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Migrasomes:the knowns,the known unknowns and the unknown unknowns:a personal perspective

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Science China(life Sciences) 2021年第1期64卷 162-166页

作者： LI Yu The State Key Laboratory of Membrane Biology Tsinghua University-Peking University Joint Centre for Life SciencesBeijing Frontier Research Center for Biological StructureSchool of life SciencesBeijingChina

I still remember the day.It was 2012.I was checking the transmission electron microscopy images from the previous day.Something unusual caught my eyes.A structure closely resembling an opened pomegranate stood outside a cell.In retrospect,I realized I had seen these structure before,but that particular image was unusual because there were several of these large structures outside the cell.

关键词： outside unusual remember

Haken 3-Manifolds in Small Covers

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Chinese Annals of Mathematics,Series B 2023年第4期44卷 549-560页

作者： lisu WU LI Yu College of Mathematics and Systems Science Shandong University of Science and TechnologyTsingtao 266590ShandongChina Department of Mathematics Nanjing UniversityNanjing 210093China

The authors prove that a 3-dimensional small cover M is a Haken manifold if and only if M is aspherical or equivalently the underlying simple polytope is a flag polytope.In addition,they find that M being Haken is als... 详细信息

关键词： Small cover Haken manifold Incompressible surface Flag polytope

Metabolomics: A useful tool for ischemic stroke research

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Journal of Pharmaceutical Analysis 2023年第9期13卷 968-983页

作者： Wentao li Chongyu Shao Chang li Huifen Zhou LI Yu Jiehong Yang Haitong Wan yu He School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou310053China School of Basic Medicine Sciences Zhejiang Chinese Medical UniversityHangzhou310053China

Ischemic stroke(IS)is a multifactorial and heterogeneous disease.Despite years of studies,effective strategies for the diagnosis,management and treatment of stroke are still lacking in clinical practice.Metabolomics is a growing field in systems biology.It is starting to show promise in the identification of biomarkers and in the use of pharmacometabolomics to help patients with certain disorders choose their course of treatment.The development of metabolomics has enabled further and more biological applications.Particularly,metabolomics is increasingly being used to diagnose diseases,discover new drug targets,elucidate mechanisms,and monitor therapeutic outcomes and its potential effect on precision medicine.In this review,we reviewed some recent advances in the study of metabolomics as well as how metabolomics might be used to identify novel biomarkers and understand the mechanisms of IS.Then,the use of metabolomics approaches to investigate the molecular processes and active ingredients of Chinese herbal formulations with anti-IS capabilities is summarized.We finally summarized recent developments in single cell metabolomics for exploring the metabolic profiles of single cells.Although the field is relatively young,the development of single cell metabolomics promises to provide a powerful tool for unraveling the pathogenesis of IS.

关键词： Metabolomics Ischemic stroke Biomarker Precision medicine Single cell metabolomics

Modification of PAE-degrading Esterase(CarEW)for Higher Degradation Efficiency Through Integrated Homology Modeling,Molecular Docking,and Molecular Dynamics Simulation

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Chemical Research in Chinese Universities 2022年第6期38卷 1400-1413页

作者： ZHOU Mengying LI Yu Key Laboratory of Resources and Environmental Systems Optimization Ministry of EducationNorth China Electric Power UniversityBeijing102206P.R.China College of Environmental Science and Engineering North China Electric Power UniversityBeijing102206P.R.China

