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Soluble E‐cadherin (sE‐cad) is an 80 kDa fragment derived from E‐cadherin that is shed from the cell surface through proteolytic cleavage and is a biomarker in various cancers that promotes invasion and migration. Alveolar epithelial destruction, aberrant lung fibroblast migration and inflammation contribute to pulmonary fibrosis. Here, we hypothesized that E‐cadherin plays an important role in lung fibrosis. In this study, we found that E‐cadherin was markedly increased in the bronchoalveolar lavage fluid (BALF) and serum of mice with pulmonary fibrosis and that blocking sE‐cad with HECD‐1, a neutralizing antibody targeting the ectodomain of E‐cadherin, effectively inhibited myofibroblast accumulation and collagen deposition in the lungs after bleomycin (BLM) exposure. Moreover, transforming growth factor‐β (TGF‐β1) induced the shedding of sE‐cad from A549 cells, and treatment with HECD‐1 inhibited epithelial–mesenchymal transition (EMT) stimulated by TGF‐β1. Fc‐E‐cadherin (Fc‐Ecad), which is an exogenous form of sE‐cad, robustly promoted lung fibroblast migration. E‐cadherin participates in bleomycin (BLM)‐induced lung fibrosis by promoting EMT in the alveolar epithelium and fibroblast activation. E‐cadherin may be a novel therapeutic target for lung fibrosis. [ABSTRACT FROM AUTHOR]

The airway epithelial barrier dysfunction plays a crucial role in pathogenesis of asthma and causes the amplification of downstream inflammatory signal pathway. S100 calcium binding protein A4 (S100A4), which promotes metastasis, have recently been discovered as an effective inflammatory factor and elevated in bronchoalveolar lavage fluid in asthmatic mice. Vascular endothelial growth factor‐A (VEGFA), is considered as vital regulator in vascular physiological activities. Here, we explored the probably function of S100A4 and VEGFA in asthma model dealt with house dust mite (HDM) extracts. Our results showed that secreted S100A4 caused epithelial barrier dysfunction, airway inflammation and the release of T‐helper 2 cytokines through the activation of VEGFA/VEGFR2 signaling pathway, which could be partial reversed by S100A4 polyclonal antibody, niclosamide and S100A4 knockdown, representing a potential therapeutic target for airway epithelial barrier dysfunction in asthma. [ABSTRACT FROM AUTHOR]

The work aims to reveal relationship between solution temperature, microstructure, and mechanical properties of Ti–5Al5Mo5V3Cr1Zr (Ti‐55 531) alloy. The alloys are prepared via solution processing in a temperature ranging from Tβ − 100 °C (where Tβ is β‐transus temperature) to Tβ + 100 °C for 2 h; and then air cooled, aged at 600 °C for 6 h, and air cooled again. Results indicate that solution temperature range (from Tβ − 100 °C to Tβ + 100 °C) can be divided into following five ranges according to performance of Ti‐55 531 alloy. The alloy presents excellent mechanical performance combining high strength and good ductility for solution temperatures ranging from Tβ − 50 °C to Tβ − 30 °C and from Tβ + 10 °C to Tβ + 30 °C. Interestingly, the Ti‐55 531 alloy exhibits a dramatically enhanced strength, while ductility drops rapidly as solution temperature exceeds Tβ + 70 °C. The enhanced strength's main reason is that grain boundary α phase changes from continuous to discontinuous with increasing solution temperature; nevertheless, the increased size of β grains results in a reduction in ductility. Thus, continuity of grain boundary α phase has a dramatical influence on performance of Ti‐55 531 alloy. [ABSTRACT FROM AUTHOR]

Herein, we aimed to determine the effect of vitamin D (Vit D) and underlying mechanisms on asthma‐induced lung injury via regulation of HIF‐1α/Notch1 (hypoxia‐inducible factor 1 alpha/neurogenic locus notch homolog protein 1) signaling during autophagy. We established an asthma mouse model using respiratory syncytial virus (RSV) nasal drop combined with ovalbumin (OVA) atomization. Mice were treated with different Vit D concentrations. Pathological changes and cell apoptosis were examined using hematoxylin–eosin (HE) staining and TUNEL (terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate (dUTP) nick end‐labeling) assay, respectively. Additionally, periodic acid–Schiff (PAS) and Masson's trichrome staining solutions were used to examine changes in lung tissue. Immunofluorescence determined LC 3B (microtubule‐associated protein 1 light chain 3B) expression in lung tissues, whereas western blotting and immunohistochemistry were used to evaluate other proteins, including HIF‐1α and Notch1. Compared with the normal group, the asthma model group exhibited pathological lung tissue deterioration, elevated fibrosis, increased apoptosis cell numbers, and upregulated autophagy. Vitamin D supplementation ameliorated pathological changes and fibrosis in the lung tissue. Furthermore, Vit D treatment significantly suppressed apoptotic cell numbers and autophagy while enhancing the HIF‐1α/Notch1 pathway. Given the HIF‐1α/Notch1 agonistic activity, Vit D treatment inhibited apoptosis cell numbers, which were increased following asthma‐induced upregulation of autophagy. Vitamin D improved asthma‐induced lung tissue injury by suppressing autophagy via regulation of HIF‐1α/Notch1 signaling in vivo. [ABSTRACT FROM AUTHOR]

