PROFESSIONAL SELF-CONSCIOUSNESS OF STUDENTS OF A PEDAGOGICAL UNIVERSITY: RESULTS OF THE RESEARCH

The article is devoted to the study of the formation of professional self-consciousness of a student - a future teacher, with an emphasis on the features of professional self-esteem as an element of professional self-consciousness. The data obtained in the article using the methods of studying professional self-esteem and professional self-knowledge allow us to pay attention to the complex procedure of entering the profession by students of a pedagogical university, passing through the crises of vocational training at 2 and 5 courses, 3rd and 4th year students are completely ready to study, work, accumulate knowledge and develop in a wider professional sense, they have a focus on self-development. The dynamics of development of students’ ideas about themselves at different stages of studying at university are shown, the emphasis is on the features of formation of professional self-esteem of  future teachers. The study opens up significant prospects for advanced training and improving the quality of students' training, taking into account the characteristics of the development of their professional self-consciousness

Unusual shift in the visible absorption spectrum of an active ctenophore photoprotein elucidated by time‑dependent density functional theory

Active hydromedusan and ctenophore Ca2+-regulated photoproteins form complexes consisting of apoprotein and strongly non-covalently bound 2-hydroperoxycoelenterazine (an oxygenated intermediate of coelenterazine). Whereas the absorption maximum of hydromedusan photoproteins is at 460–470 nm, ctenophore photoproteins absorb at 437 nm. Finding out a physical reason for this blue shift is the main objective of this work, and, to achieve it, the whole structure of the protein–substrate complex was optimized using a linear scaling quantum–mechanical method. Electronic excitations pertinent to the spectra of the 2-hydroperoxy adduct of coelenterazine were simulated with time-dependent density functional theory. The dihedral angle of 60° of the 6-(p-hydroxy)-phenyl group relative to the imidazopyrazinone core of 2-hydroperoxycoelenterazine molecule was found to be the key factor determining the absorption of ctenophore photoproteins at 437 nm. The residues relevant to binding of the substrate and its adopting the particular rotation were also identified

Evaluation of the traffic signal regulation efficiency of crossroads with unstable transport demand by time

The article describes the results of the research, whose goal is to assess the effectiveness of the traffic light operation at crossroads with unstable transport demand in terms of time and directions. The modern way of cities development consists in creation of sustainable, and, hence, safe, harmless and comfortable environment for residing. This determines the separation of urban and industrial areas, the creation of transport infrastructure, in particular crossroads, which are equipped with traffic lights. As a rule, it is characterized by unstable transport demand in the direction of entry and exit from the territory of enterprises, which causes an inadvertent increase in the idle time of vehicles in the main direction. In the course of experimental studies, the authors found that the crossroads under consideration are parts of the road network that connect the industrial and urban areas, which causes a high traffic intensity in the main areas. At the same time, the share of ineffective resolving phase for entry and exit from the territory of the enterprise reaches 70-80%, which increases the idle time of vehicles in the main direction. The authors proposed an indicator that characterizes the proportion of inefficient operation of the traffic signal

Cervical and Vaginal Microbiomes in Early Miscarriages and Ongoing Pregnancy with and without Dydrogesterone Usage

Emerging evidence suggests that the reproductive tract microbiota is a key modulator of local inflammatory and immune pathways throughout pregnancy and may subsequently impact pregnancy outcomes. In this study, our objective was to analyze the cervical and vaginal microbiomes during early pregnancy among three groups: women with healthy ongoing pregnancies, women undergoing dydrogesterone treatment, and those who experienced miscarriages. The experiment involved 51 women at 8–11 weeks of gestation. The microbiome was examined using 16S rRNA sequencing on the Ion Torrent PGM platform. Across all groups, Lactobacillus iners was predominant, suggesting that the vaginal community type CST III is common among the majority of participants. Notably, our data highlighted the significant roles of Gardnerella vaginalis and Mycoplasma girerdii in the pathogenesis of early miscarriage. Conversely, L. iners and Bifidobacterium longum have a protective effect in early pregnancy. Moreover, dydrogesterone intake appeared to influence notable differences between the cervical and vaginal microbiomes. Overall, our study enhanced our understanding of the cervical and vaginal microbiome composition in the eastern European population during early pregnancy

Lower Genital Tract Microbiome in Early Pregnancy in the Eastern European Population

Background: It is known that the features of the cervicovaginal microbiome can depend on ethnicity, which might be caused by genetic factors, as well as differences in diet and lifestyle. There is no research on the cervicovaginal microbiome of Eastern European women during early pregnancy. Methods: We evaluated the cervical and cervicovaginal microbiome of women with first-trimester pregnancy (n = 22), further delivered at term, using the 16S rRNA sequencing method. Results: The predominant bacterial species in both groups was Lactobacillus iners, followed by Prevotella copri, Ileibacterium valens, Gardnerella vaginalis and Muribaculum intestinale in the cervical samples, and Gardnerella vaginalis, Prevotella copri, Bifidobacterium longum, Ileibacterium valens and Muribaculum intestinale in the cervicovaginal samples. The cervical microbiome had higher alpha diversity; a higher abundance of Muribaculum intestinale, Aquabacterium parvum and Methyloversatilis universalis; and a lower abundance of Psychrobacillus psychrodurans. Conclusions: The Lactobacillus iners-dominated microbiome (CST III) was the predominant type of cervical and cervicovaginal microbiome in early pregnancy in the majority of the women. The presence of soil and animal bacteria in the cervicovaginal microbiome can be explained by the rural origin of patients

Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy

Rational combinations of sequence-specific inhibitors of pro-oncogenic miRNAs can efficiently interfere with specific tumor survival pathways, offering great promise for targeted therapy of oncological diseases. Herein, we uncovered the potential of multicomponent therapy by double or triple combinations of highly potent mesyl phosphoramidate (µ) antisense oligodeoxynucleotides targeted to three proven pro-oncogenic microRNAs—miR-17, miR-21, and miR-155. A strong synergism in the inhibition of proliferation and migration of B16 melanoma cells was demonstrated in vitro for pairs of µ-oligonucleotides, which resulted in vivo in profound inhibition (up to 85%) of lung metastases development after intravenous injection of µ-oligonucleotide-transfected B16 cells in mice. A clear benefit of µ-21-ON/µ-17-ON and µ-17-ON/µ-155-ON/µ-21-ON combination antitumor therapy was shown for the lymphosarcoma RLS40 solid tumor model. In vivo administration of the µ-17-ON/µ-155-ON/µ-21-ON cocktail into RLS40-bearing mice elicited fourfold delay of tumor growth as a result of strong inhibition of tumor mitotic activity. It was discovered that the cocktail of µ-21-ON/µ-17-ON/µ-155-ON led to a twofold decrease in total destructive changes in murine liver, which indicates both the reduction in toxic tumor burden and the absence of specific toxicity of the proposed therapy

The Ability of Acid-Based Natural Deep Eutectic Solvents to Co-Extract Elements from the Roots of <i>Glycyrrhiza glabra</i> L. and Associated Health Risks

The roots of licorice (Glycyrrhiza glabra L.) have been widely used in traditional and officinal medicines for the treatment of different diseases. Natural deep eutectic solvents (NADES) have become popular for the extraction of active principles from medicinal plants. However, the ability of NADES to co-extract trace elements during the isolation of target active compounds is rarely investigated. The aim of this study was to analyze the content of trace elements in acid-based NADES extracts from the roots of G. glabra and the health risks associated with them. In this study, we have tested for the first time the ability of several acid-based NADES to co-extract glycyrrhizic acid (GA) and trace elements from the roots of G. glabra. GA has been identified as the dominant phytochemical in G. glabra NADES extracts (0.145–0.495 mg/g). Due to the close pKa of lactic acid and GA, the yield of GA in lactic acid-based NADES was higher in comparison with other tested NADES. The yield of GA in NADES3-NADES5 was statistically significant and surpassed the yield of GA in water. The recovery of all elements (except Li) by all tested NADES was low (less than 6%). According to an ANOVA test, the hydrogen bond donor type plays a decisive role in the extraction of elements. A strong positive correlation between the recovery of GA and MPI was noted. The metal pollution index, hazard quotient, hazard index, and chronic daily intake were calculated and suggest that all tested NADES extracts of G. glabra roots were nontoxic and possess no health risk for both ingestion and topical application

New Hybrid Compounds Combining Fragments of Usnic Acid and Thioether Are Inhibitors of Human Enzymes TDP1, TDP2 and PARP1

Tyrosyl-DNA phosphodiesterase 1 (TDP1) catalyzes the cleavage of the phosphodiester bond between the tyrosine residue of topoisomerase 1 (TOP1) and the 3′ phosphate of DNA in the single-strand break generated by TOP1. TDP1 promotes the cleavage of the stable DNA–TOP1 complexes with the TOP1 inhibitor topotecan, which is a clinically used anticancer drug. This article reports the synthesis and study of usnic acid thioether and sulfoxide derivatives that efficiently suppress TDP1 activity, with IC50 values in the 1.4–25.2 μM range. The structure of the heterocyclic substituent introduced into the dibenzofuran core affects the TDP1 inhibitory efficiency of the compounds. A five-membered heterocyclic fragment was shown to be most pharmacophoric among the others. Sulfoxide derivatives were less cytotoxic than their thioester analogs. We observed an uncompetitive type of inhibition for the four most effective inhibitors of TDP1. The anticancer effect of TOP1 inhibitors can be enhanced by the simultaneous inhibition of PARP1, TDP1, and TDP2. Some of the compounds inhibited not only TDP1 but also TDP2 and/or PARP1, but at significantly higher concentration ranges than TDP1. Leader compound 10a showed promising synergy on HeLa cells in conjunction with the TOP1 inhibitor topotecan

Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency

The design of modified oligonucleotides that combine in one molecule several therapeutically beneficial properties still poses a major challenge. Recently a new type of modified mesyl phosphoramidate (or µ-) oligonucleotide was described that demonstrates high affinity to RNA, exceptional nuclease resistance, efficient recruitment of RNase H, and potent inhibition of key carcinogenesis processes in vitro. Herein, using a xenograft mouse tumor model, it was demonstrated that microRNA miR-21–targeted µ-oligonucleotides administered in complex with folate-containing liposomes dramatically inhibit primary tumor growth via long-term down-regulation of miR-21 in tumors and increase in biosynthesis of miR-21–regulated tumor suppressor proteins. This antitumoral effect is superior to the effect of the corresponding phosphorothioate. Peritumoral administration of µ-oligonucleotide results in its rapid distribution and efficient accumulation in the tumor. Blood biochemistry and morphometric studies of internal organs revealed no pronounced toxicity of µ-oligonucleotides. This new oligonucleotide class provides a powerful tool for antisense technology