Challenges in CO2 capture, CO2 crossover, product separation, and electrolyte recovery hinder electrocatalytic CO2 reduction (CO2R). Here, we present an integrated electrochemical recovery and separation system (ERSS) with an ion separation module (ISM) between the anode and cathode of a water electrolysis system. During ERSS operation, protons from the anolyte flow through the anodic cation exchange membrane (CEM) into the ISM, acidifying the CO2R effluent electrolyte. Cations like K+ in the ISM flow through the cathodic CEM into the catholyte to balance the OH− ions from hydrogen evolution. ERSS recycles electrolyte-adsorbed CO2, recovers KOH with a 94.0% K+ yield, and achieves an 86.2% separation efficiency for CO2R products. The recovered KOH can capture CO2 from air or flue gas or be utilized as a CO2R electrolyte, closing the CO2 capture, conversion, and utilization loop. Compared to the conventional acid-base neutralization process, ERSS saves $119.76 per ton of KOH recovered and is applicable to other aqueous alkaline electrosynthesis reactions.
{"title":"Integrated system for electrolyte recovery, product separation, and CO2 capture in CO2 reduction","authors":"Peng Wang, An Pei, Zhaoxi Chen, Peilin Sun, Chengyi Hu, Xue Wang, Nanfeng Zheng, Guangxu Chen","doi":"10.1038/s41467-025-56111-6","DOIUrl":"https://doi.org/10.1038/s41467-025-56111-6","url":null,"abstract":"<p>Challenges in CO<sub>2</sub> capture, CO<sub>2</sub> crossover, product separation, and electrolyte recovery hinder electrocatalytic CO<sub>2</sub> reduction (CO<sub>2</sub>R). Here, we present an integrated electrochemical recovery and separation system (ERSS) with an ion separation module (ISM) between the anode and cathode of a water electrolysis system. During ERSS operation, protons from the anolyte flow through the anodic cation exchange membrane (CEM) into the ISM, acidifying the CO<sub>2</sub>R effluent electrolyte. Cations like K<sup>+</sup> in the ISM flow through the cathodic CEM into the catholyte to balance the OH<sup>−</sup> ions from hydrogen evolution. ERSS recycles electrolyte-adsorbed CO<sub>2</sub>, recovers KOH with a 94.0% K<sup>+</sup> yield, and achieves an 86.2% separation efficiency for CO<sub>2</sub>R products. The recovered KOH can capture CO<sub>2</sub> from air or flue gas or be utilized as a CO<sub>2</sub>R electrolyte, closing the CO<sub>2</sub> capture, conversion, and utilization loop. Compared to the conventional acid-base neutralization process, ERSS saves $119.76 per ton of KOH recovered and is applicable to other aqueous alkaline electrosynthesis reactions.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986257","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 : 2025-01-16DOI: 10.1038/s41467-025-56055-x
Yuxiang Gao, Fenglin Deng, Ri He, Zhicheng Zhong
Two-dimensional (2D) van der Waals heterostructures consist of different 2D crystals with diverse properties, constituting the cornerstone of the new generation of 2D electronic devices. Yet interfaces in heterostructures inevitably break bulk symmetry and structural continuity, resulting in delicate atomic rearrangements and novel electronic structures. In this paper, we predict that 2D interfaces undergo “spontaneous curvature”, which means when two flat 2D layers approach each other, they inevitably experience out-of-plane curvature. Based on deep-learning-assisted large-scale molecular dynamics simulations, we observe significant out-of-plane displacements up to 3.8 Å in graphene/BN bilayers induced by curvature, producing a stable hexagonal moiré pattern, which agrees well with experimentally observations. Additionally, the out-of-plane flexibility of 2D crystals enables the propagation of curvature throughout the system, thereby influencing the mechanical properties of the heterostructure. These findings offer fundamental insights into the atomic structure in 2D van der Waals heterostructures and pave the way for their applications in devices.
