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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

Talking with Verifiers: Automatic Specification Generation for Neural Network Verification

arXiv:2603.02235v1 Announce Type: cross Abstract: Neural network verification tools currently support only a narrow class of specifications, typically expressed as low-level constraints over raw inputs and outputs. This limitation significantly hinders their adoption and practical applicability across diverse application domains where correctness requirements are naturally expressed at a higher semantic level. This challenge is rooted in the inherent nature of deep neural networks, which learn internal representations that lack an explicit mapping to human-understandable features. To address this, we bridge this gap by introducing a novel component to the verification pipeline, making existing verification tools applicable to a broader range of domains and specification styles. Our framework enables users to formulate specifications in natural language, which are then automatically analyzed and translated into formal verification queries compatible with state-of-the-art neural network verifiers. We evaluate our approach on both structured and unstructured datasets, demonstrating that it successfully verifies complex semantic specifications that were previously inaccessible. Our results show that this translation process maintains high fidelity to user intent while incurring low computational overhead, thereby substantially extending the applicability of formal DNN verification to real-world, high-level requirements.
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