Nature Communications最新文献

{"title":"Complex I protein NDUFB9 is a metabolic vulnerability in triple negative breast cancer brain metastases.","authors":"Mingxi Lin, Zhexu Wen, Cheng Zeng, Yizi Jin, Teng Zhou, Yuxin Yan, Shenglin Huang, Xin Hu, Xiaoxiang Guan, Xichun Hu, Jian Zhang","doi":"10.1038/s41467-026-72927-2","DOIUrl":"https://doi.org/10.1038/s41467-026-72927-2","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) brain metastases (BrMs) remain a therapeutic challenge. We depict the discrepancies between primary tumors and BrMs, and examine patient-matched cerebrospinal fluid and plasma to provide detailed profiles of BrMs' metabolic microenvironment. High-throughput in vivo loss of function CRISPR screens identify NDUFB9 (NADH: Ubiquinone Oxidoreductase Subunit B9) as a brain-specific metabolic vulnerability. NDUFB9-knockout selectively inhibits the BrMs outgrowth without affecting extracranial metastases. Mechanistically, TNBC cells exhibit an imbalance between aspartate upstream supply and downstream biosynthetic demand. NDUFB9-knockout disrupts mitochondrial complex I and reduces intracellular aspartate, but this alone is insufficient to inhibit TNBC proliferation. Instead, the lower asparagine concentration in the brain microenvironment induces compensatory upregulation of asparagine synthetase, which further diverts aspartate toward asparagine biosynthesis. This dual-hit mechanism exhausts the aspartate pool and restricts nucleotide biosynthesis, thereby selectively suppressing BrM outgrowth. Our findings uncover a therapeutic strategy for TNBC BrMs.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856517","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":"Anti-PD-1 plus nab-paclitaxel and bevacizumab for second-line treatment of cancer of unknown primary (Fudan CUP-002): a phase II trial.","authors":"Xiaowei Zhang, Ting Zhao, Midie Xu, Yanjing Guo, Qifeng Wang, Yanli Wang, Liangping Zhou, Silong Hu, Qinghua Xu, Xichun Hu, Xin Liu, Zhiguo Luo","doi":"10.1038/s41467-026-72745-6","DOIUrl":"https://doi.org/10.1038/s41467-026-72745-6","url":null,"abstract":"<p><p>Fudan CUP-002 study (ClinicalTrials.gov identifier: NCT04848597), an investigator-initiated prospective trial, was designed to evaluate the efficacy and safety of an anti-PD-1 antibody in combination with nab-paclitaxel and bevacizumab as a second-line treatment for cancer of unknown primary (CUP). Between June 2, 2021, and April 19, 2024, 48 eligible patients were enrolled. At data cutoff (January 10, 2025), the median follow-up was 27.1 months (95% CI, 20.2 to 37.2). The objective response rate (ORR) was 54.2% (26/48; 95% CI, 40.3% to 67.4%), and the disease control rate (DCR) was 95.8% (46/48; 95% CI, 86.0% to 98.9%). The median progression-free survival (PFS) was 13.1 months (95% CI, 8.0 to 19.6), while the median overall survival (OS) was 25.1 months (95% CI, 14.6 to 29.5). Treatment-related adverse events (TRAEs) of any grade occurred in 46 patients (95.8%). The exploratory analysis identified systemic eosinophil counts as a prognostic biomarker for treatment response and survival outcomes in second-line setting for CUP. However, current experimental systems are unable to provide the established cell lines or animal models needed to investigate therapeutic mechanisms for CUP. Our present study demonstrated that an anti-PD-1 antibody plus nab-paclitaxel and bevacizumab was effective and well-tolerated in the second-line treatment for patients with CUP.Trial registration: ClinicalTrials.gov identifier: NCT04848597.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856893","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":"Molecular insight into microtubule nucleation by the XMAP215/γ-TuRC module.","authors":"Collin T McManus, Sophie M Travis, Philip D Jeffrey, Rui Zhang, Sabine Petry","doi":"10.1038/s41467-026-72370-3","DOIUrl":"https://doi.org/10.1038/s41467-026-72370-3","url":null,"abstract":"<p><p>It has become increasingly evident in recent years that nucleation of microtubules from a diverse set of microtubule organizing centers (MTOCs) requires both the γ-tubulin ring complex (γ-TuRC) and the microtubule polymerase XMAP215. Despite their essentiality, little is known about how these nucleation factors interact and work together to generate microtubules. Using biochemical domain analysis of XMAP215 and structural approaches, we find that the XMAP215 C-terminal region interacts broadly with γ-TuRC, involving a sixth TOG domain which binds γ-tubulin. Moreover, TOG6 is required for XMAP215 to promote nucleation from γ-TuRC to its full extent. Interestingly, we find that XMAP215 also depends strongly on TOG5 for microtubule lattice binding and nucleation. We further report a cryo-EM structure of TOG5 bound to the microtubule lattice that reveals promotion of lateral interactions between tubulin dimers. While XMAP215 constructs' effects on nucleation are generally proportional to their effects on polymerization, formation of a direct complex with γ-TuRC allows cooperative nucleation activity. Thus, we propose that XMAP215's C-terminal TOGs 5 and 6 play key roles in nucleation by promoting formation of longitudinal and lateral bonds in nascent γ-TuRC-templated microtubules at cellular MTOCs.