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PAR$^2$-RAG: Planned Active Retrieval and Reasoning for Multi-Hop Question Answering

arXiv:2603.29085v1 Announce Type: new Abstract: Large language models (LLMs) remain brittle on multi-hop question answering (MHQA), where answering requires combining evidence across documents through retrieval and reasoning. Iterative retrieval systems can fail by locking onto an early low-recall trajectory and amplifying downstream errors, while planning-only approaches may produce static query sets that cannot adapt when intermediate evidence changes. We propose \textbf{Planned Active Retrieval and Reasoning RAG (PAR$^2$-RAG)}, a two-stage framework that separates \emph{coverage} from \emph{commitment}. PAR$^2$-RAG first performs breadth-first anchoring to build a high-recall evidence frontier, then applies depth-first refinement with evidence sufficiency control in an iterative loop. Across four MHQA benchmarks, PAR$^2$-RAG consistently outperforms existing state-of-the-art baselines, compared with IRCoT, PAR$^2$-RAG achieves up to \textbf{23.5\%} higher accuracy, with retrieval gains of up to \textbf{10.5\%} in NDCG.

Owl-AuraID 1.0: An Intelligent System for Autonomous Scientific Instrumentation and Scientific Data Analysis

arXiv:2603.29828v1 Announce Type: new Abstract: Scientific discovery increasingly depends on high-throughput characterization, yet automation is hindered by proprietary GUIs and the limited generalizability of existing API-based systems. We present Owl-AuraID, a software-hardware collaborative embodied agent system that adopts a GUI-native paradigm to operate instruments through the same interfaces as human experts. Its skill-centric framework integrates Type-1 (GUI operation) and Type-2 (data analysis) skills into end-to-end workflows, connecting physical sample handling with scientific interpretation. Owl-AuraID demonstrates broad coverage across ten categories of precision instruments and diverse workflows, including multimodal spectral analysis, microscopic imaging, and crystallographic analysis, supporting modalities such as FTIR, NMR, AFM, and TGA. Overall, Owl-AuraID provides a practical, extensible foundation for autonomous laboratories and illustrates a path toward evolving laboratory intelligence through reusable operational and analytical skills. The code are available at https://github.com/OpenOwlab/AuraID.

MemFactory: Unified Inference & Training Framework for Agent Memory

arXiv:2603.29493v1 Announce Type: cross Abstract: Memory-augmented Large Language Models (LLMs) are essential for developing capable, long-term AI agents. Recently, applying Reinforcement Learning (RL) to optimize memory operations, such as extraction, updating, and retrieval, has emerged as a highly promising research direction. However, existing implementations remain highly fragmented and task-specific, lacking a unified infrastructure to streamline the integration, training, and evaluation of these complex pipelines. To address this gap, we present MemFactory, the first unified, highly modular training and inference framework specifically designed for memory-augmented agents. Inspired by the success of unified fine-tuning frameworks like LLaMA-Factory, MemFactory abstracts the memory lifecycle into atomic, plug-and-play components, enabling researchers to seamlessly construct custom memory agents via a "Lego-like" architecture. Furthermore, the framework natively integrates Group Relative Policy Optimization (GRPO) to fine-tune internal memory management policies driven by multi-dimensional environmental rewards. MemFactory provides out-of-the-box support for recent cutting-edge paradigms, including Memory-R1, RMM, and MemAgent. We empirically validate MemFactory on the open-source MemAgent architecture using its publicly available training and evaluation data. Across both in-domain and out-of-distribution evaluation sets, MemFactory consistently improves performance over the corresponding base models, with relative gains of up to 14.8%. By providing a standardized, extensible, and easy-to-use infrastructure, MemFactory significantly lowers the barrier to entry, paving the way for future innovations in memory-driven AI agents.

Four Generations of Quantum Biomedical Sensors

arXiv:2603.29944v1 Announce Type: cross Abstract: Quantum sensing technologies offer transformative potential for ultra-sensitive biomedical sensing, yet their clinical translation remains constrained by classical noise limits and a reliance on macroscopic ensembles. We propose a unifying generational framework to organize the evolving landscape of quantum biosensors based on their utilization of quantum resources. First-generation devices utilize discrete energy levels for signal transduction but follow classical scaling laws. Second-generation sensors exploit quantum coherence to reach the standard quantum limit, while third-generation architectures leverage entanglement and spin squeezing to approach Heisenberg-limited precision. We further define an emerging fourth generation characterized by the end-to-end integration of quantum sensing with quantum learning and variational circuits, enabling adaptive inference directly within the quantum domain. By analyzing critical parameters such as bandwidth matching and sensor-tissue proximity, we identify key technological bottlenecks and propose a roadmap for transitioning from measuring physical observables to extracting structured biological information with quantum-enhanced intelligence.

