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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation center for Human brain Protection and National Clinical Research center for Geriatric disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

Feedback processing in the primate brain and in AI systems

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Science China(Technological sciences) 2024年第8期67卷 2297-2309页

作者： JIANG Yong HE Sheng Institute of Biophysics Chinese Academy of SciencesBeijing 100101China Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefei 230088China University of Chinese Academy of sciences Beijing 100049China

The primate brain and artificial intelligence(AI) can both be conceptualized as information processing systems, each with its own distinct biological and computational architectures. While there are parallels between them, their respective structural and functional connections show significant differences. In this paper, we examine the central role of feedback processing in both the primate brain and AI systems, which has been shown to be crucial in shaping neural processing. By reviewing the key features of feedback processes in the primate brain, which allows the brain to incorporate prior knowledge, contextual information, and taskdemands into early-stage processing, we highlight the divergence in goals and functions between biological and AI *** these differences is crucial for elucidating the cognitive capabilities of the primate brain and for addressing computational challenges in AI. In advocating “Cognition-Inspired-Computation”, we suggest that integrating insights from feedback processing in the primate brain into AI research will offer potentially significant improvements for the advancement of AI systems.

关键词： cognitive neuroscience artificial intelligence feedback processing attention learning

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

Effects of a periodic intermittent theta burst stimulation in Alzheimer's disease

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General Psychiatry 2024年第1期37卷 53-63页

作者： Xingqi Wu Yibing Yan Panpan Hu Lu Wang Yue Wu Pan Wu Zhi Geng Guixian Xiao Shanshan Zhou Gongjun Ji Bensheng Qiu Ling Wei Yanghua Tian Hesheng Liu Kai Wang Department of Neurology First ffiliated Hospital of Anhui Medical UniversityHefeiAnhuiChina School of Mental Health and Psychological sciences Anhui Medical UniversityHefeiAnhuiChina Anhui Province Key Laboratory of Cognition and Neuropsychiatric disorders HefeiAnhuiChina Collaborative Innovation center of Neuropsychiatric disorders and Mental Health HefeiAnhuiChina Department of Psychology and Sleep Medicine The Second Affliated Hospital of Anhui Medical UniversityHefeiAnhuiChina center for Biomedical Imaging University of Science and Technology of ChinaHefeiAnhuiChina institute of Artificial Intlligence Hefei Comprehensive National Science CenterHefeiAnhuiChina Department of Neuroscience Medical University of South CarolinaCharlestonSouth CarolinaUSA

Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for ***,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD *** We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with *** In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every *** included the Montreal cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the *** were evaluated at baseline and after *** longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over *** The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale *** baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at ***,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)*** D

关键词： stimulation Alzheimer maintained

Lycium barbarum glycopeptide(wolfberry extract)slows N-methyl-N-nitrosourea-induced degradation of photoreceptors

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Neural Regeneration Research 2024年第10期19卷 2290-2298页

作者： Qihang Kong Xiu Han Haiyang Cheng Jiayu Liu Huijun Zhang Tangrong Dong Jiansu Chen Kwok-Fai So Xuesong Mi Ying Xu Shibo Tang Department of Ophthalmology Aier Eye HospitalJinan UniversityGuangzhouGuangdong ProvinceChina Department of Ophthalmology The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Guangdong-Hong Kong-Macao Institute of CNS Regeneration Key Laboratory of CNS Regeneration(Ministry of Education)Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Ophthalmology Guangzhou Panyu Central HospitalGuangzhouGuangdong ProvinceChina School of Stomatology Jinan UniversityGuangzhouGuangdong ProvinceChina Aier Academician Station ChangshaHunan ProvinceChina Co-Innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina State Key Laboratory of brain and cognitive sciences Hong Kong Special Administrative RegionChina

Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum(L. barbarum) polysaccharide(LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide(Lb GP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of Lb GP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of Lb GP as a protective pre-treatment on days 1–7;intraperitoneal administration of 40 mg/kg N-methylN-nitrosourea to induce photoreceptor injury on day 7;and continuation of orally administered Lb GP on days 8–14. Treatment with Lb GP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. Lb GP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, Lb GP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration.

