Flexible electronics are a possible alternative for portable consumer applications and have many advantages. However, the circuit design for flexible electronics is still challenging, especially for ...sensitive analog circuits. Due to the different properties of flexible thin-film transistors (TFTs), conventional CMOS design techniques cannot be used directly on flexible electronics. Significant parameter variations and degradation effects of flexible TFTs further increase difficulties for circuit designers. In this paper, a reliability-aware circuit sizing approach is proposed for the analog circuits with flexible TFTs. The process variation, bending, and degradation effects of flexible TFTs in the optimization flow are considered simultaneously. Instead of optimizing the fresh yield and lifetime yield separately, a unified optimization approach is proposed to consider the two yield issues simultaneously. As shown in the experimental results, the proposed approach can further improve the lifetime yield and significantly reduce the design overhead with a fast computation time.
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•The large-scale of pure RFOs were separated from R. glutinosa by FPLC-RID.•Three RFOs were separated and purified from R. glutinosa.•FPLC-RID has the advantages of high automation ...and high efficiency.•The RFOs were identified by LC–MS/MS and GC–MS analysis.
Raffinose family oligosaccharides (RFOs) were extracted and isolated from Rehmannia glutinosa Libosch. by using microwave-assisted extraction and fast protein liquid chromatography coupled with refractive index detection (FPLC-RID). After extraction with 60% ethanol (v/v) and decolorization with MCI gel CHP20P, total oligosaccharides were purified by using FPLC-RID coupled with the Bio-Gel P2 column eluted with water at the flow rate of 0.3mL/min. Three pure oligosaccharides (DP3–DP5) were obtained with the yields of 1.72%, 7.52% and 0.51%, respectively, as well as identified as raffinose, stachyose and verbascose from the results of liquid chromatography coupled with tandem mass spectroscopy (LC–MS/MS) and gas chromatography coupled with mass spectroscopy (GC–MS) analysis. A large-scale of pure RFOs was automatically and efficiently separated from R. glutinosa by using FPLC-RID method, which was beneficial for the qualitative and quantitative analysis of RFOs in R. glutinosa and their products.
We have recently demonstrated that the greatly increased immunological activities of recombinant murine calreticulin (rCRT) are largely attributed to its self-oligomerization. Although native CRT ...(nCRT) can also oligomerize under stress conditions in vitro, whether this phenomenon could occur inside cells and the immunological activity difference between nCRT monomers and oligomers remained unclear. In this study, we illustrated the formation of CRT oligomers in tranfectant cells under "heat & low pH" (42°C/pH 6.5) condition. The mixture of nCRT oligomers and monomers (OnCRT) was obtained after 3 hr treatment of murine monomeric nCRT (MnCRT) under similar condition (42°C/pH 5.0) in vitro. The OnCRT thus obtained was better recognized by 2 monoclonal Abs from mice that had been immunized with oligomeric rCRT. Unlike MnCRT, OnCRT was able to elicit CRT-specific IgG production in mice. OnCRT also stimulated bone-marrow derived dendritic cells (BMDCs) to secrete significantly higher levels of TNF-α, IL-6 and IL-12p40 than did MnCRT in vitro. We postulate that oligomerization of soluble CRT may occur under certain pathophysiological conditions (e.g. ultrahyperpyrexia) and the resultant oligomers may exhibit exaggerated immunostimulating activities, thereby affiliating the inflammatory responses in vivo.
Agar is a common adulterant of edible bird's nest (EBN) and is often added in preparation of EBN products. Currently, there is no method that can be used to assess agar content in products because it ...is difficult to analyze a macromolecule that does not absorb UV. Herein, we report an efficient qualitative and quantitative method for detecting agar in food products based on a daughter oligosaccharide-marker approach. There are three steps: 1) acid hydrolysis of parent agar to release daughter oligosaccharides, 2) p-aminobenzoic ethyl ester (ABEE) labeling, 3) Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-QTOF-MS) analysis. Twenty-four daughter oligosaccharides found to be specific to agar were selected as qualitative authentication markers. One of them, which showed high signal abundance and satisfactory linearity with standard agar, was selected as the assay marker; and it was identified as neoagarotetraose by comparing with standard references. Based on this marker, a qualitative and quantitative analytical method was successfully developed and well-validated in terms of linearity, precision, repeatability, and accuracy. This method revealed that agar is being used as a minor adulterant (one out of 12) in EBN raw material. In this study, 60% of commercial “agar” was, in fact, starch and a significant number of EBN products labeled as having agar either did not contain agar or did not contain the amount listed on the label. It is proved that this oligomer approach can be used to improve quality control of all commercial products labeled as or containing agar. Furthermore, this oligomer approach is efficient and reliable in the quality analysis of other polymers like agar.
