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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

Deep learning-based multi-task prediction of response to neoadjuvant chemotherapy using multiscale whole slide images in breast cancer:A multicenter study

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Chinese Journal of Cancer Research 2025年第01期 28-54页

作者： Qin Wang Feng Zhao Haicheng Zhang Tongpeng Chu Qi Wang Xipeng Pan Yuqian Chen Heng Zhou Tiantian Zheng Ziyin Li Fan Lin Haizhu Xie Heng Ma Lan Liu Lina Zhang Qin Li Weiwei Wang Yi Dai Ruijun Tang Jigang Wang Ping Yang Ning Mao School of Information and Electronic Engineering Shandong Technology and Business University Big Data and Artificial Intelligence Laboratory Yantai Yuhuangding Hospital of Qingdao University Shandong Provincial Key Medical and Health Laboratory of Intelligent Diagnosis and Treatment for Women's Diseases Yantai Yuhuangding Hospital department of Radiology Yantai Yuhuangding Hospital of Qingdao University School of Computer Science and Technology Shandong Technology and Business University School of Computer Science and Information Security Guilin University of Electronic Technology School of Medical imaging Binzhou Medical University department of Radiology Jiangxi Cancer Hospital the Second Affiliated Hospital of Nanchang Medical College department of Radiology the First Affiliated Hospital of China Medical University department of Radiology Weifang Hospital of Traditional Chinese Medicine department of Medical imaging Affiliated Hospital of Jining Medical University department of Radiology the Peking University Shenzhen Hospital department of Pathology Guilin Traditional Chinese Medicine Hospital department of Pathology the Affiliated Hospital of Qingdao University Shandong Provincial Key Medical and Health Laboratory of Intelligent Diagnosis and Treatment for Women’s Diseases Yantai Yuhuangding Hospital department of Pathology Yantai Yuhuangding Hospital of Qingdao University

Objective: Early predicting response before neoadjuvant chemotherapy(NAC) is crucial for personalized treatment plans for locally advanced breast cancer patients. We aim to develop a multi-task model using multiscale whole slide images(WSIs) features to predict the response to breast cancer NAC more ***: This work collected 1,670 whole slide images for training and validation sets, internal testing sets,external testing sets, and prospective testing sets of the weakly-supervised deep learning-based multi-task model(DLMM) in predicting treatment response and pCR to NAC. Our approach models two-by-two feature interactions across scales by employing concatenate fusion of single-scale feature representations, and controls the expressiveness of each representation via a gating-based attention ***: In the retrospective analysis, DLMM exhibited excellent predictive performance for the prediction of treatment response, with area under the receiver operating characteristic curves(AUCs) of 0.869 [95% confidence interval(95% CI): 0.806-0.933] in the internal testing set and 0.841(95% CI: 0.814-0.867) in the external testing sets. For the pCR prediction task, DLMM reached AUCs of 0.865(95% CI: 0.763-0.964) in the internal testing and 0.821(95% CI: 0.763-0.878) in the pooled external testing set. In the prospective testing study, DLMM also demonstrated favorable predictive performance, with AUCs of 0.829(95% CI: 0.754-0.903) and 0.821(95% CI:0.692-0.949) in treatment response and pCR prediction, respectively. DLMM significantly outperformed the baseline models in all testing sets(P<0.05). Heatmaps were employed to interpret the decision-making basis of the model. Furthermore, it was discovered that high DLMM scores were associated with immune-related pathways and cells in the microenvironment during biological basis ***: The DLMM represents a valuable tool that aids clinicians in selecting personalized treatment strategies for breast

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Polarization variable terahertz metasurface along the propagation path

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Fundamental Research 2025年第1期5卷 124-131页

作者： Jitao Li Jingyu Liu Zhen Yue Jie Li Chenglong Zheng Fan Yang Hui Li Yating Zhang Yan Zhang Jianquan Yao Key Laboratory of Opto-Electronics Information Technology(Tianjin University) Ministry of EducationSchool of Precision Instruments and Opto-Electronics EngineeringTianjin UniversityTianjin 300072China Beijing Key Laboratory for Metamaterials and Devices Key Laboratory of Terahertz OptoelectronicsMinistry of Educationand Beijing Advanced Innovation Center for Imaging TechnologyDepartment of PhysicsCapital Normal UniversityBeijing 100048China

