iSciencePub Date : 2026-03-20Epub Date: 2026-01-29DOI: 10.1016/j.isci.2026.114852
Theresa Wrynn , Jason Osinski , Satrajit Sinha , Rose-Anne Romano
{"title":"Unveiling critical signaling pathways in the murine salivary gland and the role of midkine","authors":"Theresa Wrynn , Jason Osinski , Satrajit Sinha , Rose-Anne Romano","doi":"10.1016/j.isci.2026.114852","DOIUrl":"10.1016/j.isci.2026.114852","url":null,"abstract":"<div><div>Salivary gland (SG) development is a complex process involving coordinated signaling between epithelial and stromal cell populations. While some growth drivers and branching mechanisms are known, many intercellular communication pathways that underpin embryonic SG morphogenesis remain unidentified. We leveraged single cell RNA-sequencing datasets, from murine submandibular salivary glands at three embryonic stages to identify critical signaling networks. Using CellChat, we mapped global ligand-receptor interactions among different cell populations revealing an evolving signaling landscape during gland maturation. Our analysis highlighted both well-established and understudied pathways, including midkine (MDK) signaling. Functional experiments using embryonic SG explants demonstrated that MDK regulates branching morphogenesis via Rho-associated coiled coil containing protein kinase 1 (Rock1) signaling. Additionally, the key lineage driving transcription factor p63 was shown to act as primary mediator of the MDK/Rock1 axis. These findings uncover a comprehensive signaling code that guides SG development and offers new targets for follow-up studies into SG regeneration.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114852"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187223","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 : 2026-03-20eCollection Date: 2026-04-17DOI: 10.1016/j.isci.2026.115427
Koshiro Mitsui, Yoan Cherasse, Takeshi Sakurai, Aki Takahashi
{"title":"Lateral hypothalamus to dorsal raphe nucleus projections modulate intraspecific attack behavior in male mice.","authors":"Koshiro Mitsui, Yoan Cherasse, Takeshi Sakurai, Aki Takahashi","doi":"10.1016/j.isci.2026.115427","DOIUrl":"10.1016/j.isci.2026.115427","url":null,"abstract":"<p><p>Aggressive behavior comprises distinct components, including threat displays and direct physical attacks, that typically occur in a coordinated sequence. Here, we identify the lateral hypothalamus (LH) to dorsal raphe nucleus (DRN) projection as a key pathway that bidirectionally and selectively controls attack bites while leaving threat displays intact in male mice. Optogenetic activation of this pathway enhanced attack bites without affecting threats during intermale aggression and sustained attacks toward female intruders when such behavior would normally cease. This pathway activation also induced place avoidance, suggesting it generates aversive states that may drive aggressive arousal. Both chemogenetic and optogenetic inhibition selectively reduced attack bites without altering threat displays. These findings establish the LH-DRN projection as a functionally defined circuit that dissociates the regulation of direct physical aggression from social signaling, providing insights into how distinct aggressive components can be independently controlled and potentially contributing to maladaptive aggression patterns.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 4","pages":"115427"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721364","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 : 2026-03-20Epub Date: 2026-01-29DOI: 10.1016/j.isci.2026.114840
Yilong Cao , Chao Xu , Yuepeng Liu , Bei Shi , Xiaoling Li , Jiehan Li , Bowei Zhang , Zeyuan Zhang , Shengtao Dai , Qingyun Sun , Junfei Gu
