IF 4.5 2区综合性期刊

iScience Pub Date : 2026-10-07 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117746

Noriyoshi Manabe, Kazuyoshi Itoh, Shiho Ohno, Ayumi Miura, Aika Miyata, Sora Yashima, Sachiko Komatsu, Tsutomu Fujimura, Hisatoshi Hanamatsu, Jun-Ichi Furukawa, Kiyohiko Angata, Akira Togayachi, Kiyoko F Aoki-Kinoshita, Yoshihiro Akimoto, Tadashi Kaname, Shoko Nishihara, Yoshiki Yamaguchi

{"title":"Loss of the Asn333 high-mannose N-glycan impairs ACP3 folding and drives disease-associated dysfunction.","authors":"Noriyoshi Manabe, Kazuyoshi Itoh, Shiho Ohno, Ayumi Miura, Aika Miyata, Sora Yashima, Sachiko Komatsu, Tsutomu Fujimura, Hisatoshi Hanamatsu, Jun-Ichi Furukawa, Kiyohiko Angata, Akira Togayachi, Kiyoko F Aoki-Kinoshita, Yoshihiro Akimoto, Tadashi Kaname, Shoko Nishihara, Yoshiki Yamaguchi","doi":"10.1016/j.isci.2026.117746","DOIUrl":"10.1016/j.isci.2026.117746","url":null,"abstract":"Missense mutations disrupting N-glycosylation motifs can perturb protein folding and trafficking, yet the site-specific contributions of individual N-glycans to proteostasis remain poorly defined. Here, we delineated the functional hierarchy of three N-glycosylation sites in human prostatic acid phosphatase (ACP3). Glycoproteomic analysis showed that Asn94 and Asn220 carry predominantly complex-type N-glycans, whereas Asn333 is enriched in high-mannose structures. Glycan-deficient N94Q and N220Q variants were efficiently secreted and retained phosphatase activity, whereas N333Q and T335M accumulated intracellularly, formed endoplasmic reticulum aggregates, and lacked enzymatic activity. Molecular dynamics simulations revealed that the Asn333 high-mannose glycan forms persistent hydrogen-bond networks with surrounding residues and exhibits markedly reduced conformational flexibility, supporting a non-redundant structural role. Individuals harboring a heterozygous p.T335M variant presented severe neurodevelopmental abnormalities, linking Asn333 glycan loss to proteostasis failure in vivo. These findings establish a site-specific glycan-protein stabilizing mechanism with broad implications in glycoprotein folding and human disease.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117746"},"PeriodicalIF":4.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219899","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

An inverse-protein-folding pre-trained model for predicting the mutational effects in protein-protein interactions. 用于预测蛋白质-蛋白质相互作用中突变效应的反向蛋白质折叠预训练模型。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-10-06 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117693

Sihong Mao, Siwei Meng, Ye Xiang

引用次数: 0

Gastroprotective effects of chlorella derived lutein via anti-inflammatory antioxidant and acid enzyme modulation. 小球藻叶黄素通过抗炎、抗氧化和酸酶调节对胃的保护作用。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-10-06 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117661

Insaf Bahrini, Maha Alazami, Muna Alamoudi

引用次数: 0

Deep white-matter tracts link docosahexaenoic acid status to cognitive performance in human adolescents. 深层白质束将二十二碳六烯酸状态与人类青少年的认知表现联系起来。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-10-05 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117709

Alejandra Figueroa-Vargas, Rodrigo Valenzuela, Patricia Soto-Icaza, Francisco Zamorano, Cristián Larraín, Claudio Silva, Pamela Guevara, Sebastián Navarrete, Atilio Almagià, Violeta Arancibia, Cynthia Barrera, Daniza Ivanovic, Pablo Billeke

