A Novel Ambroxol-Derived Tetrahydroquinazoline with a Potency against SARS-CoV-2 Proteins

We report synthesis of a novel 1,2,3,4-tetrahydroquinazoline derivative, named 2-(6,8-dibromo-3-(4-hydroxycyclohexyl)-1,2,3,4-tetrahydroquinazolin-2-yl)phenol (1), which was obtained from the hydrochloride of 4-((2-amino-3,5-dibromobenzyl)amino)cyclohexan-1-ol (ambroxol hydrochloride) and salicylaldehyde in EtOH. The resulting compound was produced in the form of colorless crystals of the composition 1∙0.5EtOH. The formation of the single product was confirmed by the IR and 1H spectroscopy, single-crystal and powder X-ray diffraction, and elemental analysis. The molecule of 1 contains a chiral tertiary carbon of the 1,2,3,4-tetrahydropyrimidine fragment and the crystal structure of 1∙0.5EtOH is a racemate. Optical properties of 1∙0.5EtOH were revealed by UV-vis spectroscopy in MeOH and it was established that the compound absorbs exclusively in the UV region up to about 350 nm. 1∙0.5EtOH in MeOH exhibits dual emission and the emission spectra contains bands at about 340 and 446 nm upon excitation at 300 and 360 nm, respectively. The DFT calculations were performed to verify the structure as well as electronic and optical properties of 1. ADMET properties of the R-isomer of 1 were evaluated using the SwissADME, BOILED-Egg, and ProTox-II tools. As evidenced from the blue dot position in the BOILED-Egg plot, both human blood–brain barrier penetration and gastrointestinal absorption properties are positive with the positive PGP effect on the molecule. Molecular docking was applied to examine the influence of the structures of both R-isomer and S-isomer of 1 on a series of the SARS-CoV-2 proteins. According to the docking analysis results, both isomers of 1 were found to be active against all the applied SARS-CoV-2 proteins with the best binding affinities with Papain-like protease (PLpro) and nonstructural protein 3 (Nsp3_range 207–379-AMP). Ligand efficiency scores for both isomers of 1 inside the binding sites of the applied proteins were also revealed and compared with the initial ligands. Molecular dynamics simulations were also applied to evaluate the stability of complexes of both isomers with Papain-like protease (PLpro) and nonstructural protein 3 (Nsp3_range 207–379-AMP). The complex of the S-isomer with Papain-like protease (PLpro) was found to be highly unstable, while the other complexes are stable. © 2023 by the authors.Ministry of Science and Higher Education of the Russian FederationThis work was partially performed using resources of the Research Resource Center «Natural Resource Management and Physico–Chemical Research» (University of Tyumen). X-ray studies were conducted at the N.S. Kurnakov Institute of General and Inorganic Chemistry and were supported by the Ministry of Science and Higher Education of Russia as part of the state assignment of the Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences

Helicobacter cinaedi bacterium association with atherosclerosis and other diseases

Helicobacter is a genus of spiral-shaped Gram-negative enterohepatic bacteria whose members are capable of causing bacteremia in humans. One of the poorly studied members of this genus is the bacterium Helicobacter cinaedi. This microorganism was first isolated from human fecal samples in 1984. Although it was long considered to be associated with only immunocompromised patients, more evidence in recent years has implicated H. cinaedi in causing serious pathologies in immunocompetent populations. In addition, H. cinaedi is also reported to be associated with a few chronic or severe illnesses, such as atherosclerosis, which in turn can lead to the development of other cardiovascular pathologies: one of the leading causes of mortality worldwide. Helicobacter cinaedi often goes unnoticed in standard diagnostic methods due to its slow growth under microaerobic conditions. This often leads to significant underdetection and hence undermines the role of this bacterium in the pathogenesis of various diseases and the extent of its spread in humans. In this review, we have compiled information on pathologies associated with H. cinaedi, the occurrence of the bacterium in humans and animals, and the latest developments in diagnosing the bacterium and treating associated diseases

Magnetic Phase Separation and Magnetic Moment Alignment in Ordered Alloys FE 65

The structure and the magnetic state of ordered Fe65Al35-xMx (Mx = Ga, B; x = 0; 5 at.%) alloys are investigated using X-ray diffraction, Mössbauer spectroscopy, and magnetic measurements. The behavior of the magnetic characteristics and Mössbauer spectra of the binary alloy Fe65Al35 and the ternary alloy with gallium addition Fe65Al30Ga5 is explained in terms of the phase separation into two magnetic phases: a ferromagnetic one and a spin density wave. It is shown that the addition of boron to the initial binary alloy Fe65Al35 results in the ferromagnetic behavior of the ternary alloy

