Science Advances最新文献

Pulsed dipolar hyperfine spectroscopy for molecular distance measurements in the angstrom to nanometer scale 脉冲偶极超精细光谱在埃到纳米尺度的分子距离测量

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-07-25 DOI: 10.1126/sciadv.ady5665

Lucca Sielaff, Annemarie Kehl, Anakin Aden, Andreas Meyer, Marina Bennati

{"title":"Pulsed dipolar hyperfine spectroscopy for molecular distance measurements in the angstrom to nanometer scale","authors":"Lucca Sielaff, Annemarie Kehl, Anakin Aden, Andreas Meyer, Marina Bennati","doi":"10.1126/sciadv.ady5665","DOIUrl":"10.1126/sciadv.ady5665","url":null,"abstract":"<div >Hyperfine spectroscopy is a fundamental method in biophysical and material sciences to detect nuclear spins in vicinity of paramagnetic centers, leading to molecular structural information. Among variants of this experiment, only electron-nuclear double resonance (ENDOR) has been established to detect nuclei at interspin distances up to about 1.7 nanometers using <sup>19</sup>F labels. This limit is dictated by the ENDOR linewidth of 10 to 30 kilohertz, which appeared insurmountable given dipolar broadening of the detected nucleus with the nuclear spin bath. Herein, we present ENDOR experiments based on nuclear sublevel coherence spectroscopy that push the boundaries of ENDOR sensitivity and resolution by one order of magnitude. In particular, we introduce an experiment, in which the electron-nuclear dipolar interaction can be exquisitely extracted from other nuclear broadening mechanisms, thus enabling to access distance distributions. This methodology paves the way for structural studies using <sup>19</sup>F ENDOR in biomolecular systems. Moreover, it offers opportunities to access spin dynamics in electron-nuclear coupled spin systems.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ady5665","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705644","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

Defining the genetic determinants of CD8+ T cell receptor repertoire in the context of immune checkpoint blockade 在免疫检查点阻断的背景下确定CD8+ T细胞受体库的遗传决定因素

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-07-25 DOI: 10.1126/sciadv.adu3461

Esther S. Ng, Gusztav Milotay, Orion Tong, Chelsea A. Taylor, Shawn Sun, Guangyi Niu, Robert Watson, Bo Sun, Sophie MacKay, James J. Gilchrist, Martin Little, Benjamin P. Fairfax, Yang Luo

{"title":"Defining the genetic determinants of CD8+ T cell receptor repertoire in the context of immune checkpoint blockade","authors":"Esther S. Ng, Gusztav Milotay, Orion Tong, Chelsea A. Taylor, Shawn Sun, Guangyi Niu, Robert Watson, Bo Sun, Sophie MacKay, James J. Gilchrist, Martin Little, Benjamin P. Fairfax, Yang Luo","doi":"10.1126/sciadv.adu3461","DOIUrl":"10.1126/sciadv.adu3461","url":null,"abstract":"<div >The relationship between genetic variation and CD8<sup>+</sup> T cell receptor (TCR) repertoire usage in patients receiving immune checkpoint blockade (ICB) therapy for cancer is unexplored. We have conducted a genome-wide and human leukocyte antigen (HLA)–focused analysis of CD8<sup>+</sup> TCR repertoire to identify genetic determinants of variable gene (V-gene) and CDR3 <i>K</i>-nucleotide oligomer usage from samples taken before and after ICB (<i>n</i> = 250). We identify 11 cis and 10 trans V-gene associations, primarily to the MHC, that meet genome-wide significance. TCR clones containing HLA associated V-genes were less stable across treatment, while, at the single-cell level, genetically associated clones demonstrate subset enrichment and increased tumor reactivity expression profiles. Notably, patients with HLA-matched TCR clones demonstrate improved overall survival. Our work indicates a complex relationship between genotype and TCR repertoire in the context of ICB treatment, with implications for understanding factors relating to therapeutic response and patient outcomes.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu3461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705720","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 “Biointerface mineralization generates ultraresistant gut microbes as oral biotherapeutics” by Z. Geng et al. Z. Geng等人的研究文章《生物界面矿化产生超耐药肠道微生物作为口服生物治疗药物》的勘误。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-07-25 DOI: 10.1126/sciadv.aea2393

引用次数: 0

Structural analysis of HER2-trastuzumab complex reveals receptor conformational adaptation her2 -曲妥珠单抗复合物的结构分析揭示了受体构象适应

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-07-25 DOI: 10.1126/sciadv.adu9945

Santiago Vacca, Marcos Gragera, Alejandro Buschiazzo, David Herreros, James M. Krieger, Santiago Bonn-Garcia, Roberto Melero, Carlos OS. Sorzano, Jose M. Carazo, Ohad Medalia, Andreas Plückthun

