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Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients

World Journal of Diabetes 2024年第2期15卷 275-286页

作者： Ping Shi Yang Tian Feng Xu Lu-Na Liu Wan-Hong Wu Ying-Zhou Shi An-Qi Dai Hang-yu fang Kun-xia Li Chao Xu Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina Department of Pediatric Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityYantai 264099Shandong ProvinceChina

BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose *** in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14(MODY14).Currently,only two mutations[c.1655T>A(***552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this *** the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 *** To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 *** Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the *** exome sequencing was performed on the patients as well as their family *** pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics *** addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional ***,the impact of these variants on APPL1 protein expression and the insulin pathway were assessed,and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further *** A total of five novel mutations were identified,including four missense mutations(Asp632Tyr,Arg633His,Arg532Gln,and Ile642Met)and one intronic mutation(1153-16A>T).Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all *** Asp632Tyr and Arg633His variants also had pathogenicity based on *** addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different ***,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations

关键词： Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1 Maturity-onset diabetes of the young Bioinformatics analysis Gene mutation Domain

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改进DPC聚类算法的离群点检测与解释方法

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哈尔滨工业大学学报 2024年第8期56卷 68-85页

作者：周玉夏浩裴泽宣华北水利水电大学电气工程学院郑州450045

为解决全局离群点检测方法无法对局部离群点进行检测,以及局部异常因子在面对大量局部离群点时性能下降的问题,利用k近邻(KNN)和核密度估计方法(KDE)提出一种基于改进快速搜索和发现密度峰值聚类算法(KDPC)的离群点检测与解释方法,该方... 详细信息

为解决全局离群点检测方法无法对局部离群点进行检测,以及局部异常因子在面对大量局部离群点时性能下降的问题,利用k近邻(KNN)和核密度估计方法(KDE)提出一种基于改进快速搜索和发现密度峰值聚类算法(KDPC)的离群点检测与解释方法,该方法能够同时对数据点的全局和局部进行分析。首先,利用k近邻和核密度估计方法计算数据点的局部密度,代替传统DPC算法中根据截断距离计算的局部密度。其次,将数据点的k近邻距离之和作为全局异常值,并通过KDPC聚类算法计算簇密度以及数据点的局部异常值。最后,将数据点的全局与局部异常值进行乘积作为最终异常得分,选取异常得分最高的Top-n作为离群点,通过构建全局-局部异常值决策图对全局和局部离群点进行解释。利用人工数据集和UCI数据集进行实验并与10种常用离群点检测方法进行比较。结果表明,该方法对全局和局部离群点都有着较高的检测精度和检测性能,并且AUC方面受k值影响较小。同时,利用该方法对NBA球员数据进行分析讨论,进一步证明了该方法的实用性和有效性。

关键词：离群点检测聚类密度峰值 k近邻核密度估计

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基于改进麻雀搜索算法优化LSTM的滚动轴承故障诊断

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工程科学与技术 2024年第2期56卷 289-298页

作者：周玉房倩裴泽宣白磊华北水利水电大学电气工程学院河南郑州450045

为了对滚动轴承的工作状态及故障类别进行准确的诊断,本文采用长短时记忆(LSTM)神经网络作为分类器对滚动轴承数据集进行分类诊断。首先,从滚动轴承原始运行振动信号中提取时域和频域特征参数,组成具有高维特征参数的数据集;使用核主成... 详细信息

为了对滚动轴承的工作状态及故障类别进行准确的诊断,本文采用长短时记忆(LSTM)神经网络作为分类器对滚动轴承数据集进行分类诊断。首先,从滚动轴承原始运行振动信号中提取时域和频域特征参数,组成具有高维特征参数的数据集;使用核主成分分析(KPCA)方法对高维特征集进行降维处理,选取重要性程度高的特征构成输入特征向量。然后,针对LSTM神经网络在滚动轴承故障诊断中存在的超参数难以确定的问题,提出一种基于自适应t分布策略的麻雀搜索算法优化LSTM神经网络的故障诊断方法(tSSA–LSTM)。最后,使用凯斯西储大学滚动轴承数据中心的数据进行故障诊断精度测试、泛化性能测试及噪声环境下故障诊断性能测试等多个仿真实验,并将本文提出的诊断模型与麻雀搜索算法优化长短时记忆神经网络(SSA–LSTM)、遗传算法优化长短时记忆神经网络(GA–LSTM)、粒子群算法优化长短时记忆神经网络(PSO–LSTM)及传统LSTM诊断模型进行对比。结果表明:tSSA可以更有效地对LSTM的隐含层神经元数量、周期次数、学习率等超参数进行合理优化;所提方法的平均诊断准确率达到98.86%,交叉验证平均诊断结果为98.57%;所提方法在噪声干扰下的故障诊断准确率也优于对比方法。因此,本文提出的tSSA–LSTM模型不仅可以更精准地诊断滚动轴承故障状态,而且具有更强的泛化能力及抗干扰能力,有效地提高了滚动轴承故障诊断的性能。

