Front Immunol. 2026 Mar 16;17:1822612. doi: 10.3389/fimmu.2026.1822612. eCollection 2026.

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2026.1782545.].

PMID:41918731 | PMC:PMC13033988 | DOI:10.3389/fimmu.2026.1822612

Front Pediatr. 2026 Mar 16;14:1770578. doi: 10.3389/fped.2026.1770578. eCollection 2026.

ABSTRACT

The neonatal lung, once considered sterile, is now recognized to harbor a dynamic and complex microbiome that plays a critical role in respiratory health and disease. This review synthesizes current evidence on the composition, development, and functional impact of the lung microbiome in neonates, with a focus on its involvement in key respiratory disorders such as bronchopulmonary dysplasia, respiratory syncytial virus infection, neonatal acute respiratory distress syndrome, cystic fibrosis, and asthma predisposition. We place particular emphasis on the bidirectional communication along the gut-lung axis as a central mechanism, wherein intestinal microbiota and their metabolites modulate pulmonary immunity and inflammation. Emerging multi-omics studies that integrate microbial data with host metabolomic and immune profiles are highlighted for their role in deciphering disease-specific dysbiotic signatures and mechanistic pathways. Critically, this review advances the discussion beyond association by evaluating the translational potential of the microbiome as both a diagnostic biomarker and a therapeutic target. We provide a critical appraisal of innovative microbiome-targeted strategies-including probiotics, postbiotics, phage therapy, and bacterial lysates-and discuss the unique challenges and future directions for translating these approaches into safe, effective clinical interventions for vulnerable neonates. By bridging foundational science with clinical implications, this work aims to inform the development of novel, ecology-informed therapeutics to prevent and mitigate neonatal respiratory diseases.

PMID:41918694 | PMC:PMC13033698 | DOI:10.3389/fped.2026.1770578

Front Cell Infect Microbiol. 2026 Mar 16;16:1793213. doi: 10.3389/fcimb.2026.1793213. eCollection 2026.

ABSTRACT

The progression from cirrhosis to hepatocellular carcinoma (HCC) is a key outcome in the management of chronic liver disease. This process has a long incubation period and significant individual differences, making early warning still difficult. Clinical follow-up mainly relies on imaging examinations and alpha fetoprotein, but the ability to identify high risk precancerous states is limited. The imbalance of gut microbiota and its metabolites may occur earlier than the visible stage of tumors. They can affect barrier integrity, chronic inflammation, immune surveillance, and metabolic homeostasis through the gut liver axis, and participate in the formation of a pro tumor microenvironment. Therefore, such changes may provide more upstream risk stratification clues for the population with cirrhosis. This article summarizes previous research evidence and summarizes the common microbiome and metabolite characteristics of cirrhosis and high-risk populations, including a decrease in short chain fatty acid (SCFA) related symbiotic bacteria, an increase in inflammation related bacteria, bile acid spectrum shift, and other intestinal derived metabolite abnormalities. This article also outlines the key mechanisms that these features may correspond to, such as barrier damage and microbial translocation, immune suppression, etc. There are still significant uncertainties at present. The effect of SCFA is context dependent. Different etiologies, diets, medications, and complications can lead to significant confounding and affect cross cohort consistency. Subsequent research requires longitudinal cohort validation and the promotion of multi omics integration and the construction of interpretable predictive models to support clinical translation.

PMID:41918873 | PMC:PMC13033666 | DOI:10.3389/fcimb.2026.1793213

Front Immunol. 2026 Mar 16;17:1822612. doi: 10.3389/fimmu.2026.1822612. eCollection 2026.

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2026.1782545.].

PMID:41918731 | PMC:PMC13033988 | DOI:10.3389/fimmu.2026.1822612

Front Pediatr. 2026 Mar 16;14:1770578. doi: 10.3389/fped.2026.1770578. eCollection 2026.

