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Clinical response to azacitidine in MDS is associated with distinct DNA methylation changes in HSPCs

Nature Communications 2025年第1期16卷 1-20页

作者： Thoms, Julie A. I. Yan, Feng Hampton, Henry R. Davidson, Sarah Joshi, Swapna Saw, Jesslyn Sarowar, Chowdhury H. Lim, Xin Ying Nunez, Andrea C. Kakadia, Purvi M. Bhuyan, Golam Sarower Zou, Xiaoheng Nguyen, Mary Ghodousi, Elaheh S. Koch, Forrest C. Vafaee, Fatemeh Thompson, I. Richard Karimi, Mohammad M. Pickford, Russell Raftery, Mark J. Hough, Sally Buckland, Griselda Bailey, Michelle Ghodke, Yuvaraj Absar, Noorul Vaughan, Lachlin Pasalic, Leonardo Fong, Chun Y. Kenealy, Melita Hiwase, Devendra K. Stoddart, Rohanna I. Mohammed, Soma Lee, Linda Passam, Freda H. Larsen, Stephen R. Spring, Kevin J. Skarratt, Kristen K. Rebeiro, Patricia Presgrave, Peter Stevenson, William S. Ling, Silvia Tiley, Campbell Fuller, Stephen J. Roncolato, Fernando Enjeti, Anoop K. Hoenemann, Dirk Lemech, Charlotte Jolly, Christopher J. Bohlander, Stefan K. Curtis, David J. Wong, Jason W. H. Unnikrishnan, Ashwin Hertzberg, Mark Olivier, Jake Polizzotto, Mark N. Pimanda, John E. School of Biomedical Sciences University of New South Wales Sydney NSW Australia Bioinformatics Division Walter and Eliza Hall Institute of Medical Research Parkville VIC Australia ANU Clinical Hub for Interventional Research (CHOIR) John Curtin School of Medical Research Canberra ACT Australia Kirby Institute University of New South Wales Sydney NSW Australia School of Clinical Medicine University of New South Wales Sydney NSW Australia Australian Centre for Blood Diseases Monash University Melbourne VIC Australia Leukaemia & Blood Cancer Research Unit Department of Molecular Medicine and Pathology Faculty of Medical and Health Sciences The University of Auckland Auckland New Zealand School of Biotechnology and Biomolecular Sciences University of New South Wales Sydney NSW Australia UNSW Data Science Hub University of New South Wales Sydney NSW Australia Comprehensive Cancer Centre School of Cancer and Pharmaceutical Sciences King’s College London London United Kingdom Bioanalytical Mass Spectrometry Facility University of New South Wales Sydney NSW Australia Westmead Hospital Sydney NSW Australia ICPMR Department of Haematology Westmead Hospital Sydney NSW Australia Department of Haematology Austin Health Melbourne VIC Australia Cabrini Hospital Melbourne VIC Australia Department of Haematology Royal Adelaide Hospital Adelaide SA Australia University of New South Wales Sydney NSW Australia Royal North Shore Hospital Sydney NSW Australia Haematology Research Group Heart Research Institute Sydney NSW Australia Institute of Haematology Royal Prince Alfred Hospital Sydney NSW Australia Medical Oncology Group Liverpool Clinical School School of Medicine Western Sydney University and Ingham Institute for Applied Medical Research Liverpool NSW Australia South-West Sydney Clinical Campuses UNSW Medicine & Health Sydney NSW Australia Sydney Medical School Nepean Clinical School Faculty of Medicine and Health University of Sydney

Hypomethylating agents are frontline therapies for myelodysplastic neoplasms (MDS), yet clinical responses remain unpredictable. We conducted a phase 2 trial comparing injectable and oral azacitidine (AZA) administered over one or three weeks per four-week cycle, with the primary objective of investigating whether response is linked to in vivo drug incorporation or DNA hypomethylation. Our findings show that injection results in higher drug incorporation, but lower DNA demethylation per cycle, while global DNA methylation levels in mononuclear cells are comparable between responders and non-responders. However, hematopoietic stem and progenitor cells (HSPCs) from responders exhibit distinct baseline and early treatment-induced CpG methylation changes at regulatory regions linked to tissue patterning, cell migration, and myeloid differentiation. By cycle six—when clinical responses typically emerge—further differential hypomethylation in responder HSPCs suggests marrow adaptation as a driver of improved hematopoiesis. These findings indicate that intrinsic baseline and early drug-induced epigenetic differences in HSPCs may underlie the variable clinical response to AZA in MDS. © The Author(s) 2025.

