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Dip2a regulates stress susceptibility in the basolateral amygdala

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Neural Regeneration Research 2025年第6期20卷 1735-1748页

作者： Jing Li Zixuan He Weitai Chai Meng Tian Huali Yu Xiaoxiao He Xiaojuan Zhu Key Laboratory of Molecular Epigenetics Ministry of Education Institute of Genetics and CytologyNortheast Normal UniversityChangchunJilin ProvinceChina

Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

关键词： 5-hydroxytryptamine acute restraint stress basolateral amygdala CaMKII neurons DIP2A metabolomics neurotransmitters principal component analysis stress susceptibility tryptophan

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 {1. 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

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

Effects of P301.-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 {1. 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(P301.)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301.-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301.-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 P301.-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301. 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.P301.-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301.-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,P301.-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301. pR5 mice TAU tauopathy tubulin code

Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第9期20卷 2556-2570页

作者： Yongting Lv Hongfu Li Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Medical genetics and Center for Rare disease Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Nanhu Brain-Computer Interface institute HangzhouZhejiang Province

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely *** principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial *** biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even *** these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and *** light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and ***,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal *** fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration *** DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related *** is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease *** the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable *** review summarizes the lat

关键词： amyotrophic lateral sclerosis biomarker blood biomarkers diagnosis glial fibrillary acidic protein neurofilament light chain prognosis TAR DNA-binding protein 43

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-1.-1.1.3.2%） in the piedmont plain and 224.9 kg ha-1.-1.1.2.7%） in the central plain,*** change accelerated downward transport velocity in the DVZ (from 0.81.0.47 to 0.89±0.55 m yr-1.n the piedmont plain,and from 0.24±0.1. to 0.92±0.1. m yr-1.n 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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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 (201.RU058) 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 1.0 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 1. 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, 1.1.are detected by LRS only. Fine-mapping identifies 1.6 independent candidate causal SNPs for three immune-related cellular phenotypes, with 1. 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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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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Dietary carbohydrate intake and risk of type 2 diabetes:a 1.-year prospective cohort study

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Science China Life Sciences 2025年

作者： Lu Gan Yi Yang Bin Zhao Kai Yu Kehua Guo Fang Fang Zhiguang Zhou Demetrius Albanes Jiaqi Huang Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University CSU-Sinocare Research Center for Nutrition and Metabolic Health Xiangya School of Public Health Central South UniversityFurong Laboratory Division of Cancer Epidemiology and genetics National Cancer Institute NIH Department of Health and Human Services School of Computer Science and Engineering Central South University institute of Environmental Medicine Karolinska Institute National Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University

Despite considerable research underscoring the importance of carbohydrate intake in relation to the risk of type 2 diabetes(T2D), a comprehensive assessment of this relationship is currently lacking. We aimed to examine the associations of various types and food sources of dietary carbohydrate intake with the risk of T2D, to evaluate potential effect modification by other factors, including genetic susceptibility,and to explore the potential mediators for such associations. The present study included 1.1.872 participants of the UK Biobank who were free of prevalent cancer, cardiovascular disease, or diabetes, and had at least one validated 24-h dietary recall assessment. Multivariableadjusted age-stratified Cox proportional hazard regression models were applied to estimate hazard ratios(HRs) and 95% confidence intervals(CI) for the associations of various types and food sources of dietary carbohydrate intake with risk of T2D. During a median follow-up of1..6 years, 4,1.6 incident cases of T2D were identified. In the multivariable-adjusted models, a greater intake of fiber, carbohydrates from whole grains, and carbohydrates from non-starchy vegetables was significantly associated with a lower risk of T2D(highest vs. lowest quantile, HR [95% CI]=0.70 [0.62–0.79], 0.74 [0.67–0.82], and 0.83 [0.75–0.92], respectively, all P for trend 1.31.[1.1.–1.48] and 1.1. [1.09–1.31., respectively, both P for trend 1.% lower risk of T2D(all P values 1..The observed associations were generally similar across population subgroups, including individuals with different genetic susceptibility to T2D. Mediation analyses of the inverse association between T

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