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Current global warming and climate change under the greenhouse effect call for a thorough understanding of the spatial distribution of greenhouse gases in different atmospheric layers. Lidar systems are the most effective for remote greenhouse gas monitoring. We design a two-channel infrared OPO lidar optical system for remote DIAL/DOAS sensing of carbon dioxide and water vapor in the atmosphere. In this work, optimal geometric parameters of the transceiving channel of the lidar optical system are chosen, a need to focus laser radiation at a distance of 1 km from an observation point is demonstrated, and numerical simulations confirm the possibility of detecting lidar signals ranging from 10−7 to 10−10 W in the informative spectral range 4800–5100 cm−1 (1960–2083 nm). Laboratory experiments with the main components of the lidar system with experimentally confirmed parameters, which simulate atmospheric measurements of CO2 absorption at a calibrated sensing wavelength of 2005 nm (4987 cm−1) (pressure of 1 atm; CO2 concentration corresponding to the midlatitude summer background atmosphere) in the informative spectral range of the lidar system, enable selecting a pair of wavelengths with resonant absorption of the target gas near 2005 nm to study the background state of the atmosphere in the surface layer. Efficiency of the lidar optical system is confirmed by in situ test experiments, where backscattering signals from a topographic target with an albedo of ∼0.15 spaced 168 m apart from an observer are recorded at 60 mV when operating along a horizontal atmospheric path. The lidar system we design can be used in measuring complexes at carbon test sites. It can also be used for atmospheric monitoring in industrial centers, at background measuring stations, and in swamp areas.

GIZh-298 pharmacokinetics was studied in rats after different dosage regimens.The aim of this study was to study GIZh-298 pharmacokinetics after its multiple intragastric administration.Methods. The study was conducted on outbred male rats. The concentrations of GIZh-298 in the blood plasma were determined by HPLC with mass-spectrometric detection. Pharmacokinetic parameters were evaluated using a model-independent method.Results. After single and multiple (4 times with a dosage interval of 3 hours) intragastric administrations at 60 mg/kg dose, the test substance in the blood plasma was determined for 4 hours. The mode of administration of GIZh-298 did not affect the value of its half-life and the mean residence time. It has been established that GIZh-298 accumulates in the rats.

The third article in a series of publications devoted to the results of studying the current radiation situation in the territories of the Bryansk region bordering the Republic of Belarus presents results of studies of the content of radionuclides (137Cs and 90Sr) in samples of agricultural food products produced in the personal subsidiary plots of the population. The regularities of changing 137Cs and 90Sr content in samples of cow’s milk and potatoes depending on the level of radioactive contamination of the territory were studied; the present values of the quantities characterizing the distribution of the ratio of the activity concentration of radionuclides in agricultural food products to the density of radioactive contamination of the soil of the territory were deter -mined. The ratios of average values of 137Cs activity concentration in milk from stalled and grazing periods for cattle were analyzed. The results of the study show that some dairy product samples (less than 1%) do not meet the radiological safety criterion. Exceedances of the hygienic standards were not found in the studied samples of potatoes, vegetables, and meat of farm animals.

Introduction. Today, prevalence of neurodegenerative diseases increases. In recent years, more studies have revealed a new knowledge about the role of microglia in the development of these diseases. Animal experiments showed that peripheral inflammation causes activation of microglia in brain. All this points to the essential role of the cells in the development of neurodegeneration. Under the influence of various factors, microglia can change the phenotype and participate in both repair and damage to brain cells. Chronic herpesvirus infection caused by HSV-1 is another known factor in the development of neurodegenerative pathology. However, the exact pathogenetic mechanisms are still unknown, nevertheless, studying the virus effect on microglia has great potential. The goal of our study in this connection was to assess the effect of HSV-1 on microglia polarization in mouse strain with normal susceptibility to this virus and in strain which is more resistant to the action of HSV-1. For this purpose, changes in the cytokine profile were detected. A comparison of interstrain differences in the expression of cytokine genes was also compared in control groups. Materials and methods. The study involved infecting C57BL/6 and BALB/c mice with herpes simplex virus type 1, an isolation of microglia was based on separation steps using a discontinuous gradient density, the cytokine profile was assessed by gene expression levels using a real-time reverse transcription PCR. To calculate the relative fold gene expression of samples the 2–ΔΔCt method was used. Statistical significance was determined using the Mann–Whitney U-test. Results. There were found no interstrain differences in cytokine gene expression in control groups of different mouse strains. At the same time, gene expression differed in the experimental groups: in BALB/c mice, the expression of genes for both pro-inflammatory and anti-inflammatory cytokines increased; in C57BL/6 mice, a slight increase in the expression of IL-1β genes was observed. Conclusion. The data indicate the formation of different microglial phenotypes after HSV-1 infection in different mouse strains. Apparently, in BALB/c mice there is a switch from the pro-inflammatory M1 phenotype of microglia to the anti-inflammatory M2 phenotype, while in C57BL/6 mice the attenuation of the infectious process occurs through a return to the original M0 phenotype.

We present the results of near-Earth interplanetary space, magnetosphere, and atmosphere monitoring during large-scale solar wind disturbances at the end of August 2005. The monitoring was carried out using ground-level cosmic ray (CR) observations made at the worldwide network of neutron monitors as well as muon telescopes in Yakutsk and Novosibirsk. As a result of the analysis performed by different methods, we have obtained variation properties of CRs of different rigidities in Earth’s orbit, their pitch angle anisotropy, orientation and configuration of the interplanetary magnetic field, changes in the planetary system of geomagnetic cutoff rigidities during geomagnetic disturbances, as well as mass average air temperature over CR stations equipped with muon telescopes. For the periods of geomagnetic disturbances, we have determined parameters of magnetospheric ring current and magnetopause currents.

The pharmacokinetics of a new antiparkinsonian drug ADK-1113 after single intravenous and intragastric administrations in mice at doses of 10 and 20 mg/kg was studied. The absolute bioavailability was 10.1–16.3 % that indicates on potential possibility of preparing a dosage form for oral administration.

