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Abstract Background Chronic obstructive pulmonary disease (COPD) is a significant global health issue, suspected to elevate the risk for various cancers. This study sought to discern whether COPD serves as a risk marker or a causative factor for prevalent cancers. Methods We employed univariable MR (UVMR) analyses to investigate the causal relationship between COPD and the top ten common cancers. Sensitivity analyses were performed to validate the main findings. Multivariable MR (MVMR) and two-step MR analyses were also conducted. False-discovery-rate (FDR) was used to correct multiple testing bias. Results The UVMR analysis demonstrated notable associations between COPD and lung cancer (odds ratio [OR] = 1.42, 95%CI 1.15–1.77, FDR = 6.37 × 10–3). This relationship extends to lung cancer subtypes such as squamous cell carcinoma (LUSC), adenocarcinoma (LUAD), and small cell lung cancer (SCLC). A tentative link was also identified between COPD and bladder cancer (OR = 1.53, 95%CI 1.03–2.28, FDR = 0.125). No significant associations were found between COPD and other types of cancer. The MVMR analysis that adjusted for smoking, alcohol drinking, and body mass index did not identify any significant causal relationships between COPD and either lung or bladder cancer. However, the two-step MR analysis indicates that COPD mediated 19.2% (95% CI 12.7–26.1%), 36.1% (24.9–33.2%), 35.9% (25.7–34.9%), and 35.5% (26.2–34.8%) of the association between smoking and overall lung cancer, as well as LUAD, LUSC, and SCLC, respectively. Conclusions COPD appears to act more as a risk marker than a direct cause of prevalent cancers. Importantly, it partially mediates the connection between smoking and lung cancer, underscoring its role in lung cancer prevention strategies.

Abstract Purpose The clinical outcomes of delayed chest closure (DCC) compared with primary chest closure (PCC) following lung transplantation, including perioperative outcomes and long-term survival, remained controversial. This was the first systematic review and meta-analysis aimed to identify the short- and long-term outcomes of DCC following lung transplantation. Methods We comprehensively searched electronic literature from 4 databases up to April 1st, 2022. Dichotomous data and continuous data were pooled with odds ratio and weighted mean difference, respectively. The quality of included studies was assessed with the Newcastle–Ottawa Scale. Results Ten studies were included in the systematic review and 4 studies were included in the meta-analysis. Pooled analysis showed that DCC was associated with an increased risk of surgical site infection, prolonged hospital stays, and higher risk of primary graft dysfunction compared to PCC. The 30 day and 5 year survival were higher in PCC cohort compared with DCC cohort while differences in survival at 6 months was insignificant. Conclusion Our findings do not support the aggressive application of DCC. DCC should be cautiously applied since its association with worse perioperative outcomes and higher mortality. But it remains the life-saving steps under dangerous circumstances.

Abstract Background The deep-sea-derived microbe Streptomyces koyangensis SCSIO 5802 produces neoabyssomicins A–B (1–2) and abyssomicins 2 (3) and 4 (4). Neoabyssomicin A (1) augments human immunodeficiency virus-1 (HIV-1) replication whereas abyssomicin 2 (3) selectively reactivates latent HIV and is also active against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA). Structurally, neoabyssomicins A–B constitute a new subtype within the abyssomicin family and feature unique structural traits characteristic of extremely interesting biosynthetic transformations. Results In this work, the biosynthetic gene cluster (BGC) for the neoabyssomicins and abyssomicins, composed of 28 opening reading frames, was identified in S. koyangensis SCSIO 5802, and its role in neoabyssomicin/abyssomicin biosynthesis was confirmed via gene inactivation and heterologous expression experiments. Bioinformatics and genomics analyses enabled us to propose a biosynthetic pathway for neoabyssomicin/abyssomicin biosynthesis. Similarly, a protective export system by which both types of compounds are secreted from the S. koyangensis producer was identified, as was a four-component ABC transporter-based import system central to neoabyssomicin/abyssomicin biosynthesis. Furthermore, two regulatory genes, abmI and abmH, were unambiguously shown to be positive regulators of neoabyssomicin/abyssomicin biosynthesis. Consistent with their roles as positive regulatory genes, the overexpression of abmI and abmH (independent of each other) was shown to improve neoabyssomicin/abyssomicin titers. Conclusions These studies provide new insight into the biosynthesis of the abyssomicin class of natural products, and highlight important exploitable features of its BGC for future efforts. Elucidation of the neoabyssomicin/abyssomicin BGC now enables combinatorial biosynthetic initiatives aimed at improving both the titers and pharmaceutical properties of these important natural products-based drug leads.