关键词：麻雀搜索算法故障诊断长短时记忆神经网络特征提取滚动轴承

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Constructing a nomogram to predict overall survival of colon cancer based on computed tomography characteristics and clinicopathological factors

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World Journal of Gastrointestinal Oncology 2024年第10期16卷 4104-4114页

作者： Zhe-Xing Hu Yin Li Xuan Yang yu-xia Li Yao-Yao He xiao-Hui Niu Ting-Ting Nie xiao-fang Guo Zi-Long yuan Department of Radiology Hubei Cancer HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430079Hubei ProvinceChina Department of Radiology Wuhan Children’s HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014Hubei ProvinceChina College of Informatics Huazhong Agriculture UniversityWuhan 430070Hubei ProvinceChina

BACKGROUND The colon cancer prognosis is influenced by multiple factors,including clinical,pathological,and non-biological ***,only a few studies have focused on computed tomography(CT)imaging ***,this study aims to predict the prognosis of patients with colon cancer by combining CT imaging features with clinical and pathological characteristics,and establishes a nomogram to provide critical guidance for the individualized *** To establish and validate a nomogram to predict the overall survival(OS)of patients with colon *** A retrospective analysis was conducted on the survival data of 249 patients with colon cancer confirmed by surgical pathology between January 2017 and December *** patients were randomly divided into training and testing groups at a 1:1 *** and multivariate logistic regression analyses were performed to identify the independent risk factors associated with OS,and a nomogram model was constructed for the training *** curves were calculated using the Kaplan–meier *** concordance index(C-index)and calibration curve were used to evaluate the nomogram model in the training and testing *** Multivariate logistic regression analysis revealed that lymph node metastasis on CT,perineural invasion,and tumor classification were independent prognostic factors.A nomogram incorporating these variables was constructed,and the C-index of the training and testing groups was 0.804 and 0.692,*** calibration curves demonstrated good consistency between the actual values and predicted probabilities of *** A nomogram combining CT imaging characteristics and clinicopathological factors exhibited good discrimination and *** can aid clinicians in risk stratification and postoperative monitoring and provide important guidance for the individualized treatment of patients with colon cancer.

关键词： Colon cancer Nomogram Prognosis Overall survival Computed tomography Clinicopathology

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Research and Practice of Cardiopulmonary Rehabilitation Training Programs

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World Journal of Cardiovascular Diseases 2024年第9期14卷 557-566页

作者： Na Yan Maiding He Jinyue Jiang Juan Luo Ping Zhan Xichan wang xia Gao Jianzhu wang Na Yin fang Ye Jinghua yu Shiying Zhang Rehabilitation Medicine Qujing No. 1 Hospital Qujing China Rehabilitation Medicine Qujing Multi-Rehabilitation Hospital Qujing China

In today’s society, the incidence of cardiopulmonary diseases is increasing annually, seriously affecting patients’ quality of life. Therefore, developing a scientific and effective rehabilitation training program is of great significance. This study first analyzes the theoretical basis of cardiopulmonary rehabilitation training, including the effects of aerobic exercise, interval training, and strength training on cardiopulmonary function. Based on this, a comprehensive rehabilitation training program is designed, which includes personalized training plans, comprehensive interventions, multidisciplinary collaboration, patient education, and regular follow-up visits. The cardiopulmonary rehabilitation training plan developed in this study has certain scientific practicability, which provides a theoretical basis for cardiopulmonary rehabilitation training, and also provides a reference for medical institutions, rehabilitation centers and communities, which is helpful for promotion and application to a wider range of patients with cardiopulmonary diseases.

