Science Advances最新文献_第5页

Large-scale experimental assessment of variant effects on the structure and function of the citrate transporter SLC13A5 柠檬酸转运体SLC13A5变异对其结构和功能影响的大规模实验评估

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-06-27

Wen-An Wang, Evandro Ferrada, Christoph Klimek, Tanja Osthushenrich, Aidan MacNamara, Tabea Wiedmer, Giulio Superti-Furga

{"title":"Large-scale experimental assessment of variant effects on the structure and function of the citrate transporter SLC13A5","authors":"Wen-An Wang, Evandro Ferrada, Christoph Klimek, Tanja Osthushenrich, Aidan MacNamara, Tabea Wiedmer, Giulio Superti-Furga","doi":"","DOIUrl":"","url":null,"abstract":"<div >Citrate is an essential metabolite playing critical roles in metabolism and as a neuromodulator during cellular differentiation and development. Mutations in the human citrate transporter SLC13A5, highly expressed in neurons, have been associated with a debilitating form of epileptic encephalopathy. In this study, we used deep mutational scanning to reveal the effect of 90% of all possible single missense variants on the structure and function of SLC13A5. Computational analyses and a detailed experimental validation of 38 variants revealed an accuracy of 86% and provided mechanistic interpretations for deleterious mutations, including the effect on protein stability, trafficking, and citrate transport. Analyses of blood citrate concentration from individuals enrolled in the UK Biobank study supported our analyses. The results illustrate an unbiased mutational landscape of the citrate transporter, illuminate mechanisms of pathogenicity, and offer a platform for the analysis of specific variants as well as opportunities for the future development of intervention strategies.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 26","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx3011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503331","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

Anisotropic strain relaxation-induced directional ultrafast carrier dynamics in RuO₂ films. RuO2薄膜中各向异性应变弛豫诱导的定向超快载流子动力学。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-06-27 DOI: 10.1126/sciadv.adw7125

Seung Gyo Jeong, In Hyeok Choi, Seungjun Lee, Jin Young Oh, Sreejith Nair, Jae Hyuck Lee, Changyoung Kim, Ambrose Seo, Woo Seok Choi, Tony Low, Jong Seok Lee, Bharat Jalan

{"title":"Anisotropic strain relaxation-induced directional ultrafast carrier dynamics in RuO2 films.","authors":"Seung Gyo Jeong, In Hyeok Choi, Seungjun Lee, Jin Young Oh, Sreejith Nair, Jae Hyuck Lee, Changyoung Kim, Ambrose Seo, Woo Seok Choi, Tony Low, Jong Seok Lee, Bharat Jalan","doi":"10.1126/sciadv.adw7125","DOIUrl":"10.1126/sciadv.adw7125","url":null,"abstract":"Ultrafast light-matter interactions inspire potential functionalities in picosecond optoelectronic applications. However, achieving directional carrier dynamics in metals remains challenging due to strong carrier scattering within a multiband environment, typically expected for isotropic carrier relaxation. In this study, we demonstrate epitaxial RuO2/TiO2 (110) heterostructures grown by hybrid molecular beam epitaxy to engineer polarization selectivity of ultrafast light-matter interactions via anisotropic strain engineering. Combining spectroscopic ellipsometry, x-ray absorption spectroscopy, and optical pump-probe spectroscopy, we revealed the strong anisotropic transient optoelectronic response at an excitation energy of 1.58 eV in strain-engineered RuO2/TiO2 (110) heterostructures along both in-plane [001] and [1[Formula: see text] 0] crystallographic directions. Theoretical analysis identifies strain-induced modifications in band nesting as the underlying mechanism for enhanced anisotropic carrier relaxation observed at this excitation energy. These findings establish epitaxial strain engineering as a powerful tool for tuning anisotropic optoelectronic responses with near-infrared excitations in metallic systems, paving the way for next-generation polarization-sensitive ultrafast optoelectronic devices.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 26","pages":"eadw7125"},"PeriodicalIF":11.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512457","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 "Structure and dynamics determine G protein coupling specificity at a class A GPCR" by M. Casiraghi et al. M. Casiraghi等人的研究文章“Structure and dynamics determine G protein偶联特异性at a class a GPCR”的勘误。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-06-27 DOI: 10.1126/sciadv.adz4217