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Genomic basis for RNA alterations in cancer (vol 578, pg 129, 2020)

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NATURE 2023年第7948期614卷 E37-E37页

作者： Calabrese, Claudia Davidson, Natalie R. Demircioglu, Deniz Fonseca, Nuno A. He, Yao Lehmann, Kjong-Van Liu, Fenglin Shiraishi, Yuichi Soulette, Cameron M. Urban, Lara Greger, Liliana Li, Siliang Liu, Dongbing Perry, Marc D. Xiang, Qian Zhang, Fan Zhang, Junjun Bailey, Peter Erkek, Serap Hoadley, Katherine A. Hou, Yong Huska, Matthew R. Kilpinen, Helena Korbel, Jan O. Marin, Maximillian G. Markowski, Julia Nandi, Tannistha Pan-Hammarstrom, Qiang Pedamallu, Chandra Sekhar Siebert, Reiner Stark, Stefan G. Su, Hong Tan, Patrick Waszak, Sebastian M. Yung, Christina Zhu, Shida Awadalla, Philip Creighton, Chad J. Meyerson, Matthew Ouellette, B. F. Francis Wu, Kui Yang, Huanming Brazma, Alvis Brooks, Angela N. Goke, Jonathan Ratsch, Gunnar Schwarz, Roland F. Stegle, Oliver Zhang, Zemin European Molecular Biology Laboratory European Bioinformatics Institute Hinxton UK European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Cambridge UK Genome Biology Unit European Molecular Biology Laboratory (EMBL) Heidelberg Germany CIBIO/InBIO - Research Center in Biodiversity and Genetic Resources Universidade do Porto Vairão Portugal Berlin Institute for Medical Systems Biology Max Delbruck Center for Molecular Medicine Berlin Germany German Cancer Consortium (DKTK) partner site Berlin Germany German Cancer Research Center (DKFZ) Heidelberg Germany Berlin Institute for Medical Systems Biology Max Delbrück Center for Molecular Medicine Berlin Germany German Cancer Consortium (DKTK) Partner site Berlin Berlin Germany European Molecular Biology Laboratory Genome Biology Unit Heidelberg Germany Division of Computational Genomics and Systems Genetics German Cancer Research Center (DKFZ) Heidelberg Germany ETH Zurich Zurich Switzerland Memorial Sloan Kettering Cancer Center New York NY USA Weill Cornell Medical College New York NY USA SIB Swiss Institute of Bioinformatics Lausanne Switzerland University Hospital Zurich Zurich Switzerland Computational Biology Center Memorial Sloan Kettering Cancer Center New York NY USA Department of Biology ETH Zurich Zürich Switzerland Department of Computer Science ETH Zurich Zurich Switzerland Korea University Seoul South Korea Computational and Systems Biology Program Memorial Sloan Kettering Cancer Center New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine New York NY USA National University of Singapore Singapore Singapore Genome Institute of Singapore Singapore Singapore Computational and Systems Biology Genome Institute of Singap

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Global Taxonomic, Functional, and Phylogenetic Biogeography of Bees in Apple Orchards

