iSciencePub Date : 2025-09-12DOI: 10.1016/j.isci.2025.113552
Shixue Zheng , Chloe Chan , John M. Asara , Liang Zhang , Gerhard Wiche , Y. Rebecca Chin
{"title":"Phosphorylation of plectin by Akt3 promotes triple-negative breast cancer cell invasive migration","authors":"Shixue Zheng , Chloe Chan , John M. Asara , Liang Zhang , Gerhard Wiche , Y. Rebecca Chin","doi":"10.1016/j.isci.2025.113552","DOIUrl":"10.1016/j.isci.2025.113552","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) lacks targeted therapeutics and is aggressive with a poor prognosis. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, frequently deregulated in cancers, plays crucial roles in tumorigenesis and cancer progression. However, the distinct functions of the three Akt isoforms (Akt1, Akt2, Akt3) in these processes are not well understood. Here, we focus on Akt3, the least-studied Akt isoform, which is overexpressed in 28% of TNBC cases and significantly promotes TNBC growth, stemness, and epithelial-mesenchymal transition. Through a genome-wide proteomic screen, we identified plectin, a member of the plakin family, as an Akt3 substrate in TNBC cells. The depletion of plectin potently inhibits TNBC cell migration and invadopodia formation, albeit with mild effects on cell growth. The phosphorylation of plectin at Ser4268 by Akt promotes its colocalization with vimentin and TNBC cell migration. Our findings underscore the importance of Akt3-plectin signaling as a potential TNBC therapeutic target.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113552"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155970","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}
iSciencePub Date : 2025-09-12DOI: 10.1016/j.isci.2025.113562
Mattia Galigani , Nicolò Castellani , Barbara Italia , Sveva D’Aversa , Davide Bottari , Francesca Garbarini
{"title":"Frequency-tagging EEG reveals spontaneous categorical discrimination of visual self-identity","authors":"Mattia Galigani , Nicolò Castellani , Barbara Italia , Sveva D’Aversa , Davide Bottari , Francesca Garbarini","doi":"10.1016/j.isci.2025.113562","DOIUrl":"10.1016/j.isci.2025.113562","url":null,"abstract":"<div><div>From early development, visual and sensorimotor representations of our hands are continually linked, allowing to develop a bodily self-representation. Here, we investigated the neural mechanisms of bodily self-identity discrimination, combining electroencephalography with fast periodic visual stimulation. In two experiments, participants’ self-hand images appeared as oddball stimuli among others’ hands. To control for statistical regularity and familiarity, oddball hand images could belong to a stranger (Exp1) or the partner (Exp2). In a third behavioral experiment, we verified participants could explicitly detect the presence of the self-hand in the sequence. Results revealed a neural marker for automatic hand identity discrimination, with greater responses in egocentric than allocentric perspective only for self-hand images. This interaction effect emerged over occipital, consistently with the visual nature of the task, and also over fronto-central regions, compatibly with the involvement of a sensorimotor network. These findings support that self-hand processing relies on associating visual and sensorimotor representations.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113562"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155859","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}
iSciencePub Date : 2025-09-12DOI: 10.1016/j.isci.2025.113558
Wanying He , Minxiao Wang , Zhaoshan Zhong , Hao Chen , Shichuan Xi , Huan Zhang , Mengna Li , Wenhao Sun , Yan Zhang , Yun Wang , Xiaoxiao Guo , Lianfu Li , Zengfeng Du , Zhendong Luan , Chaolun Li , Xin Zhang
