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}
{"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 : 2025-09-12DOI: 10.1016/j.isci.2025.113569
Boyang Ren , Ruoxing Li , Chien-Yu Lin , Chanhee Park , Sheng Wang , Andrew O. Suen , John Kessler , Shiming Yang , Rosemary Kozar , Lin Zou , Brittney Williams , Ziyi Li , Peter Hu , Wei Chao
{"title":"Nucleotide motif-guided selection of plasma microRNA biomarkers in trauma","authors":"Boyang Ren , Ruoxing Li , Chien-Yu Lin , Chanhee Park , Sheng Wang , Andrew O. Suen , John Kessler , Shiming Yang , Rosemary Kozar , Lin Zou , Brittney Williams , Ziyi Li , Peter Hu , Wei Chao","doi":"10.1016/j.isci.2025.113569","DOIUrl":"10.1016/j.isci.2025.113569","url":null,"abstract":"<div><div>Trauma remains a leading cause of morbidity and mortality in part due to complex pathophysiological responses. Yet our abilities to predict these changes are limited. Plasma miRNAs have been proposed as DAMPs that drive immune response and organ injury. Here, we test a panel of plasma miRNAs—selected based on next-generation sequencing and nucleotide motifs identified via a machine-learning algorithm—for their abilities to predict subclinical pathophysiological injuries. We find marked and severity-dependent increases in the miRNA biomarkers following trauma, which are closely associated with various injury markers. AUROC indicates that these biomarkers possess strong diagnostic and predictive abilities in overall trauma severity, organ injury, coagulation, endothelial activation, and inflammation. In a combined cohort of trauma and sepsis, miR-224-5p and miR-145-5p emerge as particularly effective in differentiating the two critical illnesses. These observations offer insights into potential values of the plasma miRNAs in the prediction of critical pathophysiological injury in trauma.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113569"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155983","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.2025.113554
Chunping Tian , Xiaowei Chang , Jiajun Wu , Linfeng Xiao , Jiani Du , Qianqian Hu , Yanling Yang
{"title":"Research progress of intestinal microbiota on cognitive dysfunction after spinal cord injury","authors":"Chunping Tian , Xiaowei Chang , Jiajun Wu , Linfeng Xiao , Jiani Du , Qianqian Hu , Yanling Yang","doi":"10.1016/j.isci.2025.113554","DOIUrl":"10.1016/j.isci.2025.113554","url":null,"abstract":"<div><div>Alterations in the gut microbiota are among the most common phenomena following spinal cord injury, often accompanied by cognitive impairment. Numerous studies have reported intrinsic links among these three aspects. However, the molecular mechanisms by which the gut microbiota influence cognitive function after spinal cord injury, as well as strategies for modulating the gut microbiota to treat cognitive deficits, remain inadequately summarized. Therefore, this review provides a comprehensive summary of the key mechanisms by which gut dysbiosis contributes to cognitive impairment and discusses therapeutic strategies targeting the gut microbiota. These insights may offer a theoretical basis for further research and microbiota-based drug development for cognitive dysfunction following spinal cord injury.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113554"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155981","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 : 2025-09-11DOI: 10.1016/j.isci.2025.113526
Yunfei Xia , Meizhu Zheng , Xue Li , Kai Song , Zhisheng Teng
{"title":"Enhancing biological imaging with high-performance probes based on thermally activated delayed fluorescence","authors":"Yunfei Xia , Meizhu Zheng , Xue Li , Kai Song , Zhisheng Teng","doi":"10.1016/j.isci.2025.113526","DOIUrl":"10.1016/j.isci.2025.113526","url":null,"abstract":"<div><div>Thermally activated delayed fluorescence (TADF) materials have gained significant attention in biological imaging due to their high quantum efficiency and capacity to suppress short-lived background fluorescence. This review comprehensively analyzes recent advancements in organic TADF probes, focusing on their photophysical mechanisms, structural design, and encapsulation strategies to improve biocompatibility and photostability. We highlight their applications in organelle-targeted imaging, dynamic live-cell tracking, and <em>in vivo</em> imaging in model organisms such as zebrafish and mice. Additionally, we discuss current challenges, including oxygen sensitivity and limited long-term stability. The development of high-performance TADF probes promises to enhance imaging quality, facilitate deeper tissue penetration, and support long-term cellular studies, thereby contributing substantially to biomedical research and diagnostic imaging.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113526"},"PeriodicalIF":4.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119808","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 : 2025-09-10DOI: 10.1016/j.isci.2025.113533
Paolo Becciu , Kim Schalcher , Estelle Milliet , James L. Savage , Andrea Romano , Bettina Almasi , Alexandre Roulin
{"title":"Real-time context-dependent cooperation in parental provisioning reveals fitness payoffs in barn owls","authors":"Paolo Becciu , Kim Schalcher , Estelle Milliet , James L. Savage , Andrea Romano , Bettina Almasi , Alexandre Roulin","doi":"10.1016/j.isci.2025.113533","DOIUrl":"10.1016/j.isci.2025.113533","url":null,"abstract":"<div><div>Parental cooperation in species with extended biparental care is essential for offspring survival, yet real-time negotiation and coordination in the wild remain poorly understood. We simultaneously Global Positioning System (GPS)- and accelerometer-tracked 68 breeding pairs of barn owls (<em>Tyto alba</em>) during chick rearing, quantifying parents’ hunting effort, prey deliveries, self-feeding, nest attendance, and partner encounters. Within pairs, parental investment was highly plastic, with low repeatability of nightly provisioning shares. Females increased provisioning when males underperformed or when foraging habitat was likely poor. Parents synchronized foraging schedules and nest visits, exhibiting turn-taking-like coordination; pairs that shared provisioning more equally foraged in parallel overnight and met frequently at the nest. We detected sequential, between-night adjustments, whereby effort on one night influenced provisioning the next. Pairs maintaining more equitable care achieved higher survival and growth in their later-hatching nestlings. Our findings demonstrate how high-resolution biologging reveals dynamic behavioral mechanisms underpinning flexible biparental care under ecological variability.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113533"},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107332","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 : 2025-09-10DOI: 10.1016/j.isci.2025.113545
