{"title":"Homeostasis of glucose and lipid metabolism during physiological responses to a simulated hypoxic high altitude environment.","authors":"Yi Lin,Bingyu Li,Xinying Shi,Yangkang Chen,Shengkai Pan,Zhenzhen Lin,Zhongru Gu,Frank Hailer,Li Hu,Xiangjiang Zhan","doi":"10.1038/s41467-025-64110-w","DOIUrl":"https://doi.org/10.1038/s41467-025-64110-w","url":null,"abstract":"Homeostasis facilitates maintenance of physiological processes despite extrinsic fluctuations. In aerobic organisms, homeostasis is mainly fueled by metabolism of glucose and lipids, and requires oxygen as a metabolic substrate. Lack of oxygen can therefore trigger an imbalance of homeostasis in vivo. How animals living at high altitude hypoxic conditions can maintain homeostasis between the two types of metabolism remains largely unknown. Here, we establish a 'falconized' mouse model based on an adaptive EPAS1 genetic variant identified from saker falcons (Falco cherrug) on the Qinghai-Tibet Plateau (QTP). We show that homeostasis between glucose and lipid metabolism in the liver under chronic hypoxia is maintained in male falconized mice. This homeostasis is mediated by genetic factors and behavioral plasticity, resulting in higher survival rates even under acute hypoxia than wild type mice. Our study highlights a key role of metabolic homeostasis maintenance for survival in extreme environments, and provides potential targets for the treatment of associated metabolic diseases.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"24 1","pages":"9406"},"PeriodicalIF":16.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357716","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":"Inhibition of PGK1 ameliorates acute kidney injury through inactivating the PKM2/ALOX12/ferroptosis pathway in a study with male mice.","authors":"Xue-Xue Zhu,Xin-Yu Meng,Ao-Yuan Zhang,Chen-Yang Zhao,Yi-Ting Wei,Yuan-Yuan Wen,Jia-Bao Su,Xiao Fu,Guo Chen,An-Jing Xu,Meng-Yuan Wang,Le-Ming Ji,Neng Bao,Zheng-Yang Bao,Na Li,Qing-Bo Lu,Hai-Jian Sun","doi":"10.1038/s41467-025-64480-1","DOIUrl":"https://doi.org/10.1038/s41467-025-64480-1","url":null,"abstract":"Despite decades of studies into the mechanisms underlying acute kidney injury (AKI), the effective clinical therapies are still limited. Here we report that the development of AKI was attenuated by conditional knockout of phosphoglycerate kinase 1 (PGK1) in renal tubular epithelial cells (RTECs) and aggravated by specific overexpression of PGK1 and administration of 3-phosphoglycerate (3-PG) in male mice. PGK1 interacted with pyruvate kinase M2 (PKM2), inducing PKM2 phosphorylation, promoting the formation of the PKM2 dimer and the subsequent nuclear translocation of PKM2. In the nucleus, the interaction of PKM2 with Pknox1 potentiated the enrichment of Pknox1 within ALOX12 promoters, which resulted in ALOX12-mediated ferroptosis in RTECs. Our drug screening experiments identified L7DG as a potential PGK1 inhibitor which exhibited protective effects against ischemic/reperfusion (I/R)-induced renal injury. Overall, we establish that genetic and pharmacological inhibition of PGK1 might be proposed as an avenue for managing AKI.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"46 1","pages":"9436"},"PeriodicalIF":16.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357708","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":"The northeast materials database for magnetic materials.","authors":"Suman Itani,Yibo Zhang,Jiadong Zang","doi":"10.1038/s41467-025-64458-z","DOIUrl":"https://doi.org/10.1038/s41467-025-64458-z","url":null,"abstract":"The discovery of magnetic materials with high operating temperature ranges and optimized performance is essential for advanced applications. Current data-driven approaches are limited by the lack of accurate, comprehensive, and feature-rich databases. This study aims to address this challenge by using Large Language Models (LLMs) to create a comprehensive, experiment-based, magnetic materials database named the Northeast Materials Database (NEMAD), which consists of 67,573 magnetic materials entries ( www.nemad.org ). The database incorporates chemical composition, magnetic phase transition temperatures, structural details, and magnetic properties. Enabled by NEMAD, we trained machine learning models to classify materials and predict transition temperatures. Our classification model achieved an accuracy of 90% in categorizing materials as ferromagnetic (FM), antiferromagnetic (AFM), and non-magnetic (NM). The regression models predict Curie (Néel) temperature with a coefficient of determination (R2) of 0.87 (0.83) and a mean absolute error (MAE) of 56K (38K). These models identified 25 (13) FM (AFM) candidates with a predicted Curie (Néel) temperature above 500K (100K) from the Materials Project. This work shows the feasibility of combining LLMs for automated data extraction and machine learning models to accelerate the discovery of magnetic materials.