Unveiling the unusual i-motif-derived architecture of a DNA aptamer exhibiting high affinity for influenza A virus.

Non-canonical nucleic acid structures play significant roles in cellular processes through selective interactions with proteins. While both natural and artificial G-quadruplexes have been extensively studied, the functions of i-motifs remain less understood. This study investigates the artificial aptamer BV42, which binds strongly to influenza A virus hemagglutinin and unexpectedly retains its i-motif structure even at neutral pH.

Fullerenol C(OH): Antioxidant, Cytoprotective, Anti-Influenza Virus Activity, and Self-Assembly in Aqueous Solutions and Cell Culture Media.

Viral infections and many other dangerous diseases are accompanied by the development of oxidative stress, which is a consequence of an increase in the level of the reactive oxygen species (ROS). In this regard, the search for effective antioxidants remains highly relevant. We tested fullerenol C(OH) in the context of the connection between its self-assembly in aqueous solutions and cell culture media, antiradical activity, UV cytoprotective action, and antiviral activity against international reference strains of influenza virus A(H1N1)pdm09, A(H3N2), and B subtypes in vitro on the MDCK cell line.

[Synthesis of a Bisbenzoxazole Analogue of Hoechst 33258 as a Potential GC-Selective DNA Ligand].

Using a computer modeling approach, we proposed a structure for a potential GC-specific DNA ligand, which could form a complex with DNA in the minor groove similar to that formed by Hoechst 33258 at DNA AT-enriched sites. According to this model, , a bisbenzoxazole ligand, was synthesized. The results of spectrophotometric methods supported the complex formation of the compound under study with DNA differing in the nucleotide composition.

Towards accurate and efficient diagnoses in nephropathology: An AI-based approach for assessing kidney transplant rejection.

The Banff classification is useful for diagnosing renal transplant rejection. However, it has limitations due to subjectivity and varying concordance in physicians' assessments. Artificial intelligence (AI) can help standardize research, increase objectivity and accurately quantify morphological characteristics, improving reproducibility in clinical practice.

The Increase in the Peroxidase Activity of the Cytochrome with Substitutions in the Universal Binding Site Is Associated with Changes in the Ability to Interact with External Ligands.

Cytochrome (CytC), a one-electron carrier, transfers electrons from complex to cytochrome oxidase (CcO) in the electron-transport chain. Electrostatic interaction with the partners, complex and CcO, is ensured by a lysine cluster near the heme forming the Universal Binding Site (UBS). We constructed three mutant variants of mitochondrial CytC with one (2Mut), four (5Mut), and five (8Mut) Lys->Glu substitutions in the UBS and some compensating Glu->Lys substitutions at the periphery of the UBS for charge compensation.

Massively parallel genetic perturbation reveals the energetic architecture of an amyloid beta nucleation reaction.

Amyloid protein aggregates are pathological hallmarks of more than fifty human diseases but how soluble proteins nucleate to form amyloids is poorly understood. Here we use combinatorial mutagenesis, a kinetic selection assay, and machine learning to massively perturb the energetics of the nucleation reaction of amyloid beta (Aβ42), the protein that aggregates in Alzheimer's disease. In total, we quantify the nucleation rates of >140,000 variants of Aβ42.

The fully reduced terminal oxidase bd-I isolated from Escherichia coli binds cyanide.

Cytochrome bd-I from Escherichia coli belongs to the superfamily of prokaryotic bd-type oxygen reductases. It contains three hemes, b, b and d, and couples oxidation of quinol by dioxygen with the generation of a proton-motive force. The enzyme exhibits resistance to various stressors and is considered as a target protein for next-generation antimicrobials.

Fullerene C Conjugate with Folic Acid and Polyvinylpyrrolidone for Targeted Delivery to Tumor Cells.

The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C conjugate (FA-PVP-C) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established.

Dimeric Bis-Benzimidazole-Pyrroles DB2Py(n) - AT-Site-Specific Ligands: Synthesis, Physicochemical Analysis, and Biological Activity.