{"title":"Deep white-matter tracts link docosahexaenoic acid status to cognitive performance in human adolescents.","authors":"Alejandra Figueroa-Vargas, Rodrigo Valenzuela, Patricia Soto-Icaza, Francisco Zamorano, Cristián Larraín, Claudio Silva, Pamela Guevara, Sebastián Navarrete, Atilio Almagià, Violeta Arancibia, Cynthia Barrera, Daniza Ivanovic, Pablo Billeke","doi":"10.1016/j.isci.2026.117709","DOIUrl":"10.1016/j.isci.2026.117709","url":null,"abstract":"Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid enriched in neuronal membranes and myelin, linked to cognitive performance. Yet, nutritional interventions show inconsistent cognitive benefits due to a limited understanding of the neural pathways connecting DHA status to human cognition. We studied 99 adolescents selected from both extremes of performance on a national scholastic examination. Participants completed assessments of intellectual ability, provided erythrocyte DHA samples, and underwent multimodal MRI. Using independent component analysis and Bayesian multivariate least absolute shrinkage and selection operator (LASSO) models, we identified brain components jointly associated with DHA and cognition. Across four MRI modalities, a single deep white-matter component consistently emerged as the strongest shared pathway. Tract-resolved analyses highlighted predominant contributions from the fornix and thalamus-temporal fasciculus, with additional subcortical and cortical involvement. These components predicted cognitive measures beyond DHA and other fatty acids, outlining a plausible neural pathway through which a modifiable dietary factor relates to adolescent learning.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117709"},"PeriodicalIF":4.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214797","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

Sulfate modification CeO₂: A strategy for SF₆ photocatalytic degradation. 硫酸盐改性CeO2：光催化降解SF6的策略。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-10-05 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117751

Shan Zhu, Yue Zhao, Yang Wu, Fengxiang Ma, Tao Lin, Jun Cao, Chen Hang

引用次数: 0

Sulfonylurea receptor 1 deficiency alleviates acute lung injury by activating PARP1 in epithelial cells. 磺酰脲受体1缺乏通过激活上皮细胞中的PARP1减轻急性肺损伤。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-10-05 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117627

Xiaojuan Yin, Qiaoqiao Zhu, Li Zhao, Wenqing Ma, Liying Wang, Huiling Li, Chao Wang, Yipin Wang, Lin Xu, Haijun Zhang, Xuerong Wang, Wenbin Huang

{"title":"Sulfonylurea receptor 1 deficiency alleviates acute lung injury by activating PARP1 in epithelial cells.","authors":"Xiaojuan Yin, Qiaoqiao Zhu, Li Zhao, Wenqing Ma, Liying Wang, Huiling Li, Chao Wang, Yipin Wang, Lin Xu, Haijun Zhang, Xuerong Wang, Wenbin Huang","doi":"10.1016/j.isci.2026.117627","DOIUrl":"10.1016/j.isci.2026.117627","url":null,"abstract":"Acute lung injury (ALI) is a critical disease with high mortality, yet its mechanisms remain incompletely elucidated. In this study, we investigated sulfonylurea receptor 1 (SUR1), the regulatory subunit of ATP-sensitive potassium (KATP) channels, in the progression of ALI. We observed elevated SUR1 protein levels in the bronchoalveolar lavage fluid (BALF) of patients with sepsis-associated ALI, as well as in BALF and lung tissues of ALI mouse models. Genetic deletion of SUR1, but not Kir6.2 (the pore-forming subunit of KATP channels), significantly alleviated ALI induced by cecal ligation and puncture (CLP) or by lipopolysaccharide (LPS) intratracheal instillation. Mechanistically, SUR1 interacted with poly (ADP-ribose) polymerase 1 (PARP1), impairing DNA damage repair and promoting apoptosis and NF-κB (nuclear factor kappa B) activation in bronchial epithelial cells. Notably, glibenclamide, a clinically approved SUR1 inhibitor, significantly alleviated ALI, at least in part, by disrupting the SUR1-PARP1 interaction. Our findings identify SUR1 as a new therapeutic target and highlight the potential repurposing of glibenclamide as a therapeutic drug in ALI.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117627"},"PeriodicalIF":4.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214904","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

