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DTD1 modulates synaptic efficacy by maintaining D-serine and D-aspartate homeostasis

Science China(Life sciences) 2025年第2期68卷 467-483页

作者： Xiao Liu Chaojuan Yang Zhuoran Lin Jianing Li Bin Yin Xuepei Lei Wei Han Boqin Qiang Pengcheng Shu Chen Zhang Xiaozhong Peng State KeyLaboratoryofCommon Mechanism Research for Major Diseases Departmentof Biochemistry&Molecular BiologyMedicalPrimate Research CenterNeuroscienceCenterInstituteof Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China State Key Laboratory of Respiratory Health and Multimorbidity Beijing 100005China institute of Laboratory Animal sciences Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China School of basic medical sciences Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijing 100069China Key Laboratoryof Biomechanics and Mechanobiology(Beihang University) Ministryof EducationBeijing AdvancedInnovation Center for Biomedical EngineeringSchoolof Engineering MedicineBeihang UniversityBeijing 100191China chinese institute for Brain Research Beijing 102206China

D-serine and D-aspartate are involved in N-methyl-D-aspartate receptor(NMDAR)-related physiological and pathological ***-t RNA deacylase 1(DTD1)may biochemically contribute to D-serine or D-aspartate ***,it is unclear thus far whether DTD1 regulates D-serine or D-aspartate content in neurobiological *** the present research,we found that DTD1 was essential to maintain the D-serine or D-aspartate homeostasis,which was consistent with the phenomenon that DTD1-deficiency resulted in changes in the quantity changes of functional NMDAR subunits in postsynaptic ***,DTD1 played a considerable role in regulating dendritic morphology and synaptic *** a consequence,DTD1 affected neurobiological events,including the synaptic strength of the CA3-to-CA1 circuit,dendritic spine density of hippocampal pyramidal neurons,and behavioral performance of mice in the Morris water *** findings highlight the important role of DTD1 in synaptic transmission,neuronal morphology,and spatial learning and memory and suggest an undisclosed mechanism of DTD1 that participates the regulation of D-serine or D-aspartate homeostasis in hippocampal neurons.

关键词： D-aminoacyl-tRNA deacylase 1 D-serine D-aspartate synaptic transmission neuronal morphology spatial learning and memory

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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina institute of basic medical sciences chinese academy of medical sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

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Neural Regeneration Research 2025年第6期20卷 1582-1598页

作者： Yanxi Li Jing Xue Yuejia Ma Ke Ye Xue Zhao Fangliang Ge Feifei Zheng Lulu Liu Xu Gao Dayong Wang Qing Xia Department of Biochemistry and Molecular Biology College of Basic Medical SciencesHarbin Medical UniversityHarbinHeilongjiang ProvinceChina College of basic medical sciences Harbin Medical UniversityHarbinHeilongjiang ProvinceChina basic medical institute Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Key Laboratory of Heilongjiang Province for Genetically Modified Animals Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be a

关键词： Alzheimer's disease cell self-renewal central nervous system memory microglia nerve regeneration neurodegenerative diseases neurogenesis RNA methylation

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Accelerated warming of High Mountain Asia predicted at multiple years ahead

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Science Bulletin 2025年第3期70卷 419-428页

作者： Shuai Hu Tianjun Zhou Bo Wu Key Laboratory of Earth System Numerical Modeling and Application Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China University of the chinese academy of sciences Beijing 100049China

High-Mountain Asia(HMA)is an important source of freshwater since it holds the largest reservoir of frozen water outside the polar *** feeds ten great rivers,ultimately supporting more than 2 billion ***,the threat of accelerated glacier melt,which is a consequence of unprecedented global warming since the early 1950s,threatens water resources in the surrounding *** predictions of the near-term temperature change and synergistic mass loss of glaciers are essential but challenging to implement because of the impacts of internal climate ***,based on large ensembles of state-of-the-art decadal climate prediction experiments,we provide evidence that the internally generated surface air temperature variations in HMA can be predicted multiple years in advance,and the model initialization has robust added value to the decadal prediction ***-time decadal forecasts suggest that the HMA will experience accelerated warming in 2025-2032,where the surface warming will increase by 0.98°C(0.67 to 1.33°C;5%to 95%range)relative to the reference period 1991-2020,which is equivalent to 1.75 times the observed warming during *** decadal predictability originates from extratropical Pacific decadal variability modes,which modulate the convective heating in the tropical Pacific and influence HMA via the eastward-propagating atmospheric Kelvin *** warming in the coming decade will likely increase the shrinkage of the glacier volume over the HMA by 1.4%.This change poses unprecedented challenges,including potential water scarcity,ecosystem disruption,and increased risk of natural disasters,to HMA and surrounding regions.

