Nature Communications最新文献_第4页

Designing rigid protein fiducials to visualize GPCR conformational states 设计刚性蛋白基准可视化GPCR构象状态

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2026-10-24 DOI: 10.1038/s41467-026-78942-7

Alina A. Vo, Yuan-En Sun, Justin G. English, Michael J. Robertson

{"title":"Designing rigid protein fiducials to visualize GPCR conformational states","authors":"Alina A. Vo, Yuan-En Sun, Justin G. English, Michael J. Robertson","doi":"10.1038/s41467-026-78942-7","DOIUrl":"https://doi.org/10.1038/s41467-026-78942-7","url":null,"abstract":"G-protein coupled receptors (GPCRs) mediate precise ligand-specific signaling profiles, yet structural visualization of how ligands alter receptor conformational landscapes in the absence of signaling partners or mimetics has proven challenging. Here we show that by combining generative protein design with deep-learning based ensemble prediction we can reliably design fiducial markers to facilitate cryogenic electron microscopy (cryoEM) of GPCRs at arbitrary fusion points, enabling the visualization of previously intractable states. We validate the approach with high-throughput determination of inactive state structures of four pharmaceutically relevant GPCRs, allowing for key details of receptor pharmacology to be resolved in each case. We then engineered an extracellular fiducial marker for the prototypical β2-adrenergic receptor that enabled direct structural characterization of the rearrangement of key intracellular motifs in the absence of G-protein. Comparison with recent co-folding models highlights major gaps in current methods for predicting ligand-induced GPCR conformations. These results present a generalizable framework for accessing traditionally inaccessible structural states of small, dynamic proteins.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"14 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241988","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}

引用次数: 0

Hydrogen-stabilized dual-phase architecture enables ductility in refractory molybdenum nanowires 氢稳定的双相结构使耐火钼纳米线具有延展性

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2026-10-24 DOI: 10.1038/s41467-026-79244-8

Yuxuan Hou, Haixuan Cao, Huayu Peng, Ruilong Huang, Huaiyuan Wang, Bochun Yu, Peili Zhao, Shuangfeng Jia, He Zheng, Jianbo Wang

{"title":"Hydrogen-stabilized dual-phase architecture enables ductility in refractory molybdenum nanowires","authors":"Yuxuan Hou, Haixuan Cao, Huayu Peng, Ruilong Huang, Huaiyuan Wang, Bochun Yu, Peili Zhao, Shuangfeng Jia, He Zheng, Jianbo Wang","doi":"10.1038/s41467-026-79244-8","DOIUrl":"https://doi.org/10.1038/s41467-026-79244-8","url":null,"abstract":"Enhancing the ductility of refractory body-centered cubic (BCC) metals at the nanoscale remains challenging because limited dislocation mobility can lead to premature brittle fracture. Here, we show that a face-centered cubic (FCC)/BCC dual-phase structure can be formed in Mo nanowires (NWs) via non-equilibrium electron-stream excitation (electric current or electron-beam irradiation). Atomic-scale characterization and first-principles calculations indicate that interstitial hydrogen stabilizes the FCC phase at the NW surface. The dual-phase NWs exhibit ~41.4% uniform elongation along the [011] direction, corresponding to a ~ 300% increase relative to single-phase BCC NWs. The observed deformation involves two hydrogen-mediated processes: (1) during early plastic deformation, a two-step FCC-to-BCC transformation proceeds through fractional dislocation slip, which relieves local stress concentrations and thereby suppresses surface crack initiation; (2) hydrogen promotes dislocation nucleation by modifying surface energy and unstable stacking-fault energy, thereby sustaining plastic flow and delaying failure. These results show that hydrogen-mediated phase transformation and dislocation nucleation enhance the deformability of nanoscale Mo.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"5 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241703","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}

引用次数: 0

Critically coupled zeroth-order resonance for ultrathin nonlinear photonics 超薄非线性光子学的临界耦合零阶共振

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2026-10-24 DOI: 10.1038/s41467-026-78579-6