{"title":"Spontaneous curvature in two-dimensional van der Waals heterostructures","authors":"Yuxiang Gao, Fenglin Deng, Ri He, Zhicheng Zhong","doi":"10.1038/s41467-025-56055-x","DOIUrl":"https://doi.org/10.1038/s41467-025-56055-x","url":null,"abstract":"<p>Two-dimensional (2D) van der Waals heterostructures consist of different 2D crystals with diverse properties, constituting the cornerstone of the new generation of 2D electronic devices. Yet interfaces in heterostructures inevitably break bulk symmetry and structural continuity, resulting in delicate atomic rearrangements and novel electronic structures. In this paper, we predict that 2D interfaces undergo “spontaneous curvature”, which means when two flat 2D layers approach each other, they inevitably experience out-of-plane curvature. Based on deep-learning-assisted large-scale molecular dynamics simulations, we observe significant out-of-plane displacements up to 3.8 Å in graphene/BN bilayers induced by curvature, producing a stable hexagonal moiré pattern, which agrees well with experimentally observations. Additionally, the out-of-plane flexibility of 2D crystals enables the propagation of curvature throughout the system, thereby influencing the mechanical properties of the heterostructure. These findings offer fundamental insights into the atomic structure in 2D van der Waals heterostructures and pave the way for their applications in devices.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"50 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986258","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 : 2025-01-16DOI: 10.1038/s41467-025-55987-8
Jason Yang, Ravi G. Lal, James C. Bowden, Raul Astudillo, Mikhail A. Hameedi, Sukhvinder Kaur, Matthew Hill, Yisong Yue, Frances H. Arnold
Directed evolution (DE) is a powerful tool to optimize protein fitness for a specific application. However, DE can be inefficient when mutations exhibit non-additive, or epistatic, behavior. Here, we present Active Learning-assisted Directed Evolution (ALDE), an iterative machine learning-assisted DE workflow that leverages uncertainty quantification to explore the search space of proteins more efficiently than current DE methods. We apply ALDE to an engineering landscape that is challenging for DE: optimization of five epistatic residues in the active site of an enzyme. In three rounds of wet-lab experimentation, we improve the yield of a desired product of a non-native cyclopropanation reaction from 12% to 93%. We also perform computational simulations on existing protein sequence-fitness datasets to support our argument that ALDE can be more effective than DE. Overall, ALDE is a practical and broadly applicable strategy to unlock improved protein engineering outcomes.
{"title":"Active learning-assisted directed evolution","authors":"Jason Yang, Ravi G. Lal, James C. Bowden, Raul Astudillo, Mikhail A. Hameedi, Sukhvinder Kaur, Matthew Hill, Yisong Yue, Frances H. Arnold","doi":"10.1038/s41467-025-55987-8","DOIUrl":"https://doi.org/10.1038/s41467-025-55987-8","url":null,"abstract":"<p>Directed evolution (DE) is a powerful tool to optimize protein fitness for a specific application. However, DE can be inefficient when mutations exhibit non-additive, or epistatic, behavior. Here, we present Active Learning-assisted Directed Evolution (ALDE), an iterative machine learning-assisted DE workflow that leverages uncertainty quantification to explore the search space of proteins more efficiently than current DE methods. We apply ALDE to an engineering landscape that is challenging for DE: optimization of five epistatic residues in the active site of an enzyme. In three rounds of wet-lab experimentation, we improve the yield of a desired product of a non-native cyclopropanation reaction from 12% to 93%. We also perform computational simulations on existing protein sequence-fitness datasets to support our argument that ALDE can be more effective than DE. Overall, ALDE is a practical and broadly applicable strategy to unlock improved protein engineering outcomes.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"37 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986269","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 : 2025-01-16DOI: 10.1038/s41467-025-56042-2
Ci Kong, Yin Yang, Tiancong Qi, Shuyi Zhang
Plants, with intricate molecular networks for environmental adaptation, offer groundbreaking potential for reprogramming with predictive genetic circuits. However, realizing this goal is challenging due to the long cultivation cycle of plants, as well as the lack of reproducible, quantitative methods and well-characterized genetic parts. Here, we establish a rapid (~10 days), quantitative, and predictive framework in plants. A group of orthogonal sensors, modular synthetic promoters, and NOT gates are constructed and quantitatively characterized. A predictive model is developed to predict the designed circuits’ behavior accurately. Our versatile and robust framework, validated by constructing 21 two-input circuits with high prediction accuracy (R2 = 0.81), enables multi-state phenotype control in both Arabidopsis thaliana and Nicotiana benthamiana in response to chemical inducers. Our study achieves predictable design and application of synthetic circuits in plants, offering valuable tools for the rapid engineering of plant traits in biotechnology and agriculture.