SSRN

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SSRN 2023年

作者： Leclercq, N. Marshall, L. Weekers, T. Basu, P. Benda, D. Bevk, D. Bhattacharya, R. Bogusch, P. Bontšutšnaja, A. Bortolotti, L. Cabirol, N. Calderón-Uraga, E. Carvalho, R. Castro, S. Chatterjee, S. De La Cruz Alquicira, M. de Miranda, J.R. Dirilgen, T. Dorchin, A. Dorji, K. Drepper, B. Flaminio, S. Gailis, J. Galloni, M. Gaspar, H. Gikungu, M.W. Hatteland, B.A. Hinojosa-Diaz, A. Hostinská, L. Howlett, B.G. Hung, K.-L.J. Hutchinson, L. Jesus, R.O. Karklina, N. Khan, M.S. Loureiro, J. Men, X. Molenberg, J.-M. Mudri-Stojnić, S. Nikolic, P. Normandin, E. Osterman, J. Ouyang, F. Oygarden, A.S. Ozolina-Pole, L. Ozols, N. Saldivar, Parra A. Paxton, R.J. Pitts-Singer, T. Poveda, K. Prendergast, K. Quaranta, M. Read, S.F.J. Reinhardt, S. Rojas-Oropeza, M. Ruiz, C. Rundlöf, M. Sade, A. Sandberg, C. Sgolastra, F. Shah, S.F. Shebl, M.A. Soon, V. Stanley, D.A. Straka, J. Theodorou, P. Tobajas, E. Vaca-Uribe, J.L. Vera, A. Villagra, C. Williams, M.-K. Wolowski, M. Wood, T.J. Yan, Z. Zhang, Q. Vereecken, N.J. Boulevard du Triomphe CP 264/02 BrusselsB-1050 Belgium Naturalis Biodiversity Center Darwinweg 2 Leiden2333 CR Netherlands Centre for Pollination Studies University of Calcutta Kolkata India Department of Zoology Faculty of Science Charles University Prague Czech Republic Department of Entomology National Museum Prague Czech Republic Department of Organisms and Ecosystems Research National Institute of Biology Ljubljana Slovenia Department of Biology Faculty of Science University of Hradec Králové Hradec Králové Czech Republic Institute of Agricultural and Environmental Sciences Estonian University of Life Sciences Tartu Estonia CREA Research Centre for Agriculture and Environment Bologna Italy Departamento de Ecología y Recursos Naturales Facultad de Ciencias UNAM México City Mexico Centre for Functional Ecology Department of Life Sciences University of Coimbra Coimbra Portugal Department of Ecology Swedish University of Agricultural Sciences Uppsala750 05 Sweden School of Agriculture and Food Science and Earth Institute University College Dublin BelfieldDublin 4 Ireland Laboratory of Zoology Université de Mons Mons Belgium The Steinhardt Museum of Natural History Tel Aviv University Tel Aviv69978 Israel Department of Entomology Royal Museum for Central Africa Tervuren Belgium College of Natural Resources Royal University of Bhutan Bhutan Punakha Bhutan Division of Forest Nature and Landscape University of Leuven Leuven Belgium Institute for Plant Protection Research Agrihorts Latvia University of Life Sciences and Technologies Jelgava Latvia Department of Biological Geological and Environmental Sciences University of Bologna Bologna Italy Department of Zoology National Museums of Kenya Nairobi Kenya Division for Biotechnology and Plant Health Norwegian Institute of Bioeconomy Research Aas Norway Department of Biological Sciences University of Bergen Bergen Norway Departamento de Zoología Instituto de Biología UNAM México City

An essential prerequisite to safeguard pollinator species is characterisation of the multifaceted diversity of crop pollinators, and identification of the drivers of pollinator community changes across biogeographical gradients. The extent to which intensive agriculture is associated with the homogenisation of biological communities at large spatial scales remains poorly understood. In this study, we investigated the relationships between different drivers of bee diversity for 644 species/morphospecies in 177 commercial apple orchards across 33 countries and four global biogeographic zones. We provide evidence for a significant community-level taxonomic dissimilarity between zones, driven by biogeography. Despite taxonomic dissimilarity, species across zones belong to similar higher-level phylogenetic groups with similar combinations of ecological and behavioural traits (i.e. functional traits). This phylogenetic and functional clustering is likely due to habitat filtering caused by a perennial monoculture system managed intensively for crop production. Bee communities visiting apple orchards were largely dominated by honey bee species, while other managed/manageable and wild species were collected in lower numbers. Overall, our study sheds light on the importance of large-scale analyses contributing to the emerging fields of functional and phylogenetic biogeography, which can be related to ecosystem function to promote biodiversity as a key asset in agroecosystems in the face of global change pressures. © 2023, The Authors. All rights reserved.

关键词： Phylogenetic

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Effect of extraction time and Na2CO3 concentration on the characteristics of alginate extracted from sargassum sp. 3

Effect of extraction time and Na2CO3 concentration on the ch...

