[Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies].

BACKGROUND: MEN-1 is a rare autosomal dominant disease caused by mutations in MEN1 gene encoding the menin protein. This syndrome is characterized by the occurrence of parathyroid tumors, gastroenteropancreatic neuroendocrine tumors, pituitary adenomas, as well as other endocrine and non-endocrine tumors. If a patient with the MEN-1 phenotype carry no mutations in the MEN1 gene, the condition considers a phenocopy of syndrome (phMEN1). The possible cause of this changes could be changes in epigenetic regulation, particularly in microRNA expression that might affect menin signaling pathways. AIM: to identify differently expressed circulating miRNAs in plasma in patients with genetically confirmed MEN-1 syndrome, its phenocopies and healthy controls. MATERIALS AND METHODS: single-center, case-control study was conducted. We assessed plasma microRNA expression in patients with genetically confirmed MEN-1 (gMEN1), phMEN1 and healthy controls. Morning plasma samples were collected from fasting patients and stored at -80°C. Total RNA isolation was performed using miRNeasy Mini Kit with QIAcube. The libraries were prepared by the QIAseq miRNA Library Kit following the manufacturer. Circulating miRNA sequencing was done on Illumina NextSeq 500 (Illumina). Subsequent data processing was performed using the DESeq2 bioinformatics algorithm. RESULTS: we enrolled 21 consecutive patients with gMEN1 and 11 patients with phMEN1, along with 12 gender matched controls. Median age of gMEN1 was 38,0 [34,0; 41,0]; in phMEN1 - 59,0 [51,0; 60,0]; control - 59,5 [51,5; 62,5]. The gMEN1 group differed in age (p<0.01) but not gender (р=0.739) or BMI (р=0.116) compared to phMEN1 and controls group, the last two groups did not differ by these parameters (p>0.05). 25 microRNA were differently expressed in groups gMEN1 and phMEN1 (21 upregulated microRNAs, 4 - downregulated). Comparison of samples from the phMEN-1 group and relatively healthy controls revealed 10 differently expressed microRNAs: 5 - upregulated; 5 - downregulated. In the gMEN-1 and control groups, 26 differently expressed microRNAs were found: 24 - upregulated; 2 - downregulated. The miRNAs most differing in expression among the groups were selected for further validation by RT-qPCR (in the groups of gMEN1 vs phMEN1 - miR-3613-5p, miR-335-5p, miR-32-5p, miR-425-3p, miR-25-5p, miR-576-5p, miR-215-5p, miR-30a-3p, miR-141-3p, miR-760, miR-501-3p; gMEN1 vs control - miR-1976, miR-144-5p miR-532-3p, miR-375; as well as in phMEN1 vs control - miR-944, miR-191-5p, miR-98-5p). CONCLUSION: In a pilot study, we detected microRNAs that may be expressed differently between patients with gMEN-1 and phMEN-1. The results need to be validated using different measurement method with larger sample size.

[High tibial osteotomy with computer navigation for medial gonarthritis]. / Sravnitel'nye rezul'taty lecheniya medial'nogo gonartrita metodom vysokoi tibial'noi osteotomii s ispol'zovaniem komp'yuternoi navigatsii.

OBJECTIVE: To study significance of computer navigation for improving clinical and radiological results of medial gonarthritis treatment compared to non-invasive methods of lower limb axis correction control. MATERIAL AND METHODS: The study included 73 patients who were divided into 2 groups. The main group included 40 patients, the control group - 33 patients. In the main group, high tibial osteotomy was performed using computer navigation, in the control group - using non-invasive techniques. Clinical assessment was carried out according to the KSS, KOOS and VAS scales. We assessed the main reference angles of the lower limb considering X-ray data. RESULTS: Both groups were characterized by postoperative improvement of clinical results according to various scales. Computer navigation provided higher accuracy in most cases. We focused on target correction of 3° valgus. CONCLUSION: High tibial osteotomy with computer navigation or non-invasive techniques is an effective treatment method for medial gonarthritis. There are no significant differences in clinical results according to the KSS and KOOS scales, as well as X-ray data after correction. We found significant differences in VAS scores.

