Pub Date : 2025-12-29DOI: 10.1016/j.isci.2025.114562
Pei-Cheng Shih , Masato Hirano , Shinichi Furuya
Executing complex movement sequences from memory is crucial for skillful motor actions such as musical performance and sports. While chunking helps memorization during practice, transitions between chunks may become vulnerable during execution. Here, we developed a novel paradigm combining chunked motor sequence memorization with online sensory perturbation to show that perturbations at chunk junctions induced larger errors than those within chunks and increased pupil diameter, reflecting elevated attentional load. Subsequent training focusing on bridging chunk junctions improved performance stability, as evidenced by reduced force variability during perturbation. EEG data further revealed elevated frontal theta power in response to perturbation, indicating greater cognitive effort. Critically, this disruption was reduced after training, suggesting more efficient memory retrieval. Together, these findings underscore the vulnerability of motor sequence retrieval at chunk junctions and highlight the potential of targeted training to stabilize execution and reduce cognitive load.
{"title":"Bridging chunks during complex movement sequence execution","authors":"Pei-Cheng Shih , Masato Hirano , Shinichi Furuya","doi":"10.1016/j.isci.2025.114562","DOIUrl":"10.1016/j.isci.2025.114562","url":null,"abstract":"<div><div>Executing complex movement sequences from memory is crucial for skillful motor actions such as musical performance and sports. While chunking helps memorization during practice, transitions between chunks may become vulnerable during execution. Here, we developed a novel paradigm combining chunked motor sequence memorization with online sensory perturbation to show that perturbations at chunk junctions induced larger errors than those within chunks and increased pupil diameter, reflecting elevated attentional load. Subsequent training focusing on bridging chunk junctions improved performance stability, as evidenced by reduced force variability during perturbation. EEG data further revealed elevated frontal theta power in response to perturbation, indicating greater cognitive effort. Critically, this disruption was reduced after training, suggesting more efficient memory retrieval. Together, these findings underscore the vulnerability of motor sequence retrieval at chunk junctions and highlight the potential of targeted training to stabilize execution and reduce cognitive load.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114562"},"PeriodicalIF":4.1,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924342","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}
Pub Date : 2025-12-29DOI: 10.1016/j.isci.2025.114570
Ámbar Pérez-García , Graciela Amanda , José F. López , Marc Rußwurm , Tim H.M. van Emmerik
Plastic pollution threatens terrestrial and aquatic ecosystems, and rivers play a central role in transporting and retaining plastics across landscapes. Effective mitigation requires scalable methods to identify riverine plastic accumulation hotspots. Here, we present a semi-automated, cloud-based pipeline that integrates satellite remote sensing and machine learning to detect river plastic hotspots. High-resolution PlanetScope imagery is used to annotate training regions, which are transferred to Sentinel-2 multispectral data to train Random Forest classifiers within Google Earth Engine. The approach is evaluated across three contrasting river systems—the Citarum (Indonesia), Motagua (Guatemala), and Odaw (Ghana)—to assess transferability under diverse environmental conditions. Intra-river transfer achieves up to 99.5% accuracy, while optimized inter-river transfer yields a plastic F1-score of 79%, outperforming previously reported results of 69%. By providing an open-access Google Earth Engine application, this work enables reproducible, large-scale monitoring of riverine plastic pollution and supports the development of global, satellite-based assessment strategies.