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856729","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":"CroCoDeEL: accurate control-free detection of cross-sample contamination in metagenomic data.","authors":"Lindsay Goulet, Florian Plaza Oñate, Alexandre Famechon, Benoît Quinquis, Eugeni Belda, Edi Prifti, Emmanuelle Le Chatelier, Guillaume Gautreau","doi":"10.1038/s41467-026-72637-9","DOIUrl":"https://doi.org/10.1038/s41467-026-72637-9","url":null,"abstract":"<p><p>Metagenomic sequencing provides insights into microbial communities, but it can be compromised by technical biases, including cross-sample contamination. This phenomenon arises when microbial content is inadvertently exchanged among concurrently processed samples, distorting microbial profiles and compromising the reliability of metagenomic data and downstream analyses. Existing detection methods rely on negative controls, which are insufficiently used and do not detect cross-contamination within non-control samples. Meanwhile, strain-level bioinformatics approaches do not distinguish contamination from natural strain sharing and lack sensitivity. To fill this gap, we introduce CroCoDeEL, a decision-support tool for detecting and quantifying cross-sample contamination. Leveraging linear modeling and a pre-trained supervised model, CroCoDeEL identifies specific contamination patterns in species abundance profiles. It requires no negative controls or prior knowledge of sample processing positions, offering improved accuracy and versatility. Benchmarks across three public datasets demonstrate that CroCoDeEL can detect contaminated samples and identify their contamination sources, even at low rates (<0.1%), provided sufficient sequencing depth. Application of CroCoDeEL to several existing studies reveals previously undetected contamination.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856525","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":"Citywide indoor air sampling mirrors wastewater and clinical case surveillance of respiratory viruses.","authors":"Hannah J Barbian, Erin P Newcomer, Sofiya Bobrovska, Rachel S Poretsky, Stephanie Greenwald, Sarah M Owens, Anuj Tiwari, Rachel J Berkowitz, Samantha Smith, Dorothy Wright, Stefan J Green, Dolores Sanchez Gonzalez, Chi-Yu Lin, Adam Horton, Modou Lamin Jarju, Rosemarie Wilton, Mary K Hayden, Stephanie R Black, V Eloesa McSorley, Alyse Kittner","doi":"10.1038/s41467-026-72919-2","DOIUrl":"https://doi.org/10.1038/s41467-026-72919-2","url":null,"abstract":"<p><p>Wastewater surveillance of respiratory pathogens can provide timely estimates of viral activity and disease trends in a population. Indoor air surveillance could be used similarly with some advantages but remains largely unvalidated at the community-scale. Here, an indoor air surveillance program was employed as part of public health environmental surveillance in Chicago, Illinois, USA. Ten air samplers were placed in healthcare and congregate living settings across the city. Weekly air samples were evaluated for influenza A, influenza B, respiratory syncytial virus, and SARS-CoV-2 over two respiratory virus seasons (2023-2025). Citywide, aggregated air sample positivity and viral load were closely correlated with local clinical case and wastewater surveillance data across all respiratory viruses. Virus trends in air data often preceded clinical and wastewater, although this varied across pathogens and respiratory virus seasons. Further, whole-genome sequencing of SARS-CoV-2 showed close correlation of variant proportions across all datasets. At the building-scale, air samples obtained from a single sampling device provided efficient respiratory virus surveillance, with respiratory pathogen levels mirroring citywide clinical surveillance data. These data demonstrate that air surveillance can provide respiratory virus case and variant trend data at a building or community-scale, serving as an alternative or complementary tool for public health environmental surveillance.