iScience最新文献_第5页

Long-term ambient benzene exposure increases incident NAFLD risk through accelerated biological aging. 长期环境苯暴露通过加速生物老化增加NAFLD的发生风险。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117035

Yaxiong Li, Ziwei Peng, Jing Zhang, Hong Cao, Jingyuan Zhang

{"title":"Long-term ambient benzene exposure increases incident NAFLD risk through accelerated biological aging.","authors":"Yaxiong Li, Ziwei Peng, Jing Zhang, Hong Cao, Jingyuan Zhang","doi":"10.1016/j.isci.2026.117035","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117035","url":null,"abstract":"The contribution of ambient air pollutants to non-alcoholic fatty liver disease (NAFLD) remains undefined. This study included 401,472 adults from the UK Biobank (UKB), with residential benzene estimated at 1-km resolution from the DEFRA model (2006-2020). After multivariable adjustment in the Cox models, each interquartile-range (0.151 μg/m3) increment in benzene was associated with a 26% higher risk of incident NAFLD (hazard ratio [HR] = 1.26; 95% confidence interval [CI], 1.21-1.30), following a nonlinear exposure-response relationship. Accelerated biological aging mediated 6.5% of this association, whereas homeostatic dysregulation and allostatic load contributed modestly. Benzene exposure and polygenic risk showed no multiplicative interaction, but their cumulative effect raised NAFLD risk among highly susceptible individuals. A machine-learning model integrating benzene and covariates predicted NAFLD with good discrimination (AUC = 0.753), and an external urinary-biomarker analysis in NHANES was directionally consistent. Thus, long-term low-level benzene exposure increases incident NAFLD risk, partly through accelerated biological aging.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117035"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178433","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}

引用次数: 0

Midline thalamic neurons show early hypersynchrony during absence seizures in mouse models. 在小鼠模型中，丘脑中线神经元在失神发作期间表现出早期的高同步。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117673

Elzbieta Dulko, Scott Kilianski, Anna Grace Carns, Arya Rajesh, Isabelle Lesmana, Magdalena Pikus, Mark Beenhakker

{"title":"Midline thalamic neurons show early hypersynchrony during absence seizures in mouse models.","authors":"Elzbieta Dulko, Scott Kilianski, Anna Grace Carns, Arya Rajesh, Isabelle Lesmana, Magdalena Pikus, Mark Beenhakker","doi":"10.1016/j.isci.2026.117673","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117673","url":null,"abstract":"Generalized seizures reflect a pathological state of sudden, global neuronal hypersynchrony. The mechanisms that support the initiation and maintenance of such synchrony remain unknown. Using simultaneous single-unit and electrocorticographic recordings in two mouse models of absence epilepsy, we evaluated the activity of approximately 2,000 individual neurons across 26 brain structures. By doing so, we resolved the temporal progression of single-neuron activity prior to and during generalized seizures. Surprisingly, we observed that rhythmic, synchronized activity emerges early and gradually in both the thalamus and cortex. Moreover, while we observe that individual neurons across most structures fire rhythmically and synchronously during seizures, a small subset of midline thalamic nuclei display activity that is strongly correlated across multiple regions. Finally, disturbing neuronal activity within the midline thalamus terminates seizures. Thus, our findings collectively highlight the possible role of the midline thalamus in emergence of neuronal hypersynchrony.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117673"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178593","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}

引用次数: 0

Seeing the forest for the scenarios: Using decision trees to draw conclusions from large energy scenario sets. 从场景中看到森林：使用决策树从大型能源场景集中得出结论。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117079

Florian Baader, Stefano Moret, Wolfram Wiesemann, Iain Staffell, André Bardow

{"title":"Seeing the forest for the scenarios: Using decision trees to draw conclusions from large energy scenario sets.","authors":"Florian Baader, Stefano Moret, Wolfram Wiesemann, Iain Staffell, André Bardow","doi":"10.1016/j.isci.2026.117079","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117079","url":null,"abstract":"Energy transition studies often present hundreds of scenarios, yielding large datasets that are challenging to interpret. Alternative approaches define a few qualitative storylines, which are more accessible but disconnected from model-based evidence. Here, we show that decision trees, a popular machine learning technique, bridge this disconnect by distilling numerous scenarios into a small set of interpretable storylines centered around policy-relevant levers. We demonstrate this approach across three global and European case studies: First, we translate 1000 integrated assessment model scenarios into three storylines distinguished by their degrees of heating and industry electrification. Second, we show that 2°C warming pathways with continued fossil fuel usage only work under unusually mild climate responses. Third, we use 441 European pathways to show that high bioenergy or electrification are required for cost-effective climate neutrality. Our transferable approach helps decision-makers interpret large scenario sets by revealing how policy-relevant outputs are associated with different transition pathways.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117079"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178635","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}

引用次数: 0

Peroxisome-dependent and -independent functions of PEX19 in mouse embryonic stem cells. 小鼠胚胎干细胞中PEX19的过氧化物酶体依赖性和非依赖性功能。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117658

