Search

Background: Eosinophils are key therapeutic targets in severe asthma that are suppressed by IL5 (mepolizumab) and IL5 receptor (benralizumab) blockade. The effect of IL5 pathway biologics on recently described homeostatic (hEOs) and inflammatory (iEOs) eosinophil subsets is unknown. We aimed to determine the relative impact of mepolizumab and benralizumab treatment on eosinophil subset and phenotype, and explore clinical associations of eosinophil subsets with severe asthma characteristics and treatment response. Methods: We performed a cross‐sectional observational study of severe asthma (eosinophilic n = 32, non‐eosinophilic n = 23, mepolizumab‐treated n = 25), with longitudinal follow‐up of 30 eosinophilic participants at two timepoints (4–24 weeks, >24 weeks) post‐commencement of mepolizumab (n = 20) or benralizumab (n = 10). Blood hEOs and iEOs were measured by flow cytometry assessment of surface CD62L protein. Results: iEO proportion was significantly lower in mepolizumab‐treated participants in both the cross‐sectional and longitudinal study. Mepolizumab and benralizumab depleted iEOs to a similar extent, however a significantly greater number of hEOs remained in mepolizumab participants at follow‐up. Greater iEO proportion correlated with poorer asthma control in eosinophilic but not non‐eosinophilic asthma. Higher residual iEO proportion correlated with poorer asthma control in mepolizumab‐treated individuals. Reduced blood eosinophil viability was observed in around half of mepolizumab‐treated participants, which was associated with significantly better asthma control and spirometry. Conclusions: Mepolizumab depletes iEOs and reduces circulating eosinophil viability in severe asthma but preserves a residual population of circulatory hEOs. In contrast benralizumab depleted both iEOs and hEOs. Higher iEO abundance and eosinophil viability are associated with poorer clinical outcomes following mepolizumab‐treatment. Monitoring circulating eosinophil phenotype and viability may be useful to predict biologic treatment response in severe asthma. [ABSTRACT FROM AUTHOR]

How T-cell receptor (TCR) characteristics determine subset commitment during T-cell development is still unclear. Here, we addressed this question for innate-like T cells, mucosal-associated invariant T (MAIT) cells, and invariant natural killer T (iNKT) cells. MAIT and iNKT cells have similar developmental paths, leading in mice to two effector subsets, cytotoxic (MAIT1/iNKT1) and IL17-secreting (MAIT17/iNKT17). For iNKT1 vs iNKT17 fate choice, an instructive role for TCR affinity was proposed but recent data argue against this model. Herein, we examined TCR role in MAIT and iNKT subset commitment through scRNAseq and TCR repertoire analysis. In our dataset of thymic MAIT cells, we found pairs of T-cell clones with identical amino acid TCR sequences originating from distinct precursors, one of which committed to MAIT1 and the other to MAIT17 fates. Quantitative in silico simulations indicated that the number of such cases is best explained by lineage choice being independent of TCR characteristics. Comparison of TCR features of MAIT1 and MAIT17 clonotypes demonstrated that the subsets cannot be distinguished based on TCR sequence. To pinpoint the developmental stage associated with MAIT sublineage choice, we demonstrated that proliferation takes place both before and after MAIT fate commitment. Altogether, we propose a model of MAIT cell development in which noncommitted, intermediate-stage MAIT cells undergo a first round of proliferation, followed by TCR characteristics-independent commitment to MAIT1 or MAIT17 lineage, followed by an additional round of proliferation. Reanalyzing a published iNKT TCR dataset, we showed that this model is also relevant for iNKT cell development. [ABSTRACT FROM AUTHOR]

Accurate dosimetric calculations are essential to enhance therapeutic efficacy in Yttrium-90 (Y-90) microsphere therapy, which rely significantly on the three-dimensional imaging parameters used. This study aims to evaluate the reconstruction parameters used to generate three-dimensional images from SPECT data obtained for dosimetric calculations, and to determine the optimal reconstruction parameters. This retrospective study evaluated Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) images of 30 patients (8 women and 22 men) who underwent Transarterial Radioembolization (TARE) treatment at our clinic between 2018 and 2019 using Technetium 99mTc-labeled macroaggregated albumin (99mTc-MAA). The SPECT images were reconstructed using 20 different iterations and subset values. The perfused areas were identified using 5% and 10% threshold values. At the 5% threshold, the maximum difference from the average was 20.7% at 2 iterations and 2 subsets. For other parameters, the difference from the average was less than 2.8%. At the 10% threshold, the maximum difference from the average was 14.8% at 2 iterations and 2 subsets, with other parameters again showing a difference of less than 2.8%. For effective TARE treatment, it is recommended to set the SPECT image reconstruction parameters to higher than 5 iterations and 5 subsets following the administration of 99mTc-MAA. [ABSTRACT FROM AUTHOR]

This 14‐color, 13‐antibody optimized multicolor immunofluorescence panel (OMIP) was designed for deep profiling of neutrophil subsets in various types of human samples to contextualize neutrophil plasticity in a range of healthy and diseased states. Markers present in the OMIP allow the profiling of neutrophil subsets associated with ontogeny, migration, phagocytosis capacity, granule release, and immune modulation. For panel design, we ensured that the commonly available fluorophores FITC/AF488, PE, and APC were assigned to the intracellular subset marker Olfactomedin 4, the maturity and activation marker CD10, and whole blood subset marker CD177, respectively. These markers can be easily replaced without affecting the core identification of neutrophils, enabling antibodies to new neutrophil antigens of interest or for fluorescent substrates to assess different neutrophil functions to be easily explored. Panel optimization was performed on whole blood and purified neutrophils. We demonstrate applications on clinical samples (whole blood and saliva) and experimental endpoints (purified neutrophils stimulated through an in vitro transmigration assay). We hope that providing a uniform platform to analyze neutrophil plasticity in various sample types will facilitate the future understanding of neutrophil subsets in health and disease. [ABSTRACT FROM AUTHOR]

