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npj Cardiovascular Health 2024年第1期1卷 1-12页

作者： Felipe Takaesu Evan Yang Michael E. Davis Khalid Yasseen Hyun-Ji Park John M. Kelly Christopher K. Breuer Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology & Emory University Atlanta GA USA Biochemistry Cell and Developmental Biology Graduate Training Program Graduate Division of Biological and Biomedical Sciences Laney Graduate School Emory University Atlanta GA USA Children’s Heart Research & Outcomes (HeRO) Center Children’s Healthcare of Atlanta & Emory University Atlanta GA USA Frank H. Netter School of Medicine Quinnipiac University North Haven CT USA Department of Molecular Science and Technology Ajou University Suwon 16499 Korea Center for Regenerative Medicine Abigail Wexner Research Institute at Nationwide Children’s Hospital Columbus OH USA The Heart Center Nationwide Children’s Hospital Columbus OH USA Department of Pediatrics The Ohio State University College of Medicine Columbus OH USA

Single-ventricle defects are treated with the Glenn and Fontan procedures, which offer lifesaving relief but result in lifelong complications. To address the lack of outcome predictors, we conducted an untargeted transcriptomic analysis to identify RNA biomarkers in serum and circulating sEVs from 25 Glenn or Fontan patients with three samples exclusively used for experimental assays. Unsupervised analysis revealed a distinction between pre-op and post-op samples in both surgical groups. Differential gene expression and pathway analysis showed enrichment for pro-angiogenic cargo in post-op sEVs compared to pre-op sEVs. Wound healing assays revealed post-op Fontan sEVs induce a stronger pro-angiogenic response than pre-op Fontan sEVs. A PLSR-guided approach revealed MAPK6, GLE1, hsa-miR-340-5p, and hsa-miR-199b-5p as key transcripts in the observed wound healing response. Lastly, EV-Origin revealed decreased secretion of sEV from cardiac tissue and increased secretion from brain tissue for both Fontan and Glenn samples. This work demonstrates the potential of sEV RNAs as biomarkers for patients with Fontan physiology, enabling quicker diagnosis for Fontan-associated complications.

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Search for tetraquark states Xccs¯s¯ in Ds+Ds+(Ds*+Ds*+) final states at Belle

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Physical Review D 2022年第3期105卷 032002-032002页

作者： X. Y. Gao Y. Li C. P. Shen I. Adachi H. Aihara D. M. Asner H. Atmacan T. Aushev R. Ayad P. Behera K. Belous M. Bessner V. Bhardwaj B. Bhuyan T. Bilka A. Bobrov D. Bodrov G. Bonvicini J. Borah A. Bozek M. Bračko T. E. Browder A. Budano M. Campajola D. Červenkov M.-C. Chang P. Chang A. Chen B. G. Cheon K. Chilikin H. E. Cho K. Cho S.-J. Cho S.-K. Choi Y. Choi S. Choudhury D. Cinabro S. Cunliffe S. Das G. De Pietro R. Dhamija F. Di Capua J. Dingfelder Z. Doležal T. V. Dong D. Dossett D. Epifanov T. Ferber A. Frey B. G. Fulsom R. Garg V. Gaur N. Gabyshev A. Giri P. Goldenzweig T. Gu Y. Guan K. Gudkova C. Hadjivasiliou S. Halder O. Hartbrich K. Hayasaka H. Hayashii M. T. Hedges W.-S. Hou C.-L. Hsu T. Iijima K. Inami G. Inguglia A. Ishikawa R. Itoh M. Iwasaki Y. Iwasaki W. W. Jacobs E.-J. Jang S. Jia Y. Jin K. K. Joo J. Kahn A. B. Kaliyar K. H. Kang G. Karyan T. Kawasaki H. Kichimi C. Kiesling C. H. Kim D. Y. Kim K.-H. Kim Y.-K. Kim P. Kodyš T. Konno A. Korobov S. Korpar E. Kovalenko P. Križan R. Kroeger P. Krokovny T. Kuhr R. Kumar K. Kumara A. Kuzmin Y.-J. Kwon Y.-T. Lai T. Lam J. S. Lange M. Laurenza S. C. Lee C. H. Li J. Li L. K. Li Y. B. Li L. Li Gioi J. Libby K. Lieret D. Liventsev A. Martini M. Masuda T. Matsuda D. Matvienko S. K. Maurya F. Meier M. Merola F. Metzner K. Miyabayashi R. Mizuk G. B. Mohanty R. Mussa M. Nakao Z. Natkaniec A. Natochii L. Nayak M. Niiyama N. K. Nisar S. Nishida K. Ogawa S. Ogawa H. Ono P. Oskin P. Pakhlov G. Pakhlova T. Pang S. Pardi H. Park S.-H. Park S. Patra S. Paul T. K. Pedlar R. Pestotnik L. E. Piilonen T. Podobnik V. Popov E. Prencipe M. T. Prim M. Röhrken A. Rostomyan N. Rout G. Russo D. Sahoo S. Sandilya A. Sangal L. Santelj T. Sanuki V. Savinov G. Schnell Y. Seino K. Senyo M. E. Sevior M. Shapkin C. Sharma J.-G. Shiu F. Simon J. B. Singh A. Sokolov E. Solovieva S. Stanič M. Starič Z. S. Stottler M. Sumihama T. Sumiyoshi M. Takizawa U. Tamponi K. Tanida F. Tenchini M. Uchida K. Uno S. Uno P. Urquijo Y. Usov R. Van Tonder G. Varner A. Vinokurova E. Waheed E. Wang M.-Z. Wang X. Key Laboratory of Nuclear Physics and Ion-beam Application (MOE) and Institute of Modern Physics Fudan University Shanghai 200443 High Energy Accelerator Research Organization (KEK) Tsukuba 305-0801 SOKENDAI (The Graduate University for Advanced Studies) Hayama 240-0193 Department of Physics University of Tokyo Tokyo 113-0033 Brookhaven National Laboratory Upton New York 11973 University of Cincinnati Cincinnati Ohio 45221 National Research University Higher School of Economics Moscow 101000 Department of Physics Faculty of Science University of Tabuk Tabuk 71451 Indian Institute of Technology Madras Chennai 600036 Institute for High Energy Physics Protvino 142281 University of Hawaii Honolulu Hawaii 96822 Indian Institute of Science Education and Research Mohali SAS Nagar 140306 Indian Institute of Technology Guwahati Assam 781039 Faculty of Mathematics and Physics Charles University 121 16 Prague Budker Institute of Nuclear Physics SB RAS Novosibirsk 630090 Novosibirsk State University Novosibirsk 630090 P.N. Lebedev Physical Institute of the Russian Academy of Sciences Moscow 119991 Wayne State University Detroit Michigan 48202 H. Niewodniczanski Institute of Nuclear Physics Krakow 31-342 Faculty of Chemistry and Chemical Engineering University of Maribor 2000 Maribor J. Stefan Institute 1000 Ljubljana INFN—Sezione di Roma Tre I-00146 Roma INFN—Sezione di Napoli I-80126 Napoli Università di Napoli Federico II I-80126 Napoli Department of Physics Fu Jen Catholic University Taipei 24205 Department of Physics National Taiwan University Taipei 10617 National Central University Chung-li 32054 Department of Physics and Institute of Natural Sciences Hanyang University Seoul 04763 Korea Institute of Science and Technology Information Daejeon 34141 Yonsei University Seoul 03722 Chung-Ang University Seoul 06974 Sungkyunkwan University Suwon 16419 Iowa State University Ames Iowa 50011 Deutsches Elektronen–Synchrotron 22607 Hamburg Malaviya National Institute of Technology