Wei Fan, Yi Fang, Joshua Hartsell, Xiaoyue Wu, Xiaojiang Xu, Jian-Liang Li, Xiaojing Liu, Xiaoling Li

{"title":"Peroxisome-dependent and -independent functions of PEX19 in mouse embryonic stem cells.","authors":"Wei Fan, Yi Fang, Joshua Hartsell, Xiaoyue Wu, Xiaojiang Xu, Jian-Liang Li, Xiaojing Liu, Xiaoling Li","doi":"10.1016/j.isci.2026.117658","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117658","url":null,"abstract":"Pluripotent embryonic stem cells (ESCs) possess a unique cell cycle pattern to support self-renewal and maintain pluripotency, and remodeling of this cycle by developmental cues is a key priming step for lineage commitment. Here we report an unexpected role of PEX19, a chaperone and receptor for peroxisomal membrane proteins, in regulating cell cycle and cell fates of mouse ESCs (mESCs) through a peroxisome-independent mechanism. We show that deletion of Pex19 in mESCs disrupts peroxisome assembly, elevating reactive oxygen species and impairing peroxisomal lipid metabolism. These peroxisomal defects increase cell death and diminish pluripotency. Intriguingly, PEX19 also interacts with α-tubulin to facilitate assembly of mitotic spindles in mitotic mESCs. Consequently, loss of Pex19 disrupts cell cycle progression and hinders the exit from pluripotency upon induction of neural differentiation, ultimately preventing differentiation of neural stem cells. Our study reveals a non-canonical function of PEX19 and underscores the importance of cell cycle regulation in cell fate decisions.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117658"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178569","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}

引用次数: 0

Why cost reduction alone cannot deliver bankable carbon dioxide removal. 为什么单靠降低成本无法实现可盈利的二氧化碳去除？

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117702

Julian Henry Smart, Niall Mac Dowell

引用次数: 0

FGFR kinase isoform and activation state modulate ATPase activity. FGFR激酶异构体和激活状态调节atp酶活性。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-29 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117652

Alida Besch, Gaëlle Lamon, Yingkai Zhang, Nathaniel J Traaseth

{"title":"FGFR kinase isoform and activation state modulate ATPase activity.","authors":"Alida Besch, Gaëlle Lamon, Yingkai Zhang, Nathaniel J Traaseth","doi":"10.1016/j.isci.2026.117652","DOIUrl":"10.1016/j.isci.2026.117652","url":null,"abstract":"Fibroblast growth factor (FGF) binding to FGF receptor (FGFR) induces trans-autophosphorylation of activation loop tyrosine residues within the receptor's intracellular kinase domain, thereby activating the receptor and promoting downstream substrate phosphorylation. Here, using activity assays and 31P NMR spectroscopy on the FGFR kinase domain, we show that phosphorylation of activation loop tyrosine residues not only enhances kinase activity but also increases the rate of ATP hydrolysis by 33-fold. This ATPase activity varies among FGFR kinase isoforms, with a 5.4-fold difference between FGFR2 and FGFR3 kinases. Conversion of ATP to ADP in phosphorylation assays also promotes the reverse phosphorylation reaction, which involves phosphoryl group transfer from phosphotyrosine to ADP to regenerate ATP. Based on these observations, we hypothesize that ATPase activity occurs in cells and may decrease the local ATP/ADP ratio surrounding FGFR. Such a mechanism would reduce the favorability of phosphorylation and may promote signal termination through reverse phosphorylation.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117652"},"PeriodicalIF":4.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163846","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}

引用次数: 0

Neutrophil swarm formation on large targets. 在大目标上形成中性粒细胞群。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-29 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117186

Christian Wine, Anna Apostolopoulou, Charles P Lin, Derin Sevenler, Michael K Mansour, Daniel Irimia

引用次数: 0

A specialized CD107a⁺ macrophage subset drives hyperphagocytosis of mycobacteria. 一个特殊的CD107a+巨噬细胞亚群驱动分枝杆菌的吞噬作用。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-25 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117622

Carolina Eto, Gabriela Luiz, Hernandez M Silva, Eduarda L Munari, Daniel A G B Mendes, Bianca K Beck, Lucas Z Mascarin, Marick Starick, Maria Cecília C Canesso, Bernardo S Reis, Guilherme Silveira, Juliano Bordignon, Yonne K T de Menezes, Daniel S Mansur, Edroaldo Lummertz da Rocha, André Luiz Barbosa Báfica

