IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112840

Peifan Li (李沛璠) , Chenhao Che (车晨昊) , Dantong Gu (顾丹彤) , Xiaoling Lu (鲁小玲) , Xiao Xiao (肖潇) , Yanping Yu (俞艳萍) , Dongmei Tang (唐冬梅) , Dan You (尤丹) , Tingting Qian (钱婷婷) , Yongzhen Wu (吴拥真) , Shan Sun (孙珊)

{"title":"Randomized controlled trial of prednisone in treating acute subjective tinnitus patients with normal pure-tone thresholds","authors":"Peifan Li (李沛璠) , Chenhao Che (车晨昊) , Dantong Gu (顾丹彤) , Xiaoling Lu (鲁小玲) , Xiao Xiao (肖潇) , Yanping Yu (俞艳萍) , Dongmei Tang (唐冬梅) , Dan You (尤丹) , Tingting Qian (钱婷婷) , Yongzhen Wu (吴拥真) , Shan Sun (孙珊)","doi":"10.1016/j.isci.2025.112840","DOIUrl":"10.1016/j.isci.2025.112840","url":null,"abstract":"<div><div>The effectiveness of steroid therapy for acute subjective tinnitus (AST) without sudden hearing loss remains controversial. This randomized controlled trial evaluated the effectiveness of short-term oral prednisone (STOP) in patients with AST. The STOP group received a 14-day tapering prednisone for the initial 14 days, and both groups took Ginkgo biloba extract throughout the 3-month follow-up period. The primary outcome was the 12-week change in Tinnitus Handicap Inventory (THI) scores, assessed via intention-to-treat analysis. At the 12-week follow-up, the STOP medication significant reduced THI scores (−27 · 34 [95% CI, −31 · 14 to −23 · 55]) versus control (−15 · 37 [95% CI, −18 · 5 to −12 · 23]), with a mean difference of −11 · 97 points (95% CI, −16 · 85 to −7·09; <em>p</em> < 0 · 0001). Sensitivity analyses and post hoc analyses corroborated these findings. In summary, the STOP treatment plus Ginkgo biloba could effectively lessen the self-reported tinnitus severity in patients with AST.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112840"},"PeriodicalIF":4.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Mechanistic study of N-acetyltransferase 10 deficiency enhancing olaparib sensitivity in triple negative breast cancer by inhibiting RAD51 N4-acetylcytidine modification n -乙酰转移酶10缺乏通过抑制RAD51 n4 -乙酰胞苷修饰增强三阴性乳腺癌患者奥拉帕尼敏感性的机制研究

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112860

Hui Li , Hao Wu , Siwei Li , Qin Wang , Guozheng Li , Xin Ma , Yajie Gong , Yijun Chu , Shengye Jin , Xi Chen , Xianyu Zhang , Da Pang

{"title":"Mechanistic study of N-acetyltransferase 10 deficiency enhancing olaparib sensitivity in triple negative breast cancer by inhibiting RAD51 N4-acetylcytidine modification","authors":"Hui Li , Hao Wu , Siwei Li , Qin Wang , Guozheng Li , Xin Ma , Yajie Gong , Yijun Chu , Shengye Jin , Xi Chen , Xianyu Zhang , Da Pang","doi":"10.1016/j.isci.2025.112860","DOIUrl":"10.1016/j.isci.2025.112860","url":null,"abstract":"<div><div>The treatment of triple-negative breast cancer (TNBC) is challenging due to the lack of common treatment targets, making standard hormonal and targeted therapies ineffective. While PARP inhibitors are promising for TNBC, they are only effective in homologous recombination (HR)-deficient cells with <em>BRCA1/2</em> mutations. Nevertheless, resistance to PARP inhibitors often develops. Thus, it is imperative to identify strategies or targets that can enhance the efficacy of PARP inhibitors. In this study, we demonstrated that TNBC cells lacking N-acetyltransferase 10 (NAT10) exhibited greater sensitivity to olaparib and extensive DNA double-strand breaks (DSBs). Mechanistically, NAT10 upregulates the N4-acetylcytidine (ac4C) modification of <em>RAD51</em> mRNA, enhancing its stability and increasing RAD51 expression. Remarkably, the combination of olaparib and remodelin, an inhibitor of NAT10, induced robust anti-tumor effects <em>in vitro</em> and <em>in vivo</em> by promoting DSBs. Our findings illuminate a potential therapeutic strategy targeting NAT10 to enhance olaparib efficacy in TNBC.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112860"},"PeriodicalIF":4.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Identification of novel macrophages and bone morphogenetic protein signals causing ectopic calcification and impairing muscle regeneration 鉴定引起异位钙化和损伤肌肉再生的新型巨噬细胞和骨形态发生蛋白信号

