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Enhanced CRISPR-Cas3-mediated genome editing using circularized crRNAs. 利用环状crrna增强crispr - cas3介导的基因组编辑。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-09-08 eCollection Date: 2026-09-18 DOI: 10.1016/j.isci.2026.117481
Kouya Mikamo, Kazuto Yoshimi, Naoko Abe, Kohei Takeshita, Hiroshi Abe, Tomoji Mashimo
{"title":"Enhanced CRISPR-Cas3-mediated genome editing using circularized crRNAs.","authors":"Kouya Mikamo, Kazuto Yoshimi, Naoko Abe, Kohei Takeshita, Hiroshi Abe, Tomoji Mashimo","doi":"10.1016/j.isci.2026.117481","DOIUrl":"10.1016/j.isci.2026.117481","url":null,"abstract":"<p><p>Type I-E CRISPR-Cas3 represents a genome-editing technology in which large deletions averaging several kilobases are introduced in target regions. However, its genome-editing efficiency varies considerably across targets and cell types, making it difficult to achieve consistent results. Here, we investigated the efficacy and stability of circularized CRISPR RNAs (ccrRNAs) to enhance CRISPR-Cas3-mediated genome editing in human cells. Using <i>in vitro</i> single-strand DNA cleavage assays, we demonstrated that ccrRNA induces Cascade complex formation. Significant genome-editing activity targeting the <i>EMX1</i> and <i>B2M</i> genes was observed in cellular assays using K562 cells. Long-read sequencing identified large-scale deletion mutations at the target loci and no detectable off-target effects using ccrRNA. Furthermore, ccrRNAs exhibited extended intracellular stability compared with that for linear crRNAs, resulting in an enhanced editing efficiency. These results demonstrate that ccrRNAs enable stable, efficient, and highly specific genome editing and support the broader application of the long-range deletion system.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 9","pages":"117481"},"PeriodicalIF":4.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965943","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
Larval taste exposure creates compound-specific behavioral modifications in adult Drosophila melanogaster. 暴露在幼虫的味道中会使成年黑腹果蝇产生特定化合物的行为改变。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-09-08 eCollection Date: 2026-09-18 DOI: 10.1016/j.isci.2026.117467
Vaibhav D Menon, Christopher Creighton, Mayra Vazquez-Muñoz, Anupama Dahanukar
{"title":"Larval taste exposure creates compound-specific behavioral modifications in adult <i>Drosophila melanogaster</i>.","authors":"Vaibhav D Menon, Christopher Creighton, Mayra Vazquez-Muñoz, Anupama Dahanukar","doi":"10.1016/j.isci.2026.117467","DOIUrl":"10.1016/j.isci.2026.117467","url":null,"abstract":"<p><p>An animal's ability to taste is critical for nutrient selection and rejection of potentially toxic substances. Factors such as age, diet, environment, and internal state can also influence food-related behavioral outcomes. One such factor-exposure to taste cues during early development-remains poorly understood. Here, we evaluate how larval taste input affects adult feeding preference in <i>Drosophila melanogaster</i>. We find that larval dietary exposure to papaverine, a bitter alkaloid, attenuates feeding avoidance of papaverine in adult flies. This behavioral modification appears compound specific, occurring with papaverine but not with other bitter chemicals tested, and selective, with feeding preferences for other bitter tastants unaffected. We identify contributions of larval bitter taste function, taste projection populations, and the cyclic AMP (cAMP)-phosphodiesterase dunce in supporting this behavioral modification. Together, our findings suggest that developmental experiences with bitter compounds can change taste-mediated behaviors through defined sensory and neural circuit components.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 9","pages":"117467"},"PeriodicalIF":4.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965919","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
Exercise-induced adipose tissue ADRB2-PGC1α-FGF21 signaling protects against pathological cardiac hypertrophy. 运动诱导的脂肪组织ADRB2-PGC1α-FGF21信号可预防病理性心肌肥大。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-09-08 eCollection Date: 2026-09-18 DOI: 10.1016/j.isci.2026.117420
Feng Tan, Zhichao Wang, Yuan Cheng, Ping Jiang, Ruichun Liao, Zeqi Zheng, Qiong Duan