Introduction. It has been established that the presence of homologous recombination deficiency in a breast tumor is associated with the effectiveness of treatment. But despite the high chemosensitivity of the tumor to DNA-damaging agents, complete pathological responses to treatment are very rare. And this process may be based on a change in the somatic status of BRCA1, that is, a reversion and return of the wild-type allele occurs and the DNA repair function is restored.Aim. To evaluate changes in the presence of chromosomal aberrations and the expression profile of the main genes of homologous recombination in cell models of breast cancer under the influence of cisplatin and docetaxel.Materials and methods. The study was conducted on breast cancer tumor cell cultures: MCF-7, MDA-MB-231 and MDA-MB-468. A cell model of drug resistance was obtained for two drugs: cisplatin and docetaxel. RNA and DNA were isolated from cell suspension using the RNeasy Plus Mini Kit and QIAamp DNA Mini Kit (Qiagen, Germany), respectively. The expression level of homologous recombination genes was assessed using reverse transcription polymerase chain reaction. To assess the presence of chromosomal aberrations, microarray analysis was performed on DNA chips.Results. Restoration of normal copy number for the BRCA1, CDK12, CHEK1 and RAD51D genes in MCF-7 under the influence of cisplatin was shown. For BRCA2 and PALB2, amplifications were detected. A statistically significant increase in the expression of the BRCA1 (p = 0.04), BRCA2 (p = 0.02), PALB2 (p = 0.01) and RAD51D (p = 0.05) genes was also shown. MDAMB-231 shows that all identified loci with deletions, where the BRCA2, BARD1, CHEK2, PALB2 and RAD54L genes are localized, are restored to normal copy number by cisplatin. The appearance of amplifications was registered for BRCA1, BRIP1, FANCL, RAD51B, PARP1. A similar result was shown for docetaxel. An increase in the expression level is typical for the genes BRCA1 (p = 0.02), BRCA2 (p = 0.02), CHEK2 (p = 0.05), FANCL (p = 0.04), PALB2 (p = 0.05), RAD51C (p = 0.02), PARP1 (p = 0.02), which corresponds to the appearance of amplifications. In the MDA-MB-468 cell culture, an increase in the copy number of only the BRCA1 gene is observed. The effect of docetaxel has no effect on this cell culture. The level of BRCA1 expression increases in direct proportion to the duration of drug action.Conclusion. Thus, the study showed that under the influence of cisplatin, reversion of not only homologous recombination gene mutations, but also other disorders can occur.

Summary: The inwardly rectifying K+ channel Kir5.1 (Kcnj16) is essential in renal salt handling and blood pressure control. However, the underlying mechanisms are not fully understood. Here, we integrated transcriptomics and metabolomics to comprehensively profile the changes in genes and metabolites in the Dahl salt-sensitive (SS) rat lacking Kcnj16 to identify potential mechanisms. Consistent with the phenotype of knockout (KO) rats, the transcriptomic profile predicted reduced blood pressure, kidney damage, and increased ion transport. Canonical pathway analysis suggested activation of metabolic-related pathways while suppression of immune response-related pathways in KO rats. Untargeted metabolomic analysis revealed different metabolic profiles between wild-type (WT) and KO rats. Integration of transcriptomic and metabolomic profiles suggested altered tricarboxylic acid (TCA) cycle, amino acid metabolism, and reactive oxygen species (ROS) metabolism that are related to SS hypertension. In conclusion, besides increased ion transport, our data suggest suppressed immune response-related and altered metabolic-related pathways of SS rats lacking Kir5.1.

Mast cell tumour is one of the most common cutaneous neoplasms in dogs, ranging from well differentiated to aggressive tumors with metastases. Currently, prognosis and therapeutic definitions of canine cutaneous MCTs are based on the histological grade of malignancy. Clinical examination and treatment were performed in Dnipro veterinary clinics and pathological analysis in the Department of Animal Anatomy, Histology and Pathomorphology, Dnipro State Agrarian and Economic University (Dnipro, Ukraine). Thirty-six dogs with a history of skin neoplasia were examined. Skin MCTs were diagnosed in 23 males and 13 females, aged between 5 and 15 years. No breed predisposition was found out in tested cohort. MCTs were located on the trunk (44.4%), limbs (33.4%) and less frequently on the head and neck, axillary, inguinal and perineal areas (22.2%). MCT was detected in 8 animals where the malignancy was systemic and develops metastatic spread to internal organs. Pathological diagnosis included cytopathological examination of tumor material, pathological analysis of samples obtained by incisional biopsy using haematoxylin/eosin and toluidine blue staining. According to the diagnostic criteria (smear cellularity, presence of cells with basophilic cytoplasmic granularity, size and number of cytoplasmic granules, presence or absence of mitotic figures, nuclear pleomorphism, presence or absence of binucleations or multinucleations, anisokaryosis), benign mast cell tumour (high grade) was diagnosed in 23 animals and malignant mast cell tumour (low grade) in 13 animals. These results were confirmed by histopathological methods using haematoxylin and eosin staining. Additional staining of histological sections with toluidine blue allowed differentiation of benign mast cell tumours into high-grade (38.9%) and intermediate-grade (5%).

The article examines the peculiarities of reproduction of archetypes in the translation of an artistic work. The interpretation of the concept of ‘archetype’, its classifi cations and levels of its mental representation in the text are studied herein. While examining the issue of universal and ethnocultural archetypes, the author of the article introduces the term ‘culturally determined archetypes’. The article contains the proposals as to the actions that are to be taken by a translator in the process of reproduction of the source language archetype in the target language, outlines what exactly it is necessary to pay attention to in order to properly translate the archetype. It is noted that if the archetypes are translated inadequately or inaccurately, the integrity of the literary work may be violated due to the partial loss of the symbolic meaning, or the emotional impact on the reader. It is proposed to include the archetypal analysis of the source and target texts to the translation studies analysis.

