Triterpene glycosides from Antarctic sea cucumbers. 1. Structure of liouvillosides A1, A2, A3, B1, and B2 from the sea cucumber Staurocucumis liouvillei: new procedure for separation of highly polar glycoside fractions and taxonomic revision

Five new triterpene glycosides, liouvillosides A1 (1), A2 (2), A3 (3), B1 (4), and B2 (5), have been isolated from the Antarctic sea cucumber Staurocucumis liouviellei along with the known liouvilloside A(6), isolated earlier from the same species, and hemoiedemosides A (7) and B (8), isolated earlier from the Patagonian sea cucumber Hemioedema spectabilis. The isolation was carried out using a new chromatographic procedure including application of ion-pair reversed-phase chromatography followed by chiral chromatography on a cyclodextrin ChiraDex column. The structures of the new glycosides were elucidated using extensive NMR spectroscopy (1H and 13C NMR spectrometry, DEPT, 1H-(1)H COSY, HMBC, HMQC, and NOESY), ESI-FTMS, and CID MS/MS, and chemical transformations. Glycosides 1-3 are disulfated tetraosides and glycosides 4 and 5 are trisulfated tetraosides. Glycosides 2 and 3 contain 3-O-methylquinovose, found for the first time as a natural monosaccharide in sea cucumber glycosides. On the basis of analyses of glycoside structures a taxonomic revision is proposed.     

Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin

The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3β shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-dependent autophagic response might sensitize glioma cells to statin-induced apoptotic death.     

Bayesian Molecular Dating Analyses Combined with Mutational Profiling Suggest an Independent Origin and Evolution of SARS-CoV-2 Omicron BA.1 and BA.2 Sub-Lineages

The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of the initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track the virus’s genetic changes that drive the early evolutionary dynamics of the Omicron. Based on the Omicron dataset chosen for the improved temporal signals and sampled globally between November 2021 and January 2022, the most recent common ancestor (tMRCA) and substitution rates for BA.1 were estimated to be that of 18 September 2021 (95% highest posterior density (HPD), 4 August–22 October 2021) and 1.435 × 10⁻³ (95% HPD  =  1.021 × 10⁻³ − 1.869 × 10⁻³) substitution/site/year, respectively, whereas 3 November 2021 (95% highest posterior density (HPD) 26 September–28 November 2021) and 1.074 × 10⁻³ (95% HPD  =  6.444 × 10⁻⁴ − 1.586 × 10⁻³) substitution/site/year were estimated for the BA.2 sub-lineage. The findings of this study suggest that the Omicron BA.1 and BA.2 sub-lineages originated independently and evolved over time. Furthermore, we identified multiple sites in the spike protein undergoing continued diversifying selection that may alter the neutralization profile of BA.1. This study sheds light on the ongoing global genomic surveillance and Bayesian molecular dating analyses to better understand the evolutionary dynamics of the virus and, as a result, mitigate the impact of emerging variants on public health.     

UV Light Irradiation Effects in P-Doped Diamonds: Total Content Determination of Phosphorus Donors

Upon the UV light irradiation of single-crystal diamonds doped with phosphorus, several effects have been observed. The integral intensity of phosphorus lines in FTIR absorption spectra under UV radiation was increased. A saturation effect depending on the power of the laser radiation was demonstrated. Narrowing of the phosphorus lines, as well as the redistribution of the intensities in their doublets caused by the Jahn–Teller distortion of the donor ground state, was observed. It was found that these effects are associated with the decompensation of the phosphorus donors. An easy, fast, sensitive, and nondestructive, fully optical method for the determination of the total phosphorus donor’s concentration in semiconducting diamonds, as well as its compensation ratio, was proposed.     

Silicone Materials for Flexible Optoelectronic Devices

Polysiloxanes and materials based on them (silicone materials) are of great interest in optoelectronics due to their high flexibility, good film-forming ability, and optical transparency. According to the literature, polysiloxanes are suggested to be very promising in the field of optoelectronics and could be employed in the composition of liquid crystal devices, computer memory drives organic light emitting diodes (OLED), and organic photovoltaic devices, including dye synthesized solar cells (DSSC). Polysiloxanes are also a promising material for novel optoectronic devices, such as LEDs based on arrays of III–V nanowires (NWs). In this review, we analyze the currently existing types of silicone materials and their main properties, which are used in optoelectronic device development.     

