iScience最新文献_第2页

From diesel to electric: potential of drayage trucks transition in Southern California 从柴油到电力：南加州拖运卡车转型的潜力

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-11 DOI: 10.1016/j.isci.2025.112629

Guoliang Feng , Craig Ross Rindt , Stephen G. Ritchie

引用次数: 0

Retraction Notice to: Nuclear respiratory factor-1 negatively regulates TGF-β1 and attenuates pulmonary fibrosis 撤回通知：核呼吸因子-1负调控TGF-β1，减缓肺纤维化

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-10 DOI: 10.1016/j.isci.2025.112627

Hagir B. Suliman, Zachary Healy, Fabio Zobi, Bryan D. Kraft, Karen Welty-Wolf, Joshua Smith, Christina Barkauskas, Claude A. Piantadosi

引用次数: 0

Suppressing phagocyte activation by overexpressing the phosphatidylserine lipase ABHD12 preserves sarmopathic nerves 通过过表达磷脂酰丝氨酸脂肪酶ABHD12抑制吞噬细胞活化可保护肉瘤神经

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-09 DOI: 10.1016/j.isci.2025.112626

Caitlin B. Dingwall , Yo Sasaki , Amy Strickland , Tong Wu , Daniel W. Summers , A. Joseph Bloom , Aaron DiAntonio , Jeffrey Milbrandt

{"title":"Suppressing phagocyte activation by overexpressing the phosphatidylserine lipase ABHD12 preserves sarmopathic nerves","authors":"Caitlin B. Dingwall , Yo Sasaki , Amy Strickland , Tong Wu , Daniel W. Summers , A. Joseph Bloom , Aaron DiAntonio , Jeffrey Milbrandt","doi":"10.1016/j.isci.2025.112626","DOIUrl":"10.1016/j.isci.2025.112626","url":null,"abstract":"<div><div>Programmed axon degeneration (AxD) is a hallmark of many neurodegenerative diseases. In healthy axons, NMNAT2 inhibits SARM1, the key executioner of AxD, to keep it from depleting NAD+ and triggering axon destruction. AxD was assumed to be governed by axon-intrinsic mechanisms, independent of external factors. However, using a human disease model of neuropathy caused by hypomorphic NMNAT2 mutations resulting in chronic SARM1 activation, we demonstrated that neuronal SARM1 can initiate macrophage-mediated axon elimination long before stressed-but-viable axons would otherwise succumb to intrinsic metabolic failure. Chronic SARM1 activation causes axonal blebbing and disrupts phosphatidylserine (PS), a signaling molecule that promotes axon engulfment by macrophages. Neuronal expression of ABDH12, a PS lipase, reduces macrophage activation, preserves axons, and rescues motor function in this model, suggesting that PS dysregulation is an early SARM1-dependent axonal stress signal. Blocking macrophage-mediated axon elimination could be a promising therapeutic strategy for SARM1-dependent neurological diseases.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112626"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107556","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

How to predict effective drug combinations – moving beyond synergy scores 如何预测有效的药物组合-超越协同作用评分

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-09 DOI: 10.1016/j.isci.2025.112622

Lea Eckhart , Kerstin Lenhof , Lutz Herrmann , Lisa-Marie Rolli , Hans-Peter Lenhof

引用次数: 0

Understanding tsRNAs: From classification to disease mechanisms 了解tsRNAs：从分类到疾病机制

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-09 DOI: 10.1016/j.isci.2025.112614

Bo Fang , Kai Wang , Yinghui Li , Bo Li , Xinzhe Chen , Kun Wang , Sumin Yang

引用次数: 0

RBC balanced immuno-inflammatory signatures identify advanced breast cancer patients on CDK4/6 inhibitors at increased risk of progression and death 红细胞平衡免疫炎症特征识别CDK4/6抑制剂进展和死亡风险增加的晚期乳腺癌患者

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-09 DOI: 10.1016/j.isci.2025.112620

Jiayi Ma , Yaohui Wang , Ziping Wu , Liheng Zhou , Yanping Lin , Shuguang Xu , Jie Zhang , Jingsong Lu , Wenjin Yin

