao (or Fu Zi ) appears in the oracle-bone inscriptions from Anyang. The name is often seen in Period I inscriptions (from the time of Wu Ding) and occasionally in Period IV inscriptions (from the time of Wu Yi and Wen Ding). The two are separated by four kings (Zu Geng, Zu Jia, Lin Xin, and Kang Ding), perhaps by as much as one hundred years. Does the Fu Hao in both periods refer to the same person? How can we explain this phenomenon?In the oracle-bone records of people and their activities there are cases where one figure is active in different periods. These names are often also place names, and these figures possess a populace and products. These names are probably what is termed “Clan-Territory titles” (a term found in the Gu shi kao, as quoted in the “Zheng yi” commentary to the Zuo zhuan). Based on their clan name they served hereditarily as officials. These clan names occur in historical literature, as in “In the past, our former kings were for generations Lords of Millet (Hou Ji ), serving under the Yü and Xia “(Guo yü “Zhou Yü” ); or “The Zhong and Li clans generation after generation ordered heaven and earth, … the Sima clan for generation after generation was in charge of the history of Zhou” (Shi ji, “Taishigong zixu” ).

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Lithium metal anodes are promising alternatives to graphite for use in next-generation lithium-ion batteries due to their higher capacity (3,860 mAh/g vs. 372 mAh/g). However, Li anodes still display excessive capacity loss over cycling, leading to underwhelming Coulombic efficiency (CE, <99.9%) compared to graphite (>99.95%).1 These losses can derive from: (1) the formation of electronically isolated Li0 (often referred to as ‘dead’ or inactive’); and (2) the parasitic reactions between Li and the electrolyte that form the solid electrolyte interphase (SEI). Characterization of the Li anode has historically relied on surface characterization techniques such as XPS and FTIR, which cannot quantitatively reveal the total amounts of specific SEI phases. More precise quantification has recently become possible due to advances in chemical titration, which notably revealed that inactive Li0 is the dominant loss mechanism at low-to-moderate CE (<90%).2 At high CE (>90%), SEI losses are increasingly dominant and become the loss mode to minimize. Despite its importance, titration of SEI losses have thus far largely focused on LiH,3-5 with precise quantification of other accompanying phases still lacking. To bridge this gap, here we apply quantitative titration based on GC, ICP-AES and NMR to track an extended array of key SEI phases: semicarbonates (ROCO2Li), lithium carbide (Li2C2), olefins (RLi), LiF, P-containing phases, and total Li loss with, which teach new insights beyond inactive Li0. In 1 M LiPF6 EC/DEC, we demonstrate chemical resolution up to 71% of Li loss and 33% of SEI loss inventory. The analysis was also expanded to additional carbonate electrolytes of varying CEs (from <10% to >96%). Soluble SEI phases were particularly important at ultra-low CE (<10%), and their formation was suppressed higher CEs. Among the quantifiable SEI phases, ROCO2Li was consistently the major phase, but its proportions were invariant with CE. Instead, Li2C2, a minor phase, exhibited clear inverse correlation with CE. These results add further nuance beyond inactive Li0 to the current understanding of capacity loss, and demonstrate that, while minor phases often receive less focus and are harder to characterize, they can play governing roles in SEI function, particularly at high CE when formation of inactive Li0 is minimized. Hobold, G. M.; Lopez, J.; Guo, R.; Minafra, N.; Banerjee, A.; Shirley Meng, Y.; Shao-Horn, Y.; Gallant, B. M., Moving Beyond 99.9% Coulombic Efficiency for Lithium Anodes in Liquid Electrolytes. Nat. Energy 2021, 6 (10), 951-960. Fang, C.; Li, J.; Zhang, M.; Zhang, Y.; Yang, F.; Lee, J. Z.; Lee, M. H.; Alvarado, J.; Schroeder, M. A.; Yang, Y.; Lu, B.; Williams, N.; Ceja, M.; Yang, L.; Cai, M.; Gu, J.; Xu, K.; Wang, X.; Meng, Y. S., Quantifying Inactive Lithium in Lithium Metal Batteries. Nature 2019, 572 (7770), 511-515. Tao, M.; Xiang, Y.; Zhao, D.; Shan, P.; Sun, Y.; Yang, Y., Quantifying the Evolution of Inactive Li/Lithium Hydride and Their Correlations in Rechargeable Anode-Free Li Batteries. Nano Lett. 2022. Xu, G.; Li, J.; Wang, C.; Du, X.; Lu, D.; Xie, B.; Wang, X.; Lu, C.; Liu, H.; Dong, S.; Cui, G.; Chen, L., The Formation/Decomposition Equilibrium of LiH and Its Contribution on Anode Failure in Practical Lithium Metal Batteries. Angew. Chem. Int. Ed. Engl. 2021, 60 (14), 7770-7776. Xiang, Y.; Tao, M.; Zhong, G.; Liang, Z.; Zheng, G.; Huang, X.; Liu, X.; Jin, Y.; Xu, N.; Armand, M.; Zhang, J. G.; Xu, K.; Fu, R.; Yang, Y., Quantitatively Analyzing the Failure Processes of Rechargeable Li Metal Batteries. Sci. Adv. 2021, 7 (46), eabj3423.

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AbstractThis is one of our series papers on multistep schemes for solving forward backward stochastic differential equations (FBSDEs) and related problems. Here we extend (with non-trivial updates) our multistep schemes in [W. Zhao, Y. Fu and T. Zhou, SIAM J. Sci. Comput., 36 (2014), pp. A1731-A1751] to solve the second-order FBSDEs (2FBSDEs). The key feature of the multistep schemes is that the Euler method is used to discretize the forward SDE, which dramatically reduces the entire computational complexity. Moreover, it is shown that the usual quantities of interest (e.g., the solution tuple (Yt,Zt,At,Γt) of the 2FBSDEs) are still of high order accuracy. Several numerical examples are given to show the effectiveness of the proposed numerical schemes. Applications of our numerical schemes to stochastic optimal control problems are also presented.

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Lithium ion batteries are nowadays widely employed in a variety of applications from consumer electronics to electric vehicles. Due to the rising demand for batteries, more affordable and sustainable batteries are needed that exhibit at the same time high energy densities, high power capabilities, long cycle life, and increased safety. One concept to meet these requirements is to develop cobalt-free cathode materials of which the high-voltage spinel LNMO (LiNi0.5Mn1.5O4) is a promising material due to its high energy density and high operating voltage of 4.7 V. However, the high operating voltage has also its drawbacks. Commonly used carbonate-based electrolytes oxidize at high voltages, leading to the continuous formation of a cathode-electrolyte interface (CEI). Additionally, LNMO is prone to transition metal dissolution which not only leads to a reduced stability of the cathode active material but due to migration and deposition of the transition metals on the anode surface also to an altered solid electrolyte interface (SEI) formation and significant impedance rise of the anode.1 Both ageing mechanisms provoke increased lithium loss and high resistances and thus a poor cycling performance.2, 3 In the Horizon 2020 LC-BAT5 project HYDRA, LNMO-based prototype pouch cells are developed and built. Herein, we want to present the results from the comprehensive analysis of their performance and cycling behavior. The influence of upper cut-off voltage, charge and discharge current rate as well as temperature on the degradation are thoroughly investigated by electrochemical methods such as differential voltage analysis and impedance spectroscopy. After cycling, selected cells are opened under argon atmosphere followed by electrochemical characterization as well as physical analysis such as SEM-EDX and XPS in order to get further insights into the underlying ageing mechanisms. We thereby reveal the main degradation mechanisms as a function of the cycling conditions and derive solutions on how to increase the cycle life. 1. C. Zhan, T. Wu, J. Lu and K. Amine, Energy Environ. Sci.,11 (2), 243-257 (2018). 2. J. Ma, P. Hu, G. Cui and L. Chen, Chem. Mater.,28 (11), 3578-3606 (2016). 3. W. Li, Y.-G. Cho, W. Yao, Y. Li, A. Cronk, R. Shimizu, M. A. Schroeder, Y. Fu, F. Zou, V. Battaglia, A. Manthiram, M. Zhang and Y. S. Meng, J. Power Sources,473, (2020). Pseudo-OCV (a) and differential voltage analysis curves (b) of LNMO-graphite pouch cell cycled with 0.3C CCCV charge and 0.1C discharge at 25°C Figure 1

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The article is devoted to the oldest composer of China Du Mingxin, who was among the founders of the new musical culture in the Celestial Empire. He received his musical education at the Composition Department of the Historical and Theoretical Faculty of the Moscow State Tchaikovsky Conservatory. He graduated with high honours following an individual study program. The article is the first to publish Du Mingxin's autobiography written back in 1954 when he was a student at the Moscow State Conservatory, as well as the text of an interview given to the author of the article in 2020. At the age of 93, Du Mingxin is creating new compositions and enjoys communicating with younger composers, among whom there are many of his famous students: Shi Fu, Liu Sola, Ye Xiaogang, Qu Xiaosong, Wang Liling, Zhao Giping, Jin Ping and others. It is noted that the personality and work of Du Mingxin are very popular nowadays: about 170 articles were written about him, dozens of dissertations were defended on his work and a voluminous monograph was written. The process of studying the work of the famous Chinese composer is actively continuing.

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AbstractIn this paper, we are concerned with probabilistic high order numerical schemes for Cauchy problems of fully nonlinear parabolic PDEs. For such parabolic PDEs, it is shown by Cheridito, Soner, Touzi and Victoir [4] that the associated exact solutions admit probabilistic interpretations, i.e., the solution of a fully nonlinear parabolic PDE solves a corresponding second order forward backward stochastic differential equation (2FBSDEs). Our numerical schemes rely on solving those 2FBSDEs, by extending our previous results [W. Zhao, Y. Fu and T. Zhou, SIAM J. Sci. Comput., 36 (2014), pp. A1731-A1751.]. Moreover, in our numerical schemes, one has the flexibility to choose the associated forward SDE, and a suitable choice can significantly reduce the computational complexity. Various numerical examples including the HJB equations are presented to show the effectiveness and accuracy of the proposed numerical schemes.

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Lithium-sulfur (Li-S) batteries feature a high theoretical capacity of 1675 mAh/g and hence is considered as a promising alternative to lithium-ion batteries. However, deployment of Li-S batteries has been hindered by the low practical energy and limited cycle life.1, 2 Reducing cathode porosity is essential to balancing the electrolyte distribution in Li-S cell, conserving more pore-filling electrolyte to extend cell cycle life.3-5 However, low-porosity electrodes built with nanosized sulfur/carbon (S/C) materials suffer from high tortuosity that significantly deteriorates electrode wetting and hence sulfur utilization. Enabling operation of high-loading sulfur electrodes under both low-porosity and lean-electrolyte conditions is still a challenge and is seldom discussed. In this study,6 we demonstrated a novel and facile strategy for constructing low-tortuosity through-pores across both vertical and planar directions of electrodes by casting large particles into single-particle-layer electrodes. Through multi-scale characterizations and simulations, correlations between material/electrode structures, electrolyte permeability, polysulfide migration, and sulfur reactions were elucidated. The high-loading and dense sulfur cathode fabricated by this method delivers a high specific capacity (>1000 mAh g-1) at a very low electrolyte/sulfur (E/S) ratio of 4 μL mg-1. This study provides a novel approach to reducing the tortuosity of dense sulfur electrodes by manipulating the porosity distribution, which would be also applicable to improving the rate capability of other high-energy electrodes. More details of the progress will be discussed at the meeting. Reference. Dörfler, S.; Althues, H.; Härtel, P.; Abendroth, T.; Schumm, B.; Kaskel, S., Challenges and Key Parameters of Lithium-Sulfur Batteries on Pouch Cell Level. Joule 2020, 4 (3), 539-554. Xue, W.; Miao, L.; Qie, L.; Wang, C.; Li, S.; Wang, J.; Li, J., Gravimetric and volumetric energy densities of lithium-sulfur batteries. Current Opinion in Electrochemistry 2017, 6 (1), 92-99. Lu, D.; Li, Q.; Liu, J.; Zheng, J.; Wang, Y.; Ferrara, S.; Xiao, J.; Zhang, J. G.; Liu, J., Enabling High-Energy-Density Cathode for Lithium-Sulfur Batteries. ACS Appl Mater Interfaces 2018, 10 (27), 23094-23102. Kang, N.; Lin, Y.; Yang, L.; Lu, D.; Xiao, J.; Qi, Y.; Cai, M., Cathode porosity is a missing key parameter to optimize lithium-sulfur battery energy density. Nat Commun 2019, 10 (1), 4597. Feng, S.; Liu, J.; Zhang, X.; Shi, L.; Anderson, C.; Lin, Y.; Song, M.-K.; Liu, J.; Xiao, J.; Lu, D., Rationalizing nitrogen-doped secondary carbon particles for practical lithium-sulfur batteries. Nano Energy 2022, 103. Feng, S.; Singh, R. K.; Fu, Y.; Li, Z.; Wang, Y.; Bao, J.; Xu, Z.; Li, G.; Anderson, C.; Shi, L.; Lin, Y.; Khalifah, P. G.; Wang, W.; Liu, J.; Xiao, J.; Lu, D., Low-tortuous and dense single-particle-layer electrode for high-energy lithium-sulfur batteries. Energy & Environ. Sci. 2022.

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Background:Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs(circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases, such as, autoimmunity diseases. However, the role of circRNA in lupus nephritis has been rarely reported.Objectives:In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN.Methods:Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by RNA sequencing (RNA-seq). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Correlation analysis and receiver operating characteristic (ROC) curve were used to reveal the clinical value of selected circRNA, miRNA and mRNA. The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The degrees of renal fibrosis between the two groups were compared by Masson-trichome staining and immunohistochemistry staining.Results:159 circRNAs were significantly dysregulated in LN patients compared with NC group. The expression of hsa_circ_0123190 was significantly decreased in renal tissues of patients with LN (p=0.014), as same as the sequencing results. The area under the ROC curve of hsa_circ_0123190 in renal tissues was 0.820. Bio-informatic analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p which was also validated to interact with APLNR mRNA. APLNR mRNA expression was positively related with chronicity index (CI) of LN (R2=0.452,p=0.033). Finally, the factors of renal fibrosis, especially TGF-β (p=0.018), were more pronounced in the LN group.Conclusion:Hsa_circ_0123190 could function as a ceRNA to regulate APLNR expression involved in renal fibrosis by sponging hsa-miR-483-3p in LNReferences:[1]Aljaberi N, Bennett M, Brunner HI, Devarajan P. Proteomic profiling of urine: implications for lupus nephritis. Expert review of proteomics. 2019;16(4):303-13.[2]Zheng ZH, Zhang LJ, Liu WX, Lei YS, Xing GL, Zhang JJ, et al. Predictors of survival in Chinese patients with lupus nephritis. Lupus. 2012;21(10):1049-56.[3]Chen LL. The biogenesis and emerging roles of circular RNAs. Nature reviews Molecular cell biology. 2016;17(4):205-11.[4]Mahmoudi E, Cairns MJ. Circular RNAs are temporospatially regulated throughout development and ageing in the rat. Scientific reports. 2019;9(1):2564.[5]Liang D, Wilusz JE. Short intronic repeat sequences facilitate circular RNA production. Genes & development. 2014;28(20):2233-47.[6]Tan WL, Lim BT, Anene-Nzelu CG, Ackers-Johnson M, Dashi A, See K, et al. A landscape of circular RNA expression in the human heart. Cardiovascular research. 2017;113(3):298-309.[7]Zhao Z, Li X, Jian D, Hao P, Rao L, Li M. Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus. Acta diabetologica. 2017;54(3):237-45.[8]Ouyang Q, Huang Q, Jiang Z, Zhao J, Shi GP, Yang M. Using plasma circRNA_002453 as a novel biomarker in the diagnosis of lupus nephritis. Molecular immunology. 2018;101(undefined):531-8.[9]Luan J, Jiao C, Kong W, Fu J, Qu W, Chen Y, et al. CircHLA-C Plays an Important Role in Lupus Nephritis by Sponging miR-150. Molecular therapy Nucleic acids. 2018;10(undefined):245-53.[10]Kuschnerus K, Straessler ET, Müller MF, Lüscher TF, Landmesser U, Kränkel N. Increased Expression of miR-483-3p Impairs the Vascular Response to Injury in Type 2 Diabetes. Diabetes. 2019;68(2):349-60.[11]Huang Z, Wu L and Chen L. Apelin/APJ system: A novel potential therapy target for kidney disease. Journal of cellular physiology. 2018;233(5): 3892-900.Disclosure of Interests:None declared

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The paper focused on the description of the reduced graphene oxide (rGO) structure. This material is obtained from a multistage production process. Each of these stages has a large impact on its structure (the number and type of functional groups, number of defect or the size of the flakes), and this in turn affects its properties. We would like to visualize the reduced graphene oxide, both using a diagram showing the atomic structure, as well as by imaging using scanning electron microscopy (SEM) and atomic force microscopy (AFM). In the paper, the elementary composition of selected elements and data obtained from X-ray photoelectron spectroscopy technique (XPS) will be also presented. Full Text: PDF ReferencesX. Peng, Y. Wu, N. Chen, Z. Zhu, J. Liu, and H. Wang, "Facile and highly efficient preparation of semi-transparent, patterned and large-sized reduced graphene oxide films by electrochemical reduction on indium tin oxide glass surface", Thin Solid Films 692, 137626 (2019). CrossRef L. Guo, Y.-W. Hao, P.-L. Li, J.-F. Song, R.-Z. Yang, X.-Y. Fu, S.-Y. Xie, J. Zhao and Y.-L. Zhang, "Improved NO2 Gas Sensing Properties of Graphene Oxide Reduced by Two-beam-laser Interference", Sci. Rep. 8, 1 (2018). CrossRef Y. S. Milovanov, V.A. Skryshevsky, , O.M. Slobodian, , D.O. Pustovyi, X.Tang, J.-P. Raskin, and A.N. Nazarov, "Influence of Gas Adsorption on the Impedance of Graphene Oxide", 2019 IEEE 39th Int. Conf. Electron. Nanotechnology, ELNANO 2019 - Proc. 8783946, CrossRef M. Reddeppa, B.-G. Park, , M.-D. Kim, K.R. Peta, N.D. Chinh, D. Kim, S.-G. Kim, and G. Murali, "H2, H2S gas sensing properties of rGO/GaN nanorods at room temperature: Effect of UV illumination", Sensors Actuators B. Chem. 264, (2018). CrossRef W. L. Xu, C. Ding, , M.-S. Niu, X.-Y. Yang, F. Zheng, J. Xiao, M. Zheng and X.-T. Hao, "Reduced graphene oxide assisted charge separation and serving as transport pathways in planar perovskite photodetector", Org. Electron. 81, 105663 (2020). CrossRef K. Sarkar, M. Hossain, P. Devi, K. D. M. Rao, and P. Kumar, "Self‐Powered and Broadband Photodetectors with GaN: Layered rGO Hybrid Heterojunction", Adv. Mater. Interfaces, 6, 20 (2019). CrossRef S. Pei and H. M. Cheng, "The reduction of graphene oxide", Carbon, 50, 9 (2012). CrossRef R. Muzyka, S. Drewniak, T. Pustelny, M. Chrubasik, and G. Gryglewicz, "Characterization of Graphite Oxide and Reduced Graphene Oxide Obtained from Different Graphite Precursors and Oxidized by Different Methods Using Raman Spectroscopy", Materials 11, 7 (2018). CrossRef M.-H. Tran and H. K. Jeong, "Influence of the Grain Size of Precursor Graphite on the Synthesis of Graphite Oxide", New Phys. Sae Mulli, 63, 2 (2013). CrossRef M.-H. Tran, C.-S. Yang, S. Yang, I.-J. Kim, and H. K. Jeong, "Influence of graphite size on the synthesis and reduction of graphite oxides", Curr. Appl. Phys., 14, SUPPL. 1 (2014). CrossRef N. Sharma, Y. Jain, , M. Kumari, R. Gupta, S.K. Sharma, K. Sachdev, "Synthesis and Characterization of Graphene Oxide (GO) and Reduced Graphene Oxide (rGO) for Gas Sensing Application", Macromol. Symp. 376, 1 (2017). CrossRef M. Wei, L. Qiao, , H. Zhang, S. Karakalos, K. Ma, Z. Fu, M.T. Swihart, G. Wu, "Engineering reduced graphene oxides with enhanced electrochemical properties through multiple-step reductions", Electrochim. Acta, 258 (2017). CrossRef S. Drewniak, M. Procek, R. Muzyka, T. Pustelny, "Comparison of Gas Sensing Properties of Reduced Graphene Oxide Obtained by Two Different Methods", Sensors, 20, 11 (2020). CrossRef L. Li, R.-D. Lv, S. -C. Liu, Z. D. Chen, J. Wang, Y.-G. Wang, W. Ren, "Using Reduced Graphene Oxide to Generate Q-Switched Pulses in Er-Doped Fiber Laser", Chinese Physics Letters, 35, 11 (2018) CrossRef

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Zhao, L.-X., Qu, H.-T., Fu, Y., Gao, S. and Ye, F. 2015. Alleviation of injury from chlorimuron-ethyl in maize treated with safener 3-dichloroacetyl oxazolidine. Can. J. Plant Sci. 95: 897–903. The protective effects of herbicide safeners, including 3-dichloroacetyl-2,2-dimethyl-1,3-oxazolidine (R-28725), 3-dichloroacetyl-2,2-dimethyl-4-ethyl-1,3-oxazolidine (Racemate), and its two enantiomers (R)-3-dichloroacetyl-2,2-dimethyl-4-ethyl-1,3-oxazolidine (R-enantiomer) and (S)-3-dichloroacetyl-2,2-dimethyl-4-ethyl-1,3-oxazolidine (S-enantiomer), on reducing the phytotoxicity of chlorimuron-ethyl to maize were investigated. Soaking the seeds in safeners increased the endogenous glutathione (GSH) content and glutathione-S-transferase (GST) activity of maize. When induced by R-enantiomer, the GST activity in vivo and in vitro increased 180 and 192% compared with control, respectively. R-28725 and R-enantiomer also increased the acetolactate synthase (ALS) activity inhibited by chlorimuron-ethyl from 45 to 100 and 97% compared with the control, respectively. The kinetic parameter Vmax of GST in the maize treated with R-28725 and R-enantiomer increased by 103 and 92%, respectively, compared with the control. Our results suggest that R-28725 and R-enantiomer could significantly improve the GSH content, GST activity, and ALS activity of maize. Overall, maize could be protected from the injury caused by chlorimuron-ethyl.

