iSciencePub Date : 2025-09-02DOI: 10.1016/j.isci.2025.113491
Yongshun Liu , Wenpeng Huang , Jessica C. Hsu , Zhaonan Sun , Weibo Cai , Lei Kang
{"title":"Targeting Claudin18.2 for cancer theranostics: From molecular imaging to precision therapy","authors":"Yongshun Liu , Wenpeng Huang , Jessica C. Hsu , Zhaonan Sun , Weibo Cai , Lei Kang","doi":"10.1016/j.isci.2025.113491","DOIUrl":"10.1016/j.isci.2025.113491","url":null,"abstract":"<div><div>Claudin18.2 (CLDN18.2), a specific tight junction protein isoform, is minimally expressed in normal gastric mucosa but aberrantly overexpressed in various cancers. It plays a key role in regulating tumor cell differentiation, proliferation, and migration, making it an attractive therapeutic target, especially in gastric cancer. Moreover, molecular imaging techniques such as immuno-positron emission tomography, immuno-single photon emission computed tomography, and near-infrared fluorescence imaging enable non-invasive evaluation of CLDN18.2 expression, improving diagnosis and guiding personalized treatment. This review summarizes recent advances in CLDN18.2-targeted therapies and molecular imaging for cancer management. We outline the biomarker’s biological functions and signaling pathways across cancers, highlighting the development of precision therapeutics. We also discuss applications and limitations of CLDN18.2-targeted theranostics in digestive malignancies and address clinical translation challenges and future directions.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113491"},"PeriodicalIF":4.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107330","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 : 2025-09-02DOI: 10.1016/j.isci.2025.113488
Ruiyi Qiu , Qianqian Hu , Wenbo Liu , Meiquan Qiu , Chuanwei Yang , Binglian Zheng , Ji Yang
{"title":"Genome-wide identification and functional prediction of long non-coding RNAs in plastic growth in Alternanthera philoxeroides","authors":"Ruiyi Qiu , Qianqian Hu , Wenbo Liu , Meiquan Qiu , Chuanwei Yang , Binglian Zheng , Ji Yang","doi":"10.1016/j.isci.2025.113488","DOIUrl":"10.1016/j.isci.2025.113488","url":null,"abstract":"<div><div>Plants have a remarkable ability to alter their growth and development to adapt to fluctuating environments. Epigenetics plays a pivotal role in regulating plastic phenotypes. Based on long-read PacBio sequencing and time-course gene expression profiling, a genome-wide survey and functional prediction of lncRNAs potentially involved in submergence-induced plastic growth was conducted in <em>A. philoxeroides</em>. A total of 141 submergence-responsive lncRNAs were identified, with their <em>cis</em>- and <em>trans</em>-targeting genes being predicted. Functional annotation and validation of lncRNA targets indicated the significant roles of <em>lncRNA14247</em>, <em>lncRNA13847</em>, and <em>lncRNA12385</em> on phytohormone homeostasis by mediating crosstalk between various phytohormones upon submergence, and thereby impacting plastic development. The results also unveiled the potential roles of <em>lncRNA13847</em> and <em>lncRNA7566</em> in mediating submergence-induced growth alterations by targeting light signal components, such as PIFs. These findings highlighted the significance of lncRNAs in submergence responses and provided insights into the molecular underpinnings of phenotypic plasticity in <em>A. philoxeroides</em>.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113488"},"PeriodicalIF":4.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107466","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 : 2025-09-02DOI: 10.1016/j.isci.2025.113473
John Osei Sekyere , Jason Trama , Martin Adelson , Charulata Trikannad , Desiree DiBlasi , Rachel Schuster , Jing Jing Yang , Eli Mordechai
{"title":"Lactobacillus-rich cervicovaginal microbiome associated with lower BV, HPV, and cytology outcomes in women","authors":"John Osei Sekyere , Jason Trama , Martin Adelson , Charulata Trikannad , Desiree DiBlasi , Rachel Schuster , Jing Jing Yang , Eli Mordechai","doi":"10.1016/j.isci.2025.113473","DOIUrl":"10.1016/j.isci.2025.113473","url":null,"abstract":"<div><div>The cervicovaginal microbiome modulates susceptibility to bacterial vaginosis (BV), high-risk human papillomavirus (hrHPV) infection, and epithelial cell abnormalities that precede cervical cancer. We retrospectively analyzed 15 607 qPCR-profiled cervicovaginal specimens from U.S. women (ages 14–95; 32 states) and integrated microbiome abundances, hrHPV genotyping, Pap-cytology, and demographics. BV was present in 53% and hrHPV in 11% of samples. Lactobacillus