{"title":"Predictive genetic circuit design for phenotype reprogramming in plants","authors":"Ci Kong, Yin Yang, Tiancong Qi, Shuyi Zhang","doi":"10.1038/s41467-025-56042-2","DOIUrl":"https://doi.org/10.1038/s41467-025-56042-2","url":null,"abstract":"<p>Plants, with intricate molecular networks for environmental adaptation, offer groundbreaking potential for reprogramming with predictive genetic circuits. However, realizing this goal is challenging due to the long cultivation cycle of plants, as well as the lack of reproducible, quantitative methods and well-characterized genetic parts. Here, we establish a rapid (~10 days), quantitative, and predictive framework in plants. A group of orthogonal sensors, modular synthetic promoters, and NOT gates are constructed and quantitatively characterized. A predictive model is developed to predict the designed circuits’ behavior accurately. Our versatile and robust framework, validated by constructing 21 two-input circuits with high prediction accuracy (<i>R</i><sup><i>2</i></sup> = 0.81), enables multi-state phenotype control in both <i>Arabidopsis thaliana</i> and <i>Nicotiana benthamiana</i> in response to chemical inducers. Our study achieves predictable design and application of synthetic circuits in plants, offering valuable tools for the rapid engineering of plant traits in biotechnology and agriculture.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"45 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986305","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}
Electrochromic materials were discovered in the 1960s when scientists observed reversible changes between the light and dark states in WO3 thin films under different voltages. Since then, researchers have identified various electrochromic material systems, including transition metal oxides, polymer materials, and small molecules. However, the electrochromic phenomenon has rarely been observed in non-metallic elemental substances. Herein, we propose the development of non-metallic iodine electrodeposition-based electrochromic dynamic windows using a water-in-salt electrolyte containing iodine ions. The unique electrolyte environment and solvation structure of the water-in-salt electrolyte suppress the dissolution and shuttle effect of iodine, thereby achieving a different reaction pathway compared to traditional electrolytes. This pathway involves a reversible solid-liquid transition between solid iodine and solvated iodide ions. The iodine electrodeposition-based electrochromic dynamic window demonstrates a high optical contrast of 76.0% with near colour neutrality and excellent cycling stability. A practical 400 cm2 complementary dynamic window is fabricated to demonstrate good electrochromic performance, including high optical contrast, a near colour-neutral opaque state, fast response time, uniform modulation, and polarity-switchable functionality.
