Science最新文献

{"title":"Intermetallic nanoassemblies potentiate systemic STING activation","authors":"Xingwu Zhou,&nbsp;Xiang Ling,&nbsp;Xiaoqi Sun,&nbsp;Ziye Wan,&nbsp;Tobias Dwyer,&nbsp;Timothy C. Moore,&nbsp;Quguang Li,&nbsp;Hannah E. Dobson,&nbsp;Qi Wu,&nbsp;Xiangbo Kong,&nbsp;Fang Xie,&nbsp;Xinran An,&nbsp;Jingyao Gan,&nbsp;Kaikai Wang,&nbsp;Young Seok Cho,&nbsp;Wang Gong,&nbsp;Katherine Dong,&nbsp;Jie Zhang,&nbsp;Mariko Takahashi,&nbsp;Cheng Xu,&nbsp;Swetha Kodamasimham,&nbsp;Jie Xu,&nbsp;Vilma Yuzbasiyan-Gurkan,&nbsp;Steven B. Chinn,&nbsp;Anna Schwendeman,&nbsp;Sharon C. Glotzer,&nbsp;Yu Leo Lei,&nbsp;James J. Moon","doi":"10.1126/science.adx1893","DOIUrl":"10.1126/science.adx1893","url":null,"abstract":"<div >Natural systems use metal ions to form ordered structures that regulate biological processes, inspiring the rational design of nanotherapeutics. The cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS-STING) pathway drives antitumor immunity but has been difficult to activate systemically owing to poor pharmacology and toxicity. Here, we report CRYSTAL, a structurally ordered intermetallic nanoparticle for potent systemic STING activation. CRYSTAL self-assembles from manganese ions intercalated with cyclic dinucleotides, enabling precise structural control. At an ultralow intravenous dose (0.003 milligrams per kilogram), CRYSTAL activated STING in mice, dogs, and nonhuman primates without cytokine release syndrome. CRYSTAL induced robust tumor regression in advanced murine and rabbit models, remodeled immunosuppressive environments, and promoted host STING–dependent CD8⁺ T cell priming. CRYSTAL activated interferon responses in human head and neck squamous cell carcinoma biopsies, underscoring its translational potential for cancer immunotherapy.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827804","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":"After pulling vaccine study, CDC leader calls for new journal.","authors":"Jon Cohen","doi":"10.1126/science.aei6151","DOIUrl":"https://doi.org/10.1126/science.aei6151","url":null,"abstract":"<p><p>Jay Bhattacharya clashes with epidemiologists over widely used design.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":"564-565"},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842169","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":"Biocatalytic cascades enable manufacture of the macrocyclic peptide enlicitide","authors":"Artis Klapars,&nbsp;Anna Fryszkowska,&nbsp;Stephanie Galanie,&nbsp;Omer Ad,&nbsp;Ellen Y. Aguilera,&nbsp;Nnamdi Akporji,&nbsp;Chihui An,&nbsp;Stephanus Axnanda,&nbsp;Tewoderos M. Ayele,&nbsp;Richard S. Ayikpoe,&nbsp;Rodell C. Barrientos,&nbsp;Matthew R. Bauerle,&nbsp;Marc R. Becker,&nbsp;Kevin M. Belyk,&nbsp;Lisa Bereznitski,&nbsp;Jackson K. B. Cahn,&nbsp;Karla Camacho Soto,&nbsp;Louis-Charles Campeau,&nbsp;Kevin R. Campos,&nbsp;Anagha Chandra,&nbsp;Hsieh Yao Darryl Chang,&nbsp;Mengbin Chen,&nbsp;Zhiwei Chen,&nbsp;Wai Ling Cheung-Lee,&nbsp;Cheol K. Chung,&nbsp;Stephanie W. Chun,&nbsp;Sarah S. Co,&nbsp;Ryan D. Cohen,&nbsp;Stephen M. Dalby,&nbsp;Guilherme Dal Poggetto,&nbsp;Truc Do,&nbsp;Spencer D. Dreher,&nbsp;Riki J. Drout,&nbsp;Noah P. Dunham,&nbsp;Yi Fan,&nbsp;Ryan M. Flessner,&nbsp;Jacob H. Forstater,&nbsp;Scott P. France,&nbsp;Janaka C. Gamekkanda,&nbsp;Donald R. Gauthier Jr.,&nbsp;Agnieszka A. Gil,&nbsp;Jacob W. Greenwood,&nbsp;Noel Ha,&nbsp;Holst M. Halsey,&nbsp;Xinxin Han,&nbsp;Michael Hartmann,&nbsp;Clara Hartmanshenn,&nbsp;Yu He,&nbsp;Edgar Hernandez,&nbsp;Kaori Hiraga,&nbsp;Hsing-I Ho,&nbsp;Cynthia M. Hong,&nbsp;Alan Hruza,&nbsp;Hang Hu,&nbsp;Kari Hullen,&nbsp;Alan M. Hyde,&nbsp;Tetsuji