crispatus, L. gasseri, and L. jensenii were enriched in BV-negative and cytologically normal (NILM) samples, whereas L. iners and BV-associated anaerobes co-occurred with hrHPV and abnormal cytology. Machine-learning models confirmed age, hrHPV status, and L. crispatus abundance as the strongest multivariate predictors of BV and cytological outcomes (BV AUROC ≈0.97). Interaction analyses revealed synergistic associations between specific hrHPV genotypes and Gardnerella/Fannyhessea that further increased cytological risk. These findings underscore the clinical value of microbiome profiling and support probiotic strategies that promote protective Lactobacillus communities to reduce BV and hrHPV-related cervical pathology.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113473"},"PeriodicalIF":4.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061180","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 : 2025-09-02DOI: 10.1016/j.isci.2025.113493
Bin Fan , Jiamin Guo , Caixia Lei , Sen Yang , Zining Meng , Junyao Peng , Yongjian Yang , Yubang Shen , Yuanyou Li , Le Wang
{"title":"Haplotype-resolved genomics identifies cyp19a1a as a candidate master sex-determining gene in golden trevally (Gnathanodon speciosus)","authors":"Bin Fan , Jiamin Guo , Caixia Lei , Sen Yang , Zining Meng , Junyao Peng , Yongjian Yang , Yubang Shen , Yuanyou Li , Le Wang","doi":"10.1016/j.isci.2025.113493","DOIUrl":"10.1016/j.isci.2025.113493","url":null,"abstract":"<div><div>Teleost fish exhibit diverse genetic sex determination systems, offering opportunities to understand its genetic basis and insights into sex chromosome evolution. The golden trevally (<em>Gnathanodon speciosus</em>), a commercially important Carangidae species, was studied to uncover its sex determination mechanism. We generated haplotype-resolved, chromosome-level genome assemblies for both sexes and identified a ZW system with a ∼90 kb sex-determining region (SDR) on Chr1. Within the SDR, <em>cyp19a1a</em> is uniquely expressed from the W allele prior to gonadal differentiation. A ∼1-kb upstream region of <em>cyp19a1a</em> harbors fixed variants between sexes. Reporter gene assays reveal that these variants reduce promoter activity in the Z allele, likely silencing <em>cyp19a1aZ</em>. This suggests that allelic diversification led to the emergence of <em>cyp19a1aW</em> as the master sex-determining gene. Minimal divergence in the SDR implies a recent origin of sex chromosomes. These findings provide key genomic resources and insights into sex determination evolution in teleosts.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113493"},"PeriodicalIF":4.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107364","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 : 2025-09-02DOI: 10.1016/j.isci.2025.113484
Matteo Buffi , Silvia Giangaspero , Valerio Foiada , Loïc Puthod , Guillaume Cailleau , Aaron J. Robinson , Julia M. Kelliher , Patrick S.G. Chain , Daniel Oberson , Markus Künzler , Saskia Bindschedler , Lorenzo Pirrami , Pilar Junier
{"title":"Detection of electrical signals in fungal mycelia in response to external stimuli","authors":"Matteo Buffi , Silvia Giangaspero , Valerio Foiada , Loïc Puthod , Guillaume Cailleau , Aaron J. Robinson , Julia M. Kelliher , Patrick S.G. Chain , Daniel Oberson , Markus Künzler , Saskia Bindschedler , Lorenzo Pirrami , Pilar Junier","doi":"10.1016/j.isci.2025.113484","DOIUrl":"10.1016/j.isci.2025.113484","url":null,"abstract":"<div><div>Electrical signaling is a crucial mechanism for intercellular communication across diverse biological systems. Despite evidence of electrical activity in fungal mycelia, a standardized, reproducible method for detecting these signals is lacking. In this study, we developed a novel approach using printed circuit boards with embedded differential electrodes to record extracellular voltage fluctuations in mycelium. By incorporating a Faraday cage and short-time Fourier transform analysis, we minimized noise and extracted relevant frequency patterns. Our findings revealed electrical activity correlated with fungal growth that varied with biocide treatments. The results support the biological origin of these signals, suggesting a role in environmental adaptation. This study provides a robust framework for further exploration of fungal electrophysiology, with implications for understanding signaling mechanisms in mycelial networks.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113484"},"PeriodicalIF":4.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107371","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 : 2025-09-02DOI: 10.1016/j.isci.2025.113392