Abstract Due to the increase in bacterial resistance, improving the anti-infectious immunity of the host is rapidly becoming a new strategy for the prevention and treatment of bacterial pneumonia. However, the specific lung immune responses and key immune cell subsets involved in bacterial infection are obscure. Actinobacillus pleuropneumoniae (APP) can cause porcine pleuropneumonia, a highly contagious respiratory disease that has caused severe economic losses in the swine industry. Here, using high-dimensional mass cytometry, the major immune cell repertoire in the lungs of mice with APP infection was profiled. Various phenotypically distinct neutrophil subsets and Ly-6C+ inflammatory monocytes/macrophages accumulated post-infection. Moreover, a linear differentiation trajectory from inactivated to activated to apoptotic neutrophils corresponded with the stages of uninfected, onset, and recovery of APP infection. CD14+ neutrophils, which mainly increased in number during the recovery stage of infection, were revealed to have a stronger ability to produce cytokines, especially IL-10 and IL-21, than their CD14− counterparts. Importantly, MHC-II+ neutrophils with antigen-presenting cell features were identified, and their numbers increased in the lung after APP infection. Similar results were further confirmed in the lungs of piglets infected with APP and Klebsiella pneumoniae infection by using a single-cell RNA-seq technique. Additionally, a correlation analysis between cluster composition and the infection process yielded a dynamic and temporally associated immune landscape where key immune clusters, including previously unrecognized ones, marked various stages of infection. Thus, these results reveal the characteristics of key neutrophil clusters and provide a detailed understanding of the immune response to bacterial pneumonia.

IntroductionEuropean Nursing care Pathways (ENP) is a professional care language that utilizes software to map care processes and utilize the data for research purposes, process control, and personnel requirement calculations. However, there is a lack of internationally developed terminology systems and subset specifically designed for the nutritional management of CKD. The aim of this study was to create a subset of the standardized nursing terminology for nutrition management in patients with chronic kidney disease (CKD).Materials and methodsAccording to the guidelines for subset development, four research steps were carried out: (i) Translation of version 3.2 of the ENP (chapter on kidney diseases) and understanding of the framework structure and coding rules of the ENP; (ii) Identification of relevant six-dimensional nursing terms; (iii) Creation of a framework for the subset; (iv) Review and validation by experts.ResultsA subset for CKD nutritional care was created as part of this project, comprising 630 terms, with 17 causal relationships related to nursing diagnoses, 115 symptoms, 31 causes, 34 goals/outcomes, 420 intervention specifications and 13 resources, including newly developed care terms. All terms within the subset have been created using a six-step maintenance procedure and a clinical standard pathway for nutrition management in the SAPIM mode.Implications for nursing practiceThis terminology subset can facilitate standardized care reports in CKD nutrition management, which is used to standardize nursing practice, quantify nursing, services, guidance on care decisions, promoting the exchange and use of CKD nutrition data and serve as a reference for the creation of standardized subset of nursing terminology in China.

Since 2016, it has been possible to record and collect GNSS (Global Navigation Satellite System) raw data on Android devices. This has been a game changer in low-cost device applications. Researchers in the GNSS field have tried to answer new questions regarding Android device positioning performance, the quality of their measurements, positioning techniques that could be applied, and methods to increase the accuracy and the reliability of the PNT (Position Navigation Timing) solution. Several research groups have demonstrated accurate positioning using smartphones while also showing the potential limitations of such devices. In particular, problems related to the GNSS antenna performance have been reported; indeed, in urban scenarios, where users typically operate, the presence of multiple outliers could make the navigation solution inaccurate, if not unfeasible. Hence, techniques useful for verifying the reliability of the navigation solutions have become fundamental. The reliability of the PNT solution provided by smartphones is an open research question. In this study, traditional RAIM (Receiver Autonomous Integrity Monitoring) algorithms were adapted to the case of smartphones. Navigation solution algorithms, including FDE (Fault Detection and Exclusion), were tested using a long data collection made by a smartphone located in a harsh environment in static mode. The performance of the proposed approaches was assessed in terms of horizontal and vertical errors, solution reliability, and residual distribution. [ABSTRACT FROM AUTHOR]

Due to the increase in bacterial resistance, improving the anti-infectious immunity of the host is rapidly becoming a new strategy for the prevention and treatment of bacterial pneumonia. However, the specific lung immune responses and key immune cell subsets involved in bacterial infection are obscure. Actinobacillus pleuropneumoniae (APP) can cause porcine pleuropneumonia, a highly contagious respiratory disease that has caused severe economic losses in the swine industry. Here, using high-dimensional mass cytometry, the major immune cell repertoire in the lungs of mice with APP infection was profiled. Various phenotypically distinct neutrophil subsets and Ly-6C+ inflammatory monocytes/macrophages accumulated post-infection. Moreover, a linear differentiation trajectory from inactivated to activated to apoptotic neutrophils corresponded with the stages of uninfected, onset, and recovery of APP infection. CD14+ neutrophils, which mainly increased in number during the recovery stage of infection, were revealed to have a stronger ability to produce cytokines, especially IL-10 and IL-21, than their CD14− counterparts. Importantly, MHC-II+ neutrophils with antigen-presenting cell features were identified, and their numbers increased in the lung after APP infection. Similar results were further confirmed in the lungs of piglets infected with APP and Klebsiella pneumoniae infection by using a single-cell RNA-seq technique. Additionally, a correlation analysis between cluster composition and the infection process yielded a dynamic and temporally associated immune landscape where key immune clusters, including previously unrecognized ones, marked various stages of infection. Thus, these results reveal the characteristics of key neutrophil clusters and provide a detailed understanding of the immune response to bacterial pneumonia. [ABSTRACT FROM AUTHOR]

The paper provides comparative analysis of the seme stocks denoting good in modern English and French. The formalized analysis of lexical semantics integrating both mathematical and purely linguistic methods has been employed to conduct the research. The study shows that each word in question is internally structured and presents an organized hierarchy of lexical meanings. The seme stocks of the nouns denoting good in English and French present hierarchical systems, subdivided into subsets of polyfunctional, semes with the average degree of functionality, and monofunctional. The comparison of the seme stocks under study has shown that they differ in quantitative characteristics more than qualitative ones. The views on good are partially concurrent in the English and French language world pictures. Both cultures associate it with a good-doer, his/her inner world, social rank, acts of favour, courteous attitude to others, spiritual and material values that promote the highest happiness. The distinctive features reveal the socio-pragmatic character of the concept in English and socially conditioned - in French. [ABSTRACT FROM AUTHOR]

