Correlation between toll-like receptor 9 expression in peripheral blood dendritic cells and interferon-α antiviral sustained virological response in patients with chronic hepatitis B

Purpose: To investigate the link between dendritic cells (DC cells), toll-like receptor 9 (TLR9) and tumor necrosis factor-α (TFN-α) expressions in peripheral blood of patients with chronic hepatitis B (CHB).Methods: Peripheral blood mononuclear cells (PBMC) and CD cells were prepared from CHB patients and healthy volunteers, and the cell  proliferation was assessed. The surface expressions of CD83, CD86, CD40 and human leukocyte antigen DR (HLA-DR) on DC cells were assayed by flow cytometry, while the expressions of mRNAs of TLR9, MyD88 and NF-κB in each cell-group were determined by fluorescent quantitation PCR. Protein expressions of TLR9, MyD88 and NF-κB were analyzed by Western blot.Results: The rate of proliferation of DC cells in the CHB patients was slower than the rate in healthy volunteers (p < 0.05), and the expression of co-stimulatory molecules was significantly lower in CHB patients than in healthy volunteers (p < 0.05). The ability to stimulate T-lymphocyte proliferation of the CHB-DC group was much weaker than that of the D-NC group (p < 0.05). In fluorescent quantitation assays, the relative expressions of mRNAs of TLR9, MyD88 and NF-κB in cells of CpG-Stimulate ODN (CpG-S ODN) group were higher than those of the control group (p < 0.05), but the relative expressions of mRNAs of TLR9, MyD88 and NF-κB in the cells of the CpG-S ODN group were significantly lower (p < 0.05). Moreover, IFN-α level in the CpG-S ODN group was much higher than that in the control group (t = 6.633, p = 0.014 < 0.05). However, results from  Western blot showed that the relative expressions of TLR9, MyD88 and NF-κB in the CpG-S ODN group were lower than in the control group (p < 0.05).Conclusion: These results indicate that TLR9 on the surface of DC cells of CHB patients can eliminate HBV by generating IFN-α via regulation of MyD88 and NF-κB.Keywords: Chronic hepatitis B, Dendritic cells, TLR9, IFN-

Construction of EMT related prognostic signature for kidney renal clear cell carcinoma, through integrating bulk and single-cell gene expression profiles

Introduction: Kidney renal clear cell carcinoma (KIRC), as a main type of malignant kidney cancers, has a poor prognosis. Epithelial-mesenchymal transformation (EMT) exerts indispensable role in tumor progression and metastasis, including in KIRC. This study aimed to mine more EMT related details and build prognostic signature for KIRC.Methods: The KIRC scRNA-seq data and bulk data were downloaded from GEO and TCGA databases, respectively. The cell composition in KIRC was calculated using CIBERSORT. Univariate Cox regression analysis and LASSO Cox regression analysis were combined to determine the prognostic genes. Gene set variation analysis and cell-cell communication analysis were conducted to obtain more functional information. Additionally, functional analyses were conducted to determine the biological roles of si-LGALS1 in vitro.Results: We totally identified 2,249 significant differentially expressed genes (DEGs) in KIRC samples, meanwhile a significant distinct expression pattern was found in KIRC, involving Epithelial Mesenchymal Transition pathway. Among all cell types, significantly higher proportion of epithelial cells were observed in KIRC, and 289 DEGs were identified in epithelial cells. After cross analysis of all DEGs and 970 EMT related genes, SPARC, TMSB10, LGALS1, and VEGFA were optimal to build prognostic model. Our EMT related showed good predictive performance in KIRC. Remarkably, si-LGALS1 could inhibit migration and invasion ability of KIRC cells, which might be involved in suppressing EMT process.Conclusion: A novel powerful EMT related prognostic signature was built for KIRC patients, based on SPARC, TMSB10, LGALS1, and VEGFA. Of which, si-LGALS1 could inhibit migration and invasion ability of KIRC cells, which might be involved in suppressing EMT process

Slip behavior during tension of rare earth magnesium alloys processed by different rolling methods