Relevance. To introduce the GK-2 compound into clinical practice, it is necessary to conduct a preclinical study of its pharmacokinetics, in particular, the distribution of the studied drug in organs and tissues. The aim is to study the tissue availability of a new original compound GK-2 in rats after its intraperitoneal administration. Methods. Quantitative determination of GK-2 in blood plasma and organ/tissue homogenates of rats was carried out by high-performance liquid chromatography with mass spectrometric detection. Results. The distribution of GK-2 in organs and tissues with varying degrees of vascularization was studied in rats. It was found that after a single intraperitoneal injection of GK-2 at a dose of 150 mg/kg, the studied compound was recorded in blood plasma for 2 hours, its half-life (t1/2el) was 0.4 hours. In organs and tissues, GK-2 was detected from 1.5 to 2 hours. The tissue availability of GK-2 in the liver — blood plasma system was 18.68; "kidneys — blood plasma" — 1.26; "spleen — blood plasma" — 0.68; "skeletal muscles — blood plasma" — 0.31. For the target organ, the brain, the tissue availability was 0.24. In the brain, the time to reach the maximum concentration of GK-2 (0.77 mcg/g) was 0.34 hours. It was found that GK-2 is excreted more slowly from the brain (t1/2el was 0.75 h) than from other organs and tissues (from 0.31 h for the spleen and up to 0.47 h for the kidneys).

This study presents results of radiation-hygienic surveys of the Bryansk Oblast settlements bordering the Republic of Belarus. The data were obtained in the course of implementation of measures of the “Program of joint activities of Russia and Belarus within the framework of the Union State for the protection of the population and rehabilitation of the territories affected by the Chernobyl NPP accident” in 2019–2022. The second part of the study presents structure of population’s food preferences (diet). A general description of the diets of residents is given and the main types of local food products at the present stage of the radiation accident are identified. The current levels of consumption of locally produced food (and products of local origin) by residents of different age categories have been assessed. The obtained results of assessing the levels of food consumption have been compared with our own results of earlier studies and with the results of studies on the population of Russia and Belarus. Similarly with previous years, among agricultural food products the most consumed products are milk and potatoes and among natural food products are mushrooms. The established levels of consumption of local dairy products and beef have decreased over the past ten years and the resident consumptions of mushrooms and potatoes are in the same levels as before.

In the Tver region (Russia), the moss biomonitoring technique was applied to investigate the atmospheric deposition of potentially harmful elements. Using inductively coupled plasma–optical emission spectroscopy and a direct mercury analyzer, a total of 15 elements were identified in 144 moss samples collected in the region. To assess the degree of environmental pollution, ecological indices (pollution load index, enrichment factor, geochemical index, and contamination factor) were computed. The sources of the identified elements were characterized across the territory under investigation using multivariate statistical analysis. The results obtained were compared with the information from other Central Russian regions. GIS technologies were used to create distribution maps for the surveyed territory. Transport and power plants are the primary sources of air pollution in the region, while the influence of industry is suggested to be negligible. Compared to other Russian regions, the area under investigation can be considered relatively clean.

One of the primary sources of trace elements in the environment is wastewater used for irrigation. However, the effects of untreated wastewater containing high concentrations of chromium and zinc on vegetables and the potential human health risks associated with their consumption are poorly understood. This pot experiment aimed to address this research gap. The accumulation of chromium and zinc and their effect on the biochemical parameters of lettuce (Lactuca sativa) and green onion (Allium fistulosum L.) irrigated with untreated industrial effluents were assessed. The average concentrations of chromium and zinc in the edible parts of the vegetables ranged between 7.36 and 7.58 mg/kg dry weight and 59.8 and 833 mg/kg dry weight, respectively. The irrigation of the lettuce with the effluent containing zinc at a concentration of 2.95 mg/L led to a significant increase in the content of phenols and the antioxidant activity. A significant reduction in the chlorophyll content of the lettuce leaves and the antioxidant activity of the onion leaves was observed when the plants were irrigated with the effluent containing zinc at a concentration of 78 mg/L. No non-carcinogenic health risk from the intake of chromium and zinc was identified through the consumption of lettuce and green onion, primarily due to the fact that a smaller proportion of the total metal content was transferred to their edible parts.

Background/Objectives: This study investigates the biocompatibility and physiological impacts of silver nanoparticles (AgNPs) functionalized with Spirulina protein extract (SPE) on laboratory rats. The objective was to assess and compare the systemic distribution, organ accumulation, and changes in hematological and biochemical parameters between biofunctionalized and non-functionalized silver nanoparticles. Methods: AgNPs were functionalized with SPE. Adult Wistar rats were administered these nanoparticles to assess their distribution across various organs using ICP-MS analysis. Hematological and biochemical markers were measured to evaluate systemic effects. Results: Functionalized silver nanoparticles demonstrated preferential accumulation in the brain, liver, and testicles, with significant clearance observed post-administration. The persistence of AgNPs SPE in reproductive organs was established. Hematological analysis revealed moderate changes, suggesting mild immune activation. Biochemical tests indicated transient increases in liver enzymes, signaling reversible hepatic stress. Conclusions: The biofunctionalization of AgNPs with Spirulina protein extract modifies the nanoparticles’ systemic behavior and organ distribution, enhancing their biocompatibility while inducing minimal physiological stress. These findings support the potential of Spirulina-based coatings to mitigate the toxicity and enhance the therapeutic efficacy of nanomedical agents.

Abstract Sodium-glucose co-transporters (SGLTs) in the kidneys play a pivotal role in glucose reabsorption. Several clinical and population-based studies revealed the beneficial effects of SGLT2 inhibition on hypertension. Recent work from our lab provided significant new insight into the role of SGLT2 inhibition in a non-diabetic model of salt-sensitive hypertension, Dahl salt-sensitive (SS) rats. Dapagliflozin (Dapa) blunted the development of salt-induced hypertension by causing glucosuria and natriuresis without changes in the Renin–Angiotensin–Aldosterone System. However, our initial study used male SS rats only, and the effect of SGLT2 inhibitors on hypertension in females has not been studied. Therefore, the goal of this study was to determine whether SGLT2 inhibition alters blood pressure and kidney function in female Dahl SS rats. The result showed that administration of Dapa for 3 weeks prevented the progression of salt-induced hypertension in female rats, similar to its effects in male SS rats. Diuresis and glucose excretion were significantly increased in Dapa-treated rats. SGLT2 inhibition also significantly attenuated kidney but not heart fibrosis. Despite significant effects on blood pressure, Dapa treatment caused minor changes to electrolyte balance and no effects on kidney and heart weights were observed. Our data suggest that SGLT2 inhibition in a non-diabetic model of salt-sensitive hypertension blunts the development of salt-induced hypertension independent of sex.

