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Chitosan, the product of chitin deacetylation, is an excellent candidate for enzyme immobilization purposes. Here we demonstrate that papain, an endolytic cysteine protease (EC: 3.4.22.2) from Carica papaya latex immobilized on the matrixes of medium molecular (200 kDa) and high molecular (350 kDa) weight chitosans exhibits anti-biofilm activity and increases the antimicrobials efficiency against biofilm-embedded bacteria. Immobilization in glycine buffer (pH 9.0) allowed adsorption up to 30% of the total protein (mg g chitosan−1) and specific activity (U mg protein−1), leading to the preservation of more than 90% of the initial total activity (U mL−1). While optimal pH and temperature of the immobilized papain did not change, the immobilized enzyme exhibited elevated thermal stability and 6–7-fold longer half-life time in comparison with the soluble papain. While one-half of the total enzyme dissociates from both carriers in 24 h, this property could be used for wound-dressing materials design with dosed release of the enzyme to overcome the relatively high cytotoxicity of soluble papain. Our results indicate that both soluble and immobilized papain efficiently destroy biofilms formed by Staphylococcus aureus and Staphylococcus epidermidis. As a consequence, papain, both soluble and immobilized on medium molecular weight chitosan, is capable of potentiating the efficacy of antimicrobials against biofilm-embedded Staphylococci. Thus, papain immobilized on medium molecular weight chitosan appears a presumably beneficial agent for outer wound treatment for biofilms destruction, increasing antimicrobial treatment effectiveness.

MicroRNAs are small noncoding single-stranded RNAs that regulate gene expression. Today, we see an increasing number of studies highlighting the important role of microRNAs in the development and progression of cardiovascular diseases caused by atherosclerotic lesions of arteries. We review the available scientific data on association of the expression of these biomolecules with instability of atherosclerotic plaques in animal models and humans. We made special emphasis on miR-21, -100, -127, -133, -143/145, -221/222, and -494 because they were analyzed in more than one study. We discuss the possibility of microRNAs using in the diagnosis and therapy of atherosclerosis and its complications.

A new kind of magnetically-doped antiferromagnetic (AFM) topological insulators (TIs) with stoichiometry Bi 1.09 Gd 0.06 Sb 0.85 Te 3 has been studied by angle-resolved photoemission spectroscopy (ARPES), superconducting magnetometry (SQUID) and X-ray magnetic circular dichroism (XMCD) with analysis of its electronic structure and surface-derived magnetic properties at different temperatures. This TI is characterized by the location of the Dirac gap at the Fermi level (E F ) and a bulk AFM coupling below the Neel temperature (4–8 K). At temperatures higher than the bulk AFM/PM transition, a surface magnetic layer is proposed to develop, where the coupling between the magnetic moments located at magnetic impurities (Gd) is mediated by the Topological Surface State (TSS) via surface Dirac-fermion-mediated magnetic coupling. This hypothesis is supported by a gap opening at the Dirac point (DP) indicated by the surface-sensitive ARPES, a weak hysteresis loop measured by SQUID at temperatures between 30 and 100 K, XMCD measurements demonstrating a surface magnetic moment at 70 K and a temperature dependence of the electrical resistance exhibiting a mid-gap semiconducting behavior up to temperatures of 100–130 K, which correlates with the temperature dependence of the surface magnetization and confirms the conclusion that only TSS are located at the E F . The increase of the TSS’s spectral weight during resonant ARPES at a photon energy corresponding to the Gd 4 d -4 f edge support the hypothesis of a magnetic coupling between the Gd ions via the TSS and corresponding magnetic moment transfer at elevated temperatures. Finally, the observed out-of-plane and in-plane magnetization induced by synchrotron radiation (SR) due to non-equal depopulation of the TSS with opposite momentum, as seen through change in the Dirac gap value and the k ∥ -shift of the Dirac cone (DC) states, can be an indicator of the modification of the surface magnetic coupling mediated by the TSS.

