NaturePub Date : 2025-07-09DOI: 10.1038/d41586-025-01823-4
{"title":"Lab drowning in paperwork? Hire an in-house writer","authors":"","doi":"10.1038/d41586-025-01823-4","DOIUrl":"https://doi.org/10.1038/d41586-025-01823-4","url":null,"abstract":"Hiring a postdoc to take over writing tasks makes good sense, argues Béla Z. Schmidt.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"21 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asma Amamou, Mathilde Leboutte, Jonathan Breton, David Ribet, Pierre-Alain Thiebaut, Christine Bôle-Feysot, Charlène Guérin, Kanhia Aublé, Elise Rebollo, Lise Ratel, Benjamin Bonnard, Alexis Goichon, Louison Leblond, Moutaz Aziz, Elodie Fermant, Frédéric Jaisser, Guillaume Savoye, Rachel Marion-Letellier
{"title":"Mineralocorticoid receptor activation contributes to intestinal fibrosis through neutrophil gelatinase-associated lipocalin in preclinical models","authors":"Asma Amamou, Mathilde Leboutte, Jonathan Breton, David Ribet, Pierre-Alain Thiebaut, Christine Bôle-Feysot, Charlène Guérin, Kanhia Aublé, Elise Rebollo, Lise Ratel, Benjamin Bonnard, Alexis Goichon, Louison Leblond, Moutaz Aziz, Elodie Fermant, Frédéric Jaisser, Guillaume Savoye, Rachel Marion-Letellier","doi":"10.1038/s41467-025-61401-0","DOIUrl":"https://doi.org/10.1038/s41467-025-61401-0","url":null,"abstract":"<p>Intestinal fibrosis is a common complication in inflammatory bowel diseases with no specific therapy. Because mineralocorticoid receptor antagonism prevented inflammation and fibrosis in extra-intestinal organs, we aimed to evaluate mineralocorticoid receptor antagonism in intestinal fibrosis. Here we show that pharmacological or smooth cell specific deletion mineralocorticoid receptor antagonism prevented colon fibrosis development in male mice. In vitro, spironolactone prevented fibroblast proliferation and endothelial-to-mesenchymal transition. Neutrophil gelatinase-associated lipocalin silencing suppressed aldosterone-induced fibrosis markers and blunted colon fibrosis in mice. Chromatin immunoprecipitation showed mineralocorticoid receptor antagonist inhibits mineralocorticoid receptor binding on the neutrophil gelatinase-associated lipocalin promoter in activated smooth muscle cells. In conclusion, mineralocorticoid receptor antagonism or smooth muscle mineralocorticoid receptor deletion reduced colon fibrosis through the modulation of the neutrophil gelatinase-associated lipocalin pathway. Mineralocorticoid receptor may represent a novel therapeutic target in intestinal fibrosis and may allow the re-positioning in the field of inflammatory bowel diseases of drugs already marketed.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"5 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Host protein ARF1 is a proviral factor for SARS-CoV-2 and a candidate broad-spectrum therapeutic target","authors":"Cunhuan Zhang, Yuan-Qin Min, Heng Xue, Haiyan Zhang, Kunpeng Liu, Yichao Tian, Ziying Yang, Zihan Zhao, Hang Yang, Chao Shan, Xiulian Sun, Yun-Jia Ning","doi":"10.1038/s41467-025-61431-8","DOIUrl":"https://doi.org/10.1038/s41467-025-61431-8","url":null,"abstract":"<p>SARS-CoV-2 and its emerging variants pose continuing threats to public health. SARS-CoV-2 assembles at the ER–Golgi intermediate compartment (ERGIC), where the viral membrane (M) protein highly accumulates to act as the central driver. However, how M is concentrated in the ERGIC, which hosts factor(s), may be involved, and whether they could be exploited as broad-spectrum antiviral targets remains unclear. Here, we identify an M-interacting host protein, ARF1, as a proviral factor that bolsters the propagation of SARS-CoV-2 and its variants in cultured cells and the viral infection and pathogenicity in female K18-hACE2 mice. By its N-terminal helix, ARF1 interacts with M and facilitates M’s ERGIC accumulation and thus M-driven virion production. Consistently, pharmacological ARF1 inhibition by small molecules disrupts both ARF1 and M concentration at the ERGIC, blocking virion assembly and propagation. Furthermore, a designed peptide mimicking the M-targeted motif of ARF1 competitively blocks M-ARF1 interaction, M accumulation at the ERGIC, and viral assembly and propagation in vitro. Moreover, the peptidomimetic inhibitor exhibits therapeutic efficacy against SARS-CoV-2 infection and pathogenicity in vivo. These findings provide critical insights into the basic biology of SARS-CoV-2 and demonstrate the potential to develop pan-SARS-CoV-2 therapeutics by targeting ARF1 and/or the ARF1-M interaction interface.