Azolo[1,5-a]pyrimidine is one of the most promising scaffold in the development of potent anticancer agents. However, the structural motifs in such development are often limited to 5,7-substituted azolo[1,5-a]pyrimidines due to the well-known synthesis route and existing drugs (e.g., Dinaciclib) on their basis. To expand the understanding of rare substituent combinations in this research field, a new series of 7-amino-5-aryl-6-cyanoazolo[1,5-a]pyrimidines with various azole moieties were synthesized and studied on A172, Rd, Hos and HEK293 cell lines. The obtained derivatives were further modified by acylation to introduce an additional pharmacophore moiety. During the study of anticancer activity, compounds with a pronounced cytotoxic effect were found. The analysis of activity against the embryonal rhabdomyosarcoma (Rd) cell line suggested a mechanism of cytotoxic action causing a significant decrease in mitochondrial potential in neoplastic cells.

Acute radiation syndrome (ARS) results from high-dose ionizing radiation (IR) exposure, with bone marrow (BM) being highly susceptible due to its proliferative activity. BM injury causes pancytopenia, leading to infections, anemia, and bleeding. Mesenchymal stem cells (MSCs) hold promise for ARS treatment because of their immunomodulatory, anti-inflammatory, and regenerative properties. However, challenges such as replicative senescence, poor survival, and engraftment in irradiated microenvironments limit their efficacy. This study evaluated rapamycin-preconditioned placenta-derived MSCs (rPD-MSCs) in a mouse ARS model. Rapamycin was selected for preconditioning due to its ability to induce autophagy and modulate cytokine secretion. We assessed rapamycin-dependent modulation of autophagy-related genes and proteins, as well as hematopoietic cytokines secretion in PD-MSCs, and evaluated morphological changes in blood and BM at 7 and 21 days post-irradiation in ICR/CD1 mice. Preconditioning with rapamycin alters the secretion of granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), and Fms-related tyrosine kinase 3 ligand (Flt3LG) in PD-MSCs without affecting cell viability. rPD-MSCs better enhance hematopoietic recovery, restore bone marrow cellularity, and increase peripheral blood cell counts by elevating the secretion of hematopoietic cytokines compared to non-preconditioned cells. These results highlight rapamycin preconditioning as a promising strategy to enhance MSCs therapeutic potential for ARS, supporting further preclinical and clinical exploration.

Background: The etiology of acute respiratory infections includes more than 300 simultaneously circulating viruses. Identification of a specific pathogen is only possible using molecular genetic methods. Acute respiratory infections most commonly affect young children (under 6 years of age), school-age children, and adults over 65 years. In some cases, infection symptoms require hospitalization. Aim: To investigate the etiology of severe acute respiratory infections in children of different ages during the epidemic seasons of 2022–2024. Methods: A total of 646 nasopharyngeal swabs from patients hospitalized in pediatric hospitals in Yekaterinburg were examined using reverse transcription polymerase chain reaction. Specimens were collected according to approved criteria and tested for viral pathogens, including influenza A and B viruses (INFA, INFB) and other respiratory viruses included in the standard diagnostic panel. Results: Over two epidemic seasons, 646 children were examined: 267 in 2022–2023 and 379 in 2023–2024. During this time, more than 60.0% of severe acute respiratory infections were confirmed viral. In 2022–2023, influenza accounted for 52.2% of cases. In this period, influenza A(H1N1)pdm09 virus and influenza B virus were circulating. Among non-influenza viruses, respiratory syncytial virus (HRsV), rhinovirus (HRV), and bocavirus (HBoV) were identified. In the following season, most cases of severe acute respiratory infections were caused by respiratory viruses, including HRsV, HRV, and adenoviruses (HAdV). Influenza A(H3N2) virus predominated among influenza cases. Analysis of coinfections with several respiratory viruses in one patient showed that in 2023–2024 the frequency of mixed infections more than doubled. In most cases, respiratory viruses were responsible for coinfections. Conclusion: It is crucial to study the etiologic agents of respiratory infections in children that require hospitalization. This is especially relevant in the post-pandemic period of SARS-CoV-2, when circulation of other respiratory viruses, particularly influenza viruses, was suppressed.

The genomic diversity study of SARS-CoV-2 was conducted in the context of lifting the coronavirus restrictions and reopening Russia’s national borders. Objective. Identification of SARS-CoV-2 genovariants in Sverdlovsk and Chelyabinsk regions and Perm krai. Material and methods. A total of 1.127 nasopharyngeal smears from patients with a new coronavirus infection treated in Sverdlovsk and Chelyabinsk regions and Perm krai were studied by Sanger sequencing. Results. The paper demonstrates the dynamics of new coronavirus strains and its several mutations for the period from May to December 2022, using descriptive statistics. The study period was notable for Omicron predominance (~97%) with a greater number of amino acid mutations compared with that for Delta and Alpha variants. Omicron BA.2 subvariant prevailed during the study period from May to September and from October to December 2022, then BA.2 was displaced by BA.4/BA.5 subvariants. Conclusion. Molecular similarity analysis for assessment of SARS-CoV-2 showed the presence of atypical mutations at positions E484K, G485R, R408I in some samples, as well as an increase in the number of mutations between variants, especially in the receptor-binding domain RBD. According to the literature amino acid substitutions led to an S protein conformational alteration which in turn increased the affinity of RBD binding to ACE2 and resulted in a milder disease and higher contagiousness compared with earlier SARS-CoV-2 variants.

Objective. Study of the viral etiology of severe acute respiratory infections (SARI) in children hospitalized in a hospital in Yekaterinburg during the epidemic season of 2022—2023. Materials and methods. 267 clinical samples (nasopharyngeal swab) obtained from children hospitalized with symptoms of acute respiratory disease were studied. The etiology of the disease was deciphered by RT-PCR, using standard sets of reagents. The material was examined for the presence of influenza A and B viruses, as well as for viruses of non-influenza etiology. 267 individual patient records were analyzed. Results. As a result, it was found that cases of SARI were more often registered among younger children, the structure of SARI of influenza etiology was represented by influenza A(H1N1)pdm09 virus — 29.9% and influenza B virus — 20.7%, while it was found that most children were not vaccinated against influenza. The proportion of viruses of non-influenza etiology was represented by RS viruses (23.0%), rhinoviruses (9.2%) and bokaviruses (6.3%).

A genomic diversity study of SARS-CoV-2 was conducted in the context of lifting the coronavirus restrictions and reopening Russia’s national borders.