ABSTRACT

The neonatal lung, once considered sterile, is now recognized to harbor a dynamic and complex microbiome that plays a critical role in respiratory health and disease. This review synthesizes current evidence on the composition, development, and functional impact of the lung microbiome in neonates, with a focus on its involvement in key respiratory disorders such as bronchopulmonary dysplasia, respiratory syncytial virus infection, neonatal acute respiratory distress syndrome, cystic fibrosis, and asthma predisposition. We place particular emphasis on the bidirectional communication along the gut-lung axis as a central mechanism, wherein intestinal microbiota and their metabolites modulate pulmonary immunity and inflammation. Emerging multi-omics studies that integrate microbial data with host metabolomic and immune profiles are highlighted for their role in deciphering disease-specific dysbiotic signatures and mechanistic pathways. Critically, this review advances the discussion beyond association by evaluating the translational potential of the microbiome as both a diagnostic biomarker and a therapeutic target. We provide a critical appraisal of innovative microbiome-targeted strategies-including probiotics, postbiotics, phage therapy, and bacterial lysates-and discuss the unique challenges and future directions for translating these approaches into safe, effective clinical interventions for vulnerable neonates. By bridging foundational science with clinical implications, this work aims to inform the development of novel, ecology-informed therapeutics to prevent and mitigate neonatal respiratory diseases.

PMID:41918694 | PMC:PMC13033698 | DOI:10.3389/fped.2026.1770578

Cancer Epidemiol Biomarkers Prev. 2026 Apr 1;35(4):491-493. doi: 10.1158/1055-9965.EPI-25-1971.

ABSTRACT

Recently, stool- and blood-based cancer screening kits have been approved in clinical practice as convenient and noninvasive methods for colon cancer screening. One such test in long-standing practice has included the fecal immunochemical test (FIT), wherein home-based testing has rendered it a convenient initial assay to complement screening colonoscopy, despite limitations in diagnostic performance. In a recent original study published in the journal by Nguyen and colleagues, the feasibility and performance of combining FIT with circulating tumor cell (CTC) enumeration for predicting colorectal neoplasia and the risk of developing colorectal cancer were described. In this commentary, we highlight the potential of this combination as a novel colorectal cancer screening technique. The introduction of CTC as a potential colorectal cancer screening assay is timely, given the emergence of liquid biopsies that hold promise in their ability to detect a multitude of cancer-specific signals, from the detection of minimal residual disease to the detection of molecular alterations for precision therapies in oncology. We place the importance of their results in the context of the evolving landscape of stool- and blood-based colorectal cancer screening tests involving multitarget fecal DNA and cell-free DNA assays. See related article by Nguyen et al., Cancer Epidemiol Biomarkers Prev 2026;35:79-87.

PMID:41918361 | DOI:10.1158/1055-9965.EPI-25-1971

Cancer Immunol Immunother. 2026 Mar 31;75(4):126. doi: 10.1007/s00262-026-04368-1.

ABSTRACT

While anti-programmed death-1 (anti-PD-1) therapy has revolutionized lung cancer treatment, its efficacy remains limited by an immunosuppressive tumor microenvironment (TME). We therefore investigated whether combining anti-PD-1 inhibitor with catgut embedding at the Zusanli acupoint (CIAA) could enhance anti-tumor immunity by reprogramming the TME in a lung cancer mouse model. Combining in vivo tumor monitoring, multi-parametric immune profiling (flow cytometry, IHC, ELISA), and multi-omics analyses (transcriptomics and metabolomics), we found that the combination therapy was associated with enhanced tumor growth inhibition. This effect correlated with a comprehensive TME transformation: conversion to an immunologically active state with increased effector immune cell infiltration (CD8⁺ T, CD4⁺ T, B cells, macrophages) and decreased regulatory T cells, coupled with suppression of pro-tumorigenic factors (VEGF, IL-6). Integrated omics analysis suggests that the combined treatment may modulate tumor-stroma interaction pathways (e.g., PI3K-Akt, focal adhesion) and rewire immunometabolic networks (e.g., tryptophan metabolism). Our study provides hypothesis-generating correlative data positioning CIAA as a potential adjunct capable of remodeling the TME to potentiate anti-PD-1 therapy in lung cancer.

