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Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice

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细胞研究（英文版） 2020年第7期30卷 574-589页

作者： Yusheng Cai Huanhuan Zhou Yinhua Zhu Qi Sun Yin Ji Anqi Xue Yuting Wang Wenhan Chen Xiaojie Yu Longteng Wang Han Chen Cheng Li Tuoping Luo Hongkui Deng The MOE Key Laboratory of Cell Proliferation and Differentiation College of Life Sciences Peking-Tsinghua Center for Life Sciences and School of Basic Medical Sciences State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science Center Peking University Beijing 100191 China State Key Laboratory of Chemical Oncogenomics School of Chemical Biology & Biotechnology Peking University Shenzhen Graduate School Shenzhen Guangdong 518055 China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 China Key Laboratory of Bioorganic Chemistry and Molecular Engineering Ministry of Education and Beijing National Laboratory for Molecular Science College of Chemistry and Molecular Engineering Peking University Beijing 100871 China School of Life Sciences Joint Graduate Program of Peking-Tsinghua-NIBS Peking University Beijing 100871 China School of Life Sciences Center for Bioinformatics Center for Statistical Science Peking University Beijing 100871 China

Cellular senescence,a persistent state of cell cycle arrest,accumulates in aged organisms,contributes to tissue dysfunction,and drives age-related *** clearance of senescent cells is expected to decrease chronic,low-grade inflammation and improve tissue repair capacity,thus attenuating the decline of physical function in aged ***,selective and effective clearance of senescent cells of different cell types has proven ***,we developed a prodrug strategy to design a new compound based on the increased activity of lysosomalβ-galactosidase (β-gal),a primary characteristic of senescent *** prodrug SSK1 is specifically activated by β-gal and eliminates mouse and human senescent cells independently of senescence inducers and cell *** aged mice,our compound effectively cleared senescent cells in different tissues,decreased the senescence-and age-associated gene signatures,attenuated low-grade local and systemic inflammation,and restored physical *** results demonstrate that lysosomalβ-gal can be effectively leveraged to selectively eliminate senescent cells,providing a novel strategy to develop anti-aging interventions.

关键词： Apoptosis Senescence

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Osteoarthritis treatment via the GLP-1-mediated gut-joint axis targets intestinal FXR signaling

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Science (New York, N.Y.) 2025年第6742期388卷 eadt0548页

作者： Yang, Yuanheng Hao, Cong Jiao, Tingying Yang, Zidan Li, Hui Zhang, Yuqing Zhang, Weiya Doherty, Michael Sun, Chuying Yang, Tuo Li, Jiatian Wu, Jing Zhang, Mengjiao Wang, Yilun Xie, Dongxing Wang, Tingjian Wang, Ning Huang, Xi Li, Changjun Gonzalez, Frank J. Wei, Jie Xie, Cen Zeng, Chao Lei, Guanghua Department of Orthopaedics Xiangya Hospital Central South University Changsha China Department of Plastic and Cosmetic Surgery Xiangya Hospital Central South University Changsha China State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China Human Phenome Institute School of Life Sciences Fudan University Shanghai China Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment Ministry of Education Xiangya Hospital Central South University Changsha China Hunan Key Laboratory of Joint Degeneration and Injury Xiangya Hospital Central South University Changsha China Bioinformatics Center Xiangya Hospital Central South University Changsha China Division of Rheumatology Allergy Immunology Department of Medicine Massachusetts General Hospital Harvard Medical School Boston MA United States Mongan Institute Massachusetts General Hospital Harvard Medical School Boston MA United States Academic Rheumatology School of Medicine University of Nottingham Nottingham United Kingdom Pain Centre Versus Arthritis UK Nottingham United Kingdom School of Chinese Materia Medica Nanjing University of Chinese Medicine Nanjing China Health Management Center Xiangya Hospital Central South University Changsha China Department of Neurosurgery Xiangya Hospital Central South University Changsha China Developmental and Stem Cell Biology Program Hospital for Sick Children Toronto ON Canada Department of Molecular Genetics University of Toronto Toronto ON Canada Department of Endocrinology Endocrinology Research Center Xiangya Hospital Central South University Changsha China Laboratory of Metabolism Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD United States Department of Epidemiology and Health Statistics Xiangya School of Public Health Central South University Changsha China Bioinformatics Center Furong Laboratory Changsha China Na