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3rd International Conference on Biomass: Accelerating the Technical development and Commercialization for Sustainable Bio-Based Products and Energy, ICB 2018

作者： Hambali, Erliza Wibawa Sakti, Satya Chandra Fahmi, Mochamad Zakki Wahyudianto, Febri Eko Nuryono Yessi, P. Yani, Mohamad Sinurat, Ellya Pratama, Borneo Satria Surfactant and Bioenergy Research Centre IPB Baranangsiang Bogor Indonesia Departement of Agroindustrial Technology Institut Pertanian Bogor Indonesia Department of Chemistry Faculty of Science and Technology Universitas Airlangga Mulyorejo Surabaya Indonesia Environmental Science and Technology Study Program Department of Biology Faculty of Science and Technology Universitas Airlangga Mulyorejo Surabaya Indonesia Department of Chemistry Faculty of Mathematics and Natural Sciences Universitas Gadjah Mada Sekip Utara Yogyakarta Indonesia Inorganic and Physical Chemistry Research Division Institut Teknologi Bandung Jl. Ganesha 10 Bandung40132 Indonesia Research and Development Center for Marine and Fisheries Product Processing and Biotechnology Jakarta Indonesia Master Program of Agroindustrial Technology Faculty of Agricultural Technology Institut Pertanian Bogor Indonesia

Alginate is a polysaccharide extracted from cell walls and intracellular matrix of brown seaweed, and has been widely used for industrial purpose due to gelling capabilities in the presence of divalent cations. However, the characteristics of alginate extracted are depend on alginate gel strength and viscosity. The objective of this research was to investigate the effect of extraction time and Na2CO3 concentration on the characteristics of alginates extracted from Sargassum sp. by acid method. Alginate extractions were conducted by varying the extraction time for 1.5, 2.0 and 2.5 hours;and varying the Na2CO3 concentration of 1, 2 and 3 %. The characteristics observed are alginate yield, viscosity, pH, and water content. The alginates extracted using various Na2CO3 concentration and extraction time resulted alginates with low, medium and high viscosity. Furthermore, the yield, pH and water content of alginates extracted in this research had fulfilled the standard of Food Chemical Codex. © 2018 Published under licence by IOP Publishing Ltd.

关键词： Sodium compounds

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Sub1A gene screening for submergence stress in Indonesian local rice varieties

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AIP Conference Proceedings 2020年第1期2260卷

作者： Elhah Nailul Khasna I. Kade Karisma Gita Ardana ‘Ainun Sayyidah Zakiyah Choirun Nita Fikriani Nina Bunga Anggraini Dwi Listyorini 2Biotechnology Division Central Laboratory of Mineral and advanced Material Faculty of Mathematics and Natural Sciences Universitas Negeri Malang Jl Semarang 5 Malang 65145 Indonesia 1Department of Biology Faculty of Mathematics and Natural Sciences Universitas Negeri Malang Jl Semarang 5 Malang 65145 Indonesia 3PUIPT Disruptive Learning Innovation Universitas Negeri Malang Jl Semarang 5 Malang 65145 Indonesia 4Biotechnology Research Consortium 4in1Islamic Development Bank (IsDB)Program Indonesia

Indonesia is a country which has a different altitude within the landscape. Indonesian lowland altitude is fewer than 200 MASL which in turn makes those places prone to flooding. This problem becomes a scourge for rice farmers; therefore, it is urged to take action to maintain food security in Indonesia. Indonesia has many local rice varieties. Based on their morphological and anatomical studies, some of those varieties predicted to have some capability stand over inundations. Submergence-1A (Sub1A) has been reported to be responsible for inundation tolerance. The expression of the Sub1A gene let the rice to survive up to 14 days under inundation stress. The purpose of this study was to look up the presence of the Sub1A gene in Indonesian local rice varieties to find inundation tolerant rice variety. Sub1A gene amplified using PCR with gene-specific primers followed by electrophoresis on 1% agarose. The result of this study has found the Sub1A gene in some rice varieties proved by the presence of specific DNA fragment band.

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GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

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Nature genetics 2023年第9期55卷 1471-1482页