{"title":"Electrochromism via reversible electrodeposition of solid iodine","authors":"Shanlin Li, Yingyu Chen, Zhen Wang, Mengmeng Wang, Xianglin Guo, Xueqing Tang, Xiaoyu Wang, Wende Lai, Meiyun Tong, Changhong Wang, Shan Cong, Fengxia Geng, Yong Chen, Zhigang Zhao","doi":"10.1038/s41467-024-55348-x","DOIUrl":"https://doi.org/10.1038/s41467-024-55348-x","url":null,"abstract":"<p>Electrochromic materials were discovered in the 1960s when scientists observed reversible changes between the light and dark states in WO<sub>3</sub> thin films under different voltages. Since then, researchers have identified various electrochromic material systems, including transition metal oxides, polymer materials, and small molecules. However, the electrochromic phenomenon has rarely been observed in non-metallic elemental substances. Herein, we propose the development of non-metallic iodine electrodeposition-based electrochromic dynamic windows using a water-in-salt electrolyte containing iodine ions. The unique electrolyte environment and solvation structure of the water-in-salt electrolyte suppress the dissolution and shuttle effect of iodine, thereby achieving a different reaction pathway compared to traditional electrolytes. This pathway involves a reversible solid-liquid transition between solid iodine and solvated iodide ions. The iodine electrodeposition-based electrochromic dynamic window demonstrates a high optical contrast of 76.0% with near colour neutrality and excellent cycling stability. A practical 400 cm<sup>2</sup> complementary dynamic window is fabricated to demonstrate good electrochromic performance, including high optical contrast, a near colour-neutral opaque state, fast response time, uniform modulation, and polarity-switchable functionality.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"37 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986353","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 : 2025-01-16DOI: 10.1038/s41467-024-55591-2
Humphrey Yang, Dinesh K. Patel, Tate Johnson, Ke Zhong, Gina Olson, Carmel Majidi, Mohammad F. Islam, Teng Zhang, Lining Yao
Compliant mechanisms with reconfigurable degrees of freedom are gaining attention in the development of kinesthetic haptic devices, robotic systems, and mechanical metamaterials. However, available devices exhibit limited programmability and form-customizability, restricting their versatility. To address this gap, we propose a metastructure concept featuring reconfigurable motional freedom and tunable stiffness, adaptable to various form factors and applications. These devices incorporate passive flexures and actively stiffness-changing rods to modify kinematic freedom. A rational design pipeline informs the flexures’ topological arrangements, geometric parameters, and control signals based on targeted mobilities, enabling the creation of unitary joints with up to six degrees of freedom. Our demonstrative application examples include a wrist device that has an effective stiffness of 0.370 Nm/deg (unlocked state, 5% displacement) to 2.278 Nm/deg (locked state, 1% displacement) to enable dynamic joint mobility control, a haptic thimble device (2.27-52.815 Nmm−1 at 1% displacement) that mimics the sensation of touching physical materials ranging from soft gel to metal surfaces, and a wearable device composed of multiple joints tailored for the arm and hand to augment haptic experiences or facilitate muscle training. We believe the presented method can help democratize compliant metastructures development and expand their versatility for broader contexts.
{"title":"A compliant metastructure design with reconfigurability up to six degrees of freedom","authors":"Humphrey Yang, Dinesh K. Patel, Tate Johnson, Ke Zhong, Gina Olson, Carmel Majidi, Mohammad F. Islam, Teng Zhang, Lining Yao","doi":"10.1038/s41467-024-55591-2","DOIUrl":"https://doi.org/10.1038/s41467-024-55591-2","url":null,"abstract":"<p>Compliant mechanisms with reconfigurable degrees of freedom are gaining attention in the development of kinesthetic haptic devices, robotic systems, and mechanical metamaterials. However, available devices exhibit limited programmability and form-customizability, restricting their versatility. To address this gap, we propose a metastructure concept featuring reconfigurable motional freedom and tunable stiffness, adaptable to various form factors and applications. These devices incorporate passive flexures and actively stiffness-changing rods to modify kinematic freedom. A rational design pipeline informs the flexures’ topological arrangements, geometric parameters, and control signals based on targeted mobilities, enabling the creation of unitary joints with up to six degrees of freedom. Our demonstrative application examples include a wrist device that has an effective stiffness of 0.370 Nm/deg (unlocked state, 5% displacement) to 2.278 Nm/deg (locked state, 1% displacement) to enable dynamic joint mobility control, a haptic thimble device (2.27-52.815 Nmm<sup>−1</sup> at 1% displacement) that mimics the sensation of touching physical materials ranging from soft gel to metal surfaces, and a wearable device composed of multiple joints tailored for the arm and hand to augment haptic experiences or facilitate muscle training. We believe the presented method can help democratize compliant metastructures development and expand their versatility for broader contexts.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"94 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986307","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 : 2025-01-16DOI: 10.1038/s41467-025-56092-6
