Molecular Dynamic Simulations of Bromodomain and Extra-Terminal Protein 4 Bonded to Potent Inhibitors

Bromodomain and extra-terminal domain (BET) subfamily is the most studied subfamily of bromodomain-containing proteins (BCPs) family which can modulate acetylation signal transduction and produce diverse physiological functions. Thus, the BET family can be treated as an alternative strategy for targeting androgen-receptor (AR)-driven cancers. In order to explore the effect of inhibitors binding to BRD4 (the most studied member of BET family), four 150 ns molecular dynamic simulations were performed (free BRD4, Cpd4-BRD4, Cpd9-BRD4 and Cpd19-BRD4). Docking studies showed that Cpd9 and Cpd19 were located at the active pocket, as well as Cpd4. Molecular dynamics (MD) simulations indicated that only Cpd19 binding to BRD4 can induce residue Trp81-Ala89 partly become α-helix during MD simulations. MM-GBSA calculations suggested that Cpd19 had the best binding effect with BRD4 followed by Cpd4 and Cpd9. Computational alanine scanning results indicated that mutations in Phe83 made the greatest effects in Cpd9-BRD4 and Cpd19-BRD4 complexes, showing that Phe83 may play crucial roles in Cpd9 and Cpd19 binding to BRD4. Our results can provide some useful clues for further BCPs family search.

Construction of mathematical modelling of a population of microalgae

This article devoted to the development of the mathematic model of the technological process of the chlorella cultivation process, its features and solving of this mathematic model. The Exponential growth of microalgae population under conditions of unlimited nutrient resources and population space proceeds at a rate proportional to the number of species of predominant cells and is described by the differential equation. In the presence of several inhibitors, specific velocity equations with the number of inhibitors can be used, but, as a rule, there are practically no elements acting as inhibitors in the cultivation of Chlorella microalgae. The modeling of this particular class of objects did not take into account the effect of inhibitors on the growth of microalgae. The consumption of nutrients to support the life of microalgae is described by the differential equation. In the course of this work, the processes of cultivation of microalgae were brought together into a system of equations. As a result, a system of differential equations of the technological process of Chlorella cultivation was obtained. Thus, the obtained system of equations describes the process of cultivation of microalgae and its technological process, implemented in a periodic mode.

AXIN2 reduces the survival of porcine induced pluripotent stem cells (piPSCs)

BackgroundThe establishment of porcine pluripotent stem cells (piPSCs) is still a critical topic and challenging issue. However, all piPSCs are extremely sensitive to changes of the culture conditions.In addition, the side effect of inhibitors in culture medium confine the pluripotency and practicability. This study aimed to investigate the roles of AXIN in piPSCs and further explore the mechanism. Here, porcine AXIN1 gene and AXIN2 were knockdown, cloned, and overexpressed in piPSCs. Digital RNA-seq was performed to explore the mechanism of cell proliferation and anti-apoptosis. ResultsHere, we found (1): overexpression of the porcine AXIN2 gene significantly reduce the survivability of piPSCs, meanwhile wreck the pluripotency of piPSCs; (2): The Digital RNA-seq analysis reveals that AXIN2, as a negative effector of the WNT signaling pathway, whom after knockdown enhances the expression of genes involved in cell cycle such as CCND1, and reduced the expression of genes related to cell differentiation, cell death, and cell apoptosis. ConclusionAXIN2 could reduce the pluripotency and survival of piPSCs and also provided a potential to simplify the cultrue medium.

Rapid processing of SARS-CoV-2 containing specimens for direct RT-PCR

Widespread diagnostic testing is needed to reduce transmission of COVID-19 and manage the pandemic. Effective mass screening requires robust and sensitive tests that reliably detect the SARS-CoV-2 virus, including asymptomatic and pre-symptomatic infections with a low viral count. Currently, the most accurate tests are based on detection of viral RNA by RT-PCR. We developed a method to process COVID-19 specimens that simplifies and increases the sensitivity of viral RNA detection by direct RT-qPCR, performed without RNA purification. In the method, termed Alkaline-Glycol Processing (AG Processing), a SARS-CoV-2-containing biological specimen, such as saliva or a swab-collected suspension, is processed at pH 12.2 to 12.8 for 5 min at room temperature. An aliquot of the AG-processed specimen is used for detection of SARS-CoV-2 RNA by direct RT-qPCR. AG processing effectively lyses viruses and reduces the effect of inhibitors of RT-PCR that are present in biological specimens. The sensitivity of detecting viral RNA using AG processing is on par with methods that include a viral RNA purification step. One copy of SARS-CoV-2 virus per reaction, equivalent to 300 copies per ml of saliva, is detectable in the AG-processed saliva. The LOD is 300 viral copies per ml of initial saliva specimen. AG processing works with saliva specimens or swab specimens collected into Universal Transport Medium, is compatible with heat treatment of saliva, and was confirmed to work with a range of CDC-approved RT-qPCR products and kits. Detection of SARS-CoV-2 RNA using AG processing with direct RT-qPCR provides a reliable and scalable diagnostic test for COVID-19 that can be integrated into a range of workflows, including automated settings.

POLARIZATION STUDIES OF STEEL IN THE PRESENCE OF SYNERGETIC MIXTURES BASED ON INORGANIC OXIDIZERS AND MONOETHANOLAMINE IN SODIUM CHLORIDE SOLUTIONS

Polarization studies have shown that the effect of inhibitors containing inorganic oxidants and monoethanolamine reduces the corrosion rate of steel in 3% NaCl. This decrease unambiguously indicates a simultaneous slowing down of the cathodic reduction of molecular oxygen and the anodic reaction of metal ionization. Based on the studies carried out, it was concluded that the developed mixtures function as mixed –type inhibitors

Rapid processing of SARS-CoV-2 containing specimens for direct RT-PCR

Widespread diagnostic testing is needed to reduce transmission of COVID-19 and manage the pandemic. Effective mass screening requires robust and sensitive tests that reliably detect the SARS-CoV-2 virus, including asymptomatic and pre-symptomatic infections with a low viral count. Currently, the most accurate tests are based on detection of viral RNA by RT-PCR. We developed a method to process COVID-19 specimens that simplifies and increases the sensitivity of viral RNA detection by direct RT-qPCR, performed without RNA purification. In the method, termed Alkaline-Glycol Processing (AG processing), a SARS-CoV-2-containing biological specimen, such as saliva or a swab-collected suspension, is processed at pH 12.2 to 12.8 for 5 min at room temperature. An aliquot of the AG-processed specimen is used for detection of SARS-CoV-2 RNA by direct RT-qPCR. AG processing effectively lyses viruses and reduces the effect of inhibitors of RT-PCR that are present in biological specimens. The sensitivity of detecting viral RNA using AG processing is on par with methods that include a viral RNA purification step. One copy of SARS-CoV-2 virus per reaction, equivalent to 300 copies per ml of saliva, is detectable in the AG-processed saliva. The LOD calculated following U.S. FDA guidelines is 600 viral copies per ml of initial saliva specimen. AG processing works with saliva specimens or swab specimens collected into Universal Transport Medium (UTM), is compatible with heat treatment, and was confirmed to work with a range of CDC-approved RT-qPCR products and kits. Detection of SARS-CoV-2 RNA using AG processing with direct RT-qPCR provides a reliable and scalable diagnostic test for COVID-19 that can be integrated into a range of workflows, including automated settings.