Abstract:

Over the past century, nitrogen fertilization has fed approximately 27% of the world’s population.1 Urea and ammonia are two of the most important nitrogen fertilizers used world-widely. The current industrial production of urea is mainly realized by an energy-intensive reaction of carbon dioxide and ammonia under harsh conditions (150-200 °C, 150-250 bar) with large energy consumption, for which nearly 80% of synthesized ammonia is used.2 Furthermore, ammonia is also produced under extreme condition (350-550 °C, 150-350 bar) by an energy-consuming Haber-Bosch method.3 Therefore, it is of great significance to synthesize urea and ammonia under mild conditions to meet the demands of ever-increasing population in the world. The electrocatalytic co-reduction of CO2 and NO3 - emerges as a promising approach to realize the direct synthesis of urea via C-N coupling, with ammonia produced as a side product. However, the state-of-the-art yield rates of urea and ammonia through this electrosynthesis are typically below 1 mg h-1 mgcat -1 and 3 mg h-1 mgcat -1.4, 5 In this study, we realize high-rate production of urea on an economic Cu-based organic molecule catalyst through electrochemically coupling CO2 with NO3 -, with ammonia as another useful byproduct. The rationally design of the catalysts guarantees the accurate adsorption and activation of NO3 - and CO2, which further promotes the desired electrochemical C-N coupling in urea synthesis. Efficient urea synthesis was achieved with yield rates ranging from 2.7 to 3.6 mg h-1 mgcat -1 in a potential window of -0.49~-0.67V vs. RHE, together with ammonia with high yield rates ranging from 0.15 to 9.7 mg h-1 mgcat -1. This work proposes an appealing route of sustainable production of artificial nitrogen fertilizers with high efficiencies. Widespread adoption of this approach is promising to re-use the greenhouse gas CO2 and NO3 - from waste toward a full circulate of economy and sustainable energy consumption. The demonstrated production of nitrogen fertilizer in conjunction with renewable electricity is of great potential to meet the rising demand for global food security. Acknowledgements Research Grants Council (26206115, 16304821 and 16309418) and Innovation and Technology Commission (grant no. ITC-CNERC14EG03) of the Hong Kong Special Administrative Region. The work described in this paper was substantially supported by a fellowship award from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKUST PDFS2021-4S12). References J. W. Erisman, M. A. Sutton, J. Galloway, Z. Klimont and W. Winiwarter, Nat. Geosci., 2008, 1, 636-639. M. Yuan, J. Chen, Y. Xu, R. Liu, T. Zhao, J. Zhang, Z. Ren, Z. Liu, C. Streb, H. He, C. Yang, S. Zhang and G. Zhang, Energy Environ. Sci., 2021, 14, 6605-6615. A. J. Martín, T. Shinagawa and J. Pérez-Ramírez, Chem, 2019, 5, 263-283. C. Lv, L. Zhong, H. Liu, Z. Fang, C. Yan, M. Chen, Y. Kong, C. Lee, D. Liu, S. Li, J. Liu, L. Song, G. Chen, Q. Yan and G. Yu, Nat. Sustain., 2021, 4, 868-876. X. Wei, X. Wen, Y. Liu, C. Chen, C. Xie, D. Wang, M. Qiu, N. He, P. Zhou, W. Chen, J. Cheng, H. Lin, J. Jia, X.-Z. Fu and S. Wang, J. Am. Chem. Soc., 2022, 144, 11530-11535.

Abstract:

Thermal management for white LEDs at the encapsulant level is an important task to ensure that the device can operate at a high optical and color performance. In this study, a steady-state thermal model was built wherein the finite element method was employed using MATLAB software to identify the temperature distribution. The spatial temperature distribution of the encapsulant and blue LED die region was easily simulated and predicted. The obtained results are not only helpful in detecting the temperature behavior inside the packaging volume but also meaningful for designing the package configuration. Full Text: PDF References E.-F. Schubert, J.- K. Kim, "Solid-State Light Sources Getting Smart", Science, 308, 1274-1278 (2005). CrossRef Q.-K. Nguyen, "Emission spectrum modeling of white LEDs light source with using Gaussian function", Photonics Lett. Pol., 15, 54-56 (2023). CrossRef E. Schubert, Light-Emitting Diodes (2nd ed., Cambridge: Cambridge University Press, 2006). CrossRef C.-C. Sun, Q.-K. Nguyen, T.-X. Lee, S.-K. Lin, C.-S. Wu, T.-H. Yang, Y.-W. Yu, "Active thermal-fuse for stopping blue light leakage of white light-emitting diodes driven by constant current", Sci. Rep., 12, 12433 (2022). CrossRef Q.-K. Nguyen , B. Glorieux, G. Sebe , T.-H. Yang, Y.-W. Yu , C.-C. Sun, "Passive anti-leakage of blue light for phosphor-converted white LEDs with crystal nanocellulose materials", Sci. Rep. 13, 13039 (2023). CrossRef Q.-K. Nguyen, T.-P.-L. Nguyen, V.-T. Huynh, N.-T. Phan, and H.-T.-A. Nguyen, "An efficient decay model for studying the luminous flux behavior of phosphor-converted white light-emitting diodes", Photonics Lett. Pol., 15, 72-74 (2023). CrossRef J.- L. Davis, K.-C. Mills, G. Bobashev, K.-J. Rountree, M. Lamvik, R. Yaga, C. Johnson, "Understanding chromaticity shifts in LED devices through analytical models", Microelectron. Reliab., 84, 149-156 (2018). CrossRef M. Yazdan Mehr, A. Bahrami, W.-D. Van Driel, X.-J. Fan, J.- L. Davis, G.-Q. Zhang, "Degradation of optical materials in solid-state lighting systems", Int. Mater. Rev., 65, 102-128 (2020). CrossRef Su Y.-F., Yang S.-Y., Hung T.-Y., Lee C.- C., Chiang K.-N, "Light degradation test and design of thermal performance for high-power light-emitting diodes", Microelectron. Reliab., 52, 794-803 (2012). CrossRef K. Baran, M. Leśko, H. Wachta, and A. Różowicz, "Thermal modeling and simulation of high power LED module", AIP Conference Proceedings., 2078, 020048 (2019). CrossRef H.-K. Fu, C.-P. Wang, H.-C. Chiang, T.-T. Chen, C.-L. Chen, P.-T. Chou, "Evaluation of temperature distribution of LED module", Microelectron. Reliab., 53, 554-559 (2013). CrossRef M.-X. Chen, X. Chen, K. Xu, and L. Zheng, "Thermal simulation and analysis of flat surface flip-chip high power light-emitting diodes", J. Semicond., 34, (2013). CrossRef C.- M. Tan, P. Singh, W. Zhao, and H.-C. Kuo, "Physical Limitations of Phosphor layer thickness and concentration for White LEDs", Sci. Rep., 8, 2452 (2018). CrossRef F.P. Incropera, D.P. Dewitt. Fundamentals of Heat and Mass Transfer (Fifth Edition. New York: J. Wiley, 2002). DirectLink Q.-K. Nguyen, and T.-H.-T. Vu, "An Efficient Method for Simulating the Temperature Distribution in Regions Containing YAG:Ce3+ Luminescence Composites of White LED", J. Compos. Sci, 7, 301 (2023). CrossRef

Abstract:

Lithium-ion batteries (LIBs) are a reliable energy storage technology that have been used in various applications such as portable devices and power tools. However, the specific capacities of the electrode materials in the current LIB technology are approaching their theoretical limits which impedes their utilization in a variety of emerging applications such as long-range electric vehicles, next-generation mobile devices, and grid level energy storage and delivery. Therefore, alternative electrode materials with high specific capacity beyond the conventional LIB electrode materials are needed 1. Sulfur has been touted as a promising alternative cathode material in recent years. Sulfur offers superior theoretical capacity, and a high practical energy density when it is paired with a Li metal anode in so called Li-S batteries2. Non-toxicity, low cost and high natural abundance also make Sulfur environmentally and economically appealing. However, achieving the desired high energy density and long cycle life in Li-S batteries have been proven difficult because of the: (1) insulating nature of the two end products of charge and discharge; S8 and Li2S, (2) electrode degradation due to the volumetric change during cycling, and (3) dissolution of the Sulfur discharge products, Li-polysulfides (LiPSs), in the ether-based electrolyte, resulting in the “shuttling effect” that leads to capacity decay over extended cycling 3,4. In this work, new insights are presented on how the binder, its solvent, and dissolution process affect the electrode microstructure and performance. The Sulfur cathodes were prepared using commercially available Sulfur powder, carbon black and various binders and solvents. The cathode structures prepared using different binder and solvent combinations were characterized using scanning electron microscopy (SEM). The cycling performance of the Sulfur cathodes were tested in coin cells. The results showed considerable structural and performance variations between cathodes with similar binders but different solvents, or different treatment conditions with the same solvent. In particular, when binders were minimally dissolved in N-Methylpyrrolidone a porous shell-like structure was observed around the sulfur particles that evolved to a denser sponge-shape structure upon excessive dissolution. The porous shell structure resulted in enhanced performance and cycle life. Using spectroscopic data, it is possible that enhanced cycle life might be attributable to physical trapping of the LiPSs and providing a buffer for the volumetric change during discharge. Thus, a new perspective will be presented that the binder/solvent interaction can impact the performance of sulfur cathodes by manipulating both its structural and chemical behavior. These results are expected to provide a new understanding regarding the effect of binder and its processing on the performance of Li-S batteries and help to write a new narrative regarding electrode chemistry and preparation techniques for future applications. References M. Zhao et al., ACS Cent. Sci., 6, 1095–1104 (2020). A. Manthiram, Y. Fu, S.-H. Chung, C. Zu, and Y.-S. Su, Chem. Rev., 114, 11751–11787 (2014). A. Manthiram, Y. Fu, and Y.-S. Su, Acc. Chem. Res., 46, 1125–1134 (2013). W. Ren, W. Ma, S. Zhang, and B. Tang, Energy Storage Mater., 23, 707–732 (2019).

Abstract:

Abstract Background: Antiangiogenic drugs have demonstrated synergistic effect with anti-PD-1 antibody in advanced triple negative breast cancer (TNBC). Anlotinib is an oral multi-target tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Preclinical studies showed that metronomic chemotherapy inhibited angiogenesis and enhanced the efficacy of immunotherapy in TNBC via modulation of the tumor immune microenvironment. We hereby conducted a single-arm, multicenter, phase II trial to investigate the efficacy and safety of sintilimab (anti-PD-1 antibody) plus anlotinib and metronomic chemotherapy as a potential novel therapeutic strategy in advanced TNBC and explore potential biomarkers. Methods: Forty-four cases were planning to be included in this trial. The eligible patients who had received no more than two lines of chemotherapy for metastatic disease were enrolled and received sintilimab (200 mg iv q3w) and anlotinib (12 mg po d1-14 q3w) plus capecitabine (500 mg po, tid) or vinorelbine (40 mg po, tiw) until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR) and secondary endpoints are disease control rate (DCR), progression free survival (PFS), and overall survival (OS). The safety profile has also been assessed. Results: As of April 2023, a total of 44 patients were enrolled, and 42 patients were evaluable for efficacy. 3 patients (7.1%) achieved complete response (CR). 6 patients (14.3%) achieved partial response (PR). 25 patients (59.5%) achieved stable disease (SD).The ORR is 21.4% (95%CI 0.103-0.368) and DCR is 81.0% (95%CI 0.810-0.659). The median PFS was 5.06 months (95%CI 2.051-8.069). The most common grade 1 or 2 adverse events (AEs) include elevated thyroid stimulating hormone (52.38%, 22/42), elevated bilirubin (23.81%, 10/42), hand-foot syndrome (22.22%, 8/42), leukopenia (16.67%,7/42), nausea (14.29%, 6/42). Grade 3 AEs include elevated bilirubin (2.38%, 1/42), hypertension (2.38%, 1/42) and herpes zoster (2.38%, 1/42). No grade 4 or 5 AEs occurred. Conclusions: Our date showed that sintilimab in combination with anlotinib plus metronomic chemotherapy have shown favorable efficacy and acceptable safety profile in patients with advanced TNBC. Clinical trial information: ChiCTR2100044725 Citation Format: huihui Li, Dongdong Zhou, Zeshun Yv, Yuqian Liao, Jie Huang, Shujuan Sun, fangchao zheng, Baojiang Li, Shu Fang, Ling Qiang, Guohua Ren, Bing Bu, Pengfei Qiu, Xinzhao Wang, Chao Li, Fangli Cao, Qian Shao, Dali Han, Lihua Song, Baoxuan Zhang, Bingjie Fan, Liang Xu, Xuemei Xie, Xianguang Zhao, Lanping Liu, Wanlong Li, Zhenbo Wang, Changmin Liu, Hui Fu, Xiao Sun, Zhiqiang Shi, Fengxiang Li. Efficacy and safety of sintilimab in combination with anlotinib plus metronomic chemotherapy in advanced triple negative breast cancer (SPACE): preliminary results of a single-arm, multicenter phase II trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-07.

Abstract:

Sodium-ion batteries (NIBs) are listed as one of the ideal alternatives for lithium-ion batteries (LIBs), due to the abundant sodium resources, cost-effective electrode materials of NIBs, and same architecture of NIBs to LIBs. To enable the practical implementation of NIBs, advanced cathodes with higher energy/power densities, better safety and cycle life, as well as lower cost are required. Layered lithium transition metal oxides (LiTMO2) are one of the most successful cathode materials for commercial LIBs. Similarly, layered sodium transition metal oxides (NaxTMO2, also termed as sodium layered oxides) are of particular interest for commercial NIBs owing to their high specific capacity, a wide variety of redox-active elements, and the possibility for the manufacturers to employ established synthesis processes as their lithium counterparts. Sodium layered oxides are built up by ordered stacking of alternate alkali-metal (Na+) layers and transition metal layers (TmO2). The two-dimensional structure makes them the natural hosts for alkali-metal ions and other ions or small molecules, such as H2O. Therefore, when exposed to moist atmospheres, layered oxide materials tend to react with H2O which adsorbed on their surface and thus deteriorate their structure and electrochemical performances. Accordingly, the air-sensitive sodium layered oxides should be well protected from the moist atmospheres, rendering a higher manufacturing and preservation cost. Here, based on the reaction mechanisms, critical influencing factors, and modification methods of layered oxides in moisture, we try to reach a comprehensive understanding of the air-stability of sodium layered oxides. Moreover, future efforts to resolve the air-stability of sodium layered oxides from Argonne National Laboratory will be also presented. References 1. Han, M. H.; Gonzalo, E.; Singh, G.; Rojo, T. A comprehensive review of sodium layered oxides: powerful cathodes for Na-ion batteries. Energy Environ. Sci. 2015, 8, 81-102. 2. Zuo, W.; Qiu, J.; Liu, X.; Ren, F.; Liu, H.; He, H.; Luo, C.; Li, J.; Ortiz, G. F.; Duan, H.; Liu, J.; Wang, M. S.; Li, Y.; Fu, R.; Yang, Y. The stability of P2-layered sodium transition metal oxides in ambient atmospheres. Commun. 2020, 11, 3544. 3. Xu, G. L.; Liu, X.; Zhou, X.; Zhao, C.; Hwang, I.; Daali, A.; Yang, Z.; Ren, Y.; Sun, C. J.; Chen, Z.; Liu, Y.; Amine, K. Native lattice strain induced structural earthquake in sodium layered oxide cathodes. Commun. 2022, 13, 436. 4. Zuo, W.; Xiao, Z.; Zarrabeitia, M.; Xue, X.; Yang, Y.; Passerini, S. Guidelines for Air-Stable Lithium/Sodium Layered Oxide Cathodes. ACS Materials Letters 2022, 4, 1074-1086. 5. Fu, F.; Liu, X.; Fu, X.; Chen, H.; Huang, L.; Fan, J.; Le, J.; Wang, Q.; Yang, W.; Ren, Y.; Amine, K.; Sun, S. G.; Xu, G. L. Entropy and crystal-facet modulation of P2-type layered cathodes for long-lasting sodium-based batteries. Commun. 2022, 13, 2826.

Abstract:

Abstract The proprietary XNA (xeno nucleic acid) technology has wide applications in sensitive detection of rare mutations in different genomic platforms. These target-specific DNA oligo analogs increase assay sensitivity by blocking the polymerase-dependent amplification of wildtype sequence so only amplification of the mutant sequence occurs. Here we show that the XNA technology helps enrich rare somatic mutations in different human specimen types such as FFPE and plasma samples, using technology platforms such as Sanger sequencing, TaqMan qPCR, and NGS. XNA increases assay sensitivity to 0.1% for Sanger sequencing and qPCR. For NGS, XNA allows detection of the mutant sequence at a lower sequencing depth, thus combining XNA technology with NGS for MRD (molecular residual disease) detection could improve cancer management. In addition, We also show CRISPR mutant screening using a target-specific XNA in a SYBR Green qPCR assay. XNA can be used for rapid CRISPR mutant screening for DNA from pool or individual clones generated from gene editing experiments. In summary, XNA technology is a powerful tool when combined with existing genomic mutation detection platforms to screen for rare somatic mutations and for rapid CRISPR mutant screening. The technology is customizable as a service for easy integration with current technology platforms and applications. Citation Format: Wei Liu, Robert Brown, Andrew Fu, Shuo Shen, Michael Sha, Aiguo Zhang. XNA increases assay sensitivity in sanger sequencing, qPCR, NGS and CRISPR mutant screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6681.