Its broad spectrum of biological activity makes benzimidazole a fundamental pharmacophore in pharmaceutics. The paper describes newly synthesized AT-specific fluorescent bis-benzimidazole molecules DB2Py(n) that contain a pyrrolcarboxamide fragment of the antibiotic drug netropsin. Physico-chemical methods using absorption, fluorescence, and circular dichroism spectra have shown the ability of bis-benzimidazole- pyrroles to form complexes with DNA.

Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy.

In humans, balanced invasion of trophoblast cells into the uterine mucosa, the decidua, is critical for successful pregnancy. Evidence suggests that this process is regulated by uterine natural killer (uNK) cells, but how they influence reproductive outcomes is unclear. Here, we used our trophoblast organoids and primary tissue samples to determine how uNK cells affect placentation.

Lysozyme binding with amikacin and levofloxacin studied by tritium probe, fluorescence spectroscopy and molecular docking.

Lysozyme complexes with amikacin and levofloxacin were studied by spectroscopy approaches as well as using a tritium probe. Tritium was used as a labeling agent to trace labeled compound concentration in a system of two immiscible liquids and in the atomic form to determine the possible position of the binding site. Co-adsorption of protein and drug at the liquid-liquid interface was analyzed by scintillation phase method that allowed us to directly determine the amount of protein and drug in the mixed adsorption layer.

Empowering Renal Cancer Management with AI and Digital Pathology: Pathology, Diagnostics and Prognosis.

Renal cell carcinoma is a significant health burden worldwide, necessitating accurate and efficient diagnostic methods to guide treatment decisions. Traditional pathology practices have limitations, including interobserver variability and time-consuming evaluations. In recent years, digital pathology tools emerged as a promising solution to enhance the diagnosis and management of renal cancer.

Radiosensitizing Effect of Dextran-Coated Iron Oxide Nanoparticles on Malignant Glioma Cells.

The potential of standard methods of radiation therapy is limited by the dose that can be safely delivered to the tumor, which could be too low for radical treatment. The dose efficiency can be increased by using radiosensitizers. In this study, we evaluated the sensitizing potential of biocompatible iron oxide nanoparticles coated with a dextran shell in A172 and Gl-Tr glioblastoma cells in vitro.

Single-cell multi-omics analysis of COVID-19 patients with pre-existing autoimmune diseases shows aberrant immune responses to infection.

In COVID-19, hyperinflammatory and dysregulated immune responses contribute to severity. Patients with pre-existing autoimmune conditions can therefore be at increased risk of severe COVID-19 and/or associated sequelae, yet SARS-CoV-2 infection in this group has been little studied. Here, we performed single-cell analysis of peripheral blood mononuclear cells from patients with three major autoimmune diseases (rheumatoid arthritis, psoriasis, or multiple sclerosis) during SARS-CoV-2 infection.

Mutant Cytochrome C as a Potential Detector of Superoxide Generation: Effect of Mutations on the Function and Properties.

Cytochrome c (CytC) is a single-electron carrier between complex bc1 and cytochrome c-oxidase (CcO) in the electron transport chain (ETC). It is also known as a good radical scavenger but its participation in electron flow through the ETC makes it impossible to use CytC as a radical sensor. To solve this problem, a series of mutants were constructed with substitutions of Lys residues in the universal binding site (UBS) which interact electrostatically with negatively charged Asp and Glu residues at the binding sites of CytC partners, bc1 complex and CcO.

[DNA Sequence-Specific Ligands. 19. Synthesis, Spectral Properties, Virological and Biochemical Studies of DB3(n) Fluorescent Dimeric Trisbenzimidazoles].

In this work, we synthesized and characterized the properties of a series of new fluorescent DB3(n) narrow-groove ligands. DB3(n) compounds based on dimeric trisbenzimidazoles have the ability to bind to the AT regions of DNA. The synthesis of DB3(n), whose trisbenzimidazole fragments are linked by oligomethylene linkers of different lengths (n = 1, 5, 9), is based on the condensation of the MB3 monomeric trisbenzimidazole with α,ω-alkyldicarboxylic acids.