{"title":"River plastic hotspot detection from space","authors":"Ámbar Pérez-García , Graciela Amanda , José F. López , Marc Rußwurm , Tim H.M. van Emmerik","doi":"10.1016/j.isci.2025.114570","DOIUrl":"10.1016/j.isci.2025.114570","url":null,"abstract":"<div><div>Plastic pollution threatens terrestrial and aquatic ecosystems, and rivers play a central role in transporting and retaining plastics across landscapes. Effective mitigation requires scalable methods to identify riverine plastic accumulation hotspots. Here, we present a semi-automated, cloud-based pipeline that integrates satellite remote sensing and machine learning to detect river plastic hotspots. High-resolution PlanetScope imagery is used to annotate training regions, which are transferred to Sentinel-2 multispectral data to train Random Forest classifiers within Google Earth Engine. The approach is evaluated across three contrasting river systems—the Citarum (Indonesia), Motagua (Guatemala), and Odaw (Ghana)—to assess transferability under diverse environmental conditions. Intra-river transfer achieves up to 99.5% accuracy, while optimized inter-river transfer yields a plastic F1-score of 79%, outperforming previously reported results of 69%. By providing an open-access Google Earth Engine application, this work enables reproducible, large-scale monitoring of riverine plastic pollution and supports the development of global, satellite-based assessment strategies.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114570"},"PeriodicalIF":4.1,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975547","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}
Pub Date : 2025-12-29DOI: 10.1016/j.isci.2025.114480
Anita Wagner , Juulia H. Lautaoja-Kivipelto , Kalle Pehkonen , Antti Hassinen , Minna Kuusela , Lisa Röttger , Elena Herbers , Anna Ioannidou , Sophia Mädler , Ina Rothenaigner , Soumya Srinivasan , Sini Laasonen , M. Tanvir Rahman , Pinja Elomaa , Saija Kortetjärvi , Anneli Olsson , Olavi Ukkola , Kamyar Hadian , Matthias Mann , Hilkka Peltoniemi , Eija Pirinen
Mitochondrial abnormalities drive subcutaneous white adipose tissue dysfunction in obesity, yet in vitro models to study adipocyte mitochondria remain limited. Here, we establish a human subcutaneous adipocyte spheroid model to characterize mitochondrial metabolism under obesity-relevant conditions and drug exposure. Human preadipocyte spheroids were differentiated in ultra-low attachment plates for 3 weeks using thiazolidinedione-free medium. Matrigel embedding was incorporated into the protocol as it promoted mitochondrial network and respiration compared to scaffold-free conditions. Differentiated spheroids showed increased lipid accumulation, adipogenic gene expression, mitochondrial respiration, adiponectin secretion, and hormonal responsiveness. Lipid mixture administration during differentiation induced metabolic disturbances, including mitochondrial respiration failure, alongside increased mitochondrial biogenesis. Post-differentiation treatment with rosiglitazone, a peroxisome proliferator-activated receptor γ agonist, improved mitochondrial bioenergetics and adiponectin secretion in lipid mixture-administered adipocyte spheroids. Our model enables precise measurement of adipocyte mitochondria metabolism, providing a platform for mitochondria-focused research and drug discovery in obesity.
{"title":"In vitro model of human subcutaneous adipocyte spheroids for studying mitochondrial dysfunction and mitochondria activating compounds","authors":"Anita Wagner , Juulia H. Lautaoja-Kivipelto , Kalle Pehkonen , Antti Hassinen , Minna Kuusela , Lisa Röttger , Elena Herbers , Anna Ioannidou , Sophia Mädler , Ina Rothenaigner , Soumya Srinivasan , Sini Laasonen , M. Tanvir Rahman , Pinja Elomaa , Saija Kortetjärvi , Anneli Olsson , Olavi Ukkola , Kamyar Hadian , Matthias Mann , Hilkka Peltoniemi , Eija Pirinen","doi":"10.1016/j.isci.2025.114480","DOIUrl":"10.1016/j.isci.2025.114480","url":null,"abstract":"<div><div>Mitochondrial abnormalities drive subcutaneous white adipose tissue dysfunction in obesity, yet <em>in vitro</em> models to study adipocyte mitochondria remain limited. Here, we establish a human subcutaneous adipocyte spheroid model to characterize mitochondrial metabolism under obesity-relevant conditions and drug exposure. Human preadipocyte spheroids were differentiated in ultra-low attachment plates for 3 weeks using thiazolidinedione-free medium. Matrigel embedding was incorporated into the protocol as it promoted mitochondrial network and respiration compared to scaffold-free conditions. Differentiated spheroids showed increased lipid accumulation, adipogenic gene expression, mitochondrial respiration, adiponectin secretion, and hormonal responsiveness. Lipid mixture administration during differentiation induced metabolic disturbances, including mitochondrial respiration failure, alongside increased mitochondrial biogenesis. Post-differentiation treatment with rosiglitazone, a peroxisome proliferator-activated receptor γ agonist, improved mitochondrial bioenergetics and adiponectin secretion in lipid mixture-administered adipocyte spheroids. Our model enables precise measurement of adipocyte mitochondria metabolism, providing a platform for mitochondria-focused research and drug discovery in obesity.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114480"},"PeriodicalIF":4.1,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035714","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}
Pub Date : 2025-12-29DOI: 10.1016/j.isci.2025.114558
T.M. Mohiuddin , Chaoyu Zhang , Wenjie Sheng , Marwah Al-Rawe , Natalia El-Merhie , Felix Zeppernick , Ivo Meinhold-Heerlein , Ahmad Fawzi Hussain
Several strategies have gained attraction in cancer diagnosis and therapy, particularly to overcome the limitations associated with direct targeting approaches in radioimmunotherapy and photoimmunotherapy. Here, we have introduced a synthetic zipper-mediated pre-targeting system for near-infrared photoimmunotherapy (NIR-PIT) utilizing the IR700-conjugated Zip1-SNAP protein in combination with three scFv-ZIP2 fusion proteins targeting FOLR1, TROP2, and TF. In this two-step targeting approach, scFv-Zip2 proteins first bind to cancer-specific antigens, followed by hybridization with Zip1-SNAP-IR700 at cell surface via high-affinity zipper interaction. Upon NIR light irradiation, targeted cancer cells underwent selective phototoxicity in a concentration-dependent manner with IC50 range (∼104–1,179 nM). Notably, the treatment induced cell death in ∼86%–94% of cells and triggered ICD, as evidenced by increased (∼4– to 200-fold more) surface exposure of calreticulin, HSP70 and HSP90. These findings demonstrate that the synthetic zipper-mediated pre-targeting platform offers a promising and versatile strategy for enhancing the specificity and immunogenic potential of NIR-PIT in cancer therapy.