An Inverse Method to Obtain Porosity, Fibre Diameterand Density of Fibrous Sound Absorbing Materials

Characterization of sound absorbing materials is essential to predict its acoustic behaviour. The most commonly used models to do so consider the flow resistivity, porosity, and average fibre diameter as parameters to determine the acoustic impedance and sound absorbing coefficient. Besides direct experimental techniques, numerical approaches appear to be an alternative to estimate the material's parameters. In this work an inverse numerical method to obtain some parameters of a fibrous material is presented. Using measurements of the normal incidence sound absorption coefficient and then using the model proposed by Voronina, subsequent application of basic minimization techniques allows one to obtain the porosity, average fibre diameter and density of a sound absorbing material. The numerical results agree fairly well with the experimental data.This work has been supported by the Ministerio de Educacion y Ciencia-D.G. Investigacion (BIA2007-68098-C02-01 and BIA2007-68098-C02-02) and also from the Spanish Ministry of Foreign Affairs and Cooperation through the Inter-University and Scientific Research Cooperation Program (A/023748/09).Alba Fernández, J.; Rey Tormos, RMD.; Ramis Soriano, J.; Arenas, JP. (2011). An Inverse Method to Obtain Porosity, Fibre Diameterand Density of Fibrous Sound Absorbing Materials. Archives of Acoustics. 36(3):561-574. https://doi.org/10.2478/v10168-011-0040-xS561574363Allard, J., & Champoux, Y. (1992). New empirical equations for sound propagation in rigid frame fibrous materials. The Journal of the Acoustical Society of America, 91(6), 3346-3353. doi:10.1121/1.402824Attenborough, K. (1983). Acoustical characteristics of rigid fibrous absorbents and granular materials. The Journal of the Acoustical Society of America, 73(3), 785-799. doi:10.1121/1.389045Bies, D. A., & Hansen, C. H. (1980). Flow resistance information for acoustical design. Applied Acoustics, 13(5), 357-391. doi:10.1016/0003-682x(80)90002-xChampoux, Y., Stinson, M. R., & Daigle, G. A. (1991). Air‐based system for the measurement of porosity. The Journal of the Acoustical Society of America, 89(2), 910-916. doi:10.1121/1.1894653Crocker, M. J., & Arenas, J. P. (s. f.). Use of Sound-Absorbing Materials. Handbook of Noise and Vibration Control, 696-713. doi:10.1002/9780470209707.ch57Delany, M. E., & Bazley, E. N. (1970). Acoustical properties of fibrous absorbent materials. Applied Acoustics, 3(2), 105-116. doi:10.1016/0003-682x(70)90031-9Dunn, I. P., & Davern, W. A. (1986). Calculation of acoustic impedance of multi-layer absorbers. Applied Acoustics, 19(5), 321-334. doi:10.1016/0003-682x(86)90044-7Fellah, Z. E. A., Berger, S., Lauriks, W., Depollier, C., Aristégui, C., & Chapelon, J.-Y. (2003). Measuring the porosity and the tortuosity of porous materials via reflected waves at oblique incidence. The Journal of the Acoustical Society of America, 113(5), 2424-2433. doi:10.1121/1.1567275Fellah, Z. E. A., Berger, S., Lauriks, W., Depollier, C., & Fellah, M. (2003). Measuring the porosity of porous materials having a rigid frame via reflected waves: A time domain analysis with fractional derivatives. Journal of Applied Physics, 93(1), 296-303. doi:10.1063/1.1524025Fellah, Z. E. A., Berger, S., Lauriks, W., Depollier, C., Trompette, P., & Chapelon, J. Y. (2003). Ultrasonic measurement of the porosity and tortuosity of air-saturated random packings of beads. Journal of Applied Physics, 93(11), 9352-9359. doi:10.1063/1.1572191Fellah, Z. E. A., Mitri, F. G., Fellah, M., Ogam, E., & Depollier, C. (2007). Ultrasonic characterization of porous absorbing materials: Inverse problem. Journal of Sound and Vibration, 302(4-5), 746-759. doi:10.1016/j.jsv.2006.12.007Garai, M., & Pompoli, F. (2005). A simple empirical model of polyester fibre materials for acoustical applications. Applied Acoustics, 66(12), 1383-1398. doi:10.1016/j.apacoust.2005.04.008ISO (1998), 10534-2:1998. Acoustics - determination of sound absorption coefficient and impedance in impedance tubes - Part 2: transfer-function method, International Organization for Standardization, Geneva.Miki, Y. (1990). Acoustical properties of porous materials. Modifications of Delany-Bazley models. Journal of the Acoustical Society of Japan (E), 11(1), 19-24. doi:10.1250/ast.11.19Miki, Y. (1990). Acoustical properties of porous materials. Generalizations of empirical models. Journal of the Acoustical Society of Japan (E), 11(1), 25-28. doi:10.1250/ast.11.25Ramis, J., Alba, J., Del Rey, R., Escuder, E., & Sanchís, V. J. (2010). Nuevos materiales absorbentes acústicos basados en fibra de kenaf. Materiales de Construcción, 60(299), 133-143. doi:10.3989/mc.2010.50809Shoshani, Y., & Yakubov, Y. (2000). Numerical assessment of maximal absorption coefficients for nonwoven fiberwebs. Applied Acoustics, 59(1), 77-87. doi:10.1016/s0003-682x(99)00015-8Umnova, O., Attenborough, K., Shin, H.-C., & Cummings, A. (2005). Deduction of tortuosity and porosity from acoustic reflection and transmission measurements on thick samples of rigid-porous materials. Applied Acoustics, 66(6), 607-624. doi:10.1016/j.apacoust.2004.02.005Voronina, N. (1994). Acoustic properties of fibrous materials. Applied Acoustics, 42(2), 165-174. doi:10.1016/0003-682x(94)90005-1Voronina, N. (1996). Improved empirical model of sound propagation through a fibrous material. Applied Acoustics, 48(2), 121-132. doi:10.1016/0003-682x(95)00055-eVoronina, N. (1998). An empirical model for elastic porous materials. Applied Acoustics, 55(1), 67-83. doi:10.1016/s0003-682x(97)00098-4Voronina, N. (1999). An empirical model for rigid-frame porous materials with low porosity. Applied Acoustics, 58(3), 295-304. doi:10.1016/s0003-682x(98)00076-0Voronina, N. ., & Horoshenkov, K. . (2003). A new empirical model for the acoustic properties of loose granular media. Applied Acoustics, 64(4), 415-432. doi:10.1016/s0003-682x(02)00105-6Wang, X., Eisenbrey, J., Zeitz, M., & Sun, J. Q. (2004). Multi-stage regression analysis of acoustical properties of polyurethane foams. Journal of Sound and Vibration, 273(4-5), 1109-1117. doi:10.1016/j.jsv.2003.09.039Wilson, D. K. (1997). Simple, relaxational models for the acoustical properties of porous media. Applied Acoustics, 50(3), 171-188. doi:10.1016/s0003-682x(96)00048-

