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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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Reconstructing forest and grassland cover changes in China over the past millennium

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Science China Earth sciences 2025年第1期68卷 94-110页

作者： Fanneng HE Fan YANG Yafei WANG Key Laboratory of Land Surface Pattern and Simulation Institute of Geographic Sciences and Natural Resources Research Chinese Academy of Sciences Key research Institute of Yellow River Civilization and Sustainable Development Henan University University of Chinese Academy of sciences

Historical forest and grassland cover changes not only are critical indicators for quantifying ecological and environmental change processes but also serve as fundamental data for long-term climate change simulations and terrestrial ecosystem carbon emission assessments. However, because of limitations in historical data, quantitative estimations and spatially gridded reconstructions of these changes remain challenging, necessitating further methodological exploration. This study focused on China's present-day land area over the past millennium, objectively capturing the characteristics and drivers of forest and grassland cover changes. On this basis, using the forest transition theory and the space-for-time substitution method, we depicted the historical deforestation process as an inverted “S” curve and developed a model to reconstruct historical forest area changes based on the functional relationship between the forest area and population size dynamics. Subsequently, a gridded forest allocation model was established on the basis of deforestation tendencies. For the grassland cover, we implemented regionspecific methods, such as the cropland area deduction method and the habitat constraint method, to quantitatively reconstruct historical changes. Consequently, we obtained provincial forest and grassland area changes over the past millennium and mapped 10-km-resolution gridded data of forest and grassland cover. The results indicated the following.(1) The methods developed using population data as a proxy objectively reproduced the spatiotemporal evolution of forest and grassland cover in China over the past millennium. These feasible methods offer a novel pathway for the quantitative reconstruction of historical forest and grassland cover changes.(2) The data indicated that China's forest area generally decreased over the past millennium, characterized by a “decrease-then-increase” pattern. The forest area experienced three distinct phases: a slow decline(AD 1000

关键词： Land use and land cover change Forest Grassland Quantitative reconstruction Gridded reconstruction China historical period

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Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis

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Science China Life sciences 2025年

作者： Chuan Ye Xuemei Wang Jun Lin Chenyang Wu Yuhua Gao Chenghao Guo Yunxi Liao Ziyan Rao Shaodong Huang Weixuan Chen Ying Huang Jinpeng Sun Dongyu Zhao Changtao Jiang Center of basic Medical research Institute of Medical Innovation and ResearchPeking University Third Hospital Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Department of Biomedical Informatics School of Basic Medical SciencesPeking University State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Center for Obesity and Metabolic Disease research School of Basic Medical SciencesPeking University State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyPeking University Third Hospital National Clinical research Center for Obstetrics and Gynecology Peking University Third Hospital Department of Endocrinology and Metabolism Peking University Third Hospital Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University Department of Immunology School of Basic Medical SciencesPeking University

Adipogenesis is the healthy expansion of white adipose tissue (WAT),serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the ***,the identification of novel regulatory molecules in adipogenesis,specifically membrane receptors such as G protein-coupled receptors (GPCRs),holds significant clinical *** receptors can serve as viable targets for pharmaceuticals,offering potential for restoring metabolic homeostasis in individuals with *** utilized trajectory inference methods to analyze three distinct single-nucleus sequencing (sNuc-seq) datasets of adipose tissue and systematically identified GPCRs with the potential to regulate *** verification in primary adipose progenitor cells (APCs) of mice,we discovered that ADGRD1 promoted the differentiation of APCs,while GPR39 inhibits this *** the obese mouse model induced by a high-fat diet(HFD),both gain-of-function and loss-of-function studies validated that ADGRD1 promoted adipogenesis,thereby improving metabolic homeostasis,while GPR39 inhibited adipogenesis,leading to metabolic ***,through the analysis of 2,400 ChIP-seq data and 1,204 bulk RNA-seq data,we found that the transcription factors (TFs) MEF2D and TCF12 regulated the expression of ADGRD1and GPR39,*** study revealed the regulatory role of GPCRs in adipogenesis,providing novel targets for clinical intervention of metabolic dysfunction in obese patients.

