iScience最新文献

{"title":"Low-intensity pulsed ultrasound mitigates acute extremity compartment syndrome by mediating ferroptosis suppression.","authors":"Xiaobo Ren, Yaxin Hu, Donghua Liu, Guihua Wang, Peng Zhai, Zhenzhou Li, Lei Sun, Xin Chen, Minhua Lu","doi":"10.1016/j.isci.2026.115442","DOIUrl":"10.1016/j.isci.2026.115442","url":null,"abstract":"<p><p>Acute extremity compartment syndrome (AECS) is a severe surgical emergency with no effective non-invasive therapies available. Here, we demonstrate that low-intensity pulsed ultrasound (LIPUS) attenuates muscle damage by suppressing oxidative stress and ferroptosis. In skeletal muscle cells following hypoxia-reoxygenation (H/R), LIPUS reduced reactive oxygen species (ROS), malondialdehyde, lipid peroxides, and ferrous iron accumulation. In a rat AECS model, LIPUS (1 MHz, 0.5 W/cm², 20% duty cycle) mitigated histopathological injury and iron deposition compared with untreated controls, without affecting healthy muscle. Mechanistically, LIPUS activated the Nrf2/Gpx4 antioxidant pathway and downregulated p53 expression. These findings identify LIPUS as a non-invasive intervention that inhibits ferroptosis and improves tissue outcomes in AECS, suggesting its potential as a bedside therapeutic strategy to complement surgical management.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 4","pages":"115442"},"PeriodicalIF":4.1,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent behavioral strategies in Wistar and Wistar-Kyoto rats in a naturalistic task reveal mood disorder phenotypes.","authors":"Jackson R Ham, Robert J McDonald","doi":"10.1016/j.isci.2026.115459","DOIUrl":"https://doi.org/10.1016/j.isci.2026.115459","url":null,"abstract":"<p><p>Rodent models are essential for studying mood disorders, yet many assays rely on methods that may not reflect natural behavior. Food hoarding offers an ethologically relevant paradigm integrating reward seeking, risk assessment, and safety-seeking strategies. We assessed hoarding in Wistar-Kyoto (Kyoto) rats, a model of depression and anxiety, compared with Wistar controls. Kyoto rats, particularly females, displayed robust hoarding, frequently transporting all food items to the safe base while consuming little. In contrast, Wistars consumed more and showed greater exploratory activity, moving at higher velocity. Principal component analysis and k-means clustering identified distinct behavioral phenotypes, with Kyotos clustered into high hoarding, low exploratory profiles consistent with anxiety- or depressive-like profiles, while Wistars clustered into more exploratory phenotypes. Pose estimation revealed reduced locomotor velocity in Kyoto rats compared with Wistar controls, consistent with altered risk assessment. Overall, this task captures strain- and individual-level variation in mood-related behavior under more naturalistic conditions.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 4","pages":"115459"},"PeriodicalIF":4.1,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C2CD5 in noradrenergic neurons regulates thermogenesis and lipid homeostasis via norepinephrine secretion.","authors":"Chaitanya K Gavini, Gwenaël Labouèbe, François Gorostidi, Virginie Mansuy-Aubert","doi":"10.1016/j.isci.2026.115446","DOIUrl":"https://doi.org/10.1016/j.isci.2026.115446","url":null,"abstract":"<p><p>Thermogenesis and lipid utilization are important components of energy expenditure; they are regulated within a complex network of behavioral, hormonal, and molecular pathways that collectively maintain energy balance. Norepinephrine (NE) released by sympathetic neurons plays a critical role in modulating these processes. Here, we identify the trafficking protein C2CD5 as a key regulator of NE secretion and thermogenic function. C2CD5 is expressed in dopamine β-hydroxylase (DBH)-positive sympathetic neurons, and its expression is suppressed by obesogenic diets. Using conditional knockout mice lacking C2CD5 in DBH+ neurons, we show that loss of C2CD5 reduces NE secretion, impairs thermogenesis, lowers energy expenditure, and promotes adiposity. These effects are mitigated by NE supplementation. Our findings reveal a functional role for C2CD5 in linking sympathetic tone to systemic metabolic regulation and suggest it may represent a targetable node for metabolic disorders.