Cyclocondensation of amidines with dimethyl acetylenedicarboxylate: A convenient entry into tetramic acids

Amidines undergo cyclocondensations with dimethyl acetylenedicarboxylate (DMAD) to give highly functionalized 5‐dialkylamino‐4‐pyrrolin‐3‐ones. The products are crystalline, highly colored compounds that are uniquely functionalized and represent advanced intermediates in the construction of several other heterocyles, in particular the biologically active tetramic acids. The synthetic transformations of these compounds to tetramic acids are also described.     

Lie group analysis of gravity currents

We consider shallow water theory to study the self-similar gravity currents that describe the motion of a heavy fluid flowing into another lighter ambient fluid. Gratton and Vigo investigated the shallow water theory representing the self-similar gravity currents by using dimensional analysis [J. Gratton, C. Vigo, Self-similarity gravity currents with variable inflow revisited: Plane currents, J. Fluid. Mech. 258 (1994) 77–104]. But in this study, the self-similarity solutions of the one-layer shallow-water equations representing gravity currents are investigated by using Lie group analysis and it is shown that Lie group analysis is the generalization of the dimensional analysis for investigating the self-similarity solutions of the one-layer shallow-water equations. Applying Lie group theory, reduced equations of the shallow water equations are found. Therefore, it becomes possible to obtain the similarity forms depending on the Lie group parameters and also the self-similarity solutions for the special values of these group parameters.     

The approximation of reachable sets of control systems with integral constraint on controls

In this paper an approximation method for the construction of reachable sets of control systems with integral constraints on the control is considered. It is assumed that the control system is non-linear with respect to the phase state vector and is linear with respect to the control vector. The admissible control functions are chosen from the ball centered at the origin with radius μ₀ in L_p, p > 1. The reachable set is replaced by the set which consists of finite number of points. The estimated accuracy of the Hausdorff distance between the reachable set and the set which is approximately constructed is obtained.     

Liquid chromatography/tandem mass spectrometry based targeted proteomics quantification of P-glycoprotein in various biological samples

P-Glycoprotein (P-gp/ABCB1) is expressed in membrane barriers to exclude pharmacological substrates from cells, and therefore influences the ADME/Tox properties and efficacy of therapeutics. In the present study, a liquid chromatography/tandem mass spectrometry (LC/MS/MS)-mediated targeted proteomics was developed to quantitate P-gp protein. With the aid of in silico predictive tools, a unique 9-mer tryptic peptide of P-gp protein was synthesized (with the stable isotope labeled (SIL) peptide as internal standard) and applied for quantitative LC/MS/MS method development. For LC/MS/MS quantification, the N-glycosylation of the peptide, polymorphism and transmembrane region was intended to be excluded during the peptide selection. The lower limit of quantification was established to be 0.025 nM with the linearity of the standard curve ranging to 20 nM of P-gp signature peptides in the matrix digested surrogate bovine serum albumin. The digestion efficiency, both the accuracy (relative error) and the precision (coefficient of variation) of the method, was verified by using the synthetic quantification peptide and the synthetic surrogate substrate peptide that mimics the sequence of tryptic peptide and associated flanking tryptic cleavage sites at the N- and C-terminals. By applying the method developed, the absolute amounts of human, dog and mouse P-gp (Mdr1a) were quantified in various biological samples. LC/MS/MS-mediated P-gp quantification was achieved as a highly sensitive, selective and reproducible assay and could be directly applicable to many current research needs related to P-gp.     

Anti-Quorum Sensing Activity of Stevia Extract,Stevioside, Rebaudioside A and Their Aglycon Steviol

Governments are creating regulations for consumers to reduce their sugar intake, prompting companies to increase the ratio of artificial sweeteners in their products. However, there is evidence of some deleterious effects ascribed to the aforementioned synthetic agents and therefore consumers and food manufacturers have turned their attention to natural dietary sweeteners, such as stevia, to meet their sweetening needs. Stevia is generally considered safe; however, emerging scientific evidence has implicated the agent in gut microbial imbalance. In general, regulation of microbial behavior is known to depend highly on signaling molecules via quorum sensing (QS) pathways. This is also true for the gut microbial community. We, therefore, evaluated the possible role of these stevia-based natural sweeteners on this bacterial communication pathway. The use of a commercial stevia herbal supplement resulted in an inhibitory effect on bacterial communication, with no observable bactericidal effect. Purified stevia extracts, including stevioside, rebaudioside A (Reb A), and steviol revealed a molecular interaction, and possible interruption of Gram-negative bacterial communication, via either the LasR or RhlR receptor. Our in-silico analyses suggest a competitive-type inhibitory role for steviol, while Reb A and stevioside are likely to inhibit LasR-mediated QS in a non-competitive manner. These results suggest the need for further safety studies on the agents.     