Whether a gut-joint axis exists to regulate osteoarthritis is unknown. In two independent cohorts, we identified altered microbial bile acid metabolism with reduced glycoursodeoxycholic acid (GUDCA) in osteoarthritis. Suppressing farnesoid X receptor (FXR)-the receptor of GUDCA-alleviated osteoarthritis through intestine-secreted glucagon-like peptide 1 (GLP-1) in mice. GLP-1 receptor blockade attenuated these effects, whereas GLP-1 receptor activation mitigated osteoarthritis. Osteoarthritis patients exhibited a lower relative abundance of Clostridium bolteae, which promoted the formation of ursodeoxycholic acid (UDCA), a precursor of GUDCA. Treatment with C. bolteae and Food and Drug Administration-approved UDCA alleviated osteoarthritis through the gut FXR-joint GLP-1 axis in mice. UDCA use was associated with lower risk of osteoarthritis-related joint replacement in humans. These findings suggest that orchestrating the gut microbiota-GUDCA-intestinal FXR-GLP-1-joint pathway offers a potential strategy for osteoarthritis treatment.

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The Role of Synthetic Biology in Atmospheric Greenhouse Gas Reduction: Prospects and Challenges

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BioDesign Research 2020年第1期2020卷 1-8页

作者： Charles DeLisi Aristides Patrinos Michael MacCracken Dan Drell George Annas Adam Arkin George Church Robert Cook-Deegan Henry Jacoby Mary Lidstrom Jerry Melillo Ron Milo Keith Paustian John Reilly Richard J.Roberts Daniel Segrè Susan Solomon Dominic Woolf Stan D.Wullschleger Xiaohan Yang Department of Biomedical Engineering and Program in Bioinformatics College of EngineeringBoston UniversityBoston MA 02215USA The NOVIM Group Kohn HallUC Santa BarbaraCA 93106USA Climate Institute WashingtonDCUSA Department of Energy WashingtonDCUSA Center for Health Law Ethics&Human Rights at the Boston University School of Public HealthSchool of MedicineBoston UniversityUSA Department of Bioengineering University of CaliforniaBerkeley CAUSA Department of Genetics Harvard Medical SchoolCambridge MAUSA School for the Future of Innovation in Society Arizona State UniversityBarrett&O’Connor Washington Center1800 I StreetNWWashingtonDC 20006USA Sloan School of Management MITCambridge MAUSA Department of Chemical Engineering University of WashingtonSeattle WashingtonUSA The Ecosystems Center of the Marine Biological Laboratory in Woods Hole MAUSA Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovotIsrael Department of Soil and Crop Sciences Colorado State UniversityFort Collins CO 80523USA MIT Joint Program on the Science and Policy of Global Change MITCambridge MAUSA New England Biolabs Beverly MAUSA Department of Biology and Program in Bioinformatics Boston UniversityBoston MA 02215USA Department of Earth Atmospheric and Planetary SciencesMITCambridge MAUSA Soil and Crop Sciences Section School of Integrated Plant SciencesCornell UniversityIthaca NYUSA Environmental Sciences Division Oak Ridge National LaboratoryOak Ridge TNUSA Biosciences Division Oak Ridge National LaboratoryOak RidgeTNUSA

