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A probabilistic approach to predicting the properties of identified software vulnerabilities has been developed. The approach is based on representing the process of changing the values of the basic metrics of detected software vulnerabilities CVSS v3.0 as a random Markov process with discrete states and continuous time. When constructing systems of Kolmogorov equations, the dynamics of changes in the average intensity of changes in the values of basic metrics, depending on the current time, was taken into account. Analytical linear functions were obtained that approximate the average values of the instantaneous intensity of changes in the values of basic metrics within a quarter of the year, starting from January 1, 2017. In the interests of short-term forecasting, a probabilistic modeling of the emergence of vulnerabilities in the Astra Linux Special Edition operating system with specified properties in the form of values of basic CVSS v3.0 metrics was carried out depending on the day from the moment the last software vulnerability was discovered. The initial modeling conditions are set to the values of the basic metrics of the latest published software vulnerability. The possibility of calculating the values of stationary probabilities of occurrence of given values of the basic metrics of CVSS v3.0 vulnerabilities for long-term forecasting throughout the year is shown. Coincidence of statistical data for the fourth quarter of 2023. and the results of modeling the process of emergence of vulnerabilities with these properties confirmed the adequacy of the models and the reliability of the prediction results. The scope of application of the developed approach can be the sphere of software development and information security tools, as well as the created and operated systems for ensuring information security of significant objects of critical information infrastructure.

A novel facile approach to N-arylpyridoindazolium salts is proposed, based on direct oxidation of the ortho-pyridine substituted diarylamines, either using bis(trifluoroacetoxy)iodobenzene as an oxidant, or electrochemically, via potentiostatic oxidation. Electrochemical synthesis occurs under mild conditions; no chemical reagents are required except electric current. Both approaches can be considered as a late-stage functionalization; easily available ortho-pyridyl-substituted diarylamines are used as the precursors.

Nowadays, one of the promising ways for the development of computing systems with high performance and low energy consumption is the creation of artificial synaptic devices that imitate the functions of biological synapses. Such devices have a significant potential for effectively solving problems of pattern recognition, classification, control, and the treatment of diseases of the nervous system. The work demonstrates the imitation of synaptic behavior in a composite multiferroic heterostructure based on the piezoceramics of lead zirconate titanate (PZT) and the amorphous magnetic alloy Metglas. The characteristics of the heterostructure were measured by resonant excitation of the magnetoelectric (ME) effect and applying electric field pulses of various amplitudes and polarities. The ME coefficient αE was considered as a synaptic weight, and the output electrical voltage of the heterostructure as a postsynaptic potential. The study demonstrates the possibility of simulating long-term potentiation (LTP) and depression (LTD) in the ME heterostructure, as well as spike-timing-dependent plasticity (STDP). This work shows promise for creating neuromorphic computing systems based on multiferroic composite heterostructures.

The objective of this experiment was to evaluate the effects of a Bacillus subtilis xylanase on nutrient digestibility, intestinal health, and growth performance of broiler chickens undergoing an intestinal challenge. Nine hundred one-day-old Cobb 500 male chicks were randomly distributed into three dietary treatments with 10 replicates (30 birds/pen) until 42 d. Treatments were: Control (CT) diet, energy reduction (ER) diet, and the ER diet supplemented with B. subtilis endo 1,4-β-xylanase at 100 g/t (ER+xylanase). The ER diets had metabolizable energy reductions as per manufacturer guidelines: 80, 82, 87, and 92 kcal/kg for pre-starter, starter, grower, and finisher, respectively. All birds were challenged with Eimeria spp. on d 1 and Clostridium perfringens on d 12-14. Feed intake, body weight gain (BWG), and feed conversion ratio (FCR) were evaluated weekly. On d 17, the intestinal permeability was determined using fluorescein isothiocyanate-dextran (FITC-d) as marker. On d 21, I See Inside (ISI) methodology assessed intestinal alterations. On days 21 and 42, nutrient digestibility and cecal short-chain fatty acids (SCFA) concentrations were calculated. Data underwent ANOVA or Kruskal-Wallis tests, followed by Fisher or Dunn tests, respectively. From 0 to 42 d, broilers fed the ER+xylanase diet had greater (P = 0.046) BWG than birds fed the ER diet, while FCR showed improvements in CT and ER+xylanase diets. Broilers fed the ER+xylanase diet had improved intestinal integrity with the lowest (P = 0.017) serum FITC-d concentration and highest (P = 0.057) Mucin-2. Pancreas ISI scores were worsened (P = 0.034) in CT and ER diets compared to ER+xylanase diet. Ileal digestibility of DM and energy, and SCFA were greater (P ≤ 0.006) in broilers fed the ER+xylanase diet compared to ER diet. In conclusion, the B. subtilis xylanase supplementation improved nutrient digestibility, enhanced intestinal barrier integrity and increased SCFA concentrations which improved growth performance in broilers undergoing an intestinal challenge. Results indicated that this xylanase was able to compensate the energy reduction in corn-soy diets fed to broiler chickens.

In this study, we investigated the effect of plasma-activated liquids (PAL) on the cotton plant (Gossypium hirsutum L.) growth under laboratory and field conditions. We used two types of PAL: deionized water activated with plasma generated using a microwave plasmatron in atmospheric-pressure air flow (PAW) and a 1.5% KNO3 solution activated using plasma generated in an electrochemical cell (PAKNO3). These treatments differ in terms of their content of long-lived biologically active compounds. PAW contains a higher concentration of hydrogen peroxide (150 μM compared to 1.1 μM), while PAKNO3 is more saturated with NO2− and NO3− (1510 μM compared to 300 µM). We found that PAW improved cotton plant growth under field conditions and in a laboratory drought stress. Additionally, PAW increased field emergence and germination of heat-treated cotton seeds in the laboratory. It was revealed that PAW prevents the drought-induced disruption of the partitioning of absorbed light energy in the photosynthetic apparatus. Meanwhile, PAKNO3 has a positive effect on seed germination. The positive effect of PALs on cotton seeds and plants is thought to be due to the generation of long-lived biologically active oxygen and nitrogen species during plasma treatment of the liquid.

Abstract Osteoarthritis (OA) is one of the leading causes of disability, affecting over 500 million adults worldwide. Previous studies have found that various inflammatory factors can contribute to the pathogenesis of OA, including complement factors in the synovial fluid of OA patients. However, the pathogenesis of this disease is still not known, and the only therapy of severe OA is total joint replacements. Total joint replacements are invasive, expensive, and affect quality of life. Here we show that when human articular chondrocytes are stimulated with pro-inflammatory mediator interleukin-1β (IL-1β) there is an increase in inflammatory factors including complement component 3 (C3). We also found the transcription factor, signal transducer and activator of transcription 1 (STAT1), is responsible for increased C3 expression after IL-1β stimulation in human articular chondrocytes. A specific STAT1 inhibitor, fludarabine, attenuates the hyper-expression of C3 and delays/prevents spontaneous OA in Dunkin-Hartley guinea pigs. Since fludarabine is already clinically used for chemotherapy, this study has great translational potential as a unique disease-modifying osteoarthritis drug (DMOAD) in treating primary OA.

