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    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025.
  • Correction for Pospisil and Pillow, Revisiting the high-dimensional geometry of population responses in the visual cortex
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025.
  • Spiking world model with multicompartment neurons for model-based reinforcement learning
    by Yinqian SunFeifei ZhaoMingyang LyuYi ZengaBrain-inspired Cognitive AI Lab, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, ChinabLong-term AI, Beijing 100862, ChinacState Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, ChinadSchool of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100190, China
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceDendritic computation is key to the brain’s ability to integrate information over long timescales. Inspired by this, this study proposes a spiking neural network model that embeds dendritic mechanisms to enhance long-term memory and planning. …
  • Glomerular endothelial cells eliminate nicotinamide adenine dinucleotide to instruct CD103+ T cells in human lupus nephritis
    by Li JiaMengdi LiuHuiyan JiJiaxin LeiDanhua SuLingyi LiTing LiuFenghong YuanLin XuQinghua CaoHuimin ZhangZhenke WenaThe Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou 215123, Jiangsu Province, ChinabJiangsu Key Laboratory of Infection and Immunity, Minister of Education Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou 215123, Jiangsu Province, ChinacDepartment of Rheumatology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214000, Jiangsu Province, ChinadDepartment of Immunology, Zunyi Medical University, Zunyi 563000, Guizhou Province, ChinaeRenal Medicine, Faculty of Medicine and Health, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, St Leonards, NSW 2065, AustraliafRoyal North Shore Hospital, St Leonards, NSW 2065, AustraliagDepartment of Molecular Cell and Systems Biology, University of California, Riverside, CA 92521
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceThis study investigates how glomerular endothelial cells (ECs) drive CD103+T cells in lupus nephritis (LN), utilizing primary T cells from patients and human EC-T cell coculture systems. The authors demonstrate that ECs modulate cellular NAD+…
  • Colored HOMFLYPT counts holomorphic curves
    by Tobias EkholmVivek ShendeaDepartment of Mathematics and Centre for Geometry and Physics, Uppsala University, Uppsala 751 06, SwedenbInstitut Mittag-Leffler, Djursholm 182 60, SwedencCenter for Quantum Mathematics, Syddansk Univ., Odense 5230, DenmarkdDepartment of mathematics, University of California, Berkeley, CA 94720
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceIn 1999, Ooguri and Vafa conjectured a formula connecting two previously unrelated areas: holomorphic curve counting and the study of knot invariants. The former concerns the enumeration of solutions to certain partial differential equations, …
  • SPNS1 is an essential cellular factor for EV-A71 by acting as a transporter of viral pocket factor
    by Yu-Zhi FuFang-Fang LuoLiu YangYu-Xia ZhangJing-Yang LiSu-Yun WangYong ZhangYan-Yi WangaState Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinabUniversity of Chinese Academy of Sciences, Beijing 101408, ChinacDepartment of New Diseases, Changping Laboratory, Beijing 102206, ChinadNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, ChinaeNational Polio Laboratory, World Health Organization Polio Reference Laboratory for the Western Pacific Region, National Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceHuman enterovirus A71 (EV-A71) is a major cause of hand, foot and mouth diseases which poses a global threat to human health. Despite intensive investigations, the cellular factors that are critical for EV-A71 infection remain enigmatic, …
  • Biological fidelity: The engine driving the neuromorphic renaissance
    by Giacomo IndiveriaInstitute of Neuroinformatics, University of Zurich and ETH Zurich, Zurich CH-8057, Switzerland
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025.
