Manisha Jalan, Alessandra Brambati, Hina Shah, Niamh McDermott, Juber Patel, Yingjie Zhu, Ahmet Doymaz, Julius Wu, Kyrie S. Anderson, Andrea Gazzo, Fresia Pareja, Takafumi N. Yamaguchi, Theodore Vougiouklakis, Sana Ahmed-Seghir, Philippa Steinberg, Anna Neiman-Golden, Benura Azeroglu, Joan Gomez-Aguilar, Edaise M. da Silva, Suleman Hussain, Daniel Higginson, Paul C. Boutros, Nadeem Riaz, Jorge S. Reis-Filho, Simon N. Powell, Agnel Sfeir
{"title":"RNA transcripts serve as a template for double-strand break repair in human cells","authors":"Manisha Jalan, Alessandra Brambati, Hina Shah, Niamh McDermott, Juber Patel, Yingjie Zhu, Ahmet Doymaz, Julius Wu, Kyrie S. Anderson, Andrea Gazzo, Fresia Pareja, Takafumi N. Yamaguchi, Theodore Vougiouklakis, Sana Ahmed-Seghir, Philippa Steinberg, Anna Neiman-Golden, Benura Azeroglu, Joan Gomez-Aguilar, Edaise M. da Silva, Suleman Hussain, Daniel Higginson, Paul C. Boutros, Nadeem Riaz, Jorge S. Reis-Filho, Simon N. Powell, Agnel Sfeir","doi":"10.1038/s41467-025-59510-x","DOIUrl":"https://doi.org/10.1038/s41467-025-59510-x","url":null,"abstract":"<p>Double-strand breaks (DSBs) are toxic lesions that lead to genome instability. While canonical DSB repair pathways typically operate independently of RNA, growing evidence suggests that RNA:DNA hybrids and nearby transcripts can influence repair outcomes. However, whether transcript RNA can directly serve as a template for DSB repair in human cells remains unclear. In this study, we develop fluorescence and sequencing-based assays to show that RNA-containing oligonucleotides and messenger RNA can serve as templates during DSB repair. We conduct a CRISPR/Cas9-based genetic screen to identify factors that promote RNA-templated DSB repair (RT-DSBR). Of the candidate polymerases, we identify DNA polymerase zeta (Polζ) as a potential reverse transcriptase that facilitates RT-DSBR. Furthermore, analysis of cancer genome sequencing data reveals whole intron deletions - a distinct genomic signature of RT-DSBR that occurs when spliced mRNA guides repair. Altogether, our findings highlight RT-DSBR as an alternative pathway for repairing DSBs in transcribed genes, with potential mutagenic consequences.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"28 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930967","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}
Megan Delens, Axel Franckart, Daniel M. Harris, Nicolas Vandewalle
{"title":"3D-printed spines for programmable liquid topographies and micromanipulation","authors":"Megan Delens, Axel Franckart, Daniel M. Harris, Nicolas Vandewalle","doi":"10.1038/s41467-025-59483-x","DOIUrl":"https://doi.org/10.1038/s41467-025-59483-x","url":null,"abstract":"<p>Manipulating floating objects, whether solid or liquid, from microscopic to mesoscopic sizes, is crucial in various microfluidics and microfabrication applications. While capillary menisci naturally self-assemble and transport floating particles, their shapes and sizes are limited by the properties of the fluid and the objects involved. We herein harness the superposition of capillary menisci to curve liquid interfaces controllably. By using 3D-printed spines piercing the interface, we can finely adjust height gradients across the liquid surface to create specific liquid topographies. Thus, our method becomes a powerful tool for manipulating floating objects into programmable paths. Combining experimental demonstrations, numerical simulations, and theoretical modeling, we study the liquid elevation created by specific spine dispositions and the three-dimensional manipulation of submillimetric particles. Multiple examples showcase the method’s potential applications, including sorting and capturing particles, which could pave the way for cleaning fluid interfaces.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"33 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930991","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}
Shiyi Liu, Mingwei Wang, Liangjie Xu, Daihua Deng, Liwei Lu, Jie Tian, Dongmei Zhou, Ke Rui
