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Spatiotemporal dynamics of NF-κB/Dorsal inhibitor IκBα/Cactus in Drosophila blastoderm embryos NF-κB/背侧抑制剂i -κB α/仙人掌在果蝇胚皮胚中的时空动态

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112854

Allison E. Schloop , Sharva Vijayakumar Hiremath , Razeen Shaikh , Sadia Siddika Dima , Leslie Lizardo , Amrit Bhakta , Cranos M. Williams , Gregory T. Reeves

{"title":"Spatiotemporal dynamics of NF-κB/Dorsal inhibitor IκBα/Cactus in Drosophila blastoderm embryos","authors":"Allison E. Schloop , Sharva Vijayakumar Hiremath , Razeen Shaikh , Sadia Siddika Dima , Leslie Lizardo , Amrit Bhakta , Cranos M. Williams , Gregory T. Reeves","doi":"10.1016/j.isci.2025.112854","DOIUrl":"10.1016/j.isci.2025.112854","url":null,"abstract":"<div><div>The NF-κB/IκBα pathway regulates key cellular processes, including development, immunity, and inflammation. In <em>Drosophila</em>, the homologous Dorsal/Cactus system patterns the dorsoventral axis of the blastoderm embryo. While the inhibitor Cactus has been suggested to play multiple roles in regulating Dorsal, direct visualization of Cactus is challenging due to its rapid turnover. To overcome this challenge, we endogenously tagged Cactus with a nanobody against GFP and quantitatively imaged Cactus distribution in live embryos. We found that, like Dorsal, Cactus undergoes nuclear-cycle driven dynamics and nucleocytoplasmic shuttling. Using a mathematical model constrained by our data, we estimated Cactus nuclear and cytoplasmic concentration. Our results imply that the Dorsal gradient has increased spatial range, robustness, and precision due to the presence of Cactus in the nucleus uniformly throughout the embryo. This study provides insights into NF-κB regulation in <em>Drosophila</em> embryos and highlights the need for similar quantitative studies in other biological systems.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112854"},"PeriodicalIF":4.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471416","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

Dynamically tunable photonic manipulation and sensing in graphene array-driven Bragg gratings 石墨烯阵列驱动Bragg光栅的动态可调谐光子操纵和传感

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112848

Xiaoling Chen , Junjie Dong , Dong Zhao , Hao Ni , Fanghua Liu , Hao Wu , Miaomiao Zhao , Junfu Yang

引用次数: 0

Randomized controlled trial of prednisone in treating acute subjective tinnitus patients with normal pure-tone thresholds 强的松治疗纯音阈值正常的急性主观性耳鸣患者的随机对照试验

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

Accelerating domestication of perennial plants with genomics 加速多年生植物基因组化驯化

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112836

Renan Souza , David L. Van Tassel , Walid Korani , Alex Harkess , Josh Clevenger

引用次数: 0

Syndecan-1-mediated loading of VEGF-A into small extracellular vesicles facilitates peritubular capillary repair during AKI-to-CKD transition syndecan -1介导的VEGF-A加载到细胞外小泡中，促进了aki向ckd过渡期间小管周围毛细血管的修复

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112862

Xin Zhong , Tao-Tao Tang , Yue Zhang , Ding-Ding Xue , An-Ran Shen , Ning Li , Min Wu , Bi-Cheng Liu , Lin-Li Lv

{"title":"Syndecan-1-mediated loading of VEGF-A into small extracellular vesicles facilitates peritubular capillary repair during AKI-to-CKD transition","authors":"Xin Zhong , Tao-Tao Tang , Yue Zhang , Ding-Ding Xue , An-Ran Shen , Ning Li , Min Wu , Bi-Cheng Liu , Lin-Li Lv","doi":"10.1016/j.isci.2025.112862","DOIUrl":"10.1016/j.isci.2025.112862","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a severe clinical event with a high risk of transitioning to chronic kidney disease (CKD). Persistent hypoxia resulting from peritubular capillaries (PTCs) loss is a key factor driving this chronic transition. However, the mechanisms governing PTCs injury and repair, particularly under different AKI severity, remain unclear. This study demonstrates that small extracellular vesicle (sEV) carried VEGF-A as an essential regulator of PTCs repair and decreased as the severity of tubular injury increased. We found that VEGF-A was sorted into sEV via syndecan-1 (SDC-1), attaching to the heparan sulfate chain in moderate AKI. SDC-1 knockdown in renal tubules significantly reduced VEGF-A packaging into EVs and aggravated PTCs rarefaction and renal fibrosis. Overexpression of SDC-1 promoted the production of VEGF-A<sup>+</sup> sEV and their proliferative effects on endothelial cells. These findings demonstrate that SDC-1 contributes to the secretion of VEGF-A<sup>+</sup> sEV from moderately injured tubules, facilitating PTCs repair after AKI.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112862"},"PeriodicalIF":4.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329822","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