Purpose. To investigate the anthropogenic communication of the Cherkasy oblast as an ecosystem-forming component of the modern landscape structure of the area of research. Research materials and methods. Methods. On the principle of natural-anthropogenic coexistence general scientific and specific scientific research methods were applied. Results. The peculiarities of natural conditions and natural resources are determined by the geographical location within the borders of the Dniester-Dnieper and Left Bank-Dnieper forest-steppe regions of the East European plain country. The class of road landscapes of the study area is formed by the following types of roads, namely: automobile, dirt, forest and field roads, railways. In the landscape structure of Zvenyhorod district, the length of highways, unpaved roads, field and forest roads, railways. Uman district and Cherkasy district have the highest index of connectivity in terms of road length. The lowest indicators of the index of communication in terms of the length of highways in Zolotoniskyi district. Uman district has the highest index of communication in terms of the length of dirt roads, and Zvenigorodsky district has the lowest. Zolotoniskyi district and Cherkasy district have the highest index of communication in terms of the length of field and forest roads. The lowest indicator is Zvenigorodsky district, Uman district. Cherkasy district has the highest communication index in terms of railway length and Zvenigorodsky district has the lowest. Conclusions. The Zolotonisky district of Cherkasy region has the highest index of general anthropogenic communicability, i.e. it has the highest degree of anthropogenic transformation of the territory and anthropogenic load

Calcium propionate, as an approved food additive, is widely used as a mold inhibitor in food and feed. It is recognized as safe, but when metabolized in the gastrointestinal tract, it can affect the body’s metabolism both directly and indirectly through the intestinal microbiota. The effect of various doses of calcium propionate on the body of model animals, with the study of the quantitative and qualitative composition of their intestinal microbiome, was investigated in this experiment. Four groups of male laboratory rats were formed, which for 20 days consumed: a high-fat diet with the addition of 0.0%, 0.5%, 1.0%, 2.0% calcium propionoate. We determined changes in body weight, the condition and mass indices of the internal organs, biochemical blood parameters, the functional state of the nervous system using the “open field” method, as well as changes in the intestinal microbiota. Adding calcium propionate to a high-fat diet does not affect the rate of animals’ weight gain, nor the amount of feed and water consumed. High dose consumption of calcium propionate caused a decrease in the relative weight of the spleen and an increase in the relative weight of the kidneys, without affecting the functional state of the nervous system. With the addition of calcium propionate to a high-fat diet, only minor changes in some biochemical blood parameters were observed (increased De Ritis ratio and Ca/P ratio, moderate dyslipidemia). Calcium propionate had the most significant changes in the quantitative and qualitative composition of the intestinal microbiota in laboratory rats. Among the representatives of the microflora, the most sensitive to this substance against the background of a high-fat diet were obligate microorganisms from the genera Bifidobacterium and Lactobacillus. The antimicrobial action of calcium propionate was also demonstrated by the pathogenic Staphylococcus aureus. Amid a deficiency of obligate microflora, proliferation of transient microflora was found – facultative anaerobic and aerobic microorganisms (bacteria of the genera Klebsiella, Enterococcus, Clostridium, fungi of the genus Candida). Further research will be aimed at studying the effect of calcium propionate in various doses on the biological systems of different age group laboratory animals in a long-term experiment.

The pharmacokinetics of dimeric dipeptide mimetic of nerve growth factor GC-2 in the rat blood plasma after different routes of administration was studied. The drug was administered at dose of 150 mg/kg by single and repeatedly. After single intravenous and intraperitoneal injection, GC-2 was detected for 2 h, its half-life was 0.4 h. GC-2 absolute bioavailability after single intraperitoneal injection was 84.62 %, that indicates the prospect of development its injectable (intramuscularly) dosage form. After 4-fold (1.5 h dosing interval) intraperitoneal injection dose-independent pharmacokinetic parameters of GC-2 practically do not change compared to single administration. This indicates that GC-2 is not accumulated in the body of rats. The hypothesis of the linearity of the pharmacokinetics of GC-2 in the rats blood plasma after single intraperitoneal administration at doses of 50, 100 and 150 mg/kg was tested. It was found that the kinetics of GC-2 in the rat blood plasma is linea.

The diversity of macroinvertebrates, the structure of their communities in Bolshiye Koty Bay (Lake Baikal) was studied by a DNA metabarcoding approach using an Illumina MiSeq system. Internal primer mlCOIintF in combination with jgHCO2198 of the Folmer fragment of the COI gene were used for macroinvertebrate metabarcoding. A total of 118009 reads of the COI gene fragment (at least 313 bp in length) were obtained. The correlation of the Spearman coefficient (S = 0.6, p < 0.05) with the abundance of macroinvertebrates in the samples before DNA extraction showed that the number of reads can serve as an indirect characteristic of the abundance of a species (operational taxonomic unit, OTU). 115 OTUs belonging to the higher taxa of macroinvertebrates were identified: Porifera, 1; Platyhelminthes, 3; Annelida, 38; Arthropoda, 55; Mollusca, 18. At a high level of resolution (with homology with GenBank reference sequences ≥ 95 %, coverage ≥ 90 %), 46 taxa of macroinvertebrates comprising three communities were registered: one dominated by molluscs (Choanomphalus conf. maacki) and two dominated by chironomids (Orthocladius grega rius Linev., Sergentia baicalensis Tshern.). Communities are characterized by low species diversity according to Shannon (from 0.7 to 1.2 bits), high concentration of dominance according to Simpson (from 0.5 to 0.7) and low evenness according to Pielou (from 0.3 to 0.4). Dominants and subdominants in the communities account for 91 to 96 % of COI gene fragment reads. The spatial distribution of the dominant species identified in the communities is influenced by the geomorphological features of the bottom and the composition of sediments in the area studied. The approach proposed for studying the structure of macroinvertebrate communities based on DNA metabarcoding and next generation sequencing can be recommended for express assessment of the state of aquatic ecosystems in the monitoring.

