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Host–parasite interactions include effects on both proximate and ultimate levels: parasite infections affect individual’s fitness and play a significant role in shaping the life history of host species. Global environmental changes as well as significant shifts in abiotic factors might impact the dynamics of parasite–host interactions, especially in Arctic regions, where the climate is changing at an alarming rate. With global warming, parasites and their vectors are predicted to spread to polar latitudes, and it is crucial to follow the changes occurring in the ecosystems in the era of global changes. We studied blood parasites (Haemosporidae) of passerine birds (Passeriformes: Aves) in southwest Yamal (north-western Siberia) using genetic and morphological methods. We found an overall parasite prevalence of 76.3%, with highest values for Leucocytozoon (72.0%) and lower values for Parahaemoproteus and Plasmodium (8.9 and 8.2%, respectively). We determined 26 genetic lineages in total, five of them were novel. The most common parasite lineages were TRPIP2 (18%), BT1 (14%), novel ACAFLA06 (13%), BT2 (7%), novel ACAFLA07 (6%), BT4 (5%) for Leucocytozoon; SISKIN1 (4%) for Parahaemoproteus; TURDUS1 (4%) for Plasmodium. For redpoll (Acanthis flammea), brambling (Fringilla montifringilla), bluethroat (Luscinia svecica) and little bunting (Emberiza pusilla) overall prevalence exceeded 90%. We also found significant differences in prevalence and lineage composition between sample sites, species and sexes, and a positive correlation between number of infections and host body mass. Our study provides knowledge about haemosporidian infections in the region, which had been barely studied for blood parasites. Gathered information is essential for the future monitoring and assessing potential shifts due to global change.

Personalized neoantigen vaccines are a highly specific cancer treatment designed to induce a robust cytotoxic T-cell attack against a patient's cancer antigens. In this study, we searched ClinicalTrials.gov for neoantigen vaccine clinical trials and systematically analyzed them, a total of 147 trials. Peptide vaccines are the largest neoantigen vaccine type, comprising up to 41% of the clinical trials. However, mRNA vaccines are a growing neoantigen vaccine group, especially in the most recent clinical trials. The most common cancer types in the clinical trials are glioma, lung cancer, and malignant melanoma, being seen in more than half of the clinical trials. Small-cell lung cancer and non-small-cell lung cancer are the largest individual cancer types. According to the results from the clinical trials, neoantigen vaccines work best when combined with other cancer treatments, and popular combination treatments include immune checkpoint inhibitors, chemotherapy, and radiation therapy. Additionally, half of the clinical trials combined neoantigen vaccines with an adjuvant to boost the immune effects, with poly-ICLC being the most recurrent adjuvant choice. This study clarifies the rapid clinical trial development of personalized neoantigen vaccines as an emerging class of cancer treatment with increasingly diversified opportunities in classes, indications, and combinatorial treatments.

The FDA approval of imatinib in 2001 was a breakthrough in molecularly targeted cancer therapy and heralded the emergence of kinase inhibitors as a key drug class in the oncology area and beyond. Twenty years on, this article analyses the landscape of approved and investigational therapies that target kinases and trends within it, including the most popular targets of kinase inhibitors and their expanding range of indications. There are currently 71 small-molecule kinase inhibitors (SMKIs) approved by the FDA and an additional 16 SMKIs approved by other regulatory agencies. Although oncology is still the predominant area for their application, there have been important approvals for indications such as rheumatoid arthritis, and one-third of the SMKIs in clinical development address disorders beyond oncology. Information on clinical trials of SMKIs reveals that approximately 110 novel kinases are currently being explored as targets, which together with the approximately 45 targets of approved kinase inhibitors represent only about 30% of the human kinome, indicating that there are still substantial unexplored opportunities for this drug class. We also discuss trends in kinase inhibitor design, including the development of allosteric and covalent inhibitors, bifunctional inhibitors and chemical degraders. The FDA approval of imatinib in 2001 heralded the emergence of kinase inhibitors as a key drug class in the oncology area and beyond. This article analyses the landscape of approved and investigational therapies that target kinases and trends within it, including the most popular targets of kinase inhibitors, their expanding range of indications and strategies for kinase inhibitor design.

