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Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

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Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

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Journal of Pharmaceutical Analysis 2024年第3期14卷 348-370页

作者： Binbin Zhao Dongfeng Wei Qinghua Long Qingjie Chen Fushun Wang Linlin Chen Zefei Li Tong Li Tao Ma Wei Liu Linshuang Wang Caishui Yang Xiaxia Zhang Ping Wang Zhanjun Zhang State Key Laboratory of Cognitive neuroscience and Learning&IDG/McGovern institute for Brain Research Beijing Normal UniversityBeijing100875China institute of Gerontology Hubei University of Chinese MedicineWuhan430065China institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing100700China Medical School Hubei Minzu UniversityEnshiHubei445000China HuBei University of Science and Technology XianningHubei437100China institute of Brain and Psychological Science Sichuan Normal UniversityChengdu610066China Key Laboratory of Traditional Chinese Medicine Resource and Compound Prescription Ministry of EducationHubei University of Chinese MedicineWuhan430065China Dongfang Hospital Beijing University of Chinese MedicineBeijing100078China Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijing100700China School of Systems Science Beijing Normal UniversityBeijing100875China BABRI Centre Beijing Normal UniversityBeijing100875China

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with alterations in synaptic currents and mitochondrial ***,the specific associations between these pathological changes remain *** this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro *** investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,transmission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assessment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular *** results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD ***,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic *** cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular *** intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and ***,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial *** conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

关键词： Alzheimer's disease Synaptic currents Mitophagy Mitochondrial fusion and fission Dengzhan Shengmai capsules

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Solar-powered miniature robot for on-site oil spill treatment under magnetic steering

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Science China(Technological Sciences) 2024年第7期67卷 2164-2175页

作者： WANG Ben CHEN YunRui WANG Yun JI FengTong LI HongYuan NIU ShiChao HAN ZhiWu ZHANG YaBin GUO ZhiGuang College of chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518060China State Key Laboratory of Featured Metal Materials and Life-cycle Safety for Composite Structures Ministry of Education Key Laboratory of New Processing Technology for Nonferrous Metals and Materialsand School of ResourcesEnvironment and MaterialsGuangxi UniversityNanning 530004China Key Laboratory for Bionic Engineering Ministry of Education Jilin UniversityChangchun 130022China Hubei Collaborative Innovation Centre for Advanced Organic Chemical Materials Ministry of Education Key Laboratory for the Green Preparation and Application of Functional MaterialsHubei UniversityWuhan 430062China Wellcome Trust/Cancer Research UK Gurdon institute University of CambridgeCambridge CB21QNUK Department of Physiology Development and NeuroscienceUniversity of CambridgeCambridge CB21QNUK State Key Laboratory for Turbulence and Complex Systems Department of Mechanics and Engineering ScienceBeijing Innovation Center for Engineering Science and Advanced TechnologyCollege of EngineeringPeking UniversityBeijing 100871China

Walking on the water surface is an effective method for miniature robots to transport payloads with dramatically decreased interfacial drag. Current aquatic robots reported are generally actuated by a beam of focused light that can trigger asymmetrical deformation, enabling the directional movement through horizontal momentum transfer of photoinduced actuation force to the water. However, the operations are heavily dependent on manual manipulation of the focused light, making the long-term actuation and application of the aquatic robots in vast scenarios challenging. Herein, we developed a kind of water striderinspired robot that can autonomously manage the motion on the water surface under solar irradiation, with their direction steerable by a magnetic field. The motion of this bioinspired robot on the water surface was achieved by the use of a solar cell panel as a driving module to enable propulsive motion based on the conversion of light-electric-mechanical energies. The superhydrophobic design of its leg surfaces enables the aquatic robots with weight-bearing and drag-reducing abilities. With the assistance of magnetic navigation, the bioinspired robot can continuously and controllably locomote to the oily spill floating on the water body and collect them with high efficiency. For further demonstration, the treatment of oil spills in a campus pool with high efficiency has also been achieved. This on-site oil-spill treating strategy, taking advantage of a home-made bioinspired robot actuated by natural sunlight under magnetic steering, shows great potential applications in water-body remediation.

