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Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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Neural Regeneration research 2025年第5期20卷 1407-1408页

作者： Daniel Adam Felix Langerscheidt Hans Zempel Institute of Human genetics University Hospital CologneCologneGermany Center for molecular Medicine Cologne(CMMC) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

New glucocerebrosidase antibodies can advance research in the field of neurodegenerative disorders

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Neural Regeneration research 2025年第4期20卷 1085-1086页

作者： Charis Ma Krystyna Rytel Yu Chen Ellen Sidransky Medical genetics Branch National Human Genome Research InstituteNational Institutes of HealthBethesdaMDUSA

In medical research,there are times when the introduction of a new tool can launch scientific discovery in new *** antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)research,the dearth of validated antibodies for different applications has impeded progress in studies of disease pathogenesis and therapeutic *** recent introduction of new,rigorously evaluated antibodies can now propel research into the link between glucocerebrosidase and Parkinson’s disease(PD)as well as aspects of the pathobiology of Gaucher disease(Jong et al.,2024).

关键词： antibodies cerebro

Epigenetics in the modern era of crop improvements

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Science China Life Sciences 2025年

作者： Yan Xue Xiaofeng Cao Xiangsong Chen Xian Deng Xingwang Deng Yong Ding Aiwu Dong Chengguo Duan Xiaofeng Fang Lei Gong Zhizhong Gong Xiaofeng Gu Chongsheng He Hang He Shengbo He Xinjian He Yan He Yuehui He Guifang Jia Danhua Jiang Jianjun Jiang Jinsheng Lai Zhaobo Lang Chenlong Li Qing Li Xingwang Li Bao Liu Bing Liu Xiao Luo Yijun Qi Weiqiang Qian Guodong Ren Qingxin Song Xianwei Song Zhixi Tian Jiawei Wang Yuan Wang Liang Wu Zhe Wu Rui Xia Jun Xiao Lin Xu Zhengyi Xu Wenhao Yan Hongchun Yang Jixian Zhai Yijing Zhang Yusheng Zhao Xuehua Zhong Daoxiu Zhou Ming Zhou Yue Zhou Bo Zhu Jiankang Zhu Qikun Liu College of Life Sciences Institute of Life Science and Green Development Hebei University Biotechnology research Institute Chinese Academy of Agricultural Sciences College of Biology Hunan Key Laboratory of Plant Functional Genomics and Developmental Regulation Hunan Engineering and Technology Research Center of Hybrid Rapeseed Hunan University Institute of Advanced Agricultural Sciences School of Advanced Agricultural Sciences Peking University State Key laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Guangdong Laboratory for Lingnan Modern Agriculture South China Agricultural University National Institute of Biological Sciences Key laboratory of Seed Innovation Institute of Genetics and Developmental Biology Chinese Academy of Sciences School of Advanced Agricultural Sciences Peking-Tsinghua Center for Life Sciences Peking University Synthetic and Functional Biomolecules Center Beijing National Laboratory for Molecular Sciences Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education College of Chemistry and Molecular Engineering Peking University Key laboratory of Seed Innovation State Key Laboratory of Plant Genomics and National Center for Plant Gene Research Institute of Genetics and Developmental Biology Chinese Academy of Sciences State Key laboratory of Wheat Improvement Peking University Institute of Advanced Agricultural Sciences Shandong Laboratory of Advanced Agricultural Sciences in Weifang State Key laboratory of Crop Stress Adaptation and Improvement School of Life Sciences Henan University State Key laboratory of Maize Bio-breeding National Maize Improvement Center Department of Plant Genetics and Breeding China Agricultural University Frontiers Science Center for molecular Design Breeding China Agricultural University Center for Crop Functional Genomics and molecular Breeding China Agricultural University Sanya Institute of China Agricultural University Hainan Yazhou Bay Seed laboratory Institute of Advan

Epigenetic mechanisms are integral to plant growth, development, and adaptation to environmental stimuli. Over the past two decades,our comprehension of these complex regulatory processes has expanded remarkably, producing a substantial body of knowledge on both locus-specific mechanisms and genome-wide regulatory patterns. Studies initially grounded in the model plant Arabidopsis have been broadened to encompass a diverse array of crop species, revealing the multifaceted roles of epigenetics in physiological and agronomic traits. With recent technological advancements, epigenetic regulations at the single-cell level and at the large-scale population level are emerging as new focuses. This review offers an in-depth synthesis of the diverse epigenetic regulations, detailing the catalytic machinery and regulatory functions. It delves into the intricate interplay among various epigenetic elements and their collective influence on the modulation of crop traits. Furthermore, it examines recent breakthroughs in technologies for epigenetic modifications and their integration into strategies for crop improvement. The review underscores the transformative potential of epigenetic strategies in bolstering crop performance, advocating for the development of efficient tools to fully exploit the agricultural benefits of epigenetic insights.

