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The Сhikungunya virus (CHIKV) is a member of the Flavivirus genus, the Flaviviridae family, and is a zoonotic arbovirus infection transmitted by Aedes mosquitoes. Chikungunya fever causes explosive epidemics involving millions of cases. There is an urgent need to develop broad-spectrum antivirals. Actual is the development of a model of screening in vitro effective drugs. To select the optimal screening conditions, a comparative analysis of cell cultures sensitivity to Сhikungunya virus, strain FN198/66 was carried out. The dynamics and level of virus accumulation at different infectious doses were estimated. It is shown that the Сhikungunya virus, strain FN198/66, well propagated in transplantable cell cultures Vero V, Сl008 Vero, BHK-21/13 and TC-17. All studied cell lines can be used to screen for effective non-specific medical defenses against Сhikungunya virus.

INTRODUCTION. Chronic inflammation in the uterine cavity is a fairly common problem in women of reproductive age, which negatively affects the state of the reproductive potential of the population. AIM. To present a scientific review of domestic and foreign literature covering modern methods and approaches of physical medicine used in the rehabilitation treatment of women with chronic endometritis. CONCLUSION. After analyzing the studied sources, we can conclude that the use of restorative medicine factors significantly expands the possibilities of treating chronic endometritis. Due to the use of complex or monotherapeutic techniques based on natural and preformed physical factors, it is possible to achieve outstanding results in restoring the morphofunctional potential of the endometrium. The main obstacle to the introduction of physical medicine approaches in practical healthcare is their low background, insufficient number of randomized studies that allows to use these methods as part of clinical recommendations. Further search and study of suitable non-drug regimens for chronic inflammation in the uterine cavity is needed, which will reduce the need for drug therapy.

Сhikungunya virus (CHIKV) is a member of the Flavivirus genus, Flaviviridae family. It belongs to the zoonotic arbovirus infections transmitted by mosquitoes of the genus Aedes. In humans, this flavivirus causes a disease known as Сhikungunya fever, etymologically related to yellow fever, dengue, West Nile, and Zika. There is no specific treatment for Сhikungunya fever, as there is no vaccine or preventive measures to date. A comparative analysis of the effectiveness of chemotherapy drugs, interferon inducers and two classes of interferon α-, β-, and γ-showed that interferon drugs effectively inhibit the reproduction of CHIKV in the Vero cell culture in a wide range of concentrations. Chemotherapy drugs Triazavirin® and Ingavirin® did not affect the reproduction of CHIKV strain FN198/66 in Vero cell culture. Ribavirin® at a concentration of 100 µg/ml almost completely suppressed the reproduction of the CHIKV virus when the drug was introduced into the culture medium both before and after infection.

Introduction. In the spa treatment of patients, especially with the pathology of the digestive system, mineral waters (MW) are widely used, the biological effect of which on the body consists of the interaction of all components. Among them, a special place is occupied by trace elements involved in enzymatic catalysis, which, during internal consumption of CF, have an effect on the neuroendocrine and immune mechanisms of the body, as well as on metabolic processes in the digestive system. However, these issues, today, remain the least studied, which was the topic of this article. The quantity and quality of food consumed are important factors that determine a person’s health and quality of life. Among the nutrients necessary for a person, vitamins and minerals play an important role. They are actively involved in the assimilation of proteins, fats and carbohydrates, the regulation of physical functions, the implementation of the growth and development of the body. Trace elements change the conformation of the substrate molecule, participate in the stabilization of the active center of enzymes, and in the transfer of electrons. Food is the only source of minerals in the body. However, most people, according to domestic and foreign literature, have their deficiency in the body. Purpose of the study. To prepare a literature review using Russian and foreign sources and to present data from modern studies on the mechanism of action of drinking MV in the gastrointestinal tract. Conclusion. In the light of the above, it is natural to use various natural mineral waters as carriers of microelements, as well as for therapeutic and prophylactic purposes in patients with various pathologies, especially in diseases of the digestive system. Currently, various modes of CF intake are used, designed for certain metabolic processes in the gastrointestinal tract, and the emphasis is mainly on the state of the acid-forming function of the stomach. At the same time, little attention is paid to the influence of the micronutrient composition of CF on various aspects of the digestive process. Since until now many questions of the use of CF, their metabolism in the gastrointestinal tract (influence on digestion, absorption, interaction with vitamins, etc.), remain open and are interpreted differently, this was the reason to once again turn to this problem.

Marburg virus (MARV) infection results in severe viral hemorrhagic fever with mortalities up to 90%, and there is a pressing need for effective therapies. Here, we established a small interfering RNA (siRNA) conjugate platform that enabled successful subcutaneous delivery of siRNAs targeting the MARV nucleoprotein. We identified a hexavalent mannose ligand with high affinity to macrophages and dendritic cells, which are key cellular targets of MARV infection. This ligand enabled successful siRNA conjugate delivery to macrophages both in vitro and in vivo. The delivered hexa-mannose-siRNA conjugates rendered substantial target gene silencing in macrophages when supported by a mannose functionalized endosome release polymer. This hexa-mannose-siRNA conjugate was further evaluated alongside our hepatocyte-targeting GalNAc-siRNA conjugate, to expand targeting of infected liver cells. In MARV-Angola-infected guinea pigs, these platforms offered limited survival benefit when used as individual agents. However, in combination, they achieved up to 100% protection when dosed 24 h post infection. This novel approach, using two different ligands to simultaneously deliver siRNA to multiple cell types relevant to infection, provides a convenient subcutaneous route of administration for treating infection by these dangerous pathogens. The mannose conjugate platform has potential application to other diseases involving macrophages and dendritic cells.