关键词： miniature robot superhydrophobic water strider interfacial friction magnetic actuation

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Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George D.Bittner Department of Molecular Biosciences University of Texas at AustinAustinTXUSA Department of neuroscience University of Texas at AustinAustinTXUSA Division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

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Development of SV2A Ligands for Epilepsy Treatment:A Review of Levetiracetam,Brivaracetam,and Padsevonil

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neuroscience Bulletin 2024年第5期40卷 594-608页

作者： Peng-Peng Wu Bi-Rong Cao Fu-Yun Tian Zhao-Bing Gao Center for Neurological and Psychiatric Research and Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of Chinese Academy of Sciences Beijing100049China Zhongshan institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshan528400China

Epilepsy is a common neurological disorder that is primarily treated with antiseizure medications(ASMs).Although dozens of ASMs are available in the clinic,approximately 30%of epileptic patients have medically refractory seizures;other limitations in most traditional ASMs include poor tolerability and drug-drug ***,there is an urgent need to develop alternative ***(LEV)is a first-line ASM that is well tolerated,has promising efficacy,and has little drug-drug *** it is widely accepted that LEV acts through a unique therapeutic target synaptic vesicle protein(SV)2A,the molecular basis of its action remains *** so,the next-generation SV2A ligands against epilepsy based on the structure of LEV have achieved clinical *** review highlights the research and development(R&D)process of LEV and its analogs,brivaracetam and padsevonil,to provide ideas and experience for the R&D of novel ASMs.

关键词： Levetiracetam Epilepsy Antiseizure medications Synaptic vesicle protein 2A Brivaracetam Padsevonil

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Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第2期18卷 285-302页

作者： Di He Xunzhe Yang Liyang Liu Dongchao Shen Qing Liu Mingsheng Liu Xue Zhang Liying Cui Department of Neurology Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China Medical Doctor Program Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing100730China neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China

Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain *** evidence implicates N6-methyladenosine(m6A)modification in ALS *** RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication *** of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in *** proteome analysis demonstrated the role of dysregulated immune cell migration in *** type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were *** communication between neurons and glial cells was selectively altered in ALS *** integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

关键词： amyotrophic lateral sclerosis N^(6)-methyladenosine epi-transcriptome proteome single cell RNA sequencing analysis CX3CR1

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Enhancing sensitivity of triple-negative breast cancer to DNA-damaging therapy through chemical inhibition of the m6A methyltransferase METTL3

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Cancer Communications 2024年第2期44卷 282-286页

作者： Bianca Cesaro Alessia Iaiza Fabio Piscopo Marco Tarullo Eleonora Cesari Dante Rotili Antonello Mai Alberto Diana Michela Londero Luca Del Giacco Riccardo Masetti Alba Di Leone Chiara Naro Silvia Masciarelli Giulia Fontemaggi Claudio Sette Francesco Fazi Alessandro Fatica Department of Anatomical HistologicalForensic&Orthopedic SciencesSection of Histology&Medical EmbryologySapienza University of RomeRomeItaly Department of Biology and Biotechnologies“Charles Darwin” Sapienza University of RomeRomeItaly GSTeP Organoids Research Core Facility Fondazione Policlinico A.Gemelli Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)RomeItaly Department of Drug chemistry and Technologies Sapienza University of RomeRomeItaly Pasteur institute Cenci-Bolognetti FoundationSapienza University of RomeRomeItaly Department of BioSciences University of MilanMilanItaly Multidisciplinary Breast Center Dipartimento Scienze della Salute della Donna e del Bambino e di SanitàPubblicaCatholic University of the Sacred HeartRomeItaly Department of neuroscience Section of Human AnatomyCatholic University of the Sacred HeartRomeItaly Oncogenomic and Epigenetic Unit IRCCS Regina Elena National Cancer InstituteRomeItaly

Dear Editor,N 6-methyladenosine(m^(6)A)is a critical mRNA modi-fication catalyzed by the enzyme methyltransferase-like 3(METTL3),with implications in RNA ***3 upregulation is associated with cancer progres-sion,metast... 详细信息

关键词： cancer methyltransferase metastasis

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Debt,sleep deprivation and psychological distress among online ride-hailing drivers:evidence from China

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General Psychiatry 2024年第2期37卷 319-323页