Abstract:

Zhang, L., Wang, Y.-y., Fu, M.-z., Li, G., An, N., Li, S.-y. and Zhou, Z.-q. 2014. The effects of ovariectomy on meat performance and expression of GH/IGF-I in young goats. Can. J. Anim. Sci. 94: 619–626. Experiments were carried out to investigate the effects of ovariectomy on meat production efficiency and to explore the expression of GH/IGF-I in young goats. Animal performance, meat quality, levels of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-I), and mRNA levels of three key genes [GH Receptor (GHR), IGF-I and IGF-I Receptor (IGF-IR)] in longissimus dorsi and biceps femoris muscles were measured. The results show that carcass weight, net meat mass, fat weight and loin eye area of ovariectomized goats were higher than those of the controls, and ovariectomized goats lost 0.40 kg of bone weight (P<0.05). There was no statistically valid difference for the color, pH, water-holding capacity, or cooking rate of meat (P>0.05) between the two groups, except for the shear value, which was significantly lower in the Ovx group than in the control group (P<0.05). The results of this research show for the first time a significant trend (P<0.05) for serum GH and IGF-I in the direction of increasing in ovariectomized goats. Furthermore, the mRNA levels of GHR, IGF-I and IGF-IR in muscle were all up-regulated, except for the IGF-I gene in biceps femoris, by ovariectomy. In summary, ovariectomy showed a beneficial promotion in animal performance, but did not reduce meat quality, and increased serum GH and IGF-I and mRNA expression levels of GHR, IGF-I and IGF-IR in young female goats.

Abstract:

Qu, C., Hasan, M., Lu, K., Liu, L., Zhang, K., Fu, F., Wang, M., Liu, S., Bu, H., Wang, R., Xu, X., Chen, L. and Li, J. 2015. Identification of QTL for seed coat colour and oil content in Brassica napus by association mapping using SSR markers. Can. J. Plant Sci. 95: 387–395. Association mapping identifies quantitative trait loci (QTL) based on the strength of linkage disequilibrium (LD) between markers and functional polymorphisms across a set of diverse germplasms. In this study, we used association mapping to detect QTL and genome-wide simple sequence repeat (SSR) markers linked to seed coat colour and oil content in a population of 217 oilseed rape (Brassica napus L.) accessions. We corrected for the population structure of B. napus using 389 genome-wide SSR markers. In total, 25 and 11 SSR markers linked to seed coat colour and oil content were detected, respectively, and these two sets of markers were in different linkage groups. Nine of these markers for seed coat colour spanned the major QTL region for seed coat colour, and been mapped to chromosome A9. Six of these markers showed high levels of association with both seed coat colour and oil content, and markers H081N08.8 and KS20291 were mapped to the major QTL region for seed coat colour on chromosome A9. Another marker, CB10364, was in high LD with all determined seed coat colour and oil content traits, and was mapped to the co-localized QTL region for them on chromosome A8. These data indicate that seed coat colour was found to be an important contributor to seed oil content. Further, we show that association mapping using a heterogeneous set of genotypes is a suitable approach for complementing and enhancing previously obtained QTL information for marker-assisted selection.

Abstract:

Abstract Unlike classical Signal transducer and activator of transcription (Stat) signaling, which is transient in non-transformed cells, the aberrant activation of the family member, Stat3, occurs in malignant transformation and is implicated in breast, ovarian and many other human cancers. Thus, Stat3 remains a validated and important target for the discovery of novel anticancer drugs. Despite this, the discovery and development of potent Stat3 small molecule inhibitors has proven to be a significant challenge, and no drug is available yet in the market. We have discovered novel Stat3 irreversible azetidine inhibitors with unprecedent submicromolar potency through systematic medicinal chemistry structure activity relationship (SAR). Mechanism of action of most potent azetidine inhibitors depend on whether they are salicylic acids or not, i.e., salicylic acids preferably bind irreversibly to Stat3 Cys426 site in the DNA-binding domain (DBD), and non-salicylic acids, e.g., current lead H182, bind to Stat3 Cys468 DBD site. As expected, the inhibition of Stat3 DNA-binding activity was time dependent, with IC50 in the range of 0.27-0.87 µM at one hour incubation with active Stat3. On the other hand, azetidine salicylic acids also bind to the SH2 domain, although reversibly and at much weaker affinity, as determined in fluorescent polarization (FP) assay, with IC50 of 10-16 µM at one hour incubation, while non-salicylic acids, e.g., lead H182, present no binding affinity up to 600 µM for the SH2 domain. Despite that H182 does not bind to SH2 domain, it still inhibits its phosphorylation. Though lead compound H182 presents significant mouse in vivo efficacy, mouse in vivo pharmacokinetics shows very low plasma AUC, which correlates with quite high mouse in vitro hepatocyte CLint of 138 µL/min/106 cells; however, human in vitro hepatocyte assay gives much better results and is in the middle stability range (CLint of 14.6 µL/min/106 cells). The in vivo PK in other species, e.g., rat, is being determined. H182 represents a plausible molecule for further development. Citation Format: Yue Chen, Ning Zhai, Yinsong Zhu, Peibin Yue, Nagendra Verma, Christine Brotherton-Pleiss, Wenzhen Fu, Kayo Nakamura, Weiliang Chen, Marcus Tius, Francisco J. Lopez-Tapia, James Turkson. Novel potent azetidine-based inhibitors bind irreversibly to Stat3 DNA-binding domain (DBD) and are efficacious against tumor growth in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 514.

Abstract:

Abstract Objective: Breast Cancer is one of the most common malignant tumors in women. HER-2 is a driver gene for poor prognosis in breast cancer. Anti-HER-2 drugs have significantly improved the prognosis of patients with HER-2 positive metastatic breast cancer. There is still a lack of exploration of first-line anti-HER2 treatment options and translational studies only for patients with metastases after adjuvant and/or neoadjuvant trastuzumab therapy. This study is based on our previous clinical trial of pyrotinib in combination with albumin-bound paclitaxel in first line for patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy, with the aim of exploring the efficacy and adverse events in the enrolled patients. And to explore the markers associated with Progression Free Survival (PFS) by using Olink technique to detect blood samples from patients. To provide a better screening of the benefit population and provide guidance for the treatment of HER-2 positive metastatic breast cancer. Methods: From December 2019 to July 2023, our previous clinical trial prospectively enrolls 27 patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy. Pyrotinib (400 mg, po, qd) combined with albumin-bound paclitaxel (200 mg, ivdrip, d1, d8, q21d) was used as the first-line treatment regimen. Patients were evaluated for efficacy. Survival analysis was performed by using the Kaplan-Meier method. Blood samples were collected during treatment. We selected 21 blood samples from patients, and dynamically detected plasma protein changes by Olink technique. Differential protein analysis between groups according to hormone receptor status, trastuzumab primary/secondary resistance, and the presence of visceral metastases. And the proteins associated with PFS were analyzed. Results: Among the 27 patients whose efficacy had been evaluated, 7 patients were evaluated as CR, 18 patients as PR, and 2 patients as SD. The objective response rate was 92.6%, and the disease control rate was 100%. The median follow-up was 17.8 months and the median PFS has not yet been reached. Diarrhea is the most common adverse event. Grade 3 or higher adverse events include diarrhea, leukocytopenia, neutropenia, and hand-foot syndrome. The progression free survival was significantly worse in patients with visceral metastases (P=0.01). Results of Olink protein dynamic assay showed a significant downregulation of CEACAM5, TXLNA, PVRL4and ERBB2. Differential proteins between groups showed that there were no significant differential proteins between the hormone receptor-positive and negative groups at the baseline node, but 7 proteins were upregulated in the hormone receptor-positive group compared with the negative group at the progression node, with EMS-1, WIF-1, and hK14 being the most significant. Compared to primary resistance, trastuzumab secondary resistance appeared 4 proteins upregulated at the baseline node, with hK14 and CYR61 being the most significantly; and 33 proteins were upregulated at the progression node, with CYR61, CXL17, FURIN, and ABL1 being the most significantly. Patients with high expression of TLR3 and low expression of RET at the baseline node had longer PFS. Conclusions: This study demonstrates that pyrotinib in combination with albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and a manageable safety for patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy. PFS was shorter in patients with visceral metastases. TLR3 and RET were the proteins that significantly associated with PFS in patients. Citation Format: Huihui Li, Xiaochu Man, Sha Yin, Dongdong Zhou, Baoxuan Zhang, Shu Fang, Fangchao Zheng, Chao Li, Xinzhao Wang, Wei Huang, Linlin Wang, Qingqing He, Hui Fu, Yan Zhang, Changrui Liu, Lin Dong, Xianguang Zhao, Liang Xu, Xiao Sun, Bingjie Fan, Lihua Song, Zhengbo Zhou, Qiaorui Tan, Jinming Yu. Efficacy, safety and translational study of pyrotinib combined with albumin-bound paclitaxel as firstline treatment of HER-2 positive metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-07.

Abstract:

Lithium metal and anode-free batteries has the potential to increase the energy density and specific energy of the batteries drastically. However, when regular electrolyte materials are tried for these concepts they are plagued with problems due to degradation of the electrolyte at the interface and processes like dendrite formation which leads to poor capacity retention.[1] A strategy to mitigate these problems is to use Solid Polymer Electrolytes (SPEs), as these have better stability towards lithium metal. In order to find appropriate chemistries to use in SPE-based cells it is important to investigate and understand their anode interface, as this is where the Solid Electrolyte Interphase (SEI) is created from the degradation products during cycling. This work investigates three polyethylene oxide (PEO)-based SPEs, using lithium tetrafluoroborate (LiBF4), lithium bis(oxalate)borate (LiBOB), and lithium difluoro(oxalate)borate (LiDFOB) as the lithium conducting salts. The interfaces of these SPEs (PEO:LiBF4, PEO:LiBOB, and PEO:LiDFOB) was studied using Photo-Electron Spectroscopy (PES) with in situ lithium deposition, where lithium atoms are evaporated on top of the SPE film. The analysis of the core-level spectra before and after lithium deposition is compared to Ab Initio Molecular Dynamics (AIMD) simulations of the interface, where lithium atoms are gradually added during the simulation. These experimental and theoretical methods are meant to mimic the electrochemical plating of lithium at the lithium|SPE interface during charging of a lithium metal or anode-less cell. The interfaces of PEO:LiBOB and PEO:LiBF4 show, among other compounds, polyethylene as a breakdown product at the interface. PEO:LiDFOB shows a much lesser degree of degradation compared to the other two systems. The degradation layer is however still effective at protecting the SPE from further breakdown, as PEO:LiDFOB has a relatively high capacity retention compared to PEO:LiBF4 and PEO:LiBOB. Suggested is that the LiF provides a better electrochemical stability, while the boron and oxalate breakdown products provides a higher mechanical stability at the interface. [1] Huang WZ, Zhao CZ, Wu P, Yuan H, Feng WE, Liu ZY, Lu Y, Sun S, Fu ZH, Hu JK, Yang SJ. Anode‐Free Solid‐State Lithium Batteries: A Review. Advanced Energy Materials. 2022 Jul;12(26):2201044. Figure 1

Abstract:

Polyolefin separators are widely used for most of commercial application owing to their excellent mechanical properties, electrical insulation, and internal porous structures. The raw polyolefin materials have economic viability and possess facile mechanical extension suitable for processing as a film [1]. However, the inherent thermal property of polyolefin inevitably results in the severe thermal deformation of the separators upon the elevation of LiB temperature that has been pointed out as a major cause of fire in LiBs with the possibility of short circuits caused by lithium dendrites [2]. There have been trials to secure cycle characteristics by preventing LiB separators from shrinkage. But, even the coated polyolefin separator couldn’t have thermal stability at high temperatures above 180 oC, since the polyolefin was the base film material. Many studies have been performed to achieve high temperature stability with engineering plastics, including polyimide (PI) [1]. As PI has superior thermal stability, it has been widely applied as nonwoven separators. PI nonwoven fabric separators exhibit stability usually above 200 oC. As PI nonwoven separators have also high ionic conductivity and good electrolyte wettability, it is therefore expected to show excellent rate capability and cyclability [3]. Despite those advantages, however, PI nonwoven separators still have several issues to resolve before application of them to LiBs. One of the problems is the existence of large pores [4]. Pores over a certain size is thought to render particles in cathode active materials pass through or Li dendrites penetrate upon overcharging. Then, it can result in leakage current and internal short circuit eventually. Various studies such as particle-coating or ceramic-coating have been studied in order to figure out this problem [26]. Other than pore-size distribution or existence of large pores, it must be the electrochemical stability of PI nonwoven separator and the electrochemical cell performance with the separator at high voltage that needs to be studied and examined for the potential application to LiBs [3]. In accordance with the strong demand on high power LiB development, study on the electrochemical resistance of materials and components is highly required [5]. As PI has polar chemical structure in contrast to non-polar chemical structure of polyolefin, it would be worthy to investigate the electrochemical nature and stability under high current or high voltage. In this study, a PI nonwoven separator is modified by coating of polysiloxane to improve its electrochemical stability and properties as well as its porous structure. As the coated PI nonwoven separator should be stable up to 200 oC due to the robust PI frame and the modification via polysilicon-coating is rather simple, the feasibility of this chemical approach is demonstrated and studied including its electrochemical behaviors. Ionic conductivity, electrolyte wettability, and gas permeability of the modified separator is also examined as a set of tests for LiB application. It was electrochemically stable during LSV even at 5 V vs Li+/Li. The polysiloxane-coating maintains or improves the excellent thermal and electrical stability of the PI nonwoven separators. The full cell test demonstrated that the polysiloxane-coating enabled a cyclability of 98.6% after 100 cycles, while the PI nonwoven could not be charged due to an internal short circuit. [1] H. Lee, M. Yanilmaz, O. Toprakci, K. Fu, X. Zhang, A review of recent developments in membrane separators for rechargeable lithium-ion batteries, Energy Environ. Sci, 7, 2014, 3857. [2] X. Zhang, E. Sahraei, K. Wang, Li-ion Battery Separators, Mechanical Integrity and Failure Mechanisms Leading to Soft and Hard Internal Shorts, Sci. Rep., 6, 2016, 32578. [3] Z. Lu, F. Sui, Y. Miao, G. Liu, C. Li, W. Dong, J. Cui, T. Liu, J. Wu, C. Yang, Polyimide separators for rechargeable batteries, J. Energy Chem., 58, 2021, 170. [4] G. Dong, B. Liu, G. Sun, G. Tian, S. Qi, D. Wu, TiO2 nanoshell@polyimide nanofiber membrane prepared via a surface-alkaline-etching and in-situ complexation-hydrolysis strategy for advanced and safe LIB separator, J. Membr. Sci., 577, 2019, 249. [5] Y. Xiang, J. Li, J. Lei, D. Liu, Z. Xie, D. Qu, K. Li, T. Deng, H. Tang, Advanced Separators for Lithium-Ion and Lithium-Sulfur Batteries: A Review of Recent Progress, ChemSusChem, 9, 2016, 1. Figure 1

Abstract:

Referências 1. Keeling, M. J. & Rohani, P. Modeling infectious diseases in humans and animals. Modeling Infectious Diseases in Humans and Animals (PRINCETON UNIVERSITYPRESS, 2011). 2. Aquilanti, V., Coutinho, N. D. & Carvalho-Silva, V. H. Kinetics of Low-Temperature Transitions and Reaction Rate Theory from Non-Equilibrium Distributions. Philos. Trans. R. Soc. London A 375, 20160204 (2017). 3. Carvalho-Silva, V. H., Coutinho, N. D. & Aquilanti, V. Temperature dependence of rate processes beyond Arrhenius and Eyring: Activation and Transitivity. Front. Chem. 7, 380 (2019). 4. Center For Systems Science And Engineering Johns Hopkins University. CSSEGISandData/COVID-19 (2020). Available at: https://github.com/CSSEGISandData/COVID-19. (Accessed: 30th March 2020) 5. Machado, H. G. et al. “Transitivity”: a code for computing kinetic and related parameters in chemical transformations and transport phenomena. Molecules 24, 3478 (2019). 6. Aquilanti, V., Borges, E. P., Coutinho, N. D., Mundim, K. C. & Carvalho-Silva, V. H. From statistical thermodynamics to molecular kinetics: the change, the chance and the choice. Rend. Lincei. Sci. Fis. e Nat. 28, 787–802 (2018). 7. Arnold, B. C. Pareto and Generalized Pareto Distributions. in Modeling Income Distributions and Lorenz Curves 119–145 (Springer New York, 2008). 8. Tsallis, C. Possible Generalization of Boltzmann-Gibbs Statistics. J. Stat. Phys. 52, 479–487 (1988). 9. Jena, A. K. & Chaturvedi, M. C. Phase transformation in materials. (Prentice Hall, 1992). 10. Poccia, N. et al. Evolution and control of oxygen order in a cuprate superconductor. Nat. Mater. 10, 733–736 (2011). 11. Zhao, S., Musa, S. S., Fu, H., He, D. & Qin, J. Simple framework for real-time forecast in a data-limited situation: The Zika virus (ZIKV) outbreaks in Brazil from 2015 to 2016 as an example. Parasites and Vectors 12, 344 (2019). 12. Subbaraman, N. Coronavirus tests: researchers chase new diagnostics to fight the pandemic. Nature (2020). doi:10.1038/d41586-020-00827-6 13. Balilla, J. Assessment of COVID-19 Mass Testing: The Case of South Korea. SSRN Electron. J. (2020). doi:10.2139/ssrn.3556346 14. Anderson, R. M., Heesterbeek, H., Klinkenberg, D. & Hollingsworth, T. D. How will country-based mitigation measures influence the course of the COVID-19 epidemic? The Lancet 395, 931–934 (2020).

