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CeOx-Integrated dual site enhanced urea electrosynthesis from nitrate and carbon dioxide. ceox -集成双位点增强尿素电合成硝酸盐和二氧化碳。
IF 16.6 1区 综合性期刊
Nature Communications Pub Date : 2025-10-02 DOI: 10.1038/s41467-025-63839-8
Xu Wu,Yang Chen,Bing Tang,Qiong Yan,Deyu Wu,Heng Zhou,Hao Wang,Heng Zhang,Daoping He,Hui Li,Jianrong Zeng,Lanlu Lu,Song Yang,Tianyi Ma
{"title":"CeOx-Integrated dual site enhanced urea electrosynthesis from nitrate and carbon dioxide.","authors":"Xu Wu,Yang Chen,Bing Tang,Qiong Yan,Deyu Wu,Heng Zhou,Hao Wang,Heng Zhang,Daoping He,Hui Li,Jianrong Zeng,Lanlu Lu,Song Yang,Tianyi Ma","doi":"10.1038/s41467-025-63839-8","DOIUrl":"https://doi.org/10.1038/s41467-025-63839-8","url":null,"abstract":"Electrocatalytic urea synthesis via the co-reduction of NO 3 - and CO2 as a promising option to the conventional Bosch-Meiser remains challenged by regulating desired intermediates to simultaneously achieve a high yield and Faradaic efficiency. Here, we integrate the substrate material (SiO2) and functionally atomic sites (Cu and Sn) utilizing CeOx nanoclusters as 'adhesive', in which the CeOx and SiO2 form the composite carrier (CS) construct Cu and Sn diatomic electrocatalyst (CuSn/CS-1). Spectroscopic techniques and density functional theory calculations reveal that overall charge redistribution in the CeOx-CuSn modules forms bifunctional active sites with unique electronic properties and abundant oxygen vacancies. The Cu sites mediate the conversion of CO2 to *CO through a single carbon-coordinated structure with *CO2-, while Sn sites regulate the reduction of NO 3 - to stabilize the formation of *NH2, broadening the C-N coupling route. Oxygen vacancies provide additional electron storage sites and promote the electron flow during the electrocatalytic process. CuSn/CS-1 achieves a urea yield of 55.81 mmol g-1cat. h-1 with a Faradaic efficiency of 79.27% in H-cell at -0.7 V versus the reversible hydrogen electrode. This work overcomes the traditional trade-off between urea yield and Faradaic efficiency, providing a feasible and sustainable strategy.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"18 1","pages":"8785"},"PeriodicalIF":16.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Influence of individual models and studies on quantitative mitigation findings in the IPCC Sixth Assessment Report. 个别模式和研究对IPCC第六次评估报告中量化缓解结果的影响。
IF 16.6 1区 综合性期刊
Nature Communications Pub Date : 2025-10-02 DOI: 10.1038/s41467-025-64091-w
Ida Sognnaes,Glen P Peters
{"title":"Influence of individual models and studies on quantitative mitigation findings in the IPCC Sixth Assessment Report.","authors":"Ida Sognnaes,Glen P Peters","doi":"10.1038/s41467-025-64091-w","DOIUrl":"https://doi.org/10.1038/s41467-025-64091-w","url":null,"abstract":"Quantitative mitigation findings based on emissions scenarios submitted to the Intergovernmental Panel on Climate Change (IPCC) play an authoritative role in climate policy and decision making. We analyse the impact of the uneven representation of models and modelling studies in the IPCC Sixth Assessment Report (AR6) on statistical values that are used to present quantitative mitigation findings. We find that several key AR6 findings are influenced considerably by the model with the most scenarios, including emissions reductions by 2030 and the decline in fossil fuels consistent with 1.5 °C, and we find that the year of net-zero greenhouse gas emissions is influenced considerably by both the model and the study with the most scenarios. We find that weighting by model- or study does not provide a straightforward solution and discuss three issues related to the use of database statistics to present emissions scenarios findings. Informed by the purpose of the IPCC and the kinds of insights that can be obtained from emissions scenarios, we suggest improvements to the assessment of emissions scenarios.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"3 1","pages":"8343"},"PeriodicalIF":16.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fabrication of cytotoxic mirror image nanopores. 细胞毒性镜像纳米孔的制备。
