No abstract

Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.

Air plasma is commonly used to treat water for activation or purification, and plasma-activated water (PAW) is a promising green disinfectant that has attracted great attention in recent years. However, either the O3 discharge mode or the NOx discharge mode of air plasma lacks efficiency for water activation mainly due to the low solubility of O3, NO, and NO2. The transition process between those two modes could produce high valence NOx such as N2O5 which should be more efficient for water activation, but this process is not easy to control stable, and the water activation by N2O5 has rarely been reported before. In this letter, N2O5 is found to be produced effectively and stably by mixing the effluent gases of a NOx mode air plasma, produced by gliding arc discharge, and an O3 mode air plasma, produced by dielectric barrier discharge, and the N2O5-rich mixed gas is found much efficient for water activation. Nearly 6 logs of CFU reduction are achieved for MRSA suspension by using the PAW treated by the mixed gas, and the PAW could persist a high bactericidal effect for more than one hour after the plasma activation. Main reactive species for bactericidal effect in the PAW are discussed, and the chemical pathways for N2O5 production and its usage for water activation are illustrated.

The enzyme, sterile α motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) diminishes infection of human immunodeficiency virus type 1 (HIV-1) by hydrolyzing intracellular deoxynucleotide triphosphates (dNTPs) in myeloid cells and resting CD4+ T cells. This dNTP degradation reduces the dNTP concentration to a level insufficient for viral cDNA synthesis, thereby inhibiting retroviral replication. This antiviral enzymatic activity can be inhibited by viral protein X (Vpx). The HIV-2/SIV Vpx causes degradation of SAMHD1, thus interfering with the SAMHD1-mediated restriction of retroviral replication. Recently, SAMHD1 has been suggested to restrict HIV-1 infection by directly digesting genomic HIV-1 RNA through a still controversial RNase activity. Here, we summarize the current knowledge about structure, antiviral mechanisms, intracellular localization, interferon-regulated expression of SAMHD1. We also describe SAMHD1-deficient animal models and an antiviral drug on the basis of disrupting proteasomal degradation of SAMHD1. In addition, the possible roles of SAMHD1 in regulating innate immune sensing, Aicardi-Goutières syndrome and cancer are discussed in this review.

Deubiquitinase USP28 plays a crucial role in tumorigenesis by enhancing the stabilities of multiple cancer‐related proteins including c‐Myc, Notch1, and LSD1, and has become an attractive target for anticancer drug development. However, to date, only a few of USP28‐targeted active compounds have been developed, and the active compound‐binding pocket in USP28 has not been experimentally revealed yet. In this study, bioassay‐based high‐throughput screening was applied to discover USP28‐targeted inhibitors from the commercially available drug library. Vismodegib, an inhibitor of Hedgehog signaling pathway and FDA‐approved drug for the treatment of basal cell carcinoma, was found to exhibit inhibition activity against USP28 (IC50: 4.41 ± 1.08 μm). Multiple biophysical and biochemical techniques including NMR, ITC, thermal shift assay, HDX‐MS, and site‐directed mutagenesis analysis were then used to characterize the interaction between Vismodegib and USP28. The binding pocket in USP28 for Vismodegib, which is mainly composed of two helical structures spanning D255‐N278 and N286‐Y293, was revealed. According to the possible binding pose generated by HDX‐MS data‐defined molecular docking, the binding cavity occupied by Vismodegib in USP28 aligns well with one of the reported‐binding pockets in USP7 for its inhibitors. Furthermore, cellular assays were conducted to confirm that Vismodegib could interact with the evolutionarily related deubiquitinases USP28 and USP25 and downregulate the levels of the two enzymes' substrate proteins c‐Myc, Notch1, and Tankyrase‐1/2.