Six phthalate acid esters(PAEs)priority pollutants[dimethyl phthalate(DMP),diethyl phthalate(DEP),dibutyl phthalate(DBP or DNBP),di-n-octyl phthalate(DNOP),di 2-ethyl hexyl phthalate(DEHP),and butyl benzyl phthalate(BBP)]were opted as the research object.PAE-degrading esterase CarEW(PDB ID:1C7I)isolated from Bacillus subtilis acting as a template and an iterative saturation mutation strategy was adopted to modify key amino acids to attain efficient PAE-degrading esterase substitutes with a reasonable structure constructed by homology modeling method.Present study designed a total of 285 unit-site and multi-site substitutions of PAE-degrading esterase using the homology modeling method.Among them,207 PAE-degrading esterase substitutions,which contained the 6-site PAE-degrading esterase substitute 1C7I-6-9 with 84.21%enhancement intensity of degradation ability revealed better degradability to all the 6 PAEs after modification.Moreover,molecular dynamics simulation based on the Taguchi method reported the optimal external application environment for PAE-degrading esterase substitutes as follows:pH=6,T=35℃,the rhamnolipid concentration was 50 mg/L,the molar ratio of nitrogen to phosphorus(N:P)was 10:1,the concentration of H2O_(2) was 50 mg/L,and the voltage gradient was 1.5 V/cm.The degradation ability of PAE-degrading esterase substitutes was found to be elevated by 13.04%as compared to that of the blank control under the optimal condition.Moreover,11 highly efficient PAE-degrading esterase substitutes with thermal stability were designed.

关键词： Phthalate acid ester(PAE) PAE-degrading esterase Enzymatic modification Homology modeling Molecular docking Molecular dynamics simulation

Evolution and conservation genetics of pangolins

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Integrative Zoology 2024年第3期19卷 426-441页

作者： Tongtong GU Jingyang HU LI Yu State Key Laboratory for Conservation and Utilization of Bio-Resource in yunnan School of Life SciencesYunnan UniversityKunmingChina

Pangolins(Pholidota,Manidae)are classified as an evolutionarily distinct and globally endangered mammal due to their unique morphology(nail-like scales and a myrmecophagous diet)and being the victim of heavy poaching and worldwide trafficking.As such,pangolins serve as a textbook example for studying the special phenotypic evolutionary adaptations and conservation genetics of an endangered species.Recent years have demonstrated significant advancements in the fields of molecular genetics and genomics,which have translated to a series of important research achievements and breakthroughs concerning the evolution and conservation genetics of pangolins.This review comprehensively presents the hitherto advances in phylogeny,adaptive evolution,conservation genetics,and conservation genomics that are related to pangolins,which will provide an ample understanding of their diversity,molecular adaptation mechanisms,and evolutionary potentials.In addition,we highlight the priority of investigating species/population diversity among pangolins and suggest several avenues of research that are highly relevant for future pangolin conservation.

关键词： adaptive evolution conservation genetics conservation genomics pangolins phylogeny

Epigenetic therapies in acute myeloid leukemia: the role of hypomethylating agents, histone deacetylase inhibitors and the combination of hypomethylating agents with histone deacetylase inhibitors

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Chinese Medical Journal 2020年第6期133卷 699-715页

作者： Qing-yu Xu LI Yu Department of Hematology-Oncology International Cancer CenterShenzhen University General HospitalShenzhen University Health Science CenterShenzhenGuangdong 518000China Department of Hematology and Oncology Medical Faculty MannheimHeidelberg UniversityMannheim 68169Germany

Epigenetic regulation includes changes of DNA methylation and modifications of histone proteins and is essential for normal physiologic functions,especially for controlling gene expression.Epigenetic dysregulation plays a key role in disease pathogenesis and progression of some malignancies,including acute myeloid leukemia(AML).Epigenetic therapies,including hypomethylating agents(HMAs)and histone deacetylase(HDAC)inhibitors,were developed to reprogram the epigenetic abnormalities in AML.However,the molecular mechanisms and therapeutic effects of the two agents alone or their combination remain unknown.An overview of these epigenetic therapies is given here.A literature search was conducted through PubMed database,looking for important biological or clinical studies related to the epigenetic regimens in the treatment of AML until October 15th,2019.Various types of articles,including original research and reviews,were assessed,identified,and eventually summarized as a collection of data pertaining the mechanisms and clinical effects of HMAs and HDAC inhibitors in AML patients.We provided here an overview of the current understanding of the mechanisms and clinical therapeutic effects involved in the treatment with HMAs and HDAC inhibitors alone,the combination of epigenetic therapies with intensive chemotherapy,and the combination of both types of epigenetic therapies.Relevant clinical trials were also discussed.Generally speaking,the large number of studies and their varied outcomes demonstrate that effects of epigenetic therapies are heterogeneous,and that HMAs combination regimens probably contribute to significant response rates.However,more research is needed to explore therapeutic effects of HDAC inhibitors and various combinations of HMAs and HDAC inhibitors.

