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Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) causes a systemic inflammatory response that can worsen patient outcomes. Off-pump surgery has been associated with a reduced inflammatory response. The precise mechanisms and the role of extracellular vesicles (EVs) in this context are not fully understood. This study aimed to investigate the early immune response, including main T- and B-lymphocyte subsets, cytokine profiles, and plasma EVs, in patients undergoing off-pump (n = 18) and on-pump (n = 18) CABG. Thirty-six patients undergoing isolated CABG were enrolled in this randomized control study. Pre- and 24 h postoperative blood samples were analyzed for immune cell populations, cytokine levels, and plasma EV phenotyping. Off-pump CABG triggered a milder immune response than on-pump surgery. On-pump surgery led to greater changes in circulating EVs, particularly platelet- (CD62P+), endothelial- (CD31+), and B-cell-derived (CD19+), as well as platelet- and erythrocyte-derived aggregates (CD41+CD235a+). Levels of platelet-derived EVs, expressing both constitutional and activation markers (CD41+CD62P+) decreased in both groups of patients 24 h after surgery. On-pump cardiac procedures led to an increase in T-regulatory cell-derived EVs (CD73+CD39+), suggesting a potential mechanism for immune suppression compared to off-pump surgery. There were numerous correlations between EV levels and cytokine profiles following on-pump surgery, hinting at a close relationship. Leucocyte-derived EVs exhibited positive correlations with each other and with GRO but showed negative correlations with endothelial-derived EVs (CD90+ and CD31+). Additionally, CD73+ EVs demonstrated positive correlations with platelet counts and with erythrocyte-derived CD235a+ EVs. EV changes were significantly greater after on-pump surgery, highlighting a more pronounced response to this type of surgery and emphasizing the role of EVs as regulators of post-surgical inflammation.

This paper proposes a new model to study carbon emission issues in seven emerging (E7) economies (China, Mexico, Turkey, Russia, Brazil, Indonesia and India). It employs weighted Quantum Spherical fuzzy DEMATEL model with golden cut using 18 years data, which was ranked for carbon emission evaluation via Quantum Spherical fuzzy TOPSIS method. The data includes macroeconomic variables for the period from 2003 to 2020. Paper observes that (i) CO2 emissions from fossil fuels is the most significant factor distressing the carbon emission problem of E7 economies. It suggests that these countries need to explore alternatives to fossil fuels to handle the carbon emission problem. (ii) The CO2 emission problem in energy production can be minimized by renewable energy and nuclear energy, suggesting some financial incentives to the investors in energy explorations areas. (iii) It is also observed that due to high volatility of CO2 emissions, a negative market factor exists in consumer sentiment in consumption of oil and petroleum products. This can be compensated via energy consumption fiscal policy in taxation and encourage of extractive industries and producers of petroleum products, as well as the uneven spatial development to have a significant impact on the reduction of CO2 emission. The paper gives recommendation that E7 countries need to find alternatives to fossil fuels in order to deal effectively with the carbon emission problem.

Abstract Regulating B cell death is essential for generating antibodies and maintaining immune tolerance. B cells can die by apoptosis, and we report that human tonsil B cells, but not peripheral blood B cells also die by NETosis. This cell death is density-dependent, characterized by the loss of cell and nuclear membrane integrity, release of reactive oxygen species, and chromatin decondensation. Tonsil B cells secrete high levels of TNF, and inhibiting TNF prevented chromatin decondensation. By in situ fluorescence microscopy, B cell NETosis, as identified by the hyper citrullination of Histone-3, was localized to the light zone (LZ) of germinal centers in normal tonsil and overlapped with the B cell marker CD19/IgM. We propose a model in which stimulation of B cells in the LZ induces NETosis, driven in part by TNF. We also provide evidence that NETosis of tonsil B cells may be inhibited by an unidentified factor in tonsil. The results describe a previously unidentified form of B cell death and suggest a new mechanism to maintain B cell homeostasis during immune responses.

There are many articles on the quantitative analysis of miRNAs contained in a population of EVs of different sizes under various physiological and pathological conditions. For such analysis, it is important to correctly quantify the miRNA contents of EVs. It should be considered that quantification is skewed depending on the isolation protocol, and different miRNAs are degraded by nucleases with different efficiencies. In addition, it is important to consider the contribution of miRNAs coprecipitating with the EVs population, because the amount of miRNAs in the EVs population under study is skewed without appropriate enzymatic treatment. By studying a population of EVs from the blood plasma of healthy donors, we found that the absolute amount of miRNA inside the vesicles is commensurate with the amount of the same type of miRNA adhered to the outside of the EVs. The inside/outside ratio ranged from 1.02 to 2.64 for different investigated miRNAs. According to our results, we propose the hypothesis that high occupancy of miRNAs on the outer surface of EVs influence on the transporting RNA repertoire no less than the inner cargo received from the host cell.