Background: Aberrant expression of m6A‐related proteins contributes to the occurrence and progression of non‐small cell lung cancer (NSCLC). Current studies mainly focus on single m6A regulatory genes and their underlying mechanisms, and the expression of multiple m6A regulatory proteins in NSCLC remains unclear. Therefore, it is necessary to systematically examine these proteins, particularly in clinical specimens. Methods: Bioinformatic analysis was used to determine the expression of m6A regulatory genes and their correlation with common gene mutations, such as TP53, EGFR and KRAS, using The Cancer Genome Atlas (TCGA) and the AE‐meta databases. Immunohistochemistry was employed to analyze the protein expression of m6A regulatory proteins in 61 benign lung tissues and 316 NSCLC tissues. Statistical analysis was performed to calculate the correlation between the expression of m6A regulatory proteins and clinicopathological features, survival, and common gene mutations in lung carcinoma patients. Results: Analysis of the mRNA levels of 13 core m6A regulators, using information from TCGA and the AE‐meta databases, revealed that YTHDF1 levels were upregulated in NSCLC compared to those in adjacent normal tissues. Immunohistochemical staining showed that the expression of METTL3, ALKBH5, YTHDC2 and YTHDF1 was significantly upregulated in NSCLC tissues. Further analyses demonstrated a positive correlation between differentially expressed m6A regulatory proteins, including METTL3, ALKBH5, YTHDC2 and YTHDF1, and the poor clinicopathological features and survival of NSCLC patients. According to the statistics of NSCLC patients enrolled in the present study, the protein levels of METTL3 in patients with EGFR exon‐19 mutation were higher than those in patients with wild‐type EGFR. Conclusions: Our results indicate that m6A regulators, including METTL3, ALKBH5, YTHDC2 and YTHDF1, could serve as predictive markers of NSCLC, which will facilitate the early detection and diagnosis of NSCLC. [ABSTRACT FROM AUTHOR]

Introduction: Unlike the established evidence to use chemotherapy for urothelial carcinoma of the bladder, presently there are insufficient data to inform a recommendation on upper urinary tract urothelial carcinoma treatment. The prognosis for patients with stage T4 and positive lymph nodes is poor; however, primary tumors in the renal pelvis are associated with favorable prognoses compared to those located in the ureter. Our study aimed at investigating the effectiveness of chemotherapy in patients with pT3N0M0 renal pelvic urothelial carcinomas (RPUC) who have relative favorable prognosis. Methods: Patients with pT3N0M0 tumors who underwent radical nephroureterectomy combined with bladder cuff excision between 2005 and 2014 and registered in the Surveillance, Epidemiology, and End Results database were eligible for inclusion (n = 939). Baseline characteristics between the chemotherapy and observation groups were controlled for with inverse probability of treatment weighting (IPTW)‐adjusted analysis. Results: After the IPTW‐adjusted analysis, the 5‐year IPTW‐adjusted rates of overall survival (OS) for the chemotherapy and observation groups were 53.1% and 44.9%, respectively. The IPTW‐adjusted Kaplan‐Meier curves suggested that chemotherapy was associated with increased OS compared with observation (P =.028). In the IPTW‐adjusted Cox proportional hazards regression model, chemotherapy was associated with favorable survival benefits compared with observation (hazard ratio [HR] 0.71, 95% CI 0.52‐0.92, P =.031), and this was maintained after bootstrapping (HR 0.72, 95% CI 0.49‐0.93). Chemotherapy had a protective effect on OS benefits, which were found in a majority of the results of the subgroup analysis and were consistent with the main results (all P‐interactions > 0.05). Conclusion: Chemotherapy may provide significant OS benefits for patients with pT3N0M0 RPUC. The results of our study could strengthen the evidence for using adjuvant chemotherapy in this rare group of patients. [ABSTRACT FROM AUTHOR]