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Exploring new strategies to manipulate the order parameter of magnetic materials by electrical means is of great importance not only for advancing our understanding of fundamental magnetism but also for unlocking potential applications. A well-established concept uses gate voltages to control magnetic properties by modulating the carrier population in a capacitor structure1–5. Here we show that, in Pt/Al/Fe/GaAs(001) multilayers, the application of an in-plane charge current in Pt leads to a shift in the ferromagnetic resonance field depending on the microwave frequency when the Fe film is sufficiently thin. The experimental observation is interpreted as a current-induced modification of the magnetocrystalline anisotropy ΔHAof Fe. We show that (1) ΔHAdecreases with increasing Fe film thickness and is connected to the damping-like torque; and (2) ΔHAdepends not only on the polarity of charge current but also on the magnetization direction, that is, ΔHAhas an opposite sign when the magnetization direction is reversed. The symmetry of the modification is consistent with a current-induced spin6–8and/or orbit9–13accumulation, which, respectively, act on the spin and/or orbit component of the magnetization. In this study, as Pt is regarded as a typical spin current source6,14, the spin current can play a dominant part. The control of magnetism by a spin current results from the modified exchange splitting of the majority and minority spin bands, providing functionality that was previously unknown and could be useful in advanced spintronic devices.

High-density lipoprotein (HDL) particles in ST-segment elevation myocardial infarction (STEMI) are deficient in their anti-atherogenic function. Molecular determinants of such deficiency remain obscure.

Several methods are available to visualize and assess the kinetics and efficiency of elemental steps of protein biosynthesis. However, each of these methods has its own limitations. Here, we present a novel, simple and convenient tool for monitoring stepwise in vitro translation initiated by BODIPY-Met-tRNA. Synthesis and release of very short, 1–7 amino acids, BODIPY-labeled peptides, can be monitored using urea–polyacrylamide gel electrophoresis. Very short BODIPY-labeled oligopeptides might be resolved this way, in contrast to widely used Tris-tricine gel electrophoresis, which is suitable to separate peptides larger than 1 kDa. The method described in this manuscript allows one to monitor the steps of translation initiation, peptide transfer, translocation, and termination as well as their inhibition at an unprecedented single amino acid resolution.

The nonuniform sampling (NUS) is a powerful approach to enable fast acquisition but requires sophisticated reconstruction algorithms. Faithful reconstruction from partially sampled exponentials is highly expected in general signal processing and many applications. Deep learning (DL) has shown astonishing potential in this field, but many existing problems, such as lack of robustness and explainability, greatly limit its applications. In this work, by combining the merits of the sparse model-based optimization method and data-driven DL, we propose a DL architecture for spectra reconstruction from undersampled data, called MoDern. It follows the iterative reconstruction in solving a sparse model to build the neural network, and we elaborately design a learnable soft-thresholding to adaptively eliminate the spectrum artifacts introduced by undersampling. Extensive results on both synthetic and biological data show that MoDern enables more robust, high-fidelity, and ultrafast reconstruction than the state-of-the-art methods. Remarkably, MoDern has a small number of network parameters and is trained on solely synthetic data while generalizing well to biological data in various scenarios. Furthermore, we extend it to an open-access and easy-to-use cloud computing platform (XCloud-MoDern), contributing a promising strategy for further development of biological applications.

It is a basic assumption of stylometry that texts written by the same person show greater stylometric similarity even if published under multiple pennames. Statistical authorship attribution strongly relies on the ability of Burrows’s Delta and its variants to cluster one author together regardless of pseudonyms. At the same time, the very first computational discoveries by the founder of modern stylometry showed that a single author is capable of producing multiple voices (Burrows, 1987, Computation into Criticism: A Study of Jane Austen’s Novels and an Experiment in Method. Clarendon Press). We investigate two authors whose stylistically autonomous pennames seem to deceive Delta and override authorial signals: a Portuguese poet Fernando Pessoa and a French novelist Romain Gary. Pessoa managed to create at least three pennames (the author himself used the term ‘heteronym’) who exhibit all traits of individual human beings from the stylometric point of view. Gary’s alter ego Emile Ajar, who was an intentional literary mystification, also demonstrates traits of stylometric autonomy. At the same time, other pseudonyms used by Gary lack that autonomy completely. Our investigation shows that there appears to be a continuum between a purely formal use of a penname, which brings almost no distinction from the real name of an author, and a strong literary sub-personality such as those created by Pessoa.

