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Probabilistic genotype-phenotype maps reveal mutational robustness of RNA folding, spin glasses, and quantum circuits

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Physical Review Research 2025年第1期7卷 013118-013118页

作者： Anna Sappington Vaibhav Mohanty Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard-MIT Program in Health Sciences and Technology Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard/MIT MD-PhD Program Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Department of Chemistry and Chemical Biology Harvard University Cambridge Massachusetts 02138 USA

Recent studies of genotype-phenotype maps have reported universally enhanced phenotypic robustness to genotype mutations, a feature essential to evolution. Virtually all of these studies make a simplifying assumption that each genotype—represented as a sequence—maps deterministically to a single phenotype, such as a discrete structure. Here we introduce probabilistic genotype-phenotype (PrGP) maps, where each genotype maps to a vector of phenotype probabilities, as a more realistic and universal language for investigating robustness in a variety of physical, biological, and computational systems. We study three model systems to show that PrGP maps offer a generalized framework which can handle uncertainty emerging from various physical sources: (1) thermal fluctuation in RNA folding, (2) external field disorder in the spin-glass ground state search problem, and (3) superposition and entanglement in quantum circuits, which are realized experimentally on IBM quantum computers. In all three cases, we observe a biphasic robustness scaling which is enhanced relative to random expectation for more frequent phenotypes and approaches random expectation for less frequent phenotypes. We derive an analytical theory for the behavior of PrGP robustness, and we demonstrate that the theory is highly predictive of empirical robustness.

关键词： Quantum computers

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Incorporating Gender-Neutral Language in IRB Materials: Perceptions of IRB Professionals

Ethics and Human Research

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Ethics and Human Research 2025年第3期47卷 30-39页

作者： Nellis, Kevin L. Lichtman, Ronnie Birnbaum, Jeffrey Friedman, Stanley Zwicklbauer, Elise Executive director of Human Research Protections and Quality Assurance at the Research Foundation for the State University of New York (SUNY) Downstate Health Sciences University (DHSU) United States Midwife and Emeritus at the SUNY DHSU an adjunct at Lehman College of the City University of New York and a member of the SUNY DHSU IRB United States of pediatrics at SUNY DHSU and a principal investigator and executive director of Health & Education Alternatives for Teens (“HEAT”) and a former IRB member United States Retired distinguished teaching of physiology and pharmacology a former SUNY DHSU faculty member a former director of the MD/PhD program and former IRB vice chair United States Medical student at the SUNY DHSU College of Medicine United States

This study investigated the perceptions of institutional review board (IRB) professionals regarding the use of gender-neutral language in IRB guidance and informed consent documents, and whether respondents’ IRBs incorporated gender-neutral language in those documents. A survey was disseminated to a diverse group of IRB professionals whose emails were generated from a list received from the Office for Human Research Protections. Responses indicated substantial endorsement of gender-neutral language, although actual usage remains limited. The findings suggest that while the willingness to adopt inclusive language is high, barriers such as resource limitations and a lack of regulatory guidelines often impede its broader application. This study underscores the importance of developing explicit guidelines and resources to facilitate the adoption of gender-neutral language, enhancing inclusivity in research settings. © 2025 by The Hastings Center. All rights reserved.

关键词： gender-neutral language human research protection program (HRPP) inclusivity in research institutional review boards (IRBs) IRB consent form templates IRB forms IRB guidance language implementation survey study

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Correction to: Environmental consequences of interacting effects of changes in stratospheric ozone, ultraviolet radiation, and climate: UNEP Environmental Effects Assessment Panel, Update 2024 (Photochemical & Photobiological sciences, (2025), 24, 3, (357-392), 10.1007/s43630-025-00687-x)

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Photochemical and Photobiological sciences 2025年第5期24卷 863-865页

