O-GlcNAcylation of CSNK2A1 by OGT is Involved in the Progression of Colorectal Cancer.

Colorectal cancer (CRC) metastasis is challenging for improved clinical outcomes. The casein kinase 2 alpha 1 (CSNK2A1) is an oncogene involved in several cancers. This study aimed to investigate the influence of CSNK2A1 on CRC progression and the related molecular mechanism. The CSNK2A1 levels were predicted using bioinformatic analysis and were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Cell phenotypes were analyzed using cell-counting kit-8, colony formation, transwell assay, and western blot. Tumor growth was evaluated in a tumor-bearing mouse model in vivo. Similarly, O-GlcNAc modification of CSNK2A1 was assessed by immunoprecipitation, western blot, and immunofluorescence. Results indicated that CSNK2A1 was upregulated in CRC and was related to poor prognosis. Interference with CSNK2A1 suppressed CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition, inhibiting tumor growth. Moreover, OGT promoted the glycosylation modification of CSNK2A1, enhanced its protein stability, and reversed tumor progression when CSNK2A1 was knocked down. The CSNK2A1 might also affect CRC progression via the PI3K/AKT pathway. In conclusion, the OGT-O-GlcNAcylation-CSNK2A1 axis accelerated the malignant advancement of CRC, suggesting potential CRC therapeutic targets.

Polymorphisms of ATG5 Gene Are Associated with Autoimmune Thyroid Diseases, Especially Thyroid Eye Disease.

Objective: To explore the association of ATG5 gene polymorphisms with autoimmune thyroid diseases (AITDs) including Hashimoto's thyroiditis (HT) and Graves' illness (GD) as well as their clinical features. Methods: rs6568431, rs548234, and rs6937876 were selected to investigate the correlation of single-nucleotide polymorphisms of ATG5 gene with AITDs. Their frequencies in 824 AITD patients, including 271 HT patients and 553 GD patients, and 764 healthy controls were tested using both ligase detection reaction and multiplex polymerase chain reaction. Results: Allele A frequency of rs6568431 in AITDs patients (p = 0.016, OR = 1.201, 95% CI = 1.034 - 1.394) and allele G frequency of rs6937876 in AITDs patients (p = 0.009, OR = 1.223, 95% CI = 1.052 - 1.422) and in GD patients (p = 0.009, OR = 1.247, 95% CI = 1.056 - 1.473) were significantly higher than those in the healthy controls. The frequency of G allele (p = 5.42E - 18, OR = 0.242, 95% CI = 0.173 - 0.339) of rs6937876 was significantly higher in GD patients with ophthalmopathy. However, no relationship was found between family history, age onset, and the three SNPs. Conclusion: The study is the first to reveal the association between AITDs and ATG5 polymorphisms, and ATG5 gene is considered as a predisposing gene to AITDs, especially GDs.

Safety and operational impacts of setting speed limits below engineering recommendations.

This study quantifies the operational and safety impacts of setting posted speed limits below engineering recommendations using field data from rural roads in Montana. Vehicle operating speeds and historical crash data were collected at multiple sites with posted speed limits set equal to engineering recommendations and sites with posted speed limits set lower than engineering recommendations. Linear, quantile and logistic regression models were estimated to predict mean operating speed, 85th percentile operating speed and speed limit compliance, respectively, as a function of various roadway characteristics and level of speed enforcement. The Empirical-Bayes before-after approach was also used to develop crash modification factors (CMFs) that describe the expected change in total and fatal + injury crash frequency when setting posted speed limits lower than engineering recommendations. Because safety data were collected over a long time period, temporal adjustments were incorporated to account for yearly changes in crash reporting, traffic characteristics and other variables. The results revealed that speed limit compliance worsened as the difference between the engineering recommended and posted speed limits increased. The presence of verified heavy police enforcement reduced both mean and 85th-percentile operating speeds by approximately 4 mph and increased speed limit compliance. The safety analysis found a statistically significant reduction in total, fatal + injury, and property damage only (PDO) crash frequency at locations with posted speed limits set 5 mph lower than engineering recommendations. Locations with posted speed limits set 10 mph lower than engineering recommendations experienced a decrease in total and PDO crash frequency, but an increase in fatal + injury crash frequency. The safety effects of setting speed limits 15 to 25 mph lower than engineering recommendations were less clear, as the results were not statistically significant, likely due to the small sample of sites included in the evaluation. Overall, the results suggest that setting posted speed limits 5 mph lower than the engineering recommended practice may result in operating speeds that are more consistent with the posted speed limits and overall safety benefits.