Three-dimensional modeling of the I-TevI homing endonuclease catalytic domain, a GIY-YIG superfamily member, using NMR restraints and Monte Carlo dynamics

Using a recent version of the SICHO algorithm for in silicoprotein folding, we made a blind prediction of the tertiarystructure of the N-terminal, independently folded, catalyticdomain (CD) of the I-TevI homing endonuclease, a representativeof the GIY–YIG superfamily of homing endonucleases. Thesecondary structure of the I-TevI CD has been determined usingNMR spectroscopy, but computational sequence analysis failedto detect any protein of known tertiary structure related tothe GIY–YIG nucleases (Kowalski et al., Nucleic AcidsRes., 1999, 27, 2115–2125). To provide further insightinto the structure–function relationships of all GIY–YIGsuperfamily members, including the recently described subfamilyof type II restriction enzymes (Bujnicki et al., Trends Biochem.Sci., 2000, 26, 9–11), we incorporated the experimentallydetermined and predicted secondary and tertiary restraints ina reduced (side chain only) protein model, which was minimizedby Monte Carlo dynamics and simulated annealing. The subsequentlyelaborated full atomic model of the I-TevI CD allows the availableexperimental data to be put into a structural context and suggeststhat the GIY–YIG domain may dimerize in order to bringtogether the conserved residues of the active site.     

Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) agonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R agonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.     

Study to analyze the influence of sprouting of the wheat grain on the grinding process

Several studies have been carried out on the grinding characteristic of three species of common wheat (Triticum aestivum, ssp. vulgare). The three-day germinated kernels were pulverized in a micro hammer mill equipped with a changeable screen. The moisture of samples was 12% (w.b.). The results showed that the sprouting of wheat had a significant influence on the grinding process. The average particle size of the pulverized material obtained from the sprouted kernels was almost always significantly lower than those from the sound kernels. The highest changes were observed in the increase of the fraction of particles below a size of 200 μm, caused by sprouting. The sprouting caused a decrease in the value of specific grinding energy in all cultivars. Based on the parameters of screen openings and cultivar, the values of specific grinding energy ranged from 35.5 to 141.6 kJ kg⁻¹ and from 41.4 to 164.3 kJ kg⁻¹ for the sprouted and sound kernels, respectively. In addition, the other values of grinding energy indices confirmed that sprouting significantly reduced the grinding energy requirements. The average value of the grinding ability index was 3.9 and 4.8 kJ m⁻² for the sprouted and sound wheat, respectively. Whereas, sprouting caused a decrease in the average value of the grinding index from 71.2 to 58.0 kJ kg⁻¹ mm^0.5.     

Application of the SIMS Method in Studies of Cr Segregation in Cr-Doped CoO: I, Aspects of Quantitative Analysis

Aspects of calibration of intensities of SIMS secondary ions vs concentration as well as sputtering time vs depth are considered for Cr-doped CoO. Advantages and limitations of the SIMS method in quantitative analysis of segregation-induced concentration profiles in oxide crystals are discussed. The studies indicate a substantial effect due to charging the surface during sputtering. The depth calibration was performed by using the Ta₂O₅/Ta system as a standard. Good depth resolution was revealed. The calibration dependence of Cr intensities on concentration is characterized by a wide scatter of data caused by charging the surface. Very good shape reproducibility of the intensity ratio vs depth profiles was revealed. Therefore, normalized intensity ratios can be used for calibration.     

Anti-Inflammatory Effect of Very High Dose Local Vessel Wall Statin Administration: Poly(L,L-Lactide) Biodegradable Microspheres with Simvastatin for Drug Delivery System (DDS)

Atherosclerosis involves an ongoing inflammatory response of the vascular endothelium and vessel wall of the aorta and vein. The pleiotropic effects of statins have been well described in many in vitro and in vivo studies, but these effects are difficult to achieve in clinical practice due to the low bioavailability of statins and their first-pass metabolism in the liver. The aim of this study was to test a vessel wall local drug delivery system (DDS) using PLA microstructures loaded with simvastatin. Wistar rats were fed high cholesterol chow as a model. The rat vessels were chemically injured by repeated injections of perivascular paclitaxel and 5-fluorouracil. The vessels were then cultured and treated by the injection of several concentrations of poly(L,L-lactide) microparticles loaded with the high local HMG-CoA inhibitor simvastatin (0.58 mg/kg) concentration (SVPLA). Histopathological examinations of the harvested vessels and vital organs after 24 h, 7 days and 4 weeks were performed. Microcirculation in mice as an additional test was performed to demonstrate the safety of this approach. A single dose of SVPLA microspheres with an average diameter of 6.4 μm and a drug concentration equal to 8.1% of particles limited the inflammatory reaction of the endothelium and vessel wall and had no influence on microcirculation in vivo or in vitro. A potent pleiotropic (anti-inflammatory) effect of simvastatin after local SVPLA administration was observed. Moreover, significant concentrations of free simvastatin were observed in the vessel wall (compared to the maximum serum level). In addition, it appeared that simvastatin, once locally administered as SVPLA particles, exerted potent pleiotropic effects on chemically injured vessels and presented anti-inflammatory action. Presumably, this effect was due to the high local concentrations of simvastatin. No local or systemic side effects were observed. This approach could be useful for local simvastatin DDSs when high, local drug concentrations are difficult to obtain, or systemic side effects are present.     

