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Multi-omics approaches in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic targets and precision medicine

Front Pharmacol. 2026 Aug 28;17:1899849. doi: 10.3389/fphar.2026.1899849. eCollection 2026.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options and marked molecular heterogeneity. Despite available antifibrotic therapies, disease progression remains poorly predictable, highlighting the need for improved mechanistic understanding and therapeutic targeting. This review summarizes recent advances in multi-omics research to elucidate the molecular mechanisms underlying IPF and to identify potential biomarkers and pharmacological targets. Multi-omics studies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiome profiling, and single-cell sequencing, have revealed key pathogenic mechanisms in IPF. Genetic susceptibility factors such as MUC5B promoter variants and telomere-related genes contribute to disease risk. Epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNAs, plays a central role in fibrotic remodeling. Transcriptomic and proteomic analyses have identified dysregulated signaling pathways, including TGF-β, mTOR, cellular senescence, and extracellular matrix remodeling. Metabolomic alterations indicate disrupted lipid and amino acid metabolism. Importantly, integration of multi-omics datasets enables the identification of molecular endotypes, candidate biomarkers, and potential therapeutic targets. However, challenges including data integration, tissue heterogeneity, limited cohort size, and the need for functional validation remain important barriers to clinical translation. Continued development of multi-omics approaches may facilitate more accurate disease classification and support the development of personalized therapeutic strategies for IPF.

PMID:42729333 | PMC:PMC13561894 | DOI:10.3389/fphar.2026.1899849

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A clinically-oriented foundation model for intraoperative pathology

Nature Medicine, Published online: 10 September 2026; doi:10.1038/s41591-026-04703-0

CRISP, a vision-based pathology foundation model developed exclusively from frozen section slides, supports treatment decision-making throughout the surgical workflow with superior performance to current foundation models and extensive validation, including in a prospective cohort.
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UnitBoost: Managing Compound LLM Systems with a Merge Operator, Not a Model

arXiv:2609.09815v1 Announce Type: new Abstract: Compound LLM systems often solve a coordination problem by adding a higher-level LLM. The resulting meta-agent reads workers' outputs, writes the final answer, allocates later calls, and decides when to stop. It is expressive, but it also concentrates three control decisions in an opaque, order-sensitive model call. We ask whether the manager needs to be generative at all. UnitBoost replaces that model with a defined meta-level operator: a task-given unit map turns worker outputs into slot-value proposals, a constrained argmax assembles the output, and the slots left unfilled or unsupported become an explicit residual for the next round. The operator is order-free, records unit provenance, and gives a simple guarantee: without coupling constraints, unit-wise maximization under the same admission score dominates selection of any complete candidate. On three held-out benchmarks, it exceeds the best single candidate chosen with gold labels by 0.060-0.195 absolute task-score points and input-matched generative managers by 0.048-0.076. Replacing only the management step improves six compound-system configurations by 0.013-0.182. Residual-directed rounds raise FanOutQA cell F1 from 0.4778 to 0.5524; matched controls show that the true residual outperforms random targets and ordinary rereading, while a label-free supply signal flags exhaustion after one unproductive round. The same analysis measures three conditions in which no such gain is available (one indivisible unit, unavailable unit identity, and an endpoint that charges for every emitted unit) and quantifies cross-unit coupling as a repair cost. The manager gives up semantic freedom and gains order invariance, unit provenance, and testable failure conditions.
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Genomics and social practices at Mogou and other Gansu sites during prehistoric trans-Eurasian exchange

Ancient DNA from 149 individuals at 11 sites in Gansu, China, dated to around 4,700–3,000 years ago, reveals human population history during early transcontinental exchanges of agriculture and technology, as well as contemporary social practices, at the large Mogou cemetery.
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Targeting peripheral 5-HT2AR enhances antitumor immunity in colorectal cancer

By selectively targeting peripheral 5-HT2AR without inducing psychedelic effects, a non-brain-penetrant agonist boosts antitumor CD8+ T cell immunity and improves immunotherapy responses in preclinical models of colorectal cancer.
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MindAlign: Bridging EEG, Vision, and Language for Zero-Shot Visual Decoding

arXiv:2605.24523v1 Announce Type: cross Abstract: Visual decoding from brain signals is a key challenge at the intersection of computer vision and neuroscience, requiring methods that bridge neural representations and computational models of vision. We introduce a tri-modal contrastive framework for EEG-based visual decoding that aligns EEG, visual, and textual representations within a unified latent space. Our approach follows a two-stage design. First, we pre-train an EEG encoder via masked reconstruction on unlabeled trials, learning spatio-temporal regularities that transfer robustly to downstream tasks. Second, we jointly align EEG, image, and LLM-generated textual descriptions through contrastive learning, where text supervision acts as a semantic regularizer that injects linguistic structure into the shared space without overwhelming the primary EEG-image signal. The encoder integrates subject-specific adaptation, graph-attention over channels, and temporal-spatial convolutional embeddings. On the Things-EEG2 200-way zero-shot benchmark, our framework achieves 54.1% Top-1 and 83.4% Top-5 accuracy, substantially exceeding the strongest prior baseline (32.4% / 64.0%), with paired Wilcoxon tests confirming significance (p
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What Are We Actually Decoding? Source Attribution for Non-Invasive Brain-to-Language Retrieval

