Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like re...Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.展开更多
Bulk metallic glasses(BMGs)have attracted considerable attention in the last few decades particularly triggered by their potential applications as novel structural and/or functional materials,owing to their superior...Bulk metallic glasses(BMGs)have attracted considerable attention in the last few decades particularly triggered by their potential applications as novel structural and/or functional materials,owing to their superior strength,large elastic strain limit and relatively low Young′s modulus etc.compared to their crystalline counterparts.Here,a 3Dreconstruction application to the fractography and the morphology of shear bands was reported for a ductile Zr_(56)Co_(28)Al_(16)(at.%)BMG through a Phenom series desktop scanning electron microscope.The results of the 3Dreconstruction and the following contour analysis indicate a typical shear fracture mode for the investigated alloy.It is inferred that the fractography and the morphology of shear bands might be dependent on their composition,structure states,and loading conditions for BMGs.展开更多
基金financially supported by the National Natural Science Foundation of China,No.81771625(to XF)the Jiangsu Provincial Key Medical Discipline of China,No.ZDXKA2016013(to XF)the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF)
文摘Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.
基金supported by National Natural Science Foundation of China(51301078,51461026and51671120)the Specialized Research Fund for the Doctoral Program of Higher Education of China(20135314120002)+1 种基金the Scientific Research Foundation of Department of Education,Yunnan(2017YJS059)the Young Talents Support Program of Faculty of Materials Science and Engineering,Kunming University of Science and Technology(20140102)
文摘Bulk metallic glasses(BMGs)have attracted considerable attention in the last few decades particularly triggered by their potential applications as novel structural and/or functional materials,owing to their superior strength,large elastic strain limit and relatively low Young′s modulus etc.compared to their crystalline counterparts.Here,a 3Dreconstruction application to the fractography and the morphology of shear bands was reported for a ductile Zr_(56)Co_(28)Al_(16)(at.%)BMG through a Phenom series desktop scanning electron microscope.The results of the 3Dreconstruction and the following contour analysis indicate a typical shear fracture mode for the investigated alloy.It is inferred that the fractography and the morphology of shear bands might be dependent on their composition,structure states,and loading conditions for BMGs.