Nature最新文献

{"title":"New lasso-shaped antibiotic kills drug-resistant bacteria","authors":"","doi":"10.1038/d41586-025-00961-z","DOIUrl":"https://doi.org/10.1038/d41586-025-00961-z","url":null,"abstract":"Hear the biggest stories from the world of science | 26 March 2025","PeriodicalId":18787,"journal":{"name":"Nature","volume":"14 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713085","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":"Catalytic allylation of native hexoses and pentoses in water with indium","authors":"Tapas Adak, Travis Menard, Matthew Albritton, Federico Florit, Martin D. Burke, Klavs F. Jensen, Scott E. Denmark","doi":"10.1038/s41586-025-08690-z","DOIUrl":"https://doi.org/10.1038/s41586-025-08690-z","url":null,"abstract":"<p>Carbohydrates are an abundant, inexpensive and renewable biomass feedstock that could be a cornerstone for sustainable chemical manufacturing, but scalable and environmentally friendly methods that leverage these feedstocks are lacking. For example, 1-allyl sorbitol is the foundational building block for the polypropylene clarifying agent Millad NX 8000, which is produced on the multi-metric ton scale annually, but the manufacturing process at present requires superstoichiometric amounts of tin^1,2. The NX 8000 additives dominate about 80% of the global clarified polypropylene market³ and are used in concentrations of 0.01–1% during polypropylene production to improve its transparency and resistance to high temperatures, translating to 300–30,000 metric tons annually. The market volume of polypropylene in 2022 was approximately 79.01 million metric tons (MMT), with demand expected to rise by nearly 33% to 105 MMT by 2030 (ref. ⁴). The cost and sustainability benefits of clarified polypropylene are driving this demand, necessitating more clarifying agents⁵. Here we report a high-yielding allylation of unprotected carbohydrates in water using a catalytic amount of indium metal and either allylboronic acid or the pinacol ester (allylBpin) as donors. Aldohexoses, aminohexoses, ketohexoses and aldopentoses are all allylated in high yield under mild conditions and the indium metal is recoverable and reusable with no loss of catalytic activity. Leveraging these features, this process was translated to a scalable continuous synthesis of 1-allyl sorbitol in flow⁶ with high yield and productivity through Bayesian optimization of reaction parameters.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"57 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713185","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":"Genome-wide CRISPR screen in human T cells reveals regulators of FOXP3","authors":"Kelvin Y. Chen, Tatsuya Kibayashi, Ambre Giguelay, Mayu Hata, Shunsuke Nakajima, Norihisa Mikami, Yusuke Takeshima, Kenji Ichiyama, Ryusuke Omiya, Leif S. Ludwig, Kunihiro Hattori, Shimon Sakaguchi","doi":"10.1038/s41586-025-08795-5","DOIUrl":"https://doi.org/10.1038/s41586-025-08795-5","url":null,"abstract":"<p>Regulatory T (T_reg) cells, which specifically express the master transcription factor FOXP3, have a pivotal role in maintaining immunological tolerance and homeostasis and have the potential to revolutionize cell therapies for autoimmune diseases^1,2,3. Although stimulation of naive CD4⁺ T cells in the presence of TGFβ and IL-2 can induce FOXP3⁺ T_reg cells in vitro (iT_reg cells), the resulting cells are often unstable and have thus far hampered translational efforts^4,5,6. A systematic approach towards understanding the regulatory networks that dictate T_reg differentiation could lead to more effective iT_reg cell-based therapies. Here we performed a genome-wide CRISPR loss-of-function screen to catalogue gene regulatory determinants of FOXP3 induction in primary human T cells and characterized their effects at single-cell resolution using Perturb-icCITE-seq. We identify the RBPJ–NCOR repressor complex as a novel, context-specific negative regulator of FOXP3 expression. RBPJ-targeted knockout enhanced iT_reg differentiation and function, independent of canonical Notch signalling. Repeated cytokine and T cell receptor signalling stimulation in vitro revealed that RBPJ-deficient iT_reg cells exhibit increased phenotypic stability compared with control cells through DNA demethylation of the <i>FOXP3</i> enhancer CNS2, reinforcing FOXP3 expression. Conversely, overexpression of RBPJ potently suppressed FOXP3 induction through direct modulation of <i>FOXP3</i> histone acetylation by HDAC3. Finally, RBPJ-ablated human iT_reg cells more effectively suppressed xenogeneic graft-versus-host disease than control iT_reg cells in a humanized mouse model. Together, our findings reveal novel regulators of FOXP3 and point towards new avenues to improve the efficacy of adoptive cell therapy for autoimmune disease.