As potential cast and wrought Mg alloys,Mg-X(X=Al,Zn,Sn)based alloys have attracted great interest.This work is to develop a dataset of atomic mobilities that is valid over a wide composition range.With the obtained m...As potential cast and wrought Mg alloys,Mg-X(X=Al,Zn,Sn)based alloys have attracted great interest.This work is to develop a dataset of atomic mobilities that is valid over a wide composition range.With the obtained mobilities,and a compatible thermodynamic description,as well as thermophysical parameters,simulations are performed to predict the characteristics of precipitation evolution.Examples are presented for the isothermal aging processes in Mg-x wt.%Al(x=5.9,6,8.8,9),Mg-x wt.%Zn(x=6,6.2,8,8.65),Mg-x wt.%Sn(x=6.04,6.92,8.64)alloys.The simulated size distribution,number density and volume fraction of precipitates reasonably account for the experimental results and provide additional information for further alloy composition design and heat treatment optimization.展开更多
The purpose of this study is to use the newly synthesized molecule Sodium 8-(((carboxymethyl)amino)methyl)-4',7-bishydroxy-isoflavone-3'-sulfonate(M)as a research object,the pharmacological mechanism of the mo...The purpose of this study is to use the newly synthesized molecule Sodium 8-(((carboxymethyl)amino)methyl)-4',7-bishydroxy-isoflavone-3'-sulfonate(M)as a research object,the pharmacological mechanism of the molecule was analyzed by using a series of Systematic pharmacology methods.The results show that the M molecule has a higher drug-like DL value of 0.59 and better molecular property parameters,namely Hdon=4,Hacc=10 and AlogP=0.94;A total of 11 M molecules related targets,namely F2,ESR1,AR,F10,CA2,DPP4,CCNA2,PRSS1,CDK2,GSK3B and PTPN1;A total of 140 diseases are associated with M molecule targets,and these diseases are mainly related to cancer and cardiovascular diseases;A total of 52 pathways involve the pharmacological mechanisms of M molecules,which are mainly related to cancer and other related diseases;GO-enriched analysis showed that these targets are closely related to the regulation of peptidase activity and biological processes such as blood coagulation and hemostasis.This article clearly demonstrated the pharmacological mechanism of M molecule,which provides references for exploring the pharmacological mechanism of new compounds.展开更多
Purpose The secondary damage of spinal cord injury(SCI)starts from the collapse of the blood spinal cord barrier(BSCB)to chronic and devastating neurological deficits.Thereby,the retention of the integrity and permeab...Purpose The secondary damage of spinal cord injury(SCI)starts from the collapse of the blood spinal cord barrier(BSCB)to chronic and devastating neurological deficits.Thereby,the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI.Previous studies have demonstrated that activation of hypoxia inducible factor-1α(HIF-1α)provides anti-apoptosis and neuroprotection in SCI.Endogenous HIF-1α,rapidly degraded by prolylhydroxylase,is insufficient for promoting functional recovery.Dimethyloxalylglycine(DMOG),a highly selective inhibitor of prolylhydroxylase,has been reported to have a positive effect on axon regeneration.However,the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear.Herein,we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG.Methods The work was performed from 2022 to 2023.In this study,Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG.In the phenotypic validation experiment,the rats were randomly divided into 3 groups:sham group,SCI group,and SCI+DMOG group(10 rats for each).Histological analysis via Nissl staining,Basso-Beattie-Bresnahan scale,and footprint analysis was used to evaluate the functional recovery after SCI.Western blotting,TUNEL assay,and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB,HIF-1α,cell apoptosis,and endoplasmic reticulum(ER)stress.The one-way ANOVA test was used for statistical analysis.The difference was considered statistically significant at p<0.05.Results In this study,we observed the expression of HIF-1αreduced in the SCI model.DMOG treatment remarkably augmented HIF-1αlevel,alleviated endothelial cells apoptosis and disruption of BSCB,and enhanced functional recovery post-SCI.Besides,the administration of DMOG offset the activation of ER stress induced by SCI,but this phenomenon was blocked by tunicamycin(an ER stress activator).Finally,we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress,and inhibition of HIF-1αerased the protection from DMOG.Conclusions Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.展开更多
基金financially supported by the National Key Research and Development Program of China(No.2016YFB0701202)the Innovation Foundation for Postgraduate and Fundamental Research Funds of Central South University(No.1053320182102)China Scholarship Council(No.201906370116)for the award of a fellowship and funding。
文摘As potential cast and wrought Mg alloys,Mg-X(X=Al,Zn,Sn)based alloys have attracted great interest.This work is to develop a dataset of atomic mobilities that is valid over a wide composition range.With the obtained mobilities,and a compatible thermodynamic description,as well as thermophysical parameters,simulations are performed to predict the characteristics of precipitation evolution.Examples are presented for the isothermal aging processes in Mg-x wt.%Al(x=5.9,6,8.8,9),Mg-x wt.%Zn(x=6,6.2,8,8.65),Mg-x wt.%Sn(x=6.04,6.92,8.64)alloys.The simulated size distribution,number density and volume fraction of precipitates reasonably account for the experimental results and provide additional information for further alloy composition design and heat treatment optimization.