作者： Remi Stevelink Dorothee Kasteleijn-Nolst Trenite Bobby P. C. Koeleman Dick Lindhout Anja C. M. Sonsma Ciarán Campbell Gianpiero L. Cavalleri Norman Delanty Hany El-Naggar Austin Lacey Peter Widdess-Walsh Colin P. Doherty Siwei Chen Claire Churchhouse Mark J. Daly Yen-Chen A. Feng Daniel P. Howrigan Mitja I. Kurki Benjamin M. Neale Aarno Palotie Wei Zhou Namrata Gupta Henrike O. Heyne Bassel Abou-Khalil Kevin F. Haas R. S. Taneja Oluyomi M. Adesoji Michael Nothnagel Peter Nürnberg Thomas Sander Zaid Afawi Ilan Blatt Amos D. Korczyn Elisabetta Amadori Ganna Balagura Antonella Riva Marcello Scala Paolo Scudieri Pasquale Striano Federico Zara Michele Iacomino Francesca Madia Alison Anderson Patrick Kwan Terence J. O’Brien Slavé Petrovski K. Meng Tan Marian Todaro Joseph Anderson Danielle M. Andrade Quratulain Zulfiqar Ali Grazia Annesi Pauls Auce Andreja Avbersek Simona Balestrini Vera Braatz Claudia B. Catarino Krishna Chinthapalli Jennifer Jamnadas-Khoda Dalia Kasperavičiūte Costin Leu Josemir W. Sander Sanjay M. Sisodiya Sara Zagaglia Melanie Bahlo Karen L. Oliver Mark D. Baker Beata Fonferko-Shadrach William O. Pickrell Carmen Barba Claudia Bianchini Viola Doccini Renzo Guerrini Davide Mei Martino Montomoli Elena Parrini Annalisa Vetro Karen Barboza Fabrice Bartolomei Thomas Bast Bernhard J. Steinhoff Larry Baum Stacey S. Cherny Pak Sham Tobias Baumgartner Christian E. Elger Kerstin Hallmann Wolfram S. Kunz Rainer Surges Randi von Wrede Gábor Zsurka Betül Baykan Nerses Bebek Yeşim Kesim Albert J. Becker Susanne Schoch Felicitas Becker Caitlin A. Bennett Samuel F. Berkovic Stephanie L. Leech Brigid M. Regan Ingrid E. Scheffer Bianca Berghuis Ahmad Beydoun Wassim Nasreddine Francesca Bisulli Lidia Di Vito Lorenzo Ferri Tania Giangregorio Laura Licchetta Raffaella Minardi Barbara Mostacci Carlotta Stipa Paolo Tinuper Lorenzo Muccioli Federica Pondrelli Dheeraj R. Bobbili Emadeldin Hassanin Roland Krause Zied Landoulsi Patrick May Ingo Borggraefe Christian Bosselmann Christian Hengsbach Josua Kegele Stephen Lauxmann Department of Genetics University Medical Center Utrecht Utrecht The Netherlands Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands School of Pharmacy and Biomolecular Sciences The Royal College of Surgeons in Ireland Dublin Ireland The FutureNeuro Research Centre Dublin Ireland Department of Neurology Beaumont Hospital Dublin Ireland Department of Neurology St. James’s Hospital Dublin Ireland Analytic and Translational Genetics Unit Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston MA USA Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA Stanley Center for Psychiatric Research Broad Institute of Harvard and M.I.T Cambridge MA USA Institute for Molecular Medicine Finland (FIMM) University of Helsinki Helsinki Finland Psychiatric & Neurodevelopmental Genetics Unit Department of Psychiatry Massachusetts General Hospital and Harvard Medical School Boston MA USA Division of Biostatistics Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei Taiwan Hasso Plattner Institute Digital Health Center University of Potsdam Potsdam Germany Hasso Plattner Institute Mount Sinai School of Medicine New York City NY USA Department of Neurology Vanderbilt University Medical Center Nashville TN USA Cologne Center for Genomics (CCG) University of Cologne Faculty of Medicine and University Hospital Cologne Cologne Germany University Hospital Cologne Cologne Germany Department of Neurology Charité Universitaetsmedizin Berlin Campus Virchow-Clinic Berlin Germany Tel-Aviv University Sackler Faculty of Medicine Ramat Aviv Israel Department of Neurology Sheba Medical Center Ramat Gan Israel Department of Neurosciences Rehabilitation Ophthalmology Genetics Maternal and Child Health University of Genova Genova Italy IRCCS Istituto Giannina Gaslini Genova Italy Department of Medicine University of Melbour

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.

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Identification of plant precursor mirnas using structural robustness and secondary structures features 2017

Identification of plant precursor mirnas using structural ro...

