Репозиторий Университета

© 2020 Elsevier B.V. A sonochemical reactor was developed to study the ultrasound-assisted cyanide extraction of gold from gold ore at low temperature. The effects of ultrasound on gold leaching in low temperature and conventional conditions were investigated. At the low temperature of 10 °C, ultrasound-assisted extraction increased extraction rate of gold by 0.6%–0.8% and reduced the gold content of cyanide tailings to 0.28 g/t in the leaching of gold concentrate and cyanide tailings, respectively. At the conventional temperature of 25 °C, ultrasound-assisted extraction obtained a 0.1% higher extraction rate of gold compared with conventional extraction, with the unit consumption of NaCN reduction of 15%. The analysis of kinetic model also demonstrated that sonication indeed improved the reaction of gold leaching greatly. The mineralogy and morphology of ore were further analyzed by X-ray diffraction (XRD), scanning electron microscope (SEM) and particle size analyzer to explore the strengthening mechanism of gold leaching. The results showed that the ore particles were smashed, the ore particle surface was peeled, the passive film was destroyed and the reaction resistance decreased under ultrasonic processing. Therefore, the extraction rate of gold was improved and the extraction time was shortened significantly in ultrasound-assisted cyanide extraction.

© 2020 Elsevier B.V. It is not clear which mechanisms are responsible for changing soil biological activity following a fire. To address this knowledge gap, we measured such parameters of soil biological activity as flux rates of CH4, and CO2 and identified key environmental parameters that can influence soil biological activity. Soil samples were collected in burned and adjacent unburned control forests, along a 3000 km-long north-south transect in European Russia. A raw biological activity of tested soil samples varied significantly between forest types, but not between burned and control forest stands. Linear mixed effect modeling demonstrated a striking contrast in the importance of different drivers in sustaining a soil biological activity in the burned and control forests. The optimal model of basal soil respiration consisted of: “Soil moisture” (26%), “Fire treatment × Soil moisture × Labile soil N:P ratio” (21%), and “Fire treatment × Labile soil C × Labile soil N:P ratio” (13%). The model for CH4 in turn was defined by interactions of bulk and labile soil C with soil moisture and other factors. Our study clearly demonstrated that forest fires affect soil biological activity rather indirectly through modifying soil properties. The results enable forecasting post-fire effects on soil functioning in a changing climate under varied fire regimes.

© 2019 The Author(s) Intradialytic hypotension is a frequent complication of chronic kidney disease. According to different authors, the incidence of this condition varies in severity and being recorded in 10–70% of cases during chronic intermittent hemodialysis. The development of severe chronic intradialytic hypotension in most cases is considered as a relative contraindication to kidney transplantation due to the risk of the graft dysfunction and loss in the early postoperative period. Meanwhile, there is no consensus on the lower limit of blood pressure, which would be an absolute contraindication for kidney transplantation. In addition, patients with intradialytic hypotension have the dialysis session reduced which leads to inadequate dialysis; also, they often have such complications as thrombosis of an arteriovenous fistula, as a result of which further dialysis sessions become impossible. In such cases, renal transplantation is a risky, but lifesaving operation. We present a clinical case report of kidney allotransplantation in a female patient with a history of bilateral nephrectomy, who had been suffering from severe chronic intradialytic hypotension for three years before the operation. After allograft transplantation, her blood pressure was normalized to reference values, and the graft function fully recovered.

© 2019 The Author(s) Intradialytic hypotension is a frequent complication of chronic kidney disease. According to different authors, the incidence of this condition varies in severity and being recorded in 10–70% of cases during chronic intermittent hemodialysis. The development of severe chronic intradialytic hypotension in most cases is considered as a relative contraindication to kidney transplantation due to the risk of the graft dysfunction and loss in the early postoperative period. Meanwhile, there is no consensus on the lower limit of blood pressure, which would be an absolute contraindication for kidney transplantation. In addition, patients with intradialytic hypotension have the dialysis session reduced which leads to inadequate dialysis; also, they often have such complications as thrombosis of an arteriovenous fistula, as a result of which further dialysis sessions become impossible. In such cases, renal transplantation is a risky, but lifesaving operation. We present a clinical case report of kidney allotransplantation in a female patient with a history of bilateral nephrectomy, who had been suffering from severe chronic intradialytic hypotension for three years before the operation. After allograft transplantation, her blood pressure was normalized to reference values, and the graft function fully recovered.

