Discovery of GPR183 Agonists Based on an Antagonist Scaffold

The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca²⁺ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch.     

Melatonin and Glycine Reduce Uterus Ischemia/Reperfusion Injury in a Rat Model of Warm Ischemia

Ischemia/reperfusion injury (IRI) remains a significant problem to be solved in uterus transplantation (UTx). Melatonin and glycine have been shown to possess direct cytoprotective activities, mainly due to their antioxidative and anti-inflammatory properties. The aim of this study was to investigate the protective effects of melatonin and glycine and their combination on IRI in a rat model of warm ischemia. In this study, Sprague-Dawley rats were assigned to eight groups, including sham and IRI (n = 80). Melatonin and glycine alone or their combination were administered prior to 1 h of uterus ischemia followed by 1 h of reperfusion. Melatonin (50 mg/kg) was administered via gavage 2 h before IRI and glycine in an enriched diet for 5 days prior to intervention. Uterus IRI was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. Histology revealed that uterus IRI was significantly attenuated by pretreatment with melatonin (p = 0.019) and glycine (p = 0.044) alone as well as their combination (p = 0.003). Uterus IRI led to increased myeloperoxidase expression, which was significantly reduced by melatonin (p = 0.004), glycine (p < 0.001) or their combination (p < 0.001). The decline in superoxide dismutase activity was significantly reduced in the melatonin (p = 0.027), glycine (p = 0.038) and combined treatment groups (p = 0.015) when compared to the IRI control group. In conclusion, melatonin, glycine and their combination significantly reduced oxidative stress-induced cell damage after IRI in a small animal warm ischemia model, and, therefore, clinical studies are required to evaluate the protective effects of these well-characterized substances in uterus IRI.     

Efficient dye regeneration in solid-state dye-sensitized solar cells fabricated with melt processed hole conductors

A new method for melting hole transporting materials (HTM) into mesoporous TiO₂ electrodes to obtain solid-state dye-sensitized solar cells (DSSC) is reported. Internal coverage is determined from the efficiency of hole conductor oxidation by photo-oxidized dyes (dye regeneration), measured using transient absorption spectroscopy. High efficiency regeneration indicates complete coverage of the electrode internal surface. A high work function hole conductor (>5.2 eV) was found to give shorter regeneration lifetimes (<1 μs) and better regeneration efficiencies (>90%) than expected. Cell photocurrents were low, but improved after iodine vapor doping of the hole conductor. Counter intuitively, doping also reduced the recombination rate constant 7-fold. A solid state solar cell with power conversion efficiency of 0.075% at 1 sun is reported.     

The peculiarities of sprayed liquid’s thermal state change,as droplets are heated by conduction

The change of thermal state and phase transformation intensity of sprayed water, n-hexane, n-heptane and n-decane is numerically modelled in the case, as droplets are heated by conduction; the influence of the Knudsen layer is neglected; warming and evaporation of the droplets has no influence on the state of the carrying air flow. The research results prove that a peculiar change of the thermal state of sprayed liquid, irrespective of droplet’s dispersivity, exists in the time scale, expressed by Fourier number. The above-mentioned change can be conveniently defined by the characteristic curves, representing the change of a droplet surface, centre, and mean mass temperatures, which are sensibly influenced by temperature of gas mixture and partial pressure of liquid vapour in it. As these characteristic curves were expressed in regards to the initial and equilibrium evaporation temperatures of liquid, the universal curves, representing the change of thermal states of the examined liquids, were obtained in the time scale, expressed by Fourier number. It is shown that liquid evaporation rate and the change of a droplet dimension can also be described by characteristic curves.     

