Design, Synthesis, and Photophysical Properties of 5-Aminobiphenyl Substituted [1,2,4]Triazolo[4,3-c]- and [1,2,4]Triazolo[1,5-c]quinazolines.

Two series of novel [1,2,4]triazolo[4,3-c]- and [1,2,4]triazolo[1,5-c]quinazoline fluorophores with 4'-amino[1,1']-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki-Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation of [4,3-c]-annulated triazoloquinazolines, whereas [1,5-c] isomers are formed in acidic media as a result of Dimroth rearrangement. A 1D-NMR and 2D-NMR spectroscopy, as well as a single-crystal X-ray diffraction analysis, unambiguously confirmed the annelation type and determined the molecular structure of p-bromophenyl intermediates and target products. Photophysical properties of the target compounds were investigated in two solvents and in the solid state and compared with those of related 3-aryl-substituted [1,2,4]triazolo[4,3-c]quinazolines. The exclusion of the aryl fragment from the triazole ring has been revealed to improve fluorescence quantum yield in solution. Most of the synthesized structures show moderate to high quantum yields in solution. Additionally, the effect of solvent polarity on the absorption and emission spectra of fluorophores has been studied, and considerable fluorosolvatochromism has been stated. Moreover, electrochemical investigation and DFT calculations have been performed; their results are consistent with the experimental observation.

Simultaneous Detection of RIG-1, MDA5, and IFIT-1 Expression Is a Convenient Tool for Evaluation of the Interferon-Mediated Response.

In this study, we developed a novel, multiplex qPCR assay for simultaneous detection of RIG-1, MDA5, and IFIT-1 at the mRNA level. The assay was validated in A549 cells transfected with in vitro transcribed RNAs. Both exogenous RNA-GFP and self-amplifying (saRNA-GFP) induced significant expression of RIG-1, MDA5, IFIT-1, as well as type I and III interferons. In contrast, native RNA from intact A549 cells did not upregulate expression of these genes. Next, we evaluated RIG-1, MDA5, and IFIT-1 mRNA levels in the white blood cells of patients with influenza A virus (H3N2) or SARS-CoV-2. In acute phase (about 4 days after disease onset) both viruses induced these genes expression. Clinical observations of SARS-CoV-2 typically describe a two-step disease progression, starting with a mild-to-moderate presentation followed by a secondary respiratory worsening 9 to 12 days after the first onset of symptoms. It revealed that the expression of RIG-1, MDA5, and MxA was not increased after 2 and 3 weeks from the onset the disease, while for IFIT-1 it was observed the second peak at 21 day post infection. It is well known that RIG-1, MDA5, and IFIT-1 expression is induced by the action of interferons. Due to the ability of SOCS-1 to inhibit interferon-dependent signaling, and the distinct antagonism of SARS-CoV-2 in relation to interferon-stimulated genes expression, we assessed SOCS-1 mRNA levels in white blood cells. SARS-CoV-2 patients had increased SOCS-1 expression, while the influenza-infected group did not differ from heathy donors. Moreover, SOCS-1 mRNA expression remained stably elevated during the course of the disease. It can be assumed that augmented SOCS-1 expression is one of multiple mechanisms that allow SARS-CoV-2 to escape from the interferon-mediated immune response. Our results implicate SOCS-1 involvement in the pathogenesis of SARS-CoV-2.

Determining the correlation between olive oil consumption, BMI, and waist circumference in the adult Saudi population.

OBJECTIVE: This study aimed to explore the correlation between dietary intake of olive oil, body mass index (BMI), and waist circumference (WC). METHODS: In this cross-sectional study, we recruited 200 participants aged 20-30 years using pre-determined inclusion and exclusion criteria. Demographic data was collected via a questionnaire, while dietary data was collected for two days using a 24-hour dietary recall. Anthropometric data such as BMI and WC were collected, and all the information was entered into the Diet Organizer software and statistical package for social sciences (SPSS) software for statistical analysis. The test results were assessed on the basis of a significance level of 95% (p < 0.05). RESULTS: We did not find a significant difference in BMI and WC between high and low olive oil consumers. Carbohydrate intake was significantly higher among low olive oil consumers. Although high olive oil consumers had a significantly higher caloric intake, they had a similar BMI compared to low olive oil consumers. CONCLUSION: This study provides baseline data on the intake of olive oil in a Saudi cohort aged 20-30 years. This study suggests that high olive oil intake may have a role in maintaining body weight.

Efficient Synthesis of the N-(buta-2,3-dienyl)carboxamide of Isopimaric Acid and the Potential of This Compound towards Heterocyclic Derivatives of Diterpenoids.

The N-(2,3-butadienyl)carboxamide of isopimaric acid, that is, compound 3, was prepared through a two-step synthetic procedure starting from the natural diterpene isopimaric acid. The Pd-catalyzed cross-coupling and subsequent cyclization of terpenoid allene 3 with several aryl iodides and aryl bromides gave access to optically active diterpenoid-oxazoline derivatives in good to excellent yields. The functional group tolerance in the aryl iodides was demonstrated by several examples, including substrates with additional N-tert-butoxycarbonyl-protected amino, hydroxy, and carboxy substituents in the ortho position. The cross-coupling-cyclization reaction of those compounds with allene 3 proceeded selectively with the formation of cyclization products on the substituent in the aromatic ring. This transformation opens a potential route to the synthesis of hybrid compounds containing a tricyclic diterpenoid and several heterocycles.

The YABBY Genes of Leaf and Leaf-Like Organ Polarity in Leafless Plant Monotropa hypopitys.

Monotropa hypopitys is a mycoheterotrophic, nonphotosynthetic plant acquiring nutrients from the roots of autotrophic trees through mycorrhizal symbiosis, and, similar to other extant plants, forming asymmetrical lateral organs during development. The members of the YABBY family of transcription factors are important players in the establishment of leaf and leaf-like organ polarity in plants. This is the first report on the identification of YABBY genes in a mycoheterotrophic plant devoid of aboveground vegetative organs. Seven M. hypopitys YABBY members were identified and classified into four clades. By structural analysis of putative encoded proteins, we confirmed the presence of YABBY-defining conserved domains and identified novel clade-specific motifs. Transcriptomic and qRT-PCR analyses of different tissues revealed MhyYABBY transcriptional patterns, which were similar to those of orthologous YABBY genes from other angiosperms. These data should contribute to the understanding of the role of the YABBY genes in the regulation of developmental and physiological processes in achlorophyllous leafless plants.

CMV70-3P miRNA contributes to the CMV mediated glioma stemness and represents a target for glioma experimental therapy.

Glioblastoma multiforme (GBM) is a rapidly progressive brain tumor with a median survival of 15-19 months. Therapeutic resistance and recurrence of the disease is attributed to cancer stem cells (CSC). Here, we report that CMV70-3P miRNA encoded by CMV increases GBM CSC stemness. Inhibition of CMV70-3P expression using oligo inhibitors significantly attenuated the ability of primary glioma cells to proliferate and form neurospheres. At the molecular level, we show that CM70-3P increases expression of cellular SOX2. Collectively, these findings indicate that CMV70-3P is a potential regulator of CMV- mediated glioma progression and cancer stemness.