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Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

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Neural Regeneration Research 2024年第3期19卷 657-662页

作者： Hang Yu Mingting Shao Xi Luo Chaoqin Pang Kwok-Fai So Jiandong Yu Li Zhang Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina Department of Neurosurgery The First Affiliated Hospital of Bengbu Medical CollegeBengbuShandong ProvinceChina School of Psychology Shanghai University of SportShanghaiChina

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain *** regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains ***,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of *** assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical *** of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain *** summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

关键词： blood-brain barrier cognition hippocampus interneurons long-term potentiation microglial cell neuroinflammation spatial memory temporal epilepsy treadmill exercise

基于转录组分析智力发育过程中性别差异的关键基因

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生理学报 2024年

作者：张家玮郑小丽周海倩朱朕韩威殷东敏脑功能基因组学教育部和上海市重点实验室华东师范大学生命科学学院

智力包括了逻辑推理能力、理解能力、自我意识能力、学习能力、计划创造能力和解决问题等能力。智力发育存在性别差异，女性智力的成熟时间往往早于男性。然而，关于智力发育性别差异的关键基因及其分子网络机制尚不清楚。迄今为止，全... 详细信息

智力包括了逻辑推理能力、理解能力、自我意识能力、学习能力、计划创造能力和解决问题等能力。智力发育存在性别差异，女性智力的成熟时间往往早于男性。然而，关于智力发育性别差异的关键基因及其分子网络机制尚不清楚。迄今为止，全基因组关联分析(Genome-Wide Association Studies,GWAS)发现了507个与智力显著相关的基因。本论文首先分析了BrainSpan人脑RNA-seq数据集中大脑在各个发育阶段的转录测序数据，发现在胚胎晚期，507个智力基因在大脑中的平均表达水平男性高于女性，而在青春期则相反。接着进一步构建了大脑中表达水平具有性别差异的智力基因的互作网络，包括胚胎晚期中男性高表达的智力基因互作网络HELP-M (intelligence genes with higher expression levels in prenatal males)、青春期女性高表达的智力基因互作网络HELP-F (intelligence genes with higher expression levels in pubertal females)。结果表明，这两个网络的关键基因均是Ep300和Ctnnb1。其中Ep300在HELP-M和HELP-F中调控了53个基因的转录，Ctnnb1在HELP-M和HELP-F中调控了45个基因转录，Ctnnb1在HELP-M以及Ep300在HELP-F中分别发挥更重要的作用。对不同发育时间的大鼠进行测序验证，发现在青春期雌性大鼠前额叶皮层中HPLE-F的智力基因和关键基因Ep300、Ctnnb1表达水平显著高于雄性大鼠，并且参与了神经发育等相关生物过程。以上结果揭示了在神经发育过程中表达水平具有性别差异的智力基因网络及其关键基因。

关键词：智力发育关键基因性别差异

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

Diverse nucleotide substitutions in rice base editing mediated by novel TadA variants

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Plant Communications 2024年第8期5卷 104-112页

作者： Man Yu Yongjie Kuang Chenyang Wang Xuemei Wu Shaofang Li Dawei Zhang Wenxian Sun Xueping Zhou Bin Ren Huanbin Zhou State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China Department of Plant Pathology China Agricultural UniversityBeijing 100193China Scientific Observing and Experimental Station of Crop Pests in Guilin Ministry of Agriculture and Rural AffairsGuilin 541399China Ministry of Education Key Laboratory for Bio-Resource and Eco-Environment College of Life ScienceState Key Laboratory of Hydraulics and Mountain River EngineeringSichuan UniversityChengdu 610064China State Key Laboratory of Vegetable Biobreeding National Engineering Research Center for VegetablesBeijing Vegetable Research CenterBeijing Academy of Agriculture and Forestry ScienceBeijing 100097China State Key Laboratory of Rice Biology Institute of BiotechnologyZhejiang UniversityHangzhou 310058China Key Laboratory of Gene Editing Technologies(Hainan) Ministry of Agricultural and Rural AffairsSanya 572024China