Exponential function is a basic form of temporal signals, and how to fast acquire this signal is one of the fundamental problems and frontiers in signal processing. To achieve this goal, partial data may be acquired but result in severe artifacts in its spectrum, which is the Fourier transform of exponentials. Thus, reliable spectrum reconstruction is highly expected in the fast data acquisition in many applications, such as chemistry, biology, and medical imaging. In this work, we propose a deep learning method whose neural network structure is designed by imitating the iterative process in the model-based state-of-the-art exponentials’ reconstruction method with the low-rank Hankel matrix factorization. With the experiments on synthetic data and realistic biological magnetic resonance signals, we demonstrate that the new method yields much lower reconstruction errors and preserves the low-intensity signals much better than compared methods.

Purpose: At first, p53 was believed to be present primarily in malignant cells. In fact, p53 turned out to play a major role in vascular remodeling associated with transplantation surgery or intraluminal intervention. The purpose of this review was to describe the multiple processes which include p53 activation and to analyze its impact on cellular proliferation and migration, as well as its involvement in such conditions as pulmonary arterial hypertension, subarachnoid hemorrhage, ischemia and others. Methods: To select the initial sources for our review, we searched the PubMed database with the keywords “p53 mechanisms”, “p53 atherosclerosis”, “p53 cardiovascular”, etc. To maintain the relevance, we selected only papers published in 2018 and later. Results: Overall, p53 is proved to have a strong relationship with the whole cardiovascular system. Available data also indicate a connection of p53 to the atherosclerosis initiation and progression. P53 might become a promising therapeutic target for treatment of acute and chronic cardiovascular diseases due to its ability to influence various vascular mechanisms. Conclusion: Modifying the synthesis of this protein and the expression of the corresponding genes to create models, cellular and animal, that allow us to better understand about complex nature of the pathogenesis of atherosclerosis seems to be promising. Also, p53 can be considered as a possible target for the development of therapeutic strategies. The same is true both for the protein itself and for all participants in the pathway of its metabolism.

This article considers a combination of actuation tendons and measurement strings to achieve accurate shape sensing and direct kinematics of continuum robots. Assuming general string routing, a methodical Lie group formulation for the shape sensing of these robots is presented. The shape kinematics is expressed using arc-length-dependent curvature distributions parameterized by modal functions, and the Magnus expansion for Lie group integration is used to express the shape as a product of exponentials. The tendon and string length kinematic constraints are solved for the modal coefficients and the configuration space and body Jacobian are derived. The noise amplification index for the shape reconstruction problem is defined and used for optimizing the string/tendon routing paths, and a planar simulation study shows the minimal number of strings/tendons needed for accurate shape reconstruction. A torsionally stiff continuum segment is used for experimental evaluation, demonstrating mean (maximal) end-effector absolute position error of less than 2% (5%) of total length. Finally, a simulation study of a torsionally compliant segment demonstrates the approach for general deflections and string routings. We believe that the methods of this article can benefit the design process, sensing, and control of continuum and soft robots.

Abstract: The constructive and technological solutions of a new-generation interactive multimodal hybrid conformal sensor-correcting microsystem are presented. Functional modules of the microsystem made in the form of an ultrathin bracelet or patch with the possibility of being fixed to human skin are considered. The advantages of the proposed microsystem, its purpose and possible applications are discussed.

A commercially viable and efficient method for the synthesis of medetomidine hydrochloride (1) was developed combining two reliable synthetic approaches: the modern method for C–C bond formation through the sp2–sp3Kumada cross-coupling and the classical method for the imidazole ring formation based on the Weidenhagen reaction. The latter was earlier limited by the high toxicity of hydrogen sulfide used to recover imidazoles from the copper complexes and difficulties in working up the reaction mixture. We achieved a remarkable advance in the Weidenhagen reaction through the use of nonhazardous complexons providing less than a 10 ppm residual level of metals in the final product. In the developed method, 3-(2,3-dimethylphenyl)butan-2-one (7) is synthesized in a one-step and one-pot manner by the cross-coupling of 2-(1-bromoethyl)-2-methyl-1,3-dioxolane (14) and 2,3-dimethylphenyl magnesium bromide (10), followed by one-pot deprotection of the resulting ethylene ketal 8, and several intermediates at the next steps can be used without additional purification; these benefits enable medetomidine hydrochloride (1) to potentially be produced on a multikilogram scale.