Lipid-based mRNA chimeric antigen receptor T cells for enhanced in vitro antitumor activity. 脂质基mRNA嵌合抗原受体增强T细胞体外抗肿瘤活性。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-10-05 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117390

Haixia Gao, Yuan Fang, Zhidan Tian, Chuanxin Guo, Pei Wang, Tao Liu, Yan Sun, Pingjing Zhang, Qijun Qian

{"title":"Lipid-based mRNA chimeric antigen receptor T cells for enhanced in vitro antitumor activity.","authors":"Haixia Gao, Yuan Fang, Zhidan Tian, Chuanxin Guo, Pei Wang, Tao Liu, Yan Sun, Pingjing Zhang, Qijun Qian","doi":"10.1016/j.isci.2026.117390","DOIUrl":"10.1016/j.isci.2026.117390","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapy provides substantial clinical benefits in hematologic malignancies. However, cell engineering using conventional viral vectors is costly, labor intensive, and prone to safety risks, while electroporation-induced cellular damage limits manufacturing scalability. This study reports a safe, high-efficiency, nonviral platform for generating mRNA-engineered CAR T cells. Herein, eight ionizable lipids are synthesized and formulated into lipid nanoparticles. Systematic screening and structural optimization identified lipid 6 as the lead candidate. Transfection efficiency is validated by delivering enhanced green fluorescent protein (eGFP) mRNA into DC2.4, peripheral blood mononuclear, dendritic, and natural killer cells. Murine models confirm robust in vivo expression and a favorable safety profile. Lipid 6-mediated delivery of MUC1 mRNA generates MUC1-CAR T cells characterized by high surface receptor expression and potent cytotoxicity against MUC1-positive tumor cells. These findings establish lipid 6 as a feasible strategy for primary human T cell engineering, facilitating functional CAR expression with minimal toxicity.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117390"},"PeriodicalIF":4.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214951","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

IPO5 contributes to cetuximab resistance in colorectal cancer by modulating Ras signaling. IPO5通过调节Ras信号参与结直肠癌西妥昔单抗耐药。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-10-05 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117714

Qinzi Yuan, Siqi Lu, Xiaoxi He, Lin Zheng, Lei Liu, Yujia Chen, Wenjuan Zhang, Xiaomin Li, Yanxia Lu, Xuenong Li

{"title":"IPO5 contributes to cetuximab resistance in colorectal cancer by modulating Ras signaling.","authors":"Qinzi Yuan, Siqi Lu, Xiaoxi He, Lin Zheng, Lei Liu, Yujia Chen, Wenjuan Zhang, Xiaomin Li, Yanxia Lu, Xuenong Li","doi":"10.1016/j.isci.2026.117714","DOIUrl":"10.1016/j.isci.2026.117714","url":null,"abstract":"Resistance to cetuximab is a major challenge in colorectal cancer (CRC). Here, we show that IPO5, an importin mediating RASAL2 nuclear import, contributes to cetuximab resistance. Screening six CRC cell lines revealed an inverse correlation between IPO5 expression and cetuximab sensitivity, with higher IPO5 levels in resistant (RKO and SW620) than sensitive (LoVo and Caco2) cells. IPO5 knockdown in resistant cells restored cetuximab sensitivity, induced apoptosis (upregulated active caspase-3/BAX and downregulated BCL-2), and suppressed proliferation and xenograft growth, whereas IPO5 overexpression in sensitive cells reduced sensitivity. Mechanistically, IPO5 facilitates RASAL2 nuclear translocation via its nuclear localization signal, depleting cytoplasmic RASAL2 and increasing GTP-bound RAS to sustain AKT and MAPK activation. Consistently, IPO5 and downstream Ras effectors were elevated in resistant LoVo-CR cells. Collectively, our findings identify the IPO5/RASAL2 axis as a key contributor to cetuximab resistance in CRC by disrupting the cytoplasmic localization of RASAL2 and activating the RAS/MAPK and PI3K/AKT pathways.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117714"},"PeriodicalIF":4.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214907","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

