Nature最新文献

{"title":"Kupffer cell programming by maternal obesity triggers fatty liver disease","authors":"Hao Huang, Nora R. Balzer, Lea Seep, Iva Splichalova, Nelli Blank-Stein, Maria Francesca Viola, Eliana Franco Taveras, Kerim Acil, Diana Fink, Franzisca Petrovic, Nikola Makdissi, Seyhmus Bayar, Katharina Mauel, Carolin Radwaniak, Jelena Zurkovic, Amir H. Kayvanjoo, Klaus Wunderling, Malin Jessen, Mohamed H. Yaghmour, Lukas Kenner, Thomas Ulas, Stephan Grein, Joachim L. Schultze, Charlotte L. Scott, Martin Guilliams, Zhaoyuan Liu, Florent Ginhoux, Marc D. Beyer, Christoph Thiele, Felix Meissner, Jan Hasenauer, Dagmar Wachten, Elvira Mass","doi":"10.1038/s41586-025-09190-w","DOIUrl":"https://doi.org/10.1038/s41586-025-09190-w","url":null,"abstract":"<p>Kupffer cells (KCs) are tissue-resident macrophages that colonize the liver early during embryogenesis¹. Upon liver colonization, KCs rapidly acquire a tissue-specific transcriptional signature, mature alongside the developing liver and adapt to its functions^1,2,3. Throughout development and adulthood, KCs perform distinct core functions that are essential for liver and organismal homeostasis, including supporting fetal erythropoiesis, postnatal erythrocyte recycling and liver metabolism⁴. However, whether perturbations of macrophage core functions during development contribute to or cause disease at postnatal stages is poorly understood. Here, we utilize a mouse model of maternal obesity to perturb KC functions during gestation. We show that offspring exposed to maternal obesity develop fatty liver disease, driven by aberrant developmental programming of KCs that persists into adulthood. Programmed KCs promote lipid uptake by hepatocytes through apolipoprotein secretion. KC depletion in neonate mice born to obese mothers, followed by replenishment with naive monocytes, rescues fatty liver disease. Furthermore, genetic ablation of the gene encoding hypoxia-inducible factor-α (HIF1α) in macrophages during gestation prevents the metabolic programming of KCs from oxidative phosphorylation to glycolysis, thereby averting the development of fatty liver disease. These results establish developmental perturbation of KC functions as a causal factor in fatty liver disease in adulthood and position fetal-derived macrophages as critical intergenerational messengers within the concept of developmental origins of health and diseases⁵.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"100 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319463","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":"R9AP is a common receptor for EBV infection in epithelial cells and B cells","authors":"Yan Li, Hua Zhang, Cong Sun, Xiao-Dong Dong, Chu Xie, Yuan-Tao Liu, Ruo-Bin Lin, Xiang-Wei Kong, Zhu-Long Hu, Xiao-Yan Ma, Dan-Ling Dai, Qian-Ying Zhu, Yu-Chun Li, Ying Li, Shang-Xin Liu, Li Yuan, Peng-Hui Zhou, Song Gao, Ya-Ping Tang, Jin-Ying Yang, Ping Han, Andrew T. McGuire, Bo Zhao, Jin-Xin Bei, Erle Robertson, Yi-Xin Zeng, Qian Zhong, Mu-Sheng Zeng","doi":"10.1038/s41586-025-09166-w","DOIUrl":"https://doi.org/10.1038/s41586-025-09166-w","url":null,"abstract":"<p>Epstein–Barr virus (EBV) persistently infects more than 90% of the human population, causing infectious mononucleosis¹, susceptibility to autoimmune diseases² and multiple malignancies of epithelial or B cell-origin³. EBV infects epithelial cells and B cells through interaction between viral glycoproteins and different host receptors⁴, but it has remained unknown whether a common receptor mediates infection of its two major host cell targets. Here, we establish R9AP as a crucial EBV receptor for entry into epithelial and B cells. R9AP silencing or knockout, R9AP-derived peptide and R9AP monoclonal antibody each significantly inhibit, whereas R9AP overexpression promotes, EBV uptake into both cell types. R9AP binds directly to the EBV glycoprotein gH/gL complex to initiate gH/gL–gB-mediated membrane fusion. Notably, the interaction of R9AP with gH/gL is inhibited by the highly competitive gH/gL-neutralizing antibody AMMO1, which blocks EBV epithelial and B cell entry. Moreover, R9AP mediates viral and cellular membrane fusion in cooperation with EBV gp42–human leukocyte antigen class II or gH/gL–EPHA2 complexes in B cells or epithelial cells, respectively. We propose R9AP as the crucial common receptor of B cells and epithelial cells and a potential prophylactic and vaccine target for EBV.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"147 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319550","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":"Carbon-fibre composites can be broken down into reusable components","authors":"","doi":"10.1038/d41586-025-01876-5","DOIUrl":"https://doi.org/10.1038/d41586-025-01876-5","url":null,"abstract":"The chemical building blocks from material used to make mountain bikes can be recovered using acetic acid.