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"29 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Myers, Jiayang Xiao, Raissa K. Mathura, Ben Shofty, Victoria Gates, Joshua Adkinson, Anusha B. Allawala, Adrish Anand, Ron Gadot, Ricardo Najera, Hernan G. Rey, Sanjay J. Mathew, Kelly Bijanki, Garrett Banks, Andrew Watrous, Eleonora Bartoli, Sarah R. Heilbronner, Nicole Provenza, Wayne K. Goodman, Nader Pouratian, Benjamin Y. Hayden, Sameer A. Sheth
{"title":"Intracranial directed connectivity links subregions of the prefrontal cortex to major depression","authors":"John Myers, Jiayang Xiao, Raissa K. Mathura, Ben Shofty, Victoria Gates, Joshua Adkinson, Anusha B. Allawala, Adrish Anand, Ron Gadot, Ricardo Najera, Hernan G. Rey, Sanjay J. Mathew, Kelly Bijanki, Garrett Banks, Andrew Watrous, Eleonora Bartoli, Sarah R. Heilbronner, Nicole Provenza, Wayne K. Goodman, Nader Pouratian, Benjamin Y. Hayden, Sameer A. Sheth","doi":"10.1038/s41467-025-61487-6","DOIUrl":"https://doi.org/10.1038/s41467-025-61487-6","url":null,"abstract":"<p>Research on the neural basis of major depressive disorder suggests that it is fundamentally a disease of cortical disinhibition, where breakdowns of inhibitory neuronal systems lead to diminished emotion regulation and intrusive rumination. Subregions of the prefrontal cortex are thought to be sources of this disinhibition. However, due to limited opportunities for intracranial recordings from humans with major depression, this hypothesis has not been directly tested. Here, we use intracranial recordings from the dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortices from patients with major depression to measure daily fluctuations in self-reported depression symptom severity. Results indicate that directed connectivity within the delta frequency band, which has been linked to cortical inhibition, transiently increases intensity during negative mood. Symptom severity also shifts as connectivity patterns within the left and right prefrontal cortices become imbalanced. Our findings support the overarching hypothesis that depression worsens with prefrontal disinhibition and functional imbalance between hemispheres.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenyan Bi, Aalap D. Shah, Kimberly W. Wong, Brian J. Scholl, Ilker Yildirim
{"title":"Computational models reveal that intuitive physics underlies visual processing of soft objects","authors":"Wenyan Bi, Aalap D. Shah, Kimberly W. Wong, Brian J. Scholl, Ilker Yildirim","doi":"10.1038/s41467-025-61458-x","DOIUrl":"https://doi.org/10.1038/s41467-025-61458-x","url":null,"abstract":"<p>Computational explorations of human cognition have been especially successful when applied to visual perception. Existing models have primarily focused on rigid objects, emphasizing shape-preserving invariance to changes in viewpoint, lighting, object size, and scene context. Yet many objects in our everyday environments, such as cloths, are soft. This poses both quantitatively greater and qualitatively different challenges for models of perception, due to soft objects’ dynamic and high-dimensional internal structure, as in the changing folds and wrinkles of a cloth waving in the wind. Soft object perception is also correspondingly rich, involving distinct properties such as stiffness. Here we explore the ability of different kinds of computational models to capture visual perception of the physical properties of cloths (e.g., their degrees of stiffness) undergoing different naturalistic transformations (e.g., falling vs. waving in the wind). Across visual matching tasks, both the successes and failures of human performance are well explained by Woven: a new model that incorporates physics-based simulations to infer probabilistic representations of cloths. Woven outperforms powerful, performance-equated alternatives, including its ablations and a deep neural network, and suggests that humanlike machine vision may also require representations that transcend image statistics, and involve intuitive physics.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"72 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-07-09DOI: 10.1126/sciadv.adq4495