arXiv:2605.24524v1 Announce Type: cross Abstract: In non-invasive neural language decoding, results can be inflated by sources that are not stimulus-evoked neural evidence: decoder priors, embedding-based metrics, and non-neural structural nuisances such as signal duration. The methodological challenge is therefore attribution: a reported gain is more informative when it can be traced to a specific source. We recast stimulus-locked MEG-to-audio retrieval as an auditing framework that separates apparent performance into three sources - structural shortcuts, window-level stimulus-locked evidence, and cross-window contextual aggregation - and provides a diagnostic for each. Signal-blind Gaussian noise reaches 66.3% Rank@1 (R@1) under variable-length decoding but collapses to near chance once fixed-duration windows and stimulus-identity splits are enforced, isolating structural leakage. Under these controls, fixed-window retrieval recovers measurable MEG-audio discriminability, while an oracle sentence-bucket diagnostic shows that 95.7% of Top-1 errors select the wrong sentence, localising the residual bottleneck to sentence-level competition. We audit this contextual source with Group Context Bias (GCB), an inference-time additive logit bias that pools sentence-consistent evidence across windows while leaving the base retrieval scores and candidate pool fixed. Used as a score-space intervention, GCB makes the contextual source measurable: R@1 shifts from 44% to 52% on Gwilliams and from 22% to 29% on MOUS under the same fixed setting. GCB is auditable under this design: its effect collapses under random-grouping perturbations and vanishes when local evidence is attenuated in MEG or is near chance in EEG, supporting its use as a controlled source-attribution intervention. These results suggest that brain-to-language performance should be source-attributed, not merely reported.
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Multi-omics Analysis Reveals the Protection of a Quadruple Probiotic Mixture in Experimental Autoimmune Hepatitis

Probiotics Antimicrob Proteins. 2026 May 23. doi: 10.1007/s12602-026-11062-2. Online ahead of print.

ABSTRACT

Autoimmune hepatitis (AIH) is a chronic progressive inflammatory liver disease with a rising global incidence. The treatment of AIH remains challenging because first-line drugs show limited efficacy and systemic side effects. Gut microbiota plays a crucial role in the pathogenesis of AIH, leading to growing interest in developing probiotic-based therapies. In this study, we used multi-omics analysis to investigate the therapeutic effects of a quadruple probiotic mixture (Probiotic-quad) consisting of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus in a well-established chronic AIH murine model. Our results showed that Probiotic-quad treatment significantly alleviated AIH progression, as evidenced by lower serum liver enzyme levels, ameliorated hepatic inflammatory infiltration and histopathological damage. Metagenomic sequencing results showed that gut dysbiosis in AIH mice was partially reversed after Probiotic-quad administration. Additionally, the integrity of the intestinal epithelial barrier was restored, accompanied by a reduction in serum lipopolysaccharide levels. Untargeted metabolomic and transcriptomic analysis revealed that Probiotic-quad treatment was linked to alterations in hepatic metabolism, including the citrate cycle and tryptophan metabolism, and was associated with reduced activation of the NF-κB and NOD-like receptor signaling pathways. These findings suggest that Probiotic-quad treatment ameliorates AIH severity and is potentially associated with changes in hepatic immune responses, metabolism, gut microbiota, and intestinal barrier function, highlighting its potential as an adjuvant therapy for AIH.

PMID:42176246 | DOI:10.1007/s12602-026-11062-2

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CD300ld on pathologically activated neutrophils promotes tumor immune suppression by binding phosphatidylserine on CD8<sup>+</sup> T cells

Nature Cancer, Published online: 15 May 2026; doi:10.1038/s43018-026-01169-4

Zhao and colleagues show that CD300ld, upregulated in pathologically activated neutrophils, mediates contact-dependent suppression of cytotoxic CD8+ T cells by binding to phosphatidylserine, inhibiting antitumor immune responses.
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Pan-neurodegeneration proteomics reveals disease subtypes and molecular signatures

