Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
M. H.艾布拉姆斯是美国当代著名的人文主义批评家和浪漫主义研究大师,其代表作《镜与灯》和《自然的超自然主义》都是英美人文主义批评经典著作。学术界对于艾氏的人文主义批评实践已有丰富的研究成果,但对于他有关人文主义批评的思想...M. H.艾布拉姆斯是美国当代著名的人文主义批评家和浪漫主义研究大师,其代表作《镜与灯》和《自然的超自然主义》都是英美人文主义批评经典著作。学术界对于艾氏的人文主义批评实践已有丰富的研究成果,但对于他有关人文主义批评的思想观点却鲜有讨论。其实,艾氏一生不仅在批评实践中坚持人文主义批评传统,还在诸多批评文献中对人文主义批评的内涵、目的和方法进行了充分的论述和阐释。在他看来,文学是“人的世界”的产品,是用“灵活、微妙”的“人文话语”表达“人性关怀”,是人际交流的一种“媒介”。文学批评的目的是追求人文真实,人文追求是永无止境的,因而文学批评的方法必须是多元的。展开更多
A new concept generalized(h,m)−preinvex function on Yang’s fractal sets is proposed.Some Ostrowski’s type inequalities with two parameters for generalized(h,m)−preinvex function are established,where three local fra...A new concept generalized(h,m)−preinvex function on Yang’s fractal sets is proposed.Some Ostrowski’s type inequalities with two parameters for generalized(h,m)−preinvex function are established,where three local fractional inequalities involving generalized midpoint type,trapezoid type and Simpson type are derived as consequences.Furthermore,as some applications,special means inequalities and numerical quadratures for local fractional integrals are discussed.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
基金Supported by the National Natural Science Foundation of China(Grant No.11801342)the Natural Science Foundation of Shaanxi Province(Grant No.2023-JC-YB-043).
文摘A new concept generalized(h,m)−preinvex function on Yang’s fractal sets is proposed.Some Ostrowski’s type inequalities with two parameters for generalized(h,m)−preinvex function are established,where three local fractional inequalities involving generalized midpoint type,trapezoid type and Simpson type are derived as consequences.Furthermore,as some applications,special means inequalities and numerical quadratures for local fractional integrals are discussed.