{"title":"Synthetic zipper mediated pre-targeting system for near-infrared photoimmunotherapy","authors":"T.M. Mohiuddin , Chaoyu Zhang , Wenjie Sheng , Marwah Al-Rawe , Natalia El-Merhie , Felix Zeppernick , Ivo Meinhold-Heerlein , Ahmad Fawzi Hussain","doi":"10.1016/j.isci.2025.114558","DOIUrl":"10.1016/j.isci.2025.114558","url":null,"abstract":"<div><div>Several strategies have gained attraction in cancer diagnosis and therapy, particularly to overcome the limitations associated with direct targeting approaches in radioimmunotherapy and photoimmunotherapy. Here, we have introduced a synthetic zipper-mediated pre-targeting system for near-infrared photoimmunotherapy (NIR-PIT) utilizing the IR700-conjugated Zip1-SNAP protein in combination with three scFv-ZIP2 fusion proteins targeting FOLR1, TROP2, and TF. In this two-step targeting approach, scFv-Zip2 proteins first bind to cancer-specific antigens, followed by hybridization with Zip1-SNAP-IR700 at cell surface via high-affinity zipper interaction. Upon NIR light irradiation, targeted cancer cells underwent selective phototoxicity in a concentration-dependent manner with IC<sub>50</sub> range (∼104–1,179 nM). Notably, the treatment induced cell death in ∼86%–94% of cells and triggered ICD, as evidenced by increased (∼4– to 200-fold more) surface exposure of calreticulin, HSP70 and HSP90. These findings demonstrate that the synthetic zipper-mediated pre-targeting platform offers a promising and versatile strategy for enhancing the specificity and immunogenic potential of NIR-PIT in cancer therapy.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114558"},"PeriodicalIF":4.1,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975592","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}
Pub Date : 2025-12-29eCollection Date: 2026-01-16DOI: 10.1016/j.isci.2025.114499
Yafen Wang, Xiaoshuang Wu, Xinlei Li, Zhixin Liu, Ning An, Shunli Gu, Yang He, Mu He, Dandan Yin, Yaozhen Chen, Xingbin Hu
The destruction of red blood cells by classical complement activation can form erythrocyte ghosts in immune-mediated hemolysis. However, the mechanisms involved in clearing these membrane remnants remain to be elucidated. In this study, a combination of in vivo models, in vitro macrophage co-culture systems, proteomic screening, and functional validation assays was employed to investigate the cellular processing of erythrocyte ghosts. We demonstrated that erythrocyte ghosts are engulfed by macrophage phagocytosis. Besides, a significant downregulation of CD47, a critical "don't-eat-me" signal, is observed on the membranes of erythrocyte ghosts due to ubiquitin-proteasome-mediated degradation, facilitating their phagocytic removal by macrophages. Moreover, the E3 ubiquitin ligase MARCH 1 was identified as the principal mechanistic regulator governing the loss of CD47. These findings uncover a critical pathway for the efficient clearance of hemolytic remnants, offer alternative perspectives on post-hemolytic immune homeostasis, and suggest potential therapeutic avenues for reducing complications associated with hemolysis.
