课程文献中心 更多>>

摘要： Long-lived memory B cells developing from germinal centers (GCs) are important contributors to protective immunity. In this issue of Immunity, Luo et al. report that during primary responses, T cell-derived interleukin-9 potentiates differentiation of GC memory precursors into functional memory B cells in a manner dependent on the transcriptional regulator ZBTB18.

关键词： Human leukocyte antigen typing   Long read sequencing   Organ transplantation   Oxford nanopore technology  

摘要： BACKGROUND:Rapid turnaround time for a third-field resolution deceased donor human leukocyte antigen (HLA) typing is critical to improve organ transplantation outcomes. Third generation DNA sequencing platforms such as Oxford Nanopore (ONT) offer the opportunity to deliver rapid results at single nucleotide level resolution, in particular sequencing data that could be denoised computationally. Here we present a computational pipeline for up-to third-field HLA allele typing following ONT sequencing. RESULTS:From a R10.3 flow cell batch of 31 samples of known HLA allele types, up to 10,000 ONT reads were aligned using BWA aligner to reference allele sequences from the IPD-IMGT/HLA database. For each gene, the top two hits to reference alleles at the third field were selected. Using our pipeline, we obtained the following percent concordance at the 1st, 2nd and 3rd field: HLA-A (98.4%, 98.4%, 98.4%), HLA-B (100%, 96.8%, 96.8%), HLA-C (100%, 98.4%, 98.4%), HLA-DPA1 (100%, 96.8%, 96.8%), HLA-DPB1 (100%, 100%, 98.4%), HLA-DQA1 (100%, 98.4%, 98.4%), HLA-DQB1 (100%, 98.4%, 98.4%), HLA-DRB1 (83.9%, 64.5%, 64.5%), HLA-DRB3 (82.6%, 73.9%, 73.9%), HLA-DRB4 (100%, 100%, 100%) and HLA-DRB5 (100%, 100%, 100%). By running our pipeline on an additional R10.3 flow cell batch of 63 samples, the following percent concordances were obtained:: HLA-A (100%, 96.8%, 88.1%), HLA-B (100%, 90.5.4%, 88.1%), HLA-C (100%, 99.2%, 99.2%), HLA-DPA1 (100%, 98.4%, 97.6%), HLA-DPB1 (98.4%, 97.6%, 92.9%), HLA-DQA1 (100%, 100%, 98.4%), HLA-DQB1 (100%, 97.6%, 96.0%), HLA-DRB1 (88.9%, 68.3%, 68.3%), HLA-DRB3 (81.0%, 61.9%, 61.9%), HLA-DRB4 (100%, 97.4%, 94.7%) and HLA-DRB5 (73.3%, 66.7%, 66.7%). In addition, our pipeline demonstrated significantly improved concordance compared to publicly available pipeline HLA-LA and concordances close to Athlon2 in commercial development. CONCLUSION:Our algorithm had a > 96% concordance for non-HLA-DRB genes at 3rd field on the first batch and > 88% concordance for non-H

关键词： Cyclic voltammetry  

摘要： Methyl parathion (MP) is a widely used pesticide;it is recognized as being toxic to both target and non-target species, posing serious risks to environmental and human health. Monitoring and controlling MP residues is thus essential, necessitating the development of innovative sensors that are highly sensitive, selective, and reproducible. In the present study, an efficient electrochemical MP sensor is proposed based on silver nanoparticles (AgNPs) in conjunction with graphene oxide/ionic liquid (GO/IL) on screen printed electrodes (AgNPs@GO/IL@SPCE). The AgNPs were synthesized via a cost-effective wet-chemical process and characterized using UV-Vis spectroscopy and transmission electron microscopy (TEM). The modified electrodes were characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The active surface area and charge transfer were examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), respectively. The modified electrodes' electrocatalytic performance towards the reduction of MP was investigated by CV, complemented by semiempirical quantum chemistry calculations to elucidate the interaction and the electrochemical reduction mechanism of MP. The sensor demonstrates a remarkable limit of detection of 0.009 mu mol L-1 within a linear range of 0.025 to 200 mu mol L-1. It has an excellent analytical performance in terms of selectivity, reproducibility, and long-term stability over 60 days. The designed sensor was effectively used to inspect MP in groundwater and surface water samples, with recovery values ranging from 95.60% to 99.68%.

关键词： acute soft tissue injury   contusion   pulse radiofrequency   TNF/mTOR signaling  

