Science Advances最新文献

Identification and targeting of regulators of SARS-CoV-2–host interactions in the airway epithelium 呼吸道上皮中sars - cov -2 -宿主相互作用调节因子的鉴定和靶向

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.adu2079

Brooke Dirvin, Heeju Noh, Lorenzo Tomassoni, Danting Cao, Yizhuo Zhou, Xiangyi Ke, Jun Qian, Sonia Jangra, Michael Schotsaert, Adolfo García-Sastre, Charles Karan, Andrea Califano, Wellington V. Cardoso

{"title":"Identification and targeting of regulators of SARS-CoV-2–host interactions in the airway epithelium","authors":"Brooke Dirvin, Heeju Noh, Lorenzo Tomassoni, Danting Cao, Yizhuo Zhou, Xiangyi Ke, Jun Qian, Sonia Jangra, Michael Schotsaert, Adolfo García-Sastre, Charles Karan, Andrea Califano, Wellington V. Cardoso","doi":"10.1126/sciadv.adu2079","DOIUrl":"10.1126/sciadv.adu2079","url":null,"abstract":"<div >The impact of SARS-CoV-2 in the lung has been extensively studied, yet the molecular regulators of host-cell programs hijacked by the virus in distinct human airway epithelial cell populations remain poorly understood. Some of the reasons include overreliance on transcriptomic profiling and use of nonprimary cell systems. Here we report a network-based analysis of single-cell transcriptomic profiles able to identify master regulator (MR) proteins controlling SARS-CoV-2–mediated reprogramming in pathophysiologically relevant human ciliated, secretory, and basal cells. This underscored chromatin remodeling, endosomal sorting, ubiquitin pathways, as well as proviral factors identified by CRISPR assays as components of the viral-host response in these cells. Large-scale drug perturbation screens revealed 11 candidate drugs able to invert the entire MR signature activated by SARS-CoV-2. Leveraging MR analysis and perturbational profiles of human primary cells represents an innovative approach to investigate pathogen-host interactions in multiple airway conditions for drug prioritization.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu2079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074828","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

Structure of a photosystem I supercomplex from Galdieria sulphuraria close to an ancestral red alga 硫藻光系统I超复合体的结构，接近一种祖先红藻

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.adv7488

Koji Kato, Minoru Kumazawa, Yoshiki Nakajima, Takehiro Suzuki, Naoshi Dohmae, Jian-Ren Shen, Kentaro Ifuku, Ryo Nagao

{"title":"Structure of a photosystem I supercomplex from Galdieria sulphuraria close to an ancestral red alga","authors":"Koji Kato, Minoru Kumazawa, Yoshiki Nakajima, Takehiro Suzuki, Naoshi Dohmae, Jian-Ren Shen, Kentaro Ifuku, Ryo Nagao","doi":"10.1126/sciadv.adv7488","DOIUrl":"10.1126/sciadv.adv7488","url":null,"abstract":"<div >Red algae exhibit unique photosynthetic adaptations, characterized by photosystem I (PSI) supercomplexes containing light-harvesting complexes (LHCs), forming PSI-LHCI supercomplexes. In this study, we solved the PSI-LHCI structure of <i>Galdieria sulphuraria</i> NIES-3638 at 2.19-angstrom resolution using cryo–electron microscopy, revealing a PSI monomer core associated with seven LHCI subunits. Structural analysis uncovered the absence of phylloquinones, the common secondary electron acceptor in PSI of photosynthetic organisms, suggesting adaptation to a benzoquinone-like molecule. Phylogenetic analysis suggests that <i>G. sulphuraria</i> retains traits characteristic of an ancestral red alga, including distinctive LHCI binding and interaction patterns. Variations in LHCI composition and interactions across red algae, particularly in red-lineage chlorophyll <i>a</i>/<i>b</i>–binding–like protein and red algal LHCs, highlight evolutionary divergence and specialization. These findings not only deepen our understanding of red algal PSI-LHCI diversification but also enable us to predict features of an ancestral red algal PSI-LHCI supercomplex, providing a framework to explore evolutionary adaptations from an ancestral red alga.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv7488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074817","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