This study presents results of radiation-hygienic surveys of the Bryansk Oblast settlements bordering the Republic of Belarus. The data were obtained in the course of implementation of measures of the “Program of joint activities of Russia and Belarus within the framework of the Union State for the protection of the population and rehabilitation of the territories affected by the Chernobyl NPP accident” in 2019–2022. The first part of the study presents a general characteristic of the current state of the problem of returning the residents of radioactively contaminated territories to normal living conditions and provides information on the settlements of the surveyed region. The modern demographic composition of the population is considered; the structure of private subsidiary plots is investigated. The results described in this part of the study indicate the main ways, which are relevant for the formation of the internal exposure dose of the public at the current stage of the radiation accident.

We examined the effects of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on markers of liver injury, oxidative status, and the extent of inflammatory and apoptotic processes in rats with acetaminophen-induced liver damage. The administration of acetaminophen caused the accumulation of 8-hydroxy-2-deoxyguanosine and 8-isoprostane in the liver and serum, as well as an increase in biochemiluminescence indicators. Oxidative stress resulted in the activation of pro-inflammatory cytokine and NF-κB factor mRNA synthesis and increased levels of immunoglobulin G, along with higher activities of caspase-3, caspase-8, and caspase-9. The administration of acetaminophen also resulted in the development of oxidative stress, leading to a decrease in the level of reduced glutathione and an imbalance in the function of antioxidant enzymes. This study discovered that 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline reduced oxidative stress by its antioxidant activity, hence reducing the level of pro-inflammatory cytokine and NF-κB mRNA, as well as decreasing the concentration of immunoglobulin G. These changes resulted in a reduction in the activity of caspase-8 and caspase-9, which are involved in the activation of ligand-induced and mitochondrial pathways of apoptosis and inhibited the effector caspase-3. In addition, 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline promoted the normalization of antioxidant system function in animals treated with acetaminophen. As a result, the compound being tested alleviated inflammation and apoptosis by decreasing oxidative stress, which led to improved liver marker indices and ameliorated histopathological alterations.

Background. The relevance of the problem is related to the high prevalence of chronic endometritis (CE); its role in female infertility, implantation failures during assisted reproductive technology procedures, and recurrent miscarriage; as well as the lack of a unified strategy in the diagnosis and treatment of this pathology. The present systematic review with a meta-analysis focuses on evaluating the impact of CE and its therapy on the outcome of in vitro fertilization. In addition, the effect of CE of various severity on the outcomes of assisted reproductive technologies is analyzed. Objective. To analyze the effect of CE of varying severity and its treatment on the outcomes of in vitro fertilization. Methods. Using PubMed, Medline, Scopus, Embase, ELibrary, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry, and Russian Science Citation Index, a systematic search was conducted for articles published over the past 12 years that met the following criteria: randomized controlled trial examining the effect of CE of varying severity on fertility and ways to treat it. The following indicators were calculated: ongoing pregnancy/live birth, clinical pregnancy, and miscarriage rates. A total of 4145 patients (from ten studies) were included. A meta-analysis was performed using Stata 11.0 software (The Cochrane Collaboration, Oxford, UK). The heterogeneity was considered low at I2 50%. Results. Women with CE exhibited lower ongoing pregnancy/live birth (OR 1.97; p = 0.02) and clinical pregnancy rates (OR 2.28; p = 0.002) as compared to women without it. CE treatment increased the ongoing pregnancy/live birth (OR 5.33; p < 0.0001) and clinical pregnancy rates (OR 3.64; p = 0.0001). In vitro fertilization outcomes were comparable in women treated for CE and women without CE (ongoing pregnancy/live birth rate, clinical pregnancy rate, and miscarriage rate: p = ns). Women with severe CE exhibited lower ongoing pregnancy/live birth (OR 0.43; p = 0.003) and clinical pregnancy rates (OR 0.40; p = 0.0007). Mild CE showed no significant effect on in vitro fertilization outcomes (ongoing pregnancy/ live birth rate, clinical pregnancy rate, and miscarriage rate: p = ns). Conclusion. The conducted meta-analysis showed that CE significantly reduces the ongoing pregnancy/live birth and clinical pregnancy rates in infertile women undergoing in vitro fertilization. Noteworthy is that antimicrobial therapy in such patients improves the results of assisted reproductive technologies, which are comparable to those of patients without CE. The negative impact of this pathology on the implantation capacity of the endometrium is most often observed in the severe form, while its mild form has virtually no effect on the in vitro fertilization outcome.

Abstract Mathematical models of complex systems rely on parameter values to produce a desired behavior. As mathematical and computational models increase in complexity, it becomes correspondingly difficult to find parameter values that satisfy system constraints. We propose a Markov Chain Monte Carlo (MCMC) approach for the problem of constrained model parameter generation by designing a Markov chain that efficiently explores a model’s parameter space. We demonstrate the use of our proposed methodology to analyze responses of a newly constructed bistability-constrained model of protein phosphorylation to perturbations in the underlying protein network. Our results suggest that parameter generation for constrained models using MCMC provides powerful tools for modeling-aided analysis of complex natural processes.

Objective: assessment of the microbiome of the vagina and uterine cavity using a uterine catheter with a collet guide in infertile patients before the in vitro fertilization procedure. Materials and methods: samples of vaginal and endometrial scrapings obtained from 73 infertile women who had planned an in vitro fertilization (IVF) procedure were taken and studied. The samples were analyzed by V3-V4-V6 regions using the 16S rRNA gene sequencing method. Results: significant differences were found in the taxonomy of the endometrium and vaginal microbiome - coincidences in microbiological composition were detected in 18.2% of patients. Endometrial lactobacillus-dominant microbiocenoses occurred in 24.8% of women, vaginal — in 56.7%. Comparisons between patients with negative and positive IVF (onset of biological pregnancy) results failed to identify any microorganism associated with the success of the procedure, with endometrial microbiota biodiversity being higher among women who successfully exercised their reproductive function. The Shannon Equality Index (J) for pregnant and non-pregnant women was 0.76 (0.57–0.87) and 0.55 (0.51–0.64), respectively (p=0.002). Conclusion: the use of a developed uterine catheter with a collet guide for an adequate assessment of the endometrial microbiome is promising and justified. The correct assessment of the endometrial microbiocenosis contributes to the adequate diagnosis of pathological processes occurring in the uterine cavity, which will allow for proper therapy aimed at increasing the receptivity of the endometrium and, in the future, contributing to the realization of the reproductive function of a woman.

