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NeCAB family of neuronal calcium-binding proteins in health and disease

Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.e.Schafer Sudena Wang michael J.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal eF-hand calcium-binding proteins 1–3(NeCAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one eF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NeCAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NeCAB2 interacts with predominantly striatal G-protein-coupled receptors, while NeCAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NeCAB proteins exhibit distinct subcellular localizations: NeCAB1 is found in the nucleus and cytosol, NeCAB2 resides in endosomes and the plasma membrane, and NeCAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NeCAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NeCAB proteins by controlling the availability of protein–protein interaction domains situated between the eF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium eF hand mitochondria nervous system signal transduction

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声波激励的超小型纳机电系统磁电天线

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通信对抗 2017年第4期36卷 51-58页

作者： Tianxiang Nan Hwaider Lin Yuan Gao Alexei Matyushov Guoliang Yu Huaihao Chen Neville Sun Shengjun Wei Zhiguang Wang Menghui Li Xinjun Wang Amine Belkessam Rongdi Guo Brian Chen James Zhou Zhenyun Qian Yu Hui Matteo Rinaldi michael e.mcconney BrANDon M.Howe Zhongqiang Hu John G.Jones Gail J.Brown Nian Xiang Sun 张建强(翻译) 陈鼎鼎(审校) W.M.Keck Laboratory for Integrated Ferroics and Department of Electrical and Computer EngineeringNortheastern UniversityBostonMA 02115USA Westford Academy WestfordMA 01886USA Andover High School AndoverMA 01810USA Materials and Manufacturing Directorate Air Force Research LaboratoryWright-Patterson Air Force BaseDaytonOH 45433USA 不详

当前的小型天线依赖于电磁波的谐振,因此天线的尺寸与电磁波波长相关。典型的天线尺寸大于波长的1/10,而进一步缩小天线尺寸在近十年来都是一个公开的挑战。介绍一种通过悬浮铁氧/压电薄膜异质结构的声波激励纳机械磁电天线。这种磁电... 详细信息

当前的小型天线依赖于电磁波的谐振,因此天线的尺寸与电磁波波长相关。典型的天线尺寸大于波长的1/10,而进一步缩小天线尺寸在近十年来都是一个公开的挑战。介绍一种通过悬浮铁氧/压电薄膜异质结构的声波激励纳机械磁电天线。这种磁电天线通过其在声波谐振频率处的磁电效应接收和发射电磁波。磁电天线中的体声波激发铁磁薄膜的磁化振荡,产生电磁波的辐射;反之,天线感应电磁波的磁场,得到压电电压输出。这种磁电天线(尺寸仅为波长的千分之一)比现有小型天线的尺寸小1到2个数量级,但性能却没有降低,在便携式无线通信系统中具有很大的应用潜力。

关键词：纳米板薄膜体声波谐振器纳机电系统

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Like a G6-nal:transcriptional control of G-protein coupled receptors during oligodendroglial development

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Neural Regeneration Research 2025年第7期20卷 2001-2002页

作者： Tim Aberle michael Wegner Institut für Biochemie Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

Multilayered control of myelination:Quick,saltatory conduction of action potentials along nerve fibers requires the electrical insulation of axons by myelinating *** the central nervous system,this role is taken up by *** are marked by the expression of the lineage determinants Sox10 and Olig2 and arise from oligodendrocyte precursor cells(OPCs)during embryonal *** the majority of OPCs differentiate into mature oligodendrocytes when nearby axonal segments require myelination,a small subpopulation of OPCs persist as a progenitor ***,the timing of myelination and maintenance of the OPC pool both need to be precisely *** transcription factors either positively or negatively affect oligodendrocyte differentiation and maintenance of the OPC pool as components of a complex gene regulatory network(reviewed in Sock and Wegner,2021).Network activity is additionally influenced by extracellular signaling molecules that bind to receptors on the oligodendroglial cell surface and activate intracellular signaling *** the receptors are linked to the network is poorly understood so far,but pivotal to understanding the overall regulation of central nervous system(CNS)myelination in response to environmental *** insights were recently gained for Gpr37(Schmidt et al.,2024),a G-protein coupled receptor(GPCR)with known relevance in differentiating oligodendrocytes(Yang et al,2016).

关键词： gained insulation conduction

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emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao michael S.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-eM structures drug design intramembrane proteolysis molecular dynamics Notch

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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu michael Chopp michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of Pathology Henry Ford HospitalDetroitMIUSA Division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(seVs)isolated from cerebral endothelial cells(CeC-seVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CeC-seVs engineered to enrich their levels of miR-27a(27a-seVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CeC-seVs.27a-seVs were isolated from the conditioned medium of healthy mouse CeCs transfected with a lentiviral miR-27a expression *** eVs isolated from CeCs transfected with a scramble vector(Scra-seVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-seVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-seVs,treatment with 27a-seVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CeC-seVs carrying reduced miR-27a abolished 27a-seV-augmented axonal *** analysis revealed that 27a-seVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-seVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

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Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： Shan Ping Yu emily Choi michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA Center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

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A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

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Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： John Mitrofanis Jonathan Stone michael R.Hamblin Pierre Magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

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Interleukin-6 in epilepsy and its neuropsychiatric comorbidities: How to bridge the gap

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World Journal of Psychiatry 2025年第1期15卷 1-6页

作者： Xiao-Man Chen Shuo Zhang Shi-Qi Gao michael Xu Department of Neurology Shengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina Department of Rehabilitation Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110004Liaoning ProvinceChina International education School China Medical UniversityShenyang 110004Liaoning ProvinceChina

There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric *** editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy *** purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric ***-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with ***,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric *** summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric *** resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective ***,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.