IF 16.6 1区 综合性期刊
Nature Communications Pub Date : 2025-10-02 DOI: 10.1038/s41467-025-64025-6
Neilah Firzan Ca,Kalyanashis Jana,Sreelakshmi Radhakrishnan,Rifat Aara,Mubeena S,Radhika Nair,Harsha Bajaj,Ulrich Kleinekathöfer,Kozhinjampara R Mahendran
{"title":"Fabrication of cytotoxic mirror image nanopores.","authors":"Neilah Firzan Ca,Kalyanashis Jana,Sreelakshmi Radhakrishnan,Rifat Aara,Mubeena S,Radhika Nair,Harsha Bajaj,Ulrich Kleinekathöfer,Kozhinjampara R Mahendran","doi":"10.1038/s41467-025-64025-6","DOIUrl":"https://doi.org/10.1038/s41467-025-64025-6","url":null,"abstract":"Synthetic nanopores composed of mirror-image peptides have been reported, but not fully functional mirror-image pores. Here, we construct a monodisperse mirror-image nanopore, DpPorA and characterise its functional properties. Importantly, we alter the charge pattern and assemble a superior mirror-image pore with enhanced conductance and selectivity under different salt conditions. This pore is used for single-molecule sensing of structurally divergent biomolecules, including peptides, PEGylated polypeptides, full-length alpha-synuclein protein and cyclic sugars. Molecular dynamics simulations confirm these DpPorA are exact mirror-images of LpPorA, further revealing their structurally stable conformation. Fluorescence imaging of giant vesicles reconstituted with mirror-image peptides reveals the formation of large flexible pores facilitating size-dependent molecular transport. To explore biomedical applications, the differential cytotoxic effect of mirror-image peptides and their fluorescently tagged forms on cancer cells demonstrates a significant effect on membrane disruption and cell viability, as opposed to no effect on normal cells. We emphasize that this class of mirror-image pores can advance the development of molecular sensors and therapeutics.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"62 1","pages":"8666"},"PeriodicalIF":16.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nanoimprinted polyamide membranes for ultrafast and precise molecular sieving with low fouling. 纳米印迹聚酰胺膜的超快速和精确的分子筛选与低污染。
IF 15.7 1区 综合性期刊
Nature Communications Pub Date : 2025-10-02 DOI: 10.1038/s41467-025-64262-9
Pengrui Jin, Zhao Yang, Frederik Ceyssens, Jiakuan Yang, Shushan Yuan, Huanting Wang
{"title":"Nanoimprinted polyamide membranes for ultrafast and precise molecular sieving with low fouling.","authors":"Pengrui Jin, Zhao Yang, Frederik Ceyssens, Jiakuan Yang, Shushan Yuan, Huanting Wang","doi":"10.1038/s41467-025-64262-9","DOIUrl":"https://doi.org/10.1038/s41467-025-64262-9","url":null,"abstract":"<p><p>Polyamide membranes with ultrahigh permeance and exceptional solute selectivity present a significant opportunity to reduce energy consumption in desalination, pharmaceutical purification, and solvent recovery. We report a nanomolding phase inversion strategy for constructing high-resolution pillar-array patterns on a nanofibrous Kevlar hydrogel support, enabling controlled interfacial polymerization (IP) of polyamide active layers with pillar-arrayed