The long atmospheric residence time of CO2 creates an urgent need to add atmospheric carbon drawdown to CO2 regulatory *** and systems biology(SSB),which enables manipulation of cellular phenotypes,offers a powerful approach to amplifying and adding new possibilities to current land management practices aimed at reducing atmospheric *** participants(in attendance:Christina Agapakis,George Annas,Adam Arkin,George Church,Robert Cook-Deegan,Charles DeLisi,Dan Drell,Sheldon Glashow,Steve Hamburg,Henry Jacoby,Henry Kelly,Mark Kon,Todd Kuiken,Mary Lidstrom,Mike MacCracken,June Medford,Jerry Melillo,Ron Milo,Pilar Ossorio,Ari Patrinos,Keith Paustian,Kristala Jones Prather,Kent Redford,David Resnik,John Reilly,Richard ***,Daniel Segre,Susan Solomon,Elizabeth Strychalski,Chris Voigt,Dominic Woolf,Stan Wullschleger,and Xiaohan Yang)identified a range of possibilities by which SSB might help reduce greenhouse gas concentrations and which might also contribute to environmental sustainability and *** include,among other possibilities,engineering plants to convert CO2 produced by respiration into a stable carbonate,designing plants with an increased root-to-shoot ratio,and creating plants with the ability to self-fertilize.A number of serious ecological and societal challenges must,however,be confronted and resolved before any such application can be fully assessed,realized,and deployed.

关键词： Synthetic Roberts enable

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eIF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondrial Homeostasis, and Muscle Health

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Journal of Cleaner Production 2020年第4期79卷 575-587.e7页

作者： Lin, Yingying Li, Fajin Huang, Linlu Polte, Christine Duan, Haoran Fang, Jianhuo Sun, Li Xing, Xudong Tian, Guiyou Cheng, Yabin Ignatova, Zoya Yang, Xuerui Wolf, Dieter A. School of Pharmaceutical Sciences Fujian Provincial Key Laboratory of Innovative Drug Target Research Xiamen University Xiamen Fujian361102 China MOE Key Laboratory of Bioinformatics Center for Synthetic & Systems Biology School of Life Sciences Tsinghua University Beijing100084 China Joint Graduate Program of Peking-Tsinghua-National Institute of Biological Science Tsinghua University Beijing100084 China Biochemistry and Molecular Biology University of Hamburg Hamburg20146 Germany State Key Laboratory of Cellular Stress Biology Xiamen University Xiamen Fujian361102 China

eIF3, a multi-subunit complex with numerous functions in canonical translation initiation, is known to interact with 40S and 60S ribosomal proteins and translation elongation factors, but a direct involvement in translation elongation has never been demonstrated. We found that eIF3 deficiency reduced early ribosomal elongation speed between codons 25 and 75 on a set of ∼2,700 mRNAs encoding proteins associated with mitochondrial and membrane functions, resulting in defective synthesis of their encoded proteins. To promote elongation, eIF3 interacts with 80S ribosomes translating the first ∼60 codons and serves to recruit protein quality-control factors, functions required for normal mitochondrial physiology. Accordingly, eIF3e+/− mice accumulate defective mitochondria in skeletal muscle and show a progressive decline in muscle strength. Hence, eIF3 interacts with 80S ribosomes to enhance, at the level of early elongation, the synthesis of proteins with membrane-associated functions, an activity that is critical for mitochondrial physiology and muscle health. © 2020 Elsevier Inc.

关键词： Elongation

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Investigation of RNA-RNA Interactions Using the RISE Database

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Current Protocols in bioinformatics 2018年第1期64卷 e58/1-e58/1页

作者： Ju, Yanyan Gong, Jing Yang, Yucheng T. Zhang, Qiangfeng Cliff MOE Key Laboratory of Bioinformatics Beijing Advanced Innovation Center for Structural Biology Center for Synthetic and Systems Biology Tsinghua-Peking Joint Center for Life Sciences School of Life Sciences Tsinghua University Beijing China Department of Molecular Biophysics and Biochemistry Yale University New Haven CT United States Program in Computational Biology and Bioinformatics Yale University New Haven CT United States

