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Coronavirus disease 2019 (COVID-19) is caused by a recently identified virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease is a pandemic. Although the hallmarks of severe COVID-19 have been established, the underlying mechanisms that promote severe pathology have not been thoroughly studied. A better understanding of the immune response in severe COVID-19 patients may help guide the development of therapeutic strategies and predict immuno-pathogenicity. This study was set to determine the lymphocyte and cytokine profiles associated with COVID-19 severity. A total of 43 hospitalised COVID-19 patients were recruited for the study and whole blood samples were drawn from each patient. Complete blood counts, lymphocyte subset profiles and C-reactive protein statuses of patients were determined. Cytometric bead array was performed to analyse the cytokine profiles of each patient. The demographic characteristics showed that the median age of the patients was 48.72 years, with an interquartile range from 40 to 60 years, and 69.77% of the patients were male. COVID-19 patients exhibited significantly low CD4+ lymphocyte expansion and leucocytosis augmented by elevated neutrophil and immature granulocytes. Stratification analysis revealed that reduced monocytes and elevated basophils and immature granulocytes are implicated in severe pathology. Additionally, cytokine results were noted to have significant incidences of interleukin 17A (IL-17A) expression associated with severe disease. Results from this study suggest that a systemic neutrophilic environment may preferentially skew CD4+ lymphocytes towards T-helper 17 and IL-17A promotion, thus, aggravating inflammation. Consequently, results from this study suggest broad activity immunomodulation and targeting neutrophils and blocking IL-17 production as therapeutic strategies against severe COVID-19.Homeostasis plays a central role in our understanding how cells and organisms are able to oppose environmental disturbances and thereby maintain an internal stability. During the last two decades there has been an increased interest in using control engineering methods, especially integral control, in the analysis and design of homeostatic networks. Several reaction kinetic mechanisms have been discovered which lead to integral control. In two of them integral control is achieved, either by the removal of a single control species E by zero-order kinetics ("single-E controllers"), or by the removal of two control species by second-order kinetics ("antithetic or dual-E control"). In this paper we show results when the control species E1 and E2 in antithetic control are removed enzymatically by ping-pong or ternary-complex mechanisms. Our findings show that enzyme-catalyzed dual-E controllers can work in two control modes. In one mode, one of the two control species is active, but requires zero-order kinetics in its removal. In the other mode, both controller species are active and both are removed enzymatically. Conditions for the two control modes are put forward and biochemical examples with the structure of enzyme-catalyzed dual-E controllers are discussed.

Smoking and obesity are established risk factors of dyslipidemia, however, the interplay between them has not been well studied. This study aims to explore the joint effect of smoking and body mass index (BMI) on serum lipid profiles.

The study consisted of 9846 Chinese adults (mean age = 49.9 years, 47.6% males, 31.2% ever smokers), based on the China Health and Nutrition Survey. Serum lipid profiles included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (APO-A), and apolipoprotein B (Apo-B). The joint effect of smoking and BMI on serum lipids were examined by the four-way decomposition analysis and multivariate linear regression models.