© 2019 Elsevier Ltd Attenuation and velocity (Speed-of-Sound) in a trabecular bone were calculated and evaluated from ultrasound pulse-echoes detection and their processing, applying a single US transducer that operates in transmit/receive mode. The processing of US pulse-echoes utilized development of algorithms for the attenuation and the Speed-of-Sound in trabecular bone. These ultra-sound pulse-echoes were obtained from the front and rear surfaces of a trabecular bone sample. The motivation for this work was to develop an efficient intraosseous monitoring device that provides the Speed-of-Sound and attenuation intraoperatively and in real-time and therefore can be implemented during a surgery. Ultrasonic measurements were performed in the frequency range of 3.5–6.5 [MHz]. In these experiments, the fresh trabecular bone samples were from sheep femora and humerus. The measuring results were correlated (R2 ≥ 0.95) with those obtained previously, mainly during transmission mode studies. According to the obtained results, the presented method presumably will be utilized as a clinical tool in bone surgical procedures and therefore will be able to provide better outcomes, while monitoring intraoperatively and in real-rime intraosseous trabecular bone attenuation and its velocity: In the next stage of this study, the method will be carried out on human tissues and also intraoperatively, during human clinical trials. It is planned to perform it on long bones/tibia, vertebra, in neurosurgery – for drilling the skull and also in dental implantation surgery.

© 2019 Elsevier B.V. A detailed step-by-step procedure for revealing counterfeit and substandard tablets is presented. Non-invasive NIR measurements are used for data collection. The entire complex multi-layer object as the “packaging -coating-core” system requires special treatment at all stages of model development and validation. The influence of each layer is studied. A procedure that covers data collection, construction of the model, as well as special internal and external validation is advocated here. A special set of objects called ‘nearest of kin’ (NoK) collection, which consists of generic medications nearest to the target objects, assists in reliable assessment of the model specificity. The whole procedure summarizes the results obtained for over a thousand different dosage forms of tablets. Two real-world examples of genuine and counterfeit medicines are considered. The first example presents uncoated tablets with high concentration of active ingredient and fairly simple set excipients. Its NoK collection consists of six different manufacturers. The second example presents coated tablets with low concentration of active ingredient and rather complex set of excipients. Its NoK collection is presented by seven different manufacturers.

© 2019 Elsevier B.V. Due to their unique optical properties upconversion nanoparticles (UCNPs) provide exceptionally high contrast for imaging of true nanoparticle distribution in excised human skin. It makes possible to show penetration of solid nanoparticles in skin treated with chemical enhancers. We demonstrated tracing upconversion nanoparticles in excised human skin by means of optical microscopy at the discrete particle level sensitivity to obtain their penetration profiles, which was validated by laser-ablation inductively-coupled-plasma mass-spectrometry. To demonstrate utilities of our method, UCNPs were coated with polymers, formulated in water and chemical enhancers, and applied on excised human skin mounted on Franz cells, followed by imaging using a custom-built laser-scanning microscope. To evaluate the toxicity impact on skin by polymer-coated UCNPs, we introduced a tissue engineering model of viable epidermis made of decellularized chick embryo skin seeded with keratinocytes. UCNPs formulated in water stopped in stratum corneum, whereas UCNPs formulated in ethanol-water solution crossed stratum corneum and reached viable epidermis – hence, the enhancement effect for solid nanoparticles was detected by optical microscopy. All polymer-coated UCNPs were found nontoxic within the accepted safety levels. The keratinocyte resilience to polyethyleneimine-coated UCNPs was surprising considering cytotoxicity of polyethyleneimine to two-dimensional cell cultures.

