We have investigated the magnetic properties and micromagnetic structure of multilayer Co/Pt films with the variation of bilayer thickness (Co(0.3 × t nm)/Pt(0.5 × t nm)10). The films represent Co-Pt ...alloys with periodic Co vs Pt composition. The magnetic force microscopy and Lorentz transmission electron microscopy have demonstrated the presence of N é el-type skyrmions in the films. The density of skyrmions was found to be strongly dependent on the bilayer thickness parameter (t). The effect is attributed to Dzyaloshinskii–Moriya interaction which is known to be strongly dependent on the regularities of magnetic and nonmagnetic layers alternation. We emphasize that the investigated system represents an intermediate case between unalloyed multilayer films and uniformly mixed alloys. Despite that it demonstrates similar micromagnetic behavior with skyrmion density very well controllable by modulation of technological parameters.
•Neel-type skyrmions are formed in multilayer Co/Pt films with varying bilayer thickness and diffuse Co/Pt interface.•Skyrmion density is well correlated with Dzyaloshinskii-Moriya interaction constant.•Both skyrmion density and Dzyaloshinskii–Moriya interaction constant are strongly dependent on the bilayer thickness parameter.
We consider properties of dichroic antenna arrays on a silicon substrate with integrated cold-electron bolometers to detect radiation at frequencies of 210 and 240 GHz. This frequency range is widely ...used in cosmic microwave background experiments in space, balloon, and ground-based missions such as BICEP Array, LSPE, LiteBIRD, QUBIC, Simons Observatory, and AliCPT. As a direct radiation detector, we use cold-electron bolometers, which have high sensitivity and a wide operating frequency range, as well as immunity to spurious cosmic rays. Their other advantages are the compact size of the order of a few micrometers and the effect of direct electron cooling, which can improve sensitivity in typical closed-loop cycle
He cryostats for space applications. We study a novel concept of cold-electron bolometers with two SIN tunnel junctions and one SN contact. The amplitude-frequency characteristics measured with YBCO Josephson Junction oscillators show narrow peaks at 205 GHz for the 210 GHz array and at 225 GHz for the 240 GHz array; the separation of these two frequency bands is clearly visible. The noise equivalent power level at an operating point in the current bias mode is 5 × 10
W/√Hz.
Thin ferromagnet/heavy metal multilayer films are considered as prospective media for a magnetic recording and Co/Pd films are a good example of such materials. In this work, the magnetic properties ...and micromagnetic structure of Co/Pd multilayer films are studied with different bilayer thicknesses (Co(0.3 × t nm)/Pd(0.5 × t nm)10), but with the same ratio Co versus Pd. Transmission electron microscope and X‐ray diffraction studies allow authors to suppose that the investigated films are highly mixed alloys. Magnetic force microscopy and Lorentz transmission electron microscopy showed the presence of various micromagnetic features in the films. Along with skyrmions that are well‐known magnetic topological artifacts some new features are revealed, which are interpreted as 360° domain walls, skyrmioniums and the combination of the above two. It is found that the type and density of micromagnetic features strongly depend on the bilayer thickness parameter (t). The effect is associated with the peculiarities of interfacial magnetic interactions in the samples with highly mixed interfaces. The tooling coefficient represents a useful tool of the electron beam evaporation technique enabling wide manipulation of micromagnetic particles, in particular, skyrmioniums that are currently considered a prospective media for current driven magnetic recording.
The magnetic properties and micromagnetic structure of Co/Pd multilayer films with different bilayer thicknesses, but with the same ratio Co versus Pd are studied. A number of micromagnetic features in the films are revealed, such as skyrmions, 360° domain walls, skyrmioniums and the combination of them.