Gabriela Amorós , José S. Carrión , Federica Crivellaro , Ana B. Marín-Arroyo
{"title":"Out of the cave: Rewilding deep time at the Venice Biennale","authors":"Gabriela Amorós , José S. Carrión , Federica Crivellaro , Ana B. Marín-Arroyo","doi":"10.1016/j.isci.2025.113392","DOIUrl":"10.1016/j.isci.2025.113392","url":null,"abstract":"<div><div><em>Out of the Cave</em>, part of the 2025 Venice Architecture Biennale, reimagines prehistoric human life through scientifically grounded paleoart. This visual installation bridges deep-time knowledge with contemporary ecological and ethical issues. By integrating paleoecological data, biodiversity representation, and dietary insight, the project invites reflection on sustainability and modernity. This Backstory outlines the scientific and conceptual foundations of the artwork, offering a model for transdisciplinary practice at the intersection of biology, anthropology, and spatial design.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 9","pages":"Article 113392"},"PeriodicalIF":4.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925130","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 : 2025-09-01DOI: 10.1016/j.isci.2025.113471
Junyan Xia (夏君彦) , Yibing Nong (农一兵) , Jun Teng (滕俊) , Shafeeq A. Mohammed , Jing Liu (刘静) , Yanting Pang (庞彦廷) , Sarah Costantino , Frank Ruschitzka , Nazha Hamdani , Mahmoud Abdellatif , Qian Lin (林谦) , Francesco Paneni
{"title":"Unlocking metabolic flexibility in heart failure with preserved ejection fraction: Bridging fundamental mechanisms to clinical innovation","authors":"Junyan Xia (夏君彦) , Yibing Nong (农一兵) , Jun Teng (滕俊) , Shafeeq A. Mohammed , Jing Liu (刘静) , Yanting Pang (庞彦廷) , Sarah Costantino , Frank Ruschitzka , Nazha Hamdani , Mahmoud Abdellatif , Qian Lin (林谦) , Francesco Paneni","doi":"10.1016/j.isci.2025.113471","DOIUrl":"10.1016/j.isci.2025.113471","url":null,"abstract":"<div><div>Heart failure is often described as a condition of “energy depletion.” However, in heart failure with preserved ejection fraction (HFpEF), particularly when associated with metabolic conditions such as obesity and diabetes, the heart may face a state of fuel overload. This fuel overload disrupts mitochondrial function, leading to the heart’s inability to effectively adjust substrate utilization in response to variations in nutritional status, energy substrate availability, and hemodynamic load, resulting in loss of metabolic flexibility and subsequent adverse effects on cardiac function and structure. Thus, an in-depth analysis of the role of metabolic flexibility in the pathophysiology of HFpEF could pave the way to addressing this clinical challenge. This review addresses: (1) the alterations in metabolic flexibility observed in cardiometabolic disease and HFpEF; (2) the implications of metabolic flexibility in the staging, classification, diagnosis, and prognosis of HFpEF; and (3) current HFpEF therapeutic strategies that improve myocardial metabolic flexibility.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113471"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048009","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 : 2025-09-01DOI: 10.1016/j.isci.2025.113479
Marissa E. Linger , Sytze H.T. Jorritsma , Jonna Bloeme-ter Horst , Jessika C. Zevenhoven-Dobbe , Finn Rijlaarsdam , Emil Colstrup , Macha Beijnes , Jutte J.C. de Vries , Ramon Arens , Rajagopal Murugan , Sebenzile K. Myeni , in collaboration with BREAK COVID group
{"title":"Bivalent mRNA vaccine booster enhances immunity against XBB.1.5 more effectively than breakthrough infection in K18-hACE2 mice","authors":"Marissa E. Linger , Sytze H.T. Jorritsma , Jonna Bloeme-ter Horst , Jessika C. Zevenhoven-Dobbe , Finn Rijlaarsdam , Emil Colstrup , Macha Beijnes , Jutte J.C. de Vries , Ramon Arens , Rajagopal Murugan , Sebenzile K. Myeni , in collaboration with BREAK COVID group","doi":"10.1016/j.isci.2025.113479","DOIUrl":"10.1016/j.isci.2025.113479","url":null,"abstract":"<div><div>The rapid emergence of SARS-CoV-2 Omicron subvariants, including the highly immune-evasive XBB.1.5 lineage, continues to challenge vaccine effectiveness. We evaluated immune responses and protection against XBB.1.5 challenge in K18-hACE2 mice receiving two or three doses of a bivalent mRNA vaccine (encoding Wuhan-1 and Omicron BA.4/5 spike) or two doses followed by intranasal XBB.1.5 exposure. Homologous boosting with bivalent vaccine induced stronger neutralizing antibody and cellular immune responses than breakthrough infection against the antigenically distant XBB.1.5 variant. A two-dose series alone protected mice from severe disease, but boosting further enhanced protection, reducing lung viral RNA and inflammation. Although productive infection following intranasal exposure was not confirmed, enhanced responses and viral control suggest reactivation of immune memory. Overall, homologous boosting with the bivalent vaccine enhances cross-variant immunity and protects against XBB.1.5 in a naive mouse model, supporting the utility of updated vaccines in improving immune breadth and protection against emerging SARS-CoV-2 variants.