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According to the recent studies bezylcarboxamide fragment attached to the thiophene ring of thieno[2,3-d]pyrimidine is beneficial for antimicrobial activity of the compounds. Therefore we focused our efforts on constructing of the simple molecules such as N-(benzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides to get deeper insight into their antimicrobial activity. As the optimal procedure for preparation of target compounds we choose 1,1’-carbonyldiimidazole promoted interaction of 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid with the series of substituted benzyl amines. The obtained amides showed good activity against the strains of S. aureus and B. subtilis, which was higher for the derivative without substituents in benzene ring or the compounds with small substituents like methyl or methoxyl groups in the para-position of the benzene ring. Docking studies showed that despite the good values of the scoring functions, the conformational analysis of the ligands’ poses in the active site revealed their ability for only partial inhibition of TrmD of P. aeruginosa.

According to the World Journal of Gastroenterology, more than 5 million people worldwide suffer from inflammatory bowel disease. The use of phytotherapeutic remedies in treatment of chronic inflammatory processes can be an effective alternative in patient’s therapy. The advantage of herbal medicines is the ability to influence various links of pathogenesis, lack of addiction, and the absence of withdrawal syndrome with long-term use in chronic pathology. In order to develop a new combined remedy with anti-inflammatory activity for the treatment of colitis, thirteen herbs, which are used in official or traditional medicine in inflammatory processes, were selected among the Ukrainian flora members. To select the most promising drugs and optimize further pharmacological research, molecular docking of the main active substances of the selected herbs to the fundamental pro-inflammatory enzymes – lipoxygenase-5 (LOX-5) and cyclooxygenase-2 (COX-2) – was carried out. Native inhibitors AKBA and celecoxib, respectively, were used as the reference ligands. The selection of candidate structures for in silico research was carried out according to the bibliosemantic research and logical-structural analysis concerning anti-inflammatory effect of the substances, which are part of chemical composition of the selected herbs. Molecular docking results have shown a high affinity level for the active site of the LOX-5 inhibitor gallotannin, quercetin, inulin, sitosterine, and moderate for ellagic acid. High affinity level for the active site of the COX-2 inhibitor was found for inulin, quercetin, gallotannin, ellagic acid and urticin A, moderate one – for gallic acid. For the further pharmacological in vitro and in vivo studies for anti-inflammatory activity, medicinal herbs with the highest content of the mentioned compounds were selected: Inula helenium, Cichorium intybus, Capsella bursa-pastoris, Foeniculum vulgare, Equisetum arvense, Veronica officinalis. Besides, it is recommended to use aqueous extracts of the selected herbs for the further pharmacological studies.

Aim. To synthesize, study the antimicrobial activity and suggest antimicrobial activity mechanism for the novel derivatives of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one. Results and discussion. As the result of the targeted modification of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]-pyrimidin-4(3H)-one in position 3 with acetamide and 1,2,4-oxadiazol-5-ylmethyl substituents, the compounds, which demonstrated better antimicrobial activity in the agar well diffusion assay than the reference drug Streptomycin, were obtained. To elucidate the mechanism of action of the novel compounds, the docking studies were conducted to the active site of the 16S subunit of ribosomal RNA, the proven target for aminoglycoside antibiotics, as well as tRNA (Guanine37-N1)-methyltransferase (TrmD), which inhibitors were considered as a new potential class of antibiotics. Experimental part. By the interaction of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one with a series of N-arylchloroacetamides and 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles in DMF in the presence of K2CO3 the target compounds were obtained. The antimicrobial activity was assessed by the agar well diffusion method. The concentration of microbial cells was determined by the McFarland standard; the value was 10^7 cells in 1 mL of the media. The 18–24 hour culture of microorganisms was used for tests. For the bacteria cultivation, Müller-Hinton agar was used, Sabouraud agar was applied for C. albicans cultivation. The compounds were tested as the DMSO solution with the concentration of 100 µg/mL; the volume of the solution was 0.3 mL, the same volume was used for Streptomycin (the concentration 30 µg/mL). The docking studies were performed using Autodock Vina. Crystallographic data for the complexes of Streptomycin with the 16S subunit of ribosomal RNA (1NTB) and its active site, as well as for tRNA (Guanine37-N1)-methyltransferase (EC 2.1.1.228; TrmD) (5ZHN) and its active site were obtained from the Protein Data Bank. Conclusions. It has been determined that 2-[6-(1H-benzimidazol-2-yl)-5-methyl-4-oxothieno[2,3-d]pyrimidin-3(4H)-yl]-N-[4-(ethoxy)phenyl]acetamide, which is the most active as an antimicrobial agent among the compounds tested, also shows the best binding activity towards the active site of tRNA (guanine37-N1)-methyltransferase.