Background: Metabolic syndrome is a clinical condition that deserves special attention because it puts the individual at high cardiovascular risk, especially heart attack and stroke. Considering precision medicine, it would be advisable to evaluate the individual cardio-metabolic risk by estimating the coexistence of risk factors (abdominal obesity, low level of High-Density Lipoprotein Cholesterol, High Triglycerides, and small dense Low-Density Lipoproteins sub-classes, hypertension, and elevated fasting glycemia), which could engrave on metabolism increasing cardiovascular mortality. Objective: To identify genetic and epigenetic biomarkers may assist in the possibility of helping follow-up strategies and other measures of prevention and in metabolic risk. Methods: We searched for studies that valued the combination between epigenetic biomarkers and all factors of cardio-metabolic risk. Results: Numerous researches have investigated the molecular start of metabolic alterations, focusing on the epigenetic mark, as methylation of DNA, histone modifications and non.coding RNAs. It has been found that DNA methylation is the most searched epigenetic sign in the human genome concerning the control of gene expression. Conclusion: For the screening, diagnosis, and prognosis of metabolic syndrome and the prescription of personalized medicine, the DNA methylation biomarkers specify for subjects have been recognized as an ensuring tool. While these results are promising, further investigations are needed to unravel the complicated synergic association of the genome, epigenome and the situations related to metabolic pathology.

Aortic aneurism development is dependent on internal and external etiological factors that define the width of the therapeutic window available for the treatment of patients with such diagnosis. In this review, we provide a detailed overview of the most prominent of these factors. In particular, we discuss the input of elevated blood pressure to the remodeling of the aortic wall, describe the mechanisms of inflammatory remodeling of the aorta, and evaluate the cross-interaction of blood pressure, inflammation and immunity during the pathology development. Better understanding of this interaction will allow broadening the therapeutic options available for patients with aortic aneurism or preventive strategies for patients with known risk factors. To date, modulation of the immune signaling appears to be a promising point of the therapeutic intervention for the treatment of such patients. In this article, we also discuss the search for new diagnostic markers predicting changes in the width of the therapeutic window for the management of patients with aortic aneurysm.

Gene expression is regulated and tightly controlled by epigenetic mechanisms. Alterations of these mechanisms are frequently observed in various diseases, particularly, in various types of cancer. Malignant transformation is caused by the impairment of the mechanisms of cell differentiation and cell cycle control associated with epigenetic changes. Altered patterns of epigenetic modification associated with malignancies can potentially be reversed by some agents that act on the key proteins responsible for DNA/histone modification and chromatin remodelling. Examples of such substances include the inhibitors of DNA methyltransferases or histone deacetylase. During the recent years, a number of such substances have been evaluated as potential therapeutic agents against certain types of cancer in preclinical and clinical studies, and some of them have been approved for treatment of hematological cancers. Application of epidrugs for therapy of solid tumors remains, however, more challenging. In this review, we summarize the current knowledge on the most studied mechanisms of epigenetic modification and the available epigenetically active drugs.

Amphiphilic thermoresponsive copolymer bottlebrushes based on methoxy oligo(ethylene glycol)7methacrylate and alkoxy(C12–C14) oligo(ethylene glycol)6methacrylate have been successfully synthesized via RAFT and conventional free-radical polymerization in toluene. The thermoresponsive behavior of the copolymers in dilute aqueous solutions was studied by turbidimetry and laser light scattering. In water, the copolymer brushes form flower-like micelles with a hydrophobic core consisting of a polymer backbone and alkyl(C12–C14) groups and poly(ethylene glycol) linear chains and loops forming a hydrophilic shell. The size and aggregation number of the micelles and the cloud point of solutions were found to depend on the copolymer composition and chain length, as well as on the synthesis method. The conditions needed for the formation of uni- and multimolecular micelles were determined. Fluorescence techniques were used to determine the CMC of the copolymers and the drug loading capacity of the micelles using pyrene as a model hydrophobic drug.

