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Advances in extracellular space and immunotherapy of pre-clinical stage of Alzheimer disease

中国药理学与毒理学杂志 2019年第6期33卷 412-413页

作者： CUI De-hua ZHAO Lei wang he-cheng HAN Hong-bin Department of Neurology Key Laboratory of Magnetic Resonance Imaging and TechniquePeking University Third Hospital

The most common age-related neurodegenerative disease is Alzheimer disease(AD),the imbalance between Aβ generation and clearance accumulated in extracellular plaques(ECS). And aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles, together with loss of cholinergic neurons, synaptic alterations, and chronic inflammation within the brain. These lead to progressive impairment of cognitive function. The sporadic form of AD is characterized by an overall impairment in Aβ clearance.(1) Immunotherapy for AD: Immunotherapy targeting Aβ clearance is believed to be a promising approach and is under active clinical investigation. Autophagy is a conserved pathway for degrading abnormal protein aggregates and is crucial for Aβ clearance. We found that oral vaccination with a recombinant AAV/Aβ vaccine increased the clearance of Aβ from the brain and improved cognitive ability in AD animal models, while the underlying mechanisms were not well understood. In this study, we first demonstrated that oral vaccination with r AAV/Aβ decreased the p62 level and up-regulated the LC3 B-Ⅱ/LC3 B-Ⅰ ratio in APP/PS1 mouse brain, suggesting enhanced autophagy. Further, inhibition of the Akt/m TOR pathway may account for autophagy enhancement. We also found increased anti-Aβ antibodies in the sera of APP/PS1 mice with oral vaccination, accompanied by elevation of complement factors C1 q and C3 levels in the brain. Our results indicate that autophagy is closely involved in oral vaccination-induced Aβ clearance and modulating the autophagy pathway may be an important strategy for pre-clinical stage of AD(PCAD) prevention and intervention.(2)ECS in AD: Strategies that promote local growth of lymphatic vessels have the potential to improve clearance Aβ by meningeal lymphatics. whether enhancing clearance at the blood–brain barrier can improve lymphatic drainage function, remains to be addressed. Understanding substance transportation in brain ECS, especially in deep bra

关键词： Alzheimer disease extracellular plaques immunotherapy Aβ clearance autophagy

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Physalin B reduces Aβ secretion through down-regulation of BACE1 expression by activating FoxO1 and inhibiting STAT3 phosphorylation

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Chinese Journal of Natural Medicines 2021年第10期19卷 732-740页

作者： ZHANG Wei BAI Shan-Shan ZHANG Qi SHI Ru-Ling wang he-cheng LIU You-Cai NI Tian-Jun WU Ying YAO Zhao-Yang SUN Yi wang Ming-Yong School of Basic Medical Sciences Xinxiang Medical UniversityXinxiang 453003China Grade 2019 School of Basic Medical SciencesXinxiang Medical UniversityXinxiang 453003China School of Public health Xinxiang Medical UniversityXinxiang 453003China School of Life and Pharmaceutical Sciences Dalian University of TechnologyPanjin 124221China School of Basic Medical Sciences Sanquan College of Xinxiang Medical UniversityXinxiang 453003China School of Nursing Care Xinxiang Medical UniversityXinxiang 453003China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China School of Laboratory Medicine Xinxiang Medical UniversityXinxiang 453003China Xinxiang Key Laboratory of Immunoregulation and Molecular Diagnostics Xinxiang 453003China Central Laboratory the First Affiliated Hospital of Henan University of Science and TechnologyLuoyang 471003China

Physalin B(PB),one of the major active steroidal constituents of Solanaceae Physalis plants,has a wide variety of biological *** found that PB significantly down-regulatedβ-amyloid(Aβ)secretion in N2a/APPsw ***,the underlying mechanisms are not well *** the current study,we investigated the changes in key enzymes involved inβ-amyloid precursor protein(APP)metabolism and other APP metabolites by treating N2a/APPsw cells with PB at different *** results indicated that PB reduced Aβ secretion,which was caused by down-regulation of β-secretase(BACE1)expression,as indicated at both the protein and mRNA *** research revealed that PB regulated BACE1 expression by inducing the activation of forkhead box O1(FoxO1)and inhibiting the phosphorylation of signal transducer and activator of transcription 3(STAT3).In addition,the effect of PB on BACE1 expression and Aβsecretion was reversed by treatment with FoxO1 siRNA and STAT3 antagonist *** conclusion,these data demonstrated that PB can effectively down-regulate the expression of BACE1 to reduce Aβsecretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.