Nucleosomes represent a crucial target for the intra-S phase checkpoint in response to replication stress 核小体是响应复制应激的s期内检查点的关键靶点

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.adr3673

Xiaoqin Liu, Bo Zhang, Yu Hua, Chuanqi Li, Xizhou Li, Daochun Kong

{"title":"Nucleosomes represent a crucial target for the intra-S phase checkpoint in response to replication stress","authors":"Xiaoqin Liu, Bo Zhang, Yu Hua, Chuanqi Li, Xizhou Li, Daochun Kong","doi":"10.1126/sciadv.adr3673","DOIUrl":"10.1126/sciadv.adr3673","url":null,"abstract":"<div >The intra-S phase checkpoint is essential for stability of stalled DNA replication forks. However, the mechanisms underlying checkpoint regulation remain poorly understood. This study identifies a critical checkpoint target—the ubiquitin E3 ligase Brl2, revealing a new dimension of checkpoint regulation. Upon replication fork stalling, Brl2 undergoes phosphorylation at five serine residues by Cds1<sup>Chk2</sup> kinase, resulting in the loss of its ligase activity and a marked reduction in H2BK119ub1 levels. In the <i>brl2-5D</i> (the five serine residues are replaced with aspartic acid) and <i>htb-K119R</i> mutants, chromatin becomes highly compacted. Furthermore, the rates of stalled replication fork collapse, and dsDNA breaks are significantly reduced in <i>brl2-5D cds1<sup>Chk2</sup></i>∆ cells compared to <i>cds1<sup>Chk2</sup></i>∆ cells. Thus, this study demonstrates that nucleosomes are targeted by the intra-S phase checkpoint and highlights the checkpoint’s critical role in configuring compact chromatin structures at replication fork stalling sites. These findings may explain why ATR and Chk1 are essential for cell proliferation and embryonic development, while ATM is not.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr3673","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074790","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

Upgraded circular single-stranded DNA regulators for multiple-input multiple-output gene circuits in mammalian cells 哺乳动物细胞中用于多输入多输出基因回路的升级环状单链DNA调控因子

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.adv3396

Linlin Tang, Jinghao Wang, Kaiqi Xu, Zhen Li, Jie Song

{"title":"Upgraded circular single-stranded DNA regulators for multiple-input multiple-output gene circuits in mammalian cells","authors":"Linlin Tang, Jinghao Wang, Kaiqi Xu, Zhen Li, Jie Song","doi":"10.1126/sciadv.adv3396","DOIUrl":"10.1126/sciadv.adv3396","url":null,"abstract":"<div >Synthetic gene networks hold promise for genetic diagnostics and gene therapy but face limitations due to insufficient molecular tools. Gene-encoded circular single-stranded DNA (Css DNA) has been developed as a switchable vector to enrich regulatory components beyond protein/RNA-based systems in mammalian cells. However, the previous Css DNA regulator suffered from constrained regulatory sequence flexibility, disability of multiple-input multiple-output (MIMO) signals, and lack of endogenous orthogonal regulation. Here, we address these challenges by engineering a “bridge” design into the Css DNA regulator. These bridges function as sequence-programmable switches to control gene expression, responding to endogenous molecular signals (such as ATP, APE1, and RNase H) and enabling trans-regulation within or between Css DNAs. We exploit the orthogonality of Css DNA regulator to construct the three-input three-output genetic circuits. The upgraded Css DNA–based regulatory strategy represents a versatile and powerful platform for gene regulation and provides a promising avenue for the development of synthetic gene networks.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv3396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074792","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

Engineered high endurance in WO3-based resistive switching devices via a guided filament approach 通过导丝方法在wo3基电阻开关器件中设计了高耐用性