The roots of the medicinal plant
are rich in biologically active natural products, with triterpene saponins constituting one of their major groups. These metabolites can be efficiently extracted by ...methanol and ethanol. Due to their low toxicity, natural deep eutectic solvents (NADES) were recently proposed as promising alternative extractants for the isolation of natural products from medicinal plants. However, although NADES-based extraction protocols are becoming common in routine phytochemical work, their application in the isolation of triterpene saponins has not yet been addressed. Therefore, here, we address the potential of NADES in the extraction of triterpene saponins from the roots of
. For this purpose, the previously reported recoveries of
triterpene saponins in extraction experiments with seven different acid-based NADES were addressed by a targeted LC-MS-based quantitative approach for, to the best of our knowledge, the first time. Thereby, 20 triterpene saponins were annotated by their exact mass and characteristic fragmentation patterns in the total root material, root bark and root core of
by RP-UHPLC-ESI-QqTOF-MS, with 9 of them being identified in the roots of this plant for the first time. Triterpene saponins were successfully extracted from all tested NADES, with the highest efficiency (both in terms of the numbers and recoveries of individual analytes) achieved using a 1:1 mixture of choline chloride and malic acid, as well as a 1:3 mixture of choline chloride and lactic acid. Thereby, for 13 metabolites, NADES were more efficient extractants in comparison with water and ethanol. Our results indicate that new, efficient NADES-based extraction protocols, giving access to high recoveries of triterpene saponins, might be efficiently employed in laboratory practice. Thus, our data open the prospect of replacing alcohols with NADES in the extraction of
roots.
Pharmacopoeias are important resources for the quality control of medicinal plants and their products. Considering that approximately 80% of the world population to different extents relies on ...medicinal plants for the prevention and treatment of medical ailments the safety and suitability of medicinal plants is extremely important. Unfortunately, for many medicinal plants the active component or group of components responsible for their pharmacological activity are unknown. In such cases, the standardization of the medicinal plant material is performed using reference compounds that are either contained in the plant, but are known to not mediate the plants biological activity or are not contained in the plant at all, but find use as auxiliary reagents, for example, to help identify the necessary chromatographic zones/peaks. Additionally, many medicinal plants do not have qualitative or quantitative analysis procedures in place or use methods with low selectivity (spectrophotometry, colour reactions). In these cases, it is impossible to confidently and adequately standardize the medicinal plant material. Two other issues that complicate medicinal plant standardization include the variability of its chemical composition depending on multiple biotic and abiotic factors and the lack of sufficient data on the chemical composition of some plants. In this review, we analyzed medicinal plants common to the Eurasian Economic Union (EAEU), European, United State and Japanese Pharmacopoeias. We have analysed and systematized literature data devoted to the relation between the chemical composition and pharmacological activity of the plants presented in this review. Based on the analysed data, we have suggested more rational and adequate methods for the quality assessment and quantitative standardization of medicinal plants.
Clinical trials of targeted therapy (TT) and immunotherapy (IT) for highly aggressive advanced melanoma have shown marked improvements in response and survival rates. However, real-world data on ...treatment patterns and clinical outcomes for patients with advanced BRAF V600 mutant melanoma are ultimately scarce. The study was designed as an observational retrospective chart review study, which included 382 patients with advanced BRAF V600 mutant melanoma, who received TT in a real-world setting and were not involved in clinical trials. The data were collected from twelve medical centers in Russia. The objective response rates (ORRs) to combined BRAFi plus MEKi and to BRAFi mono-therapy were 57.4% and 39.8%, respectively. The median progression-free survival (PFS) and median overall survival (OS) were 9.2 months and 22.6 months, respectively, for the combined first-line therapy; 9.4 months and 16.1 months, respectively, for the combined second-line therapy; and 7.4 months and 17.1 months, respectively, for the combined third- or higher-line therapy. Analysis of treatment patterns demonstrated the effectiveness of the combined TT with BRAF plus MEK inhibitors in patients with brain metastases, rare types of BRAF mutations, and across lines of therapy, as well as a well-tolerated and manageable safety profile.