作者： Neale, Patrick J. Hylander, Samuel Banaszak, Anastazia T. Häder, Donat-P. Rose, Kevin C. Vione, Davide Wängberg, Sten-Åke Jansen, Marcel A. K. Busquets, Rosa Andersen, Mads P. Sulbæk Madronich, Sasha Hanson, Mark L. Schikowski, Tamara Solomon, Keith R. Sulzberger, Barbara Wallington, Timothy J. Heikkilä, Anu M. Pandey, Krishna K. Andrady, Anthony L. Bruckman, Laura S. White, Christopher C. Zhu, Liping Bernhard, Germar H. Bais, Alkiviadis Aucamp, Pieter J. Chiodo, Gabriel Cordero, Raúl R. Petropavlovskikh, Irina Neale, Rachel E. Olsen, Catherine M. Hales, Simon Lal, Aparna Lingham, Gareth Rhodes, Lesley E. Young, Antony R. Robson, T. Matthew Robinson, Sharon A. Barnes, Paul W. Bornman, Janet F. Harper, Anna B. Lee, Hanna Calderón, Roy Mackenzie Ossola, Rachele Paul, Nigel D. Revell, Laura E. Wang, Qing-Wei Zepp, Richard G. Environmental Research Center Smithsonian Institution EdgewaterMD United States Centre for Ecology and Evolution in Microbial Model Systems Linnaeus University Kalmar Sweden Unidad Académica de Sistemas Arrecifales Universidad Nacional Autónoma de México Puerto Morelos Mexico Erlangen Germany Department of Biological Sciences and Department of Civil and Environmental Engineering Rensselaer Polytechnic Institute TroyNY United States Department of Chemistry University of Turin Turin Italy Department of Marine Sciences University of Gothenburg Gotheburg Sweden School of Biological Earth and Environmental Sciences Environmental Research Institute University College Cork Cork Ireland Chemical and Pharmaceutical Sciences Kingston University London Kingston Upon Thames United Kingdom Civil Environmental & Geomatic Engineering University College London London United Kingdom Department of Chemistry and Biochemistry California State University NorthridgeCA United States Atmospheric Chemistry Observations and Modeling National Center for Atmospheric Research BoulderCO United States USDA UV-B Monitoring and Research Program Colorado State University Fort. CollinsCO United States Department of Environment and Geography University of Manitoba WinnipegMB Canada Working Group Environmental Epidemiology IUF-Leibniz Research Institute for Environmental Medicine Düsseldorf Germany Department of Environment and Health School of Public Health University of Bielefeld Bielefeld Germany School of Environmental Sciences University of Guelph GuelphON Canada Retired From Eawag Swiss Federal Institute of Aquatic Science and Technology Dübendorf Switzerland Center for Sustainable Systems School for Environment and Sustainability University of Michigan Ann ArborMI United States Climate Research Finnish Meteorological Institute Helsinki Finland Indian Academy of Wood Science Bengaluru India Chemical and Biomolecular Engineering North Carolina State University RaleighN

This work is not a product of the U.S. Government or the U.S. Environmental Protection Agency, and the author is not doing this work in any governmental capacity. This research was not performed or funded by EPA and was not subject to EPA’s quality system requirements. The views expressed in this journal article are those of the author(s) and do not necessarily represent the views or the policies of the U.S. Environmental Protection Agency. The original article has been corrected. © The Author(s), under exclusive licence to the European Photochemistry Association, European Society for Photobiology 2025.

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Dural arteriovenous fistula (DAVF) after venous sinus stent (VSS) for presumed idiopathic intracranial hypertension (IIH): A case report and literature review

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Radiology case reports 2025年第1期20卷 817-822页

作者： Fatma Shakarchi Avery Zhou Tuan Anh Nguyen Saif Aldeen Alryalat Osama Al Deyabat Fernando Ahumada Peter Mortensen Orlando Diaz Andrew G Lee Climate Centre International Red Cross Red Crescent Movement Geneva Switzerland. Health and Natural Sciences Space Generation Advisory Council Vienna Austria. University of Nevada Las Vegas School of Medicine Las Vegas NV USA. Tri-Institutional MD-PhD Program Weill Cornell/Rockefeller/Sloan-Kettering New York NY USA. Department of Ophthalmology Houston Methodist Hospital Houston TX USA. Department of Neuroradiology Houston Methodist Hospital Houston TX USA. Departments of Ophthalmology Neurology and Neurosurgery Weill Cornell Medicine New York NY USA. Department of Ophthalmology University of Texas Medical Branch Galveston TX USA. University of Texas MD Anderson Cancer Center Houston TX USA. Texas A&M College of Medicine TX USA. Department of Ophthalmology The University of Iowa Hospitals and Clinics Iowa City IA USA.

