We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repet...We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.展开更多
基于试验数据,利用扩展有限元方法(extended finite element method,XFEM)和内聚力模型(cohesive zone model,CZM),对20Cr2Ni3钢顶头表面氧化膜的断裂行为进行了数值分析,研究了氧化膜受力方向和孔洞对裂纹生长行为的影响。结果表明:氧...基于试验数据,利用扩展有限元方法(extended finite element method,XFEM)和内聚力模型(cohesive zone model,CZM),对20Cr2Ni3钢顶头表面氧化膜的断裂行为进行了数值分析,研究了氧化膜受力方向和孔洞对裂纹生长行为的影响。结果表明:氧化膜受力方向影响裂纹扩展路径,外层氧化膜裂纹尖端的J积分和应力强度因子K_I随着θ角(受力方向与氧化膜的夹角)的增大而减小,当θ角增大到90°时裂纹停止生长;外层氧化膜上孔洞使得裂纹尖端的J积分和应力强度因子K_I减小。同时,孔洞的存在使得外力传递到内层氧化膜时产生应力集中和偏移,导致内层裂纹受力不均,减小了受力方向对内层裂纹生长的影响。展开更多
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBSS00047(to PL)the National Natural Science Foundation of China,Nos.82072166(to PL),82071394(to XG)+4 种基金Science and Technology Planning Project of Tianjin,No.20YFZCSY00030(to PL)Science and Technology Project of Tianjin Municipal Health Commission,No.TJWJ2021QN005(to XG)Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-006ATianjin Municipal Education Commission Scientific Research Program Project,No.2020KJ164(to JZ)China Postdoctoral Science Foundation,No.2022M712392(to ZY).
文摘We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.
文摘基于试验数据,利用扩展有限元方法(extended finite element method,XFEM)和内聚力模型(cohesive zone model,CZM),对20Cr2Ni3钢顶头表面氧化膜的断裂行为进行了数值分析,研究了氧化膜受力方向和孔洞对裂纹生长行为的影响。结果表明:氧化膜受力方向影响裂纹扩展路径,外层氧化膜裂纹尖端的J积分和应力强度因子K_I随着θ角(受力方向与氧化膜的夹角)的增大而减小,当θ角增大到90°时裂纹停止生长;外层氧化膜上孔洞使得裂纹尖端的J积分和应力强度因子K_I减小。同时,孔洞的存在使得外力传递到内层氧化膜时产生应力集中和偏移,导致内层裂纹受力不均,减小了受力方向对内层裂纹生长的影响。