{"title":"Ubiquitination and degradation of CD47 enhances macrophage phagocytosis of hemolytic erythrocytes.","authors":"Yafen Wang, Xiaoshuang Wu, Xinlei Li, Zhixin Liu, Ning An, Shunli Gu, Yang He, Mu He, Dandan Yin, Yaozhen Chen, Xingbin Hu","doi":"10.1016/j.isci.2025.114499","DOIUrl":"10.1016/j.isci.2025.114499","url":null,"abstract":"<p><p>The destruction of red blood cells by classical complement activation can form erythrocyte ghosts in immune-mediated hemolysis. However, the mechanisms involved in clearing these membrane remnants remain to be elucidated. In this study, a combination of <i>in vivo</i> models, <i>in vitro</i> macrophage co-culture systems, proteomic screening, and functional validation assays was employed to investigate the cellular processing of erythrocyte ghosts. We demonstrated that erythrocyte ghosts are engulfed by macrophage phagocytosis. Besides, a significant downregulation of CD47, a critical \"don't-eat-me\" signal, is observed on the membranes of erythrocyte ghosts due to ubiquitin-proteasome-mediated degradation, facilitating their phagocytic removal by macrophages. Moreover, the E3 ubiquitin ligase MARCH 1 was identified as the principal mechanistic regulator governing the loss of CD47. These findings uncover a critical pathway for the efficient clearance of hemolytic remnants, offer alternative perspectives on post-hemolytic immune homeostasis, and suggest potential therapeutic avenues for reducing complications associated with hemolysis.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114499"},"PeriodicalIF":4.1,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016846","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}
Pub Date : 2025-12-27DOI: 10.1016/j.isci.2025.114462
Wenfang Li , Wenting Kong , Benjamin Tawiah , Hao Jia
Conventional cathode materials for zinc-ion batteries (ZIBs) predominantly rely on ion-insertion electrochemistry, which inherently limits their specific capacity and restricts the full realization of ZIBs’ performance potential. In contrast, cathode materials based on conversion reactions offer a promising pathway toward achieving higher energy densities. Among them, zinc-sulfur (Zn-S) and zinc-iodine (Zn-I2) batteries have attracted considerable attention for their commercial viability, yet targeted reviews addressing their reaction mechanisms, recent advances, and current challenges remain relatively scarce. To address this gap, this review provides a concise overview of the reaction mechanisms and battery configurations pertinent to conversion-type cathodes in Zn-S and Zn-I2 systems. Furthermore, it critically examines the fundamental physicochemical and structural challenges inherent to these materials, along with an evaluation of engineered solutions and emerging technological innovations designed to overcome these limitations. Finally, it outlines prospective research directions and development opportunities for advancing conversion-type cathodes in next-generation ZIBs.
{"title":"Opportunities and challenges of conversion type cathodes in zinc sulfur and zinc iodine batteries","authors":"Wenfang Li , Wenting Kong , Benjamin Tawiah , Hao Jia","doi":"10.1016/j.isci.2025.114462","DOIUrl":"10.1016/j.isci.2025.114462","url":null,"abstract":"<div><div>Conventional cathode materials for zinc-ion batteries (ZIBs) predominantly rely on ion-insertion electrochemistry, which inherently limits their specific capacity and restricts the full realization of ZIBs’ performance potential. In contrast, cathode materials based on conversion reactions offer a promising pathway toward achieving higher energy densities. Among them, zinc-sulfur (Zn-S) and zinc-iodine (Zn-I<sub>2</sub>) batteries have attracted considerable attention for their commercial viability, yet targeted reviews addressing their reaction mechanisms, recent advances, and current challenges remain relatively scarce. To address this gap, this review provides a concise overview of the reaction mechanisms and battery configurations pertinent to conversion-type cathodes in Zn-S and Zn-I<sub>2</sub> systems. Furthermore, it critically examines the fundamental physicochemical and structural challenges inherent to these materials, along with an evaluation of engineered solutions and emerging technological innovations designed to overcome these limitations. Finally, it outlines prospective research directions and development opportunities for advancing conversion-type cathodes in next-generation ZIBs.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114462"},"PeriodicalIF":4.1,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975108","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}
Pub Date : 2025-12-27DOI: 10.1016/j.isci.2025.114511
Hao Che , Zhen-Jun Li , Ling Xu , Yang-Bing Du , Song-Ou Zhang , Xiao-Jiang Ying
Colorectal cancer (CRC) therapy is challenged by drug resistance and limited treatment efficacy. Mounting evidence now positions mitochondrial dysfunction as a central mediator of these challenges, making it a compelling therapeutic target. This review synthesizes findings demonstrating that targeting mitochondrial metabolism, apoptosis, dynamics, mitophagy, and intercellular transfer effectively overcomes chemoresistance and restores treatment sensitivity in CRC models. Key mechanisms include the reversal of the Warburg effect, reactivation of intrinsic apoptosis, and disruption of mitochondrial transfer. Clinically, mitochondrial-derived biomarkers, such as cell-free mtDNA, emerge as promising tools for non-invasive monitoring and prognosis. Furthermore, advancements in targeted delivery systems and supportive interventions such as exercise, are shown to enhance therapeutic efficacy and mitigate toxicity. We conclude that integrating mitochondrial-targeted strategies represents a transformative approach for CRC treatment, with future success hinging on overcoming delivery challenges and validating these strategies in personalized models.