The technology of diffusion saturation of austenitic steels by chromium and nickel in the medium of low-melting liquid metal melts is shown. The saturation temperature was up to 1050°C, and the duration was up to 8 hours. It was found that it is the most effective to apply coatings according to the technological scheme: pre-carburization-diffusion metallization – final carburization. It was found that the coating consists of 4 layers. The surface layer has a thickness of up to 5 mkm and a microtuberance of up to 19500 MPa. The second layer, up to 12 mkm thick, has a microhardness of up to 7500 MPa. The third, up to 50 mkm thick, has a microhardness of 2300 MPa. In the fourth layer, up to 150 mkm thick, the microhardness gradually decreases from 2300 MPa to the microhardness of the base. At the same time, the total thickness of the coatings is up to 200 mkm.

The results of the experiment on the cultivation of okra vegetable crops in a farm in Osceola, Arkansas, USA using innovative biostimulants based on non-pathogenic microorganisms are presented. It is shown that the use of biostimulants contributed to a significant improvement in the morphological characteristics of plants, such as plant height, the number of side branches, leaves, fruits. In the green fruits of okra, the content of vital elements-nitrogen, sulfur, potassium, and especially iron, zinc, copper, magnesium and phosphorus-increased compared with the control variant, while the content of nitrates was significantly reduced, which suggests that biostimulants studied based on non-pathogenic microorganisms are promising.

Depression is a multifactorial disorder representing a significant public health burden. Previous studies have linked multiple single nucleotide polymorphisms with depressive phenotypes and suicidal behavior. MAD1L1 is a mitosis metaphase checkpoint protein that has been linked to depression in GWAS. Using a longitudinal EWAS approach in an adolescent cohort at two time points (n = 216 and n = 154), we identified differentially methylated sites that were associated with depression-related genetic variants in MAD1L1. Three methylation loci (cg02825527, cg18302629, and cg19624444) were consistently hypomethylated in the minor allele carriers, being cross-dependent on several SNPs. We further investigated whether DNA methylation at these CpGs is associated with depressive psychiatric phenotypes in independent cohorts. The first site (cg02825527) was hypomethylated in blood (exp(β) = 84.521, p value ~ 0.003) in participants with severe suicide attempts (n = 88). The same locus showed increased methylation in glial cells (exp(β) = 0.041, p value ~ 0.004) in the validation cohort, involving 29 depressed patients and 29 controls, and showed a trend for association with suicide (n = 40, p value ~ 0.089) and trend for association with depression treatment (n = 377, p value ~ 0.075). The second CpG (cg18302629) was significantly hypomethylated in depressed participants (exp(β) = 56.374, p value ~ 0.023) in glial cells, but did not show associations in the discovery cohorts. The last methylation site (cg19624444) was hypomethylated in the whole blood of severe suicide attempters; however, this association was at the borderline for statistical significance (p value ~ 0.061). This locus, however, showed a strong association with depression treatment in the validation cohort (exp(β) = 2.237, p value ~ 0.003) with 377 participants. The direction of associations between psychiatric phenotypes appeared to be different in the whole blood in comparison with brain samples for cg02825527 and cg19624444. The association analysis between methylation at cg18302629 and cg19624444 and MAD1L1 transcript levels in CD

The article deals with the concept of political demobilization of citizens. The weakening of citizen participation in protests is regulated through political demobilization, which divides and reduces the ability of social movements to develop. The processes of demobilization in modern Russia are most clearly reflected in the conflict between the participants of collective actions and the authorities. The applied mechanisms of demobilization have an impact on the political behavior of citizens, the development of civil activity in general, as well as on the further interaction between the government and society.Based on the data of an empirical study conducted by a survey of experts in the subjects of the Russian Federation in the period from 2014-2020, as well as the analysis of a number of protest campaigns by the case study method, the impact of demobilization measures on civil activity, the system of interaction between the authorities and society, and the reaction of citizens to the demobilization actions of the authorities is revealed.The increase in mobilization processes in 2020 indicates the existing imbalance in public relations. The increased intensity of the implementation of measures to counter protest activity leads to radicalization of online activity, the growth of apathy and social tension offline.