关键词： Physalin B β-amyloid BACE1 FoxO1 Alzheimer’s disease

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Thermogravimetric-Mass Spectrometric Study of the Pyrolysis Behavior of PVC

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Journal of China University of Mining and Technology 2007年第2期17卷 242-245页

作者： SUN Qing-lei SHI Xin-gang LIN Yun-liang ZHU he wang Xiao cheng Chuan-ge LIU Jian-hua Shandong Analysis and Test Center Shandong Academy of Science Jinan Shandong 250014 China

The pyrolysis characteristics of PVC were systematically investigated using a Netzschne TG thermo-balance coupled to a quadrupole mass spectrometer. The pyrolysis conditions were 0.1 MPa of Ar, a heating rate of 10 ℃/min and a final temperature of 1000℃. Both the thermogravimetric properties and the simultaneous evolution of gaseous products during pyrolysis were studied. The TG/DTG results showed that as the pyrolysis temperature increases the weight loss and weight loss rate of PVC increases. Near 412℃ the weight loss rate attained its peak value. At higher temperatures the rate of loss gradually decreases. The gases evolved during thermogravimetric analysis were analyzed by a mass spectrometer, monitoring the relative intensity of HC1, C6H6, light hydrocarbon and chlorine-containing gases The evolution curves showed that HC1, C6H6, light hydrocarbon and chlorine-containing gases all peak at about 416℃. This is consistent with the fact that the weight loss curves also peak at about 412℃. The extensive HCl evolution is consistent with the high chlorine content of PVC. The formation of these gases can be explained by considering these reactions： dehydrochlorination, intramolecular cyclization and the addition of HCl to unsaturated hydrocarbons.

关键词： pyrolysis PVC gas evolution TG-MS

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Magnetron sputtered nickel oxide with suppressed interfacial defect states for efficient inverted perovskite solar cells

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Journal of Energy Chemistry 2025年第1期100卷 348-355页

作者： Guoqiang Ma Qin Tan Zhaoning Li Jingwei Xiu Jiafeng wang Tianle cheng Dong he Qiang Sun Xuhang Ma Francesco Lamberti Zhubing he Department of Materials Science and Engineering Institute of Innovative Materials (I2M) Shenzhen Key Laboratory of Full Spectral Solar Electricity Generation (FSSEG)Southern University of Science and Technology (SUSTech) Core Research Facilities Southern University of Science and Technology Department of Chemical Sciences Department of Industrial Engineering University of Padova

Widely used spin-coated nickle oxide （NiOx） based perovskite solar cells often suffer from severe interfacial reactions between the NiOxand adjacent perovskite layers due to surface defect states,which inherently impair device performance in a long-term view,even with surface molecule *** this study,we developed high-quality magnetron-sputtered NiOxthin films through detailed process optimization,and compared systematically sputtered and spin-coated NiOxthin film surfaces from materials to *** sputtered NiOxfilms exhibit improved crystallinity,smoother surfaces,and significantly reduced Ni3+or Ni vacancies compared to their spin-coated ***,the interface between the perovskite and sputtered NiOxfilm shows a substantially reduced density of defect *** solar cells （PSCs） fabricated with our optimally sputtered NiOxfilms achieved a high power conversion efficiency （PCE） of up to 19.93%and demonstrated enhanced stability,maintaining 86.2% efficiency during 500 h of maximum power point tracking under one standard sun ***,with the surface modification using (4-(2,7-dibromo-9,9-dimethylacridin-10（9H）-yl)butyl)p hosphonic acid （DMAcPA）,the device PCE was further promoted to 23.07%,which is the highest value reported for sputtered NiOxbased PSCs so far.

