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| 1 | Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1显示文摘As a terpenoids natural product isolated from the plant Thunder God Vine,Celastrol is widely studied for its pharmacological activities,including anti-tumor activities.The clinical application of Celastrol is strictly limited due to its severe side effects,whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization.Target identification has a far-reaching influence on the development of innovative drugs,and omics data has been widely used for unbiased target prediction.However,it is difficult to enrich target of specific phenotype from thousands of genes or proteins,especially for natural products with broad promising activities.Here,we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds.Then peroxiredoxin 1(PRDX1)was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer.Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1.New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis.Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells.The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells.Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment.Our findings reveal that the side effects of Celastrol could be reduced via structural modification,and PRDX1 inhibition is promising for the treatment of colorectal cancer. | Heng Xu Hongfang Zhao Chunyong Ding Defang Jiang Zijie Zhao Yang Li Xiaoyu Ding Jing Gao Hu Zhou Cheng Luo Guoqiang Chen Ao Zhang Ying Xu Hao Zhang | 2023 | Signal Transduction and Targeted Therapy2023，8，3： | 3 |
| 2 | Dietary isoleucine improved flesh quality,muscle antioxidant capacity,and muscle growth associated with AKT/TOR/S6K1 and AKT/FOXO3a signaling in hybrid bagrid catfish(Pelteobagrus vachelli♀×Leiocassis longirostris♂)显示文摘Background:Muscle is the complex and heterogeneous tissue,which comprises the primary edible part of the trunk of fish and mammals.Previous studies have shown that dietary isoleucine(Ile)exerts beneficial effects on growth in aquatic animals.However,there were limited studies regarding the benefits of Ile on fish muscle and their effects on flesh quality and muscle growth.Thus,this study was conducted to explore whether dietary Ile had affected flesh quality and muscle growth in hybrid bagrid catfish(Pelteobagrus vachelli♀×Leiocassis longirostris♂).Methods:A total of 630 hybrid fish,with an initial average body weight of 33.11±0.09 g,were randomly allotted into seven experimental groups with three replicates each,and respectively fed seven diets with 5.0,7.5,10.0,12.5,15.0,17.5,and 20.0 g Ile/kg diets for 8 weeks.Results:In the present study,we demonstrated that Ile significantly:(1)increased muscle protein and lipid contents and the frequency distribution of myofibers with≤20μm and≥50μm of diameter;(2)improved pH value,shear force,cathepsin B and L activities,hydroxyproline content,resilience,cohesiveness,and decreased cooking loss,lactate content,hardness,springiness,gumminess,and chewiness;(3)decreased reactive oxygen species(ROS),malondialdehyde(MDA),and protein carbonyl(PC)contents,GCLC and Keap1 mRNA levels,and up-regulated CuZnSOD,CAT,GPX1a,GST,and Nrf2 mRNA levels;(4)up-regulated the insulin-like growth factor 1,2(IGF-1,IGF-2),insulin-like growth factor 1 receptor(IGF-1R),proliferating cell nuclear antigen(PCNA),Myf5,Myod,Myog,Mrf4,and MyHC mRNA levels,and decreased MSTN mRNAlevel;(5)increased muscle protein deposition by activating AKT-TOR-S6K1 and AKT-FOXO3a signaling pathways.Conclusion:These results revealed that dietary Ile improved flesh quality,which might be due to increasing nutritional content,physicochemical,texture parameters,and antioxidant ability;promoting muscle growth by affecting myocytes hyperplasia and hypertrophy,and muscle protein deposition associated with protein synthesis and degradation signaling pathways.Finally,the quadratic regression analysis of chewiness,ROS,and protein contents against dietary Ile levels suggested that the optimal dietary Ile levels for hybrid bagrid catfish was estimated to be 14.19,12.36,and 12.78 g/kg diet,corresponding to 36.59,31.87,and 32.96 g/kg dietary protein,respectively. | Qin Jiang Mingyao Yan Ye Zhao Xiaoqiu Zhou Long Yin Lin Feng Yang Liu Weidan Jiang Pei Wu Yan Wang Defang Chen Shiyong Yang Xiaoli Huang Jun Jiang | 2021 | Journal of Animal Science and Biotechnology2021，12，4： | 2 |
| 3 | Bacterially expressed dsRNA protects maize against SCMV infection显示文摘 | Defang Gan Jiao Zhang Haibo Jiang Tong Jiang Suwen Zhu Beijiu Cheng | 2010 | Plant Cell Reports2010，，11： | 1 |
