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disease and Economic Burden of Kashin-Beck disease—China,2021

China CDC weekly 2024年第2期6卷 40-44页

作者： Silu Cui Wenjun Que Zhe Jiao Qing Deng Xufeng Zhang Yanhong Cao Ning Liu Ailin Li Alphonse Sowanou Zhe Li Tuo Wang Yang Li Jun Yu Junrui Pei NHC key laboratory of Etiology and Epidemiology(Harbin Medical University) Key Laboratory of Etiology and EpidemiologyEducation Bureau of Heilongjiang ProvinceInstitute of Kashin-Beck Disease ControlCenter for Endemic Disease ControlChinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina NHC key laboratory of Etiology and Epidemiology(Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human HealthKey Laboratory of Etiology and EpidemiologyEducation Bureau of Heilongjiang ProvinceInstitute of Endemic Fluorosis ControlCenter for Endemic Disease ControlChinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina

What is already known about this topic?Kashin-Beck disease(KBD)is a chronic and degenerative osteoarthropathy characterized by cartilage *** is an endemic disease that is highly prevalent among the Chinese population and poses a significant health *** is added by this report?This is the first national report on the economic burden of KBD in *** to the data from 2021,KBD has caused significant disease and economic *** most substantial reduction in healthy life expectancy was observed among patients with degree II severity and those aged 60 years and older,resulting in a total indirect economic burden of 112.74 million Chinese Yuan(CNY).What are the implications for public health practice?The results of this study will contribute to informing the development of tailored prevention and control strategies by the *** strategies will include targeted policies and recommendations for appropriate healthcare and financial subsidies,which will be based on the demographic characteristics of the endemic areas.

关键词： prevention degeneration burden

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Targeting the adenosine A2A receptor for neuroprotection and cognitive improvement in traumatic brain injury and Parkinson's disease

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Chinese Journal of Traumatology 2024年第3期27卷 125-133页

作者： Yan Zhao Yuan-Guo Zhou Jiang-Fan Chen Department of Army Occupational disease State Key Laboratory of TraumaBurns and Combined InjuryResearch Institute of SurgeryDaping HospitalArmy Medical University.Chongqing400042China The Molecular Neuropharmacology laboratory and the Eye-brain Research Center The State Key Laboratory of OphthalmologyOptometry and Vision ScienceWenzhou Medical UniversityWenzhou325035Zhejiang ProvinceChina Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou325035Zhejiang ProvinceChina

Adenosine exerts its dual functions of homeostasis and neuromodulation in the brain by acting at mainly 2 G-protein coupled receptors,called A1 and A2A *** adenosine A2A receptor(A2AR)antagonists have been clinically pursued for the last 2 decades,leading to final approval of the istradefylline,an A2AR antagonist,for the treatment of OFF-Parkinson's disease(PD)*** approval paves the way to develop novel therapeutic methods for A2AR antagonists to address 2 major unmet medical needs in PD and traumatic brain injury(TBI),namely neuroprotection or improving *** this review,we first consider the evidence for aberrantly increased adenosine signaling in PD and TBI and the sufficiency of the increased A2AR signaling to trigger neurotoxicity and cognitive *** further discuss the increasing preclinical data on the reversal of cognitive deficits in PD and TBI by A2AR antagonists through control of degenerative proteins and synaptotoxicity,and on protection against TBI and PD pathologies by A2AR antagonists through control of ***,we provide the supporting evidence from multiple human prospective epidemiological studies which revealed an inverse relation between the consumption of caffeine and the risk of developing PD and cognitive decline in aging population and Alzheimer's disease ***,the convergence of clinical,epidemiological and experimental evidence supports the validity of A2AR as a new therapeutic target and facilitates the design of A2AR antagonists in clinical trials for disease-modifying and cognitive benefit in PD and TBI patients.

