The flexible chain: regulation of structure and activity of ETC complexes defines rate of ATP synthesis and sites of superoxide generation.

This review highlights current insights into the regulation of the mitochondrial respiratory chain (electron transport chain, ETC) activity. The regulation of ETC properties optimizes ATP synthesis and controls the generation of the superoxide anion radical (O ) which can be converted into other reactive oxygen species (ROS) playing a dual role by initiating signaling cascades or contributing to oxidative stress. We examine how ETC activity is influenced by the structure and conformation of its complexes, their allosteric or post-translational modifications, and their interactions with membrane lipids.

The Role of Micrornas in Mitochondrial Homeostasis and their Involvement in the Pathogenesis of Obesity and Metabolic Syndrome: A Focus on Mitomicrornas.

The maintenance of the functional potential of mitochondria is directly related to epigenetic factors, microRNAs (miRs), and mitomicroRNAs (mitomiRs). An important role in the development of metabolic syndrome (MetS)/obesity is attributed to miRs, which have pro-inflammatory or anti-inflammatory potential and can penetrate the mitochondrial matrix. Deciphering the mechanisms responsible for the transport of miRs into the mitochondria would, we believe, allow us to use the knowledge obtained to build designs for the transport of drugs/mitomiRs into cells/mitochondria with low toxicity.

Physiological Concentrations of Calciprotein Particles Trigger Activation and Pro-Inflammatory Response in Endothelial Cells and Monocytes.

Supraphysiological concentrations of calciprotein particles (CPPs), which are indispensable scavengers of excessive Ca and PO ions in blood, induce pro-inflammatory activation of endothelial cells (ECs) and monocytes. Here, we determined physiological levels of CPPs (10 μg/mL calcium, corresponding to 10% increase in Ca in the serum or medium) and investigated whether the pathological effects of calcium stress depend on the calcium delivery form, such as Ca ions, albumin- or fetuin-centric calciprotein monomers (CPM-A/CPM-F), and albumin- or fetuin-centric CPPs (CPP-A/CPP-F). The treatment with CPP-A or CPP-F upregulated transcription of pro-inflammatory genes (, , , , , , , ) and promoted release of pro-inflammatory cytokines (IL-6, IL-8, MCP-1/CCL2, and MIP-3α/CCL20) and pro- and anti-thrombotic molecules (PAI-1 and uPAR) in human arterial ECs and monocytes, although these results depended on the type of cell and calcium-containing particles.

Determination of SARS-CoV-2 Main Protease (M) Activity Based on Electrooxidation of Tyrosine Residue of a Model Peptide.

The proposed approach for determining catalytic activity of the SARS-CoV-2 main protease (M) is based on registration of the peak area of electrochemical oxidation of tyrosine residue in the model peptide substrate CGGGAVLQSGY immobilized on the surface of a graphite screen-printed electrode (SPE) modified with gold nanoparticles (AuNP). The AuNP were obtained by electrosynthesis. Steady state kinetic parameters of M in the reaction with the model peptide were determined: catalytic constant () was (3.

Mechanisms of Antioxidant Protection of Low-Density Lipoprotein Particles Against Free Radical Oxidation.

It was found out that when the patients with atherosclerosis are orally administered ubiquinone Q (CoQ), oxidation (lipid hydroperoxide content) of the low-density lipoprotein (LDL) particles sharply decreases, which confirms important role of this natural antioxidant in protecting LDL particles from free radical oxidation . Influence of the lipophilic natural antioxidants ubiquinol Q (CoQH) and α-tocopherol (α-TOH) on the kinetic parameters of Cu-induced free radical oxidation of LDL particles was investigated. In this model system, possible synergism of the antioxidant action of CoQH and α-TOH has been shown.

Effect of LRRK2 Inhibition on the Activity of Glucocerebrosidase in Patient-Specific Cells from Patients with Gaucher Disease.

Biallelic mutations in the gene encoding lysosomal enzyme glucocerebrosidase (GCase), lead to the development of the Gaucher disease (GD) and also represent a significant risk factor for the Parkinson's disease (PD). In most cases, mutations in the gene are located outside the region coding for the enzyme active site and cause a decrease in the GCase activity due to the reduction in the efficiency of transport of conformationally altered enzyme to the lysosomes. Drugs used to treat GD (enzyme replacement therapy) cannot cross the blood-brain barrier and, therefore, are not effective in the treatment of neuronal forms of GD or PD associated with mutations in the gene (GBA1-PD).

