Inducible heat shock protein 70 (Hsp70) is one of the most important HSPs for maintenance of cell integrity during normal cellular growth as well as pathophysiological conditions. Tumor necrosis factor receptor‐associated factor 6 (TRAF6) is a crucial signaling transducer that regulates a diverse array of physiological and pathological processes and is essential for activating NF‐κB signaling pathway in response to bacterial lipopolysaccharide (LPS). Here we report a novel mechanism of Hsp70 for preventing LPS‐induced NF‐κB activation in RAW264.7 macrophage‐like cells. Our results show that Hsp70 can associate with TRAF6 physically in the TRAF‐C domain and prevent TRAF6 ubiquitination. The stimulation of LPS dissociates the binding of Hsp70 and TRAF6 in a time‐dependent manner. Hsp70 inhibits LPS‐induced NF‐κB signaling cascade activation in heat‐shock treated as well as Hsp70 stable transfected RAW264.7 cells and subsequently decreases iNOS and COX‐2 expression. Two Hsp70 mutants, Hsp70ΔC(1–428aa) with N‐terminal ATPase domain and Hsp70C(428–642aa) with C‐terminal domain, lack the ability to influence TRAF6 ubiquitination and TRAF6‐triggered NF‐κB activation. Taken together, these findings indicate that Hsp70 inhibits LPS‐induced NF‐κB activation by binding TRAF6 and preventing its ubiquitination, and results in inhibition of inflammatory mediator production, which provides a new insight for analyzing the effects of Hsp70 on LPS‐triggered inflammatory signal transduction pathways.
In this study, partial fragments of potassium ion channel gene were amplified using the genomic DNA of muntjak, reevesi, crinifrons, and Elaphodus cephalophus. The PCR products were ligated to the plasmid of pMD18-T Vector by the method of direct T-A cloning. The positive clones were identified by colony PCR. The sequences of the recombinant clones were determined using M13-47/RV-M universal primers and aligned by the software CLUSTALW. The nucleotide divergences of exon were 0.90%-1.44% among three species of Muntiacus, 0.90%-1.26% between E. cephalophus and each of Muntiacus deer. In the nucleotide of intron there is 0%-1.22% difference among these muntjac deers, and the divergene reached about 1.83% between E. cephalophus and the three species of Muntiacus. Using the software of MEGA to analyse molecular phylogeny, Phylogenetic trees were constructed with neighbor-joining method and maximum parsimony method. The result showed Muntiacus, crinifrons is most closely related to muntjak, with reevesi as their sister species. E. cephalophus is in the other genus.
The tufted deer Elaphodus cephalophus are endangered animals in the world and little is understood about their mitochondrial (mt) genome. In our study, the mt genome of the tufted deer is identified--which is about 16 kb in length and contains 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and a non-coding sequence (control region). The distinguishing feature is that GTG is the start codon of the NADH4L gene and the cyt b gene has a subterminal AAA followed by the stop codon TAG. According to 12 H strand protein-coding genes and phylogenetic analysis, Elaphodus may have a sister relationship with another deer group Muntiacus.
In end-stage renal disease (ESRD), vascular calcification risk factors are essential for the survival of hemodialysis patients. To effectively assess the level of vascular calcification, the machine learning algorithm can be used to predict the vascular calcification risk in ESRD patients. As the amount of collected data is unbalanced under different risk levels, it has an influence on the classification task. So, an effective fuzzy support vector machine based on self-representation (FSVM-SR) is proposed to predict vascular calcification risk in this work. In addition, our method is also compared with other conventional machine learning methods, and the results show that our method can better complete the classification task of the vascular calcification risk.
This project aims to build up a soft robotic gripper that mimics human hands and design a closed-loop control system. A soft gripper model is established with Finite Element Method (FEM) to describ ...
Preparation of total RNA, cloning p16 cDNA, Southern Blot and in situ hybridization were used to study non-small cell lung cancer tissue. The Cloned p16 cDNA was proved by enzyme digesting. The deletion rate of p16~(INK4) gene exon 2 was 12.9% (4/31) in non-small cell lung cancer tissue by Southern blotting for PCR products. p16~(INK4) gene transcription negative rate of 22.6% (7/31) was confirmed by in situ hybridization analysis with p16~(INK4) cDNA probe. The result indicated that the cloned p16~(INK4) cDNA was correct, p16~(INK4) gene alterations plays a role in the development and progress of non-small cell lung cancer.
Background.The Kidney Disease Improving Global Outcomes (KDIGO) 2021 guidelines recommend Rituximab (RTX) as the first-line therapy and phospholipase receptor (PLA2R) antibody as a biomarker for remission and prognosis in patients with idiopathic membranous nephropathy (IMN).Methods.This study was a retrospective analysis of 70 patients with IMN treated with either rituximab (RTX) or cyclophosphamide (CTX) and steroid.Quantitative detection of PLA2R-IgG and PLA2R-IgG4 antibodies at sixth month after treatment, determined using time-resolved fluoroimmunoassay (TRFIA), were used for treatment effectiveness analysis and prognostic evaluation in patients with IMN.Results.After 12 months of therapy, the remission rate of proteinuria, including complete remission (CR) and partial remission (PR) in the RTX group and the CTX group, were 74% versus 67.5% (P=0.114),respectively.Both PLA2R-IgG and PLA2R-IgG4 levels were decreased in patients with remission of proteinuria after 6 months of therapy.Receiver operating characteristic curve (ROC) curve analysis exhibited that the AUC of PLA2R-IgG4 and the PLA2R-IgG as laboratory criteria for proteinuria remission were 0.970 versus 0.886 (P=0.0516),respectively, after 6 months of treatment.The cut-off value of PLA2R-IgG4 was 7.67 RU/mL and the sensitivity and specificity of remission rate at 6th month were 90.9% and 100%, respectively.Furthermore, the AUC of the PLA2R-IgG4 and PLA2R-IgG to predict the outcome after 12 months of treatment were 0.922 versus 0.897 (P=0.3270),respectively.With the cut-off value of PLA2R-IgG4 being 22.985 RU/mL, the sensitivity and specificity of remission rate at 12th month were 100% and 87.1%, respectively.Logistic regression analysis revealed that the PLA2R-IgG4 level (P=0.023), the rate of decrease of PLA2R-IgG4 level (P=0.034), and eGFR level (P=0.012) were significantly associated with remission.Conclusions.We found that the patients in the RTX group and CTX group
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