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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

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Multiscale Structure-Guided Latent Diffusion for Multimodal MRI Translation

arXiv:2603.12581v1 Announce Type: cross Abstract: Although diffusion models have achieved remarkable progress in multi-modal magnetic resonance imaging (MRI) translation tasks, existing methods still tend to suffer from anatomical inconsistencies or degraded texture details when handling arbitrary missing-modality scenarios. To address these issues, we propose a latent diffusion-based multi-modal MRI translation framework, termed MSG-LDM. By leveraging the available modalities, the proposed method infers complete structural information, which preserves reliable boundary details. Specifically, we introduce a style--structure disentanglement mechanism in the latent space, which explicitly separates modality-specific style features from shared structural representations, and jointly models low-frequency anatomical layouts and high-frequency boundary details in a multi-scale feature space. During the structure disentanglement stage, high-frequency structural information is explicitly incorporated to enhance feature representations, guiding the model to focus on fine-grained structural cues while learning modality-invariant low-frequency anatomical representations. Furthermore, to reduce interference from modality-specific styles and improve the stability of structure representations, we design a style consistency loss and a structure-aware loss. Extensive experiments on the BraTS2020 and WMH datasets demonstrate that the proposed method outperforms existing MRI synthesis approaches, particularly in reconstructing complete structures. The source code is publicly available at https://github.com/ziyi-start/MSG-LDM.
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Deep Expert Injection for Anchoring Retinal VLMs with Domain-Specific Knowledge

arXiv:2603.07131v1 Announce Type: cross Abstract: Large Vision Language Models (LVLMs) show immense potential for automated ophthalmic diagnosis. However, their clinical deployment is severely hindered by lacking domain-specific knowledge. In this work, we identify two structural deficiencies hindering reliable medical reasoning: 1) the Perception Gap, where general-purpose visual encoders fail to resolve fine-grained pathological cues (e.g., microaneurysms); and 2) the Reasoning Gap, where sparse visual evidence is progressively overridden by massive language priors in deeper transformer layers, leading to ungrounded hallucinations. To bridge these gaps, we propose EyExIn, a data-efficient framework designed to anchor retinal VLMs with expert knowledge via a Deep Expert Injection mechanism. Our architecture employs an Expert-Aware Dual-Stream encoding strategy that decouples visual representation into a general stream for anatomical context and a specialized expert stream for pathological semantics. To ensure high-fidelity integration, we design a Semantic-Adaptive Gated Fusion module, which dynamically amplifies subtle lesion signals while filtering irrelevant background noise. Furthermore, we introduce Adaptive Deep Expert Injection to embed persistent "Vision Anchors" by integrating fused visual features as residual biases directly into intermediate LLM layers. This mechanism creates a visual shortcut that forces the reasoning stack to remain strictly grounded in visual evidence. Extensive experiments across four benchmarks demonstrate that our model consistently outperforms massive proprietary systems. EyExIn significantly enhances domain-specific knowledge embedding and achieves state-of-the-art precision in ophthalmic visual question answering, advancing the development of trustworthy ophthalmic AI.
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