{"title":"Exercise-induced adipose tissue ADRB2-PGC1α-FGF21 signaling protects against pathological cardiac hypertrophy.","authors":"Feng Tan, Zhichao Wang, Yuan Cheng, Ping Jiang, Ruichun Liao, Zeqi Zheng, Qiong Duan","doi":"10.1016/j.isci.2026.117420","DOIUrl":"10.1016/j.isci.2026.117420","url":null,"abstract":"<p><p>Exercise induces adipose tissue activation and physiological cardiac hypertrophy, but the link between adipose tissue activation and cardiac remodeling has not been fully established. Here, we found that three weeks of swim training activated brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) in a PGC1α-dependent manner. Genetic knockout (<i>Adrb2</i> <sup><i>KO</i></sup> ) or chemical inhibition of the β<sub>2</sub>-adrenoceptor (ICI118551) suppressed PGC1α expression and BAT and iWAT activation. To test the role of adipose tissue activation in pressure overload-induced cardiac hypertrophy, abdominal aortic constriction (AAC) surgery was performed in swim-trained <i>Ppargc1a</i> <sup><i>fl/fl</i></sup> and adipose-specific knockout of <i>Ppargc1a</i> (<i>Ppargc1a</i> <sup><i>aKO</i></sup> ) mice. Compared with <i>Ppargc1a</i> <sup><i>fl/fl</i></sup> mice, the protective effect of exercise against pathological remodeling was significantly diminished in <i>Ppargc1a</i> <sup><i>aKO</i></sup> mice, whereas exogenous FGF21 administration recovered it. In summary, this study reveals that swim training activates the ADRB2-PGC1α axis and FGF21 generation in the adipose tissue, which protects against pathological cardiac remodeling.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 9","pages":"117420"},"PeriodicalIF":4.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965933","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
Uninflamed colonic tissue harbors humoral activity linked to anti-TNF therapy non-response in ulcerative colitis. 未发炎的结肠组织含有与溃疡性结肠炎抗tnf治疗无反应相关的体液活性。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-09-08 eCollection Date: 2026-09-18 DOI: 10.1016/j.isci.2026.117408
Gunnar Andreas Enerhaug Walaas, Silje Sveaas, Lusie Frostvoll Kuraas, Arun Sridhar, Kari Lillebråten, Hanne Fossen, Henrik Sahlin Pettersen, Arnar Flatberg, Atle van Beelen Granlund, Arne Kristian Sandvik, Ann Elisabet Østvik, Torunn Bruland, Ingunn Bakke
{"title":"Uninflamed colonic tissue harbors humoral activity linked to anti-TNF therapy non-response in ulcerative colitis.","authors":"Gunnar Andreas Enerhaug Walaas, Silje Sveaas, Lusie Frostvoll Kuraas, Arun Sridhar, Kari Lillebråten, Hanne Fossen, Henrik Sahlin Pettersen, Arnar Flatberg, Atle van Beelen Granlund, Arne Kristian Sandvik, Ann Elisabet Østvik, Torunn Bruland, Ingunn Bakke","doi":"10.1016/j.isci.2026.117408","DOIUrl":"10.1016/j.isci.2026.117408","url":null,"abstract":"<p><p>Anti-TNF therapy is central for treating ulcerative colitis, yet ∼40% are primary non-responders. To find pre-treatment signatures distinguishing anti-TNF non-responders from responders, we did serum cytokine profiling and laser microdissection transcriptomics on paired uninflamed and inflamed colonic epithelium and lamina propria from patients matched at baseline but differing in endoscopic outcome. Although inflammation drove more epithelial changes, the signatures separating non-responders from responders were found in uninflamed lamina propria, with elevated cell-cycle genes and a co-expression network enriched for humoral immune genes consistently higher expressed in non-responders. Cellular deconvolution localized this network to IgA plasma cells, confirmed by tissue staining, and the association was validated by pseudobulk analysis of an independent single-cell atlas. Baseline epithelial signatures or serum cytokines did not differ significantly between groups. These findings point to TNF-independent humoral activity already present in uninflamed mucosa as a candidate contributor to non-response, with implications for prediction and alternative therapies.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 9","pages":"117408"},"PeriodicalIF":4.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965927","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
Preterm birth disrupts nephron progenitor cell dynamics predisposing to renal disease. 早产破坏肾元祖细胞动力学,易患肾脏疾病。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-09-08 eCollection Date: 2026-09-18 DOI: 10.1016/j.isci.2026.117482
