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Anthrax ET activates Rac1 and RTK signaling to induce F-actin reorganization and endothelial permeability 炭疽ET激活Rac1和RTK信号，诱导f -肌动蛋白重组和内皮通透性

IF 4.1 2区综合性期刊

iScience Pub Date : 2025-10-03 DOI: 10.1016/j.isci.2025.113682

Prashant Jain , Annabel Guichard , Mahtab Moayeri , Saluja Kaduwal , Margot Mel de Fontenay , Ian Rousseau , Stephen H. Leppla , Ethan Bier

{"title":"Anthrax ET activates Rac1 and RTK signaling to induce F-actin reorganization and endothelial permeability","authors":"Prashant Jain , Annabel Guichard , Mahtab Moayeri , Saluja Kaduwal , Margot Mel de Fontenay , Ian Rousseau , Stephen H. Leppla , Ethan Bier","doi":"10.1016/j.isci.2025.113682","DOIUrl":"10.1016/j.isci.2025.113682","url":null,"abstract":"<div><div>Endothelial permeability induced by the potent adenylate cyclase edema toxin (ET) is central to bacterial dissemination and lethal vascular collapse during infections caused by <em>Bacillus anthracis</em>. Antibiotic and antitoxin treatments are ineffective against anthrax lethal toxemia once high doses of toxins have been released. This study uncovers a critical cAMP-dependent disruption of the F-actin network by ET in human brain microvascular endothelial cells (HBMECs), mediated by Rac1 and cofilin. Rac1 activation by ET leads to a loss of cell area and monolayer permeability. These effects are preceded by the rapid cAMP-independent activation of IGF1R and EGFR and their respective downstream effectors PI3K/AKT and MEK/ERK, which contribute to F-actin remodeling and permeability induced by ET. Consistent with these findings, Rac1, PI3K, and MEK inhibitors prevent ET-induced edema in a mouse footpad model, providing the <em>in vivo</em> pre-clinical validation of their therapeutic potential.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 11","pages":"Article 113682"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145322461","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

3-in-one PD-1CAR Tregs: A bioengineered cellular therapy for target engagement, activation, and immunosuppression with reparative potential 3- 1 PD-1CAR Tregs：一种具有修复潜力的靶向、激活和免疫抑制的生物工程细胞疗法

IF 4.1 2区综合性期刊

iScience Pub Date : 2025-10-03 DOI: 10.1016/j.isci.2025.113677

Shuyun Dong , Tianxiao Zhang , Yujia Zhai , Lauren C. Naatz , Noel G. Carlson , John W. Rose , Brian Evavold , Mingnan Chen

{"title":"3-in-one PD-1CAR Tregs: A bioengineered cellular therapy for target engagement, activation, and immunosuppression with reparative potential","authors":"Shuyun Dong , Tianxiao Zhang , Yujia Zhai , Lauren C. Naatz , Noel G. Carlson , John W. Rose , Brian Evavold , Mingnan Chen","doi":"10.1016/j.isci.2025.113677","DOIUrl":"10.1016/j.isci.2025.113677","url":null,"abstract":"<div><div>Chimeric Antigen Receptor (CAR) regulatory T cells (Tregs) represent a promising cell-based therapy for autoimmune diseases, yet conventional designs require multistep activation before suppressing pathogenic cells, limiting precision and efficacy. We developed a “3-in-One” CAR Treg platform targeting Programmed cell death protein 1 (PD-1), enabling direct engagement with, activation by, and suppression of PD-1<sup>+</sup> effector conventional T cells (eTconvs), key drivers of autoimmune inflammation. <sup>PD-1</sup>CAR Tregs stably expressed CAR and FoxP3, displayed high CD25, and upon PD-1 engagement, upregulated Ki67, IL-10, and TGF-β1 without producing IFNγ or IL-2, maintaining a committed regulatory phenotype. Functionally, they inhibited T cell proliferation and preferentially reduced PD-1<sup>+</sup> eTconvs, a specificity not seen in conventional Tregs. Moreover, <sup>PD-1</sup>CAR Tregs promoted oligodendrocyte precursor cell differentiation and secreted CCN3, a reparative factor, suggesting dual benefits in immune regulation and neuronal repair. These findings establish <sup>PD-1</sup>CAR Tregs as a unique therapy with both targeted suppression and tissue repair potential.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 11","pages":"Article 113677"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145322906","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

