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Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

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Journal of Pharmaceutical Analysis 2024年第3期14卷 348-370页

作者： Binbin Zhao Dongfeng Wei qinghua long Qingjie Chen Fushun Wang Linlin Chen Zefei Li Tong Li Tao Ma Wei Liu Linshuang Wang Caishui Yang Xiaxia Zhang Ping Wang Zhanjun Zhang State Key Laboratory of Cognitive Neuroscience and Learning&IDG/McGovern Institute for Brain Research Beijing Normal UniversityBeijing100875China Institute of Gerontology Hubei University of Chinese MedicineWuhan430065China Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing100700China Medical School Hubei Minzu UniversityEnshiHubei445000China HuBei University of Science and Technology XianningHubei437100China Institute of Brain and Psychological Science Sichuan Normal UniversityChengdu610066China Key Laboratory of Traditional Chinese Medicine Resource and Compound Prescription Ministry of EducationHubei University of Chinese MedicineWuhan430065China Dongfang Hospital Beijing University of Chinese MedicineBeijing100078China Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijing100700China School of Systems Science Beijing Normal UniversityBeijing100875China BABRI Centre Beijing Normal UniversityBeijing100875China

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with alterations in synaptic currents and mitochondrial ***,the specific associations between these pathological changes remain *** this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro *** investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,transmission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assessment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular *** results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD ***,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic *** cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular *** intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and ***,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial *** conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

关键词： Alzheimer's disease Synaptic currents Mitophagy Mitochondrial fusion and fission Dengzhan Shengmai capsules

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苁蓉散通过抑制内质网应激减少AD模型大鼠海马神经元细胞凋亡

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中国病理生理杂志 2024年第7期40卷 1244-1252页

作者：蔡元钦龙清华王曦曾楚华湖北民族大学医学部湖北恩施445000 云南中医药大学基础医学院云南昆明650500 湖北民族大学风湿性疾病发生与干预湖北省重点实验室湖北恩施445000 云南中医药大学云南省教育厅中医药防治神经精神疾病重点实验室云南省中西医结合慢病重点实验室云南昆明650500

目的:探究苁蓉散(Cong Rong San,CRS)对阿尔茨海默病(Alzheimer disease,AD)模型大鼠神经元损伤及内质网应激(endoplasmic reticulum stress,ERS)的影响。方法:将60只SD雄性大鼠(2月龄)随机分为对照组、模型组、低剂量CRS组、中剂量CRS... 详细信息

目的:探究苁蓉散(Cong Rong San,CRS)对阿尔茨海默病(Alzheimer disease,AD)模型大鼠神经元损伤及内质网应激(endoplasmic reticulum stress,ERS)的影响。方法:将60只SD雄性大鼠(2月龄)随机分为对照组、模型组、低剂量CRS组、中剂量CRS组、高剂量CRS组和盐酸美金刚组。Morris水迷宫实验检测大鼠的学习记忆能力;HE和尼氏染色观察大鼠海马CA1区的神经元形态;透射电镜观察大鼠海马的内质网形态;TUNEL染色观察大鼠海马CA1区神经元的凋亡情况;Western blot实验检测大鼠海马中葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)、B细胞淋巴瘤2(B-cell lymphoma-2,Bcl-2)、Bcl-2关联X蛋白(Bcl-2-ssociated X protein,Bax)、caspase-3及通路蛋白蛋白激酶R样内质网激酶(protein kinase R-like endoplasmic reticulum kinase,PERK)、p-PERK、激活转录因子4(activating transcription factor 4,ATF4)和C/EBP同源蛋白(C/EBP homologous protein,CHOP)的表达。结果:与模型组比较,中、高剂量的CRS能有效提高大鼠学习记忆能力,减少神经元的丢失,抑制ERS通路PERK-ATF4-CHOP的发生,减少海马中凋亡蛋白Bax和caspase-3的表达,增加海马中抗凋亡蛋白Bcl-2的表达。结论:CRS可以减轻AD大鼠认知损伤、海马神经元的损伤和神经元凋亡,其机制可能是抑制了ERS。