Role of Melatonin in Angiotensin and Aging

The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through oxidative stress by activating the NAD(P)H oxidase pathway, which in turn results in the production of reactive oxygen species. This radical oxygen-containing molecule has been linked to aging and several age-related disorders, including renal damage. Considering the role of angiotensin in aging, melatonin might relieve angiotensin-II-induced stress by enhancing the mitochondrial calcium uptake 1 pathway, which is crucial in preventing the mitochondrial calcium overload that may trigger increased production of reactive oxygen species and oxidative stress. This review highlights the role and importance of melatonin together with angiotensin in aging and age-related diseases.     

Stress-strain relations for elastomeric foams in uni-, bi- and tri-axial compression modes

Summary Based on suggestions given in [1], the uni-axial compressive stress-strain relations for elastomeric foams, which were developed in [2], have been extended to cover the bi- and tri-axial stress modes of compression for both open- and closed-cell elastomeric foams.The stress-strain relations for uni- and tri-axial stress compression modes were validated by comparing numerical predictions, which were based on them, to experimental results.     

Residue Analysis and Determination of IMI Herbicides in Sunflower and Soil by GC–MS

Sunflower agriculture is an important subsector that plays a key role in the economy of Turkey, contributing 1.38 million tonnes. The aim of this study is to investigate the levels of imidazolinone (IMI) group herbicides in Thrace Region, Turkey. In particular, we aimed to determine the residue levels of imazamox, a herbicide used in sunflower production in Thrace Region, in soil, different parts of plant, and seed. Five herbicides were identified in sunflower samples using solid–liquid extraction with gas chromatography–electrospray ionization mass spectrometry (GC–EI–MS) on single-quadruple instruments in selected ion monitoring (SIM) mode. The optimized conditions were found to be mobile-phase flow rate of 1 mL min^?1 and injection volume of 3 μL in programmed temperature vaporization (PTV) solvent vent mode. The recovery of imazamox, imazaquin, imazethapyr, imazapyr, and imazapic from sunflower plant and soil was 89 and 99, 104 and 105, 92 and 93, 96 and 92, and 99 and 96%, respectively.     

Effects of Zeolite as a Drug Delivery System on Cancer Therapy: A Systematic Review

Zeolites and zeolitic imidazolate frameworks (ZIFs) are widely studied as drug carrying nanoplatforms to enhance the specificity and efficacy of traditional anticancer drugs. At present, there is no other systematic review that assesses the potency of zeolites/ZIFs as anticancer drug carriers. Due to the porous nature and inherent pH-sensitive properties of zeolites/ZIFs, the compounds can entrap and selectively release anticancer drugs into the acidic tumor microenvironment. Therefore, it is valuable to provide a comprehensive overview of available evidence on the topic to identify the benefits of the compound as well as potential gaps in knowledge. The purpose of this study was to evaluate the potential therapeutic applications of zeolites/ZIFs as drug delivery systems delivering doxorubicin (DOX), 5-fluorouracil (5-FU), curcumin, cisplatin, and miR-34a. Following PRISMA guidelines, an exhaustive search of PubMed, Scopus, Embase, and Web of Science was conducted. No language or time limitations were used up to 25th August 2021. Only full text articles were selected that pertained to the usage of zeolites/ZIFs in delivering anticancer drugs. Initially, 1279 studies were identified, of which 572 duplicate records were excluded. After screening for the title, abstract, and full texts, 53 articles remained and were included in the qualitative synthesis. An Inter-Rater Reliability (IRR) test, which included a percent user agreement and reliability percent, was conducted for the 53 articles. The included studies suggest that anticancer drug-incorporated zeolites/ZIFs can be used as alternative treatment options to enhance the efficacy of cancer treatment by mitigating the drawbacks of drugs under conventional treatment.     

Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Pseudomonas aeruginosa Quorum Sensing

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein’s productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date.