Modulating mTOR Signaling as a Promising Therapeutic Strategy for Atherosclerosis

For more than a decade, atherosclerosis has been one of the leading causes of death in developed countries. The issue of treatment and prevention of the disease is especially acute. Despite the huge amount of basic and clinical research, a significant number of gaps remain in our understanding of the pathogenesis of atherosclerosis, and only their closure will bring us closer to understanding the causes of the disease at the cellular and molecular levels and, accordingly, to the development of an effective treatment. One of the seemingly well-studied elements of atherogenesis is the mTOR signaling pathway. However, more and more new details are still being clarified. Therapeutic strategies associated with rapamycin have worked well in a number of different diseases, and there is every reason to believe that targeting components of the mTOR pathway may pay off in atherosclerosis as well.     

Reactive,nonreactive, and flash spark plasma sintering of Al2O3/SiC composites—A comparative study

The influence of different SPS-based methods, that is, conventional spark plasma sintering (SPS), flash SPS (FSPS), and reactive SPS (RSPS) on the properties of Al₂O₃/SiC composite was investigated. It was shown that the application of preliminary high energy ball milling of the powders significantly enhances the sinterability of the ceramics. It was also demonstrated that FSPS provides unique conditions for rapid, that is, less than a minute, consolidation of refractory ceramics. The Al₂O₃-20 wt% SiC composite produced by FSPS possesses the highest relative density (~99%), fracture toughness (7.5 MPa m^1/2), hardness (20.3 GPa) and wear resistance among all ceramics produced by other SPS-based approaches with dwelling time 10 minutes. The RSPS ceramics hold the highest Young's modulus (390 GPa). Substitution of micron-sized Al₂O₃ particles by nano alumina does not lead to measurable enhancement of the mechanical properties.     

Local Accumulation of Lymphocytes in the Intima of Human Aorta Is Associated with Giant Multinucleated Endothelial Cells: Possible Explanation for Mosaicism of Atherosclerosis

Distribution of different types of atherosclerotic lesions in the arterial wall is not diffuse, but is characterized by mosaicism. The causes of such distribution remain to be established. At the early stages of atherogenesis, low-density lipoprotein (LDL) particles and immune cells penetrate into the intimal layer of the arterial wall through the endothelium. In adult humans, the luminal surface of the arterial wall is a heterogeneous monolayer of cells with varying morphology including typical endothelial cells (ECs) and multinucleated variant endothelial cells (MVECs). We hypothesized that distribution of MVECs in the endothelial monolayer can be related to the distribution pattern of early atherosclerotic lesions. We obtained en face preparations of intact adult (22–59 years old) aortic wall sections that allowed us to study the endothelial monolayer and the subendothelial layer. We compared the distribution of MVECs in the endothelial monolayer with the localization of early atherosclerotic lesions in the subendothelial layer, which were characterized by lipid accumulation and immune cell recruitment. In primary culture, MVECs demonstrated increased phagocytic activity compared to mononuclear ECs. Moreover, we have shown that unaffected aortic intima contained associates formed as a result of aggregation and/or fusion of LDL particles that are non-randomly distributed. This indicated that MVECs may be involved in the accumulation of LDL in the subendothelial layer through increased transcytosis. Interaction of LDL with subendothelial cells of human aorta in primary culture increased their adhesive properties toward circulating immune cells. Study of unaffected aortic intima revealed non-random distribution of leukocytes in the subendothelial layer and increased localization of CD45+ leukocytes in the subendothelial layer adjacent to MVECs. Together, our observations indicate that MVECs may be responsible for the distribution of atherosclerotic lesions in the arterial wall by participating in LDL internalization and immune cell recruitment.     

Modeling Alcohol Dehydrogenase Catalysis in Deep Eutectic Solvent/Water Mixtures

The use of oxidoreductases (EC1) in non-conventional reaction media has been increasingly explored. In particular, deep eutectic solvents (DESs) have emerged as a novel class of solvents. Herein, an in-depth study of bioreduction with an alcohol dehydrogenase (ADH) in the DES glyceline is presented. The activity and stability of ADH in mixtures of glyceline/water with varying water contents were measured. Furthermore, the thermodynamic water activity and viscosity of mixtures of glyceline/water have been determined. For a better understanding of the observations, molecular dynamics simulations were performed to quantify the molecular flexibility, hydration layer, and intraprotein hydrogen bonds of ADH. The behavior of the enzyme in DESs follows the classic dependence of water activity (a_W) in non-conventional media. At low a_W values (<0.2), ADH does not show any activity; at higher a_W values, the activity was still lower than that in pure water due to the high viscosities of the DES. These findings could be further explained by increased enzyme flexibility with increasing water content.     