作者： Wanjie Tang Jingyue Chen Simiao Wang Xianglan Jiang Yi Lu Siqi Wu Luyu Yang Meng Tian Han Zhang Yinan Zhang Jiuping Xu Zeyuan Sun Mental Health Centre Sichuan UniversityChengduSichuanChina Department of Child&Adolescent Psychiatry King's College London Institute of Psychiatry Psychology&NeuroscienceLondonUK Sichuan University Business School ChengduSichuanChina Department of Psychology King's College London Institute of Psychiatry Psychology&NeuroscienceLondonUK Sichuan University West China School of Medicine ChengduSichuanChina The University of Edinburgh School of Health in Social Science EdinburghEdinburghUK Department of Psychology University of WarwickCoventryUK Division of Psychiatry University College London Faculty of Brain SciencesLondonUK Wuxi Mental Health Center Nanjing Medical UniversityWuxiJiangsuChina King's College London Centre for the Developing Brain LondonUK

An online ride-hailing driver(ORHD)refers to a driver who takes orders and provides rental car services to passengers via an online service platform.1 ORHD plays a significant role in the urban transport system worldwide,operating through many *** to official data from the Chinese Ministry of Transport,a total of 1.6 million vehicle transport permits were issued by the end of March 2022.

关键词： services service official

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DPABINet:脑网络和图论分析工具箱

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Science Bulletin 2024年第11期69卷 1628-1631页

作者：严超赣王鑫迪鲁彬邓昭宇高青林 CAS Key Laboratory of Behavioral Science Institute of PsychologyBeijing 100101China Department of Psychology University of Chinese Academy of SciencesBeijing 100101China International Big-Data Center for Depression Research Institute of PsychologyChinese Academy of SciencesBeijing 100101China Magnetic Resonance Imaging Research Center Institute of PsychologyChinese Academy of SciencesBeijing 100101China McGill Centre for Integrative neuroscience Montreal Neurological InstituteMcGill UniversityMontréal H3A 2B4Canada

The human brain, a marvel of intricate connections, functions as a complex network comprising structurally and functionally integrated regions. This network orchestrates a multitude of complex patterns through high-le... 详细信息

关键词：图论分析脑网络工具箱

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Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

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Journal of Sport and Health Science 2024年第2期13卷 245-255页

作者： Cecilie Skarstad Norevik Aleksi M.Huuha Ragnhild N.RФsbjФrgen Linda Hildegard Bergersen Kamilla Jacobsen Rodrigo Miguel-dos-Santos Liv Ryan Belma Skender Jose Bianco N.Moreira Asgeir Kobro-Flatmoen Menno P.Witter Nathan Scrimgeour Atefe R.Tari Cardiac Exercise Research Group(CERG) Department of Circulation and Medical ImagingNorwegian University of Science and Technology7491TrondheimNorway Department of Neurology and Clinical Neurophysiology St.Olavs University Hospital7030TrondheimNorway institute of Oral Biology University of Oslo0372OsloNorway Department of Physiology Federal University of SergipeS~ao Cristov~ao49100-000SergipeBrazil Centre of Molecular Inflammation Research Department of Clinical and Molecular MedicineNorwegian University of Science and Technology7491TrondheimNorway Kavli institute for Systems neuroscience Centre for Neural Computationand Egil and Pauline Braathen and Fred Kavli Centre for Cortical MicrocircuitsNorwegian University of Science and Technology7030TrondheimNorway K.G.Jebsen Centre for Alzheimer’s Disease Norwegian University of Science and Technology7030TrondheimNorway

Background:Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s disease(AD).These beneficial effects may be partly mediated by blood-borne *** we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,and an in vivo rat model of AD to test whether such plasma impacts cognitive function,amyloid pathology,and ***:Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-βand treated with plasma collected from human male donors 3 h after a single bout of high-intensity *** in vivo studies,blood was collected from exercise-trained young male Wistar rats(high-intensity intervals 5 days/week for 6 weeks).Transgenic AD rats(McGill-R-Thyl-APP)were inj ected 5 times/fortnight for 6 weeks at2 months or 5 months of age with either(a)plasma from the exercise-trained rats,(b)plasma from sedentary rats,or(c)*** function,amyloid plaque pathology,and neurogenesis were *** plasma used for the treatment was analyzed for 23 ***:Plasma from exercised donors enhanced cell viability by 44.1%(p=0.032)and reduced atrophy by 50.0%(p<0.001)in amyloid-β-treated *** vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by~3 fold,regardless of pathological stage,when compared to saline-treated *** of 7 cytokines were significantly reduced in exercised plasma compared to sedentary ***:Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat *** effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

关键词： Cytokines High-intensity interval training Inflammation Neurons Plasma transfusion

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