引用次数: 0

Impact of diurnal temperature and relative humidity hysteresis on atmospheric dryness in changing climates. 气候变化条件下日温度和相对湿度滞后对大气干燥的影响。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-06-27 DOI: 10.1126/sciadv.adu5713

Ching-Hung Shih, Yi-Shin Jang, Tzu-Ying Yang, Cho-Ying Huang, Jehn-Yih Juang, Min-Hui Lo

{"title":"Impact of diurnal temperature and relative humidity hysteresis on atmospheric dryness in changing climates.","authors":"Ching-Hung Shih, Yi-Shin Jang, Tzu-Ying Yang, Cho-Ying Huang, Jehn-Yih Juang, Min-Hui Lo","doi":"10.1126/sciadv.adu5713","DOIUrl":"10.1126/sciadv.adu5713","url":null,"abstract":"Vapor pressure deficit (VPD), a key indicator of atmospheric dryness, is strongly influenced by diurnal cycles of temperature (T) and relative humidity (RH). While these cycles are typically inversely locked in-phase, recent research has identified diurnal hysteresis, characterized by a time lag between T and RH; yet, its impact on VPD under changing climates remains poorly understood. In this study, we examine how diurnal T/RH hysteresis modulates VPD across different climates using observational data alongside high-resolution reanalysis and simulations. Here, we find that regions exhibiting strong diurnal T/RH hysteresis, especially in some waterside and montane regions, experience earlier daily VPD peaks. We also demonstrate that global warming weakens diurnal T/RH hysteresis, leading to amplified VPD increasing trends and greater ecosystem stress. These results highlight the need for improved representation of diurnal T/RH interactions in climate models to better predict atmospheric dryness and its impacts on land-atmosphere feedbacks, ecosystems, and regional water cycles.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 26","pages":"eadu5713"},"PeriodicalIF":11.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512467","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

Revealing neurovascular coupling at a high spatial and temporal resolution in the living human retina. 揭示神经血管耦合在高空间和时间分辨率在活的人视网膜。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-06-27 DOI: 10.1126/sciadv.adx2941

Pierre Senée, Léa Krafft, Inès Loukili, Daniela Castro Farias, Olivier Thouvenin, Michael Atlan, Michel Paques, Serge Meimon, Pedro Mecê

{"title":"Revealing neurovascular coupling at a high spatial and temporal resolution in the living human retina.","authors":"Pierre Senée, Léa Krafft, Inès Loukili, Daniela Castro Farias, Olivier Thouvenin, Michael Atlan, Michel Paques, Serge Meimon, Pedro Mecê","doi":"10.1126/sciadv.adx2941","DOIUrl":"10.1126/sciadv.adx2941","url":null,"abstract":"Neurovascular coupling (NVC) regulates local blood flow in response to neuronal activity, yet its precise characterization at the capillary level has been hindered by the lack of a noninvasive, high-resolution imaging method. Here, we introduce the adaptive optics rolling slit ophthalmoscope, a unique noninvasive, label-free, high-speed, cellular-resolution clinical imaging system for assessing retinal NVC in the living human eye. Using an off-axis phase contrast approach combined with camera-based confocal slit gating, our method provides large field-of-view imaging of arterial and venular walls, enabling the study of vascular dynamics with unprecedented spatiotemporal precision. Our findings highlight that this level of precision is essential for accurately distinguishing NVC-driven vasodilation from spontaneous fluctuations, such as vasomotion and the cardiac cycle. By bridging the gap between fundamental neurovascular research and clinical applications, this approach offers a powerful tool for neuroscience research and early disease detection and monitoring of neurodegenerative and vascular disorders.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 26","pages":"eadx2941"},"PeriodicalIF":11.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512476","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

Unveiling the multifunctional use of ochre in the Middle Stone Age: Specialized ochre retouchers from Blombos Cave 揭开中石器时代赭石的多功能用途：来自布隆博斯洞穴的专业赭石修图师

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-06-27

Elizabeth C. Velliky, Francesco d’Errico, Karen L. van Niekerk, Christopher S. Henshilwood