Currently, multiple studies have indicated that CD8+ T lymphocytes play a role in causing damage to the exocrine glands through acinar injury in primary Sjögren’s syndrome (pSS). The aim of this research was to assess the imbalance of circulating CD8+ T cell subsets. We analyzed blood samples from 34 pSS patients and 34 healthy individuals as controls. We used flow cytometry to enumerate CD8+ T cell maturation stages, using as markers CD62L, CD28, CD27, CD4, CD8, CD3, CD45RA and CD45. For immunophenotyping of ‘polarized’ CD8+ T cell subsets, we used the following monoclonal antibodies: CXCR5, CCR6, CXCR3 and CCR4. The findings revealed that both the relative and absolute numbers of ‘naïve’ CD8+ T cells were higher in pSS patients compared to the healthy volunteers. Conversely, the proportions of effector memory CD8+ T cells were notably lower. Furthermore, our data suggested that among patients with pSS, the levels of cytotoxic Tc1 CD8+ T cells were reduced, while the frequencies of regulatory cytokine-producing Tc2 and Tc17 CD8+ T cells were significantly elevated. Simultaneously, the Tc1 cell subsets displayed a negative correlation with immunoglobulin G, rheumatoid factor, the Schirmer test and unstimulated saliva flow. On the other hand, the Tc2 cell subsets exhibited a positive correlation with these parameters. In summary, our study indicated that immune dysfunction within CD8+ T cells, including alterations in Tc1 cells, plays a significant role in the development of pSS.

Background: it has been suggested that chronic low-grade inflammation plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). According to previous studies, it remains unclear which cytokines influence the development of this syndrome and whether their increase is associated with the presence of excess weight/obesity or is an independent factor. The aim of our research was to determine the parameters of chronic inflammation in women with PCOS in comparison with healthy women in the normal weight and the overweight subgroups. Methods: This case-control study included 44 patients with PCOS (19 women with a body mass index (BMI) < 25 kg/m² and 25 women with a BMI ≥ 25 kg/m²) and 45 women without symptoms of PCOS (22 women with a BMI < 25 kg/m² and 23 women with a BMI ≥ 25 kg/m²). Thirty-two cytokines were analyzed in the plasma of the participants using Immunology multiplex assay HCYTA-60K-PX48 (Merck Life Science, LLC, Germany). Results: Cytokines: interleukin-1 receptor antagonist (IL-1 RA), IL-2, IL-6, IL-17 E, IL-17 A, IL-18, and macrophage inflammatory protein-1 alpha (MIP-1 α) were increased in women with PCOS compared to controls, both in lean and overweight/obese subgroups (p < 0.05). Moreover, only lean women with PCOS had higher levels of IL-1 alpha, IL-4, IL-9, IL-12, IL-13, IL-15, tumor necrosis factor (TNF- α) alpha and beta, soluble CD40 and its ligand (SCD40L), fractalkine (FKN), monocyte-chemotactic protein 3 (MCP-3), and MIP-1 β compared to the control group (p < 0.05). IL-22 was increased in the combined group of women with PCOS (lean and overweight/obese) compared to the control group (p = 0.012). Conclusion: Chronic low-grade inflammation is an independent factor affecting the occurrence of PCOS and does not depend on the presence of excess weight/obesity. For the first time, we obtained data on the increase in such inflammatory parameters as IL-9, MCP-3, and MIP-1α in women with PCOS.

This review is dedicated to the analytical literature concerning the dynamics of different approaches to renewable energy promotion. Examples of major types of green energy incentives, including carbon tax, Feed-in Tariffs, and investments in research and development are covered in the paper, as well as the barriers and limitations to such practices and the contradictions existing in the field of renewable energy. The dynamics of the means of green energy promotion over this period have been addressed. This review analyzes energy considerations and the importance of raising public awareness on the issue. The evidence collected through the literature analysis, has proven that despite of a significant amount of work done in the field in the transition to the renewable energy sources, including the implementation of various incentives, controversial aspects remain that demand attention both from economists and policymakers. Modern best practices in the field of green energy incentives can be based on government initiatives or stem from the private sector. The most widely used policies for renewable energy promotion discussed in the reviewed studies are tax incentives; however, at the same time, numerous countries are providing fossil fuels subsidies to minimize the level of inequality. Finally, the outlook of different practices concerning financing of the transition from traditional energy sources to renewable ones is presented.

