In this work,the effect of dioctadecyl dimethyl ammonium chloride（DDAC,a kind of alkyl ammonium salt） on polar β phase content and the diameter of electrospun PVDF nanofibers was investigated for the first time.Our...In this work,the effect of dioctadecyl dimethyl ammonium chloride（DDAC,a kind of alkyl ammonium salt） on polar β phase content and the diameter of electrospun PVDF nanofibers was investigated for the first time.Our experimental results show that the diameter of the electrospun PVDF nanofiber could be largely reduced and the content of polar β phase also become dominant immediately by just adding a little amount of DDAC.When the mass fraction of DDAC reached 4%,the content of polar β phase increased by about 39.1% compared with PVDF nanofibers without DDAC.Besides,the crystallinity of PVDF nanofibers also increased with the addition of DDAC.Based on the results,the possible mechanism of cooperative effect between electrospinning and DDAC on fiber diameter and formation of β phase in PVDF was discussed.展开更多
In order to rapidly respond to the complex and mutational market, a new facility layout plan based on cellular manufacturing is proposed, which gives consideration to high efficiency and flexibility. The plan designs ...In order to rapidly respond to the complex and mutational market, a new facility layout plan based on cellular manufacturing is proposed, which gives consideration to high efficiency and flexibility. The plan designs two phases of integrated cell layout, i.e., cell construction and cell system layout, on the condition of adding/removing machines. First, in view of the costs of logics and machine-relocation, the cell construction based on the alternative processing routes and intra-cell layout are integrated as a whole, which achieves cell formation, process planning and the intra-cell layout in a single step. Secondly, an approach of a continuous optimized multi-line layout for solving the cell system layout problem is proposed, which eliminates the coupling relationship from the machine-relocation and realizes an integrated design of the two phases of the cell layout. An application based on real factory data is optimally solved by the Matlab 7.0 software to validate and verify the models.展开更多
目的:在前期发现琐琐葡萄总黄酮(Flavones from Vitis vinifera L,VTF)可改善APP/PS-1双转基因(Alzheimer's disease,AD)小鼠认知功能的基础上,进一步验证“VTF是否通过重塑肠道菌群-肠-脑轴而发挥神经保护作用”,并阐明其潜在机制...目的:在前期发现琐琐葡萄总黄酮(Flavones from Vitis vinifera L,VTF)可改善APP/PS-1双转基因(Alzheimer's disease,AD)小鼠认知功能的基础上,进一步验证“VTF是否通过重塑肠道菌群-肠-脑轴而发挥神经保护作用”,并阐明其潜在机制。方法:本研究将从天然药物琐琐葡萄中提取活性成分总黄酮VTF,作用于APP/PS-1小鼠,VTF灌胃8周,通过Morris水迷宫实验评估小鼠空间学习能力;ELISA检测小鼠脑组织中IL-1β、IL-6、TNF-α因子,血清中5-HT、GABA因子的含量;苏木精-伊红(Hematoxylin and eosin staining,HE)染色法观察结肠组织形态,免疫组化法检测Occludin、Claudin、Zo-1、NLRP3蛋白表达;高通量测序检测小鼠粪便肠道菌群;结果:1)水迷宫实验结果显示:VTF低剂量组平均逃逸潜伏期缩短(P<0.05);VTF低、中剂量组有效区域运动距离,运动时间以及进入次数显著增多(P<0.01);2)结肠组织HE染色结果显示;AD模型小鼠肠粘膜膜层萎缩,隐窝丢失和绒毛断裂,而VTF干预之后小鼠上述情况均有所减轻;3)结肠组织免疫组化结果显示:VTF干预可以上调Occludin、Claudin、Zo-1等紧密连接蛋白阳性表达(P<0.01),减少NLRP3炎症相关蛋白的表达(P<0.01);4)ELISA结果:VTF各剂量组小鼠脑组织中IL-1β、IL-6、TNFα等炎症因子水平降低(P<0.01);VTF各剂量组中5-HT和GABA的含量增多(P<0.01);5)肠道菌群检测结果显示:VTF高剂量干预后的AD小鼠厚壁菌门相对丰度增多(P<0.05),与模型组小鼠相比,VTF中、高剂量组中乳杆菌科(Lactobacillaceae)相对丰度增多,VTF低剂量组中Muribaculaceae相对丰度增多,多奈哌齐组,VTF各剂量组中丹毒科(Erysipelotrichaceae)、瘤胃球菌科(Ruminococcaceae)相对丰度增多;而VTF各剂量组中毛螺菌科(Lachnospiraceae)、螺杆菌科(Helicobacteraceae),脱铁杆菌科(Deferribacteraceae)相对丰度减少。结论:这些结果表明,VTF调节肠道菌群可能具有治疗衰老过程中微生物导致脑轴和认知功能缺陷的潜力,其机制可能与改变肠道菌群组成,修复受损的肠道屏障,炎症反应和神经递质有关。因此,调节肠道微生物群可能是治疗AD相关神经疾病的一种潜在策略。展开更多