{"title":"CCT3-mediated regulation of XPO1/RB1 axis stability promotes cellular senescence and tumor progression in clear cell renal carcinoma","authors":"Yilong Cao , Chao Xu , Yuepeng Liu , Bei Shi , Xiaoling Li , Jiehan Li , Bowei Zhang , Zeyuan Zhang , Shengtao Dai , Qingyun Sun , Junfei Gu","doi":"10.1016/j.isci.2026.114840","DOIUrl":"10.1016/j.isci.2026.114840","url":null,"abstract":"<div><div>Cellular senescence’s role in clear cell renal carcinoma (ccRCC) remains unclear. We identify CCT3 as a driver of ccRCC progression by enhancing XPO1 stability via correct folding, confirmed by Co-IP and GST pull-down. This promotes nuclear export of tumor suppressors such as RB1 and p21, suppressing cellular senescence. Indeed, experimental evidence showed significantly reduced senescence-associated β-galactosidase (SA-β-gal) activity and altered expression patterns of senescence markers (e.g., p21, CDK4, and cyclin D) in the presence of increased CCT3. Functionally, CCT3 depletion induced robust G1 phase arrest, promoted cellular senescence, and markedly diminished ccRCC cell proliferation, migration, and invasion <em>in vitro</em>. Crucially, <em>in vivo</em> studies demonstrated that the combined therapeutic intervention of CCT3 knockdown and the XPO1 inhibitor Selinexor significantly suppressed tumor growth in ccRCC xenograft models, validating the therapeutic potential of targeting the CCT3-XPO1 axis. In summary, our findings unveil a novel CCT3-XPO1-RB1 axis that orchestrates ccRCC progression by impairing cellular senescence, offering a promising therapeutic avenue for ccRCC treatment.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114840"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187159","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 : 2026-03-20Epub Date: 2026-01-30DOI: 10.1016/j.isci.2026.114871
Kara Rising , Mark Bulling , Michael Sweet
{"title":"Seagrass monitoring methods: Aligning expert opinion with practice","authors":"Kara Rising , Mark Bulling , Michael Sweet","doi":"10.1016/j.isci.2026.114871","DOIUrl":"10.1016/j.isci.2026.114871","url":null,"abstract":"<div><div>Seagrass meadows are vital ecosystems, yet methods to monitor their health lack standardization, which makes data comparison challenging. To identify key approaches and evaluate alignment with expert opinion, we compared the most used health monitoring methods across 500 studies with a survey of 34 experts. The most reported methods in studies were environmental parameters (44%), percent cover (41%), biomass (40%), distribution/extent (39%), and species composition (37%). Expert importance ratings closely matched: distribution/extent and species composition (100/100), percent cover (99/100), and environmental parameters (92/100). Notably, few studies used physiological-level (10.4%) methods. Experts also anticipated growing roles for remote sensing, eDNA, and AI-assisted image analysis. Together, this study shows a consensus around core, cost-effective methods despite limited integration across biological scales. To address this gap, we propose a multi-level monitoring framework that pairs traditional indicators with early-warning metrics to strengthen seagrass conservation and restoration at broader scales.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114871"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187257","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 : 2026-03-20Epub Date: 2026-01-29DOI: 10.1016/j.isci.2026.114849
Donggun Kim , Sin Young Choi , Chae Yeon Kim , Jeong Rae Yoo , Eui Tae Kim , Jihwan Park
{"title":"Discovery of key regulators in classical monocyte phenotypes linked to COVID-19 severity using single-cell multi-omics sequencing","authors":"Donggun Kim , Sin Young Choi , Chae Yeon Kim , Jeong Rae Yoo , Eui Tae Kim , Jihwan Park","doi":"10.1016/j.isci.2026.114849","DOIUrl":"10.1016/j.isci.2026.114849","url":null,"abstract":"<div><div>Dysregulated immune responses often accompany severe COVID-19, but the underlying epigenetic mechanisms driving monocyte heterogeneity and COVID-19 progression remain unclear. Here, we applied single-cell multi-omics profiling to peripheral blood mononuclear cells across healthy and four COVID-19 severity stages. We identified two severity-associated classical monocyte subtypes-IL7R+ and CD163+, These subtypes exhibit distinct transcriptional and epigenetic landscapes. By constructing a gene regulatory network and <em>in silico</em> perturbations, we revealed that ETS1 is a key driver of IL7R + monocytes with T cell-like signaling features and that JDP2 is a repressor that maintains the profibrotic, anti-inflammatory identity of CD163+ monocytes by suppressing AP-1 activity. These subtypes were enriched in the moderate-to-critical stages and exhibited signaling pathways associated with tissue remodeling and immune suppression. Our findings define monocyte heterogeneity as linked to COVID-19 severity and identify ETS1 and JDP2 as central regulators, offering insights into immune dysregulation, potential therapeutic targets for fibrosis, and long-term sequelae.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114849"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187258","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 : 2026-03-20Epub Date: 2026-01-24DOI: 10.1016/j.isci.2026.114789