Role of β- and α-Structures of Membrane Proteins in Plasmalemma Structure Change.

Changes in the structure of plasma membranes affect functions of membranes and cells. Some of these changes could lead to the development of pathologies in an organism, which makes it important to study effects of the changes in the structure of membranes on their functions. It is considered established at present that when stress hormones and androgens interact with plasma membranes, their structure changes.

Colocalization of Neurotransmitters in Hippocampus and Afferent Systems: Possible Functional Role.

In neurophysiology, the transmitter phenotype is considered as an indicator of neuronal identity. It has become known at the end of last century that a nerve cell can produce and use several different molecules to communicate with other neurons. These could be "classical" transmitters: glutamate or gamma-aminobutyric acid (or acetylcholine, serotonin, norepinephrine), as well as secondary messengers, mainly neuropeptides released from the same neurons.

Energy-Dependent Non-Photochemical Quenching: PsbS, LhcSR, and Other Players.

The photosynthetic apparatus of plants is capable of capturing even weak fluxes of light energy. Hence, strong and rapid increase in irradiance should be dangerous for plants. To solve the problems caused by fluctuations of incident radiation (up to excessive), plants have developed a number of protective mechanisms, including non-photochemical quenching (NPQ) of excited chlorophyll states.

A Portrait of Three Mammalian Bicistronic mRNA Transcripts, Derived from the Genes , , and .

Recent advances in functional genomics have allowed identification of thousands of translated short open reading frames (sORFs) in the 5' leaders of mammalian mRNA transcripts. While most sORFs are unlikely to encode functional proteins, a small number have been shown to have evolved as protein-coding genes. As a result, dozens of these sORFs have already been annotated as protein-coding ORFs.

Rethinking the Evolutionary Origin, Function, and Treatment of Cancer.

Despite remarkable progress in basic oncology, practical results remain unsatisfactory. This discrepancy is partly due to the exclusive focus on processes within the cancer cell, which results in a lack of recognition of cancer as a systemic disease. It is evident that a wise balance is needed between two alternative methodological approaches: reductionism, which would break down complex phenomena into smaller units to be studied separately, and holism, which emphasizes the study of complex systems as integrated wholes.

4-Methylumbelliferone, an Inhibitor of Hyaluronan Synthase, Prevents the Development of Oncological, Inflammatory, Degenerative, and Autoimmune Diseases.

Hyaluronic acid (HA) is the main structure-forming polymer of the extracellular matrix. HA metabolism plays an important role in intercellular interaction in healthy organism and in various pathologies. HA is synthesized by hyaluronan synthase (HAS); mammals have three highly homologous isoforms of this enzyme: HAS1, HAS2, and HAS3.

Physical limits of natural computation as the biological constraints of morphogenesis, evolution, and consciousness: On the 100 anniversary of Efim Liberman (1925-2011).

Efim Liberman (1925-2011) introduced in 1972 the idea of natural computation realized internally by living systems. He considered the physical principles employed by living systems as essential constraints that limit the computational process occurring in the course of adaptation, morphogenesis, and neural activity. The most general limits determined by the physical fundamental constants are universal for all nature.

Global epidemiology of acute kidney injury in hospitalised patients with decompensated cirrhosis: the International Club of Ascites GLOBAL AKI prospective, multicentre, cohort study.

Background: Acute kidney injury (AKI) is a serious complication of cirrhosis. A systematic, global characterisation of AKI occurring in patients with cirrhosis is lacking. We therefore aimed to assess global differences in the characteristics, management, and outcomes of AKI in hospitalised patients with cirrhosis.

Vegetation morphology and phytobiology intervene in heavy metal contamination of surface sediments in Yangtze River Estuary.

Accumulation of heavy metals in estuaries can represent potential risks to the aquatic environment and public health. Estuarine coastal vegetation's physical form and biological function have important effects on dynamic processes and migration of pollutants in estuaries. Field observations were conducted at sites SJG and LHK in the Yangtze River Estuary (YRE) from September 2021 to February 2022 and September 2022 to December 2022.