关键词： Decadal prediction High Mountain Asia Surface air temperature Pacific decadal variabilities Glacier

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Epigenetic regulation of the inflammatory response in stroke

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Neural Regeneration Research 2025年第11期20卷 3045-3062页

作者： Jingyi Liang Fei Yang Zixiao Li Qian Li School of basic medical sciences Capital Medical UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Laboratory for Clinical Medicine Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina chinese institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijingChina beijing Key Laboratory of Cancer Invasion and Metastasis Research Capital Medical UniversityBeijingChina

Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either *** mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral *** the inflammatory response has been shown to mitigate this cascade of events in experimental stroke ***,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for *** may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in *** acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic *** agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of ***,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke *** this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome *** also discuss promising molecular targets for stroke *** evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.

关键词： DNA methylation histone modification intracerebral hemorrhage ischemic stroke neuroinflammation neuroprotection non-coding RNA RNA methylation subarachnoid hemorrhage treatment

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Rosaceae phylogenomic studies provide insights into the evolution of new genes

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Horticultural Plant Journal 2025年第1期11卷 389-405页

作者： Lan Jiang Xiaoxu Li Kun Lyu Han Wang Zhiyuan Li Wang Qi Lin Zhang Yunpeng Cao Anhui Province Key Laboratory of Non-coding RNA basic and Clinical Transformation(Wannan medical College) Central LaboratoryYijishan Hospital of Wannan Medical CollegeWuhuAnhui 241000China beijing Life Science academy Beijing 102209China CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture Wuhan Botanical GardenChinese Academy of SciencesWuhanHubei 430074China Center of Economic Botany Core Botanical GardensChinese Academy of SciencesWuhanHubei 430074China Key Laboratory for Tobacco Gene Resources Tobacco Research InstituteChinese Academy of Agricultural SciencesQingdaoShangdong 266000China school of Life sciences Anhui Agricultural UniversityHefeiAnhui 230036China School of basic medical sciences Hubei University of Chinese MedicineWuhanHubei 430065China

Rosa banksiae,known as Lady Banks'rose,is a perennial ornamental crop and a versatile herb in traditional chinese *** the lack of genomic resources,we assembled a Hi Fi and Nanopore sequencing-derived 458.58 Mb gap-free telomere-to-telomere high-quality *** genome with a scaffold N50=63.90 *** genome of *** exhibited no lineage-specific whole-genome duplication compared with other *** phylogenomic analysis of 13 Rosaceae and Arabidopsis through a comparative genomics study showed that numerous gene families were lineage-specific both before and after the diversification of *** of these genes are candidates for new genes that have evolved from parental genes through fusion *** genes are divided into three types:Type-I and Type-II genes contain two parental genes that are generated by duplication,distributed in the same and different regions of the genome,respectively;and Type-III can only be detected in one parental ***,Type-I genes are found to have more relaxed selection pressure and lower Ks values than Type-II,indicating that these newly evolved Type-I genes may play important roles in driving phenotypic *** analysis exhibited that newly formed fusion genes can regulate the phenotype traits of plant growth and development,suggesting the functional significance of these *** study identifies new fusion genes that could be responsible for phenotype evolution and provides information on the evolutionary history of recently diverged species in the Rosa *** data represents the major progress in understanding the new fusion genes evolution pattern of Rosaceae and provides an invaluable resource for phylogenomic studies in plants.

关键词： Rosa banksiae Gap-free genome Rosaceae Phenotype Evolutionary patterns

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chinese Medicine for Treatment of COVID-19:A Review of Potential Pharmacological Components and Mechanisms

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chinese Journal of Integrative Medicine 2025年第1期31卷 83-95页

作者： XU Qian-qian YU Dong-dong FAN Xiao-dan CUI He-rong DAI Qian-qian ZHONG Xiao-ying ZHANG Xin-yi ZHAO Chen YOU Liang-zhen SHANG Hong-cai Key Laboratory of chinese Internal Medicine of Ministry of Education Dongzhimen HospitalBeijing University of Chinese MedicineBeijing100700China The Geriatrics Center First Affiliated HospitalAnhui University of Chinese MedicineHefei230031China School of medical Information Engineering Guangzhou University of Chinese MedicineGuangzhou51006China institute of basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing100700China

Coronavirus disease 2019(COVID-19)is an acute infectious respiratory disease that has been prevalent since December *** medicine(CM)has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention,improvement of clinical symptoms,and control of disease *** review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel *** the basis of sorting out experimental methods in vivo and in vitro,the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related *** aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19,and to provide a basis for the research and scientific,standardized treatment of COVID-19 with CM.