{"title":"Structural analysis of HER2-trastuzumab complex reveals receptor conformational adaptation","authors":"Santiago Vacca, Marcos Gragera, Alejandro Buschiazzo, David Herreros, James M. Krieger, Santiago Bonn-Garcia, Roberto Melero, Carlos OS. Sorzano, Jose M. Carazo, Ohad Medalia, Andreas Plückthun","doi":"10.1126/sciadv.adu9945","DOIUrl":"10.1126/sciadv.adu9945","url":null,"abstract":"<div >Human epidermal growth factor receptor-2 (HER2) is a receptor tyrosine kinase, associated with a variety of malignant tumors, usually through overexpression, resulting in aberrant signaling. Trastuzumab (TZB), one of the monoclonal antibodies (mAbs) used in combination with chemotherapy, has become a major therapeutic for HER2-overexpressing cancers. Current structural understanding of HER2 and its interactions with other receptors and with different affinity agents has relied on numerous structures of individual domains of HER2. Here, we subjected purified near full-length HER2 to single-particle cryo–electron microscopy (cryo-EM) analysis. Besides the canonical conformation described in previous structural studies, we report a previously unreported conformation of the HER2 extracellular domain that is stabilized upon TZB binding, which might hamper association with HER3, a receptor with which HER2 forms an oncogenic unit. Together, our findings provide insights into the conformational dynamics of the HER2 receptor and the mechanism of action of TZB.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu9945","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705727","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

DAMPs cross-talk interpretation of MDD mechanisms DAMPs串音解释MDD机制

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-07-25 DOI: 10.1126/sciadv.adx3698

Yiyi Peng, Zhenni Chen, Yang Xu, Biqiong Ren

引用次数: 0

Erratum for the Research Article “Orally administrated liquid metal agents for inflammation-targeted alleviation of inflammatory bowel diseases” by M. Liu et al. M. Liu等人的研究文章“口服液态金属制剂用于炎症靶向性减轻炎症性肠病”的勘误。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-07-25 DOI: 10.1126/sciadv.aea4882

引用次数: 0

Human iPSC-based breast cancer model identifies S100P-dependent cancer stemness induced by BRCA1 mutation 基于人类ipsc的乳腺癌模型鉴定BRCA1突变诱导的s100p依赖性癌症干性

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-07-25 DOI: 10.1126/sciadv.adi2370

Jingxin Liu, Cai Zhao, Jiahao Chen, Pengguihang Zeng, Qingjian Li, Ranran Dai, Xingqiang Lai, Wenqian Song, Jianing Chen, Xixi Zhu, Xinyi Liu, Jun Sun, Jia Wang, Peihang Fang, Tengfei Wang, Wenjie Chen, Diana Guallar, Nan Cao, Jianli Zhao, Shicheng Su, Andy Peng Xiang, Yi Arial Zeng, Jie Li, Junchao Cai, Dung-Fang Lee, Jinxin Bei, Yongliang Huo, Hai Hu, Shengbao Suo, Dong-feng Huang, Jin Bai, Junjun Ding

{"title":"Human iPSC-based breast cancer model identifies S100P-dependent cancer stemness induced by BRCA1 mutation","authors":"Jingxin Liu, Cai Zhao, Jiahao Chen, Pengguihang Zeng, Qingjian Li, Ranran Dai, Xingqiang Lai, Wenqian Song, Jianing Chen, Xixi Zhu, Xinyi Liu, Jun Sun, Jia Wang, Peihang Fang, Tengfei Wang, Wenjie Chen, Diana Guallar, Nan Cao, Jianli Zhao, Shicheng Su, Andy Peng Xiang, Yi Arial Zeng, Jie Li, Junchao Cai, Dung-Fang Lee, Jinxin Bei, Yongliang Huo, Hai Hu, Shengbao Suo, Dong-feng Huang, Jin Bai, Junjun Ding","doi":"10.1126/sciadv.adi2370","DOIUrl":"10.1126/sciadv.adi2370","url":null,"abstract":"<div >Breast cancer is the most common malignancy in females and remains the leading cause of cancer-related deaths for women worldwide. The cellular and molecular basis of breast tumorigenesis is not completely understood partly due to the lack of human research models which simulate the development of breast cancer. Here, we developed a method for generating functional mammary-like cells (MCs) from human-induced pluripotent stem cells (iPSCs). The iPSC-MCs closely resemble human primary MCs at cellular, transcriptional, and functional levels. Using this method, a breast cancer model was generated using patient-derived iPSCs harboring germline <i>BRCA1</i> mutation. The patient iPSC-MCs recapitulated the transcriptome, clinical genomic alteration, and tumorigenic ability of breast cancer cells. We also identified S100P as an oncogene downstream of mutated <i>BRCA1</i> that promotes cancer cell stemness and tumorigenesis. Our study establishes a promising system of breast cancer for studying the mechanism of tumorigenesis and identifying potential therapeutic targets.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adi2370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705642","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 secreted protein PCYOX1L controls the surface expression of acid-sensing ion channel 1a 分泌蛋白PCYOX1L控制酸感离子通道1a的表面表达

