Pub Date : 2026-02-11DOI: 10.1038/s41467-026-69325-z
Yan Liang, Yi Xia
The influence of genetic variation on alternative splicing (AS) across immune cell types and demographic strata in European populations remains poorly understood. Here, we leveraged the OneK1K cohort, comprising 980 individuals of European ancestry with matched genotyping and single-cell RNA sequencing (scRNA-seq) data, to systematically investigate splicing variation at single-cell resolution. Across 13 immune cell types, we identified extensive cell-type-specific AS events and independent cis-splicing quantitative trait loci (cis-sQTLs), with subsets showing distinct sex- and age-biased patterns. Colocalization analysis identified numerous shared signals between cell-type-specific cis-sQTLs and GWAS loci for 30 polygenic traits, demonstrating that splicing regulation represents an important mechanism through which susceptibility loci influence complex traits. Through trans-sQTL analysis, we found that genetic variants exert distal effects on RPS24 splicing via proximal regulation of IVNS1ABP expression, a splicing regulator that interacts with the splicing factor HNRNPK. Collectively, our findings provide new insights into how genetic variation shapes splicing programs across cellular and demographic contexts in European populations, establishing a mechanistic framework for splicing-mediated regulation of complex traits.
{"title":"Single-cell resolution of splicing regulation in peripheral blood mononuclear cells uncovers heterogeneity-driven mechanisms underlying human complex traits","authors":"Yan Liang, Yi Xia","doi":"10.1038/s41467-026-69325-z","DOIUrl":"https://doi.org/10.1038/s41467-026-69325-z","url":null,"abstract":"The influence of genetic variation on alternative splicing (AS) across immune cell types and demographic strata in European populations remains poorly understood. Here, we leveraged the OneK1K cohort, comprising 980 individuals of European ancestry with matched genotyping and single-cell RNA sequencing (scRNA-seq) data, to systematically investigate splicing variation at single-cell resolution. Across 13 immune cell types, we identified extensive cell-type-specific AS events and independent cis-splicing quantitative trait loci (cis-sQTLs), with subsets showing distinct sex- and age-biased patterns. Colocalization analysis identified numerous shared signals between cell-type-specific cis-sQTLs and GWAS loci for 30 polygenic traits, demonstrating that splicing regulation represents an important mechanism through which susceptibility loci influence complex traits. Through trans-sQTL analysis, we found that genetic variants exert distal effects on RPS24 splicing via proximal regulation of IVNS1ABP expression, a splicing regulator that interacts with the splicing factor HNRNPK. Collectively, our findings provide new insights into how genetic variation shapes splicing programs across cellular and demographic contexts in European populations, establishing a mechanistic framework for splicing-mediated regulation of complex traits.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"9 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152287","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}
Pub Date : 2026-02-11DOI: 10.1038/s41467-026-69338-8
Feng Zhu, Kang Xu, Yuhe Liao, Liyan Chen, Yangsen Xu, Feng Hu, Fan He, Xirui Zhang, Yu Chen
The development of oxygen electrodes with sufficient oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activity, as well as good tolerance to contaminants, is crucial for promoting the commercialization of reversible solid oxide cells (Re-SOCs) technologies. Herein, we design and synthesize a medium-entropy oxygen electrode with a formula of Pr0.5Ba0.2Sr0.2Ca0.1CoO3-δ (ME-PBSCC). The abundant surface oxygen vacancy concentration, high electrical conductivity, rapid and stable oxygen exchange kinetics, and structural stability of the ME-PBSCC oxygen electrode ensure the efficient and poisoning-tolerant ORR/OER in ambient air and Cr-contaminated atmosphere. Specifically, Re-SOCs incorporating the PBSCC oxygen electrodes exhibit maximum power densities of 2.239 (in ambient air) and 1.859 W cm-2 (in a Cr-contaminated air) at 750 oC in fuel cell (FC) mode, and current densities of 1.10 A cm-2 at 1.3 V and 700 oC under 50% H2O (in a Cr-contaminated air) in electrolysis (EC) mode, demonstrating competitive performance for Re-SOCs. More importantly, the developed ME-PBSCC oxygen electrode has achieved the highly promising stable operation of Re-SOCs in FC, EC, and reversible modes in the presence of Cr contamination.