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Evaluating the impacts of converting grain to vegetable fields on nitrate transport in the deep vadose zone of the North China Plain

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Journal of Geographical Sciences 2025年第1期35卷 189-212页

作者： LIU Meiying MIN Leilei WU Lin ZHANG Yucui QI Yongqing WANG Shiqin LIU Binbin GENG Di SHEN Yanjun Hebei Key laboratory of Water-Saving Agriculture Key Laboratory of Agricultural Water ResourcesCenter for Agricultural Resources ResearchInstitute of Genetics and Developmental BiologyCAS School of Advanced Agricultural Sciences University of Chinese Academy of Sciences

Nitrate （NO3-） accumulation and transport processes in the thick vadose zone affect the evolution of the groundwater NO3-content in intensive agricultural *** land-use change （ALUC）,typically accompanied by substantial alterations in nitrogen fertilizer application and irrigation practices,is an important influencing *** study evaluated the changes in NO3-accumulation and transport in the deep vadose zone （DVZ,below the root zone）,and the groundwater NO3-content associated with ALUC from grain to vegetable fields in the North China Plain （NCP）.The ALUC from grain to vegetable resulted in nitrate–nitrogen （NO3--N） accumulation in DVZ increased by 235.5 kg ha-1m-1（163.2%） in the piedmont plain and 224.9 kg ha-1m-1（102.7%） in the central plain,*** change accelerated downward transport velocity in the DVZ (from 0.81±0.47 to 0.89±0.55 m yr-1in the piedmont plain,and from 0.24±0.12 to 0.92±0.12 m yr-1in the central plain) and increased NO3-leaching *** transport velocity and leaching fluxes resulted in chemical N-fertilizer entering the aquifer in several areas in the piedmont *** impact of the agricultural activity intensity changes,accompanied by the ALUC,on groundwater quantity and quality should be considered in similar regions.

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Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel Institute of Human genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

TRMT6 and TRMT61A facilitated acute pancreatitis severity via regulation of neutrophil function

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Science China Life Sciences 2025年

作者： Yuan Dong Li Su Sin Man Lam Cen Yan Yalan Deng Guotao Lu Jinkui Yang Guanghou Shui Yingmei Feng Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Department of Science and Development Beijing Youan HospitalCapital Medical University laboratory for Clinical Medicine Capital Medical University Neuroscience research Institute Peking University Center of Medical and Health AnalysisPeking University State Key laboratory of molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of Sciences Pancreatic Center Department of GastroenterologyAffiliated Hospital of Yangzhou UniversityYangzhou University Beijing Key laboratory of Diabetes research and Care Department of EndocrinologyBeijing Tongren HospitalCapital Medical University

Dear Editor,Type 2 diabetes mellitus (T2DM) has been identified as a risk factor for increased severity in acute pancreatitis (AP)(Mikóet al,2018).However,to date,no studies have simultaneously included healthy individuals,T2DM patients,and AP patients to investigate which diabetes-associated metabolites are linked to AP severity.

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Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

Therapeutic potential of exercise-hormone irisin in Alzheimer's disease

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Neural Regeneration research 2025年第6期20卷 1555-1564页

作者： Eunhee Kim Rudolph ETanzi Se Hoon Choi genetics and Aging research Unit MassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMAUSA McCance Center for Brain Health Massachusetts General HospitalBostonMAUSA

Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.

关键词： Alzheimer's disease exercise fibronectin typeⅢdomain-containing protein 5(FNDC5) irisin

Long-read sequencing reveals novel genetic polymorphisms in the major histocompatibility complex region and their impacts on the Han Chinese population

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Science China Life Sciences 2025年

作者： Cong Zhou Tingting Gong Shuhang Li Li Jin Shaohua Fan State Key laboratory of Genetic Engineering Lab for Evolutionary Synthesis School of Life Sciences Human Phenome Institute Fudan University research Unit of Dissecting the Population genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058) Chinese Academy of Medical Sciences

Human leukocyte antigen(HLA) genes in the major histocompatibility complex(MHC) region are crucial for immunity and are associated with numerous diseases and phenotypes. The MHC region's complexity and high genetic diversity make it challenging to analyze using short-read sequencing(SRS) technology. We sequence the MHC region of 100 Han Chinese individuals using both long-read sequencing(LRS) and SRS platforms at approximately 30X coverage to study genetic alterations and their potential functional impacts. LRS provides significantly greater coverage of the MHC region and eight classical HLA genes, particularly at the HLA-DRB1 locus, compared with SRS. We detect 78,249 single nucleotide polymorphisms(SNPs) using LRS, with 26.0% undetectable by SRS. Based on SNP and inferred HLA allele types, we construct an LRS-based MHC reference panel for the Han Chinese, containing approximately 2.6 times more genetic variants than the SRS-based Han-MHC reference panel. A phenome-wide association study assessing 26,024 phenotypes across 15 categories identifies significant associations for 7,879 independent variants(including 809 LRS-specific SNPs) with 409 phenotypes in nine categories. This analysis reveals 24 unreported HLA allele associations in the bioelectric and cellular categories. The conditional analysis identifies 530independent signals across the 409 phenotypes, including 28 previously unreported signals of eight classical HLA genes associated with 33phenotypes. Of the top-associated SNPs, 191 are detected by LRS only. Fine-mapping identifies 126 independent candidate causal SNPs for three immune-related cellular phenotypes, with 17 detected exclusively by LRS. Our study reveals previously unreported variants and their functional impacts in the MHC region, enhancing our understanding of genetic diversity and its potential biological implications in the Han Chinese population.

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