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Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141,DDHD2,and LHFPL5

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Frontiers of Medicine 2024年第1期18卷 81-97页

作者： Liwei Sun Xueting Yang Amjad Khan Xue Yu Han Zhang Shirui Han Xiaerbati Habulieti Yang Sun Rongrong Wang Xue Zhang McKusick-Zhang Center for Genetic Medicine State Key Laboratory for Complex Severe and Rare DiseasesInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing100005China Chongqing Key Laboratory of human Embryo Engineering Center for Reproductive MedicineNational Key Clinical Speciality Construction Project(Obstetrics and Gynecology)Chongqing Health Center for Women and ChildrenChongqing400013China Chongqing Clinical Research Center for Reproductive Medicine Women and Children’s Hospital of Chongqing Medical UniversityChongqing400013China Faculty of Biological sciences Department of ZoologyUniversity of Lakki MarwatKhyber Pakhtunkhwa28420Pakistan Institute for Medical genetics and Applied Genomics University of TübingenTübingen72076Germany Alexander von Humboldt fellowship Foundation Berlin10117Germany Department of Pediatrics The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China Department of Laboratory Medicine State Key Laboratory for Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China

Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and *** variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic ***,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and *** mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,***90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,***84^(*))were identified.A Tmem141^(***90^(*)/***90^(*))mouse model was *** studies showed impairments in learning ability and motor *** slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje *** electron microscopy showed abnormal mitochondrial ***,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse ***,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in ***,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

关键词： neurodevelopmental disorder autosomal recessive intellectual disability consanguinity spastic paraplegia hearing loss TMEM141

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A dual-RPA based lateral flow strip for sensitive,on-site detection of CP4-EPSPS and Cry1Ab/Ac genes in genetically modified crops

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Food Science and human Wellness 2024年第1期13卷 183-190页

作者： Jinbin Wang Yu Wang Xiuwen Hu Yifan Chen Wei Jiang Xiaofeng Liu Juan Liu Lemei Zhu Haijuan Zeng Hua Liu Key Laboratory of Agricultural genetics and Breeding Institute of Biotechnology ResearchShanghai Academy of Agricultural SciencesShanghai 201106China Crops Ecological Environment Security Inspection and Supervision Center(Shanghai) Ministry of Agriculture and Rural AffairsShanghai 201106China School of Life Science and Engineering Lanzhou University of TechnologyLanzhou 730050China School of Public Health Changsha Medical UniversityChangsha 410219China Academician Workstation Changsha Medical UniversityChangsha 410219China

Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and *** this study,a one-tube dual recombinase polymerase amplification(RPA)reaction system for CP4-EPSPS and Cry1Ab/Ac was proposed and combined with a lateral flow immunochromatographic assay,named“Dual-RPA-LFD”,to visualize the dual detection of genetically modified(GM)*** which,the herbicide tolerance gene CP4-EPSPS and the insect resistance gene Cry1Ab/Ac were selected as targets taking into account the current status of the most widespread application of insect resistance and herbicide tolerance traits and their stacked *** diluted plasmids,transgenic standards,and actual samples were used as templates to conduct sensitivity,specificity,and practicality assays,*** constructed method achieved the visual detection of plasmid at levels as low as 100 copies,demonstrating its high *** addition,good applicability to transgenic samples was observed,with no cross-interference between two test lines and no influence from other *** conclusion,this strategy achieved the expected purpose of simultaneous detection of the two popular targets in GM crops within 20 min at 37°C in a rapid,equipmentfree field manner,providing a new alternative for rapid screening for transgenic assays in the field.

关键词： Genetically modifi ed crops On-site detection Lateral fl ow test strips Dual recombinase polymerase amplification (RPA)

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Interaction between tumor stage and age on survival outcomes of patients with anaplastic thyroid cancer

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World Journal of Experimental Medicine 2024年第3期14卷 90-100页

作者： Ayrton I Bangolo Auda Auda John Bukasa-Kakamba Nayan Bhakta Shraboni Dey Anupriya lilhori Gowry Reddy Budoor Alqinai Aman Sidiqui Imranjot Sekhon Barbare Khatiashvili Iqra Abbas Sandra Kunnel Amer Jarri Emelyn Martinez Deborah Daoud Ishita Gupta Harshini Gompa Silvanna Pender Dana Aljaberi Hamed Aljanaahi Sandra S Kunnel Yingxia Xiao Yoontae Jung Sneha Nagpaul Afshan Naz Tejaswee Mallela Phyo Maung Maung Ibtihal Y Khalaf Soobee Kim Roua Alrestom Aditya Gajera Hiba Alkealy Deepti Kansal Sonam Dhall Sanya Satheesha Simcha Weissman Pierre Fwelo Department of Internal Medicine Palisades Medical CenterNorth BergenNJ 07047United States Department of Medicine Palisades Medical CenterNorth BergenNJ 07047United States Department of Endocrine and Metabolic Disorders University of KinshasaKinshasa KinshasaCongo Department of Epidemiology Human Geneticsand Environmental SciencesUTHealth School of Public HealthHoustonTX 77030United States