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":"9415"},"PeriodicalIF":16.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357710","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}
Xiaochen Qiu,Daoming Guan,Xiaojing Xia,Huan Ling,Jialing Hu,Yunxiang Zhang,Emory Chan,Fuyou Li,Qian Liu
{"title":"Sub-10 nm upconversion nanocrystals for long-term single-particle tracking.","authors":"Xiaochen Qiu,Daoming Guan,Xiaojing Xia,Huan Ling,Jialing Hu,Yunxiang Zhang,Emory Chan,Fuyou Li,Qian Liu","doi":"10.1038/s41467-025-64180-w","DOIUrl":"https://doi.org/10.1038/s41467-025-64180-w","url":null,"abstract":"Lanthanide-doped upconversion nanoparticles are attractive single-molecule imaging probes due to their high photostability and anti-Stokes luminescence. However, achieving both small particle size and strong brightness has remained a major challenge, as reducing size often leads to dimmer emission. Herein, we fabricate a sub-10 nm cascade actively protected upconversion nanoparticles, which shows a 33-fold enhanced upconversion efficiency at the single-particle level compared to larger ~19 nm conventional nanoparticles. Theoretical modeling and time-resolved measurements show that emission loss mainly comes from energy leakage of Er3+ ions to surface defects. By introducing a NaYbF4 layer as photon-harvesting and protective intermediate layer, we minimize this energy loss and significantly boost brightness. A monolayer of inert NaLuF4 can effectively suppress the surface quenching to Yb3+. Using these ultra-small bright probes, we successfully tracked single epidermal growth factor receptor molecules on live cells for up to one hour, revealing dynamic switching between different diffusion modes.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"70 1","pages":"9408"},"PeriodicalIF":16.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357711","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":"MultiGATE: integrative analysis and regulatory inference in spatial multi-omics data via graph representation learning.","authors":"Jishuai Miao,Jinzhao Li,Jingxue Xin,Jiajuan Tu,Muyang Ge,Ji Qi,Xiaocheng Zhou,Ying Zhu,Can Yang,Zhixiang Lin","doi":"10.1038/s41467-025-63418-x","DOIUrl":"https://doi.org/10.1038/s41467-025-63418-x","url":null,"abstract":"New spatial multi-omics technologies, which jointly profile transcriptome and epigenome/protein markers for the same tissue section, expand the frontiers of spatial techniques. Here, we introduce MultiGATE, which utilizes a two-level graph attention auto-encoder to integrate the multi-modality and spatial information in spatial multi-omics data. The key feature of MultiGATE is that it simultaneously performs embedding of the spatial pixels and infers the cross-modality regulatory relationship, which allows deeper data integration and provides insights on transcriptional regulation. We evaluate the performance of MultiGATE on spatial multi-omics datasets obtained from different tissues and platforms. Through effectively integrating spatial multi-omics data, MultiGATE both enhances the extraction of latent embeddings of the pixels and boosts the inference of transcriptional regulation for cross-modality genomic features.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"79 1","pages":"9403"},"PeriodicalIF":16.