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A mutation in TBXT causes congenital vertebral malformations in humans and mice

Journal of Genetics and Genomics 2024年第4期51卷 433-442页

作者： Shuxia Chen Yunping Lei yajun Yang Chennan Liu Lele Kuang Li Jin Richard HFinnell Xueyan Yang Hongyan Wang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic Engineering at School of Life SciencesKey Laboratory of Reproduction Regulation of NPFPCInstitute of Reproduction and DevelopmentFudan UniversityShanghai 200438China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Center for Precision Environmental Health Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonTX 77030USA MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 200438China Department of Assisted Reproduction Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Children’s Hospital Fudan University399 Wanyuan RoadShanghai 201102China

T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal *** it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well ***,we report a family with 15 CVM patients distributed across 4 *** affected individuals carry a heterozygous mutation,T c.596A>G(p.Q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and *** vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the *** determine the pathogenicity of this mutation in vivo,we generated a Q199R knock-in mouse model that recapitulates the human CVM *** heterozygous Q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral ***,we show that the Q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM.

关键词： Congenital vertebral malformation TBXT T gene Loss-of-function mutation

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Comprehensive genomic analysis of early and late-onset hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 77-81页

作者： Jialin Yang Chao Chen Song Wang Yaru Zhang Jiaohui Pang yajun Wang Qiuxiang Ou Hao Jiang Juying Liu Department of Radiation Oncology Sichuan Cancer Hospital&InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan 610041China Jinling Hospital Department of OncologyNanjing Medical UniversityNanjingJiangsu 210002China Geneseeq Research Institute Nanjing Geneseeq Technology Inc.NanjingJiangsu 210000China Department of Oncology Haian Hospital of Traditional Chinese MedicineHaianJiangsu 226600China Interventional Therapy Department Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsu 210009China

Hepatocellular carcinoma(HCC)is the major histologic type of primary liver cancer,accounting for approximately 75%of liver cancer cases.'Despite many advancements in its treatment,the prognosis and drug response of HCC patients are ***,there is an unmet clinical need to explore genomic aberrations underlying early-and lateonset HcC,which might facilitate drug discovery and provide personalized biomarker-driven treatment options for these patients.

关键词： patients prognosis cancer

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Analysis of the History and Current Situation of the Development of General Practice Teaching Clinics in China

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Open Journal of Preventive Medicine 2024年第2期14卷 29-38页

作者： Xiaotong Huo yajun Lian Graduate School Changzhi Medical College Changzhi China Department of Family Medicine Peace Hospital Changzhi Medical College Changzhi China

A summary of the exploration of the teaching mode of the general practice teaching clinic, a summary of the deficiencies of the teaching clinic and a summary of the significance of the establishment of the general practice teaching clinic are presented with a view to promoting the development of general practice and cultivating more excellent successors in general practice.

关键词： General Practice Teaching Clinic Teaching Models Teaching Deficiencies in the Clinic Significance of the Teaching Clinic

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A chromatographic method for pursuing potential GPCR ligands with the capacity to characterize their intrinsic activities of regulating downstream signaling pathway

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Chinese Chemical Letters 2024年第10期35卷 425-429页

作者： Ting Li Xinxin Zheng Lejing Qu Yuanyuan Ou Sai Qiao Xue Zhao yajun Zhang Xinfeng Zhao Qian Li Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationCollege of Life SciencesNorthwest UniversityXi'an 710069China

GPCRs are dominant targets for approved drugs and the discovery of lead compound targeting them is still ***-based screening technique is a promising platform to uncover GPCR ***,the intrinsic activities of them are seldom simultaneously determined during the *** beta2.adrenoceptor(β2.R)as a probe,this work created a strategy for screening GPCR ligands with simultaneous characterization of their downstream G protein binding responses associated with *** strategy included(i)the design and expression of a protein miniature formed byβ2.R and G proteinα-subunit(Gαs)using circularly permuted HaloTag(cpHalo)as a flexible linker;(ii)immobilization of the miniature onto silica gel by a click dehalogenation reaction;(iii)systematic characterization of the immobilized miniature by fluorescent and chromatographic studies,and(iv)simulating of ligand-inducedβ2.R-Gαs signaling cascade by chromatographic assays using GTP as an *** immobilized miniature exhibited specificity toβ2.R and Gαs antibodies and *** specificity is stable at least within fifteen days with the variation less than 1%.The intrinsic activities ofβ2.R ligands were distinguished by the changes of GTP chromatographic behaviors on Gαs-cpHalo-β2.R *** strengthened the binding affinity and kinetics of GTP with Gαs,while antagonist did not give any effect on *** the intrinsic activity evaluation,we believe,it will improve the attributes of chromatographic methods for drug discovery efforts with minimizing false-positive results.

