医学最新文献

{"title":"Parthenolide inhibits the progression of intrahepatic cholangiocarcinoma by promoting ferroptosis through inhibiting UBD.","authors":"Yuanzhu Xie, Jia Wang, Jia Zhou, Yuhuai Peng, Yizhi Wang, Yueren Wang, Yinghui Song","doi":"10.1080/15384047.2026.2664327","DOIUrl":"10.1080/15384047.2026.2664327","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the antitumor activity and molecular mechanism of Parthenolide (Par) against intrahepatic cholangiocarcinoma (ICC), a highly malignant liver tumor with poor prognosis, to explore potential new treatment strategies.</p><p><strong>Methods: </strong>Par was identified through screening an FDA compound library. <i>In vitro</i> assays were performed to assess its effects on ICC cell proliferation, colony formation, invasion, migration, cell cycle, and apoptosis. An <i>in</i> <i>vivo</i> nude mouse tumor model was used to evaluate tumor growth inhibition. Transcriptomic analysis, molecular docking, and cellular thermal shift assays were employed to identify key targets and pathways. Changes in ferroptosis-related markers, including iron ion levels, lipid peroxides, SOD activity, and GPX4 expression, were measured. Rescue experiments with the ferroptosis inhibitor ferrostatin-1 were conducted to validate the role of ferroptosis.</p><p><strong>Results: </strong>Par significantly inhibited ICC cell proliferation, colony formation, invasion, and migration, induced G2/M phase arrest, and promoted apoptosis <i>in vitro</i>; and suppressed tumor growth <i>in vivo</i>. Transcriptomic analysis showed upregulation of HMOX-1 and downregulation of Ubiquitin D (UBD) after Par treatment. Par was confirmed to bind to the UBD protein. Enrichment analysis indicated ferroptosis as a key pathway, with Par treatment leading to increased iron ions, lipid peroxide accumulation, reduced SOD activity, and downregulated GPX4. Ferrostatin-1 partially reversed Par-induced inhibitory effects.</p><p><strong>Conclusion: </strong>This study demonstrates for the first time that Par exerts anti-ICC effects related to inhibition of UBD, thereby activating the ferroptosis pathway. These findings provide a novel potential strategy and therapeutic target for ICC treatment.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2664327"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deconfounded, quantitative microbiome profiling identifies robust multiple sclerosis markers and clinical covariate associations.","authors":"Ayla Pauwels, Lindsay Devolder, Gwen Falony, Miguel D'haeseleer, Guy Nagels, Ann Van Remoortel, Muriel Derrien, Marie D'hooghe, Jeroen Raes","doi":"10.1080/19490976.2026.2681876","DOIUrl":"10.1080/19490976.2026.2681876","url":null,"abstract":"<p><p>Despite a wealth of gut microbiota studies in multiple sclerosis (MS), consistent results are lacking. Here, we study confounder effects and use of quantitative microbiome profiling (QMP) in 228 MS patients (103 untreated) and 2860 population controls (Flemish Gut Flora Project (FGFP)). Total bacterial load was lower in relapsing remitting (RR)MS, while strong fecal moisture effects, indicative of longer transit times, in MS vs. FGFP, were driven by primary progressive (PP)MS. Applying cell count and moisture in deconfounded QMP, we identified 21 differentially abundant genera in MS, with a.o. <i>Lachnobacterium</i>, <i>Blautia</i> enriched, and <i>Clostridium</i>, <i>Bacteroides</i> depleted. Deconfounded QMP across 10 published studies (1065 patients, 874 controls) did not confirm commonly detected markers (<i>Akkermansia, Roseburia</i>), yet lowered <i>Bacteroides</i>, and higher <i>Blautia</i> and <i>Methanobrevibacter</i> emerged as robust MS biomarkers. Lowered butyrate producers (<i>Butyricicoccus, Butyricimonas</i>) merit further investigation. Enterotype stratification linked the low cell count <i>Bacteroides 2</i> enterotype to low-efficacy DMTs, and the <i>Prevotella</i> enterotype to lower disease severity. Serum glial fibrillary acidic protein (GFAP), a disease progression biomarker, was identified as a covariate of gut microbial variation and inversely correlated with <i>Faecalibacterium</i> and <i>Roseburia</i> abundance in PPMS. Overall, our study provides robust disease markers and emphasizes the importance of QMP and confounder control.