© 2019 Elsevier B.V. Expression of programmed death-ligand 1 (PD-L1) in cancer cells plays an important role in cancer-immune cell interaction. The emerging evidence suggests regulation of PD-L1 expression by several tumor microenvironmental cues. However, the association of PD-L1 expression with chemical and mechanical features of the tumor microenvironment, specifically epidermal growth factor receptor (EGFR) signaling and matrix stiffness, remains elusive. Herein, we determine whether EGFR targeting and substrate stiffness affect the regulation of PD-L1 expression. Breast carcinoma cell lines, MCF7 and MDA-MB-231, were cultured under different conditions targeting EGFR and exposing cells to distinct substrate stiffness to evaluate PD-L1 expression. Furthermore, the ability to form aggregates in short-term culture of breast carcinoma cells and its effect on expression level of PD-L1 was probed. Our results indicated that PD-L1 expression was altered in response to both EGFR inhibition and substrate stiffness. Additionally, a positive association between the formation of multicellular aggregates and PD-L1 expression was observed. MDA-MB-231 cells expressed the highest PD-L1 level on a stiff substrate, while inhibition of EGFR reduced expression of PD-L1. The results suggested that both physical and chemical features of tumor microenvironment regulate PD-L1 expression through alteration of tumor aggregate formation potential. In line with these results, the in-silico study highlighted a positive correlation between PD-L1 expression, EGFR signaling, epithelial to mesenchymal transition related transcription factors (EMT-TFs) and stemness markers in metastatic breast cancer. These findings improve our understanding of regulation of PD-L1 expression by tumor microenvironment leading to evasion of tumor cells from the immune system.

© 2019 by the authors. Controlled fabrication of 45 nm width nanowire using simulated emission depletion (STED) direct laser writing with a rod-shape effective focus spot is presented. In conventional STED direct laser writing, normally a donut-shaped depletion focus is used, and the minimum linewidth is restricted to 55 nm. In this work, we push this limit to sub-50 nm dimension with a rod-shape effective focus spot, which is the combination of a Gaussian excitation focus and twin-oval depletion focus. Effects of photoinitiator type, excitation laser power, and depletion laser power on the width of the nanowire are explored, respectively. Single nanowire with 45 nm width is obtained, which is λ/18 of excitation wavelength and the minimum linewidth in pentaerythritol triacrylate (PETA) photoresist. Our result accelerates the progress of achievable linewidth reduction in STED direct laser writing.

© 2019 American Academy of Allergy, Asthma  &  Immunology Background: Mepolizumab is an anti–IL-5 antibody approved for the treatment of severe eosinophilic asthma. However, the prevalence of patients with severe asthma eligible for mepolizumab remains unknown, especially among children. Objective: To determine, in a population of patients with severe asthma from a tertiary referral center, the proportion of patients with an eosinophilic phenotype who would be eligible for mepolizumab, when stratified for the age of onset of asthma, and the prevalence of phenotypic features that favor mepolizumab therapy. Methods: An extensive database of 245 adults and children referred for severe asthma was used. The prevalence of severe asthma was estimated by using the European Respiratory Society/American Thoracic Society criteria. Patients with an eosinophilic uncontrolled phenotype qualified for mepolizumab. Results: In our cohort, 216 (88%) had severe asthma. Based on blood eosinophils of either greater than or equal to 150 cells/μL or greater than or equal to 300 cells/μL, 61%/41% had an eosinophilic phenotype, while 49%/34% were eligible for mepolizumab therapy. A greater percentage of adults (60%/47% of adults with asthma onset in adulthood [AoA] and 48%/26% adults with childhood-onset asthma [<18 years, CoA]) were eligible compared with children (33%/24%), for eosinophil counts of ≥150 and ≥300 cells/μL, respectively; P < .05. Compared with adults, children had a similar number of exacerbations while having better lung function (P < .05). Among adults, those with AoA were older, were more likely to have nasal polyps (28% vs 5%; P < .05), and had higher blood eosinophil counts (272 vs 150 cells/μL; P < .05) compared with those with CoA, with no difference in lung function noted between the 2 groups. Subjects showing greater than or equal to 500 eosinophils/μL, a strong indicator for mepolizumab therapy, had more nasal polyps, higher inhaled steroid dose, lower lung function, and AoA predominance than did those with less than 500 eosinophils/μL (P < .05). Conclusions: A smaller percentage of children with severe asthma were eligible for mepolizumab compared with their adult peers. Severe AoA has distinct phenotypic features that favor treatment with mepolizumab, including greater eosinophilia and nasal polyposis, in contrast to CoA, which appears to have fewer features of type 2 mucosal inflammation.

