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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Vagus nerve stimulation in intracerebral hemorrhage:the need for further research

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Neural Regeneration Research 2025年第11期20卷 3213-3214页

作者： Sheharyar S.Baig Ali N.Ali Arshad Majid Sheffield institute for translational Neuroscience Division of NeuroscienceThe University of SheffieldSheffieldUK

Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical *** chronic ischemic stroke,invasive VNS paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,STOP-AUST,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).

关键词： stimulation acute

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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science China(Life sciences) 2025年第1期68卷 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China Department of Gastrointestinal Cancer Center Peking University Cancer Hospital&InstituteBeijing 100142China Department of Liver Surgery&Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China

Extrachromosomal DNA(ecDNA)is a form of circular DNA mostly found in tumor *** the typical chromosomal DNA,ecDNA is circular,self-replicating,and carries complete or partial gene *** ecDNA occurrence remains a rare event in cancer,recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer,implying that ecDNA plays a central role in accelerating tumor *** has also been associated with increased tumor mutation burden,chromosomal instability,and even tumor microenvironment *** may be crucial in influencing tumor heterogeneity,drug sensitivity,oncogenic senescence,and tumor immunogenicity,leading to a worsening prognosis for tumor *** this way,several clinical trials have been conducted to investigate the importance of ecDNA in clinical *** this review,we summarize the biogenesis,characteristics,and current research methods of ecDNA,discuss the vital role of ecDNA-caused tumor heterogeneity in cancers,and highlight the potential role of ecDNA in cancer therapy.

关键词： extrachromosomal DNA cancer therapy tumor heterogeneity drug resistance tumor evolution

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Emerging potential of progranulin-dependent SorCS2 signaling in healthy and diseased nervous systems

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Neural Regeneration Research 2025年第9期20卷 2591-2593页

作者： Alena Salasova Anders Nykjær Danish Research institute of translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine and Centre of Excellence PROMEMODepartment of BiomedicineAarhus UniversityAarhusDenmark

The formation of the mammalian nervous system and its maturation into sensory,motor,cognitive,and behavioral circuits is a complex process that begins during early embryogenesis and lasts until young *** neurodevelopm... 详细信息

关键词： progr jointly CS2

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Attitude towards genetic testing for breast cancer susceptibility genes and choice of prevention strategies in Chinese women with or without breast cancer

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Cancer Biology & Medicine 2025年第1期22卷 28-32页

作者： Xue Yu Furong Kou Yuntao Xie Department of Breast Surgery Peking University International Hospital Key Laboratory of Carcinogenesis and translational Research (Ministry of Education/Beijing) Department of Comprehensive Clinical Trial WardPeking University Cancer Hospital & Institute Key Laboratory of Carcinogenesis and translational Research (Ministry of Education/Beijing) Familial and Hereditary Cancer Center Peking University Cancer Hospital & Institute

Breast cancer (BC) is now the most common cancer and the fifth leading cause of cancer-associated mortality among women in China1. Germline pathogenic variants (PVs) of BC susceptibility genes, such as the well-known BRCA1/2 genes, increase the risk of BC and other cancers (ovarian and pancreatic cancer)2,3. Recent studies have demonstrated substantial benefits of poly (adenosine diphosphate ribose) polymerase inhibitors in the treatment of BC patients who carry BRCA1/2 PVs4.

关键词： strategies chinese attitude cancer genetic genes breast choice prevention susceptibility

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Constraints on what controls millennial-scale basin-wide denudation across mountain belts,Asia

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science China Earth sciences 2025年第1期68卷 74-93页

作者： Ye YANG Steven A.BINNIE Sheng XU Cong-Qiang LIU Tibor J.DUNAI institute of Surface-Earth System science School of Earth System ScienceTianjin UniversityTianjin300072China institute of Geology and Mineralogy University of CologneCologne50674Germany

The terrestrial cosmogenic nuclide dataset consisting of 1233^(10)Be measurements of fluvial sediment samples across the Asian mountain belts is used to constrain the influence of climate,tectonics and topography on Earth-surface denudation processes.^(10)Be-derived basin-wide denudation rates were recalculated using a Monte Carlo simulation approach that relied on pixel-by-pixel production *** rates derived span four orders of magnitude,from 7.4±0.7 mm kyr^(-1)(1σ;Central Tibetan Plateau)to 9,646_(-744)^(+777)mm kyr^(-1)(1σ;Southern Tibetan Plateau),with a median of 186 mm kyr^(-1).Comparing our results with the traditional basin-wide production rate scaling model using a centroid coordinate and mean elevation,suggests that 96.6%of production rates will be underestimated using the latter method,especially for basins with a large *** bias between both methods reaches as large as 40%,caused by basin hypsometry and the nonlinear scaling of production rate with elevation and *** of the correlations between uniformly recalculated denudation rates and tectonics,climate,topography and rock lithology will facilitate the extrapolation of denudation rates in unknown basins using available *** the perspective of local scales,precipitation coupled with neotectonics-driven landslides is likely the most influential factor in subtropical Taiwan Island,while topography primarily constrains surface denudation rates in the eastern Tibetan Plateau within a narrow range of *** highland regions with glacier coverage,such as the Pamir,central and southern Tibetan Plateau high denudation rates are affected by glaciation,whereas lower precipitation and high erosion base level may limit river incision and evolving relief in the Central Tibetan *** contrast to local-scale findings highlighting a dominant factor constraining denudation rate,our large-scale quantitative analyses across the Asian mountain belts finds that(1)topographic

