{"title":"Investigation of the Regulatory Mechanisms of Gut Microbiota and Metabolites in Colorectal Cancer Development and Progression.","authors":"Zhonghua Qi, Peng Qi, Huan Tang, Ping Qi","doi":"10.1007/s43657-025-00243-8","DOIUrl":"https://doi.org/10.1007/s43657-025-00243-8","url":null,"abstract":"<p><p>Colorectal cancer ranks among the most prevalent malignancies globally, with its incidence strongly correlated with human development indices, presenting a major public health challenge. The gut microbiota and their metabolites play crucial roles in colorectal cancer pathogenesis. Recent advances in understanding tumor microenvironment immunology during cancer progression and treatment have highlighted the significant impact of the gut microbiota on tumor immunity. This review synthesizes current evidence on the complex interactions between gut microbiota, their metabolites, and colorectal cancer development, while examining the mechanisms through which microbial communities and their metabolic products contribute to carcinogenesis. Furthermore, we assess the clinical potential of microbiota-based biomarkers for colorectal cancer diagnosis. Our analysis aims to explore innovative therapeutic approaches through microbiota modulation for colorectal cancer prevention and treatment, potentially revealing novel mechanisms to combat this devastating disease.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"6 3","pages":"307-320"},"PeriodicalIF":6.2,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jin Wang, Yan Zhuang, Huihui Li, Zheng Wen, Chen Chen, Dao Wen Wang
{"title":"Mincle-Mediated Coxsackievirus-B3 Infection Induced Fulminant Myocarditis Via Trained Immunity.","authors":"Jin Wang, Yan Zhuang, Huihui Li, Zheng Wen, Chen Chen, Dao Wen Wang","doi":"10.1007/s43657-026-00325-1","DOIUrl":"https://doi.org/10.1007/s43657-026-00325-1","url":null,"abstract":"<p><p>Fulminant myocarditis (FM) is a lethal form of acute myocardial inflammation. To investigate this mechanism, we examined whether innate immunity trained by sequential exposure to lipopolysaccharide (LPS) and Coxsackievirus B3 (CVB3) could induce FM in CVB3-resistant C57BL/6J mice. Male 7-8-week-old C57BL/6J mice were used, and LPS + CVB3 double-hit treatment significantly increased mortality to 60%, accompanied by severe cardiac dysfunction (LVEF: 59.3% ± 7.8% vs. 69.7% ± 4.1%, <i>p</i> < 0.01) and markedly enhanced inflammatory cell infiltration compared to the CVB3-only group. In contrast, no significant inflammation was observed three weeks after LPS injection alone. Immunofluorescence analysis revealed that M1 macrophages dominated the inflammatory cell infiltration in the heart following CVB3 infection, with a more pronounced effect in the double-hit group than in the CVB3-only group. Furthermore, macrophage depletion alleviated inflammatory infiltration and improved cardiac function in the double-hit group. ATAC sequencing analysis demonstrated increased chromatin accessibility in bone marrow-derived macrophages three weeks after LPS injection. Single-cell RNA sequencing further indicated that macrophage-inducible C-type lectin (Mincle) plays a critical role in double-hit-induced FM and that Mincle blockade rescues cardiac dysfunction in mice with CVB3-induced myocarditis. CUT&Tag sequencing data revealed increased enrichment of histone H3 lysine 27 acetylation (H3K27ac) modifications on the Mincle gene in LPS-treated bone marrow macrophages. The p300 inhibitor protected against cardiac dysfunction in FM mice. Collectively, these findings demonstrate that low-dose LPS-induced trained immunity in macrophages exacerbates severe inflammatory infiltration and cardiac dysfunction in CVB3-infected C57BL/6J mice, leading to FM. This study provides a novel mechanistic insight into FM and establishes a mouse model for FM, identifying Mincle as a potential therapeutic target for this condition.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s43657-026-00325-1.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"6 3","pages":"274-295"},"PeriodicalIF":6.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fei Cai, Yufan Gu, Jie Gao, Guanhua Yi, Yong Zhang
