Science Advances最新文献

{"title":"BCG vaccination mitigates tau pathology and restores cognitive function in PS19 mice","authors":"Somnath Shee,&nbsp;Meixiang Huang,&nbsp;Meghraj Singh Baghel,&nbsp;Yuxin Zheng,&nbsp;Shichun Lun,&nbsp;Santosh K. Yadav,&nbsp;Nirbhay N. Yadav,&nbsp;Carlos E. Ruiz-Gonzalez,&nbsp;Sandeep Tyagi,&nbsp;Eric Nuermberger,&nbsp;Sanjay K. Jain,&nbsp;Zaver M. Bhujwalla,&nbsp;Barbara S. Slusher,&nbsp;Philip C. Wong,&nbsp;William Bishai","doi":"10.1126/sciadv.aej4603","DOIUrl":"10.1126/sciadv.aej4603","url":null,"abstract":"<div >Retrospective studies in patients with nonmuscle invasive bladder cancer have reported a significant reduction in Alzheimer’s disease incidence (12 to 78%) among Bacille Calmette-Guérin (BCG) recipients versus controls. To investigate the underlying mechanisms, we evaluated BCG in the PS19 mouse model of tauopathy. We found that BCG administration reduced hippocampal phospho-tau and microgliosis while preserving neuronal markers. In vivo volumetric T2–magnetic resonance Imaging (MRI) demonstrated attenuation of brain atrophy accompanied by increased glutamate-weighted chemical exchange saturation transfer–MRI signals. Functionally, BCG-treated mice showed improved performance in the novel object recognition test, as well as improved body-weight maintenance and survival. Transcriptomic profiling of the hippocampus revealed near complete normalization of the PS19 disease-associated gene expression signature toward that of healthy controls. Flow cytometric profiling of brain myeloid populations demonstrated a reduction in activated resident microglia, but total microglia cells remain elevated. Moreover, an increase of trained immunity marker CD80 on the recruited peripheral myeloid cells ensues following BCG treatment. Consistent with this shift in myeloid state, primary brain myeloid cells from BCG-treated mice also exhibited enhanced phagocytosis of fluorescein isothiocyanate-labeled tau fibrils and increased lactate production. Together, these findings indicate that BCG induces systemic and central nervous system myeloid cell reprogramming that limits neuroinflammation, enhances tau clearance, and rescues cognitive and neurodegenerative phenotypes in a tauopathy model. BCG is a safe, readily available therapy that merits consideration as a preventive agent against dementia.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aej4603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RanGAP1 coordinates the ER-lamina interface to drive de novo nuclear envelope reassembly in mouse embryos","authors":"Xiao-Jie Zhang,&nbsp;Cheng-Jie Zhou,&nbsp;Chun-Ru Song,&nbsp;Meng-Lei Feng,&nbsp;Fang-Rui Xue,&nbsp;Dui Sun,&nbsp;Qi Yang,&nbsp;Kang Ding,&nbsp;Zhao-Yu Jiang,&nbsp;Cheng-Guang Liang","doi":"10.1126/sciadv.aef7931","DOIUrl":"10.1126/sciadv.aef7931","url":null,"abstract":"<div >Nuclear envelope (NE) reassembly is essential for the zygote-to-totipotency transition in mammalian embryos. Beyond its classical roles in nuclear transport and maintenance of the RanGTP gradient, the function of RanGAP1 in embryonic NE reassembly has remained elusive. Here, we show that RanGAP1 localizes to the early embryonic NE, driving reassembly via a distinct structural mechanism. Trim-Away–mediated RanGAP1 depletion causes two-cell stage arrest and severe NE defects, including nuclear pore complex (NPC) loss, failed reassembly, and aberrant “fishnet” membrane structures. Mechanistically, RanGAP1 establishes a structural paradigm for endoplasmic reticulum (ER)–lamina coupling by recruiting Lamin A/C, B1, and B2 to the ER for coassembly. The acidic domain and SUMO-1 modification at Lys⁵²⁶ (K526) are essential for the NPC localization of RanGAP1. Thus, RanGAP1 orchestrates nuclear lamina (NL) assembly by targeting lamins to the ER. These findings uncover mechanisms of NE reassembly that are critical for early embryogenesis and provide insights into NE-related developmental disorders.