Experimental Evaluation of Quantum Dots and Antibodies Conjugation by Surface Plasmon Resonance Spectroscopy

The application of antibody-functionalized quantum dots (QDs) in different areas has been widely described in the literature. However, a standard routine method for obtaining information on the conjugation efficiency of QDs with antibodies in terms of the interaction of the functionalized QDs with a specific antigen is still lacking. Herein, surface plasmon resonance (SPR) spectroscopy is proposed for this purpose. Gold-coated SPR sensor disks were modified with a self-assembled monolayer of 11-mercaptoundecanoic acid, and carbodiimide cross-linker chemistry was used to covalently immobilize the CD44 biomarker on the premodified surface (Au/CD44). Meanwhile, QDs functionalized with amine-derivatized polyethylene glycol (PEG) (QDs-NH₂) were chosen for conjugation with antibodies because of their low non-specific adsorption on the Au/CD44 surface. Prior to conjugation, the surface binding capacity (B_max) and equilibrium dissociation constant (K_D) of the specific antibodies against CD44 (anti-CD44) were found to be 263.32 ± 2.44 m° and 1.00 × 10⁻⁷ ± 2.29 × 10⁻⁹ M, respectively. QDs-NH₂ and anti-CD44 were conjugated at their initial molar ratios of 1:3, 1:5, 1:10 and 1:12. SPR measurements showed that the conjugates (QDs-anti-CD44) prepared using 1:10 and 1:12 molar ratios interacted comparably with immobilized CD44 biomarkers. The equilibrium angles in the case of 10- and 12-fold concentrations of anti-CD44 were calculated to be 60.43 ± 4.51 and 61.36 ± 4.40 m°, respectively. This could be explained by the QDs-NH₂ and anti-CD44 having a similar surface loading (about four molecules per QDs-NH₂) and similar hydrodynamic diameters, which were 46.63 ± 3.86 and 42.42 ± 0.80 nm for the 1:10 and 1:12 ratios, respectively. An initial QDs-NH₂: anti-CD44 molar ratio of 1:10 was chosen as being optimal. SPR spectroscopy proved to be the right choice for QDs-anti-CD44 conjugation optimization, and can be used for the evaluation of conjugation efficiency for other nanostructures with various bio-recognition molecules.     

Study of high temperature thermal boundary conditions on active surfaces of the cylinder shaped ultrasonic transducers

Results of an experimental and numerical research of two-dimensional unsteady flow around the butt end of the model of cylinder shaped ultrasonic transducer at zero angle attack are presented. The flow formed employing linear dc plasma torch, is turbulent with Re number between 1.8 × 10⁴ and 2.2 × 10⁴ and temperature −1200 K. At this regime the flows boundary layers at the cylinder edge separate laminar and transition takes place in the free shear layers. In the shear layer strong vortex shedding and temperature fluctuations are observed. Experimentally estimated distribution of velocities and temperatures on the flat surface of circular cylinder compared with the predicted and has been established good agreement under the results. The influence of the location to distribution and quantity of dynamic and thermal parameters was investigated.     

Effects of Freeze‐Dried Vegetable Products on the Technological Process and the Quality of Dry Fermented Sausages

The aim of this study was to compare the chemical composition of freeze‐dried vegetable powders: celery, celery juice, parsnip and leek. The effect of different freeze‐dried vegetables onto the ripening process and the properties of dry fermented sausages was also evaluated. Vegetable products significantly (p < 0.05) differed in their chemical composition: celery products contained higher amounts of nitrates, total phenolic compounds and lower amounts of sucrose, parsnip had higher concentration of proteins, leek was rich in fat. The analysis of pH, water activity, lactic acid bacteria, coagulase‐positive staphylococci and coliforms content showed that the incorporation of freeze‐dried vegetables had no negative effect on the fermentation and ripening process of dry fermented sausages. In addition, the color parameters for sausages with the added lyophilised celery products were considerable (p < 0.05) more stable during these processes. At the end of the ripening process the sausages made with lyophilised celery juice were characterised by higher lightness and lower hardness than those made with the addition of other vegetable products and control. Freeze‐dried celery, celery juice, parsnip and leek have some potential for the usage as a functional ingredient or as a source for indirect addition of nitrate in the production of fermented sausages.