Analysis of experimental spectra of phosphine in the Tetradecad range near 2.3 µm using ab initio calculations.

Due to its major interest for the chemistry of planetary atmospheres and exobiology, accurate spectroscopy data of phosphine are required for the search of signatures of this molecule in astronomical observations. In this work, high resolution infrared laboratory spectra of phosphine were analyzed for the first time in the full Tetradecad region (3769-4763 cm-1) involving 26 rotationally resolved bands. Overall, 3242 lines were assigned in spectra previously recorded by Fourier transform spectroscopy at temperatures 200 K and 296 K, using a combined theoretical model based on ab initio calculations. The total nuclear motion Hamiltonian of PH3 including ab initio potential energy surface, was reduced to an effective Hamiltonian using the high-order contact transformation method adapted to vibrational polyads of the AB3 symmetric top molecules, followed by empirical optimization of the parameters. At this step, the experimental line positions were reproduced with a standard deviation of 0.0026 cm-1 that provided unambiguous identification of observed transitions. The effective dipole transition moments of the bands were obtained by fitting to the intensities obtained from variational calculations using the ab initio dipole moment surface. The assigned lines were used to newly determine 1609 experimental vibration-rotational levels up to Jmax = 18 with energy in the range 3896-6037 cm-1 that represents significant extension towards higher energies compared to previous works. Transitions for all 26 sublevels of the Tetradecad were identified but with noticeably fewer transitions for fourfold excited bands because of their weaker intensity. At the final step, pressure-broadened half widths were attached to each transition and a composite line list adopting ab initio intensities and empirical line positions corrected to the accuracy of about 0.001 cm-1 for strong and medium transitions was validated against experimental spectra available in the literature.

Multiple and spectrally robust photonic magic angles in reconfigurable α-MoO3 trilayers.

The emergence of a topological transition of the polaritonic dispersion in twisted bilayers of anisotropic van der Waals materials at a given twist angle-the photonic magic angle-results in the diffractionless propagation of polaritons with deep-subwavelength resolution. This type of propagation, generally referred to as canalization, holds promise for the control of light at the nanoscale. However, the existence of a single photonic magic angle hinders such control since the canalization direction in twisted bilayers is unique and fixed for each incident frequency. Here we overcome this limitation by demonstrating multiple spectrally robust photonic magic angles in reconfigurable twisted α-phase molybdenum trioxide (α-MoO3) trilayers. We show that canalization of polaritons can be programmed at will along any desired in-plane direction in a single device with broad spectral ranges. These findings open the door for nanophotonics applications where on-demand control is crucial, such as thermal management, nanoimaging or entanglement of quantum emitters.

[Post-traumatic pain mononeuropathies]. / Posttravmaticheskie bolevye mononeiropatii.

Neuropathic pain syndrome (NPS) caused by peripheral nerve (PN) injury is a serious clinical problem due to its prevalence, complexity of pathogenesis, significant impact on the quality of life of patients. The issues of epidemiology, pathogenesis and treatment of patients with NBS with PN injury are considered. Modern possibilities of invasive treatment of such patients are discussed.

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.

An ELISA Platform for the Quantitative Analysis of SARS-CoV-2 RBD-neutralizing Antibodies As an Alternative to Monitoring of the Virus-Neutralizing Activity.

Monitoring of the level of the virus-neutralizing activity of serum immunoglobulins ensures that one can reliably assess the effectiveness of any protection against the SARS-CoV-2 infection. For SARS-CoV-2, the RBD-ACE2 neutralizing activity of sera is almost equivalent to the virus-neutralizing activity of their antibodies and can be used to assess the level of SARS-CoV-2 neutralizing antibodies. We are proposing an ELISA platform for performing a quantitative analysis of SARS-CoV-2 RBD-neutralizing antibodies, as an alternative to the monitoring of the virus-neutralizing activity using pseudovirus or "live" virus assays. The advantage of the developed platform is that it can be adapted to newly emerging virus variants in a very short time (1-2 weeks) and, thereby, provide quantitative data on the activity of SARS-CoV-2 RBD-neutralizing antibodies. The developed platform can be used to (1) study herd immunity to SARS-CoV-2, (2) monitor the effectiveness of the vaccination drive (revaccination) in a population, and (3) select potential donors of immune plasma. The protective properties of the humoral immune response in hospitalized patients and outpatients, as well as after prophylaxis with the two most popular SARS-CoV-2 vaccines in Russia, were studied in detail using this platform. The highest RBD-neutralizing activity was observed in the group of hospitalized patients. The protective effect in the group of individuals vaccinated with Gam-COVID-Vac vaccine was 25% higher than that in outpatients and almost four times higher than that in individuals vaccinated with the CoviVac vaccine.