The four-way decomposition showed that the interplay between smoking and BMI was complicated. There was only indirect effect (the mediated effect) between smoking and BMI on TC, LDL-C and APO-B. The pure indirect effect was -0.023 for TC, -0.018 for LDL-C, and -0.00ignificant interaction effects of smoking and BMI on TG, HDL-C and APO-A, while BMI maybe a mediator for the association of smoking with TC, LDL-C and APO-B. The effects between them were rather complex. Smoking cessation is necessary, especially for those overweight.The present study aimed to examine the prevalence of dyspareunia in the post-partum period in relation to the mode of delivery. In this systematic review and meta-analysis, published articles until February 2020 were searched through the related key term based on mesh term in national and international databases. In the initial search, 1391 articles were found that after removing duplicate, unrelated or non-English and non-Persian articles, finally 20 studies with a sample size of 11354 of women who had given birth were introduced in this study. The prevalence of dyspareunia following vaginal delivery, C-section, and instrumental delivery with 95%CI was 42%(31-56%), 26%(19-34%), and 37%(28-46%) respectively. In addition, the prevalence of dyspareunia in primiparous was higher than multiparous (34%vs.24%), in breastfeeding women was higher than non-breastfeeding women (48%vs.33%), in women who non-used hormonal contraceptive methods were higher than who used hormonal contraceptive methods (43%vs.35%) and its pn to the type of delivery the prevalence of dyspareunia was estimated based on parity, breastfeeding, episiotomy and consumption of hormonal contraceptive status.What are the implications of these findings for clinical practice and/or further research? This finding will be a small step to familiarise physicians and midwives as well as people with the relationship between delivery mode and dyspareunia. In addition, in the absence of medical indications and the possibility of choosing the mode of delivery selectively, help them decide and choose the appropriate method of termination of labour and ultimately improve the mental and physical health of the birthing person, family and community.The actinorhizal plant Datisca glomerata (Datiscaceae, Cucurbitales) establishes a root nodule symbiosis with actinobacteria from the earliest branching symbiotic Frankia clade. A subfamily of a gene family encoding nodule-specific defensin-like cysteine-rich peptides is highly expressed in D. glomerata nodules. see more Phylogenetic analysis of the defensin domain showed that these defensin-like peptides share a common evolutionary origin with nodule-specific defensins from actinorhizal Fagales and with nodule-specific cysteine-rich peptides (NCRs) from legumes. In this study, the family member with the highest expression levels, DgDef1, was characterized. Promoter-GUS studies on transgenic hairy roots showed expression in the early stage of differentiation of infected cells, and transient expression in the nodule apex. DgDef1 contains an N-terminal signal peptide and a C-terminal acidic domain which are likely involved in subcellular targeting and do not affect peptide activity. In vitro studies with E. coli and Sinorhizobium meliloti 1021 showed that the defensin domain of DgDef1 has a cytotoxic effect, leading to membrane disruption with 50% lethality for S. meliloti 1021 at 20.8 μM. Analysis of the S. meliloti 1021 transcriptome showed that, at sublethal concentrations, DgDef1 induced the expression of terminal quinol oxidases, which are associated with the oxidative stress response and are also expressed during symbiosis. Overall, the changes induced by DgDef1 are reminiscent of those of some legume NCRs, suggesting that nodule-specific defensin-like peptides were part of the original root nodule toolkit and were subsequently lost in most symbiotic legumes, while being maintained in the actinorhizal lineages.The immediate precursor to murine type 1 conventional DCs (cDC1s) has recently been established and named "pre-cDC1s". Mature CD8α+ cDC1s are recognized for suppressing graft-versus-host disease (GvHD) while promoting graft-versus-leukemia (GvL), however pre-cDC1s have not previously been investigated in the context of alloreactivity or anti-tumor responses. Characterization of pre-cDC1s, compared to CD8α+ cDC1s, found that a lower percentage of pre-cDC1s express PD-L1, yet express greater PD-L1 by MFI and a greater percent PIR-B, a GvHD-suppressing molecule. Functional assays were performed ex vivo following in vivo depletion of CD8α+ DCs to examine whether pre-cDC1s play a redundant role in alloreactivity. Proliferation assays revealed less allogeneic T-cell proliferation in the absence of CD8α+ cDC1s, with slightly greater CD8+ T-cell proliferation. Further, in the absence of CD8α+ cDC1s, stimulated CD8+ T-cells exhibited significantly less PD-1 expression compared to CD4+ T-cells, and alloreactive T-cell death was significantly lower, driven by reduced CD4+ T-cell death. Tumor-killing assays revealed that T-cells primed with CD8α-depleted DCs ex vivo induce greater killing of A20 B-cell leukemia cells, particularly when antigen (Ag) is limited. Bulk RNA sequencing revealed distinct transcriptional programs of these DCs, with pre-cDC1s exhibiting activated PD-1/PD-L1 signaling compared to CD8α+ cDC1s. These results indicate distinct T-cell-priming capabilities of murine pre-cDC1s compared to CD8α+ cDC1s ex vivo, with potentially clinically relevant implications in suppressing GvHD while promoting GvL responses, highlighting the need for greater investigation of murine pre-cDC1s.This paper describes a protocol for the feasibility evaluation of the Participatory Action Research on Social and Emotional Learning (PARSEL) programme. PARSEL aims to contribute towards the development of academic achievement and resilience among urban refugee students in a community learning centre in an upper middle-income country. The evaluation is a single arm pre-post design using a mixed methods approach, with the main focus on the feasibility of the programme. Measurements of impact are also included as the secondary outcomes of the study. The programme aims to enrol students from refugee background in a community learning centre. The programme is estimated to run for 18 months and the study is due to report in the end of fourth quarter of 2022.In this work, for the performance enhancement of iron hexacyanoferrate, an electrochemically active Mn-doped iron hexacyanoferrate cathode is fabricated via a bottom-up approach. It is found that the pre-treatment of interstitial water and appropriate Mn doping are two keys to achieving higher capacity and higher stability. The interstitial water has a trade-off effect between the alleviation of volume expansion upon Na+ (de)intercalation and the retardation of Na-ion diffusion. The moisture-tailored iron hexacyanoferrate with appropriate Mn doping exhibits a high initial Coulombic efficiency of 94.8%, enhanced capacity and rate performance, and excellent cycling stability. These results benefit from the fact that the extraction/insertion of Na ions from/into the lattice via a solid-solution mechanism correspond to both the slight volume expansion and fast sodium diffusion rate; otherwise, the removal of interstitial water and a higher Mn content might lead to poor cycling stability due to excessive volume expansion resulting from rhombohedral to cubic phase transformation.

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