Hae-Seok Jeong, Soon-Jae Lee, Young-Ho Jin, Su-Hyun Gong, Q-Han Park

引用次数: 0

Phylogenomics of captured Cryptosporidium sequenced directly from patient samples identifies clade-specific genomic architecture and host-adapted lineages 直接从患者样本中测序的捕获隐孢子虫的系统基因组学鉴定了进化支特异性基因组结构和宿主适应谱系

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2026-10-24 DOI: 10.1038/s41467-026-78927-6

E. V. C. Alves-Ferreira, A. Khan, M. D. Tettey, F. Ihara, H. Vogel, S. Botchie, I. Ayi, M. C. Pawlowic, G. Robinson, R. M. Chalmers, H. A. Lorenzi, M. E. Grigg

{"title":"Phylogenomics of captured Cryptosporidium sequenced directly from patient samples identifies clade-specific genomic architecture and host-adapted lineages","authors":"E. V. C. Alves-Ferreira, A. Khan, M. D. Tettey, F. Ihara, H. Vogel, S. Botchie, I. Ayi, M. C. Pawlowic, G. Robinson, R. M. Chalmers, H. A. Lorenzi, M. E. Grigg","doi":"10.1038/s41467-026-78927-6","DOIUrl":"https://doi.org/10.1038/s41467-026-78927-6","url":null,"abstract":"Cryptosporidium causes diarrhea and high mortality in young children in Africa and southern Asia. Low oocyst counts in stool often limit whole-genome sequencing from clinical samples. Here, we enrich for Cryptosporidium genomic DNA directly from stool samples using 74,973 RNA baits (CryptoCap_75K; 8.2 Mb) derived from gene-rich areas (100% coding capacity) within the Cryptosporidium parvum genome. This method produces genome-wide sequence data with sufficient depth and breadth of coverage using as few as 25 oocysts, including divergent species such as Cryptosporidium ubiquitum. To minimize reference bias, we utilize a dual-mapping strategy that integrates reads aligned to both C. parvum and C. ubiquitum to capture lineage-specific variation. Phylogenetic networks, haplotypes, and admixture analyses identify three C. ubiquitum groups, A and B exclusive to humans, with B showing evidence of admixture, whereas C is zoonotic. Group-specific polymorphisms cluster within discrete genomic regions, suggesting conserved haploblocks associate with host adaptation. This capture-based genomics approach provides high-resolution insights into Cryptosporidium population genetics and lays the groundwork for studies of zoonotic transmission, anthroponosis, and GWAS directly from clinical material.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"14 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241629","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}

引用次数: 0

Asymmetry-induced distinct mechanisms and the transporting role of sodium in bacterial fluoride channel Fluc 不对称诱导的不同机制及钠在细菌氟离子通道中的转运作用

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2026-10-24 DOI: 10.1038/s41467-026-78935-6

Fernando Montalvillo Ortega, Kira Mills, Hedieh Torabifard

{"title":"Asymmetry-induced distinct mechanisms and the transporting role of sodium in bacterial fluoride channel Fluc","authors":"Fernando Montalvillo Ortega, Kira Mills, Hedieh Torabifard","doi":"10.1038/s41467-026-78935-6","DOIUrl":"https://doi.org/10.1038/s41467-026-78935-6","url":null,"abstract":"Bacterial fluoride channels (Fluc) conduct fluoride at rapid rates while exhibiting extraordinarily high selectivity, an unusual property among anion transporters. Fluc achieves this through an antiparallel homodimeric assembly that forms two asymmetric ion-conduction pores and hosts a centrally bound sodium of previously uncertain function. Despite extensive structural characterization, the molecular basis for Fluc’s dual-pore asymmetry, transport efficiency, and sodium involvement has remained unresolved. In this work, we performed long-timescale molecular dynamics simulations under electrophysiological conditions paired with Markov state modeling to elucidate the mechanisms of fluoride translocation. Our results support a mechanistic model in which structural asymmetry drives distinct but coexisting transport mechanisms, with Pore I operating via the Channsporter mechanism, while Pore II follows the Multi-ion mechanism. We further propose that the central sodium serves as a dynamic cofactor in fluoride transport, coupling its vertical oscillation to fluoride movement in a pore-dependent manner.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"22 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241990","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}