Lactate regulates cell differentiation of erythroid progenitor cells via histone lactylation modification 乳酸通过组蛋白乳酸化修饰调节红细胞祖细胞的分化

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112842

Qianqian Yang , Hengchao Zhang , Yan Hou , Shaoyang Gu , Lixiang Chen , Fumin Xue , Xiuyun Wu

{"title":"Lactate regulates cell differentiation of erythroid progenitor cells via histone lactylation modification","authors":"Qianqian Yang , Hengchao Zhang , Yan Hou , Shaoyang Gu , Lixiang Chen , Fumin Xue , Xiuyun Wu","doi":"10.1016/j.isci.2025.112842","DOIUrl":"10.1016/j.isci.2025.112842","url":null,"abstract":"<div><div>Lactate plays important regulatory roles in a variety of biological events by regulating metabolic homeostasis and histone lactylation. However, the role of lactate and histone lactylation in human erythropoiesis remains unclear. Here, we explored the role of lactate in erythropoiesis by adding the glycolysis inhibitor 2-deoxy-<em>d</em>-glucose (2-DG) or exogenous lactate Na-La to decrease or increase intracellular lactate levels. The results showed the inhibition of glycolysis promoted erythroid progenitors’ differentiation, blocked cell cycle, and reduced colony formation of colony-forming unit-erythroid (CFU-E), whereas elevated lactate levels delayed erythroid progenitors’ differentiation and promoted CFU-E colony formation. We also found lactate levels directly regulated H3K14la intensity. Furthermore, we showed changes in H3K14la abundance and gene expression of the cell cycle and division-related genes <em>CCNB1</em>, <em>CFL1</em>, <em>CENPA</em>, and <em>GNAI2</em>, which were associated with stem cell pluripotency and differentiation. In conclusion, our study reveals lactate affects cell differentiation of early erythroid progenitors by regulating gene expression through histone lactylation.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112842"},"PeriodicalIF":4.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329818","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

CircYAP1 inhibits osteosarcoma progression through the miR-135b-5p/FRK axis CircYAP1通过miR-135b-5p/FRK轴抑制骨肉瘤进展

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112858

Mingrui Du , Xuesan Zhang , Menglin Cong , Chengkui Cai , Qingxiang Zhang , Haixia Xin , Lanbo Yang , Qingqing Geng , Mingfu Shang , Zheng Zhang , Le Shen , Shusen Tan , Kang Han

{"title":"CircYAP1 inhibits osteosarcoma progression through the miR-135b-5p/FRK axis","authors":"Mingrui Du , Xuesan Zhang , Menglin Cong , Chengkui Cai , Qingxiang Zhang , Haixia Xin , Lanbo Yang , Qingqing Geng , Mingfu Shang , Zheng Zhang , Le Shen , Shusen Tan , Kang Han","doi":"10.1016/j.isci.2025.112858","DOIUrl":"10.1016/j.isci.2025.112858","url":null,"abstract":"<div><div>Circular RNAs (circRNAs) are implicated in the progression of various malignancies, including osteosarcoma. However, little is known about the role of circYAP1 in osteosarcoma. In the present study, the expression of circYAP1 was found to be downregulated in osteosarcoma tissues relative to adjacent normal tissues. Decreased circYAP1 expression was also found in metastatic osteosarcoma specimens relative to nonmetastatic specimens, and low circYAP1 group had a higher metastasis rate and more advanced clinical stage than high circYAP1 group. <em>In vitro</em> functional assays demonstrated the inhibitory effects of circYAP1 on osteosarcoma cell proliferation, invasion, and migration. Regarding the mechanism, circYAP1 acts as a competitive endogenous RNA (ceRNA) to sponge miR-135b-5p, whereas FRK is a direct target of miR-135b-5p. Finally, a tumor-suppressing role of circYAP1 was demonstrated in the orthotopic lung metastasis models. In conclusion, our data reveal a tumor-suppressing role of circYAP1 and circYAP1/miR-135b-5p/FRK axis in osteosarcoma, demonstrating potential therapeutic targets for osteosarcoma.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112858"},"PeriodicalIF":4.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481388","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