The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a ...search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012-2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy) carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2
. At a concentration of 52.0 μM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility - high activity (IC
= 1.06 μg/mL) and high selectivity index (SI = 78.6) - this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.
Positron annihilation lifetime spectroscopy (PALS) was applied to study the annealing of radiation-induced defects in polycrystalline tungsten (W) irradiated with 21.6 MeV protons at 100 °C up to a ...fluence of 5 × 1015 p/cm2. Three components were observed in the measured spectra: short-lifetime of 100–120 ps (positron annihilation in the defect-free W lattice), medium-lifetime of ∼190–330 ps (annihilation at mono-vacancies and small vacancy cluster containing ∼ 2–4 vacancies) and long-lifetime of ∼500 ps (annihilation in large vacancy clusters containing more than 10 vacancies). The irradiation of W with protons at 100 °C, primary, led to the formation of mono-vacancies, self-interstitial defects were created as well but migrated towards sinks during the irradiation. Onset of vacancy diffusion in W starts already at 200 °C before defect recovery stage III. After annealing at ∼400 °C, a sharp drop in the intensity of the positron medium-life component together with a simultaneous increase in positron lifetime from ∼220 to ∼280 ps is observed, and a long-life component appears. This indicates migration and annealing of vacancies and their agglomeration in large vacancy clusters. After annealing at 500–700C, the intensity of long-life component increases indicating the growth of large vacancy clusters but at 900 °C they anneal completely as the mean lifetime recovers nearly to the value measured in the un-irradiated material.
The gamma-ray background problem is known to be acute in any low-background underground experiment. The variations of this background depend on many parameters and should be taken into account when ...interpreting the results of experiments combined under the term “underground physics”. This paper is devoted to studying the long-term variations of the gamma-ray background in an underground laboratory with a scintillation detector based on a CsI crystal. Our studies have revealed a new effect in underground physics—a delayed nonlinear pumping effect for the gamma-ray background in an underground room that can lead to a significant rise of this background at an anomalously low atmospheric pressure.
We developed a new test system to detect the omicron variant of SARS-CoV-2 using allele-specific reverse transcription PCR and estimated the frequency of its detection in patients living in the ...Novosibirsk Region. Clinical samples were divided into 3 groups: samples collected from December 1 to December 30, 2021 (group 1;
n
=66), from December 30, 2021 to January 10, 2022 (group 2;
n
=20), and from January 11 to January 22, 2022 (group 3;
n
=101). Based on the identification of 5 mutations specific to SARS-CoV-2 (B.1.1.529), two systems of oligonucleotide primers and probes were developed for detecting this coronavirus genotype in clinical samples. Limit of detection (LOD
95
) was 4×10
3
genome equivalents per 1 ml of clinical sample for the first test system and 2×10
3
for the for the second test system. The omicron variant of SARS-CoV-2 was absent in group 1 of studied samples, but was detected in 20% (4/20) of group 2 samples and 88% of group 2 samples collected within less than 2 weeks of January 2022. Using developed test system, we showed that in less than 2 weeks the omicron variant has become dominant in patients, which confirms previously published data on its exceptional contagiousness.
Effect of annealing of a cold-worked CoCrFeMnNi alloy at temperatures of 500–900 °C for 1–50 h on the structure and mechanical properties was studied in the present work. Annealing for an hour ...resulted in: i) recrystallization of the face-centered cubic (fcc) matrix at 600–900 °C; ii) precipitation of a Cr-rich body-centered cubic (bcc) phase at 500–700 °C or a sigma phase particles at 600–800 °C. Moreover, an increase in the annealing time to 50 h at 600 °C resulted in a continuous growth of both the fcc grans and bcc/sigma particles and in an increase in the fraction of the sigma phase at the expense of the bcc phase particles. The fcc grains growth was found to be controlled by the pinning effect of the second phase particles. Soaking for an hour at 500–600 °C resulted in a substantial increase in strength of the alloy due to the second phases precipitation. Meanwhile annealing at the higher temperatures as well as an increase in the annealing time at 600 °C resulted in softening; however, even after 50 h annealing, the alloy demonstrated reasonably high strength. In the latter case fine fcc grains, preserved due to the pinning effect by the second phases particles, contributed to strength mainly.