structures. The rigid polyamide layers preserve pillar textures under pressurized filtration, increasing permeable area, while the nanofibrous Kevlar regulates amine diffusion to enhance polyamide layer homogeneity. The resulting nanoimprinted composite membranes with thin, structurally homogeneous, highly negatively charged polyamide layers demonstrate a water permeance of 53.9 L m<sup>-2</sup> h<sup>-1</sup> bar<sup>-1</sup> with 98.1% Na<sub>2</sub>SO<sub>4</sub> rejection, high Cl<sup>-</sup>/SO<sub>4</sub><sup>2-</sup> selectivity (45), and improved antifouling properties. In active pharmaceutical ingredients enrichment, they achieve one order of magnitude faster methanol transport, e.g., 31.3 L m<sup>-2</sup> h<sup>-1</sup> bar<sup>-1</sup>, than commercial membranes. Our nanoimprinted strategy may inspire advanced membrane designs for diverse high-value separations.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8807"},"PeriodicalIF":15.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pathogenic variants reveal candidate genes for prostate cancer germline testing for men of African ancestry. 致病变异揭示了非洲血统男性前列腺癌生殖系检测的候选基因。
IF 15.7 1区 综合性期刊
Nature Communications Pub Date : 2025-10-02 DOI: 10.1038/s41467-025-63865-6
Kazzem Gheybi, Pamela X Y Soh, Jue Jiang, Tumisang M N Mbeki, Melanie Louw, Daniel Burns, Piyushkumar Mundra, Daria Kiriy, Md Mehedi Hasan, Weerachai Jaratlerdsiri, Maphuti Tebogo Lebelo, Raymond A Campbell, Mulalo B Radzuma, Mukudeni Nenzhelele, Muvhulawa Obida, Martin Obida, Winstar M Ombuki, Micah O Oyaro, Sean M Patrick, Massimo Loda, David C Wedge, Robert G Bristow, Daniel S Brewer, Colin S Cooper, Jüri Reimand, Geraldine Cancel-Tassin, Olivier Cussenot, Chris M Hovens, Niall M Cocoran, Phillip D Stricker, Thorsten Schlomm, Gail S Prins, Karina Dalsgaard Sørensen, Joachim Weischenfeldt, Shingai B A Mutambirwa, Peter M Ngugi, David M Thomas, Zsofia Kote-Jarai, Rosalind A Eeles, M S Riana Bornman, Vanessa M Hayes
{"title":"Pathogenic variants reveal candidate genes for prostate cancer germline testing for men of African ancestry.","authors":"Kazzem Gheybi, Pamela X Y Soh, Jue Jiang, Tumisang M N Mbeki, Melanie Louw, Daniel Burns, Piyushkumar Mundra, Daria Kiriy, Md Mehedi Hasan, Weerachai Jaratlerdsiri, Maphuti Tebogo Lebelo, Raymond A Campbell, Mulalo B Radzuma, Mukudeni Nenzhelele, Muvhulawa Obida, Martin Obida, Winstar M Ombuki, Micah O Oyaro, Sean M Patrick, Massimo Loda, David C Wedge, Robert G Bristow, Daniel S Brewer, Colin S Cooper, Jüri Reimand, Geraldine Cancel-Tassin, Olivier Cussenot, Chris M Hovens, Niall M Cocoran, Phillip D Stricker, Thorsten Schlomm, Gail S Prins, Karina Dalsgaard Sørensen, Joachim Weischenfeldt, Shingai B A Mutambirwa, Peter M Ngugi, David M Thomas, Zsofia Kote-Jarai, Rosalind A Eeles, M S Riana Bornman, Vanessa M Hayes","doi":"10.1038/s41467-025-63865-6","DOIUrl":"https://doi.org/10.1038/s41467-025-63865-6","url":null,"abstract":"<p><p>Prostate cancer (PCa) germline testing, while gaining momentum, is ancestry restrictive and African exclusive. Through whole genome sequencing for 217 African ancestral cases (186 southern African, 31 Pan representative), we identify 172 potentially pathogenic variants in 78 DNA damage repair or PCa related genes. Prevalence for reported (13/217, 5.99%) and cumulative predicted (24/217, 11.06%) variants of significance (11 genes) falls below that reported for non-Africans. Conversely, BRCA1, HOXB13, CDK12, MLH1, MSH2, and BRIP1 remain unimpacted. Through pathogenic ranking based on variant frequency and functionality, clinical presentation and tumour-matched biallelic inactivation, top-ranked candidates include PREX2, POLE, FAT1, BRCA2, POLQ, LRP1B and ATM. Besides notable impact of DNA polymerases, including POLG, Fanconi anaemia genes include FANCD2, FANCA, FANCG, ERCC4, FANCE and FANCI, while DNA mismatch repair genes MSH3 and PMS1 outranked known namesakes MSH6 and PMS2. This study provides insights into the spectrum of African-relevant potentially pathogenic PCa variants, highlighting much-needed gene candidates for ancestry-inclusive germline testing.