The most typical feature of atherogenesis in humans at its early stage is the formation of foam cells in subendothelial arterial intima, which occurs as the consequence of intracellular cholesterol deposition. The main source of lipids accumulating in the arterial wall is circulating low-density lipoprotein (LDL). However, LDL particles should undergo proatherogenic modification to acquire atherogenic properties. One of the known types of atherogenic modification of LDL is enzymatic deglycosilation, namely, desialylation, which is the earliest change in the cascade of following multiple LDL modifications. The accumulating data make sialidases an intriguing and plausible therapeutic target, since pharmacological modulation of activity of these enzymes may have beneficial effects in several pathologies, including atherosclerosis. The hypothesis exists that decreasing LDL enzymatic desialylation may result in the prevention of lipid accumulation in arterial wall, thus breaking down one of the key players in atherogenesis at the cellular level. Several drugs acting as glycomimetics and inhibiting sialidase enzymatic activity already exist, but the concept of sialidase inhibition as an anti-atherosclerosis strategy remains unexplored to date. This review is focused on the potential possibilities of the repurposing of sialidase inhibitors for pathogenetic anti-atherosclerotic therapy.

Abstract: Silymarin (SM) from Silybum marianum(L.) is a sum of flavolignans (silibinin, silychristin, silydianin, and isosilibinin), exhibiting a wide spectrum of biological activity and having anti-inflammatory, antitumor, hepatoprotective, immunomodulatory effects. Using a modified emulsion method with solvent evaporation, lipid nanoparticles with silymarin (LNP-SM) were obtained, the size of which was 257 ± 6 nm, and the ? potential was –20.8 ± 1.6 mV. The efficiency of SM inclusion in the LNP-SM was 89.8%, the loading degree was 5.4%. The release of CM from the composition of the resulting nanoparticles was prolonged; after 48 h, only 68.3 ± 5.4% of the active substance was released into the dialysis medium. The dynamics of the inclusion/release of SM in the composition of LNP into the films of bacterial cellulose (BC) produced by the Gluconacetobacter hanseniiGH-1/2008 strain has been studied. It was shown, that after 24 h of incubation the maximum of BC film saturation with SM reached 0.745 ± 0.038 mg/cm2, and the maximum release was 0.520 ± 0.041 mg/cm2. It was demonstrated that both LNP-SM sols and samples of BC saturated with LNP-SM exhibited low hemolytic activity, which indicates the potential biosafety of these preparations. The preparation LNP-SM, in contrast to free SM, exhibited fungistatic action against the fungi of A. nigerand C. albicans. Both free SM and LNP-SM suppressed the growth of gram-positive bacteria; however, the effect of LNP-SM was much more effective. The minimum inhibitory concentration of the LNP-SM preparation for B. subtilisand B. coagulanswas 105 and 210 µg/mL, respectively. The possibility of developing biocompatible coating materials based on BC saturated with LNP-SM is discussed.

Background: The present review article considers some chronic diseases of vascular and metabolic genesis, the causes of which may be mitochondrial dysfunction. Very often, in the long course of the disease, complications may occur, leading to myocardial infarction or ischemic stroke and, as a result, death. In particular, a large percentage of human deaths nowadays belongs to cardiovascular diseases, such as coronary heart disease (CHD), arterial hypertension, cardiomyopathies, and type 2 diabetes mellitus. Objective: The aim of the present review was the analysis of literature sources, devoted to an investigation of a link of mitochondrial DNA mutations with chronic diseases of vascular and metabolic genesis. Results: The analysis of literature indicates the association of the mitochondrial genome mutations with coronary heart disease, type 2 diabetes mellitus, hypertension, and various types of cardiomyopathies. Conclusion: The detected mutations can be used to analyze the predisposition to chronic diseases of vascular and metabolic genesis. They can also be used to create molecular-cell models necessary to evaluate the effectiveness of drugs developed for the treatment of these pathologies. MtDNA mutations associated with the absence of diseases of vascular and metabolic genesis could be potential candidates for gene therapy of the said diseases.