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aef7931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p75NTR orchestrates chondrogenesis and mechanoadaptation to preserve temporomandibular joint development and homeostasis","authors":"Chiho Kadota-Watanabe,&nbsp;Jinsook Suh,&nbsp;Eric Yin,&nbsp;Byron Zhao,&nbsp;Jey Kim,&nbsp;Yan Zhang,&nbsp;In-Won Chang,&nbsp;Sowmya Ramesh,&nbsp;Yuna Lee,&nbsp;Joshua Chen,&nbsp;Maulik Ahuja,&nbsp;Sara Jahangiri,&nbsp;Isabelle Lao-Ngo,&nbsp;Ursula Eisinger,&nbsp;Kate Lindsey,&nbsp;Haihui Zhang,&nbsp;Fatemeh Momen-Heravi,&nbsp;Juan Du,&nbsp;James M. Gardner,&nbsp;Rebeka Silva,&nbsp;Sumit Yadav,&nbsp;Chelsea S. Bahney,&nbsp;Aaron W. James,&nbsp;Reuben H. Kim,&nbsp;Ophir D. Klein,&nbsp;Christine Hong","doi":"10.1126/sciadv.aef7786","DOIUrl":"10.1126/sciadv.aef7786","url":null,"abstract":"<div >The temporomandibular joint (TMJ) is essential for oral functions such as chewing, speaking, and swallowing. Temporomandibular disorders that impair these functions notably reduce patients’ quality of life, and few therapeutic strategies are available to ameliorate these conditions. Here, we identify the neurotrophin receptor (p75^NTR) as a central regulator of mandibular condylar cartilage development, mechanoadaptation, and homeostasis. <i>p75^NTR</i> loss causes condylar and disc hypoplasia, reduced chondrocyte number, impaired load-induced anabolism, and accelerated degeneration. Conditional deletion experiments demonstrate chondrocyte-autonomous requirements for the brain-derived neurotrophic factor (BDNF)–p75^NTR axis, which activates phosphoinositide 3-kinase AKT serine/threonine kinase and p38 mitogen-activated protein kinase signaling to promote proliferation and chondrogenic differentiation while restraining apoptosis. Degenerative human condyles exhibit reduced <i>p75^NTR</i> expression levels. Together, these data establish p75^NTR as a molecular hub integrating neurotrophic and mechanical cues to preserve postnatal TMJ architecture and highlight the BDNF-p75^NTR axis as a potential therapeutic target.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aef7786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Staphylococcus aureus wall teichoic acid structure dictates virulence potential and resistance to host defenses","authors":"Timothy J. Enroth,&nbsp;Eunjeong Lee,&nbsp;Elan Z. Eisenmesser,&nbsp;Alexander R. Horswill","doi":"10.1126/sciadv.aef7070","DOIUrl":"10.1126/sciadv.aef7070","url":null,"abstract":"<div ><i>Staphylococcus aureus</i> is a formidable pathogen and the leading cause of skin and soft tissue infections. We recently showed that the highly conserved <i>sasF</i> gene, encoding for an uncharacterized sortase-anchored surface protein, is up-regulated when <i>S. aureus</i> colonizes skin. Here, we demonstrate that SasF is an enzyme that has glycoside epimerase activity, which is required for <i>S. aureus</i> resistance to skin fatty acids. Mutants of <i>sasF</i> are highly impaired in skin colonization and acute infection models. The SasF enzyme is crucial for maintaining the structure of wall teichoic acids and proper <i>S. aureus</i> surface chemistry. To our knowledge, this is the first report of a bacterial surface epimerase in this pathogen, suggesting that SasF could be a therapeutic target.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aef7070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scentronic: An artificial intelligence–assisted olfactory interface for remote odor sharing and transmission","authors":"Chunyu Yang,&nbsp;Qi Wang,&nbsp;Chen Wang,&nbsp;Antonia Akoto-Yeboah,&nbsp;Shaoru Cheng,&nbsp;Billings Amoah,&nbsp;Yizhen Jia,&nbsp;Shulin Chen,&nbsp;Akhil Canumalla,&nbsp;Kai Zhao,&nbsp;Christopher Simons,&nbsp;Jinghua Li","doi":"10.1126/sciadv.aee9266","DOIUrl":"10.1126/sciadv.aee9266","url":null,"abstract":"<div >Recent years have witnessed the surge of human–machine interfaces (HMIs) for various applications. Olfaction is a fundamental chemical sense crucial to perception, memory, and emotion. Current limitations arise from the difficulty of accurately capturing, transmitting, and reproducing odor signals, and the lack of standardized, network-enabled platforms. This work presents an internet of things (IoT)–enabled olfactory interface for remote odor sensing and stimulation. The system integrates an artificial intelligence-assisted odor sensing platform with a wearable piezoelectric olfactory actuation system. We demonstrate the design, characterization, and application of this framework, which integrates devices, circuit architecture, and software algorithms. Applications in medical contexts include psychophysical testing to study olfactory pathways and evaluate sensory loss. We further showcase multisensory stimulation through integrated olfactory and gustatory interfaces for enhanced immersion. This study establishes a scalable framework for IoT-based olfactory interaction, advancing HMIs toward a future that includes the long-overlooked chemical senses.