•An oligosaccharide marker approach to analyze the agar quality was established.•Twenty-four qualitative and one quantitative authentication marker were found.•The quantitative authentication marker was identified to be neoagarotetraose.•This method revealed the quality mess of agar and related EBN products.
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In our searching for novel tyrosinase inhibitors from natural sources, (S)-N-trans-feruloyloctopamine isolated from garlic skin was found to be a potential mushroom tyrosinase ...inhibitor. Here, we examined the effects of the potential tyrosinase inhibitor in B16F10 cells on intracellular melanin contents, cytotoxicity, and the signaling mechanism involved in the expression of tyrosinase. The results showed the inhibitor displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin contents in a dose-dependent manner in the α-MSH-stimulated B16F10 cells. Real-time PCR and Western blot analysis showed that it inhibits melanogenesis signaling by down-regulates mRNA and protein expression levels of tyrosinase, which leads to a lower melanin contents. These results suggested that (S)-N-trans-feruloyloctopamine was an ideal tyrosinase inhibitor, and could be used in food and medical industry.
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Programmed cell death protein 1 (PD-1)/ programmed cell death protein ligand 1 (PD-L1) is the key immune checkpoint governing evasion of advanced cancer from immune surveillance. ...Immuno-oncology (IO) therapy targeting PD-1/PD-L1 with traditional antibodies is a promising approach to multiple cancer types but to which the response rate remains moderate in breast cancer, calling for the need of exploring alternative IO targeting approaches. A miRNA-gene network was integrated by a bioinformatics approach and corroborated with The Cancer Genome Atlas (TCGA) to screen miRNAs regulating immune checkpoint genes and associated with patient survival. Here we show the identification of a novel microRNA miR-4759 which repressed RNA expression of the PD-L1 gene. miR-4759 targeted the PD-L1 gene through two binding motifs in the 3′ untranslated region (3′-UTR) of PD-L1. Reconstitution of miR-4759 inhibited PD-L1 expression and sensitized breast cancer cells to killing by immune cells. Treatment with miR-4759 suppressed tumor growth of orthotopic xenografts and promoted tumor infiltration of CD8+ T lymphocytes in immunocompetent mice. In contrast, miR-4759 had no effect to tumor growth in immunodeficient mice. In patients with breast cancer, expression of miR-4759 was preferentially downregulated in tumors compared to normal tissues and was associated with poor overall survival. Together, our results demonstrated miR-4759 as a novel non-coding RNA which promotes anti-tumor immunity of breast cancer.
GLI1, as an indispensable transcriptional factor of Hedgehog signaling pathway, plays an important role in the development of pancreatic cancer (PC). DNA methyltransferases (DNMTs) mediate the ...methylation of quantity of tumor-related genes. Our study aimed to explore the relationship between GLI1 and DNMTs.
Expressions of GLI1 and DNMTs were detected in tumor and adjacent normal tissues of PC patients by immunohistochemistry (IHC). PANC-1 cells were treated by cyclopamine and GLI1-siRNA, while BxPC-3 cells were transfected with overexpression-GLI1 lentiviral vector. Then GLI1 and DNMTs expression were analyzed by qRT-PCR and western blot (WB). Then we took chromatin immunoprecipitation (ChIP) to demonstrate GLI1 bind to DNMT1. Finally, nested MSP was taken to valuate the methylation levels of APC and hMLH1, when GLI1 expression altered.
IHC result suggested the expressions of GLI1, DNMT1 and DNMT3a in PC tissues were all higher than those in adjacent normal tissues (p<0.05). After GLI1 expression repressed by cyclopamine in mRNA and protein level (down-regulation 88.1±2.2%, 86.4±2.2%, respectively), DNMT1 and DNMT3a mRNA and protein level decreased by 91.6%±2.2% and 83.8±4.8%, 87.4±2.7% and 84.4±1.3%, respectively. When further knocked down the expression of GLI1 by siRNA (mRNA decreased by 88.6±2.1%, protein decreased by 63.5±4.5%), DNMT1 and DNMT3a mRNA decreased by 80.9±2.3% and 78.6±3.8% and protein decreased by 64.8±2.8% and 67.5±5.6%, respectively. Over-expression of GLI1 by GLI1 gene transfection (mRNA increased by 655.5±85.9%, and protein increased by 272.3±14.4%.), DNMT1 and DNMT3a mRNA and protein increased by 293.0±14.8% and 578.3±58.5%, 143.5±17.4% and 214.0±18.9%, respectively. ChIP assays showed GLI1 protein bound to DNMT1 but not to DNMT3a. Results of nested MSP demonstrated GLI1 expression affected the DNA methylation level of APC but not hMLH1 in PC.
DNMT1 and DNMT3a are regulated by GLI1 in PC, and DNMT1 is its direct target gene.
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