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Genetic mutation and dysfunction of AT2 cells drive B(a)P/LPS-induced inflammation-related lung tumorigenesis: evidence and mechanism of autophagy

(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)

By: Zhihao Tang · Xianchao Zhou · Pingping Shang · Quanping Yan · Ping Lu · Yanting Lei · Chenfeng Hua · Xiaoshan Zhou · Qiao Zhang · Wei Wang · Huaiyong Chen · Jian He · Feifei Feng

9 April 2026 at 18:00

Acta Biochim Biophys Sin (Shanghai). 2026 Mar 25. doi: 10.3724/abbs.2025238. Online ahead of print.

ABSTRACT

The environmental pollutant benzo(a)pyrene (B(a)P), a representative polycyclic aromatic hydrocarbon (PAH), is a recognized carcinogen, and chronic pulmonary inflammation is closely associated with lung carcinogenesis. Although alveolar type 2 (AT2) cells are the origin of lung adenocarcinoma, the genetic and functional changes in AT2 cells and the mechanisms involved in inflammation-related lung tumorigenesis have not been elucidated. Here, C57BL/6J mice are exposed to B(a)P and the inflammatory irritant lipopolysaccharide (LPS) to establish a model of inflammation-related lung tumorigenesis. Single-cell RNA sequencing is performed on lung tissues. DNA mutations in AT2 cells are analyzed via whole-exome sequencing. The protein expression of AT2 cells in lung cancer tissue is determined by immunofluorescence staining. The results reveal that LPS promotes B(a)P-induced lung tumorigenesis; in the whole lungs of B(a)P/LPS, a decreased proportion, altered differentiation trajectory, and increased gene mutation number in AT2 cells are observed. Additionally, in B(a)P/LPS-treated lung cancer tissue, the levels of γ-H2AX DNA damage and the proliferation marker Ki67 in AT2 cells are increased, whereas the levels of differentiation markers are decreased. Single-cell RNA transcriptomics reveals that the autophagy-related genes Foxo3 and Ppp2r5, which are enriched in the PI3K-Akt pathway, and the autophagy-related genes in AT2 cells in lung cancer are decreased in the B(a)P/LPS group. Thus, chronic inflammation promotes DNA damage, gene mutation and dysfunction in AT2 cells, and decreased autophagy in AT2 cells may be an important mechanism for inflammation-related lung tumorigenesis.

PMID:41952558 | DOI:10.3724/abbs.2025238

Bridging Domains through Subspace-Aware Model Merging

cs.AI, q-bio.NC updates on arXiv.org

By: Levy Chaves · Chao Zhou · Rebekka Burkholz · Eduardo Valle · Sandra Avila

10 March 2026 at 12:00

arXiv:2603.05768v2 Announce Type: replace-cross Abstract: Model merging integrates multiple task-specific models into a single consolidated one. Recent research has made progress in improving merging performance for in-distribution or multi-task scenarios, but domain generalization in model merging remains underexplored. We investigate how merging models fine-tuned on distinct domains affects generalization to unseen domains. Through an analysis of parameter competition in the task matrix using singular value decomposition, we show that merging models trained under different distribution shifts induces stronger conflicts between their subspaces compared to traditional multi-task settings. To mitigate this issue, we propose SCORE (Subspace COnflict-Resolving mErging), a method designed to alleviate such singular subspace conflicts. SCORE finds a shared orthogonal basis by computing the principal components of the concatenated leading singular vectors of all models. It then projects each task matrix into the shared basis, pruning off-diagonal components to remove conflicting singular directions. SCORE consistently outperforms, on average, existing model merging approaches in domain generalization settings across a variety of architectures and model scales, demonstrating its effectiveness and scalability.