Conventional metasurfaces for terahertz polarization are limited to performing lateral(in the x-y plane)polarization control of the output *** such cases,the polarization state remains unchanged in each output plane along the propagation ***,we propose a terahertz polarization metasurface that operates longitudinally(i.e.,along the z-axis direction of propagation),which modifies the polarization state of each output plane throughout the propagation *** designed metasurface can control the phase delays of the left-handed and right-handed circularly polarized(LCP and RCP)components of the incident terahertz *** enables the LCP beam and RCP beam to converge to the z-axis through distinct paths,creating a Bessel *** proposed design achieved a linearly polarized terahertz wave including both LCP and RCP components with a precise phase differenceΔφat each point within a certain range along the ***Δφvaries as the propagation distance,resulting in a rotated linearly polarized output wave along the propagation path,while the rotation angle ranges from 0 toπ.Based on the variable property of longitudinal polarization,we propose an application concept of dielectric refractive index sensing,in which an additional medium is placed in the terahertz propagation path and the unknown refractive index is determined by detecting the rotation angle of the output polarization ***,the device might find potential applications in variable media excitation,terahertz communication,and terahertz radar ranging.

关键词： Terahertz Metasurface Propagation path Polarization manipulation Longitudinal polarization Refractive index sensing

Dependence of Generation of Hippocampal CAI Slow Oscillations on Electrical Synapses

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Neuroscience Bulletin 2020年第1期36卷 39-48页

作者： Yuan Xu Feng-Yan Shen Yu-Zhang Liu Lidan Wang Ying-Wei Wang Zhiru Wang Institute and Key Laboratory of brain functional Genomics of The Chinese Ministry of Education Shanghai Key Laboratory of Brain Functional GenomicsSchool of Life SciencesEast China Normal UniversityShanghai 200062China department of Anesthesiology Huashan HospitalFudan UniversityShanghai 200040China

Neuronal oscillations in the hippocampus are critical for many brain functions including learning and *** underlying mechanism of oscillation generation has been extensively investigated in terms of chemical synapses and ion ***,electrical synapses have also been indicated to play important roles,as reported in various brain areas in vivo and in brain ***,this issue remains to be further clarified,including in hippocampal ***,using the completely isolated hippocampus,we investigated in vitro the effect of electrical synapses on slow CA1 oscillations(0.5 Hz-1.5 Hz)generated intrinsically by the *** found that these oscillations were totally abolished by bath application of a general blocker of gap junctions(carbenoxolone)or a specific blocker of electrical synapses(mefloquine),as determined by whole-cell recordings in both CA1 pyramidal cells and fast-spiking *** findings indicate that electrical synapses are required for the hippocampal generation of slow CA1 oscillations.

关键词： Electrical synapse Hippocampus Oscillation CA1 Mefloquine Carbenoxolone Introduction

Plasma metabolomics combined with mass spectrometry imaging reveals crosstalk between tumor and plasma in gastric cancer genesis and metastasis

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Chinese Chemical Letters 2025年第1期36卷 506-512页

作者： Yanhua Chen Xian Ding Jun Zhou Zhaoying Wang Yunhai Bo Ying Hu Qingce Zang Jing Xu Ruiping Zhang Jiuming He Fen Yang Zeper Abliz Key Laboratory of Mass Spectrometry imaging and Metabolomics(State Ethnic Affairs Commission) Center for Imaging and Systems BiologyCollege of Life and Environmental SciencesMinzu University of ChinaBeijing 100081China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100050China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Center of Drug Clinical TrialPeking University Cancer Hospital and InstituteBeijing 100142China Beijing Engineering Research Center of Food Environment and Public Health Minzu University of ChinaBeijing 100081China Key laboratory of Ethnomedicine of Ministry of Education School of PharmacyMinzu University of ChinaBeijing 100081China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of BioBankPeking University Cancer Hospital and InstituteBeijing 100142China Pharmacy department of Beijing Chao–Yang Hospital Capital Medical UniversityBeijing 100020China

Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor *** elevated mortality rates are primarily due to its proclivity for late-stage *** the metabolic interactions between tumor microenvironment and the systemic bloodstream could help to clearly understand the mechanisms and identify precise biomarkers of tumor growth,proliferation,and *** this study,an integrative approach that combines plasma metabolomics with mass spectrometry imaging of tumor tissue was developed to investigate the global metabolic landscape of GC tumorigenesis and *** results showed that the oxidized glutathione to glutathione ratio(GSSH/GSH)became increased in non-distal metastatic GC(M0),which means an accumulation of oxidative stress in tumor ***,it was found that the peroxidation of polyunsaturated fatty acids,such as 9,10-EpOMe,9-HOTrE,etc.,were accelerated in both plasma and tumor tissues of distal metastatic GC(M1).These changes were further confirmed the potential effect of CYP2E1 and GGT1 in metastatic potential of GC by mass spectrometry imaging(MSI)and immunohistochemistry(IHC).Collectively,our findings reveal the integrated multidimensional metabolomics approach is a clinical useful method to unravel the bloodtumor metabolic crosstalk,illuminate reprogrammed metabolic networks,and provide reliable circulating biomarkers.

关键词： Metabolomics Spatial-resolved metabolomics Gastric cancer Blood-tumor metabolic crosstalk Lipid peroxidation

Association of CDH11 with Autism Spectrum Disorder Revealed by Matched-gene Co-expression Analysis and Mouse Behavioral Studies

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Neuroscience Bulletin 2022年第1期38卷 29-46页

作者： Nan Wu Yue Wang Jing-Yan Jia Yi-Hsuan Pan Xiao-Bing Yuan Key Laboratory of brain functional Genomics of Shanghai and the Ministry of Education Institute of Brain Functional GenomicsSchool of Life Science and the Collaborative Innovation Center for Brain ScienceEast China Normal UniversityShanghai200062China Hussman Institute for Autism Baltimore21201USA department of Anatomy and Neurobiology University of Maryland School of MedicineBaltimore21201USA

A large number of putative risk genes for autism spectrum disorder(ASD)have been *** functions of most of these susceptibility genes in developing brains remain unknown,and causal relationships between their variation and autism traits have not been *** aim of this study was to predict putative risk genes at the whole-genome level based on the analysis of gene co-expression with a group of high-confidence ASD risk genes(hcASDs).The results showed that three gene features–gene size,mRNA abundance,and guanine-cytosine content–affect the genome-wide co-expression profiles of *** circumvent the interference of these features in gene co-expression analysis,we developed a method to determine whether a gene is significantly co-expressed with hcASDs by statistically comparing the co-expression profile of this gene with hcASDs to that of this gene with permuted gene sets of feature-matched *** method is referred to as"matched-gene co-expression analysis"(MGCA).With MGCA,we demonstrated the convergence in developmental expression profiles of hcASDs and improved the efficacy of risk gene *** results of analysis of two recently-reported ASD candidate genes,CDH11 and CDH9,suggested the involvement of CDH11,but not CDH9,in *** with this prediction,behavioral studies showed that Cdh11-null mice,but not Cdh9-null mice,have multiple autism-like behavioral *** study highlights the power of MGCA in revealing ASD-associated genes and the potential role of CDH11 in ASD.

关键词： CDH11 Autism spectrum disorder Gene co-expression analysis Matched-gene co-expression analysis

Vascular dysfunction in Alzheimer’s disease: a biomarker of disease progression and a potential therapeutic target

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Neural Regeneration Research 2020年第6期15卷 1030-1032页

作者： Karan Govindpani Chitra Vinnakota Henry J.waldvogel Richard L.Faull Andrea Kwakowsky Centre for brain Research Department of Anatomy and Medical Imaging Faculty of Medical and Health Sciences University of Auckland

Alzheimer’s disease(AD)is a progressive neurodegenerative disorder and the predominant form of *** its initial description by Alois Alzheimer in 1906,several advances have been made in our understanding of the progression of the disease and its clinical consequences,yet the underlying etiology remains *** the stereotyped patterns of cortical and hippocampal neuronal loss and the progressive degeneration of key neurotransmitter pathways,research has traditionally been focused on factors affecting neuronal viability,including the contribution of glial dysfunction to neuronal *** a clinical perspective,the fruits of this work have been *** pathological markers of the disease,includingβ-amyloid(Aβ)plaque formation and tau hyperphosphorylation,have yielded no effective therapies,highlighted by the recent discontinuations of several high profile Aβimmunotherapy *** few current symptomatic therapies for AD are predicated on the amelioration of cholinergic or glutamatergic *** from underscoring the inadequacy of current therapeutic approaches,this also points to the importance of alternative contributors to AD *** recent years,there has been a growing appreciation for the multimodal and multifactorial nature of the condition;the case for combinatorial therapies is thus strong.