  • Computationally efficient whole-genome quantile regression at biobank scale
    by Fan WangChen WangTianying WangMarco MasalaEdoardo FiorilloMarcella DevotoFrancesco CuccaIuliana Ionita-LazaaDepartment of Biostatistics, Columbia University, New York, NY 10032, United StatesbDepartment of Statistics, Colorado State University, Fort Collins, CO 80523-1877, United StatescInstitute for Genetic and Biomedical Research, National Research Council, Monserrato 09042, ItalydDepartment of Biomedical Sciences, University of Sassari, Sassari 07100, ItalyeDepartment of Statistics, Lund University, Lund 221 00, Sweden
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceGenome-wide association studies (GWAS) for biomarkers and molecular phenotypes can lead to clinically relevant discoveries. Numerous lines of evidence from model organisms and human studies suggest that genetic associations can be highly …
  • Fluoride triggers lysis in Streptococcus mutans by inhibition of the Clp protease complex, leading to an unabated competence cascade
    by Aditya BanerjeeSophie PickelnerFaith SmithLivia M. A. TenutaRandy B. StockbridgeaDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109bDepartment of Cariology, Restorative Sciences & Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceIt has been known for decades that fluoride has antimicrobial properties, but the molecular mechanisms that underlie fluoride-induced bacterial lysis remain unknown. UsingStreptococcus mutans, the main pathogen responsible for dental caries, …
  • TAPT1 interacts with SUCO to maintain the homeostasis of newly synthesized proteins and brain development in mice
    by Jiawei GaoFuqiang YangYisheng JiangYu ZhengLu CaiXiahe HuangLi YuanYingchun WangYaqing WangZhiheng XuaInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, ChinabDepartment of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, ChinacMedical School, University of Chinese Academy of Sciences, Beijing 101408, China
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceGenetic mutations in TAPT1 cause complex skeletal dysplasia and abnormal brain structure. Here, we demonstrate that Tapt1 knockout in the brain leads to profound neurodevelopmental abnormalities, culminating in severe microcephaly, motor …
  • A balance between glycitein and glyceollins governed by isoflavone 6-hydroxylase confers soybean resistance to Phytophthora sojae
    by Qilin YangYining WangXindan XuJia YuanFengxia ZhangHao QinShihao LiJianxu LiHao LinLei LiZhixi TianGuodong WangaKey Laboratory of Seed Innovation, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, ChinabCollege of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing 100039, ChinacBiotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinadShanghai Key Laboratory of Plant Functional Genomics and Resources, Shanghai Chenshan Botanical Garden, Shanghai Chenshan Plant Science Research Center, Chinese Academy of Sciences, Shanghai 201602, ChinaeYazhouwan National Laboratory, Sanya, Hainan 572024, China
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceIn this study, we identifiedGmIF6H1(Glyma.11g108300) as a key gene for glycitein biosynthesis in soybean, catalyzing daidzein 6-hydroxylation rather than the previously assumed liquiritigenin route. Infection byPhytophthora sojaeinduced …
  • Reward-driven adaptation of movements requires strong recurrent basal ganglia–cortical loops
    by Arthur LebloisThomas BoraudDavid HanselaNeurocampus Departement, UMR 5293, Institut des Maladies Neurodégénératives, University of Bordeaux, CNRS, Bordeaux 33000, FrancebCerebral Dynamics, Plasticity and Learning Laboratory, CNRS, Université Paris Cité, Paris 75006, France
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceThe basal ganglia (BG) are essential for learning and adapting movements, yet their output is often unnecessary for executing well-learned actions. This paradox challenges existing models of BG function. Here, we present a biologically …
  • The inferred functional connectome underlying circadian synchronization in the mouse suprachiasmatic nucleus
    by K. L. NikhilBharat SinghalDaniel Granados-FuentesJr-Shin LiIstván Z. KissErik D. HerzogaDepartment of Biology, Washington University in Saint Louis, Saint Louis, MO 63130bDepartment of Electrical and Systems Engineering, Washington University in Saint Louis, Saint Louis, MO 63130cDepartment of Chemistry, Saint Louis University, Saint Louis, MO 63103
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceLinking cellular activity to network-level computation remains a major goal in neuroscience. We introduce a robust method to infer directed, functional cell–cell connectivity in large cell populations. Using information theory and live-cell …
  • MBNL loss of function in smooth muscle as a model for myotonic dystrophy associated gastrointestinal dysmotility