Aortic aneurysm (AA) and atherosclerosis (AS) of various vascular beds are asymptomatic for a long time and are relatively common pathological conditions that lead to life-threatening and disabling complications. In this review, we discuss the current understanding of the high variation in direct and inverse comorbidity of AA and AS as presented in scientific publications. Estimates of AA and AS comorbidity depend on several factors, such as the location of AA (ascending or descending thoracic aorta or abdominal aorta), familial or sporadic cases of AA, syndromic forms of AA, and/or aortic valve pathology (bicuspid aortic valve [BAV]). To identify the causes of the comorbidity of AA and AS, it is important to consider and characterise many factors in detail. These factors include clinical characteristics of the patients included in a study (age, sex) and risk factors (mainly the presence of monogenic forms and BAV, hypertension, hypercholesterolaemia, diabetes mellitus, and cigarette smoking). Additionally, it is essential to consider characteristics of the disease course and the nature of multimorbidity and to take into account pathologies not only of the cardiovascular system but also of other organ systems, with special attention to metabolic and endocrine disorders.

Diabetic foot ulcers (DFU) are a common complication of Type 2 Diabetes Mellitus (T2DM). Development of bioactive wound healing covers is an important task in medicine. The use of autologous platelet-rich plasma (PRP) consisting of growth factors, cytokines and components of extracellular matrix is a perspective approach for DFU treatment, but we previously found that some T2DM PRP samples have a toxic effect on mesenchymal stem cells (MSCs) in vitro. Here, we covalently immobilized T2DM PRP proteins on polycaprolactone (PCL) nanofibers, and the growth of endothelial cells on the PCL-COOH-PRP was investigated. Additionally, the level of NO reflecting the cytotoxic effects of PRP, angiogenin, and VEGF levels were measured in T2DM PRP samples. The results showed that the application of PCL-COOH-PRP nanofibers allows to remove the cytotoxicity of T2DM PRP and to improve endothelial cell adhesion and proliferative activity. We showed that the origin of T2DM PRP (the level of PRP toxicity or presence/absence of DFU) does not influence the efficiency of cell growth on PCL-COOH-PRP, and on the level of angiogenin, vascular epidermal growth factor (VEGF) in PRP itself.

Epigenetic mechanisms of gene regulation in context of cardiovascular diseases are of considerable interest. So far, our current knowledge of the DNA methylation profiles for atherosclerosis affected and healthy human vascular tissues is still limited. Using the Illumina Infinium Human Methylation27 BeadChip, we performed a genome-wide analysis of DNA methylation in right coronary artery in the area of advanced atherosclerotic plaques, atherosclerotic-resistant internal mammary arteries, and great saphenous veins obtained from same patients with coronary heart disease. The resulting DNA methylation patterns were markedly different between all the vascular tissues. The genes hypomethylated in athero-prone arteries to compare with atherosclerotic-resistant arteries were predominately involved in regulation of inflammation and immune processes, as well as development. The great saphenous veins exhibited an increase of the DNA methylation age in comparison to the internal mammary arteries. Gene ontology analysis for genes harboring hypermethylated CpG-sites in veins revealed the enrichment for biological processes associated with the development. Four CpG-sites located within the MIR10B gene sequence and about 1 kb upstream of the HOXD4 gene were also confirmed as hypomethylated in the independent dataset of the right coronary arteries in the area of advanced atherosclerotic plaques in comparison with the other vascular tissues. The DNA methylation differences observed in vascular tissues of patients with coronary heart disease can provide new insights into the mechanisms underlying the development of pathology and explanation for the difference in graft patency after coronary artery bypass grafting surgery.

Recently we obtained complexes between genetically modified Tobacco Mosaic Virus (TMV) particles and proteins carrying conserved influenza antigen such as M2e epitope. Viral vector TMV-N-lys based on TMV-U1 genome was constructed by insertion of chemically active lysine into the exposed N-terminal part of the coat protein. Nicotiana benthamiana plants were agroinjected and TMV-N-lys virions were purified from non-inoculated leaves. Preparation was analyzed by SDS-PAGE/Coomassie staining; main protein with electrophoretic mobility of 21 kDa was detected. Electron microscopy confirmed the stability of modified particles. Chemical conjugation of TMV-N-lys virions and target influenza antigen M2e expressed in E. coli was performed using 5 mM 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide and 1 mM N-hydroxysuccinimide. The efficiency of chemical conjugation was confirmed by Western blotting. For additional characterization we used conventional electron microscopy. The diameter of the complexes did not differ significantly from the initial TMV-N-lys virions, but complexes formed highly organized and extensive network with dense “grains” on the surface. Dynamic light scattering demonstrated that the single peaks, reflecting the complexes TMV-N-lys/DHFR-M2e were significantly shifted relative to the control TMV-N-lys virions. The indirect enzymelinked immunosorbent assay with TMV- and DHFR-M2e-specific antibodies showed that the complexes retain stability during overnight adsorption. Thus, the results allow using these complexes for immunization of animals with the subsequent preparation of a candidate universal vaccine against the influenza virus.