Brucellosis is a dangerous zoonotic disease caused by bacteria of the genus Brucella. Diagnosis of brucellosis is based on the detection in animal and human sera of antibodies to the O-polysaccharide of Brucella lipopolysaccharide. The currently employed serodiagnosis of brucellosis relies on the use of the Brucella O-polysaccharide as a diagnostic antigen. However, the existence of bacterial species, which also express O-polysaccharides structurally similar to that of Brucella, may decrease the specificity of the brucellosis detection due to false-positive test results. It has been shown that the efficiency of the test can be significantly improved by using synthetic oligosaccharides that correspond to the so-called M epitope of the Brucella O-antigen. This epitope is characterized by an α-(1→3)-linkage between d-perosamine units and is unique to Brucella. Here we report on an efficient approach to the synthesis of oligosaccharides that model the M epitope of the Brucella O-polysaccharide. The approach is based on the use of the α-(1→3)-linked disaccharide thioglycoside as the key donor block. Its application allowed the straightforward assembly of a set of four protected oligosaccharides, which includes a disaccharide, two trisaccharides, and a tetrasaccharide, in five glycosylation steps. The synthesized oligosaccharides are planned to be used in the development of diagnostic tools for identifying brucellosis in humans and domestic animals, as well as a potential vaccine against it.

Introduction. The search for affordable and accurate predictors of the outcome of COVID-19 is extremely important, as it provides the possibility to effectively correct the patient treatment tactics. Aim of the study. To develop simple and accurate criteria based on the dynamics of red blood counts that predict the outcome of COVID-19. Materials and methods. Observations were carried out in 125 patients with severe and extremely severe COVID-19, in whom indicators characterizing the state of red blood were determined in dynamics on days 1, 5, 7, 10, 14 and 21 after the hospitalization. ROC analysis was performed to calculate the threshold predictive values for survival and mortality. Results. The total number of erythrocytes and the level of hemoglobin in severe and extremely severe patients did not go beyond the acceptable limits, although showed a tendency to decrease in the group of fatal cases. On the 1st and 21st days, the number of MacroR in the deceased patients was reduced compared to those in group of survivors. It has been established that the RDW-CV test can predict the outcome of the COVID-19 with a high degree of probability at a relatively early stage of disease. RDW-SD test can be an additional predictive criterion of COVID-19 outcome. Conclusion. The RDW-CV test can be used as an effective predictor of disease outcome in patients with severe COVID-19.

Two experiments (Exp.) were conducted to evaluate the effects of a novel exogenous sfericase protease on growth performance and ileal digestibility of broiler chickens until day 35 of age. In Exp. 1, 1350 one-day-old male chicks (Cobb 500) were allocated in 54 floor pens and fed one of the three dietary treatments, with 18 replicates of 25 birds each in a completely randomized design. Diets consisted of positive control [PC; commercially relevant ME and balanced amino acids (AA)]; negative control (NC; with reduction of 6% dig. Lys and proportional reductions for adjacent AA compared to the PC), and NC supplemented with sfericase protease [30,000 New Feed Protease units (NFP)/kg]. On day 35, ileal digesta was collected to determine apparent ileal digestibility of dry matter and nitrogen (N). In Exp. 2, 1620 one-day-old male chicks (Cobb 500) were allocated in 54 floor pens having three treatments and 18 replicates of 30 birds each in a completely randomized design from day 1–35. Broilers were fed a control basal diet (Control); Control supplemented with sfericase at 30,000 NFP/kg and at 60,000 NFP/kg. In Exp. 1, from day 1–35, body weight gain (BW gain) and feed conversion ratio (FCR) of broilers improved 3.4 and 2.5% when diets were supplemented with sfericase, respectively, whereas the digestibility of N increased by 2.7% compared to the NC. In Exp. 2, diets with usual protein and AA levels and supplemented with 30,000 NFP/kg had 2.3 and 1.75% improved BW gain and FCR from day 1–35, respectively. When diets were supplemented with 60,000 NFP/kg, BW gain and FCR were enhanced by 3.9 and 3.2%, respectively compared to the Control. In conclusion, these results demonstrate that the novel sfericase protease could be successfully used in corn-soy diets with protein and AA reductions or in feed formulations with usual digestible AA levels to enhance growth performance of broilers.

Abstract Familial hypercholesterolemia (FH) patients suffer from excessively high levels of Low Density Lipoprotein Cholesterol (LDL-C), which can cause severe cardiovascular disease. Statins, bile acid sequestrants, PCSK9 inhibitors, and cholesterol absorption inhibitors are all inefficient at treating FH patients with homozygous LDLR gene mutations (hoFH). Drugs approved for hoFH treatment control lipoprotein production by regulating steady-state Apolipoprotein B (apoB) levels. Unfortunately, these drugs have side effects including accumulation of liver triglycerides, hepatic steatosis, and elevated liver enzyme levels. To identify safer compounds, we used an iPSC-derived hepatocyte platform to screen a structurally representative set of 10,000 small molecules from a proprietary library of 130,000 compounds. The screen revealed molecules that could reduce the secretion of apoB from cultured hepatocytes and from humanized livers in mice. These small molecules are highly effective, do not cause abnormal lipid accumulation, and share a chemical structure that is distinct from any known cholesterol lowering drug.

A new oxidatively stable (S)-N-benzylproline-derived ligand ((S)-N-(2-benzoyl-5-tert-butylphenyl)-1-benzylpyrrolidine-2-carboxamide) and its Ni(II)–Schiff base complexes formed of glycine, serine, and dehydroalanine are reported. A bulky tert-butyl substituent in the phenylene fragment precludes unwanted oxidative dimerization of the Schiff base complex, making it suitable for targeted electrochemically induced oxidative modification of the amino acid side chain. Experimental and DFT studies showed that the additional tert-butyl group increases the dispersion interactions in the Ni coordination environment making the complexes more conformationally rigid and provides a higher level of thermodynamically controlled stereoselectivity as compared to the parent Belokon complex. Additionally, functionalization with the tert-butyl group significantly enhances the reactivity of the deprotonated glycine complex towards electrophiles as compared to the anionic species formed from the original Belokon complex. Solubility of the t-Bu-containing ligand and its Schiff base complexes is increased, facilitating scaling-up the reaction procedure and isolation of the functionalized amino acid.