关键词： Intrinsic efficacy GPCR-G protein miniature Circularly permuted HaloTag High-performance receptor chromatography GTP binding Agonist/antagonist

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High-static-low-dynamic stiffness isolator based on an electromagnetic negative stiffness spring with long linear stroke

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Science China(Technological Sciences) 2024年第3期67卷 740-752页

作者： YUAN ShuJin WU yajun SONG DaiPing PU HuaYan MOU LiSheng HOU Lei ZHAO JingLei LI XuePing LUO Jun WU Jie HUANG XiaoXu State Key Laboratory of Mechanical Transmissions Chongqing UniversityChongqing 400044China China Aerodynamics Research and Development Center Mianyang 621000China College of Materials Science and Engineering Chongqing UniversityChongqing 400044China

Negative stiffness mechanisms can improve low-frequency vibration isolation performance and have been widely used in the vibration isolation of precision equipment. However, the negative stiffness mechanism usually introduces a nonlinear stiffness,resulting in a nonlinear response and worsening the vibration isolation performance, especially under large amplitude *** this paper, an electromagnetic spring with linear negative stiffness(ESLNS) is proposed, in which the antagonistic ampere forces of the energized coils are used to generate negative stiffness within a long linear stroke. The magnetic field distribution is improved through the design of the magnetic circuit, thereby increasing the stiffness generation efficiency. The stiffness can be adjusted bidirectionally by current within the range of positive and negative stiffness. An electromagnetic stiffness model was established based on the equivalent magnetic circuit method. Experimental measurements verified the accuracy of the model and proved the linearity of the electromagnetic spring. A vibration isolator with high static and low dynamic stiffness(HSLDS) based on the ESLNS is designed and tested. The experimental results prove that the introduction of the ESLNS can effectively expand the isolation frequency band without changing the equilibrium position. Moreover, the vibration isolator with ESLNS does not produce nonlinear response. The proposed electromagnetic spring with linear negative stiffness extends the application range of HSLDS isolators to a large amplitude vibration environment.

关键词： linear negative stiffness mechanism low-frequency vibration isolation electromagnetic spring vibration control

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The Transfer and Change of Paints in a Hit-and-run Motor Vehicle Accident

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Journal of Forensic Science and Medicine 2024年第1期10卷 24-27页

作者： Can Hu Jun Zhu Hongcheng Mei Hongling Guo Ping Wang yajun Li Trace Evidence Department Institute of Forensic ScienceMinistry of Public SecurityXichengBeijingChina

This work investigated transfer and change of paint evidences in a case of *** kinds of attachments were found on the clothes of the victim and they were initially considered paint fragments from the vehicle causing the *** spectroscopy(IR),scanning electron microscope-energy dispersive spectrometer,and Microspectrophotometry were applied for examination of paints and clothing *** was detected in one of the attachments and in the clothing fibers of the victim by IR.A traffic accident simulation experiment was designed and conducted to research whether the polyester attachments come from suspected vehicle paints or victim’s clothing *** results showed that a melt mixture of transferred paints and clothing fiber was formed after a violent *** the amount of transferred paints was too low to be detectable in the mixture,the components detected by IR were mainly from clothing ***,we inferred that only one kind of attachment and paint fragments existed on the clothes of the victim,and the polyester attachments cannot be used to indicate the composition of suspected vehicle *** fibers and paints are both common trace evidence in traffic accident cases,and more attention should be paid to the examination of transferred paints on clothing fibers.