We consider the distribution of tropospheric ozone on the territory of Russia in 2022 using data from 33 stations located in different physical and geographical zones, as well as its vertical ...distribution from results of aircraft sensing. It was shown that measurements at all measurement sites exceeded the maximum permissible daily average concentrations, determined by the national hygienic standard. In some regions, the excess over the maximum permissible concentrations of the working zone and over the maximum one-time hourly average concentrations is recorded, so that the population should be broadly warned about the monitoring results and measures should be taken to reduce the level of ozone concentration in the surface air layer.
Nanoplatforms applied for the loading of anticancer drugs is a cutting-edge approach for drug delivery to tumors and reduction of toxic effects on healthy cells. In this study, we describe the ...synthesis and compare the sorption properties of four types of potential doxorubicin-carriers, in which iron oxide nanoparticles (IONs) are functionalized with cationic (polyethylenimine, PEI), anionic (polystyrenesulfonate, PSS), and nonionic (dextran) polymers, as well as with porous carbon. The IONs are thoroughly characterized by X-ray diffraction, IR spectroscopy, high resolution TEM (HRTEM), SEM, magnetic susceptibility, and the zeta-potential measurements in the pH range of 3-10. The degree of doxorubicin loading at pH 7.4, as well as the degree of desorption at pH 5.0, distinctive to cancerous tumor environment, are measured. Particles modified with PEI were shown to exhibit the highest loading capacity, while the greatest release at pH 5 (up to 30%) occurs from the surface of magnetite decorated with PSS. Such a slow release of the drug would imply a prolonged tumor-inhibiting action on the affected tissue or organ. Assessment of the toxicity (using Neuro2A cell line) for PEI- and PSS-modified IONs showed no negative effect. In conclusion, the preliminary evaluation of the effects of IONs coated with PSS and PEI on the rate of blood clotting was carried out. The results obtained can be taken into account when developing new drug delivery platforms.
Industry 4.0 in healthcare involves use of a wide range of modern technologies including digitisation, artificial intelligence, user response data (ergonomics), human psychology, the Internet of ...Things, machine learning, big data mining, and augmented reality to name a few. The healthcare industry is undergoing a paradigm shift thanks to Industry 4.0, which provides better user comfort through proactive intervention in early detection and treatment of various diseases. The sector is now ready to make its next move towards Industry 5.0, but certain aspects that motivated this review paper need further consideration. As a fruitful outcome of this review, we surveyed modern trends in this arena of research and summarised the intricacies of new features to guide and prepare the sector for an Industry 5.0-ready healthcare system.
Tumor-derived extracellular vesicles (EVs) are active contributors in metastasis and immunosuppression in tumor microenvironment. At least some of the EVs carry tumor surface molecules such as ...tumor-associated antigens (TAAs) and/or checkpoint inhibitors, and potentially could interact with T cells or CAR T cells. Upon contact with T cells, EVs could alter their phenotype and functions by triggering signaling through TCR or CAR reprogramming them to escape immune response. We hypothesize that EVs that possess TAA on the surface will probably interact with CAR T cells which can recognize and bind corresponding TAA. This interaction between EVs and CAR T cells may change the outcome of CAR T-based cancer immunotherapy since it should affect CAR T cells. Also, EVs could serve as adjuvants and antigenic components of antitumor vaccines. Herein, we isolated EVs from B cell precursor leukemia cell line (pre-B ALL) Nalm-6 and demonstrated that recognition and binding of CD19
EVs with CD19-CAR T cells strongly depends on the presence of CD19 antigen. CD19
EVs induce secretion of pro-inflammatory cytokines (IL-2 and IFN-y) and upregulated transcription of activation-related genes (IFNG, IFNGR1, FASLG, IL2) in CD19-CAR T cells. Tumor necrosis factor receptor superfamily (TNFRSF4 and TNFRSF9) and T-cell exhaustion markers (CTLA4, LAG3, TIM3 and PDCD1LG2) were also upregulated in CD19-CAR T cells after incubation with CD19
EVs. Long-term cultivation of CD19
or PD-L1
EVs with CD19-CAR T cells led to increased terminal differentiation and functional exhaustion according to elevated expression of PD-1, TIGIT, CD57. In summary, our results suggest that chronic exposure of CD19-CAR T cells to CD19
EVs mediates activation and systemic exhaustion in antigen-specific manner, and this negative effect is accompanied by the impaired cytotoxic activity in vitro.
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