Abstract We aimed to evaluate how high-fat diet consumption can interfere with rat reproductive performance and fetal development. High-fat diet (HFD) was initiated in 30-day-old rats, distributed into two groups (n=7 animals/group): Rats receiving a standard diet and rats receiving HFD. At adulthood, the rats were mated, and on day 21 of pregnancy, the females were anesthetized, decapitated, and submitted to laparotomy to obtain visceral and periovarian adipose tissue. The uterine horns were exposed for analysis of maternal reproductive performance. The fetuses and placentas were weighed and analyzed. Pearson’s correlation test was used, and p

This study aims to determine the effectiveness of administering 80 ppm nitric oxide in reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental perfusion. Twenty-four sheep were randomized into four groups: two groups received 80 ppm NO conditioning with 90 min of cardiopulmonary bypass (CPB + NO) or 90 min of CPB and hypothermic circulatory arrest (CPB + CA + NO), while two groups received sham protocols (CPB and CPB + CA). Kidney injury was assessed using laboratory (neutrophil gelatinase-associated lipocalin, an acute kidney injury biomarker) and morphological methods (morphometric histological changes in kidney biopsy specimens). A kidney biopsy was performed 60 min after weaning from mechanical perfusion. NO did not increase the concentrations of inhaled NO2 and methemoglobin significantly. The NO-conditioning groups showed less severe kidney injury and mitochondrial dysfunction, with statistical significance in the CPB + NO group and reduced tumor necrosis factor-α expression as a trigger of apoptosis and necroptosis in renal tissue in the CPB + CA + NO group compared to the CPB + CA group. The severity of mitochondrial dysfunction in renal tissue was insignificantly lower in the NO-conditioning groups. We conclude that NO administration is safe and effective at reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental CPB.

The relevance of the study is caused by the necessity to assess the problem of flooding of one of the residential areas in Irkutsk, Irkutsk region. The flooding of urban areas is mostly seasonal. Identifying the conditions of aquicludes and well-permeable rocks, as well as, determining areas of possible groundwater accumulation using the method of electrical resistivity tomography makes it possible to develop measures to eliminate the damage caused by flooding. The objective. The work was carried out using the method of electrical resistivity tomography to assess the geological and hydrogeological conditions for flooding development, which has negative impact on residential development. Objects: bedrock monoliths characterized by high electrical resistance and being practically aquicludes; permeable zones on the land surface, which provide precipitation filtration and ground-water supply through them; areas, where the formation of vadose waters that cause the development of groundwater flooding is possible. Methods: ground geophysical prospecting using the method of electrical resistivity tomography; two- dimensional and three-dimensional inversion of electrical resistivity tomography data and its interpretation with regard to geotechnical drilling data. As a result of ground geophysical prospecting, it was established that the slope on which the assessed territory is located is an ancient landslide cirque, where the natural state of the rock mass is disturbed. Geophysical prospecting has revealed well-permeable zones on the land surface, which provide precipitation filtration and ground-water supply through them. According to electrical resistivity tomography, subzones were identified: severe flooding with groundwater level close to the land surface; moderate flooding with a groundwater level depth of 0,3 to 2 meters and weak flooding with a groundwater level depth of 2,0 to 5,0 meters.

The involvement of an α,α-cyclopropanated amino acid in the chiral Ni(II) coordination environment in the form of a Schiff base is considered as a route to electrochemical broadening of the donor–acceptor cyclopropane concept in combination with chirality induction in the targeted products. A tendency to the reductive ring-opening and the follow-up reaction paths of thus formed radical anions influenced by substituents in the cyclopropane ring are discussed. Optimization of the reaction conditions opens a route to the non-proteinogenic amino acid derivatives containing an α–β or β–γ double C=C bond in the side chain; the regioselectivity can be tuned by the addition of Lewis acids. One-pot combination of the reductive ring opening and subsequent addition of thiols allows obtaining the cysteine derivatives in practical yields and with high stereoselectivity at the removed β-stereocenter.

Performing cardiac surgery under cardiopulmonary bypass (CPB) and circulatory arrest (CA) provokes the development of complications caused by tissue metabolism, microcirculatory disorders, and endogenous nitric oxide (NO) deficiency. This study aimed to investigate the potential mechanisms for systemic organoprotective effects of exogenous NO during CPB and CA based on the assessment of dynamic changes in glycocalyx degradation markers, deformation properties of erythrocytes, and tissue metabolism in the experiment. A single-center prospective randomized controlled study was conducted on sheep, n = 24, comprising four groups of six in each. In two groups, NO was delivered at a dose of 80 ppm during CPB (“CPB + NO” group) or CPB and CA (“CPB + CA + NO”). In the “CPB” and “CPB + CA” groups, NO supply was not carried out. NO therapy prevented the deterioration of erythrocyte deformability. It was associated with improved tissue metabolism, lower lactate levels, and higher ATP levels in myocardial and lung tissues. The degree of glycocalyx degradation and endothelial dysfunction, assessed by the concentration of heparan sulfate proteoglycan and asymmetric dimethylarginine, did not change when exogenous NO was supplied. Intraoperative delivery of NO provides systemic organoprotection, which results in reducing the damaging effects of CPB on erythrocyte deformability and maintaining normal functioning of tissue metabolism.

This paper reports the design, fabrication, and results of the high-gradient conditioning and testing for a two-cell, π-mode, standing wave normal-conducting prototype booster cavity for the proposed 3 GeV proton linac upgrade at Los Alamos Neutron Science Center. Increasing the energy of proton beam from the existing 800 MeV to 3 GeV will improve resolution of the proton radiography by up to 10 times. The proposed energy boost can be achieved with a compact normal-conducting high-gradient radio-frequency (rf) linac section. The C-band section of the booster linac was designed with optimized-shaped copper accelerator cavities with distributed rf coupling. A short two-cell test prototype structure was designed for the frequency of 5.712 GHz, fabricated, and tested at the C-band Engineering Research Test Facility in New Mexico (CERF-NM) at Los Alamos National Laboratory. The maximum klystron power coupled into the test structure was 8.3 MW with 1 μs pulse length and 100 Hz repetition rate. The breakdown probabilities were recorded as functions of the accelerating gradient and peak surface fields. Operation of the test cavity at accelerating gradients of up to 100 MV/m was demonstrated.

