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Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi Pradeepkiran Priyanka Rawat Arubala P.Reddy Erika Orlov PHemachandra Reddy department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA department of Nutritional sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA department of Pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA department of Public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

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Single-cell omics: experimental workflow, data analyses and applications

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Science China Life sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua center for Life sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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Decision making module based on stochastic magnetic tunnel junctions

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 202-209页

作者： Yifan Miao Li Zhao Yajun Zhang Zhe Yuan center for Advanced Quantum Studies and department of Physics Beijing Normal University Institute for Nanoelectric Devices and Quantum Computing Fudan University Interdisciplinary center for Theoretical Physics and Information sciences Fudan University

In biological neural systems, noise is ubiquitous but does not affect the correct decisions made in the complex cognitive ***-making in biological neural system is typically achieved by accumulating input information over a period of *** by recent developments in neurosciences, we design a decision-making module based on spintronic devices, utilizing superparamagnetic tunnel junctions as artificial neurons. The feasibility of this decision-making module is verified through circuit simulations. Taking a multi-layer perceptron as an example, the module significantly improves the accuracy of the perceptron in the handwritten digit recognition task. Furthermore, the spintronic decision-making module offers advantages over the conventional pooling methods, such as adaptive decision time, high performance and the absence of analog-to-digital conversion. The decision-making module is flexible to be integrated into artificial neural networks and provides a general yet effective solution to enhance performance against device noise.

关键词： neuromorphic computing spintronics magnetic tunnel junction neural networks

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Einstein Probe discovery of EP240408a: A peculiar X-ray transient with an intermediate timescale

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 222-240页

作者： Wenda Zhang Weimin Yuan Zhixing Ling Yong Chen Nanda Rea Arne Rau Zhiming Cai Huaqing Cheng Francesco Coti Zelati Lixin Dai Jingwei Hu Shumei Jia Chichuan Jin Dongyue Li Paul O’Brien Rongfeng Shen Xinwen Shu Shengli Sun Xiaojin Sun Xiaofeng Wang Lei Yang Bing Zhang Chen Zhang Shuang-Nan Zhang Yonghe Zhang Jie An David Buckley Alexis Coleiro Bertrand Cordier Liming Dou Rob Eyles-Ferris Zhou Fan Hua Feng Shaoyu Fu Johan P.U.Fynbo Lluis Galbany Saurabh W.Jha Shuaiqing Jiang Albert Kong Erik Kuulkers Weihua Lei Wenxiong Li Bifang Liu Mingjun Liu Xing Liu Yuan Liu Zhu Liu Chandreyee Maitra Alessio Marino Itumeleng Monageng Kirpal Nandra Jeremy Sanders Roberto Soria Lian Tao Junfeng Wang Song Wang Tinggui Wang Zhongxiang Wang Qingwen Wu Xuefeng Wu Dong Xu Yanjun Xu Suijian Xue Yongquan Xue Zijian Zhang Zipei Zhu Hu Zou Congying Bao Fansheng Chen Houlei Chen Tianxiang Chen Wei Chen Yehai Chen Yifan Chen Chenzhou Cui Weiwei Cui Yanfeng Dai Dongwei Fan Ju Guan Dawei Han Dongjie Hou Haibo Hu Maohai Huang Jia Huo Zhenqing Jia Bowen Jiang Ge Jin Chengkui Li Junfei Li Longhui Li Maoshun Li Wei Li Zhengda Li Tianying Lian Congzhan Liu Heyang Liu Huaqiu Liu Fangjun Lu Laidan Luo Jia Ma Xuan Mao Haiwu Pan Xin Pan Liming Song Hui Sun Yunyin Tan Qingjun Tang Yihan Tao Hao Wang Juan Wang Lei Wang Wenxin Wang Yilong Wang Yusa Wang Qinyu Wu Haitao Xu Jingjing Xu Xinpeng Xu Yunfei Xu Zhao Xu Changbin Xue Yulong Xue Ailiang Yan Haonan Yang Xiongtao Yang Yanji Yang Juan Zhang Mo Zhang Wenjie Zhang Zhen Zhang Zhen Zhang Ziliang Zhang Donghua Zhao Haisheng Zhao Xiaofan Zhao Zijian Zhao Hongyan Zhou Yilin Zhou Yuxuan Zhu Zhencai Zhu National Astronomical Observatories Chinese Academy of sciences School of Astronomy and Space sciences University of Chinese Academy of sciences Key Laboratory of Particle Astrophysics Institute of High Energy Physics Chinese Academy of sciences Institute of Space sciences (ICE) CSIC Institut d’Estudis Espacials de Catalunya (IEEC) Max Planck Institute for Extraterrestrial Physics Innovation Academy for Microsatellites Chinese Academy of sciences department of Physics University of Hong Kong School of Physics and Astronomy University of Leicester School of Physics and Astronomy Sun Yat-sen University department of Physics Anhui Normal University Shanghai Institute of Technical Physics Chinese Academy of sciences Physics department Tsinghua University Nevada center for Astrophysics University of Nevada Las Vegas department of Physics and Astronomy University of Nevada Las Vegas South African Astronomical Observatory department of Astronomy University of Cape Town department of Physics University of the Free State Université Paris Cité CNRS Astroparticule et Cosmologie Université Paris Cité CEA Paris-Saclay IRFU/DAp-AIM department of Astronomy Guangzhou University Cosmic Dawn center (DAWN) Niels Bohr Institute University of Copenhagen department of Physics and Astronomy Rutgers the State University of New Jersey Institute for Cosmic Ray Research The University of Tokyo ESA/ESTEC department of Astronomy School of Physics Huazhong University of Science and Technology INAF-Osservatorio Astrofisico di Torino Sydney Institute for Astronomy School of Physics The University of Sydney department of Astronomy Xiamen University Institute for Frontiers in Astronomy and Astrophysics Beijing Normal University department of Astronomy University of Science and Technology School of Astronomy and Space sciences University of Science and Technology of China Institute of Deep Space sciences Deep Space Exploration Laboratory department of Astronomy School of Physics and Astronomy Yunnan University Shanghai Astronomical Observatory Chi