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 4","pages":"115446"},"PeriodicalIF":4.1,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CuET promotes cuproptosis and ferroptosis of lung cancer cells by interacting directly with polyunsaturated phospholipids.","authors":"Jie Zhang, Chengying Lei, Guangzhe Zheng, Bingxue Nie, Yiju Wei, Yanqin Lu, Shuping Zhang","doi":"10.1016/j.isci.2026.115438","DOIUrl":"https://doi.org/10.1016/j.isci.2026.115438","url":null,"abstract":"<p><p>The FDA-approved disulfiram (DSF) is metabolized to diethyldithiocarbamate-copper (CuET) <i>in vivo</i>, exhibiting excellent anti-tumor activity in various types of tumors. Although cuproptosis and ferroptosis are both reported to be involved in the tumor-killing effects of CuET, the specific crosstalk mechanism remains poorly understood. Herein, we found that CuET increased the concentration of copper ions significantly in non-small cell lung cancer (NSCLC) cells, thereby triggering the process of cuproptosis. Simultaneously, we observed an increase in lipid peroxidation (LPO) and ferroptosis. Mechanistically, CuET interacts directly with polyunsaturated phospholipids to generate free radicals, leading to LPO and ferroptosis, with limited dependence on iron accumulation. Additionally, lipid composition changes induced by CuET might also contribute to ferroptosis. <i>In vivo</i> anti-tumor experiments verified copper-mediated cell death. We uncovered that CuET induced ferroptosis through a copper-triggered, non-canonical, and radical-dependent pathway. Therefore, our data elucidate a therapeutic approach for NSCLC by co-targeting cuproptosis and ferroptosis.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 4","pages":"115438"},"PeriodicalIF":4.1,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct phosphoinositide signatures orchestrate FcεRI versus MRGPRX2 mast cell secretion.","authors":"Sewar Omari-Manaa, Roselyn Aharonov, Stephen J Galli, Hydar Ali, Ronit Sagi-Eisenberg","doi":"10.1016/j.isci.2026.115457","DOIUrl":"10.1016/j.isci.2026.115457","url":null,"abstract":"<p><p>Phosphoinositides (PIs) regulate mast cell (MC) secretory granule (SG) biogenesis and exocytosis, yet their compartment-specific roles in receptor signaling and secretion remain unclear. Using a rapamycin-inducible dimerization system to recruit site-specific lipid phosphatases to either the plasma membrane or the SGs, we assessed the impact of spatially restricted PI depletion on secretion triggered by FcεRI activation, the MRGPRX2 ligand substance P (SP), or receptor-independent calcium/phorbol ester stimulation. Our data reveal distinct and shared PI requirements for coupling FcεRI and MRGPRX2 signaling to the exocytic machinery and uncover PI derivatives that act locally at the SGs to modulate granule release. Together, these findings show that individual PIs differentially orchestrate allergic and neurogenic secretion pathways and fine-tune SG exocytosis through site-specific functions.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 4","pages":"115457"},"PeriodicalIF":4.1,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phage-based diagnostic assay for melioidosis using multiplex PCR targeting Burkholderia phage terminase genes","authors":"Patoo Withatanung ,&nbsp;Muthita Vanaporn ,&nbsp;Narisara Chantratita ,&nbsp;Sorujsiri Chareonsudjai ,&nbsp;Veerachat Muangsombut ,&nbsp;Sujintana Janesomboon ,&nbsp;Thatchanon Asawalertsaeng ,&nbsp;Martha R.J. Clokie ,&nbsp;Edouard E. Galyov ,&nbsp;Sunee Korbsrisate","doi":"10.1016/j.isci.2026.114831","DOIUrl":"10.1016/j.isci.2026.114831","url":null,"abstract":"<div><div>Conventional diagnostic approaches involve identifying the bacterial pathogen from patient samples, which can delay results and miss low-bacteremia cases. Herein, we demonstrate that <em>Burkholderia</em> phages circulating in patient blood can serve as a powerful diagnostic biomarker. Building on this, a multiplex PCR targeting the <em>Burkholderia pseudomallei</em> phage terminase gene was developed to improve melioidosis diagnosis. The assay provided 97.2% sensitivity and 100% specificity, with results obtainable within 6 h. The strength of this PCR assay is the amplification of four different multicopy <em>Burkholderia</em> phage terminase genes from serum samples, resulting in increased sensitivity under low-bacteremia conditions. To our knowledge, this study reports a phage-based PCR assay that detects phage DNA directly from melioidosis patients’ blood, representing a shift from molecular pathogen-based to phage-based diagnostics. This approach not only improves sensitivity but also opens avenues for integrating phage biology into the diagnostic landscape of infectious diseases.