Role of Fatty Acids β-Oxidation in the Metabolic Interactions Between Organs.

In recent decades, several discoveries have been made that force us to reconsider old ideas about mitochondria and energy metabolism in the light of these discoveries. In this review, we discuss metabolic interaction between various organs, the metabolic significance of the primary substrates and their metabolic pathways, namely aerobic glycolysis, lactate shuttling, and fatty acids β-oxidation. We rely on the new ideas about the supramolecular structure of the mitochondrial respiratory chain (respirasome), the necessity of supporting substrates for fatty acids β-oxidation, and the reverse electron transfer via succinate dehydrogenase during β-oxidation.

Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways.

A hallmark of neurodegenerative diseases (NDs) is the progressive loss of proteostasis, leading to the accumulation of misfolded proteins or protein aggregates, with subsequent cytotoxicity. To combat this toxicity, cells have evolved degradation pathways (ubiquitin-proteasome system and autophagy) that detect and degrade misfolded proteins. However, studying the underlying cellular pathways and mechanisms has remained a challenge, as formation of many types of protein aggregates is asynchronous, with individual cells displaying distinct kinetics, thereby hindering rigorous time-course studies.

Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways.

A hallmark of neurodegenerative diseases is the progressive loss of proteostasis, leading to the accumulation of misfolded proteins or protein aggregates, with subsequent cytotoxicity. To combat this toxicity, cells have evolved degradation pathways (ubiquitin-proteasome system and autophagy) that detect and degrade misfolded proteins. However, studying the underlying cellular pathways and mechanisms has remained a challenge, as formation of many types of protein aggregates is asynchronous, with individual cells displaying distinct kinetics, thereby hindering rigorous time-course studies.

Social Determinants of Hepatitis C Virus Infection in the United States, 2016-2021.

This cross-sectional study assessed hepatitis C virus (HCV) antibody and RNA test results performed from 2016 to 2021 at a large US clinical reference laboratory. When individual patient factors (ie, income, education, and race/ethnicity) were not available, estimates from the US Census were linked to the residential zip code. The final analytic cohort comprised 19,543,908 individuals with 23,233,827 HCV antibody and RNA test results.

Synthesis and Biological Evaluation of a Series of New Hybrid Amide Derivatives of Triazole and Thiazolidine-2,4-dione.

A series of hybrid compounds with triazole and thiazolidine nuclei connected by a linker has been synthesized and extensively studied. Various synthetic methods for the target compounds have been tested. A microbiological assessment of the obtained compounds was carried out on strains of pathogenic fungi , , multidrug-resistant , , spp.

Critical Role of Mitochondrial Fatty Acid Metabolism in Normal Cell Function and Pathological Conditions.

There is a "popular" belief that a fat-free diet is beneficial, supported by the scientific dogma indicating that high levels of fatty acids promote many pathological metabolic, cardiovascular, and neurodegenerative conditions. This dogma pressured scientists not to recognize the essential role of fatty acids in cellular metabolism and focus on the detrimental effects of fatty acids. In this work, we critically review several decades of studies and recent publications supporting the critical role of mitochondrial fatty acid metabolism in cellular homeostasis and many pathological conditions.

Mitochondrial CypD Acetylation Promotes Endothelial Dysfunction and Hypertension.

Background: Nearly half of adults have hypertension, a major risk factor for cardiovascular disease. Mitochondrial hyperacetylation is linked to hypertension, but the role of acetylation of specific proteins is not clear. We hypothesized that acetylation of mitochondrial CypD (cyclophilin D) at K166 contributes to endothelial dysfunction and hypertension.

The Structure of the Cardiac Mitochondria Respirasome Is Adapted for the β-Oxidation of Fatty Acids.

It is well known that in the heart and kidney mitochondria, more than 95% of ATP production is supported by the β-oxidation of long-chain fatty acids. However, the β-oxidation of fatty acids by mitochondria has been studied much less than the substrates formed during the catabolism of carbohydrates and amino acids. In the last few decades, several discoveries have been made that are directly related to fatty acid oxidation.

