Twist-tunable polaritonic nanoresonators in a van der Waals crystal.

Optical nanoresonators are key building blocks in various nanotechnological applications (e.g., spectroscopy) due to their ability to effectively confine light at the nanoscale. Recently, nanoresonators based on phonon polaritons (PhPs)-light coupled to lattice vibrations-in polar crystals (e.g., SiC, or h-BN) have attracted much attention due to their strong field confinement, high quality factors, and their potential to enhance the photonic density of states at mid-infrared (mid-IR) frequencies, where numerous molecular vibrations reside. Here, we introduce a new class of mid-IR nanoresonators that not only exhibit the extraordinary properties previously reported, but also incorporate a new degree of freedom: twist tuning, i.e., the possibility of controlling their spectral response by simply rotating the constituent material. To achieve this result, we place a pristine slab of the van der Waals (vdW) α-MoO3 crystal, which supports in-plane hyperbolic PhPs, on an array of metallic ribbons. This sample design based on electromagnetic engineering, not only allows the definition of α-MoO3 nanoresonators with low losses (quality factors, Q, up to 200), but also enables a broad spectral tuning of the polaritonic resonances (up to 32 cm-1, i.e., up to ~6 times their full width at half maximum, FWHM ~5 cm-1) by a simple in-plane rotation of the same slab (from 0 to 45°). These results open the door to the development of tunable and low-loss IR nanotechnologies, fundamental requirements for their implementation in molecular sensing, emission or photodetection applications.

Morphological Changes in Articular Cartilage and Free-Radical Lipid Peroxidation in Rats with Posttraumatic Osteoarthrosis.

Using the rat model of posttraumatic osteoarthrosis of the knee joint induced by surgical transection of their anterior cruciate ligaments, we showed that irreversible loss of hyaluronan by the extracellular matrix of the joint cartilage tissue against the background of oxidative stress accompanied by accumulation of intermediate LPO products in blood serum and formation of thiol system incompetence was one of the key patterns of dystrophic degeneration of the cartilage tissue. Considerable metabolic shifts were associated with structural modification of the articular hyaline cartilage: its thinning and a decrease of chondrocyte density and their abnormal spatial distribution in the matrix with predominance of solitary isolated cells with signs of karyopyknosis and karyolysis.

[The Challenges of Vaccine Development Against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Possible Vaccine Vector].

To design an effective and safe vaccine against betacoronaviruses, it is necessary to elicit a combination of strong humoral and cell-mediated immune responses as well as to minimize the risk of antibody-dependent enhancement of viral infection. This phenomenon was observed in animal trials of experimental vaccines against SARS-CoV-1 and MERS-CoV that were developed based on inactivated coronavirus or vector constructs expressing the spike protein (S) of the virion. The substitution and glycosylation of certain amino acids in the antigenic determinants of the S-protein, as well as its conformational changes, can lead to the same effect in a new experimental vaccine against SARS-CoV-2. This review outlines approaches for developing vaccines against the new SARS-CoV-2 coronavirus that are based on non-pathogenic viral vectors. For efficient prevention of infections caused by respiratory pathogens the ability of the vaccine to stimulate mucosal immunity in the respiratory tract is important. Such a vaccine can be developed using non-pathogenic Sendai virus vector, since it can be administered intranasally and induce a mucosal immune response that strengthens the antiviral barrier in the respiratory tract and provides reliable protection against infection. The mucosal immunity and the production of IgA antibodies accompanying its development reduces the likelihood of developing an antibody-dependent infection enhancement, which is usually associated only with immunopathological IgG antibodies.

Change of Antigenic Determinants of SARS-CoV-2 Virus S-Protein as a Possible Cause of Antibody-Dependent Enhancement of Virus Infection and Cytokine Storm.

A hypothesis is proposed that the cytokine storm syndrome, which complicates COVID-19 in some patients, is a consequence of antibody-dependent enhancement of virus infection, which is in turn happens due to a change in dominant antigenic determinants of SARS-CoV-2 S-protein. The antibody-dependent enhancement of virus infection is a phenomenon in which virus-specific antibodies that are not neutralizing enhance the entry of infectious virus into immune cells causing their death. Antibody-dependent enhancement has been reported for different coronaviruses. This phenomenon happens due to a decrease in the binding strength of neutralizing antibodies to the virus, which converts these antibodies into suboptimal-not neutralizing ones. According to our hypothesis, such a decrease in affinity may be associated with a change in the conformation of the viral S-protein. We believe that this conformational change is the major factor in the switching of antibodies affinity, which triggers antibody-dependent enhancement. However, other factors that contribute to antigen drift and antigenic determinant changes may also play a role.