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"36 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319581","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":"For the future","authors":"","doi":"10.1038/d41586-025-01891-6","DOIUrl":"https://doi.org/10.1038/d41586-025-01891-6","url":null,"abstract":"Messages from history.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"18 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311706","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":"Light detectors made from perovskite crystals see in full colour","authors":"Shuming Nie,&nbsp;\u0000 Viktor Gruev","doi":"10.1038/d41586-025-01705-9","DOIUrl":"10.1038/d41586-025-01705-9","url":null,"abstract":"Most pixels in cameras detect only red, green or blue light. A sensor made from perovskite materials absorbs all three, improving image brightness and resolution. Most pixels in cameras detect only red, green or blue light. A sensor made from perovskite materials absorbs all three, improving image brightness and resolution.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"642 8068","pages":"578-579"},"PeriodicalIF":50.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319583","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":"Reply to: On the effects of fault alignment on slip stability","authors":"Jaeseok Lee,&nbsp;Victor C. Tsai,&nbsp;Greg Hirth,&nbsp;Avigyan Chatterjee,&nbsp;Daniel T. Trugman","doi":"10.1038/s41586-025-09118-4","DOIUrl":"10.1038/s41586-025-09118-4","url":null,"abstract":"","PeriodicalId":18787,"journal":{"name":"Nature","volume":"642 8068","pages":"E22-E23"},"PeriodicalIF":50.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319391","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":"In vivo mapping of mutagenesis sensitivity of human enhancers","authors":"Michael Kosicki, Boyang Zhang, Vivian Hecht, Anusri Pampari, Laura E. Cook, Neil Slaven, Jennifer A. Akiyama, Ingrid Plajzer-Frick, Catherine S. Novak, Momoe Kato, Stella Tran, Riana D. Hunter, Kianna von Maydell, Sarah Barton, Erik Beckman, Yiwen Zhu, Diane E. Dickel, Anshul Kundaje, Axel Visel, Len A. Pennacchio","doi":"10.1038/s41586-025-09182-w","DOIUrl":"https://doi.org/10.1038/s41586-025-09182-w","url":null,"abstract":"<p>Distant-acting enhancers are central to human development¹. However, our limited understanding of their functional sequence features prevents the interpretation of enhancer mutations in disease². Here we determined the functional sensitivity to mutagenesis of human developmental enhancers in vivo. Focusing on seven enhancers that are active in the developing brain, heart, limb and face, we created over 1,700 transgenic mice for over 260 mutagenized enhancer alleles. Systematic mutation of 12-base-pair blocks collectively altered each sequence feature in each enhancer at least once. We show that 69% of all blocks are required for normal in vivo activity, with mutations more commonly resulting in loss (60%) than in gain (9%) of function. Using predictive modelling, we annotated critical nucleotides at the base-pair resolution. The vast majority of motifs predicted by these machine learning models (88%) coincided with changes in in vivo function, and the models showed considerable sensitivity, identifying 59% of all functional blocks. Taken together, our results reveal that human enhancers contain a high density of sequence features that are required for their normal in vivo function and provide a rich resource for further exploration of human enhancer logic.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"94 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319548","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":"‘Remarkable’ new enzymes built by algorithm with physics know-how","authors":"","doi":"10.1038/d41586-025-01897-0","DOIUrl":"https://doi.org/10.1038/d41586-025-01897-0","url":null,"abstract":"Computer approach creates synthetic enzymes 100 times more efficient than those designed by AI.