© 2019 WILEY-VCH Verlag GmbH  &  Co. KGaA, Weinheim Polydimethylsiloxane (PDMS) is a long-standing material of significant interest in microfluidics due to its unique features. As such, rapid prototyping of PDMS-based microchannels is of great interest. The most prevalent and conventional method for fabrication of PDMS-based microchips relies on softlithography, the main drawback of which is the preparation of a master mold, which is costly and time-consuming. To prevent the attachment of PDMS to the master mold, silanization is necessary, which can be detrimental for cellular studies. Additionally, using coating the mold with a cell-compatible surfactant adds extra preprocessing time. Recent advances in 3D printing have shown great promise in expediting microfabrication. Nevertheless, current 3D printing techniques are sub-optimal for PDMS softlithography. The feasibility of producing master molds suitable for rapid softlithography is demonstrated using a newly developed 3D-printing resin. Moreover, the utility of this technique is showcased for a number of widely used applications, such as concentration gradient generation, particle separation, cell culture (to show biocompatibility of the process), and fluid mixing. This can open new opportunities for biologists and scientists with minimum knowledge of microfabrication to build functional microfluidic devices for their basic and applied research.

© 2019 by the authors. Acid-sensing ion channels (ASICs), which are present in almost all types of neurons, play an important role in physiological and pathological processes. The ASIC1a subtype is the most sensitive channel to the medium's acidification, and it plays an important role in the excitation of neurons in the central nervous system. Ligands of the ASIC1a channel are of great interest, both fundamentally and pharmaceutically. Using a two-electrode voltage-clamp electrophysiological approach, we characterized lindoldhamine (a bisbenzylisoquinoline alkaloid extracted from the leaves of Laurus nobilis L.) as a novel inhibitor of the ASIC1a channel. Lindoldhamine significantly inhibited the ASIC1a channel's response to physiologically-relevant stimuli of pH 6.5-6.85 with IC50 range 150-9 μM, but produced only partial inhibition of that response to more acidic stimuli. In mice, the intravenous administration of lindoldhamine at a dose of 1 mg/kg significantly reversed complete Freund's adjuvant-induced thermal hyperalgesia and inflammation; however, this administration did not affect the pain response to an intraperitoneal injection of acetic acid (which correlated well with the function of ASIC1a in the peripheral nervous system). Thus, we describe lindoldhamine as a novel antagonist of the ASIC1a channel that could provide new approaches to drug design and structural studies regarding the determinants of ASIC1a activation.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Acid-sensing ion channel (ASIC) channels belong to the family of ligand-gated ion channels known as acid-sensing (proton-gated) ion channels. Only a few activators of ASICs are known. These are exogenous and endogenous molecules that cause a persistent, slowly desensitized current, different from an acid-induced current. Here we describe a novel endogenous agonist of ASICs-peptide nocistatin produced by neuronal cells and neutrophils as a part of prepronociceptin precursor protein. The rat nocistatin evoked currents in X. laevis oocytes expressing rat ASIC1a, ASIC1b, ASIC2a, and ASIC3 that were very similar in kinetic parameters to the proton-gated response. Detailed characterization of nocistatin action on rASIC1a revealed a proton-like dose-dependence of activation, which was accompanied by a dose-dependent decrease in the sensitivity of the channel to the protons. The toxin mambalgin-2, antagonist of ASIC1a, inhibited nocistatin-induced current, therefore the close similarity of mechanisms for ASIC1a activation by peptide and protons could be suggested. Thus, nocistatin is the first endogenous direct agonist of ASICs. This data could give a key to understanding ASICs activation regulation in the nervous system and also could be used to develop new drugs to treat pathological processes associated with ASICs activation, such as neurodegeneration, inflammation, and pain.

© 2018, MDPI AG. All rights reserved. Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come.

© 2018, Media Sphera Publishing Group. All rights reserved. Essential arterial hypertension (AH) is one of the main risk factors for the development of cognitive impairment and dementia. Cognitive decline is an early sign of brain damage as a target organ of hypertension, it occurs even in patients with uncomplicated hypertension with minimal duration of disease. Cognitive impairment progresses with increasing age and hypertension duration, as well as in non-controlled AH. In patients with hypertension, the prevalence of emotional disorders — anxiety and depression is also high. In addition to antihypertensive therapy, hypertensive patients need correction of concomitant cognitive and emotional disorders. Rat-gopantenic acid simultaneously corrects both emotional and cognitive impairment, and has a good tolerability profile as well. An analysis of the evidence base of rac-gopantenic acid showed its high efficacy in the treatment of mental disorders and good tolerability along with a positive effect on somatic disorders and results of antihypertensive therapy. Taken together, they enhance adherence to treatment and, consequently, reduce the cardiovascular risk.