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aee9266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ocean carbon sequestration during glacial climates due to combined Antarctic sea ice expansion and ocean circulation change","authors":"Sandy Grégorio,&nbsp;Jonathan M. Lauderdale,&nbsp;Louis-Philippe Nadeau,&nbsp;Raffaele Ferrari","doi":"10.1126/sciadv.ady6777","DOIUrl":"10.1126/sciadv.ady6777","url":null,"abstract":"<div >Glacial-interglacial transitions punctuate Earth’s Quaternary climate, accompanied by substantial atmospheric carbon dioxide and ocean carbon storage changes. The cause of atmospheric carbon drawdown during glaciations is uncertain, involving many mechanisms whose interactions are poorly understood. Here, we show that the combined expansion of Antarctic sea ice and associated changes in the meridional overturning efficiently sequester carbon in the ocean abyss, leading to a decline in atmospheric carbon dioxide. In contrast, changes in sea ice and circulation individually result in ocean carbon dioxide outgassing. When sea ice expansion and circulation changes act together, they enhance biological carbon storage by reducing ocean-atmosphere fluxes in the Southern Ocean, without invoking external drivers of the biological pump. This reduction inhibits the outgassing of upwelled remineralized carbon and promotes its resubduction into the abyss. Together, these results reveal a reinforcing feedback linking atmospheric cooling, Antarctic sea ice expansion, and ocean circulation changes to enhanced biological carbon storage and atmospheric carbon dioxide drawdown.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ady6777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mRNA-based RSV vaccine mRNA-1345 induces robust and durable CD4+ T cell responses against RSV in younger and older adults","authors":"Anthony DiPiazza,&nbsp;Emily Marcisak,&nbsp;Wen-Han Yu,&nbsp;Daniel Makrinos,&nbsp;Hsiao-Hsuan Kuo,&nbsp;Jenna Landy,&nbsp;Shannon McGrath,&nbsp;Xiaolin Chang,&nbsp;Maria Cavallaro,&nbsp;Christopher Wu,&nbsp;Adam Essene,&nbsp;Haining Lin,&nbsp;Laura Walker,&nbsp;Andrea Carfi,&nbsp;Jaap Oostendorp,&nbsp;Robert Paris,&nbsp;Yanbo Sun","doi":"10.1126/sciadv.aeh4436","DOIUrl":"10.1126/sciadv.aeh4436","url":null,"abstract":"<div >Respiratory syncytial virus (RSV) remains a health threat, particularly for infants, older adults, and immunocompromised individuals. Although neutralizing antibodies can help limit infection and viral replication, T cells are essential for reducing disease severity. Assessment of age-related declines in T cell function are important for vaccine evaluation. We used intracellular cytokine staining, activation-induced marker, and Meso Scale Discovery assays and single-cell multiomic profiling to evaluate RSV vaccine mRNA-1345 responses in younger and older adults. mRNA-1345 induced comparable CD4⁺ and CD8⁺ T cell responses in both cohorts, with CD4⁺ responses persisting for 24 months. The CD4⁺ response was strongly T helper 1 (T_H1)–polarized, with increased interferon-γ, interleukin-2, and tumor necrosis factor–α and minimal T_H2 cytokines. Both CD4⁺ and CD8⁺ T cells showed increased polyfunctionality that remained elevated at 2 years. Single-cell and T cell receptor repertoire analyses showed similar Pre-F–specific phenotypes, transcriptional profiles, and clonal overlap across age groups, supporting robust, durable cellular immunity after mRNA-1345 vaccination. These findings indicate shared vaccine-elicited T cell immunity in adults.