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2681876"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148162808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A geometry-informed continuous 3D IEQ framework enables more accurate dose estimation in stem cell-derived islet transplantation.","authors":"Yu Lu, Jinhui Fang, Zhongyi Jia, Pei Yang, Songtao Bi, Qianyun Liu, Zhe Yu, Jingyi Yin, Limin Chen, Rúben A Ricardo, Anup K Singh, Tongri Liu","doi":"10.1080/19382014.2026.2671454","DOIUrl":"10.1080/19382014.2026.2671454","url":null,"abstract":"<p><p>Accurate quantification of islet mass is critical for the preclinical evaluation and therapeutic application of stem cell-derived pancreatic islet organoids. Traditional methods, including Ricordi's islet equivalent (IEQ) approach and its equivalent circle diameter adaptations, often overestimate islet volume due to reliance on maximal diameters and discrete size bins. To address these limitations, we developed an automated image segmentation and three-dimensional modeling framework to quantify individual islet clusters from brightfield images. Clusters were fitted with ellipses and modeled as ellipsoids using rotation about either the minor or major axis, allowing IEQs to be calculated continuously relative to a reference 150 μm spherical islet. Major-axis (prolate) rotation provided the most conservative and physically plausible volume estimates, whereas minor-axis (oblate) rotation and diameter-based approaches systematically overestimated IEQs. Functional assessment with glucose-stimulated insulin secretion assays across multiple size categories demonstrated consistent insulin output for clusters below 250 μm, supporting the reproducibility of our 3D differentiation system. In vivo, streptozotocin-induced diabetic mice transplanted with islet doses based on major-axis modeling exhibited faster and more stable restoration of glycemia compared with groups receiving doses derived from overestimated approaches. These findings establish that major-axis ellipsoid modeling offers a mathematically consistent, conservative, and biologically relevant method for estimating IEQs, providing a practical framework to guide dosing in preclinical studies and supporting the translational development of stem cell-derived islet therapies.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"18 1","pages":"2671454"},"PeriodicalIF":1.4,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13166181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>NSUN2</i> mediates <i>SALL2</i> m5C methylation to inhibit ferroptosis and promote breast cancer progression.","authors":"Jiawei Li, Min Li, Jianran Guo, Dongbao Li, Yumin Yao, Wei Zhang, Chuanyou Cui, Bo Fu","doi":"10.1080/15384047.2026.2695501","DOIUrl":"10.1080/15384047.2026.2695501","url":null,"abstract":"<p><strong>Background: </strong>Due to the heterogeneity of breast cancer (BRCA) and the limited therapeutic efficacy in specific molecular subtypes, identifying new and effective therapeutic targets remains an urgent clinical need. The transcription factor <i>SALL2</i> has been shown to play distinct roles in tumorigenesis and progression, but its specific role in BRCA remains unclear. Therefore, this study investigates the effects of <i>SALL2</i> on BRCA progression.</p><p><strong>Methods: </strong><i>SALL2</i> expression in the TCGA and clinical BRCA tissue samples was analyzed. Cell and animal models were established to validate the effects of <i>SALL2</i> on BRCA cell proliferation, migration, and tumorigenicity. Molecular experiments were performed to investigate the association between NSUN2 and SALL2 in BRCA and cellular ferroptosis regulation by SALL2.</p><p><strong>Results: </strong><i>SALL2</i> is significantly overexpressed in BRCA tissues and cell lines, knocking down <i>SALL2</i> reduces BRCA cell growth, migration, and tumorigenesis <i>in vitro</i> and <i>in vivo</i> models. The m5C methyltransferase NSUN2, together with the reader protein YBX1, modifies <i>SALL2</i> mRNA with m5C, which stabilizes the transcript. <i>SALL2</i> then acts as a transcriptional repressor by binding directly to the promoter region of <i>ACSL4</i> and inhibiting its transcriptional activity. Suppression of <i>SALL2</i> activates ferroptotic cell death by lowering the antioxidant defences of GPX4/SLC7A11 and increasing the expression of <i>ACSL4</i> and <i>COX2</i>. Ferroptosis inhibitors can reverse the growth-inhibiting effects caused by <i>SALL2</i> depletion.</p><p><strong>Conclusion: </strong>In BRCA, <i>SALL2</i> is precisely regulated by m5C RNA methylation modification, further promoting cancer progression by inhibiting cell ferroptosis, suggesting its potential as a prognostic biomarker and a target for therapy.