Anagrelide in the management of essential thrombocythemia: a systemic review and meta-analysis.

Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm commonly treated with hydroxyurea, while anagrelide is a second-line option. Although anagrelide has thrombocyte-specific action, its comparative efficacy remains debated. This systematic review and meta-analysis aimed to measure platelet reduction, thromboembolic events, and adverse events.

Nano-chitosan hydrogel alleviates Candida albicans-induced health alterations in Nile tilapia (Oreochromis niloticus): antioxidant response, neuro-behaviors, hepato-renal functions, and histopathological investigation.

Background: Candida albicans infection induces economic losses in aquaculture practices. Currently, the success of the nanotechnology field has gained more consideration in the aquaculture sector as it bestows favorable impacts in remedies in comparison to traditional practices.

Objective: The present study was conducted to assess the role of nano chitosan gel (NCG) exposure via water in managing the deteriorating impacts triggered by C.

Response -- letter to the editor: Unraveling the neural signatures: Distinct pallidal patterns in dystonia subtypes.

We recognize the need for longitudinal measures and mechanistic understanding of the basis for phenotype to single-neuron correlations. We clarify that pallidal neuron differs across dystonia subtypes. We highlight animal studies showing how cerebellar activity can influence pallidal neuron behavior, supporting the idea of cerebellar activity transmission to the pallidum.

Osimertinib long-term tolerability in patients with EGFRm NSCLC enrolled in the AURA program or FLAURA study.

Introduction: This post-hoc analysis of the registrational FLAURA study and AURA program reports long-term safety data in epidermal growth factor receptor-mutated (EGFRm), advanced non-small cell lung cancer (NSCLC) treated with osimertinib for ≥ 36 months.

Methods: Patients from FLAURA who received first-line osimertinib and from the AURA program (AURA, AURA2, AURA3) who received ≥ second-line osimertinib were included. Patients received osimertinib 80 mg once daily.

Tidal dynamics and seasonal hydrological variations influencing organic carbon distribution in the Yangtze River estuary.

The carbon cycle process in coastal areas is extremely complex due to the coupled hydrodynamic interactions between terrestrial and marine systems. To study the spatiotemporal variations of organic carbon and their influencing mechanisms, dissolved and particulate organic carbon (DOC, POC) in water, total organic carbon (TOC) in surface sediments, water quality parameters, and sediment grain size composition were measured in five coastal sites from the Yangtze River estuary (YRE). Generalized linear mixed-effects (GLMM) model was used to identify potential processes that explained these spatiotemporal patterns.

The hidden elephant: Modified abasic sites and their consequences.

Abasic, or apurinic/apyrimidinic sites (AP sites) are among the most abundant DNA lesions, appearing in DNA both through spontaneous base loss and as intermediates of base excision DNA repair. Natural aldehydic AP sites have been known for decades and their interaction with the cellular replication, transcription and repair machinery has been investigated in detail. Oxidized AP sites, produced by free radical attack on intact nucleotides, received much attention recently due to their ability to trap DNA repair enzymes and chromatin structural proteins such as histones.

Analytical and Clinical Validation of Solo-Test Driver: A Targeted Amplicon-Based NGS Test-System for FFPE and cfDNA Analysis in Clinical Oncology Setting.

Background: Next-generation sequencing (NGS) is increasingly integrated into cancer patient management, necessitating cost-effective, reliable tests for companion diagnostics. We present the validation of the Solo-test Driver panel, a custom NGS amplicon-based tool for DNA analysis of 34 oncogenes, addressing key clinical needs.

Methods: The panel's performance was validated for detecting SNVs, CNVs, and MSI.

Advances in Optogenetics and Thermogenetics for Control of Non-Neuronal Cells and Tissues in Biomedical Research.

Optogenetics and chemogenetics are relatively new biomedical technologies that emerged 20 years ago and have been evolving rapidly since then. This has been made possible by the combined use of genetic engineering, optics, and electrophysiology. With the development of optogenetics and thermogenetics, the molecular tools for cellular control are continuously being optimized, studied, and modified, expanding both their applications and their biomedical uses.