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.adt9789

Ziyi Yuan, Babak Bakhit, Yi-Xuan Liu, Zhuotong Sun, Giulio I. Lampronti, Xinjuan Li, Simon M. Fairclough, Benson K. Tsai, Abhijeet Choudhury, Caterina Ducati, Haiyan Wang, Markus Hellenbrand, Judith L. MacManus-Driscoll

{"title":"Engineered high endurance in WO3-based resistive switching devices via a guided filament approach","authors":"Ziyi Yuan, Babak Bakhit, Yi-Xuan Liu, Zhuotong Sun, Giulio I. Lampronti, Xinjuan Li, Simon M. Fairclough, Benson K. Tsai, Abhijeet Choudhury, Caterina Ducati, Haiyan Wang, Markus Hellenbrand, Judith L. MacManus-Driscoll","doi":"10.1126/sciadv.adt9789","DOIUrl":"10.1126/sciadv.adt9789","url":null,"abstract":"<div >Resistive switching devices are promising candidates for the next generation of nonvolatile memory and neuromorphic computing applications. Despite the advantages in retention and on/off ratio, filamentary-based memristors still suffer from challenges, particularly endurance (flash being a benchmark system showing 10<sup>4</sup> to 10<sup>6</sup> cycles) and uniformity. Here, we use WO<sub>3</sub> as a complementary metal-oxide semiconductor–compatible switching oxide and demonstrate a proof-of-concept materials design approach to enhance endurance and device-to-device uniformity in WO<sub>3</sub>-based memristive devices while preserving other performance metrics. These devices show stable resistive switching behavior with >10<sup>6</sup> cycles, >10<sup>5</sup>-second retention, >10 on/off ratio, and good device-to-device uniformity, without using current compliance. All these metrics are achieved using a one-step pulsed laser deposition process to create self-assembled nanocomposite thin films that have regular guided filaments of ≈100-nanometer pitch, preformed between WO<sub>3</sub> grains and interspersed smaller Ce<sub>2</sub>O<sub>3</sub> grains.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt9789","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074813","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

A skin-mimicking multifunctional hydrogel via hierarchical, reversible noncovalent interactions 一种模拟皮肤的多功能水凝胶，通过分层，可逆的非共价相互作用

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.adv8523

Xingkui Guo, Songlin Zhang, Shubham Patel, Xiaolu Sun, You-Liang Zhu, Zechang Wei, Rongguo Wang, Xiaodong He, Zuankai Wang, Cunjiang Yu, Swee Ching Tan

{"title":"A skin-mimicking multifunctional hydrogel via hierarchical, reversible noncovalent interactions","authors":"Xingkui Guo, Songlin Zhang, Shubham Patel, Xiaolu Sun, You-Liang Zhu, Zechang Wei, Rongguo Wang, Xiaodong He, Zuankai Wang, Cunjiang Yu, Swee Ching Tan","doi":"10.1126/sciadv.adv8523","DOIUrl":"10.1126/sciadv.adv8523","url":null,"abstract":"<div >Artificial skin is essential for bionic robotics, facilitating human skin–like functions such as sensation, communication, and protection. However, replicating a skin-matched all-in-one material with excellent mechanical properties, self-healing, adhesion, and multimodal sensing remains a challenge. Herein, we developed a multifunctional hydrogel by establishing a consolidated organic/metal bismuth ion architecture (COMBIA). Benefiting from hierarchical reversible noncovalent interactions, the COMBIA hydrogel exhibits an optimal combination of mechanical and functional properties, particularly its integrated mechanical properties, including unprecedented stretchability, fracture toughness, and resilience. Furthermore, these hydrogels demonstrate superior conductivity, optical transparency, freezing tolerance, adhesion capability, and spontaneous mechanical and electrical self-healing. These unified functions render our hydrogel exceptional properties such as shape adaptability, skin-like perception, and energy harvesting capabilities. To demonstrate its potential applications, an artificial skin using our COMBIA hydrogel was configured for stimulus signal recording, which, as a promising soft electronics platform, could be used for next-generation human-machine interfaces.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv8523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074829","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: “Four SpsP neurons are an integrating sleep regulation hub in Drosophila” by X. Dai et al. X. Dai等人的研究文章“四个SpsP神经元是果蝇的一个整合睡眠调节中心”的校误。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.ady4857

