3-aryl-4H-chromene-4-ones as Antineoplastic Agents for the Treatment of Cancer

Isoflavonoids or pharmaceutically acceptable salts thereof or pharmaceutically acceptable compositions thereof for the treatment of prostate cancer or for the treatment or inhibition of prostate cancer metastasis in a patient in need thereof are disclosed

Cytisine-Linked Isoflavonoid Antineoplastic Agents for the Treatment of Cancer

Cytisine-linked isoflavonoids, or pharmaceutically acceptable salts thereof or pharmaceutically acceptable compositions thereof, are useful for the treatment of conditions in which cells have a reliance on peroxisomal HSD17B4 to degrade very long chain fatty acids and provide necessary energy for cell proliferation, such as is seen in colorectal cancer and prostate cancer, for example

Health-Saving Competence of Future Primary School Teachers: Indicators of Development

Дослідження виявило зростаючий інтерес науковців до проблеми формування здоров’язбережувальної компетентності майбутніх учителів початкових класів. Ця тенденція зумовлена необхідністю проведення соціального дослідження, щоб модернізувати підготовку майбутніх освітян, удосконалити окремі сфери. Автори досліджень розробили експериментальний тест на формування здоров’язбережувальної компетентності майбутніх учителів початкових класів. Досягнення цієї мети передбачає аналіз стану розвитку проблеми в педагогічній теорії та практиці. Дослідження систематизує життєві навички фізичного, соціального та психічного здоров'я, які сприяють формуванню здоров’язбережувальної компетентності людини. У результаті дослідження була розроблена система діагностики для визначення здоров’язбережувальної компетентності майбутніх учителів початкових класів. Аналіз науково-педагогічних джерел дав змогу виявити такі структурні компоненти підготовки до організації оздоровчої діяльності молодших школярів, як мотиваційні, змістові та технологічні. Мотиваційний компонент оцінювався за критерієм позитивного ставлення до організації здоров’язбережувальної компетентності молодших школярів та формування системи внутрішніх мотивів (інтересів, цінностей, переконань). Знання теоретичного блоку діагностували за допомогою тестів, що включали завдання з виявлення рівня засвоєння інформації про сутність здоров’язбережувальної компетентності дітей. Здатність розробляти власні варіанти педагогічних оздоровчих технологій для збереження здоров’я молодших школярів оцінювали за допомогою творчих завдань.The research revealed an increasing interest of scientists to the problem of formation of health-saving competence of future primary school teachers. This tendency is due to the need for a social inquiry to modernize the training of future educators, to improve the individual areas. The authors of research developed an experimental test of the formation of health-saving competency of future primary school teachers. Achieving this goal involves the analysis of the state of development of a particular problem in pedagogical theory and practice. The study systematizes the physical, social and mental health life skills that contribute to the formation of a person’s health-saving competence. As a result of the study, a diagnostic system was developed to determine the health-saving competency of future primary school teachers. The analysis of scientific and pedagogical sources made it possible to identify such structural components of students’ preparation for the organization of health-saving activities of younger students as motivational, content, and technological ones. The motivational component was assessed according to the criterion of students’ positive attitude towards the organization of health-saving competence of younger students and the formation of a system of internal motives (interests, values, beliefs). Knowledge of the theoretical block was diagnosed with the help of tests that included the task of identifying the level of mastery of information about the essence of health-saving competence of children. The ability to develop their own variants of pedagogical health technologies for preserving younger students was assessed with the help of the creative tasks

Trauma-informed training as a means of stabilizing the negative impact of stressful and destructive factors of war on the inner world of future specialists

Aim: To determine the conditions for the implementation of trauma-informed training as a means of stabilizing the negative impact of stressful and destructive factors of war on the inner world of future specialists. Materials and Methods: 1,100 students studying in the conditions of martial law took part in the experimental work. Results: As a result of the negative impact of the stressful and destructive factors of the war on the inner world, the future specialists the following manifestations of the deterioration of the health were established: depression (99%), sudden change of mood (92%), worsening of well-being during sudden changes in the weather (66%), irritability (52%), aggressiveness (11%), anger (7%). It was found that future specialists wanted to postpone completing the educational task until later, as they perceived it as very difficult (79%). Conclusions: The conditions for the implementation of trauma-informed studying were formulated as a means of stabilizing the negative impact of stressful and destructive factors of war on the inner world of future specialists. 1. During the organization of learning, teachers take into account the fact that psycho-traumas, which are caused by stressful and destructive factors of war, disturb students until they experience them. 2. Teachers take into account the traumatic experience of future specialists. 3. The teachers’ actions aim to restore future professionals’ sense of security, reestablish contact with other study participants, and regain control over their own lives and studies

XIV Міжнародна конференція з математичної, природничо-наукової та технологічної освіти

This paper represents a preface to the Proceedings of the XIV International Conference on Mathematics, Science and Technology Education (ICon-MaSTEd 2022) held at the Kryvyi Rih State Pedagogical University, Ukraine, 18-20 May 2022. Background information and the organizational structure of the meeting, proceedings structure, and acknowledgments of the contributions of the many people who made the conference a success are presented.Ця робота є передмовою до збірника матеріалів XIV Міжнародної конференції з математичної, природничо-наукової та технологічної освіти (ICon-MaSTEd 2022), що відбулася у Криворізькому державному педагогічному університеті, Україна, 18-20 травня 2022 року. Представлено довідкову інформацію та організаційну структуру зустрічі, структуру збірника матеріалів, а також визнання внеску багатьох людей, які зробили конференцію успішною

XIII Міжнародна конференція з математичної, природничонауково та технологічної освіти

