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Chain of Evidence: Pixel-Level Visual Attribution for Iterative Retrieval-Augmented Generation

arXiv:2605.01284v2 Announce Type: replace-cross Abstract: Iterative Retrieval-Augmented Generation (iRAG) has emerged as a powerful paradigm for answering complex multi-hop questions by progressively retrieving and reasoning over external documents. However, current systems predominantly operate on parsed text, which creates two critical bottlenecks: (1) \textit{Coarse-grained attribution}, where users are burdened with manually locating evidence within lengthy documents based on vague text-level citations; and (2) \textit{Visual semantic loss}, where the conversion of visually rich documents (e.g., slides, PDFs with charts) into text discards spatial logic and layout cues essential for reasoning. To bridge this gap, we present \textbf{Chain of Evidence (CoE)}, a retriever-agnostic visual attribution framework that leverages Vision-Language Models to reason directly over screenshots of retrieved document candidates. CoE eliminates format-specific parsing and outputs precise bounding boxes, visualizing the complete reasoning chain within the retrieved candidate set. We evaluate CoE on two distinct benchmarks: \textbf{Wiki-CoE}, a large-scale dataset of structured web pages derived from 2WikiMultiHopQA, and \textbf{SlideVQA}, a challenging dataset of presentation slides featuring complex diagrams and free-form layouts. Experiments demonstrate that fine-tuned Qwen3-VL-8B-Instruct achieves robust performance, significantly outperforming text-based baselines in scenarios requiring visual layout understanding, while establishing a retriever-agnostic solution for pixel-level interpretable iRAG. Our code is available at https://github.com/PeiYangLiu/CoE.git.

Integrated Network Toxicology and Metabolomics Elucidate Mechanisms of Carbosulfan-Induced Respiratory Toxicity in Rats

Int J Mol Sci. 2026 Feb 25;27(5):2170. doi: 10.3390/ijms27052170.

ABSTRACT

Carbosulfan is a widely used carbamate insecticide, yet its mechanisms of respiratory toxicity remain poorly understood. This study integrated network toxicology, untargeted metabolomics, and molecular docking to systematically investigate the potential mechanisms of carbosulfan-induced respiratory toxicity in male Sprague Dawley rats. Rats were administered a single oral dose of carbosulfan (125 or 250 mg/kg) and assessed after 12 h. Exposure resulted in significant pathological lung damage, characterized by disrupted alveolar architecture, inflammatory cell infiltration, and increased serum levels of the pro-inflammatory cytokines IL-6, IL-1Ξ², and TNF-Ξ±. Network toxicology analysis identified 51 potential targets associated with respiratory toxicity, with core targets including SRC, EGFR, PTGS2, CXCL8, CYP3A4, and NR3C1. Enriched pathways were primarily related to neuroactive ligand-receptor interaction, VEGF signaling, and arachidonic acid metabolism. Untargeted metabolomics revealed significant metabolic perturbations in pathways central to antioxidant defense and energy homeostasis, including glutathione metabolism, the tricarboxylic acid cycle, and arginine biosynthesis. Molecular docking confirmed stable in silico binding affinities between carbosulfan and the predicted core targets. Integrative analysis suggests that carbosulfan exposure is associated with respiratory damage, potentially through interconnected mechanisms involving oxidative stress, inflammation, and disruption of cell signaling and metabolic enzyme systems. However, given the acute high-dose nature of the model and the interpretative integration of multi-omics data, these findings should be considered hypothesis-generating. This study provides a novel system-level perspective on carbosulfan-induced respiratory toxicity and highlights key pathways and targets for future validation in chronic exposure models.

PMID:41828400 | PMC:PMC12984169 | DOI:10.3390/ijms27052170

Integrated Network Toxicology and Metabolomics Elucidate Mechanisms of Carbosulfan-Induced Respiratory Toxicity in Rats

14 March 2026 at 18:00

Int J Mol Sci. 2026 Feb 25;27(5):2170. doi: 10.3390/ijms27052170.

ABSTRACT

Carbosulfan is a widely used carbamate insecticide, yet its mechanisms of respiratory toxicity remain poorly understood. This study integrated network toxicology, untargeted metabolomics, and molecular docking to systematically investigate the potential mechanisms of carbosulfan-induced respiratory toxicity in male Sprague Dawley rats. Rats were administered a single oral dose of carbosulfan (125 or 250 mg/kg) and assessed after 12 h. Exposure resulted in significant pathological lung damage, characterized by disrupted alveolar architecture, inflammatory cell infiltration, and increased serum levels of the pro-inflammatory cytokines IL-6, IL-1Ξ², and TNF-Ξ±. Network toxicology analysis identified 51 potential targets associated with respiratory toxicity, with core targets including SRC, EGFR, PTGS2, CXCL8, CYP3A4, and NR3C1. Enriched pathways were primarily related to neuroactive ligand-receptor interaction, VEGF signaling, and arachidonic acid metabolism. Untargeted metabolomics revealed significant metabolic perturbations in pathways central to antioxidant defense and energy homeostasis, including glutathione metabolism, the tricarboxylic acid cycle, and arginine biosynthesis. Molecular docking confirmed stable in silico binding affinities between carbosulfan and the predicted core targets. Integrative analysis suggests that carbosulfan exposure is associated with respiratory damage, potentially through interconnected mechanisms involving oxidative stress, inflammation, and disruption of cell signaling and metabolic enzyme systems. However, given the acute high-dose nature of the model and the interpretative integration of multi-omics data, these findings should be considered hypothesis-generating. This study provides a novel system-level perspective on carbosulfan-induced respiratory toxicity and highlights key pathways and targets for future validation in chronic exposure models.

PMID:41828400 | PMC:PMC12984169 | DOI:10.3390/ijms27052170

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