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856468","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":"Cross-species insights into placental evolution and diseases at the single-cell resolution.","authors":"Guanghui Tan, Ao Zhang, Xuesha Cao, Jingyu Yang, Youjie Cui, Fei Wang, Tao Shi, Hengkuan Li, Haoping Wang, Huiquan Shan, Jilong Ren, Yaqi Zhou, Menghan Wang, Funong Luo, Xi Guo, Wuqiang Huo, Yingran Liu, Zhannur Niyazbekova, Xihong Wang, Zhenyu Xiao, Yi Zheng, Yu Jiang","doi":"10.1038/s41467-026-72652-w","DOIUrl":"https://doi.org/10.1038/s41467-026-72652-w","url":null,"abstract":"<p><p>The placenta is essential for fetal development, yet its molecular evolution across mammals remains elusive. Here, we present a comprehensive single-cell transcriptomic atlas of ~300,000 cells from ten species representing the four primary placental types: discoid, cotyledonary, diffuse, and zonary. Our cross-species analysis identifies trophoblast lineages as the primary drivers of placental diversification. By reconstructing differentiation trajectories, we elucidate the regulatory networks shaping trophoblast development across diverse architectures. We propose that the unique gene expression profile of human trophoblasts underlies the susceptibility to preeclampsia and miscarriage. Functional experiments demonstrate that TGIF1 acts as a key upstream regulator of extravillous trophoblast growth and migration. TGIF1 and its targets, including ADAM12, WNT3A, and ZNF831, are associated with preeclampsia and pregnancy loss. Collectively, this high-resolution framework provides fundamental insights into the molecular evolution of the placenta and its contribution to reproductive success and diseases.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856589","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":"CRISPR base editor screening identifies spectrum of MEN1 mutations impacting menin inhibitors in clinical trials.","authors":"Wallace Bourgeois, Hannah E Rice, Daniela V Wenge, Florian Perner, Hong Yue, Brandon D Regalado, George Wan, Jan C Schroeder, Alba Sommerschield, Charlie Hatton, Shivendra Singh, Sweta Singh, Shipra Bijpuria, Brian M McKeever, William H Miller, Jordan F Safer, Sumaiya Iqbal, Jennifer A Perry, Eric S Fischer, John G Doench, Gerard M McGeehan, Jevon A Cutler, Scott A Armstrong","doi":"10.1038/s41467-026-72685-1","DOIUrl":"https://doi.org/10.1038/s41467-026-72685-1","url":null,"abstract":"<p><p>Menin inhibitors have entered clinical trials for histone lysine methyltransferase 2 A (KMT2A)-rearranged and nucleophosmin 1 (NPM1)-mutant acute leukemias and are demonstrating promising activity. CRISPR base editor screening previously predicted several MEN1 (menin) mutations that have arisen in patients receiving SNDX-5613 and confer resistance. The extent to which MEN1 mutations will impact each menin inhibitor is mostly unknown. Here we show that CRISPR base editor screens can be leveraged to profile the MEN1 mutations that may impact five different menin inhibitors in clinical trials. We identify shared (M327I/V/T, G331D) and inhibitor-specific (C334R, E368K/V, V372A) resistance mutations. Co-crystal structures of menin bound to each menin inhibitor suggest resistance mechanisms related to how each inhibitor engages the KMT2A binding pocket of menin. Orthogonal in vitro and in vivo MEN1 mutation generation under therapeutic pressure suggest the MEN1 mutations identified with CRISPR base editor screening are likely to arise and impact all menin inhibitors.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856592","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":"Ultrafast charge-generation dynamics through interfacial energetic modulation for high-performance single-component organic photovoltaics with 14.8% efficiency.","authors":"Yao Li, Yongmin Luo, Yulong Hai, Xinkang Wang, Lunbi Wu, Ruijie Ma, Kezhou Fan, Top Archie Dela Peña, Sha Liu, He Yan, Kam Sing Wong, Gang Li, Tao Jia, Junwu Chen, Jiaying Wu","doi":"10.1038/s41467-026-72792-z","DOIUrl":"https://doi.org/10.1038/s41467-026-72792-z","url":null,"abstract":"<p><p>Bulk heterojunction (BHJ) organic solar cells (OSCs) have achieved high efficiencies but suffer from poor morphological stability due to phase separation after long-term operation. Single-component OSCs (SCOSCs) based on double-cable polymers (DCP), offer improved stability through covalently linked donor and acceptor units. However, their efficiency remains limited by inefficient charge generation arising from extensive intermixed morphologies. Here, we report a fluorinated double-cable polymer, DCPY2-F, which achieves an outstanding efficiency of 14.8% with high short-circuit current density of 26.83 mA cm^-2. Ultrafast pump-probe transient absorption spectroscopy reveals that fluorination of