RNA-RNA interactions (RRIs) are essential to understanding the regulatory mechanisms of RNAs. Mapping RRIs in vivo in a transcriptome-wide manner remained challenging until the recent development of several sequencing-based technologies. However, RRIs generated from large-scale studies had not been systematically collected and analyzed before. This article introduces RISE, a database of the RNA Interactome from Sequencing Experiments. RISE provides a comprehensive collection of RRIs in human, mouse, and yeast, derived from transcriptome-wide sequencing experiments, as well as targeted sequencing studies and other public databases/datasets. To facilitate better understanding of the biological roles of these RRIs, RISE also offers rich functional annotations involving RNAs, and an interactive interface to explore the analysis results. Here, we provide a brief description of the RISE website and a step-by-step protocol for using RISE to study RRIs. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

关键词： interaction RISE RNA RNA structure RNA-RNA sequencing experiments

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Artificial intelligence for modelling infectious disease epidemics

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Nature 2025年第8051期638卷 623-635页

作者： Kraemer, Moritz U. G. Tsui, Joseph L.-H. Chang, Serina Y. Lytras, Spyros Khurana, Mark P. Vanderslott, Samantha Bajaj, Sumali Scheidwasser, Neil Curran-Sebastian, Jacob Liam Semenova, Elizaveta Zhang, Mengyan Unwin, H. Juliette T. Watson, Oliver J. Mills, Cathal Dasgupta, Abhishek Ferretti, Luca Scarpino, Samuel V. Koua, Etien Morgan, Oliver Tegally, Houriiyah Paquet, Ulrich Moutsianas, Loukas Fraser, Christophe Ferguson, Neil M. Topol, Eric J. Duchêne, David A. Stadler, Tanja Kingori, Patricia Parker, Michael J. Dominici, Francesca Shadbolt, Nigel Suchard, Marc A. Ratmann, Oliver Flaxman, Seth Holmes, Edward C. Gomez-Rodriguez, Manuel Schölkopf, Bernhard Donnelly, Christl A. Pybus, Oliver G. Cauchemez, Simon Bhatt, Samir Pandemic Sciences Institute University of Oxford Oxford United Kingdom Department of Biology University of Oxford Oxford United Kingdom Department of Electrical Engineering and Computer Science University of California Berkeley Berkeley CA United States UCSF UC Berkeley Joint Program in Computational Precision Health Berkeley CA United States Division of Systems Virology Department of Microbiology and Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan Section of Epidemiology Department of Public Health University of Copenhagen Copenhagen Denmark Oxford Vaccine Group University of Oxford and NIHR Oxford Biomedical Research Centre Oxford United Kingdom Department of Epidemiology and Biostatistics Imperial College London London United Kingdom Department of Computer Science University of Oxford Oxford United Kingdom School of Mathematics University of Bristol Bristol United Kingdom MRC Centre for Global Infectious Disease Analysis School of Public Health Imperial College London London United Kingdom Department of Statistics University of Oxford Oxford United Kingdom Doctoral Training Centre University of Oxford Oxford United Kingdom Institute for Experiential AI Northeastern University MA Boston Thailand Santa Fe Institute Santa Fe NM United States World Health Organization Regional Office for Africa Brazzaville Congo WHO Hub for Pandemic and Epidemic Intelligence Health Emergencies Programme World Health Organization Berlin Germany Centre for Epidemic Response and Innovation (CERI) School for Data Science and Computational Thinking Stellenbosch University Stellenbosch South Africa African Institute for Mathematical Sciences (AIMS) South Africa Muizenberg Cape Town South Africa Genomics England London United Kingdom Scripps Research La Jolla CA United States Department of Biosystems Science and Engineering ETH Zürich Basel Switzerland Swiss Institute of Bioinformatics Lausanne Switzerland The Ethox Centre Nuffield