Tubulin-targeting agents attract undiminished attention as promising compounds for the design of anti-cancer drugs. Verubulin is a potent tubulin polymerization inhibitor, binding to colchicine-binding sites. In the present work, a series of verubulin analogues containing a cyclohexane or cycloheptane ring 1,2-annulated with pyrimidine moiety and various substituents in positions 2 and 4 of pyrimidine were obtained and their cytotoxicity towards cancer and non-cancerous cell lines was estimated. The investigated compounds revealed activity against various cancer cell lines with IC50 down to 1–4 nM. According to fluorescent microscopy data, compounds that showed cytotoxicity in the MTT test disrupt the normal cytoskeleton of the cell in a pattern similar to that for combretastatin A-4. The hit compound (N-(4-methoxyphenyl)-N,2-dimethyl-5,6,7,8-tetrahydroquinazolin-4-amine) was encapsulated in biocompatible nanocontainers based on Ca2+ or Mg2+ cross-linked alginate and it was demonstrated that its cytotoxic activity was preserved after encapsulation.

Ensuring dust and explosion safety during underground coal mining is one of the most important tasks of industrial safety and labor protection departments. The main method of preventing explosions of coal dust settled in mine workings is to process them with stone dust (rock dusting). The traditional methods of quality control of rock dusting include radioisotope, optical and chemical methods. To implement them, the devices are equipped with environmentally harmful radioactive elements, expensive optical sensors, desiccants and replaceable flasks with chemical reagents, which increases the cost of analysis and its duration. The measurement error of these devices is 10 % or more. The main purpose of the study is to develop and substantiate a new method for monitoring the dust and explosion safety of mine workings, which will be devoid of the disadvantages of the methods mentioned above. It is proposed to evaluate the quality of rock-dust distribution by a fundamentally new way – thermogravimetric. The method was tested on the dust of coal mines in Kuzbass and the Vorkuta basin, including dust samples taken in mines with actual explosions. The article presents the results of experimental studies of the processes of thermal destruction of coal and stone dust mixtures. The non-overlapping intervals of the thermogravimetric reaction are identified: moisture yield (35-132 °С); volatile matter yield from coal (380-580 °С); thermal degradation of limestone with carbon dioxide yield (650-850 °С). Methods and mathematical dependencies for processing significant and qualitative identification characteristics of thermogravimetric curves in determining the content of non-combustible components in a sample of mine dust are considered.

Space use and the use of a den during the winter period as an adaptation of the brown bear (Ursus arctos) to increase survival during a period of food shortage, are important aspects of the ecology in the practice of the population management. Despite this, the subject of the den locations in relation to space use of brown bears and movements associated with a den entry and exit were practically not considered by researchers. Using radio-telemetry methods between 1993–2012, we studied the space use of 15 brown bears in Sikhote-Alin, three in Kamchatka and two on Sakhalin. The location of 25 dens of tagged animals was determined. The majority of brown bears, mostly males, used space further from the den than from the average of all locations, and the overwhelming majority of dens were outside the core area of their home ranges. So, for brown bears, the spatial location of dens was away from preferred locations in the non-denning period. The same brown bears selected den sites in different denning seasons, both at relatively small distance from each other (1.3 km) and at a considerable distance (20.2 km). Females on Sakhalin moved to dens 7–9 days before the den entry. After leaving their dens, two females in Kamchatka moved 1.7 and 5.0 km on the first day, while on Sakhalin, two females did not move more than 0.1 km from their dens for the first 4 and 10 days. Female that gave birth to cubs in the denning period lingered the longest at the den. The distance of females from their dens and their movement activity decreased in the pre-denning period (10 days before denning, the variations in movement stabilised at a low level) and increased in the post-denning period (specifically after 10 days from the moment of emergence).

In this paper, the full electromagnetic code KARAT is presented in detail, the scope of which is a computational experiment in applied problems of engineering electrodynamics. The basis of the physical model used is Maxwell’s equations together with boundary conditions for fields, as well as material equations linking currents with field strengths. The Particle in Cell (PiC) method for the kinetic description of plasma is implemented in the code. A unique feature of the code KARAT is the possibility of the self-consistent modeling of inelastic processes, in particular, nuclear reactions, at each time step in the process of electrodynamic calculation. The aneutronic proton–boron nuclear reaction, accompanied by the release of almost only α-particles, is extremely in demand in medicine and, perhaps, in the future, will form the basis for obtaining “clean” nuclear energy. The results of a numerical simulation within the framework of the code KARAT of the key physical processes leading to the proton–boron fusion are presented and discussed both for laser-driven plasma and for a plasma oscillatory confinement scheme.

An analysis of published data and the results of our own studies reveal that the activation of a peripheral δ2-opioid receptor (δ2-OR) increases the cardiac tolerance to reperfusion. It has been found that this δ2-OR is localized in cardiomyocytes. Endogenous opioids are not involved in the regulation of cardiac resistance to reperfusion. The infarct-limiting effect of the δ2-OR agonist deltorphin II depends on the activation of several protein kinases, including PKCδ, ERK1/2, PI3K, and PKG. Hypothetical end-effectors of the cardioprotective effect of deltorphin II are the sarcolemmal KATP channels and the MPT pore.

The paper presents an analysis of the heat transfer processes in electric arc plasma conditions between the powder material and the plasma jet in different convective states. The heat transfer processes in the plasma jet generated for coating deposition are considered based on varying the conditions for the jet–powder interaction. The formed coating deposited onto the substrate acts as an indicator of the heat transfer efficiency. The heat transfer between the plasma jet and the powder material is facilitated by the turbulent nature of the plasma jet. The presented calculation results demonstrate the influence of the plasma flow turbulence on the motion of the fine powder and heating of the generated jet at the outlet of the plasma torch. An analysis of the influence of plasma flow turbulence on the acceleration and heating of fine powder particles was carried out. The experimental results allowed for the determination of the effect of the plasma jet turbulence degree on the heat transfer processes between the plasma and fine powder: the technological efficiency of the device with varying parameters of the spraying process and the flow rates of the material supply and plasma-forming gas were presented. The values of the plasma-forming gas supply rate, the material supply rate, and the Reynolds number were obtained while the other process parameters were fixed. The research was carried out within the state assignment of the Ministry of Science and Higher Education of the Russian Federation (theme No. FSEG-2023-0012).

