Nanoformulation of Glycyrrhizic acid as a potent antiviral agent against Covid-19

In many previous studies, it has been found that liquorice plant (Glycyrrhiza glabra) extracts contain more than 300 natural compounds, most of which are triterpenoids and flavonoids, and had shown promising results in clinical studies for treating many microbial and viral infections. Triterpenoids like glycyrrhizic acid have shown anti-SARS-CoV activity in- vitro. Experimentally, certain glycyrrhizic acid derivatives have shown increased activity by many folds against SARS-associated viruses. These compounds can potentially inhibit the replication cycle of SARS-associated viruses by interfering with the viral gene expression or by inhibiting the spike protein expression, which in turn inhibits the adhesion and entry of the virus. Although the therapeutic has shown great antiviral activity in vitro, but in vivo its efficiency deteriorates till it reaches the liver for metabolism. In the current review, we analyze the unique replication strategy of SARS-CoV-2 and glycyrrhizic acid as a potential drug against SARS-CoV-2. We also discuss possible nano-formulations of glycyrrhizic acid for efficient drug delivery in humans, as a potent therapeutic strategy for COVID-19.

Increased insula activity precedes the formation of subjective Gestalt

The constructive nature of human perception sometimes leads us to perceiving rather complex impressions from simple sensory input. Bistable stimuli give us a rare opportunity to study the neural mechanisms behind this process. Such stimuli can be visually interpreted as simple or as more complex on the basis of the same sensory input. Previous studies demonstrated increased activity in the superior parietal cortex when participants perceived an illusory Gestalt impression compared to a simpler interpretation of individual elements. Here we tested whether activity related to the illusory Gestalt can be detected not only during, but also prior to it, by examining the slow fluctuations of resting-state-fMRI activity before the stimulus onset. We presented 31 participants with a bistable motion stimulus, which can be perceived either as four moving dot pairs (local) or two moving illusory squares (global). This allowed us to isolate the specific neural mechanisms that accompany the experience of an illusion under matched sensory input. fMRI was used to measure brain activity in a sparse event-related design. We observed stronger IPS and putamen responses to the stimulus when participants perceived the global interpretation compared to local, confirming the previously reported role of these areas in perceptual grouping. Most importantly, we also observed that the global stimulus interpretation was preceded by an increased activity of the bilateral dorsal insula, which is known to process saliency and gate information for conscious access. Our data suggest an important role of the dorsal insula in shaping an internally generated illusory Gestalt percept.

[NiFe]-(Oxy)Sulfides Derived from NiFe2O4 for the Alkaline Hydrogen Evolution Reaction

The development of noble-metal-free electrocatalysts is regarded as a key factor for realizing industrial-scale hydrogen production powered by renewable energy sources. Inspired by nature, which uses Fe- and Ni-containing enzymes for efficient hydrogen generation, Fe/Ni-containing chalcogenides, such as oxides and sulfides, received increasing attention as promising electrocatalysts to produce hydrogen. We herein present a novel synthetic procedure for mixed Fe/Ni (oxy)sulfide materials by the controlled (partial) sulfidation of NiFe2O4 (NFO) nanoparticles in H2S-containing atmospheres. The variation in H2S concentration and the temperature allows for a precise control of stoichiometry and phase composition. The obtained sulfidized materials (NFS) catalyze the hydrogen evolution reaction (HER) with increased activity in comparison to NFO, up to −10 and −100 mA cm−2 at an overpotential of approx. 250 and 450 mV, respectively.

A Tear Metabolomic Profile Showing Increased Ornithine Decarboxylase Activity and Spermine Synthesis in Thyroid-Associated Orbitopathy

About half of patients with Graves’ disease develop an orbitopathy related to an inflammatory expansion of the periorbital adipose tissue and muscles. We used a targeted metabolomic approach measuring 188 metabolites by mass spectrometry to compare the metabolic composition of tears in patients with active (n = 21) versus inactive (n = 24) thyroid-associated orbitopathy. Among the 44 metabolites accurately measured, 8 showed a significant alteration of their concentrations between the two groups. Two short-chain acylcarnitines, propionylcarnitine and butyrylcarnitine, and spermine showed increased concentrations in the tears of patients with active orbitopathy, whereas ornithine, glycine, serine, citrulline and histidine showed decreased concentrations in this group. In addition, the ratio putrescine/ornithine, representing the activity of ornithine decarboxylase, was significantly increased in patients with active compared to inactive orbitopathy (p = 0.0011, fold change 3.75). The specificity of this candidate biomarker was maintained when compared to a control group with unclassified dry eye disease. Our results suggest that the stimulation of ornithine decarboxylase by TSH receptor autoantibodies in orbital fibroblasts could lead to increased synthesis of spermine, through the increased activity of ornithine decarboxylase, that may contribute to periorbital expansion in Graves’ ophthalmopathy.

Predictability-dependent encoding of statistical regularities in the early visual cortex

Previous research recognized that humans could extract statistical regularities of the environment to automatically predict upcoming events. However, it has remained unexplored how the brain encodes the distribution of statistical regularities if it continuously changes. To investigate this question, we devised an fMRI paradigm where participants (N = 32) completed a visual four-choice reaction time (RT) task consisting of statistical regularities. Two types of blocks involving the same perceptual elements alternated with one another throughout the task: While the distribution of statistical regularities was predictable in one block type, it was unpredictable in the other. Participants were unaware of the presence of statistical regularities and of their changing distribution across the subsequent task blocks. Based on the RT results, although statistical regularities were processed similarly in both the predictable and unpredictable blocks, participants acquired less statistical knowledge in the unpredictable as compared with the predictable blocks. Whole-brain random-effects analyses showed increased activity in the early visual cortex and decreased activity in the precuneus for the predictable as compared with the unpredictable blocks. Therefore, the actual predictability of statistical regularities is likely to be represented already at the early stages of visual cortical processing. However, decreased precuneus activity suggests that these representations are imperfectly updated to track the multiple shifts in predictability throughout the task. The results also highlight that the processing of statistical regularities in a changing environment could be habitual.