Objectives Damage accrual in SSc can be tracked using the Scleroderma Clinical Trials Consortium Damage Index (DI). Our goal was to develop a prediction model for damage accrual in SSc patients with early disease. Methods Using patients with <2 years disease duration from Canada and Australia as a derivation cohort, and from the Netherlands as a validation cohort, we used group-based trajectory modelling (GBTM) to determine 'good' and 'bad' latent damage trajectories. We developed a prediction model from this analysis and applied it to patients from derivation and validation cohorts. We plotted the actual DI trajectories of the patients predicted to be in 'good' or 'bad' groups. Results We found that the actual trajectories of damage accumulation for lcSSc and dcSSc were very different, so we studied each subset separately. GBTM found two distinct trajectories in lcSSc and three in dcSSc. We collapsed the two worse trajectories in the dcSSc into one group and developed a prediction model for inclusion in either 'good' or 'bad' trajectories. The performance of models using only baseline DI and sex was excellent with ROC AUC of 0.9313 for lcSSc and 0.9027 for dcSSc. Using this model, we determined whether patients would fall into 'good' or 'bad' trajectory groups and then plotted their actual trajectories which showed clear differences between the predicted 'good' and 'bad' cases in both derivation and validation cohorts. Conclusions A simple model using only cutaneous subset, baseline DI and sex can predict damage accumulation in early SSc. [ABSTRACT FROM AUTHOR]

Constructing permutation polynomials is a hot topic in finite fields, and permutation polynomials have many applications in different areas. Recently, several classes of permutation trinomials with index q + 1 over F q 2 were constructed. In this paper, we mainly construct permutation trinomials with index q + 1 over F q 2 . By using monomials of μ (q + 1) / 2 and - μ (q + 1) / 2 to study the permutational property of x r h (x) q - 1 on μ q + 1 , we characterize many kinds of permutation trinomials of the form x r h (x q - 1) over F q 2 . Furthermore, by using a similar method, we show several classes of permutation trinomials with index q + 1 over F 2 2 k with k being odd. [ABSTRACT FROM AUTHOR]

The relative risk and odds ratio are widely used in many fields, including biomedical research, to compare two treatments. Extensive research has been done to infer the two parameters through approximate or exact confidence intervals. However, these intervals may be liberal or conservative. A natural question is whether the intervals can be further improved in maintaining the correct confidence coefficient of an approximate interval or shortening an exact but conservative interval. In this article, when two independent binomials are observed we offer an effort to improve any of the existing intervals by applying the h$$ h $$‐function method. In particular, if the given interval is approximate, then the improved interval is exact; if the given interval is exact, then the improved interval is a subset of the given interval. This method is also applied multiple times to the improved intervals until the final resultant interval cannot be shortened any further. To demonstrate the effectiveness of the method, we use three real datasets to illustrate in detail how several good intervals in practice are improved. Two exact intervals are then recommended for estimating each of the two parameters in different scenarios. [ABSTRACT FROM AUTHOR]

Sesbania sesban (L.) Merr. is a multipurpose legume tree grown primarily for fodder and forage in the tropical and subtropical world. In this study, the Sesbania sesban collection maintained in the International Livestock Research Institute (ILRI) forage Genebank was studied using genome-wide markers generated on the DArTseq platform. Genotyping produced 84,673 and 60,626 SNP and SilicoDArT markers with a mean polymorphic information content of 0.153 and 0.123, respectively. From the generated markers, 7587 and 15,031 highly informative SNP and SilicoDArT markers, respectively, were filtered and used for genetic diversity analysis and subset development. Analysis of molecular variance (AMOVA) revealed higher variability 'within' (52.73% for SNP markers and 67.36% for SilicoDArT markers) than 'between' accessions. Hierarchical cluster analysis showed the presence of four main clusters in the collection. Mantel correlation analysis showed a lack of relationship between genetic variation of the germplasm and their geographical origin. A representative subset of 34 accessions containing germplasm from diverse origins and agro-ecologies was developed using SNP markers. The genetic diversity information generated in this study could be used for marker-assisted screening for stress tolerance, gap analysis and identification and acquisition of new distinct genotype(s) to broaden the genetic basis of the collection for future improvement programs to develop high-yielding, stress-tolerant varieties for enhancing food and environmental security in crop–livestock-based production systems. [ABSTRACT FROM AUTHOR]

Since 2016, it has been possible to record and collect GNSS (Global Navigation Satellite System) raw data on Android devices. This has been a game changer in low-cost device applications. Researchers in the GNSS field have tried to answer new questions regarding Android device positioning performance, the quality of their measurements, positioning techniques that could be applied, and methods to increase the accuracy and the reliability of the PNT (Position Navigation Timing) solution. Several research groups have demonstrated accurate positioning using smartphones while also showing the potential limitations of such devices. In particular, problems related to the GNSS antenna performance have been reported; indeed, in urban scenarios, where users typically operate, the presence of multiple outliers could make the navigation solution inaccurate, if not unfeasible. Hence, techniques useful for verifying the reliability of the navigation solutions have become fundamental. The reliability of the PNT solution provided by smartphones is an open research question. In this study, traditional RAIM (Receiver Autonomous Integrity Monitoring) algorithms were adapted to the case of smartphones. Navigation solution algorithms, including FDE (Fault Detection and Exclusion), were tested using a long data collection made by a smartphone located in a harsh environment in static mode. The performance of the proposed approaches was assessed in terms of horizontal and vertical errors, solution reliability, and residual distribution.

