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Journal of Pharmaceutical Analysis 2024年第1期14卷 140-148页

作者： Jingxian Zhang Qinsheng Chen Lianglong Zhang Biru Shi Men Yu Qingxia Huang Huiru Tang State Key Laboratory of Genetic Engineering School of Life SciencesHuman Phenome InstituteZhangjiang Fudan International Innovation CenterMetabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular PhenomicsZhongshan HospitalFudan UniversityShanghai200032China Wuhan Laboratory for Shanghai Metabolome institute(SMI)Ltd. Wuhan430000China

Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0–C26) within 10-min with good sensitivity (limit of detection 0.992), accuracy (relative error 0.998) for predicting retention time (tR) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters (tR, ion-pairs, and collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine, mouse kidney, liver, heart, lung, and muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices.

关键词： Acylcarnitine UPLC-MS/MS Quantitative structure-retention relationship Molecular phenotype

Exercise-induced microbial changes in preventing type 2 diabetes

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Science China(Life Sciences) 2024年第5期67卷 892-899页

作者： Ting Yao Hui Wang Kaiqing Lin Ruwen Wang Shanshan Guo Peijie Chen Hao Wu Tiemin Liu Ru Wang School of Exercise and Health Shanghai Frontiers Science Research Base of Exercise and Metabolic HealthShanghai University of SportShanghai 200438China Department of Physiology and Pathophysiology School of Basic Medical SciencesXi’an Jiaotong University School of MedicineXi’an 710061China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism&Integrative BiologyFudan UniversityShanghai 200433China State Key Laboratory of Genetic Engineering Human Phenome InstituteFudan Microbiome Centerand Department of Bariatric and Metabolic SurgeryHuashan HospitalFudan UniversityShanghai 201203China State Key Laboratory of Genetic Engineering Department of Endocrinology and MetabolismHuman Phenome Instituteand School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China

The metabolic benefits associated with long-term physical activity are well appreciated and growing evidence suggests that it involves the gut microbiota.Here we re-evaluated the link between exercise-induced microbial changes and those associated with prediabetes and diabetes.We found that the relative abundances of substantial amounts of diabetes-associated metagenomic species associated negatively with physical fitness in a Chinese athlete students cohort.We additionally showed that those microbial changes correlated more with handgrip strength,a simple but valuable biomarker suggestive of the diabetes states,than maximum oxygen intake,one of the key surrogates for endurance training.Moreover,the causal relationships among exercise,risks for diabetes,and gut microbiota were explored based on mediation analysis.We propose that the protective roles of exercise against type 2 diabetes are mediated,at least partly,by the gut microbiota.

关键词： gut microbiota body fat diabetes handgrip maximum oxygen intake

Rare variants in FANCJ induce premature ovarian insufficiency in humans and mice

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Journal of Genetics and Genomics 2024年第2期51卷 252-255页

作者： Xi Yang Shuting Ren Jialin Yang Yuncheng Pan Zixue Zhou Qing Chen Yunzheng Fang Lingyue Shang Feng Zhang Xiaojin Zhang Yanhua Wu State Key Laboratory of Genetic Engineering at School of Life Sciences Human Phenome InstituteObstetrics and Gynecology HospitalFudan UniversityShanghai 200438China Obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentState Key Laboratory of Genetic Engineering at School of Life SciencesFudan UniversityShanghai 200011China human phenome institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200011China State Key Laboratory of Genetic Engineering at School of Life Sciences Obstetrics and Gynecology HospitalFudan UniversityShanghai 200438China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China

Premature ovarian insufficiency(POI)is a severe female reproductive disorder that affects 1%of women in general populations(European Society for human Reproduction and Embryology[ESHRE]Guideline Group on POI et al.,2016).An increasing prevalence up to 3.7%has been reported in a recent meta-analysis(Golezar et al.,2019).POl can lead to infertility or subfertility,as well as a range of complex complications suffering multi-organ systems,seriously threatening women's health and reducing the life quality.By contrast,POl is a representative heterogeneous disease with multiple etiologies.While more than 70 causative POI genes have been identified,the etiology of more than half of the POI patients is still ambiguous(Jiao et al.,2018).Unreported POI causative genes,therefore,remain to be identified.