Super-enhancers (SEs) are regions of the genome that play a crucial regulatory role in gene expression by promoting large-scale transcriptional responses in various cell types and tissues. Recent ...research suggests that alterations in super-enhancer activity can contribute to the development and progression of various disorders. The aim of this research is to explore the multifaceted roles of super-enhancers in gene regulation and their significant implications for understanding and treating complex diseases. Here, we study and summarise the classification of super-enhancer constituents, their possible modes of interaction, and cross-regulation, including super-enhancer RNAs (seRNAs). We try to investigate the opportunity of SE dynamics prediction based on the hierarchy of enhancer single elements (enhancers) and their aggregated action. To further our understanding, we conducted an in silico experiment to compare and differentiate between super-enhancers and locus-control regions (LCRs), shedding light on the enigmatic relationship between LCRs and SEs within the human genome. Particular attention is paid to the classification of specific mechanisms and their diversity, exemplified by various oncological, cardiovascular, and immunological diseases, as well as an overview of several anti-SE therapies. Overall, the work presents a comprehensive analysis of super-enhancers across different diseases, aiming to provide insights into their regulatory roles and may act as a rationale for future clinical interventions targeting these regulatory elements.
The effect of treadmill training loads on the content of cytokines in mice skeletal muscles with metabolic disorders induced by a 16 week high fat diet (HFD) was studied. The study included ...accounting the age and biorhythmological aspects. In the experiment, mice were used at the age of 4 and 32 weeks, by the end of the experiment—respectively 20 and 48 weeks. HFD feeding lasted 16 weeks. Treadmill training were carried out for last 4 weeks six times a week, the duration 60 min and the speed from 15 to 18 m/min. Three modes of loading were applied. The first subgroup was subjected to stress in the morning hours (light phase); the second subgroup was subjected to stress in the evening hours (dark phase); the third subgroup was subjected to loads in the shift mode (the first- and third-weeks treadmill training was used in the morning hours, the second and fourth treadmill training was used in the evening hours). In 20-week-old animals, the exercise effect does not depend on the training regime, however, in 48-week-old animals, the decrease in body weight in mice with the shift training regime was more profound. HFD affected muscle myokine levels. The content of all myokines, except for LIF, decreased, while the concentration of CLCX1 decreased only in young animals in response to HFD. The treadmill training caused multidirectional changes in the concentration of myokines in muscle tissue. The IL-6 content changed most profoundly. These changes were observed in all groups of animals. The changes depended to the greatest extent on the training time scheme. The effect of physical activity on the content of IL-15 in the skeletal muscle tissue was observed mostly in 48-week-old mice. In 20-week-old animals, physical activity led to an increase in the concentration of LIF in muscle tissue when applied under the training during the dark phase or shift training scheme. In the HFD group, this effect was significantly more pronounced. The content of CXCL1 did not change with the use of treadmill training in almost all groups of animals. Physical activity, introduced considering circadian rhythms, is a promising way of influencing metabolic processes both at the cellular and systemic levels, which is important for the search for new ways of correcting metabolic disorders.
Tyrosyl-DNA phosphodiesterase 1 (TDP1) catalyzes the cleavage of the phosphodiester bond between the tyrosine residue of topoisomerase 1 (TOP1) and the 3' phosphate of DNA in the single-strand break ...generated by TOP1. TDP1 promotes the cleavage of the stable DNA-TOP1 complexes with the TOP1 inhibitor topotecan, which is a clinically used anticancer drug. This article reports the synthesis and study of usnic acid thioether and sulfoxide derivatives that efficiently suppress TDP1 activity, with IC
values in the 1.4-25.2 μM range. The structure of the heterocyclic substituent introduced into the dibenzofuran core affects the TDP1 inhibitory efficiency of the compounds. A five-membered heterocyclic fragment was shown to be most pharmacophoric among the others. Sulfoxide derivatives were less cytotoxic than their thioester analogs. We observed an uncompetitive type of inhibition for the four most effective inhibitors of TDP1. The anticancer effect of TOP1 inhibitors can be enhanced by the simultaneous inhibition of PARP1, TDP1, and TDP2. Some of the compounds inhibited not only TDP1 but also TDP2 and/or PARP1, but at significantly higher concentration ranges than TDP1. Leader compound
showed promising synergy on HeLa cells in conjunction with the TOP1 inhibitor topotecan.
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