The senescence of alveolar type II (AT2) cells impedes self-repair of the lung epithelium and contributes to lung injury in the setting of idiopathic pulmonary fibrosis (IPF). Yes-associated protein 1 (YAP1) is essential for cell growth and organ development; however, the role of YAP1 in AT2 cells during pulmonary fibrosis is still unclear. YAP1 expression was found to be downregulated in the AT2 cells of PF patients. Deletion of YAP1 in AT2 cells resulted in lung injury, exacerbated extracellular matrix (ECM) deposition, and worsened lung function. In contrast, overexpression of YAP1 in AT2 cells promoted alveolar regeneration, mitigated pulmonary fibrosis, and improved lung function. In addition, overexpression of YAP1 alleviated bleomycin (BLM) -induced senescence of alveolar epithelial cells both in vivo and in vitro. Moreover, YAP1 promoted the expression of peroxiredoxin 3 (Prdx3) by directly interacting with TEAD1. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in BLM-treated MLE-12 cells, whereas depletion of Prdx3 partially abrogated the protective effect of YAP1. Furthermore, overexpression of Prdx3 facilitated self-repair of the injured lung and reduced ECM deposition, while silencing Prdx3 attenuated the antifibrotic effect of YAP1. In conclusion, this study demonstrated that YAP1 alleviates lung injury and pulmonary fibrosis by regulating Prdx3 expression to improve mitochondrial dysfunction and block senescence in AT2 cells, revealing a potential novel therapeutic strategy for pulmonary fibrosis.

This study aimed to construct an effective nomogram based on the clinical and oxidative stress-related characteristics to predict the prognosis of stage I lung adenocarcinoma (LUAD). A retrospective study was performed on 955 eligible patients with stage I LUAD after surgery at our hospital. The relationship between systematic-oxidative-stress biomarkers and the prognosis was analyzed. The systematic oxidative stress score (SOS) was established based on three biochemical indicators, including serum creatinine (CRE), lactate dehydrogenase (LDH), and uric acid (UA). SOS was an independent prognostic factor for stage I LUADs, and the nomogram based on SOS and clinical characteristics could accurately predict the prognosis of these patients. The nomogram had a high concordance index (C-index) (0.684, 95% CI, 0.656–0.712), and the calibration curves for recurrence-free survival (RFS) probabilities showed a strong agreement between the nomogram prediction and actual observation. Additionally, the patients were divided into two groups according to the cut-off value of risk points based on the nomogram, and a significant difference in RFS was observed between the high-risk and low-risk groups (p < 0.0001). SOS is an independent prognostic indicator for stage I LUAD. These things considered, the constructed nomogram based on SOS could accurately predict the survival of those patients.

The eighth TNM staging system proposal classifies lung cancer with partial or complete atelectasis/obstructive pneumonia into the T2 category. We aimed to develop nomograms to predict the possibility of lymph node metastasis (LNM) and the prognosis for NSCLC based on atelectasis and obstructive pneumonitis. Methods: NSCLC patients over 20 years old diagnosed between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The nomograms were based on risk factors that were identified by Logistic regression. The area under the receiver operating characteristic (ROC) curve (AUC) was performed to confirm the predictive values of our nomograms. Cox proportional hazards analysis and Kaplan–Meier survival analysis were also used in this study. Results: A total of 470,283 patients were enrolled. Atelectasis/obstructive pneumonitis, age, gender, race, histologic types, grade, and tumor size were defined as independent predictive factors; then, these seven factors were integrated to establish nomograms of LNM. The AUC is 0.70 (95% CI: 0.694–0.704). Moreover, the Cox proportional hazards analysis and Kaplan–Meier survival analysis showed that the scores derived from the nomograms were significantly correlated with the survival of pathological N0 classification. Conclusion: Nomograms based on atelectasis/obstructive pneumonitis were developed and validated to predict LNM and the postoperative prognosis of NSCLC.

Background: The formation of myofibroblast foci constitutes a hallmark pathological feature of idiopathic pulmonary fibrosis (IPF), yet the mechanism remains elusive. RNA-binding motif single-stranded interacting protein 1 (RBMS1) is known to be essential for proliferation and cell cycle progression; however, its role in pulmonary fibrosis remains to be clarified. Methods: This study aimed to systematically elucidate the role and underlying mechanism of RBMS1 in pulmonary fibrosis utilising mouse primary lung fibroblasts (mPLFs), fibroblast-specific Rbms1 deletion and overexpression mice models, and lung samples from IPF patients. Results: RBMS1 was highly expressed in both IPF patient lungs and murine bleomycin-induced fibrotic lesions. Notably, elevated RBMS1 expression was observed in the cytoplasm of mPLFs following transforming growth factor (TGF)-β1 stimulation. Rbms1 promoted lung fibroblast activation, while knockdown of Rbms1 mitigated TGF-β1-induced fibrogenesis. In vivo, overexpression of Rbms1 impaired lung function and exacerbated pulmonary fibrosis, whereas fibroblast-specific deletion of Rbms1 exhibited a significant reduction in fibrosis post-bleomycin treatment. Mechanistically, Rbms1 binds to Sumo2 3′ untranslated region, enhancing the mRNA stability. Furthermore, Rbms1 induced the SUMOylation of Smad4, with lysine 158 identified as a critical SUMOylation site. Meanwhile, Sumo2 knockdown alleviated the Rbms1-driven exacerbation of pulmonary fibrosis. Importantly, nortriptyline pharmacologically inhibited RBMS1 to ameliorate pulmonary fibrosis in mice. Conclusion: Collectively, our study sheds light on the regulatory role of RBMS1 in pulmonary fibrosis, highlighting its therapeutic potential for targeted antifibrotic strategies.

Objective: This study was to explore the difference and significance of parietal pleura invasion and rib invasion in pathological T classification with non-small cell lung cancer.Methods: A total of 8681 patients after lung resection were selected to perform analyses. Multivariable Cox analysis was used to identify the mortality differences in patients between parietal pleura invasion and rib invasion. Eligible patients with chest wall invasion were re-categorized according to the prognosis. Cancer-specific survival curves for different pathological T (pT) classifications were presented.Results: There were 466 patients considered parietal pleura invasion, and 237 patients served as rib invasion. Cases with rib invasion had poorer survival than those with the invasion of parietal pleura (adjusted hazard ratio [HR]= 1.627, P =0.004). In the cohort for parietal pleura invasion, patients with tumor size ≤5cm reached more satisfactory survival outcomes than patients with tumor size >5cm (unadjusted HR =1.598, P =0.006). However, there was no predictive difference in the cohort of rib invasion. The results of the multivariable analysis revealed that the mortality with parietal pleura invasion plus tumor size ≤5cm were similar to patients with classification pT3 (P =0.761), and patients for parietal pleura invasion plus tumor size >5cm and pT4 had no stratified survival outcome (P =0.809). Patients identified as rib invasion had a poorer prognosis than patients for pT4 (P =0.037).Conclusions: Rib invasion has a poorer prognosis than pT4. Patients with parietal pleura invasion and tumor size with 5.1-7.0cm could be appropriately up-classified from pT3 to pT4.