Currently, the development of rational technologies for processing secondary resources of the fish processing industry is of considerable interest in order to obtain a wide range of food, feed, technical, medical products and biologically active additives on their basis. Of particular interest is the technology developed by the authors for obtaining dry food fermentolizates from secondary products of cutting pink salmon and silver carp. In the course of the experiment, it was found that the protein zones for the samples are mainly represented by low-molecular weight easily digestible proteins with m. m. from 13 to 33 kDa. The evaluation of the ratio of amino acids compared to the FAO standard showed that in the human body, the amino acids of fermentolizates are able to be utilized by 68-80%, which proves their high biological value. Own experimental data indicate a high availability and degree of destruction of proteins of fermentolizates by enzymes of the human gastrointestinal tract, which is from 92.39 to 96.87%. Thus, fermentopathy from secondary cuts of fish are high-value protein products.

Plants are photosynthetic organisms that depend on sunlight for energy. Besides photosynthetically active radiation (PAR; 400-700 nm), plants are exposed to ultraviolet radiation, which consists of UV-C (below 280 nm), UV-B (280-320 nm) and UV-A (320-400 nm). Plants respond differently to exposure to low or high doses of ultraviolet light, either by stimulating protective mechanisms, or by activating recovery mechanisms to cope with various types of stress. (Research purpose) The research purpose is in providing an overview of the reactions of plants to ultraviolet radiation, make a relationship between the different ranges of ultraviolet radiation, radiation doses and the effect on plants. (Materials and methods) The article presents an analysis of domestic and foreign articles on the effectiveness of plant irradiation with ultraviolet radiation. (Results and discussion) Authors examined the effects of various ranges of ultraviolet radiation on plants. It was found that some properties of plants can be enhanced with small doses of UV-C, but UV-C strongly inhibits plant growth. Exposure to UV-B causes morphological and anatomical changes in plants: an increase in branching, a decrease in internodes, twisting of leaves, a decrease in leaf area, an accumulation of screening pigments, thickening of leaves, redistribution of chlorophyll. The effects of UV-B and UV-C also affect the volatiles emitted by aromatic plants. Ultraviolet-A can improve the nutritional qualities of green crops without adversely affecting plant growth. (Conclusions) It was found that ultraviolet radiation, depending on the range, has both a harmful effect on plants and a beneficial one. It was found that with certain doses of ultraviolet radiation, the necessary qualities and properties of plants could be obtained.

This paper investigated the overlap of carburization and diffusion saturation from liquid metal medium solutions technologies. The carburization of austhenic steel able to increase of its wear resistance and microhardness to 700HV. But this kind of treatment provided to reduction of corrosion resistance. This effect conditioned by formation of chromium carbides, herewith austenite of steel impoverished of chromium. This paper proposes the new technology lets increase the durability of asthenic steels, using carburization and diffusion saturation in eutectic Pb-Bi-Li medium with adding of nickel and chromium. The most effective technology consisted of previous carburization, diffusion saturation and final carburization. First carburization provided to increase of surface layers microhardness to 2800 MPa, diffusion saturation to 7500 MPa, the final carburization to 19500 MPa. The properties of coating depended of combination of technological impact and technological modes of every stage of technological process: temperature and duration. The temperature influenced to microhardness of coating: when the temperature increased microhardness decreased. The duration of diffusion saturation influenced to thickness of diffusion layer: when the duration increased the thickness increased too