BACKGROUND Anaplastic thyroid cancer(ATC)is an aggressive,rare malignancy associated with rapid growth and metastasis,and a very poor *** investigated the clinical characteristics,survival outcomes and independent prognostic factors associated with anaplastic thyroid *** To assess to what extent the interaction between age and tumor stage affects *** A total of 622 patients diagnosed with anaplastic thyroid cancer,between 2010 and 2017 were enrolled in our study by retrieving data from the Surveillance,Epidemiology and End Results(SEER)*** analyzed demographics,clinical characteristics,overall mortality(OM)and cancer specific mortality(CSM)of *** with a P value<0.1 were incorporated into the multivariate cox model to determine the independent prognostic ***,we analyzed the interaction between age and tumor stage on *** In the multivariate analyses,the divorced/separated population had a lower OM[hazard ratio(HR)=0.63,95%CI:0.42-0.94,P<0.05]and CSM(HR=0.61,95%CI:0.40-0.92,P<0.05).OM was higher in tumors with direct extension only(HR=6.26,95%CI:1.29-30.42,P<0.05)and tumors with distant spread(HR=5.73,95%CI:1.34-24.51,P<0.05).CSM was also higher in tumors with direct extension(HR=5.05,95%CI:1.05-24.19,P<0.05)and tumors with distant spread(HR=4.57,95%CI:1.08-19.29,P<0.05).Mortality was not adversely affected by lymph node *** was lower in patients who received radiation(HR=0.66,95%CI:0.53-0.83,P<0.01),chemotherapy(HR=0.63,95%CI:0.50-0.79,P<0.01)or surgery(HR=0.53,95%CI:0.43-0.66,P<0.01).CSM was also lower in patient who received radiation(HR=0.64,95%CI:0.51-0.81,P<0.01),chemotherapy(HR=0.62,95%CI:0.50-0.78,P<0.01)or surgery(HR=0.51,95%CI:0.41-0.63,P<0.01).There was no significant interaction between age and tumor stage that affected *** In this large US SEER database retrospective study,we found the mortality to be higher in advanced stage tumors with direct extensi

关键词： Undifferentiated thyroid cancer Survival outcome Prognosis Metastasis Clinical trials Interaction

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Genetic Basis for Mucormycosis Progression in COVID-19 Patients:From Susceptibility to Severity

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Infectious Diseases & Immunity 2024年第2期4卷 86-92页

作者： Jethendra Kumar Muruganantham Ramakrishnan Veerabathiran human Cytogenetics and Genomics Laboratory Faculty of Allied Health SciencesChettinad Hospital and Research InstituteChettinad Academy of Research and EducationKelambakkamTamilnadu 603103India.

The dynamics of COVID-19 and mucormycosis reveal a complex interplay of genetic factors that influence the susceptibility,severity,and immune ***-19,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),exhibits an increased incidence of mucormycosis,particularly in individuals with comorbidities or corticosteroid *** is a fungal infection that affects the sinuses,orbits,and lungs and demands timely intervention with antifungal medications and surgery because of its life-threatening *** on the genetic underpinnings of this intersection has unveiled key insights into the pathogenicity of *** in genetic tools have exposed virulence factors,such as the CotH protein family and high-affinity iron-uptake *** susceptibility is a pivotal element in identifying individuals at risk of developing COVID-19,facilitating early detection,and allowing for personalized treatment ***9,MIF,and TYK2 are among the genes implicated in COVID-19 severity,emphasizing the intricate relationship between genetic makeup and viral *** genetic landscape extends to viral entry mechanisms,thereby affecting infection *** polymorphisms in genes such as IFNAR2,OAS3,and TYK2 are associated with COVID-19 severity,indicating shared genetic bases between severe and hospitalized *** is genetically predisposed,particularly in immunocompromised *** challenge lies in understanding the genetic factors influencing susceptibility and offering insights into pathogenesis and potential therapeutic *** transplantation adds another layer,increasing susceptibility to infections such as COVID-19 and *** impact of immunosuppression on COVID-19 severity remains elusive,necessitating ongoing research on the immunological *** the challenges posed by emerging SARSCoV-2 variants,the intricate connection between genetic factors and the