The Challenges of Vaccine Development against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Possible Vaccine Vector.

To design an effective and safe vaccine against betacoronaviruses, it is necessary to use their evolutionarily conservative antigenic determinants that will elicit the combination of strong humoral and cell-mediated immune responses. Targeting such determinants minimizes the risk of antibody-dependent enhancement of viral infection. This phenomenon was observed in animal trials of experimental vaccines against SARS-CoV-1 and MERS-CoV that were developed based on inactivated coronavirus or vector constructs expressing the spike protein (S) of the virion. The substitution and glycosylation of certain amino acids in the antigenic determinants of the S-protein, as well as its conformational changes, can lead to the same effect in a new experimental vaccine against SARS-CoV-2. Using more conservative structural and accessory viral proteins for the vaccine antigenic determinants will help to avoid this problem. This review outlines approaches for developing vaccines against the new SARS-CoV-2 coronavirus that are based on non-pathogenic viral vectors. For efficient prevention of infections caused by respiratory pathogens the ability of the vaccine to stimulate mucosal immunity in the respiratory tract is important. Such a vaccine can be developed using non-pathogenic Sendai virus vector, since it can be administered intranasally and induce a mucosal immune response that strengthens the antiviral barrier in the respiratory tract and provides reliable protection against infection.

Two-dimensional Ising model for microarray hybridization: cooperative interactions between bound target molecules.

The Langmuir adsorption model is widely used for description and quantification of microarray oligo-target hybridization. According to the model, the binding centers for adsorption of target molecules from solution are represented by oligo-probes. However, the Langmuir model does not consider the interactions between the targets adsorbed at the neighboring binding centers, which are possible due to high-density of array-bound probes. We have shown that the two-dimensional Ising model, which takes into account the nearest neighboring target molecules interactions, better describes the experimental data of oligo-target hybridization in comparison with the Langmuir model. Thus, we found an evidence for existence of positive cooperative interactions between adsorbed target molecules: so, binding of the first target molecules facilitates the binding of subsequent ones to the neighboring probes. Communicated by Ramaswamy H. Sarma.

[Oncolytic Paramyxoviruses: Mechanism of Action, Preclinical and Clinical Studies].

Preclinical studies demonstrate that a broad spectrum of human and animal malignant cells can be killed by oncolytic paramyxoviruses, which includes cells of ecto-, endo- and mesodermal origin. In clinical trials, significant reduction or even complete elimination of primary tumors and established metastases has been reported. Different routes of virus administration (intratumoral, intravenous, intradermal, intraperito-neal, or intrapleural) and single- vs. multiple-dose administration schemes have been explored. The reported side effects were grades 1 and 2, with the most common among them being mild fever. There are certain advantages in using paramyxoviruses as oncolytic agents compared to members of other virus families exist. Thanks to cytoplasmic replication, paramyxoviruses do not integrate the host genome or engage in recombination, which makes them safer and more attractive candidates for widely used therapeutic oncolysis than ret-roviruses or some DNA viruses. The list of oncolytic Paramyxoviridae members includes the attenuated measles virus, mumps virus, low pathogenic Newcastle disease, and Sendai viruses. Metastatic cancer cells frequently overexpress certain surface molecules that can serve as receptors for oncolytic paramyxoviruses. This promotes specific viral attachment to these malignant cells. Paramyxoviruses are capable of inducing efficient syncytium-mediated lysis of cancer cells and elicit strong immune stimulation, which dramatically enforces anticancer immune surveillance. In general, preclinical studies and phases I-III of clinical trials yield very encouraging results and warrant continued research of oncolytic paramyxoviruses as a particularly valuable addition to the existing panel of cancer-fighting approaches.

[Diagnostic errors in patients with giant-cell tumor, bone cyst and osteosarcoma].