{"title":"Advances in mitochondrial-targeted colorectal cancer therapy: Mechanistic insights and clinical translation","authors":"Hao Che , Zhen-Jun Li , Ling Xu , Yang-Bing Du , Song-Ou Zhang , Xiao-Jiang Ying","doi":"10.1016/j.isci.2025.114511","DOIUrl":"10.1016/j.isci.2025.114511","url":null,"abstract":"<div><div>Colorectal cancer (CRC) therapy is challenged by drug resistance and limited treatment efficacy. Mounting evidence now positions mitochondrial dysfunction as a central mediator of these challenges, making it a compelling therapeutic target. This review synthesizes findings demonstrating that targeting mitochondrial metabolism, apoptosis, dynamics, mitophagy, and intercellular transfer effectively overcomes chemoresistance and restores treatment sensitivity in CRC models. Key mechanisms include the reversal of the Warburg effect, reactivation of intrinsic apoptosis, and disruption of mitochondrial transfer. Clinically, mitochondrial-derived biomarkers, such as cell-free mtDNA, emerge as promising tools for non-invasive monitoring and prognosis. Furthermore, advancements in targeted delivery systems and supportive interventions such as exercise, are shown to enhance therapeutic efficacy and mitigate toxicity. We conclude that integrating mitochondrial-targeted strategies represents a transformative approach for CRC treatment, with future success hinging on overcoming delivery challenges and validating these strategies in personalized models.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114511"},"PeriodicalIF":4.1,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924367","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}
Pub Date : 2025-12-26eCollection Date: 2026-01-16DOI: 10.1016/j.isci.2025.114552
Gabriel Carreno-Galeano, Seema Dubey, Kenneth A Iczkowski, Peter Van Veldhuizen, Uzoma A Anele, Jamie C Messer, Murali K Ankem, Dev Karan
Immunotherapy has improved outcomes in many cancers, yet the clinical benefits remain limited in prostate cancer. We evaluated whether an adenovirus-based bivalent prostate cancer vaccine (Ad-PS2) targeting two tumor antigens could be strengthened by combination with immune checkpoint blockade. Using immunocompetent mouse models, we found that Ad-PS2 combined with low-dose anti-CTLA4 generated robust anti-tumor immunity capable of eliminating established tumors, exceeding the effects of either treatment alone. Tumor-free mice resisted subsequent tumor rechallenge, indicating durable immune protection. Tumor analysis revealed a significant increase in intratumor CD8+ T cell infiltration with Ad-PS2 and anti-CTLA4, whereas anti-PD1 alone produced minimal infiltration and, with the vaccine, provided no therapeutic advantage. These results highlight a mechanistically synergistic interaction between dual antigen-targeted vaccination and CTLA4 blockade and illustrate how rational combination immunotherapy can overcome resistance in prostate cancer. This work defines a strategy that could inform future translational approaches for improving immunologic control of prostate cancer.