Katherine Svensson, Jamil M. Lane, John J. Chelonis, Chris Gennings, David C. Bellinger, Carmen Hernández-Chávez, Ivan Pantic, Martha M. Téllez-Rojo, Robert O. Wright
{"title":"Developmental Pb exposure increases rate of forgetting on a delayed matching-to-sample task among Mexican children","authors":"Katherine Svensson, Jamil M. Lane, John J. Chelonis, Chris Gennings, David C. Bellinger, Carmen Hernández-Chávez, Ivan Pantic, Martha M. Téllez-Rojo, Robert O. Wright","doi":"10.1126/sciadv.adq4495","DOIUrl":"https://doi.org/10.1126/sciadv.adq4495","url":null,"abstract":"Lead (Pb) is a potent neurotoxicant, but few studies have evaluated its effect on neurobehavioral measures that can be used in multiple species including humans. We investigated the effect of prenatal and childhood Pb exposure on children’s rate of forgetting using a delayed matching-to-sample (DMTS) task among children 6 to 8 years of age. Blood Pb was measured during pregnancy (second and third trimesters) and at 4 to 6 years of age. A nonlinear modified power function was used to predict the forgetting rates on the DMTS task, using separate models for prenatal and childhood Pb. Higher childhood Pb [median (interquartile range), 1.7 (1.3) (μg/dl)] was associated with a faster rate of forgetting (β = −0.05; 95% confidence interval: −0.09, −0.01). Higher maternal intelligence quotient and child’s age were significantly associated with a slower rate of forgetting. We validated a unique power function statistical approach for rates of forgetting using Pb exposure.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"50 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-07-09DOI: 10.1126/sciadv.adv7377
Zujun Que, Zhichao Xi, Dan Qi, Rongchen Dai, Yang Li, Mengfan Liu, Bin Luo, Jiajun Liu, Pan Yu, Yun Yang, Erxi Wu, Hongxi Xu, Jianhui Tian
{"title":"Src/FN1 pathway activation drives tumor cell cluster formation and metastasis in lung cancer: A promising therapeutic target","authors":"Zujun Que, Zhichao Xi, Dan Qi, Rongchen Dai, Yang Li, Mengfan Liu, Bin Luo, Jiajun Liu, Pan Yu, Yun Yang, Erxi Wu, Hongxi Xu, Jianhui Tian","doi":"10.1126/sciadv.adv7377","DOIUrl":"https://doi.org/10.1126/sciadv.adv7377","url":null,"abstract":"Lung cancer remains the leading cause of cancer-related death globally, with metastasis driven by circulating tumor cells (CTCs)—particularly clusters—being a major treatment challenge. Despite their critical role, the biological differences between single CTCs and CTC clusters remain unclear. Here, we comprehensively compared their behavioral, transcriptomic, and proteomic profiles in lung cancer models. Compared with single cells, CTC clusters present enhanced metastatic potential, greater survival in the bloodstream and increased resistance to microenvironment. Mechanistically, the Src/FN1 pathway is centrally activated in clusters, promoting intercellular cohesion and protecting against immune clearance and stress in circulation. Pharmacological inhibition of Src with the clinical inhibitor KX2-391 disrupted clustering, impaired CTC survival, and reduced metastasis in preclinical models. Our findings identify the Src/FN1 pathway as a key vulnerability in CTC cluster–driven metastasis, suggesting that Src inhibitors are promising therapeutic strategies to disrupt clustering and improve outcomes in patients with metastatic lung cancer.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"109 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-07-09DOI: 10.1126/sciadv.adw1731