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8799"},"PeriodicalIF":15.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Iron and oxygen vacancies co-modulated adsorption evolution and lattice oxygen dual-path mechanism for water oxidation. 铁和氧空位共调吸附演化和点阵氧双路机制的水氧化。
IF 15.7 1区 综合性期刊
Nature Communications Pub Date : 2025-10-02 DOI: 10.1038/s41467-025-63844-x
Xiwen Tao, Li Hou, Xinyi Wang, Jing Jin, Huana Li, Faming Gao
{"title":"Iron and oxygen vacancies co-modulated adsorption evolution and lattice oxygen dual-path mechanism for water oxidation.","authors":"Xiwen Tao, Li Hou, Xinyi Wang, Jing Jin, Huana Li, Faming Gao","doi":"10.1038/s41467-025-63844-x","DOIUrl":"https://doi.org/10.1038/s41467-025-63844-x","url":null,"abstract":"<p><p>Conjointly activating metal and oxygen sites to trigger the adsorbate evolution and lattice oxygen mechanisms coupled path holds promise for balancing activity and stability in oxygen evolution reaction catalysts, yet confronting great challenges. Herein, we develop Fe species and oxygen vacancies co-regulated Ni-(oxy)hydroxide from the deep reconstruction of Fe-Ni<sub>2</sub>P/NiMoO<sub>4</sub> pre-catalyst achieving the adsorbate evolution and lattice oxygen dual-path mechanism. Experimental details and theoretical calculation analysis reveal the enhanced adsorbate evolution mechanism kinetics at the Ni sites via the co-regulation of Fe species and oxygen vacancies, while the Fe incorporation activates the O sites with preferable adsorption free energy for lattice oxygen mechanism intermediates. Benefiting from the dual-path mechanism, the activated catalyst affords an ampere-scale current density of 1.0 A cm<sup>-2</sup> at low overpotentials of 274.5 ± 4.2 and 299.1 ± 2.8 mV in alkaline freshwater and seawater, respectively, and maintains seawater electrocatalysis for 500 h in the anion exchange membrane water electrolysis. This work demonstrates a strategy to trigger the coupled mechanism for efficient and stable electrocatalytic water splitting under harsh conditions.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8788"},"PeriodicalIF":15.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Design of a combined LED and rapid-injection NMR system for structure elucidations and kinetic analyses. 用于结构解析和动力学分析的LED和快速注入核磁共振组合系统的设计。
IF 15.7 1区 综合性期刊
Nature Communications Pub Date : 2025-10-02 DOI: 10.1038/s41467-025-63848-7
Danniel K Arriaga, Ravinder Kaur, Andy A Thomas
{"title":"Design of a combined LED and rapid-injection NMR system for structure elucidations and kinetic analyses.","authors":"Danniel K Arriaga, Ravinder Kaur, Andy A Thomas","doi":"10.1038/s41467-025-63848-7","DOIUrl":"https://doi.org/10.1038/s41467-025-63848-7","url":null,"abstract":"<p><p>Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique often used for structural elucidation of various molecules. The utility of NMR for in situ reaction monitoring is represented by the numerous strategies to conduct chemical reactions inside of the spectrometer, such as rapid-injection (RI-NMR) and LED NMR. In this work, the design of a combined LED