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2695501"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING-IFN suppression.","authors":"Jiaxing Ma, Yayun Wu, Guangzheng Lin, Xin Sun, Hao Geng, Tao Zhang, Dexin Yu","doi":"10.1080/15384047.2026.2632995","DOIUrl":"10.1080/15384047.2026.2632995","url":null,"abstract":"<p><strong>Objective: </strong>Clear-cell renal cell carcinoma (ccRCC) is an immune-desert tumor. This study investigates the role of ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) as a potential therapeutic target and immune-checkpoint enzyme in ccRCC.</p><p><strong>Methods: </strong>ENPP3 expression and its link to hypoxia and prognosis were analyzed in ccRCC. Functional roles were tested using gain/loss-of-function studies <i>in vitro</i> and in xenograft models, followed by therapeutic anti-ENPP3 antibody administration, alone or with anti-PD-L1. Mechanisms were explored via promoter analysis, cGAMP measurement, flow cytometry, cytokine profiling, and <i>in vivo</i> neutralization with STING- or interferon-α/β receptor-1 (IFNAR1) blocking antibodies.</p><p><strong>Results: </strong>ENPP3 is hypoxia-inducible via HIF-1α, upregulated in ccRCC, and predicts poor prognosis. ENPP3 overexpression accelerated tumor growth, while its knockdown or antibody blockade inhibited progression and synergized with anti-PD-L1. Mechanistically, ENPP3 hydrolyzes extracellular cGAMP. Its depletion elevated extracellular cGAMP, expanded anti-tumor immune cells (M1 macrophages, cDC1s, and cytotoxic T cells), reduced Tregs, and induced a STING- and IFNAR1-dependent type I interferon signature in macrophages. The anti-tumor efficacy of ENPP3 blockade was abrogated by IFNAR1 inhibition.</p><p><strong>Conclusion: </strong>ENPP3 is a hypoxia-driven, cGAMP-targeting innate immune checkpoint in ccRCC. Its inhibition reactivates STING-dependent anti-tumor immunity, providing a strong preclinical rationale for targeting ENPP3 therapeutically.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2632995"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy impact of macrophage glycosylation on cholangiocarcinoma and its prognostic and immune microenvironment significance.","authors":"Yufen Xu, Xiaofang Xu, Yan Xu, Jianwen Duan","doi":"10.1080/21645515.2026.2635867","DOIUrl":"10.1080/21645515.2026.2635867","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) has a complex tumor microenvironment that critically influences tumor progression and therapeutic resistance. Glycosylation abnormalities have been linked to cancer growth and progression. This work was designed to develop a prognostic model based on glycosylation-related genes (GRGs) for predicting CCA outcomes and immunotherapy responses. Glycosylation patterns in macrophage subsets of CCA were analyzed via scRNA-seq. Key genes were identified by integrating module genes from WGCNA and DEGs. A risk model for CCA was established utilizing LASSO Cox regression. In vitro tests were conducted to validate the function of PGK1. The immune checkpoint blockade group exhibited elevated M1 signature scores and higher glycosylation levels. A risk model incorporating five genes (ANXA3, PGK1, PLAUR, CREB5, SPP1) for CCA was established. The high macrophage glycosylation-related risk score group had a considerable infiltration of M0 macrophages. In vitro experiments confirmed that PGK1 advanced glycation end products accumulation, drove M2 polarization of macrophages, and increased CCA cell proliferation and migration. This work proposes a glycosylation-based risk model for predicting CCA prognosis and directing therapeutic strategies. PGK1 is highlighted as a potential therapeutic target in CCA.</p>","PeriodicalId":49067,"journal":{"name":"Human Vaccines & Immunotherapeutics","volume":"22 1","pages":"2635867"},"PeriodicalIF":4.