The plant alkaloid sanguinarine has antitumour, antiangiogenic, antimicrobial and antiviral activity. However, the maximum manifestation of the therapeutic potential of sanguinarine is hindered by relatively low bioavailability and a number of side effects. To increase the bioavailability and effectiveness of the therapeutic effect, sanguinarine was introduced into the pH-sensitive liposomes by the remote loading method. The average diameter of liposome particles with sanguinarine was 107.4 ± 3.7 nm; the zeta potential -12.7 ± 1.5 mV. The effectiveness of the inclusion of sanguinarine in liposomes was 75.94 ± 2.18%. In the model experiments, the dynamics of the release of sanguinarine from liposomes was studied, and the prolonged release pattern was demonstrated. The cytotoxic activity (CTA) of liposomal sanguinarine against tumour cells of the MCF-7, HeLa and K 562 lines was studied in vitro. Liposomal sanguinarine exhibited a dose-dependent CTA for tumour cells of all the lines studied; the highest CTA was seen with HeLa cells (IC503.2 μM). For this cell line CTA of liposomal sanguinarine significantly (~2.2 times) exceeded the activity of the free drug. A comparative study of liposomal and free sanguinarine with respect to the ability to induce apoptosis of HeLa cells has also been performed. At a concentration of 5 μM the liposomal sanguinarine induced apoptosis in 41.96% of tumour cells, whereas the free sanguinarine - only in 20.32% of the cells. It is likely that the use of sanguinarine in the composition of pH-sensitive liposomes can promote its effective release from the acid medium of the endosomal compartment of tumour cells and the manifestation of a toxic effect. The presented data allow to consider liposomal sanguinarine as a promising antitumour agent.

Background: The aim of the elucidation of mechanisms implicated in the chronification of inflammation is to shed light on the pathogenesis of disorders that are responsible for the majority of the incidences of diseases and deaths, and also causes of ageing. Atherosclerosis is an example of the most significant inflammatory pathology. The inflammatory response of innate immunity is implicated in the development of atherosclerosis arising locally or focally. Modified low-density lipoprotein (LDL) was regarded as the trigger for this response. No atherosclerotic changes in the arterial wall occur due to the quick decrease in inflammation rate. Nonetheless, the atherosclerotic lesion formation can be a result of the chronification of local inflammation, which, in turn, is caused by alteration of the response of innate immunity. Objective: In this review, we discussed potential mechanisms of the altered response of the immunity in atherosclerosis with a particular emphasis on mitochondrial dysfunctions. Conclusion: A few mitochondrial dysfunctions can be caused by the mitochondrial DNA (mtDNA) mutations. Moreover, mtDNA mutations were found to affect the development of defective mitophagy. Modern investigations have demonstrated the controlling mitophagy function in response to the immune system. Therefore, we hypothesized that impaired mitophagy, as a consequence of mutations in mtDNA, can raise a disturbed innate immunity response, resulting in the chronification of inflammation in atherosclerosis.

Background: Atherosclerosis is a chronic inflammatory condition that affects different arteries in the human body and often leads to severe neurological complications, such as stroke and its sequelae. Affected blood vessels develop atherosclerotic lesions in the form of focal thickening of the intimal layer, so called atherosclerotic plaques. Objectives: Despite the high priority of atherosclerosis research for global health and the numerous preclinical and clinical studies conducted, currently, there is no effective pharmacological treatment that directly impacts atherosclerotic plaques. Many knowledge gaps exist in our understanding of the mechanisms of plaque formation. In this review, we discuss the role of mitochondria in different cell types involved in atherogenesis and provide information about mtDNA mutations associated with the disease. Results: Mitochondria of blood and arterial wall cells appear to be one of the important factors in disease initiation and development. Significant experimental evidence connects oxidative stress associated with mitochondrial dysfunction and vascular disease. Moreover, mitochondrial DNA (mtDNA) deletions and mutations are being considered as potential disease markers. Further study of mtDNA damage and associated dysfunction may open new perspectives for atherosclerosis treatment. Conclusion: Mitochondria can be considered as important disease-modifying factors in several chronic pathologies. Deletions and mutations of mtDNA may be used as potential disease markers. Mitochondria-targeting antioxidant therapies appear to be promising for the development of treatment of atherosclerosis and other diseases associated with oxidative stress and chronic inflammation.