Introduction: The search for new anticonvulsants for epilepsy treatment with higher efficacy and better tolerability remains important. The aim of the present research was an in silico and in vivo pharmacological study of N-(3,4-dimethoxyphenyl)-2-((2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)thio)acetamide (Epirimil) as a promising anticonvulsant. Materials and methods: A 1H and 13C NMR spectroscopy, LS/MS, and an elemental analysis were used to determine Epirimil structure. An ADMET analysis, as well as a docking study using anticonvulsant biotargets, e.g.: GABAAR, GABAAT, CA II, NMDAR, and AMPAR, was carried out. Anticonvulsant activity was proved, using PTZ- and MES-induced seizures in rats and mice, and neurotoxicity was determined using a rotarod test. Influence of Epirimil on the psycho-emotional state of the laboratory animals was determined by an open field test. Results and discussion: A synthesis method of a promising anticonvulsant Epirimil was modified. The calculated ADMET parameters and a molecular docking into the active sites of anticonvulsant biotargets allowed evaluating the research prospects and predicting possible mechanisms for implementing anticonvulsant activity. A prominent anticonvulsant activity of Epirimil was established using in vivo studies on the model of PTZ-induced seizures in rats and MES-induced seizures in mice. In terms of toxicity, Epirimil belongs to class IV – low toxic substances. The open field test showed that Epirimil had almost no effect on the animals’ behavioral responses: it neither changed their psycho-emotional activity, nor increased their anxiety level. ED50, TD50 and protective index of Epirimil according to its anticonvulsant activity were calculated. Conclusion: The obtained experimental results substantiate the prospects of N-(3,4-Dimethoxyphenyl)-2-((2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)thio)acetamide as a promising active pharmaceutical ingredient having a multifactor mechanism of anticonvulsant activity. Graphical abstract

6-Heteryl-5-methylthieno[2,3-d]pyrimidin-2,4(1H,3H)-diones are of great interest as the promising objects for the search of antibacterials. In this communication, we obtained 6-(imidazo[1,2-a]pyridin-2-yl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione by interaction of 6-(bromoacetyl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione with 2-aminopyridine. The obtained heterocyclic hybrid was further modified by alkylation with 2-chloroarylacetamides. Antimicrobial activity studies for the synthesized compounds using the agar well diffusion method revealed their moderate activity against S. aureus, E. coli and B. subtilis. According to the double dilution assay MIC value results for 6-(imidazo[1,2-a]pyridin-2-yl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneagainst P. aeruginosa was less than the value determined for the reference drug streptomycin. The docking study of the synthesized compounds to the active site of TrmD isolated from P. aeruginosa did not show their effective inhibitory activity.

Introduction: The virtual target-oriented screening is a necessary stage of modern drug-design. In the present study, the affinity of pyridazine derivatives for the most promising antiparkinsonian biotargets – I–III groups of metabotropic and ionotropic NMDA-glutamate receptors – was evaluated. Materials and methods: Docking of the studied ligands to the active sites of biotargets – mGluR5, mGluR3, mGluR8, NMDA GluN2B – was performed using AutoDockVina. Base of the preparation of ligands and proteins – AutoDockTools-1.5.6. A Discovery Studio Visualizer 2017/R2 was used to visualize the interpretation of the results. Results and discussion: A high degree of the affinity is predicted for group III of the metabotropic mGlu8 receptors – binding energy from -5.0 to -8.7 kcal/mol, compared to -6.1 kcal/mol of that of the reference drug (L-AP4), as well as for the ionotropic NMDA GluN2B receptors –binding energy from -8.7 to -11.6 kcal/mol, compared to -11.3 kcal/mol of that of ifenprodil. Conclusion: The prospects of the searching for glutamate receptor modulators in a number of n-substituted 4-methoxy-6-oxo-1-aryl-pyridazine-3-carboxamide derivatives are proved. Some aspects of the structure-affinity relationship are discussed.