The COVID-19 virus has caused a global emergency and has attracted the attention of healthcare professionals and the public around the world. The significant increase in the number of new cases of infection with this virus demonstrates the relevance of the search for drugs that are effective against this pathogen. The aim of this work was to evaluate the antiviral efficacy of Mefloquin® against COVID-19. The antiviral efficacy of Mefloquin® against the new pandemic virus SARS-CoV-2 was studied in in vitro experiments in Vero C1008 cell culture and in vivo on Syrian golden hamsters. The results of the study revealed that the drug Mefloquine® at a concentration of 2.0 µg ml-1, when applied after infection of cells, suppresses the reproduction of the SARS-CoV-2 virus by 1.7–1.9 lg, the inhibition rate is about 99%. When using Mefloquine, pathological changes in the lung tissue were less pronounced than in the control group. 6 days after infection, it was shown that when using Mefloquine, there was a statistically significant decrease in viral load in the lungs of infected Syrian golden hamsters, with an inhibition rate of 95.5%.

Introduction. Modern therapy defines oxidative stress as one of the key links in the pathogenesis of different diseases, which makes the search for new low molecular weight antioxidants actual [1]. The widely used methods are imperfect, since they reflects reactivity of the sample under artificial conditions [2–4]. The proposed technique of using the "Ecolum" biosensor makes it possible to preserve the advantages of in vitro methods and improve the accuracy of determination through the use of biological reactions of cells [5, 6].Aim. Studying of the antiradical and antioxidant activity of 2-aminopyrroles, using in vitro methods and quantum-chemical calculations. Materials and methods. Earlier, derivatives of 2-aminopyrroles were obtained. Antiradical activity of the compounds was studied using the DPPH test (2,2-diphenyl-1-picrylhydrazyl). Antioxidant activity was evaluated on the model of oxidative stress using the «Ecolum» biosensor. The calculation data of the indices of reactivity in the approximation of the gas phase were obtained using quantum-chemical methods.Results and discussion. The antioxidant activity test indicated a higher antioxidant potential of 2a, compared to 2b. Antiradical activity test revealed a greater antiradical potential of 2b. Quantum-chemical calculations showed that 2b is characterized by a higher ionization potential, which may indicate its greater resistance to oxidation compared to 2a.Conclusion. The study of the antiradical and antioxidant activity of 2-aminopyrroles showed the importance of developing a methodology for the search for new antioxidants, because of antiradical activity test deviations, compared to living cell reactions.

In November 2020, the Armed Forces of the Russian Federation began mass immunisation of the personnel with Gam-COVID-Vac (Sputnik V), the first Russia vaccine against the new coronavirus infection (COVID-19). Thus, it became necessary to assess post-vaccination antibody levels and the duration and intensity of humoral immunity to COVID-19.The aim of the study was to investigate the immunogenicity and efficacy of Gam-COVID-Vac in military medical staff after vaccination.Materials and methods: the authors determined the presence of specific antibodies in the serum of individuals immunised with Gam-COVID-Vac (477 volunteers) and COVID-19 convalescents (73 patients), using virus neutralisation (VN), enzyme-linked immunosorbent assay (ELISA) with reagent kits by several manufacturers, and immunoblotting. The results of the study were evaluated using analysis of variance.Results: VN detected virus neutralising antibodies in 90.7% of vaccinated subjects; ELISA, in 95.4%. Both VN and ELISA showed lower antibody levels in the vaccinated over 50 years of age. ELISA demonstrated a significantly higher concentration of anti-SARS-CoV-2 spike IgG in the Gam-COVID-Vac group than in the COVID-19 convalescent group. The correlation between antibody detection results by VN and ELISA was the strongest when the authors used their experimental reagent kit for quantitative detection of virus neutralising antibodies by competitive ELISA with the recombinant human ACE2 receptor. Having analysed the time course of neutralising antibody titres, the authors noted a significant, more than two-fold decrease in geometric means of the titres three months after administration of the second vaccine component.Conclusions: the subjects vaccinated with Gam-COVID-Vac gain effective humoral immunity to COVID-19. The decrease in titres indicates the need for revaccination in 6 months.

The competitive enzyme-linked immunosorbent assay (ELISA) used for the quantification of specific antibodies, anti-D (Rho) IgGs, in human anti-D (Rho) immunoglobulin preparations relies upon the competition between anti-D antibodies in the preparation and anti-D monoclonal antibodies (mAbs) for immunochemical binding to D-antigen epitopes of the immunosorbent, human erythrocytes of the ccDEE phenotype immobilised on a solid support. The immunosorbent is prepared in-house under laboratory conditions. The certification of the International Standard (IS) for anti-D immunoglobulin included attempts to use the CCDee phenotype, which is more common (16.01%) than the ccDEE phenotype (2.16%). It is possible to use the CCDee phenotype, as long as the user adheres to the acceptance criteria for the results, developed during method validation. The aim of this study was to develop the acceptance criteria for the results of anti-D IgG quantification in human anti-D immunoglobulin preparations by the ELISA method that would allow using CCDee erythrocytes to prepare the immunosorbent should there be no erythrocytes of the ccDEE phenotype available. Materials and methods: the study used human anti-D immunoglobulin preparations; anti-D IgG–spiked samples; the IS for anti-D immunoglobulin; the reference standard (RS) for anti-D IgG–free immunoglobulin; anti-D mAbs; and erythrocytes of the CCDee, ccDEE, and ccddee phenotypes. The authors quantified anti-D IgG antibodies by the competitive ELISA. The statistical analysis used parametric and nonpar ametric tests. Results: the study demonstrated the possibility of using CCDee erythrocytes for competitive immunochemical binding with anti-D mAbs and anti-D IgG of various human anti-D immunoglobulin preparations. The suitability of the analytical procedure with the CCDee phenotype was confirmed by validation parameters: trueness, intermediate precision, linearity, selectivity, specificity, and robustness of the method and comparability of the results obtained when using the CCDee and ccDEE phenotypes. The authors developed the acceptance criteria: the relative values of anti-D IgG content in the test sample should range within ±20% of the nominal value; the coefficient of determination (R2) should be at least 0.9; the relative standard deviation (RSD, %) of three absorbance values for each concentration should not exceed 20%. Conclusions: these acceptance criteria guarantee the reliability of assay results of anti-D IgG quantification by the ELISA, which allows them to be used by specialists of control and analytical laboratories to assess the quality of human anti-D immunoglobulin preparations.