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2017 International Conference on Biomedical Engineering and Bioinformatics, ICBEB 2017

作者： Anuntakarun, Songtham Wattanapornprom, Warin Lertampaiporn, Supatcha Biological Engineering Program Faculty of Engineering King Mongkut’s University of Technology Thonburi Bangkok Thailand Research and Development Unit Thai Ocean Industries Co.Ltd Samutprakarn Thailand Biochemical Engineering and Pilot Plant Research Development Laboratory National Center for Genetic Engineering and Biotechnology Bangkok Thailand

ISBN: (纸本)9781450352970

This work presents an identification tool for plant precursor miRNAs (pre-miRNAs) using structural robustness and derivative features which can improve performance in discriminating the plant pre-miRNAs from pseudo pre-miRNAs. The classification models were trained with plant pre-miRNAs and pseudo hairpins datasets from PlantMiRNAPred web site. The top 20 features were selected from four groups of features including sequence-based features, secondary structure features, base-pair features and a self-containment index score. In particular, the self-containment index score was found to be the highest informative feature among the 20 selected features. Ten-fold cross validation was applied to choose a classifier algorithm with the highest performance being among Support Vector Machine, Random Forest, Decision Tree, Naïve Bayes, K-nearest neighbor, Back-propagation Neural Network, Ripper and RBF network based on the ROC area and accuracy. The results demonstrated that the Random Forest model using 20 selected features achieved 97% accuracy and 94% sensitivity in test sets to discriminating real plant pre-miRNAs from others. © 2017 Association for Computing Machinery.

关键词： Decision trees

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Suppression of the human malic enzyme 2 modifies energy metabolism and inhibits cellular respiration

Communications biology

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Communications biology 2023年第1期6卷 548页

作者： Ju-Yi Hsieh Kun-Chi Chen Chun-Hsiung Wang Guang-Yaw Liu Jie-An Ye Yu-Tung Chou Yi-Chun Lin Cheng-Jhe Lyu Rui-Ying Chang Yi-Liang Liu Yen-Hsien Li Mau-Rong Lee Meng-Chiao Ho Hui-Chih Hung Department of Life Sciences National Chung Hsing University Taichung 402 Taiwan ROC. Ph.D. Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung 402 Taiwan ROC. Institute of Biological Chemistry Academia Sinica Taipei 115 Taiwan ROC. Institute of Medicine College of Medicine Chung Shan Medical University Taichung 402 Taiwan ROC. Instrument Center Office of Research and Development National Chung Hsing University Taichung 40227 Taiwan ROC. Department of Chemistry National Chung Hsing University Taichung 402 Taiwan ROC. Institute of Biological Chemistry Academia Sinica Taipei 115 Taiwan ROC. joeho@gate.sinica.edu.tw. Institute of Biochemical Sciences National Taiwan University Taipei 106 Taiwan ROC. joeho@gate.sinica.edu.tw. Department of Life Sciences National Chung Hsing University Taichung 402 Taiwan ROC. hchung@dragon.nchu.edu.tw. Ph.D. Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung 402 Taiwan ROC. hchung@dragon.nchu.edu.tw. Institute of Genomics and Bioinformatics National Chung Hsing University Taichung 402 Taiwan ROC. hchung@dragon.nchu.edu.tw. Advanced Plant and Food Crop Biotechnology Center National Chung Hsing University Taichung 402 Taiwan ROC. hchung@dragon.nchu.edu.tw.

Human mitochondrial NAD(P)-dependent malic enzyme (ME2) is well-known for its role in cell metabolism, which may be involved in cancer or epilepsy. We present potent ME2 inhibitors based on cyro-EM structures that target ME2 enzyme activity. Two structures of ME2-inhibitor complexes demonstrate that 5,5'-Methylenedisalicylic acid (MDSA) and embonic acid (EA) bind allosterically to ME2's fumarate-binding site. Mutagenesis studies demonstrate that Asn35 and the Gln64-Tyr562 network are required for both inhibitors' binding. ME2 overexpression increases pyruvate and NADH production while decreasing the cell's NAD/NADH ratio; however, ME2 knockdown has the opposite effect. MDSA and EA inhibit pyruvate synthesis and thus increase the NAD/NADH ratio, implying that these two inhibitors interfere with metabolic changes by inhibiting cellular ME2 activity. ME2 silence or inhibiting ME2 activity with MDSA or EA decreases cellular respiration and ATP synthesis. Our findings suggest that ME2 is crucial for mitochondrial pyruvate and energy metabolism, as well as cellular respiration, and that ME2 inhibitors could be useful in the treatment of cancer or other diseases that involve these processes.