The required operation of a heat exchanger with spherical filling depends on determining the heat characteristic of the porous medium. Using most existing dependencies to determine the heat-exchange coefficient in a porous medium gives contradictory results. This paper proposes a calculation method to determine heat characteristics of a porous medium (namely, spherical filling) using numerical modeling. This issue is addressed in a 3D setting using the RANS equation system k- ε RNG , a turbulence model, energy and state equations for gas flows through the porous medium represented as regular packed beds of three types. Two modes are considered, which differ in the working medium type and heat exchange process direction. Modeling is done to determine the following parameters; Re h =100…4·10 4 , Pr wb =0.57… 0.919, ε=0.2595… 0.4764, T wb =300… 1900 K, T w =300… 1900 K . The analysis results of the influence of the temperature factor, porosity, and heat physical properties of the working medium on the heat exchange are represented. Heat characteristics are given for each case scenario: about 360 reference points are obtained. A modified type of criterial dependency Nu sf (Re h ) is proposed and approximation coefficients are determined.

Despite the great potential of Hf0.5Zr0.5O2 (HZO) ferroelectrics, reliability issues, such as wake-up, fatigue, endurance limitations, imprint and retention loss, impede the implementation of HZO to nonvolatile memory devices. Herein, a study of the reliability properties in HZO-based stacks with the conventional TiN top electrode and Ru electrode, which is considered a promising alternative to TiN, is performed. An attempt to distinguish the mechanisms underlying the wake-up, fatigue and retention loss in both kinds of stacks is undertaken. Overall, both stacks show pronounced wake-up and retention loss. Moreover, the fatigue and retention loss were found to be worsened by Ru implementation. The huge fatigue was suggested to be because Ru does not protect HZO against oxygen vacancies generation during prolonged cycling. The vacancies generated in the presence of Ru are most likely deeper traps, as compared to the traps formed at the interface with the TiN electrode. Implementing the new procedure, which can separate the depolarization-caused retention loss from the imprint-caused one, reveal a rise in the depolarization contribution with Ru implementation, accompanied by the maintenance of similarly high imprint, as in the case with the TiN electrode. Results show that the mechanisms behind the reliability issues in HZO-based capacitors are very electrode dependent and simple approaches to replacing the TiN electrode with the one providing, for example, just higher remnant polarization or lower leakages, become irrelevant on closer examination.

BackgroundLaparoscopic liver resection (LLR) of posterosuperior segments (PSS) is still technically demanding procedure for highly selective patients. There is no long-term survival comparative estimation after LLR and open liver resection (OLR) for colorectal liver metastases (CRLM) located in PSS. We aimed to compare long-term overall (OS) and disease-free survival (DFS) after parenchyma-sparing LLR with expanding indications and open liver resection (OLR) of liver PSS in patients with CRLM.MethodsTwo Russian centers took part in the study. Patients with missing data, hemihepatectomy and extrahepatic tumors were excluded. One of contraindications for LLR was suspicion for tumor invasion in large hepatic vessels. Logistic regression was used for 1:1 propensity score matching (PSM).ResultsPSS were resected in 77 patients, which accounted for 42% of the total number of liver resections for CRLM. LLR were performed in 51 (66%) patients. Before and after matching, no differences were found between groups in the following factors: median size of the largest metastatic tumor; proximity to the large liver vessels; the rate of anatomical parenchyma sparing resection of PSS; a positive response to chemotherapy before and after surgery. Regardless of matching, the size of the largest metastases was above 50 mm in more than one-third of patients who received LLR. Before matching, intraoperative blood loss, ICU stay and hospital stay were significantly greater in the group of OLR. No 90-day mortality was observed within both groups. There were no differences in long-term oncological outcomes: 5-year OS after PSM was 78% and 63% after LLR and OLR, respectively; 4-year DFS after PSM was 27% in both groups.ConclusionLaparoscopic parenchyma-sparing resection of PSS for CRLM are justified in majority of patients who have an indication for OLR if performed in high volume specialized centers expertized in laparoscopic liver surgery.