关键词：苁蓉散内质网应激阿尔茨海默病神经元损伤细胞凋亡

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基于网络药理学研究大补元煎防治AD的作用机制及AMPK/SIRT1信号通路验证

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中国免疫学杂志 2024年第8期40卷 1692-1700页

作者：田梦杰龙清华曾楚华刘道忠王平袁林湖北民族大学湿性疾病发生与干预湖北省重点实验室恩施445000 湖北中医药大学老年医学研究所武汉430065

目的:通过网络药理学和分子对接技术探究大补元煎防治阿尔茨海默病(AD)的作用机制,并利用动物实验验证所发现的分子机制。方法:网络药理学分析大补元煎抗AD的有效成分及作用靶点。利用AutoDock和PyMOL软件对药物的核心成分与核心蛋白进... 详细信息

目的:通过网络药理学和分子对接技术探究大补元煎防治阿尔茨海默病(AD)的作用机制,并利用动物实验验证所发现的分子机制。方法:网络药理学分析大补元煎抗AD的有效成分及作用靶点。利用AutoDock和PyMOL软件对药物的核心成分与核心蛋白进行分子对接验证。AD模型小鼠给予大补元煎治疗,并验证所发现的核心通路。结果:共筛选出80个有效活性成分和107个疾病作用靶点。大补元煎治疗AD的作用靶点有95个,其中核心靶点有35个。GO富集发现主要涉及程序性细胞死亡过程、细胞凋亡和信号转导调节等。KEGG信号通路富集发现主要涉及磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路、Wnt信号通路、腺苷酸活化蛋白激酶(AMPK)信号通路等。Morris水迷宫实验显示,大补元煎可减少AD小鼠的平台潜伏期,并增加小鼠的穿越平台次数和目标象限时间。免疫组化实验(IHC)结果显示,大补元煎可增加AD小鼠海马CA3区神经元核抗原(NeuN)标记的阳性细胞数。免疫荧光(IF)结果显示,大补元煎可抑制AD小鼠海马CA3区胶质纤维酸性蛋白(GFAP)、离子钙结合蛋白1(IBA1)的表达水平。Western blot实验显示,大补元煎可增加AD小鼠海马中磷酸化的腺苷酸活化蛋白激酶α(AMPKα)和沉默信息调节因子1(SIRT1)的表达水平。结论:本研究探讨了大补元煎抗AD的作用机制,并发现大补元煎可通过激活AMPK/SIRT1信号通路改善AD认知损伤、神经元丢失和神经炎症。

关键词：大补元煎阿尔茨海默病网络药理学 AMPK/SIRT1信号通路

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Deformation study of bicrystalline and nano-polycrystalline structures using phase field crystal method

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Science China(Physics,Mechanics & Astronomy) 2014年第6期57卷 1046-1056页

作者： long Jian ZHANG Shuai ZHAO Yulong long qinghua YANG Tao CHEN Zheng State Key Laboratory of Solidification Processing Northwestern Polytechnical University

Deformation behaviors of bicrystalline and nano-polycrystalline structures of various tilt angles and inclination angles in two dimensions are investigated in detail using a two-mode phase field crystal *** interaction between grain boundary(GB)and dislocation is also examined in bicrystals and nano-polycrystals that both contain asymmetric and symmetric tilt GBs,with energy analysis being carried out to analyze these *** deformation simulations,we assume the volume of each simulation cell at every time step is coincident with that of the initial state just before *** simulation results show that the behaviors of symmetric and asymmetric GBs in bicrystals and nano-polycrystals differ from each other depending on tilt angle and inclination angle.A new dislocation emission mechanism of interest is observed in bicrystals which contain low angle symmetric tilt *** angle GB has a higher mobility relative to high angle GB in both bicrystalline and nano-polycrystalline structures,as does asymmetric GB to symmetric *** generation,motion,pileup and annihilation of dislocations,grain rotation and grain coalescence are observed,which is consistent with the simulation results obtained by molecular *** simulation results can provide strong guidelines for experimentation.