Let the Agent Steer: Closed-Loop Ranking Optimization via Influence Exchange

arXiv:2603.27765v2 Announce Type: replace Abstract: Recommendation ranking is fundamentally an influence allocation problem: a sorting formula distributes ranking influence among competing factors, and the business outcome depends on finding the optimal "exchange rates" among them. However, offline proxy metrics systematically misjudge how influence reallocation translates to online impact, with asymmetric bias across metrics that a single calibration factor cannot correct. We present Sortify, the first fully autonomous LLM-driven ranking optimization agent deployed in a large-scale production recommendation system. The agent reframes ranking optimization as continuous influence exchange, closing the full loop from diagnosis to parameter deployment without human intervention. It addresses structural problems through three mechanisms: (1) a dual-channel framework grounded in Savage's Subjective Expected Utility (SEU) that decouples offline-online transfer correction (Belief channel) from constraint penalty adjustment (Preference channel); (2) an LLM meta-controller operating on framework-level parameters rather than low-level search variables; (3) a persistent Memory DB with 7 relational tables for cross-round learning. Its core metric, Influence Share, provides a decomposable measure where all factor contributions sum to exactly 100%. Sortify has been deployed across two markets. In Country A, the agent pushed GMV from -3.6% to +9.2% within 7 rounds with peak orders reaching +12.5%. In Country B, a cold-start deployment achieved +4.15% GMV/UU and +3.58% Ads Revenue in a 7-day A/B test, leading to full production rollout.

InfiniteVL: Synergizing Linear and Sparse Attention for Highly-Efficient, Unlimited-Input Vision-Language Models

arXiv:2512.08829v2 Announce Type: replace-cross Abstract: Vision-Language Models (VLMs) are increasingly tasked with ultra-long multimodal understanding. While linear architectures offer constant computation and memory footprints, they often struggle with high-frequency visual perception compared to standard Transformers. To bridge this gap, we introduce \textbf{InfiniteVL}. We first develop a hybrid base model called \textbf{InfiniteVL-Base} that interleaves a small fraction of Full Attention layers with Gated DeltaNet. Empowered by a tailored distillation and fine-tuning strategy, InfiniteVL-Base matches the fundamental multimodal performance of equivalent Transformers while achieving a \textbf{1.7$\times$} decoding speedup. However, the quadratic complexity of the retained Full Attention inevitably becomes an efficiency bottleneck when scaling to ultra long context. To break this barrier, we propose a novel Long-Sequence Architectural Fine-Tuning strategy that seamlessly transforms the dense attention into vision-specific sparse mechanisms. This yields two specialized variants: \textbf{InfiniteVL-Offline} for offline retrieval and \textbf{InfiniteVL-Online} for online streaming. By eliminating the computation explosion of global attention without sacrificing high-frequency visual recall, InfiniteVL-Offline achieves Transformer-level length generalization with a \textbf{5x} prefill acceleration at 256K context. Concurrently, InfiniteVL-Online delivers robust streaming perception with a constant memory footprint and a real-time throughput of \textbf{25} FPS. Code and models are available at https://github.com/hustvl/InfiniteVL.

Gene regulatory landscape dissected by single-cell four-omics sequencing

Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10322-z

Combining single-cell parallel profiling of genome conformation, histone modifications, chromatin accessibility and gene expression reveals dynamics and intranuclear spatial clustering of epigenome profiles, enabling sophisticated analysis of the regulatory landscape across cell types and tissues.

PERMA: Benchmarking Personalized Memory Agents via Event-Driven Preference and Realistic Task Environments

arXiv:2603.23231v1 Announce Type: new Abstract: Empowering large language models with long-term memory is crucial for building agents that adapt to users' evolving needs. However, prior evaluations typically interleave preference-related dialogues with irrelevant conversations, reducing the task to needle-in-a-haystack retrieval while ignoring relationships between events that drive the evolution of user preferences. Such settings overlook a fundamental characteristic of real-world personalization: preferences emerge gradually and accumulate across interactions within noisy contexts. To bridge this gap, we introduce PERMA, a benchmark designed to evaluate persona consistency over time beyond static preference recall. Additionally, we incorporate (1) text variability and (2) linguistic alignment to simulate erratic user inputs and individual idiolects in real-world data. PERMA consists of temporally ordered interaction events spanning multiple sessions and domains, with preference-related queries inserted over time. We design both multiple-choice and interactive tasks to probe the model's understanding of persona along the interaction timeline. Experiments demonstrate that by linking related interactions, advanced memory systems can extract more precise preferences and reduce token consumption, outperforming traditional semantic retrieval of raw dialogues. Nevertheless, they still struggle to maintain a coherent persona across temporal depth and cross-domain interference, highlighting the need for more robust personalized memory management in agents. Our code and data are open-sourced at https://github.com/PolarisLiu1/PERMA.