    by Janel A. M. PetersonJesus A. FriasAndrew N. MillerKrishnakant G. SoniYi ZhangZheng XiaJohn W. DayGeoffrey A. PreidisThomas A. CooperaDepartment of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030bDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030cDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX 77030dBiomedical Engineering Department, Oregon Health and Science University, Portland, OR 97239eDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305fUnited States Department of Agriculture-Agricultural Research Service Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030gDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030hDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceGastrointestinal (GI) dysfunction is a prevalent yet understudied feature of myotonic dystrophy type 1 (DM1), affecting the quality of life for most affected individuals. We developed smooth muscle-specificMbnlknockout mice to investigate …
  • Evaluating large language models in biomedical data science challenges through a classroom experiment
    by Huifang MaZhicheng JiaDepartment of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27705Tara Al-HashimyAustin AllenNan CenOrlando ChenYongyin ChenYutian ChenTong ChengYueqi GuBeijie JiXiaohui JiangFengnan LiPeiyu LiYueshan LiangBena LiuCoco LiuElisa MaZhicheng MaVicky ShaoMengyao ShiJiang ShuLeyi SunRushi TangHanyu WangVivian WangYuxin WangKrissie WilsonRuobing XueTianyi YangAlison YuAllison YuanHaiqi ZhangVera ZhangYinuo Zhang
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceLarge language models (LLMs) are increasingly used in science and engineering, yet their real-world effectiveness in data analysis remains unclear. In this study, graduate students used LLMs to tackle biomedical data challenges on Kaggle, a …
  • Building hierarchically nested structure by rapid neural sequences
    by Bingjiang LyuLang QinXiongfei WangJianxin OuMatthew M. NourNai DingJia-Hong GaoYunzhe LiuaChangping Laboratory, Beijing 102206, ChinabSchool of Chinese as a Second Language, Peking University, Beijing 100871, ChinacCenter for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, ChinadDepartment of Neurosurgery, Laboratory for Clinical Medicine, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, ChinaeState Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, ChinafChinese Institute for Brain Research, Beijing 102206, ChinagDepartment of Psychiatry, University of Oxford, Oxford OX3 7JX, United KingdomhMax Planck University College London Centre for Computational Psychiatry and Ageing Research, London WC1B 5EH, United KingdomiKey Laboratory for Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Sciences, Zhejiang University, Hangzhou 310058, ChinajState Key Lab of Brain-Machine Intelligence, Zhejiang University, Hangzhou 310058, ChinakBeijing City Key Lab for Medical Physics and Engineering, School of Physics, Peking University, Beijing 100871, ChinalMcGovern Institute for Brain Research, Peking University, Beijing 100871, ChinamNational Biomedical Imaging Center, Peking University, Beijing 100871, China
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceThe human mind excels at building complex, multilevel structures, which we use daily from constructing a sentence to planning a multistep project. Yet, how the brain actually builds these mental hierarchies has remained largely unknown. This …
  • MultistageOT: Multistage optimal transport infers trajectories from a snapshot of single-cell data
    by Magnus TronstadJohan KarlssonJoakim S. DahlinaDepartment of Medicine Solna, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm 171 76, SwedenbDepartment of Mathematics, KTH Royal Institute of Technology, Stockholm 100 44, Sweden
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceCell differentiation is a fundamental biological process whose dysregulation leads to disease. Single-cell sequencing offers unique insight into the differentiation process, but data analysis remains a major modeling challenge—particularly in …
  • We need transparency standards for social media research that involves companies
    by Georgia TurnerIan AndersonLuisa FassiaMRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge CB2 7EF, United KingdombCalifornia Institute of Technology, Pasadena, CA 91125cDepartment of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025.
  • Contrastive independent component analysis for salient patterns and dimensionality reduction
    by Kexin WangAida MarajAnna SeigalaSchool of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138bMax Planck Institute of Molecular Cell Biology and Genetics and Center for Systems Biology, Dresden 01307, Germany
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceVisualizing data and finding patterns in data are ubiquitous problems in the sciences. Increasingly, applications seek signal and structure in a contrastive setting: a foreground dataset relative to a background dataset. The goal is to learn …
  • Correction for Lee, The effects of social media criticism against public health institutions on trust, emotions, and social media engagement
    Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025.

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