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A Non-canonical Excitatory PV RGC–PV SC Visual Pathway for Mediating the Looming-evoked Innate Defensive Response

Neuroscience Bulletin 2024年第3期40卷 310-324页

作者： Man Yuan Sen Jin Gao Tan Siyuan Song Yizong Liu Huadong Wang Yin Shen Eye Center Renmin Hospital of Wuhan UniversityWuhan UniversityWuhan430060China The Brain Cognition and Brain Disease institute Shenzhen Key Laboratory of Viral Vectors for BiomedicineShenzhen Institute of Advanced TechnologyChinese Academy of Sciences(CAS)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsNational Medical Products Administration Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsShenzhen Key Laboratory of Quality Control Technology for Virus-Based TherapeuticsGuangdong Provincial Medical Products AdministrationShenzhen518055China Jan and Dan Duncan Neurological Research institute Baylor College of MedicineHouston77030USA State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Key Laboratory of Magnetic Resonance in Biological SystemsWuhan Center for Magnetic ResonanceInnovation Academy for Precision Measurement Science and TechnologyCASWuhan430071China Frontier Science Center of Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan430071China

Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various ***,their role in transmitting visual information remains ***,we characterized PV+RGCs in the retina and explored the functions of the PV+RGC-mediated visual *** applying multiple viral tracing strategies,we investigated the downstream of PV+RGCs across the whole ***,we found that the PV+RGCs provided direct monosynaptic input to PV+excitatory neurons in the superficial layers of the superior colliculus(SC).Ablation or suppression of SC-projecting PV+RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual ***,using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs,we found that PV+RGCs are predominant glutamatergic ***,our findings indicate the critical role of PV+RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+RGCs to PV+SC neurons that regulates looming visual *** results provide a potential target for intervening and treating diseases related to this circuit,such as schizophrenia and autism.

关键词： Parvalbumin-positive retinal ganglion cell Innate fear Superior colliculus Excitatory-excitatory neuronal connection Looming-evoked defensive response Subcortical pathway

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Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

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Military Medical Research 2024年第2期11卷 180-205页

作者： Hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor biological Behaviors Wuhan 430071China Department of Pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Pathology and Molecular Diagnostics Wuhan UniversityWuhan 430071China wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain ***,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of ***:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of wuhan *** advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in *** expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting *** elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in *** Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical ***:ASPA was identified as a novel inhibitor of PCa *** expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,mig

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

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Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2312-2323页

作者： Xian Li Mengxin Xu Jingyi Yang Li Zhou Lin Liu Min Li Shasha Wang Mei-Qin Liu Zhixiang Huang Zhen Zhang Shuning Liu Yunqi Hu Haofeng Lin Bowen Liu Ying Sun Qingguo Wu Zheng-Li Shi Ke Lan Yu Chen Huimin Yan Yao-Qing Chen wuhan institute of Virology Chinese Academy of SciencesWuhanChina Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghaiChina University of Chinese Academy of Sciences BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdongChina State Key Laboratory of Virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhouJiangsuChina National Medical products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and biological products Sun Yat-sen UniversityGuanzhouChina

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the ***,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a *** long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD *** upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)*** a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary *** meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including *** findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关键词： vaccination vaccine sustained

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Nickel-Catalyzed Stereoselective Migratory Carboboration of 1,4-Cyclohexadiene

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Chinese Journal of Chemistry 2024年第4期42卷 356-362页

作者： Yaoyu Ren Lujin Wang Chao Ding Yangyang Li Guoyin Yin The institute for Advanced Studies Wuhan UniversityWuhanHubei430072 China

Multi-substituted cyclohexanes play a crucial role as scaffolds in bioactive *** significant progress has been made in synthesizing substituted cyclohexanes,methods for the stereoselective assembly of 1,3-disubstituted cyclohexanes remain *** study presents a novel approach involving nickel catalysis to achieve stereoselective carboboration of 1,*** innovative process allows for the simultaneous introduction of a boron group and an aryl or an alkyl fragment into the 1,4-cyclohexadiene framework under mild conditions,with exclusive regioselectivity and excellent cis *** resulting products feature a double carbon bond and the incorporation of the boron group,offering significant potential for subsequent transformations and downstream applications.

