❌

Normal view

Integrated proteomics and metabolomics analysis reveals mechanisms by which SFYC decoction regulates airway inflammation in asthma

J Ethnopharmacol. 2026 Mar 30;365:121612. doi: 10.1016/j.jep.2026.121612. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Airway inflammation is one of the primary pathological characteristics of asthma. Soufeng Yuchuan (SFYC) decoction, a compound formula derived from multiple traditional Chinese medicine prescriptions, is widely applied clinically and exhibits significant therapeutic efficacy against asthma. However, its anti-asthmatic mechanisms remain incompletely understood.

MATERIALS AND METHODS: Asthmatic rat models induced by ovalbumin (OVA) and ferroptosis models induced by erastin in BEAS-2B cells were established. Proteomics and metabolomics analyses were conducted on lung tissues and serum. Key ferroptosis-related targets (GPX4, SLC7A11/SLC3A2, GCLC, GSS, and VDAC2) were validated using Western blotting, RT-qPCR, and biochemical assays. The direct anti-ferroptosis effects of SFYC-containing serum were compared with ferrostatin-1 and blank serum in vitro.

RESULTS: Integrated omics analysis revealed that ferroptosis, glutathione metabolism, and ROS signaling pathways were the core targets modulated by SFYC. In vivo, SFYC significantly reduced airway inflammation and ROS accumulation, restored pulmonary GSH levels, upregulated the expression of GPX4, GCLC, GSS, SLC7A11, and SLC3A2, and downregulated VDAC2 expression (P < 0.05). In vitro, SFYC-containing serum effectively reversed erastin-induced lipid peroxidation, iron overload, GSH depletion, ROS elevation, and apoptosis in BEAS-2B cells, demonstrating comparable or superior efficacy to ferrostatin-1.

CONCLUSION: SFYC alleviates airway inflammation in asthma primarily by inhibiting ferroptosis. This study provides evidence that SFYC exerts anti-asthmatic effects, at least in part, via the regulation of ferroptosis pathways.

PMID:41921764 | DOI:10.1016/j.jep.2026.121612

Inactivating <i>SnRK1β1A</i> promotes broad-spectrum disease resistance in rice

Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10273-5

SnRK1β1A in rice promotes susceptibility to multiple fungal diseases, and disrupting this infection-inducible gene confers broad-spectrum resistance without compromising growth or yield under normal field conditions.

Single-cell multiomics uncovers an endothelial mechanosensitive PIEZO1-IL-33 axis driving pulmonary fibrosis

Nat Commun. 2026 Mar 20;17(1):2655. doi: 10.1038/s41467-026-70193-w.

ABSTRACT

Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.

PMID:41862476 | PMC:PMC13004862 | DOI:10.1038/s41467-026-70193-w

Partially Recentralization Softmax Loss for Vision-Language Models Robustness

arXiv:2402.03627v4 Announce Type: replace-cross Abstract: As Large Language Models make a breakthrough in natural language processing tasks (NLP), multimodal technique becomes extremely popular. However, it has been shown that multimodal NLP are vulnerable to adversarial attacks, where the outputs of a model can be dramatically changed by a perturbation to the input. While several defense techniques have been proposed both in computer vision and NLP models, the multimodal robustness of models have not been fully explored. In this paper, we study the adversarial robustness provided by modifying loss function of pre-trained multimodal models, by restricting top K softmax outputs. Based on the evaluation and scoring, our experiments show that after a fine-tuning, adversarial robustness of pre-trained models can be significantly improved, against popular attacks. Further research should be studying, such as output diversity, generalization and the robustness-performance trade-off of this kind of loss functions. Our code will be available after this paper is accepted

Contact-Guided 3D Genome Structure Generation of E. coli via Diffusion Transformers

arXiv:2603.07472v1 Announce Type: cross Abstract: In this study, we present a conditional diffusion-transformer framework for generating ensembles of three-dimensional Escherichia coli genome conformations guided by Hi-C contact maps. Instead of producing a single deterministic structure, we formulate genome reconstruction as a conditional generative modeling problem that samples heterogeneous conformations whose ensemble-averaged contacts are consistent with the input Hi-C data. A synthetic dataset is constructed using coarse-grained molecular dynamics simulations to generate chromatin ensembles and corresponding Hi-C maps under circular topology. Our models operate in a latent diffusion setting with a variational autoencoder that preserves per-bin alignment and supports replication-aware representations. Hi-C information is injected through a transformer-based encoder and cross-attention, enforcing a physically interpretable one-way constraint from Hi-C to structure. The model is trained using a flow-matching objective for stable optimization. On held-out ensembles, generated structures reproduce the input Hi-C distance-decay and structural correlation metrics while maintaining substantial conformational diversity, demonstrating the effectiveness of diffusion-based generative modeling for ensemble-level 3D genome reconstruction.

