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77, 95% CI = (1.25, 6.15)). Relatively high predictive values were observed from this model for training dataset (AUC = 0.791) and verification dataset (AUC = 0.668). Stratified analysis showed that the association was independent of gender. A nomogram was additionally generated to predict 5-year survival probability containing risk score and pathological stage. Its performance was evaluated by applying calibration curve. The methylation signature risk model based on 11 DMRs may be a reliable prognostic signature for MIBC, which provides new insights into development of individualized therapy for MIBC.Background Long noncoding RNA Zinc finger nuclear transcription factor, X-box binding 1-type containing 1 antisense RNA 1 (ZFAS1) has been reported to be an oncogene in various tumors. However, the role of ZFAS1 in endometrial carcinoma (EC) are not fully determined. Methods &amp; results Here, we found ZFAS1 expression was significantly upregulated in EC patients, which was significantly associated with International Federation of Gynecology and Obstetrics stage, histological grade, myometrial invasion and poor prognosis. The loss-of-function assays showed that knockdown of ZFAS1 significantly suppressed the proliferation, G1/S transition, migration and invasion in EC cells. Moreover, knockdown of ZFAS1 obviously downregulated the expression of CDK4, Cyclin D1 and N-cadherin, but upregulated E-cadherin expression. Conclusion Collectively, these results suggest that ZFAS1 might be used as potential therapeutic targets for EC treatment.The orexin peptides promote hedonic intake and other reward behaviors through different brain sites. The opioid dynorphin peptides are co-released with orexin peptides but block their effects on reward in the ventral tegmental area (VTA). We previously showed that in the paraventricular hypothalamic nucleus (PVN), dynorphin and not orexin peptides enhance hedonic intake, suggesting they have brain-site-specific effects. Obesity alters the expression of orexin and dynorphin receptors, but whether their expression across different brain sites is important to hedonic intake is unclear. We hypothesized that hedonic intake is regulated by orexin and dynorphin peptides in PVN and that hedonic intake in obesity correlates with expression of their receptors. Here we show that in mice, injection of DYN-A1-13 (an opioid dynorphin peptide) in the PVN enhanced hedonic intake, whereas in the VTA, injection of OXA (orexin-A, an orexin peptide) enhanced hedonic intake. In PVN, OXA blunted the increase in hedonic intake caused by DYN-A1-13. In PVN, injection of norBNI (opioid receptor antagonist) reduced hedonic intake but a subsequent OXA injection failed to increase hedonic intake, suggesting that OXA activity in PVN is not influenced by endogenous opioid activity. In the PVN, DYN-A1-13 increased the intake of the less-preferred food in a two-food choice task. In obese mice fed a cafeteria diet, orexin 1 receptor mRNA across brain sites involved in hedonic intake correlated with fat preference but not caloric intake. Together, these data support that orexin and dynorphin peptides regulate hedonic intake in an opposing manner with brain-site-specific effects.<br /><br /> Parkinson's disease (PD) patients have lower levels of serum 25-hydroxyvitamin D (25(OH)D) than the general population. Previous studies have suggested a negative association between 25(OH)D and clinical features of PD, but the data are inconsistent.<br /><br /> We conducted a cross-sectional, observational study. Serum 25(OH)D, disease (Hoehn-Yahr stage [HY]) and clinical symptom (Unified Parkinson Disease Rating Scale [UPDRS]) severity and global cognitive functions (Mini-Mental State Examination [MMSE]) were studied in 500 consecutive PD patients not using vitamin D supplements. Information on sunlight exposure and dietary intakes (using a 66-item food frequency questionnaire) were also collected. A convenient sample of age and sex-matched community healthy controls (<br /><br />  = 100) was included as a control group.<br /><br /> PD patients had lower 25(OH)D serum levels than controls. Deficiency status (&lt;20 ng/mL) was found in 65.6% of patients. 25(OH)D levels were independently correlated to sunlight exposure (<br /><br />  = .002) and vitamin D intake (<br /><br />  = .009). In multivariate models, using a Mendelian randomization approach, lower serum 25(OH)D was associated with more severe disease (HY, <br /><br />  = .035), worse clinical symptoms (UPDRS Part-III total score [<br /><br />  = .006] and dopaminergic [<br /><br />  = .033] and non-dopaminergic subscores [<br /><br />  = .001]) and greater global cognitive function impairment (<br /><br />  = .041). [https://www.selleckchem.com/products/bismuth-subnitrate.html click here] Neither cognitive functions nor clinical features were associated with reduced intake of vitamin D and sunlight exposure.<br /><br /> Serum 25(OH)D was negatively correlated with disease and symptoms severity, as well as with global cognitive functions. Our study adds to the evidence that low 25(OH)D may affect the progression of PD negatively. Intervention studies in this area are required.<br /><br /> Serum 25(OH)D was negatively correlated with disease and symptoms severity, as well as with global cognitive functions. Our study adds to the evidence that low 25(OH)D may affect the progression of PD negatively. Intervention studies in this area are required.How has the COVID-19 pandemic affected intimate relationships? The existing literature is mixed on the effect of major external stressors on couple relationships, and little is known about the early experience of crises. The current study used 654 individuals involved in a relationship who provided data immediately before the onset of the pandemic (December, 2019) and twice during the early stages of the pandemic (March and April, 2020). Results indicate that relationship satisfaction and causal attributions did not change over time, but responsibility attributions decreased on average. Changes in relationship outcomes were not moderated by demographic characteristics or negative repercussions of the pandemic. There were small moderation effects of relationship coping and conflict during the pandemic, revealing that satisfaction increased and maladaptive attributions decreased in couples with more positive functioning, and satisfaction decreased and maladaptive attributions increased in couples with lower functioning.