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12973474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naapinneq: strengthening Inuit maternal and child health through gathering Inuit from Kalaallit Nunaat and Nunavut.","authors":"Christine Ingemann, Nancy Mike, Ruth Montgomery-Andersen, Dina Berthelsen, Naja Riber Hougaard, Maliina Junge Jørgensen, Regine Dahl Thorleifsen Kajusen, Lisa Ivalu Lind, Kamilla Nørtoft, Aininaq Willesen, Ingelise Olesen","doi":"10.1080/22423982.2026.2634479","DOIUrl":"10.1080/22423982.2026.2634479","url":null,"abstract":"<p><p>This paper describes the initiation of the Naapinneq project and the first collaborative gathering in Iqaluit, Nunavut (Canada). While the broader project aims to revitalize culturally grounded parenting programs, this paper focuses on documenting its initiation and early collaborative learning. The focus was on the MANU program in Kalaallit Nunaat and the Inunnguiniq Parenting/Child‑rearing program in Nunavut. Using a community‑based participatory research approach, the paper draws on qualitative insights from the collaborative gathering-centered on participation in the Inunnguiniq facilitator workshop at the Qaujigiartiit Health Research Centre-and on a desk‑based comparison of core program documents. Reflections were documented through Sharing Circles, round‑table discussions, and a short questionnaire. Results highlight three interlinked insights: culturally grounded programs can support personal and collective healing; language, land, and kinship are foundational to child‑rearing; and circumpolar collaboration accelerates practice change and innovation. Project group members reported tangible changes, including adapting MANU to better reflect Kalaallit realities, initiating new collaborations, and advocating for culturally grounded approaches in early childhood and family services. Grounding parenting programs in Indigenous relational paradigms can strengthen cultural fit, community ownership, and sustained impact. Early learnings point to the healing potential of culturally grounded programs and to the value of cross‑border partnership for accelerating practice change.</p>","PeriodicalId":13930,"journal":{"name":"International Journal of Circumpolar Health","volume":"85 1","pages":"2634479"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gallic acid-driven core-shell nanovehicles enable intestinal adhesion and adipose retention for enhanced oral bioavailability of cholecalciferol.","authors":"Guangyu Fan, Jixiang Zhao, Ru Zhang, Zhuo Li, Haifeng Wu, Yang Lu, Ying Li, Zhengqi Dong","doi":"10.1080/10717544.2026.2669030","DOIUrl":"10.1080/10717544.2026.2669030","url":null,"abstract":"<p><p>Cholecalciferol (VDC), a vital form of vitamin D, is essential for maintaining calcium-phosphorus balance, promoting bone health, and regulating the immune system; however, its therapeutic potential is limited by low oral bioavailability and poor aqueous solubility. To address these issues, a multifunctional nanoparticle (NPS) was developed: VDC was first encapsulated in <i>β</i>-cyclodextrin (βCD) to form a stable βCD/VDC inclusion complex, improving solubility and physicochemical stability, and then coated with gallic acid (GA) to yield the core-shell nanovehicle GA/βCD/VDC-NPS, which leverages GA's intestinal mucoadhesive and mesenteric adipose retention. GA/βCD/VDC-NPS exhibited a particle size of 234.1 ± 5.23 nm, high encapsulation efficiency (81.2 ± 0.13%), and drug-loading capacity (20.10 ± 0.50%), and showed sustained release, with a cumulative release of 86.06 ± 2.35% at 72 h. MDCK (Madin-Darby Canine Kidney cells) cell experiments showed its cellular uptake was significantly higher than βCD/VDC or free VDC, mediated by multiple endocytic mechanisms. Pharmacokinetic analysis supported markedly enhanced oral absorption: relative to free VDC, the bioavailability of GA/βCD/VDC-NPS increased 2.87-fold in plasma, 6.75-fold in the small intestine, 3.40-fold in adipose tissue, and 3.50-fold in the stomach. Tissue distribution studies verified its enhanced accumulation and prolonged retention in intestinal regions and associated adipose depots. These findings highlight polyphenols like GA as bioactive shells that enhance intestinal adhesion and regional retention, improving oral hydrophobic drugs' pharmacokinetics. In conclusion, GA/βCD/VDC-NPS is a promising nanoplatform that resolves VDC's solubility and bioavailability issues via polyphenol-mediated surface functionalization, offering great potential for oral delivery of various hydrophobic active compounds.