The alkylation of 6-methyl-2-thioxo-2,3-dihydro-1H-pyrimidine-4-one phenacyl bromides under different conditions was investigated. It was found that during the reaction in the medium of DMF/K2CO3 a mixture of 2-(2-aryl-2-oxoethyl)thio-6-methyl-pyrimidine-4(3H)-one and 3-hydroxy-3-aryl-7-methyl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-5-one was formed. The holding of the resulting mixture in the concentrated sulphuric acid leads to the formation of cyclization products - derivatives of 3-aryl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one with high yields. Individual S-alkylated derivatives – 2-(2-aryl-2-oxoethyl)thio-6-methyl-pyrimidine-4(3H)-one - were obtained by reacting in methanol in the presence of sodium methoxide. Pharmacological screening of synthesized compounds for anticonvulsant activity on the model of pentylenetetrazole seizures in rats was carried out and some regularity “structure-activity” was established.

The most recent classification of the lung cancer expanded the diagnostic criteria of its histological subtypes and included its immunophenotypic profile. We performed the study to compare the reliability of selected markers in high-grade non-small cell lung carcinoma (NSCLC) in the oligobiopsies with the matched postoperative samples. We evaluated expression of p40, p63, TTF1, cytokeratin 5/6, cytokeratin 7, napsin A, desmoglein 3, desmocollin 3 and mucin secretion as detected by mucicarmine staining. The study cohort included 123 cases of poorly-differentiated NSCLC. The tissue oligobiopsy material was available in 38 cases. Tissue microarrays (TMAs) from all postoperative cases were constructed. Comparing the immunophenotype between postsurgical samples and oligobiopsies we found an almost perfect agreement for most of performed IHC reactions. The highest concordance of results was found for desmoglein 3, CK7, and p40, whereas the lowest – for desmocollin 3. Immunoprofile of the oligobiopsies corresponded well to that in the resection specimens. The most useful markers in poorly differentiated ADs are: TTF1 and napsin A, and for non-keratinizing SCCs: p40, p63, CK5/6 and desmoglein 3.

To describe how 17β-estradiol (E2) influence in the monocyte/macrophage response induced by S. aureus in in vitro models of murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (HPBM). MPMs (2 x 105/ml) were isolated from sham (n=3) and ovariectomized (OVX) females (n = 3) and males (n = 3) after induction by thioglycolate. The MPMs obtained from OVX females and males were treated for 24 hours with 17β-estradiol (E2) (10-7 M), and after that, inoculation with S. aureus was carried out for 6 hours. The macrophages were collected and destined to evaluate the relative gene expression of TNF-α, IL-1β, IL-6, IL-8 and TLR2. For the in vitro model of HPBMs, six men and six women of childbearing age were selected and HPBMs were isolated from samples of the volunteers’ peripheral blood. In women, blood was collected both during menstruation and in the periovulatory period. HPBMs were inoculated with S. aureus for 6 hours and the supernatant was collected for analysis of cytokines by Luminex and the HPBMs were removed for analysis of 84 genes involved in the host’s response to bacterial infections by RT-PCR array. Previous treatment with E2 decreased the gene expression and production of proinflammatory cytokines, such as TNF-α, IL-1β and IL-6 and decreased the expression of TLR2 tanto em MPMs quanto em HPBMs. The analysis of gene expression shows that E2 inhibited the NFκB pathway. It is suggested that 17β-estradiol acts as an immunoprotective in the monocyte/macrophage response induced by S. aureus.

У статті висвітлено результати експериментального дослідження з проблеми формування цифрових навичок майбутніх педагогів. Охарактеризовано вітчизняні та світові підходи щодо визначення сутності змісту цифрових навичок, використання ІКТ для їх формування. Здійснено аналіз Європейської рамки цифрової компетентності освітян (DigCompEdu) за шістьма сферами діяльності (професійне залучення; цифрові ресурси; навчання інших та самонавчання; оцінка; розширення можливостей учнів; сприяння розвитку цифрової компетентності здобувачів освіти) з метою визначення цифрових навичок, які необхідні сучасному вчителеві. Виокремлено п’ять цифрових навичок (використання цифрових пристроїв та ІКТ; пошук та критичне оцінювання цифрового контенту; модифікація та створення цифрових ресурсів; обмін інформацією та організація цифрової комунікації; вчитися й навчати використанню ІКТ), які становлять основу цифрової компетентності майбутніх педагогів, а також з'ясовано критерії та показники їх сформованості. За 100 бальною шкалою ступеня вияву показників визначено рівні сформованості цифрових навичок, а саме: незадовільний (20–59 балів); задовільний (60–74 бали); добрий (75–81 балів); дуже добрий (82–89); відмінний (90–100 балів). Результати вивчення рівнів сформованості цифрових навичок у майбутніх учителів початкових класів та вихователів закладів дошкільної освіти на констатувальному етапі дослідження засвідчили необхідність розроблення технологічного інструментарію щодо їх формування. Представлено авторську програму тренінгу «Проєктування мультимедійного середовища закладу загальної середньої освіти та закладу дошкільної освіти» із застосуванням ІКТ. Порівняльний аналіз результатів констатувального та контрольного етапів емпіричного дослідження, проведеного впродовж 2018-2020 рр. у Педагогічному інституті Київського університету імені Бориса Грінченка, засвідчив позитивну динаміку рівнів сформованості цифрових навичок студентів і довів ефективність впровадженого технологічного інструментарію. Статистичну значущість результатів дослідження перевірено з використання коефіцієнту рангової кореляції Спірмена.

