Science Advances最新文献_第9页

Organocatalyzed atroposelective dynamic kinetic resolutions via transient seven-membered cyclic hemiacetals 瞬态七元环半缩醛的有机催化atroopselective动力学分解

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-03 DOI: 10.1126/sciadv.adx8255

Qinglong Zhou, Yuhang Chen, Wei Yuan, Sai Vikrama Chaitanya Vummaleti, Xinyue Xiang, Bowen Zhu, Yonggui Robin Chi, Xinglong Zhang, Xing Yang

{"title":"Organocatalyzed atroposelective dynamic kinetic resolutions via transient seven-membered cyclic hemiacetals","authors":"Qinglong Zhou, Yuhang Chen, Wei Yuan, Sai Vikrama Chaitanya Vummaleti, Xinyue Xiang, Bowen Zhu, Yonggui Robin Chi, Xinglong Zhang, Xing Yang","doi":"10.1126/sciadv.adx8255","DOIUrl":"10.1126/sciadv.adx8255","url":null,"abstract":"<div >Catalytic atroposelective dynamic kinetic resolution via the formation of transient bridged biaryl intermediates represents an expedient route for the synthesis of axially chiral biaryls. Progress in this field has been limited to the reactions promoted by bridged biaryl intermediates with five- or six-membered rings. Herein we demonstrate the first example of a carbene-catalyzed atroposelective dynamic kinetic acylation reaction via transient seven-membered cyclic hemiacetals. The key for the success of this reaction relies on the formation and configurational instability of the transient seven-membered cyclic hemiacetal intermediate. The axially chiral biaryl aldehyde products obtained via this method can undergo a series of further transformations. Notably, one of the axially chiral biaryl aldehyde products can be used as the key and common intermediate for the asymmetric synthesis of natural product steganone. Preliminary density functional theory calculations reveal the molecular origins underlying the observed chemo- and enantioselectivity outcomes.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 40","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx8255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209985","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}

引用次数: 0

Secretory IgA amplification during immune checkpoint blockade enhances the control of tumor growth by enterotropic T cells 免疫检查点阻断期间分泌的IgA扩增增强了嗜肠性T细胞对肿瘤生长的控制

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-03 DOI: 10.1126/sciadv.aeb5308

Benedetta De Ponte Conti, Rebecca Marino, Tanja Rezzonico-Jost, Mattia Forcato, Davide Mangani, Elisabetta Notario, Giorgio Gargari, Elena Carelli, Andrea Rinaldi, Andrea Raimondi, Simone Moro, Marinella Marzano, Grazia Visci, Lisa Perruzza, Matteo Raneri, Denise Dallavalle, Giacomo Mantegazza, Ludovica Montani, Francesco Prisco, Roshan Takur, Jens Geginat, Frauke Seehusen, Samuele Notarbartolo, Graziano Pesole, Silvio Bicciato, Simone Guglielmetti, Fabio Grassi

{"title":"Secretory IgA amplification during immune checkpoint blockade enhances the control of tumor growth by enterotropic T cells","authors":"Benedetta De Ponte Conti, Rebecca Marino, Tanja Rezzonico-Jost, Mattia Forcato, Davide Mangani, Elisabetta Notario, Giorgio Gargari, Elena Carelli, Andrea Rinaldi, Andrea Raimondi, Simone Moro, Marinella Marzano, Grazia Visci, Lisa Perruzza, Matteo Raneri, Denise Dallavalle, Giacomo Mantegazza, Ludovica Montani, Francesco Prisco, Roshan Takur, Jens Geginat, Frauke Seehusen, Samuele Notarbartolo, Graziano Pesole, Silvio Bicciato, Simone Guglielmetti, Fabio Grassi","doi":"10.1126/sciadv.aeb5308","DOIUrl":"10.1126/sciadv.aeb5308","url":null,"abstract":"<div >The gut microbiota is essential for many aspects of host physiology, and secretory immunoglobulin A (sIgA) modulates its function. The microbiota community determines the efficacy of immune checkpoint blockade (ICB) in cancer immunotherapy; however, mechanisms able to improve this function are not known. Extracellular adenosine triphosphate (ATP) released by the microbiota restricts the sIgA repertoire by limiting T follicular helper (T<sub>FH</sub>) cell activity in the Peyer’s patches via stimulation of the ionotropic P2X7 receptor. We show that sIgA amplification by oral administration of the ATP hydrolyzing enzyme apyrase corrects enteropathic features of ICB and improves therapeutic efficacy. Consistent with sIgA function in reshaping the gut ecosystem and enhancing ICB, <i>IgA<sup>−/−</sup></i> mice did not show any improvement of antitumor response by apyrase administration. Mechanistically, data in mice and patients with cancer suggest that invigorated enterotropic cytotoxic T cells expressing the chemokine receptor CCR9 replenish the tumor microenvironment in a CCL25-mediated manner and control tumor growth, resulting in improved ICB efficacy.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 40","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeb5308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209997","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}

引用次数: 0

The mechanistic basis of cargo selection during Golgi maturation 高尔基成熟过程中货物选择的机理基础