TDATR: Improving End-to-End Table Recognition via Table Detail-Aware Learning and Cell-Level Visual Alignment

arXiv:2603.22819v1 Announce Type: cross Abstract: Tables are pervasive in diverse documents, making table recognition (TR) a fundamental task in document analysis. Existing modular TR pipelines separately model table structure and content, leading to suboptimal integration and complex workflows. End-to-end approaches rely heavily on large-scale TR data and struggle in data-constrained scenarios. To address these issues, we propose TDATR (Table Detail-Aware Table Recognition) improves end-to-end TR through table detail-aware learning and cell-level visual alignment. TDATR adopts a ``perceive-then-fuse'' strategy. The model first performs table detail-aware learning to jointly perceive table structure and content through multiple structure understanding and content recognition tasks designed under a language modeling paradigm. These tasks can naturally leverage document data from diverse scenarios to enhance model robustness. The model then integrates implicit table details to generate structured HTML outputs, enabling more efficient TR modeling when trained with limited data. Furthermore, we design a structure-guided cell localization module integrated into the end-to-end TR framework, which efficiently locates cell and strengthens vision-language alignment. It enhances the interpretability and accuracy of TR. We achieve state-of-the-art or highly competitive performance on seven benchmarks without dataset-specific fine-tuning.

BIRD-INTERACT: Re-imagining Text-to-SQL Evaluation for Large Language Models via Lens of Dynamic Interactions

arXiv:2510.05318v3 Announce Type: replace Abstract: Large language models (LLMs) have demonstrated remarkable performance on single-turn text-to-SQL tasks, but real-world database applications predominantly require multi-turn interactions to handle ambiguous queries, execution errors, and evolving user requirements. Existing multi-turn benchmarks fall short by treating conversation histories as static context or limiting evaluation to read-only operations, failing to reflect production-grade database assistant challenges. We introduce BIRD-INTERACT, a benchmark that restores this realism through: (1) a comprehensive interaction environment coupling each database with a hierarchical knowledge base, metadata files, and a function-driven user simulator, enabling models to solicit clarifications, retrieve knowledge, and recover from errors without human supervision; (2) two evaluation settings consisting of a pre-defined conversational protocol (c-Interact) and an open-ended agentic setting (a-Interact) where models autonomously decide when to query the user simulator or explore the environment; (3) a challenging task suite covering the full CRUD spectrum for business-intelligence and operational use cases, guarded by executable test cases. Each task features ambiguous and follow-up sub-tasks requiring dynamic interaction. The suite comprises BIRD-INTERACT-FULL (600 tasks, up to 11,796 interactions) for comprehensive performance assessment, and BIRD-INTERACT-LITE (300 tasks with simplified databases) for detailed behavioral analysis and rapid method development. Our empirical results highlight BIRD-INTERACT's difficulty: GPT-5 completes only 8.67% of tasks in c-Interact and 17.00% in a-Interact. Analysis via memory grafting and Interaction Test-time Scaling validates the importance of effective interaction for complex, dynamic text-to-SQL tasks.

UniCA: Unified Covariate Adaptation for Time Series Foundation Model

arXiv:2506.22039v2 Announce Type: replace-cross Abstract: Time Series Foundation Models (TSFMs) have achieved remarkable success through large-scale pretraining. However, their design primarily targets real-valued series, limiting their ability to handle general forecasting tasks involving diverse and often heterogeneous covariates -- such as categorical variables and multimodal data (e.g., images, text) -- which are typically task-specific and difficult to leverage during pretraining. To address this gap, we propose Unified Covariate Adaptation (UniCA), a framework to bridge TSFMs with general covariate-aware forecasting. UniCA first performs covariate homogenization to transform heterogeneous covariates into high-level homogeneous series representations and then fuses them via a unified attention-based fusion mechanism. UniCA is compatible and universal for adaptation with both homogeneous and heterogeneous covariates, incorporating extra covariate information while preserving the generalization ability of TSFMs.Extensive experiments on multiple unimodal and multimodal covariate-aware forecasting benchmarks demonstrate the superiority of UniCA, highlighting the promise of covariate-aware TSFM adaptation in real-world forecasting scenarios.Code: https://github.com/hanlu-nju/UniCA.