{"title":"In situ semi-quantitative imaging of intracellular metabolic interaction by confocal Raman microscopy","authors":"Wanying He , Minxiao Wang , Zhaoshan Zhong , Hao Chen , Shichuan Xi , Huan Zhang , Mengna Li , Wenhao Sun , Yan Zhang , Yun Wang , Xiaoxiao Guo , Lianfu Li , Zengfeng Du , Zhendong Luan , Chaolun Li , Xin Zhang","doi":"10.1016/j.isci.2025.113558","DOIUrl":"10.1016/j.isci.2025.113558","url":null,"abstract":"<div><div>Non-destructive subcellular metabolite quantification can reveal critical insights into biological interactions (e.g., endosymbiont-host crosstalk). Therefore, we developed a multivariate semi-quantitative imaging method using internal standardization to resolve simultaneous subcellular distributions of multiple metabolites, leveraging confocal Raman microscopy’s (CRM’s) high spatial resolution. The method was applied to the endosymbiotic mussel <em>Gigantidas platifrons</em>, whose symbiotic interaction mechanism has not been elucidated because symbionts cannot be cultivated. The results showed that the aggregated distribution of distinct phenotypes of symbiont strains was characterized by different glycogen abundances, indicating niche-driven metabolic strategies. Our data may provide direct evidence suggesting that symbionts supply intermediates to the host for cholesterol synthesis, potentially via vesicular trafficking. This work demonstrates CRM’s capacity for comparative, spatially resolved metabolite quantification across cellular compartments. While semi-quantitative, CRM emerges as a powerful non-invasive tool for probing metabolic network dynamics and compartmentalization in challenging biological systems where traditional methods are limited.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113558"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155972","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}
iSciencePub Date : 2025-09-12DOI: 10.1016/j.isci.2025.113457
Jean Pierre Bikorimana, Nathanael A. Caveney, Nehme EL-Hachem, Gabrielle A. Mandl, John A. Capobianco, Daniela Stanga, Jamilah Abusarah, Mark A. Hancock, Roudy Farah, Marina P. Gonçalves, Darryl Falzarano, Mingmin Liao, Glenn Hamonic, Qiang Liu, Simon Beaudoin, Sebastien Talbot, Moutih Rafei
{"title":"A Spike-Accum bioconjugate protein vaccine confers potent SARS-CoV-2-specific immunity","authors":"Jean Pierre Bikorimana, Nathanael A. Caveney, Nehme EL-Hachem, Gabrielle A. Mandl, John A. Capobianco, Daniela Stanga, Jamilah Abusarah, Mark A. Hancock, Roudy Farah, Marina P. Gonçalves, Darryl Falzarano, Mingmin Liao, Glenn Hamonic, Qiang Liu, Simon Beaudoin, Sebastien Talbot, Moutih Rafei","doi":"10.1016/j.isci.2025.113457","DOIUrl":"10.1016/j.isci.2025.113457","url":null,"abstract":"","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113457"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048011","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}
iSciencePub Date : 2025-09-12eCollection Date: 2025-10-17DOI: 10.1016/j.isci.2025.113561
Christina Holzinger, Elena A Ritschard, Pamela Imperadore, Giovanna Ponte, Caroline B Albertin, Graziano Fiorito, Oleg Simakov
{"title":"Characterization of C2H2 superfamily expansions in cephalopods and their contribution to nervous system evolution.","authors":"Christina Holzinger, Elena A Ritschard, Pamela Imperadore, Giovanna Ponte, Caroline B Albertin, Graziano Fiorito, Oleg Simakov","doi":"10.1016/j.isci.2025.113561","DOIUrl":"10.1016/j.isci.2025.113561","url":null,"abstract":"<p><p>Zinc finger proteins comprise a large family of transcription factors involved in diverse processes, from suppression of transposable elements to regulation of neuronal development. In some clades, including vertebrates and coleoid cephalopods, members of the Cys2His2-type (C2H2) class of zinc fingers were shown to be expanded and likely relevant for neuron differentiation. Using genomic data from three octopus and three squid species, we show that C2H2 evolutionary history can be subdivided into duplication steps: (1) the coleoid expansions, (2) octopus-specific expansions, and (3) squid-specific expansions. While the overall expression patterns are consistent among those expansions and are associated with nervous tissues, the coleoid-specific duplicates showed the highest expression levels compared to all other C2H2 genes. We also found that C2H2 duplicates segregated into different co-expression modules, some associated with other duplicated gene families. We propose a scenario of functional divergence of C2H2 duplicates related to regulation within the cephalopod nervous system.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"113561"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278526","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}
iSciencePub Date : 2025-09-12eCollection Date: 2025-10-17DOI: 10.1016/j.isci.2025.113551
