Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucia...Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.展开更多
Mn-rich LiFe_(1-x)Mn_(x)PO_(4)(x>0.5),which combines the high operation voltage of LiMnPO_(4)with excellent rate performa nce of LiFePO4,is hindered by its sluggish kinetic properties.Herein,thermodynamic equilibri...Mn-rich LiFe_(1-x)Mn_(x)PO_(4)(x>0.5),which combines the high operation voltage of LiMnPO_(4)with excellent rate performa nce of LiFePO4,is hindered by its sluggish kinetic properties.Herein,thermodynamic equilibrium analysis of Mn^(2+)-Fe^(2+)-Mg^(2+)-C_(2)O_(4)^(2-)-H_(2)O system is used to guide the design and preparation of insitu Mg-doped(Fe_(0.4)Mn_(0.6))_(1-x)Mg_(x)C_(2)O_(4)intermediate,which is then employed as an innovative precursor to synthesize high-performance Mg-doped LiFe_(0.4)Mn_(0.6)PO_(4).It indicates that the metal ions with a high precipitation efficiency and the stoichiometric precursors with uniform element distribution can be achieved under the optimized thermodynamic conditions.Meanwhile,accelerated Li+diffusivity and reduced charge transfer resistance originating from Mg doping are verified by various kinetic characterizations.Benefiting from the contributions of inherited homogeneous element distribution,small particle size,uniform carbon layer coating,enhanced Li+migration ability and structural stability induced by Mg doping,the Li(Fe_(0.4)Mn_(0.6))_(0.97)Mg_(0.03)PO_(4)/C exhibits splendid electrochemical performance.展开更多
本文介绍了顶岗实习信息管理平台的开发背景和意义,并对平台的开发工具ASP.NET MVC3.0和SQL Server 2008进行了详细的介绍。以软件工程思想为指导,对平台的关键功能模块和用户角色进行了深入的研究和分析,设计出了平台的主要功能模块和...本文介绍了顶岗实习信息管理平台的开发背景和意义,并对平台的开发工具ASP.NET MVC3.0和SQL Server 2008进行了详细的介绍。以软件工程思想为指导,对平台的关键功能模块和用户角色进行了深入的研究和分析,设计出了平台的主要功能模块和总体框架结构,并简要阐述了平台的开发流程。展开更多
基金supported by the National Natural Science Foundation of China(Youth Program),No.81901282(to XC)the National Natural Science Foundation of China,Nos.81401416(to PX),81870992(to PX),81870856(to XC and MZ)+3 种基金Guangdong Basic and Applied Basic Research Foundation the Science Foundation,No.2019A1515011189(to XC)Central Government Guiding Local Science and Technology Development Projects,No.ZYYD2022C17(to PX)Key Project of Guangzhou Health Commission,No.2019-ZD-09(to PX)Science and Technology Planning Project of Guangzhou,Nos.202102020029(to XC),202102010010(to PX)。
文摘Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.
基金financially supported by the National Natural Science Foundation of China(No.51904250)the China Postdoctoral Science Foundation(No.2021M692254)+2 种基金the Sichuan Science and Technology Program(No.2022YFG0098)the Fundamental Research Funds for the Central Universities(Nos.2021CDSN-02,2022SCU12002,2022CDZG-17,2022CDSN-08,2022CDZG-9)the Hohhot Science and Technology Program(No.2023-Jie Bang Gua Shuai-Gao-3)。
文摘Mn-rich LiFe_(1-x)Mn_(x)PO_(4)(x>0.5),which combines the high operation voltage of LiMnPO_(4)with excellent rate performa nce of LiFePO4,is hindered by its sluggish kinetic properties.Herein,thermodynamic equilibrium analysis of Mn^(2+)-Fe^(2+)-Mg^(2+)-C_(2)O_(4)^(2-)-H_(2)O system is used to guide the design and preparation of insitu Mg-doped(Fe_(0.4)Mn_(0.6))_(1-x)Mg_(x)C_(2)O_(4)intermediate,which is then employed as an innovative precursor to synthesize high-performance Mg-doped LiFe_(0.4)Mn_(0.6)PO_(4).It indicates that the metal ions with a high precipitation efficiency and the stoichiometric precursors with uniform element distribution can be achieved under the optimized thermodynamic conditions.Meanwhile,accelerated Li+diffusivity and reduced charge transfer resistance originating from Mg doping are verified by various kinetic characterizations.Benefiting from the contributions of inherited homogeneous element distribution,small particle size,uniform carbon layer coating,enhanced Li+migration ability and structural stability induced by Mg doping,the Li(Fe_(0.4)Mn_(0.6))_(0.97)Mg_(0.03)PO_(4)/C exhibits splendid electrochemical performance.
