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Nonpharmacological interventions for frailty and sarcopenia in older adults with gastrointestinal cancers: A Bayesian network meta-analysis. 老年胃肠癌患者虚弱和肌肉减少症的非药物干预:贝叶斯网络荟萃分析。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-10-01 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117257
Xiaoxu Wang, Xueyuan Hui, Zhongmin Fu, Yinning Guo, Lisi Duan, Wenbing Shi, Qiaona Dong, Qin Xu, Xinyi Xu
{"title":"Nonpharmacological interventions for frailty and sarcopenia in older adults with gastrointestinal cancers: A Bayesian network meta-analysis.","authors":"Xiaoxu Wang, Xueyuan Hui, Zhongmin Fu, Yinning Guo, Lisi Duan, Wenbing Shi, Qiaona Dong, Qin Xu, Xinyi Xu","doi":"10.1016/j.isci.2026.117257","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117257","url":null,"abstract":"<p><p>To compare the effects of nonpharmacological interventions on frailty, sarcopenia, and related physical-function outcomes in older adults with gastrointestinal cancers, we conducted a Bayesian random-effects network meta-analysis of 21 randomized controlled trials from 10 countries. Most interventions did not show clear benefits for frailty, sarcopenia, gait speed, Timed Up and Go performance, sit-to-stand performance, skeletal muscle index, or 6-min walk distance. Prehabilitation exercise showed a low-certainty benefit for handgrip strength, whereas enhanced nutritional support and intensive physiotherapy showed limited benefits for patient-reported physical function. However, these findings were based on small, sparsely connected networks, and the certainty of evidence was generally low or very low. No single intervention was consistently effective across outcomes. These results highlight the need for larger, cancer-specific trials using standardized outcome definitions and clearer reporting of intervention intensity, adherence, safety, and feasibility.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117257"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178613","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
Comparing soil-health- and species-based sensitivity distributions for metal risk assessment in Tianjin soils. 天津土壤金属风险评价的土壤健康和物种敏感性分布比较
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-10-01 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117644
Qiuyun Xu, Yajuan Shi, Xin Xiong, Li Qian, Liuxuan Fang, Xuan Zhou, Xiuqing Shao
{"title":"Comparing soil-health- and species-based sensitivity distributions for metal risk assessment in Tianjin soils.","authors":"Qiuyun Xu, Yajuan Shi, Xin Xiong, Li Qian, Liuxuan Fang, Xuan Zhou, Xiuqing Shao","doi":"10.1016/j.isci.2026.117644","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117644","url":null,"abstract":"<p><p>Soil contamination threatens ecosystem functioning, while conventional ecological risk assessment (ERA) based on single-species toxicity may not capture system-level responses. We developed a probabilistic soil health sensitivity distribution (SHSD) framework integrating microcosm-derived soil health indicators with joint probability modeling and applied it to Pb, Cu, and Cd risks in Tianjin soils, northern China. SHSD-derived risks were lower than species sensitivity distribution (SSD)-based estimates by 61.90%, 59.55%, and 84.38% for Pb, Cu, and Cd, respectively. Normalizing SSD toxicity data to microcosm soil conditions reduced part of the SSD-SHSD discrepancy, highlighting the influence of soil physicochemical heterogeneity. Observed SHSDs were also shifted rightward relative to additive, non-interactive predictions, indicating lower apparent sensitivity of the integrated microcosm. These findings support SHSD as a higher tier, function-oriented complement to conventional SSDs, while emphasizing the need for independent field validation before regulatory application.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117644"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178322","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
Domain-autonomous MKLP1 modules divergently regulate mitotic fidelity and polyploidy in a holocentric system. 区域自主的MKLP1模块在全新中心系统中发散调节有丝分裂保真度和多倍体。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-10-01 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117149