Infectious disease threats to individual and public health are numerous, varied and frequently unexpected. Artificial intelligence (AI) and related technologies, which are already supporting human decision making in economics, medicine and social science, have the potential to transform the scope and power of infectious disease epidemiology. Here we consider the application to infectious disease modelling of AI systems that combine machine learning, computational statistics, information retrieval and data science. We first outline how recent advances in AI can accelerate breakthroughs in answering key epidemiological questions and we discuss specific AI methods that can be applied to routinely collected infectious disease surveillance data. Second, we elaborate on the social context of AI for infectious disease epidemiology, including issues such as explainability, safety, accountability and ethics. Finally, we summarize some limitations of AI applications in this field and provide recommendations for how infectious disease epidemiology can harness most effectively current and future developments in AI. © Springer Nature Limited 2025.

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RETRACTION: RETRACTED: Crystal structure of a Baeyer-Villiger flavin-containing monooxygenase from Staphylococcus aureus MRSA strain MU50 (Retraction of 2014)

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PROTEINS-STRUCTURE FUNCTION AND bioinformatics 2018年第2期86卷 269-269页

作者： Hwang, William C. Xu, Qingping Wu, Bainan Godzik, Adam Bioinformatics Core Joint Center for Structural Genomics (JCSG) La Jolla California 92037 Bioinformatics and Systems Biology Program Sanford-Burnham Medical Research Institute La Jolla California 92037.

The above article from Proteins: Structure, Function, and bioinformatics, published online on 5 August 2014 in Wiley Online Library (http://***/doi/10.1002/prot.24661/full), has been retracted by agreement between William C. Hwang, Qingping Xu, Bainan Wu, Adam Godzik, the Editor‐in‐Chief, Bertrand E. Garcia‐Moreno, and Wiley Periodicals, Inc. The retraction has been agreed because submission was made without agreement from co‐author Adam Godzik.

关键词： Baeyer-Villiger reaction FMO antibiotics resistance methicillin vancomycin

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Correction: The genome of the soybean cyst nematode (Heterodera glycines) reveals complex patterns of duplications involved in the evolution of parasitism genes

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BMC genomics 2024年第1期25卷 537页

作者： Rick Masonbrink Tom R Maier Usha Muppirala Arun S Seetharam Etienne Lord Parijat S Juvale Jeremy Schmutz Nathan T Johnson Dmitry Korkin Melissa G Mitchum Benjamin Mimee Sebastian Eves-van den Akker Matthew Hudson Andrew J Severin Thomas J Baum Department of Plant Pathology Iowa State University Ames IA USA. Genome Informatics Facility Iowa State University Ames IA USA. Agriculture and Agri-Food Canada Saint-Jean-sur-Richelieu QC Canada. Department of Energy Joint Genome Institute Walnut Creek CA USA. HudsonAlpha Institute for Biotechnology Huntsville AL USA. Bioinformatics and Computational Biology Program Worcester Polytechnic Institute Worcester MA USA. Department of Computer Science Worcester Polytechnic Institute Worcester MA USA. Division of Plant Sciences University of Missouri Columbia MO USA. Department of Plant Sciences University of Cambridge Cambridge UK. Department of Crop Sciences University of Illinois Urbana IL USA. Genome Informatics Facility Iowa State University Ames IA USA. severin@iastate.edu.

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Correction to: Population differentiated copy number variation of Bos taurus, Bos indicus and their African hybrids

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BMC genomics 2022年第1期23卷 207页