CONSTITUTIONAL AND LEGAL PRINCIPLES OF THE LIMITS OF PERMISSIBLE INTERVENTION IN CONDUCTING BIOMEDICAL RESEARCH WITH HUMAN PARTICIPATION.

Objective: The aim: To find out the peculiarities of constitutional and legal principles of the limits of permissible intervention in conducting biomedical research with human participation.

Patients And Methods: Materials and methods: The methodological basis of the study was worldview dialectical, general scientific and specific scientific methods of learning the phenomena of state and legal reality. Common ones were widely used in the work principles of scientific knowledge - comprehensiveness, objectivity, historicism, unity of theory and practice and others.

UniProtExtractR: an app and R package for easily extracting protein-specific UniProtKB information and fine-tuning organelle resolution.

Summary: UniProtKB is a publicly accessible database of annotated protein features for numerous organisms; however, globally extracting protein entry information for data visualization and categorization can be challenging. While the UniProtKB entry syntax maintains database consistency, it simultaneously obscures key terms within long character strings. To increase accessibility, UniProtExtractR is both an app and R package that extracts desired information across nine UniProtKB categories: DNA binding, Pathway, Transmembrane, Signal peptide, Protein families, Domain [FT], Motif, Involvement in disease, and Subcellular location [CC].

When to Switch: Planning and Learning for Partially Observable Multi-Agent Pathfinding.

Multi-agent pathfinding (MAPF) is a problem that involves finding a set of non-conflicting paths for a set of agents confined to a graph. In this work, we study a MAPF setting, where the environment is only partially observable for each agent, i.e.

Influence of operation of thermal and fast reactors of the Beloyarsk NPP on the radioecological situation in river ecosystems.

The results of long-term radioecological monitoring of seven rivers in the 15-km zone of influence of the Beloyarsk Nuclear Power Plant have been presented. A comparative analysis of the content of a wide range of natural and artificial radionuclides in the main components of river ecosystems: surface waters, bottom sediments, floodplain soils, macrophytes and ichthyofauna has been made. The influence of waste technological waters of thermal (AMB-100 and AMB-200) and fast (BN-600 and BN-800) reactors of the Beloyarsk NPP on the content of radiologically significant isotopes in the water and bottom sediments of the Pyshma and Olkhovka rivers has been evaluated.

ETHICAL EXPERTISE OF BIOMEDICAL RESEARCH AS A WAY OF HUMAN RIGHTS PROTECTION.

Objective: The aim: To find out the peculiarities of ethical expertise of biomedical research as a way of human rights protection.

Patients And Methods: Materials and methods: The dialectical method of cognition, based on the epistemological possibilities of the laws and categories of dialectics, provided a study of the formation and activity of bodies and institutions responsible for the ethical examination of biomedical research. Formal and logical methods of analysis and synthesis made it possible to reveal the meaning of the concepts that make up the subject of the study, to carry out their classification, as well as to formulate intermediate and general conclusions.

[Cardiovascular effects of omega-3 polyunsaturated fatty acids: position of omega-3 polyunsaturated fatty acids in Russian and international guidelines. Council of Experts].

This Expert Council focuses on the meta-analysis of studies on the risk of atrial fibrillation (AF) in patients taking omega-3 polyunsaturated fatty acids (PUFA) and of data on the omega-3 PUFA treatment in patients with cardiovascular and kidney diseases.The major statements of the Expert Council: the meta-analysis of AF risk in patients taking omega-3 PUFA showed an increased risk of this arrhythmia. However, it should be taken into account that the risk of complications was low, and there was no significant increase in the risk of AF when omega-3 PUFA was used at a dose of ≤1 g and a standard dose of the only omega-3 PUFA drug registered in the Russian Federation, considering all AF episodes in the ASCEND study.

Long-Chain and Medium-Chain Fatty Acids in Energy Metabolism of Murine Kidney Mitochondria.