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2669030"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host and <i>Helicobacter pylori</i> HtrA protease variants converge on Wnt/β-catenin signaling to drive stomach adenocarcinoma.","authors":"Bodo Linz, Saiswaroop Rajaratnam, Nicole Tegtmeyer, Aakash Chhetri, Krishnasalini Gunanathan, Subbarao Kanchi, Suneesh Kumar Pachathundikandi, Venketesh Sivaramakrishnan, Steffen Backert","doi":"10.1080/19490976.2026.2704244","DOIUrl":"10.1080/19490976.2026.2704244","url":null,"abstract":"<p><p><i>Helicobacter pylori-</i>associated stomach adenocarcinoma (STAD) represents a highly severe malady, with up to 1 million new cases annually. Here, we examined novel human and bacterial risk determinants as well as related signal transduction events associated with STAD development. <i>H. pylori</i> serine protease HtrA cleaves the junctional protein E-cadherin, which results in the disruption of epithelial cell connections, the release and nuclear accumulation of β-catenin, and the onset of epithelial-mesenchymal transition (EMT), a hallmark of many tumors. In addition, the injection of <i>H. pylori</i> oncoprotein CagA into host epithelial cells targets β-catenin-mediated cell proliferation and other cancer signaling pathways. By analyzing over 2,000 <i>H. pylori</i> genomes, we identified single-nucleotide polymorphism (SNP) variants of HtrA and CagA that are associated with STAD progression. In addition, we investigated the role of the human serine proteases HTRA1, HTRA2, HTRA3, and HTRA4 in STAD progression and linked the genetic and expression data with specific signaling pathways. Elevated HTRA1, HTRA2, and HTRA3 expression in STAD patients correlated with upregulated extracellular matrix (ECM) receptor interactions and signaling that are critical for EMT. Moreover, <i>H. pylori-</i>positive STAD patients exhibited increased epithelial cell signaling, chronic inflammation, transcription factor Wnt/β-catenin signaling, ECM damage and metastasis, and single-cell analyses showed a strong association between HTRA1, the receptor Wnt, β-catenin, and oncogene MYC expression. Analyses of mutations in human HTRA1 and <i>H. pylori</i> HtrA revealed a role in the up- or downregulation of STAD progression. Together, our data show that SNPs in human and <i>H. pylori</i> serine protease HtrA and CagA modulate cancer signaling in complex Wnt-/β-catenin and ECM signaling networks, and that the protein variants can be causative or protective factors. A signaling model is proposed that highlights the complex interplay of human and bacterial factors in critical tumor signaling events, which could serve as predictive STAD biomarkers in patients.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2704244"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiological and virological characteristics of influenza in Zhejiang Province, China: A 15-year surveillance study.","authors":"Jialie Jin, Zhao Yu, Ying Zhu, Yanli Cao, Hangjie Zhang, Xiaoxiao Wang, Jimin Sun","doi":"10.1080/21645515.2026.2675787","DOIUrl":"10.1080/21645515.2026.2675787","url":null,"abstract":"<p><p>Understanding the complex epidemiological and virological characteristics of influenza is critical for optimizing seasonal influenza control and prevention programs; to this end, we analyzed the influenza and influenza-like illness (ILI) cases reported in Zhejiang Province from 2010 to 2025. Annual average percentage (AAP) approach was used to estimate the influenza seasonal epidemic onset and duration. Generalized additive model (GAM) was used to explore the nonlinear relationship between age and the positive rate of influenza. Spearman correlation analysis was performed to assess the association between weekly ILI% and influenza positivity rate. A total of 5,853,160 influenza cases and 8,732,124 ILI cases were reported. The ILI% ranged from 2.49 to 6.84% (mean: 4.37%), with the lowest level in 2010-2011 and the highest in 2023-2024. The median duration of seasonal influenza epidemics was 4.59 months (IQR: 2.84-5.88). Children aged 5~14 y had the highest influenza positivity rate (41.73%). Influenza virus subtypes/lineages varied significantly by seasons and age groups. A/H3N2 was the predominant pathogen during the summer seasons and the positivity rate of A/H3N2 was much higher than that of other subtypes/lineages among individuals aged ≤60 y. ILI% was positively correlated with influenza positivity during 2010-2025 except in the 2020-2021 surveillance year. This study revealed significant variations in seasonal epidemic period and age-specific distributions across influenza subtypes/lineages, as well as a marked disruption of influenza activity due to the COVID-19 pandemic.</p>","PeriodicalId":49067,"journal":{"name":"Human Vaccines & Immunotherapeutics","volume":"22 1","pages":"2675787"},"PeriodicalIF":4.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147976626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}