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Background Maintenance hemodialysis (MHD) patients have a high incidence of silent brain infarction (SBI) and are in the preclinical stage of symptomatic stroke and vascular dementia. Therefore, there is a great need to explore the risk of SBI in patients with MHD for early detection and reduction of poor prognosis. Objective To explore the risk factors for the occurrence of SBI in MHD patients, a predictive model was constructed and its performance was evaluated. Methods 486 MHD patients from 4 centers (Nanchong Central Hospital Affiliated to North Sichuan Medical College, Guangyuan Central Hospital, Suining Central Hospital, and Pengan County People's Hospital) from January 2017 to October 2022 were included. Patients with MHD were divided into an SBI group (n=102) and a non-SBI group (n=384) using the presence or absence of SBI as the outcome event, and the baseline characteristics of the two study groups were compared. Patients were randomized in a 7∶3 ratio to the modeling set (n=340) and the validation set (n=146). The predictor variables were identified through LASSO regression and multifactorial Logistic regression analyses, and a risk prediction model for the occurrence of SBI in patients with MHD was constructed and presented as a nomographic chart. The predictive performance, accuracy, and clinical utility of the model were evaluated using area under the ROC curve, calibration curve, and decision curve analysis. Results In the modeling set, 70 cases (20.6%) of MHD patients experienced SBI, while in the validation set, 32 cases (21.9%) of patients experienced SBI. The results of LASSO regression combined with multifactor logistic regression analysis showed that age (OR=1.027, 95%CI=1.005-1.050), history of alcohol consumption (OR=4.487, 95%CI=2.075-9.706), BMI (OR=1.082, 95%CI=1.011-1.156), insufficient sleep or excessive sleep (OR=6.286, 95%CI=3.560-11.282), history of chronic disease (chronic obstructive pulmonary disease, diabetes, chronic hepatitis B) (OR=1.873, 95%CI=1.067-3.347), serum lactate level (OR=1.452, 95%CI=1.152-1.897), urea reduction ratio (URR) (OR=0.922, 95%CI=0.875-0.970), and history of antiplatelet medication (OR=0.149, 95%CI=0.030-0.490) were independent influences on the occurrence of SBI in MHD patients (P

Pygopus 2 (Pygo2/PYGO2) is an evolutionarily conserved coactivator and chromatin effector in the Wnt/β-catenin signaling pathway that regulates cell growth and differentiation in various normal and malignant tissues. Although PYGO2 is highly overexpressed in a number of human cancers, the molecular mechanism underlying its deregulation is largely unknown. Here we report that Pygo2 protein is degraded through the ubiquitin/proteasome pathway and is posttranslationally stabilized through phosphorylation by activated phosphatidylinositol 3-kinase/Akt signaling. Specifically, Pygo2 is stabilized upon inhibition of the proteasome, and its intracellular level is regulated by Cullin 4 (Cul4) and DNA damage-binding protein 1 (DDB1), components of the Cul4-DDB1 E3 ubiquitin ligase complex. Furthermore, Pygo2 is phosphorylated at multiple residues, and Akt-mediated phosphorylation at serine 48 leads to its decreased ubiquitylation and increased stability. Finally, we provide evidence that Akt and its upstream growth factors act in parallel with Wnt to stabilize Pygo2. Taken together, our findings highlight chromatin regulator Pygo2 as a common node downstream of oncogenic Wnt and Akt signaling pathways and underscore posttranslational modification, particularly phosphorylation and ubiquitylation, as a significant mode of regulation of Pygo2 protein expression.

Heat stress (HS) leads to substantial economic loss of dairy industry each year. The negative effect of HS in dairy cows is becoming one of the more urgent issue due to accelerating side-effects of global warming. Various genes are involved in HS response but the information about the role of noncoding RNAs, especially circular RNAs (circRNAs) is largely unknown. In our study, we aimed to investigate the different expression profile of circRNAs between HS and Non-heat-stressed condition (NC) of Chinese Holstein cow's mammary gland. CircRNAs were identified using RNA sequencing and bioinformatics analysis. In total, 37405 circRNAs were detected and 95 were differentially expressed (DE), including 15 downregulated and 80 upregulated circRNAs in HS group compared to NC. Eight circRNAs were randomly selected to verify the RNA sequencing result. Further, Sanger sequencing validated the backsplicing site of the eight circRNAs. Moreover, results obtained from the Quantitative real time PCR (qRT-PCR) showed consistent expression trend with that of RNA sequencing. GO annotation and KEGG analysis suggested that these DE circRNAs probably involved in the energy metabolic regulation. Furthermore, we constructed ceRNA network and the result indicated that these DE circRNAs could regulate lactation through IGF1 and PRL signaling pathway. [ABSTRACT FROM AUTHOR]