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Non-small cell lung cancer (NSCLC), half of which are lung adenocarcinoma (LUAD), is one of the most widely spread cancers in the world. Telomerase, which maintains telomere length and chromosomal integrity, enables cancer cells to avoid replicative senescence. When telomerase is inhibited, cancer cells' senescence began, preventing them from growing indefinitely. Cellular senescence and telomeres are intrinsically linked. As of yet, still laking a systematic study of the involvement of telomere-senescence related genes in lung adenocarcinoma development. In this study, myeloid cells were identified as the cell type which are most correlated with cellular senescence based on its highest telomere-related gene activity. GO, KEGG, GSEA and GSVA analyses were used to explore the biological function of telomere-senescence related genes in LUAD. The combined analysis of single-cell RNA-sequencing and bulk-RNA sequencing identified a gene signature composed of 14 genes which can accurately predict the prognosis of patients with LUAD. In one training and four validation sets, patients with higher Telomere Related Gene Signature (TRGS) had a worse prognosis than those with lower TRGS. Different TRGS patient groups showed varying degrees of immune cell infiltration, frequency of gene missense mutation, sensitivity to different drugs, and tumor mutation burden (TMB). Collectively, we developed a brand new signature composed of telomere-senescence related genes that can accurately predicts patients' prognosis in LUAD, which provides new insights for future research into the role of cellular senescence in LUAD. [ABSTRACT FROM AUTHOR]

Bone morphogenetic protein (BMP)–Smad1/5/8 signaling plays a crucial regulatory role in lung development and adult lung homeostasis. However, it remains elusive whether BMP–Smad1/5/8 signaling is involved in the pathogenesis of emphysema. In this study, we downregulated BMP–Smad1/5/8 signaling by overexpressing its antagonist Noggin in adult mouse alveolar type II epithelial cells (AT2s), resulting in an emphysematous phenotype mimicking the typical pathological features of human emphysema, including distal airspace enlargement, pulmonary inflammation, extracellular matrix remodeling, and impaired lung function. Dysregulation of BMP–Smad1/5/8 signaling in AT2s leads to inflammatory destruction dominated by macrophage infiltration, associated with reduced secretion of surfactant proteins and inhibition of AT2 proliferation and differentiation. Reactivation of BMP–Smad1/5/8 signaling by genetics or chemotherapy significantly attenuated the morphology and pathophysiology of emphysema and improved the lung function in Noggin‐overexpressing lungs. We also found that BMP–Smad1/5/8 signaling was downregulated in cigarette smoke‐induced emphysema, and that enhancing its activity in AT2s prevented or even reversed emphysema in the mouse model. Our data suggest that BMP–Smad1/5/8 signaling, located at the top of the signaling cascade that regulates lung homeostasis, represents a key molecular regulator of alveolar stem cell secretory and regenerative function, and could serve as a potential target for future prevention and treatment of pulmonary emphysema. © 2023 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Current research has shown that inhibiting deoxythymidylate kinase (DTYMK) can significantly reduce development of lung cancer without liver kinase B1. However, its underlying regulatory mechanism is still unclear. We therefore aimed to investigate whether DTYMK inhibitors could suppress lung adenocarcinoma (LUAD) progression. In this study, human tissues, A549 cells, and xenograft tumors were used to explore the regulation and mechanism of DTYMK on LUAD cell proliferation and migration. Meanwhile, YMU1 (a DTYMK inhibitor) was applied to A549 cells and xenograft tumors to investigate its potential as a drug for LUAD. DTYMK was overexpressed in LUAD tissues and correlated with tumor stage. Knockdown of DTYMK suppressed cell viability, migration, and invasion. In addition, the activation of signal transducers and activators of transcription 3 (STAT3) was repressed upon DTYMK inhibition. YMU1 showed the same effect as DTYMK knockdown in vivo and in vitro. DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may have the potential to inhibit the development of LUAD. NEW & NOTEWORTHY DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may serve as a novel drug to suppress the development of LUAD.

Objective: To explore the necessity of interrupting nerve fibers of bypass thoracic sympathetic chain during edoscopic sympathicotomy (ETS) for palmar hyperhidrosis., Methods: Randomized controlled trial was performed for 200 patients of severe palmar hyperhidrosis from January 2009 to June 2011. They were randomly divided into 2 groups of R3 thoracic sympathctomy (R3) and R3 thoracic sympathicotomy plus bypass fiber resection at the same level (R3+) (n = 100 each). Clinical observations were recorded during a follow-up period of 3 years., Results: The curative rates of palmar and axillary hyperhidrosis were 100% for two groups. No statistically significant inter-group difference existed in left hand temperature increase after transecting thoracic sympathetic nerve (3.6 ± 1.4 °C vs 3.5 ± 1.3 °C), right hand increase (3.8 ± 1.3 °C vs 3.9 ± 1.1 °C), incidence of compensatory hyperhidrosis (40% vs 44%), recurrence rate (1% vs 2%) and postoperative satisfaction rate (92% vs 90%). But pain scores of R3 group was significantly lower than those of R3+ group (3.0 ± 1.9 vs 3.6 ± 1.9, P < 0.05)., Conclusion: Simple transaction of thoracic sympathetic chain during ETS is sufficient in the treatment of palmar hyperhidrosis. And it is unnecessary to transect bypass fibers.