引用次数: 0

Gut epithelial aryl hydrocarbon receptor deficiency aggravates fungal dysbiosis-mediated neutrophilic allergic airway disease in mice 小鼠肠道上皮芳烃受体缺乏加重真菌生态失调介导的嗜中性粒细胞过敏性气道疾病

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2026-10-24 DOI: 10.1038/s41467-026-78800-6

Ting Wang, Chao Lei, Zhishan Xu, Xiaotong Song, Amanguli Tuohongerbieke, Tyler Jones, Maiying Kong, Chuangli Hao, Zhengrong Chen, Yi Tan, Jun Yan, Craig J. McClain, Zhongbin Deng

{"title":"Gut epithelial aryl hydrocarbon receptor deficiency aggravates fungal dysbiosis-mediated neutrophilic allergic airway disease in mice","authors":"Ting Wang, Chao Lei, Zhishan Xu, Xiaotong Song, Amanguli Tuohongerbieke, Tyler Jones, Maiying Kong, Chuangli Hao, Zhengrong Chen, Yi Tan, Jun Yan, Craig J. McClain, Zhongbin Deng","doi":"10.1038/s41467-026-78800-6","DOIUrl":"https://doi.org/10.1038/s41467-026-78800-6","url":null,"abstract":"Fungal and bacterial dysbiosis are linked to asthma disease severity, yet how overgrowth of the commensal fungus Candida albicans contributes to disease progression is not fully understood. Here, we show that intestinal aryl hydrocarbon receptor (AhR) deficiency exacerbates house dust mite (HDM)-induced allergic airway disease (AAD) during oral Candida albicans colonization through enhanced IL-17 responsiveness and lung structural cell fucosylation. Intestinal AhR deficiency promotes exaggerated IL-17 responses that promotes neutrophil migration and accumulation in the lung and reshapes the gut microbiota, particularly reducing the abundance of Akkermansia muciniphila. Concurrently, increased fucosylation of lung structural cells enhances L-selectin glycan ligand biosynthesis, thereby promoting neutrophil adhesion and retention within inflamed lung tissue. These adherent neutrophils lead to mitochondrial dysfunction, oxidative stress, and tissue injury in epithelial and endothelial compartments. Administration of A. muciniphila or its derived outer membrane vesicles (OMVs), as well as genetic deletion of Fut2, reduces lung fucosylation, suppresses neutrophil adhesion and NET formation, and attenuates Candida albicans–exacerbated AAD. Together, these findings show that intestinal AhR signaling remotely regulates an IL-17- gut microbiota-fucosylation axis that promotes neutrophil adhesion, mitochondrial dysfunction of lung structure cell, and neutrophilic airway inflammation during Candida albicans–associated asthma.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241627","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}

引用次数: 0

An integrated cathode-electrolyte architecture with Cu dual active-sites for all-solid-state Li–CO2 batteries 一种集成的阴极电解质结构与Cu双活性位点的全固态锂-二氧化碳电池

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2026-10-24 DOI: 10.1038/s41467-026-78929-4

Yunyun Xu, Dashuai Wang, Yuejiao Li, Haifeng Qi, Zhuobin Guo, Tasmia Azam, Pratteek Das, Zhong-Shuai Wu, Hui-Ming Cheng