A search for double-heavy tetraquark state candidates Xccs¯s¯ decaying to Ds+Ds+ and Ds*+Ds*+ is presented for the first time using the data samples of 102×106 ϒ(1S) and 158×106 ϒ(2S) events, and the data samples at s=10.52, 10.58, and 10.867 GeV corresponding to integrated luminosities of 89.5, 711.0, and 121.4 fb−1, respectively, accumulated with the Belle detector at the KEKB asymmetric energy electron-positron collider. The invariant-mass spectra of the Ds+Ds+ and Ds*+Ds*+ are studied to search for possible resonances. No significant signals are observed, and the 90% confidence level upper limits on the product branching fractions [B(ϒ(1S,2S)→Xccs¯s¯+anything)×B(Xccs¯s¯→Ds+Ds+(Ds*+Ds*+))] in ϒ(1S,2S) inclusive decays and the product values of Born cross section and branching fraction [σ(e+e−→Xccs¯s¯+anything)×B(Xccs¯s¯→Ds+Ds+(Ds*+Ds*+))] in e+e− collisions at s=10.52, 10.58, and 10.867 GeV under different assumptions of Xccs¯s¯ masses and widths are obtained.

关键词： Charmed mesons Exotic mesons Lepton colliders

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Perspective on recent developments and challenges in regulatory and systems genomics

arXiv

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arXiv 2024年

作者： Zeiltinger, Julia Roy, Sushmita Ay, Ferhat Mathelier, Anthony Medina-Rivera, Alejandra Mahony, Shaun Sinha, Saurabh Ernst, Jason Stowers Institute for Medical Research Kansas CityMO64112 United States Department of Pathology & Laboratory Medicine The University of Kansas Medical Center Kansas CityKS66160 United States Department of Biostatistics and Medical Informatics University of Wisconsin-Madison Madison53715 United States Wisconsin Institute for Discovery University of Wisconsin-Madison Madison53715 United States Centers for Autoimmunity Inflammation and Cancer Immunotherapy La Jolla Institute for Immunology La Jolla CA United States Bioinformatics and Systems Biology Program University of California La Jolla San DiegoCA United States Department of Pediatrics University of California La Jolla San DiegoCA United States Nordic EMBL Partnership University of Oslo Oslo0318 Norway Department of Medical Genetics Institute of Clinical Medicine University of Oslo Oslo University Hospital Oslo Norway Department of Pharmacy University of Oslo Oslo Norway Laboratorio Internacional de Investigación sobre el Genoma Humano Universidad Nacional Autónoma de México Campus Juriquilla Blvd. Juriquilla 3001 Santiago de Querétaro76230 Mexico Center for Eukaryotic Gene Regulation Department of Biochemistry and Molecular Biology The Pennsylvania State University University ParkPA16802 United States Walter H. Coulter Department of Biomedical Engineering Georgia Institute of Technology AtlantaGA United States H. Milton Stewart School of Industrial and Systems Engineering Georgia Institute of Technology AtlantaGA United States Department of Biological Chemistry University of California Los Angeles Los AngelesCA90095 United States Computer Science Department University of California Los Angeles Los AngelesCA90095 United States Department of Computational Medicine University of California Los Angeles Los AngelesCA90095 United States Eli and Edythe Broad Center of Regenerative Medicine Stem Cell Research University of California Los Angeles Los AngelesCA90095 United States