开发具有足够的氧还原反应（ORR）和氧析反应（OER）活性以及良好的污染物耐受性的氧电极，对于促进可逆固体氧化物电池（re - soc）技术的商业化至关重要。本文设计并合成了一种分子式为Pr0.5Ba0.2Sr0.2Ca0.1CoO3-δ (ME-PBSCC)的中熵氧电极。ME-PBSCC氧电极丰富的表面氧空位浓度、高导电性、快速稳定的氧交换动力学和结构稳定性，保证了其在环境空气和cr污染大气中的高效耐毒ORR/OER。具体来说，含有PBSCC氧电极的re - soc在燃料电池（FC）模式下，在750℃时的最大功率密度为2.239（环境空气中）和1.859 W cm-2 （cr污染空气中），在电解（EC）模式下，在1.3 V和700℃下（在cr污染空气中）电流密度为1.10 a cm-2，展示了re - soc的竞争性能。更重要的是，所开发的ME-PBSCC氧电极在Cr污染下实现了re - soc在FC、EC和可逆模式下的稳定运行。
{"title":"A medium-entropy oxygen electrode enables high-performance and contaminant-tolerant reversible solid oxide cells","authors":"Feng Zhu, Kang Xu, Yuhe Liao, Liyan Chen, Yangsen Xu, Feng Hu, Fan He, Xirui Zhang, Yu Chen","doi":"10.1038/s41467-026-69338-8","DOIUrl":"https://doi.org/10.1038/s41467-026-69338-8","url":null,"abstract":"The development of oxygen electrodes with sufficient oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activity, as well as good tolerance to contaminants, is crucial for promoting the commercialization of reversible solid oxide cells (Re-SOCs) technologies. Herein, we design and synthesize a medium-entropy oxygen electrode with a formula of Pr0.5Ba0.2Sr0.2Ca0.1CoO3-δ (ME-PBSCC). The abundant surface oxygen vacancy concentration, high electrical conductivity, rapid and stable oxygen exchange kinetics, and structural stability of the ME-PBSCC oxygen electrode ensure the efficient and poisoning-tolerant ORR/OER in ambient air and Cr-contaminated atmosphere. Specifically, Re-SOCs incorporating the PBSCC oxygen electrodes exhibit maximum power densities of 2.239 (in ambient air) and 1.859 W cm-2 (in a Cr-contaminated air) at 750 oC in fuel cell (FC) mode, and current densities of 1.10 A cm-2 at 1.3 V and 700 oC under 50% H2O (in a Cr-contaminated air) in electrolysis (EC) mode, demonstrating competitive performance for Re-SOCs. More importantly, the developed ME-PBSCC oxygen electrode has achieved the highly promising stable operation of Re-SOCs in FC, EC, and reversible modes in the presence of Cr contamination.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"134 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152292","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}
Sexual dimorphism in the incidence and mortality of hepatocellular carcinoma (HCC) has been observed worldwide. Sex hormones play an essential role in determining male predominance in hepatocarcinogenesis. Here we reveal significant sexual dimorphism in regulatory T cells (Tregs). Compared with HCC in female mice/patients, tumours in male mice/patients are more enriched in Tregs. The male sex hormone androgen is shown to activate the NFκB pathway and reinforce the binding of NFκB to Ccl2 promoter loci in HCC cells, thereby promoting Ccl2 production, which facilitates the intratumoral recruitment of Tregs via the Ccl2-Ccr2 axis. Additionally, Treg infiltration shapes the HCC microenvironment through the suppression of the antitumorigenic activity of γδ T cells rather than CD8+T cells. Moreover, intratumoral hypoxia induces the secretion of Treg-derived extracellular vesicle (EV)-S100a4, which serves as a transcriptional corepressor to impede γδ T cell activation in an epigenetic manner. Overall, these results demonstrate that sex-specific differences in Tregs from HCC are related to the ability of androgen-dependent Ccl2 secretion to enable immune evasion through the suppression of γδ T cell activity.
