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Abstract Background Lung cancer still ranks first in the mortality rate of cancer. Uric acid is a product of purine metabolism in humans. Its presence in the serum is controversial; some say that its high levels have a protective effect against tumors, others say the opposite, that is, high levels increase the risk of cancer. Therefore, the aim of this study was to investigate the potential causal association between serum uric acid levels and lung cancer. Methods Mendelian randomization was used to achieve our aim. Sensitivity analyses was performed to validate the reliability of the results, followed by reverse Mendelian analyses to determine a potential reverse causal association. Results A significant causal association was found between serum uric acid levels and lung cancer in East Asian and European populations. Further sublayer analysis revealed a significant causal association between uric acid and small cell lung cancer, while no potential association was observed between uric acid and non-small cell lung cancer, squamous lung cancer, and lung adenocarcinoma. The sensitivity analyses confirmed the reliability of the results. Reverse Mendelian analysis showed no reverse causal association between uric acid and lung cancer. Conclusions The results of this study suggested that serum uric acid levels were negatively associated with lung cancer, with uric acid being a potential protective factor for lung cancer. In addition, uric acid level monitoring was simple and inexpensive. Therefore, it might be used as a biomarker for lung cancer, promoting its wide use clinical practice.

Abstract Background PD-L1 overexpression is commonly observed in various malignancies and is strongly correlated with poor prognoses for cancer patients. Moreover, PD-L1 has been shown to play a significant role in promoting angiogenesis and epithelial-mesenchymal transition (EMT) processes across different cancer types. Methods The relationship between PD-L1 and vasculogenic mimicry as well as epithelial-mesenchymal transition (EMT) was explored by bioinformatics approach and immunohistochemistry. The functions of PD-L1 in regulating the expression of ZEB1 and the EMT process were assessed by Western blotting and q-PCR assays. The impact of PD-L1 on the migratory and proliferative capabilities of A549 and H1299 cells was evaluated through wound healing, cell invasion, and CCK8 assays following siRNA-mediated PD-L1 knockdown. Tube formation assay was utilized to evaluate the presence of VM structures. Results In this study, increased PD-L1 expression was observed in A549 and H1299 cells compared to normal lung epithelial cells. Immunohistochemical analysis revealed a higher prevalence of VM structures in the PD-L1-positive group compared to the PD-L1-negative group. Additionally, high PD-L1 expression was also found to be significantly associated with advanced TNM stage and increased metastasis. Following PD-L1 knockdown, NSCLC cells exhibited a notable reduction in their ability to form tube-like structures. Moreover, the levels of key EMT and VM-related markers, including N-cadherin, MMP9, VE-cadherin, and VEGFA, were significantly decreased, while E-cadherin expression was upregulated. In addition, the migration and proliferation capacities of both cell lines were significantly inhibited after PD-L1 or ZEB1 knockdown. Conclusions Knockdown PD-L1 can inhibit ZEB1-mediated EMT, thereby hindering the formation of VM in NSCLC.

Abstract Objective The aim of this paper is to investigate the effect of long noncoding RNA (lncRNA) MIR100HG on the proliferation and metastasis of lung cancer cells by mediating the microRNA (miR)−5590‐3p/DCBLD2 axis. Methods RNA levels of MIR100HG, miR‐5590‐3p, and DCBLD2 in lung cancer tissues and cells were detected by quantitative reverse‐transcription polymerase chain reaction, and protein level was assessed by Western blot. Effects of MIR100HG or miR‐5590‐3p on proliferation, migration, and invasion of lung cancer cells were detected by Cell Counting Kit‐8, colony formation, and Transwell assays. Luciferase reporter assay and RNA‐immunoprecipitation assay confirmed the target relationship between miR‐5590‐3p and MIR100HG or DCBLD2. Results MIR100HG and DCBLD2 were highly expressed, while miR‐5590‐3p was lowly expressed in lung cancer tissues and cells. Silencing MIR100HG or upregulating miR‐5590‐3p impeded lung cancer cell proliferation, migration, and invasion. MIR100HG could up‐regulate DCBLD2 by sponging miR‐5590‐3p. Downregulation of miR‐5590‐3p partly overturned the suppressive effect of silencing MIR100HG on lung cancer cell proliferation and metastasis, and overexpression of DCBLD2 also reversed the effect of overexpression of miR‐5590‐3p on lung cancer cell proliferation and metastasis. Conclusion LncRNA MIR100HG promotes lung cancer progression by targeting and negatively regulating DCBLD2 through binding with miR‐5590‐3p.

Lung cancer, ranking second globally in both incidence and high mortality among common malignant tumors, presents a significant challenge with frequent occurrences of drug resistance despite the continuous emergence of novel therapeutic agents. This exacerbates disease progression, tumor recurrence, and ultimately leads to poor prognosis. Beyond acquired resistance due to genetic mutations, mounting evidence suggests a critical role of epigenetic mechanisms in this process. Numerous studies have indicated abnormal expression of Histone Methyltransferases (HMTs) in lung cancer, with the abnormal activation of certain HMTs closely linked to drug resistance. HMTs mediate drug tolerance in lung cancer through pathways involving alterations in cellular metabolism, upregulation of cancer stem cell-related genes, promotion of epithelial-mesenchymal transition, and enhanced migratory capabilities. The use of HMT inhibitors also opens new avenues for lung cancer treatment, and targeting HMTs may contribute to reversing drug resistance. This comprehensive review delves into the pivotal roles and molecular mechanisms of HMTs in drug resistance in lung cancer, offering a fresh perspective on therapeutic strategies. By thoroughly examining treatment approaches, it provides new insights into understanding drug resistance in lung cancer, supporting personalized treatment, fostering drug development, and propelling lung cancer therapy into novel territories.

The effect of aging treatments at various temperatures on the mechanical properties and microstructure of 10B21 cold heading steel with a 20% reduction in area (ε = 0.1) was investigated. The mechanical properties were evaluated based on tensile tests and hardness tests, while the evolution of microstructure was observed by using an optical microscope (OM), scanning electron microscope (SEM), transmission electron microscope (TEM) and X-ray diffraction (XRD). The results reveal that aging treatment enhance the strength and hardness of 10B21 cold heading steel after drawing, and the highest values of strength and hardness are attained at an aging temperature of 300 °C. Specifically, the yield and ultrahigh tensile strength after aging at 300 °C are measured at 620 MPa and 685 MPa, respectively, which are 30 MPa and 50 MPa higher than the cold-drawn sample. Moreover, the hardness after aging at 300 °C reaches 293 HV, which has an increase of 30 HV compared to the cold-drawn state. The improvement in mechanical properties may be related to the strain-aging mechanism and the increased density of dislocations. In addition, the analysis of the TEM results reveal that the presence of the second-phase Ti(C,N) contributes to pinning the dislocations, whereas the dislocations are pinned between the cementite (Fe3C) lamellar and stacked at the grain boundaries, leading to strain hardening of the material.