关键词： Nickle oxide Magnetron sputter Defect Stability Perovskite solar cell

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Constraints on holographic QCD phase transitions from PTA observations

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 71-78页

作者： Song he Li Li Sai wang Shao-Jiang wang Center for Theoretical Physics and College of Physics Jilin University School of Physical Science and Technology Ningbo University Max Planck Institute for Gravitational Physics (Albert Einstein Institute) CAS Key Laboratory of Theoretical Physics Institute of Theoretical Physics Chinese Academy of Sciences School of Fundamental Physics and Mathematical Sciences Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of Sciences (UCAS) School of Physical Sciences University of Chinese Academy of Sciences (UCAS) Theoretical Physics Division Institute of High Energy Physics Chinese Academy of Sciences

The underlying physics of QCD phase transition in the early Universe remains largely unknown due to its strong-coupling nature during the quark-gluon plasma/hadron gas transition, yet a holographic model has been proposed to quantitatively fit the lattice QCD data while with its duration of the first-order phase transition(FoPT) left undetermined. At specific baryon chemical potential, the first-order QCD phase transition agrees with the observational constraint of baryon asymmetry. It, therefore, provides a scenario for phase transition gravitational waves(GWs) within the standard model of particle physics. If these background GWs could contribute dominantly to the recently claimed common-spectrum red noise from pulsar timing array(PTA) observations, the duration of this FoPT can be well constrained, and the associated primordial black holes are still allowed by current observations.

关键词： pulsar timing array QCD phase transition gravitational waves primordial black holes

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Advances in extracellular space and immunotherapy of pre-clinical stage of Alzheimer disease

Advances in extracellular space and immunotherapy of pre-cli...

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2019全国老年痴呆与认知障碍相关疾病学术大会

作者： CUI De-hua ZHAO Lei wang he-cheng HAN Hong-bin Department of Neurology Key Laboratory of Magnetic Resonance Imaging and TechniquePeking University Third Hospital

The most common age-related neurodegenerative disease is Alzheimer disease(AD),the imbalance between Aβ generation and clearance accumulated in extracellular plaques(ECS).And aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the *** lead to progressive impairment of cognitive *** sporadic form of AD is characterized by an overall impairment in Aβ clearance.① Immunotherapy for AD:Immunotherapy targeting Aβ clearance is believed to be a promising approach and is under active clinical *** is a conserved pathway for degrading abnormal protein aggregates and is crucial for Aβ *** found that oral vaccination with a recombinant AAV/Aβ vaccine increased the clearance of Aβ from the brain and improved cognitive ability in AD animal models,while the underlying mechanisms were not well *** this study,we first demonstrated that oral vaccination with rAAV/Aβ decreased the p62 level and up-regulated the LC3 B-Ⅱ/LC3 B-Ⅰ ratio in APP/PS1 mouse brain,suggesting enhanced ***,inhibition of the Akt/mTOR pathway may account for autophagy *** also found increased anti-Aβ antibodies in the sera of APP/PS1 mice with oral vaccination,accompanied by elevation of complement factors C1 q and C3 levels in the *** results indicate that autophagy is closely involved in oral vaccination-induced Aβ clearance and modulating the autophagy pathway may be an important strategy for pre-clinical stage of AD(PCAD) prevention and intervention.②ECS in AD:Strategies that promote local growth of lymphatic vessels have the potential to improve clearance Aβ by meningeal *** enhancing clearance at the blood-brain barrier can improve lymphatic drainage function,remains to be *** substance transportation in brain ECS,especially in deep brain is essential for the compl

关键词： Alzheimer disease extracellular plaques immunotherapy Aβ clearance autophagy

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T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

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Neural Regeneration Research 2025年第5期20卷 1277-1292页

作者： Yuxiao Zheng Zilin Ren Ying Liu Juntang Yan Congai Chen Yanhui he Yuyu Shi Fafeng cheng Qingguo wang Changxiang Li Xueqian wang School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijingChina Library Beijing University of Chinese MedicineBeijingChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue *** the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the *** an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune *** review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic *** found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic ***1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain ***2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain *** interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke *** trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic ***,such studies have been relatively infrequent,and clinical experience is still *** summary,in ischemic stroke,T cell subsets and activated micro

关键词： brain immune inflammation interaction ischemic stroke mechanism microglia neuron secondary injury T cells

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企业竞争优势演化机制研究—创新和选择的共同进化

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商业研究 2006年第15期 38-41页

作者：王瑞王核成宁波大红鹰职业技术学院经管系浙江宁波315175 杭州电子科技大学管理学院浙江杭州310018

演化经济理论大量引入了生物进化论中的一些概念和思想,在经济学中,和生物系统一样,演化主要是两种机制推动的:一个是创新机制,通过系统的创新产生多样化;一个是选择机制,即在多样化中进行系统筛选。企业竞争优势的演化则是这两种机制... 详细信息