The physical and mechanical parameters of berries and the morphometric features of the structure of the bush growth habit are important criteria in predicting the use of berry harvesting equipment. In this research, six red currant cultivars have been studied. The berry separation force, the crushing force, and the strength of attachment of the berries to the stalk were assigned to the physical and mechanical parameters and were determined using the "PLODTEST-1" and "Dina-2" devices (Russia). For the optimal operation of the berry harvester, the crushing force of the berries must be more than 2 N, the berry separation force must be in the range of 0.5-1.5 N. A high correlation between the separation and crushing forces was determined (R = 0.71). During the period of technical maturity, the strength of the attachment of the berries in the raceme was more than 0.5 N and, by the end of maturation, this indicator decreased. Most of the studied cultivars have a compact, optimal bush volume. The red currant cultivars Niva, Asya and Vika are promising for mechanised harvesting.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in humans more than two years ago and caused an unprecedented socio-economic burden on all countries around the world. Since then, numerous studies have attempted to identify various mechanisms involved in the alterations of innate and adaptive immunity in COVID-19 patients, with the ultimate goal of finding ways to correct pathological changes and improve disease outcomes. State-of-the-art research methods made it possible to establish precise molecular mechanisms which the new virus uses to trigger multisystem inflammatory syndrome and evade host antiviral immune responses. In this review, we present a comprehensive analysis of published data that provide insight into pathological changes in T and B cell subsets and their phenotypes, accompanying the acute phase of the SARS-CoV-2 infection. This knowledge might help reveal new biomarkers that can be utilized to recognize case severity early as well as to provide additional objective information on the effective formation of SARS-CoV-2-specific immunity and predict long-term complications of COVID-19, including a large variety of symptoms termed the ‘post-COVID-19 syndrome’.

The pipeline of antibiotics has been for decades on an alarmingly low level. Considering the steadily emerging antibiotic resistance, novel tools are needed for early and easy identification of effective anti-infective compounds. In Gram-negative bacteria, the uptake of anti-infectives is especially limited. We here present a surprisingly simple in vitro model of the Gram-negative bacterial envelope, based on 20% (w/v) potato starch gel, printed on polycarbonate 96-well filter membranes. Rapid permeability measurements across this polysaccharide hydrogel allowed to correctly predict either high or low accumulation for all 16 tested anti-infectives in living Escherichia coli. Freeze-fracture TEM supports that the macromolecular network structure of the starch hydrogel may represent a useful surrogate of the Gram-negative bacterial envelope. A random forest analysis of in vitro data revealed molecular mass, minimum projection area, and rigidity as the most critical physicochemical parameters for hydrogel permeability, in agreement with reported structural features needed for uptake into Gram-negative bacteria. Correlating our dataset of 27 antibiotics from different structural classes to reported MIC values of nine clinically relevant pathogens allowed to distinguish active from nonactive compounds based on their low in vitro permeability specifically for Gram-negatives. The model may help to identify poorly permeable antimicrobial candidates before testing them on living bacteria.

Consumption of probiotics for health purposes has increased vastly in the past few decades, and yet the scientific evidence to support health benefits from probiotics is only beginning to emerge. As more probiotics are studied, we are beginning to understand the mechanisms of action by which they benefit human health, as well as to identify the bacterial molecules responsible for these benefits. A new era of therapeutics is on the horizon in which purified molecules from probiotics will be used to prevent and treat diseases. In this review, we summarize the active molecules from probiotic bacteria that have been shown to affect innate and adaptive immunity and have health benefits in experimental settings. We focus particularly on the cellular and molecular mechanisms of the probiotic Bacillus subtilis and its active molecule, exopolysaccharide (ESPBs).