PMID:41915222 | PMC:PMC13038699 | DOI:10.1007/s00262-026-04368-1

Zhonghua Yi Xue Za Zhi. 2026 Mar 31;106:1-7. doi: 10.3760/cma.j.cn112137-20251201-03143. Online ahead of print.

ABSTRACT

Objective: To analyze the association between molecular typing and prognosis with recurrence pattern in triple-negative breast cancer (TNBC) patients based on long-term follow-up of a multi-omics cohort. Methods: A retrospective analysis was performed on the clinical data and transcriptomic data of patients diagnosed with TNBC at Department of Breast Surgery, Fudan University Shanghai Cancer Center from January 1, 2007, to December 31, 2014. The survival status of patients was documented, and the follow-up continued until the patients' death or August 31, 2025. According to the"Fudan subtype", the patients were categorized into the basal-like immune suppressed (BLIS), immunomodulatory (IM), luminal androgen receptor (LAR), and mesenchymal-like (MES). Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was employed to evaluate the differences in overall survival (OS), disease-free survival (DFS) and recurrence-free interval (RFI) among TNBC patients with different molecular subtypes. Multivariate Cox proportional hazards regression analysis was used to assess the association between"Fudan subtype"and OS, DFS and RFI. Differential expression analysis and subsequent gene set enrichment were conducted. Competing-risk models were used to calculate the cumulative incidence of lung metastasis after accounting for competing events, and the differences were assessed using the Fine-Gray test. Results: After excluding 9 patients lost to follow-up, a total of 351 patients with TNBC were included in the analysis. The mean age at baseline was 53.46±11.36 years, and the median follow-up duration was 102.09 months. During follow-up, 72 patients died and 84 experienced recurrence or metastasis. Among them, 134 patients were classified as the BLIS subtype, with 27 deaths (20.15%); 86 patients were classified as the IM subtype, with 11 deaths (12.79%); 81 patients were classified as the LAR subtype, with 22 deaths (27.16%); and 50 patients were classified as the MES subtype, with 12 deaths (24.00%). The 10-year RFI rates for the BLIS, IM, LAR, and MES subtypes were 80.12% (95%CI: 73.41%-87.44%), 92.35% (95%CI: 86.64%-98.43%), 81.92% (95%CI: 73.39%-91.44%), and 72.95% (95%CI: 61.37%-86.71%), respectively. Kaplan-Meier survival curves showed that the differences of RFI among the four molecular subtypes of patients were statistically significant (P=0.040). Multivariate analysis showed that LAR subtype (LAR vs IM, HR=2.41, P=0.042) was the independent risk factor for DFS, and BLIS subtype (BLIS vs IM, HR=4.17, P=0.011), LAR subtype (LAR vs IM, HR=3.49, P=0.040) and MES subtype (MES vs IM, HR=3.98, P=0.019) were independent risk factors for RFI. The BLIS subtype is more likely to develop recurrence or metastasis in the early postoperative period, particularly lung metastasis. Differential gene expression analysis showed that BLIS subtype-specific genes, including those involved in proliferation and cell cycle activity, were predominantly upregulated in tumors with early recurrence or metastasis. Competing-risk analysis demonstrated that BLIS patients had a higher cumulative incidence of lung metastasis both overall and within the first 5 years after surgery compared with non-BLIS patients (both P<0.05). Conclusion: The"Fudan subtype"was significantly associated with RFI in early-stage TNBC patients. In addition, recurrence and metastasis were more likely to be observed in the early postoperative period in the BLIS subtype, particularly early lung metastasis.

PMID:41913624 | DOI:10.3760/cma.j.cn112137-20251201-03143

NPJ Precis Oncol. 2026 Mar 31. doi: 10.1038/s41698-026-01394-1. Online ahead of print.