关键词： anti-inflammation inherited retinal diseases Lycium barbarum glycopeptide N-methyl-N-nitrosourea opsin photoreceptor reactive gliosis retinal degeneration retinitis pigmentosa rhodopsin

Molecular biomarkers for vascular cognitive impairment and dementia:the current status and directions for the future

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Neural Regeneration Research 2024年第12期19卷 2579-2580页

作者： Satoshi Hosoki Perminder SSachdev Centre for Healthy brain Ageing Discipline of Psychiatry and Mental HealthSchool of Clinical MedicineFaculty of Medicine and HealthUniversity of New South WalesSydneyAustralia Department of Neurology National Cerebral and Cardiovascular CenterOsakaJapan

Dementia is a syndrome with various underlying pathologies acting independently or in concert to cause cognitive *** development of disease-specific treatments and targeted prevention strategies requires precise clinical sub-typing via etiology and pathophysiological ***,recent research advances in biomarkers,especially for Alzheimer's disease(AD)diagnosis,have improved diagnostic precision for dementia.

关键词： prevention diagnosis impairment

A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function

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Journal of Genetics and Genomics 2024年第9期51卷 922-933页

作者： Ting Li Tursunjan Aziz Guangyuan Li Lin Zhang Jihua Yao Shunji Jia School of Life sciences Fudan UniversityShanghai 200438China State Key Laboratory of Membrane Biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular *** in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4(COXPD4),a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain(MRC)*** development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical *** this study,we construct a zebrafish tufm−/−mutant that closely resembles the COXPD4 syndrome,exhibiting compromised mitochondrial protein translation,dysfunctional mitochondria with oxidative phosphorylation defects,and significant metabolic suppression of the tricarboxylic acid *** this COXPD4 zebrafish model,we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing *** data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.

关键词： Tufm Mitochondria COXPD4 Disease model Zebrafish

Asiaticoside ameliorates type 2 diabetes mellitus in rats by modulating carbohydrate metabolism and regulating insulin signaling

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Asian Pacific Journal of Tropical Biomedicine 2024年第9期14卷 401-409页

作者： B.Prathap V.Satyanarayanan K.Duraipandian P.Subashree Department of Pharmacology Karpaga Vinayaga Institute of Medical Sciences and Research CenterMaduranthakam 603308Tamil NaduIndia Department of Pharmacology SRM Medical College Hospital and Research CenterKattankulathur 603211Tamil NaduIndia Department of Anatomy Karpaga Vinayaga Institute of Medical Sciences and Research CenterMaduranthakam 603308Tamil NaduIndia Department of Ophthalmology Karpaga Vinayaga Institute of Medical Sciences and Research CenterMaduranthakam 603308Tamil NaduIndia

Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in ***:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were ***:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase *** in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase ***,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to ***:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.

关键词： Asiaticoside Type 2 diabetes mellitus Metabolic disorders Carbohydrate metabolism Insulin signaling

Exploring lysosomal biology: current approaches and methods

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Biophysics Reports 2024年第2期10卷 111-120页

作者： Qiuyuan Yin Chonglin Yang State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan and center for Life sciences School of Life Sciences Yunnan University Southwest United Graduate School

Lysosomes are the degradation centers and signaling hubs in the cell. Lysosomes undergo adaptation to maintain cell homeostasis in response to a wide variety of cues. Dysfunction of lysosomes leads to aging and severe diseases including lysosomal storage diseases(LSDs), neurodegenerative disorders,and cancer. To understand the complexity of lysosome biology, many research approaches and tools have been developed to investigate lysosomal functions and regulatory mechanisms in diverse experimental systems. This review summarizes the current approaches and tools adopted for studying lysosomes, and aims to provide a methodological overview of lysosomal research and related fields.

关键词： Lysosome Method Cultured cell C. elegans Mice