短历时可能最大降水(PMP)是核电厂设计排水设施时的主要依据。在分析某滨海核电厂厂址区域暴雨特性、天气成因和站点资料的基础上,采用P-Ⅲ型曲线和矩法进行不同频率短历时降雨数值统计计算,然后通过不同历时10000年一遇降雨设计值与24 ...短历时可能最大降水(PMP)是核电厂设计排水设施时的主要依据。在分析某滨海核电厂厂址区域暴雨特性、天气成因和站点资料的基础上,采用P-Ⅲ型曲线和矩法进行不同频率短历时降雨数值统计计算,然后通过不同历时10000年一遇降雨设计值与24 h 10000年一遇设计值进行比值计算分析得到不同短历时可能最大降水,最后通过与国内外特大暴雨记录和其他核电厂短历时PMP成果进行对比分析,表明计算结果合理,可为其他地区短历时PMP分析计算提供参考和借鉴。展开更多
Background:During Enterovirus type 71(EV71)infection,the structural viral protein 1(VP1)activates endoplasmic reticulum(ER)stress associated with peripheral myelin protein 22(PMP22)accumulation and induces autophagy.H...Background:During Enterovirus type 71(EV71)infection,the structural viral protein 1(VP1)activates endoplasmic reticulum(ER)stress associated with peripheral myelin protein 22(PMP22)accumulation and induces autophagy.However,the specific mechanism behind this process remains elusive.Methods:In this research,we used the VP1-overexpressing mouse Schwann cells(SCs)models co-transfected with a PMP22 silencing or Autocrine motility factor receptor(AMFR/gp78)overexpressing vector to explore the regulation of gp78 on PMP22 and its relationship with autophagy and apoptosis.Results:The activity of gp78 could be influenced by EV71-VP1,leading to a decrease in the ubiquitination and degradation of PMP22,resulting in PMP22 accumulation in ER.In VP1-overexpressing mouse SCs,all three ER stress sensors,including pancreatic endoplasmic reticulum kinase(PERK),activating transcription factor 6(ATF6)and inositol-requiring enzyme 1(IRE1)and the related downstream signals(C/EBP-homologous protein(CHOP)and Caspase 12)were activated,as well as the ER-resident chaperone Glucose-regulated protein 78(GRP78).In addition,VP1 upregulated the autophagy marker Microtubule-associated protein 1 light chain 3 beta(LC3B),while PMP22 silencing or gp78 overexpression reversed the phenomenon.Meanwhile,PMP22 silencing or gp78 overexpression increased proliferation of EV71-VP1-transfected mouse SCs.Conclusion:Gp78 could regulate PMP22 accumulation through ubiquitination degradation and cause ER stress and autophagy in EV71-VP1-overexpressing mouse SCs.Therefore,the gp78/PMP22/ER stress axis might emerge as a promising therapeutic target for myelin and neuronal damage induced by EV71 infection.展开更多
文摘短历时可能最大降水(PMP)是核电厂设计排水设施时的主要依据。在分析某滨海核电厂厂址区域暴雨特性、天气成因和站点资料的基础上,采用P-Ⅲ型曲线和矩法进行不同频率短历时降雨数值统计计算,然后通过不同历时10000年一遇降雨设计值与24 h 10000年一遇设计值进行比值计算分析得到不同短历时可能最大降水,最后通过与国内外特大暴雨记录和其他核电厂短历时PMP成果进行对比分析,表明计算结果合理,可为其他地区短历时PMP分析计算提供参考和借鉴。
基金The study was supported by Guangdong Natural Science Foundation(Grant Numbers 2020A1515010014,2022A1515012411)Science and Technology Key Project for People’s Livelihood of Guangzhou,China(Grant Number 202206010060)+1 种基金Guangzhou Science and Technology Bureau Basic Research Project(SL2024A03J01288)Innovative Project of Children’s Research Institute,Guangzhou Women and Children’s Medical Center,China(Grant Numbers Pre-NSFC-2019-002,NKE PRE-2019-015).
文摘Background:During Enterovirus type 71(EV71)infection,the structural viral protein 1(VP1)activates endoplasmic reticulum(ER)stress associated with peripheral myelin protein 22(PMP22)accumulation and induces autophagy.However,the specific mechanism behind this process remains elusive.Methods:In this research,we used the VP1-overexpressing mouse Schwann cells(SCs)models co-transfected with a PMP22 silencing or Autocrine motility factor receptor(AMFR/gp78)overexpressing vector to explore the regulation of gp78 on PMP22 and its relationship with autophagy and apoptosis.Results:The activity of gp78 could be influenced by EV71-VP1,leading to a decrease in the ubiquitination and degradation of PMP22,resulting in PMP22 accumulation in ER.In VP1-overexpressing mouse SCs,all three ER stress sensors,including pancreatic endoplasmic reticulum kinase(PERK),activating transcription factor 6(ATF6)and inositol-requiring enzyme 1(IRE1)and the related downstream signals(C/EBP-homologous protein(CHOP)and Caspase 12)were activated,as well as the ER-resident chaperone Glucose-regulated protein 78(GRP78).In addition,VP1 upregulated the autophagy marker Microtubule-associated protein 1 light chain 3 beta(LC3B),while PMP22 silencing or gp78 overexpression reversed the phenomenon.Meanwhile,PMP22 silencing or gp78 overexpression increased proliferation of EV71-VP1-transfected mouse SCs.Conclusion:Gp78 could regulate PMP22 accumulation through ubiquitination degradation and cause ER stress and autophagy in EV71-VP1-overexpressing mouse SCs.Therefore,the gp78/PMP22/ER stress axis might emerge as a promising therapeutic target for myelin and neuronal damage induced by EV71 infection.