{"title":"Treg-γδ T cell axis determines sexual dimorphism in hepatocarcinogenesis","authors":"Qing Liang, Qian Zhang, Wei Zhang, Rui Wang, Yinjiang Ma, Xiaoya Mai, Zhenglang Zhang, Bing Liu, Ping Lu, Huijuan Wan, Kejia Wang","doi":"10.1038/s41467-026-69603-w","DOIUrl":"https://doi.org/10.1038/s41467-026-69603-w","url":null,"abstract":"Sexual dimorphism in the incidence and mortality of hepatocellular carcinoma (HCC) has been observed worldwide. Sex hormones play an essential role in determining male predominance in hepatocarcinogenesis. Here we reveal significant sexual dimorphism in regulatory T cells (Tregs). Compared with HCC in female mice/patients, tumours in male mice/patients are more enriched in Tregs. The male sex hormone androgen is shown to activate the NFκB pathway and reinforce the binding of NFκB to Ccl2 promoter loci in HCC cells, thereby promoting Ccl2 production, which facilitates the intratumoral recruitment of Tregs via the Ccl2-Ccr2 axis. Additionally, Treg infiltration shapes the HCC microenvironment through the suppression of the antitumorigenic activity of γδ T cells rather than CD8+T cells. Moreover, intratumoral hypoxia induces the secretion of Treg-derived extracellular vesicle (EV)-S100a4, which serves as a transcriptional corepressor to impede γδ T cell activation in an epigenetic manner. Overall, these results demonstrate that sex-specific differences in Tregs from HCC are related to the ability of androgen-dependent Ccl2 secretion to enable immune evasion through the suppression of γδ T cell activity.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"24 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152293","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}
Pub Date : 2026-02-11DOI: 10.1038/s41467-026-69419-8
Gewei Yan, Guangnan Tian, Yiming Fu, Yingzhu He, Zhentao She, Kenny K Y Chen, Julie L Semmelhack, Jianan Y Qu
All-optical interrogation, based on high-resolution two-photon stimulation and imaging, has emerged as a potentially transformative approach in neuroscience, allowing for the simultaneous precise manipulation and monitoring of neuronal activity across various model organisms. However, the unintended excitation of light-gated ion channels such as channelrhodopsin (ChR) during two-photon calcium imaging with genetically encoded calcium indicators (GECIs) introduces artifactual neuronal perturbation and contaminates neural activity measurements. In this study, we propose an active pixel power control (APPC) approach, which dynamically adjusts the imaging laser power at each scanning pixel, to address the challenge. We aim to achieve simultaneous two-photon optogenetic manipulation and calcium imaging with a single femtosecond laser, while minimizing the cross-talk between manipulation and imaging. To study this technology's capabilities, we applied it to the larval zebrafish brain in vivo. Our results demonstrate that the APPC approach preserves GECI signal quality while suppressing optogenetic artifacts significantly. This enhances the accuracy of neural circuit dissection and advances the precision of all-optical interrogation, offering a robust framework for probing neural circuit dynamics and causality in vivo with high fidelity, potentially across various model organisms. Importantly, this technology can be seamlessly integrated with commonly used two-photon microscope systems in laboratories worldwide.