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-03 DOI: 10.1126/sciadv.aea0016

Rebecca J. Taylor, Nikita Zubkov, Katarzyna A. Ciazynska, Jonathan G. G. Kaufman, Grigory Tagiltsev, David J. Owen, John A. G. Briggs, Sean Munro

引用次数: 0

Chromosome architecture affects virulence and competitiveness in Agrobacterium tumefaciens C58 染色体结构影响农杆菌C58的毒力和竞争能力

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-03 DOI: 10.1126/sciadv.adx7408

Ephraim Aliu, Keunsub Lee, Ram Sanath-Kumar, Christopher Youngstrom, Lander Geadelmann, Dibyajyoti Pramanik, Qing Ji, Xindan Wang, Kan Wang

{"title":"Chromosome architecture affects virulence and competitiveness in Agrobacterium tumefaciens C58","authors":"Ephraim Aliu, Keunsub Lee, Ram Sanath-Kumar, Christopher Youngstrom, Lander Geadelmann, Dibyajyoti Pramanik, Qing Ji, Xindan Wang, Kan Wang","doi":"10.1126/sciadv.adx7408","DOIUrl":"10.1126/sciadv.adx7408","url":null,"abstract":"<div >Chromosome architecture plays a crucial role in bacterial adaptation, yet its direct impact remains unclear. Different bacterial species and even strains within the same species exhibit diverse chromosomal configurations, including a single circular or linear chromosome, two circular chromosomes, or a circular-linear combination. To investigate how these architectures shape bacterial behavior, we generated near-isogenic strains representing each configuration in <i>Agrobacterium tumefaciens</i> C58, an important soil bacterium widely used for plant genetic transformation. Strains with a single-chromosome architecture, whether linear or circular, exhibited faster growth, enhanced stress tolerance, and greater interstrain competitiveness. In contrast, bipartite chromosome strains showed higher virulence gene expression and enhanced transient plant transformation efficiency, suggesting a pathogenic adaptation. Whole-transcriptome analysis revealed architecture-dependent gene expression patterns, underscoring the profound impact of chromosome organization on <i>Agrobacterium</i> fitness and virulence. These findings highlight how chromosome structure influences bacterial adaptation and shapes evolutionary trajectories.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 40","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx7408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210013","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}

引用次数: 0

Erratum for the Research Article “A general temperature-guided language model to design proteins of enhanced stability and activity” by F. Jiang et al. F. Jiang等人的研究文章“设计增强稳定性和活性的蛋白质的通用温度引导语言模型”的勘误表。

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-03 DOI: 10.1126/sciadv.aeb7595

引用次数: 0

Translation landscape of stress granules 翻译景观应力颗粒

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-03 DOI: 10.1126/sciadv.ady6859

Yichun Wu, Xing Wang, Lingyu Meng, Zhizhao Liao, Wei Ji, Peipei Zhang, Jie Lin, Qiang Guo

引用次数: 0

Abnormal O-glycan sialylation in the mPFC contributes to depressive-like behaviors in male mice 在雄性小鼠中，mPFC中异常的o -聚糖唾液化与抑郁样行为有关

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-03 DOI: 10.1126/sciadv.ady2733

Youngsuk Seo, Inwoong Song, Ki Jung Kim, Bomi Chang, Prajitha Pradeep, Woo Suk Roh, Woojin Won, Jinhyeong Joo, Myeongju Kim, Jae Cheol Jeong, C. Justin Lee, Boyoung Lee

{"title":"Abnormal O-glycan sialylation in the mPFC contributes to depressive-like behaviors in male mice","authors":"Youngsuk Seo, Inwoong Song, Ki Jung Kim, Bomi Chang, Prajitha Pradeep, Woo Suk Roh, Woojin Won, Jinhyeong Joo, Myeongju Kim, Jae Cheol Jeong, C. Justin Lee, Boyoung Lee","doi":"10.1126/sciadv.ady2733","DOIUrl":"10.1126/sciadv.ady2733","url":null,"abstract":"<div >Depression presents challenges in understanding its biological basis and developing effective treatments. Posttranslational modifications provide critical insights into molecular mechanisms of disorders, yet their role in depression remains underexplored. Glycosylation has been particularly difficult to study due to its heterogeneous nature and analytical challenges, despite its potential to uncover previously unknown mechanisms. In this study, we demonstrate how chronic stress alters region-specific O-glycosylation across multiple brain regions, with a particular focus on the prefrontal cortex (PFC). Our findings reveal significant changes in sialylated O-glycosylation patterns mediated by <i>St3gal1</i>, a sialyltransferase essential for O-glycosylation. Notably, knockdown of <i>St3gal1</i> in nonstressed mice induced depressive-like behaviors, whereas its overexpression in stressed mice alleviated depressive symptoms, underscoring its regulatory role in stress resilience. In addition, we identify potential glycoprotein targets and downstream regulators of <i>St3gal1</i>, including neurexin 2 (NRXN2) in the medial PFC (mPFC), offering insights into molecular pathways linking O-glycosylation to depressive-like behaviors.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 40","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ady2733","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209984","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}