ForSys: Non-invasive stress inference from time-lapse microscopy ForSys：延时显微镜的非侵入性应力推断

IF 4.1 2区综合性期刊

iScience Pub Date : 2025-10-03 DOI: 10.1016/j.isci.2025.113685

Augusto Borges , Jerónimo R. Miranda-Rodríguez , Alberto S. Ceccarelli , Guilherme Ventura , Jakub Sedzinski , Hernán López-Schier , Osvaldo Chara

{"title":"ForSys: Non-invasive stress inference from time-lapse microscopy","authors":"Augusto Borges , Jerónimo R. Miranda-Rodríguez , Alberto S. Ceccarelli , Guilherme Ventura , Jakub Sedzinski , Hernán López-Schier , Osvaldo Chara","doi":"10.1016/j.isci.2025.113685","DOIUrl":"10.1016/j.isci.2025.113685","url":null,"abstract":"<div><div>During tissue development and regeneration, cells interpret and exert mechanical forces that are challenging to measure <em>in vivo</em>. Stress inference algorithms have thus emerged as powerful tools to estimate tissue stresses. Yet, effectively incorporating tissue dynamics into these algorithms remains elusive. Here, we introduce ForSys, a Python-based software that infers intercellular stresses and intracellular pressures from time-lapse microscopy. After validation, we applied ForSys to the migrating zebrafish lateral-line primordium, revealing increased stress during the cell rounding that precedes mitosis and accurately predicting the onset of epithelial rosettogenesis. We further used ForSys to study neuromast development and uncovered mechanical asymmetries linked to cell type-specific adhesion. The software performs both static and dynamic stress inference, supports command-line use, scripting, and a user-friendly graphical interface within Fiji, and accepts segmentation inputs from EPySeg and Cellpose. This versatility of ForSys enables the analysis of spatiotemporal patterns of mechanical forces during tissue morphogenesis <em>in vivo</em>.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 11","pages":"Article 113685"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145322459","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

A luminescence-based biosensor to measure endogenous UBE3A activity 一种测量内源性UBE3A活性的发光生物传感器

IF 4.1 2区综合性期刊

iScience Pub Date : 2025-10-03 DOI: 10.1016/j.isci.2025.113684

Lei Xing , Sophia U. Lamberti , Hannah C. Nourie , Trinity E. Rust , Wenxin Hu , Mark J. Zylka

引用次数: 0

Dysbiosis modulates CD8+ tissue-resident memory cells through a mechanism requiring polyamine metabolism during HIV infection 在HIV感染期间，生态失调通过一种需要多胺代谢的机制调节CD8+组织驻留记忆细胞

IF 4.1 2区综合性期刊

iScience Pub Date : 2025-10-03 DOI: 10.1016/j.isci.2025.113679

Sangeetha Jayaraman , Shanmuga Mahalingam , Michael M. Lederman , Fady Faddoul , Andre Paes da Silva , Robert Asaad , Leah P. Shriver , Natarajan Bhaskaran , Elizabeth Schneider , Grace Heine , Tobi Taylor , Samantha Horne , Ashley Yoon , Zihan Zhu , Liangliang Zhang , Adam Burgener , Gina Lewin , Pushpa Pandiyan