This paper represents a preface to the Proceedings of the XIII International Conference on Mathematics, Science and Technology Education (ICon-MaSTEd 2021) held at the Kryvyi Rih State Pedagogical University, Ukraine, 12–14 May 2021. Background information and the organizational structure of the meeting, paper overview and acknowledgments of the contributions of the many people who made the conference a success are presented.Цей документ є передмовою до матеріалів XIII Міжнародної конференції з математичної, природознавчої та технологічної освіти (ICon-MaSTEd 2021), що відбулася у Криворізькому державному педагогічному університеті, Україна, 12–14 травня 2021 р. Довідкова інформація та організаційна структура представлено зустріч, огляд документів та подяки за внесок багатьох людей, які зробили конференцію успішною

Semisynthetic Aurones Inhibit Tubulin Polymerization at the Colchicine-Binding Site and Repress PC-3 Tumor Xenografts in Nude Mice and Myc-Induced T-ALL in Zebrafish

Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the leading, biologically active analogs were (Z)-2-((2-((1-ethyl-5-methoxy-1H-indol-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-6-yl)oxy)acetonitrile (5a) and (Z)-6-((2,6-dichlorobenzyl)oxy)-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (5b) that inhibited in vitro PC-3 prostate cancer cell proliferation with IC50 values below 100 nM. A xenograft study in nude mice using 10 mg/kg of 5a had no effect on mice weight, and aurone 5a did not inhibit, as desired, the human ether-à-go-go-related (hERG) potassium channel. Cell cycle arrest data, comparisons of the inhibition of cancer cell proliferation by aurones and known antineoplastic agents, and in vitro inhibition of tubulin polymerization indicated that aurone 5a disrupted tubulin dynamics. Based on molecular docking and confirmed by liquid chromatography-electrospray ionization-tandem mass spectrometry studies, aurone 5a targets the colchicine-binding site on tubulin. In addition to solid tumors, aurones 5a and 5b strongly inhibited in vitro a panel of human leukemia cancer cell lines and the in vivo myc-induced T cell acute lymphoblastic leukemia (T-ALL) in a zebrafish model

Design methodology for immersive educational resources

Based on the analysis of sources on the problem of research, the article defines types of electronic educational resources (EER), general requirements for them, focuses on didactic and methodological requirements and existing holistic systems of psychological and pedagogical requirements for EER, presents the main types of parameters that can be used to evaluate the quality of EER, analyzes the typical structure of EER and characterizes its components. The analysis of approaches to defining the concepts of ``immersiveness'', ``immersive educational environment'', ``immersive approach in education'', ``immersive educational resources'' (IER) was carried out, on the basis of which the relationship between the virtual environment and immersive learning environment was determined, the pedagogical aspects of learning in immersive environments were considered, the classification of IER was made. The main components of IER design and implementation are analyzed, and the essence of IER design and IER design methodology is determined.In the main part of the proposed general model of the methodology of IOR design and analyzed the goals, subjects of methods, stages, and content of training, forms of organization of the educational process, methods, teaching tools, and predicted results of the methodology.In the conclusion the elements of the methodology of IЕR design are presented, in particular, a complex IЕR in the form of a distance learning course, examples of designing prototypes of immersive teaching materials, etc. are considered.Based on the analysis of sources on the problem of research, the article defines types of electronic educational resources (EER), general requirements for them, focuses on didactic and methodological requirements and existing holistic systems of psychological and pedagogical requirements for EER, presents the main types of parameters that can be used to evaluate the quality of EER, analyzes the typical structure of EER and characterizes its components. The analysis of approaches to defining the concepts of ``immersiveness'', ``immersive educational environment'', ``immersive approach in education'', ``immersive educational resources'' (IER) was carried out, on the basis of which the relationship between the virtual environment and immersive learning environment was determined, the pedagogical aspects of learning in immersive environments were considered, the classification of IER was made. The main components of IER design and implementation are analyzed, and the essence of IER design and IER design methodology is determined.In the main part of the proposed general model of the methodology of IOR design and analyzed the goals, subjects of methods, stages, and content of training, forms of organization of the educational process, methods, teaching tools, and predicted results of the methodology.In the conclusion the elements of the methodology of IЕR design are presented, in particular, a complex IЕR in the form of a distance learning course, examples of designing prototypes of immersive teaching materials, etc. are considered

Discovery and Development of Small-Molecule Inhibitors of Glycogen Synthase

The overaccumulation of glycogen appears as a hallmark in various glycogen storage diseases (GSDs), including Pompe, Cori, Andersen, and Lafora disease. Accumulating evidence suggests that suppression of glycogen accumulation represents a potential therapeutic approach for treating these GSDs. Using a fluorescence polarization assay designed to screen for inhibitors of the key glycogen synthetic enzyme, glycogen synthase (GS), we identified a substituted imidazole, (rac)-2-methoxy-4-(1-(2-(1-methylpyrrolidin-2-yl)ethyl)-4-phenyl-1H-imidazol-5-yl)phenol (H23), as a first-in-class inhibitor for yeast GS 2 (yGsy2p). Data from X-ray crystallography at 2.85 Å, as well as kinetic data, revealed that H23 bound within the uridine diphosphate glucose binding pocket of yGsy2p. The high conservation of residues between human and yeast GS in direct contact with H23 informed the development of around 500 H23 analogs. These analogs produced a structure–activity relationship profile that led to the identification of a substituted pyrazole, 4-(4-(4-hydroxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)pyrogallol, with a 300-fold improved potency against human GS. These substituted pyrazoles possess a promising scaffold for drug development efforts targeting GS activity in GSDs associated with excess glycogen accumulation