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Agulhas rings locally enhance dissipation of internal tides 阿古拉斯环局部增强了内部潮汐的消散

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.adq5963

Yang Wang, Sonya Legg

引用次数: 0

Mid-infrared group IV nanowire laser 中红外四族纳米线激光器

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.adt6723

Youngmin Kim, Simone Assali, Junyu Ge, Sebastian Koelling, Manlin Luo, Lu Luo, Hyo-Jun Joo, James Tan, Xuncheng Shi, Zoran Ikonic, Hong Li, Oussama Moutanabbir, Donguk Nam

{"title":"Mid-infrared group IV nanowire laser","authors":"Youngmin Kim, Simone Assali, Junyu Ge, Sebastian Koelling, Manlin Luo, Lu Luo, Hyo-Jun Joo, James Tan, Xuncheng Shi, Zoran Ikonic, Hong Li, Oussama Moutanabbir, Donguk Nam","doi":"10.1126/sciadv.adt6723","DOIUrl":"10.1126/sciadv.adt6723","url":null,"abstract":"<div >Semiconductor nanowires have shown great potential for enabling ultracompact lasers for integrated photonics platforms. Despite the impressive progress in developing nanowire lasers, their integration into Si photonics platforms remains challenging largely because of the use of III-V and II-VI semiconductors as gain media. Recently, group IV nanowires, particularly direct bandgap GeSn nanowires capable of emitting above 2 μm, have emerged as promising cost-effective gain media for Si-compatible nanowire lasers, but there has been no successful demonstration of lasing from this seemingly promising nanowire platform. Herein, we report the experimental observation of lasing above 2 μm from a single bottom-up grown GeSn nanowire. By harnessing strain engineering and optimized cavity designs simultaneously, the single GeSn nanowire achieves an amplified material gain that can sufficiently overcome minimized optical losses, resulting in single-mode lasing with an ultralow threshold of ~5.3 kilowatts per square centimeter. Our finding paves the way for all–group IV mid-infrared photonic-integrated circuits with Si-compatible lasers for on-chip classical and quantum applications.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt6723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074755","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

Should we think of observationally constrained multidecade climate projections as predictions? 我们应该把受观测限制的几十年气候预测视为预测吗？

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.adt6485

Tong Li, Francis W. Zwiers, Xuebin Zhang

{"title":"Should we think of observationally constrained multidecade climate projections as predictions?","authors":"Tong Li, Francis W. Zwiers, Xuebin Zhang","doi":"10.1126/sciadv.adt6485","DOIUrl":"10.1126/sciadv.adt6485","url":null,"abstract":"<div >Empirical evidence indicates that the range of model-projected future warming can be successfully narrowed by conditioning the projected warming on past observed warming. We demonstrate that warming projections conditioned on the entire instrumental annual surface temperature record are of sufficiently high quality and should be considered as long-term predictions rather than merely as projections. We support this view by considering the skill of predicted 20- and 50-year lead temperature changes under the Shared Economic Pathway (SSP)1-2.6 and SSP5-8.5 emission scenarios in climates of different sensitivities. Using climate model simulations, we show that adjusting raw multimodel projections of future warming with the Kriging for Climate Change (KCC) method eliminates most biases and reduces the uncertainty of warming projections irrespective of the sensitivity of the climate being considered. Simpler methods, or using only the more recent part of the temperature record, provide less effective constraints. The high-skill future warming predictions obtained via KCC have a serious place in informing global climate policies.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt6485","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074791","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