{"title":"An integrated cathode-electrolyte architecture with Cu dual active-sites for all-solid-state Li–CO2 batteries","authors":"Yunyun Xu, Dashuai Wang, Yuejiao Li, Haifeng Qi, Zhuobin Guo, Tasmia Azam, Pratteek Das, Zhong-Shuai Wu, Hui-Ming Cheng","doi":"10.1038/s41467-026-78929-4","DOIUrl":"https://doi.org/10.1038/s41467-026-78929-4","url":null,"abstract":"All-solid-state Li–CO2 batteries are limited by sluggish interfacial CO2 redox kinetics and the incomplete decomposition of insulating Li2CO3 at rigid solid-solid-gas interfaces. Here, we report an integrated cathode-electrolyte architecture in which copper atomic clusters and single atoms are co-anchored on freestanding N-doped carbon nanotubes and coupled with a succinonitrile/Li1+xAlyGe2-y(PO4)3-based solid-state electrolyte. The conformal ion-conducting phase and conductive nanotube scaffold provide coupled pathways for Li+, electrons and CO2 at the cathode interface. Electronic coupling between the copper atomic clusters and single atoms induces charge transfer from the former to the latter (~0.457 e−), rendering the Cu cluster sites partially cationic and facilitating the activation of carbonate intermediates. This dual-site configuration changes the discharge pathway and lowers the reaction energy of the rate-determining step to 2.412 eV. The assembled battery delivers a discharge capacity of 21356 mAh g−1 at 200 mA g−1 and operates for 260 cycles (>1000 h) at 500 mA g−1 with an energy efficiency of 78%. This work provides an interfacial design strategy for solid-state Li–CO2 batteries by coupling continuous transport pathways with electronically regulated dual Cu active sites.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"4 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242016","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}

引用次数: 0

Molecular insights into GPR55 modulation reveal an atypical activation mechanism and glycosylation-dependent efficacy regulation 对GPR55调控的分子洞察揭示了非典型激活机制和糖基化依赖性功效调控

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2026-10-24 DOI: 10.1038/s41467-026-78538-1

Tobias Claff, Chamalee Demalgiriya-Gamage, Andhika B. Mahardhika, Nikolaos Angelos Stamos, Frederik Bangnowski, Xue Sun, Katharina L. Dürr, Carol V. Robinson, Rainer Haney, Lee Frego, Herbert Nar, Christa E. Müller, Rebecca Ebenhoch, Jörg T. Kley, Dietmar Weichert

{"title":"Molecular insights into GPR55 modulation reveal an atypical activation mechanism and glycosylation-dependent efficacy regulation","authors":"Tobias Claff, Chamalee Demalgiriya-Gamage, Andhika B. Mahardhika, Nikolaos Angelos Stamos, Frederik Bangnowski, Xue Sun, Katharina L. Dürr, Carol V. Robinson, Rainer Haney, Lee Frego, Herbert Nar, Christa E. Müller, Rebecca Ebenhoch, Jörg T. Kley, Dietmar Weichert","doi":"10.1038/s41467-026-78538-1","DOIUrl":"https://doi.org/10.1038/s41467-026-78538-1","url":null,"abstract":"GPR55 is a lipid-activated G protein-coupled receptor (GPCR) implicated in metabolism, inflammation, and neurodegeneration. Lysophosphatidylinositol (LPI) species are proposed as endogenous agonists, but progress in understanding GPR55 function has still been limited by suboptimal chemical probes. Here, we present cryo-electron microscopy (cryo-EM) structures of GPR55 in both inactive and active states. The inactive-state structure bound to the inverse agonist CID16020046 facilitated the rational design of an improved in vitro tool compound, BI-8310. Surprisingly, mutation of a glycosylation site in extracellular loop 2 converted CID16020046 into a potent agonist, enabling co-structure determination of the active, G13-bound receptor. Comparative analysis of both states bound to the same ligand provides insights into an atypical activation mechanism that diverges from the typical helix VI outward movement observed in other GPCRs. Functional mutagenesis, N-glycoproteomics, and hydrogen-deuterium exchange mass spectrometry (HDX-MS) substantiate the findings. These results establish a basis for targeted modulation of GPR55 in pathophysiological conditions.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"21 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241981","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}

引用次数: 0

Label-free, real-time optical biopsy with a handheld quantitative phase microscope 无标签，实时光学活检与手持式定量相显微镜

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2026-10-24 DOI: 10.1038/s41467-026-78971-2

Zhe Guang, Srinidhi Bharadwaj, Zhaobin Zhang, Zhenmin Li, Stewart Neill, Jeffrey J. Olson, Francisco E. Robles