The ecotopic difference in the accumulation of Ni, Zn, Mn, Al, Se, Cs, La and Sm in bryophyte Ceratodon purpureus (Hedw.) Brid was studied during a long-term experiment in the anthropogenically disturbed environment of Donbass. The concentrations of elements in moss gametophytes were determined by neutron activation analysis. The moss samples were exposed from November 2018 through May 2019 at 24 test plots in the central Donbass with varying degrees of technogenic transformation of geosystems. When comparing ecologically stressed areas with intact or restored ecotopes, the difference in the accumulation of Ni was 6.9 times, Zn – 10.2, Mn – 6.3, Al – 5.3, Se – 9.6, Cs – 3.9, La – 5.9, and Sm – 5.4 times. There were structural and functional modifications in the leaf apparatus of bryophyte, suitable for using in further phytomonitoring studies for express diagnostics. According to the results of the factor analysis, two groups of pollutants were identified, differing in the source of origin: (1) Al, Ni, Mn, and Zn, (2) Cs, Se, La, and Sm. The obtained data are considered as part of the primary screening of biogeochemical characteristics in the Donbass in 2018–2019. Within the gradient of toxic load and local impact, the leading role of mining and metallurgical facilities in the pollution of natural ecosystems of Donbass was proved.

Background. Preeclampsia (PE) complicates 28% of pregnancies worldwide, negatively impacting the pregnant woman and the fetus. Therefore, its prevention remains relevant. It is believed that the cause of PE, especially early PE, is a placentation disorder. It warrants studying drugs that can improve placenta development. The leadership in this matter is maintained by acetylsalicylic acid, which, according to the ASPRE study, reduced the incidence of PE at 34 weeks of pregnancy by 82%. The use of low molecular weight heparins (LMWH), dipyridamole, and antioxidants for PE prevention remains controversial and continues to be studied by foreign and Russian scientists. Aim. To assess the efficacy of acetylsalicylic acid, LMWH, dipyridamole (Curantyl), and bovine blood derivates (Actovegin) in the Russian population of pregnant women at high risk for PE prevention. Materials and methods. The study included 244 patients. We reviewed the archived case records of 103 patients diagnosed with severe PE, who delivered in 2019 at the State Clinical Hospital №24, and 141 pregnant women from the Maternity clinic №3 at the Veresaev Moscow State Clinical Hospital, where the risk of PE was assessed as high, according to the results of extended combined screening of the first trimester of pregnancy. Eighty-nine pregnant women received acetylsalicylic acid at a dose of 75 mg and 54 at a dose of 150 mg. In addition, 22 patients received LMWH, 6 dipyridamole, and 3 Actovegin. The absolute risks, the risk ratio, and statistical significance when taking drugs in each risk group were calculated to assess the efficacy of acetylsalicylic acid and other drugs for PE prevention in the above risk groups. Results. The resulting weak inverse correlation (r=-0.31) between the PE severity at delivery and the dose of acetylsalicylic acid indicates that an increase in the acetylsalicylic acid dose was associated with a decrease in the PE severity. The effectiveness of combinations of various drugs for PE prevention was assessed by analyzing factor correspondences. Two-dimensional scaling of the most likely combinations showed that most patients received acetylsalicylic acid in the high-risk group with no PE. Additional use of LMWH, Curantyl, and Actovegin did not reduce the risk of PE. Conclusion. Acetylsalicylic acid is the only pharmaceutical method for preventing PE in high-risk groups. Higher doses of acetylsalicylic acid are associated with lower PE severity.

Objective: to identify the presence of chronic endometritis in patients with adenomyosis and its cumulative role in the formation of reproductive losses. Materials and methods: 101 women of reproductive age with grade II adenomyosis and habitual miscarriage were examined. The comparison group (group 2) consisted of 49 patients with grade II adenomyosis without a history of early reproductive losses. The control group (group 3) consisted of 50 healthy patients. In order to diagnose chronic endometritis, a comprehensive immunohistochemical study of the expression of specific immunological markers of chronic endometritis (natural killer CD56, B cells (CD20), plasma cells (CD138) and activated lymphocytes (HLA-DR) with antibodies and the determination of CD68 macrophages was carried out. Polymerase chain reaction in the “real-time” mode (PCR) was used to determine the types and amount of endometrial microbiota. Statistical data processing was carried out in the environment of the STATISTICA package. Results: despite the absence of pathogenic and conditionally pathogenic microflora, according to the results of microbiological examination from the vagina and cervical canal of all examined patients, statistically significant differences in the detection frequencies of various microbiota taxa of crops from the uterine cavity were obtained. Patients with reproductive losses on the background of adenomyosis had microbiological and immunohistochemical signs of chronic endometritis of moderate and mild severity. The presence of chronic endometritis combined with adenomyosis contributes to the occurrence of pronounced endothelial dysfunctions, eventually leading to a violation of reproductive function in patients with a combination of HE and adenomyosis. Conclusion: The similar symptoms of adenomyosis and CE, a reliable association of adenomyosis with CE in patients with habitual miscarriage requires the inclusion of immunohistochemical and microbiological examination of the endometrium in the volume of pre-gravidar examination, even if there are negative results of microbiological examination of the environment of the cervical canal.

