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This review addresses the neurotoxic and neuroprotective impact of illicit substance consumption in PD, presenting clinical evidence and molecular and cellular mechanisms of this association. This research area is utterly important for contemporary society since illicit drugs' legalization is under discussion which may have consequences both for the onset of PD and for the treatment of its symptoms.The folate receptor (FR) is a promising cell membrane-associated target for molecular imaging and radionuclide therapy of cancer (FR-α) and potentially also inflammatory diseases (FR-β) through use of folic acid-based radioconjugate. FR is often overexpressed by cells of epithelial tumors, including tumors of ovary, cervix, endometrium, lungs, kidneys, etc. In healthy tissues, FR can be found in small numbers by the epithelial cells, mainly in the kidneys. Selleckchem ZD1839 Extremely high undesired accumulation of the folate radioconjugates in the renal tissue is a main drawback of FR-targeting concept. In the course of this work, we aimed to reduce the undesirable accumulation of folate radioconjugates in the kidneys by introducing a histidine/glutamic acid tag into their structure. Two folic acid based compounds were synthesized NODAGA-1,4-butanediamine-folic acid (FA-I, as control) and NODAGA-[Lys-(HE)2]-folic acid (FA-II) which contains a (His-Glu)2 fragment. In vitro studies with FR (+) cells (KB and others) showed that both compounds have specificity for FR. Introduction of (HE)2-tag does not affect FR binding ability of the conjugates. In vivo biodistribution studies with normal laboratory animals, as well as with KB tumor bearing animals, were carried out. The results showed that introduction of the (HE)2 tag into the structure of folate radioconjugates can significantly reduce the accumulation of these compounds in non-target tissues and important organs (the accumulation in the kidneys is reduced 2-4 times), leaving the accumulation in tumor at least at the same level, and even increasing it.A rivet-inspired method of decorating aramid fiber (AF) with silica particles (SiO2) is proposed to produce SiO2@AF hybrid materials that have largely enhanced interfacial interaction with the rubber matrix. AF was firstly surface-modified with polyacrylic acid (PAA) to obtain PAA-AF, and SiO2 was silanized with 3-aminopropyltriethoxysilane to obtain APES-SiO2. Then, SiO2@AF was prepared by chemically bonding APES-SiO2 onto the surface of PAA-AF in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). With the incorporation of SiO2@AF into the rubber matrix, SiO2@AF hybrid materials with high surface roughness can play a role as 'rivets' to immobilize large numbers of rubber chains on the surface. The tear strength and tensile strength of rubber composite that filling 4 phr SiO2@AF are dramatically increased by 97.8% and 89.3% compared to pure rubber, respectively. Furthermore, SiO2@AF has superiority in enhancing the cutting resistance of rubber composites, in contrast with unmodified AF and SiO2. SiO2@AF is suitable to be applied as a novel reinforcing filler in rubber composites for high performance.Lung cancer (LC) represents the topmost mortality-causing cancer in the U.S. LC patients have overall poor survival rate with limited available treatment options. Dysregulation of the mesenchymal epithelial transition factor (c-MET) and cyclooxygenase 2 (COX2) initiates aggressive LC profile in a subset of patients. The Mediterranean extra-virgin olive oil (EVOO)-rich diet already documented to reduce multiple malignancies incidence. (-)-Oleocanthal (OC) is a naturally occurring phenolic secoiridoid exclusively occurring in EVOO and showed documented anti-breast and other cancer activities via targeting c-MET. This study shows the novel ability of OC to suppress LC progression and metastasis through dual targeting of c-MET and COX-2. Western blot analysis and COX enzymatic assay showed significant reduction in the total and activated c-MET levels and inhibition of COX1/2 activity in the lung adenocarcinoma cells A549 and NCI-H322M, in vitro. In addition, OC treatment caused a dose-dependent inhibition of the HGF-induced LC cells migration. Daily oral treatment with 10 mg/kg OC for 8 weeks significantly suppressed the LC A549-Luc progression and prevented metastasis to brain and other organs in a nude mouse tail vein injection model. Further, microarray data of OC-treated lung tumors showed a distinct gene signature that confirmed the dual targeting of c-MET and COX2. Thus, the EVOO-based OC is an effective lead with translational potential for use as a prospective nutraceutical to control LC progression and metastasis.The rapid growth of Additive Manufacturing (AM) in the past decade has demonstrated a significant potential in cost-effective production with a superior quality product. A numerical simulation is a steep way to learn and improve the product quality, life cycle, and production cost. To cope with the growing AM field, researchers are exploring different techniques, methods, models to simulate the AM process efficiently. The goal is to develop a thermo-mechanical weld model for the Directed Energy Deposition (DED) process for 316L stainless steel at an efficient computational cost targeting to model large AM parts in residual stress calculation. To adapt the weld model to the DED simulation, single and multi-track thermal simulations were carried out. Numerical results were validated by the DED experiment. A good agreement was found between predicted temperature trends for numerical simulation and experimental results. A large number of weld tracks in the 3D solid AM parts make the finite element process simulation challenging in terms of computational time and large amounts of data management. The method of activating elements layer by layer and introducing heat in a cyclic manner called a thermal cycle heat input was applied. Thermal cycle heat input reduces the computational time considerably. The numerical results were compared to the experimental data for thermal and residual stress analyses. A lumping of layers strategy was implemented to reduce further computational time. The different number of lumping layers was analyzed to define the limit of lumping to retain accuracy in the residual stress calculation. The lumped layers residual stress calculation was validated by the contour cut method in the deposited sample. Thermal behavior and residual stress prediction for the different numbers of a lumped layer were examined and reported computational time reduction.
Here's my website: https://www.selleckchem.com/products/Gefitinib.html
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