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"12 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713189","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":"Phosphate-enabled mechanochemical PFAS destruction for fluoride reuse","authors":"Long Yang, Zijun Chen, Christopher A. Goult, Thomas Schlatzer, Robert S. Paton, Véronique Gouverneur","doi":"10.1038/s41586-025-08698-5","DOIUrl":"https://doi.org/10.1038/s41586-025-08698-5","url":null,"abstract":"<p>Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are persistent, bioaccumulative and anthropogenic pollutants that have attracted the attention of the public and private sectors because of their adverse impact on human health¹. Although various technologies have been deployed to degrade PFASs with a focus on non-polymeric functionalized compounds (perfluorooctanoic acid and perfluorooctanesulfonic acid)^2,3,4, a general PFAS destruction method coupled with fluorine recovery for upcycling is highly desirable. Here we disclose a protocol that converts multiple classes of PFAS, including the fluoroplastics polytetrafluoroethylene and polyvinylidene fluoride, into high-value fluorochemicals. To achieve this, PFASs were reacted with potassium phosphate salts under solvent-free mechanochemical conditions, a mineralization process enabling fluorine recovery as KF and K₂PO₃F for fluorination chemistry. The phosphate salts can be recovered for reuse, implying no detrimental impact on the phosphorus cycle. Therefore, PFASs are not only destructible but can now contribute to a sustainable circular fluorine economy.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"57 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713292","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":"Empower families to lead the design of their ageing loved ones’ health care","authors":"Shahmir H. Ali","doi":"10.1038/d41586-025-00893-8","DOIUrl":"10.1038/d41586-025-00893-8","url":null,"abstract":"Rather than assuming that relatives of older people will step up to fill systemic gaps in health care, communities need research and policies that align with families’ existing routines. Rather than assuming that relatives of older people will step up to fill systemic gaps in health care, communities need research and policies that align with families’ existing routines.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"639 8056","pages":"840-840"},"PeriodicalIF":50.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/d41586-025-00893-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703152","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":"STING agonist-based ER-targeting molecules boost antigen cross-presentation","authors":"Xiafeng Wang, Zhangping Huang, Lixiao Xing, Liru Shang, Juan Jiang, Caiguanxi Deng, Wei Yu, Lin Peng, Hao Yang, Xiaohong Zheng, Xinmin Liu, Haolan Yang, Yixin Chen, Yongyong Li, Jing Liu, Xi Xie, Wei Xu, Xiaojun Xia, Zezhong Liu, Wanli Liu, Shibo Jiang, Yingyue Zeng, Lu Lu, Ji Wang","doi":"10.1038/s41586-025-08758-w","DOIUrl":"https://doi.org/10.1038/s41586-025-08758-w","url":null,"abstract":"<p>CD8⁺ T cell immune responses are critical for combating infectious diseases and tumours^1,2,3. Antigen cross-presentation, primarily occurring at the endoplasmic reticulum (ER) of dendritic cells, is essential for protein-based vaccines to induce CD8⁺ T cell responses⁴. Current efforts have focused on antigen delivery at the tissue and cellular levels, whereas subcellular delivery has been limited to facilitating antigen escape from lysosomes into the cytosol. In the absence of a small-sized high-affinity ER-targeting molecule, the importance of the ‘last mile’ from the cytosol to the ER remains elusive. Here we developed stimulator of interferon genes (STING) agonist-based ER-targeting molecules (SABER), which effectively deliver antigens to the ER and cluster key machinery in cross-presentation to form microreactors by folding the ER membrane. Conjugation of SABER to various antigens substantially enhances the induction of CD8⁺ T cell immune responses to tumour neoantigens and conserved viral epitopes, far exceeding that achieved by mixtures of antigens with STING agonists or conventional adjuvants. SABER also retains a potent adjuvant effect, effectively enhancing the ability of a SARS-CoV-2 subunit vaccine to induce broadly neutralizing antibodies. This study provides a high-affinity ER-targeting delivery system and vaccine adjuvant, demonstrating that precise subcellular delivery targeting the last mile of cross-presentation can lead to a qualitative leap.