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112841

Linan Shi , Zhifeng He , Toru Hiraga , Ziyang Liu , Teruhito Yamashita , Rina Iwamoto , Toshihide Mizoguchi , Yuko Nakamichi , Yoshiaki Kubota , Nobuyuki Udagawa , Yasuhiro Kobayashi

{"title":"Identification of novel macrophages and bone morphogenetic protein signals causing ectopic calcification and impairing muscle regeneration","authors":"Linan Shi , Zhifeng He , Toru Hiraga , Ziyang Liu , Teruhito Yamashita , Rina Iwamoto , Toshihide Mizoguchi , Yuko Nakamichi , Yoshiaki Kubota , Nobuyuki Udagawa , Yasuhiro Kobayashi","doi":"10.1016/j.isci.2025.112841","DOIUrl":"10.1016/j.isci.2025.112841","url":null,"abstract":"<div><div>Ectopic calcification is an abnormal regenerative response occurring in various tissues following injury, surgery, or genetic mutations. However, its underlying mechanisms remain unclear. By comparing three macrophage depletion methods using clodronate liposome, Csf1r neutralizing antibody, and macrophage-specific <em>Csf1r</em> gene deletion (<em>Csf1r cKO</em>), we found that F4/80(+)Csf1r(−) macrophages were specifically increased in calcified muscles in notexin-injected mice and BaCl<sub>2</sub>-injected <em>Csf1r cKO</em> mice. Mechanistically, bone morphogenetic protein (BMP) signaling was found to contribute to ectopic calcification. Reanalysis of public single-cell sequencing data and lineage-tracing analysis using <em>Cdh5</em><sup><em>creERT2</em></sup> mice revealed that endothelial-to-mesenchymal transition (EndoMT) is also a key contributor to ectopic calcification, as evidenced by the high expression of EndoMT-related markers in mesenchymal progenitor cells. Notably, the administration of BMP inhibitors reduced calcification and promoted muscle regeneration. Thus, F4/80(+)Csf1r(−) macrophages and BMP signals represent promising therapeutic targets for preventing ectopic calcifications triggered by trauma, burns, infections, or surgical interventions.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112841"},"PeriodicalIF":4.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Gaze following in pigeons increases with the number of demonstrators 鸽子的注视跟随随着示威者的数量增加而增加

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112857

Mathilde Delacoux , Akihiro Itahara , Fumihiro Kano

引用次数: 0

A 3D printing UV-curing resin that enables continuous color change of elastomers 一种3D打印uv固化树脂，可使弹性体连续变色

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112867

Yiyang Gao , Qihao Jiang , Yanming Liu

引用次数: 0

Genetic signatures in the highly virulent subtype B human immunodeficiency virus-1 conferring resistance to broadly neutralizing antibodies 高毒力乙型人类免疫缺陷病毒-1亚型的遗传特征赋予对广泛中和抗体的抗性

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112847

Manukumar Honnayakanahalli Marichannegowda , Georgina Agyekum , Cinthya Zelaya Aparicio , Alonso Heredia , Yin Wang , Hongshuo Song

引用次数: 0

Functional impact of the hyperduplication genomophenotype in high copy number endometrial cancer 高拷贝数子宫内膜癌中超重复基因表型的功能影响

