Previous studies have suggested that in addition to respiratory system cancers, exposure to external airborne agents (EAAs) may also affect the risk of digestive tract cancer. However, previous epidemiological studies have been limited. To clarify this relationship, we conducted a Workers' Korea National Health Insurance Service cohort study. The EAA exposure group comprised participants who had ever visited a hospital as an inpatient for 'lung diseases due to external agents'. The reference population comprised men from the general working population. The EAA exposure group and reference group included a total of 98,666 and 79,959,286 person-years, respectively. Age-adjusted standardized incident rates (SIRs) with 95% confidence intervals (95%CI) were calculated for each 5-year age stratum. The SIR (95% CI) of EAA exposure was 1.30 (1.19-1.38) for all digestive tract cancers. The highest risk associated with EAA exposure was observed for oral cancer, followed by esophageal and stomach cancers [SIRs (95%CI) 3.96 (3.02-4.78), 3.47(2.60-4.25), and 1.34(1.17-1.47), respectively.] These statistically significant associations did not be attenuated in a subgroup analysis using logistic regression adjusted for age, smoking and alcohol consumption. Our findings suggest that EAA exposure should address risk reduction of both digestive tract and respiratory system cancers.Lifestyle factors may affect mental health and play a critical role in the development of neurodegenerative diseases including Alzheimer's disease (AD). However, whether the temperatures of daily beverages have any impact on cognitive function and AD development has never been studied. https://www.selleckchem.com/products/importazole.html In this study, we investigated the effects of daily drinking water temperatures on cognitive function and AD development and progression in mice and the underlying mechanisms. Cognitive function of mice was assessed using passive avoidance test, open field test, and Morris water maze. Wild-type Kunming mice receiving intragastric water (IW, 10 mL/kg, 2 times/day) at 0 °C for consecutive 15 days displayed significant cognitive defects accompanied by significant decrease in gain of body weight, gastric emptying rate, pepsin activity, and an increase in the energy charge in the cortex when compared with mice receiving the same amount of IW at 25 °C (a temperature mimicking most common drinking habits in human), suggesting the altered neuroenergetics may cause cognitive decline. Similarly, in the transgenic APPwse/PS1De9 familial AD mice and their age- and gender-matched wild-type C57BL/6 mice, receiving IW at 0 °C, but not at 25 °C, for 35 days caused a significant time-dependent decrease in body weight and cognitive function, accompanied by a decreased expression of PI3K, Akt, the glutamate/GABA ratio, as well as neuropathy with significant amyloid lesion in the cortex and hippocampus. All of these changes were significantly aggravated in the APPwse/PS1De9 mice than in the control C57BL/6 mice. These data demonstrate that daily beverage at 0 °C may alter brain insulin-mediated neuroenergetics, glutamate/GABA ratio, cause cognitive decline and neuropathy, and promote AD progression.Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, but there is no effective drug available for GBM. Avasimibe is a potent inhibitor of acyl-coenzyme A cholesterol acyltransferase-1 (ACAT-1), which was used to treat atherosclerosis. Experimental evidence and bioinformatics have shown that avasimibe has anticancer activity. In this study we investigated the anticancer effects of avasimibe on human glioblastoma cells and the underlying mechanisms. Our results showed that avasimibe dose-dependently inhibited the proliferation of U251 and U87 human glioblastoma cells with IC50 values of 20.29 and 28.27 μM, respectively, at 48 h. Avasimibe (7.5, 15, 30 μM) decreased the DNA synthesis, and inhibited the colony formation of the tumor cells. Treatment of avasimibe also dose-dependently increased the apoptotic rate of tumor cells, decreased the mitochondrial membrane potential, induced the activity of caspase-3/7, and increased the protein expression of cleaved caspase-9, cleaved PARP and Bax in U251 and U87 cells. RNA-sequencing analyses revealed that avasimibe suppressed the expression of CDK2, cyclin E1, CDK4, cyclin D, CDK1, cyclin B1, Aurora A, and PLK1, while induced the expression of p53, p21, p27, and GADD45A, which was validated by Western blot analysis. These results demonstrated that avasimibe induced mitochondria-dependent apoptosis in glioblastoma cells, which was associated with arresting the cell cycle at G0/G1 phase and G2/M phase by regulating the p53/p21 pathway, p53/GADD45A and Aurora A/PLK1 signaling pathways. In U87 xenograft nude mice model, administration of avasimibe (15, 30 mg·kg-1·d-1, ip, for 18 days) dose-dependently inhibit the tumor growth. Taken together, our results demonstrated that avasimibe might be a promising chemotherapy drug in the treatment of GBM.High infiltration of M2-polarized macrophages in the primary tumor indicates unfavorable prognosis and poor overall survival in the patients with triple-negative breast cancer (TNBC). Thus, reversing M2-polarized tumor-associated macrophages in the tumors has been considered as a potential therapeutic strategy for TNBC. Sphingomyelin synthase 2 (SMS2) is the key enzyme for sphingomyelin production, which plays an important role in plasma membrane integrity and function. In this study we investigated whether SMS2 inhibitor or SMS2 gene knockout could reduce macrophages M2 polarization and tumor progression in a mouse model of TNBC. We showed that SMS2 mRNA expression was linked to immunosuppressive tumor microenvironment and poor prognosis in TNBC patients. The knockout of SMS2 or application of 15w (a specific SMS2 inhibitor) markedly decreased the generation of M2-type macrophages in vitro, and reduced the tumor weight and lung metastatic niche formation in a 4T1-TNBC mouse model. We further demonstrated that the in vivo antitumor efficacy of 15w was accompanied by a multifaceted remodeling of tumor immune environment reflecting not only the suppression of M2-type macrophages but also diminished levels of regulatory T cells and myeloid-derived suppressor cells leading to a dramatically improved infiltration of antitumor CD8+ T lymphocytes. Collectively, our results reveal a novel and important role of SMS2 in the protumorigenic function and may offer a new strategy for macrophage-targeted anticancer therapy.