CrystaL: Spontaneous Emergence of Visual Latents in MLLMs

arXiv:2602.20980v2 Announce Type: replace-cross Abstract: Multimodal Large Language Models (MLLMs) have achieved remarkable performance by integrating powerful language backbones with large-scale visual encoders. Among these, latent Chain-of-Thought (CoT) methods enable implicit reasoning in continuous hidden states, facilitating seamless vision-language integration and faster inference. However, existing heuristically predefined supervision signals in latent CoT provide limited guidance for preserving critical visual information in intermediate latent states. To address this limitation, we propose CrystaL (Crystallized Latent Reasoning), a single-stage framework with two paths to process intact and corrupted images, respectively. By explicitly aligning the attention patterns and prediction distributions across the two paths, CrystaL crystallizes latent representations into task-relevant visual semantics, without relying on auxiliary annotations or external modules. Extensive experiments on perception-intensive benchmarks demonstrate that CrystaL consistently outperforms state-of-the-art baselines, achieving substantial gains in fine-grained visual understanding while maintaining robust reasoning capabilities.

IntPro: A Proxy Agent for Context-Aware Intent Understanding via Retrieval-conditioned Inference

arXiv:2603.03325v1 Announce Type: cross Abstract: Large language models (LLMs) have become integral to modern Human-AI collaboration workflows, where accurately understanding user intent serves as a crucial step for generating satisfactory responses. Context-aware intent understanding, which involves inferring user intentions from situational environments, is inherently challenging because it requires reasoning over both the immediate context and the user's underlying motivations that drive their behavior. Moreover, existing approaches often treat intent understanding as a static recognition task, overlooking users' accumulated intent patterns that could provide valuable references for more accurate and generalizable understanding. To address this gap, we propose IntPro, a proxy agent that learns to adapt to individual users via retrieval-conditioned intent inference. We design intent explanations that abstract how contextual signals connect to expressed intents, and store them in an individual intent history library for retrieval. We train IntPro through supervised fine-tuning on retrieval-conditioned trajectories and multi-turn Group Relative Policy Optimization (GRPO) with tool-aware reward functions, enabling the agent to learn when to leverage historical intent patterns and when to infer directly. Experiments across three diverse scenarios (Highlight-Intent, MIntRec2.0, and Weibo Post-Sync) demonstrate that IntPro achieves strong intent understanding performance with effective context-aware reasoning capabilities across different scenarios and model types.

IR$^3$: Contrastive Inverse Reinforcement Learning for Interpretable Detection and Mitigation of Reward Hacking

arXiv:2602.19416v1 Announce Type: new Abstract: Reinforcement Learning from Human Feedback (RLHF) enables powerful LLM alignment but can introduce reward hacking - models exploit spurious correlations in proxy rewards without genuine alignment. Compounding this, the objectives internalized during RLHF remain opaque, making hacking behaviors difficult to detect or correct. We introduce IR3 (Interpretable Reward Reconstruction and Rectification), a framework that reverse-engineers, interprets, and surgically repairs the implicit objectives driving RLHF-tuned models. We propose Contrastive Inverse Reinforcement Learning (C-IRL), which reconstructs the implicit reward function by contrasting paired responses from post-alignment and baseline policies to explain behavioral shifts during RLHF. We then decompose the reconstructed reward via sparse autoencoders into interpretable features, enabling identification of hacking signatures through contribution analysis. Finally, we propose mitigation strategies - clean reward optimization, adversarial shaping, constrained optimization, and feature-guided distillation - that target problematic features while preserving beneficial alignment. Experiments across multiple reward model configurations show that IR3 achieves 0.89 correlation with ground-truth rewards, identifies hacking features with over 90% precision, and significantly reduces hacking behaviors while maintaining capabilities within 3% of the original model.

Feature Representation Transferring to Lightweight Models via Perception Coherence

arXiv:2505.06595v3 Announce Type: replace-cross Abstract: In this paper, we propose a method for transferring feature representation to lightweight student models from larger teacher models. We mathematically define a new notion called \textit{perception coherence}. Based on this notion, we propose a loss function, which takes into account the dissimilarities between data points in feature space through their ranking. At a high level, by minimizing this loss function, the student model learns to mimic how the teacher model \textit{perceives} inputs. More precisely, our method is motivated by the fact that the representational capacity of the student model is weaker than the teacher model. Hence, we aim to develop a new method allowing for a better relaxation. This means that, the student model does not need to preserve the absolute geometry of the teacher one, while preserving global coherence through dissimilarity ranking. Importantly, while rankings are defined only on finite sets, our notion of \textit{perception coherence} extends them into a probabilistic form. This formulation depends on the input distribution and applies to general dissimilarity metrics. Our theoretical insights provide a probabilistic perspective on the process of feature representation transfer. Our experiments results show that our method outperforms or achieves on-par performance compared to strong baseline methods for representation transferring.
❌