Lilian Marie Boll, Sergio Vázquez Montes de Oca, Marta E. Camarena, Robert Castelo, Joaquim Bellmunt, Júlia Perera-Bel, M. Mar Albà
{"title":"Predicting immunotherapy response of advanced bladder cancer through a meta-analysis of six independent cohorts","authors":"Lilian Marie Boll, Sergio Vázquez Montes de Oca, Marta E. Camarena, Robert Castelo, Joaquim Bellmunt, Júlia Perera-Bel, M. Mar Albà","doi":"10.1038/s41467-025-56462-0","DOIUrl":"https://doi.org/10.1038/s41467-025-56462-0","url":null,"abstract":"<p>Advanced bladder cancer patients show very variable responses to immune checkpoint inhibitors (ICIs) and effective strategies to predict response are still lacking. Here we integrate mutation and gene expression data from 707 advanced bladder cancer patients treated with anti-PD-1/anti-PD-L1 to build highly accurate predictive models. We find that, in addition to tumor mutational burden (TMB), enrichment in the APOBEC mutational signature, and the abundance of pro-inflammatory macrophages, are major factors associated with the response. Paradoxically, patients with high immune infiltration do not show an overall better response. We show that this can be explained by the activation of immune suppressive mechanisms in a large portion of these patients. In the case of non-immune-infiltrated cancer subtypes, we uncover specific variables likely to be involved in the response. Our findings provide information for advancing precision medicine in patients with advanced bladder cancer treated with immunotherapy.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"29 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452224","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":"A nanotwinned-alloy strategy enables fast sodium deposition dynamics","authors":"Guodong Zou, Jinming Wang, Yong Sun, Weihao Yang, Tingting Niu, Jinyu Li, Liqun Ren, Zhi Wei Seh, Qiuming Peng","doi":"10.1038/s41467-025-56957-w","DOIUrl":"https://doi.org/10.1038/s41467-025-56957-w","url":null,"abstract":"<p>Sodium (Na) metal batteries are considered promising solutions for next-generation electrochemical energy storage because of their low costs and high energy densities. However, the slow Na dynamics result in unfavorable Na deposition and dendrite growth, which compromise cycling performance. Here we propose a nanotwinned alloy strategy prepared by high-pressure solid solution followed by Joule-heating treatment to address sluggish Na dynamics, achieving homogeneous Na deposition. By employing cost-effective Al-Si alloys for validation, Si solubility of 10 wt.% is extended through a high-pressure solid solution, and nanotwinned-Si particles, with a volume fraction of 82.7%, are subsequently formed through Joule-heating treatment. The sodiophilic nanotwinned-Si sites exhibit a high diffusion rate, which reduces the nondimensional electrochemical Damköhler number to far below 1, shifting the diffusion-controlled deposition behavior to reaction-controlled deposition. This transition facilitates spherical Na deposition and dendrite-free growth, allowing a symmetric cell to achieve stable Na plating/stripping over 5300 h at 5 mA cm<sup>−2</sup> with a cumulative capacity of 13.25 Ah cm<sup>−2</sup>. This strategy is also demonstrated in another CuAg system with nanotwinned Ag structures.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"15 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452188","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}
Weikang Xue, Yuanhua Chen, Ziyi Lei, Yuanxia Wang, Jiaze Liu, Xin Wen, Fang Xu, Pu Chen, Zhengxing Wu, Youngnam N. Jin, Yanxun V. Yu
{"title":"Calcium levels in ASER neurons determine behavioral valence by engaging distinct neuronal circuits in C. elegans","authors":"Weikang Xue, Yuanhua Chen, Ziyi Lei, Yuanxia Wang, Jiaze Liu, Xin Wen, Fang Xu, Pu Chen, Zhengxing Wu, Youngnam N. Jin, Yanxun V. Yu","doi":"10.1038/s41467-025-57051-x","DOIUrl":"https://doi.org/10.1038/s41467-025-57051-x","url":null,"abstract":"<p>The valence of stimuli is shaped by various factors, including environmental cues, internal states, genetic variability, and past experience. However, the mechanisms behind this flexibility remain elusive. In the nematode <i>C. elegans</i>, we found that ethanol, an olfactory stimulus, can elicit opposite chemotaxis responses – attraction vs. aversion – depending on NaCl concentration, demonstrating the role of environmental factors in altering valence. Remarkably, a single chemosensory neuron, ASER, orchestrate this bidirectional ethanol chemotaxis by integrating information from both stimuli – ethanol and NaCl – into its neuronal activity dynamics. Specifically, different calcium dynamics in the ASER neuron differentially activate the signaling molecule CMK-1, thereby engaging different downstream interneurons and leading to opposite chemotaxis directions. Consistently, optogenetic manipulations of the ASER neuron reverse the chemotaxis directions, by altering its calcium dynamics. Our findings reveal a mechanism by which a single neuron integrates multisensory inputs to determine context-dependent behavioral valence, contributing to our current understanding of valence encoding.