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mrMLM v4.0.2: An R Platform for Multi-locus Genome-wide Association Studies

Genomics, Proteomics & Bioinformatics 2020年第4期18卷 481-487页

作者： Ya-Wen Zhang Cox Lwaka Tamba Yang-Jun Wen Pei li Wen-Long Ren yuan-li ni Jun Gao yuan-Ming Zhang Crop Information Center College of Plant Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China Department of Mathematics Egerton UniversityEgerton 536-20115Kenya State Key Laboratory of Crop Genetics and Germplasm Enhancement Nanjing Agricultural UniversityNanjing 210095China Department of Epidemiology and Medical Statistics School of Public HealthNantong UniversityNantong 226019China College of Informatics Huazhong Agricultural UniversityWuhan 430070China

Previous studies have reported that some important loci are missed in single-locus genome-wide association studies(GWAS),especially because of the large phenotypic error in field experiments.To solve this issue,multi-locus GWAS methods have been recommended.However,only a few software packages for multi-locus GWAS are available.Therefore,we developed an R software named mr MLM v4.0.2.This software integrates mr MLM,FASTmr MLM,FASTmr EMMA,p LARm EB,p KWm EB,and ISIS EM-BLASSO methods developed by our lab.There are four components in mr MLM v4.0.2,including dataset input,parameter setting,software running,and result output.The fread function in data.table is used to quickly read datasets,especially big datasets,and the do Parallel package is used to conduct parallel computation using multiple CPUs.In addition,the graphical user interface software mr MLM.GUI v4.0.2,built upon Shiny,is also available.To confirm the correctness of the aforementioned programs,all the methods in mr MLM v4.0.2 and three widely-used methods were used to analyze real and simulated datasets.The results confirm the superior performance of mr MLM v4.0.2 to other methods currently available.False positive rates are effectively controlled,albeit with a less stringent significance threshold.mr MLM v4.0.2 is publicly available at Bio Code(https://***/biocode/tools/BT007077)or R(https://***/web/packages/mr MLM.GUI/index.html)as an open-source software.

关键词： Genome-wide association study linear mixed model mrMLM Multi-locus genetic model R

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Reconstruct recent multi-population migration history by using identical-by-descent sharing

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Journal of Genetics and Genomics 2024年第6期51卷 642-651页

作者： Wenxiao Zhang Kai yuan Ru Wen Haifang li Xumin ni School of Mathematics and Statistics Bejing Jiaotong UniversityBeijing 100044China The Stanley Center for Psychiatric Research Broad Institute of MIT and HarvardCambridgeMA 02142USA Baidu Incorporated Bejing 100085China

Identical-by-descent(IBD)is a fundamental genomic characteristic in population genetics and has been widely used for population history reconstruction.However,limited by the nature of IBD,which could only capture the relationship between two individuals/haplotypes,existing IBD-based history inference is constrained to two populations.In this study,we propose a framework by leveraging IBD sharing in multipopulation and develop a method,MatrixiBD,to reconstruct recent multi-population migration history.Specifically,we employ the structured coalescent theory to precisely model the genealogical process and then estimate the IBD sharing across multiple populations.Within our model,we establish a theoretical connection between migration history and IBD sharing.Our method is rigorously evaluated through simulations,revealing its remarkable accuracy and robustness.Furthermore,we apply MatrixiBD to Central and South Asia in the Human Genome Diversity Project and successfully reconstruct the recent migration history of three closely related populations in South Asia.By taking into account the IBD sharing across multiple populations simultaneously,MatrixlBD enables us to attain clearer and more comprehensive insights into the history of regions characterized by complex migration dynamics,providing a holistic perspective on intricate patterns embedded within the recent population migration history.

