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Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

Neural Regeneration Research 2025年第4期20卷 990-1008页

作者： Lan Zhang Jingge Wei Xilei Liu Dai Li Xiaoqi Pang Fanglian Chen Hailong Cao Ping Lei Haihe laboratory of Cell Ecosystem Department of GeriatricsTianjin Medical University General HospitalTianjinChina Tianjin geriatrics Institute Tianjin Medical University General HospitalTianjinChina Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalNational Key Clinical SpecialtyTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjinChina Department of Urology Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institution Tianjin Medical University General HospitalTianjinChina

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent *** is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of *** microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive *** article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative *** article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial ***,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s *** findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

关键词： age aging Alzheimer’s disease astrocytes cognitive decline dementia gut microbiota gut–brain axis microbial metabolites neuroinflammation Parkinson’s disease

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An artificial intelligence diabetes management architecture based on 5G

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Digital Communications and Networks 2024年第1期10卷 75-82页

作者： Ruochen Huang Wei Feng Shan Lu Tao shan Changwei Zhang Yun Liu Department of geriatrics The First Affiliated Hospital of Nanjing Medical UniversityNanjing210096China Department of Information The First Afliated Hospital of Nanjing Medical UniversityNanjing210096China Department of Medical Informatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing211166China Department of Outpatient The First Affiliated Hospital of Nanjing Medical UniversityNanjing210096China Jiangsu key laboratory of Wireless Communications Nanjing University of Posts and TelecommunicationsNanjing210003China

Along with the development of 5G network and Internet of Things technologies,there has been an explosion in personalized healthcare *** the 5G and Artificial Intelligence(Al)is introduced into diabetes management architecture,it can increase the efficiency of existing systems and complications of diabetes can be handled more effectively by taking advantage of *** this article,we propose a 5G-based Artificial Intelligence Diabetes Management architecture(AIDM),which can help physicians and patients to manage both acute complications and chronic *** AIDM contains five layers:the sensing layer,the transmission layer,the storage layer,the computing layer,and the application *** build a test bed for the transmission and application ***,we apply a delay-aware RA optimization based on a double-queue model to improve access efficiency in smart hospital wards in the transmission *** application layer,we build a prediction model using a deep forest *** on real-world data show that our AIDM can enhance the efficiency of diabetes management and improve the screening rate of diabetes as well.

关键词： Diabetes 5G Artificial intelligence Deep forest Smart hospital ward

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Mitochondrial energy metabolism in diabetic cardiomyopathy:Physiological adaption,pathogenesis,and therapeutic targets

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Chinese Medical Journal 2024年第8期137卷 936-948页

作者： Wanlin Ye Kun Han Maodi Xie Sheyu Li Guo Chen Yanyan Wang Tao Li Department of Anesthesiology Laboratory of Mitochondria and MetabolismNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Anesthesiology West China Second University HospitalSichuan UniversityChengduSichuan 610041China key laboratory of Birth Defects and Related Diseases of Women and Children Sichuan UniversityMinistry of EducationChengduSichuan 610041China Department of Endocrinology and Metabolism Division of Guideline and Rapid RecommendationCochrane China CenterMAGIC China CenterChinese Evidence-Based Medicine CenterWest China HospitalSichuan UniversityChengduSichuan 610041China Nursing key laboratory of Sichuan Province West China HospitalSichuan UniversityChengduSichuan 610041China

Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes,which could eventually develop heart failure and leads to the death of the *** blood glucose control and medications to heart failure show beneficial effects on this disease,there is currently no specific treatment for diabetic *** the past few decades,the pathophysiology of diabetic cardiomyopathy has been extensively studied,and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic *** this review,we summarize the latest research in the field of diabetic cardiomyopathy,focusing on mitochondrial damage and adaptation,altered energy substrates,and potential therapeutic targets.A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.

