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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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LTE FDD传播模型校正

移动通信 2014年第8期38卷 22-26页

作者：曾发龙罗帆湖北邮电规划设计有限公司湖北武汉430023

通过对友谊路局等3个密集市区和设计院等3个一般市区的实际CW路测,并对测试数据进行过滤和筛选,采用迭代拟合及均方差最小的方法,校正2.1G LTE FDD的Cost-231-哈塔经验传播模型的C0和C1参数,得到适合规划区域的2.1G LTE FDD密集市区和... 详细信息

通过对友谊路局等3个密集市区和设计院等3个一般市区的实际CW路测,并对测试数据进行过滤和筛选,采用迭代拟合及均方差最小的方法,校正2.1G LTE FDD的Cost-231-哈塔经验传播模型的C0和C1参数,得到适合规划区域的2.1G LTE FDD密集市区和一般市区的传播模型。通过校正后的传播模型,计算密集市区和一般市区的覆盖半径及站间距,以指导LTE网络建设。

关键词： Cost-231-哈塔路测传播模型

Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

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Neural Regeneration Research 2025年第11期20卷 3259-3272页

作者： Huidong Li faqin Li Zhaoyi Chen Erwen Wu Xiaoxi Dai Danni Li Haojie An Shiyi zeng Chunyan Wang Li Yang Cheng long School of Life Sciences South China Normal UniversityGuangzhouGuangdong ProvinceChina School of Life Sciences Guangzhou UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Major Obstetric Diseases The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research Panyu Central HospitalGuangzhouGuangdong ProvinceChina

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear ***(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B *** is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly *** studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like ***,the precise role of CYLD in glutamatergic neurons is largely ***,we first proposed involvement of CYLD in cued fear *** next constructed transgenic model mice with specific deletion of Cyld from glutamatergic *** results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male ***,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male ***,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial *** may contribute,at least in part,to cued fear expression.

关键词： basolateral amygdala cued fear expression cylindromatosis deubiquitinase glutamate receptor 1 glutamatergic neuron microglial activation N-methyl-D-aspartate receptor 1 neuronal activation synaptic transmission

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体绘制源和反射-衰减模型

中国图象图形学报（A辑） 2000年第5期5卷 425-429页

作者：李飞鹏廖孟扬曾发龙王思贤武汉测绘科技大学测绘遥感信息工程国家重点实验室武汉430072 武汉大学图象及信息技术研究所武汉430072

为解决医学图象三维可视化中三维体数据显示的问题 ,在综合了体绘制源 -衰减模型和兰伯特漫反射余弦定律的基础上 ,提出了体绘制源和反射 -衰减光照模型 .新的模型假定三维标量数据场中的每一点都既是点光源 ,又能够反射外部入射光 ,并... 详细信息

为解决医学图象三维可视化中三维体数据显示的问题 ,在综合了体绘制源 -衰减模型和兰伯特漫反射余弦定律的基础上 ,提出了体绘制源和反射 -衰减光照模型 .新的模型假定三维标量数据场中的每一点都既是点光源 ,又能够反射外部入射光 ,并且反射光的分布遵循兰伯特漫反射余弦定律 .由以上假定推导出体绘制的基本运算公式 .实验结果表明 ,体绘制源和反射 -衰减模型是一种性能优良的体光照模型。

关键词：三维可视化体绘制医学图象计算机图形学

Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

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Neural Regeneration Research 2025年第1期20卷 159-173页

作者： Man Han Deyang zeng Wei Tan Xingxing Chen Shuyuan Bai Qiong Wu Yushan Chen Zhen Wei Yufei Mei Yan zeng Brain Science and Advanced Technology Institute Wuhan University of Science and TechnologyWuhanHubei ProvinceChina Geriatric Hospital Affiliated to Wuhan University of Science and Technology WuhanHubei ProvinceChina School of Public Health Wuhan University of Science and TechnologyWuhanHubei ProvinceChina

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral *** studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and *** how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress *** this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of *** focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine *** determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic ***,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

关键词： amygdala chronic mild stress chronic social defeat stress corticolimbic system depression hippocampus medial prefrontal cortex nucleus accumbens social stress models ventral tegmental area

Role of metabolic dysfunction and inflammation along the liver-brain axis in animal models with obesity-induced neurodegeneration

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Neural Regeneration Research 2025年第4期20卷 1069-1076页

作者： Evridiki Asimakidou Eka Norfaishanty Saipuljumri Chih Hung Lo Jialiu zeng Department of Clinical Neurosciences University of CambridgeCambridgeUK School of Applied Science Republic PolytechnicSingaporeSingapore Lee Kong Chian School of Medicine Nanyang Technological UniversitySingaporeSingapore

The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s ***-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this *** lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory *** and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting *** insulin resistance further exacerbates brain insulin resistance and *** interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal ***,translating these findings to clinical practice requires further investigation into human *** conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and *** these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.

关键词： Alzheimer’s disease inflammatory cytokines insulin resistance lipid

The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan long Jiajia Liu Yu Wang Haidong Guo Guohong Cui Department of Neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina School of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory

Multi-Stage Voltage Control Optimization Strategy for Distribution Networks Considering Active-Reactive Co-Regulation of Electric Vehicles

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Energy Engineering 2025年第1期122卷 221-242页

作者： Shukang Lyu Fei zeng Huachun Han HuiyuMiao Yi Pan Xiaodong Yuan Electric Power Research Institute State Grid Jiangsu Electric Power Co.Ltd.Nanjing211103China

The high proportion of uncertain distributed power sources and the access to large-scale random electric vehicle(EV)charging resources further aggravate the voltage fluctuation of the distribution network,and the existing research has not deeply explored the EV active-reactive synergistic regulating characteristics,and failed to realize themulti-timescale synergistic control with other regulatingmeans,For this reason,this paper proposes amultilevel linkage coordinated optimization strategy to reduce the voltage deviation of the distribution ***,a capacitor bank reactive power compensation voltage control model and a distributed photovoltaic(PV)activereactive power regulationmodel are ***,an external characteristicmodel of EVactive-reactive power regulation is developed considering the four-quadrant operational characteristics of the *** optimization model of the distribution network is then constructed considering the time-series coupling constraints of multiple types of voltage regulators.A multi-timescale control strategy is proposed by considering the impact of voltage regulators on active-reactive EV energy consumption and PV energy ***,a four-stage voltage control optimization strategy is proposed for various types of voltage regulators with multiple time ***-objective optimization is solved with the improvedDrosophila algorithmto realize the power fluctuation control of the distribution network and themulti-stage voltage control *** results validate that the proposed voltage control optimization strategy achieves the coordinated control of decentralized voltage control resources in the distribution *** effectively reduces the voltage deviation of the distribution network while ensuring the energy demand of EV users and enhancing the stability and economic efficiency of the distribution network.

关键词： Electric vehicle(EV) distribution network multi-stage optimization active-reactive power regulation voltage control

Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

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Neural Regeneration Research 2025年第9期20卷 2520-2537页

作者： Chonglin Su Taiqi Huang Meiyu Zhang Yanyu Zhang Yan zeng Xingxing Chen Brain Science and Advanced Technology Institute Hubei Province Key Laboratory of Occupational Hazard Identification and ControlSchool of MedicineWuhan University of Science and TechnologyWuhanHubei ProvinceChina

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental *** the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and *** glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic *** interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive *** appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive *** with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor *** review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive *** emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive *** provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

关键词： brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders neuroplasticity stress