A pan-neurodegeneration atlas built from multilayer, deep proteomics of 2,279 brain samples across 6 major diseases integrates whole proteome, detergent-insoluble proteome, and posttranslational modifications to enable intra- and inter-disease comparisons to reveal disease-specific subtypes and dysregulated pathways, while identifying shared changes such as GPNMB upregulation and NPTX2 downregulation.
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BAAI Cardiac Agent: An intelligent multimodal agent for automated reasoning and diagnosis of cardiovascular diseases from cardiac magnetic resonance imaging

arXiv:2604.04078v1 Announce Type: cross Abstract: Cardiac magnetic resonance (CMR) is a cornerstone for diagnosing cardiovascular disease. However, it remains underutilized due to complex, time-consuming interpretation across multi-sequences, phases, quantitative measures that heavily reliant on specialized expertise. Here, we present BAAI Cardiac Agent, a multimodal intelligent system designed for end-to-end CMR interpretation. The agent integrates specialized cardiac expert models to perform automated segmentation of cardiac structures, functional quantification, tissue characterization and disease diagnosis, and generates structured clinical reports within a unified workflow. Evaluated on CMR datasets from two hospitals (2413 patients) spanning 7-types of major cardiovascular diseases, the agent achieved an area under the receiver-operating-characteristic curve exceeding 0.93 internally and 0.81 externally. In the task of estimating left ventricular function indices, the results generated by this system for core parameters such as ejection fraction, stroke volume, and left ventricular mass are highly consistent with clinical reports, with Pearson correlation coefficients all exceeding 0.90. The agent outperformed state-of-the-art models in segmentation and diagnostic tasks, and generated clinical reports showing high concordance with expert radiologists (six readers across three experience levels). By dynamically orchestrating expert models for coordinated multimodal analysis, this agent framework enables accurate, efficient CMR interpretation and highlights its potentials for complex clinical imaging workflows. Code is available at https://github.com/plantain-herb/Cardiac-Agent.
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ATLAS: A Layered Constraint-Guided Framework for Structured Artifact Generation in LLM-Assisted MDE

arXiv:2510.25890v3 Announce Type: replace-cross Abstract: ATLAS is a constraint-guided generation framework for structured engineering artifacts whose outputs must satisfy explicit schemas, domain rules, and audit requirements. Rather than treating a large language model as a standalone generator, ATLAS places generation inside a model-driven workflow that separates domain representation, constraint compilation, and post-generation validation. ATLAS combines three components. A metamodel-integration stage builds a typed representation of domain entities and relations; in this study, it operates over authoritative AUTOSAR meta-model assets. An Integrated Constraint Model (ICM) compiles heterogeneous requirements into two operational layers: generation-time structural constraints and post-generation semantic/logical obligations. Constraint-Guided, Validation-Backed Generation (CVG) then combines Layer~1 constrained decoding, Layer~2 backend validation, and audit-guided repair. In the AUTOSAR instantiation, these Layer~2 obligations are realized through SHACL/SMT-style checks, illustrating how the same ICM can be connected to domain-specific validation backends. We evaluate ATLAS on AUTOSAR artifact generation at both single-file and multi-file scales. In the evaluated AUTOSAR setting, ATLAS consistently produces schema-valid single-file outputs and preserves perfect file completeness and XSD validity at multi-file scale, while SHACL/SMT checks and result analysis continue to expose residual system-level defects. The empirical picture is therefore one of bounded automation: ATLAS secures structural validity and turns higher-level failures into explicit, diagnosable objects within the generation workflow.
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RASA: Routing-Aware Safety Alignment for Mixture-of-Experts Models

arXiv:2602.04448v2 Announce Type: replace-cross Abstract: Mixture-of-Experts (MoE) language models introduce unique challenges for safety alignment due to their sparse routing mechanisms, which can enable degenerate optimization behaviors under standard full-parameter fine-tuning. In our preliminary experiments, we observe that naively applying full-parameter safety fine-tuning to MoE models can reduce attack success rates through routing or expert dominance effects, rather than by directly repairing Safety-Critical Experts. To address this challenge, we propose RASA, a routing-aware expert-level alignment framework that explicitly repairs Safety-Critical Experts while preventing routing-based bypasses. RASA identifies experts disproportionately activated by successful jailbreaks, selectively fine-tunes only these experts under fixed routing, and subsequently enforces routing consistency with safety-aligned contexts. Across two representative MoE architectures and a diverse set of jailbreak attacks, RASA achieves near-perfect robustness, strong cross-attack generalization, and substantially reduced over-refusal, while preserving general capabilities on benchmarks such as MMLU, GSM8K, and TruthfulQA. Our results suggest that robust MoE safety alignment benefits from targeted expert repair rather than global parameter updates, offering a practical and architecture-preserving alternative to prior approaches.
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HISA: Efficient Hierarchical Indexing for Fine-Grained Sparse Attention