Bing Zhang, Xiao-Ning Liu, Mei-Ting Song, Meng-Fan Qin, Shu-Shu Tian, Yu Lin, Dan-Dan Li, Lun-Guang Yao, Camilo Ayra-Pardo, Yun-Chao Kan
{"title":"Domain-autonomous MKLP1 modules divergently regulate mitotic fidelity and polyploidy in a holocentric system.","authors":"Bing Zhang, Xiao-Ning Liu, Mei-Ting Song, Meng-Fan Qin, Shu-Shu Tian, Yu Lin, Dan-Dan Li, Lun-Guang Yao, Camilo Ayra-Pardo, Yun-Chao Kan","doi":"10.1016/j.isci.2026.117149","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117149","url":null,"abstract":"<p><p>While the kinesin MKLP1 is a well-established regulator of cytokinesis, whether its individual domains possess autonomous functions has remained unexplored. Here, using the holocentric <i>Bombyx mori</i> BmN4 system, we show that isolated head, stalk, and tail domains of MKLP1 exhibit distinct subcellular localization patterns and exert divergent control over mitosis. These domains differentially regulate cell-cycle progression, with the head and stalk inducing G2/M arrest, whereas the tail, and to a lesser extent the head, promotes polyploidization. Despite these divergent outcomes, all three domains converge on a shared pathological activity, aberrantly recruiting γ-tubulin, disrupting spindle organization, and compromising chromosome segregation. The domains also exert opposing effects on EdU incorporation, with the head suppressing EdU labeling and the stalk and tail enhancing it. Together, our findings redefine MKLP1 as a composite platform of regulatory modules, whose uncoupling reveals a principle of kinesin organization with broad implications for mitotic robustness and genomic stability.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117149"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178440","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
Microenvironment shapes Staphylococcus aureus phenotypes in children with cystic fibrosis over time. 随着时间的推移,微环境会影响囊性纤维化儿童的金黄色葡萄球菌表型。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-10-01 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117708
Stefania A Robaldi, Rosana Pereda, Maria Constanza Pautasso, Enrique Blasko, Ailen Fretes, Trinidad Jaureguialzo, Mateo Diaz Appella, Mariana B Galeano, Maria Jose Rial, Silvina Smith, Eugenia Ginestet, Norma Gonzalez, Javier M González, Andrea Smania, Alejandro J Vila, Claudia Sola, Pablo M Cassanelli, Paula M Tribelli
{"title":"Microenvironment shapes <i>Staphylococcus aureus</i> phenotypes in children with cystic fibrosis over time.","authors":"Stefania A Robaldi, Rosana Pereda, Maria Constanza Pautasso, Enrique Blasko, Ailen Fretes, Trinidad Jaureguialzo, Mateo Diaz Appella, Mariana B Galeano, Maria Jose Rial, Silvina Smith, Eugenia Ginestet, Norma Gonzalez, Javier M González, Andrea Smania, Alejandro J Vila, Claudia Sola, Pablo M Cassanelli, Paula M Tribelli","doi":"10.1016/j.isci.2026.117708","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117708","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> is a common pathogen in children with cystic fibrosis (CF), frequently preceding or coexisting with <i>Pseudomonas aeruginosa</i>. The impact of transient <i>P. aeruginosa</i> infection and therapeutic intervention on <i>S. aureus</i> phenotypic shaping remains poorly understood. We characterized 546 isolates from a longitudinal cohort of sixteen pediatric patients in CF follow-up, either monoinfected or coinfected, over eighteen months. Isolates were grouped into three phenotypic clusters. Monoinfected patients were enriched in a cluster with high pigment and biofilm, whereas transient <i>P. aeruginosa</i> detection was associated with a shift toward reduced pigment and biofilm, while coinfected patients maintained stable phenotypes. Phenotypes were determined by the airway microenvironment rather than by clonal background. In two monoinfected patients, this shift coincided with transient infection and ciprofloxacin treatment with increased MRSA; <i>in vitro</i>, MRSA predominated over MSSA when both <i>P. aeruginosa</i> and ciprofloxacin were present, underscoring the need to monitor <i>S. aureus</i> phenotypic transitions.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117708"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178588","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
