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Neurogenesis dynamics in the olfactory bulb:deciphering circuitry organization, function, and adaptive plasticity

Neural Regeneration Research 2025年第6期20卷 1565-1581页

作者： Moawiah M.Naffaa department of Psychology and Neuroscience Duke UniversityDurhamNCUSA department of cell Biology Duke University School of MedicineDurhamNCUSA

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased

关键词： network adaptability neurogenesis neuronal communication olfactory bulb olfactory learning olfactory memory synaptic plasticity

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ImSpiRE: image feature-aided spatial resolution enhancement method

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Science China Life Sciences 2025年第1期 272-283页

作者： Yuwei Hua Yizhi Zhang Zhenming Guo Shan Bian Yong Zhang State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center Institute for Regenerative MedicineDepartment of NeurosurgeryShanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji University

The resolution of most spatially resolved transcriptomic technologies usually cannot attain the single-cell level, limiting their applications in biological discoveries. Here, we introduce ImSpiRE, an image feature-aided spatial resolution enhancement method for in situ capturing spatial transcriptome. Taking the information stored in histological images, ImSpiRE solves an optimal transport problem to redistribute the expression profiles of spots to construct new transcriptional profiles with enhanced resolution, together with extending the gene expression profiles into unmeasured regions. Applications to multiple datasets confirm that ImSpiRE can enhance spatial resolution to the subspot level while contributing to the discovery of tissue domains, signaling communication patterns, and spatiotemporal characterization.

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DNA End Resection:Facts and Mechanisms

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Genomics, Proteomics & Bioinformatics 2016年第3期14卷 126-130页

作者： Ting Liu Jun Huang department of cell Biology and Program in Molecular cell Biology Zhejiang University School of Medicine Life Sciences Institute and Innovation Center for cell signaling Network Zhejiang University

DNA double-strand breaks（DSBs）,which arise following exposure to a number of endogenous and exogenous agents,can be repaired by either the homologous recombination（HR）or non-homologous end-joining（NHEJ） pathways in eukaryotic cells.A vital step in HR repair is DNA end resection,which generates a long 30single-stranded DNA（ss DNA） tail that can invade the homologous DNA *** generation of 30 ss DNA is not only essential for HR repair,but also promotes activation of the ataxia telangiectasia and Rad3-related protein（ATR）.Multiple factors,including the MRN/X complex,C-terminal-binding protein interacting protein（Ct IP）/Sae2,exonuclease 1（EXO1）,Bloom syndrome protein（BLM）/Sgs1,DNA2 nuclease/helicase,and several chromatin remodelers,cooperate to complete the process of end *** we review the basic machinery involved in DNA end resection in eukaryotic cells.

关键词： DNA end resection Homologous recombination DNA double-strand breaks Chromatin remodeling factors Genome stability

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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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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The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

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Neural Regeneration Research 2025年第1期20卷 209-223页

作者： Shi-Yan Sun Lingyun Nie Jing Zhang Xue Fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang Hefei National Research Center for Physical Sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS Center for Excellence in Molecular cell Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Brain Research Center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and ***-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains *** this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative ***,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic *** of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and *** down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive *** together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

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Modeling and measurement of curing properties of photocurable polymer containing magnetic particles and microcapsules

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Microsystems & Nanoengineering 2017年第1期3卷 175-183页

作者： Masato Yasui Koji Ikuta Laboratory for cell signaling dynamics RIKEN Quantitative Biology Center6-2-3 FuruedaiSuitaOsaka 565-0874Japan Graduate School of Information Science and Technology The University of Tokyo7-3-1 HongoBunkyo-kuTokyo 113-8685Japan

In microstereolithography,three-dimensional microstructures are created by scanning an ultraviolet laser on a photocurable resin and stacking several such layers to form the desired *** mixing different types of particles in the resin,the formed microstructures exhibit various physical *** example,the magnetism and density of the microstructure can be controlled by adding magnetic particles and microcapsules to the *** method has been used to fabricate magnetic *** such functional resins are useful,the incorporated magnetic particles and microcapsules can affect the fabrication resolution,making it difficult to fabricate microstructures with high ***,it is necessary to understand the effects of such microparticles and microcapsules on the fabrication *** this study,we propose a simple model of curing resins containing magnetic particles and microcapsules to explain the effects of the magnetic particles and *** proposed model can explain the observed curing characteristics of a resin that contains particles for all concentrations as well as for different types of magnetic particles and ***,using the proposed model,we discuss how to improve the characteristics of resins containing microparticles to realize the high-resolution fabrication of three-dimensional microstructures with desirable material properties.

关键词： Magnetic particles Microcapsules Microstereolithography Photocurable model Photocurable polymer Resin

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LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling

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Bone Research 2014年第1期2卷 43-54页

作者： Changjun Li Bart O Williams Xu Cao Mei Wan department of Orthopaedic Surgery Johns Hopkins University School of Medicine Center for Skeletal Disease and Tumor Metastasis and Laboratory of cell signaling and Carcinogenesis Van Andel Research Institute

Lipoprotein receptor-related protein 6 （LRP6） plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells （MSCs）, skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin＋ MSCs by crossing nestin-Cre mice with LRP6 flox mice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin＋ cells demonstrated reductions in body weight and body length at I and 3 months of age. Bone architecture measured by microCT （uCT） showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6 mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix＋ osteoprogenitors and osteocalcin＋ osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.