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"12 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319580","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":"Vertically stacked monolithic perovskite colour photodetectors","authors":"Sergey Tsarev,&nbsp;Daria Proniakova,&nbsp;Xuqi Liu,&nbsp;Erfu Wu,&nbsp;Gebhard J. Matt,&nbsp;Kostiantyn Sakhatskyi,&nbsp;Lorenzo L. A. Ferraresi,&nbsp;Radha Kothandaraman,&nbsp;Fan Fu,&nbsp;Ivan Shorubalko,&nbsp;Sergii Yakunin,&nbsp;Maksym V. Kovalenko","doi":"10.1038/s41586-025-09062-3","DOIUrl":"10.1038/s41586-025-09062-3","url":null,"abstract":"Modern colour image sensors face challenges in further improving sensitivity and image quality because of inherent limitations in light utilization efficiency1. A major factor contributing to these limitations is the use of passive optical filters, which absorb and dissipate a substantial amount of light, thereby reducing the efficiency of light capture2. On the contrary, active optical filtering in Foveon-type vertically stacked architectures still struggles to deliver optimal performance owing to their lack of colour selectivity, making them inefficient for precise colour imaging3. Here we introduce an innovative architecture for colour sensor arrays that uses multilayer monolithically stacked lead halide perovskite thin-film photodetectors. Perovskite bandgap tunability4 is utilized to selectively absorb the visible light spectrum’s red, green and blue regions, eliminating the need for colour filters. External quantum efficiencies of 50%, 47% and 53% are demonstrated for the red, green and blue channels, respectively, as well as a colour accuracy of 3.8% in ΔELab outperforming the state-of-the-art colour-filter array and Foveon-type photosensors. The image sensor design improves light utilization in colour sensors and paves the way for the next generation of highly sensitive, artefact-free images with enhanced colour fidelity. A colour sensor array based on multilayer monolithically stacked lead halide perovskite thin-film photodetectors achieves higher quantum efficiency and superior colour accuracy compared to conventional filter-based image sensors.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"642 8068","pages":"592-598"},"PeriodicalIF":50.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41586-025-09062-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319549","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":"Impacts of climate change on global agriculture accounting for adaptation","authors":"Andrew Hultgren,&nbsp;Tamma Carleton,&nbsp;Michael Delgado,&nbsp;Diana R. Gergel,&nbsp;Michael Greenstone,&nbsp;Trevor Houser,&nbsp;Solomon Hsiang,&nbsp;Amir Jina,&nbsp;Robert E. Kopp,&nbsp;Steven B. Malevich,&nbsp;Kelly E. McCusker,&nbsp;Terin Mayer,&nbsp;Ishan Nath,&nbsp;James Rising,&nbsp;Ashwin Rode,&nbsp;Jiacan Yuan","doi":"10.1038/s41586-025-09085-w","DOIUrl":"10.1038/s41586-025-09085-w","url":null,"abstract":"Climate change threatens global food systems1, but the extent to which adaptation will reduce losses remains unknown and controversial2. Even within the well-studied context of US agriculture, some analyses argue that adaptation will be widespread and climate damages small3,4, whereas others conclude that adaptation will be limited and losses severe5,6. Scenario-based analyses indicate that adaptation should have notable consequences on global agricultural productivity7–9, but there has been no systematic study of how extensively real-world producers actually adapt at the global scale. Here we empirically estimate the impact of global producer adaptations using longitudinal data on six staple crops spanning 12,658 regions, capturing two-thirds of global crop calories. We estimate that global production declines 5.5&nbsp;× 1014 kcal annually per 1 °C global mean surface temperature (GMST) rise (120 kcal per person per day or 4.4% of recommended consumption per 1 °C; P &lt; 0.001). We project that adaptation and income growth alleviate 23% of global losses in 2050 and 34% at the end of the century (6% and 12%, respectively; moderate-emissions scenario), but substantial residual losses remain for all staples except rice. In contrast to analyses of other outcomes that project the greatest damages to the global poor10,11, we find that global impacts are dominated by losses to modern-day breadbaskets with favourable climates and limited present adaptation, although&nbsp;losses in low-income&nbsp;regions losses are also substantial. These results indicate a scale of innovation, cropland expansion or further adaptation that might be necessary to ensure food security in a changing climate. Analysis of data on six stable crops, capturing two-thirds of global crop calories, allows estimation of&nbsp;agricultural impacts and the potential of global producer adaptations to reduce&nbsp;output losses owing to climate change.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"642 8068","pages":"644-652"},"PeriodicalIF":50.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41586-025-09085-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319688","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}