{"title":"Dysbiosis modulates CD8+ tissue-resident memory cells through a mechanism requiring polyamine metabolism during HIV infection","authors":"Sangeetha Jayaraman , Shanmuga Mahalingam , Michael M. Lederman , Fady Faddoul , Andre Paes da Silva , Robert Asaad , Leah P. Shriver , Natarajan Bhaskaran , Elizabeth Schneider , Grace Heine , Tobi Taylor , Samantha Horne , Ashley Yoon , Zihan Zhu , Liangliang Zhang , Adam Burgener , Gina Lewin , Pushpa Pandiyan","doi":"10.1016/j.isci.2025.113679","DOIUrl":"10.1016/j.isci.2025.113679","url":null,"abstract":"<div><div>Polyamines play crucial roles in modulating T lymphocyte functions. Here, we demonstrate that the oral mucosa of people living with HIV (PLWH), characterized by active polyamine metabolic pathways, exhibits significantly diminished IFN-γ expression and reduced abundance of CD8<sup>+</sup> tissue-resident memory (T<sub>RM</sub>) cells. Salivary 16S rRNA sequencing revealed elevated levels of <em>Fusobacteria,</em> negatively correlating with the levels of CD8<sup>+</sup> T<sub>RM</sub>-like cells in PLWH. <em>In vitro</em> experiments showed that <em>Fusobacterium nucleatum</em> (FN) produced putrescine, which is known to be enriched in PLWH mucosa. Polyamines, HIV infection, and FN led to EIF-5A hypusination, diminished IFN-γ expression in CD8<sup>+</sup> T cells, which impaired the proliferation of TRM-like cells in tonsil organoid cells. The inhibition of polyamine synthesis and EIF-5A hypusination restored IFN-γ expression and T<sub>RM</sub>-like cells. Collectively, these results highlight an essential role of polyamines in the critical interplay between oral resident microbiota, immunometabolic regulation, and immune competence during chronic viral infections.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 11","pages":"Article 113679"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145322458","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

Far-field wireless power transmission module with MEMS-based laser steering for optogenetic applications 远场无线电力传输模块与基于mems的激光转向光遗传学应用

IF 4.1 2区综合性期刊

iScience Pub Date : 2025-10-03 DOI: 10.1016/j.isci.2025.113672

Yongdae Kim , Beom Ki Kim , Kwang-Seop Kim

{"title":"Far-field wireless power transmission module with MEMS-based laser steering for optogenetic applications","authors":"Yongdae Kim , Beom Ki Kim , Kwang-Seop Kim","doi":"10.1016/j.isci.2025.113672","DOIUrl":"10.1016/j.isci.2025.113672","url":null,"abstract":"<div><div>In this study, we propose a far-field wireless power transmission system utilizing a mobile laser steering module (MOLASM) for optogenetic applications. The system integrates a MEMS-based active micromirror and features a battery-free architecture, enabling a miniaturized, lightweight, and mobile operation. This design allows for precise laser steering while maintaining a compact form factor. Additionally, laser superimposition using multiple MOLASMs enhances wirelessly transmitted power, ensuring scalable and adaptable` energy delivery for diverse experimental needs. High-efficiency photovoltaic module harvests energy from precisely targeted laser beams emitted from MOLASM, enabling continuous, wire-free operation without the need for external recharging or replacement. To validate the feasibility of this concept, we designed, implemented, and experimentally evaluated the dynamic beam steering and power delivery performance of the MOLASM system. The results demonstrate its effectiveness in wirelessly powering optogenetic probes over far-field distances, providing a flexible and practical solution for neuromodulation studies.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 11","pages":"Article 113672"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145322503","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

Eupatilin ameliorates spinal cord injury by inhibiting damage-associated microglia and optimizing the regenerative microenvironment 尤帕替林通过抑制损伤相关小胶质细胞和优化再生微环境来改善脊髓损伤

IF 4.1 2区综合性期刊

iScience Pub Date : 2025-10-01 DOI: 10.1016/j.isci.2025.113687

Zide Wang , Zhe Meng , Yaosai Liu , Boyan Su , Guoxi Luan , Peihai Zhang , Jia Yang , Kaiyuan Yang , Guihuai Wang , Xiumei Wang , Beibei Yu , Weitao Man