Current Trends in Pretreatment and Fractionation of Lignocellulose as Reflected in Industrial Patent Activities

The pretreatment process to disintegrate lignocellulose and to fractionate its three main components hemicellulose, cellulose, and lignin, is a crucial step to enable sustainable and economic value chains based on biomass feedstock. This review provides an overview of the recent patenting activities on pretreatment. Most of these activities focus on optimization of different known processes to improve economics, such as increased catalyst efficiency, effluents recirculation, or lignin valorization. However, also a number of patents and demonstration activities based on emerging concepts for pretreatments are observed.     

Dual,Site‐Specific Modification of Antibodies by Using Solid‐Phase Immobilized Microbial Transglutaminase

Microbial transglutaminase (MTG) was stably solid‐phase immobilized on glass microbeads by using a second‐generation dendronized polymer. Immobilized MTG enabled the efficient generation of site‐specifically conjugated proteins, including antibody fragments, as well as whole antibodies through distinct glutamines and, unprecedentedly, also through lysines with various bifunctional substrates with defined stoichiometries. With this method, we generated dual, site‐specifically modified antibodies comprising a fluorescent probe and a metal chelator for radiolabeling—a strategy anticipated to design antibodies for imaging and simultaneous therapy. Furthermore, we provide evidence that immobilized MTG features higher siteselectivity than soluble MTG.     

Dissolution,Transport and Reaction at a DICY/DGEBA Interface

The curing of an epoxy consisting of the solid hardener dicyandiamide (DICY) and the resin diglycidyl ether of bisphenol A (DGEBA) is studied in a system consisting of a tablet of DICY embedded in liquid DGEBA. Dissolution of DICY within the liquid DGEBA in combination with the transport of dissolved DICY from the tablet border into DGEBA and the chemical reaction of both reactants is studied by scanning Brillouin microscopy and infrared spectroscopy. Scanning Brillouin microscopy demonstrates the spatial and temporal evolution of the static and dynamic hypersonic properties in the course of curing in the vicinity of the DICY tablet. Infrared spectroscopy performed on epoxy pieces extracted from the final sample at different distances from the tablet surface give information about the spatial evolution of the curing process. The results achieved by both techniques are finally combined to yield a better understanding of the curing of DICY-based epoxies, which transform upon curing from strongly heterogeneous systems towards increasingly homogeneous systems.     

Concentration effects in the base-catalyzed hydrolysis of oligo(ethylene glycol)- and amine-containing methacrylic monomers

Concentration effects in the base-catalyzed hydrolysis of water-soluble methacrylates (3-(N,N-dimethylaminoethyl) methacrylate (DMAEMA), 2-hydroxyethyl methacrylate (HEMA) and oligo(ethylene glycol) methacrylates (OEGMAs)) have been studied. These monomers are rapidly hydrolyzed in the presence of bases at the room temperature in dilute aqueous solutions, but the reaction rate decreases sharply in highly concentrated solutions. A clear correlation was found between a form of the viscosity isotherm for DMAEMA solutions and the concentration dependence of the autocatalytic hydrolysis rate which indicates the connection of process kinetics with the structure of solutions. These data should be considered when carrying out homo- and copolymerization of the previously mentioned monomers in aqueous solutions.     

Interaction of W<Subscript>2</Subscript>B<Subscript>5</Subscript> with Me<Superscript>IV,V</Superscript>C carbides

It is established that the W₂B₅-Me^IV,VC join in the W-B-C-Me^IV,V quaternary systems is quasibinary, while polythermal joins are described by eutectic phase diagrams. It is shown that the eutectic composition and temperature correlate with the melting points of carbides and the Me ^d C content varies from 50 mol % in the W₂B₅-VC system to 4–6 mol % in the W2B5-TaC system. The existence of Me ^d C-Me ^d B₂-W₂B₅ ternary eutectic systems promising for the development of new ceramics is proved.     

Increase in energy and land use by a bio-based chemical industry

About 80% of the chemical products are still based on crude oil. Bio-based materials will increasingly gain importance. As the fraction of oxygen is normally higher in biomass than in crude oil as well as in the derived conventional products, this implies a need to develop new synthesis pathways. Depending on the types of new synthesis pathways, the effects of a complete raw-material change on land and exergy use differ. Here, different synthesis pathways starting from glucose and plant oil to different kinds of end products are evaluated utilizing material and exergy balances. These evaluations are carried out under today's and future conditions and constraints, like yield, demand of organic chemicals and world population. The analysis in this paper shows that the land and energy use can be significantly reduced, if the products are adapted to the chemical structure of their bio-based feedstock.