关键词： Clothing fibers hit‑and‑run traffic accident infrared spectroscopy paints trace evidence transfer

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Camellia sinensis CsMYB4a participates in regulation of stamen growth by interaction with auxin signaling transduction repressor CsAUX/IAA4

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The Crop Journal 2024年第1期12卷 188-201页

作者： Guoliang Ma Mingzhuo Li Yingling Wu Changjuan Jiang Yifan Chen Dawei Xing Yue Zhao yajun Liu Xiaolan Jiang Tao Xia Liping Gao School of Life Science Anhui Agricultural UniversityHefei 230036AnhuiChina Plant for Human Health Institute Department of Plant and Microbial BiologyNorth Carolina State UniversityKannapolisNC 28081USA State Key Laboratory of Tea Plant Biology and Utilization/Key Laboratory of Tea Biology and Tea Processing of Ministry of Agriculture/Anhui Provincial Laboratory of Tea Plant Biology and Utilization Anhui Agricultural UniversityHefei 230036AnhuiChina

Subgroup 4(Sg4)members of the R2.3-MYB are generally known as negative regulators of the phenylpropanoid pathway in *** previous research showed that a R2.3-MYB Sg4 member from Camellia sinensis(CsMYB4a)inhibits expression of some genes in the phenylpropanoid pathway,but its physiological function in the tea plant remained ***,CsMYB4a was found to be highly expressed in anther and filaments,and participated in regulating filament *** analysis and exogenous auxin treatment showed that the target of CsMYB4a might be the auxin signal ***/indole-3-acetic acid 4(AUX/IAA4),a repressor in auxin signal transduction,was detected from a yeast two-hybrid screen using CsMYB4a as *** silencing assays showed that both CsIAA4 and CsMYB4a regulate filament *** plants overexpressing CsIAA4 were insensitive to exogenous a-NAA,consistent with overexpression of ***-protein interaction experiments revealed that CsMYB4a interacts with N-terminal of CsIAA4 to prevent CsIAA4 *** out of the endogenous NtIAA4 gene,a CsIAA4 homolog,in tobacco alleviated filament growth inhibition and a-NAA insensitivity in plants overexpressing *** results strongly suggest that CsMYB4a works synergistically with CsIAA4 and participates in regulation of the auxin pathway in stamen.

关键词： AUX/IAA4 Auxin signaling CsMYB4a Subgroup 4 R2.3-MYB

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Transcriptomic Analysis Reveals the Formation Mechanism of Anthocyanins Light-Independent Synthesis in Chrysanthemum

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1599-1621页

作者： Fangye Liu Jiaping Qu yajun Li Jiawei Fan Yumeng Cui Jingwen Wu Xueqi Gu Xia Li He Huang Beijing Advanced Innovation Center for Tree Breeding by Molecular Design Beijing Key Laboratory of Ornamental Plants Germplasm Innovation&Molecular BreedingNational Engineering Research Center for FloricultureBeijing Laboratory of Urban and Rural Ecological EnvironmentKey Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants of Education MinistrySchool of Landscape ArchitectureBeijing Forestry UniversityBeijing100083China Urban Construction School Beijing City UniversityBeijing100083China

Chrysanthemum×morifolium is a horticultural crop which plays a vital role in theﬂower industry with signiﬁ-cant economic value and has a cultivation history of over three thousand years in *** accumulation of anthocyanins is always affected by ***,we revealed that anthocyanin accumulation is highly dependent on light in‘2.2.135’genotype chrysanthemum,while it is light-independent in‘2.01402.genotype ***,no literature has been reported regarding the non-photosensitive chrysanthemum in anthocya-nins light-independent synthesis *** the phenotype analysis of 44 F1 generations,we found that light-independence is a dominant trait which can be stable inherited by *** transcriptome of the rayﬂorets of‘2.2.135’and‘2.01402.under light and bagging treatment were sequenced and *** on weighted gene co-expression network analysis(WGCNA),K-means analysis,and Real-Time Quantitative Poly-merase Chain Reaction(RT-qPCR)analysis,16 genes were highly correlated with the anthocyanin *** anthocyanin content of rayﬂorets treated with different light-quality conditions indicated that blue light signiﬁ-cantly affected anthocyanin *** Yeast one-hybrid analysis,CmBIC1.1 and CmBIC1.2.can directly regulate the anthocyanin structural gene *** our study,we revealed the important characteristics of light-independent anthocyanin synthesis in chrysanthemums and screened regulatory factors in light-depen-dent and light-independent anthocyanin synthesis *** results laid the groundwork for subsequent ana-lysis of the molecular mechanism involved in the light-independent synthesis of anthocyanins in chrysanthemums.

