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Background: The budding uninhibited by benzimidazoles (BUB) family is involved in the cell cycle process as mitotic checkpoint components. Abnormal proliferation is a vital process in the development of lung adenocarcinoma (LUAD). Nevertheless, the roles of BUB1 in LUAD remain unclear. In this study, we evaluated the prognostic value and biological functions of BUB1 in LUAD using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), clinical LUAD samples, and in vitro experiments. Methods: The expression, prognostic significance, functions, immune infiltration, and methylation of BUB1 in LUAD were comprehensively analyzed using TCGA, GEO, Gene Expression Profiling Interactive Analysis, Metascape, cBioPortal, MethSurv, and cancerSEA databases. Furthermore, we performed a battery of in vitro experiments and immunohistochemistry (IHC) to verify the bioinformatics results. Results: Multivariate analysis revealed that BUB1 overexpression was an independent prognostic factor (hazard ratio = 1.499, p = 0.013). Functional enrichment analysis showed that BUB1 was correlated with cell cycle, proliferation, DNA repair, DNA damage, and invasion (p < 0.05). Finally, in vitro experiments showed that downregulation of BUB1 inhibited the proliferation, migration, and invasion of LUAD cells and promoted LUAD cell apoptosis. IHC also showed that BUB1 was overexpressed in LUAD (p < 0.001) and was significantly associated with poor prognosis (p < 0.001). Conclusions: Our bioinformatics and IHC analyses revealed that BUB1 overexpression was an adverse prognostic factor in LUAD. In vitro experiments demonstrated that BUB1 promoted tumor cell proliferation, migration, and invasion in LUAD. These results indicated that BUB1 was a promising biomarker and potential therapeutic target in LUAD. [ABSTRACT FROM AUTHOR]

The leakage of landfill leachate (LL) into environmental media would be happened even in the sanitary/controlled landfill, due to the deterioration of geomembrane and the blockage of drainage system after long-term operation. Considering the complex composition and high concentration of pollutants in LL, its toxicity assessment should be conducted as a whole liquid contaminant. Therefore, the impacts of LL on Caenorhabditis elegans (C. elegans) were investigated under the condition of different exposure time and exposure volume fraction (EVF). The stimulating effects on locomotion behavior and growth of C. elegans were observed after acute (24 h) exposure to LL, which were increased firstly and then decreased with the increase of EVF. Meanwhile, the intestinal barrier was not affected by LL, and levels of reactive oxygen species (ROS) and cell apoptosis significantly decreased. However, stimulation and inhibition effects on locomotion behavior and growth of C. elegans were observed when subacute (72 h) exposure to 0.25%–0.5% and 1%–4% of LL, respectively. The intestinal injury index and levels of ROS and cell apoptosis significantly increased when EVF were 2% and 4%. Although the acute exposure of LL had resulted in obviously biological adaptability and antioxidant defense in C. elegans , the protective mechanisms failed to be induced as the exposure time increased (subacute exposure). The toxic effects were confirmed by the down-regulation of genes associated with antioxidant defense and neurobehavior, accompanied by the up-regulation of intestinal injury and cell apoptosis related genes. Moreover, the disturbance of metabolic pathways that associated with locomotion behaviors, growth, and antioxidant defense provided good supplementary evidence for the confirmation of oxidative stress in C. elegans. The research results verified the potential of C. elegans as model organism to determine the complex toxic effects of LL. [Display omitted] • Acute expose to landfill leachate (LL) can active antioxidant defense of C. elegans. • Protective mechanisms failed to be induced when subacute exposure to LL. • The toxic effects of LL were confirmed by the expression change of related genes. • Disturbances in metabolic pathway confirm oxidative stress response of C. elegans. • Metabonomic results verify the response of phenotypic and molecular indexes. [ABSTRACT FROM AUTHOR]

Carbon disulfide (CS 2 ) exposure can cause embryo implantation loss but the mechanism remains unclear. Earlier study revealed that the 4th day of gestation (GD4) and GD5 were the most sensitive exposure time on which the number of implanted embryos decreased obviously in mice. Leukemia inhibitory factor (LIF) in maternal uterine tissue is involved in embryo implantation, which is produced by endometrium and Th2 cells that participate in cellular adhesion of maternal–fetal interface. We herein investigated the effect of CS 2 on the expression of LIF in uterine tissue and its regulatory mechanism in Kunming mice. Exposure was on GD3, GD4, GD5 and GD6, respectively, single administration (631.4 mg/kg), and the indexes were arranged in time series after exposure. The results showed that LIF gene breakage was captured at the 18th hour after exposure by Comet-FISH and the protein and mRNA of LIF in uterine tissue were down-regulated after exposure through the peri-implantation period. In addition, sex steroid hormones, progesterone (P 4 ) and oestrogen (E 2 ) were detected since they can stimulate synthesis of LIF from endometrial cells. Results showed that P 4 and E 2 in serum were down-regulated at all the endpoints of CS 2 exposure groups. These findings suggested that the down-regulated LIF induced by the decreased P 4 and E 2 after mice exposure to CS 2 might be important reasons for implantation disorders. [ABSTRACT FROM AUTHOR]