Scientists have long established that fatty acids are the primary substrates for kidney mitochondria. However, to date we still do not know how long-chain and middle-chain fatty acids are oxidized at the mitochondrial level. Our previous research has shown that mitochondria from the heart, brain, and kidney oxidize palmitoylcarnitine at a high rate only in the presence of succinate, glutamate, or pyruvate.

Pathfinding in stochastic environments: learning planning.

Among the main challenges associated with navigating a mobile robot in complex environments are partial observability and stochasticity. This work proposes a stochastic formulation of the pathfinding problem, assuming that obstacles of arbitrary shapes may appear and disappear at random moments of time. Moreover, we consider the case when the environment is only partially observable for an agent.

Optical Kerr nonlinearity of dielectric nanohole array metasurface in proximity to anapole state.

Metasurfaces have attracted a great deal of attention from researchers due to their prominent optical properties. In particular, metasurfaces may consist of structures possessing optical anapole resonances with strong field confinement and substantially suppressed scattering. As a result, such nanostructures display enhanced nonlinear optical properties.

Antifungal Thiazolidines: Synthesis and Biological Evaluation of Mycosidine Congeners.

Novel derivatives of Mycosidine (3,5-substituted thiazolidine-2,4-diones) are synthesized by Knoevenagel condensation and reactions of thiazolidines with chloroformates or halo-acetic acid esters. Furthermore, 5-Arylidene-2,4-thiazolidinediones and their 2-thioxo analogs containing halogen and hydroxy groups or di(benzyloxy) substituents in 5-benzylidene moiety are tested for antifungal activity in vitro. Some of the synthesized compounds exhibit high antifungal activity, both fungistatic and fungicidal, and lead to morphological changes in the yeast cell wall.

Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria.

We present evidence that metabolic syndrome (MetS) represents the postreproductive stage of the human postembryonic ontogenesis. Accordingly, the genes governing this stage experience relatively weak evolutionary selection pressure, thus representing the metabolic phenotype of distant ancestors with β-oxidation of long-chain fatty acids (FAs) as the primary energy source. Mitochondria oxidize at high-rate FAs only when succinate, glutamate, or pyruvate are present.

Hierarchical intrinsically motivated agent planning behavior with dreaming in grid environments.

Biologically plausible models of learning may provide a crucial insight for building autonomous intelligent agents capable of performing a wide range of tasks. In this work, we propose a hierarchical model of an agent operating in an unfamiliar environment driven by a reinforcement signal. We use temporal memory to learn sparse distributed representation of state-actions and the basal ganglia model to learn effective action policy on different levels of abstraction.

Evaluation of New Antimicrobial Agents Based on (1-Indol-3-yl)methylium Salts: Activity, Toxicity, Suppression of Experimental Sepsis in Mice.

The antimicrobial activity and toxicity of three novel synthetic antibacterial agents containing (1-indol-3-yl)methylium fragment were studied in vitro and in vivo. All compounds in vitro revealed high activity (minimal inhibitory concentration (MIC) 0.13-1.

[Integral tests of the hemostasis system in assessing the efficiency of acetylsalicylic acid in patients with ischemic heart disease].

Despite the fact that acetylsalicylic acid (ASA) is the "gold" standard for the prevention of cardiovascular complications in patients with coronary heart disease (CAD), a number of patients still have risks of atherothrombosis. In the present study, the antithrombotic effect of ASA in patients with CAD was assessed in platelet-rich plasma (PRP) using integral tests of the hemostasis study: the T-TAS system (Total Thrombus-formation Analysis System) and the thrombin generation test (TGT). The study involved 34 patients with stable CAD (11 women, 23 men) and people (15 women, 18 men) in the control group.

[Surgical treatment of mega aorta syndrome: a single-center experience].

Objective: To present our experience in the treatment of severe patients with mega aorta syndrome.

Material And Methods: There were 49 patients with mega aorta syndrome for the period from May 2015 to March 2021. All patients underwent total aortic replacement from sinotubular junction (with staged aortic root repair, if necessary) to abdominal aorta bifurcation.

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

Thousands of interactions assemble proteins into modules that impart spatial and functional organization to the cellular proteome. Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. The first, BioPlex 3.