TXNRD1-driven enteric glial remodeling promotes neuronal dysfunction in Hirschsprung disease. txnrd1驱动的肠神经胶质重塑促进巨结肠疾病的神经元功能障碍。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-10-01 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117636
Yanyi Li, Yuanli Wang, Zhu Jin, Chengyan Tang, Xinrong Xia, Yuan Gong, Qing Du, Lu Huang, Zeping Li, Yu Liao, Shengyin He, Bo Wang, Yuanmei Liu, Zebing Zheng
{"title":"TXNRD1-driven enteric glial remodeling promotes neuronal dysfunction in Hirschsprung disease.","authors":"Yanyi Li, Yuanli Wang, Zhu Jin, Chengyan Tang, Xinrong Xia, Yuan Gong, Qing Du, Lu Huang, Zeping Li, Yu Liao, Shengyin He, Bo Wang, Yuanmei Liu, Zebing Zheng","doi":"10.1016/j.isci.2026.117636","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117636","url":null,"abstract":"<p><p>Hirschsprung disease (HSCR) is characterized by distal intestinal aganglionosis and persistent dysfunction of the enteric nervous system after surgical treatment. Here, we integrated single-cell transcriptomics, network-based virtual perturbation analysis, proteomics, human tissue validation, enteric glial cell assays, neuron-glia co-culture systems, and an <i>Ednrb</i> conditional knockout (cKO) mouse model to investigate TXNRD1-dependent enteric glial remodeling in HSCR. We found that thioredoxin reductase 1 (TXNRD1) enrichment was associated with expansion of an SPP1-high/CXCL9-low enteric glial state and selective ERK/MAPK activation. TXNRD1 overexpression increased oxidative stress, impaired enteric glial migration and neurotrophic support, and induced neuronal dysfunction through suppression of GDNF/GFRα1/RET signaling. TXNRD1 inhibition alleviated HSCR-like phenotypes in <i>Ednrb</i> cKO mice. These findings identify TXNRD1-driven redox-dependent enteric glial remodeling as a mechanism contributing to neuronal dysfunction and HSCR progression.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117636"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178640","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
Genome-wide mapping of the Galleria mellonella transcription start sites during fungal infection and treatment. 真菌感染和治疗过程中mellongalleria转录起始位点的全基因组定位。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-10-01 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117675
Imad Abugessaisa, Mickey Konings, Ri-Ichiroh Manabe, Michihira Tagami, Jessica Severin, Akira Hasegawa, Tsugumi Kawashima, Hiroko Kinoshita, Shohei Noma, Chitose Takahashi, Annelies Verbon, Yasushi Okazaki, Wendy W J van de Sande, Takeya Kasukawa
{"title":"Genome-wide mapping of the <i>Galleria mellonella</i> transcription start sites during fungal infection and treatment.","authors":"Imad Abugessaisa, Mickey Konings, Ri-Ichiroh Manabe, Michihira Tagami, Jessica Severin, Akira Hasegawa, Tsugumi Kawashima, Hiroko Kinoshita, Shohei Noma, Chitose Takahashi, Annelies Verbon, Yasushi Okazaki, Wendy W J van de Sande, Takeya Kasukawa","doi":"10.1016/j.isci.2026.117675","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117675","url":null,"abstract":"<p><p><i>Galleria mellonella</i> is an emerging experimental model, but its current genome annotation lacks transcription start site (TSS) information. Because TSS annotation is essential for understanding transcriptional regulation, we used low quantity single strand CAGE (LQ-ssCAGE) to map cap analysis of gene expression (CAGE)-defined TSSs from 72 <i>G. mellonella</i> larval samples. Among these, 36 larvae were infected with the fungal pathogen <i>Madurella mycetomatis</i> and 36 served as healthy controls, allowing identification of TSSs under both infected and healthy conditions. Infected and healthy larvae were treated with itraconazole or ravuconazole. To assess key characteristics of the CAGE data, TSS peaks and putative enhancers were intersected with the existing genome annotation for annotation and characterization. This analysis identified two sets of TSS peaks, permissive and robust, representing the first draft TSS atlas for <i>G. mellonella</i>. The atlas-derived annotations showed a markedly stronger core promoter sequence signature than the NCBI reference annotation, supporting improved resolution and accuracy of TSS annotation in the atlas.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117675"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178448","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