Antiseptics are an essential line of defense against bacterial and viral infections in modern medical practice. Many of them are supposed to act on microbial membranes. However, the detailed mechanisms of their action are still elusive. Here, we utilized coarse-grained molecular dynamics simulations to investigate interactions of different types of cationic antiseptics (CAs) with a model bacterial membrane. The simulations revealed qualitatively distinct patterns of dynamic and structural alterations of membrane induced by different types of antiseptics although none of them caused disintegration or solubilization of the bilayer even at the highest explored concentration. At the same time, the adsorption of antiseptics rendered membranes more vulnerable to poration under exposure to the external electric field. We further discuss the possible relation of the enhanced pore formation induced by CAs to their cytotoxic action.

The data for birnessite deposited from alkaline permanganate solutions under two- and single step potentiostatic modes are reported. The analysis of capacity vs. scan rate dependences confirmed higher contribution of interfacial recharging to capacity of the compact nanoporous deposits as compared to more resistive ramified deposits with morphology typical for natural birnessite. Two-step mode allowed us to fabricate mm-thick deposits with satisfactory adhesion and the essential content of more favorable compact birnessite.

Atherosclerosis is a chronic arterial disease characterized by vascular inflammation, accumulation of lipids in the arterial wall, and formation and growth of atherosclerotic plaques followed by ischemia. In subclinical atherosclerosis, cholesterol retention in subendothelial cells leads to induction of local inflammation, generation of foam cells and lesion formation, followed by a chain of other pathogenic events. Atherosclerotic progression can frequently be fatal, since plaque rupture may lead to thrombosis and acute events, such as myocardial infarction, stroke and sudden death. Traditional anti-atherosclerotic therapy is mainly focused on improving the blood lipid profile and does not target various stages of plaque progression. Obviously, treating the disease at initial stages is better than beginning treatment at advanced stages and, in that regard, current atherosclerosis management can be improved. Cholesterol retention is an important component of atherogenesis that precedes plaque formation. Therapeutic targeting of cholesterol retention may be beneficial for preventing further atherogenic progression. For this purpose, we suggest using herbal preparations due to good tolerability and suitability for long-lasting treatment. We developed test systems based on cultured human intimal aortic cells for rapid screening of potential anti-atherogenic drugs. With the help of these test systems, we selected several natural substances with significant anti-atherogenic activity and further use these compounds to prepare herbal preparations for anti-atherosclerotic therapy. These preparations were clinically tested and showed good safety and a potent anti-atherogenic potential.

Hydrophilic colloids (PSS-[Ln2(TCAi)2] and PSS-[LnCAi], where i= 1, 2, or 3 and Ln = Gd or Tb) were prepared by precipitation of Gd(III) or Tb(III) complexes with tetrathiacalix[4]arenes (TCAi) and calix[4]arenes bearing two 1,3-diketone groups (CAi) from dimethylformamide to an aqueous solution of poly(sodium 4-styrenesulfonate) (PSS). Dynamic light scattering and transmission electron microscopy demonstrated the formation of nanoparticles coated by the polymer. Luminescence decay measurements on Tb(III)-based colloids allowed hydration numbers of 2 and 4 per metal ion to be determined for PSS-[Ln2(TCAi)2] and PSS-[LnCAi] samples, respectively. Longitudinal and transverse water proton relaxivity values measured at 20.8 MHz were remarkably high for the PSS-[GdCAi] colloids but unexpectedly low for the PSS-[Gd2(TCAi)2] ones. 1H fast field cycling nuclear magnetic resonance relaxometry was applied to shed light on the origin of the different relaxation enhancement in the investigated systems. Extremely slow exchange with the bulk of water molecules coordinated to Gd(III) and the scarce accessibility of Gd(III) sites to water were highlighted as the main causes of limited relaxivity.