The article contains diagnostic error analysis of 439 patients with giant-cell tumor (176), bone cyst (158) and osteosarcoma (105) aged 4-75 for theperiod of 1990-2015. Morphological investigation of surgical material taken from the pathological focus sowed that diagnostic errors in clinical and X-ray examinations comprised up to 40.6% in giant -cell cases, 37.2% in bone cyst cases and 34.2% (p<0.05) in osteosarcoma cases.

[IN VIVO EVALUATION OF POLYCAPROLACTONE-HYDROXYAPATITE SCAFFOLD BIOCOMPATIBILITY].

Biocompatibility is one of the main and very important properties for scaffolds. The aim of the present study was to investigate cells population dynamics in vivo in the process of original polycaprolactone-hydroxyapatite scaffold colonization, as well as tissue reactions to the implantation to assess the biocompatibility of the matrix. It has been found that tissue reactive changes in white rats subside completely up to the 21st day after subcutaneous polycaprolactone-hydroxyapatite scaffold implantation. Matrix was actively colonized by connective tissue cells in the period from the 7th to the 21st day of the experiment. However, intensive scaffold vascularization started from the 14th day after implantation. These findings suggest a high degree of the polycaprolactone-hydroxyapatite scaffold biocompatiblilitye.

Mechanisms of Oncolysis by Paramyxovirus Sendai.

Some viral strains of the Paramyxoviridae family may be used as anti-tumor agents. Oncolytic paramyxoviruses include attenuated strains of the measles virus, Newcastle disease virus, and Sendai virus. These viral strains, and the Sendai virus in particular, can preferentially induce the death of malignant, rather than normal, cells. The death of cancer cells results from both direct killing by the virus and through virus-induced activation of anticancer immunity. Sialic-acid-containing glycoproteins that are overexpressed in cancer cells serve as receptors for some oncolytic paramyxoviruses and ensure preferential interaction of paramyxoviruses with malignant cells. Frequent genetic defects in interferon and apoptotic response systems that are common to cancer cells ensure better susceptibility of malignant cells to viruses. The Sendai virus as a Paramyxovirus is capable of inducing the formation of syncytia, multinuclear cell structures which promote viral infection spread within a tumor without virus exposure to host neutralizing antibodies. As a result, the Sendai virus can cause mass killing of malignant cells and tumor destruction. Oncolytic paramyxoviruses can also promote the immune-mediated elimination of malignant cells. In particular, they are powerful inducers of interferon and other cytokynes promoting antitumor activity of various cell components of the immune response, such as dendritic and natural killer cells, as well as cytotoxic T lymphocytes. Taken together these mechanisms explain the impressive oncolytic activity of paramyxoviruses that hold promise as future, efficient anticancer therapeutics.

[Structural and functional characteristics of bone tissue and blood cytokines in health and disease of the joints].

Change of structural and functional state of bone in patients with primary osteoarthrosis of the hip joint compared to healthy individuals is characterized by decreased bone formation with a relative predominance of resorption. Osteopenic syndrome develops in the background of evident imbalance of a blood cytokine profile with increasing the level of proinflammatory and the variability of the level of anti-inflammatory cytokines.

[Reversion of sedation and general anaesthesia--agonist-antagonist technique].

OBJECTIVE: To study an expediency and efficacy of application of different reverses drugs (naloxone, flumazenil, neostigmine, galantamine, sugammadex) either their separate or combined using. METHODS: We studied 119 patients underwent endoluminal endoscopic procedures and surgeries on trachea-bronchial tree and intestines under sedation or general anaesthesia. RESULTS: The article deals with conceptual approaches to the reversal of residual effects of opioids, benzodiazepine sedation and neuromuscular block (the so-called agonist-antagonist technique). CONCLUSIONS: A reversion of neuromuscular block without using of antagonists' combination does not provide complete recovery of psychomotor and cognitive functions for rapid socialization of patients after anaesthesia.

[Analysis of binding of oligonucleotides on microarrays: hybridization energy isotherms].

The study reports a thermodynamic model describing microarray oligo-target hybridization. The relationship between hybridization signal intensity and Gibbs free energy change for oligo-target duplex formation was our function of interest. The behavior of this function that we called energetical hybridization isotherm in response to target concentration change was modeled considering different ratios of oligo-probes/target concentrations. The results of modeling were compared with the relevant and currently available from literature microarray adsorption experiment.