{"title":"Active pixel power control for crosstalk-free All-optical neural interrogation.","authors":"Gewei Yan, Guangnan Tian, Yiming Fu, Yingzhu He, Zhentao She, Kenny K Y Chen, Julie L Semmelhack, Jianan Y Qu","doi":"10.1038/s41467-026-69419-8","DOIUrl":"https://doi.org/10.1038/s41467-026-69419-8","url":null,"abstract":"<p><p>All-optical interrogation, based on high-resolution two-photon stimulation and imaging, has emerged as a potentially transformative approach in neuroscience, allowing for the simultaneous precise manipulation and monitoring of neuronal activity across various model organisms. However, the unintended excitation of light-gated ion channels such as channelrhodopsin (ChR) during two-photon calcium imaging with genetically encoded calcium indicators (GECIs) introduces artifactual neuronal perturbation and contaminates neural activity measurements. In this study, we propose an active pixel power control (APPC) approach, which dynamically adjusts the imaging laser power at each scanning pixel, to address the challenge. We aim to achieve simultaneous two-photon optogenetic manipulation and calcium imaging with a single femtosecond laser, while minimizing the cross-talk between manipulation and imaging. To study this technology's capabilities, we applied it to the larval zebrafish brain in vivo. Our results demonstrate that the APPC approach preserves GECI signal quality while suppressing optogenetic artifacts significantly. This enhances the accuracy of neural circuit dissection and advances the precision of all-optical interrogation, offering a robust framework for probing neural circuit dynamics and causality in vivo with high fidelity, potentially across various model organisms. Importantly, this technology can be seamlessly integrated with commonly used two-photon microscope systems in laboratories worldwide.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165717","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}
Pub Date : 2026-02-11DOI: 10.1038/s41467-026-69151-3
Pablo Lechón-Alonso, Srilena Kundu, Paula Lemos-Costa, José A. Capitán, Stefano Allesina
Darwin already recognized that competition is fiercest among conspecifics, a principle that later made intraspecific competition central to ecological theory through concepts such as niche differentiation and limiting similarity. Beyond shaping coexistence, strong intraspecific competition can also stabilize community dynamics by ensuring that populations return to equilibrium after disturbance. Here we investigate a more fundamental question: how intraspecific competition influences the very existence of a steady state (feasibility) in large random ecological communities dominated by competition. We show that, in analogy with classical results on stability, there is a critical level of intraspecific competition above which a feasible steady state is guaranteed to exist. We derive a general expression for the probability of feasibility and prove that, asymptotically (as species number grows), the transition to stability occurs before the transition to feasibility with probability one. Thus, in large competitive communities, any feasible equilibrium is automatically stable. This ordering persists even when many species in the initial pool cannot coexist and extinctions occur: the dynamics prune the community, shifting feasibility and stability thresholds but never reversing their order. These results imply that large competitive communities generically converge to a globally stable equilibrium, making sustained oscillations or chaos unlikely—consistent with experimental observations.
{"title":"Robust coexistence in competitive ecological communities","authors":"Pablo Lechón-Alonso, Srilena Kundu, Paula Lemos-Costa, José A. Capitán, Stefano Allesina","doi":"10.1038/s41467-026-69151-3","DOIUrl":"https://doi.org/10.1038/s41467-026-69151-3","url":null,"abstract":"Darwin already recognized that competition is fiercest among conspecifics, a principle that later made intraspecific competition central to ecological theory through concepts such as niche differentiation and limiting similarity. Beyond shaping coexistence, strong intraspecific competition can also stabilize community dynamics by ensuring that populations return to equilibrium after disturbance. Here we investigate a more fundamental question: how intraspecific competition influences the very existence of a steady state (feasibility) in large random ecological communities dominated by competition. We show that, in analogy with classical results on stability, there is a critical level of intraspecific competition above which a feasible steady state is guaranteed to exist. We derive a general expression for the probability of feasibility and prove that, asymptotically (as species number grows), the transition to stability occurs before the transition to feasibility with probability one. Thus, in large competitive communities, any feasible equilibrium is automatically stable. This ordering persists even when many species in the initial pool cannot coexist and extinctions occur: the dynamics prune the community, shifting feasibility and stability thresholds but never reversing their order. These results imply that large competitive communities generically converge to a globally stable equilibrium, making sustained oscillations or chaos unlikely—consistent with experimental observations.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"91 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152269","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}
Pub Date : 2026-02-11DOI: 10.1038/s41467-026-69372-6
Ruize Liu, Tzu-Ting Chen, Yan Xia, Shu-Chin Lin, Tian Ge, Chia-Yen Chen, Yen-Chen Anne Feng, Hailiang Huang, Yen-Feng Lin
Methylation quantitative trait loci (mQTL) studies have predominantly focused on European populations (EUR), limiting understanding of the genetic regulation of DNA methylation in other populations. We conduct an East Asian (EAS) mQTL analysis, integrating data from three independent samples comprising 7619 Han Chinese individuals. We identified 331,048 mCpGs, including 28,978 novel mCpGs in EAS. While observing substantial sharing of mQTL between EUR and EAS, we also identify EAS-specific mQTLs, often driven by variants with low minor allele frequencies in EUR. We found that mQTLs enriched for disease and trait heritability, especially for matched-ancestry mQTLs, underscoring their utility for interpreting GWAS results and highlighting the role of DNA methylation in diseases. Our EAS mQTL resource provides valuable insights into the genetic architecture of DNA methylation and its contribution to complex traits.