From Editor to Dense Geometry Estimator

arXiv:2509.04338v2 Announce Type: replace-cross Abstract: Leveraging visual priors from pre-trained text-to-image (T2I) generative models has shown success in dense prediction. However, dense prediction is inherently an image-to-image task, suggesting that image editing models, rather than T2I generative models, may be a more suitable foundation for fine-tuning. Motivated by this, we conduct a systematic analysis of the fine-tuning behaviors of both editors and generators for dense geometry estimation. Our findings show that editing models possess inherent structural priors, which enable them to converge more stably by ``refining" their innate features, and ultimately achieve higher performance than their generative counterparts. Based on these findings, we introduce \textbf{FE2E}, a framework that pioneeringly adapts an advanced editing model based on Diffusion Transformer (DiT) architecture for dense geometry prediction. Specifically, to tailor the editor for this deterministic task, we reformulate the editor's original flow matching loss into the ``consistent velocity" training objective. And we use logarithmic quantization to resolve the precision conflict between the editor's native BFloat16 format and the high precision demand of our tasks. Additionally, we leverage the DiT's global attention for a cost-free joint estimation of depth and normals in a single forward pass, enabling their supervisory signals to mutually enhance each other. Without scaling up the training data, FE2E achieves impressive performance improvements in zero-shot monocular depth and normal estimation across multiple datasets. Notably, it achieves over 35\% performance gains on the ETH3D dataset and outperforms the DepthAnything series, which is trained on 100$\times$ data. The project page can be accessed \href{https://amap-ml.github.io/FE2E/}{here}.

LoD-Loc v3: Generalized Aerial Localization in Dense Cities using Instance Silhouette Alignment

arXiv:2603.19609v2 Announce Type: replace-cross Abstract: We present LoD-Loc v3, a novel method for generalized aerial visual localization in dense urban environments. While prior work LoD-Loc v2 achieves localization through semantic building silhouette alignment with low-detail city models, it suffers from two key limitations: poor cross-scene generalization and frequent failure in dense building scenes. Our method addresses these challenges through two key innovations. First, we develop a new synthetic data generation pipeline that produces InsLoD-Loc - the largest instance segmentation dataset for aerial imagery to date, comprising 100k images with precise instance building annotations. This enables trained models to exhibit remarkable zero-shot generalization capability. Second, we reformulate the localization paradigm by shifting from semantic to instance silhouette alignment, which significantly reduces pose estimation ambiguity in dense scenes. Extensive experiments demonstrate that LoD-Loc v3 outperforms existing state-of-the-art (SOTA) baselines, achieving superior performance in both cross-scene and dense urban scenarios with a large margin. The project is available at https://nudt-sawlab.github.io/LoD-Locv3/.

BadminSense: Enabling Fine-Grained Badminton Stroke Evaluation on a Single Smartwatch

arXiv:2603.21825v2 Announce Type: replace-cross Abstract: Evaluating badminton performance often requires expert coaching, which is rarely accessible for amateur players. We present BadminSense, a smartwatch-based system for fine-grained badminton performance analysis using wearable sensing. Through interviews with experienced badminton players, we identified four system design requirements with three implementation insights that guide the development of BadminSense. We then collected a badminton strokes dataset on 12 experienced badminton amateurs and annotated it with fine-grained labels, including stroke type, expert-assessed stroke rating, and shuttle impact location. Built on this dataset, BadminSense segments and classifies strokes, predicts stroke quality, and estimates shuttle impact location using vibration signal from an off-the-shelf smartwatch. Our evaluations show that BadminSense achieves a stroke classification accuracy of 91.43%, an average quality rating error of 0.438, and an average impact location estimation error of 12.9%. A real-world usability study further demonstrates BadminSense's potential to provide reliable and meaningful support for daily badminton practice.

When Right Meets Wrong: Bilateral Context Conditioning with Reward-Confidence Correction for GRPO

arXiv:2603.13134v1 Announce Type: new Abstract: Group Relative Policy Optimization (GRPO) has emerged as an effective method for training reasoning models. While it computes advantages based on group mean, GRPO treats each output as an independent sample during the optimization and overlooks a vital structural signal: the natural contrast between correct and incorrect solutions within the same group, thus ignoring the rich, comparative data that could be leveraged by explicitly pitting successful reasoning traces against failed ones. To capitalize on this, we present a contrastive reformulation of GRPO, showing that the GRPO objective implicitly maximizes the margin between the policy ratios of correct and incorrect samples. Building on this insight, we propose Bilateral Context Conditioning (BICC), a mechanism that allows the model to cross-reference successful and failed reasoning traces during the optimization, enabling a direct information flow across samples. We further introduce Reward-Confidence Correction (RCC) to stabilize training by dynamically adjusts the advantage baseline in GRPO using reward-confidence covariance derived from the first-order approximation of the variance-minimizing estimator. Both mechanisms require no additional sampling or auxiliary models and can be adapted to all GRPO variants. Experiments on mathematical reasoning benchmarks demonstrate consistent improvements across comprehensive models and algorithms. Code is available at \href{https://github.com/Skylanding/BiCC}{https://github.com/Skylanding/BiCC}.