关键词： COVID-19 Mucormycosis Pathogenesis genetics basis

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Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

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Science China(Life sciences) 2024年第7期67卷 1325-1337页

作者： Chengcheng Song Yingying Qin Yan Li Bingyi Yang Ting Guo Wenqing Ma Dian Xu Keyan Xu Fangfang Fu Li Jin Yanhua Wu Shuyan Tang Xiaojun Chen Feng Zhang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringInstitute of Medical Genetics and GenomicsFudan UniversityShanghai 200011China human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250021China State Key Laboratory of Reproductive Medicine and Offspring Health Key Laboratory of Reproductive Endocrinology of Ministry of EducationNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthShandong UniversityJinan 250021China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China Department of Gynecology the Tenth People’s Hospital of Tongji UniversityShanghai 200072China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health Hospital of China Welfare InstituteShanghai 200030China

Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of *** represents a significant detriment to female ***,the known POI-causative genes currently account for only a fraction of *** elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in *** a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 *** variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 ***,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling *** analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and *** further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian ***,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse *** conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

关键词： POI RNF111 female fertility ovarian reserve

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Iron metabolism and arthritis: Exploring connections and therapeutic avenues

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中华医学杂志(英文版) 2024年第14期137卷 1651-1662页

作者： Zhuo Dachun Xiao Wenze Tang Yulong Jiang Shuai Geng Chengchun Xie Jiangnan Ma Xiaobei Zhang Qing Tang Kunhai Yu Yuexin Bai Lu Zou Hejian Liu Jing Wang Jiucun Department of Rheumatology Shanghai Pudong Hospital Human Phenome Institute Zhangjiang Fudan International Innovation Center Fudan University Shanghai China State Key Laboratory of Genetic Engineering School of Life Science Fudan University Shanghai China Department of Vascular Surgery Shanghai Pudong Hospital Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling Fudan University Pudong Medical Center Shanghai China Department of Anthropology and human genetics School of Life Sciences Ministry of Education Key Laboratory of Contemporary Anthropology Fudan University Shanghai China Division of Rheumatology Huashan Hospital State Key Laboratory of Genetic Engineering School of Life Science Fudan University Shanghai China Institute of Rheumatology Immunology and Allergy Allergy and Disease Research Center Fudan University Shanghai China Research Unit of Dissecting the Population genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058) Chinese Academy of Medical Sciences Beijing China

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

关键词： Iron metabolism Arthritis Inflammation Immunity Rheumatoid arthritis Psoriatic arthritis Gouty arthritis

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Application of CRISPR/Cas12i.3 for targeted mutagenesis in broomcorn millet(Panicum miliaceum L.)

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Journal of Integrative Plant Biology 2024年第8期66卷 1544-1547页

作者： Yuhe Bai Shengnan Liu Yan Bai Zhisong Xu Hainan Zhao Haiming Zhao Jinsheng Lai Ya Liu Weibin Song State Key Laboratory of Maize Bio-breeding Key Laboratory of Genome Editing Research and ApplicationMinistry of Agriculture and Rural AffairsDepartment of Plant Genetics and BreedingNational Maize Improvement CenterCollege of Agronomy and BiotechnologyChina Agricultural UniversityBeijing 100193China National Agricultural Technology Extension&Service Center Beijing 100125China Beijing Key Laboratory of Maize DNA Fingerprinting and Molecular Breeding Beijing Academy of Agriculture and Forestry SciencesBeijing 100097China

As the global human population continues to grow and is predicted to reach 10 billion by 2050,the demand for food volume and quality raises a tremendous challenge(OECD/FAO,2017).The worldwide arable land area is decre... 详细信息

关键词： arable continue raise

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Inattentiveness in attention-deficit/hyperactivity disorder

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Neuroscience Bulletin 2013年第1期29卷 103-110页

作者： Ariane Sroubek Mary Kelly Xiaobo Li Ferkauf Graduate School of Psychology at Yeshiva University Department of Pediatrics and behavioral sciences at Albert Einstein College of Medicine Yeshiva University Gruss Magnetic Resonance Research Center and behavioral sciences at Albert Einstein College of Medicine Yeshiva University Department of Radiology and behavioral sciences at Albert Einstein College of Medicine Yeshiva University Department of Neuroscience and behavioral sciences at Albert Einstein College of Medicine Yeshiva University Department of psychiatry and behavioral sciences at Albert Einstein College of Medicine Yeshiva University