{"title":"RBC balanced immuno-inflammatory signatures identify advanced breast cancer patients on CDK4/6 inhibitors at increased risk of progression and death","authors":"Jiayi Ma , Yaohui Wang , Ziping Wu , Liheng Zhou , Yanping Lin , Shuguang Xu , Jie Zhang , Jingsong Lu , Wenjin Yin","doi":"10.1016/j.isci.2025.112620","DOIUrl":"10.1016/j.isci.2025.112620","url":null,"abstract":"<div><div>The association of immuno-inflammatory parameters, especially RBC balanced signatures, with survival outcomes and adverse events still require investigation for advanced breast cancer (ABC) patients receiving cyclin-dependent kinase 4/6 inhibitor (CDKI). Herein, RBC balanced immuno-inflammatory (RBC-IMM) score was developed and capable of predicting progression-free survival (PFS) events (<em>p</em> < 0.001), death (<em>p</em> < 0.001) and grade 3/4 leukopenia (<em>p</em> = 0.010). RBC-IMM score also predicted PFS more accurately than classical-IMM score (AUC = 0.766 and 0.596 respectively, <em>p</em> = 0.005). Besides, clinico+RBC_index exhibited superior performance to clinico_index for 18-month PFS through machine learning (training set: AUC = 0.830 and 0.764 respectively; testing set: AUC = 0.894 and 0.715 respectively). Additionally, liquid chromatography-tandem mass spectrometry identified phosphatidylcholine notably involved in RBC-CDKI interaction, contributing to the construction of clinico+PtdCho_index with better PFS prediction than clinico_index (AUC = 0.854 and 0.733 respectively). These findings indicate that RBC-IMM related parameters have the advantage of identifying benefit and safety in CDKI-treated ABC patients over classical indicators.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112620"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123600","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

Complex regulatory network of programmed death-ligand 1 in cancer: Cancer immunomodulation from molecular mechanisms to clinical applications 癌症中程序性死亡配体1的复杂调控网络：从分子机制到临床应用的癌症免疫调节

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-09 DOI: 10.1016/j.isci.2025.112615

Yifei Zhang , Keyu Yin , Runsheng Ma , Yuxiao Sun , Longlong Wang , Detao Yin

{"title":"Complex regulatory network of programmed death-ligand 1 in cancer: Cancer immunomodulation from molecular mechanisms to clinical applications","authors":"Yifei Zhang , Keyu Yin , Runsheng Ma , Yuxiao Sun , Longlong Wang , Detao Yin","doi":"10.1016/j.isci.2025.112615","DOIUrl":"10.1016/j.isci.2025.112615","url":null,"abstract":"<div><div>Immune checkpoint therapy targeting PD-L1/PD-1 represents a key cancer treatment strategy. PD-L1 binds PD-1 on T cells, suppressing activation and enabling tumor immune escape. Although the blockade of the PD-L1/PD-1 pathway has demonstrated significant anti-tumor effects, the overall response rate remains suboptimal in solid tumors. Therefore, understanding the molecular mechanisms underlying PD-L1 deregulation is essential for enhancing the efficacy of PD-L1/PD-1 blockade therapies. As our comprehension of the regulatory mechanisms governing the PD-L1/PD-1 pathway continues to evolve, ongoing exploration of new immunotherapy targets remains critical. This article provides a comprehensive review of recent research concerning the regulation of PD-L1 expression. It encompasses aspects such as its structural characteristics, genomic alterations and rearrangements, epigenetic modifications, inflammatory signaling pathways, oncogenic signaling pathways, microRNA regulation, and post-translational modifications. Additionally, this article illustrates notable advancements and limitations regarding the application of PD-L1 as an immunotherapeutic target in current clinical settings.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112615"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123594","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

Direct Arp2/3-vinculin binding is required for pseudopod extension, but only on compliant substrates and in 3D 假足延伸需要直接结合arp2 /3-血管蛋白，但仅在柔顺的底物上和3D中

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-09 DOI: 10.1016/j.isci.2025.112623

Tadamoto Isogai , Kevin M. Dean , Philippe Roudot , Evgenia V. Azarova , Kushal Bhatt , Meghan K. Driscoll , Shaina P. Royer , Nikhil Mittal , Bo-Jui Chang , Sangyoon J. Han , Reto Fiolka , Gaudenz Danuser

