All That Glitters Is Not Silver—A New Look at Microbiological and Medical Applications of Silver Nanoparticles

Silver and its nanoparticles (AgNPs) have different faces, providing different applications. In recent years, the number of positive nanosilver applications has increased substantially. It has been proven that AgNPs inhibit the growth and survival of bacteria, including human and animal pathogens, as well as fungi, protozoa and arthropods. Silver nanoparticles are known from their antiviral and anti-cancer properties; however, they are also very popular in medical and pharmaceutical nanoengineering as carriers for precise delivery of therapeutic compounds, in the diagnostics of different diseases and in optics and chemistry, where they act as sensors, conductors and substrates for various syntheses. The activity of AgNPs has not been fully discovered; therefore, we need interdisciplinary research to fulfil this knowledge. New forms of products with silver will certainly find application in the future treatment of many complicated and difficult to treat diseases. There is still a lack of appropriate and precise legal condition regarding the circulation of nanomaterials and the rules governing their safety use. The relatively low toxicity, relative biocompatibility and selectivity of nanoparticle interaction combined with the unusual biological properties allow their use in animal production as well as in bioengineering and medicine. Despite a quite big knowledge on this topic, there is still a need to organize the data on AgNPs in relation to specific microorganisms such as bacteria, viruses or fungi. We decided to put this knowledge together and try to show positive and negative effects on prokaryotic and eukaryotic cells.     

Metabolomics Comparison of Drug-Resistant and Drug-Susceptible Pseudomonas aeruginosa Strain (Intra- and Extracellular Analysis)

Pseudomonas aeruginosa is a common human pathogen belonging to the ESKAPE group. The multidrug resistance of bacteria is a considerable problem in treating patients and may lead to increased morbidity and mortality rate. The natural resistance in these organisms is caused by the production of specific enzymes and biofilm formation, while acquired resistance is multifactorial. Precise recognition of potential antibiotic resistance on different molecular levels is essential. Metabolomics tools may aid in the observation of the flux of low molecular weight compounds in biochemical pathways yielding additional information about drug-resistant bacteria. In this study, the metabolisms of two P. aeruginosa strains were compared—antibiotic susceptible vs. resistant. Analysis was performed on both intra- and extracellular metabolites. The ¹H NMR method was used together with multivariate and univariate data analysis, additionally analysis of the metabolic pathways with the FELLA package was performed. The results revealed the differences in P. aeruginosa metabolism of drug-resistant and drug-susceptible strains and provided direct molecular information about P. aeruginosa response for different types of antibiotics. The most significant differences were found in the turnover of amino acids. This study can be a valuable source of information to complement research on drug resistance in P. aeruginosa.     

Modulation of Prostanoids Profile and Counter-Regulation of SDF-1α/CXCR4 and VIP/VPAC2 Expression by Sitagliptin in Non-Diabetic Rat Model of Hepatic Ischemia-Reperfusion Injury

Molecular mechanisms underlying the beneficial effect of sitagliptin repurposed for hepatic ischemia-reperfusion injury (IRI) are poorly understood. We aimed to evaluate the impact of IRI and sitagliptin on the hepatic profile of eicosanoids (LC-MS/MS) and expression/concentration (RTqPCR/ELISA) of GLP-1/GLP-1R, SDF-1α/CXCR4 and VIP/VPAC1, VPAC2, and PAC1 in 36 rats. Animals were divided into four groups and subjected to ischemia (60 min) and reperfusion (24 h) with or without pretreatment with sitagliptin (5 mg/kg) (IR and SIR) or sham-operated with or without sitagliptin pretreatment (controls and sitagliptin). PGI₂, PGE₂, and 13,14-dihydro-PGE₁ were significantly upregulated in IR but not SIR, while sitagliptin upregulated PGD₂ and 15-deoxy-12,14-PGJ₂. IR and sitagliptin non-significantly upregulated GLP-1 while Glp1r expression was borderline detectable. VIP concentration and Vpac2 expression were downregulated in IR but not SIR, while Vpac1 was significantly downregulated solely in SIR. IRI upregulated both CXCR4 expression and concentration, and sitagliptin pretreatment abrogated receptor overexpression and downregulated Sdf1. In conclusion, hepatic IRI is accompanied by an elevation in proinflammatory prostanoids and overexpression of CXCR4, combined with downregulation of VIP/VPAC2. Beneficial effects of sitagliptin during hepatic IRI might be mediated by drug-induced normalization of proinflammatory prostanoids and upregulation of PGD₂ and by concomitant downregulation of SDF-1α/CXCR4 and reinstating VIP/VCAP2 signaling.     

