T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells

Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62LhighCD44low Sca-1+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells. © 2013 Li et al

Identification of Molecular Signatures in Epicardial Adipose Tissue in Heart Failure With Preserved Ejection Fraction

AIMS: The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non-coding RNAs (lncRNAs) in EAT that might modulate HFpEF development. METHODS: RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real-time PCR (qRT-PCR). Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of differentially expressed RNAs was performed to predict enriched functions. RESULTS: HFpEF patients had higher EAT thickness and NT-proBNP levels than the control group. A total of 64 471 transcripts were detected including 35 395 protein-coding sequences, corresponding to 16 854 genes in EAT. RNA-seq identified a total of 741 dysregulated mRNA transcripts (394 up-regulated and 347 down-regulated) and 334 differentially expressed lncRNA transcripts (222 up-regulated and 112 down-regulated) in the HFpEF group compared with the control group (P \u3c 0.05). qRT-PCR analysis confirmed that two lncRNAs ENST00000561775 (P = 0.0194) and ENST00000519093 (P = 0.027) and an mRNA POSTN (P = 0.003) were differentially expressed. Functional enrichment analysis of the differentially expressed mRNAs suggested their potential roles in immune response involving cytokine interaction and chemokine signalling. CONCLUSIONS: We are the first group to report on the lncRNA and mRNA landscape in EAT in HFpEF patients. Our study suggests the possible role of lncRNAs in EAT

GWAS Identifies Novel Susceptibility Loci on 6p21.32 and 21q21.3 for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers

Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×$10^{−19}$) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×$10^{−8}$), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×$10^{−4}$; rs455804: OR = 0.84, P = 6.92×$10^{−3}$). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC

Construction of genetic map in barley using sequence-related amplified polymorphism markers, a new molecular marker technique

Sequence-related amplified polymorphism (SRAP) markers, a novel polymerase chain reaction (PCR)-based molecular marker technique, were successfully applied in map construction, cultivar identification, diversity evaluation, comparative genomics and gene location of different plant species. The molecular genetic map of SRAP markers in Steptoe / Morex doubled haploid (DH) population was constructed in this study, using 216 SRAP markers and 312 simple sequence repeat (SSR) markers. Overall, 21 of the 216 SRAP markers generated 78 polymorphic loci, and 98 of 312 SSR markers produced 107 polymorphic loci. Among the 185 loci, 175 loci (70 SRAP loci and 105 SSR loci) were assigned to nine linkage groups. The map covered 1475 cM with a mean density of 8.7 cM per locus. In total, 33 of all the loci (17.84%) showed significant segregation distortion. Moreover, 23 of the 33 loci (69.7%) skewed towards the parent Steptoe, whereas the remaining loci (21.3%) deviated towards the parent Morex and some of these distorted loci tended to cluster at the end of linkage groups, while others were dispersed on linkage groups in a decentralized fashion. The three putative segregation distortion regions (SDRs) were detected on chromosomes 2H, 4H and 5H, respectively. This linkage map indicates its importance in quantitative trait loci (QTLs) mapping, marker-assisted selection (MAS) and integrative analysis for further genetic studies with other linkage maps in barley.Keywords: Barley, sequence-related amplified polymorphism (SRAP), molecular genetic map, simple sequence repeat (SSR), doubled haploid (DH) populatio

Marine fish species recognition based on improved YOLOv5s

ObjectiveIn order to improve the recognition accuracy of different kinds of marine fish, an improved YOLOv5s marine fish species recognition method was proposed.MethodsK⁃means++algorithm was used to cluster the real frames of marine fish, and more matching anchor frames were obtained with the self built data set. CIoU Loss function was replaced by SIoU Loss function as the boundary box regression algorithm to improve the accuracy and rate of convergence of the boundary box regression. Improved some C3 modules of the backbone network, and integrated CA coordination attention mechanism into the C3 module, which improved the recognition accuracy and detection speed of the model while reducing the number of model parameters. Finally, optimized the path aggregation network of the model to enhance the feature fusion ability of the network.ResultsThe experimental results showed that the improved Our⁃YOLOv5s model had a mAP of 98.4% and a detection speed of 64 s-1 in the dataset, which was 2.4% and 6 s-1 higher than the original model, respectively.ConclusionThe model can meet the real⁃time detection requirements of marine fish

Assessment of genetic diversity in chinese hulless barley accessions for qualitative traits