Athar Amleh, Mehran Piran, Julie L M Moreau, Aviad Schnapp, Alexander N Combes, Oded Volovelsky, Morris Nechama
{"title":"Preterm birth disrupts nephron progenitor cell dynamics predisposing to renal disease.","authors":"Athar Amleh, Mehran Piran, Julie L M Moreau, Aviad Schnapp, Alexander N Combes, Oded Volovelsky, Morris Nechama","doi":"10.1016/j.isci.2026.117482","DOIUrl":"10.1016/j.isci.2026.117482","url":null,"abstract":"<p><p>Preterm birth is associated with a substantially increased lifetime risk of chronic kidney disease, yet the developmental mechanisms driving this association remain unclear. Using an established mouse model of preterm birth, we demonstrate that premature extrauterine life uncouples nephron progenitor cell (NPC) proliferation from differentiation. Although the nephrogenic window is transiently extended, it fails to rescue nephron endowment. Transcriptomic and biochemical analyses reveal that preterm NPCs mount an immediate stress response, marked by unfolded protein response and endoplasmic reticulum stress signatures. This molecular stress coincides with a disruption of the precise temporal dynamics required for efficient differentiation, predisposing to a permanent nephron deficit. Long-term follow-up confirms that these early defects manifest as adult glomerular hypertrophy, proteinuria, and tubular injury. Our findings identify stress-associated dysregulation of NPC dynamics as a central mechanism linking prematurity to lifelong kidney vulnerability, highlighting the perinatal period as a critical therapeutic window.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 9","pages":"117482"},"PeriodicalIF":4.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965936","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
ARNTL2 promotes metastatic phenotypes through SERPINE1 transcription in KRAS G12D pancreatic cancer. 在KRAS G12D胰腺癌中,ARNTL2通过SERPINE1转录促进转移表型。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-09-08 eCollection Date: 2026-09-18 DOI: 10.1016/j.isci.2026.117479
Xiaohan Shi, Xiaoyi Yin, Suizhi Gao, Xinqian Wu, Huan Wang, Beilei Wang, Xiongfei Xu, Kailian Zheng, Wei Jing, Gang Li, Shiwei Guo, Gang Jin
{"title":"ARNTL2 promotes metastatic phenotypes through SERPINE1 transcription in KRAS G12D pancreatic cancer.","authors":"Xiaohan Shi, Xiaoyi Yin, Suizhi Gao, Xinqian Wu, Huan Wang, Beilei Wang, Xiongfei Xu, Kailian Zheng, Wei Jing, Gang Li, Shiwei Guo, Gang Jin","doi":"10.1016/j.isci.2026.117479","DOIUrl":"10.1016/j.isci.2026.117479","url":null,"abstract":"<p><p>Despite the prevalence of the KRAS G12D mutation in approximately 40% of pancreatic ductal adenocarcinoma (PDAC) cases and its association with the poorest prognosis among KRAS variants, the downstream transcriptional effectors driving its aggressive metastatic phenotype remain poorly defined. Through integrated bioinformatics and experimental validation, we identified ARNTL2 as a factor associated with KRAS G12D-mutant PDAC. ARNTL2 directly bound to the SERPINE1 promoter to activate its expression, establishing an ARNTL2-SERPINE1 axis that orchestrated epithelial-mesenchymal transition and drove metastasis <i>in vitro</i> and <i>in vivo</i>. Rescue experiments confirmed SERPINE1 as the indispensable downstream mediator. Clinical validation demonstrated that ARNTL2 and SERPINE1 protein levels correlated positively and stratified patients into distinct prognostic subgroups. Furthermore, this axis altered sensitivity to selective KRAS G12D inhibition <i>in vitro</i>. These findings identify an experimentally supported ARNTL2-SERPINE1 transcriptional axis in KRAS G12D-mutant PDAC that warrants further validation in genotype-faithful and clinically relevant models.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 9","pages":"117479"},"PeriodicalIF":4.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965965","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
CT-based radiomics and ablation margin quantification for predicting local tumor progression in Stage I NSCLC after radiofrequency ablation. 基于ct的放射组学和消融边缘量化预测射频消融后I期NSCLC局部肿瘤进展。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-09-08 eCollection Date: 2026-09-18 DOI: 10.1016/j.isci.2026.117406