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462127","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":"Polymer-like tetramer acceptor enables stable and 19.75% efficiency binary organic solar cells","authors":"Jianxiao Wang, Cheng Sun, Yonghai Li, Fuzhen Bi, Huanxiang Jiang, Chunming Yang, Xichang Bao, Junhao Chu","doi":"10.1038/s41467-025-57118-9","DOIUrl":"https://doi.org/10.1038/s41467-025-57118-9","url":null,"abstract":"<p>Limited by large batch differences and inferior polymerization degree of current polymer acceptors, the potential high efficiency and stability advantages of all-polymer solar cells (all-PSCs) cannot be fully utilized. Alternatively, largely π-extended and structurally definite oligomer acceptors are effective strategies to realize the overall performance of polymer acceptors. Herein, we report a linear tetramer acceptor namely 4Y-BO with identical molecular skeleton and comparable molecular-weight relative to the control polymer acceptor PY-BO. The structurally definite tetramer shows refined film-forming kinetics and improved molecular ordering, offering uniform crystallinity with polymer donor and hence well-defined fibrous heterojunction textures. Encouragingly, the PM6:4Y-BO devices achieve an efficiency up to 19.75% (certified efficiency:19.58%), largely surpassing that of the control PM6:PY-BO device (15.66%) and ranks the highest among solar cells based on oligomer and polymer acceptors. More noticeably, thermal stability, photostability and mechanical flexibility are collectively enhanced for PM6:4Y-BO devices. Our study provides an important approach for fabricating high performance and stable organic photovoltaics.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452210","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}
Jinfeng Xu, Tao Wang, Xiaoyi Wang, Christian Körner, Xianyong Cao, Eryuan Liang, Yongping Yang, Shilong Piao
{"title":"Late Quaternary fluctuation in upper range limit of trees shapes endemic flora diversity on the Tibetan Plateau","authors":"Jinfeng Xu, Tao Wang, Xiaoyi Wang, Christian Körner, Xianyong Cao, Eryuan Liang, Yongping Yang, Shilong Piao","doi":"10.1038/s41467-025-57036-w","DOIUrl":"https://doi.org/10.1038/s41467-025-57036-w","url":null,"abstract":"<p>The influence of paleoclimate in shaping current biodiversity pattern is widely acknowledged. However, it remains unclear how the upper paleo-range limit of trees, which dictated the habitat of endemic alpine species, affects the variability in endemic alpine species composition across space over the Tibetan Plateau. We integrated satellite-derived upper range limit of trees, dendrochronological data, and fossil pollen records with a paleoclimate dataset in a climate-driven predictive model to reconstruct the spatio-temporal upper range limit of trees at 100-year intervals since the Last Glacial Maximum. Our results show that trees distributed at the lowest elevations during the Last Glacial Maximum (~3426 m), and ascended to the highest elevations during the Holocene Climatic Optimum (~4187 m), a level ~180 m higher than the present-day (~4009 m). The temporal fluctuations in paleo-range limits of trees play a more important role than paleoclimate in shaping the current spatial pattern of beta-diversity of endemic flora, with regions witnessing higher fluctuations having lower beta-diversity. We therefore suggest that anthropogenic-caused climate change on decadal-to-centennial timescales could lead to higher fluctuations in range limits than orbitally-forced climate variability on centennial-to-millennium timescales, which consequently could cause spatial homogenization of endemic alpine species composition, threatening Tibetan endemic species pool.