Dural arteriovenous fistulas (DAVFs) are rare but significant intracranial vascular malformations that are usually idiopathic and can lead to severe complications like venous hypertension and intracranial hemorrhage. We present 2 cases of DAVF occurring after venous sinus stenting (VSS) for presumed idiopathic intracranial hypertension (IIH) in a 51-year-old and a 52-year-old female. In both patients, Cognard type 1 DAVF was detected by Catheter angiography and successfully obliterated with Onyx™ embolization. These cases suggest that VSS may either unmask pre-existing DAVFs by altering intracranial pressure dynamics or induce new fistula formation by angiogenic factors or stent-induced hemodynamic changes. Clinicians should maintain an index of suspicion for DAVF in patients with persistent symptoms post-VSS and catheter angiography might be needed to detect the DAVFs.

关键词： Case report Dural arteriovenous fistula Idiopathic intracranial hypertension Venous sinus stent

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Changing life expectancy in European countries 1990–2021: a subanalysis of causes and risk factors from the Global Burden of Disease Study 2021

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The Lancet Public health 2025年第3期10卷 e172-e188页

作者： Steel, Nicholas Bauer-Staeb, Clarissa Maria Mercedes Ford, John A. Abbafati, Cristiana Abdalla, Mohammed Altigani Abdelkader, Atef Abdi, Parsa Zuñiga, Roberto Ariel Abeldaño Abiodun, Olugbenga Olusola Abolhassani, Hassan Abu-Gharbieh, Eman Abukhadijah, Hana J. Abu-Zaid, Ahmed Addo, Isaac Yeboah Addolorato, Giovanni Adekanmbi, Victor Adetunji, Juliana Bunmi Adeyeoluwa, Temitayo Esther Agardh, Emilie E. Agyemang-Duah, Williams Ahmad, Danish Ahmed, Ayman Ahmed, Syed Anees Akinosoglou, Karolina Akkaif, Mohammed Ahmed Al Awaidy, Salah Al Hasan, Syed Mahfuz Al Zaabi, Omar Ali Mohammed Aldridge, Robert W. Algammal, Abdelazeem M. Al-Gheethi, Adel Ali Saeed Ali, Abid Ali, Mohammed Usman Ali, Syed Shujait Ali, Waad Alicandro, Gianfranco Alif, Sheikh Mohammad Al-Jumaily, Adel Allebeck, Peter Alrawashdeh, Ahmad Al-Rifai, Rami H. Alsabri, Mohammed A. Alshahrani, Najim Z. Aluh, Deborah Oyine Al-Wardat, Mohammad Al-Zyoud, Walid A. Amiri, Sohrab Anderlini, Deanna Andrei, Catalina Liliana Anil, Abhishek Anvari, Saeid Anyasodor, Anayochukwu Edward Appiah, Seth Christopher Yaw Aquilano, Michele Arabloo, Jalal Arafat, Mosab Areda, Demelash Aremu, Abdulfatai Armani, Keivan Armocida, Benedetta Ärnlöv, Johan Asaduzzaman, Muhammad Astell-Burt, Thomas Aujayeb, Avinash Ausloos, Marcel Azadnajafabad, Sina Aziz, Shahkaar Azzam, Ahmed Y. Babu, Giridhara Rathnaiah Badache, Andreea Corina Badiye, Ashish D. Bahramian, Saeed Baig, Atif Amin Baker, Jennifer L. Bansal, Hansi Bärnighausen, Till Winfried Barone, Mark Thomaz Ugliara Barrow, Amadou Barteit, Sandra Bashir, Shahid Bashiru, Hameed Akande Basso, João Diogo Bastan, Mohammad-Mahdi Basu, Sanjay Batra, Kavita Bauckneht, Matteo Baune, Bernhard T. Beghi, Massimiliano Beiranvand, Maryam Béjot, Yannick Bell, Michelle L. Bello, Olorunjuwon Omolaja Belo, Luis Beloukas, Apostolos Beneke, Alice A. Bettencourt, Paulo J.G. Bhagavathula, Akshaya Srikanth Bhala, Neeraj Bhaskar, Sonu Bisulli, Francesca Bjørge, Tone Bodunrin, Aadam Olalekan Carvajal, Alejandro Botero Bouaoud, Souad Brayne, Carol Brenner, H Department of Primary Care and Public Health University of East Anglia Norwich United Kingdom Office for Health Improvement and Disparities Department of Health and Social Care London United Kingdom Department of Legal and Economic Studies La Sapienza University Rome Italy Rome Italy Hull York Medical School University of Hull Hull United Kingdom Department of Mathematics and Sciences Ajman University Ajman United Arab Emirates Department of Medicine Memorial University St. John's NL Canada Postgraduate Department University of Sierra Sur Miahuatlan de Porfirio Diaz Mexico Yhteiskuntadatatieteen keskus (Centre for Social Data Science) Helsinki Finland Department of Internal Medicine Federal Medical Centre Abuja Nigeria Research Center for Immunodeficiencies Tehran University of Medical Sciences Tehran Iran Department of Medical Biochemistry and Biophysics Karolinska Institutet (Karolinska Institute) Stockholm Sweden Department of Clinical Sciences University of Sharjah Sharjah United Arab Emirates Department of Biopharmaceutics and Clinical Pharmacy University of Jordan Amman Jordan Medical Research Center Hamad Medical Corporation Doha Qatar Department of Biochemistry and Molecular Medicine Alfaisal University Riyadh Saudi Arabia College of Graduate Health Sciences University of Tennessee Memphis TN United States School of Medicine Sydney NSW Australia Centre for Social Research in Health University of New South Wales Sydney NSW Australia Internal Medicine and Alcohol Related Disease Unit Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy Department of Medical and Surgical Sciences Università Cattolica di Roma (Catholic University of Rome) Rome Italy Department of Obstetrics and Gynecology University of Texas Medical Branch Galveston TX United States Department of Biochemistry Osun State University Osogbo Nigeria Department of Pharmacology and Therapeutics University of Medical Sciences Ondo Ondo Nigeria Department of Veteri