{"title":"Combined prostate cancer vaccine plus immune checkpoint inhibition synergizes to eliminate prostate cancer.","authors":"Gabriel Carreno-Galeano, Seema Dubey, Kenneth A Iczkowski, Peter Van Veldhuizen, Uzoma A Anele, Jamie C Messer, Murali K Ankem, Dev Karan","doi":"10.1016/j.isci.2025.114552","DOIUrl":"10.1016/j.isci.2025.114552","url":null,"abstract":"<p><p>Immunotherapy has improved outcomes in many cancers, yet the clinical benefits remain limited in prostate cancer. We evaluated whether an adenovirus-based bivalent prostate cancer vaccine (Ad-PS2) targeting two tumor antigens could be strengthened by combination with immune checkpoint blockade. Using immunocompetent mouse models, we found that Ad-PS2 combined with low-dose anti-CTLA4 generated robust anti-tumor immunity capable of eliminating established tumors, exceeding the effects of either treatment alone. Tumor-free mice resisted subsequent tumor rechallenge, indicating durable immune protection. Tumor analysis revealed a significant increase in intratumor CD8<sup>+</sup> T cell infiltration with Ad-PS2 and anti-CTLA4, whereas anti-PD1 alone produced minimal infiltration and, with the vaccine, provided no therapeutic advantage. These results highlight a mechanistically synergistic interaction between dual antigen-targeted vaccination and CTLA4 blockade and illustrate how rational combination immunotherapy can overcome resistance in prostate cancer. This work defines a strategy that could inform future translational approaches for improving immunologic control of prostate cancer.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114552"},"PeriodicalIF":4.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016839","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}
Pub Date : 2025-12-26eCollection Date: 2026-01-16DOI: 10.1016/j.isci.2025.114529
Hendrik J Engelenburg, Aletta M R van den Bosch, J Q Alida Chen, Cheng-Chih Hsiao, Marie-José Melief, Adil Harroud, Inge Huitinga, Jörg Hamann, Joost Smolders
[This corrects the article DOI: 10.1016/j.isci.2025.112430.].
[这更正了文章DOI: 10.1016/j.i ssn .2025.112430.]。
{"title":"Erratum: Multiple sclerosis severity variant in <i>DYSF-ZNF638</i> locus associates with neuronal loss and inflammation.","authors":"Hendrik J Engelenburg, Aletta M R van den Bosch, J Q Alida Chen, Cheng-Chih Hsiao, Marie-José Melief, Adil Harroud, Inge Huitinga, Jörg Hamann, Joost Smolders","doi":"10.1016/j.isci.2025.114529","DOIUrl":"https://doi.org/10.1016/j.isci.2025.114529","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.isci.2025.112430.].</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114529"},"PeriodicalIF":4.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12797034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970356","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}
Pub Date : 2025-12-26DOI: 10.1016/j.isci.2025.114557
Ines Velazquez-Quesada , Vahid Alizadeh , Kara Allison , Elizaveta Belova , Svetllana Kallogjerovic , Natasha Hesketh , Xiaotian Zhang , Gareth Thomas , Erkan Tüzel , Bojana Gligorijevic
Peripheral innervation is increasingly recognized as a critical regulator of tumor progression, yet in vitro models that enable controlled study of axon-cancer cell interactions remain limited. Here, we present the Device for Axon-Cancer cell Interaction Testing in 2D and 3D (DACIT), a microfluidic platform that spatially separates neuronal somas from axons and cancer cells. This configuration supports experimental designs where compartments can be exposed to either identical or distinct conditions. Moreover, the channel height allows the incorporation and monitoring of tumor spheroids, enabling quantification of tumor growth and 3D invasion. We demonstrate DACIT compatibility with common cellular assays, including immunofluorescence, invadopodia assays, pharmacological perturbations, live-cell imaging, and 3D spheroid invasion. Together, these features establish DACIT as a versatile tool to interrogate how peripheral axons influence cancer cell behavior.
{"title":"DACIT device for axon cancer cell interaction testing in 2D and 3D","authors":"Ines Velazquez-Quesada , Vahid Alizadeh , Kara Allison , Elizaveta Belova , Svetllana Kallogjerovic , Natasha Hesketh , Xiaotian Zhang , Gareth Thomas , Erkan Tüzel , Bojana Gligorijevic","doi":"10.1016/j.isci.2025.114557","DOIUrl":"10.1016/j.isci.2025.114557","url":null,"abstract":"<div><div>Peripheral innervation is increasingly recognized as a critical regulator of tumor progression, yet <em>in vitro</em> models that enable controlled study of axon-cancer cell interactions remain limited. Here, we present the Device for Axon-Cancer cell Interaction Testing in 2D and 3D (DACIT), a microfluidic platform that spatially separates neuronal somas from axons and cancer cells. This configuration supports experimental designs where compartments can be exposed to either identical or distinct conditions. Moreover, the channel height allows the incorporation and monitoring of tumor spheroids, enabling quantification of tumor growth and 3D invasion. We demonstrate DACIT compatibility with common cellular assays, including immunofluorescence, invadopodia assays, pharmacological perturbations, live-cell imaging, and 3D spheroid invasion. Together, these features establish DACIT as a versatile tool to interrogate how peripheral axons influence cancer cell behavior.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114557"},"PeriodicalIF":4.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924368","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}
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