{"title":"New insight into the role of SOCS family in immune regulation and autoimmune pathogenesis","authors":"Shiyi Liu, Mingwei Wang, Liangjie Xu, Daihua Deng, Liwei Lu, Jie Tian, Dongmei Zhou, Ke Rui","doi":"10.1016/j.jare.2025.05.020","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.020","url":null,"abstract":"<h3>Background</h3>Suppressor of cytokine signaling (SOCS) proteins regulate signal transduction by interacting with cytokine receptors and signaling proteins and targeting associated proteins for degradation. Recent studies have demonstrated that the SOCS proteins serve as crucial inhibitors in cytokine signaling networks and play a pivotal role in both innate and adaptive immune responses.<h3>Aim of Review</h3>In this review, we aim to discuss recent advancements in understanding the complex functions of SOCS proteins in various immune cells, as well as the effects of SOCS proteins in human health and diseases. Increasing evidence indicates that SOCS proteins are frequently dysregulated in developing autoimmune diseases, suggesting that therapeutic targeting of SOCS proteins could provide clinical benefit.<h3>Key Scientific Concepts of Review</h3>This review provides a comprehensive understanding of SOCS proteins in immune regulation and autoimmune pathogenesis, it also highlights the role of SOCS-related mimetic peptides in immunotherapy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"9 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antimycin A inhibits alpha-herpesvirus replication by disrupting the formation of pyrimidinosomes","authors":"Yong-Qi Guo, Meng-Hang Wang, Ning Tang, Yu-Bo Zhao, Li-Jing Wo, De-Xin Liang, Rui Huang, Yan-Dong Tang, Ying-Jie Sun, Xin Yin","doi":"10.1016/j.jare.2025.05.016","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.016","url":null,"abstract":"<h3>Introduction</h3>Alpha-herpesvirus poses significant health risks to humans and challenges to animal husbandry. Currently, the clinically approved antiviral drug Acyclovir exhibits limitations, including drug resistance and adverse effects. The development of broad-spectrum antiviral agents against alpha-herpesvirus is urgently needed.<h3>Objective</h3>This study aimed to discover a novel antiviral drug with the capacity to broadly inhibit various alpha-herpesviruses.<h3>Methods</h3>In this study, we conducted a high-content screening of 1,500 chemical compounds to identify potential antiviral candidates. The antiviral mechanisms were explored using phenotypic experiments, untargeted metabolomics, and molecular docking.<h3>Results</h3>We discovered that Antimycin A effectively inhibits the replication of various alpha-herpesviruses, including herpes simplex virus 1 (HSV-1), bovine herpesvirus 1 (BHV-1), and pseudorabies virus (PRV). Our study revealed that Antimycin A inhibits viral replication by disrupting the formation of pyrimidinosomes that are essential for efficient viral infection. Finally, Antimycin A effectively inhibited viral infection, prevented tissue damage, and enhanced survival in PRV-infected BALB/c mice, confirming its <em>in vivo</em> efficacy.<h3>Conclusion</h3>Antimycin A emerges as a promising lead candidate for the development of antiviral therapies against alpha-herpesvirus infections.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931232","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}
Umar Danjuma Maiwada , Gaber Sallam Salem Abdalla , Narinderjit Singh Sawaran Singh , Anas A. Salameh
{"title":"Efficient energy utilization in LTE networks with intelligent handover mechanisms","authors":"Umar Danjuma Maiwada , Gaber Sallam Salem Abdalla , Narinderjit Singh Sawaran Singh , Anas A. Salameh","doi":"10.1016/j.jrras.2025.101599","DOIUrl":"10.1016/j.jrras.2025.101599","url":null,"abstract":"<div><div>As mobile data traffic surges and the number of connected devices rises, energy efficiency has become a critical concern in Long-Term Evolution (LTE) networks. Traditional handover algorithms in LTE systems prioritize metrics such as signal strength and load balancing, often overlooking the impact on energy consumption. This study addresses that gap by proposing an intelligent, data-driven handover optimization framework designed to reduce energy usage in heterogeneous LTE environments. The core objective is to enhance network sustainability without significantly compromising Quality of Service (QoS). To achieve this, we introduce a machine learning-based handover decision mechanism that integrates user behavior prediction and workload balancing. Thus, analyzing both user mobility patterns and network conditions, the proposed system identifies optimal timing and target cells for handovers. This proactive strategy minimizes unnecessary signaling and handover attempts, which are common sources of energy waste in traditional approaches. The framework includes a Mobility Load Balancing (MLB) algorithm that extends beyond conventional metrics, incorporating energy-awareness as a key factor in decision-making. Simulations demonstrate that our intelligent handover mechanism delivers substantial energy savings while maintaining service quality at acceptable levels. Specifically, it outperforms standard LTE handover methods by significantly reducing redundant handovers