CRISPR-mediated base editors have been widely used to correct defective alleles and create novel alleles by artificial evolution for the rapid genetic improvement of *** editing capabilities of base editors strictly rely on the performance of various nucleotide modification *** with the welldeveloped adenine base editors(ABEs),cytosine base editors(CBEs)and dual base editors suffer from unstable editing efficiency and patterns at different genomic loci in rice,significantly limiting their ***,we comprehensively examined the base editing activities of multiple evolved TadA8e variants in *** found that both TadA-CDd and TadA-E27R/N46L achieved more robust C-to-T editing than previously reported hyperactive hAID*D,and TadA-CDd outperformed TadA-E27R/N46L.A C-to-G base editor(CGBE)engineered with TadA-CDd and OsUNG performed highly efficient C-to-G editing in rice compared with that of *** addition,a dual base editor constructed with a single protein,TadDE,enabled simultaneous,highly efficient C-to-T and A-to-G editing in ***,our results demonstrate that TadA8e derivatives improve both CBEs and dual base editors in rice,providing a powerful way to induce diverse nucleotide substitutions for plant genome editing.

关键词： CRISPR TadA variants cytosine base editing dual base editor rice

Novel heterozygous USH1C mutation impacts hair cell mechanotransduction and causes progressive hearing loss

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Science Bulletin 2024年第2期69卷 167-172页

作者： Yanyan Jia Gaogan Jia Luo Guo Nan Song Yu-Meng Wang Luoying Jiang Yilai Shu Yan Chen Shujia Zhu Huawei Li Wenyan Li ENT Institute and Otorhinolaryngology Department of Eye&ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China NHC Key Laboratory of Hearing Medicine(Fudan University) Shanghai 200031China The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science Fudan UniversityShanghai 200032China Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology Shanghai 201210China Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Department of Cardiology and Institute for Developmental and Regenerative Cardiovascular MedicineXinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200092China

Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.

关键词： mec hearing approximate

qSTA2-2,a novel QTL that contributes to seed starch synthesis in Zea mays L.

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Journal of Integrative Agriculture 2024年第4期23卷 1118-1133页

作者： Minghao Cai Xuhui Li Zhi Liang Jie Wang Delin Li Zhipeng Yuan Riliang Gu Jianhua Wang Li Li State Key Laboratory of Maize Bio-breeding/Key Laboratory of Crop Heterosis Utilization Ministry of Education/Beijing Innovation Center for Crop Seed Technology/College of Agronomy and BiotechnologyChina Agricultural UniversityBeijing 100193China Institute of Nanfan&Seed Industry Guangdong Academy of ScienceGuangzhou 510316China Institute of Crop Sciences Chinese Academy of Agricultural SciencesBeijing 100081China

The seed storage materials accumulate during seed development,and are essential for seed germination and seedling *** we employed two bi-parental populations of an F2:3 population developed from a cross of improved 220(I220,small seeds with low starch)and PH4CV(large seeds with high starch),as well as recombinant-inbred lines(RILs)of X178(high starch)and its improved introgression line I178(low starch),to identify the genes that control seed storage *** identified a total of 12 QTLs for starch,protein and oil,which explained 3.44-10.79%of the phenotypic *** them,qSTA2-1 identified in F2:3 and qSTA2-2 identified in the RILs partially overlapped at an interval of 7.314-9.554 Mb,and they explained 3.44-10.21%of the starch content variation,so they were selected for further *** mapping of qSTA2-2 with the backcrossed populations of ^(I220)/PH4CV in each generation narrowed it down to a 199.7 kb interval that contains 14 open reading frames(ORFs).Transcriptomic analysis of developing seeds from the near-isogenic lines(NILs)of ^(I220)/PH4CV(BC_(5)F_(2))showed that only 11 ORFs were expressed in 20 days after pollination(DAP)*** of them were upregulated and six of them were downregulated in NIL^(I220),and the differentially expressed genes(DEGs)between NIL^(I220) and NIL^(PH4CV) were enriched in starch metabolism,hormone signal transduction and glycosaminoglycan *** the eleven NIL^(I220) differential expressed ORFs,ORF4(Zm00001d002260)and ORF5(Zm00001d002261)carry 75%protein sequence similarity,both encodes an glycolate oxidase,were the possible candidates of *** analysis and validation indicated that mutation of the qSTA2-2 locus resulted in the dysfunction of ABA accumulation,the embryo/endosperm ratio and the starch and hormone levels.