Itoh,&nbsp;Chey M. Jones,&nbsp;Woo-Ok Jung,&nbsp;Kanan Kanuga,&nbsp;James Levi Knippel,&nbsp;Joshua N. Kolev,&nbsp;Jongrock Kong,&nbsp;Birgit Kosjek,&nbsp;Sara Koynov,&nbsp;Michael H. Kress,&nbsp;Bharath Krishnamurthi,&nbsp;Jeffrey T. Kuethe,&nbsp;Thomas T. Kwok,&nbsp;Alfred Y. Lee,&nbsp;Joshua Lee,&nbsp;Qiuhan Li,&nbsp;Shasha Li,&nbsp;Jing Liao,&nbsp;Wenjun Liu,&nbsp;Gurpreet Longia,&nbsp;Emma Madrigal,&nbsp;Peter E. Maligres,&nbsp;Kevin M. Maloney,&nbsp;Erin L. McCarthy,&nbsp;John A. McIntosh,&nbsp;Samaneh Mesbahi-Vasey,&nbsp;Margaret Miller,&nbsp;Mansi Modi,&nbsp;Jeffrey C. Moore,&nbsp;Debopreeti Mukherjee,&nbsp;Grant S. Murphy,&nbsp;Jennifer Victoriano Obligacion,&nbsp;Weilan Pan,&nbsp;Julia Parzecki,&nbsp;Anisha Patel,&nbsp;Teng Peng,&nbsp;Byron K. Peters,&nbsp;Tiffany Piou,&nbsp;Carlos A. Pons Siepermann,&nbsp;Christopher K. Prier,&nbsp;Akasha K. Purohit,&nbsp;Yangzhong Qin,&nbsp;Erik L. Regalado,&nbsp;Mikhail Reibarkh,&nbsp;Nelo R. Rivera,&nbsp;Sandra A. Robaire,&nbsp;Lee Robison,&nbsp;Syamantak Roy,&nbsp;Rebecca T. Ruck,&nbsp;Katie A. Rykaczewski,&nbsp;Christopher H. Schuster,&nbsp;Erica L. Schwalm,&nbsp;Andrew N. Singh,&nbsp;Eric Sirota,&nbsp;Alexandra C. Sun,&nbsp;Weijuan Tang,&nbsp;David A. Thaisrivongs,&nbsp;Nimisha Thakur,&nbsp;Weidong Tong,&nbsp;Van Truong,&nbsp;Ryan Tsoi,&nbsp;Qiang Tu,&nbsp;Ben W. H. Turnbull,&nbsp;Ophelia Ukaegbu,&nbsp;David A. Vargas,&nbsp;Juan E. Velasquez,&nbsp;Deeptak Verma,&nbsp;Heather Wang,&nbsp;Tao Wang,&nbsp;Xiao Wang,&nbsp;Ying Wang,&nbsp;Zhixun Wang,&nbsp;Matthew S. Winston,&nbsp;Chunyu Wu,&nbsp;Brian M. Wyvratt,&nbsp;Kai-Jiong Xiao,&nbsp;Yingju Xu,&nbsp;Jia-Xuan Yan,&nbsp;Hao Yang,&nbsp;Victoria Zhang,&nbsp;Yongqian Zhang,&nbsp;Michelle Zheng,&nbsp;Wendy Zhong","doi":"10.1126/science.aed8713","DOIUrl":"10.1126/science.aed8713","url":null,"abstract":"<div >Historically, many compelling therapeutic targets have been accessible only by injectable biologic drugs. Macrocyclic peptides, such as the proprotein convertase subtilisin/kexin type 9 inhibitor enlicitide for the treatment of atherosclerotic cardiovascular disease, are beginning to unlock these targets to orally administered therapies to enable broader patient access. We report the convergent biocatalytic assembly of enlicitide from simple building blocks enabled by a suite of engineered enzymes to catalyze selective peptide fragment formation, coupling, and macrocyclization in a protecting group–free manner. Together with efficient crystallizations that obviate the need for chromatography, this approach reduces the number of steps by greater than half compared with prior state-of-the-art methods, addressing long-standing synthetic challenges and offering a sustainable blueprint for the scalable development of complex peptide therapeutics.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827815","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":"Arrest of Fauci aide for records violations decried as political.","authors":"Jon Cohen","doi":"10.1126/science.aei6152","DOIUrl":"https://doi.org/10.1126/science.aei6152","url":null,"abstract":"<p><p>David Morens's indictment centers on help he gave nonprofit that funded China research blamed for pandemic.