ABSTRACT

VDAC2's known role in cancer and immune regulation via enhancing the CD8⁺ T cell-mediated killing, and it is worth systematically digging out the role of VDAC2 in pan-cancer based on this research. Bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomic analyses were utilized to explore the role of VDAC2 from multiple perspectives in pan-cancers. RT-PCR, cell co-culture, CCK-8 assay, Transwell invasion assays, and ELISA were performed to validate the expression level and biological function. VDAC2 was upregulated in the majority of pan-cancers, and functional enrichment analyses displayed that VDAC2 may take part in the biological progress of energy metabolism, mitochondrial damage and cell proliferation. The landscape of VDAC2 expression and immune infiltration was constructed, and the VDAC2-BAK1-IFNγ pathway was identified in digestive cancer. VDAC2 had the potential to serve as a novel prognostic, screening cancer indicator and immune therapeutic target sensitive to various drugs. Overexpression of VDAC2 significantly promoted gastric cancer cell proliferation, invasion and immune invasion, as validated in vitro experiments. In short, our pan-cancer analysis constructed a comprehensive landscape of VDAC2's oncogenic role, establishing VDAC2 + -BAK1-IFNγ as an important pathway in tumor progression and immune evasion. VDAC2 emerges not only as a valuable prognostic biomarker but also as a promising novel therapeutic target.

PMID:41917254 | DOI:10.1038/s41698-026-01394-1

Food Funct. 2026 Mar 31. doi: 10.1039/d5fo04958j. Online ahead of print.

ABSTRACT

The probiotic yeast Saccharomyces boulardii is renowned for its clinical efficacy, which is intrinsically linked to its exceptional ability to survive the harsh gastrointestinal (GI) environment. However, a comprehensive understanding of the molecular mechanisms and regulatory pathways underlying the stress tolerance of S. boulardii remains limited. This study employed an integrated transcriptomic and proteomic approach to systematically map the dynamic responses of S. boulardii to simulated GI transit. Our analysis revealed that the intestinal phase posed a significantly greater challenge than the gastric phase, triggering extensive molecular reprogramming. A core adaptive strategy was the marked upregulation of the central carbon metabolism, particularly glycolysis, as evidenced by the concerted overexpression of key enzymes at both transcriptional and translational levels, indicating a heightened demand for energy to fuel stress defence mechanisms. Furthermore, significant enrichment was observed in the pathways related to nitrogen and fatty acid metabolism. Integration of the multi-omics datasets highlighted the complexity of the regulatory response, with frequent discordance between mRNA and protein abundance underscoring the importance of post-transcriptional regulation. This study provides a detailed molecular profile of the stress tolerance network in S. boulardii, elucidating the strategic metabolic rewiring and multi-layered regulation that underpin its probiotic resilience. The findings offer valuable insights and a foundational resource for the future development of enhanced probiotic therapies.

PMID:41914832 | DOI:10.1039/d5fo04958j

NPJ Precis Oncol. 2026 Mar 31. doi: 10.1038/s41698-026-01394-1. Online ahead of print.

ABSTRACT

VDAC2's known role in cancer and immune regulation via enhancing the CD8⁺ T cell-mediated killing, and it is worth systematically digging out the role of VDAC2 in pan-cancer based on this research. Bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomic analyses were utilized to explore the role of VDAC2 from multiple perspectives in pan-cancers. RT-PCR, cell co-culture, CCK-8 assay, Transwell invasion assays, and ELISA were performed to validate the expression level and biological function. VDAC2 was upregulated in the majority of pan-cancers, and functional enrichment analyses displayed that VDAC2 may take part in the biological progress of energy metabolism, mitochondrial damage and cell proliferation. The landscape of VDAC2 expression and immune infiltration was constructed, and the VDAC2-BAK1-IFNγ pathway was identified in digestive cancer. VDAC2 had the potential to serve as a novel prognostic, screening cancer indicator and immune therapeutic target sensitive to various drugs. Overexpression of VDAC2 significantly promoted gastric cancer cell proliferation, invasion and immune invasion, as validated in vitro experiments. In short, our pan-cancer analysis constructed a comprehensive landscape of VDAC2's oncogenic role, establishing VDAC2 + -BAK1-IFNγ as an important pathway in tumor progression and immune evasion. VDAC2 emerges not only as a valuable prognostic biomarker but also as a promising novel therapeutic target.