Jingjing Wu, Tanchun Yu, Shiqi Liu, Jie Wang, Peng Yin, Jiangmei Liu, Yalan Li, Rujia Miao, Hong Yuan, Yao Lu, Maigeng Zhou
{"title":"Mortality risk and vulnerability to hot nights in mainland China.","authors":"Jingjing Wu, Tanchun Yu, Shiqi Liu, Jie Wang, Peng Yin, Jiangmei Liu, Yalan Li, Rujia Miao, Hong Yuan, Yao Lu, Maigeng Zhou","doi":"10.1016/j.isci.2025.113551","DOIUrl":"10.1016/j.isci.2025.113551","url":null,"abstract":"<p><p>Although high temperatures pose major public health risks, limited research has focused on nighttime heat, especially in developing countries. Evidence on the health impacts of hot nights for vulnerable groups remains scarce. We conducted a nationwide time-series study using data from China's Disease Surveillance Point system between 2015 and 2019 (May-September). Hot nights, defined as daily minimum temperatures above the 95th percentile, were assessed using hot night excess (HNE) and hot night duration (HND). We evaluated all-cause and cardiovascular mortality risks associated with hot night exposure and identified vulnerable populations through stratified analyses. Hot nights significantly increased both all-cause and cardiovascular mortality across mainland China, with peaking immediately and lasting up to five days. Older adults and females were particularly susceptible. These findings highlight the urgent need to address the health impacts of nighttime heat, especially among vulnerable populations, and support the development of targeted strategies to reduce heat-related mortality.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"113551"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12514547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278638","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}
iSciencePub Date : 2025-09-12eCollection Date: 2025-10-17DOI: 10.1016/j.isci.2025.113568
Juncong Hu, Liming Zhang, Zhibin Wang, Lei Shi, Yang Zhang, Tangyou Mao, Xiaowei Chen, Wenjing Pei
{"title":"Modulation of distinct gut microbiota signatures in acute and chronic DSS-colitis by Bawei Huangqin enema in mice.","authors":"Juncong Hu, Liming Zhang, Zhibin Wang, Lei Shi, Yang Zhang, Tangyou Mao, Xiaowei Chen, Wenjing Pei","doi":"10.1016/j.isci.2025.113568","DOIUrl":"https://doi.org/10.1016/j.isci.2025.113568","url":null,"abstract":"<p><p>Intestinal microbiota plays a key role in ulcerative colitis (UC), and its composition may vary between the disease's acute (AUC) and chronic (CUC) stages. Using dextran sulfate sodium-induced mice models of AUC and CUC, this study characterized their distinct microbial dysbiosis patterns and evaluated the efficacy of a traditional Chinese medicine formula, Bawei Huangqin Enema (BHE). BHE treatment effectively alleviated colonic inflammation in both models. This was achieved by remodeling the gut microbiota in a stage-specific manner and by enhancing intestinal barrier integrity through the upregulation of tight junction proteins Occludin and MUC2. These findings highlight the distinct microbial features of AUC versus CUC and suggest that BHE's therapeutic potential derives from its dual regulation of the microbiome and intestinal barrier, supporting a multi-target approach for managing UC.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"113568"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12539248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342368","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}
iSciencePub Date : 2025-09-12eCollection Date: 2025-10-17DOI: 10.1016/j.isci.2025.113556
Mingdong Liu, Ahmed Rishiq, Yoav Charpak-Amikam, Fubin Li, Ofer Mandelboim
{"title":"NKp46 recognizes the hyphal form of Candida albicans and mediates protective antifungal immunity.","authors":"Mingdong Liu, Ahmed Rishiq, Yoav Charpak-Amikam, Fubin Li, Ofer Mandelboim","doi":"10.1016/j.isci.2025.113556","DOIUrl":"10.1016/j.isci.2025.113556","url":null,"abstract":"<p><p><i>Candida albicans</i> is an opportunistic fungal pathogen whose ability to switch between yeast and hyphal forms is central to its virulence. Natural killer (NK) cells are critical components of innate antifungal defense, yet the mechanisms by which they detect fungal morphology have remained unclear. We show that NKp46 (NCR1 in mice), an activating receptor on NK cells, directly recognizes the hyphal form of C. albicans but not yeast. Using image flow cytometry and receptor-ligand binding assays with NKp46-Ig and NCR1-Ig fusion proteins, we demonstrate that NKp46 engagement is mediated through its D2 domain and is independent of sialic acid interactions. Functional blockade of NKp46 significantly reduces NK cell degranulation and fungal killing, while NCR1-deficient mice display heightened susceptibility to systemic candidiasis. These findings identify NKp46 as a critical sensor of fungal morphology and highlight its importance in shaping early antifungal immunity.