Modelling and Analysis of Expansion Joints' Effect on Dynamic Performance of Railway Rigid Overhead System.

This study focuses on developing a comprehensive model of a rigid overhead system, which includes essential components such as the suspension structure, positioning clamp, and expansion joint. The modelling approach utilizes finite element theory and beam elements to accurately represent the displacement, stiffness, and mass characteristics of the system. The models also incorporate the suspension structure and positioning line clamp, which play crucial roles in suspending and positioning the busbar. Various suspension structures and positioning line clamps are evaluated based on their dynamic characteristics. The expansion joint, responsible for connecting different anchor sections of the rigid overhead system, undergoes a detailed analysis. Different assembly scenarios, including ideal and deflected assembly conditions, are considered. To simulate the dynamic behaviour of the expansion joint, additional beams are introduced into the system model. The primary finding of the analysis is that the maximum stresses observed in the constructed expansion joint model, under different temperature conditions and normal/deflected assembly conditions, remain within the permissible stress limits of the material. This indicates a high level of safety. However, certain areas exhibit stress concentration, particularly at the sliding block B and sliding rod A positions. This stress concentration is primarily attributed to the unique assembly form of the expansion joint. To improve stress distribution and enhance service reliability, the analysis suggests optimizing the installation deflection angle and geometric design of the expansion joint. Furthermore, the concentrated mass at the expansion joint significantly impacts the current collection quality of the pantograph-overhead system. Mitigating this negative impact can be achieved by reducing the mass of the expansion joint.

Melatonin attenuates expression of cyclooxygenase-2 (COX-2) in activated microglia induced by lipopolysaccharide (LPS).

Lipopolysaccharide (LPS) is a known neurotoxin and utilized most extensively as a microglial activator for induction of inflammatory neurodegeneration. Melatonin (MEL) is the main secretory product of pineal gland reported to be responsible for a variety of physiological functions. However, the molecular mechanisms underlying the influence of MEL on microglia activation remain unclear. The aim of this study was to investigate the effect of MEL on cyclooxygenase-2 (COX-2) levels in LPS-induced microglia. The results of RT-PCR and Western blot analysis showed that MEL significantly inhibited LPS-mediated upregulation of COX-2 in microglia. Data from ELISA demonstrated that prostaglandin E2 (PGE2), the downstream effector of COX-2, concentrations were also reduced. In addition, MEL was found to decrease activation of ERK1/2, JNK, p38 MAPK, and NF-κB, the upstream signal pathways of COX-2. Taken together, evidence indicates that MEL may attenuate upregulation of COX-2 by blocking the MAPK/NF-κB signaling pathway in LPS-stimulated microglia.

Hypoxia-sensitive LINC01436 is regulated by E2F6 and acts as an oncogene by targeting miR-30a-3p in non-small cell lung cancer.

Dysregulation of long noncoding RNA (lncRNA) is known to be involved in numerous human diseases, including lung cancer. However, the precise biological functions of most lncRNA remain to be elucidated. Here, we identified a novel up-regulated lncRNA, LINC01436 (RefSeq: NR_110419.1), in non-small cell lung cancer (NSCLC). High expression of LINC01436 was significantly associated with poor overall survival. Notably, LINC01436 expression was transcriptionally repressed by E2F6 under normoxia, and the inhibitory effect was relieved in a hypoxic microenvironment. Gain- and loss-of-function studies revealed that LINC01436 acted as a proto-oncogene by promoting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays in nude mice confirmed that LINC01436 promoted tumor growth and metastasis in vivo. Mechanistically, LINC01436 exerted biological functions by acting as a microRNA (miR)-30a-3p sponge to regulate the expression of its target gene EPAS1. Our findings characterize LINC01436 as a new hypoxia-sensitive lncRNA with oncogenic function in NSCLC, suggesting that LINC01436 may be a potential biomarker for prognosis and a potential target for treatment.

Plasma exosome levels in non-small-cell lung cancer: Correlation with clinicopathological features and prognostic implications.