Development of CNN and LSTM fusion model for early fault warning in hydro turbine units. 水轮机机组早期故障预警CNN与LSTM融合模型的建立。
IF 4.5 2区 综合性期刊
iScience Pub Date : 2026-10-01 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117740
Yu Zhu, Yanmu Chen, Xiaxia Xiang, Jiayu Wang, Shengbo Wang, Xiaomo Jiang, Yeming Lu
{"title":"Development of CNN and LSTM fusion model for early fault warning in hydro turbine units.","authors":"Yu Zhu, Yanmu Chen, Xiaxia Xiang, Jiayu Wang, Shengbo Wang, Xiaomo Jiang, Yeming Lu","doi":"10.1016/j.isci.2026.117740","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117740","url":null,"abstract":"<p><p>Early fault detection is important for the safe and stable operation of large hydro turbine units under complex and variable operating conditions. This study develops an early fault warning framework for high dimensional multisource monitoring data by integrating Kendall rank correlation-based parameter grouping, systematic data governance, sparse principal component analysis, and a CNN LSTM prediction model. Fifty two operating parameters are organized into six groups and transformed into six sparse state features. The CNN LSTM model captures local correlations and temporal evolution, achieving R<sup>2</sup> values of 0.947, 0.955, 0.848, 0.701, 0.687, and 0.853 for SPCA1 to SPCA6. Prediction residuals combined with 2σ and 3σ thresholds identify early degradation before the recorded fault, with warning lead times of up to 33 time steps. The framework provides a practical approach for condition monitoring and hierarchical early warning of large hydro turbine units.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117740"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178382","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
Global early-life cohorts for nutrition-neurodevelopment research including over 100 datasets representing over one million children. 用于营养-神经发育研究的全球早期生活队列,包括代表100多万儿童的100多个数据集。
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.2026.117562
Stefanie Perrier, Anna N Foster, Sanhita Sunil Sawant, Faith Nassiwa, Ankush Kesri, Chuan-Heng Hsiao, Rutvi Vyas, P Ellen Grant, Kathleen T Durant, Sarah U Morton, Yangming Ou
{"title":"Global early-life cohorts for nutrition-neurodevelopment research including over 100 datasets representing over one million children.","authors":"Stefanie Perrier, Anna N Foster, Sanhita Sunil Sawant, Faith Nassiwa, Ankush Kesri, Chuan-Heng Hsiao, Rutvi Vyas, P Ellen Grant, Kathleen T Durant, Sarah U Morton, Yangming Ou","doi":"10.1016/j.isci.2026.117562","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117562","url":null,"abstract":"<p><p>The first 1,000 days of brain development are sensitive to nutrient availability, and large longitudinal early-life cohorts provide an opportunity to study early nutritional influences on neurodevelopment in generally healthy populations. We aimed to identify international pregnancy and birth cohorts with at least 1,000 children collecting early-life nutrition data, including maternal nutrition during pregnancy or lactation, breastfeeding, and solid-food feeding, along with later child neurodevelopmental outcomes. In total, 104 pregnancy and birth cohorts were identified, representing over 1.17 million children across 41 countries. Cohorts spanned six continents, with the largest participant representation from high- and upper middle-income settings. Maternal diet during pregnancy and breastfeeding status were the most frequently captured nutrition domains, while neurodevelopmental assessments varied across developmental periods, using over 200 assessment tools. These cohorts support future harmonized analyses of early nutrition and neurodevelopment, and further work will benefit from international collaboration, shared data standards, and pooled or federated infrastructures.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117562"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178510","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
M2 type tumor-associated macrophage-derived CCL-18 promotes glioma cell proliferation but does not mediates glioma recurrence after radiotherapy. M2型肿瘤相关巨噬细胞来源的CCL-18促进胶质瘤细胞增殖,但不介导胶质瘤放疗后复发。
