Role of ABCA7 in Human Health and in Alzheimer’s Disease

Several studies, including genome wide association studies (GWAS), have strongly suggested a central role for the ATP-binding cassette transporter subfamily A member 7 (ABCA7) in Alzheimer’s disease (AD). This ABC transporter is now considered as an important genetic determinant for late onset Alzheimer disease (LOAD) by regulating several molecular processes such as cholesterol metabolism and amyloid processing and clearance. In this review we shed light on these new functions and their cross-talk, explaining its implication in brain functioning, and therefore in AD onset and development.     

Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase).     

TGFβ-1 Induced Cross-Linking of the Extracellular Matrix of Primary Human Dermal Fibroblasts

Excessive cross-linking is a major factor in the resistance to the remodelling of the extracellular matrix (ECM) during fibrotic progression. The role of TGFβ signalling in impairing ECM remodelling has been demonstrated in various fibrotic models. We hypothesised that increased ECM cross-linking by TGFβ contributes to skin fibrosis in Systemic Sclerosis (SSc). Proteomics was used to identify cross-linking enzymes in the ECM of primary human dermal fibroblasts, and to compare their levels following treatment with TGFβ-1. A significant upregulation and enrichment of lysyl-oxidase-like 1, 2 and 4 and transglutaminase 2 were found. Western blotting confirmed the upregulation of lysyl hydroxylase 2 in the ECM. Increased transglutaminase activity in TGFβ-1 treated ECM was revealed from a cell-based assay. We employed a mass spectrometry-based method to identify alterations in the ECM cross-linking pattern caused by TGFβ-1. Cross-linking sites were identified in collagens I and V, fibrinogen and fibronectin. One cross-linking site in fibrinogen alpha was found only in TGFβ-treated samples. In conclusion, we have mapped novel cross-links between ECM proteins and demonstrated that activation of TGFβ signalling in cultured dermal fibroblasts upregulates multiple cross-linking enzymes in the ECM.     

汽车密封件双料一体旋转模具设计

针对PP+TPE汽车密封件设计了大型双料一体旋转注射模,介绍了二次合模的精确定位、可控注射系统、顶出平衡设计。该模具技术能够使两种性能完全不同的材料按照指定区域分布,并且达到塑件尺寸的精度需求,实现同时与钣金、玻璃、塑件等不同材质的零件进行复合配套。本项目实施后,在模具精度、寿命等方面接近或部分达到国外同类产品先进水平,而价格仅为国外产品的40%,性价比优势明显。     

Insight into the impact of zinc doping on the structural,surface, and biological properties of magnasium oxide nanoparticles stabilized by Vateria indica (L.) fruit extract

The present study is an attempt to delineate the effect of zinc doping on the green synthesized magnesium oxide (MgO) NPs. Pure (MgOVI) and zinc doped (ZnMgOVI) NPs were synthesized employing an aqueous fruit extract of V. indica as capping and reducing agents. The various analytical techniques viz. FTIR, PXRD, FESEM, and EDS spectroscopy together with elemental mapping analyses substantiated the formation of pure and doped NPs with crystallite sizes 23.74 and 25.41 nm. The study of surface properties through BET analysis unfolded the formation of mesoporous NPs with a surface area of 7.4 and 5.3 m²g^-1 for pure and doped NPs respectively. Additionally, the refinement of obtained PXRD data through Rietveld refinement corroborated the changes in cell parameters after zinc doping. The anti-inflammatory activity carried out unveiled the biocompatibility of obtained NPs by exhibiting a % HRBCS of 83.65 ± 0.002 and 85.69 ± 0.003 for MgOVI and ZnMgOVI NPs. The in-vitro antidiabetic activity of MgOVI and ZnMgOVI NPs performed revealed their excellent α-amylase inhibition activity (86.29 ± 0.001and 86.44 ± 0.002%). Furthermore, the NPs also displayed anti-microbial activities against Staphylococcus aureus, Bacillus subtulis, Pseudomonas aeroginosa, Pseudomonas syringae, and Escherichia coli. Thus the studies have evinced the superlative antidiabetic and antimicrobial potentialities of MgOVI and ZnMgOVI NPs with high biocompatibility.     

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer.     

Direct writing of textured ceramics using anisotropic nozzles

Direct writing is a unique means to align anisotropic particles for the fabrication of textured ceramics by templated grain growth (TGG). We show that alignment of tabular barium titanate (BT) template particles (20–40 μm width and 0.5–2 μm thickness) in a PIN-PMN-PT matrix powder (d₅₀ = 280 nm) is significantly improved during direct writing using anisotropic nozzles at high printing rates. The particle orientation distribution in as-printed filaments, and the texture orientation distribution in sintered ceramic filaments are shown to directly correlate with COMSOL Multiphysics-predicted torque distributions for direct writing with aspect ratio 2, 3 and 5 oval nozzles. Electromechanical strain properties of the textured piezoelectric ceramics significantly improved relative to random ceramics when printed with anisotropic nozzles. Simulations of aspect ratio 20 nozzles and nozzles with interior baffles demonstrate significantly increased torque and near elimination of constant shear stress cores (i.e. plug flow).