Gustavo Della-Flora Nunes, Lindsay A. Osso, Johana A. Haynes, Lauren Conant, Michael A. Thornton, Michael E. Stockton, Katherine A. Brassell, Amanda Morris, Yessenia I. Mancha Corchado, John A. Gaynes, Anthony R. Chavez, Michaelanne B. Woerner, Deidre A. MacKenna, Aryan Alavi, Anne Danks, Alon Poleg-Polsky, Rohan Gandhi, Jeffrey A. Vivian, Daniel J. Denman, Ethan G. Hughes
Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, and aging. Because remyelination is often incomplete, better understanding endogenous remyelination and developing remyelination therapies that restore neural function are clinical imperatives. Here, we use in vivo two-photon microscopy and electrophysiology to study the dynamics of endogenous and therapeutic-induced cortical remyelination and functional recovery after cuprizone-mediated demyelination in mice. We focus on the visual pathway, which is uniquely positioned to provide insights into structure-function relationships during de/remyelination. We show endogenous remyelination is driven by recent oligodendrocyte loss and is highly efficacious following mild demyelination, but fails to restore the oligodendrocyte population when high rates of oligodendrocyte loss occur quickly. Testing a thyromimetic (LL-341070) compared to clemastine, we find it better enhances oligodendrocyte gain and hastens recovery of neuronal function. The therapeutic benefit of the thyromimetic is temporally restricted, and it acts exclusively following moderate to severe demyelination, eliminating the endogenous remyelination deficit. However, we find regeneration of oligodendrocytes and myelin to healthy levels is not necessary for recovery of visual neuronal function. These findings advance our understanding of remyelination and its impact on functional recovery to inform future therapeutic strategies.
{"title":"Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function","authors":"Gustavo Della-Flora Nunes, Lindsay A. Osso, Johana A. Haynes, Lauren Conant, Michael A. Thornton, Michael E. Stockton, Katherine A. Brassell, Amanda Morris, Yessenia I. Mancha Corchado, John A. Gaynes, Anthony R. Chavez, Michaelanne B. Woerner, Deidre A. MacKenna, Aryan Alavi, Anne Danks, Alon Poleg-Polsky, Rohan Gandhi, Jeffrey A. Vivian, Daniel J. Denman, Ethan G. Hughes","doi":"10.1038/s41467-025-56092-6","DOIUrl":"https://doi.org/10.1038/s41467-025-56092-6","url":null,"abstract":"<p>Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, and aging. Because remyelination is often incomplete, better understanding endogenous remyelination and developing remyelination therapies that restore neural function are clinical imperatives. Here, we use in vivo two-photon microscopy and electrophysiology to study the dynamics of endogenous and therapeutic-induced cortical remyelination and functional recovery after cuprizone-mediated demyelination in mice. We focus on the visual pathway, which is uniquely positioned to provide insights into structure-function relationships during de/remyelination. We show endogenous remyelination is driven by recent oligodendrocyte loss and is highly efficacious following mild demyelination, but fails to restore the oligodendrocyte population when high rates of oligodendrocyte loss occur quickly. Testing a thyromimetic (LL-341070) compared to clemastine, we find it better enhances oligodendrocyte gain and hastens recovery of neuronal function. The therapeutic benefit of the thyromimetic is temporally restricted, and it acts exclusively following moderate to severe demyelination, eliminating the endogenous remyelination deficit. However, we find regeneration of oligodendrocytes and myelin to healthy levels is not necessary for recovery of visual neuronal function. These findings advance our understanding of remyelination and its impact on functional recovery to inform future therapeutic strategies.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986175","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}
Silencers, the yin to enhancers’ yang, play a pivotal role in fine-tuning gene expression throughout the genome. However, despite their recognized importance, comprehensive identification of these regulatory elements in the genome is still in its early stages. We developed a method called Ss-STARR-seq to directly determine the activity of silencers in the whole genome. In this study, we applied Ss-STARR-seq to human cell lines K562, LNCaP, and 293 T, and identified 134,171, 137,753, and 125,307 silencers on a genome-wide scale, respectively, these silencers function in various cells in a cell-specific manner. Silencers exhibited a substantial enrichment of transcriptional-inhibitory motifs, including REST, and demonstrated overlap with the binding sites of repressor transcription factors within the endogenous environment. Interestingly, H3K27me3 did not reflect silencer activity but facilitated the silencer’s inhibitory role on gene expression. Additionally, the silencer did not have any significant histone markers at the genome-wide level. Our findings unveil that aspect-silencers not only transition into enhancers throughout diverse cell lines but also achieve functional conversion with insulators. Regarding to biological effects, knockout experiments underscored the functional redundancy and specificity of silencers in regulating gene expression and cell proliferation. In summary, this study pioneers the elucidation of the genome-wide silencer landscape in human cells, delineates their global regulatory features, and identifies specific silencers influencing cancer cell proliferation.