Predicting how genetic variation affects phenotypic outcomes at the organismal, cellular, and molecular levels requires deciphering the cis-regulatory code, the sequence rules by which non-coding regions regulate genes. In this perspective, we discuss recent computational progress and challenges towards solving this fundamental problem. We describe how cis-regulatory elements are mapped and how their sequence rules can be learned and interpreted with sequence-to-function neural networks, with the goal of identifying genetic variants in human disease. We also discuss how studies of the 3D chromatin organization could help identifying long-range regulatory effects and how current methods for mapping gene regulatory networks could better describe biological processes. We point out current gaps in knowledge along with technical limitations and benchmarking challenges of computational methods. Finally, we discuss newly emerging technologies, such as spatial transcriptomics, and outline strategies for creating a more general model of the cis-regulatory code that is more broadly applicable across cell types and individuals. © 2024, CC BY-NC-SA.

关键词： Molecular docking

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Search for the decay Bs0→η′KS0

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Physical Review D 2022年第5期106卷 L051103-L051103页

作者： T. Pang V. Savinov I. Adachi H. Aihara D. M. Asner H. Atmacan V. Aulchenko T. Aushev R. Ayad V. Babu P. Behera K. Belous M. Bessner V. Bhardwaj B. Bhuyan T. Bilka A. Bobrov D. Bodrov G. Bonvicini J. Borah A. Bozek M. Bračko P. Branchini T. E. Browder A. Budano M. Campajola D. Červenkov P. Chang A. Chen B. G. Cheon K. Chilikin H. E. Cho K. Cho S.-J. Cho S.-K. Choi Y. Choi S. Choudhury D. Cinabro S. Cunliffe S. Das G. De Pietro R. Dhamija F. Di Capua J. Dingfelder Z. Doležal T. V. Dong D. Dossett S. Dubey D. Epifanov T. Ferber A. Frey B. G. Fulsom R. Garg V. Gaur N. Gabyshev A. Giri P. Goldenzweig E. Graziani T. Gu K. Gudkova C. Hadjivasiliou S. Halder K. Hayasaka H. Hayashii M. T. Hedges C.-L. Hsu T. Iijima K. Inami G. Inguglia A. Ishikawa R. Itoh M. Iwasaki Y. Iwasaki W. W. Jacobs E.-J. Jang S. Jia Y. Jin K. K. Joo J. Kahn D. Kalita A. B. Kaliyar K. H. Kang G. Karyan T. Kawasaki C. Kiesling C. H. Kim D. Y. Kim K.-H. Kim Y.-K. Kim K. Kinoshita P. Kodyš T. Konno A. Korobov S. Korpar E. Kovalenko P. Križan R. Kroeger P. Krokovny T. Kuhr R. Kumar K. Kumara A. Kuzmin Y.-J. Kwon Y.-T. Lai T. Lam J. S. Lange S. C. Lee C. H. Li J. Li L. K. Li Y. Li L. Li Gioi J. Libby K. Lieret D. Liventsev A. Martini M. Masuda T. Matsuda D. Matvienko F. Meier M. Merola F. Metzner K. Miyabayashi R. Mizuk G. B. Mohanty R. Mussa M. Nakao Z. Natkaniec A. Natochii L. Nayak M. Niiyama N. K. Nisar S. Nishida K. Ogawa S. Ogawa H. Ono P. Oskin P. Pakhlov G. Pakhlova S. Pardi H. Park S.-H. Park A. Passeri S. Patra S. Paul T. K. Pedlar R. Pestotnik L. E. Piilonen T. Podobnik V. Popov E. Prencipe M. T. Prim A. Rostomyan N. Rout G. Russo D. Sahoo S. Sandilya A. Sangal L. Santelj T. Sanuki G. Schnell Y. Seino K. Senyo M. E. Sevior M. Shapkin C. Sharma C. P. Shen J.-G. Shiu F. Simon J. B. Singh A. Sokolov E. Solovieva S. Stanič M. Starič J. F. Strube M. Sumihama T. Sumiyoshi M. Takizawa U. Tamponi K. Tanida N. Taniguchi F. Tenchini K. Trabelsi M. Uchida K. Uno S. Uno P. Urquijo R. Van Tonder G. Varner A. Vinokurova E. Waheed E. Wang M.-Z. Wang X. L. W University of Pittsburgh Pittsburgh Pennsylvania 15260 High Energy Accelerator Research Organization (KEK) Tsukuba 305-0801 SOKENDAI (The Graduate University for Advanced Studies) Hayama 240-0193 Department of Physics University of Tokyo Tokyo 113-0033 Brookhaven National Laboratory Upton New York 11973 University of Cincinnati Cincinnati Ohio 45221 Budker Institute of Nuclear Physics SB RAS Novosibirsk 630090 Novosibirsk State University Novosibirsk 630090 National Research University Higher School of Economics Moscow 101000 Department of Physics Faculty of Science University of Tabuk Tabuk 71451 Deutsches Elektronen-Synchrotron 22607 Hamburg Indian Institute of Technology Madras Chennai 600036 Institute for High Energy Physics Protvino 142281 University of Hawaii Honolulu Hawaii 96822 Indian Institute of Science Education and Research Mohali SAS Nagar 140306 Indian Institute of Technology Guwahati Assam 781039 Faculty of Mathematics and Physics Charles University 121 16 Prague P.N. Lebedev Physical Institute of the Russian Academy of Sciences Moscow 119991 Wayne State University Detroit Michigan 48202 H. Niewodniczanski Institute of Nuclear Physics Krakow 31-342 Faculty of Chemistry and Chemical Engineering University of Maribor 2000 Maribor J. Stefan Institute 1000 Ljubljana INFN-Sezione di Roma Tre I-00146 Roma INFN-Sezione di Napoli I-80126 Napoli Università di Napoli Federico II I-80126 Napoli Department of Physics National Taiwan University Taipei 10617 National Central University Chung-li 32054 Department of Physics and Institute of Natural Sciences Hanyang University Seoul 04763 Korea Institute of Science and Technology Information Daejeon 34141 Yonsei University Seoul 03722 Chung-Ang University Seoul 06974 Sungkyunkwan University Suwon 16419 Iowa State University Ames Iowa 50011 Malaviya National Institute of Technology Jaipur Jaipur 302017 Indian Institute of Technology Hyderabad Telangana 502285 University of Bonn 53115 Bonn Institute of Theoretical an