{"title":"A specialized CD107a+ macrophage subset drives hyperphagocytosis of mycobacteria.","authors":"Carolina Eto, Gabriela Luiz, Hernandez M Silva, Eduarda L Munari, Daniel A G B Mendes, Bianca K Beck, Lucas Z Mascarin, Marick Starick, Maria Cecília C Canesso, Bernardo S Reis, Guilherme Silveira, Juliano Bordignon, Yonne K T de Menezes, Daniel S Mansur, Edroaldo Lummertz da Rocha, André Luiz Barbosa Báfica","doi":"10.1016/j.isci.2026.117622","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117622","url":null,"abstract":"Macrophages are essential for pathogen clearance, yet phagocytic specialization among subsets is poorly defined. Bone marrow-derived macrophages cultured with L929 supernatant or macrophage colony-stimulating factor (M-CSF) separate into FSCloSSCloF4/80loCD11blo (FSCloSSClo) and FSChiSSChiF4/80hiCD11bhi (FSChiSSChi) subsets. Transcriptomic and functional analyses reveal that FSCloSSClo cells possess a hyperphagocytic program driven by enhanced actin cytoskeleton regulators (e.g., Arp2/3) and pro-inflammatory signaling (NF-κB). These cells excel at internalizing Mycobacterium tuberculosis virulent H37Rv and BCG through actin-mediated, cytochalasin D-sensitive mechanisms. High surface CD107a (LAMP1) expression marks this hyperphagocytic subset and correlates strongly with mycobacterial uptake. FSCloSSClo macrophages produce more TNF and IL-6 upon mycobacterial or Toll-like receptor 2 (TLR2)/TLR5 stimulation yet retain IFN-γ-mediated killing capacity. In vivo, CD107a+ alveolar macrophages in BCG-infected lungs preferentially capture bacilli and upregulate CD195, recapitulating the in vitro phenotype. These findings establish CD107a as a key surface marker of a hyperphagocytic macrophage subset, providing new mechanistic understanding relevant to tuberculosis host defense and therapeutic development.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117622"},"PeriodicalIF":4.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190130","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}

引用次数: 0

Short term overfeeding disrupts small intestinal barrier integrity and activates hepatic immunity in healthy men. 在健康男性中，短期过度进食会破坏小肠屏障的完整性并激活肝脏免疫。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-22 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117724

Nora S Nägele, Malte P Suppli, Hannah Gilliam-Vigh, Natalia Petersen, Bolette Hartmann, Filip K Knop, Asger B Lund, Benjamin A H Jensen

{"title":"Short term overfeeding disrupts small intestinal barrier integrity and activates hepatic immunity in healthy men.","authors":"Nora S Nägele, Malte P Suppli, Hannah Gilliam-Vigh, Natalia Petersen, Bolette Hartmann, Filip K Knop, Asger B Lund, Benjamin A H Jensen","doi":"10.1016/j.isci.2026.117724","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117724","url":null,"abstract":"Obesity is associated with intestinal barrier dysfunction and low-grade inflammation, prompting investigations of early human adaptations to overnutrition. In a controlled \"holiday-style\" overfeeding model, healthy men underwent a 2-week hypercaloric, sedentary lifestyle with 8-week follow-up (ClinicalTrials.gov NCT04859322). A targeted gastrointestinal uptake and translocation (GUT) plasma panel showed increased citrulline, consistent with enhanced epithelial absorptive capacity, and mucosa-restricted immune activation, reflected by elevated anti-lipopolysaccharide (LPS) immunoglobulin (Ig)A, without systemic 16S rRNA changes. A dynamic zonulin-like signal and hepatic inflammatory markers (serum amyloid A (SAA), C-reactive protein, interleukin-32) also increased after overfeeding. Most perturbations normalized after return to habitual lifestyle, but anti-LPS IgA, SAA, lipocalin-2, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 remained elevated, indicating a partially persistent inflammatory imprint. These findings reveal how overfeeding episodes reshape epithelial, mucosal, and hepatic immune responses and highlight plasma biomarker panels as scalable tools to interrogate intestinal function and gut-liver crosstalk in human studies.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117724"},"PeriodicalIF":4.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178664","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}

引用次数: 0

Pharmacological protection from a sugar-rich diet through inhibition of Ras/MAPK signaling. 通过抑制Ras/MAPK信号传导对高糖饮食的药理保护。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-09-22 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117656

Mihails Laskovs, Jacob S Cook, Andrew R Pitt, Corinne M Spickett, Cathy Slack

{"title":"Pharmacological protection from a sugar-rich diet through inhibition of Ras/MAPK signaling.","authors":"Mihails Laskovs, Jacob S Cook, Andrew R Pitt, Corinne M Spickett, Cathy Slack","doi":"10.1016/j.isci.2026.117656","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117656","url":null,"abstract":"Consumption of sugar-rich diets adversely affects health and reduces life expectancy through the excessive production and storage of triacylglycerides (TAGs), leading to metabolic dysfunction. Here, we show that in Drosophila, pharmacological inhibition of Ras/mitogen-activated protein kinase (MAPK) signaling using the highly specific MEK inhibitor, trametinib, mitigates several of the detrimental effects of a high-sugar diet by reducing TAG accumulation, restoring TAG composition, and increasing survival. Notably, Ras/MAPK activity is required for the transcriptional response to elevated sugar intake, including expression of the glucagon-like hormone, Akh. We further demonstrate that adipokinetic hormone (AKH) is essential for the protective effects of trametinib under high-sugar conditions. Together, our findings support Ras/MAPK signaling as an important link between dietary sugar and metabolic dysfunction and show that its pharmacological inhibition can uncouple excess sugar intake from adverse metabolic outcomes.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117656"},"PeriodicalIF":4.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178711","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}

引用次数: 0