Scarce research into the secondary metabolites of the fungi Pseudogymnoascus spp. has shown a hidden biosynthetic potential for biologically active compounds. This work investigated the biosynthesis of secondary metabolites by two Pseudogymnoascus fungal strains, VKM F-4518 and VKM F-4519, isolated from the surface soil layer of the Kolyma Lowland, Russia, in the Arctic. In these strains, 16-membered trilactone macrolides, (+)-macrosphelides A and B, were identified using 1D and 2D NMR, UHRMS, and optical rotation data. In the fungi of this genus, these metabolites were found for the first time. The studied strains are highly active producers of macrosphelide A, which is being considered as a promising agent for the cure of cancer. Using the antiSMASH secondary metabolite analysis tool, we found that the genome of strain VKM F-4518 contained 32 of the biosynthetic clusters of the secondary metabolite genes (BGC) and that of VKM F-4519 had 17 BGCs. Based on the comparison of the cluster of macrotriolide genes from the fungus Paraphaeosphaeria sporulosa, we found the complete supposed cluster BGCs of macrosphelides in the genomes of two Pseudogymnoascus strains using the BLAST+ program.

The basic element of the design of a power module is a metallized ceramic substrate. In this work, the formation of metallization coatings by the method of thermal transfer of metallization pastes (Mo-Mn-Si + binder) for alumina and aluminum nitride ceramics was carried out. The fixing of the metallization coating on the ceramic substrate was performed by firing at a temperature of 1320 °C. The subsequent deposition of the copper layer was carried out by the method of cold gas-dynamic spraying (CGDS) followed by annealing of the deposited coating. For high-quality adhesion, the optimum annealing temperature was 1000 °C.

The methods of theoretical description of the patterns of changes in thermodynamic properties depending on the composition and structure of solution components are a priority direction in the development of the theory of solutions. This article is devoted to the establishment of relationships between the thermodynamic properties, composition of solutions, and the structure of their components. The study of the thermodynamic properties of binary solutions formed by a common solvent (ethylbenzene) and substances of the homologous series of n-alkylbenzenes contributes to the establishment of the aforementioned relationships. In the production of ethylbenzene and its homologues, solutions based on n-alkylbenzenes are quite common. Alkylbenzenes are widely used in various fields of science and chemical technology as solvents, extractants, and plasticisers. Using the ebuliometric method, we measured the boiling points of solutions of four binary systems formed by ethylbenzene and n-alkylbenzenes under various pressure values. Compositions of equilibrium vapour phases of the binary systems were calculated using the obtained isotherms of saturated vapour pressure of the solutions. Using the Runge-Kutta method, the composition of the vapour phases of the solutions of the systems was calculated by the numerical integration of the Duhem–Margules equation on a computer. The obtained data on the vapour-liquid equilibrium became the basis for calculating the thermodynamic functions of the systems’ solutions. The Gibbs and Helmholtz energy values, the enthalpies of vaporisation and mixing, the internal energy, and entropy of solutions were calculated. The thermodynamic properties of the solutions were calculated using a comparison of the values baed on two standards: an ideal solution and an ideal gas. It was found that the values of the Helmholtz energy linearly depend on the molar mass of the substance (the number of –CH2– groups in a molecule) in the homologous series of n-alkylbenzenes. An increase in the Helmholtz energy values for n-alkylbenzenes in the homologous series is associated with a linear increase in the molar volume of liquid substances and an exponential decrease in the saturated vapour pressure of substances. For binary solutions of constant molar concentrations formed by ethylbenzene and n-alkylbenzenes, the Helmholtz energy linearly depends on the molar mass (number of –CH2– groups in the molecule) of n-alkylbenzene in the homologous series. We obtained an equation that makes it possible to predict the thermodynamic properties of solutions of binary systems with high accuracy. The equation accelerates the process of studying vapour-liquid phase equilibria and thermodynamic properties of solutions of binary systems by 300 times. The determined patterns confirm the hypothesis of the additive contribution of functional groups to the thermodynamic properties of solutions. This hypothesis underlies the statistical theory of group models of solutions. The thermodynamic patterns determined by this study can also be used to solve a wide range of technological issues in the chemical industry.

Magnetic field sensors using magnetoelectric (ME) effects in planar ferromagnetic-piezoelectric heterostructures convert a magnetic field into an output voltage. The parameters of ME sensors are determined by characteristics of the magnetic constituent. In this work, the low-frequency ME effects in heterostructures comprising a layer of antiferromagnetic hematite α-Fe2O3 crystal with easy-plane anisotropy and a piezoelectric layer are studied. The effects arise due to a combination of magnetostriction and piezoelectricity because of mechanical coupling of the layers. The field dependences of magnetization and magnetostriction of the hematite crystal are measured. The resonant ME effects in the hematite-piezopolymer and hematite-piezoceramic structures are studied. The strong coupling between magnetic and acoustic subsystems of hematite results in a tuning of the acoustic resonance frequency by the magnetic field. For the hematite layer, the frequency tuning was found to be ~37% with an increase in the bias field up to 600 Oe. For the hematite-PVDF heterostructure, the frequency tuning reached ~24% and the ME coefficient was 58 mV/(Oe∙cm). For the hematite-piezoceramic heterostructure, the frequency tuning was ~4.4% and the ME coefficient 4.8 V/(Oe∙cm). Efficient generation of the second voltage harmonic in the hematite-piezoceramic heterostructure was observed.

Beta-lactam antibiotics remain one of the most commonly prescribed drug classes, but they are limited by their propensity to cause hypersensitivity reactions (e.g., from allergy to anaphylaxis) as well as by the emergence of bacteria with a myriad of resistance mechanisms such as β-lactamases. While development efforts continue to focus on overcoming resistance, there are ongoing concerns regarding cross-contamination of β-lactams during manufacturing and compounding of these drugs. Additionally, there is a need to reduce levels of drugs such as β-lactam antibiotics in waste-water to mitigate the risk of environmental exposure. To help address future development of effective remediation chemistries and processes, it is desired to better understand the structural relationship among the most common β-lactams. This study includes the creation of a class-wide structural ordering of the entire β-lactam series, including both United States Food and Drug Association (US-FDA)-approved drugs and experimental therapies. The result is a structural relational map: the “Lactamome,” which positions each substance according to architecture and chemical end-group. We utilized a novel method to compare the structural relationships of β-lactam antibiotics among the radial cladogram and describe the positioning with respect to efficacy, resistance to hydrolysis, reported hypersensitivity, and Woodward height. The resulting classification scheme may help with the development of broad-spectrum treatments that reduce the risk of occupational exposure and negative environmental impacts, assist practitioners with avoiding adverse patient reactions, and help direct future drug research.

A synthesis of dispiro derivatives from 5-methylidene-2-chalcogenimidazolones and azomethine ylides generated from isatins and N-substituted α-amino acids has been developed.