关键词： Receptor,Adenosine A2A Adenosine A2 receptor antagonists Parkinson's disease brain injuries,traumatic

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The pathogenesis of Parkinson’s disease and crosstalk with other diseases

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BIOCELL 2024年第8期48卷 1155-1179页

作者： TINGTING LIU DINGYOU GUO JIANSHE WEI Institute for brain Sciences Research School of Life SciencesHenan UniversityKaifeng475004China

In China,Parkinson’s disease(PD)is the second most prevalent central nervous system(CNS)degenerative illness affecting middle-aged and older *** disorders including resting tremor,bradykinesia,myotonia,postural instability,and gait instability are the predominant clinical *** two main types of PD are sporadic and familial,with sporadic PD being the more prevalent of the *** environment,genetics,mitochondrial dysfunction,oxidative stress,inflammation,protein aggregation and misfolding,loss of trophic factors,cell death,and gut microbiota may all have a role in the etiology of *** is inversely connected with other cancers and positively correlated with COVID-19,diabetes mellitus(DM),melanoma,and ischemic heart disease(IHD)*** disease progression,managing motor and non-motor symptoms,and avoiding and controlling dysfunction in the middle and later phases of the disease are the key areas of research and development for its ***,the development and progression of PD can be slowed down by using conventional pharmacology,natural items,and innovative *** article reviews the pathogenesis of PD,its correlations with other non-genetic diseases,and the research progress of drugs and technologies for alleviating PD.

关键词： Parkinson’s disease Mitochondrial dysfunction Oxidative stress Inflammation Cancer Therapies

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Current controversies in glia-to-neuron conversion therapy in neurodegenerative diseases

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Neural Regeneration Research 2024年第4期19卷 723-724页

作者： Peng Cao Jianan Li Zhuxi Liu Guobiao Liang Department of Neurosurgery General Hospital of the Northern Theater Command of Chinese People's Liberation Army key laboratory of Precision Medical Research on Major Chronic disease Shengjing Hospital of China Medical University

Loss of neurons and disruption of neural circuits are associated with many neurological diseases,including neurodegenerative diseases and mental *** most prevalent pathological feature of neurodegenerative diseases is the aggregate loss of certain neuronal *** example,the loss of dopamine(DA)neurons in the substantia nigra pars compacta has been defined as a pathological hallmark of Parkinson’s disease(PD;Kamath et al.,2022).

关键词： diseases degenerative al.

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Efficacy of exercise rehabilitation for managing patients with Alzheimer's disease

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Neural Regeneration Research 2024年第10期19卷 2175-2188页

作者： Dan Li Jinning Jia Haibo Zeng Xiaoyan Zhong Hui Chen Chenju Yi Department of Pathology The First Affiliated Hospital of Gannan Medical UniversityGanzhouJiangxi ProvinceChina Department of Pathology Huichang County People’s HospitalGanzhouJiangxi ProvinceChina School of Life Sciences Faculty of ScienceUniversity of Technology SydneyUltimoNSWAustralia Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong ProvinceChina Shenzhen key laboratory of Chinese Medicine Active Substance Screening and Translational Research ShenzhenGuangdong ProvinceChina Guangdong Provincial key laboratory of brain Function and disease GuangzhouGuangdong ProvinceChina

Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low-and middle-income countries.

关键词： Alzheimer's disease cerebrovascular function cognitive function epigenetic regulation exercise hippocampal neurogenesis mitochondria neuroinflammation neuronal plasticity

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Toward understanding the role of genomic repeat elements in neurodegenerative diseases

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Neural Regeneration Research 2025年第3期20卷 646-659页

作者： Zhengyu An Aidi Jiang Jingqi Chen Institute of Science and Technology for brain-Inspired Intelligence Fudan UniversityShanghaiChina MOE Frontiers Center for brain Science Fudan UniversityShanghaiChina MOE key laboratory of Computational Neuroscience and brain-Inspired Intelligence Fudan UniversityShanghaiChina Zhangjiang Fudan International Innovation Center ShanghaiChina

Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

关键词： Alzheimer's disease ataxia deep learning long-read sequencing neurodegeneration neurodegenerative diseases Parkinson's disease repeat element structural variant

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Single-cell transcriptomic atlas of goat ovarian aging

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Journal of Animal Science and Biotechnology 2024年第1期15卷 146-161页