关键词： Population genetics IBD sharing Migration history Structured coalescent theory Gene flow

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ZNF554 Inhibits Endometrial Cancer Progression via Regulating RBM5 and Inactivating WNT/β-Catenin Signaling Pathway

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Current Medical Science 2024年第2期44卷 406-418页

作者： Cheng-cheng ZHU Heng-liang SUN Teng-fei LONG yuan-yuan LYU Jiang-li liU Guan-tai ni Anhui Medical University Hefei 230032China Department of Obstetrics and Gynecology The First Afiliated Hospital of Wannan Medical CollegeWuhu 241001China

Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant tumors.This study aimed to examine the involvement of ZNF554 in the development of UCEC.Methods:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay.Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection.CCK-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and invasion.Propidium iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle distribution.qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels.Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines.Decreased expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in UCEC.ZNF554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle arrest.In contrast,a decrease in ZNF554 expression resulted in the opposite effect.Mechanistically,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling pathway.Moreover,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression onβ-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase inβ-catenin and p-GSK-3βcaused by the suppression of ZNF554.In v

关键词： zinc finger protein 554 endometrial carcinoma RNA binding motif 5 Wingless/β-catenin signaling pathway

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Protein lipidation in health and disease:molecular basis,physiological function and pathological implication

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1423-1465页

作者： yuan yuan Peiyuan li jianghui li Qiu Zhao Ying Chang Xingxing He Department of Gastroenterology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Gastroenterology Zhongnan Hospital of Wuhan UniversityWuhanChina Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases WuhanChina

Posttranslational modifications increase the complexity and functional diversity of proteins in response to complex external stimuli and internal changes.Among these,protein lipidations which refer to lipid attachment to proteins are prominent,which primarily encompassing five types including S-palmitoylation,N-myristoylation,S-prenylation,glycosylphosphatidylinositol(GPl)anchor and cholesterylation.lipid attachment to proteins plays an essential role in the regulation of protein trafficking,localisation,stability,conformation,interactions and signal transduction by enhancing hydrophobicity.Accumulating evidence from genetic,structural,and biomedical studies has consistently shown that protein lipidation is pivotal in the regulation of broad physiological functions and is inextricably linked to a variety of diseases.Decades of dedicated research have driven the development of a wide range of drugs targeting protein lipidation,and several agents have been developed and tested in preclinical and clinical studies,some of which,such as asciminib and lonafarnib are FDA-approved for therapeutic use,indicating that targeting protein lipidations represents a promising therapeutic strategy.Here,we comprehensively review the known regulatory enzymes and catalytic mechanisms of various protein lipidation types,outline the impact of protein lipidations on physiology and disease,and highlight potential therapeutic targets and clinical research progress,aiming to provide a comprehensive reference for future protein lipidation research.

关键词： lipid ation primarily

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Microglial Calcium Homeostasis Modulator 2:Novel Anti-neuroinflammation Target for the Treatment of Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第4期40卷 553-556页

作者： yuan Dong li Tang Neuropsychiatry Research Institute The Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdao266000China Qingdao Institute of Measurement Technology Qingdao266000China

Neurodegenerative diseases,including Alzheimer's disease(AD)and Parkinson's disease(PD),are the most common causes of dementia.Current drugs for such diseases can only provide temporary help with the symptoms,leaving the discovery of new drugs urgently in need.Microglial cells are the local immune cells in the nervous system and have been recognized as the key player in neuroinflammation that contributes to the process of neurodegeneration[1],raising the discussion of aiming microglia as the therapeutic target for clinical treatment of neurodegenerative diseases.

关键词： inflammation degenerative drugs

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Pseudomonotonicity of Nonlinear Transformations on Euclidean Jordan Algebras

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Acta Mathematicae Applicatae Sinica 2024年第1期40卷 192-204页

作者： yuan-Min li School of Mathematics and Statistics Xidian UniversityXi’an710071China

In this paper, we have introduced the concepts of pseudomonotonicity properties for nonlinear transformations defined on Euclidean Jordan algebras. The implications between this property and other P-properties have been studied. More importantly, we have solved the solvability problem of the nonlinear pseudomonotone complementarity problems over symmetric cones.