Yue Li, Sarah Jacques, Hanmant Gaikwad, Morgan Nebbia, Nirmal K. Banda, V. Michael Holers, Stephen A. Tomlinson, Robert I. Scheinman, Andrew Monte, Laura Saba, Erika Lasda, Jay Hasselberth, Nicolas Busquet, Wioleta M. Zelek, S. Moein Moghimi, Dmitri Simberg
{"title":"Enhanced immunocompatibility and hemocompatibility of nanomedicines across multiple species using complement pathway inhibitors","authors":"Yue Li, Sarah Jacques, Hanmant Gaikwad, Morgan Nebbia, Nirmal K. Banda, V. Michael Holers, Stephen A. Tomlinson, Robert I. Scheinman, Andrew Monte, Laura Saba, Erika Lasda, Jay Hasselberth, Nicolas Busquet, Wioleta M. Zelek, S. Moein Moghimi, Dmitri Simberg","doi":"10.1126/sciadv.adw1731","DOIUrl":"https://doi.org/10.1126/sciadv.adw1731","url":null,"abstract":"The activation of complement by nanomedicines triggers immune uptake and proinflammatory responses. Complement pathway inhibitors could offer strategies to address these challenges. Here, we assess the efficacy of inhibitors with various nanoparticles, including dextran superparamagnetic iron oxide nanoworms, polyethylene glycol (PEG) liposomal drugs, and mRNA lipid nanoparticles. In human sera, inhibitors of the alternative pathway iptacopan and danicopan exhibit variable efficacies, ranging from high nanomolar to incomplete inhibition. However, both iptacopan and danicopan display poor efficacy with PEGylated liposomal doxorubicin. Sutimlimab, an inhibitor of the classical pathway, demonstrates poor efficacy with PEGylated liposomal doxorubicin, even in sera with anti-PEG antibodies. Iptacopan displays donor-dependent inhibition of the uptake of nanoparticles in human blood. Bolus coadministration of iptacopan with nanoworms in mice, rats, and dogs inhibits C3 opsonization and uptake by granulocytes. Iptacopan also alleviates nanoparticle-induced lethargy in rats and severe hypotension in dogs. These data suggest that complement inhibitors can enhance the immunocompatibility and hemocompatibility of nanomedicines in a donor-dependent manner.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"93 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-07-09DOI: 10.1126/sciadv.adw0562
Yang Teng, Wenbo Li, Xiaochen Wang, Rusong Zhang, Ying Shen, Ruifeng Wu, Jiawen Liu, Mingyi Zhang, Christian Roos, Jinhua Li, Jing Li, Jiwei Qi, Ming Li
{"title":"Integrating population genomics and environmental data to predict adaptation to climate change in post-bottleneck Tibetan macaques","authors":"Yang Teng, Wenbo Li, Xiaochen Wang, Rusong Zhang, Ying Shen, Ruifeng Wu, Jiawen Liu, Mingyi Zhang, Christian Roos, Jinhua Li, Jing Li, Jiwei Qi, Ming Li","doi":"10.1126/sciadv.adw0562","DOIUrl":"https://doi.org/10.1126/sciadv.adw0562","url":null,"abstract":"Rapid climate change represents a profound threat to biodiversity. Understanding the local adaptations and their vulnerabilities to climate change are imperative for developing conservation measures. Here, we combined a multidisciplinary approach to determine the local adaptations of an endemic and near-threatened primate, aiming to reveal its potential to cope with future climate change. Results suggest that climatic fluctuations played an important role in shaping its demographic trajectory and genetic structure. In addition, Tibetan macaques have experienced a severe bottleneck in the recent past, with highly deleterious mutations partially removed, but moderately deleterious mutations accumulating. The severe bottleneck and lower genetic diversity may have reduced their potential to adapt to environmental change, which will compromise long-term viability. Furthermore, we found that the eastern group exhibited higher genomic offsets and loss of suitable habitat in response to climate change. Overall, we emphasize the importance of integrating population genomics and environmental data to predict the adaptation of post-bottleneck populations to rapid climate change.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"51 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}