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"183 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713304","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":"The full lethal impact of massive cuts to international food aid","authors":"Saskia Osendarp, Marie Ruel, Emorn Udomkesmalee, Masresha Tessema, Lawrence Haddad","doi":"10.1038/d41586-025-00898-3","DOIUrl":"https://doi.org/10.1038/d41586-025-00898-3","url":null,"abstract":"The sudden withdrawal of almost half of global funding for nutrition suddenly will have dire consequences for decades.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"57 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703147","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":"Some assembly required","authors":"","doi":"10.1038/d41586-025-00922-6","DOIUrl":"https://doi.org/10.1038/d41586-025-00922-6","url":null,"abstract":"The personal touch.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"29 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703352","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":"AI is transforming peer review — and many scientists are worried","authors":"Miryam Naddaf","doi":"10.1038/d41586-025-00894-7","DOIUrl":"10.1038/d41586-025-00894-7","url":null,"abstract":"Artificial intelligence software is increasingly involved in reviewing papers, provoking interest and unease. Artificial intelligence software is increasingly involved in reviewing papers, provoking interest and unease.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"639 8056","pages":"852-854"},"PeriodicalIF":50.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/d41586-025-00894-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703156","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":"irCLIP-RNP and Re-CLIP reveal patterns of dynamic protein assemblies on RNA","authors":"Luca Ducoli, Brian J. Zarnegar, Douglas F. Porter, Robin M. Meyers, Weili Miao, Nicholas M. Riley, Suhas Srinivasan, Leandra V. Jackrazi, Yen-Yu Yang, Zhouxian Li, Yinsheng Wang, Carolyn R. Bertozzi, Ryan A. Flynn, Paul A. Khavari","doi":"10.1038/s41586-025-08787-5","DOIUrl":"https://doi.org/10.1038/s41586-025-08787-5","url":null,"abstract":"<p>RNA-binding proteins (RBPs) control varied processes, including RNA splicing, stability, transport and translation^1,2,3. Dysfunctional RNA–RBP interactions contribute to the pathogenesis of human disease^1,4,5; however, characterizing the nature and dynamics of multiprotein assemblies on RNA has been challenging. Here, to address this, non-isotopic ligation-based ultraviolet-light-induced cross-linking and immunoprecipitation⁶ was combined with mass spectrometry (irCLIP-RNP) to identify RNA-dependent associated proteins (RDAPs) co-bound to RNA with any RBP of interest. irCLIP-RNP defined landscapes of multimeric protein assemblies on RNA, revealing patterns of RBP–RNA associations, including cell-type-selective combinatorial relationships between RDAPs and primary RBPs. irCLIP-RNP also defined dynamic RDAP remodelling in response to epidermal growth factor (EGF), revealing that EGF-induced recruitment of UPF1 adjacent to HNRNPC promotes splicing surveillance of cell proliferation mRNAs. To identify the RNAs simultaneously co-bound by multiple studied RBPs, a sequential immunoprecipitation irCLIP (Re-CLIP) method was also developed. Re-CLIP confirmed binding relationships observed in irCLIP-RNP and identified HNRNPC and UPF1 RBP co-binding on <i>RND3</i> and <i>DDX3X</i> mRNAs. irCLIP-RNP and Re-CLIP provide a framework to identify and characterize dynamic RNA–protein assemblies in living cells.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"22 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713167","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}