| 4 | Effects of Annealing on Pt/Co Multilayer Films显示文摘Annealing effects are helpful guides to study Pt/Co multilayer interface diffusions.However,the results reported till now are different.Here we report the increase in coercivity Hc and the decrease in Kerr rotationθk after being annealed in vacuum or argon atmosphere.We attribute these effects to the formation of CoPt3 compound. | JIANG Zhihong SHEN Defang SHI Tiansheng GUO Changlin GUO Rongfa | 1994 | Chinese Physics Letters1994，11，3： | 0 |
| 5 | Cubic H_(3)S stabilized by halogens:High-temperature superconductors at mild pressure显示文摘Superconductivity in compressed sulfur hydride(H_(3)S)at above 200 K has attracted great interest in the study of hydrogen-based superconductors.However,the pressure required to stabilize H_(3)S is 150 GPa,posing significant challenges for experiments.Therefore,it is essential to find a strategy to reduce this pressure.In this study,by introducing halogen atoms into the H-S system,we discovered that hydrogen-based superconductors of H_(6)SX(X=Cl and Br)can be dynamically stable at mild pressures(5 GPa for H_(6)SCl and H_(6)SBr),as confirmed by first-principles calculations.Through the analysis of the bond properties,we revealed that introducing halogen elements would strengthen the H–S covalent bonds to reduce the dynamically stable pressure of H_(3)S.Our study provides a scheme to reduce the superconducting pressure of hydrogen-based superconductors. | Zihao Huo Defang Duan Qiwen Jiang Zihan Zhang Tian Cui | 2023 | Science China(Physics,Mechanics & Astronomy)2023，66，11： | 0 |
| 6 | Overexpression of Kdr in adult endocardium induces endocardial neovascularization and improves heart function after myocardial infarction显示文摘Dear Editor,Coronary artery disease is a leading cause of mortality and morbidity worldwide.Blockade of effective blood flow to heart muscles results in cardiac ischemia and myocardial infarction(MI).Many angiogenic factors are known to be elicited during MI,indicating a natural response of the heart to induce the formation of new coronary vessels in an attempt to revascularize the ischemic myocardium. However,coronary vascular endothelial cells(VECS)do not have sufficient angiogenic potential to effectively repopulate all ischemic regions,and clinical trials aiming at inducing revascularization through the delivery of pro-angiogenic molecules after ischemia have invariably failed. | Zhen Jiang Zhengkai Lu Shan Kou Teng Feng Yuanxin Wei Zibei Gao Defang Deng Jufeng Meng Chao-Po Lin Bin Zhou Hui Zhang | 2021 | Cell Research2021，31，4： | 0 |
| 7 | High T_(c) superconductivity in layered hydrides XH_(15) (X = Ca, Sr, Y, La) under high pressures显示文摘The theoretical predictions and experimental synthesis of H_(3)S and LaH_(10) superconductors with record high superconducting transition temperatures(T_(c))have promoted the hydrogen-based superconducors to be a research hotspot in the field of solid-state physics.Here,we predict an unprecedented layered structure CaH15,with high T_(c) of 189 K at 200 GPa using ab initio calculations.As concerns the novel structure,one layer is made of a hydrogen nonagon,the other layer consists of a Ca atom and six H_(2) molecular units surrounding the Ca atom.This layered structure was also found in SrH_(15),YH_(15),and LaH_(15) at high pressures,each materials exhibit high T_(c) especially YH_(15) can reach above 200 K at 220 GPa.It represents the second class of layered superhydrides with high value of Tc after pentagraphene like HfH10. | Yue Chen Zhengtao Liu Ziyue Lin Qiwen Jiang Mingyang Du Zihan Zhang Hao Song Hui Xie Tian Cui Defang Duan | 2022 | Frontiers of physics2022，17，6： | 0 |
| 8 | First-principles study on the conventional superconductivity of N-doped fcc-LuH_(3)显示文摘Recently,room-temperature superconductivity has been reported in a nitrogen-doped lutetium hydride at near-ambient pressure[Dasenbrock-Gammon et al.,Nature 615,244(2023)].The superconducting properties might arise from Fm3m-LuH_(3)−δNε.Here,we systematically study the phase diagram of Lu–N–H at 1 GPa using first-principles calculations,and we do not find any thermodynamically stable ternary compounds.In addition,we calculate the dynamic stability and superconducting properties of N-doped Fm3m-LuH_(3) using the virtual crystal approximation(VCA)and the supercell method.The R3m-Lu_(2)H_(5)N predicted using the supercell method could be dynamically stable at 50 GPa,with a T_(c) of 27 K.According to the VCA method,the highest T_(c) is 22 K,obtained with 1%N-doping at 30 GPa.Moreover,the doping of nitrogen atoms into Fm3m-LuH_(3) slightly enhances T_(c),but raises the dynamically stable pressure.Our theoretical results show that the T_(c) values of N-doped LuH_(3) estimated using the Allen–Dynes-modified McMillan equation are much lower than room temperature. | Zihao Huo Defang Duan Tiancheng Ma Zihan Zhang Qiwen Jiang Decheng An Hao Song Fubo Tian Tian Cui | 2023 | Matter and Radiation at Extremes2023，8，3： | 0 |
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