关键词： epilepsy Interleukin-6 Neuropsychiatric comorbidities Depression Tocilizu-mab Neuroinflammation Interleukin-6 receptor blockade

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Oligodendrocyte pathology in fetal alcohol spectrum disorders

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Neural Regeneration Research 2022年第3期17卷 497-502页

作者： Nune Darbinian michael e.Selzer Center for Neural Repair and Rehabilitation(Shriners Hospitals Pediatric Research Center) Lewis Katz School of Medicine at Temple UniversityPhiladelphiaPAUSA

The pathology of fetal alcohol syndrome and the less severe fetal alcohol spectrum disorders includes brain *** studies have shed light on the molecular mechanisms underlying these white matter *** models of fetal alcohol syndrome and human studies have shown suppressed oligodendrocyte differentiation and apoptosis of oligodendrocyte precursor *** exposure led to reduced expression of myelin basic protein and delayed myelin basic protein expression in rat and mouse models of fetal alcohol syndrome and in human histopathological *** studies have reported increased expression of many chemokines in dysmyelinating disorders in central nervous system,including multiple sclerosis and fetal alcohol *** ethanol exposure reduced levels of the neuroprotective insulin-like growth factor-1 in fetal and maternal sheep and in human fetal brain tissues,while ethanol increased the expression of tumor necrosis factor α in mouse and human *** matter lesions have been induced in the developing sheep brain by alcohol exposure in early *** fetal alcohol syndrome models have shown reduced axon diameters,with thinner myelin sheaths,as well as reduced numbers of oligodendrocytes,which were also morphologically aberrant *** of markers for mature myelination,including myelin basic protein,also were *** accumulating knowledge concerning the mechanisms of ethanol-induced dysmyelination could lead to the development of strategies to prevent dysmyelination in children exposed to ethanol during fetal *** studies using fetal oligodendrocyte-and oligodendrocyte precursor cell-derived exosomes isolated from the mother's blood may identify biomarkers for fetal alcohol syndrome and even implicate epigenetic changes in early development that affect oligodendrocyte precursor cell and oligodendrocyte function in *** combining various imaging modalities with mo

关键词： alcohol development dysmyelination ethanol fetal alcohol syndrome fetal brain myelin basic protein neurodegeneration oligodendrocyte injury oligodendrocyte precursor cells

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ecological restoration for sustainable development in China

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National Science Review 2023年第7期10卷 60-71页

作者： Bojie Fu Yanxu Liu michael e.Meadows State Key Laboratory of Urban and Regional ecology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences State Key Laboratory of earth Surface Processes and Resource ecology Faculty of Geographical Science Beijing Normal University School of Geographic and Oceanographic Sciences Nanjing University College of Geography and environmental Sciences Zhejiang Normal University Department of environmental and Geographical Science University of Cape Town

Facing the need for transdisciplinary research to promote ecological restoration that achieves both social and ecological benefits,research on past restoration efforts that have directly or indirectly contributed to regional or national sustainable development warrants *** China as an example,in this review,we address three basic research questions that can be summarized as follows:ecological restoration—of what,for whom and to what purpose?Accordingly,a landscape pattern—ecosystem service—sustainable development’ co-evolutionary framework is proposed here to describe landscape-scale ecological restoration and its impact on landscape patterns and ecological processes,ecosystem services for human well-being,sustainable livelihoods and socioeconomic *** the strategic pattern of national ecological security to the pattern of major projects to protect and restore major national ecosystems,the spatial pattern of China’ s ecological restoration is more geographically *** major function-oriented zoning to systematic ecological protection and restoration,and for the purpose of achieving the Beautiful China Initiative,there are three stages of ecosystem services management:classification,synergy and integration,*** difference in geographic processes should be considered in the key re quirements of ecological restoration for China’ s five national strategies for regional sustainable-development *** understanding of the relationship between humans and nature in different geographical contexts is a scientific prerequisite to support policymaking related to ecological *** promote greater harmony between humans and nature,we propose four important research directions:(ⅰ) understanding coupling processes among key components,(ⅱ) identifying ecosystem service flows,(ⅲ) evaluating social-ecological benefits and(ⅳ) supporting adaptive management for regional sustainable development.

关键词： social-ecological system landscape pattern ecological process ecosystem services sustainable livelihoods policymaking

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