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We describe a stereodefined synthesis of the newly identified non-natural phosphorothioate cyclic dinucleotide (CDN) STING agonist, BMT-390025. The new route avoids the low-yielding racemic approach using P(III)-based reagents, and the stereospecific assembly of the phosphorothioate linkages are forged via the recently invented P(V)-based platform of the so-called PSI (Ψ) reagent system. This P(V) approach allows for the complete control of chirality of the P-based linkages and enabled conclusive evidence of the absolute configuration. The new approach offers robust procedures for preparing the stereodefined CDN in eight steps starting from advanced nucelosides, with late-stage direct drop isolations and telescoped steps enabling an efficient scale-up that proceeded in an overall 15% yield to produce multigram amounts of the CDN.We employed the density functionaly theory (DFT)-predicted regioselectivity of the intramolecular Scholl reaction in phenanthrene and dibenzo[g,p]chrysene frameworks to obtain π-extended mono and double [7]helicenes, respectively. The formation of these helical structures occurs despite the buildup of a large strain energy up to 30 kcal/mol compared with their most stable isomers. The twisted and strained structures were characterized and analyzed by experimental (NMR, UV-vis, emission, electrochemistry, and single-crystal X-ray diffraction) techniques and were further supported by DFT calculations.
Acute asthma exacerbations are a common cause for emergency department (ED) visits and hospitalizations in children. Since the outbreak of coronavirus disease 2019 (COVID-19) and the education system closure/total lockdown in Israel on March 2020, we have noticed a decrease in pediatric ED visits and an increase in hospitalizations of asthma exacerbations.
to examine the patterns of ED visits for asthma exacerbations during COVID-19 outbreak, in comparison to the previous year.
A retrospective study comparing asthma related ED visits and hospitalizations among children aged 2-18 years at a tertiary center in southern Israel. Three time periods were selected 2020 A (prelockdown, 2/1/20 to 3/14/20), 2020 B (lockdown, 3/15/20 to 5/15/20) and 2020 C (postlockdown, 5/16/20 to 6/30/20) and compared to the three parallel time periods in 2019. Data regarding demographics, number of ED visits and clinical severity parameters were collected and analyzed.
Five hundred and twelve children visited the ED for asthmtion rate and longer LOS.3-Chloroquinoline-2,4-diones react with cyanide ions in dimethyl formamide to give 3-cyanoquinoline-2,4-diones in small yields due to the strong hindrance of the substituent at the C-3 atom. Good yields can be achieved if the substituent at this position is the methyl group. In the methanol solution, the reaction proceeds by an addition mechanism to form 2-oxo-1a,2,3,7b-tetrahydrooxireno[2,3-c]quinoline-7b-carbonitriles, from which 4-hydroxy-3-methoxy-2-oxo-1,2,3,4-tetrahydroquinoline-4-carbonitriles are subsequently formed by opening of the epoxide ring with methanol. Some minor products of these reactions have also been isolated. The 1 H, 13 C and 15 N NMR spectra of the prepared compounds were measured, and all resonances were assigned using appropriate two-dimensional spectra.Perovskites are attracting an increasing interest in the wide community of photovoltaics, optoelectronic, and detection, traditionally relying on lead-based systems. This Minireview provides an overview of the current status of experimental and computational results available on Ge-containing 3D and low-dimensional halide perovskites. While stability issues analogous to those of tin-based materials are present, some strategies to afford this problem in Ge metal halide perovskites (MHPs) for photovoltaics have already been identified and successfully employed, reaching efficiencies of solar devices greater than 7 % at up to 500 h of illumination. Interestingly, some Ge-containing MHPs showed promising nonlinear optical responses as well as quite broad emissions, which are worthy of further investigation starting from the basic materials chemistry perspective, where a large space for properties modulation through compositions/alloying/fnanostructuring is present.Ticks carry a diverse community of microorganisms including non-pathogenic symbionts, commensals, and pathogens, such as viruses, bacteria, protozoans, and fungi. The assessment of tick-borne microorganisms (TBM) in tortoises and their ticks is essential to understand their eco-epidemiology, and to map and monitor potential pathogens to humans and other animals. learn more The aim of this study was to characterize the diversity of microorganisms found in ticks collected from the spur-thighed tortoise (Testudo graeca) in North Africa and Anatolia. Ticks feeding on wild T. graeca were collected, and pathogens were screened by polymerase chain reaction using group-specific primers. In total, 131 adult Hyalomma aegyptium ticks were collected from 92 T. graeca in Morocco (n = 48), Tunisia (n = 2), Algeria (n = 70), and Turkey (n = 11). Bacteria and protozoa detected included Hemolivia mauritanica (22.9%), Midichloria mitochondrii (11.4%), relapsing-fever borreliae (8.4%), Ehrlichia spp. (7.6%), Rickettsia spp. (3.4%), Borrelia burgdorferi s.l. (0.9%), Francisella spp. (0.9%), and Wolbachia spp. (0.8%). The characterization of Rickettsia included R. sibirica mongolitimonae (Algeria), R. aeschlimannii (Turkey), and R.africae (Morocco). Hemolivia mauritanica and Ehrlichia spp. prevalence varied significantly with the sampling region/country. We did not detect significant associations in microorganism presence within ticks, nor between microorganism presence and tick mitochondrial DNA haplogroups. This is the first report of Francisella persica-like, relapsing fever borreliae, M. mitochondrii, and Wolbachia spp. in H. aegyptium ticks collected from wild hosts from the South and Eastern Mediterranean region, and of R. sibirica mongolitimonae and R. africae in H. aegyptium from Algeria and Morocco, respectively. Given that T. graeca is a common species in commercial and non-commercial pet trade, the evaluation of the role of this species and its ticks as hosts for TBM is particularly relevant for public health.
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