关键词： Alzheimer degeneration dysfunction

Self-assembling chemically modified siRNA nanorings for RNAi therapy and neuroprotection in Alzheimer's disease

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Science China Chemistry 2025年

作者： Yifan Jiang Lisha Li Xiao Fang Tao Zeng Lichao Su Yichang Liu Ying Wu Jinyu Li Peng Lyu Zhonglei Lu Chunhua Lu Huanghao Yang New Cornerstone Science Laboratory Ministry of Education Key Laboratory for Analytical Science of Food Safety and BiologyCollege of Chemistry Fuzhou University Fujian Key Laboratory of Medical Analysis Fujian Academy of Medical Sciences department of Neurosurgery Fujian Institute of Brain Disorders and Brain Science Fujian Clinical Research Center for Neurological Diseases First Affiliated Hospital Fujian Medical University National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies College of Chemistry Fuzhou University College of Biological Science and Technology Fuzhou University School of Medicine Fuzhou University

The development of RNA interference(RNAi) therapy offers a potential solution for Alzheimer's disease(AD). However, the brain-blood barrier(BBB) with its selective permeability and pharmacokinetic-related challenges poses restrictions on the delivery of small interfering RNA(siRNA) to the central nervous system(CNS). In this study, we demonstrate that the incorporation of 2'-fluoro(2'-F) substitutions and L-carnitine modification facilitates the self-assembly of siRNA through triple interaction, leading to the formation of nanorings, called LCSF-NR. Based on the enhanced cellular uptake and lysosomal escape by 2'-F substitution and the transport across the BBB promoted by L-carnitine, the nanorings realized the improved braintargeted delivery of siRNA, both in zebrafish and mice models. Moreover, our findings highlight the therapeutic potential of LCSF-NR formulation in an AD zebrafish model through a synergistic effect of downregulating the β-site APP cleavage enzyme1(BACE1) gene and L-carnitine-mediated neuroprotection, effectively inhibiting pathological processes. Overall, these results suggest that the chemical modification-based siRNA self-assembly strategy enables trans-BBB delivery and presents a concise approach for synergistic therapy of AD.

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First-episode psychiatric disorder risk from SARS-Co V-2 infection:A clinical analysis with Chinese psychiatric inpatients

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Journal of Biomedical Research 2025年第1期39卷 50-60页

作者： Ya Xie Zifeng Xu Yumin Zhang Yisheng Li Pengyu Du Chun Wang Clinical Mental Health Center the Affiliated Brain Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Medical School of Nanjing University NanjingJiangsu 210008China

The extensive spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)throughout China in late 2022 has underscored the correlation between this virus and severe psychiatric ***,there remains a lack of reported clinical and pathological ***,we retrospectively reviewed the electronic medical records of psychiatric inpatients for seven days from early January ***-one inpatients who developed first-episode psychiatric disorders within two weeks after SARS-CoV-2 infection were recruited,while 24 uninfected first-episode psychiatric inpatients were selected as *** analyses of clinical manifestations,routine laboratory tests,and imaging examinations were *** investigation demonstrated a 330%increase in the incidence of first-episode psychiatric inpatients after SARS-CoV-2 infection in 2023,compared with the preceding year without SARS-CoV-2 *** cases exhibited psychiatric symptoms within one week of SARS-CoV-2 infection,which resolved after approximately two weeks,with no residual symptoms after three ***-way ANOVA demonstrated a significant difference in the highest fever temperature between inpatients with and without psychotic *** inpatients displayed elevated levels of interleukin-4,interleukin-8,and interferon-α,but decreased levels of eosinophils and *** findings suggest that SARS-CoV-2 may contribute to the development of psychiatric disorders,likely mediated by the virus-induced inflammatory response and neuronal dysfunction in the context of psychological distress.

关键词： COVID-19 SARS-CoV-2 psychiatric disorders inflammation interleukins