{"title":"Direct Arp2/3-vinculin binding is required for pseudopod extension, but only on compliant substrates and in 3D","authors":"Tadamoto Isogai , Kevin M. Dean , Philippe Roudot , Evgenia V. Azarova , Kushal Bhatt , Meghan K. Driscoll , Shaina P. Royer , Nikhil Mittal , Bo-Jui Chang , Sangyoon J. Han , Reto Fiolka , Gaudenz Danuser","doi":"10.1016/j.isci.2025.112623","DOIUrl":"10.1016/j.isci.2025.112623","url":null,"abstract":"<div><div>A critical step in cell morphogenesis is the extension of actin-dense pseudopods, controlled by actin-binding proteins (ABPs). While this process is well-understood on glass coverslips, it is less so in compliant three-dimensional environments. Here, we knocked out a series of ABPs in osteosarcoma cells and evaluated their effect on pseudopod extension on glass surfaces (2D) and in collagen gels (3D). Cells lacking the longest Arp3 gene variant, or with attenuated Arp2/3 activity, had the strongest reduction in pseudopod formation between 2D and 3D. This was largely due to reduced activity of the hybrid Arp2/3-vinculin complex, which was dispensable on glass. Our data suggests that concurrent formation of actin branches <em>and</em> nascent adhesions, supported by Arp2/3-vinculin interactions, is essential to form mechanically stable links between fibrous extracellular matrix and actin in 3D. This highlights how experiments on stiff, planar substrates may conceal actin architectural features that are essential for morphogenesis in 3D.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112623"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123599","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

Reciprocal regulation of Solo and Src orchestrates Src trafficking to promote mesenchymal cell migration Solo和Src的相互调控协调Src运输，促进间充质细胞迁移

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-09 DOI: 10.1016/j.isci.2025.112618

Florian Meyer , Cristiana Lungu , Bettina Noll , David Benz , Felix Fränkle , Miguel Â. Ferreira , Raluca Tamas , Monilola A. Olayioye

{"title":"Reciprocal regulation of Solo and Src orchestrates Src trafficking to promote mesenchymal cell migration","authors":"Florian Meyer , Cristiana Lungu , Bettina Noll , David Benz , Felix Fränkle , Miguel Â. Ferreira , Raluca Tamas , Monilola A. Olayioye","doi":"10.1016/j.isci.2025.112618","DOIUrl":"10.1016/j.isci.2025.112618","url":null,"abstract":"<div><div>Rho GTPases are key regulators of cell motility and membrane trafficking, influencing critical processes such as epithelial-mesenchymal transition (EMT). Among them, the small GTPase RhoB plays a pivotal role, but the mechanisms underlying its regulation remain largely unclear. We have previously identified the Rho guanine nucleotide exchange factor (RhoGEF) Solo (ARHGEF40) as a regulator of endosomal RhoB in epithelial cells. Here, we find that Solo is upregulated in breast cancer cells with high EMT scores and promotes cell motility through its RhoGEF activity. Solo’s ability to enhance migration is further regulated by phosphorylation at tyrosine 242, mediated by the proto-oncogene Src. By combining high-resolution imaging with photoconversion assays, we further demonstrate that Solo regulates Src trafficking dynamics, localization, and consequently signaling at focal adhesions. Together, our data identify Solo as a novel feedback regulator of Src and a key driver of the motility of breast cancer cells with mesenchymal characteristics.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112618"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123679","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

Promoting vascular stability through Src inhibition and Tie2 activation: A model-based analysis 通过Src抑制和Tie2激活促进血管稳定性：基于模型的分析

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-09 DOI: 10.1016/j.isci.2025.112625

Yu Zhang , Christopher D. Kontos , Brian H. Annex , Aleksander S. Popel

{"title":"Promoting vascular stability through Src inhibition and Tie2 activation: A model-based analysis","authors":"Yu Zhang , Christopher D. Kontos , Brian H. Annex , Aleksander S. Popel","doi":"10.1016/j.isci.2025.112625","DOIUrl":"10.1016/j.isci.2025.112625","url":null,"abstract":"<div><div>Dysregulated angiogenesis signaling leads to pathological vascular growth and leakage, and is a hallmark of many diseases including cancer and ocular diseases. In peripheral arterial disease, the concomitant increase in vascular permeability presents significant challenges in therapeutic efforts to improve perfusion by stimulating vascular growth. Building a mechanistic understanding of the endothelial control of vascular growth and permeability signaling is crucial to guide our efforts to identify therapeutic strategies that permit blood vessel growth while maintaining vascular stability. We develop a mechanistic systems biology model of the endothelial signaling network formed by the vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-Tie pathways, two major signaling pathways regulating vascular growth and stability. Our model, calibrated and validated against experimental data, reveals the mechanisms through which chronic Ang1 stimulation protects endothelial cells from VEGF-induced hyperpermeability, and predicts that combining Src inhibition with Tie2 activation can inhibit vascular leakage without disturbing angiogenesis signaling.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112625"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107631","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