Cultivated barley (Hordeum vulgare L.) has been proven to be an economically important model plant and having large genetic diversity among the species. The effective exploitation of qualitative characters in barley can be measured by its genetic diversity and interrelationship. This study aims to determine the assessment of genetic diversity in Chinese hulless barley accessions for qualitative traits. Presently, in this study, the genetic diversity of 208 Chinese hulless barley from different Provinces of China, 111 genotypes were from the Tibet plateau, 30 Sichuan, 2 USA, 1 Canada, 12 Gansu, 51 Qinghai, 1 Yunnan was investigated; collected. Almost all the qualitative traits including crude protein, fiber, starch, neutral detergent fiber, and acid detergent fiber exhibited significantly high variability (p≤0.0001) among the cultivars. The data were analyzed using Statistics 8.1. In this study, significantly high variation was observed between starch content and neutral detergent fiber (23.64% and 11.54%). However, the highest diversity is based on the magnitude of the coefficient of variation exhibited in crude protein (13.82%), starch (12.87%), and fiber (12.17%). There was a significantly positive correlation between fiber, acid detergent fiber, and neutral detergent fiber except for starch content with crude protein and fiber that exhibited a significant negative correlation (r= -0.38*** and r= -0.92***). A large genetic diversity was observed through cluster analysis among all the 208 barley accessions, distance coefficient ranging between 0.28 and 75.86. The histogram revealed that frequency distributions of 208 different genotypes of hulless barley crop with all five different characters, crude protein, fiber, starch, neutral detergent fiber, and acid detergent fiber, showed normal distribution. It is concluded that this hulless barley study showed genetic diversity among the accessions and confirmed genetic diversity in various traits used

Dynamic Hydrogel-Metal-Organic Framework System Promotes Bone Regeneration in Periodontitis Through Controlled Drug Delivery

Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar bone repair due to the unique bacterial microenvironment\u27s impact on immune responses. This study explores a novel approach utilizing Metal-Organic Frameworks (MOFs) (comprising magnesium and gallic acid) for promoting bone regeneration in periodontitis, which focuses on the physiological roles of magnesium ions in bone repair and gallic acid\u27s antioxidant and immunomodulatory properties. However, the dynamic oral environment and irregular periodontal pockets pose challenges for sustained drug delivery. A smart responsive hydrogel system, integrating Carboxymethyl Chitosan (CMCS), Dextran (DEX) and 4-formylphenylboronic acid (4-FPBA) was designed to address this problem. The injectable self-healing hydrogel forms a dual-crosslinked network, incorporating the MOF and rendering its on-demand release sensitive to reactive oxygen species (ROS) levels and pH levels of periodontitis. We seek to analyze the hydrogel\u27s synergistic effects with MOFs in antibacterial functions, immunomodulation and promotion of bone regeneration in periodontitis. In vivo and in vitro experiment validated the system\u27s efficacy in inhibiting inflammation-related genes and proteins expression to foster periodontal bone regeneration. This dynamic hydrogel system with MOFs, shows promise as a potential therapeutic avenue for addressing the challenges in bone regeneration in periodontitis

Elevated IL-6 Receptor Expression on CD4+ T Cells contributes to the increased Th17 Responses in patients with Chronic Hepatitis B

<p>Abstract</p> <p>Background</p> <p>Increased numbers of Interleukin-17-producing CD4⁺T cells (Th17) have been found in association with hepatitis B virus (HBV)-induced liver injury. However, the mechanism underlying the increase of Th17 responses in patients with HBV infection remains unclear. In this study, we investigate the possible regulatory mechanisms of increased Th17 responses in patients with chronic hepatitis B(CHB).</p> <p>Methods</p> <p>Th17 response and IL-6R expression on CD4⁺T cells in peripheral blood samples were determined by flow cytometry. Cytokines TGF-β, IL-1β, IL-6 and IL-17 in plasma and/or supernatant samples were determined by ELISA and the IL-17 and IL-6R mRNA levels were quantified by quantitative real-time reverse polymerase chain reaction.</p> <p>Results</p> <p>All these data indicated that the frequency of periphery Th17 cells is significantly correlated with the percentage of CD4<b>⁺</b>T cells expressing IL-6R in CHB patients. CD4⁺T cells from patients with CHB, but not those from healthy donors, produced higher levels of IL-17 and had more IL-6R expression upon stimulation with the HBV core antigen (HBcAg) in vitro. The PMA/ionomycin and HBcAg -stimulated up-regulation of IL-17 production by CD4⁺T cells could be reversed by a neutralizing antibody against IL-6R.</p> <p>Conclusion</p> <p>we showed that enhancement of IL-6R expression on CD4⁺T cells upon HBV infection contributes to increased Th17 response in patients with CHB.</p

Predictive Value of a Combination of the Age, Creatinine and Ejection Fraction (ACEF) Score and Fibrinogen Level in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Background: The purpose of this study was to explore whether consideration of FIB levels might improve the predictive value of the ACEF score in patients with ACS. Methods: A total of 290 patients with ACS were enrolled in this study. The clinical characteristics and MACE were recorded. Results: Multivariate logistic regression analysis revealed that the FIB level (odds ratio=7.798, 95%CI, 3.44–17.676, P<0.001) and SYNTAX score (odds ratio=1.034, 95%CI, 1.001–1.069, P=0.041) were independent predictors of MACE. On the basis of the regression coefficient for FIB, the ACEF-FIB was developed. The area under the ROC of the ACEF-FIB scoring system in predicting MACE after PCI was 0.753 (95%CI 0.688–0.817, P<0.001), a value greater than those for the ACEF score, SYNTAX score and Grace score (0.627, 0.637 and 0.570, respectively). Conclusion: ACEF-FIB had better discrimination ability than the other risk scores, according to ROC curve analysis, net reclassification improvement and integrated discrimination improvement