Effect of the Coat Protein N-Terminal Domain Structure on the Structure and Physicochemical Properties of Virions of Potato Virus X and Alternanthera Mosaic Virus.

The amino acid sequences of the coat proteins (CPs) of the potexviruses potato virus X (PVX) and alternanthera mosaic virus (AltMV) share ~40% identity. The N-terminal domains of these proteins differ in the amino acid sequence and the presence of the N-terminal fragment of 28 residues (ΔN peptide) in the PVX CP. Here, we determined the effect of the N-terminal domain on the structure and physicochemical properties of PVX and AltMV virions.

G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Mismatch Repair Pathway.

The human pathogen uses a homologous recombination to undergo antigenic variation and avoid an immune response. The surface protein pilin (PilE) is one of the targets for antigenic variation that can be regulated by mismatch repair (MMR) and a G-quadruplex (G4) located upstream of the promoter. Using bioinformatics tools, we found a correlation between variability and deletion of DNA regions encoding ngMutS or ngMutL proteins, the main participants in methyl-independent MMR.

Spatial multiomics map of trophoblast development in early pregnancy.

The relationship between the human placenta-the extraembryonic organ made by the fetus, and the decidua-the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia.

Interaction of Amphipathic Peptide from Influenza Virus M1 Protein with Mitochondrial Cytochrome Oxidase.

The Bile Acid Binding Site (BABS) of cytochrome oxidase (CcO) binds numerous amphipathic ligands. To determine which of the BABS-lining residues are critical for interaction, we used the peptide P4 and its derivatives A1-A4. P4 is composed of two flexibly bound modified α-helices from the M1 protein of the influenza virus, each containing a cholesterol-recognizing CRAC motif.

Usnic Acid-Mediated Exchange of Protons for Divalent Metal Cations across Lipid Membranes: Relevance to Mitochondrial Uncoupling.

Usnic acid (UA), a unique lichen metabolite, is a protonophoric uncoupler of oxidative phosphorylation, widely known as a weight-loss dietary supplement. In contrast to conventional proton-shuttling mitochondrial uncouplers, UA was found to carry protons across lipid membranes via the induction of an electrogenic proton exchange for calcium or magnesium cations. Here, we evaluated the ability of various divalent metal cations to stimulate a proton transport through both planar and vesicular bilayer lipid membranes by measuring the transmembrane electrical current and fluorescence-detected pH gradient dissipation in pyranine-loaded liposomes, respectively.

Individual heme a and heme a contributions to the Soret absorption spectrum of the reduced bovine cytochrome c oxidase.

Bovine cytochrome c oxidase (CcO) contains two hemes, a and a, chemically identical but differing in coordination and spin state. The Soret absorption band of reduced aa-type cytochrome c oxidase consists of overlapping bands of the hemes a and a. It shows a peak at ∼444 nm and a distinct shoulder at ∼425 nm.

SERS-based biosensor with Raman-active external responsive element for rapid determination of adenosine monophosphate.

Phosphorylated adenosine derivatives are important biological molecules with diverse biological functions connected with the energetic balance of the cell, biosynthesis of cell components and regulation of protein activity. Measurement of these compounds provides information about the cell signalling in the body as well as the quantity of microorganisms in the environment. Surface-enhanced Raman spectroscopy (SERS) is an optical method that provides a unique spectrum of a substance at low concentrations.

[Safety and efficacy of laparoscopic approach for widespread appendicular peritonitis].

Objective: To analyze treatment outcomes in patients with acute appendicitis complicated by widespread peritonitis.

Material And Methods: The study included 165 patients acute appendicitis complicated by widespread peritonitis. Inclusion criteria: acute appendicitis complicated by widespread peritonitis MIP grade 1-2 in reactive or toxic phase (grading system by Simonyan K.