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Cullin 4A (Cul4A) reportedly has oncogenic roles in several cancer types by regulating tumor suppressors through the ubiquitination and proteolysis of the tumor suppressor. In addition, Cul4A is associated with chemosensitivity to chemotherapy drugs. This study investigated the association between Cul4A and lung cancer cell chemosensitivity to paclitaxel, particularly with respect to the role of the p33 inhibitor of the growth 1 (p33ING1b) tumor suppressor. The results showed that the Cul4A knockdown upregulated the p33ING1b expression in lung cancer cells and increased the lung cancer cell and mice tumor xenograft chemosensitivity to paclitaxel. The Cul4A knockdown also inhibited the growth and increased the apoptosis in the tumor xenografts treated with paclitaxel. Notably, the p33ING1b overexpression increased the lung cancer cell chemosensitivity to paclitaxel, but the p33ING1b knockdown reduced the chemosensitivity. A further analysis demonstrated that Cul4A regulates the expression of p33ING1b through protein-protein interactions, ubiquitination, and protein degradation. In conclusion, the present findings suggest that Cul4A mediates the chemosensitivity of lung cancer cells to paclitaxel by regulating p33ING1b. These findings may offer novel insights into future therapeutic strategies for lung cancer that target Cul4A.

: Cullin 4A (Cul4A) is overexpressed in a number of cancers and has been established as an oncogene. This study aimed to elucidate the role of Cul4A in lung cancer invasion and metastasis. We observed that Cul4A was overexpressed in non-small cell lung cancer (NSCLC) tissues and the overexpression of Cul4A was associated with poor prognosis after surgical resection and it also decreased the expression of the tumor suppressor protein annexin A10 (ANXA10). The knockdown of Cul4A was associated with the upregulation of ANXA10, and the forced expression of Cul4A was associated with the downregulation of ANXA10 in lung cancer cells. Further studies showed that the knockdown of Cul4A inhibited the invasion and metastasis of lung cancer cells, which was reversed by the further knockdown of ANXA10. In addition, the knockdown of Cul4A inhibited lung tumor metastasis in mouse tail vein injection xenograft models. Notably, Cul4A regulated the degradation of ANXA10 through its interaction with ANXA10 and ubiquitination in lung cancer cells. Our findings suggest that Cul4A is a prognostic marker in NSCLC patients, and Cul4A plays important roles in lung cancer invasion and metastasis through the regulation of the ANXA10 tumor suppressor.

Background: Metabolic syndrome (MetS), a major contributor to cardiovascular and metabolic diseases, has been linked with exposure to air pollution. However, the relationship between air pollutants and the five components of MetS [abdominal obesity, elevated triglyceride, decreased high-density lipoprotein cholesterol (HDL-C), elevated blood pressure, and elevated fasting blood glucose levels], has not been clearly described. Objective: We examined the association between long-term exposure to air pollutants and the occurrence of MetS and its components by using a longitudinal cohort in Taiwan. Methods: The MJ Health Research Foundation is a medical institute that conducts regular physical examinations. The development of MetS, based on a health examination and the medical history of an MJ cohort of 93,771 participants who were enrolled between 2006 and 2016 and had two or more examinations, was compared with estimated exposure to air pollutants in the year prior to health examination. The exposure levels to fine particulate matter [PM with an aerodynamic diameter of [less than or equal to]2.5 [micro]m (P[M.sub.2.5])] and nitrogen dioxide (N[O.sub.2]) in the participants' residential areas were estimated using a hybrid Kriging/land-use regression (LUR) model executed using the XGBoost algorithm and a hybrid Kriging/LUR model, respectively. Cox regression with time-dependent covariates was conducted to estimate the effects of annual air pollutant exposure on the risk of MetS and its components. Results: During the average follow-up period of 3.4 y, the incidence of MetS was 38.1/1,000 person-years. After mutual adjustment and adjustments for potential covariates, the results indicated that every 10-[micro]g/[m.sup.3] increase in annual P[M.sub.2.5] concentration was associated with an increased risk of abdominal obesity [adjusted hazard ratio (aHR) = 1.07; 95% confidence interval (CI): 1.01, 1.14], hypertriglyceridemia (aHR=1.17; 95% CI: 1.11, 1.23), low HDL-C (aHR= 1.09; 95% CI: 1.02, 1.17), hypertension (aHR = 1.15; 95% CI: 1.09, 1.21), and elevated fasting blood glucose (aHR = 1.15; 95% CI: 1.10, 1.20). Furthermore, P[M.sub.2.5] and N[O.sub.2] may increase the risk of developing MetS among people who already 'have' some components of MetS. Discussion: Our findings suggest that in apparently healthy adults undergoing physical examination, exposure to P[M.sub.2.5] and N[O.sub.2] might be associated with the occurrence of MetS and its components. https://doi.org/10.1289/EHP10611, Introduction In the 2017 Global Burden of Disease Study, cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) accounted for 31.8% (17.8 million) and 1.8% (1 million), respectively, of all-cause [...]

Sodium and aluminum (Na-Al) co-doped ZnO thin films (NAZO) were prepared on the quartz glass substrate by sol-gel spin-coating method. The effect of different Na-Al co-doped concentration on crystallization, microstructure and photoelectric properties of ZnO films were investigated. The results show that all NAZO thin films samples grow along the c-axis of the preferred orientation; appropriate Na-Al co-doped concentration can improve the ZnO films crystallization, increase the carrier mobility; meanwhile, six columnar grain structure crystal particles can be observed on the NAZO films surface. With the changing of Na-Al co-doped concentration, the highest mean optical transmittance reaches 95%. Because of the difference of the solid solution ratio, the appropriate concentration can improve the efficiency of doping Na-Al element, which enhances the carrier concentration of the film inside and the resistivity decreases; the lowest resistivity of NAZO thin films is 4.7×10-2Ω·cm.