arXiv:2603.28458v3 Announce Type: replace-cross Abstract: Token-level sparse attention mechanisms, exemplified by DeepSeek Sparse Attention (DSA), achieve fine-grained key selection by scoring every historical key for each query through a lightweight indexer, then computing attention only on the selected subset. While the downstream sparse attention itself scales favorably, the indexer must still scan the entire prefix for every query, introducing an per-layer bottleneck that grows prohibitively with context length. We propose HISA (Hierarchical Indexed Sparse Attention), a plug-and-play replacement for the indexer that rewrites the search path from a flat token scan into a two-stage hierarchical procedure: (1) a block-level coarse filtering stage that scores pooled block representations to discard irrelevant regions, followed by (2) a token-level refinement stage that applies the original indexer exclusively within the retained candidate blocks. HISA preserves the identical token-level top-sparse pattern consumed by the downstream Sparse MLA operator and requires no additional training. On kernel-level benchmarks, HISA achieves up to speedup at 64K context. On Needle-in-a-Haystack and LongBench, we directly replace the indexer in DeepSeek-V3.2 and GLM-5 with our HISA indexer, without any finetuning. HISA closely matches the original DSA in quality, while substantially outperforming block-sparse baselines.
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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.
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JFTA-Bench: Evaluate LLM's Ability of Tracking and Analyzing Malfunctions Using Fault Trees

arXiv:2603.22978v1 Announce Type: new Abstract: In the maintenance of complex systems, fault trees are used to locate problems and provide targeted solutions. To enable fault trees stored as images to be directly processed by large language models, which can assist in tracking and analyzing malfunctions, we propose a novel textual representation of fault trees. Building on it, we construct a benchmark for multi-turn dialogue systems that emphasizes robust interaction in complex environments, evaluating a model's ability to assist in malfunction localization, which contains $3130$ entries and $40.75$ turns per entry on average. We train an end-to-end model to generate vague information to reflect user behavior and introduce long-range rollback and recovery procedures to simulate user error scenarios, enabling assessment of a model's integrated capabilities in task tracking and error recovery, and Gemini 2.5 pro archives the best performance.
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EVA: Efficient Reinforcement Learning for End-to-End Video Agent

arXiv:2603.22918v1 Announce Type: cross Abstract: Video understanding with multimodal large language models (MLLMs) remains challenging due to the long token sequences of videos, which contain extensive temporal dependencies and redundant frames. Existing approaches typically treat MLLMs as passive recognizers, processing entire videos or uniformly sampled frames without adaptive reasoning. Recent agent-based methods introduce external tools, yet still depend on manually designed workflows and perception-first strategies, resulting in inefficiency on long videos. We present EVA, an Efficient Reinforcement Learning framework for End-to-End Video Agent, which enables planning-before-perception through iterative summary-plan-action-reflection reasoning. EVA autonomously decides what to watch, when to watch, and how to watch, achieving query-driven and efficient video understanding. To train such agents, we design a simple yet effective three-stage learning pipeline - comprising supervised fine-tuning (SFT), Kahneman-Tversky Optimization (KTO), and Generalized Reward Policy Optimization (GRPO) - that bridges supervised imitation and reinforcement learning. We further construct high-quality datasets for each stage, supporting stable and reproducible training. We evaluate EVA on six video understanding benchmarks, demonstrating its comprehensive capabilities. Compared with existing baselines, EVA achieves a substantial improvement of 6-12% over general MLLM baselines and a further 1-3% gain over prior adaptive agent methods. Our code and model are available at https://github.com/wangruohui/EfficientVideoAgent.
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Tuning the sensitivity of mechanosensory receptors through histidine scanning

Histidine scanning represents a broadly applicable technique for the identification of critical interaction sites within TCRs and other mechanosensory receptors to enhance receptor signaling strength and augment therapeutic efficacy via the catch bond mechanism.
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Divergent tumor immunity determined by bacteria-cancer cell engagement

In a preclinical breast cancer metastasis model, the same bacteria strain, when present intracellularly versus extracellularly, exerts opposing effects on tumor immunity by inducing divergent neutrophil states, highlighting the intricacy in bacterial-host engagement for shaping tumor immunity.
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SkillsBench: Benchmarking How Well Agent Skills Work Across Diverse Tasks

arXiv:2602.12670v3 Announce Type: replace Abstract: Agent Skills are structured packages of procedural knowledge that augment LLM agents at inference time. Despite rapid adoption, there is no standard way to measure whether they actually help. We present SkillsBench, a benchmark of 86 tasks across 11 domains paired with curated Skills and deterministic verifiers. Each task is evaluated under three conditions: no Skills, curated Skills, and self-generated Skills. We test 7 agent-model configurations over 7,308 trajectories. Curated Skills raise average pass rate by 16.2 percentage points(pp), but effects vary widely by domain (+4.5pp for Software Engineering to +51.9pp for Healthcare) and 16 of 84 tasks show negative deltas. Self-generated Skills provide no benefit on average, showing that models cannot reliably author the procedural knowledge they benefit from consuming. Focused Skills with 2--3 modules outperform comprehensive documentation, and smaller models with Skills can match larger models without them.
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