PMID:41917254 | DOI:10.1038/s41698-026-01394-1

Cancer Immunol Immunother. 2026 Mar 31;75(4):126. doi: 10.1007/s00262-026-04368-1.

ABSTRACT

While anti-programmed death-1 (anti-PD-1) therapy has revolutionized lung cancer treatment, its efficacy remains limited by an immunosuppressive tumor microenvironment (TME). We therefore investigated whether combining anti-PD-1 inhibitor with catgut embedding at the Zusanli acupoint (CIAA) could enhance anti-tumor immunity by reprogramming the TME in a lung cancer mouse model. Combining in vivo tumor monitoring, multi-parametric immune profiling (flow cytometry, IHC, ELISA), and multi-omics analyses (transcriptomics and metabolomics), we found that the combination therapy was associated with enhanced tumor growth inhibition. This effect correlated with a comprehensive TME transformation: conversion to an immunologically active state with increased effector immune cell infiltration (CD8⁺ T, CD4⁺ T, B cells, macrophages) and decreased regulatory T cells, coupled with suppression of pro-tumorigenic factors (VEGF, IL-6). Integrated omics analysis suggests that the combined treatment may modulate tumor-stroma interaction pathways (e.g., PI3K-Akt, focal adhesion) and rewire immunometabolic networks (e.g., tryptophan metabolism). Our study provides hypothesis-generating correlative data positioning CIAA as a potential adjunct capable of remodeling the TME to potentiate anti-PD-1 therapy in lung cancer.

PMID:41915222 | DOI:10.1007/s00262-026-04368-1

Food Funct. 2026 Mar 31. doi: 10.1039/d5fo04958j. Online ahead of print.

ABSTRACT

The probiotic yeast Saccharomyces boulardii is renowned for its clinical efficacy, which is intrinsically linked to its exceptional ability to survive the harsh gastrointestinal (GI) environment. However, a comprehensive understanding of the molecular mechanisms and regulatory pathways underlying the stress tolerance of S. boulardii remains limited. This study employed an integrated transcriptomic and proteomic approach to systematically map the dynamic responses of S. boulardii to simulated GI transit. Our analysis revealed that the intestinal phase posed a significantly greater challenge than the gastric phase, triggering extensive molecular reprogramming. A core adaptive strategy was the marked upregulation of the central carbon metabolism, particularly glycolysis, as evidenced by the concerted overexpression of key enzymes at both transcriptional and translational levels, indicating a heightened demand for energy to fuel stress defence mechanisms. Furthermore, significant enrichment was observed in the pathways related to nitrogen and fatty acid metabolism. Integration of the multi-omics datasets highlighted the complexity of the regulatory response, with frequent discordance between mRNA and protein abundance underscoring the importance of post-transcriptional regulation. This study provides a detailed molecular profile of the stress tolerance network in S. boulardii, elucidating the strategic metabolic rewiring and multi-layered regulation that underpin its probiotic resilience. The findings offer valuable insights and a foundational resource for the future development of enhanced probiotic therapies.

PMID:41914832 | DOI:10.1039/d5fo04958j

Zhonghua Yi Xue Za Zhi. 2026 Mar 31;106:1-7. doi: 10.3760/cma.j.cn112137-20251201-03143. Online ahead of print.