DCPY2 into DCPY2-F accelerates interfacial charge transfer and long-range charge separation dynamics. The pump-push-probe transient absorption spectroscopy and steady-state electroluminescence show that the faster interfacial charge transfer arises from a reduced reorganization energy and a correspondingly accelerated molecular reorganization process (2.5 ps vs. 0.8 ps). Despite comparable acceptor aggregate sizes with DCPY2, DCPY2-F also shows faster long-range charge separation dynamics, which we attribute to a narrower charge transfer states (CTs) energetic distribution. Molecular dynamics simulations further reveal that fluorination strengthens non-covalent interactions, promoting well-aligned intermolecular donor-acceptor interfaces. These structurally and energetically ordered interfacial CT states enable ultrafast and efficient charge generation. In corresponding binary blends, fluorination similarly enhances charge-transfer dynamics and photocurrent. These findings establish a unified fluorination strategy for accelerating charge generation dynamics in both SCOSCs and blends, and provide a mechanistic understanding for improving charge generation for high-performance single-component systems.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856864","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":"Using satellite imagery to map rural marketplaces and monitor their activity at high frequency.","authors":"Tillmann von Carnap, Reza M Asiyabi, Paul Dingus, Anna Tompsett","doi":"10.1038/s41467-026-72865-z","DOIUrl":"https://doi.org/10.1038/s41467-026-72865-z","url":null,"abstract":"<p><p>In many rural areas of low- and middle-income countries, weekly gatherings of buyers and sellers are the most tangible manifestation of the market economy. Identifying and tracking these markets could provide insights into economic activity in data-scarce settings. However, because these markets are informal and dispersed across often-remote regions, systematic data are sparse. We develop, test, and apply a method that leverages distinctive temporal patterns in satellite imagery to detect periodic markets. Using secondary data from Kenya, Malawi, and Mozambique, we first confirm that we detect markets with high sensitivity and specificity. We then map 1,776 markets in Ethiopia and track their activity at up-to-weekly frequency between 2017 and 2024. Market activity follows seasonal agricultural cycles and responds to weather and conflict shocks. Once locations are identified, the method can be automated to track market activity at high frequency, allowing detection of changing conditions where other high-frequency data are limited.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856904","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":"Built-in electric field activates endogenous redox couple for self-sustained Fenton-like reaction.","authors":"Shurun Yang, Si Sun, Hong Chen, Peng Zhou, Chuan-Shu He, Yang Wang, Yang Mu, Bo Lai","doi":"10.1038/s41467-026-72595-2","DOIUrl":"https://doi.org/10.1038/s41467-026-72595-2","url":null,"abstract":"<p><p>Heterogeneous catalyst systems hold significant potential for advanced water treatment, yet achieving sustainable catalytic processes capable of continuously generating reactive species remains a substantial challenge. In this work, we develop an integrated oxidation-reduction system that synergistically couples peracetic acid (PAA) with H₂O₂ under the guidance of an interfacial built-in electric field (BEF). Through a programmable self-assembly approach, a porous nitrogen-doped carbon (NC) layer encapsulating Co/CoO heterojunction was constructed. Experimental and theoretical results confirm that strong electronic coupling between metallic Co and semiconductor CoO spontaneously generates a robust BEF. This field not only optimizes the electronic configuration to enhance PAA adsorption and activation, but also enables the selective adsorption of H₂O₂ from the mixed oxidant solution. The adsorbed H₂O₂ acts as an electron donor to sustain the Co(II)/Co(III) redox cycle, facilitating continuous reactive oxygen species (ROS) generation for approximately 120 min. The system demonstrates exceptional catalytic performance, achieving high contaminant removal rate constants (0.3 to 0.6 min^-1) with an ultralow catalyst dosage of 15 mg L^-1 and significantly improved PAA utilization efficiency. This BEF-mediated \"dual-enhancement\" strategy offers a sustainable and efficient route for water purification by enabling high oxidant utilization while minimizing catalyst consumption.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856860","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}