Nanoparticles are heterologous small composites that are usually between 1 and 100 nanometers in size. They are applied in many areas of medicine with one of them being drug delivery. Nanoparticles have a number of advantages as drug carriers which include reduced toxic effects, increased bioavailability, and their ability to be modified for specific tissues or cells. Due to the exciting development of nanotechnology concomitant with advances in biotechnology and medicine, the number of clinical trials devoted to nanoparticles for drug delivery is growing rapidly. Some nanoparticles, lipid-based types, in particular, played a crucial role in the developing and manufacturing of the two COVID-19 vaccines—Pfizer and Moderna—that are now being widely used. In this analysis, we provide a quantitative survey of clinical trials using nanoparticles during the period from 2002 to 2021 as well as the recent FDA-approved drugs (since 2016). A total of 486 clinical trials were identified using the clinicaltrials.gov database. The prevailing types of nanoparticles were liposomes (44%) and protein-based formulations (26%) during this period. The most commonly investigated content of the nanoparticles were paclitaxel (23%), metals (11%), doxorubicin (9%), bupivacaine and various vaccines (both were 8%). Among the FDA-approved nanoparticle drugs, polymeric (29%), liposomal (22%) and lipid-based (21%) drugs were the most common. In this analysis, we also discuss the differential development of the diverse groups of nanoparticles and their content, as well as the underlying factors behind the trends.

Brain cancer is a formidable challenge for drug development, and drugs derived from many cutting-edge technologies are being tested in clinical trials. We manually characterized 981 clinical trials on brain tumors that were registered in ClinicalTrials.gov from 2010 to 2020. We identified 582 unique therapeutic entities targeting 581 unique drug targets and 557 unique treatment combinations involving drugs. We performed the classification of both the drugs and drug targets based on pharmacological and structural classifications. Our analysis demonstrates a large diversity of agents and targets. Currently, we identified 32 different pharmacological directions for therapies that are based on 42 structural classes of agents. Our analysis shows that kinase inhibitors, chemotherapeutic agents, and cancer vaccines are the three most common classes of agents identified in trials. Agents in clinical trials demonstrated uneven distribution in combination approaches; chemotherapy agents, proteasome inhibitors, and immune modulators frequently appeared in combinations, whereas kinase inhibitors, modified immune effector cells did not as was shown by combination networks and descriptive statistics. This analysis provides an extensive overview of the drug discovery field in brain cancer, shifts that have been happening in recent years, and challenges that are likely to come. SIGNIFICANCE STATEMENT: This review provides comprehensive quantitative analysis and discussion of the brain cancer drug discovery field, including classification of drug, targets, and therapies.

The recent trends in the world output of titanium-containing concentrates and titanium sponge – intermediate product in the production of metallic titanium – has been studied. The differences in the dynamics of these indicators have been found due to the fact that titanium-containing concentrates are used not only as raw materials for the production of titanium metal. The clusters of the world's major producers of titanium-containing concentrates and titanium sponge have been identified. The range of factors potentially influencing the titanium sponge price dynamics has been studied; the independence of this dynamics from fluctuations in supply and demand and the price of raw materials has been shown. The results of activity of JSC “Corporation VSMPO-AVISMA” were analyzed. The study shows that the main factor determining the sales profit margin of the Corporation is the dynamics of the exchange rate; a quantitative assessment of the degree of such influence has been made.