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.2026.117695
Jiangpeng Fan, Yufei Mao, Li Liu, Zhongyu Ren, Zidong Zhou, Yuanqi Ma, Xiangrong Lu, Guimei Cui, Xu Zhang, Xiuping Zhou
{"title":"M2 type tumor-associated macrophage-derived CCL-18 promotes glioma cell proliferation but does not mediates glioma recurrence after radiotherapy.","authors":"Jiangpeng Fan, Yufei Mao, Li Liu, Zhongyu Ren, Zidong Zhou, Yuanqi Ma, Xiangrong Lu, Guimei Cui, Xu Zhang, Xiuping Zhou","doi":"10.1016/j.isci.2026.117695","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117695","url":null,"abstract":"<p><p>Most of glioma patients still experience relapse after radiotherapy owing to the formation of tumor immunosuppressive microenvironment. However, the comprehensive landscape of immune cell infiltration and the molecular mechanisms mediating glioma recurrence remains unclear. Bulk RNA sequencing (RNA-seq) analysis revealed the significant changes in the immune system including increased total tumor-associated macrophages (TAMs) and elevated M2-TAMs in recurrent glioma accepting radiotherapy. Meanwhile, C-C motif chemokine 18 (CCL-18) was the highest elevated molecule after radiotherapy. Consistently, the aforementioned results were confirmed in tissue microarray containing 23 paired gliomas. <i>In vitro</i>, radiation promoted TAM polarization into M2-TAMs, accompanying CCL-18 secretion. However, CCL-18 promoted non-irradiated glioma proliferation but did not mediate glioma recurrence after radiotherapy. Mechanistically, the pro-tumor effect of CCL-18 was weakened by the down-regulation of CCL-18 receptors on glioma accepting radiotherapy. Our study indicates CCL-18 does not mediate glioma recurrence but has the potential to serve as a biomarker for recurrent gliomas.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117695"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178570","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
Targeting mutant NPM1-expressing AML with T cell receptor-like antibodies. 用T细胞受体样抗体靶向表达npm1的AML突变体。
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.2026.117630
Yunda Hong, Dabing Chen, Jingjing Xu, Yanxin Chen, Yang Shi, Zikang Wang, Congling Gan, Zihan Wang, Qian Li, Jiahua Gao, Huilin Guo, Ningshao Xia, Yangtao Wu, Tianying Zhang, Quan Yuan, Ting Yang, Jianda Hu
{"title":"Targeting mutant NPM1-expressing AML with T cell receptor-like antibodies.","authors":"Yunda Hong, Dabing Chen, Jingjing Xu, Yanxin Chen, Yang Shi, Zikang Wang, Congling Gan, Zihan Wang, Qian Li, Jiahua Gao, Huilin Guo, Ningshao Xia, Yangtao Wu, Tianying Zhang, Quan Yuan, Ting Yang, Jianda Hu","doi":"10.1016/j.isci.2026.117630","DOIUrl":"https://doi.org/10.1016/j.isci.2026.117630","url":null,"abstract":"<p><p>This study developed T cell receptor (TCR)-like antibodies targeting the intracellular neoantigen derived from the common NPM1 type A mutation (NPM1<sup>mutA</sup>) in acute myeloid leukemia (AML), presented by HLA-A∗02:01. Hybridoma technology was employed to generate a murine monoclonal antibody (m2E2) specifically recognizing the NPM1<sup>mutA</sup> <sub>283-291</sub>-HLA-A∗02:01 complex. The lead antibody was humanized (hu2E2) and engineered into bispecific formats engaging CD3 or CD16, alongside an Fc-enhanced variant (hu2E2-GAALIE). <i>In vitro</i>, these antibodies mediated potent antibody-dependent cellular cytotoxicity (ADCC) against NPM1<sup>mutA</sup>-positive AML cell lines, inducing apoptosis and cytokine release. <i>In vivo</i>, a single dose of hu2E2 variants significantly suppressed tumor growth in NCG mice engrafted with OCI-AML3-LUC cells. Fc silencing abolished antitumor efficacy, confirming FcγR-dependent mechanisms. Critically, m2E2 specifically bound to primary CD33<sup>+</sup> blasts from HLA-A∗02:01-positive, NPM1-mutated AML patients. These findings demonstrate a potent immunotherapeutic strategy for targeting intracellular oncogenic peptides in AML and support further clinical development of TCR-like antibodies.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117630"},"PeriodicalIF":4.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178709","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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