Pediatric palliative care (PPC) is a priority to improve pediatric hematology oncology (PHO) care in Eurasia. However, there are limited regional opportunities for PPC education. We describe the adaptation and implementation of a bilingual end-user Education in Palliative and End-of-Life Care (EPEC)-Pediatrics course for PHO clinicians in Eurasia.Due to COVID-19, this course was delivered virtually, consisting of prerecorded, asynchronous lectures, and a bilingual workshop with interactive lectures and small group sessions. A pre-postcourse design was used to evaluate the knowledge acquisition of the participants including their knowledge alignment with World Health Organization (WHO) guidance, ideal timing of palliative care, and comfort in providing palliative care to their patients. Questions were mostly quantitative with multiple choice or Likert scale options, supplemented by free-text responses.A total of 44 (76%) participants from 14 countries completed all components of the course including pre- and postcourse assessments. Participant alignment with WHO guidance improved from 75% in the pre- to 90% in the postcourse assessments (p 0.001). After participation, 93% felt more confident controlling the suffering of children at the end of life, 91% felt more confident in prescribing opioids and managing pain, and 98% better understood how to hold difficult conversations with patients and families. Most participants (98%) stated that they will change their clinical practice based on the skills and knowledge gained in this course.We present a successful regional adaptation of the EPEC-Pediatrics curriculum, including novel delivery of course content via a virtual bilingual format. This course resulted in significant improvement in participant attitudes and knowledge of PPC along with an understanding of the ideal timing of palliative care consultation and comfort in providing PPC to children with cancer. We plan to incorporate participant feedback to improve the course and repeat it annually to improve access to high-quality palliative care education for PHO clinicians in Eurasia.

Over the two years that have passed since the WHO announced on March 11, 2020, a pandemic of the new coronavirus disease COVID-19, more than 460 million cases of the disease have been detected in the world, of which more than five million have been fatal. During the natural evolution of the COVID-19 pathogen, dominant variants emerge that account for most new infections. The WHO constantly monitors coronavirus mutations that potentially pose an epidemiological danger. Currently, the WHO divides modified variants of the SARS-CoV-2 virus into

The outbreak of a new coronavirus disease,COVID-19, started in December 2019 in China continues to be one of the most important realities of our time influencing all spheres of human activity March 11, 2022 marks two years since the WHO declared a pandemic it is expected that the number of cases by this time may reach the mark 500 million. Taking into account the widespread spread of infection, spontaneous appearance during the natural evolution of the pathogen new highly pathogenic variants of the COVID-19 pathogen for humans the most important is the implementation of anti-epidemic measures representing a set of measures, aimed at preventing the importation and spread of infection. The purpose of the presented article is a analysis of the anti-epidemic measures carried out in the Russian Federation in the context of a COVID-19 pandemic. Anti-epidemic measures include the implementation of measures, directed towards all links of epidemic: on the source, on the transmission path and on the receptive collective. From a wide range of sanitary and anti-epidemic measures carried out nationwide (including organizational and administrative, socio-economic, isolation and quarantine and others) the development of various methods of detection and identification of the COVID-19 pathogen, methods of serodiagnostics with which you can predict indicator of herd immunity, means of prevention and treatment of the disease, means and methods of disinfection is considered. As such measures, the development of means for detecting and identifying the pathogen, means of prevention and treatment of the disease, methods of serodiagnostics, with the help of which it is possible to predict indicator of herd immunity, means and methods of disinfection are considered. An assessment of the effectiveness of the developed tools of diagnostics, prevention and treatment in relation to new variants of the SARS-CoV-2 virus was carried out. The creation of a laboratory model to study an experimental infection which increases efficiency and reliability of ongoing preclinical studies of medical protective equipment is also important.

Background The family Filoviridae consists of several virus members known to cause significant mortality and disease in humans. Among these, Ebola virus (EBOV), Marburg virus (MARV), Sudan virus (SUDV), and Bundibugyo virus (BDBV) are considered the deadliest. The sole US FDA approved filovirus vaccine, Ervebo®, is indicated only for EBOV infections with limited heterologous protection against other filoviruses. In clinical trials, Ervebo® was shown to rapidly protect humans against Ebola disease ten days plus post immunization. Whether multivalent formulations of similar recombinant vesicular stomatitis virus (rVSV)-based vaccines could likewise confer rapid protection is unclear. Methodology/Findings Here, we tested the ability of a highly attenuated, quadrivalent pan-filovirus Vesiculovax vaccine (rVSV-Filo) to elicit fast-acting protection against MARV, EBOV, SUDV, and BDBV. Groups of cynomolgus monkeys were vaccinated seven days before exposure to each of the four viral pathogens. All subjects (100%) immunized one-week prior survived MARV, SUDV, and BDBV challenge; 80% of subjects survived EBOV challenge. Survival correlated with lower viral load, higher glycoprotein-specific IgG titers, and the expression of B cell-, cytotoxic cell-, and antigen presentation-associated transcripts. Conclusions/Significance These results demonstrate multivalent Vesiculovax vaccines are suitable for filovirus outbreak management. The highly attenuated nature of the rVSV-Filo vaccine may be preferable to the Ervebo® “delta G” platform, which induced arthralgia, cutaneous vasculitis, and dermatitis in a subset of recipients.