ABSTRACT

Objective: To analyze the association between molecular typing and prognosis with recurrence pattern in triple-negative breast cancer (TNBC) patients based on long-term follow-up of a multi-omics cohort. Methods: A retrospective analysis was performed on the clinical data and transcriptomic data of patients diagnosed with TNBC at Department of Breast Surgery, Fudan University Shanghai Cancer Center from January 1, 2007, to December 31, 2014. The survival status of patients was documented, and the follow-up continued until the patients' death or August 31, 2025. According to the"Fudan subtype", the patients were categorized into the basal-like immune suppressed (BLIS), immunomodulatory (IM), luminal androgen receptor (LAR), and mesenchymal-like (MES). Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was employed to evaluate the differences in overall survival (OS), disease-free survival (DFS) and recurrence-free interval (RFI) among TNBC patients with different molecular subtypes. Multivariate Cox proportional hazards regression analysis was used to assess the association between"Fudan subtype"and OS, DFS and RFI. Differential expression analysis and subsequent gene set enrichment were conducted. Competing-risk models were used to calculate the cumulative incidence of lung metastasis after accounting for competing events, and the differences were assessed using the Fine-Gray test. Results: After excluding 9 patients lost to follow-up, a total of 351 patients with TNBC were included in the analysis. The mean age at baseline was 53.46±11.36 years, and the median follow-up duration was 102.09 months. During follow-up, 72 patients died and 84 experienced recurrence or metastasis. Among them, 134 patients were classified as the BLIS subtype, with 27 deaths (20.15%); 86 patients were classified as the IM subtype, with 11 deaths (12.79%); 81 patients were classified as the LAR subtype, with 22 deaths (27.16%); and 50 patients were classified as the MES subtype, with 12 deaths (24.00%). The 10-year RFI rates for the BLIS, IM, LAR, and MES subtypes were 80.12% (95%CI: 73.41%-87.44%), 92.35% (95%CI: 86.64%-98.43%), 81.92% (95%CI: 73.39%-91.44%), and 72.95% (95%CI: 61.37%-86.71%), respectively. Kaplan-Meier survival curves showed that the differences of RFI among the four molecular subtypes of patients were statistically significant (P=0.040). Multivariate analysis showed that LAR subtype (LAR vs IM, HR=2.41, P=0.042) was the independent risk factor for DFS, and BLIS subtype (BLIS vs IM, HR=4.17, P=0.011), LAR subtype (LAR vs IM, HR=3.49, P=0.040) and MES subtype (MES vs IM, HR=3.98, P=0.019) were independent risk factors for RFI. The BLIS subtype is more likely to develop recurrence or metastasis in the early postoperative period, particularly lung metastasis. Differential gene expression analysis showed that BLIS subtype-specific genes, including those involved in proliferation and cell cycle activity, were predominantly upregulated in tumors with early recurrence or metastasis. Competing-risk analysis demonstrated that BLIS patients had a higher cumulative incidence of lung metastasis both overall and within the first 5 years after surgery compared with non-BLIS patients (both P<0.05). Conclusion: The"Fudan subtype"was significantly associated with RFI in early-stage TNBC patients. In addition, recurrence and metastasis were more likely to be observed in the early postoperative period in the BLIS subtype, particularly early lung metastasis.

PMID:41913624 | DOI:10.3760/cma.j.cn112137-20251201-03143

Cell Rep Med. 2026 Mar 30:102708. doi: 10.1016/j.xcrm.2026.102708. Online ahead of print.