摘要： Objective: Acute traumatic muscle injuries are common and result in substantial loss of time and risk of recurrence. Pulsed radiofrequency (PR) is a strategy that has been gradually adopted for treating muscle injuries in clinical practice. However, the molecular mechanism underlying its therapeutic effects is currently *** and Methods: In this study, we screened the gene expression profiles of rats with muscle contusion obtained from the online dataset GSE162565. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the differentially expressed genes were conducted. Further, we established an acute soft tissue injury (ASTI) rat model and applied PR treatment. Muscle swelling rate analysis, malondialdehyde (MAD) and superoxide dismutase (SOD) content, inflammatory cytokine release, and hematoxylin and eosin staining of the gastrocnemius muscles of ASTI and ASTI + PR rats were performed, and the results were compared with those of control rats. Further, we evaluated the gene expression of Ccl1, interleukin-6 (IL-6), nuclear factor-kappa-B-inhibitor alpha (Nfkbia), Akt1, Jun, Fos, and Caps3 in the model and PR-treated groups, all of which are key genes in the tumor necrosis factor (TNF)/mechanistic target of rapamycin (mTOR) signaling pathway according to the KEGG ***: The results revealed that 52 genes involved in the TNF/mTOR signaling pathway were closely associated with ASTI progression in rats. PR treatment significantly reduced the malondialdehyde content but increased the SOD content in ASTI model rat muscles, efficiently alleviated muscle contusions and reduced TNF-alpha and IL-1 beta production. Moreover, PR treatment significantly decreased Ccl1, IL-6, and Nfkbia expression but increased Akt1, Jun, Fos, and Caps3 levels in ASTI models. These data indicate that PR alleviated ASTI in rats by mediating redox homeostasis and the inflammatory response, which might be modulated by the TNF/mTOR signaling

关键词： Immunoassay   Immunomarker   Tissue regeneration   Wound healing   Wound infection   Wound micro-environment   Wound swabbing  

摘要： BACKGROUND:Chronic wounds, such as diabetic foot ulcers, venous leg ulcers, and post-surgical wound healing disorders pose a significant challenge due to prolonged healing, risk of infection, and impaired quality of life. Persistent inflammation and impaired tissue remodeling are common in these wounds. Traditional diagnostic methods, including visual inspection and microbiological cultures, offer limited insight into the wound micro-environment. Immunomarker profiling could provide a deeper understanding of the molecular mechanisms underpinning wound healing, offering potential biomarkers for infection status and healing progression. METHODS:This observational, multi-center cohort study, part of the 'Wound-BIOME' project, analyzed 110 swab samples from patients with acute and chronic wounds using multiplex immunoassays. Clinical parameters such as wound type, healing status, regeneration stage, and microbial burden were recorded. Total protein concentration was assessed, and 35 key immunomarkers, including cytokines (e.g. IL- 1α, IL- 1β), chemokines (CCL2, CXCL8, CXCL10), growth factors (FGF- 2, VEGF) and matrix metalloproteinases (MMP- 7, MMP- 9, MMP- 13), were quantified. Statistical analyses were performed to correlate immunomarker levels with clinical outcomes. RESULTS:Pro-inflammatory markers, such as IL- 1β, IL- 18 and chemokines like CCL2 and CXCL8, were significantly elevated in non-healing and infected wounds compared to healing wounds. The study identified two new immunomarker ratios - IL- 1β/IL- 1RA and CXCL8/CXCL10 - as potential predictors of wound healing status. The IL- 1β/IL- 1RA ratio showed the highest accuracy for distinguishing healing from non-healing wounds (AUC = 0.6837), while the CXCL8/CXCL10 ratio was most effective in identifying infection (AUC = 0.7669). CONCLUSIONS:Immunomarker profiling via wound swabbing offers valuable insights into the wound healing process. Elevated levels of pro-inflammatory cytokines and MMPs are associated with

关键词： T regulatory cells   autoimmunity   experimental autoimmune encephalomyelitis   interleukin-2  

摘要： Experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin basic protein (MBP) is a self-limiting disease model of multiple sclerosis. CD4CD25Foxp3T cells play a role in limiting autoimmune disease but treatment with antigen naïve CD4CD25 cells does not reduce EAE. This study examined if in vitro activation by MBP and rIL-2 induced CD4CD25Foxp3 cells that could inhibit EAE. Culture of CD4CD8CD25cells from naïve rats with MBP and rIL-2 induced activated Treg that reduced the severity of clinical EAE and infiltration of CD8T cells and macrophage into brain stem. CD4CD25T cells activated by an irrelevant autoantigen and rIL-2 did not suppress EAE. Resting CD4CD25T cells activated by autoantigen and rIL-2 have mRNA for Infgr, Il12rb2, Il5 but not Tbet, Gata3, Ilr5ra or Ifng. These changes in mRNA expression are the markers of Ts1 cells. A proportion of CD4CD8CD25 cells activated by MBP/rIL-2 were induced to express CD8α, CD8β and CD62L. Depletion of CD4CD8αCD25 cells removed the capacity of MBP and rIL-2 activated CD4CD25T cells to suppress EAE. This study demonstrated that in vitro activation of CD4CD8CD25 cells by MBP/rIL-2 induced relevant antigen-specific Treg within days, which expressed CD8α, CD8β and CD62L with a Ts1 phenotype and that had greater potency than freshly isolated antigen naive CD4CD25Treg in suppressing clinical severity of EAE and immune inflammation in CNS. These findings may guide development of antigen-specific Treg for therapy.

关键词： Chronic infectious disease   Direct-acting antiviral (DAA) treatment   Global Health Sector Strategy (GHSS)   HCV elimination goals   HCV treatment access   Hepatitis C (HCV)   Liver disease   Viral hepatitis elimination