Background The primary route of infection by Ebola virus (EBOV) and other pathogenic filoviruses in humans is through contact of contaminated body fluids with mucosal surfaces. Despite this, filoviruses hold capacity for delivery by both large and small particle artificial aerosols, and thus present potential for intentional misuse. Previous studies have shown that high doses of EBOV (≥ 1000 PFU) delivered by small particle aerosol cause uniform lethality in nonhuman primates (NHP) while only a few small studies have assessed lower doses in NHPs. Methods To further characterize the pathogenesis of EBOV infection via the small particle aerosol route, we challenged cohorts of cynomolgus monkeys with low doses (10 PFU, 1 PFU, 0.1 PFU) of EBOV variant Makona, which may help to define risks associated with small particle aerosol exposures. Results Despite using challenge doses several orders of magnitude lower than previously published studies, infection via this route was uniformly lethal across all cohorts; however, the time to death was delayed in a dose-dependent manner between aerosol-challenged cohorts, as well as in comparison to animals challenged via the intramuscular route. Here, we describe the observed clinical and pathological details including serum biomarkers, viral burden, and histopathological changes leading to death. Conclusions Our observations in this model highlight the striking susceptibility of NHPs, and by extension, likely humans, via small particle aerosol exposure to EBOV and emphasize the need for further development of rapid diagnostics and potent postexposure prophylactics in the event of intentional release via deployment of an aerosol-producing device.

The Ruddlesden–Popper (RP) layered perovskite structure is of great interest due to its inherent tunability, and the emergence and growth of the compositionally complex oxide (CCO) concept endows the RP family with further possibilities. Here, a comprehensive assessment of thermodynamic stabilization, local order/disorder, and lattice distortion was performed in the first two reported examples of lanthanum-deficient Lan+1BnO3n+1 (n = 1, B = Mg, Co, Ni, Cu, Zn) obtained via various processing conditions. Chemical short-range order (CSRO) at the B-site and the controllable excess interstitial oxygen (δ) in RP-CCOs are uncovered by neutron pair distribution function analysis. Reverse Monte Carlo analysis of the data, Metropolis Monte Carlo simulations, and extended x-ray absorption fine structure analysis implies a modest degree of magnetic element segregation on the local scale. Further, ab initio molecular dynamics simulations results obtained from special quasirandom structure disagree with experimentally observed CSRO but confirm Jahn–Teller distortion of CuO6 octahedra. These findings highlight potential opportunities to control local order/disorder and excess interstitial oxygen in layered RP-CCOs and demonstrate a high degree of freedom for tailoring application-specific properties. They also suggest a need for expansion of theoretical and data modeling approaches in order to meet the innate challenges of CCO and related high-entropy phases.

The use of neodymium-doped nanocrystalline powders of yttrium-gadolinium oxide and yttrium gadolinium garnet to increase the sensitivity of local fluorescent optical temperature sensors is considered. Based on the temperature dependences of the neodymium fluorescence spectra in this powders, univariate (using fluorescence intensity ratio from thermally coupled energy levels of the activator) and multivariate (using the partial least squares method) calibration models are developed. When using the spectral range 860 – 950 nm falling into the first biological transparency window (700 – 980 nm), both calibration models have a standard deviation of about 10 % and are comparable in accuracy. The spectral variables selection by searching combination moving window in the multivariate model made it possible to reduce the root mean square error for yttrium-gadolinium oxide by more than 12 times (from 9.8 to 0.8 °C), and for yttrium-gadolinium garnet by more than 2 times(from 8.7 to 4.0 °С). The result obtained indicatesthe proposed neodymium-doped nanocrystalline powders and multivariate methods of calibration can be used to localise areas with febrile temperatures for biological and medical purposes.

Molecular dynamics simulations were used to study deformation-induced face-centered cubic (fcc) to body-centered cubic (bcc) transformation during uniaxial compression of an 80Fe-20Ni (at%) alloy with and without precipitates. Our purpose was to better understand recent experimental results in an Fe-Ni-based medium-entropy alloy where certain precipitates were found to constrain the fcc to bcc transformation. We find that larger precipitates and smaller spacings between precipitates hinder the phase transformation by impeding relaxation of internal elastic strains. These results deconvolute the individual effects of precipitate size and spacing and help interpret the experimental results where only their combined effects could be measured. Using atomistic modelling, we investigate the individual effects of precipitate size and spacing in phase transition and help interpret the experimental results where only their combined effects could be measured.

The wind force acting on full-grown pine trees as they free fall was calculated based on comparison of the results of the field experiment and numerical simulation using Borisevich and Vikhrenko’s 2018 model. A number of improvements were proposed to increase the accuracy of the method. Field experiments of the free fall of five pine trees previously cut were carried out. Then, computer simulations of their motion assuming the linear dependence of drag force on air velocity were performed. Comparisons of the data of the field experiments and computer simulations showed that the linear dependence with a constant scaling parameter gives a good approximation of the drag force at a wide range of air velocity values. Error analysis was carried out to assess the quality of the numerical model. At all times during the movement, the deviations in the center mass positions observed in the field experiment and obtained in the numerical experiment do not exceed the diameter of the tree stem. The scaling parameter for five full-grown Scots pines (Pinus sylvestris L.) growing in stands ranged between 25.5 and 90.0 kg/s.