The FDA approval of imatinib in 2001 was a breakthrough in molecularly targeted cancer therapy and heralded the emergence of kinase inhibitors as a key drug class in the oncology area and beyond. Twenty years on, this article analyses the landscape of approved and investigational therapies that target kinases and trends within it, including the most popular targets of kinase inhibitors and their expanding range of indications. There are currently 71 small-molecule kinase inhibitors (SMKIs) approved by the FDA and an additional 16 SMKIs approved by other regulatory agencies. Although oncology is still the predominant area for their application, there have been important approvals for indications such as rheumatoid arthritis, and one-third of the SMKIs in clinical development address disorders beyond oncology. Information on clinical trials of SMKIs reveals that approximately 110 novel kinases are currently being explored as targets, which together with the approximately 45 targets of approved kinase inhibitors represent only about 30% of the human kinome, indicating that there are still substantial unexplored opportunities for this drug class. We also discuss trends in kinase inhibitor design, including the development of allosteric and covalent inhibitors, bifunctional inhibitors and chemical degraders.

The article considers the modern legal policy in the antimonopoly sphere in terms of the establishment and application of administrative coercion measures. The relevance of the study is determined by the fact that the effectiveness of the antimonopoly policy of the state depends on the state of development of administrative enforcement tools, since administrative enforcement measures provide prevention, suppression of anticompetitive actions, punishment of perpetrators. The aim is to determine the content, objectives of legal policy and factors that reduce the quality of its implementation in this direction. Strategic planning in the antimonopoly sphere is analyzed and critically evaluated, insufficient specification of prospects for improving administrative-preventive and administrative-preventive mechanisms, considered as key instruments of antimonopoly policy, is revealed.

The analysis of the strengths and weaknesses of the existing technologies aimed at improving the performance properties of carbide-tipped tools is presented. The results of studies into the process of diffusion metallization by titanium of a carbide-tipped tool TK type from the media of fusible liquid-metal solutions is given. The influence of titanium diffusion coatings on the durability of carbide tools is investigated. A method of providing formation on hard alloys for wear-resistant titanium high-quality functional coatings is described. The thickness of the coating varies depending on the temperature and exposure time, and ranges from 4 to 6 μm. The hardness of the coatings obtained depends on the temperature of the coating and modes of pre-carburizing, and varies from 24100 to 30000 MPa. The microstructure of the coatings is investigated. The coating consists of two layers: the coating and the transition zone, the size and hardness of which depends on the conditions of pre-carburization and modes of application of the coating. The dependence of the coatings thickness on the duration of the plates exposure in the melt, the temperature of coating composition from the coated hard alloy is investigated.

The purpose of the study is to assess the present experience of introducing information and communication technologies in the medical institutions, reveal its positive aspects, weak points and growth conditions. Methodology. For appropriate assessment, we used our own approach, including a combination of methods to get the highest reliable assessment and reasonably determine the forward-looking trend of the development and the tools for its practical implementation. Recommendations. We examined the main trends in the digitalization of the healthcare system. Also, we assessed health information technologies (HIT) used or recommended for use due to the analysis of their subject-object direction and effectiveness. We find out valuable social communication tools to minimize the cost of resources (financial, organizational, managerial) and implementation time of digitalization in healthcare. Results. The analysis reflected the need for higher attention of researchers and public authorities to the satisfaction of patients’ needs in high-quality and available medical services.

The objective of the research is to reveal and comprehend the peculiarities of the status (complex of rights of their restrictions) of the citizens in the conditions of pandemic COrona VIrus Disease-19, in particular, of the new category of minorities – people at the age of 65+ years old. The methodological base of the research is the universal, general scientific and specific scientific cognitive methods used by the legal science in the object-subject scope of cognition of the general theory of law. The process of research was focused on the comparativistics, and the historical and legal, comparative and legal, technical and other special methods of scientific cognition were applied. To estimate the situation the empiric data of the three sociological researches when questioning the dwellers of Yaroslavl Region were used. The results of the research of the comfort level of the senior citizens in the specified conditions obtained during the analysis of the legislation, and its practical application and the data of sociological researches became the conclusions that the prohibited activities do not only protect from risks but also create the new ones – intellectual, psychic and physical moments. The authors believe that as the emergency situations cannot be settled by the current pandemic, the state has to correct its regulatory and legal and managerial positions taking into account the own experience and recommendations of the specialists, including those regarding the status of a new group of minorities that is the citizens at the age of 65+ years old. The novelty of the research was stipulated by the formulated recommendations to form the optimal regulatory and legal limits of the positive discrimination of the mentioned category of citizens.