{"title":"Genetic regulation of methylation across East Asian and European populations","authors":"Ruize Liu, Tzu-Ting Chen, Yan Xia, Shu-Chin Lin, Tian Ge, Chia-Yen Chen, Yen-Chen Anne Feng, Hailiang Huang, Yen-Feng Lin","doi":"10.1038/s41467-026-69372-6","DOIUrl":"https://doi.org/10.1038/s41467-026-69372-6","url":null,"abstract":"Methylation quantitative trait loci (mQTL) studies have predominantly focused on European populations (EUR), limiting understanding of the genetic regulation of DNA methylation in other populations. We conduct an East Asian (EAS) mQTL analysis, integrating data from three independent samples comprising 7619 Han Chinese individuals. We identified 331,048 mCpGs, including 28,978 novel mCpGs in EAS. While observing substantial sharing of mQTL between EUR and EAS, we also identify EAS-specific mQTLs, often driven by variants with low minor allele frequencies in EUR. We found that mQTLs enriched for disease and trait heritability, especially for matched-ancestry mQTLs, underscoring their utility for interpreting GWAS results and highlighting the role of DNA methylation in diseases. Our EAS mQTL resource provides valuable insights into the genetic architecture of DNA methylation and its contribution to complex traits.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"35 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152289","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}
Pub Date : 2026-02-11DOI: 10.1038/s41467-026-69494-x
Jiayu Du, Wenqi Wang, Yang Fu, Xin Li, Jie Tan, Hao Li, Xu Chen, Fuqiang Chu, Qi Min, Chi Yan Tso
Ice accumulation poses a significant threat to aviation safety and energy infrastructure. Photothermal superhydrophobic surfaces offer a promising anti-/deicing strategy; however, their excessive heat absorption in summer accelerates material degradation and exacerbates urban heat island effects, highlighting the urgent need for dynamic thermal regulation. In this study, we present a self-regulated photothermal storage superhydrophobic film with a trilayer design, comprising a photothermal phase-change base layer, a freeze-resistant thermochromic hydrogel interlayer, and a transparent superhydrophobic top layer. This multifunctional design enables seasonal adaptability, achieving 92% solar absorptance for efficient anti-/deicing in winter and 62% solar modulation to mitigate overheating in summer. This dual mode prolongs freezing time by 10-fold at −20 °C and lowers surface temperature by up to 17 °C in hot weather, demonstrating substantial potential for global building energy-savings. Additionally, its ultraviolet-blocking capability and durable superhydrophobicity ensure long-term durability performance in harsh environments. This work not only addresses the critical overheating challenge in photothermal materials but also advances the development of next-generation anti-icing systems.