关键词： Mitochondria Mitochondrial energy metabolism Diabetic cardiomyopathies Physiology Physiological adaption Pathogenesis Therapeutics

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Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease

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Chinese Medical Journal 2024年第4期137卷 450-456页

作者： Yuwen Zhao Lixia Qin Hongxu Pan Tingwei Song Yige Wang Xiaoxia Zhou Yaqin Xiang Jinchen Li Zhenhua Liu Qiying Sun Jifeng Guo Xinxiang Yan Beisha Tang Qian Xu Department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Neurology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Bioinformatics Center National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of geriatrics Xiangya HospitalCentral South UniversityChangshaHunan 410008China Centre for Medical Genetics and Hunan key laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China key laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangshaHunan 410008China

Background:Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease(PD)risk factors;however,no comprehensive analyses of these genes in patients with PD have been ***,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with ***:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 ***,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 ***:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,***-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset ***,the significance did not pass the Bonferroni ***,72 and 1730 common variants were found in the WES and WGS cohorts,***,single-variant logistic association analyses did not identify significant associations between common variants and ***:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese ***,we highlight the complexity of PD and the need for extensive research elucidating its etiology.

关键词： Parkinson’s disease Transcription factors Dopaminergic neurons Genetic Variants

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The m^(6)A reader YTHDC2 maintains visual function and retinal photoreceptor survival through modulating translation of PPEF2 and PDE6B

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Journal of Genetics and Genomics 2024年第2期51卷 208-221页

作者： Yeming Yang Xiaoyan Jiang Junyao Chen Lu Liu Guo Liu Kuanxiang Sun Wenjing Liu Xianjun Zhu Qiuyue Guan The Sichuan Provincial key laboratory for Human Disease Gene Study Center for Medical GeneticsSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of geriatrics Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019RU026) Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduSichuan 610072China Qinghai key laboratory of Qinghai Tibet Plateau Biological Resources Chinese Academy of Sciences and Qinghai Provincial Key Laboratory of Tibetan Medicine ResearchNorthwest Institute of Plateau BiologyXiningQinghai 810008China Henan Eye Institute Henan Eye HospitalPeople's Hospital of Zhengzhou UniversityHenan Provincial People's HospitalZhengzhouHenan 450003China

Inherited retinal dystrophies (IRDs) are major causes of visual impairment and irreversible blindness worldwide, while the precise molecular and genetic mechanisms are still elusive. N6-methyladenosine (m^(6)A) modification is the most prevalent internal modification in eukaryotic mRNA. YTH domain containing 2 (YTHDC2), an m^(6)A reader protein, has recently been identified as a key player in germline development and human cancer. However, its contribution to retinal function remains unknown. Here, we explore the role of YTHDC2 in the visual function of retinal rod photoreceptors by generating rod-specific Ythdc2 knockout mice. Results show that Ythdc2 deficiency in rods causes diminished scotopic ERG responses and progressive retinal degeneration. Multi-omics analysis further identifies Ppef2 and Pde6b as the potential targets of YTHDC2 in the retina. Specifically, via its YTH domain, YTHDC2 recognizes and binds m^(6)A-modified Ppef2 mRNA at the coding sequence and Pde6b mRNA at the 5′-UTR, resulting in enhanced translation efficiency without affecting mRNA levels. Compromised translation efficiency of Ppef2 and Pde6b after YTHDC2 depletion ultimately leads to decreased protein levels in the retina, impaired retinal function, and progressive rod death. Collectively, our finding highlights the importance of YTHDC2 in visual function and photoreceptor survival, which provides an unreported elucidation of IRD pathogenesis via epitranscriptomics.

关键词： Epitranscriptomics N^(6)-methyladenosine(m^(6)A) Inherited retinal dystrophies YTHDC2 Retina function Photoreceptor degeneration

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Non-proteolytic ubiquitination of HBx controls HBV replication

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Virologica Sinica 2024年第2期39卷 338-342页

