The Nocardia rubra cell wall skeleton (Nr-CWS) for external use is an immune enhancer, which has been widely used in human cervix diseases such as cervical erosion, but the mechanism of Nr-CWS ...enhancing immunity is still unclear. The purpose of this study was to explore the effect and mechanism of Nr-CWS on the local immune status of cervical tissue in patients with high-risk human papillomavirus (HR-HPV) infection and cervical precancerous lesion, cervical intraepithelial neoplasia (CIN). The recruited patients with HR-HPV infection and CIN were treated with Nr-CWS. The specimens were taken from these patients before and after local application of Nr-CWS respectively. The normal control specimens were tested simultaneously. Serial section analysis of immunohistochemistry and co-expression analysis were performed to characterize populations of T cells and the expressions of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1). The levels of cytokines in local cervical tissue were also detected. Nr-CWS significantly increased T cells including CD4
, CD8
T cells, and reduced the expression of PD-L1 in the patients' local cervical tissues. Co-expression analyses showed that the proportions of PD-1
CD4
cells in CD4
T cells and PD-1
CD8
cells in CD8
T cells decreased after Nr-CWS application. Furthermore, the increase in the number of immune cells was accompanied by increased pro-inflammatory cytokines interleukin-12 (IL-12), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and decreased suppressive cytokine IL-10. The results indicate that Nr-CWS, as an immunotherapeutic agent for HR-HPV infection and CIN, plays an immune promoting role related to the upregulation of T cell subsets and the inhibition of PD-1/PD-L1 pathway.
A solvent-free mechanochemical extraction (SFMCE) technology was applied to the extraction of chondroitin sulfate (CS) from
shark cartilage. This process was carried out via mechanical pretreatment ...(MPT) and mechanochemical treatment (MCT) in AGO-2 high-intensity planetary activator at room temperature under solvent-free condition. The yield of CS was increased from 8.50
±
0.16% to 9.33
±
0.14% and the purity of product was improved from 86.4
±
0.88% to 95.1
±
0.65%. The effectiveness of the MCT was confirmed by HPLC–ELSD analysis. The energy cost was decreased obviously due to the decrease of extraction time from 3
h to 3
min. SFMCE method was proved to be a high-efficient and energy-saving technique.
The waiting spectra of the sets consisting of pairs of sequences with prescribed quantitative waiting time indicators are determined. More precisely,let R（x,y） and R（x,y） be the lower and upper ...quantitative waiting time indicators of y by x respectively in the symbolic space Σm（integer m 2） and define the level sets Sα,β={（x,y）∈Σ2m：R（x,y）=α,R（x,y）=β},where 0αβ∞,it is shown that the sets Sα,βare all of Hausdorff dimension 2.Besides,some further extensions of this result are also made.
Objective Gluco-toxicity is a term used to convey the detrimental effect of hyperglycemia on β-cell function through impaired insulin synthesis. Although it is known that the expression and activity ...of several key insulin transcription regulators is inhibited, other molecular mechanisms that mediate gluco-toxicity are poorly defined. Our objective was to explore the role of hepcidin in β-cell gluco-toxicity. Design We first confirmed that high glucose levels inhibited hepcidin expression in the mouse insulinoma cell line, MIN6. The downregulation of hepcidin decreased Pdx-1 expression, which reduced insulin synthesis. Methods MIN6 cells were exposed to high glucose concentrations (33.3 mmol/L). Glucose-stimulated insulin secretion (GSIS) and serum hepcidin levels were measured by ELISA. The mRNA levels of insulin1, insulin2, Pdx-1 and hepcidin were measured by real-time polymerase chain reaction. Western blot analysis was used to detect the changes in PDX-1 expression. Transient overexpression with hepcidin was used to reverse the downregulation of Pdx-1 and insulin synthesis induced by gluco-toxicity. Results Exposure of MIN6 cells to high glucose significantly decreased GSIS and inhibited insulin synthesis as well as Pdx-1 transcriptional activity and expression at both the mRNA and protein levels. High glucose also decreased hepcidin expression and secretion. Hepcidin overexpression in MIN6 cells partially reversed the gluco-toxicity-induced downregulation of Pdx-1 and insulin expression and improved GSIS. The restoration of insulin synthesis by transfection of a hepcidin overexpression plasmid confirmed the role of hepcidin in mediating the gluco-toxic inhibition of insulin synthesis. Conclusions Our observations suggest that hepcidin is associated with gluco-toxicity-reduced pancreatic β-cell insulin synthesis in type 2 diabetes by inhibiting Pdx-1 expression.
In this article, a new method of option pricing in the form of fuzzy number is established based on fuzzy number binary tree model. Firstly,by using the operation rules of fuzzy number addition and ...number multiplication in cut set form, the fuzzy number binary tree model is equivalently transformed into two families of classical binary tree models which change with the level value, and some properties of the two binary tree model families are obtained, which are related to solve the problem of fuzzy option pricing. Then, based on the results obtained by us, the concepts of fuzzy set option price and fuzzy number option price are defined, and a sufficient condition is obtained for fuzzy set option price to be fuzzy number option price in the fuzzy number binary tree model. And then, for the convenience of practical application, the concepts of fold line fuzzy set and fuzzy number option price are introduced, a sufficient condition for fold line fuzzy set option price to be fold line fuzzy number option price is obtained, and a specific solution method of the fold line set and the fold line fuzzy number option pricing are set up. At last, two specific examples are given to show how to solve the fold line set and the fold line fuzzy number option price.