关键词： 1,4-Cyclohexadiene Carboboration Nickel Chain-walking Stereoselectivity Difunctionalization

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Visible-light-activated aziridination reaction enables simultaneous resolving of C=C bond location and the sn-position isomers in lipids

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Chinese Chemical Letters 2024年第4期35卷 481-485页

作者： Qiongqiong Wan Yanan Xiao Guifang Feng Xin Dong Wenjing Nie Ming Gao Qingtao Meng Suming Chen The institute for Advanced Studies Renmin Hospital of Wuhan UniversityWuhan UniversityWuhan 430072China

There is a close relationship between the biological functions of lipids and their structures, and various isomers greatly increases the complexity of lipid structures. The C=C bond location and sn-position are two of the essential attributes that determine the structures of unsaturated lipids. However, simultaneous identification of both attributes remains challenging. Here, we develop a visible-light-activated aziridination reaction system, which enables the dual-resolving of the C=C bond location and sn-position isomerism of in lipids when combines with liquid chromatography-mass spectrometry(LC-MS). Based on the derivatization of C=C bonds with Ph I=NTs, their location in lipids could be easily identified by tandem MS. Especially, the sn-position isomers of unsaturated phosphatidylcholine(PC) can be separated and quantified by LC-MS after the derivatization. By using the proposed method, the significant changes of the sn-position isomers ratios of PC in mouse brain ischemia were revealed. This study offers a powerful tool for deep lipid structural biology.

关键词： Aziridination Lipid isomers C=C bond location sn-Position Mass spectrometry

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Microbial phenolic metabolites 3-(3',4'-dihydroxyphenyl)propanoic acid and 3',4'-dihydroxyphenylacetic acid prevent obesity in mice fed high-fat diet

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Food Science and Human Wellness 2024年第1期13卷 327-338页

作者： Wanbing Chen Ruonan Liu Xiaoling Zhu Qun Lu Hong Yang Rui Liu College of Food Science and Technology Huazhong Agricultural UniversityWuhan 430000China Key Laboratory of Environment Correlative Dietology(Huazhong Agricultural University) Ministry of educationWuhan 430000China wuhan Engineering Research Center of Bee products on Quality and Safety Control Wuhan 430000China Key Laboratory of Urban Agriculture in Central China Ministry of Agriculture and Rural AffairsWuhan 430000China Hubei Provincial institute for Food Supervision and Test Wuhan 430070China

Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in ***,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid(DHPA)and 3’,4’-dihydroxyphenylacetic acid(DHAA),two main metabolites of dietary polyphenols,on obesity remains poorly *** this study,DHPA and DHAA were found to alleviate obesity,as well as regulate insulin resistance,lipid metabolism,and oxidative stress response in high-fat diet(HFD)***,the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome,but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion,tyrosine metabolism,pentose phosphate and tricarboxylic acid(TCA)cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)*** analysis revealed that the differential metabolites are strongly associated with body weight,blood glucose,insulin level,and superoxide dismutase(SOD)enzyme *** results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose,lipid and tyrosine metabolism pathways.

关键词： Obesity Dietary polyphenol metabolites Gut microbiota Metabonomics

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Fine mapping and cloning of the sterility gene Bra2Ms in nonheading Chinese cabbage(Brassica rapa ***)

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Journal of Integrative Agriculture 2024年第4期23卷 1195-1204页

作者： Liping Song Xia Li Liguang Tang Chuying Yu Bincai Wang Changbin Gao Yanfeng Xie Xueli Zhang Junliang Wang Chufa Lin Aihua Wang wuhan Vegetable Research institute Wuhan Academy of Agricultural SciencesWuhan 430345China Biotechnology and Genetic Resources institute Yunnan Academy of Agricultural SciencesKunming 650000China

The application of a male-sterile line is an ideal approach for hybrid seed production in non-heading Chinese cabbage(Brassica rapa ***).However,the molecular mechanisms underlying male sterility in *** are still largely *** previously obtained the natural male sterile line WS24-3 of non-heading Chinese cabbage and located the male sterile locus,Bra2Ms,on the A2 *** observations revealed that the male sterility of WS24-3 resulted from disruption of the meiosis process during pollen *** mapping of Bra2Ms delimited the locus within a physical distance of about 129 kb on the A2 chromosome of *** Bra039753 gene encodes a plant homeodomain(PHD)-finger protein and is considered a potential candidate gene for ***039753 was significantly downregulated in sterile line WS24-3 compared to the fertile line at the meiotic anther *** analysis of Bra039753 identified a 369 bp fragment insertion in the first exon in male sterile plants,which led to an amino acid insertion in the Bra039753 *** addition,the 369 bp fragment insertion was found to cosegregate with the male sterility *** study identified a novel locus related to male sterility in non-heading Chinese cabbage,and the molecular marker obtained in this study will be beneficial for the marker-assisted selection of excellent sterile lines in non-heading Chinese cabbage and other Brassica crops.