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeh4436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classical quantum chemical solution of the FeMo-cofactor model to chemical accuracy and its implications","authors":"Huanchen Zhai,&nbsp;Chenghan Li,&nbsp;Xing Zhang,&nbsp;Zhendong Li,&nbsp;Seunghoon Lee,&nbsp;Garnet Kin-Lic Chan","doi":"10.1126/sciadv.aeg7106","DOIUrl":"10.1126/sciadv.aeg7106","url":null,"abstract":"<div >We use classical quantum chemistry methods to estimate the ground-state energy to chemical accuracy in a model of the FeMo cofactor of nitrogenase, which is widely studied as a target of quantum computing. Our result relies on the insight that the ground-state problem can be characterized as one of ranking many competing, but largely single-configuration, states. This allows a combination of systematic high-order coupled cluster and density matrix renormalization group calculations together with an extrapolation protocol to obtain an accurate energy. Within the model, we identify several spin isomer candidates for the ground state that are degenerate to chemical accuracy. Beyond this model, we characterize the impact of additional electronic excitations and the cluster and protein geometric fluctuations on the low-lying electronic landscape. We find that many features of the landscape are retained in more detailed representations of nitrogenase, which points to the complexity of spectroscopic interpretations of the electronic structure of the FeMo cofactor.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeg7106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prioritizing reducing impacts on species to minimize residual reserves","authors":"Aharon G. Fleury,&nbsp;Casey C. O’Hara,&nbsp;Jason D. Everett,&nbsp;Benjamin S. Halpern,&nbsp;Carissa J. Klein,&nbsp;Anthony J. Richardson,&nbsp;Daniel C. Dunn","doi":"10.1126/sciadv.aeh8129","DOIUrl":"10.1126/sciadv.aeh8129","url":null,"abstract":"<div >International conservation goals have driven rapid expansion of protected areas. This growth has favored quantity over quality, and often results in residual reserves (i.e., areas where species already experience minimal anthropogenic impact). Spatial prioritization is commonly used to help design protected area networks that represent species while minimizing costs to stakeholders. This approach can result in the siting of protected areas that do not decrease impacts on species of conservation concern. Here, we show how measures of cumulative impacts on species can be used in a spatial prioritization to site protected areas to reduce impacts on species of conservation concern. We use a trait-based vulnerability framework and anthropogenic stressor maps to quantify cumulative impacts from four human activities, and incorporate those impacts into spatial prioritizations. We demonstrate that the inclusion of cumulative impacts on species in spatial prioritization can more efficiently protect biodiversity, balance socioeconomic objectives, and avoid residual reserve outcomes.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeh8129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Climatic niche conservatism shapes the macroevolution, extinction, and survivorship of crocodile-line archosaurs","authors":"Alfio Alessandro Chiarenza,&nbsp;Alexandra F. C. Howard,&nbsp;Grace L. Varnham,&nbsp;Alex Farnsworth,&nbsp;Paul J. Valdes,&nbsp;Philip D. Mannion","doi":"10.1126/sciadv.aeg2217","DOIUrl":"10.1126/sciadv.aeg2217","url":null,"abstract":"<div >Crocodylians are iconic thermophiles. Over 250 million years, crocodile-line archosaurs endured hyperthermals, climatic and range shifts, and two mass extinctions. Whether this niche conservatism reflects a deep evolutionary constraint or recent adaptation to novel climates remains unclear. We integrate present-day occurrences with a time-scaled phylogeny of &gt;400 fossil and extant species. Niche models calibrated on living crocodylians were projected across 245 million years and compared with paleophylogeographic reconstructions. Macroevolutionary model fitting shows that temperature and precipitation exhibit strong phylogenetic structure, best described by bounded Ornstein-Uhlenbeck dynamics, indicating long-term niche conservatism. Poleward expansions in warm intervals and contractions in cool phases reflect tracking of conserved optima rather than niche evolution. Unlike non-avian dinosaurs, low-latitude suitability persisted across all but the most extreme end-Cretaceous scenarios, with recovery expanding from tropical refugia. Thermal and precipitation regimes shifted near the Cenomanian/Turonian hyperthermal (∼93.9 Ma) and Eocene/Oligocene aridification transition (∼33.9 Ma), respectively. Climatic niche conservatism is therefore ancient in crocodile-line archosaurs, but not completely static.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeg2217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}