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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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Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage

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Neural Regeneration research 2025年第4期20卷 1015-1030页

作者： Ruoyu Huang Qiuyu Pang Lexin Zheng Jiaxi Lin Hanxi Li Lingbo Wan Tao Wang Department of Forensic Science School of Basic Medicine and Biological SciencesSuzhou Medicine College of Soochow UniversitySuzhouJiangsu ProvinceChina

Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and *** plays a key role in the establishment and maintenance of the central nervous *** brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and *** brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental ***,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system *** hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and *** cholesterol levels are associated with the risk of intracerebral ***,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell *** cholesterol accumulation in the brain has been found after intracerebral *** this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell *** also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

关键词： cell death cholesterol metabolism intracerebral hemorrhage myelination therapeutic target

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Anomalous quality factor evolution of induced transparency in a virtualized coupled-oscillator system

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 148-155页

作者： Yunhan Yang Han Jia Tuo Liu Yuzhen Yang Jun Yang Key Laboratory of Noise and Vibration research Institute of Acoustics Chinese Academy of Sciences University of Chinese Academy of sciences State Key Laboratory of Acoustics Institute of Acoustics Chinese Academy of Sciences

The phenomenon of induced transparency, characterized by a high quality(Q) factor, holds significant importance in the fields of high-precision sensing, energy storage and wave manipulation. Conventional transparency systems are often constrained by the limited experimentally accessible parameter space and the lack of independent control over intrinsic parameters, thereby hindering advanced research on high-Q effects. Here we propose a virtualized coupled-oscillator system that enables reconfigurable induced transparency in the reflection spectrum. By virtually incorporating a pair of coupled oscillators into an individual acoustic meta-atom, we achieve the manipulation of induced transparency in a decoupled, wide-ranging, and elaborate manner. Exploiting the diverse evolutions across the intrinsic parameter space, we show experimentally a counter-intuitive increase in the Q-factor of the transparency window, which is attributed to the enhanced dissipation of the bright ***, a constant group delay at the center frequency is observed accompanying this evolution. Our work demonstrates an intriguing platform as well as a novel strategy to engineer high-Q induced transparency phenomenon, and paves the way towards applications in programmable acoustic sensors, filters and slow-wave devices.

关键词： induced transparency acoustic meta-atom high quality-factor scattering programmable intrinsic parameter

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Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

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Neural Regeneration research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang Department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Neurosurgery Surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

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Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

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Science China Life sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng Huang Zhijun Wu Baitao Liu Hongjie Huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang Yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe Laboratory of Cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key Laboratory of Sports Injuries Engineering research Center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University Health Science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences research unit of Medical Science research Management/basic and Clinical research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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Applications of in-situ solid-state nuclear magnetic resonance in methanol to olefins reaction

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Science China Chemistry 2025年第1期68卷 134-151页

作者： Jing Niu Shutao Xu Yingxu Wei Zhongmin Liu National Engineering research Center of Lower-Carbon Catalysis Technology Dalian Institute of Chemical PhysicsChinese Academy of Sciences State Key Laboratory of Catalysis Dalian Institute of Chemical Physics Chinese Academy of Sciences University of Chinese Academy of sciences

The methanol-to-olefins（MTO） reaction offers an alternative pathway for the production of low-carbon olefins from non-oil feedstocks. Fundamental research has been impeded by a lack of comprehensive understanding of its underlying mechanism,despite the significant progress made in industry. In-situ solid-state nuclear magnetic resonance（ss NMR） spectroscopy has emerged as a pivotal tool, offering crucial insights into key species under real-time operando conditions. Furthermore, the host–guest interaction between zeolites or surface species residing on zeolites and the reactant/active intermediates is revealed by the combination of in-situ13C MAS NMR and 2D correlation spectroscopy. Moreover, recent technological advancements in hyperpolarization（HP） methods, including HP129Xe NMR and dynamic nuclear polarization（DNP）, have significantly improved the sensitivity of ss NMR, enabling detailed structural and kinetic analysis as well as the detection of trace species. In this feature article, we summarized recent advancements in（in-situ） ss NMR spectroscopy applied to MTO reaction processes,encompassing mechanistic investigations at various stages and the intricate host–guest interactions. These theoretical insights into the dynamic evolution of MTO reactions lay a solid foundation for the optimization of catalytic processes and the development of efficient catalysts, thereby advancing the techniques towards more sustainable and economical production route for olefins.

关键词： MTO zeolites in-situ ssNMR reactive intermediates reaction mechanism

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MET receptor tyrosine kinase promotes the generation of functional synapses in adult cortical circuits

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Neural Regeneration research 2025年第5期20卷 1431-1444页

作者： Yuehua Cui Xiaokuang Ma Jing Wei Chang Chen Neha Shakir Hitesch Guirram Zhiyu Dai Trent Anderson Deveroux Ferguson Shenfeng Qiu basic Medical sciences University of Arizona College of Medicine-PhoenixPhoenixAZUSA Department of Medicine University of Arizona College of Medicine-PhoenixPhoenixAZUSA

Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse *** have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine *** investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing *** found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection *** findings are further corroborated by increased synaptic activity and transient generation of immature silent *** MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and *** data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult *** findings may have implications for regenerative therapy in aging and neurodegeneration conditions.

关键词： aging circuit connectivity cortical circuits molecular mechanisms neural regeneration neurodegeneration synapses

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