Search

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.

Abstract Conventional electrospinning produces nanofibers with smooth surfaces that limit biomineralization ability. To overcome this disadvantage, we fabricated a tetramethylpyrazine (TMP)-loaded matrix-mimicking biomineralization in PCL/Gelatin composite electrospun membranes with bubble-shaped nanofibrous structures. PCL/Gelatin membranes (PG), PCL/Gelatin membranes containing biomineralized hydroxyapatite (HA) (PGH), and PCL/Gelatin membranes containing biomineralized HA and loaded TMP (PGHT) were tested. In vitro results indicated that the bubble-shaped nanofibrous surface increased the surface roughness of the nanofibers and promoted mineralization. Furthermore, sustained-release TMP had an excellent drug release efficiency. Initially released vigorously, it reached stabilization at day 7, and the slow-release rate stabilized at 61.0 ± 1.8% at 28 days. All membranes revealed an intact cytoskeleton, cell viability, and superior adhesion and proliferation when stained with Ghost Pen Cyclic Peptide, CCK-8, cell adhesion, and EdU. In PGHT membranes, the osteogenic and vascularized gene expression of BMSCs and human vascular endothelial cells was significantly upregulated compared with that in other groups, indicating the PGHT membranes exhibited an effective vascularization role. Subsequently, the membranes were implanted in a rat cranium defect model for 4 and 8 weeks. Micro-CT and histological analysis results showed that the PGHT membranes had better bone regenerative patterns. Additionally, the levels of CD31 and VEGF significantly increased in the PGHT membrane compared with those in other membranes. Thus, PGHT membranes could accelerate the repair of cranium defects in vivo via HA and TMP synergistic effects. Graphical Abstract

Abstract Combining information from multispectral images into a fused image is informative and beneficial for human or machine perception. Currently, multiple photodetectors with different response bands are used, which require complicated algorithms and systems to solve the pixel and position mismatch problem. An ideal solution would be pixel-level multispectral image fusion, which involves multispectral image using the same photodetector and circumventing the mismatch problem. Here we presented the potential of pixel-level multispectral image fusion utilizing colloidal quantum dots photodiode array, with a broadband response range from X-ray to near infrared and excellent tolerance for bending and X-ray irradiation. The colloidal quantum dots photodiode array showed a specific detectivity exceeding 1012 Jones in visible and near infrared range and a favorable volume sensitivity of approximately 2 × 105 μC Gy−1 cm−3 for X-ray irradiation. To showcase the advantages of pixel-level multispectral image fusion, we imaged a capsule enfolding an iron wire and soft plastic, successfully revealing internal information through an X-ray to near infrared fused image.

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.

Plankton is an important component of a healthy shallow lake aquatic system, and the diversity and stability of its community structure are impacted by numerous environmental factors. However, knowledge about the relative importance of these factors is limited. This study presents a case study conducted in semi-arid, shallow eutrophic lakes in China to evaluate the relative importance of physical, chemical, and nutritional characteristics of water quality and light effects on the spatiotemporal distributions of diversity and stability of plankton communities. The findings showed that the plankton community was the least diverse in winter and the most stable during the spring-to-summer transition. The results of partition variation showed that physical and chemical indicators, nutritional parameters, and light effects explained >70 % of the zooplankton community dynamics, compared with 37 % for phytoplankton. For phytoplankton community composition, physical and chemical parameters, followed by light, had the greatest influence. Further analysis showed that phytoplankton were influenced primarily by nutrients, water depth, and pH. Similarly, the diversity and stability of the zooplankton exhibited physical and chemical parameter responses, and the influence of nutrients also played a significant role. Structural equation modelling showed that light had minimal direct effect on the plankton and affected the plankton indirectly through changes in total nitrogen and NO3-N. This study estimates the distribution of plankton community in a shallow eutrophic lake, quantifying the relative effects of different environmental drivers on plankton diversity and stability, and provides an in-depth understanding for improving the lake water quality and controlling nutrients pollution.

Background: Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related mortality. Lysophosphatidylglycerol acyltransferase (LPGAT1) regulates the biosynthesis of triacylglycerol, which is essential for maintaining phospholipid homeostasis and modulating the structural integrity of mitochondrial membranes. LPGAT1 has been demonstrated to be differentially expressed in normal lung tissue and LUAD tissues, and can serve as a metabolically relevant gene with potential prognostic value. However, the potential role of LPGAT1 in LUAD is still unknown. This study sought to determine the role of LPGAT1 in LUAD progression. Methods: LPGAT1 expression was examined in LUAD cells and tumor tissues from LUAD patients. The effect of LPGAT1 was then assessed in both cell and animal models after LPGAT1 was knocked down by RNA interference. Results: LPGAT1 was upregulated in LUAD tissues. Overexpression of LPGAT1 was associated with an unfavorable prognosis in LUAD patients, as revealed by univariate and multivariate Cox analyses. Knockdown of LPGAT1 abrogated tumor growth and proliferation in both cell and animal models. Conclusions: This study demonstrates that LPGAT1 promotes proliferation and inhibits apoptosis in LUAD. Hence, LPGAT1 may provide new treatment strategies for LUAD.

Adipose tissue is endocrine organ that responds by secreting numerous hormones that regulate metabolism in skeletal muscle and the liver. The aim of this study was to compare the levels of spexin and adiponectin in patients with non-alcoholic fatty liver and evaluate the relationship between circulating adipocytokines and insulin resistance. Two groups of subjects were evaluated: 41 non-alcoholic fatty liver subjects (age 35.17 ​± ​12.29 year, BMI 30.97 ​± ​2.75 ​kg/m2) and 38 normal controls (age 38.47 ​± ​11.63 year, BMI 22.83 ​± ​3.00 ​kg/m2). Plasma concentrations of spexin and adiponectin were determined using immunosorbent assay kits. Insulin resistance was assessed using the homeostasis model assessment (HOMA-IR) formula derived from fasting insulin and glucose levels. Compared to normal controls, plasma concentrations of spexin and adiponectin were significantly lower in patients with non-alcoholic fatty liver (P ​

This article is a reflection on the nature of “changing with the times” that is put forward in theBook of Lord Shang. The author challenges the modern, predominantly Marxist, portrayal of Shang Yang as the exceptional Warring States master promoting a progressive view of history. TheBook of Lord Shangdoes not prioritize future over the present or present over the past, nor does it envision a large-scale rational understanding of the historical trends, nor the possibility to improve human nature. Like other late Zhou, Qin, and Han sources, some chapters of the book promote the capacity to change with the times as a political expediency in concrete contexts. The author utilizes this understanding to dismiss the still popular conceptualization of Shang Yang as a “progressive” thinker. If this oppressive ideology promoted the idea of progress, then the very idea of progress should be called into question, according to the author. [ABSTRACT FROM PUBLISHER]