{"title":"Unveiling the multifunctional use of ochre in the Middle Stone Age: Specialized ochre retouchers from Blombos Cave","authors":"Elizabeth C. Velliky, Francesco d’Errico, Karen L. van Niekerk, Christopher S. Henshilwood","doi":"","DOIUrl":"","url":null,"abstract":"<div >Ochre, an iron-rich pigment, is widely associated with symbolic communication, but its functional applications in the Middle Stone Age (MSA) remain poorly understood. Experimental and ethnographic evidence suggests ochre being useful for hide tanning, hafting adhesives, and skin protection, although direct archeological evidence is scarce. We address this gap by presenting ochre tools from Blombos Cave, South Africa, found in Still Bay to pre–Still Bay layers dated 90 to 70,000 years ago. Seven ochre pieces were deliberately modified into lithic retouchers, showing clear use-wear patterns and evidence of intentional shaping. Targeted experiments confirm that some were used for pressure flaking and were rejuvenated to maintain function. These findings provide direct evidence of ochre being used to retouch lithic artifacts during the MSA, highlighting its role in technological systems of this period. The results emphasize the multifunctionality of ochre and suggest that such curated tools may have held personal, cultural, or technological significance within early modern human communities.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 26","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads2797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502958","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

Tumor-targeting nanocarriers amplified immunotherapy of cold tumors by STING activation and inhibiting immune evasion 肿瘤靶向纳米载体通过STING激活和抑制免疫逃避放大冷肿瘤的免疫治疗

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-06-27

Jinhua Zhao, Aiping Tong, Jing Liu, Mingxia Xu, Peng Mi

{"title":"Tumor-targeting nanocarriers amplified immunotherapy of cold tumors by STING activation and inhibiting immune evasion","authors":"Jinhua Zhao, Aiping Tong, Jing Liu, Mingxia Xu, Peng Mi","doi":"","DOIUrl":"","url":null,"abstract":"<div >The low immunogenicity and immune escape are bottlenecks for effective tumor immunotherapy. Here, we synthesized multifunctional polymers comprising a photosensitizer and cationic and thiol derivates and engineered a galactose-installed stimulator of interferon genes (STING) agonist and programmed death ligand 1 (PD-L1) small interfering RNA (siPDL1)–encapsulated nanocarriers (cGAMP-siPDL1@GalNPs) for synergistic immunotherapy of low immunogenic tumors through stimulating robust immune responses. cGAMP-siPDL1@GalNPs efficiently delivered the drugs into cancer cells by targeting the galactose receptors to trigger photo-/redox-/pH-activated drug release. cGAMP-siPDL1@GalNPs stimulated robust antitumor immunity via STING activation and immunogenic cell death (ICD) and inhibited immune escape via knockdown of PD-L1 expression in tumors, which synergistically regulated the immune-suppressive tumor microenvironment. Upon laser irradiation, the nanocarriers efficiently eradicated primary melanoma and orthotopic triple-negative breast tumors and induced ICD effects, which synergically inhibited the distant tumor and spontaneous lung metastasis with improved survival rates. This study presents a strategy for developing nanocarriers to activate antitumor immunity and regulate immune invasion for effective immunotherapy.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 26","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr1728","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503328","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

Flexible multichannel muscle impedance sensors for collaborative human-machine interfaces. 用于协作人机界面的柔性多通道肌肉阻抗传感器。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-06-27 DOI: 10.1126/sciadv.adv3359

Junwei Li, Kunlin Wu, Jingcheng Xiao, Tianyu Chen, Xudong Yang, Jie Pan, Yu Chen, Yifan Wang

{"title":"Flexible multichannel muscle impedance sensors for collaborative human-machine interfaces.","authors":"Junwei Li, Kunlin Wu, Jingcheng Xiao, Tianyu Chen, Xudong Yang, Jie Pan, Yu Chen, Yifan Wang","doi":"10.1126/sciadv.adv3359","DOIUrl":"10.1126/sciadv.adv3359","url":null,"abstract":"The demand for advanced human-machine interfaces (HMIs) highlights the need for accurate measurement of muscle contraction states. Traditional methods, such as electromyography, cannot measure passive muscle contraction states, while optical and ultrasonic techniques suffer from motion artifacts due to their rigid transducers. To overcome these limitations, we developed a flexible multichannel electrical impedance sensor (FMEIS) for noninvasive detection of skeletal muscle contractions. By applying an imperceptible current, the FMEIS can target multiple deep muscles by capturing electric-field ripples generated by their contractions. With an ultrathin profile (~220 micrometers), a low elastic modulus (212.8 kilopascals) closely matching human skin, and engineered adhesive sensor surfaces, the FMEIS conforms nicely to human skin with minimized motion artifacts. The FMEIS achieved high accuracy in both hand gesture recognition and muscle force prediction using machine learning models. With demonstrated performance across multiple HMI applications, including human-robot collaboration, exoskeleton control, and virtual surgery, FMEIS shows great potential for future real-time collaborative HMI systems.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 26","pages":"eadv3359"},"PeriodicalIF":11.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512464","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