Abstract:

The effect of photon processing (FO) on the formation of a heterojunction in the TiO2/QD’sCdS interface obtained by applying separately synthesized CdS quantum dots to the TiO2 film in the rutile phase has been studied. The changes of luminescence spectra and absorption of the investigated samples after this treatment discovered. It is shown that the separation of charge carriers occurs only after irradiation of samples with a powerful light pulse of a xenon lamp. REFERENCES Kapilashrami M., Zhang Y. , Liu Y.-S., Hagfeldt A., Guo J. Probing the Optical Property and Electronic Structure of TiO2 Nanomaterials for Renewable Ener gy Applications. Chem. Rev., 2014, v. 114, pp. 9662–9707. https://doi.org/10.1021/cr5000893 Dang T. C., Pham D. L., Le H. C., Pham V. H. TiO2/CdS nanocomposite fi lms: fabrication, characterization, electronic and optical properties. Adv. Nat. Sci. Nanosci. Nanotechnol., 2010, v. 1, p. 015002. https://doi.org/10.1088/2043-6254/1/1/015002 Qian X., Qin D., Bai Y., Li T., Tang X., Wang E., Dong S., Photosensitization of TiO2 nanoparticulate thin fi lm electrodes by CdS nanoparticles. J. Solid State Electrochem., 2001, v. 5, pp. 562–567. https://doi.org/10.1007/s100080000179 Baker D. R., Kamat P. V. Photosensitization of TiO2 nanostructures with CdS quantum dots: Particulateversus tubular support architectures. Adv. Funct. Mater., 2009, v. 19, pp. 805–811. https://doi.org/10.1002/adfm.200801173 Cheng S., Fu W., Yang H., Zhang L., Ma J., Zhao H., Sun M., Yang L. Photoelectrochemical performance of multiple semiconductors (CdS/CdSe/ZnS) cosensitized TiO2 photoelectrodes. J. Phys. Chem. C, 2012, v. 116, pp. 2615–2621. https://doi.org/10.1021/jp209258r Khlyap H. Physics and technology of semiconductor thin fi lm-based active elements and devices. Bentham Science Publisher, 2012. https://doi.org/10.2174/97816080502151090101 Milnes A. G., Feucht D. L. Hetero junctions and metal-semiconductor junctions. Academic Press, 418 p. https://doi.org/10.1016/B978-0-12-498050-1.X5001-6 Ievlev V. M., Latyshev A. N., Kovneristyi Y. K., Turaeva T. L., Vavilova V. V., Ovchinnikov O. V., Selivanov V. N., Serbin O. V. Mechanism of the photonic activation of solid-phase processes. High Energy Chem., 2005, v. 39, pp. 397–402. https://doi.org/10.1007/s10733-005-0078-2 Ievlev V. M., Kushchev S. B., Latyshev A. N., Ovchinnikov O. V., Leonova L. Y, Solntsev K. A., Soldatenko S. A., Smirnov M. S., Sinelnikov A. A., Vozgorkov A. M., Ivikova M. A. Relation of absorption band edge of rutile fi lms and their structure. Inorg. Mater. Appl. Res., 2014, v. 5, pp. 14–21. https://doi.org/10.1134/s2075113314010055 Korolev N. V., Smirnov M. S., Ovchinnikov O. V, Shatskikh T.S. Energy structure and absorption spectra of colloidal CdS nanocrystals in gelatin matrix. Phys. E Low-Dimensional Syst. Nanostructures, 2015, v. 68, pp. 159–163. https://doi.org/10.1016/j.physe.2014.10.042. Ghazzal M. N., Wojcieszak R., Raj G., Gaigneaux E.M. Study of mesoporous cds-quantumdot-sensitized TiO2 fi lms by using x-ray photoelectron spectroscopy and afm. Beilstein J. Nanotechnol, 2014, v. 5, pp. 68–76. https://doi.org/10.3762/bjnano.5.6 Ahire R. R., Sagade A. A., Deshpande N. G., Chavhan S. D., Sharma R., Singh F. Engineering of nanocrystalline cadmium sulfi de thin fi lms by using swift heavy ions. J. Phys. D. Appl. Phys., 2007, v. 40, pp. 4850–4854. https://doi.org/10.1088/0022-3727/40/16/014 Ekimov A., Onushchenko A.A. Size quantization of the electron energy spectrum in a microscopic semiconductor crystal. JETP Lett., 1984, v. 40, pp. 1136–1139. Rolo A. G., Stepikhova M. V., Filonovich S. A., Ricolleau C., Vasilevskiy M. I., Gomes M. J. M. Microstructure and photoluminescence of CdS-doped silica fi lms grown by RF magnetron sputtering. Phys. Status Solidi Basic Res., 2002, v. 232, pp. 44–49. https://doi.org/10.1002/1521-3951(200207)232:1<44::AIDPSSB44> 3.0.CO;2-4 Smyntyna V., Skobeeva V., Malushin N. The nature of emission centers in CdS nanocrystals, Radiat. Meas., 2007, v. 42, pp. 693–696. https://doi.org/10.1016/j.radmeas.2007.01.068 Ehemba A. K., Socé M. M., Domingo J. J., Cisse S., Dieng M. Optimization of the properties of the back surface fi eld of a Cu (In, Ga) Se2 thin fi lm solar cell. American Journal of Energy Research, 2017, v. 5(2), pp. 57–62. https://doi.org/10.12691/ajer-5-2-5

Abstract:

Functioning devices exploiting the properties of organic chromophores, e.g. in the context of photovoltaics, organic electronics, light-emitting devices, and photodetectors, often rely on the assembly of the molecules into appropriate solids and their interfacing to electrodes. In this context, recently the MOF-based approach [1] is receiving increasing attention. In this case, the organic chromophores (anthracene, pentacene, naphthalene-diimides, perylene-diimides, porphyrins, phthalocyanines, ...) are equipped with at least two coupling units so as to yield ditopic linkers suited for the coupling to metal- or metal-oxo nodes, thus yielding metal-organic frameworks (MOFs). Although the standard form of MOFs, powders, are not well suited for the integration of the arrayed chromophores into devices, in the past decade a number of methods able to yield high quality, monolithic MOF thin films deposited on a variety of substrates have been developed. Sophisticated fabrication methods, including layer-by-layer approaches yield films of impressive optical quality.[2] Optical absorption properties of condensed chromophores are often strongly affected by inter-molecular interactions. The periodic structure of MOFs provides the basis for a rational design of such assemblies, and e.g. J-aggregates have been first simulated and then realized experimentally.[3] In addition, band-structure effects like indirect band gaps can be realized in such periodic arrangements.[4] Finally, the implementation of chiral linkers allows to realize chiroptical phenomena, including the emission of circular polarized light and helicity-sensitive photodetectors.[5] Lbl architectures also allow the fabrication of heterostructures with built-in interfaces,[6] with interesting application e.g. in the context of photon up-conversion. A particularly attractive option is to exploit the porous nature of the MOFs in connection with the lbl method. An interesting example is the loading of C60 into the pores of SURMOFs and the subsequent integration into devices, e.g. in the context of photoconductivity [7] or organic diodes.[8] In the context of nonlinear optical properties, using sophisticated assembly strategies were recently used to fabricate non-centrosymmetric SURMOFs with built-in electric fields and large SHG activity.[9] In this presentation we well present selected successful examples of integrating organic chromophores into SURMOFs and the subsequent fabrication of functioning devices. We will in particular highlight the close interaction with theory. Such an advanced in-silico conquering of chemical spaces is mandatory, since the number of known MOFs (> 100.000) is so large that experimental trial-and-error approaches are highly inefficient. References: [1] R. Haldar, L. Heinke, Ch. Wöll, Adv. Mater., 2020, 32, 1905 (2020) [2] L. Heinke, Ch. Wöll, Adv. Mater., 31, 1970184 (2019) [3] J. Liu, W. Zhou, J. Liu, I. Howard, G. Kilibarda, S. Schlabach, D. Coupry, M. Addicoat, S. Yoneda, Y. Tsuitsui, T. Sakurai, S. Seki, Z. Wang, P. Lindemann, E. Redel, Th. Heine, Ch. Wöll, Angew. Chemie Int. Ed. 54, 7441 (2015) [4] R. Haldar, A. Mazel, M. Krstic, Q. Zhang, M. Jakoby, I. A. Howard, B. S. Richards, N. Jung, D. Jacquemin, S. Diring, W. Wenzel, F. Odobel, Ch. Wöll, Nat. Comm., 10, 2048 (2019) [5] Y.H. Xiao, P. Weidler, S.S. Lin, C. Wöll, Z.G. Gu, J. Zhang, Adv. Functional Materials 32 (34), 2204289 (2022) [6] R. Haldar und Ch. Wöll, Nano Research, 14, 355-368 (2021) [7] X. Liu, M. Kozlowska, T. Okkali, D. Wagner, T. Higashino, G. Brenner-Weiß, S. M. Marschner, Z. Fu, Q. Zhang, H. Imahori, S. Bräse, W. Wenzel, C. Wöll, L. Heinke, Angew.Chem.Int. Ed. 58, 9590, (2019) [8] A. Chandresh, X. Liu, Ch. Wöll, L. Heinke, Adv. Sci., 8, 2001884 , (2021) [9] A. Nefedov, R. Haldar, Z. Xu, H. Kühner, D. Hofmann, D. Goll, B. Sapotta, S. Hecht, M. Krstić, C. Rockstuhl, W. Wenzel, S. Bräse, P. Tegeder, E. Zojer, Ch. Wöll, Adv. Mat. 2103287 (2021)

Abstract:

Abstract Aims: TFX06 is an investigational oral complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD) (Wu J, et al., 2023 AACR annual meeting). A Phase 1/2, multicenter, open-label dose-escalation and dose-expansion study (CTR20230789) was initiated in China to evaluate TFX06 in previously heavily treated patients with ER+/HER2- locally advanced and/or metastatic breast cancer. The primary objectives were to assess safety and tolerability, recommended Phase 2 dose (RP2D), and pharmacokinetics (PK). Methods: A 3+3 dose-escalation design was implemented. TFX06 tablets were orally administered at 60 mg/100 mg daily for 28 days of treatment cycle until disease progression or intolerant to TFX06. As of the cut-off date (Sept. 15, 2023), the Phase 1 study enrolled five patients with Stage IV diseases with distant metastases. Three were treated with TFX06 at 60 mg, the starting dose and two at the next dose level of 100 mg. Median age of patients were 50 years (39-65) with a ECOG score of 0-1. Two out of five patients carried estrogen receptor 1 (ESR1) mutations (ctDNA). Prior anticancer treatments included one or two lines of endocrine therapies, including fulvestrant, and/or one or two lines of chemotherapies. Clinical responses by investigator according to RECIST v1.1 were performed every two cycles to explore preliminary efficacy. Results: Three patients in 60 mg and one in 100 mg dose cohorts completed dose-limiting toxicity (DLT) observation period. No DLT observed. All treatment related adverse events (TRAEs) were grade 1-2 in severity, including nausea, drowsiness, decreases in WBC and neutrophils, and anemia. Analyses of plasma concentrations of TFX06 in all three patients receiving 60 mg revealed a similar PK profile with small variations in Cmax. The average steady-state Cmax and Cmin of TFX06 were 101 ng/mL and 65 ng/mL, respectively, and the Cmax of TFX06 was approximately 4-fold higher than that of fulvestrant administered intramuscularly at 500 mg in clinic (28 ng/mL). Two patients in the 60 mg cohort were evaluable for response assessment. One patient discontinued due to progressive disease (PD) after two cycles of treatment. This patient experienced a 17.1% decrease in target lesions in the lung; however, new metastases to bone observed. The other patient who carried ESR1 D538G mutation showed a decrease of 91% in ESR1 mutation burden 8 days after treatment, and a decrease of 34.2% in target lesions (partial response, PR), including a substantial shrinkage of 78.6% in the brain lesion (target lesion), as well as complete responses (CR) of non-target lesions in lung after 4 cycles of treatment. This patient remains on the study as of the cut-off date. Conclusions: Based on the preliminary results, oral administration of TFX06 at 60 or 100 mg once daily had favorable safety and PK profiles. TRAEs, such as gastrointestinal toxicities, bradycardia, and visual disturbances were not observed. Pleasingly, TFX06 demonstrated early extracranial and intracranial antitumor activity (PR) in a patient with a brain metastasis. Citation Format: Zhaojian Fu, Zhiye Zhang, Jia Song, Yang Chen, Douglas Fang, Wei Sha, Jian Zhang, Charles Ding. TFX06, a next-generation oral CERAN/SERD, shows favorable safety and PK profile, extracranial and intracranial efficacy in patients with ER+/HER2- breast cancer: Preliminary results from a phase 1/2 first-in-human trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-01.

Abstract:

Abstract The Janus kinase 2 (JAK2) gene is located on chromosome 9p24.1 and encodes a non-receptor tyrosine kinase that plays a central role in cytokine and growth factor signaling. The JAK2 protein is especially important for controlling the production of blood cells from hematopoietic stem cells. In fact, the JAK2 mutation at amino acid 617 (Valine 617 to Phenylalanine, V617F) is the most frequently detected mutation in myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). This dominant gain-of-function V617F mutation results in constitutive tyrosine phosphorylation activity, leading to uncontrolled blood cell production, including increased numbers of erythrocytes, neutrophils, and platelets. To detect the JAK2 V617F mutation in DNA from patient blood samples, we developed a unique real-time PCR assay using our proprietary XNA technology that enables the assay to selectively amplify the mutant sequence by using a synthetic DNA analog XNA (Xenonucleic Acid). The JAK2 V617F mutation detection assay is designed to detect a valine-to-phenylalanine mutation at amino acid 617 (V617F). PCR primers, TaqMan probes, and XNA were designed for the JAK2 V617F mutation, along with primers and probes for an internal control gene in the duplex setting. The analytical performance of the assay was verified and validated using a variety of control samples. The results revealed that the XNA completely suppressed the amplification of wildtype sequence while only the V617F mutant sequence was amplified. The JAK2 V617F mutation detection assay is highly reproducible with intra- and inter-assay coefficients of variation of less than 10%. Results for the assay’s analytical sensitivity indicated that V617F could be detected with about 0.25% mutant allele frequency in 10 ng DNA input. In addition, no significant cross-amplification between V617F and V617I was observed. Thus, the JAK2 V617F mutation detection assay is specific for the V617F mutation. The JAK2 V617F mutation detection assay, using XNA-based technology, provides high sensitivity and specificity to detect the JAK2 V617F mutation. Thus, this assay would be a useful tool for clinical decision-making in determining the presence of the JAK2 V617F mutation in DNA from patient blood samples. Citation Format: Shuo Shen, Robert Brown, Daniel Kim, Larry Pastor, Andrew Y. Fu, Pushpinder Kaur, Alisha Babu, Wei Liu, Aiguo Zhang, Hiromi Tanaka, Michael Y. Sha. A novel XNA technology-based assay to detect JAK2 V617F mutation by real-time PCR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7295.

Abstract:

Abstract Colorectal cancer (CRC) is the second most common cause of cancer deaths when men and women are combined in the U.S. Early detection in the precancerous stage is key to reducing the CRC morbidity and mortality rates. Thus, there is a critical need for a cost-effective, time-efficient, and convenient clinical tool for early CRC detection. We have developed a multiplex qPCR assay (ColoScapeTM) to detect CRC-associated genetic and epigenetic changes from liquid biopsy samples (i.e., cell-free DNA) using our proprietary QClamp® XNA technology. The QClamp® XNA technology is very unique and enables the ColoScapeTM assay to selectively amplify the mutant and methylated DNA target sequences by using a synthetic DNA analog XNA (Xenonucleic Acid). This study demonstrates the analytical performance for detecting low-abundant mutated and methylated gene copies, as well as assess the clinical performance using plasma cell-free DNA samples from patients with CRC or advanced adenomas (≥1 cm) and from individuals with normal colonoscopies. The ColoscapeTM test is currently designed to detect mutations in 8 genes with 61 mutations and 7 methylated markers. The test consists of two parts: (i) the detection of mutations in 8 genes (APC, KRAS, BRAF, TP53, CTNNB1, NRAS, SMAD4, and PIK3CA) and (ii) the detection of 7 methylation targeted genes. For the assay analytical performance, the ColoScapeTM test shows that XNA effectively suppressed the wild-type background amplifications and led to amplify mutation and methylation target sequences dominantly, providing a high level of analytical sensitivity and specificity. The ColoScapeTM test is highly reproducible with intra- and inter-assay coefficient of variation of &lt;10% and the cross-reactivity within the assay was limited and negligible. The results for the assay analytical sensitivity indicated that each target could be detected between 0.1% and 0.5% variant allele frequency in 10 ng cfDNA. The preliminary assay clinical specificity and sensitivity were 100% (95% CI: 91.3-100%) and 86% (95% CI: 66-95%) respectively for CRC and 91% specificity (95% CI: 75%-98%) and 60% sensitivity (95% CI: 17%-93%) for advanced adenomas. In summary, the ColoScape test utilizing the XNA-based technology provides high sensitivity and high specificity to CRC and advanced adenomas with a great potential to be used as an early screening test. Citation Format: Hiromi Tanaka, Shuo Shen, Mauro Scimia, Larry Pastor, Jonathan Li, Andrew Y. Fu, Daniel Kim, Rui Ni, Aiguo Zhang, Michael Y. Sha. ColoScape test: a molecular assay to detect early-stage colorectal cancer in plasma cell-free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6505.

Abstract:

Abstract Background PARP-1 has a well-established role in DNA repair. PARP-1 selective inhibitors are a new subclass of PARPi that offer potential for improved tolerability. NMS-03305293 (NMS-293) is an oral, brain-penetrant PARP-1 selective inhibitor with strong antitumor activity in BRCA mutated preclinical models. Furthermore, NMS-293 is synergistic with temozolomide (TMZ) in glioblastoma mouse models. Methods Two phase I/I-II dose-escalation/expansion studies assessed safety, tolerability, and preliminary antitumor activity of NMS-293. Both are actively recruiting. In PARPA-293-001 (NCT04182516), NMS-293 was administered orally, ranging from 20 mg (QD) to 160 mg (BID) for 21 or 28 days on 28-day cycle in adult patients with advanced/metastatic, relapsed/refractory solid tumors who have exhausted standard treatment options. In PARPA-293-002 (NCT04910022), NMS-293 was administered in a range of doses orally, QD or BID on days 1-7 plus TMZ 150mg/m2 QD on days 1-5 in repeated 28-day cycle in adult patients with recurrent diffuse gliomas. Tumor responses were measured by investigator-assessed RANO criteria. Results The unpooled safety database at the data-cut-off (02-AUG-23), includes 45 patients in PARPA-001 and 21 patients in PARPA-002. PARPA-001 showed an MTD of 100 mg BID for 28 days on a 28-day cycle, a dose with meaningful PK relative to preclinical activity. PARPA-002 dose finding is ongoing with no DLTs as of cutoff date. The most frequent (≥10%) any-grade treatment related adverse events (TRAEs) in PARPA-001 were reversible QTcF prolongation, nausea, asthenia, decreased appetite and vomiting, mainly mild/moderate. In PARPA-002, with discontinuous NMS-293 plus TMZ, no G≥3 TRAEs were reported. The most frequent (≥10%) any-grade TRAEs were: nausea, fatigue, vomiting, decreased appetite, and platelet count decreased, mainly G1 adverse events. Overall, no dose-dependent trends of myelosuppression have been observed. 14 recurrent glioma patients across dose levels in PARPA-002 were evaluable for tumor response. A patient with glioblastoma had confirmed partial response (PR) with duration 7.6+ weeks, remaining on treatment at cutoff date. A patient with grade 3 IDH-mutant astrocytoma had unconfirmed PR with ongoing tumor shrinkage at 16.1+ weeks. A patient with glioblastoma had complete radiological disappearance of enhancing non-target lesions, remaining on treatment at cutoff date. NMS-293 PK profiles showed an increase in exposure with the dose with approximately 5 to 13 hours half-life. Conclusion NMS-293, a PARP-1 selective, brain penetrant inhibitor was well tolerated in phase I clinical trials with no dose dependent trends of myelosuppression. Furthermore, NMS-293 showed encouraging clinical activity in combination with TMZ in difficult-to-treat recurrent glioma patients. Citation Format: Marjolein Geurts, Dorothee Gramatzki, Sara Merler, Matteo Duca, Fabio Girardi, Ugur T. Sener, Domenico Roberti, Grazia Saturno, Patrizia Crivori, Alessia Montagnoli, Lisa Mahnke, Siqing Fu, Paola Gaviani, Kurt A. Jaeckle, Jian Zhang, Yehui Shi, Valentina Guarneri, Michael Weller, Sani H. Kizilbash, Martin J. van den Bent, Michele Milella, Silvia Damian. Initial results from 2 Phase I studies of NMS-03305293, a selective PARP1 inhibitor [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_A12.