关键词： Cardiopulmonary Function Rehabilitation Training Program Aerobic Exercise Interval Training

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Machine learning-based prediction of pregnancy outcomes in couples with non-obstructive azoospermia using micro-TESE for ICSI: a retrospective cohort study

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Reproductive and Developmental Medicine 2024年第1期8卷 24-31页

作者： Lei Jia pei-Gen Chen Li-Na Chen Cong fang Jing Zhang Pan-yu Chen Reproductive Medicine Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510275China GuangDong Engineering Technology Research Center ofFertility Preservation The Sixth Affiliated HospitalSun Yatsen UniversityGuangzhou 510275China Biomedical Innovation Center The Sixth Affliated HospitalSun Yat-sen UniversityGuangzhou 510275China

Objective:To develop a clinically applicable tool for predicting clinical pregnancy,providing individualized patient counseling,and helping couples with non-obstructive azoospermia(NOA)decide whether to use fresh or cryopreserved spermatozoa for oocyte insemination before microdissection testicular sperm extraction(mTESE).Methods:A total of 240 couples with NOA who underwent mTESE-ICSI were divided into two groups based on the type of spermatozoa used for intracytoplasmic sperm injection(ICSI):the fresh and cryopreserved *** evaluating several machine learning algorithms,logistic regression was *** LASSO regression and 10-fold cross-validation,the factors associated with clinical pregnancy were ***:The area under the curves(AUCs)for the fresh and cryopreserved groups in the Logistic Regression-based prediction model were 0.977 and 0.759,*** with various modeling algorithms,Logistic Regression outperformed machine learning in both groups,with an AUC of 0.945 for the fresh group and 0.788 for the cryopreserved ***:The model accurately predicted clinical pregnancies in NOA couples.

关键词： Cryopreserved spermatozoa Fresh spermatozoa Logistic regression Microdissection testicular sperm extraction

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Micro/nano flow chemistry by Beyond Limits Manufacturing

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Chinese Chemical Letters 2024年第5期35卷 3-12页

作者： peiwen Liu fang Zhao Jing Zhang yunpeng Bai Jinxing Ye Bo Bao Xinggui Zhou Li Zhang Changlu Zhou Xinhai yu Peng Zuo Jianye xia Lian Cen Yangyang Yang Guoyue Shi Lin Xu Weiping Zhu yufang Xu Xuhong Qian State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of Chemical BiologySchool of PharmacyEast China University of Science and TechnologyShanghai 200237China State Key Laboratory of Chemical Engineering School of Chemical EngineeringEast China University of Science and TechnologyShanghai 200237China State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for BiomanufacturingEast China University of Science and TechnologyShanghai 200237China School of Biomedical and Pharmaceutical Sciences Guangdong University of TechnologyGuangzhou 510006China School of Mechanical and Power Engineering East China University of Science and TechnologyShanghai 200237China Shanghai Key Laboratory of Green Chemistry and Chemical Processes Department of ChemistrySchool of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241China

In September 2018,we proposed the cutting-edge concept of“Beyond Limits Manufacturing”(BLM).BLM technology is based on the three-dimensional inner engraving or precise outer engraving of ultra-fast laser,to invent micro/nano scale flow chips or devices,which makes it possible for the microform,integration,economy,safety,high efficiency,green and intelligence of research,development and manufacturing process,so as to realize transformational manufacturing in the era of Industry *** this paper,we reviewed the representative results we made in the field of micro/nano flow chemistry during the implementation of the BLM major project(December 2019 to August 2023),and discussed its application prospects in micro/nano flow chemistry.

关键词： Beyond Limits Manufacturing Flow chemistry Pharmaceutical manufacturing Microreactor

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Study of tree shrew biology and models: A booming and prosperous field for biomedical research

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Zoological Research 2024年第4期45卷 877-909页