{"title":"Eupatilin ameliorates spinal cord injury by inhibiting damage-associated microglia and optimizing the regenerative microenvironment","authors":"Zide Wang , Zhe Meng , Yaosai Liu , Boyan Su , Guoxi Luan , Peihai Zhang , Jia Yang , Kaiyuan Yang , Guihuai Wang , Xiumei Wang , Beibei Yu , Weitao Man","doi":"10.1016/j.isci.2025.113687","DOIUrl":"10.1016/j.isci.2025.113687","url":null,"abstract":"<div><div>Microglia represent critical therapeutic targets in spinal cord injury (SCI), with damage-associated microglia (DAM) playing key roles in neuroinflammation and tissue repair. Through integrated in-silico analysis of single-cell RNA sequencing (scRNA-seq) and microarray datasets, we identified DAM subsets specific to acute SCI characterized by hub genes <em>Fcer1g</em>, <em>Grn</em>, and <em>Gusb</em>. Using a C57BL/6 mouse spinal cord contusion model, we validated increased DAM accumulation post-injury and demonstrated their propensity to transition toward homeostatic microglia (MG2). Eupatilin treatment promoted DAM-to-MG2 differentiation, as confirmed through bulk and scRNA-seq analyses, revealing supportive gene expression changes. These findings establish DAM as functionally distinct microglial populations in acute SCI and identify Eupatilin as a therapeutic agent that facilitates beneficial microglial polarization. This work provides mechanistic insights into microglial dynamics during SCI and suggests targeted modulation of DAM-to-MG2 transitions as a promising therapeutic strategy for promoting inflammation resolution and functional recovery.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 11","pages":"Article 113687"},"PeriodicalIF":4.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145322501","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

The directionality of collective cell delamination is governed by tissue architecture and cell adhesion in a Drosophila carcinoma model 在果蝇癌模型中，集体细胞分层的方向性是由组织结构和细胞粘附控制的

IF 4.1 2区综合性期刊

iScience Pub Date : 2025-09-30 DOI: 10.1016/j.isci.2025.113663

Marta Mira-Osuna , Steffen Plunder , Eric Theveneau , Roland Le Borgne

{"title":"The directionality of collective cell delamination is governed by tissue architecture and cell adhesion in a Drosophila carcinoma model","authors":"Marta Mira-Osuna , Steffen Plunder , Eric Theveneau , Roland Le Borgne","doi":"10.1016/j.isci.2025.113663","DOIUrl":"10.1016/j.isci.2025.113663","url":null,"abstract":"<div><div>Epithelial cells contact each other and the extracellular matrix via cell junctions, establishing mechanochemical barriers. During collective delamination, epithelia-derived tumors detach from the tissue with a directionality that dictates their malignancy. How cell junctions contribute to this process and how the directionality of delamination is regulated remains unknown. We used the <em>Drosophila Ras</em><sup><em>V12</em></sup> carcinoma model and found that the loss of septate junctions in epithelial cells triggers apoptosis, whereas in <em>Ras</em><sup><em>V12</em></sup>-cells promotes collective delamination. We found that apical and basal delamination differ in cell identity, polarity, and junctional remodeling, occurring exclusively in squamous and pseudostratified epithelia, respectively. We performed mathematical simulations using a 2D agent-based model and found that tissue architecture and preferential adhesion between mutant cells and with wild-type neighbors regulate the directionality of delamination. Apical delamination initiates with cells constricting apically, emitting apical protrusions, and forming an apical neck via preferential adhesion to collectively detach from the tissue.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 11","pages":"Article 113663"},"PeriodicalIF":4.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145322341","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

The cutaneous response to a mosquito bite is influenced by the diurnal rhythm 皮肤对蚊子叮咬的反应受昼夜节律的影响

IF 4.1 2区综合性期刊

iScience Pub Date : 2025-09-30 DOI: 10.1016/j.isci.2025.113666

Hamidah Raduwan , Jinhee Park , Alejandro Marín López , Mathias H. Skadow , Tse-Yu Chen , Richard A. Flavell , Albert C. Shaw , Ruth R. Montgomery , Erol Fikrig

引用次数: 0

Numerical discrimination in Danionella 丹尼欧菌的数值鉴别

IF 4.1 2区综合性期刊

iScience Pub Date : 2025-09-30 DOI: 10.1016/j.isci.2025.113667

Mirko Zanon , Scott E. Fraser , Giorgio Vallortigara

引用次数: 0