Evolution of lake microbial structure and function under climatic and anthropogenic forcings: Insights from sedimentary ancient DNA. 气候和人为强迫下湖泊微生物结构和功能的演化：来自沉积古DNA的启示。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-10-03 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117760

Xinjie Shi, Hai Xu, Wanzhu Li, Jing Wang, Yunping Song, Meiling Yang, Baoli Wang, Cong-Qiang Liu

{"title":"Evolution of lake microbial structure and function under climatic and anthropogenic forcings: Insights from sedimentary ancient DNA.","authors":"Xinjie Shi, Hai Xu, Wanzhu Li, Jing Wang, Yunping Song, Meiling Yang, Baoli Wang, Cong-Qiang Liu","doi":"10.1016/j.isci.2026.117760","DOIUrl":"10.1016/j.isci.2026.117760","url":null,"abstract":"Structure and function of lake microorganisms are sensitive to environmental disturbances; yet their differential responses to climatic and anthropogenic forcings over centennial scales remain poorly understood. Here, we analyzed a sediment core from Lake Daihai in northern China, combining metagenomics and stable isotope analyses. Our results revealed that microbial community assembly was dominated by deterministic processes, whereas stochasticity increased notably after 1850, coinciding with the termination of the Little Ice Age and intensified human impacts. Notably, microbial community structure evolved at a rate approximately one order of magnitude faster than community function. This decoupling was mediated by functional redundancy associated with bacterial keystone taxa, ultimately resulting in more negative sedimentary carbon and nitrogen isotopic compositions nearly a century later. Gene-level functional redundancy further buffered ecosystem function variability across biological scales. Collectively, our findings integrate omics and geochemical approaches to advance the understanding of lake ecological evolution under complex multi-forcing regimes.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117760"},"PeriodicalIF":4.5,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178457","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

An atlas of sarbecovirus infectivity across diverse ACE2 orthologs. 不同ACE2同源物的sarbecvirus传染性图谱。

IF 4.5 2区综合性期刊

iScience Pub Date : 2026-10-03 eCollection Date: 2026-10-16 DOI: 10.1016/j.isci.2026.117769

Yeqing Sun, Ziqi Cheng, Xi Wu, Kefang Liu, Lin Wang, Dongchun Yang, Weijin Huang, Jianhui Nie

{"title":"An atlas of sarbecovirus infectivity across diverse ACE2 orthologs.","authors":"Yeqing Sun, Ziqi Cheng, Xi Wu, Kefang Liu, Lin Wang, Dongchun Yang, Weijin Huang, Jianhui Nie","doi":"10.1016/j.isci.2026.117769","DOIUrl":"10.1016/j.isci.2026.117769","url":null,"abstract":"Sarbecoviruses pose a substantial zoonotic threat, yet the determinants governing their host range remain incompletely defined. To systematically investigate host entry mechanisms, we generated a panel of vesicular stomatitis virus (VSV) pseudoviruses representing 46 sarbecoviruses and assessed their infectivity across 66 angiotensin-converting enzyme 2 (ACE2) orthologs. This analysis produced a high-resolution host-entry landscape with direct implications for cross-species transmission risk. We found that all severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) isolates, WIV1, and pangolin-derived sarbecoviruses demonstrated broad ACE2 usage, whereas no sarbecovirus utilized alternative entry factors including neuropilin-1, CD147, AXL, or TMEM106B. Notably, ACE2 orthologs from Rhinolophus affinis and Miniopterus schreibersii supported infection by nearly all clade 1 sarbecoviruses, identifying highly permissive host receptors. We also identified residues 27 and 42 of ACE2 as critical determinants of sarbecovirus host tropism. Together, these findings define host entry constraints relevant to receptor-based risk assessment and inform surveillance and pandemic preparedness.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117769"},"PeriodicalIF":4.5,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178520","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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