Green TPUs from Prepolymer Mixtures Designed by Controlling the Chemical Structure of Flexible Segments

This study concerns green thermoplastic polyurethanes (TPU) obtained by controlling the chemical structure of flexible segments. Two types of bio-based polyether polyols—poly(trimethylene glycol)s—with average molecular weights ca. 1000 and 2700 Da were used (PO3G1000 and PO3G2700, respectively). TPUs were prepared via a two-step method. Hard segments consisted of 4,4′-diphenylmethane diisocyanates and the bio-based 1,4-butanodiol (used as a chain extender and used to control the [NCO]/[OH] molar ratio). The impacts of the structure of flexible segments, the amount of each type of prepolymer, and the [NCO]/[OH] molar ratio on the chemical structure and selected properties of the TPUs were verified. By regulating the number of flexible segments of a given type, different selected properties of TPU materials were obtained. Thermal analysis confirmed the high thermal stability of the prepared materials and revealed that TPUs based on a higher amount of prepolymer synthesized from PO3G2700 have a tendency for cold crystallization. An increase in the amount of PO3G1000 at the flexible segments caused an increase in the tensile strength and decrease in the elongation at break. Melt flow index results demonstrated that the increase in the amount of prepolymer based on PO3G1000 resulted in TPUs favorable in terms of machining.     

Catalytic graphene formation in coal tar pitch- derived carbon structure in the presence of SiO2 nanoparticles

A simple and effective way to manufacture graphene from a coal tar pitch (CTP) is demonstrated. Silica (SiO₂) nanoparticles were used to modify the CTP as carbon precursor. A silica nanofiller introduced into the CTP matrix underwent carboreduction during heat treatment to 2000 °C, resulting in the formation of silicon carbide. Surfaces of SiC grains were sites for graphene formation. The influence of SiO₂ on the structure and microstructure of CTP- based carbon matrix, after annealing up to 2800 °C, was studied. Carbon samples were analyzed using X- ray Diffraction (XRD), Transmission Electron Microscopy (TEM) and Raman Spectroscopy. Crystallite sizes (L_a, L_c) and interplanar distance (d₀₀₂) were determined. The presence of SiO₂ in CTP carbon precursor favored the crystallites’ growth in the ‘a′ crystallographic graphite direction, and inhibited their growth on the ‘c′ axis. The crystallites composing of graphene layers, were characterized by an elongated dimension in the ‘a′ axis direction. Above 2000 °C silicon carbide decomposed, followed by the sublimation of silicon from the carbon matrix.     

Sustainable synthesis of cyclic carbonates from bio‐based polyether polyol: the structure characterization,rheological behaviour and thermal properties

The cycloaddition of CO₂ to epoxides represents a green efficient method to form bis(cyclic carbonate)s. The main purpose of the work reported in this paper was to examine the effect of the gas flow rate (20, 40, 60 and 100 mL min^–1) during carbonation on the conversion yield, chemical structure, rheological behaviour and thermal properties of the prepared compounds. A series of new bis(cyclic carbonate)s was obtained from bio‐based polyether polyol. The syntheses were performed in the absence of toxic solvents and the process did not require the use of elevated pressure. The progressive structural changes and the presence of characteristic chemical groups were monitored by attenuated total reflection Fourier transform infrared spectroscopy. The characterization of the structure by ¹H NMR and ¹³C NMR also confirmed the formation of cyclic carbonate moieties. The non‐Newtonian behaviour and the optimal mathematical model (Herschel–Bulkley) were verified by rheological measurements. The materials obtained could be used as a chemical intermediate to synthesize advanced materials based upon polyurethanes without using isocyanates. © 2019 Society of Chemical Industry     

Effect of Acute Sprint Exercise on Myokines and Food Intake Hormones in Young Healthy Men

Physical exercise is known to influence hormonal mediators of appetite, but the effect of short-term maximal intensity exercise on plasma levels of appetite hormones and cytokines has been little studied. We investigated the effect of a 30 s Wingate Test, followed by a postprandial period, on appetite sensations, food intake, and appetite hormones. Twenty-six physically active young males rated their subjective feelings of hunger, prospective food consumption, and fatigue on visual analogue scales at baseline, after exercise was completed, and during the postprandial period. Blood samples were obtained for the measurement of nesfatin-1, ghrelin, leptin, insulin, pancreatic polypeptide (PP), human growth factor (hGH) and cytokine interleukin-6 (IL-6), irisin and plasma lactate concentrations, at 30 min before exercise, immediately (210 s) after exercise, and 30 min following a meal and at corresponding times in control sedentary males without ad libitum meal intake, respectively. Appetite perceptions and food intake were decreased in response to exercise. Plasma levels of irisin, IL-6, lactate, nesfatin-1 and ghrelin was increased after exercise and then it was returned to postprandial/control period in both groups. A significant rise in plasma insulin, hGH and PP levels after exercise was observed while meal intake potentiated this response. In conclusion, an acute short-term fatiguing exercise can transiently suppress hunger sensations and food intake in humans. We postulate that this physiological response involves exercise-induced alterations in plasma hormones and the release of myokines such as irisin and IL-6, and supports the notion of existence of the skeletal muscle–brain–gut axis. Nevertheless, the detailed relationship between acute exercise releasing myokines, appetite sensations and impairment of this axis leading to several diseases should be further examined.     

电弧炉粉尘等温还原的动力学研究

为使还原条件与实际电弧炉生产相接近,在等温条件下对电弧炉粉尘球团的还原过程动力学进行了研究。电弧炉粉尘与还原剂碳和粘接剂石灰均匀混合后制粒,经干燥后将球闭置于恒定温度的加热炉中,利用电子称定时对球团重量进行检测。金属还原率的计算中,考虑了球团的失重、铅和锌在高温下挥发。经研究,电弧炉粉尘的还原分为二个阶段,还原初期由化学反应控制而还原后期由扩散控制,并建立了每一阶段的还原动力学方程,确定了有关的动力学参数表观活化能和频率因子。