关键词： Acute myeloid leukemia Decitabine 5-azacytidine Histone deacetylase inhibitors Intensive chemotherapy

Opportunities and challenges in studies of mammalian hybrid speciation

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Science China(life Sciences) 2024年第3期67卷 614-617页

作者： Hong Wu yuxing Zhang LI Yu State Key Laboratory for Conservation and Utilization of Bio-Resource in yunnan School of Life SciencesYunnan UniversityKunming 650091China

Revealing the mechanisms of speciation remains one of the most attractive and challenging issues in the field of evolutionary biology, and is also key to understanding the biodiversity present in nature.

关键词： biodiversity attractive evolutionary

HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第8期23卷 666-681页

作者： Cancan LUO Tiantian yu Ken H.YOUNG LI Yu Department of Hematology the Second Affiliated Hospital of Nanchang University Nanchang 330006China Jiangxi ProvinceKey Laboratory of Hematology Nanchang 330006 China Department of Hematopathology Duke University School of MedicineDuke University Medical CenterDurhamNC 27710USA

Diffuse large B-cell lymphoma(DLBCL) is an aggressive type of non-Hodgkin’s lymphoma. A total of 10%-15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog(MYC) and/or B-cell lymphoma-2(BCL2) translocation or amplification. BCL2 inhibitors have potent anti-tumor effects in DLBCL;however, resistance can be acquired through up-regulation of alternative anti-apoptotic proteins. The histone deacetylase(HDAC) inhibitor chidamide can induce BIM expression, leading to apoptosis of lymphoma cells with good efficacy in refractory recurrent DLBCL. In this study, the synergistic mechanism of chidamide and venetoclax in DLBCL was determined through in vitro and in vivo models. We found that combination therapy significantly reduced the protein levels of MYC, TP53, and BCL2 in activated apoptotic-related pathways in DLBCL cells by increasing BIM levels and inducing cell apoptosis. Moreover, combination therapy regulated expression of multiple transcriptomes in DLBCL cells, involving apoptosis, cell cycle, phosphorylation, and other biological processes, and significantly inhibited tumor growth in DLBCL-bearing xenograft mice. Taken together, these findings verify the in vivo therapeutic potential of chidamide and venetoclax combination therapy in DLBCL, warranting pre-clinical trials for patients with DLBCL.

关键词： Diffuse large B-cell lymphoma(DLBCL) Histone deacetylase(HDAC)inhibitor Venetoclax MYC BCL2 TP53

Improved adaptive genetic algorithm based RFID positioning

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Journal of Systems Engineering and Electronics 2022年第2期33卷 305-311页

作者： LI Yu WU Honglan SUN Youchao Civil Aviation College Nanjing University of Aeronautics and AstronauticsNanjing 211100China

The existing active tag-based radio frequency identi-fication(RFID)localization techniques show low accuracy in practical applications.To address such problems,we propose a chaotic adaptive genetic algorithm to align the passive tag ar-rays.We use chaotic sequences to generate the intersection points,the weakest single point intersection is used to ensure the convergence accuracy of the algorithm while avoiding the optimization jitter problem.Meanwhile,to avoid the problem of slow convergence and immature convergence of the algorithm caused by the weakening of individual competition at a later stage,we use adaptive rate of change to improve the optimiza-tion efficiency.In addition,to remove signal noise and outliers,we preprocess the data using Gaussian filtering.Experimental results demonstrate that the proposed algorithm achieves high-er localization accuracy and improves the convergence speed.

关键词： radio frequency identification(RFID)positioning im-proved genetic algorithm Gaussian filter passive tags