and base station power usage. This research not only contributes to the theoretical understanding of energy-efficient radio network (RN) management but also provides a practical solution for telecom operators aiming to deploy greener LTE infrastructures. Also, leveraging machine learning techniques, the proposed model supports more sustainable operations and helps networks better manage the increasing data demands of the Internet of Things (IoT) era. In summary, our work introduces a novel, intelligent approach to LTE handover management that aligns energy efficiency with service performance. The findings suggest that intelligent, predictive algorithms can play a pivotal role in creating more sustainable and cost-effective wireless networks.</div></div>","PeriodicalId":16920,"journal":{"name":"Journal of Radiation Research and Applied Sciences","volume":"18 3","pages":"Article 101599"},"PeriodicalIF":1.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Conary Meyer, Alessandra Arizzi, Tanner Henson, Sharon Aviran, Marjorie L. Longo, Aijun Wang, Cheemeng Tan
{"title":"Designer artificial environments for membrane protein synthesis","authors":"Conary Meyer, Alessandra Arizzi, Tanner Henson, Sharon Aviran, Marjorie L. Longo, Aijun Wang, Cheemeng Tan","doi":"10.1038/s41467-025-59471-1","DOIUrl":"https://doi.org/10.1038/s41467-025-59471-1","url":null,"abstract":"<p>Protein synthesis in natural cells involves intricate interactions between chemical environments, protein-protein interactions, and protein machinery. Replicating such interactions in artificial and cell-free environments can control the precision of protein synthesis, elucidate complex cellular mechanisms, create synthetic cells, and discover new therapeutics. Yet, creating artificial synthesis environments, particularly for membrane proteins, is challenging due to the poorly defined chemical-protein-lipid interactions. Here, we introduce MEMPLEX (Membrane Protein Learning and Expression), which utilizes machine learning and a fluorescent reporter to rapidly design artificial synthesis environments of membrane proteins. MEMPLEX generates over 20,000 different artificial chemical-protein environments spanning 28 membrane proteins. It captures the interdependent impact of lipid types, chemical environments, chaperone proteins, and protein structures on membrane protein synthesis. As a result, MEMPLEX creates new artificial environments that successfully synthesize membrane proteins of broad interest but previously intractable. In addition, we identify a quantitative metric, based on the hydrophobicity of the membrane-contacting amino acids, that predicts membrane protein synthesis in artificial environments. Our work allows others to rapidly study and resolve the “dark” proteome using predictive generation of artificial chemical-protein environments. Furthermore, the results represent a new frontier in artificial intelligence-guided approaches to creating synthetic environments for protein synthesis.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"5 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comprehensive synthesis and anticoagulant evaluation of a diverse fucoidan library","authors":"Si-Cong Chen, Xianjin Qin, Nanyu Xiong, Lisha Lin, Yanfen Wu, Qin Li, Dongyue Sun, De-Cai Xiong, Cassandra E. Callmann, Mingyi Wu, Xin-Shan Ye","doi":"10.1038/s41467-025-59632-2","DOIUrl":"https://doi.org/10.1038/s41467-025-59632-2","url":null,"abstract":"<p>Fucoidan, a sulfated glycan derived from brown algae, has garnered significant attention for its anticoagulant properties. However, the structural complexity and heterogeneity of naturally extracted fucoidan have hindered a comprehensive understanding of its structure-activity relationship, limiting the development of fucoidan-based anticoagulant drugs. To address this challenge, we synthesize a diverse library of 58 distinct fucoidans with multiple contiguous 1,2-<i>cis</i> glycosidic bonds, ranging from disaccharides to dodecasaccharides, using a highly efficient preactivation-based one-pot glycosylation strategy. This library includes compounds with various sulfation patterns (2,3-<i>O</i>-<i>di-</i>, 3,4-<i>O</i>-<i>di-</i>, and 2,3,4-<i>O</i>-<i>tri</i>-sulfation) encompassing nearly all possible fucoidan structures. In vitro anticoagulant assays demonstrate that both molecular size and degree of sulfation play crucial roles in anticoagulant potency. Notably, compounds <b>29</b>, <b>30</b>, <b>37</b>, and <b>58</b> significantly prolong human plasma activated partial thromboplastin time (APTT), comparable to the effect of enoxaparin, without affecting prothrombin time (PT) or thrombin time (TT). This selective inhibition of the intrinsic coagulation pathway suggests a reduced risk of bleeding, highlighting the therapeutic potential of these fucoidans as safer anticoagulant agents.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"23 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932411","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}