Attention-deficit/hyperactivity disorder （ADHD） is a neurodevelopmental disorder with a long-term impact on functioning, productivity and quality of life of patients. This impact is largely due to the symptoms of inattentiveness. However, despite its impairing role in the lives of ADHD patients, inattentiveness has been studied relatively less frequently than have symptoms of impulsivity/hyperactivity and problems with executive function. This review therefore seeks to integrate the neuropsychological theories and current findings in the research fields of neuropsychology, neurophysiology, and neuroimaging, in an attempt to gain a more complete understanding of the role that inattentiveness plays in ADHD, as well as to suggest directions for future studies. The need for a more comprehensive understanding of inattentiveness and ADHD, which integrates findings from each of the three disciplines mentioned above, is emphasized.

关键词： attention-deficit/hyperactivity disorder inattentiveness brain pathways neuropathology

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Control of de novo root regeneration efficiency by developmental status of Arabidopsis leaf explants

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Journal of genetics and Genomics 2019年第3期46卷 133-140页

作者： Jing Pan Fei Zhao Guifang Zhang Yu Pan Lijun Sun Ning Bao Peng Qin Lyuqin Chen Jie Yu Yijing Zhang Lin Xu National Key Laboratory of Plant Molecular genetics CAS Center for Excellence in Molecular Plant Sciences Shanghai Institute of Plant Physiology and Ecology Chinese Academy of Sciences University of Chinese Academy of sciences School of Life sciences Nantong University School of Public Health Nantong University Department of Instrument Science and Engineering Shanghai Jiao Tong University departments of Neurosurgery Psychiatry and Behavioral Sci-ences Stanford University School of Medicine

De novo root regeneration(DNRR) has wide applications in agriculture such as those related to cutting technology. Detached Arabidopsis thaliana leaf explants can regenerate adventitious roots without added hormones. The regenerative ability is highly dependent on the developmental status of the leaf. An immature leaf has a higher regenerative ability, while a mature leaf is difficult to regenerate. Using RNASeq analysis, we showed that the expression levels of many genes, including those in the auxin network,changed during leaf maturation. Particularly, the expression levels of many YUCCA(YUC) genes in the auxin biosynthesis pathway are responsive to leaf maturation. Overexpression of YUC1 in the yuc-1 D dominant mutant rescued the rooting defects caused by leaf maturation. In addition, YUC4 expression levels were also affected by circadian rhythms. The regenerative ability was reduced in both immature and mature mutant leaf explants from the new wuschel-related homeobox 11-3(wox11-3) and wox12-3 mutant alleles created by the CRISPR/Cas9 method. Overall, the transcriptome and genetic data, together with the auxin concentration analysis, indicate that the ability to upregulate auxin levels upon detachment may be reduced during leaf maturation. Thus, multiple developmental and environmental signals may converge to control auxin accumulation, which affects the efficiency of the WOX11/12-mediated DNRR from leaf explants.

关键词： De novo root regeneration WOX11 Arabidopsis Developmental status Circadian rhythms YUCCA

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Establishment of a humanized ST6GAL1 mouse model for influenza research

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Animal Models and Experimental Medicine 2024年第3期7卷 337-346页

作者： Lyu Chao Han Feng Gao Qian Lv Limin Lu Ziwei Lu Shuangshuang Li Xiaoyan Hu Yuechao Yang Mengjie Zhao Yingze Liu Jun Lu Xuancheng Duo Shuguang National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and PreventionBeijingChina Institute of Zoology Chinese Academy of SciencesBeijingChina NHC Key Laboratory of Biosafety National Key Laboratory of Intelligent Tracking and Forecasting for Infectious DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Zhejiang Provincial Key Laboratory of Medical genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouChina

Background:This study aimed to construct and characterize a humanized influenza mouse model expressing ***:humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of *** manipulated embryos were transferred into the oviducts of pseudopregnant female *** offspring were identified using *** exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for *** of the humanized gene was tested by performing immunohistochemical(IHC)*** and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were ***:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT *** mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection *** IHC results revealed that hST6GAL1 was expressed in the lungs of humanized ***,the hematologic and biochemical parameters of the positive mice were within the normal ***:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

关键词： hST6GAL1 humanized mice influenza animal model

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