关键词： ^(10)Be-derived denudation rate Climate change Tectonic uplift Topographic gradient Asian mountains

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Improved oxygen electrocatalysis at Fe N4 and Co N4 sites via construction of axial coordination

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Chinese Chemical Letters 2025年第2期36卷 482-487页

作者： Ze Zhang Lei Yang Jin-Ru Liu Hao Hu Jian-Li Mi Chao Su Bei-Bei Xiao Zhi-Min Ao School of Energy and Power Engineering Jiangsu University of Science and Technology institute for Computation in Molecular and Materials science School of Chemistry and Chemical Engineering Nanjing University of Science and Technology institute for Advanced Materials School of Materials Science and Engineering Jiangsu University Advanced Interdisciplinary institute of Environment and Ecology Beijing Normal University

The quest for efficient and durable catalysts using abundant resources has garnered significant interest in the field of bifunctional oxygen *** this contribution,we have designed a FeN4or CoN4embedded graphene-based bilayer as active layer and TMC3or TMN3doped graphene as supporting layer,named as FeN4/TMC3or FeN4/TMN3and CoN4/TMC3or CoN4/TMN3,wherein TM strands for transition *** on density functional theory calculations,our results demonstrate that the interaction formed between dual metal atoms in the bilayer interspace leads to the coordination environment altered from flat four-coordination to spatial five-coordination,further stabilizing the bilayer structure and impairing its affinity toward the O-containing *** to thermodynamic analysis,the bilayers of CoN4/CoN3,FeN4/FeC3,FeN4/CoC3,FeN4/NiC3,FeN4/ZnC3,FeN4/FeN3,FeN4/CrN3and FeN4/ZnN3are attractively promising for bifunctional oxygen electrocatalysis due to the small overpotential differenceΔη between oxygen reduction and oxygen evolution that are less than 1 *** functional theory calculations combined with machine learning analysis directly identify the key role played by the interbinding formed between bilayers,that boosts catalytic activity,which establishes a predictable framework for a fast screen for graphene-based bilayer vertical *** work opens up a new path for designing the efficient electrocatalysts via modification of coordination environment.

关键词： Density functional theory Machine learning Oxygen electrocatalysis Thermodynamic analysis

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Integrating artificial intelligence into radiological cancer imaging: from diagnosis and treatment response to prognosis

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Cancer Biology & Medicine 2025年第1期22卷 6-13页

作者： Sunyi Zheng Xiaonan Cui Zhaoxiang Ye Tianjin Medical University Cancer institute and Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine Tianjin Key Laboratory of Digestive Cancer Key Laboratory of Cancer Prevention and Therapy Department of Radiology

Cancer poses a serious threat to human health worldwide and is a leading cause of death1. The analysis of radiological imaging is crucial in early detection, accurate diagnosis, effective treatment planning, and ongoing monitoring of patients with cancer. However, several challenges impede the effectiveness of cancer imaging analysis in clinical practice.

关键词： intelligence prognosis imaging cancer from artificial diagnosis integrating into radiological

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AI empowers exploration of protein universe

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science China(Life sciences) 2025年第2期68卷 588-589页

作者： Wuke Wang Xingxu Huang Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated Hospitaland Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China

Deaminases which perform the function of converting cytosine to thymine are ubiquitous in nature with over 120,000 known variants,each exhibiting significant ***,gene editing technologies have remarkably revealed that these deaminases share similar ***,the mining of novel proteins has been conducted through sequence alignment and the categorization of conserved regions to identify functional modules within protein sequences.

关键词： functions powers alignment

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Interface compatibility between sulfide solid electrolytes and Ni-rich oxide cathode materials:Factors,modification,perspectives

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Journal of Energy Chemistry 2025年第2期101卷 233-262页

作者： Tianwen Yang Haijuan Pei Haijian Lv Shijie Lu Qi Liu Daobin Mu Beijing Key Laboratory of Environmental science and Engineering School of Materials Science an Engineering Beijing Institute of Technology State Key Laboratory of Space Power-Sources Technology Shanghai Institute of Space Power-Sources

All-solid-state batteries(ASSBs) assembled with sulfide solid electrolytes(SSEs) and nickel(Ni)-rich oxide cathode materials are expected to achieve high energy density and safety,representing potential candidates for the next-generation energy storage ***,interfacial issues between SSEs and Nirich oxide cathode materials,attributed to space charge layer,interfacial side reactions,and mechanical contact failure,significantly restrict the performances of *** interface degradation is closely related to the components of the composite cathode and the process of electrode *** on the influencing factors of interface compatibility between SSEs and Ni-rich oxide cathode,this article systematically discusses how cathode active materials(CAMs),electrolytes,conductive additives,binders,and electrode fabrication impact the interface *** addition,the strategies for the compatibility modification are ***,the challenges and prospects of intensive research on the degradation and modification of the SSE/Ni-rich cathode material interface are *** review is intended to inspire the development of high-energy-density and high-safety all-solid-state batteries.

关键词： All–solid–state batteries Influencing factors Interface compatibility Ni–rich oxide cathode Sulfide solid electrolyte

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