Colon cancer is the third leading cause of death from cancer worldwide with less than 10% survival rate at the late stage. Although mutations of certain genes have been implicated in familial colon cancer development, the etiology of the majority of colon cancer remains unknown. Herein, we identified TYRO3 as a potential oncogene. Immunohistochemical staining results demonstrated that levels of TYRO3 were markedly elevated in polyps and colon cancer cells and were negatively correlated with prognosis. Overexpression of TYRO3 enhanced cell motility, invasion, anchorage-independent growth and metastatic ability, while knockdown of TYRO3 impaired all these processes. Results from meta-analysis showed that TYRO3 was associated with epithelial-mesenchymal transition (EMT) signatures. Gain-of-function and loss-of-function experiments demonstrated that expression of SNAI1, the master regulator of EMT, was regulated by TYRO3 and played a major role in mediating TYRO3-induced EMT processes. The murine model also demonstrated that Tyro3 and Snai1 were upregulated in the early stage of colon cancer development. To provide a proof-of-concept that TYRO3 is a druggable target in colon cancer therapy, we raised anti-TYRO3 human antibodies and showed that treatment with the human antibody abolished TYRO3-induced EMT process. More importantly, administration of this anti-TYRO3 antibody increased drug sensitivity in primary cultured colon cancer cells and xenografted mouse tumors. These findings demonstrate that TYRO3 is a novel oncogene and a druggable target in colon cancer.

Doping at the rare-earth site by divalent alkaline-earth ions in perovskite lattice has witnessed a variety of magnetic and electronic orders with spatially correlated charge, spin and orbital degrees of freedom. Here, we report an antisite disorder driven spontaneous exchange bias effect as a result of hole carrier (Sr(2+)) doping in La(2-x)Sr(x)CoMnO6 (0 < x < 1) double perovskites. X-ray diffraction and Raman spectroscopy have evidenced an increase in disorder with the increase of Sr content up to x  =  0.5 and thereby a decrease from x  =  0.5 to 1. X-ray absorption spectroscopy has revealed that only Co is present in the mixed valence of Co(2+) and Co(3+) states with Sr doping to compensate the charge neutrality. Magnetotransport is strongly correlated with the increase of antisite disorder. The antisite disorder at the B-site interrupts the long-range ferromagnetic order by introducing various magnetic interactions and instigates reentrant glassy dynamics, phase separation and canted type antiferromagnetic behavior with the decrease of temperature. This leads to a novel magnetic microstructure with unidirectional anisotropy that causes a spontaneous exchange bias effect that can be tuned with the amount of antisite disorder.

This study evaluated geographic accessibility and utilized assessment indices to investigate disparities in elderly community care resource distribution. The data were derived from Taiwanese governmental data in 2017, including 3,148,283 elderly individuals (age 65+), 7681 villages, and 1941 community care centers. To identify disparities in geographic accessibility, we compared the efficacy of six measurements and proposed a composite index to identify levels of resource inequality from the Gini coefficient and “median-mean” skewness. Low village-level correlation (0.038) indicated inconsistencies between the demand populations and community care center distribution. Method M6 (calculated accessibility of nearest distance-decay accounting for population of villages, supplier loading, and elderly walkability) was identified as the most comprehensive disparity measurement. Community care policy assessment requires a comprehensive and weighted calculation process, including the elderly walkability distance-decay factor, demand population, and supplier loading. Three steps were suggested for elderly policy planning and improvement in future.

Objective To assess the criterion validity, construct validity and test-retest reliability of the traditional Chinese language version of the Menopause Rating Scale (MRS-TC version). Methods This was an observational, cross-sectional study covering hospital and community samples of 317 women aged 39-62 years. Two questionnaires were administered, namely, the MRS-TC version, made up of 11 items in three dimensions, and the World Health Organization Quality of Life-BREF (WHOQOL-BREF). The intraclass correlation coefficient was used to examine the test-retest reliability of the questionnaire on two separate occasions, 2 weeks apart. The internal consistency was assessed with Cronbach's α. To evaluate criterion validity, the relationship between the individual items and dimension scores of both instruments was estimated. Pearson's correlation was used to assess convergent and discriminant validity; construct validity was evaluated by comparing the mean scores of menopausal and non-menopausal women for each of the MRS dimensions. Results The final questionnaire comprised 11 items in three dimensions. The intra-class correlation (ICC) for the test-retest reliability ranged from 0.83 to 0.93; values of Cronbach's α for psychological, somatic, and urogenital symptom domains were 0.88, 0.68, and 0.59, respectively. For the convergent and discriminant validity, the correlations between the individual questionnaire and the WHOQOL-BREF were significant; those with the MRS dimensions were significantly negatively associated for the physical, psychological, social and environmental domains. Conclusion The MRS-TC version using the traditional Chinese language is a reliable and valid questionnaire for assessing menopausal symptoms and global quality of life in climacteric women.