Abstract:

The concept of water-in-salt electrolytes (WISEs)1, implying highly concentrated aqueous solutions, has completely rejuvenated the aqueous systems. These electrolytes can be depicted as few water molecules surrounded by cations and anions forming ion pairs. This change of solvation structure compared to standard electrolytes increases the electrochemical stability window. For example, using 20 molal (molality: m, moles per kg) lithium (bistrifluoromethanesulfonyl(imide) (LiTFSI) aqueous solutions, a stability window of 3 V is reached.1 While WISEs open the way for sustainable systems, these solutions only use expensive and toxic lithium salts. To move towards more sustainable elements, one can envision magnesium and associated salts: safer, less expensive and more abundant than lithium. Yet, the state-of-the-art on water-in-salt aqueous Mg batteries is scarce,2,3 with potential windows reaching only 2-2.3 V. There is no clear understanding of the mechanisms at work but the low solubility of Mg salts could account for the narrow potential window. Rationalizing reactivity of water-in-salt solutions on a fundamental level is critical to design efficient strategies to increase the voltage window of concentrated aqueous Mg batteries. We investigated the Mg(TFSI)2/H2O system with radiolysis, a technique which provides a chemical approach4 to exacerbate in a short time the degradation mechanisms. The aging process with radiolysis is much shorter than the electrochemical one and mimics the products of salt and solvent degradation observed during long battery operation. We performed radiolysis to study and compare Mg(TFSI)2 and LiTFSI-based electrolytes with different molalities. Degradation products formed after irradiation were identified using Nuclear Magnetic Resonance spectroscopy (NMR) for the liquid phase, and with gas chromatography coupled to mass spectrometry (GC-MS) and micro-gas chromatography (μ-GC) for the gas phase. For example, the evolution of the amount of H2 and CO2 gases in the case of LiTFSI or Mg(TFSI)2/H2O electrolytes show large discrepancies, hinting at a preferential anion degradation in the Mg system. Overall, the nature of the degradation species strongly depends on the molality, with degradation routes driven by the water or the anion at low or high molalities. Finally, radiolysis allows to identify minor species, providing a view of the long-term (un)stability of these electrolytes. References 1. L. Suo, O. Borodin, T. Gao, M. Olguin, J. Ho, X. Fan, C. Luo, C. Wang, K. Xu, Science 2015, 350, 938–943. 2. F. Wang, X. Fan, T. Gao, W. Sun, Z. Ma, C. Yang, F. Han, K. Xu, C. Wang, ACS Cent. Sci. 2017, 3, 1121–1128. 3. X. Tang, D. Zhou, B. Zhang, S. Wang, P. Li, H. Liu, X. Guo, P. Jaumaux, X. Gao, Y. Fu, C. Wang, C. Wang, G. Wang, Nat. Commun. 2021, 12, 2857. 4. D. Ortiz, I. Jiménez Gordon, J.-P. Baltaze, O. Hernandez‐Alba, S. Legand, V. Dauvois, G. Si Larbi, U. Schmidhammer, J.-L. Marignier, J.-F. Martin, J. Belloni, M. Mostafavi, S. Le Caër, ChemSusChem 2015, 8, 3605–3616.

Abstract:

Abstract Background: BRCA1 promoter methylation (PM) is an early initiating event in cancer, occurring in 3 to 65.2% of all breast tumors, and 30 to 65% of triple negative tumors. BRCA1 PM has been associated with defective homologous recombination repair (HRR), early onset of breast and ovarian cancer, and improved clinical response to adjuvant chemotherapy. Historically, there has been no diagnostic assay that comprehensively evaluates both BRCA1 PM and genomic alterations in cell-free circulating tumor DNA (ctDNA). Here, we describe the novel detection of BRCA1 PM and genomic alterations in a cohort of patients with breast cancer using GuardantINFINITY, a liquid biopsy assay interrogating 800+ genes and genome-wide methylation detection. Method: We assessed for BRCA1 PM in ctDNA from 274 patients with late-stage breast cancer. Genomic sequencing of 800+ genes and PM profiling of 398 genes was performed by GuardantINFINITY. The positive calling threshold for PM was established by comparing cell-free DNA derived from patients with cancer and cancer-free donors. The limit of detection (LoD) was determined through in silico and experimental titrations of ctDNA from clinical samples and cell lines with known gene PM into the plasma of cancer-free donors. Results: Among the 274 patients with advanced breast cancer, 8 (2.9%) had germline pathogenic mutations in BRCA1, BRCA2, or ATM. BRCA1 PM was detected in 11/274 (4.0%) patients at the predefined threshold of &gt;99% specificity. BRCA1 PM detection in this cohort was 8.9% (8/90) when excluding samples with low tumor shedding (&lt;1% epigenomic tumor fraction in cfDNA). Among the 11 patients with BRCA1 PM detected in ctDNA, one had a co-occurring somatic BRCA1 nonsense variant (p.S361*); none of the remaining patients with BRCA1 PM had another HRR-related mutation detected in cfDNA. Among patients without BRCA1 PM detected, pathogenic somatic alterations were detected in BRCA2, ATM, and CHEK2 in 25 (9.4%) patients. In silico simulations using clinical samples with BRCA1 PM indicated an LoD of 0.0408%. BRCA1 PM was not detected in 3210 individual and mixed cancer-free clinical samples, indicating a high specificity for BRCA1 PM calls. Conclusion: GuardantINFINITY, a plasma-based diagnostic assay, detected both BRCA1 PM and genomic alterations in this unspecified advanced breast cancer cohort. The BRCA1 PM detection rates of 4.0-8.9% are consistent with values previously reported in the literature. As BRCA1 PM has important prognostic and therapeutic implications for the management of breast (as well as ovarian) cancers, additional studies are warranted to further describe the PM patterns across breast cancer subtypes and how these patterns both influence and are influenced by disease evolution and therapeutic response. Liquid biopsy thus serves as a suitable method to noninvasively identify and monitor changes in both genomics and epigenomics. Citation Format: Jennifer Yen, Sai Chen, Colby Jenkins, Brooke Overstreet, Yu Fu, Jun Zhao, Tingting Jiang, Leylah Drusbosky, Stephen Pettitt, Michael Dorschner, Lauren Lawrence, Han-Yu Chuang, Andrew Tutt. BRCA1 promoter methylation in sporadic breast cancer patients detected by liquid biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6603.

Abstract:

Making the production of “green” hydrogen (H2) cost-effective requires the development of high-performance and affordable low-temperature water electrolyzers (LTWE).1 Currently, the most mature technology for H2 production using renewable electricity is the liquid alkaline electrolysis (AE). This technology suffers several major drawbacks such as gas crossover, relatively low current density, and the use of highly corrosive concentrated alkaline solutions (20-40% KOH). Proton exchange membrane (PEM) electrolysis, a valid alternative to AE technology, already commercialized on a large scale, enables operation on pure water thus eliminating corrosion, reducing gas crossover and allowing higher current density. However, the main drawback of PEM electrolyzers is the need of very expensive and rare platinum group metals (PGMs) such as Ir and Pt as catalysts for oxygen evolution reaction (OER) at the anode and hydrogen evolution reaction (HER) at the cathode, respectively.2 Recent advancements in performance and stability of anion exchange membranes (AEMs) have enabled a new type of alkaline membrane-based LTWE operating on pure water and with PGM-free catalysts.3,4 If successful, this new AEM-LTWE technology will allow to overcome the drawbacks of AEs and PEM-LTWEs while benefiting from their respective advantages in a major breakthrough in the production of “green” H2 at a low cost. In this scenario crucial is the development of high-performance PGM-free electrocatalysts for both OER and HER. Due to the operation at high potentials, carbon-based catalysts and supports cannot be used at the anode. Therefore, the most common PGM-free anode catalysts are based on transition metal oxides, which suffer, however, from low surface area and electronic conductivity, limiting the electrocatalytic performance.5,6 The catalysts with the most promising OER activity in alkaline environment are Ni-based alloys, oxides, and (oxy)hydroxides.7 The combination of Ni with other first-row transition metals such as Fe and Co was found to increase the OER catalytic activity.8,9 In this work, we present a new method for synthesizing NiFe OER catalysts. The catalyst was synthesized via a sol-gel method, followed by a thermal treatment. The impact on the OER activity in alkaline liquid electrolyte of different synthesis parameters such as the Ni-to-Fe atomic ratio, the addition of a third transition metal (e.g., Co, Mn), the thermal treatment temperature and atmosphere were investigated. Then, the most promising electrocatalysts were tested in an AEM-LTWE operating with pure water and supporting electrolyte solution. Bimetallic HER PGM-free catalysts were also developed by combining one a first-row transition metal, e.g. Ni, with a second-row transition metal, e.g. Mo. These HER catalysts were synthesized by either (i) using the sol-gel approach described above or (ii) via a metal organic framework (MOF) method similar to the one used in the synthesis of “atomically dispersed” M-N-C catalysts for oxygen reduction reaction.10 References A. M. Oliveira, R. R. Beswick, and Y. Yan, Curr. Opin. Chem. Eng., 33, 100701 (2021). H. A. Miller et al., Sustain. Energy Fuels, 4, 2114–2133 (2020). J. Xiao et al., ACS Catal., 11, 264–270 (2021). D. Li et al., Nat. Energy, 5, 378–385 (2020). Q. Gao et al., Chem. Eng. J., 331, 185–193 (2018). D. Xu et al., ACS Catal., 9, 7–15 (2019). S. Fu et al., Nano Energy, 44, 319–326 (2018). G. Zhang et al., Appl. Catal. B Environ., 286, 119902 (2021). P. Chen and X. Hu, Adv. Energy Mater., 10, 1–6 (2020). Y. He et al., Energy Environ. Sci., 12, 250–260 (2019).

Abstract:

Polymer electrolyte fuel cells (PEFCs) have become increasingly appealing over internal combustion engines because of their high efficiency, low operating temperature, and zero CO2 emissions. Nevertheless, the transportation sector necessitates high durability and reliability, which may be difficult to predict for emerging technologies. A crucial aspect is the ability of the thin membranes that conduct ions in PEFCs to endure the chemical and mechanical stresses that arise during dynamic operations. For mechanical fatigue, temperature and relative humidity (RH) fluctuations induce dynamic stresses that lead to the formation and propagation of microcracks in the membrane. As the membrane is confined by other components in the membrane-electrode assembly (MEA), changes in temperature and humidity can generate thermal and swelling strains in the membrane, leading to dynamic and residual stresses [1]. The US Department of Energy sets a passing criterion of 20,000 RH cycles for mechanical fatigue assessment. However, many modern reinforced membranes have already passed this threshold without failing [2]. Therefore, Ref [3] introduced a pressure differential between the cathode and anode sides of the membrane at 80°C to speed up the testing. In this research, the pressure differential-accelerated mechanical stress test (ΔP-AMST) method was applied to a reinforced membrane at two different temperatures and with four times faster humidity cycles in a wider range of ΔPs. This objective is to project the mechanical fatigue lifetime from the ΔP-AMST to the membrane under its in-situ conditions by using the critical accumulated plastic dissipation energy (CAPDE) in ΔP-AMSTs and the plastic dissipation energy (PDE) during a single cycle of humidity that the membrane experiences under complete fuel cell settings. The first step involves performing a series of ∆P-AMST, and in the second step, a finite element model (FEM) for ∆P-AMST based on the developed constitutive model for the tensile tests that covers temperature, humidity, and swelling strain impacts is built, and therefore its S-N curve is extracted. Next, a FEM model for a complete fuel cell is created, and the mechanical fatigue life is estimated by dividing the CAPDE in ∆P-AMST by the PDE in one cycle of the in-situ modeled membrane by considering amplitude stress as a link between the full fuel cell model and ∆P-AMST, as illustrated in Figure 1 and verified by previous studies [4,5]. In the final step, we will also discuss opportunities to integrate the present mechanical fatigue model with a chemical degradation module to simulate its impacts on fatigue lifetime. This integration includes the two main effects of chemical degradation, which are reflected in the thickness of the reinforced membrane [6] and its updated CAPDE [7]. Acknowledgments The authors gratefully acknowledge AVL Fuel Cell Canada and Mitacs for supporting this project. The authors also thank Roger Penn and Amy Nelson for technical advice. References [1] Alavijeh AS, Bhattacharya S, Thomas O, Chuy C, Yang Y, Zhang H, et al. Effect of hygral swelling and shrinkage on mechanical durability of fuel cell membranes. J Power Sources 2019;427:207–14. [2] Rodgers MP, Bonville LJ, Mukundan R, Borup RL, Ahluwalia R, Beattie P, et al. Perfluorinated sulfonic acid membrane and membrane electrode assembly degradation correlating accelerated stress testing and lifetime testing. ECS Trans 2013;58:129. [3] Alavijeh AS, Bhattacharya S, Thomas O, Chuy C, Kjeang E. A rapid mechanical durability test for reinforced fuel cell membranes. J Power Sources Adv 2020;2:100010. [4] Chen J, Goshtasbi A, Soleymani AP, Ricketts M, Waldecker J, Xu C, et al. Effects of cycle duration and test hardware in relative humidity cycling of a polymer electrolyte membrane. J Power Sources 2020;476:228576. [5] Hasan M, Chen J, Waldecker JR, Santare MH. Predicting fatigue lifetimes of a reinforced membrane in polymer electrolyte membrane fuel cell using plastic energy. J Power Sources 2022;539:231597. [6] Liu H, Chen J, Hissel D, Hou M, Shao Z. A multi-scale hybrid degradation index for proton exchange membrane fuel cells. J Power Sources 2019;437:226916. [7] Sun X, Shi S, Fu Y, Chen J, Lin Q, Hu J, et al. Embrittlement induced fracture behavior and mechanisms of perfluorosulfonic-acid membranes after chemical degradation. J Power Sources 2020;453:227893. Figure 1

Abstract:

BackgroundOlder adults with ANCA-associated vasculitis (AAV) have differences in clinical presentation, as well as increased mortality and risk of infections, when compared to younger adults. Despite a high incidence of AAV in older adults, these individuals are underrepresented in clinical trials. Frailty, a geriatric syndrome associated with increased morbidity and mortality, has not been adequately studied in older adults with AAV. Better characterization of outcomes and risk factors in these patients is needed to inform treatment.ObjectivesTo compare the risks of and factors associated with early (within 2 years) end-stage renal disease (ESRD), severe infection, and death in adults with a new diagnosis of AAV who are ≥ 75 years old vs 65-74 years old.MethodsPatients ≥ 65 years were included from the 2002-2019 Mass General Brigham AAV cohort, a consecutive inception cohort. EGPA patients were excluded. Covariates including demographics, disease characteristics, and comorbidities (Charlson comorbidity index) were assessed at baseline. Disease activity at time of diagnosis was assessed using the Birmingham Vasculitis Activity Score (BVAS/WG). Frailty was measured at baseline using a claims frailty index, and pre-established cut-offs were utilized to define degrees of frailty (robust, pre-frail, mildly frail, and moderately/severely frail).[1]Death and ESRD were ascertained from linkage to national registries and/or medical records. Severe infections were identified utilizing inpatient data and/or death certificates. The cumulative incidence of death, ESRD and severe infections within 2 years were estimated. In univariate analyses, we assessed factors associated with outcomes within 2 years.Results298 individuals were included. Most patients were female (61%), white (86%), MPO-ANCA+ (80%), and had renal involvement (72%). Patients ≥ 75 years old (n=156) had a median age of 81 years, while median age was 69 years in the 65-74 years group.The cumulative incidence at 2 years of the composite outcome of ESRD/death (23.1% [95% CI 16.5, 29.7]) vs 5.6% [95% CI 1.8, 9.4]) and severe infection (34.0% [95% CI 26.5, 41.4] vs 12% [95% CI 6.6, 17.3]) higher in AAV patients ≥ 75 vs 65-74 years old. Age ≥ 75 years was associated with an increased risk of ESRD/death (hazard ratio (HR) 4.42, 95% CI 2.05-9.51); frailty was not (HR 2.71, 95% CI 0.63,11.72) (Table 1). In contrast, frailty (HR 19.39, 95% CI 2.77,135.66) as well as age ≥ 75 years (HR 3.21, 95 CI% 1.87, 5.52), pulmonary involvement (HR 1.98, 95% CI 1.23, 3.18), and higher baseline comorbidity burden (HR 1.13, 95% CI 1.06, 1.20) were associated with severe infection risk.ConclusionCompared to AAV patients aged 65-74 years, AAV patients ≥ 75 years had a higher incidence of death/ESRD and severe infections. Older age but not baseline frailty was associated with ESRD/mortality risk whereas frailty was a very strong risk factor for severe infection. These findings highlight the need for innovative considerations beyond age when assessing outcome risks in AAV.Reference[1]Kim DH, et al.J Gerontol A Biol Sci Med Sci.2019;74(8):1271-1276Table 1.Univariate analyses of factors associated with composite outcome and severe infections within 2 yearsFactorsComposite outcome (ESRD/Death)Severe infectionHR (95% CI)HR (95% CI)Age ≥ 75 years (Ref, 65-74 years)4.42 (2.05, 9.51)3.21 (1.87, 5.52)Female sex (Ref, male)0.75 (0.41, 1.35)0.70 (0.44, 1.12)Comorbidities (CCI per 1 unit)1.07 (0.97, 1.19)1.13 (1.06, 1.20)FrailtyRobustPre-frailFrailREF1.85 (0.44, 7.80)2.71 (0.63, 11.72)REF4.01 (0.56, 28.72)19.39 (2.77, 135.66)BVAS (per 1 unit)1.14 (0.99, 1.31)1.05 (0.94, 1.18)Organ involvementRenal (Ref, none)Pulmonary (Ref, none)1.58 (0.76, 3.29)1.75 (0.95, 3.20)1.26 (0.74, 2.16)1.98 (1.23, 3.18)Induction Regimen (CYC-based vs not)1.45 (0.72, 2.94)1.07 (0.64, 1.78)ESRD = end-stage renal disease, HR = hazard ratio, CI = confidence interval, CCI = Charlson Comorbidity Index, BVAS = Birmingham Vasculitis Activity Score, CYC = cyclophosphamideFigure 1.Composite outcome (A) and severe infections (B) by frailty status at baseline.Acknowledgements:NIL.Disclosure of InterestsSebastian E. Sattui Consultant of: Sanofi (unpaid)., Grant/research support from: Dr. Sattui is supported by a Rheumatology Research Foundation RISE Pilot Award and the Bristol Myers Squibb Foundation Winn Career Development Award. Dr. Sattui has received research funding from AstraZeneca., Xiaoqing Fu: None declared, Claire Cook: None declared, Shruthi Srivatsan: None declared, Yuqing Zhang: None declared, Zachary Wallace Consultant of: Dr. Wallace reports consulting fees from Viela Bio, Horizon, Zenas Biopharma, and MedPace, and serves on advisory boards for Horizon, Shinogi, and Visterra/Otsuka., Grant/research support from: Dr. Wallace ZSW is funded by NIH/NIAMS [K23AR073334 and R03AR078938] and the Rheumatology Research Foundation [K Supplement]. Dr. Wallace reports research support from Bristol-Myers Squibb and Principia/Sanofi.