关键词： QTL mapping seed starch transcriptomic analysis hormone

Dopamine Switches Affective States Under Acute Sleep Deprivation

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Neuroscience Bulletin 2024年第8期40卷 1205-1208页

作者： Zhou-Cai Luo Tian-Ming Gao State Key Laboratory of Organ Failure Research Key Laboratory of Mental Health of the Ministry of EducationGuangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired IntelligenceGuangdong-Hong Kong Joint Laboratory for Psychiatric DisordersGuangdong Province Key Laboratory of Psychiatric DisordersGuangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi DiseasesDepartment of NeurobiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

The transition of affective states manifests affective regulation,wherein individuals adaptively adjust their emotional states to cope with changes in the external environment,reflecting their sensitivity and adaptability to environmental *** process of affective state transition is complex,involving both instantaneous and persistent changes influenced by environmental,behavioral,and pharmacological *** underlying neural mechanisms encompass alterations in neurotransmitter release,neural circuit activity,and the plasticity of brain structures[1].

关键词： alterations Dopamine neural

Inferring the Effects of Protein Variants on Protein-Protein Interactions with Interpretable Transformer Representations

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Research 2024年第2期2023卷 473-489页

作者： Zhe Liu Wei Qian Wenxiang Cai Weichen Song Weidi Wang Dhruba Tara Maharjan Wenhong Cheng Jue Chen Han Wang Dong Xu Guan Ning Lin Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineSchool of Biomedical EngineeringShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Psychotic Disorders ShanghaiChina School of Information Science and Technology Institute of Computational BiologyNortheast Normal UniversityChangchunChina Department of Electrical Engineering and Computer Science University of MissouriColumbiaMO 65211USA Christopher S.Bond Life Sciences Center University of MissouriColumbiaMO 65211USA

Identifying pathogenetic variants and inferring their impact on protein-protein interactions sheds light on their functional consequences on *** by the availability of experimental data on the consequences of protein interaction,most existing methods focus on building models to predict changes in protein binding ***,we introduced MIPPI,an end-to-end,interpretable transformer-based deep learning model that learns features directly from sequences by leveraging the interaction data from *** was specifically trained to determine the types of variant impact(increasing,decreasing,disrupting,and no effect)on protein-protein *** demonstrate the accuracy of MIPPI and provide interpretation through the analysis of learned attention weights,which exhibit correlations with the amino acids interacting with the ***,we showed the practicality of MIPPI in prioritizing de novo mutations associated with complex neurodevelopmental disorders and the potential to determine the pathogenic and driving ***,we experimentally validated the functional impact of several variants identified in patients with such ***,MIPPI emerges as a versatile,robust,and interpretable model,capable of effectively predicting mutation impacts on protein-protein interactions and facilitating the discovery of clinically actionable variants.

关键词： consequences weights versatile

Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

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Neural Regeneration Research 2025年第2期20卷 326-342页

作者： Yi Ji Chaoyi Yang Xuerui Pang Yibing Yan Yue Wu Zhi Geng Wenjie Hu Panpan Hu Xingqi Wu Kai Wang Department of Neurology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders HefeiAnhui ProvinceChina Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health HefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina Department of Psychology and Sleep Medicine The Second Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and *** Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients *** transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological *** the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and *** has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological ***,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of *** study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated *** review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s *** mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also ***,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.

关键词： Alzheimer’s disease amyloid deposition apoptotic mechanisms biomarker neural regeneration neurodegeneration repetitive transcranial magnetic stimulation synaptic plasticity