BACKGROUND: Biomarker studies revealed important clinical significance of exosome for cancer patients. However, there is currently no consensus on exosome quantification methods. METHODS: Bicinchoninic acid (BCA) method, acetylcholinesterase (AChE) method and nanoparticle tracking analysis (NTA) were utilized to quantify 20 plasma exosome samples, and interrelations between these three methods were explored. Associations of plasma exosome levels with characteristics and prognosis of 208 non-small-cell lung cancer (NSCLC) patients were investigated. RESULTS: Results of the three methods for exosome quantification were significantly correlated with each other. Correlation coefficient between AChE and NTA (r= 0.79, P< 0.001) was greater than that between BCA and NTA (r= 0.64, P= 0.003). Plasma exosome levels of 208 NSCLC patients were then quantified with AChE method. Exosome level was significantly associated with tumour stage (P< 0.001) and the history of chronic obstructive pulmonary disease (P= 0.023). Cox proportional hazard analysis demonstrated that higher exosome level was independently associated with poorer overall survival (P= 0.033; hazard ratio = 1.72, 95% confidence interval: 1.05-2.83). CONCLUSIONS: Plasma exosome level correlates with tumor stage and the history of chronic obstructive pulmonary disease, and may serve as a prognostic factor for NSCLC.

Long non-coding RNA MUC5B-AS1 promotes metastasis through mutually regulating MUC5B expression in lung adenocarcinoma.

Long non-coding RNAs (lncRNAs) have been involved in the process of cancer occurrence, progression, and treatment. Lung cancer-related lncRNAs are still an emerging field, thus we sought to identify novel functional lncRNAs as candidate targets in lung cancer. Here, we identified one novel lncRNA, MUC5B-AS1 (Ensembl: ENST00000532061.2). MUC5B-AS1 was upregulated in lung adenocarcinoma tissues compared with normal lung tissues. Moreover, MUC5B-AS1 promoted lung cancer cell migration and invasion in vitro and promoted lung cancer cell metastasis in vivo. MUC5B-AS1 and its cognate sense transcript MUC5B were highly co-expressed and mutually regulated in lung adenocarcinoma. Mechanistically, MUC5B-AS1 promoted cell migration and invasion by forming an RNA-RNA duplex with MUC5B, thereby increasing MUC5B expression levels in lung adenocarcinoma. The high expression of MUC5B was significantly associated with poor outcomes in lung adenocarcinoma. Our findings highlight MUC5B-AS1 functions as an oncogenic lncRNA in tumor metastasis and implicate MUC5B-AS1 as an attractive candidate target for lung adenocarcinoma treatment.

Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer.

Exosomal miRNAs are proposed as excellent candidate biomarkers for clinical applications. However, little is known about their potential roles as prognostic biomarkers in lung cancer. In this study, we explored the prognostic value of plasma exosomal microRNAs (miRNAs) for non-small-cell lung cancer (NSCLC). Using a quantitative polymerase chain reaction (qPCR) array panel, we analyzed 84 plasma exosomal miRNAs in 10 lung adenocarcinoma patients and 10 matched healthy controls. The qPCR array showed 30 aberrantly expressed exosomal miRNAs. Nine candidate miRNAs were selected based on differential expression and previous reports for further evaluating their prognostic roles in 196 NSCLC patients. Elevated levels of exosomal miR-23b-3p, miR-10b-5p and miR-21-5p were independently associated with poor overall survival (with hazard ratio [95% confidence interval]: 2.42 (1.45 - 4.04), P = 0.001; 2.22 (1.18 - 4.16), P = 0.013; 2.12 (1.28 - 3.49), P = 0.003, respectively). When compared to the clinical prognostic variables only model, adding the three exosomal miRNA signatures significantly improved survival predictive accuracy with an increase of time-dependent area under the receiver operating characteristic curve from 0.88 to 0.91 (P=0.015). Our results indicated that plasma exosomal miR-23b-3p, miR-10b-5p and miR-21-5p are promising non-invasive prognostic biomarkers of NSCLC.