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113479"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107327","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 : 2025-09-01DOI: 10.1016/j.isci.2025.113474
Jonathan A. DiRusso , Lingyu Zhan , Yu Tao , Allison L. Wang , Xinyu Xiang , Alexander C. Robbins , Azra J. Cruz , Wanlu Liu , Amander T. Clark
{"title":"Sex-specific expression and function of TRIM28 during mouse primordial germ differentiation","authors":"Jonathan A. DiRusso , Lingyu Zhan , Yu Tao , Allison L. Wang , Xinyu Xiang , Alexander C. Robbins , Azra J. Cruz , Wanlu Liu , Amander T. Clark","doi":"10.1016/j.isci.2025.113474","DOIUrl":"10.1016/j.isci.2025.113474","url":null,"abstract":"<div><div>Mammalian primordial germ cells (PGCs) are embryonic precursors to the adult germline and must facilitate high-fidelity transfer of genomic material from one generation to the next. Transposable elements (TEs) represent an ongoing threat to genomic fidelity and are therefore tightly controlled during embryonic germline development. Here, we find that some TEs change in accessibility during normal PGC differentiation, while others are constitutively repressed by tripartite motif-containing 28 (TRIM28), a master TE regulator. We find that TRIM28 itself is regulated in a sex-specific manner and represses sex-specific TEs. In both testicular and ovarian PGCs, TRIM28 protects against upregulation of 2-cell (2C)-associated genes, dysregulation of PGC differentiation, and incomplete activation of DAZL. This perturbs testicular and ovarian PGCs differently, with testicular PGCs failing to differentiate in embryonic life while ovarian PGCs inefficiently enter meiosis leading to a diminished ovarian reserve by the onset of sexual maturity.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113474"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107360","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 : 2025-09-01DOI: 10.1016/j.isci.2025.113475
Hsiuyi V. Chen , Siew-Wai Fong , Yun Shan Goh , Matthew Zirui Tay , Angeline Rouers , Zi Wei Chang , Andrea Wei Ming Chua , Liang Hui Loo , SCOPE cohort Study Group , Jean-Marc Chavatte , Raymond Tzer Pin Lin , Yee-Sin Leo , Chiea Chuen Khor , David C. Lye , Laurent Renia , Barnaby Edward Young , Lisa F.P. Ng
{"title":"Human indels as predictors of antibody responses to COVID-19 vaccines","authors":"Hsiuyi V. Chen , Siew-Wai Fong , Yun Shan Goh , Matthew Zirui Tay , Angeline Rouers , Zi Wei Chang , Andrea Wei Ming Chua , Liang Hui Loo , SCOPE cohort Study Group , Jean-Marc Chavatte , Raymond Tzer Pin Lin , Yee-Sin Leo , Chiea Chuen Khor , David C. Lye , Laurent Renia , Barnaby Edward Young , Lisa F.P. Ng","doi":"10.1016/j.isci.2025.113475","DOIUrl":"10.1016/j.isci.2025.113475","url":null,"abstract":"<div><div>Vaccine efficacy varies significantly among adults. This variability underlies the limitation of a one-size-fits-all vaccination strategy and the need for more personalized approaches. We investigated factors influencing inter-individual variability in antibody responses to COVID-19 mRNA vaccine among adults. Neutralizing antibody (nAb) levels after the first vaccine dose were associated with infection outcomes within 1 year after vaccination, suggesting their potential as a correlate of protection. Age, sex, and Chinese ethnicity were associated with nAb and anti-spike protein antibody levels. Two indels located at chr1:31433042 and chr15:76311269 showed significant association with antibody responses. Leveraging these host factors, we developed a Random Forest model that predicted vaccine-induced antibody responses with 72.7% accuracy for mRNA vaccine and 76.9% for the Sinopharm COVID-19 inactivated virus vaccine. These findings support predictive modeling as a tool to identify individuals at risk of low vaccine responses, enabling more targeted and effective vaccination strategies.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113475"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048004","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}