演化经济理论大量引入了生物进化论中的一些概念和思想,在经济学中,和生物系统一样,演化主要是两种机制推动的:一个是创新机制,通过系统的创新产生多样化;一个是选择机制,即在多样化中进行系统筛选。企业竞争优势的演化则是这两种机制的共同进化,推动竞争优势的更替或是持续。

关键词：企业竞争优势创新机制选择机制

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阳澄西湖浮游藻类功能群演替特征及其与环境因子的关系

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中国环境科学 2019年第7期39卷 3027-3039页

作者：葛优周彦锋王晨赫尤洋中国水产科学研究院淡水渔业研究中心农业部淡水渔业和种质资源利用重点实验室江苏无锡214081 南京农业大学无锡渔业学院江苏无锡214081

采用浮游藻类功能群、RDA(冗余分析)、多元回归分析等方法,对阳澄西湖浮游藻类功能群的演替特征及其影响因子进行了研究.2015年3月~2016年2月逐月对阳澄西湖浮游藻类和环境因子进行调查分析,结果表明,阳澄西湖浮游藻类可划分为21个功能... 详细信息

采用浮游藻类功能群、RDA(冗余分析)、多元回归分析等方法,对阳澄西湖浮游藻类功能群的演替特征及其影响因子进行了研究.2015年3月~2016年2月逐月对阳澄西湖浮游藻类和环境因子进行调查分析,结果表明,阳澄西湖浮游藻类可划分为21个功能群,其中10个功能群(B、D、E、G、J、Lo、S1、X1、X2、Y)为该湖的优势功能群,反映的生境特征表明该湖为分层敏感,扰动较少且混合程度较高的中-富营养浅水水体.阳澄西湖不同季节优势功能群演替规律为:由春季的B+X2+Y+X1+J+D,经夏季的B+X2+Y+X1+J+G+S1+Lo+E和秋季的B+X2+Y+Lo+E,转变为B+X2+Y+X1+***分析结果显示,阳澄西湖浮游藻类功能群分布受环境影响较为明显,但不同季节影响因子不同.整体上,水温(T)、pH值、溶解氧(DO)、氨氮(NH 4+-N)和浊度(Tur)是影响阳澄西湖浮游藻类功能群分布格局的主要因素.

关键词：阳澄西湖藻类功能群优势度环境因子

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宁夏沙坡头国家自然保护区鸟类景观生态安全格局构建

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生态学报 2017年第16期37卷 5531-5541页

作者：王原何成刘荣国吴洪斌陈骁强安徽师范大学国土资源与旅游学院芜湖241002 宁夏沙坡头国家级自然保护区管理处中卫751700 上海栖新生态环境咨询有限公司上海200082

随着宁夏沙坡头国家自然保护区的旅游发展与荒漠化进程,保护区内不同类型的鸟类均面临着日益增加的自然及人为干扰胁迫,鸟类群落的丰富度下降趋势显著。为了改善保护区内鸟类生物多样性现状,优化鸟类栖息地空间结构,基于现有鸟类调查与... 详细信息

随着宁夏沙坡头国家自然保护区的旅游发展与荒漠化进程,保护区内不同类型的鸟类均面临着日益增加的自然及人为干扰胁迫,鸟类群落的丰富度下降趋势显著。为了改善保护区内鸟类生物多样性现状,优化鸟类栖息地空间结构,基于现有鸟类调查与研究资料,筛选影响鸟类活动的各类阻力指数,建立鸟类活动最小累积阻力面,运用最小阻力模型构建景观生态安全格局。研究结果表明:源地面积为1690.67 hm^2,占保护区总体面积的12.09%;廊道共13条;辐射道共85条;战略点共8个;保护关键区面积为2634.48 hm^2,占保护区总体面积的18.76%。在此基础上,针对不同类型的重点保护地块、保护热点及栖息地之间的联系廊道提出鸟类保护的空间格局优化建议。详细梳理了阻力面模型的构建方法,改进了相关技术环节,为我国自然保护区生物多样性景观安全格局优化提供了科学的方法与实践指导。

关键词：鸟类保护最小累积阻力景观安全格局宁夏沙坡头国家自然保护区

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