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112850

Angela Florio , James Smadbeck , Sarah H. Johnson , Wan-Hsin Lin , Dorsay Sadeghian , Sotiris Sotiriou , Rebeca Salvatori , Ryan W. Feathers , Taylor Berry , Lindsey Kinsella , Faye R. Harris , Alexa F. McCune , Stephen J. Murphy , Mohamed F. Ali , Abdulmohammad Pezeshki , Michael T. Barrett , Leah Grcevich , Ilaria Capasso , Luigi Antonio De Vitis , Gabriella Schivardi , George Vasmatzis

{"title":"Functional impact of the hyperduplication genomophenotype in high copy number endometrial cancer","authors":"Angela Florio , James Smadbeck , Sarah H. Johnson , Wan-Hsin Lin , Dorsay Sadeghian , Sotiris Sotiriou , Rebeca Salvatori , Ryan W. Feathers , Taylor Berry , Lindsey Kinsella , Faye R. Harris , Alexa F. McCune , Stephen J. Murphy , Mohamed F. Ali , Abdulmohammad Pezeshki , Michael T. Barrett , Leah Grcevich , Ilaria Capasso , Luigi Antonio De Vitis , Gabriella Schivardi , George Vasmatzis","doi":"10.1016/j.isci.2025.112850","DOIUrl":"10.1016/j.isci.2025.112850","url":null,"abstract":"<div><div>High copy-number endometrial cancers (HCNECs) are dominated by excessive duplications scattered across the genome, termed here as the hyperduplication genomophenotype (HDGP). We identified locations and sizes of duplications in 171 endometrial cancer cases and designated 71 HCNEC cases as HDGP. We also investigated the response to the pan-ERBB inhibitor afatinib in a subset of HDGP-EC cases with <em>ERBB2/ERBB3</em> duplications using a patient-derived three-dimensional culture model. Our analysis demonstrates that beyond tandem duplications there is a more general pattern involving coordinated duplication of multiple distant regions of the genome, demonstrating preferential selectivity to overexpressed potential oncogenes within a broad network. This suggests that HDGP increases tumor fitness and resistance to therapy by perturbing important gene networks in concert rather than only driver genes, suggesting a mechanistic basis for the ineffectiveness of targeted drugs in these patients and highlighting the need for combination therapies in these highly aggressive cases.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112850"},"PeriodicalIF":4.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Enhanced reverse zoonotic potential and immune evasion by omicron JN.1 variant 组粒JN.1变异体增强反向人畜共患病潜能和免疫逃避

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-06 DOI: 10.1016/j.isci.2025.112824

Jiaxin Hu , Fuwen Zan , Yixin He , Xiuyuan Ou , Xiaolu Tang , Yan Liu , Xing Lu , Pei Li , Zhixia Mu , Siwen Dong , Yahan Chen , Lin Tan , Mengmeng Cao , Pinghuang Liu , Terrence Tsz-Tai Yuen , Jian Lu , Zhaohui Qian

{"title":"Enhanced reverse zoonotic potential and immune evasion by omicron JN.1 variant","authors":"Jiaxin Hu , Fuwen Zan , Yixin He , Xiuyuan Ou , Xiaolu Tang , Yan Liu , Xing Lu , Pei Li , Zhixia Mu , Siwen Dong , Yahan Chen , Lin Tan , Mengmeng Cao , Pinghuang Liu , Terrence Tsz-Tai Yuen , Jian Lu , Zhaohui Qian","doi":"10.1016/j.isci.2025.112824","DOIUrl":"10.1016/j.isci.2025.112824","url":null,"abstract":"<div><div>SARS-CoV-2 infects not only humans but also animals, posing reverse zoonotic risks. As SARS-CoV-2 rapidly evolves, JN.1 has become dominant globally. In this study, we determined the susceptibility of XBB.1.16, EG.5.1, BA.2.86, and JN.1 to 27 different animal angiotensin-converting enzyme 2 (ACE2) orthologs using pseudoviruses, and found that JN.1 displayed substantially higher overall reverse zoonotic risk potential compared to other variants except for EG.5.1. Live virus infection experiments further confirmed higher infectivity of JN.1 than BA.2.86. Mechanistic analyses revealed that L455S might be responsible for substantial increase in overall fusogenecity and infectivity by lowering S protein thermostability. Additionally, we also found that L455S mutation enhanced immune evasion of SARS-CoV-2, and XBB breakthrough infection increased levels of neutralization antibodies against JN.1. Together, our findings offer a better mechanistic understanding of CoV entry, host range, evolution, and immunogenicity and highlight the importance of surveillance of susceptible hosts to prevent potential outbreaks.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112824"},"PeriodicalIF":4.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Combining light-induced aggregation and biotin proximity labeling implicates endolysosomal proteins in early α-synuclein oligomerization 结合光诱导聚集和生物素接近标记涉及早期α-突触核蛋白寡聚的内溶酶体蛋白

