In 2018, a previously unknown Ebola virus, Bombali virus, was discovered in Sierra Leone. We describe detection of Bombali virus in Guinea. We found viral RNA in internal organs of 3 Angolan ...free-tailed bats (Mops condylurus) trapped in the city of N'Zerekore and in a nearby village.
Chiral amino acids (AAs), being the main “building” blocks of the living organisms, are also an important class of organic compounds which broadly applied in synthetic chemistry, biochemistry, ...catalysis and the designing of new drugs. According to the industrial‐commodity market, chiral non‐proteinogenic AAs containing various functional groups come to the fore. To date, radical cross‐coupling reactions are becoming an option as an attractive powerful tool for AA syntheses. Owing to mild reaction conditions and high functional‐group tolerance, radical chemistry represents an ideal strategy for the synthesis of challenging complex non‐proteinogenic AAs. Moreover, the radical cross‐coupling allows introducing AA residue into drug scaffolds and natural compounds. In the present review, we wish to summarize and discuss all the reported to date methods of the asymmetric synthesis of AAs using radical chemistry by presenting a comprehensive account of the literature in this field going back to 1990. We especially emphasize on a radical chemistry approach and, exclusively, on stereoselective synthesis of various α‐, β‐, γ‐AAs and derivatives employing a different type of radical initiators starting from AIBN and organostannes and ending with powerful photoredox catalysis. Furthermore, the mechanism of the reported reactions will be discussed.
A (series) range of potential dimorpholinoquinazoline-based inhibitors of the PI3K/Akt/mTOR cascade was synthesized. Several compounds exhibited cytotoxicity towards a panel of cancer cell lines in ...the low and sub-micromolar range. Compound 7c with the highest activity and moderate selectivity towards MCF7 cells which express the mutant type of PI3K was also tested for the ability to inhibit PI3K-(signaling pathway) downstream effectors and associated proteins. Compound 7c inhibited the phosphorylation of Akt, mTOR, and S6K at 125–250 nM. It also triggered PARP1 cleavage, ROS production, and cell death via several mechanisms. Inhibition of PI3Kα was observed at a concentration of 7b 50 µM and of 7c 500 µM and higher, that can indicate minority PI3Kα as a target among other kinases in the titled cascade for 7c. In vivo studies demonstrated an inhibition of tumor growth in the colorectal tumor model. According to the docking studies, the replacement of the triazine core in gedatolisib (8) by a quinazoline fragment, and incorporation of a (hetero)aromatic unit connected with the carbamide group via a flexible spacer, can result in more selective inhibition of the PI3Kα isoform.
Currently, there are no effective drugs for the treatment of amyotrophic lateral sclerosis (ALS). Only two drugs—edaravone and riluzole—have been approved, but they have very limited efficacy. The ...aim of this work was to modify the structural core of the Edaravone—phenylpyrazolone moiety and combine it with aminoadamantane pharmacophore in order to expand the spectrum of its action to a number of processes involved in the pathogenesis of ALS. New conjugates of edaravone derivatives with 1-aminoadamantanes combined with alkylene or hydroxypropylene spacers were synthesized, and their biological activity was investigated. Compounds were found that could inhibit lipid peroxidation and calcium-related mitochondrial permeability, block fast sodium currents of CNS neurons, and reduce aggregation of the mutated form of the FUS-protein typical to ALS. So, the proposed modification of the edaravone molecule has allowed the obtaining of new original structures that combine some prospective therapeutic mechanisms against key chains of the pathogenesis of ALS. The identified lead compounds can be used for further optimization and development of new promising drugs on this basis for the treatment of ALS.
Borrelia miyamotoi is distantly related to B. burgdorferi and transmitted by the same hard-body tick species. We report 46 cases of B. miyamotoi infection in humans and compare the frequency and ...clinical manifestations of this infection with those caused by B. garinii and B. burgdorferi infection. All 46 patients lived in Russia and had influenza-like illness with fever as high as 39.5°C; relapsing febrile illness occurred in 5 (11%) and erythema migrans in 4 (9%). In Russia, the rate of B. miyamotoi infection in Ixodes persulcatus ticks was 1%-16%, similar to rates in I. ricinus ticks in western Europe and I. scapularis ticks in the United States. B. miyamotoi infection may cause relapsing fever and Lyme disease-like symptoms throughout the Holarctic region of the world because of the widespread prevalence of this pathogen in its ixodid tick vectors.
Macrophages, the key cells of innate immunity, possess wide phenotypical and functional heterogeneity. In vitro studies showed that microenvironment signals could induce the so-called polarization of ...macrophages into two phenotypes: classically activated macrophages (M1) or alternatively activated macrophages (M2). Functionally, they are considered as proinflammatory and anti-inflammatory/pro-regenerative, respectively. However, in vivo studies into macrophage states revealed a continuum of phenotypes from M1 to M2 state instead of the clearly distinguished extreme phenotypes. An important role in determining the type of polarization of macrophages is played by energy metabolism, including the activity of oxidative phosphorylation. In this regard, hypoxia and ischemia that affect cellular energetics can modulate macrophage polarization. Here, we overview the data on macrophage polarization during metabolic shift–associated pathologies including ischemia and ischemia/reperfusion in various organs and discuss the role of energy metabolism potentially triggering the macrophage polarization.