作者： Xiangpeng Sheng Yi Yang Min Zhu Linlin Zhou Fang Zhu Yuanfei Zhu Siying Dong Hui Kong Honghua Wang Ji Jiang Mingyue Wan Mingyang Feng Qiang Deng Yumin Xu Qing You Ronggui Hu State key laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China State key laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China key laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Department of Thoracic Surgery Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China Shanghai key laboratory of Plant Molecular Sciences College of Life SciencesShanghai Normal UniversityShanghai 200234China Department of Pathogenic Biology West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China School of Medicine Guizhou UniversityGuiyang 550025China key laboratory of Medical Molecular Virology(MOE&moh) School of Basic Medical SciencesFudan UniversityShanghai 200032China Department of Hospital Infection Management Department of Infectious DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Dear Editor,Although effective vaccines and antiviral therapies are available,hepatitis B virus(HBV)infection is still a serious global health *** HBV infection remains the principal cause of liver cirrhosis and hepatocellular carcinoma(HCC).HBV is a small DNA virus,owning a~3.2 kb genome that encodes several proteins:viral DNA polymerase,core antigen(HBcAg),E antigen(HBeAg),three surface antigens(PreS1/PreS2/HBsAg),and a regulatory X protein(HBx)(Lamontagne et al.,2016).X protein,named for its lack of homology with any known proteins,is a 154 aa protein that plays an essential role in HBV biology and regulates the development of HCC(Yang et al.,2022).Although previous studies have strongly expanded our understanding of HBx,the regulation of HBx is not completely elucidated.

关键词： infection cirrhosis

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Intelligent design and construction of novel APN-based theranostic probe driven by advanced computational methods

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Chinese Chemical Letters 2024年第2期35卷 352-357页

作者： Yingli Zhu Jie Qian Kunqian Yu Jing Hou Yeshuo Ma Fei Chen Jie Dong Wenbin Zeng Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410083China National Engineering Research Center of Rice and Byproduct Deep Processing School of Food Science and EngineeringCentral South University of Forestry and TechnologyChangsha 410004China State key laboratory of Drug Research Drug Discovery and Design CenterShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of geriatrics Third Xiangya HospitalCentral South UniversityChangsha 410013China

Multifunctional molecules with both optical signal and pharmacological activity play an important role in drug development,disease diagnosis,and basic theoretical *** N(APN),as a representative tumor biomarker with anti-tumor potential,still lacks a high-precision theranostic probe specifically targeting *** this study,a novel quaternity design strategy for APN theranostic probe was *** proposed strategy utilizes advanced machine learning and molecular dynamics simulations,and cleverly employs the strategy of conformation-induced fluorescence recovery to achieve multi-objective optimization and integration of functional *** this strategy,a unique“Off-On”theranostic probe,ABTP-DPTB,was ingeniously constructed to light up APN through fluorescence restoration,relying on conformation-induced effects and solvent *** from the common diagnostic probes,the intelligent design with non-substrated linkage makes ABTP-DPTB for long-term in-situ *** fabricated probe was used for detecting and inhibiting APN in various environments,with a better in vitro inhibitory than golden-standard drug bestatin.

关键词： Theranostic probe Artificial intelligence Conformational restriction Fluorescence restoration Design strategy

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Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis Infection

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Infectious Diseases & Immunity 2024年第1期4卷 10-24页

作者： Cong Peng Fan Jiang Yinping Liu Yong Xue Peng Cheng Jie Wang Liang Wang Wenping Gong Hebei North University Zhangjiakou 075000Hebei ProvinceChina Beijing key laboratory of New Techniques of Tuberculosis Diagnosis and Treatment Senior Department of TuberculosisEighth Medical Center of PLA General HospitalBeijing 100091China Department of geriatrics Eighth Medical Center of PLA General HospitalBeijing 100091China Section of Health No.94804 Unit of the Chinese People's Liberation ArmyShanghai 200434China

Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and ***,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection ***,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic ***:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and *** responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead *** study was conducted from April 2022 to December 2022 in the SeniorDepartment of Tuberculosis at the 8thMedical Center of PLA General Hospital,*** samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic ***:A novel MEBDB,designated as CP19128P,was ***19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell *** silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune ***19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(P<0.001).Moreover,CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and *** IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from

关键词： Tuberculosis Latent tuberculosis infection Active tuberculosis Multiepitope-based diagnostic biomarker Bioinformatics:Immunoinformatics