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":"565-566"},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842195","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":"Tuft dendrites in frontal motor cortex enable flexible learning","authors":"Eduardo Maristany de las Casas,&nbsp;Kris Killmann,&nbsp;Moritz Drüke,&nbsp;Lukas Münster,&nbsp;Christian Ebner,&nbsp;Robert Sachdev,&nbsp;Dieter Jaeger,&nbsp;Matthew E. Larkum","doi":"10.1126/science.adx4358","DOIUrl":"10.1126/science.adx4358","url":null,"abstract":"<div >Flexible learning relies on integrating sensory and contextual information to adjust behavioral output in different environments. The anterolateral motor cortex (ALM) is a frontal area critical for action selection in rodents. We found that inputs critical to decision-making converge on the apical tuft dendrites of layer 5b pyramidal neurons in ALM. We therefore investigated the role of these dendrites in a rule-switching paradigm. Activation of dendrite-inhibiting layer 1 interneurons impaired relearning, without affecting previously learned behavior. This inhibition profoundly suppressed global calcium activity in dendritic shafts but not local transients in spines, while additionally reducing burst firing. Moreover, excitatory synaptic inputs to tuft dendrites exhibited rule-dependent clustering. We conclude that dendritic calcium signaling is a key computational component of flexible learning.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827812","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":"Safeguard water infrastructure amid conflict","authors":"Xue Xiao,&nbsp;Yichen Tao","doi":"10.1126/science.aeh5255","DOIUrl":"10.1126/science.aeh5255","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827821","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":"Forecasting volcanic eruptions across scales","authors":"Magnús T. Gudmundsson,&nbsp;Christopher J. Bean","doi":"10.1126/science.adn6821","DOIUrl":"10.1126/science.adn6821","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827825","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":"Data-driven decisions in a fast-and-loose world","authors":"Jonathan Wai","doi":"10.1126/science.aef6641","DOIUrl":"10.1126/science.aef6641","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827809","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":"Climate-induced range shifts support local plant diversity but don’t reduce extinction risk","authors":"Junna Wang,&nbsp;Brunno F. Oliveira,&nbsp;Frances C. Moore,&nbsp;Daniel J. Kozar,&nbsp;Yongshuo Fu,&nbsp;Xiaoli Dong","doi":"10.1126/science.aea1676","DOIUrl":"10.1126/science.aea1676","url":null,"abstract":"<div >Climate change is driving widespread plant range shifts, yet their consequences for extinction and biodiversity remain unclear as realistic range shift dynamics have rarely been incorporated into global-scale biodiversity models. We integrate species-specific range shift velocities into species distribution models to project distributions of 67,664 plant species (18% of all global flora) by 2081 to 2100. Across emissions scenarios, 7 to 16% of species are projected to lose &gt;90% of their range, placing them at high risk of extinction. These losses are driven primarily by climate-induced habitat loss, rather than dispersal limitation. Although range shifts offer little relief from global extinctions, they are projected to increase local plant richness across 28% of Earth’s land. Facilitating range shifts may thus sustain local richness but not reduce global extinctions.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827816","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 scientist agents violate research integrity rules.","authors":"Nicola Jones","doi":"10.1126/science.aei6154","DOIUrl":"https://doi.org/10.1126/science.aei6154","url":null,"abstract":"<p><p>Advanced AI systems are shown to make up data and \"p-hack\" their results.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":"569"},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842172","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}