关键词： bone LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling stem

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COX-2 in liver,from regeneration to hepatocarcinogenesis:What we have learned from animal models?

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World Journal of Gastroenterology 2010年第12期16卷 1430-1435页

作者： Paloma Martín-Sanz Rafael Mayoral Marta Casado Lisardo Boscá Biomedical Network Center for the Study of Hepatic and Digestive Diseases(CIBERehd) department of Metabolism and cell signaling Institute of Biomedical Research "Alberto Sols"(CSIC-UAM) department of Pathology and Molecular and cellular Therapy Institute of Biomedicine of Valencia(IBV-CSIC)

The use of animals lacking genes or expressing genes under the control of cell-specific promoters has signifi cantly increased our knowledge of the genetic and molecular basis of physiopathology,allowing testing of functional hypotheses and validation of biochemical and pharmacologic approaches in order to understand cell ***,with unexpected frequency,gene knockout animals and,more commonly,animal models of transgenesis give experimental support to even opposite conclusions on gene *** we summarize what we learned on the role of cyclooxygenase 2(COX-2) in liver and revise the results obtained in 3 independent models of mice expressing a COX-2 transgene specifi cally in the *** challenge with pro-inflammatory stimuli,the animals behave very differently,some transgenic models having a protective effect but others enhancing the *** addition,one transgene exerts differential effects on normal liver physiology depending on the transgenic animal model used.

关键词： Cyclooxygenase 2 Prostaglandins Liver diseases Apoptosis Inflammation Animal models

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Dynamic changes of protein corona compositions on the surface of zinc oxide nanoparticle in cell culture media

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Frontiers of Chemical Science and Engineering 2019年第1期13卷 90-97页

作者： Vo-Van Giau Yoon-Hee Park Kyu-Hwan Shim Sang-Wook Son Seong-Soo A. An department of Bionanotechnology and Gachon Medical Research Institute Gachon University and Gachon Medical Research Institute Seongnam Korea Laboratory of cell signaling and Nanomedicine Department of Dermatology and Division of Brain Korea 21 Project for Biomedical Science Korea University College of Medicine Seoul Korea

The potential applications of nanomaterials used in nanomedicine as ingredients in drug delivery systems and in other products continue to expand. When nanomaterials are introduced into physiological environments and driven by energetics, they readily associate proteins forming a protein corona (PC) on their surface. This PC could result in an alteration of the nanomatcrial's surface characteristics, affecting their interaction with cells due to conformational changes in adsorbed protein molecules. However, our current understanding of nanobiological interactions is still very limited. Utilizing a liquid chromatography-mass spectroscopy/mass spectroscopy technology and a Cytoscape plugin (ClueGO) approach, we examined the composition of the PC for a set of zinc oxide nanoparticles (ZnONP) from cell culture media typically and further analyzed the biological interaction of identified proteins, respectively. In total, 36 and 33 common proteins were investigated as being bound to ZnONP at 5 min and 60 min, respectively. These proteins were further analyzed with ClueGO, a Cytoscape plugin, which provided gene ontology and the biological interaction processes of identified proteins. Proteins bound to the surface of nanoparticles that may modify the structure, therefore the function of the adsorbed protein could be consequently affect the complicated biological processes.

关键词： ZnONPs nanoparticles protein corona ClueGO

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Rumex acetosella Inhibits Platelet Function via Impaired MAPK and Phosphoinositide 3-Kinase signaling

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Chinese Journal of Integrative Medicine 2022年第9期28卷 802-808页

作者： Bo-Ra Jeon Muhammad Irfan Seung Eun Lee Jeong Hoon Lee Man Hee Rhee Laboratory of Physiology and cell signaling College of Veterinary MedicineKyungpook National UniversityDaegu41566Republic of Korea department of Herbal Crop Research National Institute of Horticultural and Herbal Science(NIHHS)Eumseong27709Republic of Korea

Objective:To examine the antiplatelet and antithrombotic activity of Rumex acetosella ***:Standard light aggregometry was used for platelet aggregation,intracellular calcium mobilization assessed using Fura-2/AM,granule secretion(ATP release)by luminometer,and fibrinogen binding to integrin α_(Ⅱb)β_(3) detected using flow *** blotting is carried out to determine the phosphorylation of mitogen-activated protein kinase(MAPK)and phosphoinositide 3-kinase(PI3K)/Akt ***:Rumex acetosella displayed the ability to inhibit platelet aggregation,calcium mobilization,granule secretion,and fibrinogen binding to integrin α_(Ⅱb)β_(3).Rumex acetosella has also down-regulated MAPK and PI3K/Akt phosphorylation(all Psignaling,and it may protect against the development of platelet-related cardiovascular diseases.

关键词： antiplatelet ethnomedicine integrinα_(Ⅱb)β_(3) mitogen-activated protein kinase Rumex acetosella L.

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