{"title":"A self-regulated photothermal anti-/deicing film for all-season applications","authors":"Jiayu Du, Wenqi Wang, Yang Fu, Xin Li, Jie Tan, Hao Li, Xu Chen, Fuqiang Chu, Qi Min, Chi Yan Tso","doi":"10.1038/s41467-026-69494-x","DOIUrl":"https://doi.org/10.1038/s41467-026-69494-x","url":null,"abstract":"Ice accumulation poses a significant threat to aviation safety and energy infrastructure. Photothermal superhydrophobic surfaces offer a promising anti-/deicing strategy; however, their excessive heat absorption in summer accelerates material degradation and exacerbates urban heat island effects, highlighting the urgent need for dynamic thermal regulation. In this study, we present a self-regulated photothermal storage superhydrophobic film with a trilayer design, comprising a photothermal phase-change base layer, a freeze-resistant thermochromic hydrogel interlayer, and a transparent superhydrophobic top layer. This multifunctional design enables seasonal adaptability, achieving 92% solar absorptance for efficient anti-/deicing in winter and 62% solar modulation to mitigate overheating in summer. This dual mode prolongs freezing time by 10-fold at −20 °C and lowers surface temperature by up to 17 °C in hot weather, demonstrating substantial potential for global building energy-savings. Additionally, its ultraviolet-blocking capability and durable superhydrophobicity ensure long-term durability performance in harsh environments. This work not only addresses the critical overheating challenge in photothermal materials but also advances the development of next-generation anti-icing systems.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"3 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152295","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}
Pub Date : 2026-02-11DOI: 10.1038/s41467-026-68819-0
Qingwei Niu, Simon Vu, Yuanjiang Xu, Mingxing Qian, Anastasiia Rudenko, Jin Ye, Jianwei Zeng, Wei Huang, Douglas F. Covey, Rui Zhang, Ziao Fu, Polina V. Lishko
The inwardly rectifying potassium channel Kir7.1 is essential for the physiological function of diverse tissues, including the retinal pigment epithelium and the gestational myometrium. Loss-of-function mutations in KCNJ13, which encodes Kir7.1, or conditional ablation of Kir7.1 in the retinal pigment epithelium, lead to early-onset vision loss. Despite strong genetic evidence supporting Kir7.1 as a therapeutic target, its regulation by endogenous ligands—beyond phosphoinositides—remains poorly understood. Here, we report cryo-electron microscopy structures of human Kir7.1 in multiple functional states at resolutions ranging from 2.8 Å to 4.0 Å. These structures uncover the molecular basis of Kir7.1 modulation by PI4,5P2, its selectivity, rectification, and identify a distinct steroid-binding site that may mediate cooperative channel gating. Our data suggest that endogenous cholesterol acts as an inhibitory ligand, which is displaced by select activating steroids. These activating steroids work in concert with PI4,5P2 to promote channel opening through profound changes in cytoplasmic domains, and the linker region. Electrophysiological analyses define a pharmacological landscape of Kir7.1 activators, providing innovative tools to probe and modulate channel function in both physiological and pathological contexts.
{"title":"Bioactive lipid-mediated structural and functional regulation of the essential human potassium channel Kir7.1","authors":"Qingwei Niu, Simon Vu, Yuanjiang Xu, Mingxing Qian, Anastasiia Rudenko, Jin Ye, Jianwei Zeng, Wei Huang, Douglas F. Covey, Rui Zhang, Ziao Fu, Polina V. Lishko","doi":"10.1038/s41467-026-68819-0","DOIUrl":"https://doi.org/10.1038/s41467-026-68819-0","url":null,"abstract":"The inwardly rectifying potassium channel Kir7.1 is essential for the physiological function of diverse tissues, including the retinal pigment epithelium and the gestational myometrium. Loss-of-function mutations in KCNJ13, which encodes Kir7.1, or conditional ablation of Kir7.1 in the retinal pigment epithelium, lead to early-onset vision loss. Despite strong genetic evidence supporting Kir7.1 as a therapeutic target, its regulation by endogenous ligands—beyond phosphoinositides—remains poorly understood. Here, we report cryo-electron microscopy structures of human Kir7.1 in multiple functional states at resolutions ranging from 2.8 Å to 4.0 Å. These structures uncover the molecular basis of Kir7.1 modulation by PI4,5P2, its selectivity, rectification, and identify a distinct steroid-binding site that may mediate cooperative channel gating. Our data suggest that endogenous cholesterol acts as an inhibitory ligand, which is displaced by select activating steroids. These activating steroids work in concert with PI4,5P2 to promote channel opening through profound changes in cytoplasmic domains, and the linker region. Electrophysiological analyses define a pharmacological landscape of Kir7.1 activators, providing innovative tools to probe and modulate channel function in both physiological and pathological contexts.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"18 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152257","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}
