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Abstract Background MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma. Methods In this case–control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women. Results We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma. Conclusions The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.

A graphene modified electrode was prepared to establish an electrochemical method for the determination of ascorbic acid. The graphene modified electrode (ERGO/GCE) was prepared by one-step electrodeposition using electrochemical reduction technique. Electrochemical behavior of ascorbic acid (ascorbic acid, AA) on the modified electrode was investigated by cyclic voltammetry (cyclic voltammetry, CV). The results showed that the as-prepared graphene modified electrode had obvious electrocatalytic effect against ascorbic acid. In the phosphate buffer solution with ph=6.5, AA has an irreversible oxidation peak in the range of -0.4~0.8 V scanning potential. Under the optimized experimental conditions, the concentration of AA is linearly related to its oxidation peak current in the range of 1.1x10-3 mol/L~2x10-5, the correlation coefficient was 0.991, and the lowest detection limit was 9x10-6 mol/L (S/N 3). The stability and anti-interference of the modified electrode were investigated. The results showed that the electrode had good stability and strong anti-interference ability. The content of AA in fruit orange beverage was detected by modified electrode, and the recovery rate was between 97.95%~98.68%. Electrochemical method established in this paper can be used for the determination of AA in orange juice, and the results are satisfactory. [ABSTRACT FROM AUTHOR]

Recent realization of high sodium‐ion conductivities (>10−2 S cm−1) in inorganic solid electrolytes (ISEs) at room temperature will certainly trigger a boom in all‐solid‐state sodium batteries (ASS‐SBs). However, their electrochemical stable windows and compatibility to high capacity/voltage electrodes are unsatisfactory. Developing ideal ISEs that deliver high Na+ ion conductivities, good electrochemical/chemical stability, and compatible electrode/ISE interface is key for the success of high‐performance ASS‐SBs. In this review, focus is mainly on the fundamentals and strategies to optimize ASS‐SB performances from the aspects of ISE and interface, and note that interfacial issues are also ISE‐related. The latest progress in ISEs, including fundamentals of the sodium‐ion conduction mechanism, key parameters dominating the Na+ ion conduction in terms of crystal structure, lattice dynamics, point defects, and grain boundaries, and prototyping strategies for cell design, are elaborated from the perspectives of material and defect chemistry. The key challenges and future opportunities are discussed, and rational solutions are provided. [ABSTRACT FROM AUTHOR]

Abstract Background There is an urgent need to discover more sensitive and specific biomarkers to improve early diagnosis and screen high-risk patients for pancreatic ductal adenocarcinoma (PDAC). Pancreatic juice is an ideal specimen for PDAC biomarkers discovery, because it is an exceptionally rich source of proteins released from pancreatic cancer cells. Methods To identify novel potential biomarkers for PDAC from pancreatic juice, we carried out difference gel electrophoresis (DIGE) and tandem mass spectrometry (MS/MS) to compare the pancreatic juice profiling from 9 PDAC patients and 9 cancer-free controls. Of the identified differently expressed proteins, three up-regulated proteins in pancreatic cancer juice, matrix metalloproteinase-9 (MMP-9), oncogene DJ1 (DJ-1) and alpha-1B-glycoprotein precursor (A1BG), were selected for validation by Western blot and immunohistochemistry. Serum MMP-9 levels were also detected by enzyme linked immunosorbent assay (ELISA). Results Fourteen proteins were up-regulated and ten proteins were down-regulated in cancerous pancreatic juice compared with cancer-free controls. Increased MMP-9, DJ-1 and A1BG expression in cancerous pancreatic juice were confirmed by Western blot. Immunohistochemical study showed MMP-9, DJ-1 and A1BG positively expressed in 82.4%, 72.5% and 86.3% of pancreatic cancer tissues, significantly higher than that in normal pancreas tissues. Up-regulation of DJ-1 was associated with better differentiation (p < 0.05). Serum MMP-9 levels were significantly higher in PDAC (255.14 ng/ml) than those in chronic pancreatitis (210.22 ng/ml, p = 0.009) and healthy control (203.77 ng/ml, p = 0.027). Conclusion The present proteome analysis revealed MMP-9, DJ-1 and A1BG proteins as elevated in pancreatic juice from PDAC, which suggest their further utility in PDAC diagnosis and screening. This is the first time A1BG was identified as a potential biomarker in pancreatic cancer associated samples. The measurement of serum MMP-9 might be clinically useful for PDAC diagnosis.