引用次数: 0

Attentional switching in larval zebrafish 斑马鱼幼体的注意力转换

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-03 DOI: 10.1126/sciadv.ads4994

Kumaresh Krishnan, Akila Muthukumar, Scott Sterrett, Paula Pflitsch, Adrienne L. Fairhall, Mark Fishman, Armin Bahl, Hanna Zwaka, Florian Engert

{"title":"Attentional switching in larval zebrafish","authors":"Kumaresh Krishnan, Akila Muthukumar, Scott Sterrett, Paula Pflitsch, Adrienne L. Fairhall, Mark Fishman, Armin Bahl, Hanna Zwaka, Florian Engert","doi":"10.1126/sciadv.ads4994","DOIUrl":"10.1126/sciadv.ads4994","url":null,"abstract":"<div >Decision-making strategies in the face of conflicting or uncertain sensory input have been successfully described in many species. We analyze large behavioral datasets of larval zebrafish engaged in a “coherent dot” optomotor assay and find that animal performance is bimodal. Performance can be separated into two “states”—an engaged (attentive) state with high performance, where fish consistently turn in the direction of coherent motion, and a second, disengaged (inattentive) state, where performance drops to chance. A hidden Markov model is sufficient to model these transitions and can be incorporated into a drift-diffusion model framework that has previously been used to model perceptual decision-making in larval zebrafish. Furthermore, we fit a mixture model of performance distributions and extract two latent variables termed “focus” and “competence” that are largely influenced by parents and environmental context, respectively. This quantitative framework can potentially help to identify a genetic basis and a neural mechanism for attention that extends across organisms.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 40","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads4994","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209993","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}

引用次数: 0

Water-flow electric-gating effect on a van der Waals surface 范德华表面的水流电门效应

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-03 DOI: 10.1126/sciadv.adx5747

Hua Kang, Yang Yue, Jiayu Liang, Xuejun Wang, Dingding Jiang, Hangyan Chen, Yunqi Liu, Qinghong Yuan, Dacheng Wei

{"title":"Water-flow electric-gating effect on a van der Waals surface","authors":"Hua Kang, Yang Yue, Jiayu Liang, Xuejun Wang, Dingding Jiang, Hangyan Chen, Yunqi Liu, Qinghong Yuan, Dacheng Wei","doi":"10.1126/sciadv.adx5747","DOIUrl":"10.1126/sciadv.adx5747","url":null,"abstract":"<div >Since the early 19th century, electric effects at fluid-solid interfaces have been widely studied, which primarily originate from migration of ions or their interactions with functional groups on solid surfaces. However, the intrinsic electric effect of moving water molecules on a pristine van der Waals surface has seldom been explored. Here, we find a water-flow electric-gating effect on graphene, WSe<sub>2</sub>, and MoS<sub>2</sub> without dangling bonds or functional groups. It is an intrinsic electric effect, different from a traditional ion-reliant or functional group–dependent fluid electrokinetic effect. On the basis of this finding, we develop a water-flow gated transistor (WGT) capable of transducing flow signals down to 600 nanometers per second into electrical signals, achieving a voltage responsivity up to 1.53 × 10<sup>4</sup> volts per meter-second, about two orders of magnitude higher than existing hydroelectronic devices. The WGTs can serve as a basic unit of hydroelectronics, enabling efficient signal transduction and logical calculation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 40","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx5747","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209999","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}

引用次数: 0

Mechanochemical waves in focal adhesions during cell migration 细胞迁移过程中局灶黏附中的机械化学波

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-03 DOI: 10.1126/sciadv.adw6425

Marc A. Fernández-Yagüe, Elijah N. Marquez, Chetan S. Poojari, Jianping Fu, Yingxiao Wang, Aránzazu del Campo, Andrés J. García

{"title":"Mechanochemical waves in focal adhesions during cell migration","authors":"Marc A. Fernández-Yagüe, Elijah N. Marquez, Chetan S. Poojari, Jianping Fu, Yingxiao Wang, Aránzazu del Campo, Andrés J. García","doi":"10.1126/sciadv.adw6425","DOIUrl":"10.1126/sciadv.adw6425","url":null,"abstract":"<div >Focal adhesions (FAs) are dynamic structures central to cell migration, serving as mechanotransduction sites linking the extracellular matrix (ECM) to intracellular signaling pathways such as FA kinase (FAK). How FAK becomes activated in response to cell-ECM adhesive forces at single FAs to facilitate directional motion is poorly understood. Using micropillar-based force microscopy and FA-targeted FRET biosensors, we monitored real-time traction forces and FAK activity at individual FAs during assembly and disassembly. Our results demonstrate oscillatory temporal coupling of traction force and FAK activity in high-tension FAs before FA disassembly. Cross-correlation analyses revealed that force precedes FAK activation, guiding FA turnover. Atomistic molecular simulations unveiled a force-induced mechanism where traction forces disrupt autoinhibitory FERM-kinase interactions in FAK, enabling catalytic activity without structural unfolding. Our findings provide mechanistic insights into the spatiotemporal integration of mechanical forces and biochemical signaling in cell migration.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 40","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adw6425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210000","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}

引用次数: 0