We report the results of the first search for the decay Bs0→η′KS0 using 121.4 fb−1 of data collected at the ϒ(5S) resonance with the Belle detector at the KEKB asymmetric-energy e+e− collider. We observe no signal... 详细信息

关键词： Branching fraction Hadronic decays Particle decays Particle phenomena Rare decays

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Jet modification via π0-hadron correlations in Au+Au collisions at sNN=200 GeV

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Physical Review C 2024年第4期110卷 044901页

作者： N. J. Abdulameer U. Acharya A. Adare S. Afanasiev C. Aidala N. N. Ajitanand Y. Akiba H. Al-Bataineh J. Alexander M. Alfred K. Aoki N. Apadula L. Aphecetche J. Asai H. Asano E. T. Atomssa R. Averbeck T. C. Awes B. Azmoun V. Babintsev M. Bai G. Baksay L. Baksay A. Baldisseri N. S. Bandara B. Bannier K. N. Barish P. D. Barnes B. Bassalleck A. T. Basye S. Bathe S. Batsouli V. Baublis C. Baumann A. Bazilevsky M. Beaumier S. Beckman S. Belikov R. Belmont R. Bennett A. Berdnikov Y. Berdnikov L. Bichon A. A. Bickley B. Blankenship D. S. Blau J. G. Boissevain J. S. Bok H. Borel V. Borisov K. Boyle M. L. Brooks J. Bryslawskyj H. Buesching V. Bumazhnov G. Bunce S. Butsyk C. M. Camacho S. Campbell B. S. Chang W. C. Chang J. L. Charvet C.-H. Chen D. Chen S. Chernichenko M. Chiu C. Y. Chi I. J. Choi J. B. Choi R. K. Choudhury T. Chujo P. Chung A. Churyn V. Cianciolo Z. Citron B. A. Cole M. Connors P. Constantin R. Corliss M. Csanád T. Csörgő D. d'Enterria T. Dahms S. Dairaku T. W. Danley K. Das A. Datta M. S. Daugherity G. David K. DeBlasio K. Dehmelt A. Denisov A. Deshpande E. J. Desmond O. Dietzsch A. Dion P. B. Diss M. Donadelli V. Doomra J. H. Do O. Drapier A. Drees K. A. Drees A. K. Dubey J. M. Durham A. Durum D. Dutta V. Dzhordzhadze Y. V. Efremenko F. Ellinghaus H. En'yo T. Engelmore A. Enokizono R. Esha K. O. Eyser B. Fadem N. Feege D. E. Fields M. Finger, Jr. M. Finger D. Firak D. Fitzgerald F. Fleuret S. L. Fokin Z. Fraenkel J. E. Frantz A. Franz A. D. Frawley K. Fujiwara Y. Fukao T. Fusayasu P. Gallus C. Gal P. Garg I. Garishvili H. Ge F. Giordano A. Glenn H. Gong M. Gonin J. Gosset Y. Goto R. Granier de Cassagnac N. Grau S. V. Greene M. Grosse Perdekamp T. Gunji T. Guo H.-Å. Gustafsson T. Hachiya A. Hadj Henni J. S. Haggerty K. I. Hahn H. Hamagaki H. F. Hamilton J. Hanks R. Han S. Y. Han E. P. Hartouni K. Haruna S. Hasegawa T. O. S. Haseler K. Hashimoto E. Haslum R. Hayano M. Heffner T. K. Hemmick T. Hester X. He J. C. Hill A. Hodges M. Hohlmann R. S. Hollis W. Holzmann K. Homma B. Hong T. Horaguchi D. Hornback T. Debrecen University H-4010 Debrecen Egyetem tér 1 Hungary HUN-REN ATOMKI H-4026 Debrecen Bem tér 18/c Hungary Atlanta Georgia 30303 USA University of Colorado Boulder Colorado 80309 USA Joint Institute for Nuclear Research 141980 Dubna Moscow Region Russia Department of Physics University of Massachusetts Amherst Massachusetts 01003-9337 USA Department of Physics University of Michigan Ann Arbor Michigan 48109-1040 USA Chemistry Department Stony Brook University SUNY Stony Brook New York 11794-3400 USA RIKEN Nishina Center for Accelerator-Based Science Wako Saitama 351-0198 Japan RIKEN BNL Research Center New Mexico State University Las Cruces New Mexico 88003 USA Department of Physics and Astronomy Howard University Washington DC 20059 USA KEK High Energy Accelerator Research Organization Tsukuba Ibaraki 305-0801 Japan Kyoto University Kyoto 606-8502 Japan Iowa State University Ames Iowa 50011 USA Department of Physics and Astronomy Stony Brook University SUNY Stony Brook New York 11794-3800 USA SUBATECH (Ecole des