基金The study was funded by the Middle-Aged and Young Teachers in Colleges and Universities in Guangxi Basic Ability Promotion Project(No.2017KY0581)and Natural Science Foundation of Guangxi Province(No.2018GXNSFAA138140).
文摘The purpose of this study is to use the newly synthesized molecule Sodium 8-(((carboxymethyl)amino)methyl)-4',7-bishydroxy-isoflavone-3'-sulfonate(M)as a research object,the pharmacological mechanism of the molecule was analyzed by using a series of Systematic pharmacology methods.The results show that the M molecule has a higher drug-like DL value of 0.59 and better molecular property parameters,namely Hdon=4,Hacc=10 and AlogP=0.94;A total of 11 M molecules related targets,namely F2,ESR1,AR,F10,CA2,DPP4,CCNA2,PRSS1,CDK2,GSK3B and PTPN1;A total of 140 diseases are associated with M molecule targets,and these diseases are mainly related to cancer and cardiovascular diseases;A total of 52 pathways involve the pharmacological mechanisms of M molecules,which are mainly related to cancer and other related diseases;GO-enriched analysis showed that these targets are closely related to the regulation of peptidase activity and biological processes such as blood coagulation and hemostasis.This article clearly demonstrated the pharmacological mechanism of M molecule,which provides references for exploring the pharmacological mechanism of new compounds.
基金supported by Natural Science Foundation of Ningbo Municipality(2021J260,2021J033 and 2023J165).
文摘Purpose The secondary damage of spinal cord injury(SCI)starts from the collapse of the blood spinal cord barrier(BSCB)to chronic and devastating neurological deficits.Thereby,the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI.Previous studies have demonstrated that activation of hypoxia inducible factor-1α(HIF-1α)provides anti-apoptosis and neuroprotection in SCI.Endogenous HIF-1α,rapidly degraded by prolylhydroxylase,is insufficient for promoting functional recovery.Dimethyloxalylglycine(DMOG),a highly selective inhibitor of prolylhydroxylase,has been reported to have a positive effect on axon regeneration.However,the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear.Herein,we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG.Methods The work was performed from 2022 to 2023.In this study,Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG.In the phenotypic validation experiment,the rats were randomly divided into 3 groups:sham group,SCI group,and SCI+DMOG group(10 rats for each).Histological analysis via Nissl staining,Basso-Beattie-Bresnahan scale,and footprint analysis was used to evaluate the functional recovery after SCI.Western blotting,TUNEL assay,and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB,HIF-1α,cell apoptosis,and endoplasmic reticulum(ER)stress.The one-way ANOVA test was used for statistical analysis.The difference was considered statistically significant at p<0.05.Results In this study,we observed the expression of HIF-1αreduced in the SCI model.DMOG treatment remarkably augmented HIF-1αlevel,alleviated endothelial cells apoptosis and disruption of BSCB,and enhanced functional recovery post-SCI.Besides,the administration of DMOG offset the activation of ER stress induced by SCI,but this phenomenon was blocked by tunicamycin(an ER stress activator).Finally,we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress,and inhibition of HIF-1αerased the protection from DMOG.Conclusions Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.