{"title":"Key Mucins in Early Diagnosis of Pancreatic Ductal Adenocarcinoma and Biliary Tract Cancer: A Meta-Analysis.","authors":"Fei Cai, Yufan Gu, Jie Gao, Guanhua Yi, Yong Zhang","doi":"10.1007/s43657-025-00288-9","DOIUrl":"10.1007/s43657-025-00288-9","url":null,"abstract":"<p><p>The aim of the study was to evaluate the diagnostic accuracy of mucins in pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC) based on available evidence and to assess their role in differential diagnosis. A comprehensive search was conducted across PubMed/MEDLINE, Web of Science, Embase and Cochrane Library from database inception to September 2024. All immunoassay-based cases or clinical studies that investigated mucin (MUC) in relation to PDAC or BTC were included. The pooled sensitivity and specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), the area under the summary receiver operating characteristic (SROC) curve, and the area under the curve (AUC) for several mucins in diagnosing PDAC and BTC were assessed. A total of 56 studies involving 6823 patients were included in the analysis. Current mucin-based diagnostic approaches for PDAC and BTC primarily focus on mucin 1 (MUC1), mucin 2 (MUC2), mucin 4 (MUC4), mucin 5AC (MUC5AC), and mucin 6 (MUC6). Among them, MUC1 demonstrated exceptional diagnostic performance in PDAC with a sensitivity of 0.96 and a specificity of 0.76 and in BTC with a sensitivity of 0.80 and a specificity of 0.93. Additionally, MUC4 also exhibited good diagnostic efficacy in PDAC, with a sensitivity of 0.77 and a specificity of 0.76. MUC5AC demonstrated significant diagnostic efficacy in PDAC with a sensitivity of 0.79 and a specificity of 0.61 and in BTC with a sensitivity of 0.69 and a specificity of 0.77. However, the other two proteins, MUC2 and MUC6, exhibited poor diagnostic performance for PDAC and BTC, with a sensitivities of less than 0.47 and a specificities of less than 0.68. In conclusion, this meta-analysis of patients with PDAC and BTC indicates that MUC markers may have high diagnostic accuracy, particularly some specific key mucins. The differential expression of the same mucin in both cancers as well as in their corresponding benign diseases offers valuable insights into the differential diagnosis.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s43657-025-00288-9.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"6 3","pages":"257-273"},"PeriodicalIF":6.2,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intronic Polyadenylation and Cellular Senescence: A Novel Perspective.","authors":"Shuxin Chen, Lei Li","doi":"10.1007/s43657-025-00256-3","DOIUrl":"https://doi.org/10.1007/s43657-025-00256-3","url":null,"abstract":"","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"6 3","pages":"336-338"},"PeriodicalIF":6.2,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quercetin Facilitates Vesicle Release and Inhibits Endocytosis at a Central Synapse.","authors":"Yiming Gao, Yue Xu, Hui Zhang, Yixuan Lu, Shun Li, Lei Xue","doi":"10.1007/s43657-025-00248-3","DOIUrl":"https://doi.org/10.1007/s43657-025-00248-3","url":null,"abstract":"<p><p>Quercetin has demonstrated significant potential in treating neurological diseases due to its neuroprotective effects. It has been reported to modulate neuronal excitability, thereby protecting neurons from excessive excitotoxic damage. However, the mechanisms by which quercetin modulates synaptic transmission remain elusive. In this study, we investigated the effects of quercetin on synaptic transmission using whole-cell patch-clamp techniques at the calyx of Held. We found that 100 μM quercetin increased excitatory postsynaptic currents. We also recorded presynaptic calcium currents at the giant presynaptic nerve terminal and found that quercetin did not affect calcium influx but increased the release probability of synaptic vesicles. Using whole-cell capacitance measurements, we found that quercetin significantly inhibited vesicle endocytosis without affecting exocytosis. To further address the underlying cellular mechanisms, we applied specific calmodulin inhibitors, myosin light chain kinase peptide or calmodulin binding-domain peptide in the presence of quercetin. None of the calmodulin inhibitors induced additional inhibition of endocytosis, indicating the involvement of calmodulin in quercetin-induced inhibition of endocytosis. Similarly, blocking calcineurin with calcineurin autoinhibitory peptide or cyclosporine A did not induce further inhibition of endocytosis, suggesting the involvement of calcineurin downstream of calmodulin. To explore the physiological significance of quercetin, we found that it could enhance short-term depression during repetitive stimulation. This effect was attributed to both an increase in vesicle release probability and a slowing down of endocytosis. Therefore, for the first time, we report that quercetin increases vesicle release and inhibits endocytosis via the calmodulin/calcineurin signaling pathway, providing new insights into its neuroprotective effects.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"6 3","pages":"230-246"},"PeriodicalIF":6.2,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fengsen Liu, Yu Ping, Miaomiao Li, Kaiyuan Guo, Lei Zhang, Peng Wu, Yijun Tian, Jinyan Liu, Yi Zhang