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"176 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462121","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":"Unconventional (anti)ferroelectricity in van der Waals group-IV monochalcogenides","authors":"Fengrui Sui, Yilun Yu, Ju Chen, Ruijuan Qi, Rui Ge, Yufan Zheng, Beituo Liu, Rong Jin, Shijing Gong, Fangyu Yue, Junhao Chu","doi":"10.1038/s41467-025-57138-5","DOIUrl":"https://doi.org/10.1038/s41467-025-57138-5","url":null,"abstract":"<p>Fundamentally, ferroelectrics must belong to a noncentrosymmetric space group, limiting the exploration of more new ferroelectric materials. We circumvent this limitation by triggering structure distortion and inducing ferroelectricity in centrosymmetric van der Waals group-IV monochalcogenide GeSe semiconductor that features unexpected intrinsic out-of-plane antiferroelectricity. Double-type and single-type hysteresis loops from electric measurements, bonding distortion observed in in-situ atomic imaging, and perpendicular polarization uncovered by first-principles calculations, confirm the intrinsic out-of-plane antiferroelectricity and the antiferroelectric–ferroelectric transition induced by the vertical external electric-field. The hidden out-of-plane antiferroelectricity and field induced ferroelectric polarization in spatial-inversion symmetric GeSe makes it a new member of van der Waals layered semiconductors with both in-plane and out-of-plane ferroelectricity, and possibly, can be extended to all group-IV monochalcogenides and other centrosymmetric van der Waals layered materials.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"14 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462883","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}
Gabriela Rabeschini, U. Martin Persson, Chris West, Thomas Kastner
{"title":"Choosing fit-for-purpose biodiversity impact indicators for agriculture in the Brazilian Cerrado ecoregion","authors":"Gabriela Rabeschini, U. Martin Persson, Chris West, Thomas Kastner","doi":"10.1038/s41467-025-57037-9","DOIUrl":"https://doi.org/10.1038/s41467-025-57037-9","url":null,"abstract":"<p>Understanding and acting on biodiversity loss requires robust tools linking biodiversity impacts to land use change, the biggest threat to terrestrial biodiversity. Here we estimate agriculture’s impact on the Brazilian Cerrado’s biodiversity using three approaches—countryside Species-Area Relationship, Species Threat Abatement and Restoration and Species Habitat Index. By using same input data, we show how indicator scope and design affects impact assessments and resulting decision-support. All indicators show agriculture expansion’s increasing pressure on biodiversity. Results suggest that metrics are complementary, providing distinctly different insight into biodiversity change drivers and impacts. Meaningful applications of biodiversity indicators therefore require compatibility between focal questions and indicator choice regarding temporal, spatial, and ecological perspectives on impact and drivers. Backward-looking analyses focused on historical land use change and accountability are best served by the countryside-Species Area Relationship and the Species Habitat Index. Forward-looking analyses of impact risk hotspots and global extinctions mitigation are best served by the Species Threat Abatement and Restoration.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"25 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452221","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}
Nils Bäcker, Julia Ast, Domenica Martorana, Christian Renicke, Jil Berger, Cristopher-Nils Mais, Marvin Christ, Thorsten Stehlik, Thomas Heimerl, Valentin Wernet, Christof Taxis, Jan Pané-Farré, Michael Bölker, Judith M. Klatt, Björn Sandrock, Kay Oliver Schink, Gert Bange, Johannes Freitag
{"title":"Peroxisomal core structures segregate diverse metabolic pathways","authors":"Nils Bäcker, Julia Ast, Domenica Martorana, Christian Renicke, Jil Berger, Cristopher-Nils Mais, Marvin Christ, Thorsten Stehlik, Thomas Heimerl, Valentin Wernet, Christof Taxis, Jan Pané-Farré, Michael Bölker, Judith M. Klatt, Björn Sandrock, Kay Oliver Schink, Gert Bange, Johannes Freitag","doi":"10.1038/s41467-025-57053-9","DOIUrl":"https://doi.org/10.1038/s41467-025-57053-9","url":null,"abstract":"<p>Peroxisomes are single membrane-bounded oxidative organelles with various metabolic functions including β-oxidation of fatty acids. Peroxisomes of many species confine certain metabolic enzymes into sub-compartments sometimes visible as electron dense cores. Why these structures form is largely unknown. Here, we report that in the smut fungus <i>Ustilago maydis</i> detergent resistant core structures are enriched for different enzymes excluding several key enzymes of