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357712","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":"Particle decoration enables solution-processed perovskite integration with fully-textured silicon for efficient tandem solar cells.","authors":"Naihe Liu,Gao Zhang,Meng Wei,Lijun Yang,Hangyu Gu,Lirong Zeng,Xin Zhang,Yuwei Geng,Ying Zhu,Chengxia Shen,Yongyi Wu,Tao Li,Wei Wang,Xiaolei Li,Kaifu Qiu,Peicheng Wei,Guanjun Yang,Jinsong Huang,Bo Chen","doi":"10.1038/s41467-025-64546-0","DOIUrl":"https://doi.org/10.1038/s41467-025-64546-0","url":null,"abstract":"Perovskite/silicon tandem solar cells can exceed Shockley-Queisser limit, but achieving complete coverage of 2-4 μm pyramids on industrial fully-textured silicon with solution-processed perovskite film remains challenging. We address this issue by spray-coating alumina particles onto fully-textured silicon, creating a super-hydrophilic rough surface that both enhances wet film coverage and provides guided nucleation sites. Although super-hydrophilic effect enhances wetting, it alone is insufficient to achieve complete coverage of pyramids by perovskite film. Beyond enhanced wetting, alumina particles promote uniform nucleation at particle-decorated sites across pyramids by lowering nucleation barrier and suppressing valley-preferred nucleation, which enables near-conformal deposition of perovskite film on pyramids. Additionally, alumina particles reduce nonradiative recombination and extend carrier lifetimes. Using this approach, we achieve a efficiency of 32.74% for perovskite/silicon tandem solar cells with one-step solution-processed perovskite on fully-textured silicon. This strategy offers a pathway for seamless integration of perovskite and silicon photovoltaics into high-performance tandem devices.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"15 1","pages":"9435"},"PeriodicalIF":16.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357825","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":"Engineering unnatural cells with a 21st amino acid as a living epigenetic sensor.","authors":"Yu Hu,Yixian Wang,Linqi Cheng,Chenhang Wang,Yijie Liu,Yufei Wang,Yuda Chen,Shudan Yang,Yiming Guo,Shiyu Jiang,Kaiqiang Yang,Han Xiao","doi":"10.1038/s41467-025-64448-1","DOIUrl":"https://doi.org/10.1038/s41467-025-64448-1","url":null,"abstract":"Living animals rely extensively on post-translational modifications (PTMs) to regulate protein activity, stability, subcellular localization, and protein-protein interactions. These modifications are tightly controlled by the balance of \"writer\" and \"eraser\" enzymes, which add or remove PTMs on proteins. Current strategies to measure writer and eraser activities in living animals largely depend on invasive methods, such as single-cell sequencing, quantitative mass spectrometry, or activity-based probes, which often lack cell or tissue specificity. In this study, we report the development of autonomous cells-both prokaryotic and eukaryotic-with the ability to biosynthesize and genetically encode acetyllysine using the genetic code expansion technology. These engineered living sensors with a site-specific acetyllysine modification can be transplanted into living animals, enabling real-time monitoring of PTM dynamics in living cells and animals. We further demonstrate the utility of these cells in tracking deacetylase activity and assessing the effects of deacetylase inhibitors on PTM dynamics in living animals in real time.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"50 1","pages":"9388"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351551","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}
Pier-Olivier Martel,Rustelle Janse van Vuuren,Julia Degrémont,Sarah Turmel-Couture,Armi M Chaudhari,Eden Dologuele,Lucie Beaulieu,Alexandre Clouet,Patrick Narbonne
{"title":"Niche-associated Type IV collagen promotes GLP-1/Notch receptor activation in the C. elegans germline.","authors":"Pier-Olivier Martel,Rustelle Janse van Vuuren,Julia Degrémont,Sarah Turmel-Couture,Armi M Chaudhari,Eden Dologuele,Lucie Beaulieu,Alexandre Clouet,Patrick Narbonne","doi":"10.1038/s41467-025-64394-y","DOIUrl":"https://doi.org/10.1038/s41467-025-64394-y","url":null,"abstract":"Basement membranes are thin and dense proteinaceous layers that surround tissues to maintain their structure. With age, chronic inflammation typically stiffens this basement membrane through a phenomenon called fibrosis, which is reflected by increasing levels of the basement membrane's main structural component, type IV collagen (COL IV). Tissue fibrosis and elevated Notch signalling are two co-occurring hallmarks of many inflammation-linked diseases, including cancer, but their in vivo relationship has not been clearly defined. Here we show that EMB-9/COL IV accumulation around the C. elegans germline stem cell niche promotes GLP-1/Notch receptor activation in germline stem cells. Moreover, we find that contrasting with previous beliefs, reducing GLP-1/Notch activity in vivo leads to a generalized dramatic increase in EMB-9/COL IV levels, and thereby promotes fibrosis. The generalized fibrosis that comes along with inflammaging may therefore act as a root cause for cancer by promoting Notch signalling, and perhaps other ligand-receptor interactions.