Mines de Nantes CNRS-IN2P3 Université de Nantes) BP 20722-44307 Nantes France Laboratoire Leprince-Ringuet Ecole Polytechnique CNRS-IN2P3 Route de Saclay F-91128 Palaiseau France Oak Ridge National Laboratory Oak Ridge Tennessee 37831 USA Physics Department IHEP Protvino State Research Center of Russian Federation Institute for High Energy Physics Protvino 142281 Russia Collider-Accelerator Department Florida Institute of Technology Melbourne Florida 32901 USA Dapnia CEA Saclay F-91191 Gif-sur-Yvette France University of California-Riverside Riverside California 92521 USA Los Alamos National Laboratory Los Alamos New Mexico 87545 USA University of New Mexico Albuquerque New Mexico 87131 USA Abilene Christian University Abilene Texas 79699 USA Baruch College City University of New York New York New York 10010 USA PNPI Petersburg Nuclear Physics Institute Gatchina Leningrad region 188300 Russia Institut für

High-momentum two-particle correlations are a useful tool for studying jet-quenching effects in the quark-gluon plasma. Angular correlations between neutral-pion triggers and charged hadrons with transverse momenta in the range 4–12 GeV/c and 0.5–7 GeV/c, respectively, have been measured by the PHENIX experiment in 2014 for Au+Au collisions at sNN=200 GeV. Suppression is observed in the yield of high-momentum jet fragments opposite the trigger particle, which indicates jet suppression stemming from in-medium partonic energy loss, while enhancement is observed for low-momentum particles. The ratio and differences between the yield in Au+Au collisions and p+p collisions, IAA and ΔAA, as a function of the trigger-hadron azimuthal separation, Δϕ, are measured for the first time at the BNL Relativistic Heavy Ion Collider. These results better quantify how the yield of low-pT associated hadrons is enhanced at wide angle, which is crucial for studying energy loss as well as medium-response effects.

关键词： Particle correlations & fluctuations Relativistic heavy-ion collisions Hadrons Pions Hadron colliders

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A Small-Molecule Drug for the Self-Checking of Mitophagy

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Angewandte Chemie 2025年第10期137卷

作者： Ms. Yanan Gao Mr. Qingjie Bai Ms. Youxiao Ren Dr. Xintian Shao Mr. Mengrui Zhang Dr. Luling Wu Prof. Simon E. Lewis Prof. Tony D. James Prof. Xiaoyuan Chen Prof. Qixin Chen State Key Laboratory of Advanced Drug Delivery and Release Systems School of Pharmaceutical Sciences Neck-Shoulder and Lumbocrural Pain Hospital Medical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong 250117 PR China Department of Chemistry University of Bath Bath BA2 7AY U.K. School of Chemistry and Chemical Engineering Henan Normal University Xinxiang 453007 People's Republic of China Departments of Diagnostic Radiology Chemical and Biomolecular Engineering and Biomedical Engineering Yong Loo Lin School of Medicine and College of Design and Engineering National University of Singapore Singapore 119074 Singapore Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore Nanomedicine Translational Research Program Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore Theranostics Center of Excellence (TCE) Yong Loo Lin School of Medicine National University of Singapore 11 Biopolis Way Helios Singapore 138667 Institute of Molecular and Cell Biology Agency for Science Technology and Research (A*STAR) 61 Biopolis Drive Proteos Singapore 138673 Singapore Department of Pharmacy and Pharmaceutical Sciences National University of Singapore Lower Kent Ridge Road 4 Science Drive 2 117544 Singapore