Abstract Background Systemic lupus erythematosus (SLE) is characterized by loss of immune tolerance and imbalance of immune cell subsets. Natural killer (NK) cells contribute to regulate both the innate and adaptive immune response. In this study, we aimed to detect alterations of peripheral NK cells and explore intrinsic mechanisms involving in NK cell abnormality in SLE. Methods Blood samples from healthy controls (HCs) and patients with SLE and rheumatoid arthritis (RA) were collected. The NK count, NK subsets (CD56bright, CD56dimCD57−, and CD56dimCD57+), phenotypes, and apoptosis were evaluated with flow cytometer. Mitochondrial reactive oxygen species (mtROS) and total ROS levels were detected with MitoSOX Red and DCFH-DA staining respectively. Published data (GSE63829 and GSE23695) from Gene Expression Omnibus (GEO) was analyzed by Gene Set Enrichment Analysis (GSEA). Results Total peripheral NK count was down-regulated in untreated SLE patients in comparison to that in untreated RA patients and HCs. SLE patients exhibited a selective reduction in peripheral CD56dimCD57+ NK cell proportion, which was negatively associated with disease activity and positively correlated with levels of complement(C)3 and C4. Compared with HCs, peripheral CD56dimCD57+ NK cells from SLE patients exhibited altered phenotypes, increased endogenous apoptosis and higher levels of mtROS and ROS. In addition, when treated with hydrogen peroxide (H2O2), peripheral CD56dimCD57+ NK cell subset was more prone to undergo apoptosis than CD56dimCD57− NK cells. Furthermore, this NK cell subset from SLE patients exhibited impaired cytotoxicity in response to activated CD4+ T cells in vitro. Conclusion Our study demonstrated a selective loss of mature CD56dimCD57+ NK cell subset in SLE patients, which may caused by preferential apoptosis of this subset under increased oxidative stress in SLE. The attenuated in vitro cytotoxicity of CD56dimCD57+ NK cells may contribute to the impaired ability of eliminating pathogenic CD4+ T cells in SLE.

Treatment of young children with atypical or recurrent purulent soft tissue infections (PSTD) that do not respond well to surgery and antibiotics is most challenging. PSTD occurs against the background of impaired functioning of the immune system and, first of all, the system of neutrophilic granulocytes (NG). The vector effect of immunotropic therapy on a specific NG subsets may allow the correction of NG dysfunctions without compromising host protection, including strategies to enhance, inhibit or restore their functions.The aim of study: to evaluate in vitro the modulating effects of arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine (HP) on the transformed phenotype of 4 NG subsets, as well as on the functional activity of NG in children with purulent-inflammatory soft tissue diseases.We studied samples of peripheral blood (PB) from young children 2-4 years old: 17 children with atypical acute PSTD and 10 apparently healthy children. At stage I, a comparative assessment of the content and phenotype of 4 NG subsets CD16+CD62L+СD63- , CD16+CD62L+СD63+, СD64- CD16+CD32+CD11b+, СD64+CD16+CD32+CD11b+, phagocytic and microbicidal functions of NG was carried out. At stage II, the in vitro system determined the effects of HP on NG in children with PSTD according to the studied parameters. By the method of flow cytometry (FC500 “Beckman Coulter” (USA), conjugates of MkAT “Beckman Coulter International S.A.” (France)), the relative number of NGs of the studied subsets and the density of receptor expression (MFI) were determined. To assess the phagocytic function of NG a microbiological method was used to assess the completeness of phagocytosis with S. aureus (strain 209). The activity of NG NADPH oxidase was investigated in the NBT-spontaneous test (NBTsp.) and in the in vitro NBT-induced test (NBTind.). A comparative study of PB samples from conventionally healthy children and children with PSTD made it possible to identify various variants of transformation of the phenotype of the studied NG subsets, associated with defects in their functional activity. In the in vitro system the effects of HP were demonstrated, manifested by a decrease in the amount of CD16+CD62L+CD63+NG and an increase in CD16+CD62L+CD63- NG, modulation of the negatively altered phenotype of subsets CD64- CD32+CD16+CD11b+NG and CD64+CD32+CD16+CD11b+NG, aimed at restoring phagocytic function and maintaining the tension of NADPH oxidases.As a result of the study it was found the immunomodulatory effects of HP, which is manifested in the reorientation of NG from the pro-inflammatory phenotype to the anti-inflammatory one, which can be used in the future when creating personalized targeted immunotherapy aimed at correcting defective functioning NG in early children, suffering from PSTD.

Abstract Background γδT cells play an important role in the mucosa inflammation and immunity-associated disorders. Our previous study reported that γδ T cells producing IL-17 were involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, their subset characteristic profile in this kind of disease remains unclear. Thus the current study’s aim is to investigate the functionally predominant subset and its role in PI-IBS. Methods The total T cells were collected from the peripheral blood of patients with PI-IBS. The peripheral proportion of Vδ1 and Vδ2 subset was detected by FACS after stained with anti δ1-PE and anti δ2-APC. The local colonic proportion of this two subsets were measured under laser confocal fluorescence microscope. Vδ1 γδ T cells were enriched from the total peripheral T cells by minoantibody-immuno-microbeads (MACS) method and cultured, functionally evaluated by CCK-8 assay (proliferation), CD69/CD62L molecules expression assay (activation) and ELISA (IL-17 production) respectively. Results 1. Vδ1 γδ T cells significantly increased while Vδ2 γδ T cells remained unchanged in both the peripheral blood and local colonic tissue from PI-IBS patients (p

Dendritic cells (DC) play critical roles in linking innate and adaptive immunity. DC are heterogenous and there are subsets with various distinct functions. One DC subset, conventional type 1 DC (cDC1), can be defined by expression of CD8α/CD103 in mice and CD141 in humans, or by expression of a chemokine receptor, XCR1, which is a conserved marker in both mice and human. cDC1 are characterized by high ability to ingest dying cells and to cross-present antigens for generating cytotoxic CD8 T cell responses. Through these activities, cDC1 play crucial roles in immune responses against infectious pathogens or tumors. Meanwhile, cDC1 involvement in homeostatic situations is not fully understood. Analyses by using mutant mice, in which cDC1 are ablated in vivo , revealed that cDC1 are critical for maintaining intestinal immune homeostasis. Here, we review the homeostatic roles of cDC1, focusing upon intestinal immunity. [ABSTRACT FROM AUTHOR]

Let A ⊂ ℤN, and We define the pseudorandom measure of order k of the subset A as follows where the maximum is taken over all D = (c1,c2,⋯,ck) ∈ ℤk with 0 ≼ c1< c2< ⋯