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114831"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187156","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}

{"title":"THBS1 upregulation by KLF7 in hypopharyngeal squamous cell carcinoma contributes to lung metastasis through the p38 MAPK signaling","authors":"Huijuan Cheng ,&nbsp;Dongfang Tang ,&nbsp;Shousen Hu ,&nbsp;Zizi Zhang ,&nbsp;Weiwei Wang","doi":"10.1016/j.isci.2026.114816","DOIUrl":"10.1016/j.isci.2026.114816","url":null,"abstract":"<div><div>This study aimed to analyze the specific role of thrombospondin-1 (THBS1) in hypopharyngeal squamous cell carcinoma (HPSCC) and its mechanism. The expression of histone deacetylase 6 (HDAC6), Kruppel-like factor 7 (KLF7), and THBS1 in the tumor and peritumor tissues of patients with HPSCC, HPSCC cells, and human oral keratinocytes was examined. The function of the HDAC6/KLF7/THBS1/p38 MAPK axis in HPSCC cells was explored using lentivirus-mediated genetic interventions in combination with EdU, colony formation, wound healing, Transwell assays, and Western blot assays. An <em>in vivo</em> lung metastasis model in nude mice was constructed by the tail vein injection of FaDu cells. HDAC6 expression was significantly downregulated in HPSCC, losing the removal capacity of H3K9ac marks at the KLF7 promoter, leading to the upregulation of KLF7, which in turn induced THBS1 transcription to activate p38 MAPK signaling and promote the epithelial-mesenchymal transition (EMT) and lung metastasis of HPSCC cells. These findings indicate that HDAC6 hinders KLF7/THBS1/p38 MAPK axis transduction and curtails HPSCC malignant progression by impairing EMT.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114816"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187149","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}

{"title":"PBX3 regulates mast cell parthanatos via TOP2A mediated DNA damage in allergic rhinitis.","authors":"Shuhong Wu, Xinhua Zhu, Wen Xie, Jiali Liu, Chunhua Li, Meiqun Wang, Haisen Peng","doi":"10.1016/j.isci.2026.115426","DOIUrl":"https://doi.org/10.1016/j.isci.2026.115426","url":null,"abstract":"<p><p>This study explores the regulatory roles of TOP2A and PBX3 in mast cell sensitization and allergic rhinitis (AR). We induced mast cell differentiation from Balb/c mouse bone marrow cells via IL-3 and SCF, and found markedly increased TOP2A expression. TOP2A plays a key role in mast cell parthanatos, survival, mitochondrial function, and degranulation. Overexpression enhanced cell survival, reduced apoptosis, and maintained mitochondrial membrane potential (MMP), while knockdown reversed these effects. Additionally, TOP2A regulates DNA damage, senescence, and inflammation, particularly PARP-1 expression linked to DNA damage. To explore its upstream regulation, we found that PBX3 directly binds to the TOP2A promoter to regulate transcription. High PBX3 expression correlates closely with aggravated AR symptoms, while PBX3 knockdown significantly alleviated AR symptoms in mice, including reduced sneezing, nose rubbing, nasal discharge, and decreased infiltration of inflammatory cells, eosinophils, and mast cells. In conclusion, PBX3 plays an important role in regulating TOP2A expression, DNA damage, cell senescence, inflammation, and mitochondrial function, making it a potential target for AR treatment.