The existing biological models of diffuse alveolar damage (DAD) in mice have many shortcomings. To offset these shortcomings, we have proposed a simple, nonsurgical, and reproducible method of unilateral total damage of the left lung in ICR mice. This model is based on the intrabronchial administration of a mixture of bacterial lipopolysaccharide (LPS) from the cell wall of S. enterica and α-galactosylceramide (inducing substances) to the left lung.Using computer tomography of the lungs with endobronchial administration of contrast material, we have been able to perform an operative intravital verification of the targeted delivery of the inducer. The model presented is characterized by more serious and homogeneous damage of the affected lung compared to the existing models of focal pneumonia; at the same time, our model is characterized by longer animal survival since the right lung remains intact.The model is also characterized by diffuse alveolar damage of the left lung, animal survival of 100%, abrupt increases in plasma levels of TNFa, INFg, and IL-6, and significant myocardial overload in the right heart. It can be used to assess the efficacy of innovative drugs for the treatment of DAD and ARDS as the clinical manifestations that are developed in patients infected with SARS-CoV-2. Morphological patterns of lungs in the noninfectious ("sterile") model of DAD induced by LPS simultaneously with α-galactosylceramide (presented here) and in the infectious model of DAD induced by SARS-CoV-2 have been compared.The DAD model we have proposed can be widely used for studying the efficacy of candidate molecules for the treatment of infectious respiratory diseases, such as viral pneumonias of different etiology, including SARS-CoV-2.

Since the Dabie bandavirus (DBV; former SFTS virus, SFTSV) was identified, the epidemics of severe fever with thrombocytopenic syndrome (SFTS) caused by this virus have occurred in several countries in East Asia. The rapid increase in incidence indicates that this infectious agent has a pandemic potential and poses an imminent global public health threat.The analysis of molecular evolution of SFTS agent that includes its variants isolated in China, Japan and South Korea was performed in this review. The evolution rate of DBV and the estimated dates of existence of the common ancestor were ascertained, and the possibility of reassortation was demonstrated.The evolutionary rates of DBV genome segments were estimated to be 2.28 × 10-4 nucleotides/site/year for S-segment, 2.42 × 10-4 for M-segment, and 1.19 × 10-4 for L-segment. The positions of positive selection were detected in the viral genome.Phylogenetic analyses showed that virus may be divided into two clades, containing six different genotypes. The structures of phylogenetic trees for S-, M- and L-segments showed that all genotypes originate from the common ancestor.Data of sequence analysis suggest that DBV use several mechanisms to maintain the high level of its genetic diversity. Understanding the phylogenetic factors that determine the virus transmission is important for assessing the epidemiological characteristics of the disease and predicting its possible outbreaks.

Objective. Selection of indicators of lymphocyte populations in rhesus macaques determined by flow cytometry to evaluate variations of cellular constituent of their immune status.Materials and methods. Blood of 11 healthy rhesus macaque males, 2,0–2,5 years old, weighing 2,5–3,0 kg, was used. Monkeys were examined simultaneously in each of 7 months of observation (since May till November). Immunophenotyping was conducted by FC500 cytofluorimeter using Affymetrix eBioscience monoclonal antibodies. The following cellular constituent indicators of immune status were differentiated: total T lymphocytes (phenotype CD2+CD20-); total B lymphocytes (phenotype CD2-CD20+); natural killer cells (phenotype CD2+CD56+); T helper cells (phenotype CD2+CD4+); cytotoxic T lymphocytes (phenotype CD2+CD8+); double-positive T lymphocytes (phenotype CD4+CD8+) and T lymphocytes positive by antigens CD2 and CD20 (phenotype CD2+CD20+).Results and discussion. Statistical analysis of the obtained results revealed the absence of the effect of research time factor on the stated indicators. To assess changes in the cellular constituent of immune status of rhesus macaques, it is possible to use indicators that are less variable: total T and B lymphocytes, T helper cells, cytotoxic T lymphocytes and T lymphocytes with phenotype (CD2+CD20+). The use of CD56 as a marker of natural killer cells of rhesus macaques is impractical due to its low expression and a small size of the population bearing this marker. The research results may form the basis of the normative indicators of the subpopulation cell composition of immune system in rhesus macaques, which will allow the study of infected animals when assessing the quality of medical products in relation to dangerous and particularly dangerous infections.

The most effective means of combating the COVID-19 pandemic s the formation of herd immunity, with the formation of an immune population to infection. Vaccination rates are continuously increasing. In early February 2021, WHO announced that the number of people vaccinated against the disease for the first time exceeded the number of infected. In early June 2021 the vaccinated number exceeded 2 billion which is more than 12 times the total number infected for the entire duration of the pandemic. The high rate of vaccination leads to the formulation of a number of questions concerning the effectiveness of vaccines currently used for mass immunization the level of herd immunity, necessary to stop the spread of the disease, the actual duration of the vaccination carried out, long-term prospects of the platforms, used in the creation of vaccines. The purpose of this paper is to substantiate reasoned answers to the questions posed.

Ebola fever is an acute, highly contagious viral disease with a mortality rate that can reach 90%. There are currently no licensed therapeutic agents specific to Ebola in the world. Monoclonal antibodies (MAbs) with viral-neutralizing activity and high specificity to the Ebola virus glycoprotein (EBOV GP) are considered as highly effective potential antiviral drugs. Over the past decade, nanobodies (single-domain antibodies, non-canonical camelid antibodies) have found wide use in the diagnosis and treatment of various infectious and non-infectious diseases. In this study, a panel of nanobodies specifically binding to EBOV GP was obtained using recombinant human adenovirus 5, expressing GP (Ad5-GP) for alpaca (Vicugna pacos) immunization, for the first time. Based on specific activity assay results, affinity constants, and the virus-neutralizing activity against the recombinant vesicular stomatitis virus pseudotyped with EBOV GP (rVSV-GP), the most promising clone (aEv6) was selected. The aEv6 clone was then modified with the human IgG1 Fc fragment to improve its pharmacokinetic and immunologic properties. To assess the protective activity of the chimeric molecule aEv6Fc, a lethal model of murine rVSV-GP infection was developed by using immunosuppression. The results obtained in lethal model mice have demonstrated the protective effect of aEv6Fc. Thus, the nanobody and its modified derivative obtained in this study have shown potential protective value against Ebola virus.

