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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William j.Flerlage Mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn j.W.So Konstantin Feinberg Marina Manoraj jenny Cheung jennifer Zhang Kaveh Mirmoeini jPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

Unstable Allotetraploid Tobacco Genome due to Frequent Homeologous Recombination, -. Segmental Deletion, and Chromosome Loss

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Molecular Plant 2018年第7期11卷 914-927页

作者： Shumin Chen Feihong Ren Lei Zhang Yong Liu Xuejun Chen Yuanmei Li Liang Zhang Bin Zhu Pan.Zeng Zaiyun Li Robert M. larkin Hanhui Kuang Key Laboratory of Horticultural Plant Biology Ministry of Education Key Laboratory of Horticultural Crop Biology and Genetic Improvement (Central Region) MOA College of Horticulture and Forestry Sciences Huazhong Agricultural University Wuhan 430070 People's Republic of China Yunan Academy of Tobacco Agricultural Science Kunming Yunnan Province People's Republic of China College of Plant Science Huazhong Agricultural University Wuhan 430070 People's Republic of China These authors contributed equally to this article.

The types of mutations and their corresponding frequencies are difficult to measure in complex genomes. In this study, a high-throughput method was developed to identify spontaneous loss-of-function alleles for the resistance gene N and the transgenic avirulence gene P50 in allotetraploid tobacco. A total of 2134 loss- of-function alleles of the N gene were identified after screening 14 million F1 hybrids. Analysis of these mutants revealed striking evolutionary patterns for genes in polyploids. Only 14 of the loss-of-function mutations were caused by spontaneous point mutations or indels, while the others were caused by home- ologous recombination （with a frequency of 1/12 000） or chromosome loss （1/15 000）. Loss of the chromosome with the PS0 insertion occurred at a similar frequency （1/13 000）, and the frequency of spon- taneous segmental deletion in this chromosome was 1/16 000. Both homeologous recombination and chromosome loss considerably decreased the viability of the mutants. Our data suggest that the high mutation rate in polyploids is probably due to the occurrence of homeologous recombination and the toler- ance of large mutations such as chromosome loss in polyploid genomes. Frequent mutations tend to drive polyploids to extinction unless a novel mutation helps the polyploid to effectively compete with diploids or find a new ecological niche.

关键词： polyploid genome evolution homeologous recombination chromosome loss spontaneous mutation

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亚洲高山流域千年尺度地表剥蚀的制约因素

中国科学:地球科学 2025年第1期 75-94页

作者：杨业 Steven A.BINNIE 徐胜刘丛强 Tibor j.DUNAI 天津大学地球系统科学学院表层地球系统科学研究院 Institute of Geology and Mineralogy University of Cologne

本研究利用前人1233个亚洲高山流域沉积物宇宙成因核素10Be数据统一计算了地表剥蚀速率,以约束构造、气候和地形如何影响和控制地表剥蚀过程.基于高程数据逐个像元的核素产率,使用蒙特卡洛模拟方法重新计算了10Be流域剥蚀速率.剥蚀速率... 详细信息

本研究利用前人1233个亚洲高山流域沉积物宇宙成因核素10Be数据统一计算了地表剥蚀速率,以约束构造、气候和地形如何影响和控制地表剥蚀过程.基于高程数据逐个像元的核素产率,使用蒙特卡洛模拟方法重新计算了10Be流域剥蚀速率.剥蚀速率变化范围从（7.4±0.7）mm ka-1（1σ;青藏高原内部）到（9,646744+777）mm ka-1（1σ;青藏高原南部）跨四个数量级,中位数为186mm ka-1.逐个像元计算的核素产率与传统模型使用质心坐标和平均高程计算的核素产率相比,后者96.6%核素产率被低估,其中高程差越大越被低估.两种方法计算的产率偏差可达40%,究其原因可能是流域高程分布不均和核素产率随海拔和纬度呈非线性变化.通过量化地表剥蚀速率与构造、气候、地形和岩性之间的相关性将有助于推演未知流域的剥蚀速率.从局部小尺度分析,亚热带台湾岛地区剥蚀速率可能主要受降水和新构造驱动的山体滑坡影响,而降水变化范围较窄的青藏高原东部的剥蚀速率主要受控于地形;冰川覆盖的高原地区剥蚀速率受冰川作用影响,如帕米尔、青藏高原内部和南部地区;青藏高原内部剥蚀速率较低是因为较低的降水和较高的侵蚀基准面,从而限制了河流的下切和地表起伏度演化.与局部小尺度强调单一主控因素不同,本研究对亚洲高山流域宏观大尺度进行量化分析发现:（1）地形指标（包括坡度、地形起伏度和河道陡峭指数）与剥蚀速率在千年尺度呈现一致的幂函数关系,而非简单线性;（2）剥蚀速率与气候（包括与海拔相关的降水、温度和植被覆盖度）和新构造活动（地震核密度分布）呈近似幂函数关系,为次要控制因素;（3）岩性与剥蚀速率没有明显的相关性,可能受限于流域复杂的岩性混合和低分辨率的可侵蚀指数数据.