The rapid development in bacterial resistance to many groups of known antibiotics forces the researchers to discover antibacterial drug candidates with previously unknown mechanisms of action, one of the most relevant being the inhibition of tRNA (Guanine37-N1)-methyltransferase (TrmD). The discovery of selective TrmD inhibitors in the series of carboxamide derivatives of thienopyrimidines became a background for further modification of the similar structures aimed at the development of promising antibacterial agents. As part of this research, we carried out the construction of heterocyclic hybrids bearing the moieties of thieno[2,3-d]pyrimidine and benzimidazole starting from 3,5-dimethyl-4-oxo-2-thioxo-1H-thieno[2,3-d]pyrimidine-6-carboxylic acid, which was used as the pivotal intermediate. The hybrid molecule of 6-(1H-benzimidazol-2-yl)-3,5-dimethyl-2-thioxo-1H-thieno[2,3-d]pyrimidin-4-one prepared via condensation of the carboxylic acid with ortho-phenylenediamine was further alkylated with aryl/hetaryl chloroacetamides and benzyl chloride to produce the series of S-alkyl derivatives. The results of molecular docking studies for the obtained series of S-alkyl benzimidazole-thienopyrimidines showed their high affinity to the TrmD isolated from the P. aeruginosa. The results of antimicrobial activity screening revealed the antimicrobial properties for all of the studied molecules against both Gram-positive and Gram-negative bacteria and the Candida albicans fungal strain. The highest antimicrobial activity was determined for 2-{[6-(1H-benzimidazol-2-yl)-3,5-dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl]thio}-N-(4-isopropylphenyl)acetamide, which also had the highest affinity to the TrmD inhibitor’s binding site according to the docking studies results.

c-Jun N-terminal kinase (JNK) plays a central role in stress signaling pathways implicated in important pathological processes, including rheumatoid arthritis and ischemia-reperfusion injury. Therefore, inhibition of JNK is of interest for molecular targeted therapy to treat various diseases. We synthesized 13 derivatives of our reported JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime and evaluated their binding to the three JNK isoforms and their biological effects. Eight compounds exhibited submicromolar binding affinity for at least one JNK isoform. Most of these compounds also inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) activation and interleukin-6 (IL-6) production in human monocytic THP1-Blue cells and human MonoMac-6 cells, respectively. Selected compounds (4f and 4m) also inhibited LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. We conclude that indenoquinoxaline-based oximes can serve as specific small-molecule modulators for mechanistic studies of JNKs, as well as potential leads for the development of anti-inflammatory drugs.

Розглянуто загальні підходи до моделювання військових конфліктів. Побудовано ймовірнісно-статистичну модель для встановлення ймовірності настання військового конфлікту у вигляді байєсової мережі. Складність моделювання військового конфлікту полягає у високій динаміці взаємодійних систем з багатьма невідомими або невимірюваними змінними і параметрами. У створеній моделі враховано неповноту та нечіткість наявної інформації. Побудована модель має на меті не тільки виявлення існуючих взаємозв’язків та залежностей між вибраними процесами, а i прогнозування ймовірності виникнення майбутніх конфліктів на основі результатів аналізу поточної ситуації. Проведено моделювання з використанням наявних статистичних даних, виконано серію обчислювальних експериментів та аналіз отриманих результатів. Статистичні дані для формування вибірки даних взято з відкритих джерел. За побудованою моделлю оцінено ймовірність внутрішнього та зовнішнього конфліктів в Україні. Отримані числові результати відповідають реальній ситуації.