Empowering Semantic-Sensitive Underwater Image Enhancement with VLM

arXiv:2603.12773v1 Announce Type: cross Abstract: In recent years, learning-based underwater image enhancement (UIE) techniques have rapidly evolved. However, distribution shifts between high-quality enhanced outputs and natural images can hinder semantic cue extraction for downstream vision tasks, thereby limiting the adaptability of existing enhancement models. To address this challenge, this work proposes a new learning mechanism that leverages Vision-Language Models (VLMs) to empower UIE models with semantic-sensitive capabilities. To be concrete, our strategy first generates textual descriptions of key objects from a degraded image via VLMs. Subsequently, a text-image alignment model remaps these relevant descriptions back onto the image to produce a spatial semantic guidance map. This map then steers the UIE network through a dual-guidance mechanism, which combines cross-attention and an explicit alignment loss. This forces the network to focus its restorative power on semantic-sensitive regions during image reconstruction, rather than pursuing a globally uniform improvement, thereby ensuring the faithful restoration of key object features. Experiments confirm that when our strategy is applied to different UIE baselines, significantly boosts their performance on perceptual quality metrics as well as enhances their performance on detection and segmentation tasks, validating its effectiveness and adaptability.

Visual-ERM: Reward Modeling for Visual Equivalence

arXiv:2603.13224v1 Announce Type: cross Abstract: Vision-to-code tasks require models to reconstruct structured visual inputs, such as charts, tables, and SVGs, into executable or structured representations with high visual fidelity. While recent Large Vision Language Models (LVLMs) achieve strong results via supervised fine-tuning, reinforcement learning remains challenging due to misaligned reward signals. Existing rewards either rely on textual rules or coarse visual embedding similarity, both of which fail to capture fine-grained visual discrepancies and are vulnerable to reward hacking. We propose Visual Equivalence Reward Model (Visual-ERM), a multimodal generative reward model that provides fine-grained, interpretable, and task-agnostic feedback to evaluate vision-to-code quality directly in the rendered visual space. Integrated into RL, Visual-ERM improves Qwen3-VL-8B-Instruct by +8.4 on chart-to-code and yields consistent gains on table and SVG parsing (+2.7, +4.1 on average), and further strengthens test-time scaling via reflection and revision. We also introduce VisualCritic-RewardBench (VC-RewardBench), a benchmark for judging fine-grained image-to-image discrepancies on structured visual data, where Visual-ERM at 8B decisively outperforms Qwen3-VL-235B-Instruct and approaches leading closed-source models. Our results suggest that fine-grained visual reward supervision is both necessary and sufficient for vision-to-code RL, regardless of task specificity.

How to Build a Quantum Supercomputer: Scaling from Hundreds to Millions of Qubits

arXiv:2411.10406v3 Announce Type: replace-cross Abstract: In the span of four decades, quantum computation has evolved from an intellectual curiosity to a potentially realizable technology. Today, small-scale demonstrations have become possible for quantum algorithmic primitives on hundreds of physical qubits. Nevertheless, there are significant outstanding challenges in quantum hardware, fabrication, software architecture, and algorithms on the path towards a full-stack scalable quantum computing technology. Here, we provide a comprehensive review of these scaling challenges. We show how to facilitate scaling by adopting existing semiconductor technology to build much higher-quality qubits, employing systems engineering approaches, and performing distributed heterogeneous quantum-classical computing. We provide a detailed resource and sensitivity analysis for quantum applications on surface-code error-corrected quantum computers given current, target, and desired hardware specifications based on superconducting qubits, accounting for a realistic distribution of errors. We provide comprehensive resource estimates for several utility-scale applications including quantum chemistry calculations, catalyst design, NMR spectroscopy, and Fermi-Hubbard simulation. We show that orders of magnitude enhancement in performance could be obtained by a combination of hardware improvements and tight quantum-HPC integration. Furthermore, we introduce high-performance architectures for quantum-probabilistic computing with custom-designed accelerators to tackle today's industry-scale classical optimization, machine learning, and quantum simulation tasks in a cost-effective manner.

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-1β, and TNF-α. 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

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-1β, and TNF-α. 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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