Kimberly A. Van Orden, April Buttaccio, Yeates Conwell
{"title":"The 5D indicators of suicide risk in older adults who are lonely","authors":"Kimberly A. Van Orden, April Buttaccio, Yeates Conwell","doi":"10.1111/nyas.15354","DOIUrl":"https://doi.org/10.1111/nyas.15354","url":null,"abstract":"Loneliness is associated with suicide ideation, attempts, and deaths in later life. The objective of this study is to describe characteristics of suicide risk among older adults who report clinically significant loneliness grounded in our conceptual model of the 5Ds of late life suicide. Our sample comprises 291 adults aged 60 years and older who screened positive for loneliness (UCLA 3‐Item Loneliness Scale score of 6 and above) and subsequently completed baseline eligibility interviews for a clinical trial. Interviews obtained information on loneliness severity, suicide ideation, and the 5Ds of late life suicide: (1) depression (PROMIS depression), (2) deadly means (firearms access), (3) disease (number of chronic conditions), (4) disconnection (objective disconnection, Lubben Social Network Scale; subjective disconnection, UCLA Loneliness Scale), and (5) disability (World Health Organization Disability Assessment Schedule). Subjects demonstrated a high frequency of characteristics associated with suicide risk, with the most common presentation (38%) being the presence of 3Ds—subjective disconnection (loneliness), multimorbidity, and disability. While few subjects presented with only subjective disconnection (loneliness), there was diversity in which other Ds were present and in which combination, suggesting heterogeneous presentations. Upstream suicide prevention efforts could target older adults with loneliness to reach a population with numerous compounding indicators of risk.","PeriodicalId":8250,"journal":{"name":"Annals of the New York Academy of Sciences","volume":"1 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unlocking single-atom induced electronic metal-support interactions in electrocatalytic one-electron water oxidation for wastewater purification","authors":"Sen Lu, Xuechuan Li, Guan Zhang, Shaobin Wang","doi":"10.1038/s41467-025-59722-1","DOIUrl":"https://doi.org/10.1038/s41467-025-59722-1","url":null,"abstract":"<p>Electro-oxidation is a promising green technology for decentralized wastewater purification. However, its efficacy is primarily constrained by the selectivity and efficiency of hydroxyl radical (•OH) generation through one-electron water oxidation. In this study, we elucidate the mechanism of electronic metal-support interactions (EMSI) of Ni single-atoms on antimony-doped tin oxide anode (Ni/ATO) to enhance •OH production and overall water treatment efficiency. We experimentally and theoretically investigate both the structural evolution process and micro-interface mechanisms associated with the EMSI effects induced by Ni single-atoms. The optimized electronic structures in the interfacial catalysts under EMSI conditions and the co-catalytic role of Ni single-atoms synergistically facilitate selective and efficient •OH generation, resulting in over a fivefold increase in its steady-state concentration and tenfold enhancement in pseudo-first-order rate constant of sulfamethoxazole degradation compared to those on bare ATO. With the EMSI, rapid electron transfer channels were established for a marked enhancement in the adsorption, conversion, and dissociation of interfacial H<sub>2</sub>O molecules. Notably, it is revealed that Ni single-atoms serve as co-catalytic sites, exhibiting a “H-pulling effect” that is crucial for •OH generation. The Ni/ATO anode demonstrates great efficiency in degrading various refractory organic pollutants, and effectively treats real pharmaceutical wastewater with low energy consumption. Furthermore, it presents remarkable stability and adaptability, while maintaining a minimal environmental footprint during wastewater treatment processes. This work addresses the theoretical gaps between EMSI effects and co-catalysis in electro-oxidation systems, while providing a robust technological solution for wastewater purification.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"39 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930964","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}