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-06 DOI: 10.1016/j.isci.2025.112823

Maxime Teixeira , Razan Sheta , Dylan Musiol , Vetso Ranjakasoa , Jérémy Loehr , Jean-Philippe Lambert , Abid Oueslati

{"title":"Combining light-induced aggregation and biotin proximity labeling implicates endolysosomal proteins in early α-synuclein oligomerization","authors":"Maxime Teixeira , Razan Sheta , Dylan Musiol , Vetso Ranjakasoa , Jérémy Loehr , Jean-Philippe Lambert , Abid Oueslati","doi":"10.1016/j.isci.2025.112823","DOIUrl":"10.1016/j.isci.2025.112823","url":null,"abstract":"<div><div>Alpha-synuclein (α-syn) aggregation is a defining feature of Parkinson’s disease (PD) and related synucleinopathies. Despite significant research efforts focused on understanding α-syn aggregation mechanisms, the early stages of this process remain elusive, largely due to limitations in experimental tools that lack the temporal resolution to capture these dynamic events. Here, we introduce UltraID-LIPA, an innovative platform that combines the light-inducible protein aggregation (LIPA) system with the UltraID proximity-dependent biotinylation assay to identify α-syn-interacting proteins and uncover key mechanisms driving its oligomerization. UltraID-LIPA successfully identified 38 α-syn-interacting proteins, including both established and previously unreported candidates, highlighting the accuracy and robustness of the approach. Notably, a strong interaction with endolysosomal and membrane-associated proteins was observed, supporting the hypothesis that interactions with membrane-bound organelles are pivotal in the early stages of α-syn aggregation. This powerful platform provides new insights into dynamic protein aggregation events, enhancing our understanding of synucleinopathies and other proteinopathies.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112823"},"PeriodicalIF":4.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Assessment model of blast injury: A narrative review 爆炸损伤评价模型：综述

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-06 DOI: 10.1016/j.isci.2025.112830

Rui Liang , Hong Wang , Junhong Gao , Jianmin Wang , Wenjuan Zhang , Airong Qian

{"title":"Assessment model of blast injury: A narrative review","authors":"Rui Liang , Hong Wang , Junhong Gao , Jianmin Wang , Wenjuan Zhang , Airong Qian","doi":"10.1016/j.isci.2025.112830","DOIUrl":"10.1016/j.isci.2025.112830","url":null,"abstract":"<div><div>Craniocerebral and pulmonary injuries are primary blast-induced damages, assessed via numerical simulations, animal models, and postmortem human surrogates (PMHS). Recent years, the successful development of shock wave cell models and organoid models has provided new research directions for evaluation of blast injuries. Particularly human-derived organoids that can highly simulating the structure and function of human organs, significantly enhancing the physiological relevance of the models. Additionally, AI-based models (machine/deep learning) show promise in blast injury prediction and assessment. This review systematically summarizes the biological effects of explosive shock waves, the application of conventional assessment models and their limitations, and emerging technologies—cell/organoid models and AI applications. The utilization of cell models, human-derived organoid models, and AI models for the assessment of blast-induced biological injuries and subsequent research holds significant importance for understanding the cellular mechanisms of injury, protective research, and injury warning systems.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112830"},"PeriodicalIF":4.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

iScience最新文献