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Parameter Efficient Multi-Class Intelligent Scheduling for Multimodal Online Distributed Industrial Anomaly Detection
Cross-Stage Attention Multi-Expert Network for Radiologist-Inspired Breast Ultrasound Diagnosis
Decoding ML Decision: An Agentic Reasoning Framework for Large-Scale Ranking System
A cell type-specific mechanism driving the rapid antidepressant effects of transcranial magnetic stimulation
Hepatotoxicity Prediction and Multi-omics Reveal Mitochondrial and Lipid Metabolic Dysregulation in PM<sub>2.5</sub>-Induced Liver Fibrosis
Environ Health (Wash). 2025 Nov 14;4(3):513-521. doi: 10.1021/envhealth.5c00401. eCollection 2026 Mar 20.
ABSTRACT
Prolonged exposure to fine particulate matter (PM2.5) has been linked to chronic liver injury and cancer. However, an alternative risk assessment method to prospective longitudinal studies of exposome-metabolome interactions for liver inflammation-associated hepatocellular carcinoma (HCC) is lacking. This study investigates the risk of long-term real-world PM2.5 exposure in hepatocarcinogenesis through machine learning techniques. Shotgun mass spectrometry (MS) imaging data were acquired from mouse models across a continuum of fibrosis, cirrhosis, and HCC for training a multiclass classification model to identify "No Risk", "Cancer Risk", and "Cancer". Direct infusion-MS data from PM2.5-exposed mouse livers were analyzed to classify risk. By integrating data-driven and knowledge-based approaches, 14 disease progression biomarkers were identified for modeling. Our results suggest that chronic real-world PM2.5 exposure can induce liver fibrosis, presenting cancer risk. Incorporating metabolomics, lipidomics, and transcriptomics, we propose PM2.5 exposure induces mitochondrial dysfunction, activates AMPK signaling, and increases ceramide accumulation, potentially mediating insulin resistance that contributes to nonalcoholic fatty liver disease and HCC progression. This work represents a significant advancement in assessing hepatotoxicity of environmental toxicants by reducing reliance on traditional animal testing methods. It also underscores the potential of emerging technologies in transforming our understanding of PM2.5 exposure, paving the way for targeted interventions.
PMID:41883379 | PMC:PMC13010293 | DOI:10.1021/envhealth.5c00401
Regulatory mechanisms of ALKBH5/CIITA axis in the synergistic modulation of hepatocellular carcinoma radiotherapy and immunotherapy
Genes Immun. 2026 Mar 10. doi: 10.1038/s41435-026-00382-6. Online ahead of print.
ABSTRACT
The prognosis for hepatocellular carcinoma remains grim. Combining radiotherapy with immune checkpoint blockade (ICB) has shown potential to enhance therapeutic outcomes, yet there is a pressing need for further advancements. Our previous research demonstrated that this combined approach suppresses ALKBH5 gene expression and increases m6A modification levels in hepatocellular carcinoma tissues. High-throughput sequencing and detailed molecular analysis revealed that inhibiting ALKBH5 amplifies CIITA m6A modifications post-therapy. This modulation triggers MHC II molecule expression in tumors, facilitating the presentation of tumor-associated antigens to CD4 + T lymphocytes and the recruitment of CD8 + T cells for an anti-tumor immune response. Building on these findings, we engineered a CIITA vector with a specific site mutation to confirm that the regulation of CIITA by the combined radiotherapy and immunotherapy is mediated through m6A methylation. Consequently, we established a comprehensive network involving ALKBH5, CIITA, MHC II, and CD4+ and CD8 + T cells. To elucidate the role and underlying molecular mechanisms of this combined therapy in reshaping the tumor immune microenvironment for hepatocellular carcinoma, we employed multi-omics approaches across in vitro, animal model, and clinical multi-dimensional studies, offering novel insights for enhancing treatment efficacy.
PMID:41807814 | DOI:10.1038/s41435-026-00382-6