Ziwen Yuan , Yafang Chen , Sicong Liu , Jiyuan Yang , Can Tang , Xuan He , Shifang Wang , Xudong Wang
{"title":"Advances in the study of nucleolar small RNAs in colorectal cancer","authors":"Ziwen Yuan , Yafang Chen , Sicong Liu , Jiyuan Yang , Can Tang , Xuan He , Shifang Wang , Xudong Wang","doi":"10.1016/j.isci.2026.114789","DOIUrl":"10.1016/j.isci.2026.114789","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is an important public health challenge worldwide, which has led to a continuous search for more precise diagnostic strategies. Recent studies have revealed that small nucleolar RNAs (snoRNAs) play an important role in CRC. In this article, we first summarize the molecular characteristics and physiological functions of snoRNAs, and then we discuss their mechanisms of action in colorectal carcinogenesis. A key focus is on the emerging potential of snoRNAs as liquid biopsy biomarkers and their prospects for clinical translation in cancer management.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114789"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187229","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 : 2026-03-20Epub Date: 2026-01-31DOI: 10.1016/j.isci.2026.114861
Guiqiu Li , Ying Wei , Wenzheng Wang , Zhili Hu , Qiaowen Yang , Lili He , Yun Gao , Xiulan Lai
{"title":"Multi-omics and machine learning-based profiling of severity signatures in Mycoplasma pneumoniae infection in children","authors":"Guiqiu Li , Ying Wei , Wenzheng Wang , Zhili Hu , Qiaowen Yang , Lili He , Yun Gao , Xiulan Lai","doi":"10.1016/j.isci.2026.114861","DOIUrl":"10.1016/j.isci.2026.114861","url":null,"abstract":"<div><div><em>Mycoplasma pneumoniae</em> pneumonia (MPP) is a common respiratory infection in children; however, the mechanisms driving its progression to severe disease remain poorly understood. This study employs a comprehensive proteomic and metabolomic approach to elucidate severity-related pathways and identify potential biomarkers for improved diagnosis and targeted therapy. By analyzing blood proteomes from pediatric patients with varying MPP severities alongside healthy controls, and integrating multi-omics data from bronchoalveolar lavage fluid (BALF), we uncovered key severity-associated proteins and metabolites linked to inflammatory and metabolic dysregulation such as efferocytosis pathway, and Fanconi anemia pathway. Machine learning analysis further identified 8 critical biomarkers that accurately distinguished between mild and severe MPP cases. The identification of severity-specific biomarkers offers a foundation for enhanced diagnostic precision, improved disease stratification, and the development of targeted therapeutic strategies to optimize the management of severe MPP in pediatric patients.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114861"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187221","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 : 2026-03-20Epub Date: 2026-01-29DOI: 10.1016/j.isci.2026.114856
Wei Zhou , Zhao Wei , Ning Feng , Mi Luo , Bingpeng Qu , Qiren Luo , Jianbing Zhang
{"title":"Urban forest plant diversity affects soil organic carbon by regulating functional genes in Nanning","authors":"Wei Zhou , Zhao Wei , Ning Feng , Mi Luo , Bingpeng Qu , Qiren Luo , Jianbing Zhang","doi":"10.1016/j.isci.2026.114856","DOIUrl":"10.1016/j.isci.2026.114856","url":null,"abstract":"<div><div>Urban forests serve as reservoirs of soil organic carbon (SOC) within ecosystems and play a critical role in the carbon (C) cycle. However, the regulatory mechanisms underlying SOC dynamics across urbanization gradients in urban forests remain poorly understood. In this study, we investigated the interrelationships among plant diversity, SOC and its oxidation-stable fractions, and functional genes across an urbanization gradient encompassing an urban center (UC), subcenter, suburb, and exurb. Our findings revealed that urbanization significantly enhanced plant diversity and altered SOC dynamics. UC exhibited higher plant diversity and increased concentrations of active SOC fractions. Although urbanization did not significantly affect microbial α-diversity, it selectively enriched the relative abundance of specific taxa. C sequestration-related functional genes, particularly K15635 and K01965, were strongly associated with the regulation of SOC dynamics in the urban forest. Our findings underscore the importance of conserving diverse tree communities to enhance the C-sequestration function of urban forests.