Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
P2P2B模式下云服务投入是工业互联网(industrial internet of things,IIoT)平台的关键战略决策之一.构建由IIoT平台、龙头企业、潜在客户构成的演化博弈模型,研究IIoT平台在公有云研发投入和私有云研发投入中的策略选择,及其与龙头企业...P2P2B模式下云服务投入是工业互联网(industrial internet of things,IIoT)平台的关键战略决策之一.构建由IIoT平台、龙头企业、潜在客户构成的演化博弈模型,研究IIoT平台在公有云研发投入和私有云研发投入中的策略选择,及其与龙头企业的生态合作问题.结果表明:虽然公有云存在数据泄露隐患,但较高的规模收益仍会吸引IIoT平台投入公有云研发,而平台搭建期内龙头企业的高合作意愿会促使平台投入私有云,随着龙头企业合作研发的比例增加,平台又将改变其投入策略.驱动龙头企业合作的因素可以是成本收益、技术提升等直接因素,也可以是规模收益、数据泄露概率等间接因素.最后,基于平台生命周期探讨了初创期、平台搭建期与生态系统期IIoT平台的系统稳定策略,并得到相应的管理启示.展开更多
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
文摘P2P2B模式下云服务投入是工业互联网(industrial internet of things,IIoT)平台的关键战略决策之一.构建由IIoT平台、龙头企业、潜在客户构成的演化博弈模型,研究IIoT平台在公有云研发投入和私有云研发投入中的策略选择,及其与龙头企业的生态合作问题.结果表明:虽然公有云存在数据泄露隐患,但较高的规模收益仍会吸引IIoT平台投入公有云研发,而平台搭建期内龙头企业的高合作意愿会促使平台投入私有云,随着龙头企业合作研发的比例增加,平台又将改变其投入策略.驱动龙头企业合作的因素可以是成本收益、技术提升等直接因素,也可以是规模收益、数据泄露概率等间接因素.最后,基于平台生命周期探讨了初创期、平台搭建期与生态系统期IIoT平台的系统稳定策略,并得到相应的管理启示.