© 2018, Pleiades Publishing, Ltd. Aptamers are widely used as molecular recognition elements for detecting and blocking functional biological molecules. Since the common “alphabet” of DNA and RNA consists of only four letters, the chemical diversity of aptamers is less than the diversity of protein recognition elements built of 20 amino acids. Chemical modification of nucleotides enlarges the potential of DNA/RNA aptamers. This review describes the latest achievements in a variety of approaches to aptamers selection with an extended genetic alphabet.

© 2018, Pleiades Publishing, Ltd. Solubilization with pluronic F-127 gave water-soluble forms of hydrophobic photosensitizers—steroid derivatives of pyropheophorbide a. Solubilization was performed by evaporating the chloroform co-solutions of photosensitizer and pluronic (triple block copolymer of ethylene and propylene oxide) and subsequently dissolving the resulting dry residue in water. The concentration ratios of modified pyropheophorbide–pluronic at which the photosensitizer completely passed into the aqueous phase were determined. Among the starting hydrophobic photosensitizers, pyropheophorbide–dihydrotestosterone possessed the highest activity in photosensitized oxidation of anthracene with singlet oxygen in chloroform, while after solubilization, pyropheophorbide–testosterone was most active in the test (for photodynamic therapy) oxidation of tryptophan in aqueous solutions.

© 2018 Elsevier B.V. Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine (CBZ) with the Pgp. This study investigates the effect of the Pgp inhibitor verapamil on the anticonvulsant effect of CBZ and its nanoparticulate formulation in the rat model of isoniazid-induced epilepsy. Verapamil significantly increased the anticonvulsant effect of CBZ and reduced its effective dose by at least 30% (from 30 mg/kg to 20 mg/kg). Binding of carbamazepine to the poloxamer 188-coated PLGA nanoparticles enabled a 30-fold increase of its anticonvulsive effect, as compared to the free drug. The inhibition of Pgp did not influence the effectivity of carbamazepine encapsulated in nanoparticles.

© 2018 Elsevier B.V. Background: To examine efficacy of Subetta as an add-on to insulin therapy in patients with type 1 diabetes mellitus (T1DM) a multicenter, double-blind, placebo-controlled, randomized clinical trial was performed. Derived by technological treatment of antibodies to insulin receptor β-subunit and endothelial NO synthase Subetta was previously proved to activate insulin signaling pathway. Methods: A total of 144 randomized patients with poor glycemic control in basal-bolus insulin regime were included in intention-to-treat analysis in Subetta add-on therapy or placebo (n = 72 in both groups). Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), basal and prandial insulin doses, number of hypoglycemia episodes confirmed by self-monitoring of blood glucose were recorded for 36 weeks. Results: The baseline characteristics of subjects did not differ between the two groups. HbA1c mean (±standard deviation) change was −0.59 ± 0.99% (95% CI −0.84 to −0.37) after 36 weeks in Subetta (vs. −0.20 ± 1.14%; 95% CI −0.44 to 0.11 in placebo; p = 0.028). The rate of overall hypoglycemia events was 7.9 per patient year (95% CI 7.1–8.6) in Subetta group and 7.6 (95% CI 6.9–8.4) in Placebo group (p = 0.63). The basal and total insulin doses did not change at the end of 36 weeks in both groups. Conclusions: Subetta add-on therapy boosting insulin activity and improving glycemic control in patients with T1DM is proved to be beneficial. Clinical trial registration: ClinicalTrials.gov identifier: NCT01868594.

© The Author(s) 2018. Earlier studies have shown that combination of antibodies to S100 protein and to cannabinoid receptor type 1 in released-active form (Brizantin) may possess anxiolytic properties and decrease nicotine dependence. Released-active form of antibodies is a novel approach that permits to modify natural functions of the target molecule (antigen) under investigation. The aim of the present study was to evaluate the anxiolytic-like effect of Brizantin in the light–dark test in mice, according to its ability to influence the number of entries into the lit compartment and the total time spent there. Three doses of Brizantin (2.5, 5, and 10 mL/kg) were compared with diazepam (1 mg/kg), placebo, and vehicle control. Anxiolytic-like effect of the tested drug was shown to be dose dependent, with an increasing trend from 2.5 to 10 mL/kg. Brizantin in its highest dose significantly increased studied behavioral parameters, although its effect was less pronounced than that of the reference drug diazepam (1 mg/kg).