关键词： insufficiency fertility

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International human phenome institutes(Shanghai) ShanghaiChina human phenome institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

Circulating Lipoproteins Mediate the Association Between Cardiovascular Risk Factors and Cognitive Decline:A Community‑Based Cohort Study

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Phenomics

Phenomics 2024年第1期4卷 51-55页

作者： Jialin Li Qingxia Huang Yingzhe Wang Mei Cui Kelin Xu Chen Suo Zhenqiu Liu Yanpeng An Li Jin Huiru Tang Xingdong Chen Yanfeng Jiang State Key Laboratory of Genetic Engineering Human Phenome InstituteZhangjiang Fudan International Innovation Centerand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan University2005 Songhu RdShanghai 200438China Fudan University Taizhou institute of Health Sciences Taizhou 225326China State Key Laboratory of Genetic Engineering School of Life SciencesMetabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular PhenomicsHuman Phenome InstituteZhongshan HospitalFudan University2005 Songhu RdShanghai 200438China Department of Neurology Huashan HospitalFudan UniversityShanghai 200040China Ministry of Education Key Laboratory of Public Health Safety Department of BiostatisticsSchool of Public HealthFudan UniversityShanghai 200032China Ministry of Education Key Laboratory of Public Health Safety Department of EpidemiologySchool of Public HealthFudan UniversityShanghai 200032China Shanghai institute of Infectious Disease and Biosecurity Shanghai 200032China Yiwu Research institute of Fudan University Yiwu 322000ZhejiangChina International human phenome institute(Shanghai) Shanghai 201203China Greater Bay Area institute of Precision Medicine(Guangzhou) Fudan UniversityGuangzhou 511462China

Cardiovascular health metrics are now widely recognized as modifable risk factors for cognitive decline and dementia.Metabolic perturbations might play roles in the linkage of cardiovascular diseases and dementia.Circulating metabolites profling by metabolomics may improve understanding of the potential mechanism by which cardiovascular risk factors contribute to cognitive decline.In a prospective community-based cohort in China(n=725),312 serum metabolic phenotypes were quantifed,and cardiovascular health score was calculated including smoking,exercise,sleep,diet,body mass index,blood pressure,and blood glucose.Cognitive function assessments were conducted in baseline and follow-up visits to identify longitudinal cognitive decline.A better cardiovascular health was signifcantly associated with lower risk of concentration decline and orientation decline(hazard ratio(HR):0.84–0.90;p<0.05).Apolipoprotein-A1,high-density lipoprotein(HDL)cholesterol,cholesterol ester,and phospholipid concentrations were signifcantly associated with a lower risk of longitudinal memory and orientation decline(p<0.05 and adjusted-p<0.20).Mediation analysis suggested that the negative association between health status and the risk of orientation decline was partly mediated by cholesterol ester and total lipids in HDL-2 and-3(proportion of mediation:7.68–8.21%,both p<0.05).Cardiovascular risk factors were associated with greater risks of cognitive decline,which were found to be mediated by circulating lipoproteins,particularly the medium-size HDL components.These fndings underscore the potential of utilizing lipoproteins as targets for early stage dementia screening and intervention.

关键词： Cardiovascular risk factors Lipoproteins Lipids Cognition Cognitive decline

Considerations for exerkine research focusing on the response to exercise training

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Journal of Sport and Health Science 2024年第2期13卷 130-132页

作者： Ian A.J.Darragh Brendan Egan School of Health and human Performance Dublin City UniversityGlasnevinDublin D09 V209Ireland Florida institute for human and Machine Cognition PensacolaFL 32502USA

García-Hermoso and colleagues1 recently published a systematic literature review and meta-analysis on exercise training-induced changes in exerkine concentrations in type 2diabetes mellitus patients,providing a contemporary view on how exerkines respond to exercise training.That review prompted us to highlight 2 additional considerations that should be taken into account when studying the response of exerkines to exercise training.Firstly,whether exerkines can exhibit discordant responses to acute exercise compared to exercise training,and secondly,the need to consider the residual effects of the most recent exercise bout.