Positive allosteric modulators (PAMs) of AMPA receptors represent attractive candidates for the development of drugs for the treatment of cognitive and neurodegenerative disorders. Dimeric molecules have been reported to have an especially potent modulating effect, due to the U-shaped form of the AMPA receptor’s allosteric binding site. In the present work, novel bis(pyrimidines) were studied as AMPA receptor modulators. A convenient and flexible preparative approach to bis(pyrimidines) containing a hydroquinone linker was elaborated, and a series of derivatives with varied substituents was obtained. The compounds were examined in the patch clamp experiments for their influence on the kainate-induced currents, and 10 of them were found to have potentiating properties. The best potency was found for 2-methyl-4-(4-((2-methyl-5,6,7,8-tetrahydroquinazolin-4-yl)oxy)phenoxy)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidine, which potentiated the kainate-induced currents by up to 77% in all tested concentrations (10−12–10−6 M). The results were rationalized via the modeling of modulator complexes with the dimeric ligand binding domain of the GluA2 AMPA receptor, using molecular docking and molecular dynamics simulation. The prediction of ADMET, physicochemical, and PAINS properties of the studied bis(pyrimidines) confirmed that PAMs of this type may act as the potential lead compounds for the development of neuroprotective drugs.

Reactions of oxirane ring opening provide a powerful tool for regio- and stereoselective synthesis of polyfunctional and heterocyclic compounds, widely used in organic chemistry and drug design. Cyclooctane, alongside other medium-sized rings, is of interest as a novel molecular platform for the construction of target-oriented leads. Additionally, cyclooctane derivatives are well known to be prone to transannular reactions, which makes them a promising object in the search for novel approaches to polycyclic structures. In the present work, a series of cyclooctanediones was studied in Corey-Chaykovsky reactions, and novel spirocyclic bis(oxiranes) containing cyclooctane core, namely, 1,5-dioxadispiro[2.0.2.6]dodecane and 1,8-dioxadispiro[2.3.2.3]dodecane, were synthesized. Ring opening of the obtained bis(oxiranes) upon treatment with sodium azide was investigated, and it was found that the reaction path is determined by the reciprocal orientation of oxygen atoms in the oxirane moieties. Diastereomers of the bis(oxiranes) with cis-orientation underwent independent ring opening, supplying corresponding diazidodiols, while in the case of stereoisomers with trans-orientation, domino-like reactions occurred, including intramolecular nucleophilic attack and the formation of a novel three- or six-membered O-containing ring. Summarily, a straightforward approach to polyfunctional compounds containing cyclooctane or oxabicyclo[3.3.1]nonane cores, employing bis(oxiranes), was elaborated.

The major intracellular polyamines spermine and spermidine are abundant and ubiquitous compounds that are essential for cellular growth and development. Spermine catabolism is mediated by spermine oxidase (SMOX), a highly inducible flavin-dependent amine oxidase that is upregulated during excitotoxic, ischemic, and inflammatory states. In addition to the loss of radical scavenging capabilities associated with spermine depletion, the catabolism of spermine by SMOX results in the production of toxic byproducts, including H2O2 and acrolein, a highly toxic aldehyde with the ability to form adducts with DNA and inactivate vital cellular proteins. Despite extensive evidence implicating SMOX as a key enzyme contributing to secondary injury associated with multiple pathologic states, the lack of potent and selective inhibitors has significantly impeded the investigation of SMOX as a therapeutic target. In this study, we used a virtual and physical screening approach to identify and characterize a series of hit compounds with inhibitory activity against SMOX. We now report the discovery of potent and highly selective SMOX inhibitors 6 (IC50 0.54 μM, Ki 1.60 μM) and 7 (IC50 0.23 μM, Ki 0.46 μM), which are the most potent SMOX inhibitors reported to date. We hypothesize that these selective SMOX inhibitors will be useful as chemical probes to further elucidate the impact of polyamine catabolism on mechanisms of cellular injury.

Abstract This study aimed at evaluating the levels of different maternal exercise intensities on maternal and fetal outcomes. Wistar rats were mated and the pregnant rats were distributed into four experimental groups (n = 13 animals/group): Control (Not exercise group - 0% of the anaerobic threshold- AT), mild (20%), moderate (80%), and heavy-exercise intensity (140% of AT). These AT were matched to the load of 0, 1, 4 and 7% of the body weight of the animal related to swimming-induced physical intensity. In pregnancy, biomarkers related to maternal blood gases, oxidative stress, metabolism, and reproductive performance, and outcomes of their offspring were analyzed. The mild and moderate-swimming caused no change on implantation, live fetus numbers and oxidative stress status. However, the rats submitted to mild-exercise presented respiratory alkalosis and the heavy-exercise group showed respiratory acidosis. In addition, fetuses of the heavy-exercise dams were smaller for gestational age and lower serum adiponectin levels compared to those of other groups. In conclusion, the moderate-exercise intensity caused beneficial effects for maternal environment and the mild and moderate-exercise presented similar fetal repercussions. Nevertheless, the heavy-exercise intensity caused maternal metabolic alterations that damaged the fetal growth. Therefore, these findings confirm that physical intensity should be carefully conducted to avoid maternal complications and, consequently, compromised fetal repercussions.

The application of non-planar scaffolds in drug design allows for the enlargement of the chemical space, and for the construction of molecules that have more effective target–ligand interactions or are less prone to the development of resistance. Among the works of the last decade, a literature search revealed spirothiazamenthane, which has served as a lead in the development of derivatives active against resistant viral strains. In this work, we studied the novel molecular scaffold, which resembles spirothiazamenthane, but combines isoxazoline as a heterocycle and cyclooctane ring as a hydrophobic part of the structure. The synthesis of new 3-nitro- and 3-aminoisoxazolines containing spiro-fused or 1,2-annelated cyclooctane fragments was achieved by employing 1,3-dipolar cycloaddition of 3-nitro-4,5-dihydroisoxazol-4-ol 2-oxide or tetranitromethane-derived alkyl nitronates with non-activated alkenes. A series of spiro-sulfonamides was obtained by the reaction of 3-aminoisoxazoline containing a spiro-fused cyclooctane residue with sulfonyl chlorides. Preliminary screening of the compounds for antiviral, antibacterial, antifungal and antiproliferative properties in vitro revealed 1-oxa-2-azaspiro[4.7]dodec-2-en-3-amine and 3a,4,5,6,7,8,9,9a-octahydrocycloocta[d]isoxazol-3-amine with activity against the influenza A/Puerto Rico/8/34 (H1N1) virus in the submicromolar range, and high values of selectivity index. Further study of the mechanism of the antiviral action of these compounds, and the synthesis of their analogues, is likely to identify new agents against resistant viral strains.