Every year, 570,000 new cases of cervical cancer (CC) are diagnosed in the world, and 311,000 people die from this disease. CC is the fourth most common type of cancer and therefore the fourth leading cause of cancer death in women worldwide. Numerous data on the occurrence and development of cervical cancer indicate an association in most cases (up to 90 %) with human papillomaviruses (HPV) of high carcinogenic risk (HCR).CC prevention strategies are based on screening, and deaths from this oncopathology can be prevented through vaccination and treatment with early detection of the disease.In this review, much attention is paid to current issues of detection and prevention of HPV-associated pathologies, and cervical cancer in particular, aiming to summarize and analyze the latest international literature data on this issue. As a result of this study, it was shown that for countries implementing the National program of vaccination against HPV of high carcinogenic risk, a decrease in the incidence of both cervical pathologies of varying severity and other cancers associated with the HPV carriage was registered.While effective implementation of actual experience and future advances in human papillomavirus vaccine prophylaxis may make it possible for all countries to move to the high levels of vaccination coverage required to eliminate HPV-associated pathologies, the results also suggest that the path to complete cervical cancer elimination as a global public health problem can be extremely difficult due to a number of existing limitations.

The aim of the study. In recent years, non-alcoholic fatty liver disease (NAFLD) has been considered a hepatic manifestation of the metabolic syndrome. The main consequence of NAFLD is chronic hepatic inflammation, which leads to dyslipidemia, inflammation, increased oxidative stress, and endothelial dysfunction. Immune activation in response to interaction with agents of a metabolic nature induces the release of pro-inflammatory cytokines in the liver, which subsequently cause iron сhomeostasis disorder. This leads to a frequent association of NAFLD with anemia of various etiology. In this regard, we considered it important to assess the severity of the systemic inflammatory response in NAFLD in the experiment in order to -diagnose anemia of chronic inflammation.Materials and methods. The study was carried out on 26 male Wistar rats, which were divided into control and experimental groups. In animals of the experimental group, NAFLD was modeled according to the generally accepted method. In order to assess metabolic disorders, we determined the main biochemical parameters, a complete blood count with the calculation of erythrocyte indices, the concentration of the main pro-inflammatory cytokines – interleukin (IL) 1, IL-6. Results. In laboratory rats with NAFLD, a statistically significant increase of intrahepatic enzymes in blood serum was found. The state of the erythrocyte lineage of hematopoiesis in the experimental group progressively worsened and caused the development of anemic syndrome. Synchronously, a statistically significant increase in serum levels of IL-1, IL-6 was recorded, which confirms the correlation of NAFLD with anemia of chronic inflammation.Conclusions. A high concentration of IL-1, IL-6 cytokines in NAFLD inhibits iron absorption in the duodenum, leads to the activation of macrophages, blocking the release of iron processed from aging erythrocytes into plasma. Further study of the mechanisms of anemia in NAFLD provides important therapeutic targets in the treatment of both NAFLD and its comorbidities.

The object of this research is the process of perception of individual objects in photos and videos for further analysis of the situation in the city. The subject of the research is image processing for selection, classification, and further use of the obtained information about the objects in the photo. The goal is to create information technology for the segmentation of individual segments in photos and videos obtained with the help of unmanned aerial vehicles (in particular, drones) in urban scenes. Main tasks: analysis of existing methods of data segmentation; implementation of an algorithm that would perform segmentation of data by various terrain objects; software testing; and formation of research results. The following results were obtained: existing models of image segmentation were examined for limitations and shortcomings. On the basis of identified shortcomings, the requirements for the developed system were formed. During the analysis of the subject area, the main problems were identified and described and the task to be automated was determined. During the design of algorithms for solving problems, the sequence of the execution of each process was determined. The design of the software included a description of the information space of the system and the user interface. The user interface was chosen after analyzing the main types of user interfaces. To assess the quality of the data processing, existing metrics were used – IoU, pixel accuracy, and the discrepancy matrix. During testing, errors that occur during data segmentation and their causes were determined, after their elimination, the correct result of image segmentation was shown. Conclusions. The scientific novelty of the obtained results is that although there is still no segmentation method that fully satisfies all needs for the analysis of the category of images obtained by drones, the developed software allows uploading images and templates to them as benchmarks for artificial intelligence. perform segmentation and verify the correctness of this segmentation visually and using the IoU metric, the mismatch matrix. The software can be improved by automating the process of creating a reference pattern, training the model on more data, and integrating the created software into a larger system that would work directly with the drone.

Formulation of the problem. During of his activities, man sought to harmonize the territory that surrounded him. The environment had to perform not only utilitarian functions, but also aesthetic ones, to satisfy the needs of man in the contemplation of the «beautiful». This aspiration led to the formation and development of a special group of man-made landscapes – garden and park landscapes. Garden and park landscapes are the «smart» group of man-made landscapes, which constructively combines natural components with components formed as a result of economic, art human activity. The aim of the work. To develop and substantiate the periodization of the formation of garden and park landscapes of Central Europe for their detailed knowledge and rational development. The research methods. The performed periodization is based on two main research principles: historical and on the principle of natural-anthropogenic coexistence. General scientific and specific scientific research methods have been used. Presentation of the main research material. In the history of formation and functioning of garden and park landscapes of Central Europe it is necessary to distinguish the following periods: sacral; regular, in the structure of which the following directions are singled out and justified: residential, sacral-regular, and proper regular; landscape with romantic and realistic directions; constructive and eclectic. Each of these periods is characterized by the dominance in the structure of the landscape of natural or anthropogenic component, regular or landscape style of organization of the landscape, has a different level of transformation of the natural basis, a certain functional load, different owners. The landscape structure is formed by the corresponding types and subtypes of garden and park landscapes, which change according to the selected periods. The article shows the change in the genetic structure of garden and park landscapes in accordance with reasonable periods and directions of formation and development. Garden and park landscapes of Central Europe were organized within the channel, floodplain, floodplain-terrace, slope and watershed types of areas, the landscape structure of which was formed by the corresponding types and subtypes of man-made landscapes, represented by park plantings, regular gardens, ponds, canals, paths, stairs, palace, outbuildings, sculpture, garden furniture, etc. It is established that garden and park landscapes performed various functions, namely: economic, aesthetic, sacred, memorial, medical, are places of short-term rest and material manifestation of power and spirituality of owners.