关键词： acute exercise prompt

The Protocol of Ultrasonic Backscatter Measurements of Musculoskeletal Properties

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Phenomics

Phenomics 2024年第1期4卷 72-80页

作者： Dongsheng Bi Lingwei Shi Boyi Li Ying Li Chengcheng Liu Lawrence HLe Jingchun Luo Sijia Wang Dean Ta Center for Biomedical Engineering School of InformationScience and TechnologyFudan University2005 SonghuRoadYangpu DistrictShanghai 200438China Academy for Engineering and Technology Fudan UniversityShanghai 200433China Department of Radiology and Diagnostic Imaging University of AlbertaEdmonton T6G2B7Canada human phenome institute Fudan UniversityShanghai 201203China Shanghai institute of Nutrition and Health Chinese Academyof SciencesShanghai 200031China

This study aims to introduce the protocol for ultrasonic backscatter measurements of musculoskeletal properties based on a novel ultrasonic backscatter bone diagnostic(UBBD)instrument.Dual-energy X-ray absorptiometry(DXA)can be adopted to measure bone mineral density(BMD)in the hip,spine,legs and the whole body.The muscle and fat mass in the legs and the whole body can be also calculated by DXA body composition analysis.Based on the proposed protocol for backscatter measurements by UBBD,ultrasonic backscatter signals can be measured in vivo,deriving three backscatter parameters[apparent integral backscatter(AIB),backscatter signal peak amplitude(BSPA)and the corresponding arrival time(BSPT)].AIB may provide important diagnostic information about bone properties.BSPA and BSPT may be important indicators of muscle and fat properties.The standardized backscatter measurement protocol of the UBBD instrument may have the potential to evaluate musculoskeletal characteristics,providing help for promoting the application of the backscatter technique in the clinical diagnosis of musculoskeletal disorders(MSDs),such as osteoporosis and muscular atrophy.

关键词： Ultrasonic backscatter Musculoskeletal disorders Bone mineral density Muscle mass Fat mass

Genetically modified non-human primate models for research on neurodegenerative diseases

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Zoological Research 2024年第2期45卷 263-274页

作者： Ming-Tian Pan Han Zhang Xiao-Jiang Li Xiang-Yu Guo Guangdong Key Laboratory of Non-human Primate Research Guangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

关键词： Neurodegeneration Non-human primate Macaque monkey Animal model Gene modification

De Novo Dissecting the Three‑Dimensional Facial Morphology of 2379 Han Chinese Individuals

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Phenomics

Phenomics 2024年第1期4卷 1-12页

作者： Hui Qiao Jingze Tan Shaoqing Wen Menghan Zhang Shuhua Xu Li Jin State Key Laboratory of Genetic Engineering Center for Evolutionary BiologyCollaborative Innovation Center for Genetics and DevelopmentSchool of Life SciencesFudan UniversityShanghai 200438China Ministry of Education Key Laboratory of Contemporary Anthropology Human Phenome InstituteZhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China institute of Archaeological Science Fudan UniversityShanghai 200433China institute of Modern Languages and Linguistics Fudan UniversityShanghai 200433China Department of Liver Surgery and Transplantation Liver Cancer institute Zhongshan HospitalFudan UniversityShanghai 200032China

Phenotypic diversity,especially that of facial morphology,has not been fully investigated in the Han Chinese,which is the largest ethnic group in the world.In this study,we systematically analyzed a total of 14,838 facial traits representing 15 categories with both a large-scale three-dimensional(3D)manual landmarking database and computer-aided facial segmented phenotyping in 2379 Han Chinese individuals.Our results illustrate that homogeneous and heterogeneous facial morphological traits exist among Han Chinese populations across the three geographical regions:Zhengzhou,Taizhou,and Nanning.We identifed 1560 shared features from extracted phenotypes,which characterized well the basic facial morphology of the Han Chinese.In particular,heterogeneous phenotypes showing population structures corresponded to geographical subpopulations.The greatest facial variation among these geographical populations was the angle of glabella,left subalare,and right cheilion(p=3.4×10^(−161)).Interestingly,we found that Han Chinese populations could be classifed into northern Han,central Han,and southern Han at the phenotypic level,and the facial morphological variation pattern of central Han Chinese was between the typical diferentiation of northern and southern Han Chinese.This result was highly consistent with the results revealed by the genetic data.These fndings provide new insights into the analysis of multidimensional phenotypes as well as a valuable resource for further facial phenotype-genotype association studies in Han Chinese and East Asian populations.

关键词： Phenotypes Three-dimensional facial imaging Facial morphology Han Chinese

Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

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Animal Models and Experimental Medicine 2024年第1期7卷 3-11页

作者： Hanwei Yue Lin Bai NHC Key Laboratory of human Disease Comparative Medicine Institute of Laboratory Animal SciencesCAMS and PUMCChao-yang DistrictBeijingChina

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

关键词： antitumor antiviral CAR-T humanized immune system model humanized mice preclinical research