The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global healthcare, underscoring the importance of exploring the virus's effects on infected individuals beyond ...treatments and vaccines. Notably, recent findings suggest that SARS-CoV-2 can infect the gut, thereby altering the gut microbiota. This study aimed to analyze the gut microbiota composition differences between COVID-19 patients experiencing mild and severe symptoms. We conducted 16S rRNA metagenomic sequencing on fecal samples from 49 mild and 43 severe COVID-19 cases upon hospital admission. Our analysis identified a differential abundance of specific bacterial species associated with the severity of the disease. Severely affected patients showed an association with
,
, and others, while milder cases were linked to
,
,
, and additional species. Furthermore, a network analysis using SPIEC-EASI indicated keystone taxa and highlighted structural differences in bacterial connectivity, with a notable disruption in the severe group. Our study highlights the diverse impacts of SARS-CoV-2 on the gut microbiome among both mild and severe COVID-19 patients, showcasing a spectrum of microbial responses to the virus. Importantly, these findings align, to some extent, with observations from other studies on COVID-19 gut microbiomes, despite variations in methodologies. The findings from this study, based on retrospective data, establish a foundation for future prospective research to confirm the role of the gut microbiome as a predictive biomarker for the severity of COVID-19.
Non-steroidal anti-inflammatory drugs (NSAIDs) are an important class of medications; however, they have some drawbacks. We are developing a new NSAID with pronounced anti-inflammatory and analgesic ...activities and a very low toxicity—(Z)-3-(2-oxo-2-(p-tolyl)ethylidene)piperazin-2-one (piron). In this work, we describe the synthesis of the main metabolite of piron—(Z)-4-(2-(3-oxopiperazin-2-ylidene)acetyl)benzoic acid. The anti-inflammatory activity of the synthesized metabolite was determined in vivo.
Crohn's disease is associated with gut dysbiosis. Independent studies have shown an increase in the abundance of certain bacterial species, particularly Escherichia coli with the adherent-invasive ...pathotype, in the gut. The role of these species in this disease needs to be elucidated.
We performed a metagenomic study investigating the gut microbiota of patients with Crohn's disease. A metagenomic reconstruction of the consensus genome content of the species was used to assess the genetic variability.
The abnormal shifts in the microbial community structures in Crohn's disease were heterogeneous among the patients. The metagenomic data suggested the existence of multiple E. coli strains within individual patients. We discovered that the genetic diversity of the species was high and that only a few samples manifested similarity to the adherent-invasive varieties. The other species demonstrated genetic diversity comparable to that observed in the healthy subjects. Our results were supported by a comparison of the sequenced genomes of isolates from the same microbiota samples and a meta-analysis of published gut metagenomes.
The genomic diversity of Crohn's disease-associated E. coli within and among the patients paves the way towards an understanding of the microbial mechanisms underlying the onset and progression of the Crohn's disease and the development of new strategies for the prevention and treatment of this disease.
Background and Purpose
Acid‐sensing ion channels (ASICs) play an important role in synaptic plasticity and learning, as well as in nociception and mechanosensation. ASICs are involved in pain and in ...neurological and psychiatric diseases, but their therapeutic potential is limited by the lack of ligands activating them at physiological pH.
Experimental Approach
We extracted, purified and determined the structure of a bisbenzylisoquinoline alkaloid, lindoldhamine, (LIN) from laurel leaves. Its effect on ASIC3 channels were characterized, using two‐electrode voltage‐clamp electrophysiological recordings from Xenopus laevis oocytes.
Key Results
At pH 7.4 or higher, LIN activated a sustained, proton‐independent, current through rat and human ASIC3 channels, but not rat ASIC1a or ASIC2a channels. LIN also potentiated proton‐induced transient currents and promoted recovery from desensitization in human, but not rat, ASIC3 channels.
Conclusions and Implications
We describe a novel ASIC subtype‐specific agonist LIN, which induced proton‐independent activation of human and rat ASIC3 channels at physiological pH. LIN also acts as a positive allosteric modulator of human, but not rat, ASIC3 channels. This unique, species‐selective, ligand of ASIC3, opens new avenues in studies of ASIC structure and function, as well as providing new approaches to drug design.
The recovery period after traumatic brain injury (TBI) is often complicated by secondary damage that may last for days or even months after trauma. Two proteins, Hsp70 and glyceraldehyde-3-phosphate ...dehydrogenase (GAPDH), were recently described as modulating post-traumatic processes, and in this study, we test them as targets for combination therapy using an inhibitor of GAPDH aggregation (derivative of hydrocortisone RX624) and an inducer of Hsp70 synthesis (the pyrrolylazine derivative PQ-29). The protective effect of the combination on C6 rat glioblastoma cells treated with the cerebrospinal fluid of traumatized animals resulted in an increase in the cell index and in a reduced level of apoptosis. Using a rat weight drop model of TBI, we found that the combined use of both drugs prevented memory impairment and motor deficits, as well as a reduction of neurons and accumulation of GAPDH aggregates in brain tissue. In conclusion, we developed and tested a new approach to the treatment of TBI based on influencing distinct molecular mechanisms in brain cells.
Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn's disease (CD). The phylogeny of E. coli isolated from Crohn's disease patients (CDEC) was controversial, and ...while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related.
We performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already published genomes of CD strains and other pathogenic and non-pathogenic strains. CDEC was shown to belong to A, B1, B2 and D phylogenetic groups. The plasmid and several operons from the reference CD-associated E. coli strain LF82 were demonstrated to be more often present in CDEC genomes belonging to different phylogenetic groups than in genomes of commensal strains. The operons include carbon-source induced invasion GimA island, prophage I, iron uptake operons I and II, capsular assembly pathogenetic island IV and propanediol and galactitol utilization operons.
Our findings suggest that CDEC are phylogenetically diverse. However, some strains isolated from independent sources possess highly similar chromosome or plasmids. Though no CD-specific genes or functional domains were present in all CD-associated strains, some genes and operons are more often found in the genomes of CDEC than in commensal E. coli. They are principally linked to gut colonization and utilization of propanediol and other sugar alcohols.
Cyclization of 1-hydrazinyl-3,3-dimethyl-3,4-tetrahydro-5
H
-benzo
c
azepine with ethyl orthoformate gave 5,5-dimethyl-6,7-dihydro-5
H
benzo
c
-1,2,4-triazolo3,4-
a
azepine, and its reaction with ...acetic acid afforded 3,5,5-trimethyl-9,10-dimethoxy-6,7-dihydro-5
Н
-benzo
c
-1,2,4-triazolo3,4-
a
azepine. Nitrosation of 1-hydrazino-3,3-dimethyl-3,4-tetrahydro-5
H
-benzo
c
azepine led to the formation of substituted 6,7-dihydro-5
H
-benzo
c
tetrazolo5,1-
a
azepines.
Sea anemones (Actiniaria) are intensely popular objects of study in venomics. Order Actiniaria includes more than 1,000 species, thus presenting almost unlimited opportunities for the discovery of ...novel biologically active molecules. The venoms of cold-water sea anemones are studied far less than the venoms of tropical sea anemones. In this work, we analysed the molecular venom composition of the cold-water sea anemone Cnidopus japonicus. Two sets of NGS data from two species revealed molecules belonging to a variety of structural classes, including neurotoxins, toxin-like molecules, linear polypeptides (Cys-free), enzymes, and cytolytics. High-throughput proteomic analyses identified 27 compounds that were present in the venoms. Some of the toxin-like polypeptides exhibited novel Cys frameworks. To characterise their function in the venom, we heterologously expressed 3 polypeptides with unusual Cys frameworks (designated CjTL7, CjTL8, and AnmTx Cj 1c-1) in E. coli. Toxicity tests revealed that the CjTL8 polypeptide displays strong crustacean-specific toxicity, while AnmTx Cj 1c-1 is toxic to both crustaceans and insects. Thus, an improved NGS data analysis algorithm assisted in the identification of toxins with unusual Cys frameworks showing no homology according to BLAST. Our study shows the advantage of combining omics analysis with functional tests for active polypeptide discovery.
In this work, the subject of research is hydrodynamics, and in particular, the hydraulic resistance of a boiling two-phase flow moving in vertical and inclined pipes of evaporators of ship ...refrigeration units. Such movement is typical for various types of industrial heat exchange equipment, including the development of promising types of evaporators, for example, vertical devices for ships in which in-tube boiling of liquid refrigerant occurs. Experiments were carried out to study hydraulic resistance in vertical pipes with different channel diameters and lengths. The main dependencies of the various components of hydraulic resistance that arise during the movement of a boiling two-phase flow are presented. Based on the data obtained, the prospects of transitioning ship evaporators of refrigeration units to a vertical arrangement of heat exchange tubes are shown. When applied to ship refrigeration machines, we can say that the transition to vertical units has its advantages, primarily in reducing pressure losses. The resulting set of data allows us to recommend the design of vertical evaporators for auxiliary ship installations.
A physical pendulum controlled by a motor located at a fixed point of suspension is considered in the work. The task is to bring and stabilize this pendulum in the upper unstable equilibrium ...position. Such a pendulum can be considered as a model of a person standing on an individual Segway-type vehicle. Two engine control algorithms based on the readings of the rotation angle and angular velocity sensors of the pendulum are considered. One of these algorithms maximizes the area of attraction of the upper equilibrium position, the second algorithm allows you to bring the pendulum to this position with minimal energy costs. Computer graphic illustrations help to understand the essence of these control algorithms. The construction of such drawings and animations based on the results of integrating differential equations of the controlled movement of a pendulum under various control laws is a meaningful educational task. This problem is solved by master's students of the Department of Robotics, Mechatronics, Dynamics and Strength of Machines of the National Research University Moscow Power Engineering Institute when they study the course "Stability and stabilization of motion of dynamic systems." The article discusses an example of performing such computational and graphical work using the Mathematica computer algebra system. Students present the result of the assignment in the form of a Mathematica program, a file with the nb extension. Such a program, as is known, contains text and executable cells, which allows you to ask not only questions involving symbolic transformations, numerical and analytical solutions, graphic constructions. It is also possible to formulate theoretical problems, the answer to which must be given in the form of text. The package Mathematica is available freely online on WolframCloud. To complete the task, the freely distributed computer algebra system Maxima can be used.
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