Molecular Origin of Blood-Based Infrared Spectroscopic Fingerprints**

Infrared spectroscopy of liquid biopsies is a time- and cost-effective approach that may advance biomedical diagnostics. However, the molecular nature of disease-related changes of infrared molecular fingerprints (IMFs) remains poorly understood, impeding the method's applicability. Here we probe 148 human blood sera and reveal the origin of the variations in their IMFs. To that end, we supplemented infrared spectroscopy with biochemical fractionation and proteomic profiling, providing molecular information about serum composition. Using lung cancer as an example of a medical condition, we demonstrate that the disease-related differences in IMFs are dominated by contributions from twelve highly abundant proteins-that, if used as a pattern, may be instrumental for detecting malignancy. Tying proteomic to spectral information and machine learning advances our understanding of the infrared spectra of liquid biopsies, a framework that could be applied to probing of any disease.** A previous version of this manuscript has been deposited on a preprint server (http://arxiv.org/abs/2102.00765)

Phenomenon of mathematical fluency.

This study explored the longitudinal relationship between motivation and acquisition of a second modern foreign language (MFL). Participants were 11 to 12 year-old pupils attending the first year of secondary school. They constituted a naïve population as formal MFL learning in the United Kingdom begins in secondary school. MFL achievement, assessed using national curriculum standards, and self-report measures of motivation were collected at four time points throughout the year. Previous motivation was found to be the only predictor of motivation at the end of the academic year. In the same way, previous achievement was the only predictor of final achievement. Results showed that the correlational relationship between motivation and achievement over time was stable, with modest effect size. Cross-lagged panel analysis was adopted in order to assess the causality of the observed relationship between motivation and achievement. However, no cross-lagged relationships were observed in this sample. Once accounting for the stability of the constructs and their cross-sectional (contemporaneous) relationship, no further variance was explained by cross-lagged relationships between motivation and achievement at different time points

Determination of Cs-137 in Natural Waters in the Sverdlovsk and Chelyabinsk Regions

The content of Cs-137 in natural water samples was analyzed using NKF-GDT sorbent for concentrating. Water bodies with increased radionuclide content were identified.Исследование выполнено при финансовой поддержке РФФИ и Правительства Свердловской области в рамках научного проекта № 20-43-660055