Sex-specific evolution of a Drosophila sensory system via interacting cis- and trans-regulatory changes

The evolution of gene expression via cis-regulatory changes is well established as a major driver of phenotypic evolution. However, relatively little is known about the influence of enhancer architecture and intergenic interactions on regulatory evolution. We address this question by examining chemosensory system evolution in Drosophila. D. prolongata males show a massively increased number of chemosensory bristles compared to females and males of sibling species. This increase is driven by sex-specific transformation of ancestrally mechanosensory organs. Consistent with this phenotype, the Pox neuro transcription factor (Poxn), which specifies chemosensory bristle identity, shows expanded expression in D. prolongata males. Poxn expression is controlled by non-additive interactions among widely dispersed enhancers. Although some D. prolongata Poxn enhancers show increased activity, the additive component of this increase is slight, suggesting most changes in Poxn expression are due to epistatic interactions between Poxn enhancers and trans-regulatory factors. Indeed, the expansion of D. prolongata Poxn enhancer activity is only observed in cells that express doublesex (dsx), the gene that controls sexual differentiation in Drosophila and also shows increased expression in D. prolongata males due to cis-regulatory changes. Although expanded dsx expression may contribute to increased activity of D. prolongata Poxn enhancers, this interaction is not sufficient to explain the full expansion of Poxn expression, suggesting that cis-trans interactions between Poxn, dsx, and additional unknown genes are necessary to produce the derived D. prolongata phenotype. Overall, our results demonstrate the importance of epistatic gene interactions for evolution, particularly when pivotal genes have complex regulatory architecture.

The phenomenon of NFT (non-fungible tokens) as an accounting entity

The emergence of the digital economy and increased activity in cyberspace have led to the creation of new technologies and digital products such, as non-fungible tokens (NFT). The article presents the arguments that justify the need to study NFT as an object of legal relations and an object of accounting. A brief description of these items has been given; their types and market of circulation have been studied, and, also the current legal provisions, Russian accounting standards and international financial reporting standards have been analysed. To define NFT as an accounting object, the types of accounting objects enshrined in Federal Law No. 402-FZ “On Accounting” have been considered and the criteria for their attribution in relation to NFT have been analysed. The legal and accounting problems associated with the emergence of a new object have been highlighted and the ways for further research in the field of creating an accounting methodology for NFT as a specific and highly promising digital product have been defined.

Chemical composition and phytotoxicity of essential oils of Croton doctoris S. Moore (Euphorbiaceae)

Essential oils from the stems and leaves of Croton doctoris were analyzed by gas chromatography and mass spectrometry, resulting in 22 identified compounds. The effects of these essential oils on the germination, root and shoot growth, total chlorophyll content, potential root respiration, peroxidase activity, catalase, superoxide dismutase, and mitotic index in lettuce and onion were determined. Antioxidant, antimicrobial, and cytotoxic activity were also investigated. The results revealed that the stem oil consisted of 15 compounds, of which caryophyllene oxide (24.5%) and E-caryophyllene (13.3%) were the major constituents. The leaf oil contained E-caryophyllene (39.6%) and α-humulene (13.2%) as major compounds. The oils inhibited the germination and growth of lettuce and onion seedlings and reduced chlorophyll content, root respiration, and cell division. They also caused oxidative stress, indicated by the increased activity of the evaluated antioxidant enzymes. These abnormal physiological processes contributed to the inhibition of plant growth. The most pronounced phytotoxic effects were observed in the stem oil. The cytotoxicity tests indicated that leaf oil was more active than stem oil, resulting from the presence of biologically active sesquiterpenes that inhibit the growth of cancer cells.

Activity of genes of matrix metalloproteinases and their inhibitors in the Ligamentum flavum of patients with stenosing processes in spinal canal and dural sac

New data have been obtained for assessing the expression of genes of metalloproteinases and their tissue inhibitors (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1 and TIMP-2) in the Ligamentum flavum in patients with lumbar stenosis of spinal canal and dural sac. The features of the metabolism of the extracellular matrix (ECM) were revealed, the data obtained were compared with those for previously studied candidate genes. The search for relationships with the features of the ECM metabolic characteristics was carried out.The aim. To study the expression of genes of metalloproteinases and their tissue inhibitors in intraoperative biopsies of the Ligamentum flavum of patients with lumbar stenosis of the spinal canal and dural sac.Materials and methods. A group of 33 people (17 women, 16 men) with lumbar stenosis of the spinal canal and dural sac was studied; the average age is 45.73 ± 1.95 years. RNA was isolated from intraoperative biopsies of the Ligamentum flavum, reverse transcription was performed, and PCR using specific primers was performed.Results. In Ligamentum flavum of patients with stenosing processes of the spinal canal and dural sac, an increased activity of MMP-1 and insufficient response of TIMP-1 and TIMP-2 were found; the expression of MMP-1 increased synchronously with Dio2, and both genes decreased their activity with increasing age of the patient. In patients with Ligamentum flavum ossification, the MMR-8 gene was more actively expressed, and the synthesis of the mRNA of the MMR-9 gene decreased compared to the subgroup without ossification.