Background: The immunological changes associated with COVID-19 are largely unknown. Methods: Patients with COVID-19 showing moderate (n = 18; SpO2 > 93%, respiratory rate > 22 per minute, CRP > 10 mg/L) and severe (n = 23; SpO2 < 93%, respiratory rate >30 per minute, PaO2/FiO2 ≤ 300 mmHg, permanent oxygen therapy, qSOFA > 2) infection, and 37 healthy donors (HD) were enrolled. Circulating T- and B-cell subsets were analyzed by flow cytometry. Results: CD4+Th cells were skewed toward Th2-like phenotypes within CD45RA+CD62L− (CM) and CD45RA–CD62L− (EM) cells in patients with severe COVID-19, while CM CCR6+ Th17-like cells were decreased if compared with HD. Within CM Th17-like cells “classical” Th17-like cells were increased and Th17.1-like cells were decreased in severe COVID-19 cases. Circulating CM follicular Th-like (Tfh) cells were decreased in all COVID-19 patients, and Tfh17-like cells represented the most predominant subset in severe COVID-19 cases. Both groups of patients showed increased levels of IgD-CD38++ B cells, while the levels of IgD+CD38− and IgD–CD38− were decreased. The frequency of IgD+CD27+ and IgD–CD27+ B cells was significantly reduced in severe COVID-19 cases. Conclusions: We showed an imbalance within almost all circulating memory Th subsets during acute COVID-19 and showed that altered Tfh polarization led to a dysregulated humoral immune response.

This paper investigates the effects of digital production and information technologies on the development of logistic systems of different kinds: megalogistic, macrologistic, and micrologistic. The notions of a logistic system and types of logistic systems imply that logistics is considered in its broad sense as a modern methodology for managing all types of flows that appear in the process of socioeconomic activities of society and business: material, information, energy, financial and labor flows. The methodology discussed in this paper gives the answer to the question of what impact digital production and information technologies have on the development of various types of logistic systems. The methodology includes building a mathematical model in which the endogenous variables of the model reflect the resulting variables of the logistic system, while the exogenous variables reflect digital production and information technologies. The mathematical model is a system of interdependent dynamic econometric equations. Each equation is an autoregressive distributed lags model. In the model, the current values of an endogenous variable depend on their previous values, as well as on the current and previous values of other endogenous and exogenous variables. The novelty of the research is in the developed methodology for a comprehensive assessment of the impact made by digitalization on a totality of the interrelated and interdependent resulting indicators of the logistic system. A comprehensive assessment of the impact made by digitalization on a totality of interrelated and interdependent indicators of the logistic system is understood as a change in the indicators of the logistic system due to the effect of digitalization. The proposed methodology for a comprehensive assessment was empirically tested for Salesforce company.

New investigation results point to the potential participation of extracellular vesicles (EVs) in the pathogenesis of coronavirus infection, its progression, and mechanisms of the therapy effectiveness. This dictates the necessity to transfer scientific testing technologies to medical practice. Here, we demonstrated the method of phenotyping and quantitative analysis of plasma EVs based on differential centrifugation, immunostaining, and high-sensitivity multicolor flow cytometry. We used EV markers that were potentially associated with SARS-CoV-2 dissemination via vesicles and cell-origination markers, characterizing objects from different cell types that could influence clinical manifestation of COVID-19. Plasma levels of CD235a+ and CD14+ EVs in patients with moderate infection were significantly increased while CD8+ and CD19+ EVs were decreased comparing with HD. Patients with severe infection had lower levels of CD4+, CD19+, and CD146+ EVs than HD. These findings demonstrate that EV concentrations in COVID-19 are severity related. Moreover, the three-point dynamic assessment demonstrated significant loss of CD63+ and CD147+ plasma EVs. The used method can be a convenient tool for vital infection pathogenesis investigation and for COVID-19 diagnostics.

The methodology and basic elements of the business process of one-stage economic assessment of organizational projects for personnel management at Russian enterprises are presented. The aim of the study is to analyze and develop clear criteria for assessing the effectiveness of projects and improving personnel management systems for enterprises of different industries and types of activities. The economic and financial assessment of projects aimed at the development of personnel management systems is based on the general methodology for the commercial assessment of projects, which is presented in the so-called United Nations Industrial Development Organization (UNIDO) methodology. The article proposes the resulting model “maximum costs of the HRM”. The features of the proposed methodology are based on the assumption of future digitalization and are associated with the need for a preliminary calculation of the maximum possible project costs, localization of the projects under consideration at existing enterprises, and the mandatory separation of project goals for increasing sales or reducing the number of personnel. In accordance with the different objectives of the projects, a certain order and special indicators of decision-making are proposed. Companies with a different structure of costs could be assessed via the proposed model and the results presented in the article. The model allows us to create an information base for reasonable decision-making on HR management (HRM) projects and future digitalization of settlements.