关键词： non-heading Chinese cabbage male sterility Bra2Ms fine mapping PHD-finger protein

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A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers

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Biomedical and Environmental Sciences 2024年第5期37卷 445-456页

作者： HU Wei Qiong ZHOU Wei Guang ZHOU Guang Wei LIAO Jia Xi SHI Jia Xing XIE FengYang LI Shou Heng WANG Yong FENG Xian Hong GU Xiu Li CHEN Bi Feng Department of biological Science and Technology School of ChemistryChemical Engineering and Life SciencesWuhan University of TechnologyWuhan 430070HubeiChina institute of WUT-AMU Wuhan University of TechnologyWuhan 430070HubeiChina Department of Clinical Laboratory Wuhan Xinzhou District People’s HospitalWuhan 430499HubeiChina Department of Reproductive Genetics Wuhan Huake Reproductive HospitalWuhan 430013HubeiChina

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than ***,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer *** A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were *** of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger ***-four eligible studies were included in the *** After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese *** meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese *** The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

关键词： LEPR gene rs1137101 Digestive system cancers Genetic susceptibility Meta-analysis

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Riparian habitat quality as an indicator of land use/land cover effects on riverine water quality

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Geography and Sustainability 2024年第1期5卷 135-143页

作者： Shijie Gu Siyue Li School of Environmental Ecology and biological Engineering Key Laboratory for Green Chemical Process of Ministry of EducationHubei Key Laboratory of Novel Reactor and Green Chemical TechnologyWuhan Institute of TechnologyWuhan 430205China

Riparian land use/land cover(LULC)plays a crucial role in maintaining riverine water quality by altering the transport of pollutants and ***,establishing a direct relationship between water quality and LULC is challenging due to the multi-indicator nature of both *** quality encompasses a multitude of physical,chemical,and biological parameters,while LULC represents a diverse array of land use *** habitat quality(RHQ)serves as an indicator of ***,it remains to be seen whether RHQ can act as a proxy of LULC for assessing the impact of LULC on riverine water *** study examines the interplay between RHQ,LULC and water quality,and develops a comprehensive indicator to predict water *** measured several water quality parameters,including pH(potential of hydrogen),TN(total nitrogen),TP(total phosphorus),T_(water)(water temperature),DO(dissolved oxygen),and EC(electrical conductivity)of the Yue and Jinshui Rivers draining to the Han River during 2016,2017 and *** water quality index(WQI)was further *** is assessed by the InVEST(Integrated Valuation of Ecosystem Services and Tradeoffs)*** study found noticeable seasonal differences in water quality,with a higher WQI observed in the dry *** RHQ was strongly correlated with LULC *** positively correlated with WQI,and DO concentration and vegetation land were negatively correlated with T_(water),TN,TP,EC,cropland,and construction *** correlations were stronger in the rainy ***-dominated land,such as construction land and cropland,significantly contributed to water quality degradation,whereas vegetation promoted water *** models showed that the RHQ explained variations in WQI better than LULC *** study concludes that RHQ is a new and comprehensive indicator for predicting the dynamics of riverine water quality.

关键词： Water quality index Land use/land cover Riparian habitat quality Drinking water source areas

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Engineered AAV13 variants with enhanced transduction and confined spread

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Zoological Research 2024年第4期45卷 781-790页

作者： Neng-Song Luo Yu-Xiang Cai Zeng-Peng Han Xiao-Kai Sui Wen-Jia Yuan Zi-Lian Zhang Hao-Dong Guo Jie Wang Kun-Zhang Lin Fu-Qiang Xu wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Shenzhen Key Laboratory of Viral Vectors for Biomedicine Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Key Laboratory of Magnetic Resonance in biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Key Laboratory of Quality Control Technology for Virus-Based Therapeutics Guangdong Provincial Medical Products AdministrationNMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsBrain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China University of Chinese Academy of Sciences Beijing 100049China Zhongnan Hospital Wuhan UniversityWuhanHubei 430072China Brain Case Biotechnology Co. Ltd.ShenzhenGuangdong 518107China College of Life Sciences Wuhan UniversityWuhanHubei 430072China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Precise targeting of specific regions within the central nervous system(CNS)is crucial for both scientific research and gene therapy in the context of brain ***-associated virus 13(AAV13)is known for its restricted diffusion range within the CNS,making it an ideal choice for precise labeling and administration within small brain ***,AAV13 mediates relatively low expression of target ***,we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction *** first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 *** then inserted the 7m8 peptide,known to enhance cell transduction,into positions 587/588 and 585/586 of the AAV13 capsid,resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8,*** found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells compared to AAV13,while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice,with AAV13-587-7m8 infection retaining a limited spread *** modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.

关键词： Adeno-associated virus 13 AAV13-YF AAV13-587-7m8 AAV13-585-7m8 transduction efficiency

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