RESUMEN
Ubiquitin-specific protease 30 (USP30) is a deubiquitinating enzyme (DUB) belonging to the USP subfamily, which was found localized in the mitochondrial outer membrane and peroxisomes owing to its unique transmembrane domain. Structural study revealed that USP30 employed a unique catalytic triad and molecular architecture to preferentially cleave the Lys6 linked ubiquitin chains. USP30 plays an essential role in several cellular events, such as the PINK1/Parkin-mediated mitophagy, pexophagy, BAX/BAK-dependent apoptosis, and IKKß-USP30-ACLY-regulated lipogenesis/tumorigenesis, and is tightly regulated by post-translational modification including phosphorylation and mono-ubiquitination. Dysregulation of USP30 is associated with a range of physiological disorders, such as neurodegenerative disease, hepatocellular carcinoma, pulmonary disorders, and peroxisome biogenesis disorders. Nowadays, scientists and many biopharmaceutical companies are making much effort to explore USP30 inhibitors including natural compounds, phenylalanine derivatives, N-cyano pyrrolidines, benzosulphonamide, and other compounds. For the treatment of pulmonary disorders, the study in Mission Therapeutics of USP30 inhibitor is already in the pre-clinical stage. In this review, we will summarize the current knowledge of the structure, regulation, emerging physiological role, and target inhibition of USP30, hoping to prompt further investigation and understanding of it.
RESUMEN
Objectives: To non-invasively predict the coexistence of isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in adult-type diffuse gliomas using apparent diffusion coefficient (ADC) histogram and direct ADC measurements and compare the diagnostic performances of the two methods. Materials and methods: A total of 118 patients with adult-type diffuse glioma who underwent preoperative brain magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) were included in this retrospective study. The patient group included 40 patients with coexisting IDH mutation and MGMT promoter methylation (IDHmut/MGMTmet) and 78 patients with other molecular status, including 32 patients with IDH wildtype and MGMT promoter methylation (IDHwt/MGMTmet), one patient with IDH mutation and unmethylated MGMT promoter (IDHmut/MGMTunmet), and 45 patients with IDH wildtype and unmethylated MGMT promoter (IDHwt/MGMTunmet). ADC histogram parameters of gliomas were extracted by delineating the region of interest (ROI) in solid components of tumors. The minimum and mean ADC of direct ADC measurements were calculated by placing three rounded or elliptic ROIs in solid components of gliomas. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the diagnostic performances of the two methods. Results: The 10th percentile, median, mean, root mean squared, 90th percentile, skewness, kurtosis, and minimum of ADC histogram analysis and minimum and mean ADC of direct measurements were significantly different between IDHmut/MGMTmet and the other glioma group (P < 0.001 to P = 0.003). In terms of single factors, 10th percentile of ADC histogram analysis had the best diagnostic efficiency (AUC = 0.860), followed by mean ADC obtained by direct measurements (AUC = 0.844). The logistic regression model combining ADC histogram parameters and direct measurements had the best diagnostic efficiency (AUC = 0.938), followed by the logistic regression model combining the ADC histogram parameters with statistically significant difference (AUC = 0.916) and the logistic regression model combining minimum ADC and mean ADC (AUC = 0.851). Conclusion: Both ADC histogram analysis and direct measurements have potential value in predicting the coexistence of IDHmut and MGMTmet in adult-type diffuse glioma. The diagnostic performance of ADC histogram analysis was better than that of direct ADC measurements. The combination of the two methods showed the best diagnostic performance.
RESUMEN
OBJECTIVES: The Tibetan-Yi Corridor located on the eastern edge of Tibetan Plateau is suggested to be the key region for the origin and diversification of Tibeto-Burman speaking populations and the main route of the peopling of the Plateau. However, the genetic history of the populations in the Corridor is far from clear due to limited sampling in the northern part of the Corridor. MATERIALS AND METHODS: We collected blood samples from 10 Tibetan and 10 Han Chinese individuals from Gansu province and genotyped about 600,000 genome-wide single nucleotide polymorphisms (SNPs). RESULTS: Our data revealed that the populations in the Corridor are all admixed on a genetic cline of deriving ancestry from Tibetans on the Plateau and surrounding lowland East Asians. The Tibetan and Han Chinese groups in the north of the Plateau show significant evidence of low-level West Eurasian admixture that could be probably traced back to 600â¼900 years ago. DISCUSSION: We conclude that there have been huge population migrations from surrounding lowland onto the Tibetan Plateau via the Tibetan-Yi Corridor since the initial formation of Tibetans probably in Neolithic Time, which leads to the current genetic structure of Tibeto-Burman speaking populations.