Sibin Wang, Tianling Lyu, Zhongliang Zhang, Peng Yuan, Zenan Chen, Peng Du, Yi Zhao, Xinyuan Guo, Zichuan Jin, Yueyong Xiao, Yang Chen, Xiao Zhang
{"title":"CT-based radiomics and ablation margin quantification for predicting local tumor progression in Stage I NSCLC after radiofrequency ablation.","authors":"Sibin Wang, Tianling Lyu, Zhongliang Zhang, Peng Yuan, Zenan Chen, Peng Du, Yi Zhao, Xinyuan Guo, Zichuan Jin, Yueyong Xiao, Yang Chen, Xiao Zhang","doi":"10.1016/j.isci.2026.117406","DOIUrl":"10.1016/j.isci.2026.117406","url":null,"abstract":"<p><p>Local tumor progression (LTP) compromises durable local control after radiofrequency ablation (RFA) for stage I non-small cell lung cancer. We developed a three-dimensional minimum ablation margin (3D MAM) quantification workflow and evaluated its integration with post-ablation CT radiomics for individualized LTP prediction. This dual-center retrospective study included 217 patients divided into training, internal validation, and external validation cohorts. Automated segmentation, deformable image registration, and Visualization Toolkit (VTK)-based analysis enabled quantitative 3D margin assessment. An insufficient MAM ( <math><mo><</mo> <mn>5</mn></math> mm) was identified in 147 patients (67.7%). MAM <math><mo>≥</mo> <mn>5</mn></math> mm was independently associated with lower odds of LTP (odds ratio, 0.06; 95% confidence interval, 0.02-0.16). Among nine machine-learning classifiers, the random forest model showed consistent discrimination across cohorts, with areas under the curve of 0.877, 0.851, and 0.889. Combining quantitative margin assessment with CT radiomics may support risk-adapted surveillance after lung RFA.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 9","pages":"117406"},"PeriodicalIF":4.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966008","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
Time-of-day variation in motivation for everyday behaviors: A cluster-based approach to understanding individual differences. 日常行为动机的时间变化:以集群为基础的理解个体差异的方法。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-09-07 eCollection Date: 2026-09-18 DOI: 10.1016/j.isci.2026.117366
John Axelsson, Roshan Cools, Leonie J T Balter
{"title":"Time-of-day variation in motivation for everyday behaviors: A cluster-based approach to understanding individual differences.","authors":"John Axelsson, Roshan Cools, Leonie J T Balter","doi":"10.1016/j.isci.2026.117366","DOIUrl":"10.1016/j.isci.2026.117366","url":null,"abstract":"<p><p>Motivation governs everyday behavior and is often disrupted in psychiatric conditions, yet how motivation varies within the day, and how these patterns differ between individuals remains unclear. Here, we examined diurnal patterns of momentary subjective motivation for everyday activities, their translation into behavior, and how these patterns vary by trait-based measures linked to motivation. At baseline, 538 participants (424 women, 112 men, 2 non-binary, aged 18-77 years) completed questionnaires indexing psychiatric traits associated with altered motivation, revealing four clusters differing in appetitive motivation, and depressive features with varying levels of goal-directed behavior. Participants (<i>n</i> = 410) then completed ecological momentary assessments between ∼08:00 and 23:00, reporting momentary motivation for, and recent engagement in, everyday behaviors. Across clusters, motivation for recovery (rest, being alone) outweighed motivation for activity (socializing and exercise), creating a \"motivational gap\" (defined as the relative difference between recovery-oriented and activity-oriented motivations) that was largest in the morning and late evening and smallest around mid-day, with cluster-specific differences. Momentary motivation translated into subsequent behavior, with the strength of this coupling varying by time-of-day and motivational cluster. These findings identify diurnal motivation as an underrecognized source of individual variabilit in motivational state and behavioral.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 9","pages":"117366"},"PeriodicalIF":4.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981755","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
Nine anthropometric insulin resistance indices predict mortality and life expectancy across glucose states. 9个人体测量胰岛素抵抗指数预测血糖状态下的死亡率和预期寿命。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-09-07 eCollection Date: 2026-09-18 DOI: 10.1016/j.isci.2026.117400