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 4","pages":"115426"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Socio-economic and environmental sustainability of biomanufactured food and agricultural products: An integrated assessment framework","authors":"Reihaneh Bandari ,&nbsp;Barton Loechel ,&nbsp;Robert E. Speight ,&nbsp;Andrea Walton ,&nbsp;Walter Okelo ,&nbsp;Aditi Mankad","doi":"10.1016/j.isci.2025.114624","DOIUrl":"10.1016/j.isci.2025.114624","url":null,"abstract":"<div><div>Biomanufacturing of food and agricultural products is increasingly being recognized as a transformative solution to sustainability challenges such as climate change, resource scarcity, and food security. Biomanufactured products—including precision-fermented food ingredients, microbial proteins for feed, and bio-based agricultural chemicals and treatments—offer promising benefits but can also be disruptive, posing socio-economic, environmental, and governance challenges when commercialized. This study presents a comprehensive sustainability assessment framework to evaluate these impacts. We conducted a systematic review of 57 peer-reviewed studies and key gray literature to examine the sustainability implications of biomanufactured food, feed, and agricultural inputs. Twenty key sustainability indicators were categorized into environmental, societal, governance, and economic dimensions, enabling a structured evaluation of both benefits and challenges. Large-scale biomanufacturing of food and agricultural products offers opportunities to diversify and complement the food system through sustainable alternatives to conventional agriculture, delivering environmental gains such as reduced greenhouse gas emissions, land and water use, and pollution, while generating less waste compared to conventional crop and livestock farming and enhancing biodiversity. These products have the potential to enhance food security, nutrition, and health, but face adoption barriers related to regulatory complexities, ethical considerations, and public acceptance. Economically, they promise growth, innovation, new jobs, and supply chain resilience, but require high initial investment and may disrupt conventional farming markets. This holistic assessment, along with comparing hypothetical stakeholder-specific perspectives from government, industry, environmental scientists, and consumers, provides actionable insights for policymakers and industry leaders, underscoring the need to carefully manage the transition to biomanufactured systems to balance innovation with sustainability trade-offs.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114624"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508419","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}

{"title":"Risk of exotic disease introduction and propagation in the Austrian swine trade network","authors":"Gavrila Amadea Puspitarani ,&nbsp;Hannah Schuster ,&nbsp;Ewan Colman ,&nbsp;Amélie Desvars-Larrive","doi":"10.1016/j.isci.2026.114868","DOIUrl":"10.1016/j.isci.2026.114868","url":null,"abstract":"<div><div>Importation of live pigs poses a significant risk for introducing exotic diseases, threatening animal health, welfare, and food security. Using daily Austrian pig movement records from 2021, we modeled the introduction of an infectious disease. Within-holding infection dynamics were simulated with a stochastic susceptible-exposed-infectious-removed (SEIR) with ASF-like parameters; between-holding transmission occurred via direct trade and indirect local spread within 5-km radius. Across simulations, the epidemic affected 0.2% of pigs and 2% of holdings, reaching 10% of municipalities. Most holding-to-holding transmission was short-distance (54.9% intra-municipal; inter-municipal transmission averaged 7.8 km), but rare long-distance events (mean 5.6 events per simulation; &gt;2 SD above mean trade distance) facilitated large-scale outbreaks. Early-stage projections predicted final size and progression more precisely than later forecasts, supporting timely targeted interventions. Static networks overestimated affected municipalities by 8.9-fold. The first 40 days were critical for epidemic control when introduction occurred in a low-trade period (January), shrinking to 20 days during high-trade periods (April).</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114868"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187148","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}