{"title":"Uncovering the whole genome silencers of human cells via Ss-STARR-seq","authors":"Xiusheng Zhu, Lei Huang, Chao Wang, Guoli Li, Biao Deng, Dashuai Kong, Xiaoxiao Wang, Rongrong Chang, Yi Gu, Qiuhan Wen, Siyuan Kong, Yuwen Liu, Yubo Zhang","doi":"10.1038/s41467-025-55852-8","DOIUrl":"https://doi.org/10.1038/s41467-025-55852-8","url":null,"abstract":"<p>Silencers, the yin to enhancers’ yang, play a pivotal role in fine-tuning gene expression throughout the genome. However, despite their recognized importance, comprehensive identification of these regulatory elements in the genome is still in its early stages. We developed a method called Ss-STARR-seq to directly determine the activity of silencers in the whole genome. In this study, we applied Ss-STARR-seq to human cell lines K562, LNCaP, and 293 T, and identified 134,171, 137,753, and 125,307 silencers on a genome-wide scale, respectively, these silencers function in various cells in a cell-specific manner. Silencers exhibited a substantial enrichment of transcriptional-inhibitory motifs, including REST, and demonstrated overlap with the binding sites of repressor transcription factors within the endogenous environment. Interestingly, H3K27me3 did not reflect silencer activity but facilitated the silencer’s inhibitory role on gene expression. Additionally, the silencer did not have any significant histone markers at the genome-wide level. Our findings unveil that aspect-silencers not only transition into enhancers throughout diverse cell lines but also achieve functional conversion with insulators. Regarding to biological effects, knockout experiments underscored the functional redundancy and specificity of silencers in regulating gene expression and cell proliferation. In summary, this study pioneers the elucidation of the genome-wide silencer landscape in human cells, delineates their global regulatory features, and identifies specific silencers influencing cancer cell proliferation.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"74 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986263","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}
Although rare non-coding variants (RVs) play crucial roles in complex traits and diseases, understanding their mechanisms and identifying disease-associated RVs continue to be major challenges. Here we constructed a comprehensive atlas of alternative polyadenylation (APA) outliers (aOutliers), including 1334 3′ UTR and 200 intronic aOutliers, from 15,201 samples across 49 human tissues. These aOutliers exhibit unique characteristics from transcription or splicing outliers, with a pronounced RV enrichment. Mechanistically, aOutlier-RVs alter poly(A) signals and splicing sites, and perturbation indeed triggers APA events. Furthermore, we developed a Bayesian-based APA RV prediction model, which successfully pinpointed a specific set of 1799 RVs impacting 278 genes with significantly large disease effect sizes. Notably, we observed a convergence effect between rare and common cancer variants, exemplified by regulation in the DDX18 gene. Together, this study introduced an APA-enhanced framework for genome annotation, underscoring APA’s role in uncovering functional RVs linked to complex traits and diseases.