Multivariate models were developed on the basis of raw low-resolution LIBS spectra of reference samples of lowalloy steels for calibration of the concentrations of the six chemical elements (C, Mn, Si, Cr, Ni, and Cu) that are the main technological and alloying additives. The multivariate models for the C (mean-square deviation for the tested dataset 0.06%) and Mn (0.12%) content are quantitative with sufficient accuracy for practical application, semiquantitative for Si (0.09%) and Ni (0.07%), and qualitative for Cr (0.13%) and Cu (0.08%)

The emergence of the novel henipavirus, Langya virus, received global attention earlier this month after the virus sickened over three dozen people in China. There is heightened concern henipaviruses as respiratory pathogens could spark another pandemic, most notably the deadly Nipah virus (NiV). NiV causes near annual outbreaks in Bangladesh and India and induces a highly fatal respiratory disease and encephalitis in humans. No licensed countermeasures against this pathogen exist. An ideal NiV vaccine would confer both fast-acting and long-lived protection. Recently, we reported the generation of a recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the NiV glycoprotein (rVSV-ΔG-NiVBG) that protected 100% of nonhuman primates from NiV-associated lethality within a week. Here, to evaluate the durability of rVSV-ΔG-NiVBG, we vaccinated African green monkeys (AGMs) one year prior to challenge with a uniformly lethal dose of NiV. The rVSV-ΔG-NiVBG vaccine induced stable and robust humoral responses, whereas cellular responses were modest. All immunized AGMs (whether receiving a single dose or prime-boosted) survived with no detectable clinical signs or NiV replication. Transcriptomic analyses indicated adaptive immune signatures correlated with vaccine-mediated protection. While vaccines for certain respiratory infections (e.g., COVID-19) have yet to provide durable protection, our results suggest rVSV-ΔG-NiVBG elicits long-lasting immunity.

Background Antibodies targeting envelope glycoproteins have been shown in some instances to enhance infection by subverting Fc receptor and complement function, or by directly inducing fusion with cellular membranes. The potential for antibody dependent enhancement (ADE) of infection raises concern that passive immunization with a therapeutic anti-viral antibody could increase risk of disease. As part of the nonclinical package characterizing the risk profile of the SARS-CoV-2 neutralizing monoclonal antibody bamlanivimab, studies were conducted to evaluate the potential for ADE of infection in vitro and in a non-human primate model of COVID-19. Methods In vitro assays were performed in primary human macrophage, Raji, or THP-1 cells exposed to SARS-CoV-2 in the presence of bamlanivimab ranging from approximately IC50 to more than 100-fold above or below the IC50. Samples were evaluated for demonstration of productive viral infection. Bamlanivimab binding to C1q and FcR were quantified, and activity was studied by cell-based assays. In vivo studies were performed in African green monkeys (AGM) infected with SARS-CoV-2 virus following sub-saturating or saturating doses of bamlanivimab or IgG control. Viral loads, clinical pathology, and histology endpoints were assessed to determine if bamlanivimab enhanced SARS-CoV-2 replication or clinical illness. Mixed model repeated measures were used to evaluate virology statistics. Results Bamlanivimab did not increase viral RNA production in FcγR-expressing cell lines, despite demonstration of effector function. No significant differences were found among the AGM groups in terms of weight, temperature, or food intake. Treatment with bamlanivimab reduced viral loads in nasal and oral swabs and BAL fluid relative to control groups. Viral antigen was not detected in lung tissue from animals treated with the highest dose of bamlanivimab. Microscopic findings along with decreases in viral loads in bamlanivimab-treated animals indicated that ADE of disease was not observed in this study. Conclusions Sub-saturating doses of bamlanivimab treatment do not induce ADE of SARSCoV2 infection in either in vitro or an AGM model of infection. Findings suggest that high affinity monoclonal antibodies pose a low risk of mediating ADE in patients and further supports their safety profile as a treatment of COVID-19 disease.

The most common nematode in rabbits is passalurosis, and climate change in Ukraine in recent decades has altered the epizootic manifestation of this parasitosis, which predetermines the relevance of this study. Therefore, the purpose of this paper was to establish the epizootic situation regarding the passalurosis invasion and to investigate the pathological and histological changes in both the large and small intestines of rabbits with a high degree of damage by Passalurus ambiguus. The study used the McMaster method, the improved method of incomplete helminthological dissection according to K.I. Scriabin Private households in the Polissia zone of Ukraine were found to be the most vulnerable in terms of passalurosis infestation, where 37.70-41.67% of sick rabbits were registered. In the seasonal aspect, the highest infection of animals was found in winter (invasion extensiveness (IE) was 35.27%), with a peak in January (IE = 35.29%), the lowest – in summer (IE = 25.79%). Rabbits aged 1 to 2 years had the highest incidence of the pathogen Passalurus ambiguus (82.76%). It was found that with a high degree of damage (invasion intensiveness (II) – 2446.67 ± 422.11 eggs in 1 g of faeces) rabbits with passalurosis had catarrhal and catarrhal-haemorrhagic inflammation, swelling of the mucous membrane of the intestines with dotted or striped haemorrhages. The destruction of the villi of the mucous membrane of the small, caecum, and colon, crypt cells and infiltration by lymphocytes and monocytes, severe swelling of the submucosal base and muscle membrane, and a state of granular dystrophy of all smooth muscle cells of the muscle membrane were established. The detection of seasonal, age-related, and pathological-histological changes in rabbits with passalurosis will allow controlling the degree of infection of animals and promptly taking effective countermeasures, which predetermines the practical value of this study