Structural Integrity of the A147T Polymorph of Mammalian TSPO

Ligands of the transmembrane protein TSPO are used for imaging of brain inflammation, but a common polymorphism in TSPO complicates their application to humans. Here we determined the three‐dimensional structure and side‐chain dynamics of the A147T polymorph of mammalian TSPO in complex with the first‐generation ligand PK11195. We show that A147T TSPO is able to retain the same structural and dynamic profile as the wild‐type protein and thus binds PK11195 with comparable affinity. Our study is important for the design of more potent diagnostic and therapeutic ligands of TSPO.     

Evaluation of the effectiveness of the fire retardant mixture containing potassium carbonate using a cone calorimeter

This article presents the results of investigations obtained for a wood fire retardant agent which is currently under production. Experiments were conducted using a mixture of potassium carbonate and urea in accordance with the PN‐C‐04914 standard (the Polish equivalent of ISO 5660‐1). Wood samples of Scots pine (Pinus sylvestris L.) were treated with the above mixture as well as with its individual components. It was observed that impregnation of samples with potassium carbonate and a mixture of potassium carbonate and urea has an advantageous influence on the reduction of the heat release and the heat of combustion, and also prolongs the time to ignition. Urea alone failed to exert a fire‐retardant effect on wood samples. Copyright © 2011 John Wiley & Sons, Ltd.     

Modulation of CD14 and TLR4⋅MD‐2 Activities by a Synthetic Lipid A Mimetic

Monosaccharide lipid A mimetics based on a glucosamine core linked to two fatty acid chains and bearing one or two phosphate groups have been synthesized. Compounds 1 and 2 , each with one phosphate group, were practically inactive in inhibiting LPS‐induced TLR4 signaling and cytokine production in HEK‐blue cells and murine macrophages, but compound 3 , with two phosphate groups, was found to be active in efficiently inhibiting TLR4 signal in both cell types. The direct interaction between compound 3 and the MD‐2 coreceptor was investigated by NMR spectroscopy and molecular modeling/docking analysis. This compound also interacts directly with the CD14 receptor, stimulating its internalization by endocytosis. Experiments on macrophages show that the effect on CD14 reinforces the activity on MD‐2 ? TLR4 because compound 3 's activity is higher when CD14 is important for TLR4 signaling (i.e., at low LPS concentration). The dual targeting of MD‐2 and CD14, accompanied by good solubility in water and lack of toxicity, suggests the use of monosaccharide 3 as a lead compound for the development of drugs directed against TLR4related syndromes.     

Semirational Protein Engineering of CYP153AM.aq.‐CPRBM3 for Efficient Terminal Hydroxylation of Short‐ to Long‐Chain Fatty Acids

The regioselective terminal hydroxylation of alkanes and fatty acids is of great interest in a variety of industrial applications, such as in cosmetics, in fine chemicals, and in the fragrance industry. The chemically challenging activation and oxidation of non‐activated C?H bonds can be achieved with cytochrome P450 enzymes. CYP153A_M.aq.‐CPR_BM3 is an artificial fusion construct consisting of the heme domain from Marinobacter aquaeolei and the reductase domain of CYP102A1 from Bacillus megaterium. It has the ability to hydroxylate medium‐ and long‐chain fatty acids selectively at their terminal positions. However, the activity of this interesting P450 construct needs to be improved for applications in industrial processes. For this purpose, the design of mutant libraries including two consecutive steps of mutagenesis is demonstrated. Targeted positions and residues chosen for substitution were based on semi‐rational protein design after creation of a homology model of the heme domain of CYP153A_M.aq., sequence alignments, and docking studies. Site‐directed mutagenesis was the preferred method employed to address positions within the binding pocket, whereas diversity was created with the aid of a degenerate codon for amino acids located at the substrate entrance channel. Combining the successful variants led to the identification of a double variant—G307A/S233G—that showed alterations of one position within the binding pocket and one position located in the substrate access channel. This double variant showed twofold increased activity relative to the wild type for the terminal hydroxylation of medium‐chain‐length fatty acids. This variant furthermore showed improved activity towards short‐ and long‐chain fatty acids and enhanced stability in the presence of higher concentrations of fatty acids.     