作者： Yong-Gang Yao Li Lu Rong-Jun Ni Rui Bi Ceshi Chen Jia-Qi Chen Eberhard Fuchs Marina Gorbatyuk Hao Lei Hongli Li Chunyu Liu Long-Bao Lv Kyoko Tsukiyama-Kohara Michinori Kohara Claudia Perez-Cruz Gregor Rainer Bao-Ci Shan fang Shen An-Zhou Tang Jing wang Wei xia Xueshan xia Ling Xu Dandan yu Feng Zhang Ping Zheng Yong-Tang Zheng Jumin Zhou Jiang-Ning Zhou Key Laboratory of Genetic Evolution and Animal Models Yunnan Key Laboratory of Animal Models and Human Disease MechanismsKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility) and National Resource Center for Non-Human PrimatesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China Mental Health Center and Psychiatric Laboratory West China HospitalSichuan UniversityChengduSichuan 610041China Sichuan Clinical Medical Research Center for Mental Disorders ChengduSichuan 610044China German Primate Center Leibniz Institute of Primate ResearchGöttingen 37077Germany Department of Optometry and Vision Science School of OptometryUniversity of Alabama at BirminghamBirminghamAL 35294USA State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Innovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Transboundary Animal Diseases Center Joint Faculty of Veterinary MedicineKagoshima UniversityKagoshima-cityKagoshima 890-8580Japan Department of Microbiology and Cell Biology Tokyo Metropolitan Institute of Medical ScienceTokyo 156-8506Japan Pharmacology Department CinvestavMexico City 07360Mexico Department of Medicine University of FribourgFribourg CH-1700Switzerland Beijing Engineering Research Center of Radiog

The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with *** recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain ***,the limited availability of tree shrews globally remains a substantial challenge in the ***,determining the key questions best answered using tree shrews constitutes another *** shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative *** these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical *** review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this *** emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew *** use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.

关键词： Tree shrew Animal model Neurodegenerative diseases Infectious diseases Neuroscience Phenome

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Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor

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Science China(Life Sciences) 2024年第7期67卷 1502-1513页

作者： Luo-yuan xia Xue-Feng wang xiao-Ming Cui Yi-Ming Zhang Zhen-Fei wang En-Tao Li Chang-Fa Fan Ke Song yuan-Guo Li Run-Ze Ye fang-Xu Li Dai-yun Zhu Jie Zhang Zhuang-Zhuang Shi Ming-Zhu Zhang Liang-Jing Li Shi-Jing Shen Song Jin Ya-Wei Zhang Wei-Guang Fu Lin Zhao Wen-Hao wang Tie-Cheng wang You-Chun wang Jia-Fu Jiang Yan-Ling Hu Na Jia yu-Wei Gao Wu-Chun Cao Institute of EcoHealth School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China Changchun Veterinary Research Institute Changchun 130122China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug ControlBeijing 102629China National Institutes for Food and Drug Control Beijing 102629China Life Sciences Institute Guangxi Medical UniversityNanning 530020China College of Life Sciences Shandong Normal UniversityJinan 250014China Research Unit of Discovery and Tracing of Natural Focus Diseases Chinese Academy of Medical SciencesBeijing 100071China

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins,showing a potential threat to *** we report the infectivity and pathogenicity of the SARS-CoV-2-related virus,PCoV-GX/P2V,which was isolated from a Malayan pangolin(Manis javanica).PCoV-GX/P2V could grow in human hepatoma,colorectal adenocarcinoma cells,and human primary nasal epithelial *** replicated more efficiently in cells expressing human angiotensin-converting enzyme 2(hACE2)as SARS-CoV-2 *** intranasal inoculation to the hACE2-transgenic mice,PCoV-GX/P2V not only replicated in nasal turbinate and lungs,but also caused interstitial pneumonia,characterized by infiltration of mixed inflammatory cells and multifocal alveolar *** population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V *** findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

关键词： pangolin SARS-CoV-2-related virus infectivity pathogenicity human cell lines human ACE2 receptor hACE2-transgenic mice

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Two antibodies show broad,synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

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Protein & Cell 2024年第2期15卷 121-134页

作者： Hui Sun Tingting Deng Yali Zhang Yanling Lin Yanan Jiang Yichao Jiang Yang Huang Shuo Song Lingyan Cui Tingting Li Hualong Xiong Miaolin Lan Liqin Liu yu Li Qianjiao fang Kunyu yu Wenling Jiang Lizhi Zhou yuqiong Que Tianying Zhang Quan yuan Tong Cheng Zheng Zhang Hai yu Jun Zhang Wenxin Luo Shaowei Li Qingbing Zheng Ying Gu Ningshao xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China State Key Laboratory of Vaccines for Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China xiang An Biomedicine Laboratory Xiamen 361102China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalSchool of MedicineSouthem University of Science and TechnologyShenzhen 518112China The Second Affliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China

Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or *** rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus ***,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron ***-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric *** antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant ***,these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

关键词： SARS-CoV-2 broad neutralizing antibody rearrangement synergistic neutralization

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