关键词： 10Be剥蚀速率气候变化构造抬升地形梯度亚洲高山流域

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DEVELOPMENT OF COMMON WHEAT GERM-PLASM RESISTANT TO BARLEY YELLOW DWARF VIRUS BY BIOTECHNOLOGY

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Science China Chemistry 1991年第9期34卷 1055-1062页

作者：辛志勇徐惠君陈孝林志珊周广和钱幼亭成卓敏 P. j. larkin P. BANKS R. APPELS B. GLARKE AND R. I. S. BRETTELL Institute of Crop Breeding and Cultivation GAAS Institute of Plant Protection GAAS CSIRO Division of Plant IndustryAustralia

Barley yellow dwarf virus (BYDV) is one of the most serious wheat diseases in China. So far no resistance has been described in common wheat. A certain level of BYDV resistance was found in thirteen Triticeae species. Thinopyrum intermedium, two octoploids derived from TH. intermedium/wheat, Zhong 4 awnless and TAF46, and one disomic addition line, L1 derived from TAF46, showed good resistance to BYDV by enzyme linked immunosorbent assay (ELISA). Two wheat/TA. intermedium translocation lines, CPI 119880 and CPI 119899, showing good BYDV resistance were developed from L1 by using both CSph mutant and tissue culture. It is found that their BYDV resistance was controlled by a single dominant gene. Two cDNA probes pEleAcc3 and pPjN8 (E1-T1) were screened for detecting Th. intermedium DNA in wheat background. A specific band for the DNA of Th. intermedium and its derivatives was found in Southern hybridization. It is also possible to determine the size of the alien segment by comparing the relative density of the specific band. Therefore, this can be used as a marker to identify the BYDV resistance in wheat breeding program.

关键词： wheat yellow dwarf virus barley yellow dwarf virus Thinopyrum intermedium addition line translocation line cDNA probe.

Deciphering Water Oxidation Catalysts: The Dominant Role of Surface Chemistry over Reconstruction Degree in Activity Promotion

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NANO-MICRO LETTERS 2025年第1期17卷 1-15页

作者： An, Li Li, jianyi Sun, Yuanmiao Zhu, jiamin Seow, justin Zhu Yeow Zhang, Hong Zhang, Nan Xi, Pinxian Xu, Zhichuan j. Yan, Chun-Hua Lanzhou Univ Frontiers Sci Ctr Rare Isotopes Key Lab Nonferrous Met Chem & Resources Utilizat G State Key Lab Appl Organ ChemColl Chem & Chem Eng Lanzhou 730000 Peoples R China Nanyang Technol Univ Sch Mat Sci & Engn Singapore 639798 Singapore Chinese Acad Sci Fac Mat Sci & Energy Engn Shenzhen Inst Adv Technol Inst Technol Carbon Neutral Shenzhen 518055 Peoples R China Yunnan Univ Natl Ctr Int Res Photoelect & Energy Mat Electron Microscopy Ctr Sch Mat & EnergyKey Lab Electromagnet Mat & Devic Kunming 650091 Peoples R China Baotou Res Inst Rare Earths State Key Lab Baiyunobo Rare Earth Resource Res & Baotou 014030 Peoples R China Peking Univ Beijing Natl Lab Mol Sci State Key Lab Rare Earth Mat Chem & Applicat PKU HKU Joint Lab Rare Earth Mat & Bioinorgan Chem Beijing 100871 Peoples R China

Demonstrate that the key factor to determine the activity of reconstructed surfaces is the surface chemistry, instead of reconstruction degree using the popular perovskite LaNi1-xFexO3 oxides as model *** content can influence both the surface reconstruction degree, the activation degree, and the activity of reconstructed *** oxygen evolution reaction activity of reconstructed catalysts is primarily governed by the chemistry of the reconstructed surface species. Water splitting hinges crucially on the availability of electrocatalysts for the oxygen evolution reaction. The surface reconstruction has been widely observed in perovskite catalysts, and the reconstruction degree has been often correlated with the activity enhancement. Here, a systematic study on the roles of Fe substitution in activation of perovskite LaNiO3 is reported. The substituting Fe content influences both current change tendency and surface reconstruction degree. LaNi0.9Fe0.1O3 is found exhibiting a volcano-peak intrinsic activity in both pristine and reconstructed among all substituted perovskites in the LaNi1-xFexO3 (x = 0.00, 0.10, 0.25, 0.50, 0.75, 1.00) series. The reconstructed LaNi0.9Fe0.1O3 shows a higher intrinsic activity than most reported NiFe-based catalysts. Besides, density functional theory calculations reveal that Fe substitution can lower the O 2p level, which thus stabilize lattice oxygen in LaNi0.9Fe0.1O3 and ensure its long-term stability. Furthermore, it is vital interesting that activity of the reconstructed catalysts relied more on the surface chemistry rather than the reconstruction degree. The effect of Fe on the degree of surface reconstruction of the perovskite is decoupled from that on its activity enhancement after surface reconstruction. This finding showcases the importance to customize the surface chemistry of reconstructed catalysts for water oxidation.

关键词： Oxygen evolution reaction Perovskite oxides Doping Activation and reconstruction

Spin-correlation function of the fully frustrated Ising model and ±j Ising spin glass on a square lattice

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Chinese Physics B 2013年第6期22卷 549-552页

作者： M Y Ali j Poulter Department of Mathematics Faculty of ScienceMahidol University

In this work we study the correlation function of the ground state of a two-dimensional fully frustrated Ising model as well as spin glass. The Pfaffian method is used to calculate free energy and entropy as well as the correlation function. We estimate the exponent of spin correlation function for the fully frustrated model and spin glass. In this paper an overview of the latest results on the spin correlation function is presented.

关键词： spin glass correlation function exponent square lattice

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