Its pro-apoptotic effect produces a pro-survival effect that cannot be underestimated. This review extensively covers in vitro and in vivo experiments and clinical studies investigating TRAIL. It also provides a summary of the current knowledge on the TRAIL signalling pathway and its involvement in pathogenesis, diagnosis and therapeutics of CNS disorders as a basis for future research.Anaerobic choline metabolism by human gut microbiota to produce trimethylamine (TMA) has recently evolved as a potential therapeutic target because of its association with chronic kidney disease and increased cardiovascular risks. Limited examples of choline analogues have been reported as inhibitors of bacterial enzyme choline TMA-lyase (CutC), a key enzyme regulating choline anaerobic metabolism. We used a new workflow to discover CutC inhibitors based on focused screening of a diversified library of small molecules for intestinal metabolic stability followed by in vitro CutC inhibitory assay. This workflow identified a histidine-based scaffold as a CutC inhibitor with an IC50 value of 1.9±0.2 μM. Remarkably, the identified CutC inhibitor was able to reduce the production of TMA in whole-cell assays using various bacterial strains as well as in complex gut microbiota environment. The improved efficiency of the new scaffold identified in this study in comparison to previously reported CutC inhibitors would enable optimization of potential leads for in vivo screening and clinical translation. Finally, docking studies and molecular-dynamic simulations were used to predict putative interactions created between inhibitor and CutC.Acylglycerol kinase (AGK) uses adenosine triphosphate (ATP) and acylglycerol to generate adenosine diphosphate (ADP) and acyl-sn-glycerol 3-phosphate in cells. Recent evidence has demonstrated that dysregulated AGK expression is associated with the development of various human cancers. This study investigated the effects of AGK on gastric cancer cell proliferation and carcinogenesis and explored the underlying molecular events. AGK expression was up-regulated in gastric cancer and was associated with poor prognosis in gastric cancer patients. 4Phenylbutyricacid AGK overexpression increased gastric cancer proliferation, invasion capacity and the expression of the epithelial-mesenchymal transition markers in vitro. Conversely, the knockdown of AGK expression reduced gastric cancer cell proliferation in vitro and in nude mouse tumour cell xenografts. Importantly, AGK expression was associated with the YAP1 expression in gastric cancer cells and tissues. YAP1 expression also transcriptionally induced AGK expression through the binding of TEAD to the AGK gene promoter. However, AGK expression inhibited the activation of the Hippo pathway proteins and induced YAP1 nuclear localization to enhance the transcription activity of YAP1/TEADs. In conclusion, the study demonstrates that AGK is not only a novel target of the Hippo-YAP1 pathway, but that it also positively regulates YAP1 expression, thus forming a YAP1-AGK-positive feedback loop.

Benign paroxysmal positional vertigo (BPPV) is a common, self-limited, and favorable prognostic peripheral vestibular disorder. BPPV is transmitted in an autosomal dominant fashion, but most cases occur sporadically. Little research has been reported regarding the mutation spectrum of sporadic BPPV in a large cohort. This study attempted to identify the causative candidate variants associated with BPPV in VDR, LOXL1, and LOXL1-AS1.

An amplicon-targeted next-generation sequencing (NGS) method for VDR, LOXL1, and LOXL1-AS1, was completed in 726 BPPV patients and 502 normal controls. A total of 30 variants (20 variants from VDR, nine variants from LOXL1, seven variants from LOXL1-AS1) were identified in these two groups.

Three of 30 variants were nonsynonymous mutations, but no significant difference was found between the BPPV group and the control group via association analysis. A single nucleotide variant (SNV), rs1078967, was identified that is located in intron 1 of LOXL1. The allelic frequency distribution differed significantly between the BPPV group and the control group (p=0.002). Genotypic frequency was also significantly different (p=0.006), as determined by gene-based analyses.

This report is the first to analyze the variant spectrum of BPPV in a large Chinese population.

This report is the first to analyze the variant spectrum of BPPV in a large Chinese population.Accumulating evidence suggests that circular RNAs have the abilities to regulate gene expression during the progression of sepsis-associated acute kidney injury. Circular RNA VMA21 (circVMA21), a recent identified circular RNA, could reduce apoptosis to alleviate intervertebral disc degeneration in rats and protect WI-38 cells from lipopolysaccharide-induced injury. However, the role of circVMA21 in sepsis-associated acute kidney injury (sepsis-associated AKI) is unknown. In this study, we first demonstrated that circVMA21 alleviated sepsis-associated AKI by reducing apoptosis and inflammation in rats and HK-2 cells. Additionally, to explore the molecule mechanism underlying the amelioration, after the bioinformatics analysis, we confirmed that miR-9-3p directly bound to circVMA21 by luciferase and RNA immunoprecipitation assay, and the effector protein of miR-9-3p was SMG1. Furthermore, the oxidative stress caused by sepsis-associated AKI was down-regulated by circVMA21. In conclusion, circVMA21 plays an important role in the regulating sepsis-associated AKI via adjusting miR-9-39/SMG1/inflammation axis and oxidative stress.The purpose of this commentary was to outline several key considerations and challenges for medical imaging departments during a global pandemic. Five public hospital medical imaging departments were identified in South-East Queensland, Australia, to provide insight into their response to the COVID-19 pandemic. Common themes were identified, with the four considered most pertinent documented in this commentary. Similar operational considerations and challenges were identified amongst all sites. This commentary intends to serve as a starting point for medical imaging departments in considering the planning and implementation of services in a pandemic scenario.