[INVESTIGATION OF SURGICAL CORRECTION OF ANTERIOR APICAL PROLAPSE OF THE PELVIC ORGANS USING A COMBINED TECHNIQUE, MONOLATERAL CYRENE POSTERIOR IN COMBINATION WITH ANTERIOR COLPORRHAPHY].

Objective - to evaluate the results of surgical correction of anterior apical prolapse of the pelvic organs with a combined technique monolateral CYRENE posterior (using monofilament polypropylene tape CYRENE) in combination with anterior colporrhaphy. A prospective cohort study included 240 patients with urogenital prolapse. The subjects were followed up for three months, and the anatomical outcome according to the POP-Q System classification, intra- and postoperative complications, absence or presence of relapse, quality of life and sex life were assessed. A relapse was considered to be grade 3 or more anterior prolapse, grade 2 or more central prolapse. Quality of life and sex life were assessed using the PFDI-20, PFIQ-7 and PSIQ-12 questionnaires. The average age of women was 57.8 years. All 240 patients had grade 3 cystocele, prolapse of the anterior vaginal wall, and prolapse of the uterus. In 23 (9.6%) patients, de novo urinary incontinence developed, 8 patients had stress urinary incontinence before surgery, 6 of them persisted stress urinary incontinence after surgery, 2 of them stress urinary incontinence was arrested without the simultaneous use of a mid-urethral sling. According to questionnaires, the quality of life improved in 225 (96.9%) women according to PFDI-20 and in 210 (90.5%) according to PFIQ-7. There were no changes in the quality of sex life. Anatomically, 235 (96.9%) achieved the desired result (Ba≤ II, C≤ I according to the POPQ System). At the same time, in 36 (15%), 3 months after the operation, cystocele of the 2nd degree was revealed. In all cases, there was minimal blood loss, in 9 cases (3.75%) there was a hematoma of the anterior vaginal wall that did not require additional intervention, at discharge had signs of organization and was completely stopped 6 weeks after surgery; 3 (1.25%) patients had urinary retention after surgery. Dyspareunia was not identified in any patient. The study of the treatment of urogenital prolapse using a combined technique, monolateral CYRENE posterior in combination with anterior colporrhaphy, demonstrates high efficiency and relative safety. The technique showed excellent anatomical results for apical prolapse and good for anterior prolapse. A small number and low significance of postoperative complications were revealed. Longer postoperative follow-up is needed to assess long-term results and long-term prospects in order to form a more complete understanding of this technique.

[Pathomorphological alterations in the kidneys in acute and chronic alcohol intoxication]. / Patomorfologicheskie izmeneniya v pochkakh pri ostroi i khronicheskoi alkogol'noi intoksikatsii.

The literature review presents data on pathomorphological changes in the kidneys in acute and chronic alcohol intoxication. A lack of consensus among researchers on the direct toxic damage to renal tissue by ethanol is demonstrated. Analysis of the literature showed that the issue of attributing microscopic changes detected in the kidneys to characteristic or specific signs remains controversial. Some authors identify several characteristic microscopic patterns in the kidney tissue in alcohol intoxication: thickening of glomeruli basal membranes, narrowing of glomerular capsule tubular lumen. Fatty dystrophy of the proximal tubules is most often indicative of concomitant conditions related to alcohol intoxication, such as ketoacidosis. In alcohol intoxication, some changes in the kidneys occur variably, such as dyscirculatory, dystrophic, pigmentary, necrotic, and autolytic changes. Data on the causes of their occurrence are often contradictory from different authors. The authors of this review believe that this issue can be resolved using up-to-date histochemical, immunohistochemical, and morphometric test methods.

