Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy(SAE).OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury.However,its regulat...Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy(SAE).OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury.However,its regulatory function in microglial pyroptosis and involvement in SAE remains unclear.In this study,we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury.Furthermore,OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice.Mechanistically,OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation,thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation.In conclusion,this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.展开更多
目前在电力行业中广泛应用的SF6气体具有严重的温室效应,寻找一种绝缘性能优良的环保型替代气体成为研究热点。近年来,C3F7CN及其混合气体凭借出色的绝缘性能和环保特性得到了国内外学者的广泛关注。目前针对其放电分解机理的研究较少...目前在电力行业中广泛应用的SF6气体具有严重的温室效应,寻找一种绝缘性能优良的环保型替代气体成为研究热点。近年来,C3F7CN及其混合气体凭借出色的绝缘性能和环保特性得到了国内外学者的广泛关注。目前针对其放电分解机理的研究较少。首先,基于ReaxFF反应分子动力学方法和密度泛函理论,从微观层面模拟研究了C3F7CN/CO2混合气体的分解机理。基于构建的C3F7CN/CO2混合气体模型,研究了温度对C3F7CN分解过程的影响,分析了其可能的分解路径、产物类型及分布等。计算结果表明,C3F7CN在局部过热或放电等故障条件下分解容易产生CF3·、C3F7·、C·、CF3CFCN·、CF2·和F·等各类自由基,上述自由基复合将产生CF4、C2F6、C3F8、CF3CN、CO等产物。其次,利用气体绝缘试验平台和气相色谱质谱联用仪(gas chromatography mass spectrometer,GC-MS),试验分析了其多次击穿后的分解产物。试验结果表明,混合气体多次击穿后的主要分解产物是CF4、C2F6、CF3CN。这些产物分子均具有比较好的绝缘能力,保障了C3F7CN/CO2混合气体的绝缘性能不被破环。相关结论为进一步探究C3F7CN/CO2混合气体的绝缘特性及协同效应等课题提供理论依据和工程指导。展开更多
基金supported by the Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(JSDW202249)the Natural Science Foundation of Jiangsu Province(BK20211108)+4 种基金a Scientific Research Project of the Health Commission of Nantong(MS2023035)Nantong Natural Science Foundation(JC2023114)the Scientific Research Innovation Team of Kangda College of Nanjing Medical University(KD2022KYCXTD005)Nantong University Clinical Medicine Special Project(2022JY005)the Postgraduate Research&Practice Innovation Program of Jiangsu province(KYCX23_3416).
文摘Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy(SAE).OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury.However,its regulatory function in microglial pyroptosis and involvement in SAE remains unclear.In this study,we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury.Furthermore,OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice.Mechanistically,OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation,thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation.In conclusion,this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
文摘目前在电力行业中广泛应用的SF6气体具有严重的温室效应,寻找一种绝缘性能优良的环保型替代气体成为研究热点。近年来,C3F7CN及其混合气体凭借出色的绝缘性能和环保特性得到了国内外学者的广泛关注。目前针对其放电分解机理的研究较少。首先,基于ReaxFF反应分子动力学方法和密度泛函理论,从微观层面模拟研究了C3F7CN/CO2混合气体的分解机理。基于构建的C3F7CN/CO2混合气体模型,研究了温度对C3F7CN分解过程的影响,分析了其可能的分解路径、产物类型及分布等。计算结果表明,C3F7CN在局部过热或放电等故障条件下分解容易产生CF3·、C3F7·、C·、CF3CFCN·、CF2·和F·等各类自由基,上述自由基复合将产生CF4、C2F6、C3F8、CF3CN、CO等产物。其次,利用气体绝缘试验平台和气相色谱质谱联用仪(gas chromatography mass spectrometer,GC-MS),试验分析了其多次击穿后的分解产物。试验结果表明,混合气体多次击穿后的主要分解产物是CF4、C2F6、CF3CN。这些产物分子均具有比较好的绝缘能力,保障了C3F7CN/CO2混合气体的绝缘性能不被破环。相关结论为进一步探究C3F7CN/CO2混合气体的绝缘特性及协同效应等课题提供理论依据和工程指导。