{"title":"Artificial Intelligence-Driven Multiomics and Clinical Investigation Identify Macrophage Migration Inhibitory Factor as a Pan-Cancer Biomarker.","authors":"Fengsen Liu, Yu Ping, Miaomiao Li, Kaiyuan Guo, Lei Zhang, Peng Wu, Yijun Tian, Jinyan Liu, Yi Zhang","doi":"10.1007/s43657-026-00322-4","DOIUrl":"10.1007/s43657-026-00322-4","url":null,"abstract":"<p><p>Early cancer detection remains challenging due to the lack of reliable pan-cancer screening methods, particularly blood-based biomarkers. Using a novel three-tiered validation framework combining artificial intelligence (AI)-powered literature mining of 180,000 PubMed articles (1950-2024), multiomics integration across major databases, and extensive clinical validation, we identified macrophage migration inhibitory factor (MIF) as a promising blood-based biomarker for pan-cancer detection. Multiomics analysis revealed consistent MIF upregulation across 21 cancer types at the transcriptional level and across 12 cancer types at the protein level. Clinical validation in independent cohorts (<i>n</i> = 4,269) showed that serum MIF protein levels discriminated effectively between cancer patients and healthy controls (median AUC = 0.994) and between cancer and benign conditions (median AUC = 0.881). Notably, comparative analyses showed that MIF demonstrated superior or comparable performance to established cancer-specific markers, including AFP for hepatocellular carcinoma (MIF AUC = 0.885 vs. AFP AUC: 0.744-0.887) and CA125 for ovarian cancer (MIF AUC = 0.831 vs. CA125 AUC: 0.58-0.71). Meta-analysis of 28 cohorts (<i>n</i> = 5,347) confirmed the diagnostic efficacy of MIF (pooled AUC: 0.782). This cost-effective, blood-based ELISA approach establishes MIF as a valuable tool for broad applications in cancer screening.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s43657-026-00322-4.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"6 3","pages":"213-229"},"PeriodicalIF":6.2,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HuNT: A Reference Transcriptome Atlas for Human Normal Tissues.","authors":"KaiLin Tang, XinYan Xu, XinYue Tang, XinWen Wu, ZiHao Li, Jian Gao, ShiYue Zhang, SaiFeng Mo, ZiKun Chen, Mou Zhang, Hao Ding, Yao Shi, YiHeng Wang, YiXin Chen, MoHan Chen, ZhiWei Cao","doi":"10.1007/s43657-025-00250-9","DOIUrl":"https://doi.org/10.1007/s43657-025-00250-9","url":null,"abstract":"<p><p>With the rapid development of transcriptomics technology, gene expression profiles of normal human tissues have been frequently utilized as valuable references to study aging and disease mechanisms. Although individual databases have been established, most human tissues remain under-sampled. Meanwhile, profiles from RNA-seq and microarray platforms must be analyzed separately due to inherent distribution bias, further weakening the statistical power of health samples. Here, we constructed a comprehensive transcriptome atlas for human normal tissues (HuNT) containing 29,769 samples covering 74 human normal tissue types or parts, 70% and 37% larger than those in the well-known GTEx database in terms of sample size and tissue diversity, respectively. More importantly, instead of separate calculation, integrative analysis has been enabled for hybrid samples across RNA-seq and microarray profiles per tissue type. Based on the largest human sample collection so far, HuNT provides the latest information on: (1) tissue-specific genes, (2) stably and highly expressed housekeeping genes for each tissue, (3) gene expression landscape across all human tissues, and (4) top correlated genes for a query in a specified tissue. A case study of four widely-acknowledged biomarkers is also illustrated in the paper. With future data accumulation, HuNT may be useful to provide not only gene expression landscapes in human normal tissues, but also benchmarks to derive interesting marker genes and even therapeutic targets. HuNT is now freely accessible at http://hunt.badd-cao.net/.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s43657-025-00250-9.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"6 3","pages":"247-256"},"PeriodicalIF":6.2,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}