[Clinical and functional outcomes of valgus osteotomy in patients with medial gonarthrosis (preliminary results)]. / Rezul'taty val'giziruyushchei osteotomii u patsientov s medial'nym gonartrozom (predvaritel'nye rezul'taty).

OBJECTIVE: To analyze gait biomechanics before and after corrective osteotomies around the knee joint in patients with medial gonarthrosis. MATERIAL AND METHODS: The study recruited 5 patients (6 surgeries) with medial gonartrosis and varus knee deformity. Gait biomechanics was analyzed in preoperative period and 6 months later. The control group consisted of 20 healthy people. RESULTS: Knee joint biomechanics was almost normal in postoperative period. Amplitude of knee joint flexion was increased. Moreover, hip joint flexion-extension amplitude was increased on both sides and often exceeded normal values. Clinical results showed significant increase in IKS (from 55 to 89.6) and VAS score (from 7.7 to 2.3). Postoperative correction angle varied within 1.5-2° of valgus. CONCLUSION: Corrective osteotomy around the knee joint is effective for medial gonarthrosis. We obtained favorable clinical results and limb axis correction after surgery without significant hypercorrection. Gait biomechanics was also improved.

[Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly].

BACKGROUND: Neurosurgery is the most effective treatment for acromegaly. As most of the patients present with macroadenomas, surgical treatment is not always successful, even with the expert level of a neurosurgeon. Assessment of the postoperative remission rates in acromegaly preoperative predictors of treatment efficacy is an urgent task of modern research. AIM: To assess the short-term and long-term remission of acromegaly after endoscopic transnasal adenomectomy in a tertiary medical center and assess preoperative predictors of the treatment effectiveness. MATERIALS AND METHODS: A single-center, prospective, uncontrolled study was conducted. We included patients with active acromegaly who did not receive medical therapy with somatostatin analogues and were referred for endoscopic transsphenoidal adenomectomy. Plasma miRNA expression was assessed by quantitative reverse transcription PCR. Postoperative samples of adenomas were sent for study, with the determination of the immunohistochemical staining for somatostatin receptors 2 and 5 subtypes and morphology was performed on postoperative adenoma samples. RESULTS: The study included 44 patients: 32.8% men, median age 47.0 [34.0; 55.0], IGF-1 744.75 ng/ml [548.83;889.85], growth hormone 9.5 ng/ml [4.94; 17.07]. Tumor volume 832 mm3 [419.25; 2532.38]. Early postoperative remission was achieved in 35 patients (79.5%). Patients who achieved short-term remission had higher IGF-1 and basal growth hormone levels. Median follow-up was 19.0 months [12.5;29.0]. Long-term remission was achieved in 61.4% (27 patients), no remission in 9 (20.5%), recurrency in 2 patients (4.5%), 6 patients were to follow-up (13.6%). In patients with long-term remission, we observed lower growth hormone and IGF-1 levels. No differences in miRNA expression was observesd. The predictive value of basal GH before surgery for long-term remission was assessed: area under the curve 0.811 (95% CI: 0.649; 0.973). A cut-off value of 15.55 ng/mL corresponded to a sensitivity of 70.0% (34.8%; 93.3%), a specificity of 85.7% (67.3%; 96.0%), an accuracy of 81.6% (65 .7%; 92.3%), PPV 63.6% (39.3%; 82.5%), NPV 88.9% (75.4%; 95.4%). CONCLUSION: Rates of short-term and long-term remission after endoscopic transsphenoidal adenomectomy in our cohort is 79,5% и 61,4%, respectively, and is comparable with literature data for expert pituitary centers. Preoperative GH shows potential value in predicting the long-term remission of acromegaly, but further studies in a larger sample are needed to obtain more accurate cut-off values.

The value of indicators characterizing the state of the cardiovascular system in assessing the hospital prognosis of COVID-19 patients.

