Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility

Performance study of ad hoc on-demand distance vector (AODV) for ad hoc wireless networks

An ad hoc wireless network is a network composed of mobile communication devices, which is designed to provide communication capability to satisfy the need of a temporary nature in an infrastructure-less environment. A routing protocol is necessary in ad hoc networks to ensure effective communication among nodes. This thesis presents a simulation-based study on the performance evaluation of Ad hoc on-demand distance vector (AODV) routing protocol, which is one of the core routing protocols being promoted by the Mobile Ad Hoc Networking (MANET) group of the Internet Engineering Task Force.​Master of Science (Communications Engineering

Mesoporous Polymer-Derived Ceramic Membranes for Water Purification via a Self-Sacrificed Template

Membrane separation has been widely used in water purification, and mesoporous ceramic membranes show a high potential in the future because of their high stability and resistance to harsh environments. In the current study, a novel polymer-derived ceramic silicon oxycarbide (SiOC) membrane was developed via a preceramic reactive self-sacrificed method and was further applied in a homemade dead-end system for water purification. A cyclosiloxane hybrid polymer was selected as the precursor and polydimethylsiloxane (PDMS) was used as the sacrificial template. Membrane pores were formed because of template removal during the sintering process, creating channels for water transportation. The pore size and porosity could be readily adjusted by changing the amounts and types of PDMS used in the fabrication process. The as-prepared SiOC membrane showed a high water permeability (140 [email protected] bar) and high removal rate of rhodamine B (RhB), demonstrating its potential applications in water treatment. This work would provide an easy and scalable method to prepare ceramic membranes with a controlled pore size, which could be used for different water treatment applications

High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC Pathway

Background: Nicotinamide mononucleotide (NMN) is the physiological circulating NAD precursor thought to elevate the cellular level of NAD+ and to ameliorate various age-related diseases. An inseparable link exists between aging and tumorigenesis, especially involving aberrant energetic metabolism and cell fate regulation in cancer cells. However, few studies have directly investigated the effects of NMN on another major ageing-related disease: tumors. Methods: We conducted a series of cell and mouse models to evaluate the anti-tumor effect of high-dose NMN. Transmission electron microscopy and a Mito-FerroGreen-labeled immunofluorescence assay (Fe2+) were utilized to demonstrate ferroptosis. The metabolites of NAM were detected via ELISA. The expression of the proteins involved in the SIRT1–AMPK–ACC signaling were detected using a Western blot assay. Results: The results showed that high-dose NMN inhibits lung adenocarcinoma growth in vitro and in vivo. Excess NAM is produced through the metabolism of high-dose NMN, whereas the overexpression of NAMPT significantly decreases intracellular NAM content, which, in turn, boosts cell proliferation. Mechanistically, high-dose NMN promotes ferroptosis through NAM-mediated SIRT1–AMPK–ACC signaling. Conclusions: This study highlights the tumor influence of NMN at high doses in the manipulation of cancer cell metabolism, providing a new perspective on clinical therapy in patients with lung adenocarcinoma

Long Non-coding RNA PVT1 Promotes Cell Proliferation and Migration by Silencing ANGPTL4 Expression in Cholangiocarcinoma

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with a low survival rate and limited treatment options. Long non-coding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many kinds of human cancers. It was discovered in this study that the lncRNA PVT1, whose expression is significantly elevated in CCA, could be a molecular marker of CCA. Experiments indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo. According to RNA sequencing (RNA-seq) analysis, PVT1 knockdown dramatically influenced target genes associated with cell angiogenesis, cell proliferation, and the apoptotic process. RNA immunoprecipitation (RIP) analysis demonstrated that, by binding to epigenetic modification complexes (PRC2), PVT1 could adjust the histone methylation of the promoter of ANGPTL4 (angiopoietin-like 4) and, thus, promote cell growth, migration, and apoptosis progression. The data verified the significant functions of PVT1 in CCA oncogenesis, and they suggested that PVT1 could be a target for CCA intervention. Keywords: cholangiocarcinoma, lncRNA PVT1, ANGPTL

Effect of NNK and beta-adrenoceptors on the expression p-ERK1/2, cyclin-D1, Bcl-2, VEGF, and Bax.

<p>NNK promoted the expression of p-ERK1/2, cyclin-D1, Bcl-2, and VEGF, and decreased the expression of Bax in KYSE410 (A) and HET-1A (B) cells. Knockdown of beta-adrenoceptors decreased the expression of p-ERK1/2, cyclin D1, Bcl-2, and VEGF, and increased the expression of Bax. More importantly, down-regulation of both beta1- and beta2-adrenoceptors before treatment with NNK reversed the NNK-associated protein expression, and beta2-adrenoceptors showed a more significant effect. Beta-actin served as an endogenous control. Independent experiments were repeated three times. Negative is representative of nonspecific control siRNA for beta-adrenoceptors.</p

Effect of NNK and beta-adrenoceptors on cell migration and invasion.

<p>Variously treated KYSE410 cells were seeded in Boyden chambers for migration or invasion assays. At the end of the experiments, migratory or invasive cells that were on the bottom surface were fixed, stained with hematoxylin and eosin, and then counted under a microscope at 200×. Data were obtained from three independent experiments. ^ε p<0.05 compared with the blank group; ^ζ p<0.05 compared with the negative group; ^ξ p<0.05 compared with the negative+NNK group. Negative is representative of nonspecific control siRNA for beta-adrenoceptors.</p

Effect of NNK, atenolol, and ICI118551 on the tumorigenicity of ESCC cells <i>in</i> vivo.

<p>KYSE410 cells were subcutaneously injected into the right posterior flank of nude mice. At 1 week post-implantation, the mice were randomized into six groups with six animals in each group to receive various treatments: DMSO, atenolol (10 mg/kg/day), ICI118551 (10 mg/kg/day), NNK (1.2 mg/kg/day), atenolol+NNK, and ICI118551+NNK. <b>A,</b> Representative images of the subcutaneous tumors formed in nude mice. <b>B,</b> Histograms showing the average tumor volume ± SD per group. <b>C,</b> VEGF expression in tumors. <b>D</b>, Histological scores of VEGF expression in each group. <b>E,</b> CD31 expression in tumors. <b>F,</b> Microvessel density (MVD) of each group. Data are the means ± SD. ^ε p<0.05 compared with the blank group; ^ξ p<0.05 compared with the NNK group.</p

Expression of beta1- and beta2-adrenoceptors.

<p>A, Western blotting showed the expression of beta1- and beta2-adrenoceptors in KYSE410 cells, an ESCC cell line, and HET-1A cells, an immortalized esophageal epithelial cell line. B and C, siRNA-induced down-regulation of beta1- and beta2-adrenoceptor mRNA and protein expression was confirmed by RT-PCR (B) and western blotting (C), respectively. GAPDH and beta-actin served as endogenous controls. Negative is representative of nonspecific control siRNA for beta-adrenoceptors.</p