B cells are unique antigen-presenting cells because their antigen presentation machinery is closely tied to the B cell receptor. Autoreactive thymic B cells can efficiently present cognate self-antigens to mediate CD4+ T cell-negative selection. However, the nature of thymocyte-thymic B cell interaction and how this interaction affects the selection of thymic B cell repertoire and, in turn, the T cell repertoire are not well understood. Here we demonstrate that a large percentage of thymic B cells have undergone class switching intrathymically. Thymic B cell class switching requires cognate interaction with specific T cells. Class-switched thymic B cells have a distinct repertoire compared with unswitched thymic B cells or splenic B cells. Particularly, autoreactive B cell specificities preferentially expand in the thymus by undergoing class switching, and these enriched, class-switched autoreactive thymic B cells play an important role in CD4 T cell tolerance.

This article suggests a mathematical justification of the possibility of transition to progressive taxation on personal incomes, allowing socially redistribute the tax burden between different groups without losing the total amount of tax yield to the state budget from personal income tax. The methods of the transition from a flat to a progressive tax scale of income taxation developed. A generalized mathematical model of transition to progressive taxation, which allows evaluating all possible options for the proposed reform of flat rate transformation, is suggested. An algorithm of modeling progressive income taxation is proposed, which takes into account the likelihood of tax evasion. In the following parts of the article a probabilistic model of progressive income taxation and a mechanism to optimize the level of tax rates is formed. A linear progressive tax scale with and without tax evasion are developed based on actual statistics.

This paper examines a new approach to defining the task of personnel management in the digital age, taking into account the fundamental changes in internal communications stemming from an increasing use of digital platforms such as intranet, blogs, bulletin boards, instant messaging, and social networking sites. Personnel social media presence plays internal communication roles and thus relates to technologies of social profile analysis regarding employee interaction within the digital economy. The research aims at examining the task of personnel management based on data deriving from social media, for instance social networking sites and other social media tools, with the development of a relevant model for personnel management assessment. It could be shown that communication becomes one of the important aspects of personnel management, which consists of, i.e., human resources planning, recruitment, onboarding, assessment of individual work effects, as well as staff training, rewarding and motivating employees. Effective communication is a prerequisite for carrying out the above-mentioned tasks and performing work effectively. This means that the digital management of personnel can be viewed as a complex task, assuming that organizations operate less by using any formal connections and more by instilling in employees such feelings as feeling inspired, technologically advanced, and proud (on the basis of social media analytics). This paper presents theoretical foundations for developing a model for personnel management with consideration of the distinct employee features based on social media data and included in the assessment process. This allows the same approaches to be used for future research and modeling for assessing team effectiveness. In this paper, a methodological and instrumental solution to the current problem of creating the most effective work team in a digital ecosystem is proposed. The tools proposed to make it possible to create the most potentially effective work team based on the automated processing of natural information contained online on social profiles of potential members of the work team. At the same time, the level of communication compatibility acts as the criterion for the potential effectiveness of the work team. This is an innovative solution for the existing method of managing personnel.

The biological role of the protein encoded by the alternative open reading frame (core+1/ARF) of the Hepatitis C virus (HCV) genome remains elusive, as does the significance of the production of corresponding antibodies in HCV infection. We investigated the prevalence of anti-core and anti-core+1/ARFP antibodies in HCV-positive blood donors from Cambodia, using peptide and recombinant protein-based ELISAs. We detected unusual serological profiles in 3 out of 58 HCV positive plasma of genotype 1a. These patients were negative for anti-core antibodies by commercial and peptide-based assays using C-terminal fragments of core but reacted by Western Blot with full-length core protein. All three patients had high levels of anti-core+1/ARFP antibodies. Cloning of the cDNA that corresponds to the core-coding region from these sera resulted in the expression of both core and core+1/ARFP in mammalian cells. The core protein exhibited high amino-acid homology with a consensus HCV1a sequence. However, 10 identical synonymous mutations were found, and 7 were located in the aa(99-124) region of core. All mutations concerned the third base of a codon, and 5/10 represented a T>C mutation. Prediction analyses of the RNA secondary structure revealed conformational changes within the stem-loop region that contains the core+1/ARFP internal AUG initiator at position 85/87. Using the luciferase tagging approach, we showed that core+1/ARFP expression is more efficient from such a sequence than from the prototype HCV1a RNA. We provide additional evidence of the existence of core+1/ARFP in vivo and new data concerning expression of HCV core protein. We show that HCV patients who do not produce normal anti-core antibodies have unusually high levels of anti-core+1/ARFP and harbour several identical synonymous mutations in the core and core+1/ARFP coding region that result in major changes in predicted RNA structure. Such HCV variants may favour core+1/ARFP production during HCV infection.