Mitophagy, particularly in the context of drugs that disrupt mitochondrial membrane potential (MMP), represents a critical focus in pharmacology. However, the discovery and evaluation of MMP-disrupting drugs are often hampered using commercially available marker molecules that target similar or identical zones. These markers can significantly interfere with, obscure, or amplify the functional effects of MMP-targeting drugs, frequently leading to clinical failures. In response to this challenge, we propose a “one-two punch” drug design strategy that integrates both target-zone drug functionality and non-target zone biological reporting within a single small-molecule drug. We have developed a novel proof-of-concept mitophagy self-check drug ( MitoSC ) that exhibits dual-color and dual-localization properties. The functional component of this system is a variable MitoSC that disrupts mitochondrial membrane potential (MMP) homeostasis, thereby inducing mitophagy. Upon activation, this component transforms into a blue-fluorescent monomer ( MitoSC-fun ) specifically within the mitochondrial target zone. Concurrently, the biological reporting component is represented by a red-fluorescent monomer ( MitoSC-rep ) that localizes to lysosomes, the non-target zone. As mitophagy progresses, the fluorescent signals from MitoSC-rep (lysosomes) and MitoSC-fun (mitochondria) converge, enabling real-time monitoring of the mitophagic process. This strategy combines potent drug functionality with robust biological reporting, thereby minimizing interference and eliminating the complexities associated with external detection. Our findings underscore the potential of a single-molecule drug to exert target-zone specific actions while simultaneously providing non-target zone self-checking, offering a new perspective for drug design.

关键词： Mitochondria Lysosomes Subcellular dynamics Dual localization Self-checking drug

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Synergistic Glutathione Depletion and STING Activation to Potentiate Dendritic Cell Maturation and Cancer Vaccine Efficacy

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Angewandte Chemie 2024年第10期136卷

作者： Dr. Jianping Liu Dr. Ye Zhang Bowei Yang Dr. Yingbo Jia Prof. Rui-Tian Liu Dr. Lingwen Ding Prof. Zheyu Shen Prof. Xiaoyuan Chen Departments of Diagnostic Radiology Surgery Chemical and Biomolecular Engineering and Biomedical Engineering Yong Loo Lin School of Medicine and College of Design and Engineering National University of Singapore Singapore 119074 Singapore Nanomedicine Translational Research Program Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore School of Biomedical Engineering Southern Medical of University Guangzhou Guangdong 510515 P. R. China CAS Key Laboratory of Nano-Bio Interface Suzhou Institute of Nano-Tech and Nano-Bionics Chinese Academy of Sciences Suzhou Jiangsu 215123 P. R. China State Key Laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences Beijing 100190 P. R. China Department of Pathology Yong Loo Lin School of Medicine National University of Singapore Singapore 119074 Singapore Clinical Imaging Research Center Center for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore Institute of Molecular and Cell Biology Agency for Science Technology and Research (A*STAR) 61 Biopolis Drive Proteos Singapore 138673 Singapore

Dendritic cell (DC) maturation and antigen presentation are key factors for successful vaccine-based cancer immunotherapy. This study developed manganese-based layered double hydroxide (Mn-LDH) nanoparticles as a self-adjuvanted vaccine carrier that not only promoted DC maturation through synergistically depleting endogenous glutathione (GSH) and activating STING signaling pathway, but also facilitated the delivery of model antigen ovalbumin (OVA) into lymph nodes and subsequent antigen presentation in DCs. Significant therapeutic-prophylactic efficacy of the OVA-loaded Mn-LDH (OVA/Mn-LDH) nanovaccine was determined by the tumor growth inhibition in the mice bearing B16-OVA tumor. Our results showed that the OVA/Mn-LDH nanoparticles could be a potent delivery system for cancer vaccine development without the need of adjuvant. Therefore, the combination of GSH exhaustion and STING pathway activation might be an advisable approach for promoting DC maturation and antigen presentation, finally improving cancer vaccine efficacy.

关键词： Antigen Delivery DC Maturation GSH Depletion ROS Upregulation STING Activation

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Fungal diversity notes 1512–1610: taxonomic and phylogenetic contributions on genera and species of fungal taxa

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Fungal Diversity 2022年第6期117卷 1-272页

