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Hatfield Lamm posted an update 6 months, 1 week ago
ndependent simulations and determined regions of under-sampling on the potential energy landscape. The results suggest that conducting multiple independent simulations using a diverse set of de novo predicted structures is a promising approach to achieve sufficient sampling. This approach avoids undesirable outcomes, such as the problem of the RNA aptamer being trapped in a local minimum. For others wishing to conduct multiple independent simulations, the analysis protocol presented in this study is a guide for examining overall sampling and determining if more simulations are necessary for sufficient sampling.A series of novel anticancer hydrazinotriazolothiadiazine-based derivatives were designed based on the structure-activity relationship of the previously reported anticancer triazolothiadiazines. These derivatives were synthesized and biologically screened against full NCI-60 cancer cell lines revealing compound 5l with a potential antiproliferative effect. 5l was screened over 16 kinases to study its cytotoxic mechanism which showed to inhibit glycogen synthase kinase-3 β (GSK-3β) with IC50 equal to 0.883 μM and 14-fold selectivity over CDK2. Also, 5l increased active caspase-3 levels, induced cell cycle arrest at the G2-M phase, and increased the percentage of Annexin V-fluorescein isothiocyanate-positive apoptotic cells in PC-3 prostate cancer-treated cells. Molecular docking and dynamics were performed to predict the binding mode of 5l in the GSK-3β ATP binding site. 5l can be utilized as a starting scaffold for developing potential GSK-3β inhibitors.Anthraquinone (AQ) levels in some Indonesian dried tea leaves samples from different plantation areas and their brewed tea samples were determined by gas chromatography-tandem mass spectrometry methods. The mean lower bound, middle bound, and upper bound of AQ levels in 59 dried tea leaves samples were 82.2, 82.8, and 83.4 μg/kg, respectively, while their 95%th percentile values were identical at 190.3 μg/kg (0.1903 mg/kg). In a transfer rate study, the mean and 95%th AQ levels in 30 dried tea leaves samples with AQ level ≥ LOQ (limit of quantification) were 128.6 and 194.5 μg/kg (0.1945 mg/kg), while those of their corresponding brewed tea samples were 2.1 and 3.4 μg/kg, respectively. The mean and 95%th transfer rates of AQ into brewed tea samples were 51.99 and 88.17%. Using these data and taking into account daily tea consumption, calculated cancer potency slope factor, benchmark dose of 10% effect at lower bound 95% confidence interval of AQ, and average body weight, the risk characterization due to exposure to this compound from tea consumption was calculated and stated as incremental lifetime cancer risk (ILCR) and margin of exposure (MOE). The overall results revealed that AQ levels in dried tea leaves up to the highest level found in the samples lead to an ILCR of not more than 10-6 and an MOE of not less than 104 and hence was predicted to give sufficient consumer protection.Ankylosing spondylitis (AS) is a chronic immune-mediated disease. Various immune cells play an essential role in the AS pathogenesis. However, the specific pathogenesis of AS has not been well understood. Proteomic profiles of peripheral blood mononuclear cells (PBMCs) were applied to reveal the specific pathogenesis of AS. Quantitative proteomic analyses were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based methods to investigate the protein profiling of PBMCs from new-onset AS patients (n = 9) and healthy controls (n = 9). We identified 782 differentially expressed proteins (DEPs) and 527 differentially phosphorylated proteins (DPPs) between AS patients and healthy controls. The subcellular location of DEPs and DPPs showed that most of the DEPs were from the cytoplasm (n = 296, 38%), were extracellular (n = 141, 18%), and from the nucleus (n = 114, 15%); most of the DPPs were from the cytoplasm (n = 37, 34%), nucleus (n = 35, 32%), and plasma membrane (n = 10, 9%). We further identified 89 proteins with both expression and phosphorylation differences. The functional annotation of the 89 differentially expressed and phosphorylated proteins enriched in the antigen processing and presentation pathway. Four DEPs with six phosphorylated positions were found in the antigen processing and presentation pathway. The differentially expressed and phosphorylated proteins may be helpful to uncover the pathogenesis of AS. The six AS-specific proteins may serve as candidate markers for AS diagnosis and new treatment targets.Near-critical mixtures of limited miscibility are significant for chemical physics, soft matter physics, and a variety of challenging applications. Their basic properties can be tuned by compressing or a systematic change of one of the components. This report addresses these issues, based on experimental studies in nitro-compound (nitrobenzene, o-nitrotoluene, and 1-nitropropane) and n-alkane (from pentane to eicosane) critical mixtures. Studies reveal new patterns for the evolution of the critical consolute temperature (TC) and concentration (xC, mole fraction) within the tested homologous series TC(n) ∼ n2 and xC(n) ∼ n1/2. They also show two paths of the high-pressure impact (i) dTC(P)/dP > 0 and overlapping of normalized TC(P) dependences and (ii) the crossover dTC(P)/dP 0 with increasing n-alkane length. WZ4003 concentration The consistent parameterization of all TC(P) dependencies is introduced. Supplementary nonlinear dielectric effect studies indicate a possible molecular origin of the phenomenon. The coexistence curve under high pressure is in the agreement with the isomorphism postulate for critical phenomena but with a surprisingly strong distortion from the Cailletet-Mathias law of the rectilinear diameter. The new and reliable method for estimating the critical concentration and temperature is proposed. It explores the analysis of relative volumes occupied by coexisting phases.Establishing the dynamics of wetting film thinning and rupture during the bubbles attached on the coal surface is extremely important for flotation. However, studying the dynamics of bubble attachment from the molecular level using molecular dynamics simulation (MDS) has rarely been reported. In this work, the dynamics of bubble attachment at three different coal surfaces with varying degrees of coalification were studied using MDS. In the bubble attachment process, the wetting film between the bubble and coal surface gradually become thinner until it ruptures. By comparing the bubble attachment dynamics on three different coal surfaces, the results indicate that the bubble attachment rate on the surface with strong hydrophobicity is faster than that on the surface with weak hydrophobicity. Besides, the number of hydrogen bonds between the molecules of the wetting film is decreased with the attachment of bubbles; however, it is sharply decreased on the BC surface and slowly reduces on the LRC surface before the film rupture.
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