and rapid-injection NMR (LED-RI-NMR) apparatus is described and showcased in kinetic studies for three photochemical reactions. The simple design of the LED-RI-NMR system allows for the introduction of both light and reagents into NMR samples for in situ reaction monitoring of reactive intermediates. The distinguishing features of the LED-RI-NMR system described herein include the ability to explore and intercept photogenerated intermediates via RI-NMR and explore the photochemical properties of fleeting intermediates generated by RI-NMR. We demonstrate the versatility of this experimental tool for the kinetic study of organophotoredox cycloadditions, Wolff rearrangements, and azobenzene isomerization reactions.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8791"},"PeriodicalIF":15.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Direct and efficient synthesis of nucleosides through the ortho-(tert-butylethynyl)phenyl thioglycosides (BEPTs) protocol. 通过邻(叔丁基乙基)苯基硫苷(BEPTs)协议直接和有效地合成核苷。
IF 15.7 1区 综合性期刊
Nature Communications Pub Date : 2025-10-02 DOI: 10.1038/s41467-025-63874-5
Hui Liu, Ming-Yang Wang, Hua Xie, Yanli Qiu, Tian Mao, Xiaomei Shen, Xu-Xue Liu, Jing-Jing Guo, Ming-Ze Tang, Jin-Xi Liao, Yuan-Hong Tu, De-Yong Liu, Jian-Song Sun
{"title":"Direct and efficient synthesis of nucleosides through the ortho-(tert-butylethynyl)phenyl thioglycosides (BEPTs) protocol.","authors":"Hui Liu, Ming-Yang Wang, Hua Xie, Yanli Qiu, Tian Mao, Xiaomei Shen, Xu-Xue Liu, Jing-Jing Guo, Ming-Ze Tang, Jin-Xi Liao, Yuan-Hong Tu, De-Yong Liu, Jian-Song Sun","doi":"10.1038/s41467-025-63874-5","DOIUrl":"https://doi.org/10.1038/s41467-025-63874-5","url":null,"abstract":"<p><p>Nucleosides are highly biologically relevant compounds, and are widely clinically used as drugs for the treatment of virus/bacteria infections and cancers. However, efficient chemical synthesis of nucleoside is highly difficult due to the low reactivity of nucleobases acceptors, challenging the existing synthetic protocols. Here we show an alternative synthetic protocol with judiciously designed o-(tert-butylethynyl)phenyl thioglycosides (BEPTs) as donors. The protocol is featured by stable glycosylation donors and high efficiency, direct glycosylation without the need for preactivation/silylation of nucleobases, broad substrate scope, capacity in furnishing 2-deoxy-nucleosides, cost efficiency, scalability, and significantly improved reaction speed, and exhibits favorable and profound solvent effects for hexafluoroisopropanol (HFIP). To check the practicality of the protocol, efficient preparation of angustmycin A and dJ is accomplished. The reaction mechanisms are systematically investigated, providing deep insights to the BEPT protocol.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8802"},"PeriodicalIF":15.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dual membrane receptor degradation via folate receptor targeting chimera. 通过叶酸受体靶向嵌合体降解双膜受体。
IF 15.7 1区 综合性期刊
Nature Communications Pub Date : 2025-10-02 DOI: 10.1038/s41467-025-63882-5
Zhen Wang, Zhixin Li, Jenny Högström, Hiroyuki Inuzuka, Rui Jing, Peiqiang Yan, Tao Hou, Yihang Qi, Daoyuan Huang, Jingchao Wang, Ting Wu, Xiaoying Shi, Bolin Liu, Taru Muranen, Dingpeng Zhang, Wenyi Wei