关键词： Chrysanthemum non-photosensitive transcriptome anthocyanin biosynthesis

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Tumor Receptor-Seeking Dyes for Rapid Intraoperative Definition of Tumor Margin and Histopathological Morphology

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CCS Chemistry 2024年第10期6卷 2577-2593页

作者： yajun Wang Feiran Zhang Yunlong Jia Tianyang Han Chengbin Zhang Limei Qu Yuewei Zhang Shoujun Zhu State Key Laboratory of Supramolecular Structure and Materials Center for Supramolecular Chemical BiologyCollege of ChemistryJilin UniversityChangchun 130012 Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry The First Hospital of Jilin UniversityChangchun 130021 School of Chemistry and Pharmaceutical Engineering Jilin Institute of Chemical TechnologyJilin 132022 Department of Pathology The First Hospital of Jilin UniversityChangchun 130021

Histopathological diagnosis is a crucial part of surgical treatment,as it determines further treatment decisions and prognosis for *** to the heterogeneity of tumors,traditional histopathological diagnosis relies on histological and cytological morphological analysis of cryo-slides by well-trained pathologists,which is subjective,time-consuming,and lacks considerable ***,we engineer a series of tumor receptor-seeking dyes to automatically label and visually depict the tumor contour with antibody-free *** meso-chlorine on the cyclohexyl ring of dyes can covalently react with specific thiol groups in various tumor signature proteins to form stable dye@protein *** dye@protein complexes have significantly amplified fluorescence signals in tumor sites,enabling highresolution delineation of tumormargins and providing histological morphology information to potentially determine tumor *** orthogonal effect not only avoids errors caused by individual signature proteins,but also amplifies the fluorescence difference between tumor and normal ***,our method is easy to operate with a minimal detection time of only 4 *** tumor receptor-seeking dyes successfully assess tumor-positive margins from 66 resected breast tumor samples and 2. intraoperative cancer patients with 100%accuracy,providing a newgeneration technique for intraoperative pathologic diagnosis of tumor biopsy.

关键词： tumor receptor-seeking dyes tumor-positive margins chemoselective covalent labeling nearinfrared imaging histopathological morphology

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Association between Mental Health Literacy and Workplace Well-Being of Chinese Grassroots Civil Servants:The Chain Mediating Effects of Regulatory Emotional Self-Efficacy and Resilience

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International Journal of Mental Health Promotion 2024年第7期26卷 559-568页

作者： Yi Tang yajun Zhao Zihan Jin Shengnan Wu Zhijun Zhang Ju Zhou Ling Zhou Chongqing Academy of Governance Chongqing400041China School of Education and Psychology Southwest Minzu UniversityChengdu610041China School of Educational Sciences Chongqing Normal UniversityChongqing401331China Department of Psychology and Behavioral Sciences Zhejiang UniversityHangzhou310030China Nanping Experimental Primary School Chongqing400060China

This study aimed to investigate the relationship between mental health literacy(MHL)and workplace well-being(WWB)of Chinese grassroots civil servants,with regulatory emotional self-efﬁcacy(RESE)and resilience as mediating variables.A questionnaire survey was conducted among Chinese grassroots civil servants,with a valid sample size of 2.73 after excluding missing values and conducting relevant data *** PROCESS was used to examine the relationship between MHL,RESE,resilience,and *** study found that MHL among grassroots civil servants was positively and signiﬁcantly correlated with WWB(r=0.73,p2.,95%CI[0.2.,0.2.]).Resilience partially mediated the relationship between MHL and WWB(β=0.2.,95%CI[0.19,0.2.]).MHL had a positive effect on WWB through the chain mediating effect of RESE and resilience(β=0.05,95%CI[0.03,0.07]).There is a close relationship between MHL and WWB,where Chinese grassroots civil servants with higher levels of MHL can develop stronger RESE and resilience,leading to higher *** results of this study remind organizational institutions of Chinese grassroots civil servants that enhancing MHL,RESE,and resilience is an important pathway to promoting their WWB.

关键词： Mental health literacy workplace well-being regulatory emotional self-efﬁcacy resilience Chinese grassroots civil servants

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