Consider the random intervals In（W） ：= （wn -en/2,Wn ＋en/2）（mod 1） with their centers wn being i.i.d, but not necessary uniformly distributed on the circle T = R/Z and with their lengths decreasing to ...zero. Using the dimension theory in dynamical systems, we give conditions on which the circle is finitely or infinitely often covered by intervals {In （ w ） } n≥ 1.
Cytokines are small proteins that have an essential role in the immune and inflammatory responses. The repertoire of cytokines is becoming diverse and expanding. Here we report the identification and ...characterization of a novel cytokine designated as chemokine-like factor 1 (CKLF1). The full-length cDNA of CKLF1 is 530 bp long and a single open reading frame encoding 99 amino acid residues. CKLF1 bears no significant similarity to any other known cytokine in its amino acid sequence. Expression of CKLF1 can be partly inhibited by interleukin 10 in PHA-stimulated U937 cells. Recombinant CKLF1 is a potent chemoattractant for neutrophils, monocytes and lymphocytes; moreover, it can stimulate the proliferation of murine skeletal muscle cells. These results suggest that CKLF1 might have important roles in inflammation and in the regeneration of skeletal muscle.
It has been proposed that immune injury is the central mechanism of pathogenesis of the infectious disease, severe acute respiratory syndrome (SARS). To gain a better understanding of immune injury ...in the spleen, we investigated the number and distribution of various immune cell types in the spleens of SARS patients. We performed autopsies on six confirmed SARS cases, with six normal subjects as controls; spleen samples from these autopsies were examined with hematoxylin and eosin (H&E) sections, in situ hybridization for SARS virus genomic sequences, and immunohistochemistry with seven monoclonal antibodies to five cell types. The number and distribution of these cells were measured and analyzed using an image analysis system. SARS genomic sequences were detected in all SARS spleens. The SARS spleens all had severe damage to the white pulp and showed an alteration of the normal distribution of various cell types. Immunocytes in the red pulp were decreased by 68.0–90.7% except for CD68 macrophages and human leukocyte antigen (HLA)‐DR positive antigen‐presenting cells (APC), which were decreased to a lesser degree. On average, CD68 macrophages were increased in size by 2.21‐fold. We hypothesize that the collapse of the splenic immune system plays a key role in the clinical outcome of these patients.—Zhan, J., Deng, R., Tang, J., Zhang, B., Tang, Y., Wang, J. K., Li, F., Anderson, V. M., McNutt, M. A., Gu, J. The spleen as a target in severe acute respiratory syndrome (SARS). FASEB J. 20, 2321–2328 (2006)
Cytokines are small proteins that have an essential role in the immune and inflammatory responses. The repertoire of cytokines is becoming diverse and expanding. Here we report the identification and ...characterization of a novel cytokine designated as chemokine-like factor 1 (CKLF1). The full-length cDNA of CKLF1 is 530bp long and a single open reading frame encoding 99 amino acid residues. CKLF1 bears no significant similarity to any other known cytokine in its amino acid sequence. Expression of CKLF1 can be partly inhibited by interleukin 10 in PHA-stimulated U937 cells. Recombinant CKLF1 is a potent chemoattractant for neutrophils, monocytes and lymphocytes; moreover, it can stimulate the proliferation of murine skeletal muscle cells. These results suggest that CKLF1 might have important roles in inflammation and in the regeneration of skeletal muscle.
A flexible solid‐state asymmetric supercapacitor based on bendable film electrodes with 3D expressway‐like architecture of graphenes and “hard nano‐spacer” is fabricated via an extended filtration ...assisted method. In the designed structure of the positive electrode, graphene sheets are densely packed, and Ni(OH)2 nanoplates are intercalated in between the densely stacked graphenes. The 3D expressway‐like electrodes exhibit superior supercapacitive performance including high gravimetric capacitance (≈573 F g‐1), high volumetric capacitance (≈655 F cm‐3), excellent rate capability, and superior cycling stability. In addition, another hybrid film of graphene and carbon nanotubes (CNT) is fabricated as the negative electrodes for the designed asymmetric device. In the obtained graphene@CNT films, CNTs served as the hard spacer to prevent restacking of graphene sheets but also as a conductive and robust network to facilitate the electrons collection/transport in order to fulfill the demand of high‐rate performance of the asymmetric supercapacitor. Based on these two hybrid electrode films, a solid‐state flexible asymmetric supercapacitor device is assembled, which is able to deliver competitive volumetric capacitance of 58.5 F cm‐3 and good rate capacity. There is no obvious degradation of the supercapacitor performance when the device is in bending configuration, suggesting the excellent flexibility of the device.
The fabrication of a flexible solid‐state asymmetric supercapacitor, based on bendable film electrodes with 3D expressway‐like architecture of graphenes and “hard nano‐spacer” via an extended filtration assisted method, is reported. The 3D expressway‐like electrode exhibits superior supercapacitive performance including high gravimetric capacitance (≈573 F g‐1), high volumetric capacitance (≈655 F cm‐3), excellent rate capability, and superior cycling stability.
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