OBJECTIVES/GOALS: The goal of this project was to conduct a preliminary assessment of in vivo feasibility early on in the drug-discovery process in an effort to expedite the translation of novel drug scaffolds to potential clinical candidates. The data gathered in this study will be used to direct analog synthesis of our current lead compounds through rational drug design. METHODS/STUDY POPULATION: Based on virtual and physical high-throughput screening efforts and subsequent similarity searching, we identified a set of potent and selective spermine oxidase (SMOX) inhibitors adhering to a common structural scaffold. In order to address potential barriers to in vivo use, we then conducted a robust optimization analysis in an effort to identify analogs with improved drug-like characteristics. Docking simulations to predict binding were performed and visualized using molecular modeling software (MOE and PyMol). ADMET properties were calculated using a variety of software resources including SwissADME and CDD Vault. RESULTS/ANTICIPATED RESULTS: Through these optimization efforts, we were able to successfully identify analogs with improved drug-like characteristics, including increases in predicted CNS penetration, isosteric replacement of metabolically labile functional groups, increased lipophilicity, and elimination of structural attributes suggestive of off-target activity. Analogs were ranked according to predicted binding and properties of in vivo feasibility. Compounds achieving the highest scores were then selected as scaffolds to guide analog synthesis. DISCUSSION/SIGNIFICANCE: Despite evidence implicating induction of SMOX as a mechanism contributing to neuronal pathology, the lack of potent and selective inhibitors with profiles conducive for in vivo use has significantly impeded clinical investigation of this target. In this presentation, rational drug design focusing on translational optimization will be discussed.

The number of organic compounds has exceeded 40 million and increases by 300 thousand each year. In order to perform technological calculations of the production process, storage and transportation of materials we need the know the thermodynamic properties and the rate of fi re and explosion hazard of the substances used. It is, therefore, important to develop methods of forecasting fi re danger indicators and thermodynamic properties of substances, based on a minimal amount of experimental data. To solve this problem it is necessary to determine the relationship between the molecular characteristics and thermodynamic properties of substances in homologous series. The objects of the present study are substances of n-alkylketones homologous series. We have measured the saturation vapour pressure and the density of liquid substances in the series at various temperatures. Using the experimental data and the ideal gas parameters (standard liquid volume and temperature) we calculated the inner energy, the entropy, and the Helmholtz energy. The analysis proved that values of the thermodynamic functions of substances additively depend on the molar weight of n-alkylketones in the homologous series. Existing literature on the problem also demonstrates that similar dependence is observed for the fl ash point of n-alkylketones. Taking into account the fact that the named properties generally tend to change, we can establish a linear correlation between the fl ash point values and the Helmholtz energy of the substances in the homologous series. The corresponding equations were obtained. The established regularities and equations based on them, allow us to forecast the properties of homologous series of substances with enough accuracy for practical applications.

The multicaloric effect is defined as the adiabatic reversible temperature change in multiferroic materials induced by the application of an external electric or magnetic field, and it was first theoretically proposed in 2012. The multicaloric effects in multiferroics, as well as other similar caloric effects in single ferroics, such as magnetocaloric, elastocaloric, barocaloric, and electrocaloric, have been the focus of much research due to their potential commercialization in solid-state refrigeration. In this short communication article, we examine the thermodynamics of the multicaloric effect for solid-state heating applications. A possible thermodynamic multicaloric heating cycle is proposed and then implemented to estimate the solid-state heating effect for a known electrocaloric system. This work offers a path to implementing caloric and multicaloric effects to efficient heating systems, and we offer a theoretical estimate of the upper limit of the temperature change achievable in a multicaloric cooling or heating effect.

In this work, we, for the first time, manufactured a plasma-chemical reactor operating at a frequency of 0.11 MHz. The reactor allows for the activation of large volumes of liquids in a short time. The physicochemical properties of activated liquids (concentration of hydrogen peroxide, nitrate anions, redox potential, electrical conductivity, pH, concentration of dissolved gases) are characterized in detail. Antifungal activity of aqueous solutions activated by a glow discharge has been investigated. It was shown that aqueous solutions activated by a glow discharge significantly reduce the degree of presence of phytopathogens and their effect on the germination of such seeds. Seeds of cereals (sorghum and barley) and fruit (strawberries) crops were studied. The greatest positive effect was found in the treatment of sorghum seeds. Moreover, laboratory tests have shown a significant increase in sorghum drought tolerance. The effectiveness of the use of glow-discharge-activated aqueous solutions was shown during a field experiment, which was set up in the saline semi-desert of the Northern Caspian region. Thus, the technology developed by us makes it possible to carry out the activation of aqueous solutions on an industrial scale. Water activated by a glow discharge exhibits antifungicidal activity and significantly accelerates the development of the grain and fruit crops we studied. In the case of sorghum culture, glow-discharge-activated water significantly increases drought resistance.

A convenient synthetic approach to novel functionalized bis(isoxazoles), the promising bivalent ligands of the AMPA receptor, was elaborated. It was based on the heterocyclization reactions of readily available electrophilic alkenes with the tetranitromethane-triethylamine complex. The structural diversity of the synthesized compounds was demonstrated. In the electrophysiological experiments using the patch clamp technique on Purkinje neurons, the compound 1,4-phenylenedi(methylene)bis(5-aminoisoxazole-3-carboxylate) was shown to be highly potent positive modulator of the AMPA receptor, potentiating kainate-induced currents up to 70% at 10−11 M.

Fbxo4 tumour suppressor is part of a SCF E3 ligase which has two known substrates. Here, the authors identify Fxr1 as a substrate of SCFFbxo4 and identify an inherent regulatory feedback loop in head and neck squamous cell carcinoma that results in the bypass of senescence and neoplastic progression.

Abstract Mitochondrial dysfunction is associated with numerous acute and chronic degenerative diseases. The beta-2 adrenergic receptor (β2AR) agonist formoterol induces mitochondrial biogenesis (MB), but other β2AR agonists, such as clenbuterol, do not. We sought to identify the MB signaling pathway of formoterol and the differences in signaling between these two ligands that result in the differential induction of MB. While formoterol and clenbuterol increased cAMP, only formoterol increased the phosphorylation of Akt and its downstream target eNOS. The increase in Akt phosphorylation was Gβγ- and PI3K-dependent, and the increase in eNOS phosphorylation was Gβγ- and Akt-dependent. Only formoterol increased cGMP. Formoterol induced MB as measured by increases in uncoupled cellular respiration and PGC-1α and NDUFS1 mRNA expression and was blocked by inhibitors of Gβγ, Akt, NOS, and soluble guanylate cyclase. To identify distinct receptor-ligand interactions leading to these differences in signaling, we docked formoterol and clenbuterol to six structures of the β2AR. Compared to clenbuterol, the methoxyphenyl group of formoterol interacted more frequently with V114 and F193, while its formamide group interacted more frequently with C191. These data indicate that the unique structural features of formoterol allow it to interact with the β2AR to activate the Gβγ-Akt-eNOS-sGC pathway to induce MB.