Background: Decades of steady improvements in life expectancy in Europe slowed down from around 2011, well before the COVID-19 pandemic, for reasons which remain disputed. We aimed to assess how changes in risk factors and cause-specific death rates in different European countries related to changes in life expectancy in those countries before and during the COVID-19 pandemic. Methods: We used data and methods from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to compare changes in life expectancy at birth, causes of death, and population exposure to risk factors in 16 European Economic Area countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, and Sweden) and the four UK nations (England, Northern Ireland, Scotland, and Wales) for three time periods: 1990–2011, 2011–19, and 2019–21. Changes in life expectancy and causes of death were estimated with an established life expectancy cause-specific decomposition method, and compared with summary exposure values of risk factors for the major causes of death influencing life expectancy. Findings: All countries showed mean annual improvements in life expectancy in both 1990–2011 (overall mean 0·23 years [95% uncertainty interval [UI] 0·23 to 0·24]) and 2011–19 (overall mean 0·15 years [0·13 to 0·16]). The rate of improvement was lower in 2011–19 than in 1990–2011 in all countries except for Norway, where the mean annual increase in life expectancy rose from 0·21 years (95% UI 0·20 to 0·22) in 1990–2011 to 0·23 years (0·21 to 0·26) in 2011–19 (difference of 0·03 years). In other countries, the difference in mean annual improvement between these periods ranged from –0·01 years in Iceland (0·19 years [95% UI 0·16 to 0·21] vs 0·18 years [0·09 to 0·26]), to –0·18 years in England (0·25 years [0·24 to 0·25] vs 0·07 years [0·06 to 0·08]). In 2019–21, there was an overall decrease in mean annual life expectancy a

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Regulatory T cells constrain T cells of shared specificity to enforce tolerance during infection

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Science (New York, N.Y.) 2025年第6740期387卷 eadk3248页