WHO has declared the outbreak of monkeypox as a public health emergency of international concern. In less than three months, monkeypox was detected in more than 30 000 people and spread to more than 80 countries around the world. It is believed that the immunity formed to smallpox vaccine can protect from monkeypox infection with high efficiency. The widespread use of Vaccinia virus has not been carried out since the 1980s, which raises the question of the level of residual immunity among the population and the identification of groups requiring priority vaccination. We conducted a cross-sectional serological study of remaining immunity among Moscow residents. To do this, a collection of blood serum samples of age group over 30 years old was formed, an in-house ELISA test system was developed, and a virus neutralization protocol was set up. Serum samples were examined for the presence of IgG antibodies against Vaccinia virus (n=2908), as well as for the ability to neutralize plaque formation with a Vaccinia virus MNIIVP-10 strain (n=299). The results indicate the presence of neutralizing antibody titer of 1/20 or more in 33.3 to 53.2% of people older than 45 years. Among people 30-45 years old who probably have not been vaccinated, the proportion with virus neutralizing antibodies ranged from 3.2 to 6.7%. Despite the higher level of antibodies in age group older than 66 years, the proportion of positive samples in this group was slightly lower than in people aged 46-65 years. The results indicate the priority of vaccination in groups younger than 45, and possibly older than 66 years to ensure the protection of the population in case of spread of monkeypox among Moscow residents. The herd immunity level needed to stop the circulation of the virus should be at least 50.25 – 65.28%.

Ebola outbreak in eastern parts of the Democratic Republic of the Congo in 2018–2020 proved that the virus remains highly hazardous for humans, and the outbreak in West Africa in 2014–2016, which was the largest Ebola outbreak in history, showed that it could be imported to other continents, including Russia. In 1993 the Federal State Budgetary Institution “48th Central Scientific Research Institute” of the Russian Ministry of Defence developed a specific equine immunoglobulin for emergency prophylaxis of Ebola in risk groups. The evaluation and improvement of the product’s properties is an important area in the development of biological defence technologies.The aim of the studywas to examine the properties of the equine anti-Ebola immunoglobulin which had been stored for a long time at 2–8 °C.Materials and methods:the authors studied batches of heterologous anti-Ebola immunoglobulin that had been stored for 17–22 years. The properties of the product were evaluated according to the requirements of the State Pharmacopoeia of the Russian Federation, 14th ed. (Ph. Rus. 14 ed.). The specific activity of the product was determined in a plaque reduction neutralisation test using Ebola virus and African green monkey kidney cells (GMK-AH-1(D)). Immunoglobulin molecular parameters were determined by size-exclusion high-performance liquid chromatography using the test methods described in the European Pharmacopoeia 9.6 and Ph. Rus. 14 ed.Results:the storage of anti-Ebola immunoglobulin for 17–22 years at 2–8 °C resulted in a four-fold reduction of the level of virus-neutralising antibodies against Ebola, decrease in the proportion of monomers from 98 to 74–90%, increase in the proportion of dimers and polymers, and formation of immunoglobulin molecules’ fragments. Signs of toxicity for mice were observed in one of the three product batches.Conclusions:the obtained results suggest the need to perform more studies to test the quality of antiEbola immunoglobulin batches that were stored for shorter periods of time in order to assess the stability of their initial characteristics.

Reducing the dimensions of ferroelectric materials down to the nanoscale has strong implications on the ferroelectric polarization pattern and on the ability to switch the polarization. As the size of ferroelectric domains shrinks to the nanometer scale, the heterogeneity of the polarization pattern becomes increasingly pronounced, enabling a large variety of possible polar textures in nanocrystalline and nanocomposite materials. Critical to the understanding of fundamental physics of such materials and hence their applications in electronic nanodevices is the ability to investigate their ferroelectric polarization at the nanoscale in a nondestructive way. We show that contact Kelvin probe force microscopy cKPFM combined with a k means response clustering algorithm enables to measure the ferroelectric response at a mapping resolution of 8 nm. In a BaTiO3 thin film on silicon composed of tetragonal and hexagonal nanocrystals, we determine a nanoscale lateral distribution of discrete ferroelectric response clusters, fully consistent with the nanostructure determined by transmission electron microscopy. Moreover, we apply this data clustering method to the cKPFM responses measured at different temperatures, which allows us to follow the corresponding change in the polarization pattern as the Curie temperature is approached and across the phase transition. This work opens up perspectives for mapping complex ferroelectric polarization textures such as curled swirled polar textures that can be stabilized in epitaxial heterostructures and more generally for mapping the polar domain distribution of any spatially highly heterogeneous ferroelectric materials

The review considers the relevant aspects of laboratory diagnosis of rabies. The methods of laboratory diagnostics of rabies infection, standardized by WHO in 2018, and their use in the Russian Federation are presented. The scheme of laboratory diagnostics of rabies, applied by specialists of the “48th CRI” of the Ministry of Defense of Russia, for the study of biological samples from deceased people is outlined. Between 2002 and 2018, the study of biomaterial was carried out using molecular-biological, virological methods of diagnosis and in some cases electron microscopy, which allowed to detect and identify the pathogen in 257 samples from 71 people, to certify and deposit new isolates of the rabies virus. Accumulation and analysis of the lessons learned in the application of molecular-biological method of rabies diagnosis allows us to recommend the use of RT-PCR, real-time RT-PCR sets (having a certificate of state registration) in healthcare and veterinary medicine practice to identify the causative agent of rabies infection. The use of molecular-biological methods is promising in terms of the development of rabies diagnosis to improve epidemiological surveillance and raise the efficiency of the biological protection of the population of the Russian Federation.