Abstract:

This study presents the effects of the geometry of the notches on the fatigue life, crack initiation, and growth in mixed mode and first mode of the fracture. For this purpose, some samples were tested with U-shaped notches with different radii and depths and various orientations with respect to the loading directions under fatigue loads. Using the fatigue crack growth rates, the Paris law coefficients were obtained for the used material in different conditions. It was shown that these coefficients are independent of the geometry of the samples. Fatigue crack growth behaviors in the mixed mode tests were also in good agreement with the result of the numerical simulations. Predictions of the maximum tangential stress criterion and numerical simulation for the position of the crack initiation on the notch root were compared with the tested observations, which showed good agreement. The fatigue life of the test samples was compared with the analytical results provided by the Manson-Coffin law. It was shown that a 25% decrease in notch depth increases the fatigue life by 3 times, also, an increase of 0.5 mm in the notch radius increases the fatigue life by 40%. Finally, the fracture surface of the samples was checked using an optical microscope. This study showed that the fracture surfaces have one or two lateral shear lips and plane stress conditions were established. REFERENCES [1] X.-L. Zheng, Modelling fatigue crack initiation life, Int. J. Fatigue, 15 (1993) 461-466, https://doi.org/10.1016/0142-1123(93)90257-Q. [2] M. De Freitas, L. Reis, B. Li, Evaluation of small crack growth models for notched specimen under axial/torsional fatigue loading, Facta universitatis-series: Mechanics, Automatic Control and Robotics, 3 (2003) 657-669, [3] H. Zhang, A. Fatemi, Short fatigue crack growth from a blunt notch in plate specimens, Int. J. 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Fontanari, Experimental investigation on the propagation of fatigue cracks emanating from sharp notches, Meccanica, 43 (2008) 201-210, https://doi.org/10.1007/s11012-008-9129-3. [9] A. Akhavan Safar, A. Vrdi, M. Zorofi, Numerical and analytical investigation of the fatigue life of the notched sample and its comparison with the experimental results, in: 16th Annual Conference on Mechanical Engineering, Kerman, Iran, 2008. [10] Y. Hu, Z. Hu, S. Cao, Theoretical study on Manson-Coffin equation for physically short cracks and lifetime prediction, Sci. China Technol. Sci., 55 (2012) 34-42, https://doi.org/10.1007/s11431-011-4581-z. [11] Y. Li, H. Wang, D. Gong, The interrelation of the parameters in the Paris equation of fatigue crack growth, Eng. Fract. Mech., 96 (2012) 500-509, https://doi.org/10.1016/j.engfracmech.2012.08.016. [12] F. Gómez, M. Elices, F. Berto, P. Lazzarin, A generalised notch stress intensity factor for U-notched components loaded under mixed mode, Eng. Fract. Mech., 75 (2008) 4819-4833, https://doi.org/10.1016/j.engfracmech.2008.07.001. [13] S. Iida, A.S. Kobayashi, Crack-propagation rate in 7075-T6 plates under cyclic tensile and transverse shear loadings, J. Fluids Eng., 91 (1969) 764-769, https://doi.org/10.1115/1.3571219. [14] J. Qian, A. Fatemi, Mixed mode fatigue crack growth: a literature survey, Eng. Fract. Mech., 55 (1996) 969-990, https://doi.org/10.1016/S0013-7944(96)00071-9. [15] F. Erdogan, G. Sih, On the crack extension in plates under plane loading and transverse shear, J. Fluids Eng., 85 (1963) 519-525, https://doi.org/10.1115/1.3656897. [16] E.E. Gdoutos, Problems of mixed mode crack propagation, (1984), [17] A.T. Yokobori, T. Yokobori, K. Sato, K. Syoji, Fatigue crack growth under mixed modes I and II, Fatigue Fract. Eng. Mater. Struct., 8 (1985) 315-325, https://doi.org/10.1111/j.1460-2695.1985.tb00430.x. [18] L. Pook, The fatigue crack direction and threshold behaviour of mild steel under mixed mode I and III loading, Int. J. Fatigue, 7 (1985) 21-30, https://doi.org/10.1016/0142-1123(85)90004-0. [19] M. Louah, G. Pluvinage, A. Bia, Mixed mode fatigue crack growth using the Brasilian disc, Virginia Univ, Fatigue 87, 2 (1987), [20] H. Nayeb-Hashemi, S. Hwang, P. Poles, Crack closure phenomena in modes I and II interactions, Fatigue'87., 2 (1987) 979-996, [21] T. Hyde, A. Chambers, A compact mixed-mode (cmm) fracture specimen, J. Strain Anal. Eng. Des., 23 (1988) 61-66, https://doi.org/10.1243/03093247V232061. [22] M. Brown, Analysis and design methods in multiaxial fatigue, in: Advances In Fatigue Science and Technology, Springer, 1989, pp. 387-401. [23] C. Wang, S. Wang, Modified Generalized Maximum Tangential Stress Criterion for Simulation of Crack Propagation and Its Application in Discontinuous Deformation Analysis, Eng. Fract. 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Abstract:

Background:Levilimab (LVL) is a novel anti-IL6Rmonoclonal antibody against IL6Rα. Cytokine release syndrome plays the key role in the pathogenesis of a range of life-threatening conditions including the acute respiratory distress syndrome in severely ill COVID-19 patients. Thus, the use of LVL could be considered as anti-cytokine therapy with a potency to prevent the complications and progression of respiratory failure in COVID-19.Objectives:We analyzed the changes in the serum concentrations of inflammatory markers (Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and IL-6) in patients treated with LVL or placebo as part of a phase III multicenter randomized double-blind placebo-controlled adaptive-design CORONA clinical study aimed to evaluate the efficacy and safety of LVL in subjects with severe COVID-19 (NCT04397562).Methods:A total of 217 patients were enrolled in the study, 206 patients were randomized, and 204 patients received the investigational product (IP, LVL or placebo).Study included men and non-pregnant women aged ≥18 years, hospitalized for severe COVID-19 pneumonia, receiving standard therapy according to the national guidelines. Patients with acute respiratory failure with the need in invasive respiratory support, septic shock, multiple organ failure or life expectancy less than 24 hours could not participate in the study. The use of other monoclonal antibodies and glucocorticoids for the treatment of COVID-19 were not allowed.Subjects were stratified according to the CRP level (CRP ≤ 7 mg/L; CRP > 7 mg/L) and then randomized (1:1) into 2 groups to receive LVL 324 mg or placebo. LVL/placebo were administered as a single subcutaneous injection, investigator and patients were unaware of the received therapy.Among secondary endpoints of the study changes from baseline in ESR, CRP and IL-6 concentrations were assessed. CRP level and ESR were measured before the IP administration and on Days 3, 5, 7, 14, 21, 29 and 30. Blood samples for the measurement of IL-6 concentration were obtained before the IP administration and then every day for 2 weeks after administration.Results:We observed the pronounced decrease of ESR in LVL group compared to Placebo group. The difference was statistically significant on Days 3 and 7: the median ESR change from baseline was -3 mm/h and +3 mm/h on Day 3, -11 mm/h and -3.1 mm/h on Day 7, in LVL and Placebo groups, respectively (p=0.0319 and p=0.0110, Days 3 and 7). The statistically significant difference in the change of CRP level was detected between the groups on Day 3: -26.6±41.9 mg/L and -19.2±58.2 mg/L in LVL and Placebo groups, respectively (p=0.0241). Numerically the same dynamics of ESR and CRP was observed over entire study period.The dynamics of IL-6 serum concentrations in LVL and Placebo groups was strikingly different. After LVL administration we detected the rapid significant increase in IL-6 concentration due to IL-6 receptors inhibition. Maximum change from baseline was observed on Day 3 (+91.9±117.7 pg/mL), on Day 14 the value was +31.9±62.7 pg/mL.In the Placebo group, the IL-6 concentration increased slightly until Day 4 (+5,1±76,5 pg/mL), and then decreased significantly (-39.2±55.1 pg/mL on Day 14) due to clinical improvement in this group.Conclusion:The significant differences in the dynamics of ESR, CRP and IL-6 after LVL administration compared to placebo confirmed the pharmacodynamic effect and its potency to prevent the excessive release of inflammatory substances in severely ill COVID-19 patients.References:[1]Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X, Zhang X, Pan A, Wei H. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970-10975. doi: 10.1073/pnas.2005615117. Epub 2020 Apr 29. PMID: 32350134; PMCID: PMC7245089.Acknowledgements:We thank all contributors to the CORONA study.Disclosure of Interests:Nikita Lomakin: None declared, Bulat Bakirov: None declared, Gaziiavdibir Musaev: None declared, Denis Protsenko: None declared, Olga Moiseeva: None declared, Elena Pasechnik: None declared, Vladimir Popov: None declared, Elena Smolyarchuk: None declared, Ivan Gordeev: None declared, Michail Gilyarov: None declared, Daria Fomina: None declared, V Mazurov: None declared, Maria Morozova Employee of: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Dmitrii Bogdan Employee of: JSC BIOCAD, Anton Lutskii Employee of: JSC BIOCAD, Arina Zinkina-Orihan Employee of: JSC BIOCAD, Iulia Linkova Employee of: JSC BIOCAD, Anton Seleznev Employee of: JSC BIOCAD.

Abstract:

A quitosana, polissacarídeo linear obtido a partir do exoesqueleto de crustáceos e artrópodes, tem sido pesquisada em Odontologia por suas diversas propriedades terapêuticas. O objetivo do presente estudo foi realizar uma revisão da literatura sobre as aplicações atuais e as possibilidades terapêuticas da quitosana na odontologia. A busca foi realizada através do banco de dados eletrônico do Pubmed, utilizando os descritores Quitosana, Odontologia e Biomateriais. Foram incluídas pesquisas científicas utilizando quitosana em diversas áreas da odontologia e excluídas revisões de literatura e estudos não odontológicos, sendo selecionados 13 artigos. A quitosana induz resposta transcricional e anti-inflamatória em fibroblastos gengivais sobre citocinas inflamatórias, fatores transformadores do crescimento (TGF -β) e fatores de crescimento tumoral (TNF-α) que estão diretamente relacionados à atividade patológica periodontal. Nas infecções endodônticas persistentes, a substância atua criando ligações de hidrogênio e liberação de íons cálcio, o que potencializa a ação dos irrigadores intracanal, além de causar menos estresse oxidativo. Para a odontologia restauradora, a quitosana demonstrou eficácia como auxiliar no condicionamento da dentina e mostrou potencial para induzir a migração de odontoblastos na proteção do complexo dentino-pulpar. A substância atua como uma cura de feridas orais devido à sua capacidade de estimular a formação de fibroblastos e novos vasos sanguíneos, além de células anti-inflamatórias. Descritores: Biopolímeros; Biomateriais; Biotecnologia. Referências Zhao X, Li P, Guo B, Ma PX. Antibacterial and conductive injectable hydrogels based on quaternized chitosan-graft-polyaniline/oxidized dextran for tissue engineering. Acta Biomater. 2015;26:236-48. Tomihata K, Ikada Y. In vitro and in vivo degradation of films of chitin and its deacetylated derivatives. Biomaterials. 1997;18(7):567-75 Citgez B, Cengiz AN, Akgun I, Uludag M, Yetkin G, Bahat N, Ozcan O, Polat N, Akcakaya A, Karatepe O. Effects of chitosan on healing and strength of colonic anastomosis in rats. Acta Cir Bras. 2012;27(10):707-12. Azevedo VVC, Chaves SA, Bezerra DC, Lia Fook MV, Costa ACFM. Quitina e Quitosana: aplicações como biomateriais. Rev Eletr Mater Proc. 2007;2(3):27-34. Tavaria FK, Costa EM, Pina-Vaz I, Carvalho MF, Pintado MM. A quitosana como biomaterial odontológico: estado da arte. Rev Bras Eng Bioméd. 2013;29(1):110-20. Ueno H, Nakamura F, Murakami M, Okumura M, Kadosawa T, Fujinag T. Evaluation effects of chitosan for the extracellular matrix production by fibroblasts and the growth factors production by macrophages. Biomaterials. 2001;22(15):2125-30. Shahid F, Abuzaytoun R. Chitin, chitosan, and co-products: chemistry, production, applications, and health effects. Adv Food Nutr Res. 2005;49(1):93-135. Croisier F, Jerome C. Chitosan-based biomaterials for tissue engineering. Eur Polym J. 2013;49(1):780-92. Giovino C, Ayensu I, Tetteh J, Boateng JS. An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles. Colloids Surf B Biointerfaces. 2013;112(1):9-15. Wieckiewicz M, Boening KW, Grychowska N, Paradowska-Stolarz,U. Clinical Application of Chitosan in Dental Specialities. Mini Rev Med Chem. 2017;17(5):401-9. Ravi Kumar MNV. A análise dos pedidos de quitina e quitosana. R React Funct 2000;46(1):1-27. Chen CK, Chang NJ, Wu YT, Fu E, Shen EC, Feng CW, Wen ZH. Bone Formation Using Cross-Linked Chitosan Scaffolds in Rat Calvarial Defects. Implant Dent. 2018;27(1):15-21 Pavez L, Tobar N, Chacon C, Arancibia R, Martinez C, Tapia et al. Chitosan triclosan particles modulate inflammatory signaling in gingival fibroblasts. J Periodontal Res. 2017; 53(2):232-39. Moraes PC, Marques ICS, Basso FG, Rosseto HL, Pires de Sousa FCP, Costa CAS et al. Repair of Bone Defects with Chitosan- Collagen Biomembrane and Scaffold Containing Calcium Aluminate Cement. Braz Dent J. 2017;28(3):287-95. Aydin UZ, Akpinar KE, Hepokur C, Erdönmez D. Assessment of toxicity and oxidative DNA damage of sodium hypochlorite, chitosan and propolis on fibroblast cells. Braz Oral Res. 2018;32(1):1-8. Özdoğan AI, Ilarslan YD, Kösemehmetoğlu K, Acka G, Kutlu HB, Comerdov E et al. In Vivo Evaluation of Chitosan Based Local Delivery Systems for Atorvastatin in Treatment of Periodontitis. Int J Pharm. 2018;25(1):470-76. Paiola FG, Lopes FC, Mazzi-Chaves JF, Pereira RD, Oliveira HF, Queiroz AM et al. How to improve root canal filling in teeth subjected to radiation therapy for câncer. Braz Oral Res. 2018;32(1):1-9. Farhadian N, Godiny M, Moradi S, Hemati Azandaryani A, Shahlaei M. Chitosan/gelatin as a new nano-carrier system for calcium hydroxide delivery in endodontic applications: Development, characterization and process optimization. Mater Sci Eng C Mater Biol Appl. 2018;92:540-46. Subhi H, Reza F, Husein A, Al Shehadat SA, Nurul AA. Gypsum-Based Material for Dental Pulp Capping: Effect of Chitosan and BMP-2 on Physical, Mechanical, and Cellular Properties. Int J Biomater. 2018;2018:3804293. Soares DG, Anovazzi G, Bordini EAF, Zuta UO, Silva Leite MLA, Basso FG, Hebling J, de Souza Costa CA. Biological Analysis of Simvastatin-releasing Chitosan Scaffold as a Cell-free System for Pulp-dentin Regeneration. J Endod. 2018;44(6):971-76. Işılay Özdoğan A, Akca G, Şenel S. Development and in vitro evaluation of chitosan based system for local delivery of atorvastatin for treatment of periodontitis. Eur J Pharm Sci. 2018;124:208-16. Kesim B, Burak AK, Ustun Y, Delikan E, Gungor A. Effect of chitosan on sealer penetration into the dentinal tubules. Niger J Clin Pract. 2018;21(10):1284-90. Guo JM, Makvandi P, Wei CC, Chen JH, Xu HK, Breschi L, Pashley DH, Huang C, Niu LN, Tay FR. Polymer conjugation optimizes EDTA as a calcium-chelating agent that exclusively removes extrafibrillar minerals from mineralized collagen. Acta Biomater. 2019;90:424-40. Susanto A, Susanah S, Priosoeryanto BP, Satari MH, Komara I. The effect of the chitosan-collagen membrane on wound healing process in rat mandibular defect. J Indian Soc Periodontol. 2019;23(2):113-18.

Abstract:

The pandemic of COVID-19 has afflicted every individual and has initiated a cascade of directly or indirectly involved events in precipitating mental health issues. The human species is a wanderer and hunter-gatherer by nature, and physical social distancing and nationwide lockdown have confined an individual to physical isolation. The present review article was conceived to address psychosocial and other issues and their aetiology related to the current pandemic of COVID-19. The elderly age group has most suffered the wrath of SARS-CoV-2, and social isolation as a preventive measure may further induce mental health issues. Animal model studies have demonstrated an inappropriate interacting endogenous neurotransmitter milieu of dopamine, serotonin, glutamate, and opioids, induced by social isolation that could probably lead to observable phenomena of deviant psychosocial behavior. Conflicting and manipulated information related to COVID-19 on social media has also been recognized as a global threat. Psychological stress during the current pandemic in frontline health care workers, migrant workers, children, and adolescents is also a serious concern. Mental health issues in the current situation could also be induced by being quarantined, uncertainty in business, jobs, economy, hampered academic activities, increased screen time on social media, and domestic violence incidences. The gravity of mental health issues associated with the pandemic of COVID-19 should be identified at the earliest. Mental health organization dedicated to current and future pandemics should be established along with Government policies addressing psychological issues to prevent and treat mental health issues need to be developed. References World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard. 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Abstract:

Parents play an important role in the development of their children. This research reflects the role of parents in developing children. Through four stages of identification, screening, eligibility, and acceptable results, this method uses a systematic literature review using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) method. The findings from the fourteen articles examined show that parenting skills play an important role in a child's growth and development from birth to death. The determining factor in the development of physical, motoric, moral, language, social-emotional, and life skills aspects is the role of both parents as important teachers for children from birth to adulthood. Parents can also use a variety of parenting strategies and skills, many of which they have learned throughout their lives and passed on to their children, to help their children grow. 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Abstract:

The three major groups of antifungal agents are there that are used in clinical use, azoles, polyenes, and allylamine/thiocarbamates, all own their antifungal activities to inhibit the reactivity of microbial or stop direct interaction of microbial with healthy cells.3 Microbial organometallic assimilation, the bioaccessibility, bioavailability, and bioaccumulation properties of inorganic metals in different antimicrobial moieties that are interrelated and classified as abiotic (e.g., organic carbon) and biotic (e.g., uptake and metabolism).4 IntroductionThe development of antifungal and antibacterial agents is different because of unpredictable consequences of the cellular events and features of the organisms. Hence, substantial attention has been focused on developing a more detailed understanding of the mechanisms of antimicrobial resistance, improved methods to detect resistance when it occurs search new antimicrobial options in treating infections caused by resistant organisms, and methods to prevent the emergence and spread of resistance in the first place since such efforts initiated.1 Most of the attention has devoted to the study of antibiotic resistance in bacteria for several reasons: (i) bacterial infections are responsible for the bulk of community-acquired and nosocomial infections; (ii) the large and expanding number of antibacterial classes offers a more diverse range of resistance mechanisms to study; and (iii) the ability to move bacterial resistance determinants into standard well-characterized bacterial strains facilitates the detailed study of molecular mechanisms of resistance in bacterial species.2 Moreover, the three major groups of antifungal agents are there that are used in clinical use, azoles, polyenes, and allylamine/thiocarbamates, all own their antifungal activities to inhibit the reactivity of microbial or stop direct interaction of microbial with healthy cells.3 Microbial organometallic assimilation, the bioaccessibility, bioavailability, and bioaccumulation properties of inorganic metals in different antimicrobial moieties that are interrelated and classified as abiotic (e.g., organic carbon) and biotic (e.g., uptake and metabolism).4 Modifying factors determine the amount of an inorganic metal that interacts at biological surfaces and binds it and finally was absorbed across the membranes.5 A major challenge is to consistently and accurately measure quantitative differences in bioavailability between multiple forms of inorganic metals in the environment. Microbes interact with metals and minerals in natural and synthetic environments, altering their physical and chemical state, with metals and minerals also able to affect microbial growth, activity, and survival. Additionally, many minerals are biogenic in origin, and the formation of such biominerals is of global geological and industrial significance, as well as provides important structural components for many organisms, including important microbial groups i.e. diatoms, foraminifera, and radiolarian. The current article summarizes each category of antimicrobial agents in order to illustrate the diverse modes of coordination/association of the ligands having different donor atoms (N. S. and O. etc.). This phenomenon is usually achieved by increasing asymmetry in the mode of coordination of these ligands as a donor of electrons. Wherever it was found appropriate, the comments relating to the physiological role, biochemical mechanism, environmental significance, and bioremediation potential of the microbial biotransformation are included (Fig. 1).6 Figure 1. During the following steps of metal usage, the acquired metal is transferred through intracellular trafficking pathways, which may include diverse storage compartments to be directed to cofactor assembly systems and final microorganism targeting can be achieved.7 Several of these used metals, organic moieties and related channeling routes, which have been described recently since their evolution, provide first insights into the later steps of metal assimilation and help in the characterization of an essential part of the cellular metal homeostasis network. Overall, so many challenges existed in this concept of antimicrobial drugs, and a few of them are related to the molecular entities of antimicrobial drugs. But, others have been concerned with the emergence of microbial resistance to the drugs applied and gradually limiting the efficiency of these antimicrobial remedies.8 But in the current, no solution is available, although the innovation of effective antimicrobial drugs is continuing. Several efforts have done for increasing the life of current drugs and designing of new antimicrobial drugs that will have to solve the problem of short life expectancy through scientific or adopting new strategies such as vaccination and other approaches for disease resistors are being tracked. The main causes of the resistance investigated and a few of them are as follows: innate features of the microbial, multiplying abilities of microbial, non-multiplying state, mutation, or gene transfer.9 In accordance with scientific evidence reported, it is easy to destroy the multiplying microbial quickly by existing antimicrobial drugs, but in the case of non-multiplying or slowly multiplying microbial, it is not quite easy. These findings elaborate on the need for highly effective antimicrobial drugs and conventional prolonged courses of drugs.10 One of the solutions that can be applied for it is; by applying the combination of antimicrobial drugs of both the categories, one class of drugs that target non-multiplying and other types of drugs that treat multiplying microbial.11 Sometimes these simple strategies can work and be an effective solution for the problem that can into existence because of the emergence of antimicrobial resistance.12 The other option is to develop a new class of antimicrobial agents that could remain effective for extended periods comparatively than presently existing antimicrobial drugs. The phenomenon of resistance especially emerged in the microbial impact and specific needs are there to deal it by applying antibacterial drugs and during treatment also, it can become a severe problem for the health of human beings. Therefore, the concern to have potential antimicrobial drugs is good whys and wherefores for it and is at the top of the current priority that is in demand. Antimicrobial drugs were developed by following a concept, which can induce new features to the organic moiety of the proposed drug to empower the central metal atom as well.13 Then, the developed antimicrobial drugs will have more potential to inhibit the multiplication processes of the microbial, and that is why it is considered a key concept in the discovery of antibacterial drugs. Among them, several other options are available that can be adopted for developing antimicrobial drugs, an alternative novel strategy is one of them.14 According to this concept, the primarily alleviate the current need, and after that incorporates new functional and many required features required for drug resistance, that are generated by interacting the potential moieties and effective metal combinations. These predetermined abilities were developed for targeting the non-multiplying latent.15 These strategies are helpful in the development of antimicrobial drugs that can prolong the duration of antimicrobial impact and enhanced the abilities that can break the microbialresistance. These routes of discovery are also helpful against prolonged suboptimal bactericidal growth, which is considered the main cause for the emergence of resistance.16 These settings of resistance and unhealthy biological features exist not only in the target pathogen, but also presented a different class of tissues and organs i.e. the gut, and throat. These pathogens can initiate fatal diseases in healthy tissues. The proper analysis of these strategies proved that long-term use of antimicrobial drugs can deal with microbial resistance in a better way comparatively than a shorter period. These results encourage researchers in dealing with the emergence of resistance initiated by the microbial.17 But, in some cases, the approach of a long course can develop more complications in the patients and as a result, it will enhance the power of resistance. In the current situation, the use of drug libraries can be applied to avoid such situations. Newly developed antimicrobial drugs should be screened against non-multiplying bacteria for the discovery of potential antimicrobial drugs that can destroy the microbial and originated resistance responsible for initiating the disease too. This opinion covers the approaches useful in the discovery of novel antimicrobial drugs by applying classic screening, by the analysis of structural changes done in drugs, by genome hunting; and by adopting a novel route that targets non-multiplying, latent microbial.18 The author tried his best to correlate all the original facts and concerning the chemistry of drug resistance with a special focus on antimicrobial drugs and concerned resistance mechanism underlying in the context of bioaccessibility, bioavailability, and bioaccumulation.19 In the end, it is a better way to adopt the latest scientific approach available, recently discovered tools and theories. By doing so, greater chances and much hope are there to be successful in the discovery of novel antimicrobial drugs that will reduce the emergence of resistance caused by the antimicrobial agents and treat the diseases in a better way. References: Ghannoum, M. A.; Rice, L. B. 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Abstract:

Nitrogen is a paramount important essential element for all living organisms. It has been found to bea crucial structural component of proteins, nucleic acids, enzymes and other cellular constituents which are inevitable for all forms of life. In the atmosphere, the percentage of nitrogen is very high (N2, 78%) compared to other inorganic gases. However, most organisms have practically no direct access to this nitrogen. While plants can not directly uptake nitrogen from atmosphere, they are capable of assimilating other forms of nitrogen, for example ammonium (NH4+) and nitrate (NO3-). For agricultural crop production, artificial fixation of nitrogen is heavily utilized and it is an expensive process that requires high temperatures (at least 400 °C) and pressures (around 200 atm). It has been conspicuously demonstrated that indiscriminate use of fertilizer hampers soil physical, chemical and micro biological properties and also a potential risk to environment e.g. water quality. Besides, chemically manufactured fertilizers are depleted from soils in various ways, for instance; denitrifying bacteria, volatilization, and leaching. Consequently, it results relatively poor availability of nitrogen to get into plants. On the flipside, only 1-2% of the nitrogen fixation in the world occurs through the natural process of lightening. Notably, microbial fixation is well characterized in diazotrophs for example; Rhizobia and Frankia, and blue-green algae. Against the backdrop, we are accentuated on an environmentally friendlyand themost sustainable approach to increase productivity for legume and non-legume crops. Till today, the term biological nitrogen fixation (BNF) has received much attention as a sustainable alternative; this process facilitates atmospheric nitrogen to convert into ammonia by rhizobia in specialized plan organs termed “root nodules”. This review article seeks to better understand plant mechanisms involved in the development of root nodules in soybean. Soybean (Glycine max) is one of the most important oil crops and a source of animal feed protein in the world. It has a salient feature to fix atmospheric nitrogen through symbioses with compatible rhizobia that yields to determinate type nodule (Oldroyd, Murray et al. 2011). Biological nitrogen fixation in soybean nodules reduces the use of chemical nitrogen fertilizers resulting in cost-savings to producers and minimizes environmental damage due to nitrogen run-off. A better understanding of how nodules form and function is important for selection or generation of soybean genotypes with better nitrogen fixation capacity. Soybean nodules originate from root cortex via de novo cell differentiation (Oldroyd 2013). Consequently, two major nodule development zones are formed for instance; the nodule primordium (Npr) in the middle and it is encircled by nodule parenchyma (Npa). At later time point, the Npr gives rise to N-fixation zone and the Npa holds vascular bundles. It is not clear what early signaling pathways driving the conspicuous development of the nodule zones. My research is aimed at filling this knowledge gap by illustrating the molecular signatures that paves the way to cellular differentiation in root nodule development in soybean. Based on initial evidence obtained by the Subramanian lab, we hypothesize that microRNAs (miRNAs) play important regulatory roles in spatio-temporal expression of their target genes during nodule developmental in soybean. For instance, the regulation of auxin sensitivity by miR160 has been found to be crucial for formation of nodule primordia and vasculature in the parenchyma (Marie Turner 2013). Against this backdrop, this review article focused on nuclear and cytoplasmic transcriptome as well as miRNA profiles of parenchyma and primordial tissues and determine the relative abundance and differentially expressed mRNAs and regulatory role of miRNAs in cell differentiation and nodule development. Root nodule a sustainable alternative to fix atmospheric nitrogen Atmospheric nitrogen percentage is very high (N2, 78%) compared to other inorganic gases (Mary Elvira 1932). However, most of the organisms have practically no direct access to this nitrogen. Nevertheless, plants can not directly uptake nitrogen from atmosphere but they are capable of assimilating only very specific forms of nitrogen, for example ammonium (NH4+) and nitrate (NO3-) (Bytnerowicz and Fenn 1996, Peter M. Vitousek 1997) (Sponseller, Gundale et al. 2016). Virtually, nitrogen has been found to be a crucial structural component of proteins, nucleic acids, enzymes, and other cellular constituents which are inevitable for all forms of life (O'Brien, Vega et al. 2016). For agricultural crop production, artificial fixation of nitrogen is heavily utilized. It is an expensive process that requires high temperatures (approx. 400 °C) and pressures (approx. 200 atm) (Witschi 2000). It has been conspicuously demonstrated that indiscriminate use of N fertilizer hampers the diversity of the bacterial community and decreases soil C and N concentrations (Verzeaux, Alahmad et al. 2016). Notably, it has been demonstrated as a potential risk to environment e.g. water quality (Zhao, Sha et al. 2016) (Sponseller, Gundale et al. 2016). Besides, chemically manufactured fertilizers are depleted from soils in various ways, for instance; denitrifying bacteria, volatilization, and leaching (Johnson 1996, Peter M. Vitousek 1997). Consequently, it results relatively poor availability of nitrogen to get into plants. On the flipside, over 90 % of the nitrogen fixation in the world occurs through the natural process of lightening and microorganisms. Furthermore, microbial fixation is well characterized in diazotrophs for example; Rhizobia and Frankia, and blue-green algae (Cheng 2008). It has been demonstrated that Bradyrhizobium strains substantially escalated soybean grain yield, and protein content up to 57% and 26%, respectively (Zimmer, Messmer et al. 2016). Against the backdrop, we are accentuated on an environmentally friendly and a sustainable approach to increase the productivity for legume and non-legume crops. Literature mining depicted that biological nitrogen fixation in soybean nodules reduces the use of chemical nitrogen fertilizers resulting in cost-savings to producers and minimizes environmental damage due to nitrogen run-off. Rhizobia infection leads to the root nodule development In the natural environment, plants are continuously confronted with pathogenic and symbiotic microbes. Symbioses involves mutual exchange of diffusible signal molecules, first endophytic bacteria (rhizobia) are attracted by the plant root exudates flavonoids which are perceived and triggered the bacterial nodulation (nod) genes. Consequently, the bacteria synthesize specific lipochito-oligosaccharides, called nodulation (Nod) factors. This signal is perceived by the LysM receptor like kinase of host plant, it induces the root hair curling, and bacteria get access into the host epidermis through infection threads (ITs) and initiate cell division within the root cortex, leading to the progression of the root nodule meristem. In later stages of the interaction, bacteria are released from the infection threads into the plant cells, surrounded by membrane of plant origin. These bacteria multiply within the host cells and differentiate into the nitrogen fixing bacteroids (Udvardi and Day 1997) (Oldroyd 2013). Till now, integration of genetic and genomic approaches has revealed twenty-six genes to be involved in nodule development of Medicago truncatualaand Lotus japonicum (Kouchi, Imaizumi-Anraku et al. 2010). In addition, deep sequencing of the Medicago truncatularoot transcriptome has uncovered thousands of genes to be induced during Nod factor signaling and its resulting ethylene (ET) biosynthesis throughout the multiple development stages of indeterminate nodule (Larrainzar, Riely et al. 2015). Albeit the molecular mechanism of such regulation is not well understood. There has been a large-scale transcriptome analysis of B. japonicum-inoculated and mock-inoculated soybean root hairs. It has showed that a total of 1,973 soybean genes differentially expressed during root hair infection, particularly NFR5 and NIN genes (Libault, Farmer et al. 2010). Nevertheless, the signaling mechanisms directing the cellular differentiation of nodule are not known. Soybean root nodule organogenesis Soybean (Glycine max) has a genome size of 1.1 to1.5 Gb, it is partially diploidized tetraploid. It is one of the most important oil crops and a source of animal feed protein in the world (soybase.org/sb_about.php). It has a salient feature to fix atmospheric nitrogen through symbioses with compatible rhizobia that yields to determinate type nodule (Udvardi and Day 1997) (Oldroyd, Murray et al. 2011). Notwithstanding of the economic and environmental importance, there has been very few studies about quantitative trait loci (QTL) that controlling BNF traits, for instance nodule number, ration of nodule dry weight with nodule number, and shoot dry weight (SDW). It has been reported via composite interval mapping that approximately six QTLs bears very small effect on BNF traits (Santos, Geraldi et al. 2013). Besides, it has been demonstrated in earlier studies that nodules originate from root cortex via de novo cell differentiation into two different cell types, parenchymal and primordium (Celine Charon 1997) (Oldroyd&Downie 2008; Oldroyd 2013). In addition, early nodulin genes in legume for instance; Enod 40 gene reported to be expressed in root pericycle during the rhizobia infection and later it occupied in the dividing cortical cells (H. Kouchi and S. Hata 1993). Among the two major nodule development zones, the nodule primordium (Npr) in the middle which is encircled by nodule parenchyma (Npa). At later time point, the Npr gives rise to N-fixation zone and the Npa holds vascular bundles. Lately, a β- expansin gene, GmEXPB2 fused with GUS reporter gene which was observed to be preferentially expressed in nodule vascular trace and nodule vascular bundles. It indicated that GmEXPB2 might be crucial for nodule organogenesis. Over expression of GmEXPB2 contrast to suppressed GmEXPB2 transgenic lines found to be escalated nodule number, nodule mass and nitrogenase activity. It further suggested that GmEXPB2 might have influenced over root architecture, nodule formation and development, and profoundly yielding to biological N2 fixation (Li, Zhao et al. 2015). Even though, it is not clear what early signaling pathways driving the conspicuous development of the nodule zones. Against the back drop, to understand the regulation of auxin sensitivity by miR160 which is believed to be crucial for the formation of nodule primordia (Marie Turner 2013). Figure 1 a. Illustrating the progression of root nodule development through Rhizobial bacterial infection in the plant root leading to the determinate nodule (Oldroyd 2013). b. Nodule development zones A. Nodule primordial zone (Enod 40 gene) in the middle B. surrounding parenchyma (Enod 2 gene), differentiated from cortex (collected from Sen Subramanian lab). Regulatory small RNAs biogenesis and its molecular functions Regulatory small RNAs are ranged between 20 to 24 nucleotides which are ubiquitous elements of endogenous plant transcriptomics, a common response to exogenous viral infections and introduced double-stranded RNA (Axtell 2013). Three core enzymes families, for instance; RNAdependent RNA polymerase (RDR), Dicer like (DCL), and Argonaute (AGO) proteins paves the way of small RNA biogenesis and function in plants. Firstly, ribonuclease type III or DICERLIKE1 involves in the yield of a fold-back precursor RNA or primary miRNA (primiRNA) transcripts using an RNA templates in the nuclei. Later, the resulting miRNA-miRNA duplex which is originated in nucleus then translocated into cytoplasm. The guided miRNAmolecule is incorporated into ARGONAUTE (AGO) to form an active RISC complex to specific target RNAs that are complementary to the miRNA, and this process eventually follows up mRNA cleavage, represses the translation of the mRNAs or Chromatin modification. This phenomenon accentuated as an inhibition or silencing of the gene expression, which play a crucial role in the developmental process in plant and animal (Chapman and Carrington 2007) (Axtell 2013). Fig. 2 Regulation of gene expression events via RISC complex (modified from https://www.google.com/?gws_rd=ssl#q=mirna+picture+in+plants accessed on 7th February, 2016) Fig. 3 Gene expression events occurring in typical plant cell (modified https://www.google.com/search?q=transcription+and+translation accessed on 7th February, 2016) It has been found in several studies that most plant miRNAs are non-coding RNA, and small 21-24 nucleotide long (Cuperus, Fahlgren et al. 2011). It requires DCL1-clade DCL for their biogenesis and AGO1-clade AGO for their function (Wu, Zhou et al. 2010, Manavella, Koenig et al. 2012). In rice (Oryza sativa), DCL3 has been reported in the biogenesis of 24nt long miRNA that incorporated in AGO4 to regulate the target gene expression primarily through mRNA cleavage (Wu, Zhou et al. 2010). Argonaute proteins (AGO) form RNA inducing silencing complexes (RISC) with small RNAswhich is known as post-transcriptional gene silencing. It has typically four domains, for instance:N-terminal, PAZ, MID and PIWI domains. The MID-PIWI lobes are belongs to the C-terminus. It has been studied that MID-domains contains the specificity loop to recognize and bind to the 5’-phosphate of smRNAs. The PIWI domains contained the catalytic active site D-E-D-H/D. PAZ domain anchored the 2-nt overhang at the 3’ end of miRNAs. The N-terminal domain involved in the separation of miRNA-miRNA duplex and the slicer activity of the mRNA (Song, Smith et al.2004). There has been an expansion and duplications of AGO family members during plantevolution (Singh, Gase et al. 2015). The functional diversification of AGOs is indicating sRNAdirected regulatory pathways. The binding preference of AGO and sRNA is mainly assigned by the sequence of sRNA. In Arabidopsis, 10 AGO have been extensively studied (Liu et al. 2014). It has been demonstrated that AtAGO10 like AtAGO1, it recognized distinct structural features in miR165/miR166 duplex than involved by AtGO1. AtAGO10 found to regulate shoot apical meristem by decoying miR165/miR166 and subsequent repression of homeodomain-leucinezipper (HD-ZIP) gene expression (Zhu, Hu et al. 2011). Notably, 22 AGO proteins have been reported in Soybean (Glycine max). It has been found that genome duplication in Soybean resulted such a proliferation of AGOs. For example: its genome encodes two copies of AGO1, AGO2, AGO5, AGO4/9, AGO6 and AGO7 (Xiang Liu 2014). However, the molecular function of the plant AGO genes yet not very clear. There are several miRNA families that are conserved across the vast evolutionary distances from flowering plants to mosses (Cuperus, Fahlgren et al. 2011). It has been observed in another study that miRNA, and its target pairing found to be stable for a prolonged periods of plant evolution. On the flip side, another group demonstrated that conserved plant miRNAs and their targets are to somehow flexible. For instance; miR159 is a highly conserved miRNA that targets not only a subset of MYB mRNAs but also observed to target a non MYB mRNA, SGN-U567133 (Buxdorf, Hendelman et al. 2010). A mutant tomato transgenic line (miR159-resistant line) showed higher level of the SGN-U567133 transcript and exhibited defects in leaf and flower development. This result suggests that miR159 involves in a post-transcriptional regulation. Additionally, it is found to be crucial for the normal tomato development. Recently, the identification of miRNAs in the regulation of photoperiodic pathways in soybean have been reported through high throughput sequencing and qRT-PCR. Six libraries were constructed using Illumina Solexa, for instance; 0, 8, and 16 h under short day treatment, similar time points considered for the long the long day treatment. A total of 163 miRNAs families were reported which covered 318 plant miRNAs, and unclassified 81 novel predicted miRNAs. As expected, significant differences in abundance between short day and long day treatment was observed (Wenbin Li 2015). These findings provided evidence of miRNA in the regulation of flowering time that ultimately affects the seed yield and quality of soybean. The complex regulatory network of miRNA-mRNA interactions during viral infection has been revealed via small RNA seq (sRNA), degradome seq, and genome-wide transcriptome analysis. There has been a total of 253 soybean miRNAs found to be two-folds abundance compared with mock-inoculated control demonstrated through sRNA seq analysis. Among them 105 miRNAs were identified as potential targets of 125 transcripts that has been validated by degradome seq analyses. In addition, 2679 genes were detected via genome wide transcriptomic analysis. These genes have been differentially expressed during infection of soybean mosaic virus and among them 71 genes projected to induce in defense response (Hui Chen 2016). These findings suggested the regulatory role miRNA that governed the target gene expression during viral infection. Furthermore, the regulatory role of microRNAs (miRNAs) during Soybean- Bradyrhizobium japonicum mutualistic association was studied first by Subramanian et al. 2008. They sequenced approximately 350000 small RNAs of soybean root sample which were inoculated with B. japonicum. It helps to detect 20 conserved miRNAs loci based on the similarity to miRNAs in another plant species. In addition, 35 novel miRNAs were identified based on potential hairpin forming precursors in Soybean EST as well as shotgun genomic sequences (Subramanian, Fu et al. 2008). These findings advocated the potential role of miRNAs in the regulation of legumerhizobiumsymbiosis. In another study, 120 hairpin-forming precursor genes have been identified in soybean by Turner et al. In addition, they reported three novel miRNAs for instance; miR160, miR164 and miR393 found to be involved in auxin signaling (Turner, Yu et al. 2012). Moreover, the plant hormone auxin is thought to have a pivotal role in nodule organogenesis in determinate and indeterminate type of nodule. It indicates a redundancy and diversity of miRNAs family members that governs the formation of root nodule. It has been illustrated that auxin receptor gene family hushed by over expressed microRNA393. These plant roots found to be hypersensitive to auxin and yielded normal nodule. This observation advocated that only minimal/reduced auxin signaling is required for determinate nodule development. Likewise, overexpressed microRNA160 hushed a set of repressor auxin response transcription factor. These plant roots were hypersensitive to auxin and observed not to be reluctant in epidermal responses to rhizobia. Notably, it yielded to lower sized nodule primordium (Marie Turner 2013). This observation indicated that auxin hypersensitivity inhibits nodule organogenesis Organ specific expression of profile of miRNA and the potential targets were also studied. Two genes (Glyma10g10240 and Glyma17g05920) which were the target of miR169 but detected to be highly expressed in soybean nodule. Likewise, three potential targets of gma-new-miR13587 demonstrated to be highly expressed in the nodules than in the roots. As expected, gma-newmiR13587 found to be poorly expressed in the nodules than in the roots (Turner, Yu et al. 2012). There was an inverse expression pattern observed in between roots and nodules. Li et al., studied the transgene expression of three novel miRNAs namely, miR482, miR1512, and miR1515 in Soybean. They noticed a significant increase of nodule numbers while root length and later root density were normal in all tested miRNA lines. As expected, there were differential expression of these miRNAs in supernodulating and nonnodulating soybean mutants. They reported that 6 novel miRNAs decoyed 22 predicted target genes. And it was estimated via real time polymerase chain reaction and qRT-PCR (Li, Deng et al. 2010). It advocates that miRNAs have the signatory roles in soybean nodule development. Sequencing of small RNAs and Parallel analysis of RNA ends (PARE) libraries revealed to identify 284 nodule miRNAs, more than 500 target genes, and including 178 novel soybean miRNAs. It has been reported that ENOD93 only found to be expressed in nodule tissue not in other plant parts of Soybean. Ectopic expression of miR393j-3p and RNAi silencing approach to ENOD93 expression showed a significant reduction in nodule formation (Zhe Yan 2015). Therefore, this study showed a list of miRNAs and their potential target of nodulation genes. In the model legume (Medicago truncatula), 25 conserved miRNA families and 100 novel miRNA reads were detected by high-throughput sequencing. The expression of MtHAP2-1 (encodes a CCAAT binding transcription factor) to meristematic zones was restricted by miR169a which is found to be critical for the development of indeterminate type of nodule (Combier, Frugier et al. 2006). In another study, HDZIPIII transcripts were inhibited by overexpression of miR166, it dropped the number of symbiotic nodule and lateral root (Boualem, Laporte et al. 2008). To get insights into key genes of nodule zones, transcript profiles of specific cells/tissues were investigated at different time points from indeterminate nodules of M. truncatulausing laser capture micro dissection. It has been demonstrated from the comprehensive gene expression map that selected genes enriched in different cell/tissue types (Limpens, Moling et al. 2013). These findings indicated that organ specific gene expression could be controlled by the presence or absence of miRNAs. Recently, Agrobacterium rhizogenesmediated hairy root transformation has been applied as tool for exploring cell type specific gene expression in tomato. Cell type or tissue specific promoter introduced into INTACT and TRAP constructs via gateway cloning technology to develop binary vectors. INTACT method used to capture biotin tagged nuceli from specific cell types and TRAP method used for profiling of mRNAs or foot printing of individual ribosomes (Ron 2014). TRAP methodology is not required tissue fixation or single cell suspension. It has been successfully used to date in organisms ranging from D. melanogaster to mice and human cultured cells. Multiple ribosomes or Polyribosomes (polysomes) are engaged in translation on a single mRNA. To evaluate the translation state of an mRNA, ribosomal subunits, ribosomes, and polysomes can be isolated from detergent-treated cell extracts (Heiman, Kulicke et al. 2014). In this study, we would perform polysome isolation deploying gene cassettes ENOD40p:HF-GFP-RPL18 for primordial tissues, and ENOD2p:HF-GFP-RPL18 for parenchymal tissues in Glycine max root nodules that express an epitope tagged version of ribosomal protein L18. Over the last one decade, there has been several microarrays-based studies which characterized transcriptional variations deployed in nodule formation. It has been embedded with couple of shortcomings, for instance; relative late time points study, incomplete representation of plant genes,discrimination of close paralogs, and reduced sensitivity. Lately, next generation sequencingtechnology have widened the horizon of transcription analyses in different legume species to detectsymbiosis induced changes in late nodule developmental stages. Against this backdrop, we areaccentuated to reveal early transcriptional changes induced in determinate type of soybean noduleby Bradyrhizobium japonicum. In determinate type of nodule, two major nodule development zones are formed for instance, the nodule primordium (Npr) in the middle and it is encircled by nodule parenchyma (Npa). At later time point, the Npr converted to N-fixation zone and the Npa contained vascular bundles. Of these facts, it is not clear what early signaling pathways driving the conspicuous development of thenodule zones. In this context, mechanisms regulate the distinct gene expression profiles in Npr andNpa cell types has not understood clearly. The proposed research study is aimed at filling this knowledge gap byillustrating the molecular signatures that paves the way to cellular differentiation in root noduledevelopment in soybean considering four different time points (5 dai, 7 dai, 10 dai& 14 dai). The hypothesisis microRNAs(miRNAs) play important regulatory roles in spatio-temporal expression of their target genesduring nodule developmental in soybean. For example, a gradient of microRNA localizationbetween nodule primordium and parenchyma cells could result in distinct differentiation of thesecell types. To test this hypothesis, one has to obtain both cell type-specific miRNA andtranscriptome (miRNA target) profiles. Since, the majority of miRNA regulation occurs in thecytoplasm, we reasoned that comparison of nuclear and ribosomal transcriptome profiles wouldreveal genes whose expression is potentially regulated by post transcriptional mechanisms such asmiRNA cleavage. Combining this information with cell type-specific miRNA profiles, andto test the above hypothesis and identify key miRNA-target pairs important for nodule celldifferentiation. The use of translating ribosome affinity purification (TRAP) of nodule zonecells, namely from parenchyma and primordial tissues, to obtain cytoplasmic transcriptomes data. Techniques to determine cell type specific expression profiles: TRAP methods TRAP is termed translating ribosome affinity purification, combines cell-type-specific transgene expression with affinity purification of translating ribosomes. It supersedes the need for tissue fixation, and facilitates to study the cell type-specific mRNA profiles of any genetically defined cell type. It has been successfully used to date in organisms ranging from D. melanogaster to mice, and human cultured cells. Multiple ribosomes or Polyribosomes (polysomes) are engaged in translation on a single mRNA. To evaluate the translation state of an mRNA, ribosomal subunits, ribosomes, and polysomes can be isolated from detergent-treated cell extracts. In this study, the polysome isolation using gene cassettes ENOD40p:HF-GFP-RPL18 for primordial tissues, and ENOD2p:HF-GFP-RPL18 for parenchymal tissues in Glycine max root nodules that express an epitope tagged version of ribosomal protein L18 RPL18(Heiman, Kulicke et al. 2014, Ron 2014). Relative abundance and differentially expressed mRNAs profile in two different tissue specific zones would help to understand the effect of regulatory role of miRNAs in cell differentiation and nodule development. References: Axtell, M. J. (2013). "Classification and comparison of small RNAs from plants." Annu Rev PlantBiol 64: 137-159. 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"Arabidopsis Argonaute10 specifically sequesters miR166/165 to regulate shoot apical meristem development." Cell 145(2): 242-256.