PurposeThis study aims to discuss the function mechanism of regulatory T cells and its subsets in the pathogenic process of myasthenia gravis by contracting the activation levels of those cells in peripheral blood among healthy people, patients with ocular myasthenia gravis (oMG) and patients with generalized myasthenia gravis (gMG).MethodHealthy people, newly diagnosed oMG patients, and gMG patients were enrolled in this study. The percentage of the CD3+CD4+CD25+ Treg cells, CD3+CD4+CD25+Foxp3+ Treg cells, CD3+CD4+CD25+Foxp3hi CD45RA–aTreg cells, CD3+CD4+CD25+Foxp3loCD45RA–n-sTreg cells, and CD3+CD4+CD25+ Foxp3loCD45RA+rTreg cells in the peripheral blood were examined by flow cytometry. And then analyzed the differences of Treg cells and its subsets among the study members.ResultsThe percentage of the CD4+CD25+Treg cells in the peripheral blood of oMG patients and gMG patients were both lower than that of healthy people (p < 0.05), the percentage of patients with oMG had no distinct difference with that of patients with gMG (p = 0.475), however. Also, the percentage of CD3+CD4+CD25+Foxp3+Treg cells in the oMG and gMG patients’ group were both lower than that of healthy group. And the percentage of CD25+Foxp3+Treg cells in the peripheral blood of patients with oMG and healthy people were both higher than that of patients with gMG (p < 0.05). The percentage of rTreg in the CD3+CD4+CD25+Treg of the peripheral blood for both gMG and oMG patients’ group were lower than healthy group (p < 0.05), but there was no statistical significance between the oMG and gMG patients’ group (p = 0.232). The percentage of the aTreg cells in the CD3+CD4+CD25+Treg cells of the peripheral blood for the oMG patients was higher than that of gMG patients (p < 0.05), but both of them were lower than healthy group (p < 0.05). The percentage of n-sTreg cells in the peripheral blood descended among the gMG patients’ group, oMG patients’ group, and healthy group (p < 0.05).ConclusionThe changes in the number and function of Treg cells and its subsets can cause the impairment of negative immune regulation, which may mediate the triggering of oMG and its progression to gMG.

Dendritic cells (DC) play critical roles in linking innate and adaptive immunity. DC are heterogenous and there are subsets with various distinct functions. One DC subset, conventional type 1 DC (cDC1), can be defined by expression of CD8α/CD103 in mice and CD141 in humans, or by expression of a chemokine receptor, XCR1, which is a conserved marker in both mice and human. cDC1 are characterized by high ability to ingest dying cells and to cross-present antigens for generating cytotoxic CD8 T cell responses. Through these activities, cDC1 play crucial roles in immune responses against infectious pathogens or tumors. Meanwhile, cDC1 involvement in homeostatic situations is not fully understood. Analyses by using mutant mice, in which cDC1 are ablated in vivo, revealed that cDC1 are critical for maintaining intestinal immune homeostasis. Here, we review the homeostatic roles of cDC1, focusing upon intestinal immunity.

Background and aims: Gamma–delta (γδ) T cells are involved in the development of diverse liver and autoimmune diseases, whereas the role of γδ T cells in primary biliary cholangitis (PBC) remains unclear. Methods: We analyzed the number, phenotypes, and functional molecules of both circulating and hepatic γδ T cells in PBC patients and healthy controls (HCs) by flow cytometric analysis and immunohistochemistry. Results: We identified two distinct functional subsets of circulating γδ T cells according to the CD3/TCRγδ complex: the TCRγδhigh and TCRγδlow subsets. Approximately, three-quarters of cells in the TCRγδhigh subset were Vδ1 T cells, while Vδ2 T cells were enriched in the TCRγδlow subset in HCs. The frequency and absolute number of circulating TCRγδlow cells were significantly decreased in PBC patients compared with HCs (p < 0.001). Furthermore, the frequency of TCRγδlow cells was correlated with disease severity and ursodeoxycholic acid (UDCA) response. TCRγδlow cells exhibited a similar apoptotic and proliferative phenotype, but enhanced liver-homing chemokine receptor (CXCR6) expression in PBC patients compared with HCs. In addition, circulating TCRγδlow cells were more activated and produced higher granzyme B (GZMB) in PBC patients compared with HCs. Finally, compared with heathy liver controls, hepatic γδ T cells were increased and infiltrated in the inflamed portal tracts in PBC liver. Furthermore, the number of hepatic γδ T cells was correlated with cholestatic markers and UDCA response. Conclusion: The circulating TCRγδlow subset may migrate to the liver via the CXCR6-CXCL16 axis and be involved in the pathogenesis of PBC by increasing GZMB production. [ABSTRACT FROM AUTHOR]

Relevance. Neutrophilic granulocytes (NG) are the first cells of the immune system to migrate to the tumor and are actively involved in the implementation of a full-fledged antitumor response through the mechanisms of direct killing of tumor cells, extracellular lysis (NET), and through the activation of antibody-dependent cellular cytotoxicity (ADCC), inhibition of angiogenesis, initiation of other cells with antitumor activity. The aim of the study was to study the effect of cytokines IFN, IFN, G-CSF on the CD62L+CD63- and CD62L+CD63+ subsets and the microbicidal activity of NGs in patients with colorectal cancer (CRC) in vitro. Materials and methods. We studied samples of peripheral blood (PB) of 10 patients of both sexes 38-70 years old with newly diagnosed untreated CRC stage II-III (study group) and 10 healthy volunteers (comparison group). The subsets CD62L+CD63+ NG, CD62L+CD63- NG were assessed by flow cytometry (CYTOMICS FC500, Beckman Coulter, USA), the microbicidal functions of NG were tested by cytochemical methods: activity of NADPH - oxidases, myeloperoxidase (MP), level of cationic protein (CP) in spontaneous tests and under additional stress of S. aureus . The effect of IFN, IFN, G-CSF cytokines on subsets and the microbicidal activity of NG in vitro was studied in both study groups. Microsoft Exel 2016 and StatPlus 2010 were used for statistical processing of the obtained data using nonparametric tests: Me (Q1; Q3), Mann-Whitney U-test and Wilcoxon test . Results . The features of transformation of CD62L+ CD63-NG and CD62L+ CD63+ NG subsets of PB in CRC have been established, that allows to get an idea of the NG ability to roll and readiness to activate the microbicidal arsenal, various defects of spontaneous and induced microbicidal activity of oxygendependent and oxygen-independent mechanisms of NG. The effects of cytokine influence on NG in CRC in vitro have been shown, which indicates the possibility of regulating the receptor and microbicidal functions of NG, and, on the other hand, suggests defects in NG perception of regulatory stimuli, that is confirmed by the progression of tumor growth.

