Simple regulation of c-Jun N-terminal kinase(JNK) or p38 mitogen-activated protein kinase(MAPK) pathways is not enough to trigger cell apoptosis.However,activation of the stress activated pathway(JNK/p38 MAPK) t...Simple regulation of c-Jun N-terminal kinase(JNK) or p38 mitogen-activated protein kinase(MAPK) pathways is not enough to trigger cell apoptosis.However,activation of the stress activated pathway(JNK/p38 MAPK) together with inhibition of the growth factor activated extracellular signal-regulated kinase(ERK) pathway can promote cell apoptosis.We hypothesized that inhibition of the JNK or p38 pro-apoptotic pathway and activating the ERK pathway could be the mechanism of anti-apoptosis following cerebral ischemia/reperfusion injury.To investigate the mechanism of the protective effect of electroacupuncture on cerebral ischemia/reperfusion injury in JNK knockout mice,mouse models of cerebral ischemia/reperfusion injury were established by Longa’s method.Electroacupuncture was conducted at acupoints Chize(LU5),Hegu(LI4),Sanyinjiao(SP6) and Zusanli(ST36) 1.5 hours after ischemia/reperfusion injury for 20 minutes,once a day.The neurological function was evaluated using neurological deficit scores.The expression of phospho-extracellular signal-regulated kinase(p-ERK) and phospho-p38(p-p38) in JNK knockout mice was detected using double-labeling immunofluorescence and western blot assay.The m RNA expression of ERK and p38 was measured by quantitative real-time polymerase chain reaction.Electroacupuncture improved neurological function,increased the immunoreactivity and relative expression of p-ERK and reduced that of p-p38 in the cerebral cortex and hippocampus on the injured side.Electroacupuncture increased m RNA expression of ERK,but decreased that of p38 in the cerebral cortex and hippocampus on the injured side.In conclusion,electroacupuncture upregulated the protective ERK pathway and inhibited the pro-apoptotic p38 pathway,thereby exerting a neuroprotective effect and improving the neurological function in JNK knockout mice.展开更多
We report an enhanced rejuvenation in hot-drawn micrometer metallic glassy wires(MG wires)with the size reduction.Compared to metallic glasses(MGs)in bulk form,the modulus and hardness for the micro-scale MG wires,tes...We report an enhanced rejuvenation in hot-drawn micrometer metallic glassy wires(MG wires)with the size reduction.Compared to metallic glasses(MGs)in bulk form,the modulus and hardness for the micro-scale MG wires,tested by nanoindentation methods,are much lower and decrease with the decreasing size,with a maximum decrease of〜26%in modulus and^17%in hardness.This pronounced rejuvenation is evidenced by the larger sub-Tg relaxation enthalpy of the MG wires.The pronounced rejuvenation is physically related to the higher energy state induced by a combined effect of severely thermomechanical shearing and freezing the shear How into a constrained small-volume region.Our results reveal that the internal states and properties of MGs can be dramatically changed by a proper modulation of temperature,flow stress and size.展开更多
基金supported by the National Natural Science Foundation of China,No.81173355
文摘Simple regulation of c-Jun N-terminal kinase(JNK) or p38 mitogen-activated protein kinase(MAPK) pathways is not enough to trigger cell apoptosis.However,activation of the stress activated pathway(JNK/p38 MAPK) together with inhibition of the growth factor activated extracellular signal-regulated kinase(ERK) pathway can promote cell apoptosis.We hypothesized that inhibition of the JNK or p38 pro-apoptotic pathway and activating the ERK pathway could be the mechanism of anti-apoptosis following cerebral ischemia/reperfusion injury.To investigate the mechanism of the protective effect of electroacupuncture on cerebral ischemia/reperfusion injury in JNK knockout mice,mouse models of cerebral ischemia/reperfusion injury were established by Longa’s method.Electroacupuncture was conducted at acupoints Chize(LU5),Hegu(LI4),Sanyinjiao(SP6) and Zusanli(ST36) 1.5 hours after ischemia/reperfusion injury for 20 minutes,once a day.The neurological function was evaluated using neurological deficit scores.The expression of phospho-extracellular signal-regulated kinase(p-ERK) and phospho-p38(p-p38) in JNK knockout mice was detected using double-labeling immunofluorescence and western blot assay.The m RNA expression of ERK and p38 was measured by quantitative real-time polymerase chain reaction.Electroacupuncture improved neurological function,increased the immunoreactivity and relative expression of p-ERK and reduced that of p-p38 in the cerebral cortex and hippocampus on the injured side.Electroacupuncture increased m RNA expression of ERK,but decreased that of p38 in the cerebral cortex and hippocampus on the injured side.In conclusion,electroacupuncture upregulated the protective ERK pathway and inhibited the pro-apoptotic p38 pathway,thereby exerting a neuroprotective effect and improving the neurological function in JNK knockout mice.
基金the National Key Research and Development Program of China under Grant Nos.2018YFA0703603,2017YFB0903902,and 2016YFB0300501the National Natural Science Foundation of China under Grant Nos.51822107,11790291,51671121,and 51761135125+2 种基金the National Natural Science Foundation of Guangdong Province under Grant No.2019B030302010the Key Research Program of Frontier Sciences(QYZDY-SSW-JSC017)the Strategic Priority Research Program of Chinese Academy of Sciences under Grant No.XDB30000000.
文摘We report an enhanced rejuvenation in hot-drawn micrometer metallic glassy wires(MG wires)with the size reduction.Compared to metallic glasses(MGs)in bulk form,the modulus and hardness for the micro-scale MG wires,tested by nanoindentation methods,are much lower and decrease with the decreasing size,with a maximum decrease of〜26%in modulus and^17%in hardness.This pronounced rejuvenation is evidenced by the larger sub-Tg relaxation enthalpy of the MG wires.The pronounced rejuvenation is physically related to the higher energy state induced by a combined effect of severely thermomechanical shearing and freezing the shear How into a constrained small-volume region.Our results reveal that the internal states and properties of MGs can be dramatically changed by a proper modulation of temperature,flow stress and size.