Generalized Resampling Scheme With Application to Spectral Density Matrix in Almost Periodically Correlated Class of Time Series

The aim of this article is to introduce new resampling scheme for nonstationary time series, called generalized resampling scheme (GRS). The proposed procedure is a generalization of well known in the literature subsampling procedure and is simply related to existing block bootstrap techniques. To document the usefulness of GRS, we consider the example of model with almost periodic phenomena in mean and variance function, where the consistency of the proposed procedure was examined. Finally, we prove the consistency of GRS for the spectral density matrix for nonstationary, multivariate almost periodically correlated time series. We consider both zero mean and non‐zero mean case. The consistency holds under general assumptions concerning moment and α‐mixing conditions for multivariate almost periodically correlated time series. Proving the consistency in this case poses a difficulty since the estimator of the spectral density matrix can be interpreted as a sum of random matrixes whose dependence grow with the sample size.     

Mechanical properties and thermal stability of tungsten boride films deposited by radio frequency magnetron sputtering

Tungsten and boron compounds belong to the group of superhard materials since their hardness could exceed 40?GPa. In this study, the properties of the tungsten boride WB_x coatings deposited by radio frequency magnetron sputtering were investigated. The sputtering was performed from specially prepared targets that were composed of boron and tungsten mixed in a molar ratio of 2.5 and sintered in Spark Plasma Sintering (SPS) process. WB films were deposited on silicon (100) and stainless steel 304 substrates at temperatures of 23 ÷ 770?°C. Microstructure, chemical and phase composition were investigated by using Scanning Electron Microscope (SEM), X-Ray Photoelectron Spectroscopy (XPS) and X-Ray Diffraction (XRD), respectively. The mechanical properties like Vickers hardness and Young's modulus were obtained by using nanoindentation test at a load of 5 ÷ 100 mN. The friction coefficient and wear resistance of αWB coatings were investigated in scratch test and reciprocal sliding wear instrumentation. Moreover, in order to investigate thermal properties, the αWB films were annealed at 1000?°C in argon/air for 1?h and at 250?°C for 2?h in air atmosphere. Results of our research confirm that αWB coatings can be considered as an alternative to superhard materials in the production of wear resistant, long-lasting tools.     

Multi-objective decision support system in numerical reliability optimization of modern electronic packaging

Nowadays, numerical prototyping methods in electronic packaging are widely used. This is mainly due to cost and time reduction and improved functionality and reliability of final products. Recently, there has been a lot of interest and work conducted on advanced numerical optimization, which can be directly applied to prototyping. So far, the optimization is focused on one criteria while neglecting problem of multi-objectivity, which is not the best approach from practical point of view. Nevertheless, such an approach is jusitified from the point of view of complex analysis, interdisciplinary issues and reduced accuracy of numerical models. In reality, there are usually many criteria which, in order to solve the problem, have to be taken into consideration. There are many multi-objective methods, of which the Pareto set approach is mostly cited in the literature. The “problem” of multi-objective optimization is that not a single optimal solution has resulted but the set of equivalent optimal solutions. This set of equivalent optimal solutions is referenced as “the Pareto set”. From the mathematical point of view, every value from this set can be treated as optimal for certain assumed constraints. However, there could be some additional conditions which cannot be applied to optimization process and some of the results from the Pareto set are more likely (i.e., the fabrication process will be more repeatable) then the others. So, the question is: which value from the Pareto set should be taken to further processing? There are two possibilities: asking an expert for the advice or use the decision making system. Decision making methods based on multi-objective optimization could be referenced as “Multiple criteria decision making” (MCDM) or “Multiple criterial decision aid” (MCDA) systems. There are several groups of these methods: (a) mathematical multi-objective programming, (b) artificial intelligence methods, (c) simple arithmetic methods, and (d) advanced mathematical methods. The current paper will focus on designing and application of the decision support system for multi-objective numerical reliability optimization of electronic packaging. The work will be based on the self developed numerical tool based on Python Scrippting language and will present its application to selected microelectronic packages based on its numerical model elaborated in ABAQUS.