Defects in the functioning of neutrophilic granulocytes (NG) are accompanied by various purulent-inflammatory diseases that have a persistent-relapsing course. The bactericidal activity of NG, the processes of intracellular and extracellular killing of bacteria, is directly dependent on their phenotypic features: the expression level of functionally significant membrane receptors CD64, CD16, CD32, CD11b triggering effector processes. It was shown that there are subsets of NG with different phenotypic characteristics and the course and outcome of infectious and inflammatory diseases directly depends on their usefulness. Despite the large amount of accumulated information, the question of the transformation of NG subpopulations phenotype during NG response formation in children with local purulent processes of soft tissues - a small purulent infection (SPI) remains poorly understood. Purpose: to evaluate the local and systemic effector function of neutrophilic granulocytes (phagocytosis, NET formation) with clarification of the phenotype of functionally significant CD64-CD16+CD32+CD11b+, CD64+CD16+CD32+CD11b+ and CD64-CD16+CD32-CD11b+ NG subpopulations in peripheral blood (PB) in children with SPI. Materials and methods. We evaluated the phagocytic function of NG in 60 PB samples of children 5-9 years old, on the 2-3rd day of acute purulent process, before surgery, in smears - prints taken from the local focus of purulent inflammation and 17 PB samples of conditionally healthy children. Also the ability to form NET was additionally determined in smears-prints in children with SPI. In parallel, in PB we evaluated:% NG simultaneously carrying CD64, CD16, CD32, CD11b receptors and their expression density (MFI) by flow cytometry (CYTOMICS FC500, Beckman Coulter, USA). Statistical data processing was performed in the Microsoft Exel 2016 and Stat Plus 2010 software packages. Nonparametric criteria were used: median (Me) and interquartile range (Q1; Q3), Mann-Whitney U-test and Wilcoxon test. Results . We found a significant increase in the content of the NG subpopulation with a negatively transformed phenotype CD64-CD16+CD32-CD11b+ with defects in the expression of CD64 and CD32 receptors, which is the cause of inadequate inclusion of NG in inflammatory processes, disruption of phagocytic activity at the systemic and local levels and the occurrence of SPI in children. The formation of NET in the first stage is necessary to supplement the effector function of NG in order to compensate for disorders of phagocytosis.

Abstract Background Breast cancer stem cells (BCSCs) are typically seed cells of breast tumor that initiate and maintain tumor growth. MiR-7, as a cancer inhibitor, decreases the BCSC subset and inhibits tumor progression through mechanisms that remain unknown. Methods We examined miR-7 expression in breast cancer and developed a BCSC-driven xenograft mouse model, to evaluate the effects of miR-7 overexpression on the decrease of the BCSC subset in vitro and in vivo. In addition, we determined how miR-7 decreased the BCSC subset by using the ALDEFLUOR, lentivirus infection, dual-luciferase reporter, and chromatin immunoprecipitation-PCR assays. Results MiR-7 was expressed at low levels in breast cancer tissues compared with normal tissues, and overexpression of miR-7 directly inhibited lncRNA XIST, which mediates the transcriptional silencing of genes on the X chromosome, and reduced epithelium-specific antigen (ESA) expression by increasing miR-92b and inhibiting slug. Moreover, miR-7 suppressed CD44 and ESA by directly inhibiting the NF-κB subunit RELA and slug in breast cancer cell lines and in BCSC-driven xenografts, which confirmed the antitumor activity in mice injected with miR-7 agomir or stably infected with lenti-miR-7. Conclusions The findings from this study uncover the molecular mechanisms by which miR-7 inhibits XIST, modulates the miR-92b/Slug/ESA axis, and decreases the RELA and CD44 expression, resulting in a reduced BCSC subset and breast cancer growth inhibition. These findings suggest a potentially targeted treatment approach to breast cancer.

Sesbania sesban (L.) Merr. is a multipurpose legume tree grown primarily for fodder and forage in the tropical and subtropical world. In this study, the Sesbania sesban collection maintained in the International Livestock Research Institute (ILRI) forage Genebank was studied using genome-wide markers generated on the DArTseq platform. Genotyping produced 84,673 and 60,626 SNP and SilicoDArT markers with a mean polymorphic information content of 0.153 and 0.123, respectively. From the generated markers, 7587 and 15,031 highly informative SNP and SilicoDArT markers, respectively, were filtered and used for genetic diversity analysis and subset development. Analysis of molecular variance (AMOVA) revealed higher variability ‘within’ (52.73% for SNP markers and 67.36% for SilicoDArT markers) than ‘between’ accessions. Hierarchical cluster analysis showed the presence of four main clusters in the collection. Mantel correlation analysis showed a lack of relationship between genetic variation of the germplasm and their geographical origin. A representative subset of 34 accessions containing germplasm from diverse origins and agro-ecologies was developed using SNP markers. The genetic diversity information generated in this study could be used for marker-assisted screening for stress tolerance, gap analysis and identification and acquisition of new distinct genotype(s) to broaden the genetic basis of the collection for future improvement programs to develop high-yielding, stress-tolerant varieties for enhancing food and environmental security in crop–livestock-based production systems.