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114856"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187217","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":"Defeated major resistance loci may act as Trojan horses compromising resistance pyramiding in grapevine","authors":"Tyrone Possamai , Sabine Wiedemann-Merdinoglu , Marie-Céline Lacombe , Marie-Annick Dorne , Erik Griem , René Fuchs , Jochen Bogs , Raymonde Baltenweck , Komlan Avia , Didier Merdinoglu , Philippe Hugueney","doi":"10.1016/j.isci.2026.114800","DOIUrl":"10.1016/j.isci.2026.114800","url":null,"abstract":"<div><div>Resistance breeding offers invaluable perspectives for environment-friendly crop protection, but its success may be limited by the breakdown of plant resistance by pathogen strains. With the breeding and use of varieties carrying multiple genetic resistances, grapevine (<em>Vitis</em> spp.) represents a distinctive model for perennials to investigate the agreement that pyramiding broadens and enhances the efficacy and durability of resistance. To this end, grapevine progenies segregating for four major resistance loci against <em>Plasmopara viticola</em> (<em>Rpvs</em>) were used to evaluate single and pyramided loci when confronted with naive and <em>Rpv</em>-breaking pathogen strains. In pyramiding, undefeated and defeated <em>Rpvs</em> provided either beneficial, neutral, or detrimental quantitative effects, depending on the loci combination and pathogen strain. In particular, the fact that defeated loci may compromise resistance highlighted important implications for the breeding of perennials. Thorough phenotypic investigations of pyramiding schemes emerge as a critical step for the effective and durable management of genetic resistances.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 3","pages":"Article 114800"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187214","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 : 2026-03-20eCollection Date: 2026-04-17DOI: 10.1016/j.isci.2026.115435
Konstantina Vasilakou, Philippe Nimmegeers, Pieter Billen, Steven Van Passel
{"title":"Prospective water scarcity footprint under climate change applied to bio-based sustainable aviation fuel production pathways.","authors":"Konstantina Vasilakou, Philippe Nimmegeers, Pieter Billen, Steven Van Passel","doi":"10.1016/j.isci.2026.115435","DOIUrl":"10.1016/j.isci.2026.115435","url":null,"abstract":"<p><p>The transition of aviation from fossil to sustainable aviation fuels (SAFs) raises concerns about its water requirements in an increasingly water-stressed world, highlighting the need for integrated water footprint assessments under climate change. This study first develops novel water scarcity footprint factors projected monthly and annually until 2099 at a 0.5° × 0.5° global resolution under eight climate change scenarios. Significant regional and temporal disparities are revealed, with future factors differing by more than 50% from historical values in many regions. Applying these dynamic factors to projected global SAF production shows that Asia contributes to more than 50% of the global future water scarcity footprint, while North America exhibits lower impacts despite high production volumes. By demonstrating that historical factors underestimate future impacts, particularly under high-emission scenarios, these findings emphasize the importance of prospective environmental assessments to ensure that energy transition does not endanger water security.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 4","pages":"115435"},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721303","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}