The Structure and Performance of Short Glass Fiber/High-Density Polyethylene/Polypropylene Composite Pipes Extruded Using a Shearing–Drawing Compound Stress Field

Glass fiber reinforced polyolefin composite materials have many advantages regarding their performance and have been widely used in many fields. However, there are few reports on the simultaneously bidirectional self-enhancement of glass fiber reinforced polyethylene/polypropylene composite pipe. To self-reinforce the pipe’s circular and axial properties simultaneously, short glass fiber reinforced high-density polyethylene/polypropylene (SGF/HDPE/PP) pipes were extruded using a shearing–drawing two-dimensional compound stress field pipe-extrusion device. The effects of the rotating speed of the rotating shear sleeve on the orientation, heat behavior, microstructure, and tensile strength of the pipe were investigated in this paper. The microstructure was observed using scanning electron microscopy (SEM), and the crystal diffraction was analyzed using a polycrystalline X-ray diffractometer (WAXD), the heat behavior was measured using a differential scanning calorimeter (DSC), and the tensile strength was tested using a universal electronic tensile testing machine. The results showed that the shear induction effect induced by the shear rotating promoted the formation of the oriented structure of the crystal plate and SGFs along the circular and axial directions of the pipe simultaneously. Furthermore, it increased the crystallinity of the system, and self-improved the pipe’s circular and axial tensile strength at the same time

Real time Object Tracking based on Local Texture Feature with Correlation Filter

International audienceObject tracking is a fundamental problem in computer vision, therefore attracts many researchers and there has been many influential algorithms in the list few years. A good feature descriptor is half of the success. In this paper, we propose an effective tracking algorithm based on texture feature with correlation filter. We improve the tracking precision by Haar-like feature and speed it up via discrete Fourier transform. The feature which is a good representation of the target can be obtained via dense sampling. What is more important is that the feature containing a great deal of information of the target appears only in the form of low-dimension. With the property of circluant matrix, we can translate the processes of training and testing into Fourier domain, which can cut the computation and reduce the time complexity. Our algorithm is proved to have better performance especially in deformation and rotation in the benchmark datasets

Experimental observation of the effect of immunotherapy on CD4+ T cells and Th1/Th2 cytokines in mice with allergic rhinitis

Abstract The present study aims to investigate the effect of immunotherapy in a mouse model of allergic rhinitis (AR) and to explore the possible molecular mechanisms of action. An animal model of AR was established by sensitization and challenge of BALB/c mice with house dust mite (HDM) extract. The mice were injected subcutaneously with HDM for immunotherapy. AR nasal symptoms were evaluated according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The nasal mucosa and lung tissue architecture and inflammatory status by histological analysis; the infiltration of eosinophils in nasal lavage fluid (NALF) of mice was observed by Diff-Quik stain; ELISA-based quantification of serum HDM-specific IgE and TH1/TH2 cytokine concentration; and flow cytometry detected the number of serum CD4+/CD8+ cells to evaluate the mechanism of immunotherapy. It was found that after immunotherapy, the AR symptom score was reduced, the number of eosinophils in NALF was reduced, and the infiltration of inflammatory cells and tissue damage in the nasal mucosa and lung tissue were alleviated. Immunotherapy can increase the number of CD4+ T cells in the peripheral blood, increase the ratio of CD4+/CD8+ cells, increase the expression of Th1 cytokines such as IL-2 and IFN-γ, reduce the expression of Th2 cytokines such as IL-4 and IL-5. The results showed that repeated intraperitoneal injection of crude extract of HDM for sensitization, followed by nasal drops can effectively construct a mouse model of AR, and subcutaneous injection of immunotherapy in mice can reduce allergic inflammation in model mice and improve the inflammatory infiltration of the nasal cavity in allergic rhinitis. Immunotherapy can reduce the expression of inflammatory factors in AR, improve Th1/Th2 balance, and may play a role in the treatment of AR by improving the function of immune cells

Exosomal circEhmt1 Released from Hypoxia-Pretreated Pericytes Regulates High Glucose-Induced Microvascular Dysfunction via the NFIA/NLRP3 Pathway

Diabetic retinopathy (DR) is a frequently occurring microvascular complication induced by long-term hyperglycemia. Pericyte-endothelial cell crosstalk is critical for maintaining vascular homeostasis and remodeling; however, the molecular mechanism underlying that crosstalk remains unknown. In this study, we explored the crosstalk that occurs between endothelial cells and pericytes in response to diabetic retinopathy. Pericytes were stimulated with cobalt chloride (CoCl2) to activate the HIF pathway. Hypoxia-stimulated pericytes were cocultured with high glucose- (HG-) induced endotheliocytes. Cell viability was determined using the CCK-8 assay. Western blot studies were performed to detect the expression of proteins associated with apoptosis, hypoxia, and inflammation. ELISA assays were conducted to analyze the release of IL-1β and IL-18. We performed a circRNA microarray analysis of exosomal RNAs expressed under normoxic or hypoxic conditions. A FISH assay was performed to identify the location of circEhmt1 in pericytes. Chromatin immunoprecipitation (CHIP) was used to identify the specific DNA-binding site on the NFIA-NLRP3 complex. We found that pericyte survival was negatively correlated with the angiogenesis activity of endotheliocytes. We also found that hypoxia upregulated circEhmt1 expression in pericytes, and circEhmt1 could be transferred from pericytes to endotheliocytes via exosomes. Moreover, circEhmt1 overexpression protected endotheliocytes against HG-induced injury in vitro. Mechanistically, circEhmt1 was highly expressed in the nucleus of pericytes and could upregulate the levels of NFIA (a transcription factor) to suppress NLRP3-mediated inflammasome formation. Our study revealed a critical role for circEhmt1-mediated NFIA/NLRP3 signaling in retinal microvascular dysfunction and suggests that signaling pathway as a target for treating DR