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Epileptic brain network mechanisms and neuroimaging techniques for the brain network

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Neural Regeneration Research 2024年第12期19卷 2637-2648页

作者： Yi Guo Zhonghua Lin Zhen Fan Xin Tian Department of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Sichuan Provincial Center for Mental Health Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of geriatrics Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Neurology Chongqing Key Laboratory of NeurologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Epilepsy can be defined as a dysfunction of the brain network,and each type of epilepsy involves different brain-network changes that are implicated diffe rently in the control and propagation of interictal or ictal *** more detailed information on brain network alterations can help us to further understand the mechanisms of epilepsy and pave the way for brain network-based precise therapeutic approaches in clinical *** increasing number of advanced neuroimaging techniques and electrophysiological techniques such as diffusion tensor imaging-based fiber tra ctography,diffusion kurtosis imaging-based fiber tractography,fiber ball imagingbased tra ctography,electroencephalography,functional magnetic resonance imaging,magnetoencephalography,positron emission tomography,molecular imaging,and functional ultrasound imaging have been extensively used to delineate epileptic *** this review,we summarize the relevant neuroimaging and neuroelectrophysiological techniques for assessing structural and functional brain networks in patients with epilepsy,and extensively analyze the imaging mechanisms,advantages,limitations,and clinical application ranges of each technique.A greater focus on emerging advanced technologies,new data analysis software,a combination of multiple techniques,and the construction of personalized virtual epilepsy models can provide a theoretical basis to better understand the brain network mechanisms of epilepsy and make surgical decisions.

关键词： electrophysiological techniques epilepsy functional brain network functional magnetic resonance imaging functional near-infrared spectroscopy machine leaning molecular imaging neuroimaging techniques structural brain network virtual epileptic models

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ZIF-8 coated gold nanospheres: A multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells

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Nano Research 2024年第3期17卷 1772-1784页

作者： Miao Lei Weiye Cai Luetao Zou Bin Yu Lin Chen Yang Cao Shanlin Xiang Chao Song Jiandu Lei Wei Jiang Zhenming Hu Department of Orthopedics Orthopedic Laboratory of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University Luzhou 646699China Department of Orthopedics The Third Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Department of Radiology The First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China Department of Orthopedics Chongqing University Three Gorges HospitalChongqing 404000China Department of geriatrics The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550025China Beijing key laboratory of Lignocellulosic Chemistry College of Material Science and TechnologyBeijing Forestry UniversityBeijing 100083China

Photothermal therapy(PTT)has been widely used in the treatment of tumors,but its efficacy is greatly limited by the inability of precise drug delivery and the increase of heat shock proteins(HSPs)caused by high *** article describes a therapeutic strategy to enhance PTT with starvation therapy in conjunction with ferroptosis mechanism.A nanoparticle platform ZIF-8@GA was constructed by wrapping together glucose oxidase(GOX)and gold nanospheres(AuNPs)loaded with dihydroartemisinin(DHA)with zeolitic imidazolate framework-8(ZIF-8).This platform can take advantage of the micro-environment of osteosarcoma(OS)cells,featuring low pH and high reactive oxygen species(ROS),for precision drug *** can effectively catalyze glucose to produce gluconic acid and H_(2)O_(2),and DHA can also induce ROS production in OS *** produced by GOX and DHA can further generate lipid peroxidation(LPO)and lead to ferroptosis of OS *** the same time,ROS and LPO produced can inhibit the expression of HSPs,thereby increasing the therapeutic effect of *** vitro experiments show that the nanoparticles are pH and ROS responsive.1μg/mL GOX combined with 0.2μg/mL DHA promotes ferroptosis of OS cells,and increases the killing effect of near-infrared(NIR)on OS *** in vivo experiments showed that the nano drug-delivery platform combined with PTT can effectively inhibit the growth of OS ***,this study provides a new idea for the treatment of OS with biomaterials combined with various treatment methods.

关键词： zeolitic imidazolate framework-8(ZIF-8) gold nanospheres(AuNPs) photothermal therapy(PTT) starvation therapy ferroptosis

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