To expand the practical application of rare earth magnesium alloys, rare earth magnesium alloy sheets with no cracks and good plasticity were prepared by cross rolling. The plastic deformation behavior and fracture mechanism of cross rolling and conventional rolling were investigated, and the results showed that the twins after cross rolling have a certain effect on stimulating the activation of the slip systems with lower Schmid factor. The basal slip was dominant in conventional-rolled sheets. However, the plastic deformation process of cross-rolled magnesium alloys is dominated by both basal slip and non-basal slip, especially the second-order pyramidal slip. This is because cross-rolling reduces the critical shear stress of non-basal slip. Although the slip transfer between ordinary rolling grains is good, the activated slip cannot coordinate the c-axis strain. At the same time, the slender precipitation hinders the movement of dislocations and aggravates the strain concentration, which is likely to cause the generation of ledges and further develop into cracks. In the cross-rolling process, the short and flocculent precipitation decreases the resistance of dislocation movement, and the activated non-basal slip can coordinate the strain of the c-axis, which can better coordinate the deformation and reduce the possibility of cracking

Quasi-In-Situ Analysis of As-Rolled Microstructure of Magnesium Alloys during Annealing and Subsequent Plastic Deformation

In this paper, quasi-in situ experiments were carried out on rolled AZ31 magnesium alloy sheets to track the recrystallization behavior of the rolled microstructure during the heat treatment process and the plastic deformation behavior during the stretching process. The as-rolled microstructures are classified into five characteristics and their plastic deformation behaviors are described. The research shows that annealing recrystallization leads to grain reorganization, resulting in the diversity of grain orientation, and it is easier to activate basal slip. Recrystallization preferentially nucleates in the regions with high stress, while it is difficult for recrystallization to occur in regions with low stress, which leads to the uneven distribution of the as-rolled structure of magnesium alloys. Slip can be better transmitted between small grains, while deformation between large and small grains is difficult to transmit, which can easily lead to the generation of ledges. Incomplete recrystallization is more likely to accumulate dislocations than complete recrystallization, and ledges are formed in the early stage of deformation. Microcracks are more likely to occur between strain-incompatible grains. It is of great significance to promote the application of rolled AZ31 magnesium alloys for the development of heat treatment and subsequent plastic working of rolled magnesium alloys

Enhanced Formability of Magnesium Alloy Rolled Plates by 101¯2 Tensile Twinning and Recrystallization

To solve the problem of poor formability of magnesium alloys, the bending and straightening process was used to successfully introduce large-volume 101¯2 tensile twins and dynamic recrystallization into the plates, and the comprehensive mechanical properties of the plates were improved, in which the anisotropy index (Lankford value: r¯) decreased by 77%, and the corresponding Erishen value (IE) increased by 88%. The research shows that most of the continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX) inherit the grain orientation of the parent grains, and a few have deviations from the parent grains. The twinning-assisted dynamic recrystallization (TDRX) can effectively inherit the grain orientation of the parent grain and retain the orientation relationship of the 101¯2 tensile twin. The cooperation of the pre-set tensile twinning and various dynamic recrystallization processes leads to the deflection of the basal plane, which effectively weakens the basal texture and promotes the activation of various non-basal slip systems. Combined with grain refinement strengthening and dislocation strengthening, the magnesium alloy plate, after bending and straightening, obtains good comprehensive mechanical properties

BRPF1 bridges H3K4me3 and H3K23ac in human embryonic stem cells and is essential to pluripotency

Summary: Post-translational modifications (PTMs) on histones play essential roles in cell fate decisions during development. However, how these PTMs are recognized and coordinated remains to be fully illuminated. Here, we show that BRPF1, a multi-histone binding module protein, is essential for pluripotency in human embryonic stem cells (ESCs). BRPF1, H3K4me3, and H3K23ac substantially co-occupy the open chromatin and stemness genes in hESCs. BRPF1 deletion impairs H3K23ac in hESCs and leads to closed chromatin accessibility on stemness genes and hESC differentiation as well. Deletion of the N terminal or PHD-zinc knuckle-PHD (PZP) module in BRPF1 completely impairs its functions in hESCs while PWWP module deletion partially impacts the function. In sum, we reveal BRPF1, the multi-histone binding module protein that bridges the crosstalk between different histone modifications in hESCs to maintain pluripotency