Background     Heart damage is one of complications of the novel coronavirus infection. Searching for available predictors for in-hospital death and survival that determine the tactic of managing patients with COVID-19, is a challenge of the present time.Aim      To determine the role echocardiographic (EchoCG) parameters in evaluation of the in-hospital prognosis for patients with the novel coronavirus infection, COVID-19.Material and methods  The study included 158 patients admitted for COVID-19. EchoCG was performed for all patients. The role of left ventricular (LV) ejection fraction (EF) was analyzed in various age groups. EchoCG data were compared with the clinical picture, including the severity of respiratory failure (RF), blood oxygen saturation (SрО2), data of computed tomography (CT) of the lungs, and blood concentration of troponin. Comorbidity was analyzed, and the highest significance of individual pathologies was determined.Results LV EF ≤40 % determined the worst prognosis of patients with COVID-19 (p<0.0001), including the age group older than 70 years (р=0.013). LV EF did not correlate with the degree of lung tissue damage determined by CT upon admission (р=0.54) and over time (р=0.23). The indexes that determined an adverse in-hospital prognosis to a considerable degree were pericardial effusion (p<0.0001) and pulmonary hypertension (p<0.0001). RV end-diastolic dimension and LV end-diastolic volume did not determine the in-hospital mortality and survival. Blood serum concentration of troponin I higher than 165.13 µg/l was an important predictor for in-hospital death with a high degree of significance (р<0.0001). Th degree of RF considerably influenced the in-hospital mortality (р<0.0001). RF severity was associated with LV EF (р=0.024). The SpO2 value determined an adverse immediate prognosis with a high degree of significance (р=0.0009). This parameter weakly correlated with LV EF (r=0.26; p=0.0009). Patients who required artificial ventilation (AV) constituted a group with the worst survival rate (р<0.0001). LV EF was associated with a need for AV with a high degree of significance (р=0.0006). Comorbidities, such as chronic kidney disease, postinfarction cardiosclerosis and oncologic diseases, to the greatest extent determined the risk of fatal outcome.Conclusion      EchoCG can be recommended for patients with COVID-19 at the hospital stage to determine the tactics of management and for the in-hospital prognosis.

Ion trapping model of the ac conductivity in disordered solids.

In this paper, we develop an approach based on ions trapping to describe the conductivity spectra in disordered solids. Applying the multiple trapping model and the diffusion equation for ions, we obtained a new expression for the ac conductivity, which allows us to describe the conductivity spectra in wide ranges of frequencies and temperatures. In the high-temperature region, the new expression for the ac conductivity reproduces the Jonscher behavior, and with decreasing temperatures transforms into an expression of the NCL-type. A new expression for the ac conductivity was successfully tested on the conductivity spectra of ion-conducting glasses.

Hyperspectral Nanoimaging of van der Waals Polaritonic Crystals.

Phonon polaritons (PhPs) in van der Waals (vdW) crystal slabs enable nanoscale infrared light manipulation. Specifically, periodically structured vdW slabs behave as polaritonic crystals (vdW-PCs), where the polaritons form Bloch modes. Because the polariton wavelengths are smaller than that of light, conventional far-field spectroscopy does not allow for a complete characterization of vdW-PCs or for revealing their band structure. Here, we perform hyperspectral infrared nanoimaging and analysis of PhPs in a vdW-PC slab made of h-BN. We demonstrate that infrared spectra recorded at individual spatial positions within the unit cell of the vdW-PC can be associated with its band structure and local density of photonic states (LDOS). We thus introduce hyperspectral infrared nanoimaging as a tool for the comprehensive analysis of polaritonic crystals, which could find applications in the reconstruction of complex polaritonic dispersion surfaces in momentum-frequency space or for exploring exotic electromagnetic modes in topological photonic structures.

[The Influence of Adiponectin on Production of Apolipoproteins A-l and E by Human Macrophages].