作者： Klawon, David E J Pagane, Nicole Walker, Matthew T. Ganci, Nicole K. Miller, Christine H. Gai, Eric Rodriguez, Donald M. Ryan-Payseur, Bridgett K. Duncombe, Ryan K. Adams, Erin J. Maienschein-Cline, Mark Freitag, Nancy E. Germain, Ronald N. Wong, Harikesh S. Savage, Peter A. Department of Pathology University of Chicago Chicago IL United States Ragon Institute of Mass General MIT and Harvard Cambridge MA United States Program in Computational and Systems Biology Massachusetts Institute of Technology Cambridge MA United States Interdisciplinary Scientist Training Program University of Chicago Chicago IL United States Department of Microbiology and Immunology University of Illinois Chicago Chicago IL United States Department of Biochemistry and Molecular Biology University of Chicago Chicago IL United States Research Informatics Core Research Resources Center University of Illinois Chicago Chicago IL United States Department of Pharmaceutical Sciences University of Illinois Chicago Chicago IL United States Lymphocyte Biology Section Laboratory of Immune System Biology National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD United States Department of Biology Massachusetts Institute of Technology Cambridge MA United States

During infections, CD4+ Foxp3+ regulatory T (Treg) cells must control autoreactive CD4+ conventional T (Tconv) cell responses against self-peptide antigens while permitting those against pathogen-derived "nonself" peptides. We defined the basis of this selectivity using mice in which Treg cells reactive to a single prostate-specific self-peptide were selectively depleted. We found that self-peptide-specific Treg cells were dispensable for the control of Tconv cells of matched specificity at homeostasis. However, they were required to control such Tconv cells and prevent autoimmunity toward the prostate after exposure to elevated self-peptide during infection. Notably, the Treg cell response to self-peptide did not affect protective Tconv cell responses to a pathogen-derived peptide. Thus, self-peptide-specific Treg cells promoted self-nonself discrimination during infection by selectively controlling Tconv cells of shared self-specificity.

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Lyra: An Efficient and Expressive Subquadratic Architecture for Modeling Biological Sequences

arXiv

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arXiv 2025年

作者： Ramesh, Krithik Siddiqui, Sameed M. Gu, Albert Mitzenmacher, Michael D. Sabeti, Pardis C. Broad Institute of MIT and Harvard CambridgeMA02142 United States Massachusetts Institute of Technology CambridgeMA02139 United States Computational and Systems Biology Program Massachusetts Institute of Technology CambridgeMA02139 United States Machine Learning Department Carnegie Mellon University PittsburgPA15213 United States School of Engineering and Applied Sciences Harvard University CambridgeMA02138 United States Department of Organismic and Evolutionary Biology Harvard University CambridgeMA02138 United States Department of Immunology and Infectious Diseases Harvard T.H. Chan School of Public Health Harvard University BostonMA02115 United States Howard Hughes Medical Institute Chevy ChaseMD20815 United States

Deep learning architectures such as convolutional neural networks and Transformers have revolutionized biological sequence modeling, with recent advances driven by scaling up foundation and task-specific models. The computational resources and large datasets required, however, limit their applicability in biological contexts. We introduce Lyra, a subquadratic architecture for sequence modeling, grounded in the biological framework of epistasis for understanding sequence-to-function relationships. Mathematically, we demonstrate that state space models efficiently capture global epistatic interactions and combine them with projected gated convolutions for modeling local relationships. We demonstrate that Lyra is performant across over 100 wide-ranging biological tasks, achieving state-of-the-art (SOTA) performance in many key areas, including protein fitness landscape prediction, biophysical property prediction (e.g. disordered protein region functions) peptide engineering applications (e.g. antibody binding, cell-penetrating peptide prediction), RNA structure analysis, RNA function prediction, and CRISPR guide design. It achieves this with orders-of-magnitude improvements in inference speed and reduction in parameters (up to 120,000-fold in our tests) compared to recent biology foundation models. Using Lyra, we were able to train and run every task in this study on two or fewer GPUs in under two hours, democratizing access to biological sequence modeling at SOTA performance, with potential applications to many fields. © 2025, CC BY-NC-ND.