As promising candidates for next-generation energy storage devices in electrical and electronic systems, lead-free multilayer ceramic capacitors face increasingly high performance requirements. To counteract the usual trade-off between energy storage density and efficiency, we here propose a high-entropy design that directly harnesses diverse oxide symmetries to targetedly engineer competing orders and tune the composition into the crossover region between relaxor ferroelectric and superparaelectric states. Atomic-scale structural analysis reveals high-entropy ceramic develops pronounced local polarization fluctuation and dispersed oxygen octahedral rotations, which enhance relaxor behavior and reduce switching barrier. Consequently, superior recoverable energy density of 20.64 J cm-3 and high efficiency of 94.2% are obtained in our designed high-entropy Bi0.5Na0.5TiO3-based multilayer ceramic capacitors, along with excellent thermal/anti-fatigue stability and charge-discharge capabilities. This work provides a transferable strategy to engineer competing orders in lead-free dielectric materials and successfully achieves high-entropy multilayer ceramic capacitors with superior energy storage performance.
{"title":"Superior energy storage performance via engineering crossover region with competing orders in high-entropy multilayer capacitors","authors":"Tao Deng, Jiyang Xie, Zhen Liu, Liqiang He, Zhichao Hong, Haonan Peng, Dong Wang, Cosme Milesi-Brault, Teng Lu, Yonghong Chen, Zhisheng Lin, Wanbiao Hu, Brahim Dkhil, Yun Liu, Genshui Wang, Junhao Chu","doi":"10.1038/s41467-026-69279-2","DOIUrl":"https://doi.org/10.1038/s41467-026-69279-2","url":null,"abstract":"As promising candidates for next-generation energy storage devices in electrical and electronic systems, lead-free multilayer ceramic capacitors face increasingly high performance requirements. To counteract the usual trade-off between energy storage density and efficiency, we here propose a high-entropy design that directly harnesses diverse oxide symmetries to targetedly engineer competing orders and tune the composition into the crossover region between relaxor ferroelectric and superparaelectric states. Atomic-scale structural analysis reveals high-entropy ceramic develops pronounced local polarization fluctuation and dispersed oxygen octahedral rotations, which enhance relaxor behavior and reduce switching barrier. Consequently, superior recoverable energy density of 20.64 J cm-3 and high efficiency of 94.2% are obtained in our designed high-entropy Bi0.5Na0.5TiO3-based multilayer ceramic capacitors, along with excellent thermal/anti-fatigue stability and charge-discharge capabilities. This work provides a transferable strategy to engineer competing orders in lead-free dielectric materials and successfully achieves high-entropy multilayer ceramic capacitors with superior energy storage performance.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"38 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152259","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}
Pub Date : 2026-02-11DOI: 10.1038/s41467-026-69379-z
Marcus Siems, Yinan Cao, Maryam Tohidi-Moghaddam, Tobias H. Donner, Konstantinos Tsetsos
Humans and other animals navigate decisions by sequentially attending to (sampling) subsets of the available information. The internal dynamics of the selective sampling of decision-relevant information remain unknown. Here we use magnetoencephalography recordings and neural decoding to track the spontaneous dynamics of the locus and strength of covert attention as human participants performed a three-alternative perceptual choice task. The strength of covert attention fluctuated rhythmically around 11 Hz. A shift of attention from one alternative to another tends to occur at the trough of this oscillation, presumably enabling comparisons. These shifts further reset the attentional oscillation. By contrast, at the peak of the oscillation, attention tends to increase the focus on the currently sampled alternative, presumably deepening processing of that alternative. We propose intrinsic attentional oscillations as a core mechanism governing the flexible sampling of decision alternatives.
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