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"113556"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278677","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":"Urothelial collective-gliding response acts as a toll-like receptor 4-associated defense mechanism","authors":"Ning Zhang , Takeshi Sano , Katsuhiro Ito , Shinji Ito , Ryosuke Ikeuchi , Hideaki Takada , Kenji Nakamura , Toru Sakatani , Akihiro Hamada , Masashi Takeda , Kaoru Murakami , Yuki Kita , Takayuki Sumiyoshi , Takayuki Goto , Ryoichi Saito , Osamu Ogawa , Michiyuki Matsuda , Takashi Kobayashi","doi":"10.1016/j.isci.2025.113553","DOIUrl":"10.1016/j.isci.2025.113553","url":null,"abstract":"<div><div>Collective cell migration (CCM) is characterized by the coordinated movement of cell groups while maintaining cell-to-cell cohesion. Despite extensive research on CCM, the collective migration of mature epithelial cells over the extracellular matrix in response to external stimuli has not been reported. Using intravital imaging in mice, we identified urothelial CCM (UCCM) triggered by immunogenic substances, including bladder cancer cells (MB49) and uropathogenic <em>Escherichia coli</em> (UPEC). Integrin signaling inhibitors suppress UCCM, significantly enhancing MB49 tumor growth and UPEC bladder infection. UCCM initiation involves Toll-like receptor 4 (TLR4), we designated this TLR4-associated UCCM as the urothelial collective-gliding response (UCGR). Downstream of integrin signaling, urothelial matrix metalloproteinases (MMP)-8 and MMP-9 mediate UCGR. Intravesical instillation of these factors accelerates UCCM and inhibits tumor growth and infection. UCGR may represent a TLR4-associated defense mechanism, offering potential therapeutic strategies for bladder disorders such as refractory cystitis and recurrent non-muscle invasive bladder cancer after endoscopic resection.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113553"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155969","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}
iSciencePub Date : 2025-09-12eCollection Date: 2025-10-17DOI: 10.1016/j.isci.2025.113548
Ruoxi Pi, Nancy Q Zhao, Allison J Bien, Thanmayi Ranganath, Christof Seiler, Susan Holmes, Alexander Marson, David N Nguyen, Catherine A Blish
{"title":"NKp30 and NKG2D contribute to natural killer cell-mediated recognition of HIV-infected cells.","authors":"Ruoxi Pi, Nancy Q Zhao, Allison J Bien, Thanmayi Ranganath, Christof Seiler, Susan Holmes, Alexander Marson, David N Nguyen, Catherine A Blish","doi":"10.1016/j.isci.2025.113548","DOIUrl":"10.1016/j.isci.2025.113548","url":null,"abstract":"<p><p>Natural killer (NK) cells respond rapidly in early HIV-1 infection. HIV-1 prevention and control strategies harnessing NK cells could be enabled by mechanistic understanding of how NK cells recognize HIV-infected T cells. Here, we profiled the phenotype of human primary NK cells responsive to autologous newly HIV-infected CD4 T cells <i>in vitro</i>. We characterized the patterns of NK cell ligand expression on CD4 T cells at baseline and after infection with a panel of transmitted/founder HIV-1 strains to identify key receptor-ligand pairings. CRISPR editing of CD4 T cells to knock out the NKp30 ligand B7-H6, or the NKG2D ligand MICB reduced NK cell responses to HIV-infected cells in some donors. Blockade of NKp30 or NKG2D on NK cells compromised their specificity of killing HIV-infected cells. Collectively, we identified receptor-ligand pairs including NKp30:B7-H6 and NKG2D:MICB that contribute to NK cell recognition of HIV-infected cells.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"113548"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12514549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278718","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}