Adiponectin is an adipose tissue hormone affecting energy and lipoprotein metabolism and modulating inflammatory responses. However, the role of this adipokine in atherogenesis remains poorly understood. The aim of this study was to investigate the effect of adiponectin on the production of apolipoproteins (apo) A-l and E by human macrophages (MP). The study was conducted on macrophage-like cells of the THP-1 cell line of two differentiation terms, 3 and 5 days (3d and 5d). Adiponectin (10 µg/mL) stimulated the expression of apoA-1 gene at the mRNA level in 5d MP, but not in 3d MP. The level of apoE mRNA in MP under the action of adiponectin was not affected. Adiponectin suppressed macrophage TNF gene expression, while it induced the expression of IL-10 gene in 5d MP. The secreted levels of apoA-1 and apoE proteins under the action of adiponectin in macrophages of both periods of differentiation remained unchanged, while the level of the surface apoA-1 protein in 5d MP was decreasing. Incubation of 5d MP with the PPARα nuclear receptor antagonist MK-886 or with the nuclear receptor LXR agonist TO-901317 resulted in cancellation of the stimulating effect of adiponectin on apoA-1 gene expression. These data indicate that adiponectin, in addition to its anti-inflammatory action, has a modulating effect on production of apoA-1 by macrophages. The latter is probably one of the mechanisms of the influence of this adipokine on atherogenesis.

Planar refraction and lensing of highly confined polaritons in anisotropic media.

Refraction between isotropic media is characterized by light bending towards the normal to the boundary when passing from a low- to a high-refractive-index medium. However, refraction between anisotropic media is a more exotic phenomenon which remains barely investigated, particularly at the nanoscale. Here, we visualize and comprehensively study the general case of refraction of electromagnetic waves between two strongly anisotropic (hyperbolic) media, and we do it with the use of nanoscale-confined polaritons in a natural medium: α-MoO3. The refracted polaritons exhibit non-intuitive directions of propagation as they traverse planar nanoprisms, enabling to unveil an exotic optical effect: bending-free refraction. Furthermore, we develop an in-plane refractive hyperlens, yielding foci as small as λp/6, being λp the polariton wavelength (λ0/50 compared to the wavelength of free-space light). Our results set the grounds for planar nano-optics in strongly anisotropic media, with potential for effective control of the flow of energy at the nanoscale.

[Neurogenic intermittent claudication in patients with degenerative lumbar stenosis]. / Neirogennaya peremezhayushchayasya khromota u bol'nykh s poyasnichnym degenerativnym stenozom.

OBJECTIVE: To study the clinical manifestations of neurogenic intermittent claudication (NIC) in patients with degenerative lumbar stenosis (DLS). MATERIAL AND METHODS: The neurological status, intensity and nature of pain syndrome, and pain-free walking distance were evaluated in 83 NIC patients with DPS, who underwent surgical treatment. RESULTS: The predominance of the clinical picture of sensorimotor pain (n=30; 36.1%) and isolated pain (n=31; 37.3%) forms of NIC was established. Isolated sensory (n=1; 1.2%), sensorimotor (n=3; 3.6%), and motor-pain (n=4; 4.8%) forms were significantly less common. In 6 (7.2%) patients, there was a pain-free form of NIC. In most patients, surgical treatment led to regression of neurological symptoms and an increase in the distance of pain-free walking. No relationship was found between the demographic and clinical characteristics of patients (gender, age, pain severity, pain-free walking distance), MRI results and the features of NIC clinical picture. In 4 patients, the phenomenon of pacing was revealed in the form of an increase in pain at the beginning of walking and a significant decrease or complete regression as walking continues. CONCLUSION: The clinical picture of NIC is polymorphic, its pain-free course is possible. The decision on the feasibility of surgical treatment of patients with PLS is possible taking into account the clinical picture of NIC and MRI results.

Non-magnetic shell coating of magnetic nanoparticles as key factor of toxicity for cancer cells in a low frequency alternating magnetic field.

This work is devoted to studying the effects of non-magnetic shell coating on nanoparticles in a low frequency alternating magnetic field (LF AMF) on tumor cells in vitro. Two types of iron oxide nanoparticles with the same magnetic core with and without silica shells were synthesized. Nanoparticles with silica shells significantly decreased the viability of PC3 cancer cells in a low frequency alternating magnetic field according to the cytotoxicity test, unlike uncoated nanoparticles. We showed that cell death results from the intracellular membrane integrity failure, and the calcium ions concentration increase with the subsequent necrosis. Transmission electron microscopy images showed that the uncoated silica nanoparticles are primarily found in an aggregated form in cells. We believe that uncoated nanoparticles lose their colloidal stability in an acidic endosomal environment after internalization into the cell due to surface etching and the formation of aggregates. As a result, they encounter high endosomal macromolecular viscosity and become unable to rotate efficiently. We assume that effective rotation of nanoparticles causes cell death. In turn, silica shell coating increases nanoparticles stability, preventing aggregation in endosomes. Thus, we propose that the colloidal stability of magnetic nanoparticles inside cells is one of the key factors for effective magneto-mechanical actuation.