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-07-25 DOI: 10.1126/sciadv.adw4064

Sven Kuspiel, Maria Schilling, Felicitas Weiß, Alison Wiesehahn, Lea Strüver, Günther Schmalzing, Dominik Wiemuth, Stefan Gründer

引用次数: 0

Improving real-time ultrasound spine imaging with a large-aperture array 改进大孔径阵列实时超声脊柱成像

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-07-25 DOI: 10.1126/sciadv.adw2601

Ning Lu, Josquin Foiret, Yutong Guo, Byung Chul Yoon, Katherine W. Ferrara

{"title":"Improving real-time ultrasound spine imaging with a large-aperture array","authors":"Ning Lu, Josquin Foiret, Yutong Guo, Byung Chul Yoon, Katherine W. Ferrara","doi":"10.1126/sciadv.adw2601","DOIUrl":"10.1126/sciadv.adw2601","url":null,"abstract":"<div >Ultrasound offers a safe, low-cost alternative to computed tomography (CT) and magnetic resonance imaging for spinal diagnostics and intervention by enabling real-time imaging. However, the complex structure of the spine and acoustic shadowing from bones present challenges for ultrasonography. This study addresses these limitations using an 8.8-centimeter 384-element large-aperture array and full aperture-based imaging protocols. Volumetric scanning across multiple vertebrae was accomplished in 5 seconds using ultrafast, diverging wave acquisition. In seven healthy volunteers, the large-aperture array and diverging wave transmission improved resolution, contrast, and visualization of the spinal canal, venous plexuses, and facet joints compared with conventional probes. A comparison between the coregistered CT and ultrasound scan confirmed the imaging accuracy. A simulated lumbar puncture demonstrated needle tip visualization throughout the trajectory into the spinal canal. The results suggest that large-aperture arrays, coupled with diverging wave imaging sequences, are a valuable tool for spine imaging and image-guided intervention.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adw2601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705721","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 phase evolution of complex oxides toward precise solid-state synthesis 揭示复合氧化物向精确固态合成的相演化

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-07-25 DOI: 10.1126/sciadv.adx3927

Lin Yang, Zhewen Zhu, Yitian Feng, Daxian Zuo, Shi Huang, Yao Yang, Lihui Zhou, Stephen J. Harris, Lin Zeng, Yizhou Zhu, Jiayu Wan

{"title":"Unveiling phase evolution of complex oxides toward precise solid-state synthesis","authors":"Lin Yang, Zhewen Zhu, Yitian Feng, Daxian Zuo, Shi Huang, Yao Yang, Lihui Zhou, Stephen J. Harris, Lin Zeng, Yizhou Zhu, Jiayu Wan","doi":"10.1126/sciadv.adx3927","DOIUrl":"10.1126/sciadv.adx3927","url":null,"abstract":"<div >The precise synthesis of high-purity materials is crucial in accelerating materials discovery. However, the lack of theoretical understanding and practical guidance poses challenges, particularly for materials with compositional and structural complexity. Here, we propose a feasible principle toward synthesizing complex inorganic solids. This principle involves the introduction of an inducer that induces crucial intermediates, which in turn guide the synthesis pathway toward the target materials through structural templating, named inducer-facilitated assembly through structural templating (i-FAST). We validate this principle with three distinct oxides: garnet Li<sub>6.5</sub>La<sub>3</sub>Zr<sub>1.5</sub>Ta<sub>0.5</sub>O<sub>12</sub>, perovskite BaCo<sub>0.8</sub>Sn<sub>0.2</sub>O<sub>3</sub>, and pyrochlore Gd<sub>1.5</sub>La<sub>0.5</sub>Zr<sub>2</sub>O<sub>7</sub>. This structural templating approach enables synthesis along predesigned pathways, forming intermediates that are thermodynamically favored for prior formation and kinetically preferred for the final product, resulting in precisely synthesizing high-purity target materials. This study not only represents a substantial advancement in comprehending the interplay between thermodynamics/kinetics and phase evolution in complex solid synthesis but also provides an effective strategy for guiding exploratory solid-state synthesis.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx3927","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705726","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