ABSTRACT

Intratumor heterogeneity (ITH) undermines transcriptome-based stratification in intrahepatic cholangiocarcinoma (iCCA). Here, we integrate multi-omics data from multi-region, single-region, and single-cell RNA sequencing cohorts to systematically characterize gene expression ITH. We uncover that immune and stromal heterogeneity are primary drivers of ITH, leading to misclassification of a median 27.8% of tumors by existing subtyping systems. To overcome this, we identify a low-intratumor-heterogeneity/high-intertumor-variability (LIHV) gene set and develop an ITH-insensitive classification system defining five subgroups: inflammatory (SI), metabolic (SII), atypical (SIII-1), immune-silent (SIII-2), and neurodegenerative (SIII-3). These subgroups exhibit distinct clinical outcomes, molecular features, immune landscapes, and therapeutic vulnerabilities. GPRC5A and VTCN1 serve as robust immunohistochemical biomarkers for SI and SIII tumors, while serum CEA and CA19-9 identify inflammatory iCCA. Therapeutically, HSP90 inhibition synergizes with anti-PD1 in inflammatory iCCA, whereas combined anti-PD1 and anti-TIM3 suppresses neurodegenerative iCCA. Collectively, our study provides a robust molecular framework and actionable therapeutic strategies for iCCA.

PMID:41916296 | DOI:10.1016/j.xcrm.2026.102708

Int J Gen Med. 2026 Mar 24;19:590621. doi: 10.2147/IJGM.S590621. eCollection 2026.

ABSTRACT

Inflammatory bowel disease (IBD) involves chronic intestinal inflammation driven by gut-brain axis imbalance, fostering complications through an "inflammation-neuro-coagulation" triad. Current staging systems inadequately capture the dynamics of this multidimensional network. Therefore, integrated multi-omics analyses-including metagenomics, metabolomics, and single-cell transcriptomics-are essential to construct dynamic models that monitor coagulation, microbiome, and metabolism for precise assessment of disease activity and thrombotic or bleeding risks. Interventions targeting gut-brain axis nodes, such as eliminating tissue factor-positive (TF⁺) T cells or modulating vagal activity, show potential to disrupt the inflammation-coagulation cycle, although rigorous randomized trials are still needed. Artificial intelligence (AI)-assisted systems that integrate real-time biomarker monitoring with multi-omics predictions represent a novel paradigm for managing IBD-related coagulation dysfunction. Key challenges include elucidating gut-brain-liver axis regulation of coagulation and characterizing platelet functional heterogeneity. Future efforts must prioritize ethically compliant multi-omics platforms and racially stratified risk models to advance personalized coagulation management in IBD.

PMID:41913906 | PMC:PMC13033200 | DOI:10.2147/IJGM.S590621

Cancer Biol Med. 2026 Mar 30:j.issn.2095-3941.2026.0045. doi: 10.20892/j.issn.2095-3941.2026.0045. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) remains a major global health burden characterized by late-stage diagnosis and high postoperative recurrence rates. This review presents a surgery-centered precision management framework integrating 3 synergistic components: early detection, precision surgery, and recurrence prevention. Early detection strategies incorporate multiparameter risk models including the gender, age, AFP-L3, AFP, and DCP (GALAD) as well as age, sex, AFP, and PIVKA-II (ASAP) scores, alongside circulating tumor DNA methylation-based liquid biopsy, thus enabling tumor identification at stages amenable to curative resection. Precision surgery optimizes patient selection through refined staging systems including the Chinese liver cancer staging (CNLC), and functional assessments including the albumin-bilirubin (ALBI) grade, whereas conversion therapy and minimally invasive approaches extend surgical eligibility to selected patients with intermediate-stage disease. To mitigate the risk of postoperative recurrence, distinguishing between early and late recurrence patterns and monitoring minimal residual disease are critical strategies. Perioperative systemic therapies, particularly immune checkpoint inhibitor-based combinations, show promise for eradicating micrometastatic disease. This integrated framework provides a cohesive, evidence-based approach to personalized HCC management aimed at maximizing curative potential and long-term survival.

PMID:41913379 | DOI:10.20892/j.issn.2095-3941.2026.0045

EMBO Mol Med. 2026 Mar 30. doi: 10.1038/s44321-026-00410-y. Online ahead of print.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

PMID:41912871 | DOI:10.1038/s44321-026-00410-y

Cancer Lett. 2026 Mar 28;648:218465. doi: 10.1016/j.canlet.2026.218465. Online ahead of print.

