Clinical Validation of the Proenkephalin (PENK) Methylation Urine Test for Monitoring Recurrence of Non-muscle-invasive Bladder Cancer.

Background and objective: To assess the effectiveness of a urine-based proenkephalin (PENK) methylation test using linear target enrichment-quantitative methylation-specific polymerase chain reaction (mePENK test) for detection of non-muscle-invasive bladder cancer (NMIBC) recurrence compared to cytology and the NMP22 test. Methods: We first conducted a retrospective case-control study involving 54 patients with primary BC and 29 healthy individuals. We then prospectively enrolled 186 patients (January to December 2022) undergoing cystoscopy surveillance after transurethral resection of bladder tumor, of whom 59 had recurrent tumors. We analyzed voided urine samples for PENK methylation levels in urinary DNA. Cystoscopy with histology was used as the reference standard for assessing the diagnostic accuracy of the mePENK test in detecting BC recurrence. We calculated the sensitivity and specificity using receiver operating characteristic curve analysis. Survival differences were determined using the Kaplan-Meier method and Cox proportional-hazards model. A p < 0.05 was considered statistically significant. Key findings and limitations: In the case-control study, the PENK test had sensitivity of 83.3% and specificity of 100%. For NMIBC patients undergoing cystoscopy surveillance, the sensitivity was 76.3% (95% confidence interval [CI] 63.4-86.4%) and the specificity was 85% (95% CI 77.6-90.7%), outperforming cytology (sensitivity: 28.8%, 95% CI 17.8-42.1%; p < 0.001; specificity: 97.6%, 95% CI 93.2-99.5%) and the NMP22 test (sensitivity: 54.2%, 95% CI 40.7-67.2%; p = 0.016; specificity 81.9%, 95% CI 74.1-88.2%). In the high-risk group, the mePENK test had sensitivity of 89.7% (95% CI 75.8-97.1%) and a negative predictive value of 96.9%. For the group with low/intermediate risk, the sensitivity was 41.7%. In the group with negative cystoscopy, recurrence-free survival was shorter for patients with positive than for those with negative mePENK results (245 vs 503 d), with a hazard ratio of 9.4 (p < 0.001). The main study limitation is the small sample size. Conclusions and clinical implications: The mePENK test showed good performance for detection of NMIBC recurrence and has potential for use for prognosis and prediction. Patient summary: We found that a test used to analyze urine samples showed good performance in detecting recurrence of NMIBC. This noninvasive mePENK test may help in personalized follow-up care for patients with NMIBC.

Licensing Effect of Pro-Environmental Behavior in Metaverse.

The Metaverse is an important virtual venue in people's daily lives. This study examined whether pro-environmental behaviors in the Metaverse with a self-customized avatar lead to licensing effects, thereby reducing pro-environmental intention in reality. In addition, the study examined the mediating effect of self-presence on the relationship between avatar customization and pro-environmental behavior. A laboratory experiment was conducted using ZEPETO, a Metaverse platform. A total of 60 participants were randomly assigned to the self-customized avatar condition or the assigned avatar condition, and they engaged in pro-environmental behaviors on the Metaverse platform. Participants with self-customized avatars had less intention to engage in pro-environmental behavior in reality after engaging in pro-environmental behavior in the Metaverse than those with assigned avatars. Furthermore, self-presence partially mediated the relationship between avatar customization and pro-environmental intention.

Fus3 and Tpk2 protein kinases regulate the phosphorylation-dependent functions of RNA helicase Dhh1 in yeast mating and Ste12 protein expression.

Decapping of mRNA is a key regulatory step for mRNA decay and translation. The RNA helicase, Dhh1, is known as a decapping activator and translation repressor in yeast Saccharomyces cerevisiae. Dhh1 also functions as a gene-specific positive regulator in the expression of Ste12, a mating-specific transcription factor. A previous study showed that the N-erminal phosphorylation of Dhh1 regulates its association with the mRNA-binding protein, Puf6, to affect the protein translation of Ste12. Here, we investigated the roles of the phosphorylated residues of Dhh1 in yeast mating process and Ste12 expression. The phospho-deficient mutation, DHH1-T10A, was associated with decreased diploid formation during mating and decreased level of the Ste12 protein in response to α-mating pheromone. A kinase overexpression analysis revealed that Ste12 protein expression was affected by overexpression of Fus3 MAP kinase or Tpk2 kinase. Tpk2 was shown to be responsible for phosphorylation of Dhh1 at Thr10. Our study shows that overexpression of Fus3 or Tpk2 alters the Dhh1-Puf6 protein interaction and thereby affects Ste12 protein expression.

Novel, electrolyte solutions comprising fully inorganic salts with high anodic stability for rechargeable magnesium batteries.

Herein the first inorganic magnesium salt solution capable of highly reversible magnesium electrodeposition is presented. Synthesized by acid-base reaction of MgCl2 and Lewis acidic compounds such as AlCl3, this salt class demonstrates upwards of 99% Coulombic efficiency, deposition overpotential of <200 mV, and anodic stability of 3.1 V.