{"title":"Impact of rare non-coding variants on human diseases through alternative polyadenylation outliers","authors":"Xudong Zou, Zhaozhao Zhao, Yu Chen, Kewei Xiong, Zeyang Wang, Shuxin Chen, Hui Chen, Gong-Hong Wei, Shuhua Xu, Wei Li, Ting Ni, Lei Li","doi":"10.1038/s41467-024-55407-3","DOIUrl":"https://doi.org/10.1038/s41467-024-55407-3","url":null,"abstract":"<p>Although rare non-coding variants (RVs) play crucial roles in complex traits and diseases, understanding their mechanisms and identifying disease-associated RVs continue to be major challenges. Here we constructed a comprehensive atlas of alternative polyadenylation (APA) outliers (aOutliers), including 1334 3′ UTR and 200 intronic aOutliers, from 15,201 samples across 49 human tissues. These aOutliers exhibit unique characteristics from transcription or splicing outliers, with a pronounced RV enrichment. Mechanistically, aOutlier-RVs alter poly(A) signals and splicing sites, and perturbation indeed triggers APA events. Furthermore, we developed a Bayesian-based APA RV prediction model, which successfully pinpointed a specific set of 1799 RVs impacting 278 genes with significantly large disease effect sizes. Notably, we observed a convergence effect between rare and common cancer variants, exemplified by regulation in the <i>DDX18</i> gene. Together, this study introduced an APA-enhanced framework for genome annotation, underscoring APA’s role in uncovering functional RVs linked to complex traits and diseases.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"15 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986302","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 : 2025-01-16DOI: 10.1038/s41467-025-55890-2
Simon A. Schroeter, Alice May Orme, Katharina Lehmann, Robert Lehmann, Narendrakumar M. Chaudhari, Kirsten Küsel, He Wang, Anke Hildebrandt, Kai Uwe Totsche, Susan Trumbore, Gerd Gleixner
Heavy precipitation, drought, and other hydroclimatic extremes occur more frequently than in the past climate reference period (1961–1990). Given their strong effect on groundwater recharge dynamics, these phenomena increase the vulnerability of groundwater quantity and quality. Over the course of the past decade, we have documented changes in the composition of dissolved organic matter in groundwater. We show that fractions of ingressing surface-derived organic molecules increased significantly as groundwater levels declined, whereas concentrations of dissolved organic carbon remained constant. Molecular composition changeover was accelerated following 2018’s extreme summer drought. These findings demonstrate that hydroclimatic extremes promote rapid transport between surface ecosystems and groundwaters, thereby enabling xenobiotic substances to evade microbial processing, accrue in greater abundance in groundwater, and potentially compromise the safe nature of these potable water sources. Groundwater quality is far more vulnerable to the impact of recent climate anomalies than is currently recognized, and the molecular composition of dissolved organic matter can be used as a comprehensive indicator for groundwater quality deterioration.
{"title":"Hydroclimatic extremes threaten groundwater quality and stability","authors":"Simon A. Schroeter, Alice May Orme, Katharina Lehmann, Robert Lehmann, Narendrakumar M. Chaudhari, Kirsten Küsel, He Wang, Anke Hildebrandt, Kai Uwe Totsche, Susan Trumbore, Gerd Gleixner","doi":"10.1038/s41467-025-55890-2","DOIUrl":"https://doi.org/10.1038/s41467-025-55890-2","url":null,"abstract":"<p>Heavy precipitation, drought, and other hydroclimatic extremes occur more frequently than in the past climate reference period (1961–1990). Given their strong effect on groundwater recharge dynamics, these phenomena increase the vulnerability of groundwater quantity and quality. Over the course of the past decade, we have documented changes in the composition of dissolved organic matter in groundwater. We show that fractions of ingressing surface-derived organic molecules increased significantly as groundwater levels declined, whereas concentrations of dissolved organic carbon remained constant. Molecular composition changeover was accelerated following 2018’s extreme summer drought. These findings demonstrate that hydroclimatic extremes promote rapid transport between surface ecosystems and groundwaters, thereby enabling xenobiotic substances to evade microbial processing, accrue in greater abundance in groundwater, and potentially compromise the safe nature of these potable water sources. Groundwater quality is far more vulnerable to the impact of recent climate anomalies than is currently recognized, and the molecular composition of dissolved organic matter can be used as a comprehensive indicator for groundwater quality deterioration.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"74 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986352","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}