作者： Ruvishika S.Jayawardena Kevin D.Hyde Song Wang Ya‑Ru Sun Nakarin Suwannarach Phongeun Sysouphanthong Mohamed A.Abdel‑Wahab Faten A.Abdel‑Aziz Pranami D.Abeywickrama Vanessa P.Abreu Alireza Armand AndréAptroot Dan‑Feng Bao Dominik Begerow Jean‑Michel Bellanger Jadson D.P.Bezerra Digvijayini Bundhun Mark S.Calabon Ting Cao Taimy Cantillo João LVRCarvalho Napalai Chaiwan Che‑Chih Chen Régis Courtecuisse Bao‑Kai Cui Ulrike Damm Cvetomir M.Denchev Teodor T.Denchev Chun Y.Deng Bandarupalli Devadatha Nimali Ide Silva Lidiane Ados Santos Nawal K.Dubey Sylvain Dumez Himashi SFerdinandez André L.Firmino Yusufon Gaforov Achala J.Gajanayake Deecksha Gomdola Sugantha Gunaseelan Shucheng‑He Zin H.Htet Malarvizhi Kaliyaperumal Martin Kemler Kezhocuyi Kezo Nuwan DKularathnage Marco Leonardi Ji‑Peng Li Chunfang Liao Shun Liu Michael Loizides Thatsanee Luangharn Jian Ma Hugo Madrid S.Mahadevakumar Sajeewa S.N.Maharachchikumbura Dimuthu S.Manamgoda María P.Martín Niranjan Mekala Pierre‑Arthur Moreau Yan‑Hong Mu Pasouvang Pahoua Dhandevi Pem Olinto L.Pereira Wiphawanee Phonrob Chayanard Phukhamsakda Mubashar Raza Guang‑Cong Ren Andrea C.Rinaldi Walter Rossi Binu C.Samarakoon Milan CSamarakoon Vemuri V.Sarma Indunil C.Senanayake Archana Singh Maria F.Souza Cristina M.Souza‑Motta Adriano A.Spielmann Wenxin Su Xia Tang XingGuo Tian Kasun M.Thambugala Naritsada Thongklang Danushka S.Tennakoon Nopparat Wannathes DingPeng Wei Stéphane Welti Subodini N.Wijesinghe Hongde Yang Yunhui Yang Hai‑Sheng Yuan Huang Zhang Jingyi Zhang Abhaya Balasuriya Chitrabhanu SBhunjun Timur S.Bulgakov Lei Cai Erio Camporesi Putarak Chomnunti Y.S.Deepika Mingkwan Doilom Wei‑Jun Duan Shi‑Ling Han Naruemon Huanraluek EBGareth Jones NLakshmidevi Yu Li Saisamorn Lumyong Zong‑Long Luo Surapong Khuna Jaturong Kumla Ishara S.Manawasinghe Ausana Mapook Wilawan Punyaboon Saowaluck Tibpromma Yong‑Zhong Lu JiYe Yan Yong Wang Center of Excellence in Fungal Research Mae Fah Luang UniversityChiang Rai 57100Thailand School of Science Mae Fah Luang UniversityChiang Rai 57100Thailand Innovative Institute for Plant Health Zhongkai University of Agriculture and EngineeringGuangzhou 510225P.R.China Department of Plant Pathology College of AgricultureGuizhou UniversityGuiyang 550025GuizhouChina Research Center of Microbial Diversity and Sustainable Utilization Chiang Mai UniversityChiang Mai 50200Thailand Department of Biology Faculty of ScienceChiang Mai UniversityChiang Mai 50200Thailand Biotechnology and Ecology Institute Ministry of Agriculture and ForestryP.O.Box:811Vientiane CapitalLao PDR Department of Botany and Microbiology Faculty of ScienceSohag UniversitySohag 82524Egypt Beijing Key Laboratory of Environment-Friendly Management on Fruit Diseases and Pests in North China Institute of Plant ProtectionBeijing Academy of Agriculture and Forestry SciencesBeijing 100097China Departamento de Fitopatologia Universidade Federal de ViçosaViçosaMinas GeraisBrazil Laboratório de Botânica/Liquenologia Instituto de BiociênciasUniversidade Federal de Mato Grosso do SulAvenida Costa e Silva S/NBairro UniversitárioCampo GrandeMato Grosso do Sul CEP 79070-900Brazil College of Agriculture and Biological Sciences Dali UniversityDali 671003YunnanChina Department of Entomology and Plant Pathology Faculty of AgricultureChiang Mai UniversityChiang Mai 50200Thailand Institute of Plant Science and Microbiology Universität HamburgOrganismic Botany and MycologyOhnhorststr.1822609 HamburgGermany CEFE CNRSUniv.MontpellierEPHEIRDINSERM1919Route de Mende34293 Montpellier Cedex 5France Setor de Micologia Departamento de Biociências e TecnologiaInstituto de Patologia Tropical e Saúde PúblicaUniversidade Federal de GoiásRua 235S/NSetor UniversitárioGoiâniaGO CEP:74605-050Brazil Division of Biological Sciences College of Arts and SciencesUniversity of the Philippines Visayas5023 MiagaoIloiloPhilippines CA