Integrated analysis reveals the regulatory mechanism of the neddylation inhibitor MLN4924 on the metabolic dysregulation in rabbit granulosa cells

Abstract Background Neddylation, an important post-translational modification (PTM) of proteins, plays a crucial role in follicular development. MLN4924 is a small-molecule inhibitor of the neddylation-activating enzyme (NAE) that regulates various biological processes. However, the regulatory mechanisms of neddylation in rabbit ovarian cells have not been emphasized. Here, the transcriptome and metabolome profiles in granulosa cells (GCs) treated with MLN4924 were utilized to identify differentially expressed genes, followed by pathway analysis to precisely define the altered metabolisms. Results The results showed that 563 upregulated and 910 downregulated differentially expressed genes (DEGs) were mainly enriched in pathways related to cancer, cell cycle, PI3K-AKT, progesterone-mediated oocyte maturation, and PPAR signaling pathway. Furthermore, we characterized that MLN4924 inhibits PPAR-mediated lipid metabolism, and disrupts the cell cycle by promoting the apoptosis and proliferation of GCs. Importantly, we found the reduction of several metabolites in the MLN4924 treated GCs, including glycerophosphocholine, arachidic acid, and palmitic acid, which was consistent with the deregulation of PPAR signaling pathways. Furthermore, the increased metabolites included 6-Deoxy-6-sulfo-D-glucono-1,5-lactone and N-Acetyl-D-glucosaminyldiphosphodolichol. Combined with transcriptome data analyses, we identified genes that strongly correlate with metabolic dysregulation, particularly those related to glucose and lipid metabolism. Therefore, neddylation inhibition may disrupt the energy metabolism of GCs. Conclusions These results provide a foundation for in-depth research into the role and molecular mechanism of neddylation in ovary development

Multiplex LC-MS/MS Assays for Clinical Bioanalysis of MEDI4276, an Antibody-Drug Conjugate of Tubulysin Analogue Attached via Cleavable Linker to a Biparatopic Humanized Antibody against HER-2

Bioanalysis of complex biotherapeutics, such as antibody-drug conjugates (ADCs), is challenging and requires multiple assays to describe their pharmacokinetic (PK) profiles. To enable exposure-safety and exposure-efficacy analyses, as well as to understand the metabolism of ADC therapeutics, three bioanalytical methods are typically employed: Total Antibody, Antibody Conjugated Toxin or Total ADC and Unconjugated Toxin. MEDI4276 is an ADC comprised of biparatopic humanized antibody attached via a protease-cleavable peptide-based maleimidocaproyl linker to a tubulysin toxin (AZ13599185) with an approximate average drug-antibody ratio of 4. The conjugated payload of MEDI4276 can undergo ester hydrolysis to produce the conjugated payload AZ13687308, leading to the formation of MEDI1498 (de-acetylated MEDI4276). In this report, we describe the development, validation and application of three novel multiplex bioanalytical methods. The first ligand-binding liquid chromatography coupled with tandem mass spectrometry (LBA-LC-MS/MS) method was developed and validated for simultaneous measurement of total antibody and total ADC (antibody-conjugated AZ13599185) from MEDI4276. The second LBA-LC-MS/MS assay quantified total ADC (antibody-conjugated AZ13687308) from MEDI1498. The third multiplex LC-MS/MS assay was used for simultaneous quantification of unconjugated AZ13599185 and AZ13687308. Additional stability experiments confirmed that quantification of the released warhead in the presence of high concentrations of MEDI4276 was acceptable. Subsequently, the assays were employed in support of a first-in-human clinical trial (NCT02576548)

Quasi 3D polymerization in C60 bilayers in a fullerene solvate

The polymerization of fullerenes has been an interesting topic for almost three decades. A rich polymeric phase diagram of C60 has been drawn under a variety of pressure-temperature conditions. However, only linear or perpendicular linkages of C60 are found in the ordered phases. Here we used a unique bilayer structural solvate, C60∙1,1,2-trichloroethane (C60∙1TCAN), to generate a novel quasi-3D C60 polymer under high pressure and/or high temperature. Using Raman, IR spectroscopy and X-ray diffraction, we observe that the solvent molecules play a crucial role in confining the [2+2] cycloaddition bonds of C60s forming in the upper and lower layers alternately. The relatively long distance between the two bilayers restricts the covalent linkage extended in a single individual bilayer. Our studies not only enrich the phase diagram of polymeric C60, but also facilitate targeted design and synthesis of unique C60 polymers