{"title":"Label-free, real-time optical biopsy with a handheld quantitative phase microscope","authors":"Zhe Guang, Srinidhi Bharadwaj, Zhaobin Zhang, Zhenmin Li, Stewart Neill, Jeffrey J. Olson, Francisco E. Robles","doi":"10.1038/s41467-026-78971-2","DOIUrl":"https://doi.org/10.1038/s41467-026-78971-2","url":null,"abstract":"We present a compact, handheld quantitative phase imaging microscope that enables label-free, real-time optical imaging of bulk tissues with clear cellular and subcellular histological detail, effectively providing an “optical biopsy.” The approach uses quantitative oblique back-illumination microscopy (qOBM) to obtain quantitative phase information of opaque samples using epi-illumination. The probe has a wide-field, non-scanning architecture that achieves 0.8 µm lateral and 5 µm axial resolution across a 300 µm × 300 µm field of view at 25 frames per second. The probe is also low-cost, contains no moving components, is easy to use and can operate through a sterile sheath, addressing key barriers to clinical implementation. To demonstrate its utility, we image (1) human skin in vivo, (2) murine and human brain tumors ex vivo, and (3) swine brain in vivo under typical neurosurgical conditions. By providing real-time, label-free histological information in a robust and accessible handheld format, this technology creates broad opportunities for future clinical translation, including intraoperative and point-of-care histological tissue assessment.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"9 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241702","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}

引用次数: 0

Democratizing reliable knowledge-seeking with MyGPT: a privacy-first, open-source retrieval-augmented generation platform 民主化可靠的知识寻求与MyGPT：一个隐私优先，开源检索增强生成平台

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2026-10-24 DOI: 10.1038/s41467-026-78509-6

Jaimin Patel, Jude Downing, Hugh Ferguson, Thika You, Duccio Malinverni, Steve Mathew D. A, Inês Chen, Madison Sluter, Beth Moorefield, Katalin Paréj, Mukundan Ragavan, Cindy Morris, Dinesh Keerthi, Desiree Becerra Armada, Bálint Mészáros, Vikas D. Trivedi, Shahinur Alam, Anthony Woodard, Dan Alford, Sagar Pathak, Cai Li, Renato Umeton, Carlos Rodriguez-Galindo, Catherine G. Lam, Stephen Gottschalk, Charalampos G. Kalodimos, M. Madan Babu

{"title":"Democratizing reliable knowledge-seeking with MyGPT: a privacy-first, open-source retrieval-augmented generation platform","authors":"Jaimin Patel, Jude Downing, Hugh Ferguson, Thika You, Duccio Malinverni, Steve Mathew D. A, Inês Chen, Madison Sluter, Beth Moorefield, Katalin Paréj, Mukundan Ragavan, Cindy Morris, Dinesh Keerthi, Desiree Becerra Armada, Bálint Mészáros, Vikas D. Trivedi, Shahinur Alam, Anthony Woodard, Dan Alford, Sagar Pathak, Cai Li, Renato Umeton, Carlos Rodriguez-Galindo, Catherine G. Lam, Stephen Gottschalk, Charalampos G. Kalodimos, M. Madan Babu","doi":"10.1038/s41467-026-78509-6","DOIUrl":"https://doi.org/10.1038/s41467-026-78509-6","url":null,"abstract":"Large language models (LLMs) have transformed knowledge discovery, but their use in sensitive domains is limited by privacy concerns and risks of data leakage. Moreover, LLMs may hallucinate when queried about information outside their training data, undermining their reliability for scientific, clinical, or policy-related tasks. We present MyGPT, a fully open-source, privacy-preserving retrieval-augmented-generation (RAG) platform that uses open-source LLMs and operates locally or within secure institutional environments. MyGPT empowers users to query user-defined libraries such as biomedical literature, confidential clinical documents, and multilingual global health policies, while ensuring that sensitive data never leaves the secure environment. We introduce confidence metrics, including “relevance scores” and “hallucination index,” and provide explicit source citation from the library within a single interface to assess contextual support for generated answers. MyGPT offers a cost-effective, modular, open-source alternative to commercial LLM services and democratizes knowledge-seeking across multiple domains, including use at remote facilities without internet access.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"9 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241986","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}

引用次数: 0