关键词： Euclidean Jordan algebra nonlinear transformation complementarity problem pseudomonotone

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Perspective of alkaline zinc-based flow batteries

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Science China Chemistry 2024年第1期67卷 260-275页

作者： Zhizhang yuan Xianfeng li Division of Energy Storage Dalian National Laboratory for Clean Energy(DNL)Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 110623China

Energy storage technologies have been identified as the key in constructing new electric power systems and achieving carbon neutrality,as they can absorb and smooth the renewables-generated electricity.Alkaline zinc-based flow batteries are well suitable for stationary energy storage applications,since they feature the advantages of high safety,high cell voltage and low cost.Currently,many alkaline zinc-based flow batteries have been proposed and developed,e.g.,the alkaline zinc–iron flow battery and alkaline zinc–nickel flow battery.Their development and application are closely related to advanced materials and battery configurations.In this perspective,we will first provide a brief introduction and discussion of alkaline zinc-based flow batteries.Then we focus on these batteries from the perspective of their current status,challenges and prospects.The bottlenecks for these batteries are briefly analyzed.Combined with the practical requirements and development trends of alkaline zinc-based flow battery technologies,their future development and research direction will be summarized.

关键词： energy storage alkaline zinc-based flow batteries advanced materials battery structure

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A deep learning model enabled multi-event recognition for distributed optical fiber sensing

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Science China(Information Sciences) 2024年第3期67卷 291-307页

作者： Yujiao li Xiaomin CAO Wenhao ni Kuanglu YU Institute of Information Science School of Computer and Information TechnologyBeijing Jiaotong University Beijing Key Laboratory of Advanced Information Science and Network Technology Beijing Jiaotong University

Fiber optic sensors that utilize backscattered light offer distributed real-time measurements and have been seen tremendous improvements in sensing distance and spatial resolution over the last decades.However, these improvements in sensor capabilities lead to a significant increase in the amount of data that needs to be processed. Traditional processing schemes are no longer adequate, so the development of novel signal processing methods is critical. Phase-sensitive optical time domain reflectometry(Φ-OTDR) is now applied in various applications for multi-event recognition, and it would usually be difficult, sometimes even unrealistic to label all the acquired samples due to its real-time and seamless monitoring nature. To fully take advantage of the information contained within the large number of unlabeled samples, which were formerly not utilized and hence wasted, we propose a semi-supervised model to boost the event classification performance of Φ-OTDR. The model extracts respectively the temporal features and the spatial bidirectional features together with a dual attention mechanism. Its classification accuracy has been improved up to 96.9%with only 1230 labeled samples. In addition, our model shows significant advantages when the number of labeled samples is reduced. Importantly, our method improves the accuracy of multi-event classification without any modification to the optical setup.

关键词： $\Phi$-OTDR event recognition semi-supervised learning mean teacher MT-ACNN-SA-BiLSTM

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nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia:effects on neurobehavioral phenotypes

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Neural Regeneration Research 2024年第12期19卷 2760-2772页

作者： Xiaowen Xu Xinxin Wang li Zhang Yiming Jin lili li Meifang Jin lianyong li Hong ni Division of Brain Science Institute of Pediatric ResearchChildren’s Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Pediatric Orthopedics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

关键词： brain injury cerebral palsy hypoxia hypoxic-ischemic brain injury inflammation neuroprotection nicotinamide adenine dinucleotide neonate nicotinamide adenine dinucleotide proteomics

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Current status of early gastric cancer screening research

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Cancer Biology & Medicine 2024年第3期21卷 218-222页

作者： Can Hu li yuan Xiangdong Cheng Department of Gastric surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Key Laboratory of Prevention Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang ProvinceHangzhou 310022China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer Zhejiang Cancer HospitalHangzhou 310022China

Gastric cancer is a predominant threat to the health and well-being of China's residents. Data from the World Health Organization(WHO) in 2020 revealed that gastric cancer in China notably accounted for 44.0% of new c... 详细信息

关键词： cancer Gastric gastric

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