The hypoxic tumor microenvironment induces epithelial-mesenchymal transition (EMT) in tumor cells and increases tumor cell malignancy. Previous studies indicated that malfunction of Wnt signaling is observed in some lung cancer patients. Athough crosstalk between hypoxia and Wnt signaling in tumor cells has recently been revealed, the detailed underlying mechanisms have not been well defined. In the present study, we demonstrated that hypoxia in lung adenocarcinoma cells can enhance Wnt signaling activity by stabilizing β-catenin and altering its localization into the nucleus. Overexpression of HIF-2α increased β-catenin expression, promoted cell mobility, and induced morphological changes to a greater degree than HIF-1α overexpression. Knockdown of HIF-2α decreased β-catenin expression and inhibited hypoxia-induced cell mobility. Moreover, we identified that phosphorylational activation of AKT1 by hypoxia and HIF-2α was required for Wnt activation upon hypoxia treatment. Downregulation of HIF-2α and β-catenin reduced colony formation when cells were exposed to long-term hypoxia treatment. Taken together, our data support that hypoxia activates PI3K/AKT as well as Wnt signaling in a HIF-2α-dependent manner, thus elevating the resistance of lung cancer cells to chronic hypoxia-induced stress.

Erectile dysfunction (ED) affects millions of men worldwide. Men with ED generally complain failure to attain or maintain an adequate erection during sexual activity. The prevalence of ED is strongly correlated with age, affecting about 40% of men at age 40 and nearly 70% at age 70. A variety of chronic diseases, including diabetes, ischemic heart disease, congestive heart failure, hypertension, depression, chronic renal failure, obstructive sleep apnea, prostate disease, gout, and sleep disorder, were reported to be associated with ED. In this study, data retrieved from a subset of the National Health Insurance Research Database (NHIRD) of Taiwan were used for designing the clinical decision support system (CDSS) for predicting ED incidences in men. The positive cases were male patients aged 20-65 who were diagnosed with ED between Jan. 2000 and Dec. 2010 confirmed by at least 3 outpatient visits or at least one inpatient visit, while the negative cases were randomly selected from the database without a history of ED and were frequency (1:1), age, and index year matched with the ED patients. Data of a total of 2,832 ED patients and 2,832 non-ED patients, each consisting of 41 features including index age, 10 comorbidities, and 30 other comorbidity-related variables, were retrieved for designing the predictive models. Integrated genetic algorithm (GA) and support vector machine (SVM) was adopted to design the CDSSs with 2 experiments of independent training and testing (ITT) conducted to verify their effectiveness. In the 1st ITT experiment, data extracted from Jan. 2000 till Dec. 2005 (61.51%, 1,742 positive cases and 1,742 negative cases) were used for training and validating and the data retrieved from Jan. 2006 till Dec. 2010 were used for testing (38.49%); whereas in the 2nd ITT experiment, data in the training set (77.78%) were extracted from Jan. 2000 till Dec. 2007 and those in the testing set (22.22%) were retrieved afterward. Tenfold cross validation and 3 different objective functions were adopted for obtaining the optimal models with best predictive performance in the training phase. The testing results show that the CDSSs achieved a predictive performance with accuracy, sensitivity, specificity, g-mean, and area under ROC curve (AUC) of 74.72-76.65%, 72.33-83.76%, 69.54-77.10%, 0.7468-0.7632, and 0.766-0.817, respectively. In conclusion, the CDSSs designed based on cost-sensitive objective functions as well as salient comorbidity-related features achieve satisfactory predictive performance for predicting ED incidences.

Integrating experiential and institutional perspectives on ecotourism programs is currently a hot topic in the management of sustainable marine tourism. We establish a preference model of ecotourism management with multiple attributes to evaluate tourist preferences and the welfare values under various marine ecotourism scenarios in a marine national park. The empirical results show that tourists would prefer to alter the status quo by increasing the number of park-related experiential activities, improving the quality of the interpretation, and establishing local funds in the community ecosystem. Our results will help park managers create a sustainable marine policy that considers tourists’ preferences.

In this study, we applied an evaluation model of multiple attributes of sport-based tourism to the marketing strategy for a marathon event in Kinmen (Taiwan) based on a choice experiment methodology. We found that the participants appreciated the experience of authentic cuisine and the availability of marathon souvenirs. They also preferred engaging in ecotourism activities and supporting the establishment of a sport development fund. We applied market segmentation by dividing the participants into two groups. Those in the first group were primarily younger, had higher incomes, and had participated previously in the Kinmen Marathon. Those in the second group primarily had lower incomes, were over 40 years old, and were participating in the Kinmen Marathon for the first time. Both groups preferred entertainment, educational, and esthetic experiences, but only the first group desired an escapist experience. We propose three marketing strategies for sport tourism experiences as a reference for future practice in Kinmen sport tourism.