The paper is the Part III of the large research, dedicated to both revision of the system of basic logical categories and generalization of modern predicate logic to functional logic. We determinate and contrapose modern fregean logistics and proposed by the author ultrafregean logistics, next we descibe values and arguments of functions, arguments of relations, relations themselves, sets (classes) and subsets (subclasses) as derivative categories (concepts) of ultrafregean logistics. Logictics is a part of metalogic, independent of semantics. Fregean logictics is a metalogical theory, based on the quadruple ; it generates predicate logic. Ultrafregean logictics is based on the quadruple , where the notion a function is a generalization of the notion of a predicate and the notion of representation is a generalization of the notion of equality; this logictics generates functional logic. For the completely correct denotation of the functional values we need the chorchian symbolics with parenthesis. Predicates are usually identified with relations. A relation is the derived and even definable category of ultrafregean logictics. Namely, relations are representations by functions (of one of their arguments). We show that Frege could realy establish this definition and the notion (category) of representation but, unfortunately, rejected this course of thought. Next, we show that every n-ary relation can be solved for some its argument via some (n-1)-ary function. A set, or class, is a derived and not definable category of ultrafregean logictics. The universal way to introduce the sets is Frege's abstraction principle. We formulate this principle for functional logic and show that the notion of a set is a quantified notion, so there is the dual existential notion of a nonempty subset, involved by the same abstraction principle. [ABSTRACT FROM AUTHOR]

The set of prime numbers p ≥ 5 is divided into two nonoverlapping subset P1 = {6k1 - 1}, P2 = {6k2 + 1}, where ki ⋲ A (i = 1,2). Subsets A1, A2 of natural numbers is defined by differences Ai = N\Bi, where B1, B2 are subset {j1}, {j2} defining subsets {6j1 – 1}, {6j2 + 1} of odd composite numbers. In [1] is proved two theorems permitting easily find by means of arithmetic progression subset Bi for ji £ a ⋲ N. The tables of numbers ki for a = 500 are defined and some characteristic of subsets P1, P2 are given.

Background: γδT cells play an important role in the mucosa inflammation and immunity-associated disorders. Our previous study reported that γδ T cells producing IL-17 were involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, their subset characteristic profile in this kind of disease remains unclear. Thus the current study's aim is to investigate the functionally predominant subset and its role in PI-IBS.Methods: The total T cells were collected from the peripheral blood of patients with PI-IBS. The peripheral proportion of Vδ1 and Vδ2 subset was detected by FACS after stained with anti δ1-PE and anti δ2-APC. The local colonic proportion of this two subsets were measured under laser confocal fluorescence microscope. Vδ1 γδ T cells were enriched from the total peripheral T cells by minoantibody-immuno-microbeads (MACS) method and cultured, functionally evaluated by CCK-8 assay (proliferation), CD69/CD62L molecules expression assay (activation) and ELISA (IL-17 production) respectively.Results: 1. Vδ1 γδ T cells significantly increased while Vδ2 γδ T cells remained unchanged in both the peripheral blood and local colonic tissue from PI-IBS patients (p < 0.05). 2. When cultured in vitro, the Vδ1 γδ T cells remarkably proliferated, activated and produced IL-17 (p < 0.05).Conclusions: Our results suggest that Vδ1 γδ T cells was the predominant γδ T cells subset in both peripheral and intestinal tissue, and was the major IL-17 producing γδ T cells in PI-IBS. [ABSTRACT FROM AUTHOR]

Design activity is the initial step in manufacturing. In smart factory, these activities should be interconnected. The final cost of a product is affected by decisions which are made in these activities. Since 1980, Design for Manufacturing and Assembly (DFMA) approaches has been developed to guide planners to produce products which are easy to fabricate and assemble. Designing products for recyclability is constrained by environmental and economic targets. Numerous Design for Assembly (DFA) laws and parameters can be employed to measure the recyclability index of product designs. Parallel assembly and disassembly techniques using human and robot collaboration can also improve the design quality by choosing the shorter way to completely dismantle the product or to dismantle wear parts. The implementation of these approaches has created a revolution in today's industry, by many improvements as reduce product cost, shorter time to market, better quality, and few suppliers of standard parts. In this paper, a novel method to parallel dismantle a product is presented. To improve the design quality of the product, a set of assessment metrics were considered as recyclability for reusing aspect, total disassembly time of the product, parallelism aspect, and design efficiency. A comparative example is used to demonstrate the added value of the proposed approach. [ABSTRACT FROM AUTHOR]

Copyright of Industrial Minerals & Processing / Huagong Kuangwu yu Jiagong is the property of Industrial Minerals & Processing Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Neutrophils that reside in the bone marrow are swiftly recruited from circulating blood to fight infections. For a long time, these first line defenders were considered as microbe killers. However their role is far more complex as cross talk with T cells or dendritic cells have been described for human or mouse neutrophils. In cattle, these new roles are not documented yet. We identified a new subset of regulatory neutrophils that is present in the mouse bone marrow or circulate in cattle blood under steady state conditions. These regulatory neutrophils that display MHC-II on the surface are morphologically indistinguishable from classical MHC-IIneg neutrophils. However MHC-IIpos and MHC-IIneg neutrophils display distinct transcriptomic profiles. While MHC-IIneg and MHC-IIpos neutrophils display similar bacterial phagocytosis or killing activity, MHC-IIpos only are able to suppress T cell proliferation under contact-dependent mechanisms. Regulatory neutrophils are highly enriched in lymphoid organs as compared to their MHC-IIneg counterparts and in the mouse they express PDL-1, an immune checkpoint involved in T-cell blockade. Our results emphasize neutrophils as true partners of the adaptive immune response, including in domestic species. They open the way for discovery of new biomarkers and therapeutic interventions to better control cattle diseases.

Neutrophils that reside in the bone marrow are swiftly recruited from circulating blood to fight infections. For a long time, these first line defenders were considered as microbe killers. However their role is far more complex as cross talk with T cells or dendritic cells have been described for human or mouse neutrophils. In cattle, these new roles are not documented yet. We identified a new subset of regulatory neutrophils that is present in the mouse bone marrow or circulate in cattle blood under steady state conditions. These regulatory neutrophils that display MHC-II on the surface are morphologically indistinguishable from classical MHC-IIneg neutrophils. However MHC-IIpos and MHC-IIneg neutrophils display distinct transcriptomic profiles. While MHC-IIneg and MHC-IIpos neutrophils display similar bacterial phagocytosis or killing activity, MHC-IIpos only are able to suppress T cell proliferation under contact-dependent mechanisms. Regulatory neutrophils are highly enriched in lymphoid organs as compared to their MHC-IIneg counterparts and in the mouse they express PDL-1, an immune checkpoint involved in T-cell blockade. Our results emphasize neutrophils as true partners of the adaptive immune response, including in domestic species. They open the way for discovery of new biomarkers and therapeutic interventions to better control cattle diseases. [ABSTRACT FROM AUTHOR]

Microglial heterogeneity has been the topic of much discussion in the scientific community. Elucidation of their plasticity and adaptability to disease states triggered early efforts to characterize microglial subsets. Over time, their phenotypes, and later on their homeostatic signature, were revealed, through the use of increasingly advanced transcriptomic techniques. Recently, an increasing number of these “microglial signatures” have been reported in various homeostatic and disease contexts. Remarkably, many of these states show similar overlapping microglial gene expression patterns, both in homeostasis and in disease or injury. In this review, we integrate information from these studies, and we propose a unique subset, for which we introduce a core signature, based on our own research and reports from the literature. We describe that this subset is found in development and in normal aging as well as in diverse diseases. We discuss the functions of this subset as well as how it is induced.