This article is the 14th in the Fungal Diversity Notes series,wherein we report 98 taxa distributed in two phyla,seven classes,26 orders and 50 families which are described and *** in this study were collected from Australia,Brazil,Burkina Faso,Chile,China,Cyprus,Egypt,France,French Guiana,India,Indonesia,Italy,Laos,Mexico,Russia,Sri Lanka,Thailand,and *** are 59 new taxa,39 new hosts and new geographical distributions with one new *** 59 new species comprise Angustimassarina kunmingense,Asterina lopi,Asterina brigadeirensis,Bartalinia bidenticola,Bartalinia caryotae,Buellia pruinocalcarea,Coltricia insularis,Colletotrichum fexuosum,Colletotrichum thasutense,Coniochaeta caraganae,Coniothyrium yuccicola,Dematipyriforma aquatic,Dematipyriforma globispora,Dematipyriforma nilotica,Distoseptispora bambusicola,Fulvifomes jawadhuvensis,Fulvifomes malaiyanurensis,Fulvifomes thiruvannamalaiensis,Fusarium purpurea,Gerronema atrovirens,Gerronema favum,Gerronema keralense,Gerronema kuruvense,Grammothele taiwanensis,Hongkongmyces changchunensis,Hypoxylon inaequale,Kirschsteiniothelia acutisporum,Kirschsteiniothelia crustaceum,Kirschsteiniothelia extensum,Kirschsteiniothelia septemseptatum,Kirschsteiniothelia spatiosum,Lecanora immersocalcarea,Lepiota subthailandica,Lindgomyces guizhouensis,Marthe asmius pallidoaurantiacus,Marasmius tangerinus,Neovaginatispora mangiferae,Pararamichloridium aquisubtropicum,Pestalotiopsis piraubensis,Phacidium chinaum,Phaeoisaria goiasensis,Phaeoseptum thailandicum,Pleurothecium aquisubtropicum,Pseudocercospora vernoniae,Pyrenophora verruculosa,Rhachomyces cruralis,Rhachomyces hyperommae,Rhachomyces magrinii,Rhachomyces platyprosophi,Rhizomarasmius cunninghamietorum,Skeletocutis cangshanensis,Skeletocutis subchrysella,Sporisorium anadelphiae-leptocomae,Tetraploa dashaoensis,Tomentella exiguelata,Tomentella fuscoaraneosa,Tricholomopsis lechatii,Vaginatispora favispora and Wetmoreana *** new combin

关键词： 59 New taxa 39 New records Ascomycota Basidiomycota Dothideomycetes Lecanoromycetes Leotiomycetes Sordariomycetes Ustilaginomycotina

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An experimental study on the turbulent flow over two-dimensional plateaus

An experimental study on the turbulent flow over two-dimensi...

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Wind Energy Symposium, 2018

作者： Zheng, Kuan Tian, Wei Qin, Jiang Hu, Hui School of Aeronautics and Astronautics Shanghai Jiao Tong University Shanghai200240 China School of Energy Science and Engineering Harbin Institute of Technology Harbin150001 China Department of Aerospace Engineering Iowa State University AmesIA50010 United States

ISBN: (数字)9781624105227

ISBN: (纸本)9781624105227

Turbulent wind flow over complex terrain is very important for wind energy exploitation. In the present study, the flow characteristics over two-dimensional plateaus were studied in atmospheric boundary layer (ABL) wind tunnel through PIV measurements. The effects of windward and leeward slopes on turbulent flow characteristics were studied. The results indicates that the flow velocity decreases upstream of the windward side compared with the undisturbed flow, as the block effect of plateau. A flow separation takes place as the slope is steep, and the effect is far downstream of the plateau. The effects of slopes and steps are not evident, with the main difference occurring near the ground. © 2018 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.

关键词： Flow separation

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Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure

Extracellular vesicle

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Extracellular vesicle 2022年 1卷 100013页

作者： Hyun-Ji Park John M Kelly Jessica R Hoffman Felipe Takaesu William Schwartzman Anudari Ulziibayar Takahiro Kitsuka Eric Heuer Asigul Yimit Raphael Malbrue Cole Anderson Adrienne Morrison Aymen Naguib Christopher Mckee Andrew Harrison Brian Boe Aimee Armstrong Arash Salavitabar Andrew Yates Toshiharu Shinoka Sergio Carrillo Christopher K Breuer Michael E Davis Wallace H. Coulter Department of Biomedical Engineering Emory University School of Medicine & Georgia Institute of Technology Atlanta GA USA. Department of Molecular Science and Technology Ajou University Republic of Korea. Center for Regenerative Medicine Abigail Wexner Research Institute at Nationwide Children's Hospital Columbus OH USA. The Heart Center Nationwide Children's Hospital Columbus OH USA. Department of Pediatrics The Ohio State University College of Medicine Columbus OH USA. Molecular & Systems Pharmacology Graduate Training Program Graduate Division of Biological & Biomedical Sciences Laney Graduate School Emory University Atlanta GA USA. The Ohio State University College of Medicine Columbus OH USA. The Ohio State University College of Veterinary Medicine Columbus OH USA. Biomedical Engineering Graduate Program The Ohio State University Columbus OH USA. Department of Surgery The Ohio State University Wexner Medical Center Columbus OH USA. Department of Surgery Nationwide Children's Hospital Columbus OH USA. Children's Heart Research & Outcomes (HeRO) Center Children's Healthcare of Atlanta & Emory University Atlanta GA USA.

Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.

关键词： Extracellular vesicle Fontan model Hemodynamics MiRNA RNA sequencing

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