The monograph deals with legislation related to the Russian revolutionary transformation of 1917, the events of 1917 are analyzed from the point of view of theory of state and law. The main attention is paid to such aspects, which, on the one hand, seem important and relevant in the context of modern state-legal development, on the other hand, are still insufficiently investigated. For students and teachers, as well as all those interested in this issue.

In the work we presented the indicators usage of the the organism functional reserves for the objective estimation of the clinical functional conditions peculiarities and the results of patients treatment with lumbar osteochondrosis at the level of sanatorium-and-spa treatment. 120 patients were involved into the investigation. We proved that usage of “Detensor”- therapy improves the results of the complex sanatorium-and-spa treatment of the given category of patients. It allows achieving quicker regress of clinical manifestations of the disease and more expressed increase of the functional reserves of the organism.

The article represents the substantiation of application of organism functional reserve parameters for objective evaluation of clinic-functional condition and results of treatment in case of patients with neurocirculatory dystonia at rehabilitation stage. 204 patients subjected to influence of low frequency bioresonance electrotherapy (device HiTop) were studied. Course application efficiency of this method in complex rehabilitation in case of neurocirculatory dystonia was proved.

This work examines laser radiation absorption in water and blood at the wavelengths that are used in endovenous laser treatment (EVLT): 0.81–1.06, 1.32, 1.47, 1.5 and 1.56 μm. It is shown that the best EVLT conditions are ensured by 1.56-μm radiation. Analysis of published data suggests that even higher EVLT efficacy may be achieved at wavelengths of 1.68 and 1.7 μm.

The after-effect of long-term application of various doses and combinations of mineral fertilizers (NPK, N) to pine crops on sandy Al-Fe-humus podzolized podbur soils was studied in the middle taiga of Karelia, near Lake Rindozero. The pine crops established by seeding in 1962 were fertilized in 1970, 1975, 1979 and 1985. The setup was N, NPK, and control (not fertilized). By the time of the survey the sample plots were occupied by 53‑year-old pure pine stands. Thirty years after the last treatment, 10 replications of forest floor samples were taken from each 0.5 ha plot to determine the stock, and 3 soil pits were made in each plot to take samples from specific genetic horizons for chemical analysis. In the sample plots, the most significant changes compared to the control were observed in the forest floor and the underlying eluvial horizon. The productivity of the resultant pine stands was promoted considerably, especially by NPK fertilization. Statistical treatment of the data revealed a significant increase in the forest floor stock upon fertilization in all the treatments as compared to the control. Mean tree diameter and height, as well as the stands’ growing stock were enlarged.

The electrochemical reduction of N -(2-nitro-4-R-phenyl)pyridinium chlorides (R = CF 3 , CN, CO 2 Et) at a lead cathode in HCl/Pr i OH/H 2 O affords the corresponding 7-R-pyrido[1,2-a]benzimidazoles in 70–94% yields.

The electrochemical reduction of N -(2-nitro-4-R-phenyl)pyridinium chlorides (R = CF 3 , CN, CO 2 Et) at a lead cathode in HCl/Pr i OH/H 2 O affords the corresponding 7-R-pyrido[1,2-a]benzimidazoles in 70–94% yields.

Ferroelectric films in the paraelectric phase exhibit two undesirable properties: hysteresis in the voltage-capacitance characteristics and a significant relaxation time of the capacitance. Our experiments show that suppression of both of these is achieved by using ultraviolet (UV) radiation with wavelengths corresponding to the material forbidden gap. Experimentally we also observed UV radiation induced modulation of thin film permittivity without an applied electric field. The observed phenomena are believed to have the same origin: UV light causes generation of non-equilibrium charge carriers and space charge redistribution inside thin ferroelectric films.