关键词： phase field crystal grain boundary dislocation deformation mechanism

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Molecular Mechanism and Molecular Design of Lubricating Oil Antioxidants

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China Petroleum Processing & Petrochemical Technology 2024年第2期26卷 135-145页

作者： Su Shuo long Jun Duan qinghua Zhou Han Zhao Yi SINOPEC Research Institute of Petroleum Processing Co.Ltd. Beijing 100083

To overcome the limitations of traditional experimental“trial and error”methods in lubricant additive design,a new molecular design method based on molecular structure parameters is established *** molecular mechanism of the antioxidant reaction of hindered phenol,diphenylamine,and alkyl sulfide are studied via molecular *** results show that the strong electron-donating ability and high hydrogen-donating activity of the antioxidant molecule and the low hydrogen-abstracting activity of free radicals formed after dehydrogenation are the internal molecular causes of the shielding of phenol and diphenylamine from scavenging peroxy free radicals,and the strong electron-donating ability is the internal molecular cause of the high activity of thioether in decomposing alkyl hydrogen *** on this antioxidant molecular mechanism,a molecular design rule of antioxidant is proposed,namely“high EHOMO,large Q(S),low bond dissociation energy BDE(O—H)and BDE(N—H)”.Two new antioxidants,PAS-I and PAS-II,are designed and prepared by chemical bonding of hindered phenol,diphenylamine,and sulfur *** results show that these antioxidants both have excellent antioxidant effects in lubricating oil,and that PAS-II is the superior antioxidant,consistent with theoretical predictions.

关键词： lubricating oil antioxidant molecular mechanism molecular design antioxidant performance

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Diagnostic Study of an Extreme Explosive Cyclone over the Kuroshio/Kuroshio Extension Region

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Journal of Ocean University of China 2024年第3期23卷 605-617页

作者： ZHANG Shuqin LIAO qinghua LIU Chunlei GAO Xiaoyu long Jingchao LI Pengyuan XU Jianjun College of Ocean and Meteorology Guangdong Ocean UniversityZhanjiang 524088China South China Sea Institute of Marine Meteorology Guangdong Ocean UniversityZhanjiang 524088China CMA-GDOU Joint Laboratory for Marine Meteorology Guangdong Ocean UniversityZhanjiang 524088China Key Laboratory of Climate Resources and Environment in Continental Shelf Sea and Deep Sea of Department of Education of Guangdong ProvinceGuangdong Ocean UniversityZhanjiang 524088China State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesBeijing 100081China Department of Marine Meteorology Ocean-Atmosphere Interaction and Climate LaboratoryKey Laboratory of Physical OceanographyOcean University of ChinaQingdao 266100China

Explosive cyclones(ECs)occur frequently over the Kuroshio/Kuroshio Extension *** most rapidly intensified EC over the Kuroshio/Kuroshio Extension region during the 42 years(1979-2020)of cold seasons(October-April)was studied to reveal the variations of the key factors at different explosive-developing *** EC had weak low-level baroclinicity,mid-level cyclonic-vorticity advection,and strong low-level water vapor convergence at the initial explosive-developing *** low-level baroclinicity and mid-level cyclonic-vorticity advection increased substantially during the maximum-deepening-rate *** diagnostic analyses using the Zwack-Okossi equation showed that diabatic heating was the main contributor to the initial rapid intensification of this *** cyclonic-vorticity advection and warm-air advection enhanced rapidly in the middle and upper troposphere and contributed to the maximum rapid intensification,whereas the diabatic heating weakened slightly in the mid-low *** relative contribution of the diabatic heating decreased from the initial explosive-developing stage to the maximum-deepening-rate stage due to the enhancement of other factors(the cyclonic-vorticity advection and warm-air advection).Furthermore,the physical factors contributing to this EC varied with the explosive-developing *** non-key factors at the initial explosive-developing stage need attention to forecast the rapid intensification.