ABSTRACT

Cancer remains a leading cause of death worldwide, with lineage plasticity emerging as a hallmark that drives therapy resistance and tumor progression by enabling cancer cells to alter identity and evade targeted therapies. Although genomic and transcriptomic aberrations correlate with lineage plasticity, the absence of scalable cross-cancer markers to rapidly identify plastic subtypes has limited predictive utility. Homeobox (HOX) genes encode transcription factors that define tissue identity through distinct expression patterns, or HOX codes, within specific lineages. By analyzing multi-omics data encompassing 39 HOX genes across more than 80,000 RNA-seq samples across 23 cancer types spanning 114 cancer subtypes, we found that HOX code expression robustly stratifies lineage-constrained and lineage-plastic states at a cross-cancer level. This framework revealed previously unrecognized lineage-plastic subtypes in prostate cancer, lung cancer, and acute myeloid leukemia (AML), each displaying distinct HOX code divergence compared to non-plastic counterparts. Differential expression analysis across these representative malignancies identified RUNX1T1 as a consistent regulator associated with HOX-defined plastic states. We validated RUNX1T1 upregulation in bulk and single-cell RNA-seq from extensive preclinical and clinical cohorts and demonstrated that RUNX1T1 is functionally required for lineage-plastic programs in prostate cancer models. AI-based structural modeling and co-immunoprecipitation established the NCOR/HDAC3 complex as a critical binding partner of RUNX1T1. CUT&RUN profiling revealed that RUNX1T1 remodels chromatin by globally reducing active enhancer marks, thereby repressing lineage-defining differentiation programs and reshaping HOX positional identity. Selective pharmacologic inhibition of HDAC3 or targeted gene silencing via lipid nanoparticles suppressed the growth of lineage-plastic cancer cells, uncovering a therapeutically actionable vulnerability. Together, these findings establish RUNX1T1 as a cross-lineage regulator of HOX code-defined plasticity and identify the RUNX1T1-HDAC axis as a targetable mechanism underlying cancer lineage plasticity.

PMID:41912135 | DOI:10.1016/j.canlet.2026.218465

Microb Pathog. 2026 Mar 28;215:108464. doi: 10.1016/j.micpath.2026.108464. Online ahead of print.

ABSTRACT

Despite the clinical application of Ophiopogon japonicus in idiopathic pulmonary fibrosis (PF), its key anti-fibrotic components and underlying mechanisms remain poorly defined. Using a bleomycin-induced murine PF model, we systematically compared the efficacy of the total extract (OJTE), polysaccharides (OJTP), saponins (OJTS), and flavonoids (OJTF). The active component was further investigated via integrated metagenomics and metabolomics (serum/feces) to decipher the gut-lung axis mechanism. All O. japonicus components attenuated lung injury and collagen deposition, with OJTP demonstrating the most potent efficacy (reducing lung hydroxyproline content by 42.12% (p < 0.01) compared to the model group). Multi-omics analysis revealed that OJTP remodeled the gut microbiota, notably enriching probiotic strains such as Muribaculaceae bacterium (log₂FC = 2.17) and Duncaniella muricolitica (log₂FC = 2.06), as well as the polysaccharide-utilizing species Prevotella sp. MGM2 (log₂FC = 2.79). Concomitantly, OJTP significantly altered host metabolism, upregulating key metabolites including urobilinogen (p < 0.0001) and 5-amino valeric acid betaine (5-AVAB, p < 0.002). These metabolites are implicated in porphyrin and amino acid metabolism, respectively. Correlation networks further established strong associations between these OJTP-modulated microbes and metabolites. Our study first identifies OJTP as the primary bioactive component of O. japonicus against PF. We propose a novel trans-organ mechanism wherein OJTP ameliorates PF via orchestrating a "gut microbiota-metabolite" axis, highlighting the therapeutic potential of targeting polysaccharide-probiotic synergy.

PMID:41912071 | DOI:10.1016/j.micpath.2026.108464