Fault Current Limitation in Electrical Power Networks Containing HTS Cable and HTS Fuse

Numerical calculations of parameters of an electrical power network where an HTS fuse is used as a fault current limiting device have been done. The calculations were performed for networks containing different types of HTS cables as well. The design of HTS fuse was developed based on the numerical calculation for the network-rated parameters considering the special types 2G HTS tape characteristics. The distinctive feature of these tapes is the minimal thickness (about 30 µm) of the substrate at the critical current 450–600 A. The tests were performed at a voltage of 1 kV and demonstrated the ability of circuit breaking at fault currents about 3–4 kA. A comparison of experimental results with the calculations allows us to conclude that the HTS fuse of this design can operate as a fault current limiting device in electrical power networks at various rated voltage levels.     

A Feasibility Study of High-Entropy Alloy Coating Deposition by Detonation Spraying Combined with Laser Melting

In this work, a new two-stage approach to the deposition of high-entropy alloy coatings is proposed. At the first stage, a composite precursor coating is formed by detonation spraying of the metal powder mixtures. At the second stage, the precursor coating is re-melted by a laser, and the formation of multi-component solid solution phases can be expected upon solidification. The feasibility of the proposed approach was validated using three different mixtures of Fe, Ni, Cu, Co and Al powders. It was shown that detonation spraying allows forming composite coatings with a uniform distribution of the lamellae of different metals. The results of the structural analysis of the laser-treated coatings suggest that complete alloying occurred in the melt and face-centered cubic solid solutions formed in the coatings upon cooling.     

Chronic biopsy proven post‐COVID myoendocarditis with SARS‐Cov‐2 persistence and high level of antiheart antibodies

PurposeTo study the clinical signs and mechanisms (viral and autoimmune) of myoendocarditis in the long‐term period after COronaVIrus Disease 2019 (COVID‐19).MethodsFourteen patients (nine male, 50.1 ± 10.2 y.o.) with biopsy proven post‐COVID myocarditis were observed. The diagnosis of COVID‐19 was confirmed by IgG seroconversion. The average time of admission after COVID‐19 was 5.5 [2; 10] months. An endomyocardial biopsy (EMB) of the right ventricle was obtained. The biopsy analysis included polymerase chain reaction diagnosis of viral infection, morphological, immunohistochemical (IHC) examination with antibodies to CD3, CD45, CD68, CD20, SARS‐Cov‐2 spike, and nucleocapsid antigens. Coronary atherosclerosis was ruled out in all patients over 40 years.ResultsThe new cardiac symptoms (congestive heart failure 3–4 New York Heart Association class with severe right ventricular involvement, various rhythm, and conduction disturbances) appeared 1–5 months following COVID‐19. Magnetic resonance imaging showed disseminated or focal subepicardial and intramyocardial late gadolinium enhancement, hyperemia, edema, and increased myocardial native T1 relaxation time. Antiheart antibodies levels were increased 3–4 times in 92.9% of patients. The mean left ventricular (LV) ejection fraction (EF) was 28% (24.5; 37.8). Active lymphocytic myocarditis was diagnosed in 12 patients, eosinophilic myocarditis in two patients. SARS‐Cov‐2 RNA was detected in 12 cases (85.7%), in association with parvovirus B19 DNA—in one. Three patients had also endocarditis (infective and nonbacterial, with parietal thrombosis). As a result of steroid and chronic heart failure therapy, the EF increased to 47% (37.5; 52.5).ConclusionsCOVID‐19 can lead to long‐term severe post‐COVID myoendocarditis, that is characterized by prolonged persistence of coronavirus in cardiomyocytes, endothelium, and macrophages (up to 18 months) in combination with high immune activity. Corticosteroids and anticoagulants should be considered as a treatment option of post‐COVID myoendocarditis.     

Collagen-Carboxymethylcellulose Biocomposite Wound-Dressings with Antimicrobial Activity

Microbial infections associated with skin diseases are frequently investigated since they impact on the progress of pathology and healing. The present work proposes the development of freeze-dried, glutaraldehyde cross-linked, and non-cross-linked biocomposite dressings with a porous structure, which may assist the reepithelization process through the presence of collagen and carboxymethylcellulose, along with a therapeutic antimicrobial effect, due to silver nanoparticles (AgNPs) addition. Phisyco-chemical characterization revealed the porous morphology of the obtained freeze-dried composites, the presence of high crystalline silver nanoparticles with truncated triangular and polyhedral morphologies, as well as the characteristic absorption bands of collagen, silver, and carboxymethylcellulose. In vitro tests also assessed the stability, functionality, and the degradability rate of the obtained wound-dressings. Antimicrobial assay performed on Gram-negative (Escherichia coli), Gram-positive (Staphyloccocus aureus) bacteria, and yeast (Candida albicans) models demonstrated that composite wound dressings based on collagen, carboxymethylcellulose, and AgNPs are suitable for skin lesions because they prevent the risk of infection and have prospective wound healing capacity. Moreover, the cell toxicity studies proved that the obtained materials can be used in long time treatments, with no cytotoxic effects.