Global health risks lurking in livestock resistome. 牲畜抗性组潜藏的全球健康风险。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-06-27 DOI: 10.1126/sciadv.adt8073

Bintao Li, Lan Jiang, Timothy Johnson, Guangdong Wang, Wei Sun, Gehong Wei, Shuo Jiao, Jie Gu, James Tiedje, Xun Qian

{"title":"Global health risks lurking in livestock resistome.","authors":"Bintao Li, Lan Jiang, Timothy Johnson, Guangdong Wang, Wei Sun, Gehong Wei, Shuo Jiao, Jie Gu, James Tiedje, Xun Qian","doi":"10.1126/sciadv.adt8073","DOIUrl":"10.1126/sciadv.adt8073","url":null,"abstract":"Livestock farming consumes more than 70% of global antibiotics annually, making livestock manures an important vector of anthropogenically influenced antibiotic resistance genes (ARGs). The global pattern of the livestock resistome, its driving mechanisms, and transmission potential to the clinic are not well assessed. We analyzed 4017 livestock manure metagenomes from 26 countries and constructed a comprehensive catalog of livestock ARGs and metagenome-assembled genomes. Livestock resistome is a substantial reservoir of known (2291 subtypes) and latent ARGs (3166 subtypes) and is highly connectable to human resistomes. We depicted the global pattern of livestock resistome and prevalence of clinically critical ARGs, highlighting the role of farm and human antibiotic stewardship in shaping livestock resistome. We developed a risk-assessment framework by integrating mobility potential, clinical significance, and host pathogenic relevance, and prioritized higher risk livestock ARGs, producing a predictive global map of livestock resistome risks that can help guide research and policy.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 26","pages":"eadt8073"},"PeriodicalIF":11.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512465","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

Metabolic regulation of visual acuity. 视力的代谢调节。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-06-27 DOI: 10.1126/sciadv.adx2050

Douglas Emery, Eric Vukmanic, Yekai Wang, Mark Eminhizer, Fuhua Wang, Xiaoqin Lu, Wei Wang, Ashwini Kini, Yao Chen, Enzo Fortuny, Robert F James, Yongqing Liu, Jianhai Du, Douglas C Dean

{"title":"Metabolic regulation of visual acuity.","authors":"Douglas Emery, Eric Vukmanic, Yekai Wang, Mark Eminhizer, Fuhua Wang, Xiaoqin Lu, Wei Wang, Ashwini Kini, Yao Chen, Enzo Fortuny, Robert F James, Yongqing Liu, Jianhai Du, Douglas C Dean","doi":"10.1126/sciadv.adx2050","DOIUrl":"10.1126/sciadv.adx2050","url":null,"abstract":"Photoreceptors signal ON and OFF pathways via a synapse with bipolar cells that are transmitted to retinal ganglion cells (RGCs) for luminance and contrast detection. Retinal neurons metabolize glucose whose transport is mediated by photoreceptor contact with the adjacent retinal pigment epithelium (RPE). Rod loss in retinitis pigmentosa (RP) reduces RPE contact, diminishing glucose transport. We show diminished glucose leads to light hyperresponsiveness driven by deregulated ON cone bipolar signaling. Transmission of this constitutive signal to RGCs causes ON > OFF signaling imbalance and failure to detect luminance and contrast changes. Our results suggest that the aspartate-malate shuttle in GABAergic amacrine cells metabolizes glucose to γ-aminobutyric acid (GABA), which in turn regulates the ON cone bipolar signal. GABAA receptor agonists such as Ativan are a widely prescribed first-line therapy for seizures initiated by low brain GABA, and we show that Ativan restores ON cone bipolar cell regulation in RP where retinal GABA is diminished, reestablishing luminance and contrast detection.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 26","pages":"eadx2050"},"PeriodicalIF":11.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512469","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