Neutrophils are amongst the most abundant immune cells within the periodontal tissues and oral cavity. As innate immune cells, they are first line defenders at the tooth-mucosa interface, and can perform an array of different functions. With regard to these, it has been observed over many years that neutrophils are highly heterogeneous in their behavior. Therefore, it has been speculated that neutrophils, similarly to other leukocytes, exist in distinct subsets. Several studies have investigated different markers of neutrophils in oral health and disease in recent years in order to define potential cell subsets and their specific tasks. This research was inspired by recent advancements in other fields of medicine in this field. The aim of this review is to give an overview of the current evidence regarding the existence and presence of neutrophil subsets and their possible functions, specifically in the context of periodontitis, gingivitis, and periodontal health.

The research has shown that the functional state of neutrophilic granulocytes (NG) is determined by the state of NG subpopulation phenotype composition in evaluating the simultaneous expression of CD16, CD32, CD11b membrane markers with considering the density of expressed molecules. The change in NG subpopulations phenotype indicates active or defective inclusion of NG in the immune response in inflammation. Various inducers of endo- and exogenous nature activate NG and promote translocation from cytoplasmic granules and vesicles or expression to the surface cytoplasmic membrane of receptor molecules. In this regard, our interest was in studying the expression peculiarities of CD16, CD32, CD11b NG receptors in patients with atypically occurring bacterial infections (chronic sinusitis) and the possibility of remodeling the NG phenotype under the influence of glucosaminylmuramyl dipeptide (GMDP) and IFNγ in vitro. Subjects of this study were blood samples of patients with chronic sinusitis and conditionally healthy individuals. Flow rate cytometry at CYTOMICS FC500 (Beckman Coulter, USA) was used to evaluate the % NGs expressing CD16, CD32, CD11b, and the fluorescence intensity of these molecules (MFI) before and after incubation with the test substances. Flow cytometry (CYTOMICS FC500, Beckman Coulter, USA) were used to evaluate amount (%) of NGs expressing CD16, CD32, CD11b and mean fluorescence intensity of these molecules (MFI) before and after incubation with the test substances. The studies showed that in patients with chronic sinusitis with persistent recurrent course the presence is characterized by transformed phenotype CD16dimCD32midCD11bbr of CD16+CD32+CD11b+NG subpopulation. We have shown that the revealed changes in the level of expression of trigger membrane receptors do not allow NG to fully engage in inflammatory process and to realize its effector and regulatory functions. Under the influence of GMDP and IFNγ regulatory molecules was demonstrated high mobilization capacity of the studied NGs for functionally significant membrane receptors in realization of various functions.

A short historical information about formulas and polynomials gener­ating subsets of prime numbers is given. Examples of subsets of prime numbers by using generalized arithmetic progression are obtained. It is proved that prime numbers of the sets Ml are the first (l + 1)/2 members of the generalized arithmetic progression with first member (l + 3)/2 and denominator d = 2.

Multi-user multiple input multiple output (MU-MIMO) is a basic technique which has been widely investigated for its ability to increase system capacity. However, the inter-user interference (IUI) is one of the obstacles to obtain system capacity. With the help of pre-coding technique, the IUI can be canceled or reduced at the base station (BS). Vector perturbation (VP) is one of the most celebrated precoding schemes that can approach system capacity. By perturbing users' data vector with a certain integer vector offset at the BS, the VP scheme can offer the users a higher effective signal-to-noise ratio. To reach the theory bound of VP, the BS has to select the optimal integer vector from all candidate integer vectors globally. This exhaustive search has been proved to be NP-hard, which is hard to be implemented. In this paper, we analyze several state-of-the-art modified low-complexity VP schemes and propose the subset VP (SVP) scheme to reduce the complexity of the VP. The basic principle of the SVP is that some vectors are selected as the optimal vector with high probability, whereas the others are scarcely selected. So, we try to form a subset consists of vectors with a relatively higher probability. First, we calculate the probability of all candidate vectors which have been selected as the optimal vector. Second, we propose a method to divide all vectors into several subgroups. Vectors in the same subgroup have a similar probability, whereas vectors in different subgroups have distinguished probability. Third, we build a subset that is comprised of several subgroups in which vectors have a relatively higher probability. Simulation results show that we get almost the same bit-error rate performance with a significant complexity reduction.

Summary: Dysfunction of natural killer (NK) cells is associated with poor prognosis in hepatocellular carcinoma (HCC). We explored the phenotypic and functional characteristics of peripheral blood NK cells in HCC patients following sorafenib treatment.Peripheral blood samples were collected from 60 HCC patients in a single centre (2015~2017) and 45 healthy donors. The percentage and cytoplasmic granule production of NK cells were analysed. Subset proportions were evaluated for their associations with the modified Response Evaluation Criteria in Solid Tumors (mRECIST), time to progression, and median overall survival (OS).Compared with baseline, the percentages of total and CD56dimCD16+ NK cells increased after two months of treatment, while the percentage of CD56brightCD16− NK cells decreased, leading to a dramatically reduced ratio of CD56bright and CD56dim NK cells (ratiobri/dim). Patients with low ratiobri/dim exhibited better mRECIST responses and longer median OS than those with high ratiobri/dim. The expression levels of granzyme B and perforin in total NK cells and in both subsets of cells were increased after treatment.This study showed that sorafenib could affect the proportions and functions of peripheral CD56brightCD16− and CD56dimCD16+ NK cells, which was associated with the outcomes including OS of HCC patients. [ABSTRACT FROM AUTHOR]