COVID-19 in Russia: Clinical and Immunological Features of the First-Wave Patients.

The coronavirus disease outbreak in 2019 (COVID-19) has now achieved the level of a global pandemic and affected more than 100 million people on all five continents and caused over 2 million deaths. Russia is, needless to say, among the countries affected by SARS-CoV-2, and its health authorities have mobilized significant efforts and resources to fight the disease. The paper presents the result of a functional analysis of 155 patients in the Moscow Region who were examined at the Central Clinical Hospital of the Russian Academy of Sciences during the first wave of the pandemic (February-July, 2020). The inclusion criteria were a positive PCR test and typical, computed tomographic findings of viral pneumonia in the form of ground-glass opacities. A clinical correlation analysis was performed in four groups of patients: (1) those who were not on mechanical ventilation, (2) those who were on mechanical ventilation, and (3) those who subsequently recovered or (4) died. The correlation analysis also considered confounding comorbidities (diabetes, metabolic syndrome, hypertension, etc.). The immunological status of the patients was examined (levels of immunoglobulins of the M, A, G classes and their subclasses, as well as the total immunoglobulin level) using an original SARS-CoV-2 antibody ELISA kit. The ELISA kit was developed using linear S-protein RBD-SD1 and NTD fragments, as well as the N-protein, as antigens. These antigens were produced in the prokaryotic E. coli system. Recombinant RBD produced in the eukaryotic CHO system (RBD CHO) was used as an antigen representing conformational RBD epitopes. The immunoglobulin A level was found to be the earliest serological criterion for the development of a SARS-CoV-2 infection and it yielded the best sensitivity and diagnostic significance of ELISA compared to that of class M immunoglobulin. We demonstrated that the seroconversion rate of "early" N-protein-specific IgM and IgA antibodies is comparable to that of antibodies specific to RBD conformational epitopes. At the same time, seroconversion of SARS-CoV-2 N-protein-specific class G immunoglobulins was significantly faster compared to that of other specific antibodies. Our findings suggest that the strong immunogenicity of the RBD fragment is for the most part associated with its conformational epitopes, while the linear RBD and NTD epitopes have the least immunogenicity. An analysis of the occurrence rate of SARS-CoV-2-specific immunoglobulins of different classes revealed that RBD- and N-specific antibodies should be evaluated in parallel to improve the sensitivity of ELISA. An analysis of the immunoglobulin subclass distribution in sera of seropositive patients revealed uniform induction of N-protein-specific IgG subclasses G1-G4 and IgA subclasses A1-A2 in groups of patients with varying severity of COVID-19. In the case of the S-protein, G1, G3, and A1 were the main subclasses of antibodies involved in the immune response.

Enabling propagation of anisotropic polaritons along forbidden directions via a topological transition.

Polaritons with directional in-plane propagation and ultralow losses in van der Waals (vdW) crystals promise unprecedented manipulation of light at the nanoscale. However, these polaritons present a crucial limitation: their directional propagation is intrinsically determined by the crystal structure of the host material, imposing forbidden directions of propagation. Here, we demonstrate that directional polaritons (in-plane hyperbolic phonon polaritons) in a vdW crystal (α-phase molybdenum trioxide) can be directed along forbidden directions by inducing an optical topological transition, which emerges when the slab is placed on a substrate with a given negative permittivity (4H-silicon carbide). By visualizing the transition in real space, we observe exotic polaritonic states between mutually orthogonal hyperbolic regimes, which unveil the topological origin of the transition: a gap opening in the dispersion. This work provides insights into optical topological transitions in vdW crystals, which introduce a route to direct light at the nanoscale.