Background:The absence of effective animal models for sporadic Alzheimer's disease(AD)remains a pivotal barrier to therapy development.Because methanol metabolism produces endogenous formaldehyde,a neurotoxic agen...Background:The absence of effective animal models for sporadic Alzheimer's disease(AD)remains a pivotal barrier to therapy development.Because methanol metabolism produces endogenous formaldehyde,a neurotoxic agent linked to cognitive decline,this study investigated whether chronic,low-dose methanol exposure could recapitulate AD-like pathology and cognitive deficits in rhesus monkey,thereby establishing a nonhuman primate animal model driven by this environmental-metabolic insult.Methods:Adult rhesus monkeys received low-concentration methanol for 9 months.Behavioral tests for cognition,locomotion,sleep,and vision were conducted.Postmortem analyses involved histopathological examination,immunohistochemistry,immunofluorescence,and Western blot to evaluate neuronal integrity,microglial activation,and the expression of key proteins associated with AD(amyloid-β[Aβ],phosphorylated tau,TAR DNA-binding protein 43[TDP-43])and cellular stress(synaptic markers,mitochondrial fission,autophagy,and apoptosis-related proteins).Results:Chronic methanol exposure led to progressive cognitive and memory impairment without significant motor or visual deficits.Neuropathology revealed brain atrophy,neuronal loss,synaptic damage,microglial activation,and mitochondrial structural disorganization.Critically,the exposed animals exhibited hallmark AD-like molecular alterations,including increased Aβ deposition,tau hyperphosphorylation,and TDP-43 dysregulation.Furthermore,neurotoxicity was associated with elevated urinary formaldehyde,enhanced mitochondrial fission,increased autophagy,and elevated apoptosis.Conclusion:Chronic low-dose methanol exposure in rhesus monkeys recapitulates progressive cognitive deficits and AD-like neuropathological features.This model,driven by endogenous formaldehyde toxicity,effectively mimics key aspects of sporadic AD.Our findings shed light on the neurotoxic mechanisms of methanol and propose a reproducible and translationally relevant nonhuman primate model for studying AD pathogenesis and evaluating potential therapeutics.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.51421061 and 51210005)
文摘In this work,the effect of dioctadecyl dimethyl ammonium chloride（DDAC,a kind of alkyl ammonium salt） on polar β phase content and the diameter of electrospun PVDF nanofibers was investigated for the first time.Our experimental results show that the diameter of the electrospun PVDF nanofiber could be largely reduced and the content of polar β phase also become dominant immediately by just adding a little amount of DDAC.When the mass fraction of DDAC reached 4%,the content of polar β phase increased by about 39.1% compared with PVDF nanofibers without DDAC.Besides,the crystallinity of PVDF nanofibers also increased with the addition of DDAC.Based on the results,the possible mechanism of cooperative effect between electrospinning and DDAC on fiber diameter and formation of β phase in PVDF was discussed.
文摘In order to rapidly respond to the complex and mutational market, a new facility layout plan based on cellular manufacturing is proposed, which gives consideration to high efficiency and flexibility. The plan designs two phases of integrated cell layout, i.e., cell construction and cell system layout, on the condition of adding/removing machines. First, in view of the costs of logics and machine-relocation, the cell construction based on the alternative processing routes and intra-cell layout are integrated as a whole, which achieves cell formation, process planning and the intra-cell layout in a single step. Secondly, an approach of a continuous optimized multi-line layout for solving the cell system layout problem is proposed, which eliminates the coupling relationship from the machine-relocation and realizes an integrated design of the two phases of the cell layout. An application based on real factory data is optimally solved by the Matlab 7.0 software to validate and verify the models.