During a 2-year period in 2005–2007, we conducted surveillance of group A rotaviruses and other enteric agents among patients hospitalized with acute gastroenteritis in 8 different cities of the ...Russian Federation. Fecal specimens were gathered from 3208 children (including 2848 children aged <5 years) and 1354 adults who were admitted to hospitals in Moscow, St. Petersburg, Chelyabinsk, Nizhnii Novgorod, Tyumen, Khabarovsk, Makhachkala, and Yakutsk. Polymerase chain reaction was performed to detect rotaviruses of groups A and C, noroviruses of genogroups I and II, astrovirus, sapovirus, and enteric adenoviruses (group F). Group A rotavirus was the most common viral pathogen detected among children aged <5 years (43.6%), followed by norovirus (12.5%), whereas norovirus was the pathogen most commonly detected in adults (11.9%). P and G genotypes were determined for 515 rotavirus specimens, and the most prevalent genotypes were G1P8 (44.9%), G4P8 (40.0%), G2P4 (8.5%), and G3P8 (6.6%). This study is the first multicenter study of rotaviruses in the Russian Federation and documents the important burden of disease caused by this pathogen, which soon may be preventable by vaccination
Heart rhythm disorders are one of the most common complications of coronavirus infection. Heart rhythm disorders can develop in 6-17% of hospitalized patients, and in convalescents, COVID-19 can ...manifest itself up to 12 months after the completion of the acute phase of the disease. Among the mechanisms for the development of cardiac arrhythmias, there are a direct cytopathic effect of SARS-CoV-2 on the myocardium, systemic inflammatory response syndrome, electrolyte imbalance, hypoxia, the use of antibacterial, antimalarial and antiviral drugs, exudative pericarditis, autonomic dysfunction. The main COVID-19-mediated heart rhythm disorders are sinus tachycardia and bradycardia, atrial fibrillation, ventricular tachycardia, long QT syndrome. Despite a significant amount of research, the literature data on the prevalence of certain types of cardiac arrhythmias (especially in COVID-19 convalescents), as well as methods for their correction, are somewhat contradictory and need to be clarified. Taking into account the impact of arrhythmia on the quality of life and mortality, active monitoring of convalescents of coronavirus infection, identification and development of approaches to the treatment of heart rhythm disorders in patients who have had COVID-19, seem to be relevant and promising areas in modern cardiology.
•Systems of classically interacting dipoles are presented, together with energy bounds.•The structures are the Platonic, Archimedean and Catalan solids.•Non-trivial equilibrium structures are studied ...in full detail for the first time.•Catalan solids are studied from the physical point of view for the first time.•Incommensurate equilibrium dipole angles appear, as well as dipolar structures.
Several magnetic materials consisting of dipoles owe their properties to the specific nature of the dipole-dipole interaction. In the present work, we study systems of dipoles where the particles are arranged on various types of three-dimensional structures. However, these solids are not arbitrary. They constitute the well-known Platonic, Archimedean and Catalan solids. We systematically study them in order to fill a gap in the literature that does not contemplate this interaction in the previous solids, despite the fact that they are encountered in many different physical systems. In particular, in the regime of strong dipole moments where a classical treatment is possible, we shall provide not only the minimum energy but also the precise orientations of all their dipoles. We will numerically obtain the minimum energy configuration where all vertices possess the same classic dipole, either electric or magnetic.
A family of well-defined Λ- and Δ-diastereomeric octahedral cationic chiral-at-cobalt complexes were obtained by a simple two-step reaction of (R,R)-1,2-diaminocyclohexane, ...(R,R)-1,2-diphenylethylenediamine, or (S)-2-(aminomethyl)pyrrolidine and substituted salicylaldehydes with a cobalt(III) salt. It was observed for the first time that the use of an excess of cobalt(III) salt provides both the enantiopure Λ and Δ forms of the corresponding cobalt(III) complexes 1 and 2 in a ratio of diastereomers ranging from 1:1.6 to >20:1 (Λ/Δ) and in 31–95% combined yields. The obtained complexes were robust, air- and bench-stable, soluble in most of organic solvents, and insoluble in water. Through variation of the substituents in the phenyl ring of the salicylaldehyde moiety, it was shown that both steric and electronic effects of substituents have a significant impact on the formation of Λ and Δ isomers. Next, the efficacies of the enantiopure metal-templated complexes 1–3 were investigated in three benchmark asymmetric reactions in order to compare their catalytic activity. The chiral cobalt(III) complexes 1–3 were tested as enantioselective hydrogen-bond-donor catalysts in such important reactions as the Michael addition of the O’Donnell substrate to methyl acrylate, epoxidation of chalcone, and trimethylsilylcyanation of benzaldehyde. It was clearly demonstrated that the chirality at the cobalt center has an impact on the stereochemical outcome of the reactions. In particular, the Λ(R,R)-1 and Δ(R,R)-1 complexes acted as “pseudoenantiomeric” catalysts in the epoxidation and trimethylsilylcyanoation reactions, providing both enantiomers of the products with up to 57% enantiomeric excess.
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