关键词： chinese medicine COVID-19 SARS-CoV-2 substance component mechanism experimental method

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/ OAK and CHOICE-01 trials

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Science China(Life sciences) 2025年第1期68卷 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General HospitalBeijing 100091China Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Burning Rock Biotech Guangzhou 510300China CAMS Key Laboratoryof Translational Research on LungCancer State Key Laboratoryof Molecular OncologyDepartmentof Medical OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China institute of basic Medicine and Cancer(IBMC) Chinese Academy of SciencesHangzhou 310000China Department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Hangzhou 310022China

In non-small cell lung cancers,the non-squamous and squamous subtypes(nsqNSCLC and sqNSCLC)exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor(ICI)-based *** our inhouse training cohort(n=85),the presence of the LRP1B deleterious mutation(LRP1B-del)was associated with longer and shorter progression-free survival(PFS)on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs(P=0.040)and sqNSCLCs(P=0.014),*** the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio(HR)=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del(HR=1.05,P=0.64).Conversely,sqNSCLCs without LRP1Bdel benefited more from atezolizumab(HR=0.60,P=0.002)than those with LRP1B-del(HR=1.30,P=0.31).Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1Bdel in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

关键词： non-squamous NSCLC squamous NSCLC LRP1B deleterious mutations predictive biomarker immune checkpoint inhibitor

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A Case Study on Garbage Code Redistribution Methods for Heart Failure at City Level by Two Approaches

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Biomedical and Environmental sciences 2025年第1期38卷 119-125页

作者： Liqun Liu Zemin Cai Xuewei Wang Chunping Wang Xiangyun Ma Xianfeng Meng Bofu Ning Ning Li Xia Wan institute of basic medical sciences Chinese Academy of Medical Sciences(CAMS)and School of Basic MedicinePeking Union Medical College(PUMC)Beijing 100005China State Key Laboratory of Respiratory Health and Multimorbidity Beijing 100005China School of Public Health Weifang Medical UniversityWeifang 261042ShandongChina Xuanwei Center for Disease Control and Prevention Xuanwei 655400YunnanChina Weifang Center for Disease Control and Prevention Weifang 261061ShandongChina

Cause of death surveillance data is most important for developing effective health policies,whose quality is crucially affected by the accuracy of the underlying cause of death(UCOD)provided in death *** World Health Organization(WHO)has clearly defined a UCOD as“the disease or injury which initiated the train of morbid events leading directly to death,or the circumstance of the accident or violence which produced the fatal injuries”[1].

关键词： injuries initiated distribution

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Gut microbial characteristics of the damp-heat constitution:a population-based multicenter cross-sectional study

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Journal of Traditional chinese Medicine 2025年第1期45卷 140-151页

作者： LI Tianxing ZHU Linghui WANG Xueke TANG Jun YANG Lingling PANG Guoming LI Huang WANG Liying DONG Yang ZHAO Shipeng LI Yingshuai LI Lingru institute of basic Theory for chinese Medicine China Academy of Chinese Medical Sciences National institute of TCM Constitution and Preventive Medicine Beijing University of Chinese Medicine the Second Clinical medical College Henan University of Chinese Medicine Department of Hepatobiliary Spleen and Stomach the First Affiliated Hospital of Zhejiang Chinese Medical University Henna Province Hospital of Traditional chinese Medicine Department of Endocrinology Kaifeng Hospital of traditional Chinese Medicine State Key Laboratory of Dampness Syndrome of chinese Medicine the Second Affiliated Hospital of Guangzhou University of Chinese Medicine College of chinese Medicine Beijing University of Chinese Medicine Graduate School of China academy of chinese medical sciences

OBJECTIVE: To investigate the difference in gut microbiota between population with damp-heat constitution(DHC) and balanced constitution(BC). METHODS: A multi-centered cross-sectional casecontrol study was conducted, which included 249 participants with damp-heat constitution or balanced constitution. Baseline information of participants was collected, and stool samples were collected for gut microbiota analysis. Principal coordinate analysis, linear discriminant analysis effect size analysis, receiver operating characteristic, random forest model, and phylogenetic investigation of communities by reconstruction of unobserved states methods were used to reveal the relationship between gut microbiota and the damp-heat constitution. RESULTS: Compared to those in the BC group, the richness and diversity of the microbiota, specifically those of several short-chain fatty acid producing genera such as Barnesiella, Coprobacter, and Butyricimonas, were significantly decreased in the DHC group. Regarding biological functions, flavonoid biosynthesis, propanoate metabolism, and nucleotide sugar metabolism were suppressed, while arachidonic acid metabolism and glutathione metabolism were enriched in the DHC group. Finally, a classifier based on the microbiota was constructed to discriminate between the DHC and BC populations. CONCLUSION: The gut microbiota of the DHC population exhibits significantly reduced diversity and is closely related to inflammation, metabolic disorders, and liver steatosis, which is consistent with clinical observations, thus serving as a potential diagnostic tool for traditional chinese medicine constitution discrimination.

关键词： PICRUSt Traditional chinese medicine constitution balanced constitution cross-sectional studies damp-heat constitution inflammatory microbiota multicenter study

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