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Author Correction: Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids

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Nature medicine 2025年第2期31卷 699页

作者： Mattia Francesco Maria Gerli Giuseppe Calà Max Arran Beesley Beatrice Sina Lucinda Tullie Kylin Yunyan Sun Francesco Panariello Federica Michielin Joseph R Davidson Francesca Maria Russo Brendan C Jones Dani Do Hyang Lee Savvas Savvidis Theodoros Xenakis Ian C Simcock Anna A Straatman-Iwanowska Robert A Hirst Anna L David Christopher O'Callaghan Alessandro Olivo Simon Eaton Stavros P Loukogeorgakis Davide Cacchiarelli Jan Deprest Vivian S W Li Giovanni Giuseppe Giobbe Paolo De Coppi Department of Surgical Biotechnology Division of Surgery and Interventional Science University College London London UK. m.gerli@ucl.ac.uk. Great Ormond Street Institute of Child Health University College London London UK. m.gerli@ucl.ac.uk. Department of Surgical Biotechnology Division of Surgery and Interventional Science University College London London UK. Great Ormond Street Institute of Child Health University College London London UK. Politecnico di Milano Milan Italy. Stem Cell and Cancer Biology Laboratory The Francis Crick Institute London UK. Armenise/Harvard Laboratory of Integrative Genomics Telethon Institute of Genetics and Medicine Pozzuoli Italy. Elizabeth Garrett Anderson Institute for Women's Health University College London London UK. Department of Development and Regeneration Woman and Child and UZ Leuven Clinical Department of Obstetrics and Gynaecology KU Leuven Leuven Belgium. Department of Medical Physics and Biomedical Engineering University College London London UK. Department of Radiology Great Ormond Street Hospital London UK. Department of Respiratory Sciences University of Leicester Leicester UK. Specialist Neonatal and Paediatric Surgery Great Ormond Street Hospital for Children NHS Foundation Trust London UK. Department of Translational Medicine University of Naples Federico II Naples Italy. Genomics and Experimental Medicine Program Scuola Superiore Meridionale Naples Italy. Great Ormond Street Institute of Child Health University College London London UK. p.decoppi@ucl.ac.uk. Department of Development and Regeneration Woman and Child and UZ Leuven Clinical Department of Obstetrics and Gynaecology KU Leuven Leuven Belgium. p.decoppi@ucl.ac.uk. Specialist Neonatal and Paediatric Surgery Great Ormond Street Hospital for Children NHS Foundation Trust London UK. p.decoppi@ucl.ac.uk. Medical and Surgical Department of the Fetus Newborn and Infant Ospedale Pediatrico Bambino Gesù IRCCS Rome Italy. p.decoppi@ucl.ac.uk. NIHR G

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Quality and readability of online information resources on insomnia

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Frontiers of Medicine 2017年第3期11卷 423-431页

作者： Yan Ma Albert C. Yang Ying Duan Ming Dong Albert S. Yeung Division of Interdisciplinary Medicine and Biotechnology Department of Medicine Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 02215 USA Sleep Medicine Center Airforee General Hospital Beijing 100142 China IBM Software Development Lab Littleton MA 01460 USA Depression Clinical and Research Program Massachusetts General Hospital Harvard Medical School Boston MA 02114 USA

The internet is a major source for health information. An increasing number of people, including patients with insomnia, search for remedies online; however, little is known about the quality of such information. This study aimed to evaluate the quality and readability of insomnia-related online information. Google was used as the search engine, and the top websites on insomnia that met the inclusion criteria were evaluated for quality and readability. The analyzed websites belonged to nonprofit, commercial, or academic organizations and institutions such as hospitals and universities. Insomnia-related websites typically included definitions （85%）, causes and risk factors （100%）, symptoms （95%）, and treatment options （90%）. Cognitive behavioral therapy for insomnia （CBT-I） was the most commonly recommended approach for insomnia treatment, and sleep drugs are frequently mentioned. The overall quality of the websites on insomnia is moderate, but all the content exceeded the recommended reading ease levels. Concerns that must be addressed to increase the quality and trustworthiness of online health information include sharing metadata, such as authorship, time of creation and last update, and conflicts of interest; providing evidence for reliability; and increasing the readability for a layman audience.

关键词： insomnia intemet readability information quality health literacy cognitive behavioral therapy treatment

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