Single-phase high- and medium-entropy alloys with face-centred cubic (fcc) structure can exhibit high tensile ductility1,2 and excellent toughness2,3, but their room-temperature strengths are low1–3. Dislocation obstacles such as grain boundaries4, twin boundaries5, solute atoms6 and precipitates7–9 can increase strength. However, with few exceptions8–11, such obstacles tend to decrease ductility. Interestingly, precipitates can also hinder phase transformations12,13. Here, using a model, precipitate-strengthened, Fe–Ni–Al–Ti medium-entropy alloy, we demonstrate a strategy that combines these dual functions in a single alloy. The nanoprecipitates in our alloy, in addition to providing conventional strengthening of the matrix, also modulate its transformation from fcc-austenite to body-centred cubic (bcc) martensite, constraining it to remain as metastable fcc after quenching through the transformation temperature. During subsequent tensile testing, the matrix progressively transforms to bcc-martensite, enabling substantial increases in strength, work hardening and ductility. This use of nanoprecipitates exploits synergies between precipitation strengthening and transformation-induced plasticity, resulting in simultaneous enhancement of tensile strength and uniform elongation. Our findings demonstrate how synergistic deformation mechanisms can be deliberately activated, exactly when needed, by altering precipitate characteristics (such as size, spacing, and so on), along with the chemical driving force for phase transformation, to optimize strength and ductility. Increased strength and ductility in a medium-entropy alloy of Fe, Ni, Al and Ti is demonstrated using nanoprecipitates that simultaneously hinder phase transformation and block dislocation motion.

The article discusses the influence of temperature and type of vegetable oil on the rate of its thermal oxidation when deep-fried. To determine the degree of thermal oxidation of oils, the spectroscopic method was used; the measurements were carried out in the range from 200–250 nm. The issue of the safety of oils in the fast food system is considered.

The synthesis of the products of the 1,3-propanesultone ring opening during its interaction with amides of pyridinecarboxylic acids has been carried out. The dependence of the yield of the reaction products on the position (ortho-, meta-, para-) of the substituent in the heteroaromatic fragment and temperature condition was revealed. In contrast to the meta- and para-substituted substrates, the reaction involving ortho-derivatives at the boiling point of methanol unexpectedly led to the formation of a salt. On the basis of spectroscopic, X-Ray, and quantum-chemical calculation data, a model of the transition-state, as well as a mechanism for this alkylation reaction of pyridine carboxamides with sultone were proposed in order to explain the higher yields obtained with the nicotinamide and its N-methyl analog compared to ortho or meta parents. Based on the analysis of ESP maps, the positions of the binding sites of reagents with a potential complexing agent in space were determined. The in silico evaluation of possible biological activity showed that the synthetized compounds revealed some promising pharmacological effects and low acute toxicity.

Phase equilibria in the ethylene carbonate (EC)–sulfolane (SL) binary system were investigated using differential scanning calorimetry in a temperature range from –150 to +50°C to construct a phase diagram of the system. The EC–SL system belongs to a simple eutectic type, with a eutectic point of –16°C at 70 wt % of SL. It was noted that the EC-SL solutions have a tendency to supercooling in the composition range from 50 to 75 wt % of SL; the metastable liquid phase is characterized by a glass transition temperature Tg = –105°C. Reaching of an equilibrium state is hindered in the middle region of compositions; this can be explained in terms of strong dipole-dipole interactions between EC and SL molecules, whose intensity increases with decreasing temperature. Quantum-chemical calculations of the Gibbs energy of the formation of isolated dimers of various types, performed by the M052X method based on density-functional theory, confirm this assumption.

Introduction . The pandemic spread of a new coronavirus infection, COVID-19, has caused a global emergency and attracted the attention of public health professionals and the population of all countries. A significant increase in the number of new cases of SARS-CoV-2 infection demonstrates the urgency of finding drugs effective against this pathogen. The aim of this work was to evaluate the in vitro antiviral efficacy of human recombinant alpha-2b interferon (IFN-α2b) against SARS-CoV-2 virus. Material and methods . The experiments had been carried out on Vero Cl008, the continuous line of African green monkey ( Chlorocebus sabaeus ) kidney cells. The effectiveness of the drugs was assessed by the suppression of viral reproduction in vitro . The biological activity was determined using titration of a virus-containing suspension in a Vero Cl008 cell culture by the formation of negative colonies. Results . The antiviral efficacy of the IFN-α2b-based medications, which have a high safety profile and proven efficacy in the prevention and treatment of influenza and acute respiratory viral infections (ARVI), has been studied against the new pandemic SARS-CoV-2 virus in vitro experiments in Vero C1008 cell culture. IFN-α2b effectively inhibits the reproduction of the virus when applied both 24 hrs before and 2 hrs after infection. In the IFN-α2b concentration range 10 2 –10 6 IU/ml a complete suppression of the reproduction of the SARS-CoV-2 virus had been demonstrated. Discussion . IFN-α2b demonstrated in vitro high antiviral activity against SARS-CoV-2. In addition, the substance has a high chemotherapeutic index (>1000). Conclusion . Medications for intranasal use based on IFN-α2b have high antiviral activity and are promising drugs for in vivo study in terms of prevention and treatment of COVID-19.