В статті висвітлено деякі аспекти практико орієнтованої підготовки майбутнього вчителя початкової школи в процесі вивчення педагогічних дисциплін засобами проектної діяльності. Подано авторський досвід використання навчальних проектів, зокрема, з дисциплін «Основи педагогіки» та «Теорія і методика виховання». Розкрито особливості реалізації в освітньому процесі ВНЗ діяльнісного, особистісного, компетентнісного підходів.

The need for lifelong education is urged in the context of constant social transformations, unprecedented challenges, total digitalization of communicative transactions, virtualization of many types of professional activity. Journalism is one of the most sensitive to transformational challenges. Therefore, a journalist must respond objectively, flexibly, tolerantly, adequately, professionally, responsibly and social transformations and challenges to the current realities. To do this, he/she must be prepared for lifelong learning. It is the journalist's readiness for lifelong learning that is an indicator of the quality of his/her specialized education. The research aimed to empirically establish the skills of journalists related to lifelong learning, and to develop a programme for the implementation of the lifelong learning principles in the professional training of journalists. General scientific methods, surveys of research respondents, qualitative and quantitative analysis of the obtained data, modelling are the methods used. A model of modern journalist training in the context of lifelong learning was formed, a program for the implementation of lifelong learning principles in specialized education of journalists was developed. The results of the research can be used for the development of individual trainings, seminars, compilation of collections of didactic tools for the formation of the ability of modern journalists to education throughout life. Prospects for further research in this area are: experimental testing of our proposed program for the implementation of the principles of lifelong learning in the training of journalists; development of diagnostic tools to establish the levels of readiness of journalism students and practicing journalists for lifelong learning.

У статті висвітлено основні методологічні підходи до моделювання профільної школи. Обґрунтовано саме ті, що уможливлюють найбільш повне розкриття потенціалу сільської школи, а саме: тісні зв’язки з соціокультурним середовищем; внутрішня диференціація, що визначається особистісними сенсами учнів до профільної професійно зорієнтованої шкільної освіти. Зміст статті розроблено за результатами теоретичного аналізу проблем моделювання освітніх систем і вивчення стану діяльності профільних шкіл у сільській місцевості. Подано алгоритм моделювання профільної (старшої) школи з урахуванням специфічних чинників освітніх середовищ у сільській місцевості. Узагальнення та рекомендації, що подано в змісті статті можуть бути принагідними для розроблення концепцій профільного навчання та моделювання профільних шкіл у сільській місцевості.

Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel. Coppermycin-1 reacts selectively with Cu(I) to release puromycin, which is then incorporated into nascent peptides during protein translation, thus leaving a permanent and dose-dependent marker for labile copper that can be visualized with standard immunofluorescence assays. We showcase the utility of this platform for screening labile Cu(I) pools across the National Cancer Institute's 60 (NCI-60) human tumor cell line panel, identifying cell types with elevated basal levels of labile copper. Moreover, we use Coppermycin-1 to show that lung cancer cells with heightened activation of nuclear factor-erythroid 2-related factor 2 (NRF2) possess lower resting labile Cu(I) levels and, as a result, have reduced viability when treated with a copper chelator. This work establishes that methods for labile copper detection can be used to assess cuproplasia, an emerging form of copper-dependent cell growth and proliferation, providing a starting point for broader investigations into the roles of transition metal signaling in biology and medicine. [ABSTRACT FROM AUTHOR]

According to the recent studies bezylcarboxamide fragment attached to the thiophene ring of thieno[2,3-d]pyrimidine is beneficial for antimicrobial activity of the compounds. Therefore we focused our efforts on constructing of the simple molecules such as N-(benzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides to get deeper insight into their antimicrobial activity. As the optimal procedure for preparation of target compounds we choose 1,1'-carbonyldiimidazole promoted interaction of 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid with the series of substituted benzyl amines. The obtained amides showed good activity against the strains of S. aureus and B. subtilis, which was higher for the derivative without substituents in benzene ring or the compounds with small substituents like methyl or methoxyl groups in the para-position of the benzene ring. Docking studies showed that despite the good values of the scoring functions, the conformational analysis of the ligands' poses in the active site revealed their ability for only partial inhibition of TrmD of P. aeruginosa. [ABSTRACT FROM AUTHOR]