文摘目的:在前期发现琐琐葡萄总黄酮(Flavones from Vitis vinifera L,VTF)可改善APP/PS-1双转基因(Alzheimer's disease,AD)小鼠认知功能的基础上,进一步验证“VTF是否通过重塑肠道菌群-肠-脑轴而发挥神经保护作用”,并阐明其潜在机制。方法:本研究将从天然药物琐琐葡萄中提取活性成分总黄酮VTF,作用于APP/PS-1小鼠,VTF灌胃8周,通过Morris水迷宫实验评估小鼠空间学习能力;ELISA检测小鼠脑组织中IL-1β、IL-6、TNF-α因子,血清中5-HT、GABA因子的含量;苏木精-伊红(Hematoxylin and eosin staining,HE)染色法观察结肠组织形态,免疫组化法检测Occludin、Claudin、Zo-1、NLRP3蛋白表达;高通量测序检测小鼠粪便肠道菌群;结果:1)水迷宫实验结果显示:VTF低剂量组平均逃逸潜伏期缩短(P<0.05);VTF低、中剂量组有效区域运动距离,运动时间以及进入次数显著增多(P<0.01);2)结肠组织HE染色结果显示;AD模型小鼠肠粘膜膜层萎缩,隐窝丢失和绒毛断裂,而VTF干预之后小鼠上述情况均有所减轻;3)结肠组织免疫组化结果显示:VTF干预可以上调Occludin、Claudin、Zo-1等紧密连接蛋白阳性表达(P<0.01),减少NLRP3炎症相关蛋白的表达(P<0.01);4)ELISA结果:VTF各剂量组小鼠脑组织中IL-1β、IL-6、TNFα等炎症因子水平降低(P<0.01);VTF各剂量组中5-HT和GABA的含量增多(P<0.01);5)肠道菌群检测结果显示:VTF高剂量干预后的AD小鼠厚壁菌门相对丰度增多(P<0.05),与模型组小鼠相比,VTF中、高剂量组中乳杆菌科(Lactobacillaceae)相对丰度增多,VTF低剂量组中Muribaculaceae相对丰度增多,多奈哌齐组,VTF各剂量组中丹毒科(Erysipelotrichaceae)、瘤胃球菌科(Ruminococcaceae)相对丰度增多;而VTF各剂量组中毛螺菌科(Lachnospiraceae)、螺杆菌科(Helicobacteraceae),脱铁杆菌科(Deferribacteraceae)相对丰度减少。结论:这些结果表明,VTF调节肠道菌群可能具有治疗衰老过程中微生物导致脑轴和认知功能缺陷的潜力,其机制可能与改变肠道菌群组成,修复受损的肠道屏障,炎症反应和神经递质有关。因此,调节肠道微生物群可能是治疗AD相关神经疾病的一种潜在策略。
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-034Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01+1 种基金PUMC Innovation Fund for Graduate Students,Grant/Award Number:2017-1001-07National Natural Science Foundation of China,Grant/Award Number:82161138027。
文摘Background:The absence of effective animal models for sporadic Alzheimer's disease(AD)remains a pivotal barrier to therapy development.Because methanol metabolism produces endogenous formaldehyde,a neurotoxic agent linked to cognitive decline,this study investigated whether chronic,low-dose methanol exposure could recapitulate AD-like pathology and cognitive deficits in rhesus monkey,thereby establishing a nonhuman primate animal model driven by this environmental-metabolic insult.Methods:Adult rhesus monkeys received low-concentration methanol for 9 months.Behavioral tests for cognition,locomotion,sleep,and vision were conducted.Postmortem analyses involved histopathological examination,immunohistochemistry,immunofluorescence,and Western blot to evaluate neuronal integrity,microglial activation,and the expression of key proteins associated with AD(amyloid-β[Aβ],phosphorylated tau,TAR DNA-binding protein 43[TDP-43])and cellular stress(synaptic markers,mitochondrial fission,autophagy,and apoptosis-related proteins).Results:Chronic methanol exposure led to progressive cognitive and memory impairment without significant motor or visual deficits.Neuropathology revealed brain atrophy,neuronal loss,synaptic damage,microglial activation,and mitochondrial structural disorganization.Critically,the exposed animals exhibited hallmark AD-like molecular alterations,including increased Aβ deposition,tau hyperphosphorylation,and TDP-43 dysregulation.Furthermore,neurotoxicity was associated with elevated urinary formaldehyde,enhanced mitochondrial fission,increased autophagy,and elevated apoptosis.Conclusion:Chronic low-dose methanol exposure in rhesus monkeys recapitulates progressive cognitive deficits and AD-like neuropathological features.This model,driven by endogenous formaldehyde toxicity,effectively mimics key aspects of sporadic AD.Our findings shed light on the neurotoxic mechanisms of methanol and propose a reproducible and translationally relevant nonhuman primate model for studying AD pathogenesis and evaluating potential therapeutics.