Abstract:

Šiame straipsnyje tyrinėjama klasikinio daoizmo pagrindėjų - Laozi ir Zhuangzi - idėjų transformacija įtakingoje Kinijos menininkų intelektualų (wenrenhua) estetikoje. Darbas pagrįstas autentiškais šaltiniais (klasikinio daoizmo tekstais - “Laozi”, “Zhuangzi” bei tapybos teorijos ir estetikos veikalais - Gu Kaizhi “Lun hua”(“Apie tapybą”), “Hua Yuntaishan ji” (“Užrašai apie tai, kaip tapyti Debesų terasos kalną”), Zong Bingo “Hua shanshui xu” (“Įvadas į peizažinę tapybą”), Wang Wei (415-145) “Xu hua” (“Įvadas į tapybą”), Xie He “Guhua pinlu” (“Senosios tapybos principai”), Wang Wei (701-769) “Shanshui jue” (“Peizažinės tapybos paslaptys”), “Shanshui lun” (“Apie peizažinę tapybą”, Shi Tao “Kugua heshang hualu” (“Vienuolio, vardu Kartus Moliūgas, pasakojimai apie tapybą”), Su Shi, Mi Fu, Ni Zanio, Zhao Mengfu, Dong Qichango ir kt. traktatais. Remiantis daoistiniais filosofiniais-estetiniais principais (Dao, qi (gyvybinė energija), ziran (spontaniškumas, savaimingumas), pu (pirminis paprastumas), xu (tuštumas) ir kt.) bei pamatinėmis menininkų intelektualų estetikos kategorijomis (shen (dvasia), yi (idėja-mintis), qi (gyvybinė energija), ziran (spontaniškumas, savaimingumas), pu (pirminis paprastumas), sheng (gyvybė, gyvybingumas) bei jų deriniais - zhuan shen, shenqi, shengqi ir kt.) atskleidiama, kaip Laozi ir Zhuangzi idėjos iš esmės nulėmė visą tolesnę wenrenhua estetikos sklaidą.

Abstract:

LANGUAGE NOTE | Document text in Chinese; abstract also in English. 本文對《杜陵詩律五十一格》（存錄於朝鮮本《木天禁語》，1555年刊。簡稱《五十一格》）進行考察結論如下。第一，該書爲詩格著作，但在選詩上具有七律專門、整首采錄、重視夔州詩等特點，同時從拗體、起承轉结等方面論詩，由此判斷該書非唐五代之作。第二，根據起承轉結内容的存在，對起承轉合起源于元代楊仲弘或宋代經義的學說發出質疑，提出元代的起承轉合論來源於以《五十一格》、“三氏杜詩注”爲代表的杜詩研究。三，根據范德機的律詩篇法十三格，以及爲范氏言明的十三格與《詩苑類格》的承繼關係提出：《五十一格》中從全詩角度分析句聯關係的論詩手法，可能在李淑《詩苑類格》（1039年）中已經存在，《五十一格》的成書可能在該書前後。第四，根據詩序的特殊排列，尤其是連章組詩的分離現象推測：本書没有受到王洙杜詩集的影響，從而否定了所有杜詩研究都以王洙本爲資料來源的傳統學說。第五，根據《五十一格》中前後注並存以及繼承篇“三氏杜詩注”的存在推測：此書在相當長的時期内受到了廣泛重視和研究。第六，通過與趙次公杜注比較得出：《五十一格》可能產生於經典式注釋方法運用於杜詩研究之前，其成書可能早於趙次公注及王洙注。 The results of my investigation conducted on the work entitled Du Ling’s Prosody: 51 Patterns (Du Ling shi lü wu shi yi ge) (as recorded in the Korean edition, Secrets of the Tang Imperial College〈Mutian jinyu〉, published in 1555, or called the 51 Patterns in short) are as follows. First, the book in question is an analysis in the forms and meter of regulated verse (shi). However, because of the following characteristics, this paper determines that it is not a work of the late Tang or early 5 Dynasties periods: in its choice of poems, the 51 Patterns focuses exclusively on qilü; it records poems in their entirety; it displays a preference for Du Fu’s Kuizhou period verse; and at the same time it discusses regulated verse in terms of such aspects as aoti, or non-conforming verse, and the qi cheng zhuan jie (introduction/ elucidation/ reversal/ conclusion) method of analysis. Second, judging from the presence of the qi cheng zhuan jie method, this paper questions the assumption that this method of analysis originated with Yang Zhonghong in the Yuan Dynasty, or with the Song Dynasty imperial examination system, and suggests that the origins of the qi cheng zhuan jie method lie in the early works of Du Fu poetry studies, the 51 Patterns and Three Du Fu Commentators” (San shi Du shi zhu) for example. Third, on the basis of the 13 patterns of regulated verse composition given by the Yuan poet Fan Deji (Fan Guo, 1272-1339) , which the poet himself explicitly states to be derived from Li Shu’s Typology of Poetry (Shi yuan lei ge, 1039) , this paper suggests that the critical method of analyzing the relationships between the lines of a poem from the standpoint of its entirety, may have already existed in Typology of Poetry; therefore the 51 Patterns was possibly completed around the same time as the Typology. Fourth, on the basis of the peculiar ordering of the poems in the 51 Patterns, especially in its separation of some pieces which belong to a series of poems under the same title in later collections, this paper speculates that the work was not influenced by Wang Zhu’s Collected Poems of Du Fu ( Wang Zhu Du shi ji, 1039; published in 1059) , and thus it contradicts the traditional theory that all Du Fu Poetry studies take the Wang Zhu collection as their source material. Fifth, on the basis of the coexistence of both original and later commentaries in this work, as well as the existence of the subsequent piece, “Three Du Fu Commentators”, which carries on the work of the 51 Patterns, this paper speculates that the 51 Patterns enjoyed a relatively long period of extensive serious consideration and study. Finally, through a comparison with Zhao Cigong’ s Du Fu commentaries, this paper concludes that the 51 Patterns may have been produced before the standard classical method of annotation was applied to Du Fu poetry studies.

Abstract:

Alloys used in engines are subjected to challenging environments characterized by thermal and mechanical cyclic loadings during start-up and shut-down processes. These conditions can significantly increase the occurrence of fatigue failure mechanisms. Therefore, this study focuses on investigating the low cycle fatigue (LCF) behavior of directionally-solidified alloy at two distinct temperatures, namely 600 °C and 800 °C. Strain-controlled LCF tests were conducted at the specified temperatures, utilizing constant total strain amplitudes of 0.4%, 0.6%, 0.8%, and 1% under a totally reversed loading ratio (R = -1). The Coffin-Manson model, based on plastic deformation, along with a hysteresis energy-based criterion model, were employed to predict and evaluate fatigue life and LCF behavior. Notably, the hysteresis energy and Coffin-Manson models exhibited superior capability in predicting LCF life at 800 °C compared to 600 °C. REFERENCES Salehnasab, J. Marzbanrad, E. 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Abstract:

LANGUAGE NOTE | Document text in Chinese; abstract also in English. 稱美杜甫詩爲“詩史”，始於晚唐孟綮《本事詩》。推崇安史之亂前後杜甫所作敘事詩，以爲富於“推見至隱”之《春秋》書法，識見超拔，可謂杜詩知音。杜甫《祭遠祖當陽君文》，贊揚遠祖杜預：“《春秋》主解，稿隸躬親”，感慨“鳴呼筆跡，流宕何人”？文中杜甫既以“不敢忘本，不敢違仁”自惕自勉，發爲詩歌，遂多“推見至隱”之《春秋》書法。諸如微婉顯晦、據事直書、褒貶勸懲、諱言諱書等，宋代詩學討論之“詩史”論述，杜甫敘事歌行，多有具體而微之體現。本論文考察杜甫詩史，專取《春秋》書法爲視角，援引20餘首杜甫敘事歌行爲例，結合65則宋代詩話筆記，8則明清詩話之論述，借鏡兩宋《公羊》學、《左傳》學之理論，聨結經學、史學，與文學作一學科整合之探討。同時類比白居易、元稹、韓愈、李商隱等有關楊貴妃、馬嵬坡諸詩篇，以見宋人以《春秋》書法論詩之一斑。從此可見《春秋》與詩，皆杜甫“吾家事”，於是詩與《春秋》相表裏，而蔚爲詩史之特筆書寫。 Meng Qi’s Ben Shi Shi (本事詩) began to praise Du Fu’s poetry as “Shishi” (詩史) in late Tang. Meng praised highly for Du Fu’s narrative poems during An Shi Rebellion (安史之亂), and affirmed it’s “represent the obvious to the concealed” and Chun Qiu Shufa (《春秋》書法). He was indeed a transcendent insight and the expert of Du’s poetry. Du Fu “Ji Yuan Jie Dangyang text” (《祭遠祖當陽君文》) commend his ancestor Du Yu: “Chun Qiu is mainly for explanation, Personally writing draft”, sighed “Wuhu handwriting, who owns it?" In the text, Du Fu encouraged and alerted himself as "Not forgetting his roots, not disobeying illegally” for poetries. Chun Qiu Shufa of “Represent the obvious to the concealed” like the Song Dynasty poetics called “Shishi”, Du Fu's XuShiGexing (敍事歌行) almost showed Specifically such as implicit declare obscurely, traightforwarded recording according to events, praised good belittled evil, Said and written indirectly etc. This paper inspects Du Fu’s ‘‘Shishi”, detailed others neglected, varied different from the same. Chun Qiu Shufa of Du Fu's XuShiGexing inspected 60 of Song Dynasty Shihua (詩話) and Biji (筆記), expositions of 6 of the Ming and Qing Dynasties Shihua. To learn northern and southern Song the theory of Gong Yang study (《公羊》學) and ZuoZhuan study (《左傳》學), linking the morality, historiography and literature, discussed the integration of subjects for a study. To analog Bai Juyi (白居易), Yuan Zhen (元稹), Han Yu (韓愈), Li Shangyin (李商隱) s’ various poems about Yang Guifei (楊貴妃), Ma WeiPo (馬嵬坡), understood Chun Qiu Shufa reflected poems.

Abstract:

Vitamin E (VitE) is a potent antioxidant and contributes as an apoptosis inhibitor by preventing apoptotic death by suppressing cell membrane scrambling with phosphatidylserine translocation and caspase activites. Fas ligand (FasL) is well known to induce cell apoptosis. Activation of phosphoinositide 3 kinase (PI3K) signalling is stimulated by VitE. The present study addressed the effects of VitE on survival of mouse dendritic cells (DCs) and signalling molecules underlying. To this end, mouse bone marrow cells were isolated and cultured to attain bone marrow-derived DCs (BMDCs). The cells were treated with FasL in the presence or absence of VitE. Western blotting and FACS analysis were performed to determine expression of signalling molecules and their involvement in DC apoptosis. As a result, FasL treatment resulted in activation of caspase 8 and an increased number of Annexin V+ cells, the effects were significantly suppressed when VitE was present in the cell culture. Importantly, the anti-apoptotic effects of VitE were abolished by using pharmacological inhibition of PI3K signaling with LY294002. Our results showed that VitE inhibited FasL-mediated DC apoptosis through PI3K signalling, the effect is expected to facilitate the survival of DCs and promote the immune response against pathogens. Keywords Caspase, Dendritic cell; Fas ligand; PI3K and vitamin E. References [1] J. Banchereau, R.M. Steinman, Dendritic cells and the control of immunity, Nature 392 (1998) 245-52.[2] E. Ingulli, A. Mondino, A. Khoruts, M.K. Jenkins, In vivo detection of dendritic cell antigen presentation to CD4(+) T cells, J Exp Med 185 (1997) 2133-41.[3] C. Yang, H.Z. Liu, Z.X. Fu, PEG-liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase-8, Cell Biol Int 36 (2012) 289-96.[4] Q.G. Yan, J.G. Shi, F. Zhang, Q.T. Zhao, X.W. Pang, R. Chen, P.Z. Hu, Q.L. Li, Z. Wang, G.S. 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