关键词： Convolutional neural networks

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A Two-Step GRIN Lens Coating for In Vivo Brain Imaging

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Neuroscience Bulletin 2019年第3期35卷 419-424页

作者： Yupeng Yang Lifeng Zhang Zhenni Wang Bo Liang Giovanni Barbera Casey Moffitt Yun Li Da-Ting Lin Hefei National Laboratory for Physical Sciences at the Microscale School of Life SciencesUniversity of Science and Technology of ChinaHefei 230027China Intramural Research Program National Institute on Drug AbuseNational Institutes of HealthBaltimoreMD 21224USA Department of Zoology and Physiology University of Wyoming College of Arts and SciencesLaramieWY 82071USA

The complex spatial and temporal organization of neural activity in the brain is important for informationprocessing that guides behavior. Hence, revealing the realtime neural dynamics in freely-moving animals is fundamental to elucidating brain function. Miniature fluorescence microscopes have been developed to fulfil this requirement. With the help of GRadient INdex(GRIN)lenses that relay optical images from deep brain regions to the surface, investigators can visualize neural activity during behavioral tasks in freely-moving animals. However, the application of GRIN lenses to deep brain imaging is severely limited by their availability. Here, we describe a protocol for GRIN lens coating that ensures successful long-term intravital imaging with commercially-available GRIN lenses.

关键词： Grin lens Coating Toxic Neurodegeneration

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Top 10 Public health Challenges for 2024: Charting a New Direction for Global health Security

Public Health Challenges

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Public health Challenges 2025年第1期4卷

作者： Lucero-Prisno, Don Eliseo Shomuyiwa, Deborah Oluwaseun Kouwenhoven, M.B.N. Dorji, Thinley Adebisi, Yusuff Adebayo Odey, Goodness Ogeyi George, Nsikakabasi Samuel Ajayi, Oluwatomisin Temidayo Ekerin, Olabode Manirambona, Emery Xu, Lin Obnial, Joseph Christian Viola, Adriana Miranda Ogunkola, Isaac Olushola Ahmed, Mohamed Mustaf Ogaya, Jerico B. Huang, Junjie Sium, Abraham Fessehaye Suntay, Marcus Lester R. Chung, William K. De Paz, Pearl Irish V. Elmi, Hassan Sh Abdirahman Hersi, Omar Osman Gabaake, Kebabonye P. Baricaua, Teresita Dirie, Najib Isse Yepes, Prose Ivy G. Wilson, Donald John Tofaeono-Pifeleti, Rossana Tapia, Ederson Delos Trino Wong, Martin CS Department of Global Health and Development London School of Hygiene and Tropical Medicine London United Kingdom Department of Health Promotion and Behavior College of Public Health University of Georgia Athens GA United States Global Health Focus Lagos Nigeria Department of Physics Xi'an Jiaotong-Liverpool University Suzhou China Department of Internal Medicine Central Regional Referral Hospital Gelephu Bhutan College of Social Sciences University of Glasgow Glasgow United Kingdom Department of Health Policy London School of Economics and Political Science (LSE) London United Kingdom School of Medicine and Population Health University of Sheffield Sheffield United Kingdom Institute of Public Health Jagiellonian University Kraków Poland Department of Public Health State AIDS and STIs Control Program Ministry of Health Kaduna Nigeria School of Public Health University of Port Harcourt Port Harcourt Nigeria College of Medicine and Health Sciences University of Rwanda Kigali Rwanda Department of Thoracic Surgery The First Affiliated Hospital School of Medicine Zhejiang University Zhejiang Hangzhou China National Coalition of Independent Scholars Battleboro VT United States Global Health Focus Asia Bandung Indonesia YouthRise Dublin Ireland Faculty of Medicine and Health Sciences SIMAD University Mogadishu Somalia Department of Medical Technology Institute of Health Sciences and Nursing Far Eastern University Manila Philippines The Jockey Club School of Public Health and Primary Care Faculty of Medicine Chinese University of Hong Kong Hong Kong Department of Obstetrics and Gynecology St. Paul's Hospital Millennium Medical College Addis Ababa Ethiopia Office of the President World Surgical Foundation Manila Philippines Department of Biology Krieger School of Arts and Sciences Johns Hopkins University Baltimore MD United States Research and Development Office Biliran Province State University Naval Biliran Philippines Department of Biology Amo