Yi Tang, Yameng Xu, Zilong Yue, Wencai Wang, Song Wen, Haiyang Wang, Lingyun Liu, Juncang Wu, Zhonghua Sun
{"title":"Nine anthropometric insulin resistance indices predict mortality and life expectancy across glucose states.","authors":"Yi Tang, Yameng Xu, Zilong Yue, Wencai Wang, Song Wen, Haiyang Wang, Lingyun Liu, Juncang Wu, Zhonghua Sun","doi":"10.1016/j.isci.2026.117400","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117400","url":null,"abstract":"<p><p>We compared the impact of insulin resistance indicators (triglyceride-glucose index, TyG) combined with different obesity metrics on long-term survival rates across varying states of glucose metabolism. In 11,787 U.S. adults aged ≥45 years from NHANES (1999-2018; mortality follow-up through December 31, 2019) and 12,915 participants from CHARLS for external validation, we examined nine TyG-derived indices using glycemic-status-stratified Cox models and flexible dose-response analyses, and assessed their predictive utility and clinical net benefit. The TyG index combined with a body shape index (TyG-ABSI) showed relatively consistent associations with all-cause and cardiovascular mortality and comparatively favorable incremental predictive performance; external validation in CHARLS supported its association with all-cause mortality, although its standalone discriminatory ability was modest. Higher TyG-ABSI was also associated with shorter life expectancy and a larger estimated population-attributable fraction, supporting its potential role in risk stratification across glucose metabolism states.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 9","pages":"117400"},"PeriodicalIF":4.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987547","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
Oxytocin receptor signaling contributes to the mitochondrial integrity and maintain gastric mucosal homeostasis in male mice. 催产素受体信号参与雄性小鼠线粒体完整性和维持胃粘膜稳态。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-09-07 eCollection Date: 2026-09-18 DOI: 10.1016/j.isci.2026.117425
Yuko Maejima, Shoko Yokota, Megumi Yamachi, Takayuki Yabe, Eugenio Vecchi, Miho Aoki, Saki Shimoyama, Tomoyuki Ono, Daisuke Nakajima, Yoko Teruuchi, Masao Fukushima, Shizu Hidema, Katsuhiko Nishimori, Hitoshi Kubo, Satoshi Waguri, Songji Zhao, Heidi de Wet, Kenju Shimomura
{"title":"Oxytocin receptor signaling contributes to the mitochondrial integrity and maintain gastric mucosal homeostasis in male mice.","authors":"Yuko Maejima, Shoko Yokota, Megumi Yamachi, Takayuki Yabe, Eugenio Vecchi, Miho Aoki, Saki Shimoyama, Tomoyuki Ono, Daisuke Nakajima, Yoko Teruuchi, Masao Fukushima, Shizu Hidema, Katsuhiko Nishimori, Hitoshi Kubo, Satoshi Waguri, Songji Zhao, Heidi de Wet, Kenju Shimomura","doi":"10.1016/j.isci.2026.117425","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117425","url":null,"abstract":"<p><p>The role of oxytocin receptor (OXTR) signaling in the stomach remains poorly understood. This study investigates the physiological and pathophysiological role of OXTR signaling in parietal cells. Using wild type (wt), OXT null and OXTR null mice fed either a standard diet (SD) or a high fat diet (HFD), we examined the effects of OXT and OXTR signaling on gastric mucosa histology and function. SD-fed mice lacking active OXTR/OXT showed mucosal hyperplasia, which was reversed by subcutaneous OXT administration in OXT null mice. HFD-fed wt mice developed typical gastric mucosal hyperplasia, parietal cell atrophy with mitochondrial damage, and impaired <sup>18</sup>F-fluorodeoxyglucose uptake. Subcutaneous OXT administration ameliorated these effects in HFD-fed wt mice, but not in OXTR null mice, suggesting that OXTR activation likely preserves mitochondrial integrity. Our findings support the hypothesis that OXTR signaling in parietal cells is essential for maintaining gastric mucosal metabolic homeostasis and protects against diet-induced gastric pathology.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 9","pages":"117425"},"PeriodicalIF":4.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987552","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
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