{"title":"Dual membrane receptor degradation via folate receptor targeting chimera.","authors":"Zhen Wang, Zhixin Li, Jenny Högström, Hiroyuki Inuzuka, Rui Jing, Peiqiang Yan, Tao Hou, Yihang Qi, Daoyuan Huang, Jingchao Wang, Ting Wu, Xiaoying Shi, Bolin Liu, Taru Muranen, Dingpeng Zhang, Wenyi Wei","doi":"10.1038/s41467-025-63882-5","DOIUrl":"https://doi.org/10.1038/s41467-025-63882-5","url":null,"abstract":"<p><p>Cancer drug resistance poses a significant challenge in oncology, often driven by intricate cross-talk among membrane-bound receptors that compromise mono-targeted therapies. We develop a dual membrane receptor degradation strategy leveraging Folate Receptor α (FRα) to address this issue. Folate Receptor α Targeting Chimeras-dual (FolTAC-dual) are engineered degraders designed to selectively and simultaneously degrade distinct receptor pairs: (1) EGFR/HER2 and (2) PD-L1/VISTA. Through modular optimization of modality configurations and geometries, we identify the \"string\" format as the most effective construct. Mechanistic studies demonstrate an ~85% increase in EGFR-binding affinity compared to the conventional knob-into-hole design, likely contributing to the improved efficiency of dual-target degradation. Proof-of-concept studies reveal that EGFR and HER2 FolTAC-dual effectively counteracts resistance in Trastuzumab/Lapatinib-resistant HER2-positive breast cancer models, while PD-L1 and VISTA FolTAC-dual rejuvenates immune responses in PD-L1 antibody-resistant syngeneic mouse models. These findings establish FolTAC-dual as a promising dual-degradation platform for clinical translation.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8804"},"PeriodicalIF":15.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Crotonate enhances intestinal regeneration after injury via HBO1-mediated H3K14 crotonylation. Crotonate通过hbo1介导的H3K14 crotonylation促进损伤后肠道再生。
IF 16.6 1区 综合性期刊
Nature Communications Pub Date : 2025-10-02 DOI: 10.1038/s41467-025-63869-2
Yanhui Xiao,Shicheng Yu,Mengxian Zhang,Nanshan Zhong,Shan Hua,Zhi Fang,Zhe Zhang,Huidong Liu,Ronghui Tan,Yuan Liu,Ye-Guang Chen
{"title":"Crotonate enhances intestinal regeneration after injury via HBO1-mediated H3K14 crotonylation.","authors":"Yanhui Xiao,Shicheng Yu,Mengxian Zhang,Nanshan Zhong,Shan Hua,Zhi Fang,Zhe Zhang,Huidong Liu,Ronghui Tan,Yuan Liu,Ye-Guang Chen","doi":"10.1038/s41467-025-63869-2","DOIUrl":"https://doi.org/10.1038/s41467-025-63869-2","url":null,"abstract":"The intestinal epithelium undergoes rapid turnover driven by Lgr5+ intestinal stem cells at the crypt base, and can recover upon damage. Histone crotonylation plays a critical role in chromatin regulation and gene expression. However, the role of histone crotonylation, specifically H3K14 crotonylation (H3K14cr) in the intestine remains poorly understood. Here we demonstrate that both crotonate and H3K14cr levels are increased in the regenerating crypts. Treatment with sodium crotonate significantly alleviates dextran sulfate sodium induced colitis, an effect largely dependent on HBO1-mediated H3K14cr. Notably, HBO1 deficiency severely dampens regeneration, correlating with reduced H3K14ac and H3K14cr levels, decreased chromatin accessibility at transcriptional start sites, and impaired expression of stem and fetal genes. Single-cell RNA sequencing analysis reveals that HBO1 is expressed in stem cells and regenerative cells during recovery after irradiation, further supporting the critical role of HBO1 in intestinal regeneration. Together, our findings uncover a mechanism by which crotonate, HBO1, and H3K14cr contribute to epithelial regeneration and suggest that crotonate may represent a promising therapeutic agent for the treatment of gastrointestinal diseases.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"33 1","pages":"8800"},"PeriodicalIF":16.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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