We report the discovery of a peculiar X-ray transient,EP240408a,by Einstein Probe （EP） and follow-up studies made with EP,Swift,NICER,GROND,ATCA and other ground-based multiwavelength *** new transient was first detected with Wide-field X-ray Telescope （WXT） on board EP on April 8th,2024,manifested in an intense yet brief X-ray flare lasting for *** flare reached a peak flux of 3.9×10-9erg cm-2s-1in 0.5-4 ke V,～300 times brighter than the underlying X-ray emission detected throughout the *** and more precise follow-up observations by EP/FXT,Swift and NICER confirmed the finding of this new *** X-ray spectrum is non-thermal in 0.5-10 ke V,with a power-law photon index varying *** X-ray light curve shows a plateau lasting for ～4 d,followed by a steep decay till becoming undetectable ～10 d after the initial *** on its temporal property and constraints from previous EP observations,an unusual timescale in the range of 7-23 d is found for EP240408a,which is intermediate between the commonly found fast and long-term *** counterparts have been found in optical and near-infrared,with the earliest observation at 17 h after the initial X-ray detection,suggestive of intrinsically weak emission in these *** demonstrate that the remarkable properties of EP240408a are inconsistent with any of the transient types known so far,by comparison with,in particular,jetted tidal disruption events,gamma-ray bursts,X-ray binaries and fast blue optical *** nature of EP240408a thus remains an *** suggest that EP240408a may represent a new type of transients with intermediate timescales of the order of～10 *** detection and follow-ups of more of such objects are essential for revealing their origin.

关键词： X-ray transients ${\bm~{Einstein~~Probe}}$

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Emerging insights into the function of very long chain fatty acids at cerebellar synapses

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Neural Regeneration Research 2025年第6期20卷 1709-1710页

作者： Martin-Paul Agbaga Mohiuddin Ahmad department of Cell Biology and Ophthalmology University of Oklahoma Health Sciences Centerand Dean McGee Eye InstituteOklahoma CityOKUSA

Very long chain-saturated and-polyunsaturated fatty acids(VLC-SFA and VLC-PUFA, respectively) are a functionally important class of fatty acids containing 28 carbons or more in their acyl chain. They are synthesized by the elongation of very long fatty acids-4(ELOVL4) enzyme, expressed mainly in the brain, retina, skin, testes, and meibomian gland, where these fatty acids are found(Agbaga et al., 2008). Further, these organs exhibit tissuespecific VLC-PUFA and VLC-SFA biosynthesis and incorporation into complex lipids for specific functions. In the brain, skin, and Meibomian glands, the ELOVL4 mainly makes VLC-SFA, which are incorporated into complex sphingolipids. In the retina, the ELOVL4 makes VLC-PUFA that are incorporated into phosphatidylcholine, that are critical for visual function, while in testes and sperm, the VLC-PUFA are incorporated into sphingolipids that are critical for fertility(Yeboah et al., 2021).

关键词： functions function insight

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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 trial

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Science China Life sciences 2025年第1期 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 Hospital department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

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 LRP1B-del 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 LRP1B-del 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.

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Remaking a connection:molecular players involved in post-injury synapse formation

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Neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： Diogo Tomé Ramiro D.Almeida iBiMED-Institute of Biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CNC-center for Neuroscience and Cell Biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate *** several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after ***,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

关键词： viable injury instru

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon J.Brown Rafael J.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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Glial response in the midcingulate cortex in Huntington’s disease

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Neural Regeneration Research 2025年第1期20卷 207-208页

作者： Thulani H.Palpagama Andrea Kwakowsky center for Brain Research and department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： Huntington degeneration cortex

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Understanding the link between type 2 diabetes mellitus and Parkinson's disease:role of brain insulin resistance

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Neural Regeneration Research 2025年第11期20卷 3113-3123页

作者： Theodora Ntetsika Sergiu-Bogdan Catrina Ioanna Markaki department of Clinical Neuroscience Karolinska InstituteStockholmSweden department of Neurology Karolinska University HospitalStockholmSweden department of Molecular Medicine and Surgery Karolinska InstituteStockholmSweden center for Diabetes Academic Specialist CenterStockholmSweden center for Neurology Academic Specialist CenterStockholmSweden

Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic *** data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular *** insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological *** contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.

关键词： brain insulin resistance brain insulin signaling diabetes type 2 GLP-1 receptor agonists GLP-1 signaling insulin resistance insulin signaling neurodegeneration Parkinson's disease targeted therapy

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