Abstract Tendon healing involves mechanosensitive cells that adapt to mechanical stimuli through mechanotransduction, resulting in increased tissue strength. However, detailed insights into this process in response to different loads remain limited. We aimed to investigate how different loading regimes impact the spatial composition of elastin and collagens during Achilles tendon healing. Histological analysis was conducted on healing rat Achilles tendons exposed to (1) full loading, (2) reduced loading, or (3) minimal loading. Histological analysis included Hematoxylin & Eosin and immunohistochemical staining targeting elastin, Collagen 1, Collagen 3, and CD31. Our results showed that the impact of mechanical stimuli on healing tendons varied with the degree of loading. Unexpectedly, minimal loading led to higher staining intensity for collagens and elastin. However, tendons exposed to minimal loading appeared thinner and exhibited a less organized matrix structure, with fewer, less aligned, and more rounded cells. Additionally, our findings indicated an inverse correlation between angiogenesis and load level, with more blood vessels in tendons subjected to less loading. Tissue integrity improved by 12 weeks post-injury, but the healing process continued and did not regain the structure seen in intact tendons even after 20 weeks. This study reveals a load-dependent effect on matrix alignment, cell density, and cell alignment.

The schwa sound [ə] in the English language remains challenging and it appears to be overlooked by EFL learners. In practice, the word ‘submit’ is mispronounced by English learners: */sʌbˈmɪt/, instead of /səbˈmɪt/. Some studies have discussed schwa but their data sources were not the Holy Quran. Hence, this article investigated the schwa sound in English vocabulary items collected from the Holy Quran and represented by the letters 'o' and 'u' as in ‘polite’ and ‘submit’. Employing a descriptive qualitative method, the researchers collected 97 vocabulary items containing schwa sounds taken from surah Al-Baqarah verses 1-286. The results indicate that the schwa term that represents the unstressed syllable can be renewed with the terms proposed in this study such as 'astressed' and 'disaccented'. In addition, to maintain the schwa term, a change of its pronunciation is proposed becoming /ʃwə/ and not /ʃwɑː/. Most of the written vowels 'o' and 'u' are pronounced in a strong form, and unstressed vowels 'o' and 'u' are pronounced as a schwa. The appearance of unstressed schwa in the vowels 'o' and 'u' is not determined by its location whether it is in the first or second syllable. Schwa could appear anywhere as long as he was not stressed. Schwa was not found in stressed syllables. Lastly, all -ion [ən] and -ous [əs] suffixes must be pronounced with a schwa. The results imply that EFL learners ought to consult an excellent dictionary to ensure correct pronunciation. Future researchers are expected to examine further patterns of a schwa sound in English vocabulary items to assist EFL learners in improving their pronunciation.

BackgroundCertain species from the normal respiratory tract microbiota have recently been proposed to positively influence human health. Corynebacterium propinquum and C. pseudodiphtheriticum (Corynebacteria) are two Gram-positive species that frequently colonize the upper respiratory tract and strongly associate with a reduced incidence of respiratory tract infections. The specific role of Corynebacteria during respiratory health and disease is, however, largely uncharacterized.MethodRespiratory tract epithelial cells NCI-H292 and BALB/cByJ mice were inoculated with Corynebacteria (C. propinquum 2018M3 and 2019M4, and C. pseudodiphtheriticum 2019M8 and 2020M12) alone or with subsequent challenge with Streptococcus pneumoniae (pneumococci). The inflammatory response and the bacterial burden of both species over time were determined by Western blot, luciferase assay, cytokine bead array, flow cytometry and viable plate counts on blood agar plates.ResultsClinical isolates of Corynebacteria were well tolerated by human cells and mice. Corynebacteria induced a transient inflammatory response during healthy conditions in the absence of known pathogens. Pre-exposure or nasal priming with Corynebacteria did not affect subsequent acquisition of pneumococci but were associated with a modulated inflammatory response in vitro and in vivo as well as with a reduced pneumococcal burden in the respiratory tract of mice. This indicates that the presence of C. propinquum or C. pseudodiphtheriticum may protect against severe pneumococcal infections.ConclusionsIn this study, we delineate the role of Corynebacteria from the normal microbiota that epidemiologically associate with respiratory health. We show that the presence of Corynebacteria modulates the inflammatory response to pneumococci and associate with faster decrease in pneumococcal burden, primarily in the lower respiratory tract. Our data indicate that Corynebacteria has potential to protect against severe pneumococcal infections.