Laura Horvathova , Priscilla Kinderman , Thijs Janzen , Baukje Nynke Hoogeboom , Franz J. Weissing , Nadine van Montfoort , Toos Daemen , Darshak K. Bhatt
{"title":"Alphavirus replicons encoding IFN-γ enhance cancer virotherapy by overcoming macrophage-mediated suppression","authors":"Laura Horvathova , Priscilla Kinderman , Thijs Janzen , Baukje Nynke Hoogeboom , Franz J. Weissing , Nadine van Montfoort , Toos Daemen , Darshak K. Bhatt","doi":"10.1016/j.isci.2025.113545","DOIUrl":"10.1016/j.isci.2025.113545","url":null,"abstract":"<div><div>Interference by tumor-associated macrophages may significantly reduce the efficacy of therapeutic viruses designed to infect cancer cells and activate anti-tumor T cells. Using a computational model, we hypothesized that viruses encoding a T cell-stimulating signal, like interferon-gamma (IFN-γ), could overcome this barrier. We engineered an alphavirus-based replicon expressing IFN-γ and evaluated its effect in various human-derived tumor-immune coculture systems and an <em>in vivo</em> murine model. While alphavirus replicons do not replicate in macrophages, macrophages acted as a barrier, limiting tumor infection in a frequency-dependent but phenotype-independent manner. Nonetheless, T cell activation occurred even when only a fraction of infected tumor cells expressed IFN-γ, regardless of macrophage presence, frequency, or phenotype. Additionally, viral stimulation drove macrophage repolarization toward a pro-inflammatory phenotype favoring T cell activation. These findings highlight a strategy for optimizing virotherapy in macrophage-rich tumors by designing viruses that stimulate T cell activation, ensuring therapeutic efficacy.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113545"},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155973","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 : 2025-09-10DOI: 10.1016/j.isci.2025.113541
Elisa Zuccoli , Haya Al Sawaf , Mona Tuzza , Sarah L. Nickels , Alise Zagare , Jens C. Schwamborn
{"title":"Reproducibility of PD patient-specific midbrain organoid data for in vitro disease modeling","authors":"Elisa Zuccoli , Haya Al Sawaf , Mona Tuzza , Sarah L. Nickels , Alise Zagare , Jens C. Schwamborn","doi":"10.1016/j.isci.2025.113541","DOIUrl":"10.1016/j.isci.2025.113541","url":null,"abstract":"<div><div>Midbrain organoids are advanced <em>in vitro</em> cellular models for disease modeling. They have been used successfully over the past decade for Parkinson’s disease (PD) research and drug development. The three-dimensional structure and multicellular composition allow disease research under more physiological conditions than is possible with conventional 2D cellular models. However, there are concerns in the field regarding the organoid batch-to-batch variability and thus the reproducibility of the results. In this manuscript, we generate multiple independent midbrain organoid batches derived from healthy individuals or glucocerebrosidase (GBA)-N370S mutation-carrying PD patients to evaluate the reproducibility of the GBA-N370S mutation-associated PD transcriptomic and metabolic signature as well as selected protein abundance. Our analysis shows that GBA-PD-associated phenotypes are reproducible across organoid generation batches and time points. This proves that midbrain organoids are not only suitable for PD <em>in vitro</em> modeling but also represent robust and highly reproducible cellular models.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113541"},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119804","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 : 2025-09-10DOI: 10.1016/j.isci.2025.113538
Tina Kwok , Ildefonso A. Silva-Junior , Sara Korpe , Haidong Dong , Jessica N. Lancaster
{"title":"Macrophage repolarization by immune checkpoint blockade drives T cell engagement in the tumor microenvironment","authors":"Tina Kwok , Ildefonso A. Silva-Junior , Sara Korpe , Haidong Dong , Jessica N. Lancaster","doi":"10.1016/j.isci.2025.113538","DOIUrl":"10.1016/j.isci.2025.113538","url":null,"abstract":"<div><div>Immunotherapy combinations can improve patient outcomes, yet the interactions within the tumor microenvironment (TME) that drive therapeutic synergy are poorly understood. Tumor establishment drives monocyte recruitment and differentiation into tumor-associated macrophages (TAMs), which have essential roles in coordinating immune responses and are thus attractive targets for therapeutic modulation. In a murine model of combination anti-programmed cell death protein 1 (PD-1) and its ligand (anti-PD-L1) checkpoint blockade, tumor control was associated with increased infiltration of CD8<sup>+</sup> T cells and M1-like repolarization of TAMs. Live-cell imaging of the tumor microenvironment revealed close contacts between tumor-infiltrating CD8<sup>+</sup> T cells and TAMs, in which the extent of the contact interfaces increased with combination immunotherapy. Treatment with anti-PD-L1 was able to increase macrophage expression of pro-inflammatory factors and phagocytic activity, suggesting a role for TAMs in reactivating CD8<sup>+</sup> T cells in the TME. However, co-treatment with anti-PD-1 was ultimately necessary for tumor control, indicating the need for combination targeting of the TME.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113538"},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119805","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}