作者： Dejun Xu Shuaifei Song Fuguo Wang Yawen Li Ziyuan Li Hui Yao Yongju Zhao Zhongquan Zhao Chongqing key laboratory of Herbivore Science College of Animal Science and TechnologySouthwest UniversityChongqing 400715China

Background The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process,and ovarian aging is shown by a decrease in the number and quality of ***,little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging,especially in ***,the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell *** For the first time,we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn,young and aging goats,and identified nine ovarian cell types with distinct gene-expression *** enrichment analysis showed that ovarian cell types were involved in their own unique biological processes,such as Wnt beta-catenin signalling was enriched in germ cells,whereas ovarian steroidogenesis was enriched in granulosa cells(GCs).Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system,oxidative phosphorylation,and ***,we identified a series of dynamic genes,such as AMH,CRABP2,THBS1 and TIMP1,which determined the fate of ***,FOXO1,SOX4,and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian *** This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell typespecific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.

关键词： Goat Granulosa cells Ovarian aging Single-cell transcriptomic

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Effects of Maillard reaction and its product AGEs on aging and age-related diseases

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Food Science and Human Wellness 2024年第3期13卷 1118-1134页

作者： Huan Peng Yuqi Gao Chenye Zeng Rui Hua Yannan Guo Yida Wang Zhao Wang Protein Science key laboratory of the Ministry of Education School of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China

Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino *** certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules *** this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective *** the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly *** on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle *** also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.

关键词： Maillard reaction Advanced glycation end products Physiologic aging Pathological aging Drug intervention

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Current therapies for osteoarthritis and prospects of CRISPR-based genome,epigenome,and RNA editing in osteoarthritis treatment

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Journal of Genetics and Genomics 2024年第2期51卷 159-183页

作者： Yuxi Chen Xiao Luo Rui Kang Kaixin Cui Jianping Ou Xiya Zhang Puping Liang MOE key laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdong 510275China Center for Reproductive Medicine The Third Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhouGuangdong 510630China

Osteoarthritis(OA)is one of the most common degenerative joint diseases worldwide,causing pain,disability,and decreased quality of *** balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of ***,there is a lack of effective therapeutic strategies for OA *** the development of CRISPR-based genome,epigenome,and RNA editing tools,OA treatment has been improved by targeting genetic risk factors,activating chondrogenic elements,and modulating inflammatory *** by cell therapy and in vivo delivery vectors,genome,epigenome,and RNA editing tools may provide a promising approach for personalized OA *** review summarizes CRISPR-based genome,epigenome,and RNA editing tools that can be applied to the treatment of OA and provides insights into the development of CRISPR-based therapeutics for OA ***,in-depth evaluations of the efficacy and safety of these tools in human OA treatment are needed.

关键词： Osteoarthritis Genome editing Epigenone editing RNA editing

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Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1147-1164页

作者： Yan Guo Pan Xiang Xiaojiao Sun Wei Liu Jiafeng Zhou Bin Yin Lin Hou Boqin Qiang Huiliang Li Pengcheng Shu Xiaozhong Peng Department of Molecular Biology and Biochemistry Institute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina State key laboratory of Common Mechanism Research for Major diseases Beijing 100005China Wolfson Institute for Biomedical Research University College LondonGower StreetLondon WC1E 6BTUK Chinese Institute for brain Research Beijing 102206China State key laboratory of Respiratory Health and Multimorbidity Beijing 100005China Institute of laboratory Animal Science Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits,and this process requires the proper recruitment of adaptor molecules to selectively activate downstream ***,we identified that DOK6,a member of the Dok(downstream of tyrosine kinases)family,is required for the maintenance of peripheral axons,and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice,manifested as impaired sensory,abnormal posture,paw deformities,blocked nerve conduction,and ***,Dok6 is highly expressed in peripheral neurons but not in Schwann cells,and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding,axon destruction,and hindered retrograde axonal ***,DOK6 acts as an adaptor protein for selectivitymediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and ***6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation,including MAP1B,Tau and Dynein for axonal transport,and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and *** finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.

关键词： impaired restrain peripheral

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