The growing restriction of antibiotic growth promoters (AGP) use in farming animals has raised a concern regarding the viability of the animal production system. In this new context, feed additives with proven positive impact on intestinal health may be used as strategy to avoid losses on performance. The aim of this study was to evaluate the effects of a protected blend of organic acids and essential oils [P(OA+EO)] on growth performance, nutrient digestibility, and intestinal health of broiler chickens. A total of 1,080 Cobb × Cobb 500 male broilers were randomly distributed in four treatments with 10 replicates (27 birds/each). Treatments were as follow: non-challenged control; challenged control; AGP (enramycin at 10 g/t); and P(OA+EO) at 300 g/t. All birds on challenged groups were challenged with Eimeria spp. at 1 day and with Clostridium perfringens at 11, 12, and 13 days. Body weight gain (BWG), feed intake and feed conversion ratio (FCR) were evaluated until 42 days. At 17 days, one bird per pen was orally gavaged with fluorescein isothiocyanate-dextran (FITC-d) and blood samples were collected for FITC-d detection to assess intestinal permeability. At 21 days, apparent ileal nutrient and energy (IDE) digestibility, intestinal macroscopic and histologic alterations (ISI) and, expression of mucin2 (MUC2), claudin1 (CLDN1), and occludin (OCLN) genes in the jejunum were evaluated. From 1 to 42 days, birds from the non-challenged and P(OA+EO) groups had greater (P < 0.001) BWG compared to challenged control and AGP groups. The challenged control group presented the worst FCR (P < 0.001). IDE was 106 kcal/kg greater when broilers were fed P(OA+EO) compared to the challenged control group. Broilers supplemented with P(OA+EO) had improved intestinal integrity with lower blood FITC-d concentration and ISI scores, and greater expression of MUC2, CLDN1, and OCLN genes compared to the challenged control group (P < 0.05). In conclusion, the P(OA+EO) and the AGP led to increased growth performance, nutrient digestibility and intestinal health of challenged broilers. A marked difference occurred in favor of the P(OA+EO), suggesting that this blend may be used to improve intestinal health and broiler growth performance in AGP free programs.

Resumo: Em diversos países, a tuberculose bovina, causada por Mycobacterium bovis, é tanto um problema econômico quanto de saúde pública. Mundialmente, são implementados programas de erradicação da enfermidade com políticas baseadas em testes tuberculínicos e abate dos animais reativos, porém pouco se sabe sobre os custos e a efetividade das políticas de erradicação. O presente estudo avaliou a relação de custo-efetividade dos protocolos de diagnóstico da tuberculose bovina, em uma abordagem multidisciplinar, empregados em um rebanho naturalmente infectado. Após realização da análise de custo-efetividade (C/Ef) dos protocolos diagnósticos ante-mortem observou-se que o Teste Cervical Comparativo (C/Ef=4,68), quando utilizado isoladamente, é a escolha diagnóstica mais custo-efetiva para um rebanho naturalmente infectado. Para os protocolos confirmatórios de diagnóstico post-mortem a histopatologia (C/Ef=17,47) associada ao Teste Cervical Simples e Teste Cervical Comparativo foi a escolha mais custo-efetiva para os animais do rebanho estudado. Entretanto, o único protocolo eficaz em diagnosticar 100% dos animais infectados foi o uso em conjunto do teste humoral ELISA associado ao teste celular IFN.

The paper is devoted to the development and performance testing of a soil conditioner based on leonardite humic substances (LHS) modified with 3-aminopropyltriethoxysilane (APTES). The modified HS were obtained by adding APTES to LHS solution at different mass ratios of LHS and APTES, followed by the investigation of siloxane structures using 31Si NMR spectroscopy. The Urbic Technosol was used as a model soil. The size and amount of water-stable soil aggregates were estimated using wet sieving and laser diffraction, respectively. Toxicity was evaluated by monitoring microbial substrate-induced respiration (SIR) and seedling bioassay. Laboratory column experiments demonstrated an increase in water-stability of the 3–5 mm soil aggregates after LHS-APTES application. Field tests showed an increase in the average weighted diameter of micro aggregates (from 59 to 73 μm) and water-stable macroaggregates (from 1.6 to 2.9 mm) due to the LHS-APTES amendment. A substantial increase in SIR from 5 to 9 mg CO2 (kg h)−1 was detected. Better survival of seedlings was observed. The obtained beneficial results indicate that APTES-modified HS can be successfully used as a soil conditioner. The formation of extended siloxane networks was suggested as the main mechanism of the observed improvement in the structure of the amended soils.

A strategy for stereoselective synthesis of molecular platform for targeted delivery of bimodal therapeutic or theranostic agents to the prostate-specific membrane antigen (PSMA) receptor was developed. The proposed platform contains a urea-based, PSMA-targeting Glu-Urea-Lys (EuK) fragment as a vector moiety and tripeptide linker with terminal amide and azide groups for subsequent addition of two different therapeutic and diagnostic agents. The optimal method for this molecular platform synthesis includes (a) solid-phase assembly of the polypeptide linker, (b) coupling of this linker with the vector fragment, (c) attachment of 3-aminopropylazide, and (d) amide and carboxylic groups deprotection. A bimodal theranostic conjugate of the proposed platform with a cytostatic drug (docetaxel) and a fluorescent label (Sulfo-Cy5) was synthesized to demonstrate its possible sequential conjugation with different functional molecules.

Abstract Fructose consumption has increased worldwide, and it has been associated with the development of metabolic diseases such as insulin resistance (IR) and steatosis. The aim was to evaluate if lower fructose concentrations may cause pancreatic structural abnormalities, leading to a glucose intolerance without steatosis in male rats. Young male rats orally received 7% fructose solution for 12 weeks. Body weight, food, water, and energy intake were measured. An oral glucose tolerance test (OGTT) was performed. After final experimental period, all rats were anaesthetized and killed. Blood samples were collected for biochemical analyses and organs (liver and pancreas) were processed for morphological analyses. Fructose consumption was not associated with lipid accumulation in liver. However, fructose administration was associated with an increased area under curve from OGTT and an increased percentage of insulin-positive cells, high beta cell mass and reduced pancreatic islet area. Fructose supplementation (7%) did not cause steatosis, but it led to abnormal morphology and function of pancreatic islet cells, contributing for glucose intolerance development. Our findings demonstrate that even low fructose concentrations may cause deleterious effects in animals.