As we navigate the complex landscape of global public health in 2024, this article provides a comprehensive exploration of challenges, ranging from infectious diseases, mental health, and substance use to environmental sustainability and emerging technologies. The aftermath of the COVID-19 pandemic underscores the critical need to strengthen health systems, increase public financing, and foster effective international collaboration. The intricacies of global geopolitics, diplomacy, and public health highlight the importance of countries that do not address shared challenges through enhanced cooperative mechanisms and joint initiatives. From the imperative of global health security to the persistence of non-communicable diseases and health disparities, this study delves into multifaceted issues, advocating for collective action, targeted interventions, and a commitment to prioritizing public health on a global scale. Focusing on addressing root causes and fostering equity, this study emphasizes the role of sustainable practices, community engagement, and intersectionality of research in building a resilient global health landscape. In this dynamic environment, 2024 calls for a unified global vision that encourages nations to collaborate more effectively to build a healthier and more resilient global community, ultimately paving the way for a future characterized by a shared commitment to public health challenges. © 2024 The Author(s). Public health Challenges published by John Wiley & Sons Ltd.

关键词： artificial intelligence climate fund ethics global health health equity pandemic accord technology

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Circular RMST cooperates with lineage-driving transcription factors to govern neuroendocrine transdifferentiation

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Cancer Cell 2025年第5期43卷 891-904.e10页

作者： Teng, Mona Guo, Jiacheng Xu, Xin Ci, Xinpei Mo, Yulin Kohen, Yakup Ni, Zuyao Chen, Sujun Guo, Wang Yuan Bakht, Martin Ku, Shengyu Sigouros, Michael Luo, Wenqin Macarios, Colette Maya Xia, Ziting Chen, Moliang Ul Haq, Sami Yang, Wen Berlin, Alejandro van der Kwast, Theo Ellis, Leigh Zoubeidi, Amina Zheng, Gang Ming, Jie Wang, Yuzhuo Cui, Haissi Lok, Benjamin H. Raught, Brian Beltran, Himisha Qin, Jun He, Housheng Hansen Department of Medical Biophysics Temerty Faculty of Medicine University of Toronto Toronto ON Canada Princess Margaret Cancer Centre University Health Network Toronto ON Canada Shanghai Institute of Nutrition and Health Chinese Academy of Sciences Shanghai China Institute of Medical Science Temerty Faculty of Medicine University of Toronto Toronto ON Canada Division of Medical Oncology Dana Farber Cancer Institute Boston MA United States Englander Institute for Precision Medicine Weill Cornell Medicine New York NY United States Department of Urology Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China Department of Chemistry University of Toronto Toronto ON Canada Department of Chemical Engineering and Applied Chemistry University of Toronto Toronto ON Canada Department of Breast and Thyroid Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China Center for Prostate Disease Research Murtha Cancer Center Research Program Department of Surgery Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. Bethesda MD United States Vancouver Prostate Centre Vancouver BC Canada Department of Urologic Sciences Faculty of Medicine University of British Columbia Vancouver BC Canada Radiation Medicine Program Princess Margaret Cancer Centre Toronto ON Canada

Circular RNA (circRNA) is a class of noncoding RNA with regulatory potentials. Its role in the transdifferentiation of prostate and lung adenocarcinoma into neuroendocrine prostate cancer (NEPC) and small cell lung cancer (SCLC) remains unexplored. Here, we identified circRMST as an exceptionally abundant circRNA predominantly expressed in NEPC and SCLC, with strong conservation between humans and mice. Functional studies using shRNA, siRNA, CRISPR-Cas13, and Cas9 consistently demonstrate that circRMST is essential for tumor growth and the expression of ASCL1, a master regulator of neuroendocrine fate. Genetic knockout of Rmst in NEPC genetic engineered mouse models prevents neuroendocrine transdifferentiation, maintaining tumors in an adenocarcinoma state. Mechanistically, circRMST physically interacts with lineage transcription factors NKX2-1 and SOX2. Loss of circRMST induces NKX2-1 protein degradation through autophagy-lysosomal pathway and alters the genomic binding of SOX2, collectively leading to the loss of ASCL1 transcription. © 2025 The Author(s)

关键词： circular RNA lineage plasticity neuroedocrine prostate cancer noncoding RNA RNA protein interactions small cell lung cancer transcription factors

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