作者： Jisung Jang Endashaw Terefe Kwondo Kim Young Ho Lee Gurja Belay Abdulfatai Tijjani Jian-Lin Han Olivier Hanotte Heebal Kim Interdisciplinary Program in Bioinformatics Seoul National University Seoul Republic of Korea. Addis Ababa University MCMB Department Addis Ababa Ethiopia. International Livestock Research Institute (ILRI) Addis Ababa Ethiopia. Arsi University Asella Ethiopia. Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences Seoul National University Seoul Republic of Korea. The Centre for Tropical Livestock Genetics and Health (CTLGH) The Roslin Institute The University of Edinburgh Edinburgh UK. CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources Institute of Animal Science Chinese Academy of Agricultural Sciences (CAAS) Beijing China. Livestock Genetics Program International Livestock Research Institute (ILRI) Nairobi Kenya. School of Life Sciences University of Nottingham Nottingham UK. Interdisciplinary Program in Bioinformatics Seoul National University Seoul Republic of Korea. heebal@snu.ac.kr. Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences Seoul National University Seoul Republic of Korea. heebal@snu.ac.kr. eGnome Inc. Seoul South Korea. heebal@snu.ac.kr.

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Comparing the Efficacy and Safety of Treating Chronic Hepatitis B Infection during Pregnancy with Lamivudine,Telbivudine,and Tenofovir:A Meta-analysis

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Journal of Clinical and Translational Hepatology 2019年第3期7卷 197-212页

作者： Shahnaz Sali Mohammad Darvishi Mojtaba GhasemiAdl Meisam Akhlaghdoust Azin Mirzazadeh Somayeh Elikaei Behjati Hossein Sheikh-Zeinolabedini Shervin Shokouhi Soheil Tavakolpour Infectious Diseases and Tropical Medicine Research Center Shahid Beheshti University of Medical SciencesTehranIran Department of Aerospace and Subaquatic Medicine Infectious Diseases and Tropical Medicine Research Center(IDTMRC)AJA University of Medical SciencesTehranIran Pharmaceutical Sciences Research Center Tehran University of Medical SciencesTehranIran Pars Advanced and Minimally Invasive Medical Manners Research Center Pars HospitalIran University of Medical SciencesTehranIran Joint Bioinformatics Graduate Program University of Arkansas Little Rock and University of Arkansas for Medical SciencesLittle RockARUSA The Genetics Department at Islamic Azad University Science and Research BranchTehranIran Infectious Diseases and Tropical Medicine Research Center Shahid Beheshti University of Medical SciencesTehran 198396-3113Iran

Background and Aims:The perinatal transmission of hepatitis B virus(HBV)remains an important global health ***,a systematic review and meta-analysis were conducted to evaluate the evidence regarding the efficacy and maternal/fetal safety of treating pregnant women with lamivudine,telbivudine(LdT),and tenofovir(TDF).Methods:A PubMed and Scopus search resulted in 1,076 records,which were reduced to 36,containing 7,717 pregnant women with chronic HBV infection and 7467 infants meeting the inclusion *** latest search was in August ***:Treatment with LdT,but not lamivudine and TDF,could significantly reduce the hepatitis B virus surface antigen-positive rate(odds ratio(OR)=0.37)in infants;it also led to higher rates of hepatitis B e antigen loss(OR=12.14),hepatitis B e antigen seroconversion(OR=8.93),and alanine aminotransferase normalization in mothers(OR=1.49).Each of these treatments was able to significantly reduce HBV DNA positivity at birth(total OR=0.19)and mother-to-child-transmission of HBV(total OR=0.15),and to cause higher rates of HBV DNA suppression in mothers(total OR=25.53).However,nucleos(t)ide analogues might also be involved in creatine kinase elevation(total OR=7.48).In contrast,no significant association was found between nucleos(t)ide analogue therapy and preterm/premature births,congenital malformation,low birth weight,and abortion or fetal/infant *** results suggested LdT's high capability of preventing ***,TDF failed to show significant associations to a reduced risk of mother-to-child-transmission,probably due to the low number of patients ***:Although using either lamivudine,LdT,orTDF could lead to more favorable maternal/fetal outcomes,LdT seemed to show more potential in resolving certain infant-and maternal-related *** studies on the safety profile of such treatments are required.

关键词： Hepatitis B virus Antiviral therapy Tenofovir Telbivudine Lamivudine Nucleos(t)ide analogues Pregnancy

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