In recent years, there has been a significant increase in the number of patients with malignancies treated with immune checkpoint inhibitors (ICIs), including the anti-programmed cell death protein 1 (anti–PD-1) agent pembrolizumab. One of the important aspects of conducting clinical trials with ICIs is the assessment of the risk of developing immune-related adverse events (irAEs).The aim of the study was to evaluate the safety of a pembrolizumab biosimilar (BCD-201, Pembroria) compared with a reference medicinal product using the results of a phase I clinical trial and the available medical literature.Materials and methods. A phase I double-blind, randomised, controlled clinical trial (BCD-201-1) has been conducted in patients with advanced melanoma and non-small-cell lung cancer (n=131). Patients were randomly allocated in a 1:1 ratio to receive either BCD-201 (Pembroria) or the reference medicinal product (Keytruda®), administered intravenously at a dose of 200 mg every 3 weeks for up to 24 weeks or until disease progression or unacceptable toxicity is observed. Since the trial results remain blinded at the time of this writing, treatment group data are masked.Results. The study demonstrated the equivalence of pharmacokinetics and comparable safety profiles of pembrolizumab biosimilar and reference medicinal products. Both medicinal products were well tolerated; the frequency of all-grade irAEs was comparable between treatment groups (21.2% in Group 1 vs 21.5% in Group 2). Most irAEs were mild to moderate, with the exception of a case of Grade 3 diarrhoea and immune-mediated enterocolitis in one study subject; there were no statistically significant differences in the median time to development of irAEs between treatment groups (Р=0.22, two-sided Wilcoxon test).Conclusions. The analysed period of the BCD-201-1 trial demonstrated comparable safety characteristics of Pembroria and Keytruda®, which is consistent with the published safety data on the latter. Information on the similarity of long-term safety profiles of the pembrolizumab biosimilar and the reference medicinal product will be obtained from ongoing clinical trials.

Introduction. Influenza is one of the most pressing global health problems. Despite the wide range of available anti-influenza drugs, the viral drug resistance is an increasing concern and requires the search for new approaches to overcome it. A promising solution is the development of drugs with action that is based on the inhibition of the activity of cellular genes through RNA interference. Aim. Evaluation in vivo of the preventive potential of miRNAs directed to the cellular genes FLT4, Nup98 and Nup205 against influenza infection. Materials and methods. The A/California/7/09 strain of influenza virus (H1N1) and BALB/c mice were used in the study. The administration of siRNA and experimental infection of animals were performed intranasally. The results of the experiment were analyzed using molecular genetic and virological methods. Results. The use of siRNA complexes Nup98.1 and Nup205.1 led to a significant decrease in viral reproduction and concentration of viral RNA on the 3rd day after infection. When two siRNA complexes (Nup98.1 and Nup205.1) were administered simultaneously, a significant decrease in viral titer and concentration of viral RNA was also noted compared with the control groups. Conclusions. The use of siRNAs in vivo can lead to an antiviral effect when the activity of single or several cellular genes is suppressed. The results indicate that the use of siRNAs targeting the cellular genes whose expression products are involved in viral reproduction is one of the promising methods for the prevention and treatment of not only influenza, but also other respiratory infections.

The unrestrained development of cycling tourism requires an appropriate response from the State both at the legislative level and in the form of appropriate actions, namely: the construction of cycling infrastructure, the creation of which will positively affect the development of both transport and tourist infrastructure. This is explained by the conclusion that such concepts as «transport infrastructure», «cycling infrastructure» and «tourist infrastructure» are quite strongly interrelated and sensitive to each other in case of quantitative and qualitative changes in any of these infrastructures. In fact, the development of cycling infrastructure throughout the country will create conditions for the further development of domestic and inbound cycling tourism. The creation of cycling infrastructure in Ukraine (as part of the transport infrastructure) will lead to an increase in traffic safety and transport accessibility for cycling tourists of a significant number of the touristic, natural, historical and cultural resources. And this, in turn, will require the tourist infrastructure entities to continue its development in terms of providing appropriate specialized services to cycling tourists and meeting the standard needs of a growing number of tourists (for example, in the form of accommodation, catering, information, advertising, etc.). In addition to the direct development of the transport, cycling, and tourist infrastructures, related spheres of economic activity will be developed, ensuring their creation, existence and uninterrupted functioning. It is also important that the development of cycling infrastructure and the development of cycling tourism will lead to an increase in the number of jobs, profitability of transport, tourism and other spheres of economic activity and the State in general. And the most important in the case of creating a cycling infrastructure is the ability to meet the existing demand from potential and existing consumers of such services.

Object of study. The evaluation of the interaction between breast milk opportunistic microorganisms abundance and the milk whey antimicrobial activity at different periods of lactation. Materials and methods. 100 samples of breast milk from healthy breastfeeding mothers were inoculated on solid selective media, and then pure cultures of microorganisms were identified by MALDI-TOF mass spectrometry. The antimicrobial activity of the whey against a model culture of Candida albicans was evaluated by spectrophotometry. Results. 270 isolates represented by 36 species of 13 genera of opportunistic bacteria were obtained. None of the 100 samples contained opportunistic fungi. Staphylococci (7 species) and streptococci (11 species) were predominant. The most common were staphylococci S. epidermidis (70.2%) and S. aureus (20.8%), and streptococci S. mitis (27.7%) and S. oralis (21.8%). The total contamination (median) of opportunistic bacteria in the colostrum was 79 103 CFU/ml, transitional milk 4 103 CFU/ml, mature milk 5 102 CFU/ml. The antimicrobial activity of colostrum whey was 87.489.4%; transitional milk 88.2%; mature milk 63.481.9%. The total contamination had a high inverse correlation with the lactation period (r = 0.806) and a high positive correlation with the antimicrobial activity of whey (r = 0.699). Meanwhile, a significant decrease in contamination was noted after 1 month from the beginning of lactation, while a significant decrease in antimicrobial activity was observed after 8 months. Conclusions. The decrease of the breast milk contamination by opportunistic bacteria during the lactation period was found to be primary compared to the decrease of the whey antimicrobial activity. Thus, changes in the whey antimicrobial protection factors occur in response to changes of the opportunistic microbiota abundance.