the β-oxidation pathway. This confinement contributes to generation of peroxisome subpopulations that differ in their enzyme content. We identify short amino acid motifs necessary and sufficient for protein self-assembly into aggregates in vitro. The motifs trigger enrichment in cores in vivo and are active in mammalian cells. Perturbation of core assembly via variation of such motifs affects peroxisome function in <i>U. maydis</i> strains challenged with fatty acids. Thus, protein core structures serve to compartmentalize the lumen of peroxisomes thereby preventing interference of biochemical reactions. Metabolic compartmentalization of peroxisomes via assembly of specific proteins may occur in other organisms as well.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"29 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462885","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}
Regina B. Troyanovsky, Indrajyoti Indra, Sergey M. Troyanovsky
{"title":"Actin-dependent α-catenin oligomerization contributes to adherens junction assembly","authors":"Regina B. Troyanovsky, Indrajyoti Indra, Sergey M. Troyanovsky","doi":"10.1038/s41467-025-57079-z","DOIUrl":"https://doi.org/10.1038/s41467-025-57079-z","url":null,"abstract":"<p>Classic cadherins, specifically E-cadherin in most epithelial cells, are transmembrane adhesion receptors, whose intracellular region interacts with proteins, termed catenins, forming the cadherin-catenin complex (CCC). The cadherin ectodomain generates 2D adhesive clusters (E-clusters) through cooperative <i>trans</i> and <i>cis</i> interactions, while catenins anchor the E-clusters to the actin cytoskeleton. How these two types of interactions are coordinated in the formation of specialized cell-cell adhesions, adherens junctions (AJ), remains unclear. Here, we focus on the role of the actin-binding domain of α-catenin (αABD) by showing that the interaction of the αABD with actin generates actin-bound linear CCC oligomers (CCC/actin strands) incorporating up to six CCCs. This actin-driven CCC oligomerization, which is cadherin ectodomain independent, preferentially occurs along the actin cortex enriched with key basolateral proteins, myosin-1c, scribble, and DLG1. In cell-cell contacts, the CCC/actin strands integrate with the E-clusters giving rise to the composite oligomers, E/actin clusters. Targeted inactivation of strand formation by point mutations emphasizes the importance of this oligomerization process for blocking intercellular protrusive membrane activity and for coupling AJs with the actomyosin-derived tensional forces.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"50 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452215","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}
Yeongmok Lee, Elsa Demes-Causse, Jaemin Yoo, Seo Young Jang, Seoyeon Jung, Justyna Jaślan, Geum-Sook Hwang, Jejoong Yoo, Alexis De Angeli, Sangho Lee
{"title":"Structural basis for malate-driven, pore lipid-regulated activation of the Arabidopsis vacuolar anion channel ALMT9","authors":"Yeongmok Lee, Elsa Demes-Causse, Jaemin Yoo, Seo Young Jang, Seoyeon Jung, Justyna Jaślan, Geum-Sook Hwang, Jejoong Yoo, Alexis De Angeli, Sangho Lee","doi":"10.1038/s41467-025-56940-5","DOIUrl":"https://doi.org/10.1038/s41467-025-56940-5","url":null,"abstract":"<p>In plant cells, ALMTs are key plasma and vacuolar membrane-localized anion channels regulating plant responses to the environment. Vacuolar ALMTs control anion accumulation in plant cells and, in guard cells, they regulate stomata aperture. The activation of vacuolar ALMTs depends on voltage and cytosolic malate, but the underlying molecular mechanisms remain elusive. Here we report the cryo-EM structures of ALMT9 from <i>Arabidopsis thaliana</i> (AtALMT9), a malate-activated vacuolar anion channel, in plugged and unplugged lipid-bound states. In all these states, membrane lipids interact with the ion conduction pathway of AtALMT9. We identify two unplugged states presenting two distinct pore width profiles. Combining structural and functional analysis we identified conserved residues involved in ion conduction and in the pore lipid interaction. Molecular dynamics simulations revealed a peculiar anion conduction mechanism in AtALMT9. We propose a voltage-dependent activation mechanism based on the competition between pore lipids and malate at the cytosolic entrance of the channel.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"31 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462129","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}