[Reparative regeneration of rat soft tissues is affected by a wound-healing composite].

We researched influence of original wound-healing composite, including chitosan and nanoparticles of copper and zinc, on specific of reparative regeneration of an experimental soft tissue full layer rat's wounds, which were conditionally aseptic and infected. The composite stimulation of reparative regeneration is related both to its antibacterial effect, and to the influence on the state of structural biopolymers of the connecting tissue.

[Relationship between the structure-functional state of the heart and brain natriuretic peptide level in patients with arterial hypertension].

We studied relationship between structure-functional parameters of left and right cardiac chambers and N-terminal pro-brain natriuretic peptide (NT-proBNP) level in 118 patients with arterial hypertension (AH) (35 men, 83 women) and 17 healthy volunteers. Methods comprised 24-hour arterial pressure monitoring (APM), two-dimensional echocardiography (echoCG), Doppler echoCG, and tissue echoCG of mitral and tricuspid atrioventricular annuli, treadmill test, 6-min walk test, and measurement of NT-proBNP level in blood plasma. In patients with AH blood plasma NT-proBNP level was significantly higher than in a group of healthy persons of similar age. Elevation of this biochemical marker was accompanied by significant change of characteristics of remodeling of left and right parts of the heart, abnormalities of left ventricular diastolic function according to transmitral blood flow, disturbances of left ventricular diastolic and systolic function according to tissue Doplerography data. Comparative analysis of structure-functional parameters of the heart and NT-proBNP level in patients with AH allowed to reveal more significant changes of parameters of diastolic and systolic remodeling, local and global diastolic and systolic left ventricular function in patients with NT-proBNP levels more than 306 mol/ml. Factors determining NT-proBNP level in patients with AH were age, free right ventricular wall thickness, and body mass index.

[Analysis of DNA-ligand binding in solution and on biochips].

Ligand binding to DNA, as well as to microarrays, requires a system approach to description and analysis. This type of approach implies a fixed sequence of operations. Firstly, it is necessary to make a description of a binding scheme that realizes ligand and polymer in common spatial way. Secondly, a physical model of binding is required. Thirdly, a mathematical binding model should be constructed on the basis of the binding scheme and the physical model of binding. Every analysis of experimental data needs this preliminary work. A mathematical apparatus and classification of binding models have to follow on. Classification of different binding isotherms by different binding models is the direct problem. The inverse problem is a reconstruction of parameters of a binding model by experimental binding isotherm curves. The inverse problem can only be solved after solving the direct problem. An example of classification of binding models by oligonucleotides or proteins binding cooperativity and polymer properties like homo- or heteropolymer is presented.

[Properties of hybridization isotherms upon binding of ligands on microchips].

A simple thermodynamic model describing the microarray oligo-target hybridization has been constructed. The relationship between the hybridization signal intensity and Gibbs free energy for oligo-target duplex formation has been considered. The behavior of this function, which we called energetical hybridization isotherm, in response to target concentration change was modeled at different ratios of oligo-probes/target concentrations. The results of modeling were compared with the relevant and currently available data from microarray adsorption experiments.

[Effect of systemic chemotherapy on clinical status and biological and immunologic markers in patients with breast cancer].

Complex examination of breast cancer patients (102, aged 35-63) receiving systemic polychemotherapy was carried out to make a case for a course of immunotherapy. Cycles of chemotherapy were given to all patients. Basal immunological status revealed T-cell and non-specific immunity suppression, disordered cytokine regulation, lowered nitrite concentration and enhanced SOD and catalase levels. Chemotherapy was followed by more frequent immunopathological syndromes and graver immunosuppression. The dynamics of biochemical parameters was characterized by decreasing antioxidant system activity.

[Accelerated senescence of armed conflicts participants suffering from the consequences of war cranial-cerebral trauma and alcoholism].

The matter under studies was the way accelerated senescence of armed conflicts participants with brain injuries depends on alcohol addiction developed after the injuries and on dysfunction of neurohumoral regulation of heart activity. It has been established that the posttraumatic alcohol addiction considerably activates the processes of accelerated senescence and lipid peroxidation connected with it, depresses the system of antioxidant protection and enhances the progress of dysfunctions in neurohumoral regulation of heart activity.