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":"9363"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351604","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":"FAP+ fibroblasts orchestrate tumor microenvironment remodeling in renal cell carcinoma with tumor thrombus.","authors":"Jiacheng Ma,Yan Huang,Jie Chen,Yang Li,Rongyan Yao,Xiubin Li,Qiyang Liang,Xinran Chen,Cheng Peng,Kan Liu,Yuanjun Zhai,Xu Zhang,Xin Ma,Xiaowen Wang,Qingbo Huang,Fuchu He","doi":"10.1038/s41467-025-64447-2","DOIUrl":"https://doi.org/10.1038/s41467-025-64447-2","url":null,"abstract":"Tumor thrombus (TT) worsens prognosis and complicates surgery in renal cell carcinoma (RCC), yet its formation mechanisms remain unclear. Here, we perform integrative single-cell and spatial transcriptomic analyses on 71 tissues and 48 sections from RCC patients with or without TT. The cellular and spatial atlas reveals distinct TT-associated tumor microenvironment remodeling characterized by the enrichment of FAP+ fibroblasts. These FAP+ fibroblasts are spatially contiguous to aggressive cancer cells and promote their malignant phenotypes in vitro. Their abundance inversely correlates with functional NK cells, suggesting roles in tumor invasion and immune evasion. Furthermore, single-cell multiomics analysis identifies tumor pericytes as a source of FAP+ fibroblasts and delineates transcription factor dynamics underlying pericyte-fibroblast transition. Finally, high levels of FAP+ fibroblasts are associated with poor prognosis and predict a weaker response to anti-VEGF-based therapy. In conclusion, our study highlights FAP+ fibroblasts as drivers of aggressive RCC with TT, suggesting potential therapeutic targets.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"69 1","pages":"9387"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351607","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":"Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages.","authors":"Shivani Sahu,Navin Baid,Deepali Aggarwal,Ankita Sharma,Manisha Gun,Sahanawaz Molla,Anunay Sinha,Ambey Prasad Dwivedi,Amit Tuli,Mahak Sharma,Sanjeev Khosla,Varadharajan Sundaramurthy,Ashwani Kumar","doi":"10.1038/s41467-025-64404-z","DOIUrl":"https://doi.org/10.1038/s41467-025-64404-z","url":null,"abstract":"Mycobacterium tuberculosis is a model intracellular pathogen. The spatial-localization of M. tuberculosis inside macrophages is poorly defined. Here, we determine the spatial-localization of M. tuberculosis inside macrophages with reference to the nucleus. Few M. tuberculosis cells are perinuclear, while most are peripheral. Perinuclear M. tuberculosis are transported to lysosomes, have low Adenosine Triphosphate/Adenosine Diphosphate, are non-replicating, and tolerate front-line anti-tubercular medicines. M. tuberculosis pathogenicity determines its spatial location. Virulent M. tuberculosis strains are peripheral. However, avirulent M. tuberculosis strains or attenuated deletion mutants are transported to lysosomes in the perinuclear area. Early Secreted Antigenic Target-6 and Culture Filtrate Protein-10 play a critical role in inhibiting mycobacterial transport to the perinuclear space. Induction of centripetal transport of pathogenic M. tuberculosis-laden cargoes to perinuclear region enhances M. tuberculosis's delivery to the lysosomes and reduces mycobacterial growth. Interferon-γ directs M. tuberculosis to lysosomes by modulating their perinuclear localization. Interferon-γ upregulates Transmembrane protein 55B and JNK-interacting protein 4 via transcription factor EB. Increased transmembrane protein 55B and JNK-interacting protein 4 levels tether M. tuberculosis-laden cargoes to the dynein motor, causing their perinuclear delivery to lysosomes. These findings shed light on how mycobacterial metabolism, reproduction, and drug susceptibility are connected to virulence-guided spatial localization.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"50 1","pages":"9368"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351613","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}
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