关键词： explosive cyclone diabatic heating cyclonic-vorticity advection rapid intensification the Kuroshio/Kuroshio Extension region

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When Does Sora Show:The Beginning of TAO to Imaginative Intelligence and Scenarios Engineering

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 809-815页

作者： Fei-Yue Wang Qinghai Miao Lingxi Li qinghua Ni Xuan Li Juanjuan Li Lili Fan Yonglin Tian Qing-long Han School of Artificial Intelligence University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory for Management and Control of Complex Systems Chinese Academy of SciencesBeijing 100190China Faculty of Innovation Engineering Macao University of Science and TechnologyMacao 999078China Department of Electrical and Computer Engineering Indiana University-Purdue University IndianapolisIndianapolisIN 46202USA Faculty of Innovation Engineering Macao University of Science and TechnologyMacao 999078China Virtual Reality Fundamental Research Laboratory Department of Mathematics and TheoriesPeng Cheng LaboratoryShenzhen 518000China State Key Laboratory of Multimodal Artificial Intelligence Systems Institute of AutomationChinese Academy of SciencesBeijing 100190China School of Information and Electronics Beijing Institute of TechnologyBeijing 100081China School of Science Computing and Engineering TechnologiesSwinburne University of TechnologyMelbourneVIC 3122Australia

DURING our discussion at workshops for writing“What Does ChatGPT Say:The DAO from Algorithmic Intelligence to Linguistic Intelligence”[1],we had expected the next milestone for Artificial Intelligence(AI)would be in the direction of Imaginative Intelligence(II),i.e.,something similar to automatic wordsto-videos generation or intelligent digital movies/theater technology that could be used for conducting new“Artificiofactual Experiments”[2]to replace conventional“Counterfactual Experiments”in scientific research and technical development for both natural and social studies[2]-[6].Now we have OpenAI’s Sora,so soon,but this is not the final,actually far away,and it is just the beginning.

关键词： something Intelligence replace

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湖南省地方志利用概况

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中国地方志 2005年第3期 36-38页

作者：隆清华湖南省长沙市德雅村省地方志编纂委员会市县志处 410003

湖南省地方志利用情况主要分 4个方面 :一、为社会各界提供全面、科学的地情资料 ;二、为领导决策提供有益的历史借鉴 ;三、为当地经济、文化建设提供科学的历史依据 ;四、为海内外经济、文化交流提供宣传平台。

关键词：地方志湖南省利用情况地情资料历史借鉴领导决策历史依据文化建设文化交流科学经济

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A stable implicit nodal integration-based particle finite element method(N-PFEM)for modelling saturated soil dynamics

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第6期16卷 2172-2183页

作者： Liang Wang Xue Zhang Jingjing Meng qinghua Lei Department of Earth Sciences ETH ZürichZürich8092Switzerland Department of Civil Engineering and Industrial Design University of LiverpoolLiverpoolL693BXUK Department of Civil Environmental and Natural Resources EngineeringLuleåUniversity of TechnologyLuleå97187Sweden Department of Earth Sciences Uppsala UniversityUppsala75105Sweden

In this study,we present a novel nodal integration-based particle finite element method(N-PFEM)designed for the dynamic analysis of saturated *** approach incorporates the nodal integration technique into a generalised Hellinger-Reissner(HR)variational principle,creating an implicit PFEM *** mitigate the volumetric locking issue in low-order elements,we employ a node-based strain smoothing *** discretising field variables at the centre of smoothing cells,we achieve nodal integration over cells,eliminating the need for sophisticated mapping operations after re-meshing in the *** express the discretised governing equations as a min-max optimisation problem,which is further reformulated as a standard second-order cone programming(SOCP)***,pore water pressure,and displacements are simultaneously determined using the advanced primal-dual interior point ***,our numerical model offers improved accuracy for stresses and pore water pressure compared to the displacement-based PFEM *** experiments demonstrate that the N-PFEM efficiently captures both transient and long-term hydro-mechanical behaviour of saturated soils with high accuracy,obviating the need for stabilisation or regularisation techniques commonly employed in other nodal integration-based PFEM *** work holds significant implications for the development of robust and accurate numerical tools for studying saturated soil dynamics.

关键词： Particle finite element method Nodal integration Dynamic saturated media Second-order cone programming(SOCP)

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Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin long Chuanhua Ge Yueyang Zhao Yuanjie Liu qinghua Zeng Qing Tang Zhifang Dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina Department of Anatomy Chongqing Medical UniversityChongqingChina Department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

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