Compared with the HLA‐B*38:02:01:01 allele, HLA‐B*38:97 differs by a single nucleotide substitution. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive lymphomas exhibiting increased glucose uptake. However, some DLBCLs featuring relatively low 18F-fluorodeoxyglucose (18F-FDG) uptake denoted by the maximum standardized uptake value (SUVmax) on PET/CT have been identified. The biologic correlates of such a heterogeneity have remained largely unknown. Herein, we immunohistochemically detected and found low FDG-avid DLBCL cases featuring lower expression of some key molecules involved in B-cell receptor (BCR) signaling (pSYK) and glucose metabolism (GLUT1 and HK2). Besides, BCR-deficient DLBCL xenografts were found displaying lower SUVmax and expressions of pSYK, GLUT1, and HK2. Further immunoblotting demonstrated expressions of GLUT1 and HK2 in BCR-dependent DLBCLs could be down-regulated by a chemical SYK inhibition, whereas the inhibitory effects were not observed in BCR-deficient tumors. These findings suggest low FDG-avid DLBCLs display a silent BCR signaling and PET/CT might be utilized to tailor the BCR signaling-inhibitory treatment. [ABSTRACT FROM AUTHOR]

Background: B cells can function as antigen-presenting cells by presenting antigens captured by the B-cell receptor (BCR) on Class II Major Histocompatibility Complex (MHC II) to T cells. In addition, B-cells can also maintain immune homeostasis by expressing PD-L1 and suppressing T-cell activity. Epstein-Barr virus (EBV) infection can disrupt B-cell function and lead to B cell malignancies, including diffuse large B-cell lymphoma (DLBCL). Here we show that EBV-positive DLBCL (EBV+ DLBCL) has decreased expression of BCR and MHC II, but over-expressed PD-L1, which may lead to immune evasion. Methods: An EBV+ DLBCL cohort (n = 30) and an EBV- DLBCL control cohort (n = 83) were established. Immunostaining of PD-L1, MHC II, MHC II Transactivator (CIITA) and pBTK was performed on automated stainer. H-score was used to denote the results of staining of PD-L1 and pBTK. Break apart and deletion of CIITA locus was studied by fluorescent in situ hybridization. Surface immunoglobulin mean fluorescent insensitivity (MFI) was detected by flow cytometry to demonstrate the level BCR. Results: EBV+ DLBCL showed significantly lower expression of CIITA and MHC II compared to EBV- DLBCL. Genetic aberrations involving CIITA were also more common in EBV+ DLBCL, with 23% break apart events and 6% deletion events, comparted to 2% break apart and 0% deletion in EBV- DLBCL. In addition to the loss of antigen presentation molecule, the antigen capture receptor, BCR, was also down-regulated in EBV+ DLBCL. Accordingly, BCR signaling was also significantly decreased in EBV+ DLBCL as denoted by the respective pBTK levels. Conclusions: EBV+ DLBCL shows over expression of the T-cell inhibitory ligand, PD-L1. Antigen capture and presentation system were disrupted, and T-cell inhibitory molecule was hijacked in EBV+ DLBCL, which may contribute to immune escape in this high risk disease. Therapies targeting these aberrations may improve the outcome of patients with EBV+ DLBCL. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is an autosomal recessive lysosomal storage disorder due to an inherited deficiency of [Beta]-glucuronidase. A naturally occurring mouse model for this disease was discovered at The Jackson Laboratory and shown to be due to homozygosity for a 1-bp deletion in exon 10 of the gus gene. The murine model MPS VII ([gus.sup.mps/mps]) has been very well characterized and used extensively to evaluate experimental strategies for lysosomal storage diseases, including bone marrow transplantation, enzyme replacement therapy, and gene therapy. To enhance the value of this model for enzyme and gene therapy, we produced a transgenic mouse expressing the human [Beta]-glucuronidase cDNA with an amino acid substitution at the active site nucleophile (E540A) and bred it onto the MPS VII ([gus.sup.mps/mps]) background. We demonstrate here that the mutant mice bearing the active site mutant human transgene retain the clinical, morphological, biochemical, and histopathological characteristics of the original MPS VII ([gus.sup.mps/mps]) mouse. However, they are now tolerant to immune challenge with human [Beta]-glucuronidase. This 'tolerant MPS VII mouse model' should be useful for preclinical trials evaluating the effectiveness of enzyme and/or gene therapy with the human gene products likely to be administered to human patients with MPS VII.