Hepatitis B Virus-Like Particle: Targeted Delivery of Plasmid Expressing Short Hairpin RNA for Silencing the Bcl-2 Gene in Cervical Cancer Cells

Gene therapy research has advanced to clinical trials, but it is hampered by unstable nucleic acids packaged inside carriers and there is a lack of specificity towards targeted sites in the body. This study aims to address gene therapy limitations by encapsidating a plasmid synthesizing a short hairpin RNA (shRNA) that targets the anti-apoptotic Bcl-2 gene using truncated hepatitis B core antigen (tHBcAg) virus-like particle (VLP). A shRNA sequence targeting anti-apoptotic Bcl-2 was synthesized and cloned into the pSilencer 2.0-U6 vector. The recombinant plasmid, namely PshRNA, was encapsidated inside tHBcAg VLP and conjugated with folic acid (FA) to produce FA-tHBcAg-PshRNA VLP. Electron microscopy revealed that the FA-tHBcAg-PshRNA VLP has an icosahedral structure that is similar to the unmodified tHBcAg VLP. Delivery of FA-tHBcAg-PshRNA VLP into HeLa cells overexpressing the folate receptor significantly downregulated the expression of anti-apoptotic Bcl-2 at 48 and 72 h post-transfection. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay demonstrated that the cells’ viability was significantly reduced from 89.46% at 24 h to 64.52% and 60.63%, respectively, at 48 and 72 h post-transfection. As a conclusion, tHBcAg VLP can be used as a carrier for a receptor-mediated targeted delivery of a therapeutic plasmid encoding shRNA for gene silencing in cancer cells.     

Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells

We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.     

Ce3+/Tb3+-coactived NaMgBO3 phosphors toward versatile applications in white LED,FED, and optical anti-counterfeiting

Ce³⁺/Tb³⁺ co-doped NaMgBO₃ phosphors were successfully synthesized by solid-state method. Under 381 nm excitation, the cyan emission owing to the 5d → 4f of Ce³⁺ ions and green emissions arising from the ⁵D₄ → ⁷F_J (J = 6, 5, 4, and 3) transitions of Tb³⁺ ions were seen in all the phosphors. Through theoretical analysis, one knows that the energy transfer from Ce³⁺ to Tb³⁺ ions with high efficiency of 83.74% was contributed by dipole–dipole transition. Furthermore, the internal quantum efficiency of NaMgBO₃:0.01Ce³⁺,0.03Tb³⁺ phosphor was 54.28%. Compared with that of at 303 K, the emission intensity of the developed products at 423 K still kept 73%, revealing the splendid thermal stability of the studied phosphors. Through utilizing the resultant phosphors as cyan-green components, the fabricated white-LED device exhibited an excellent correlated color temperature of 2785 K, high color-rendering index of 85.73, suitable luminance efficiency of 25.00 lm/W, and appropriate color coordinate of (0.4279, 0.3617). Aside from the superior photoluminescence, the synthesized phosphors also exhibited excellent cathode-luminescence properties which were sensitive to the current and accelerating voltage. Furthermore, the NaMgBO₃:0.01Ce³⁺,0.03Tb³⁺ phosphors with multi-mode emissions were promising candidates for optical anti-counterfeiting. All the results indicated that the Ce³⁺/Tb³⁺ co-doped NaMgBO₃ phosphors were potential multi-platforms toward white-LED, field emission displays, and optical anti-counterfeiting applications.     

Accurate modeling and prediction of surface roughness by computer vision in turning operations using an adaptive neuro-fuzzy inference system

Modeling and prediction of surface roughness of a workpiece by computer vision in turning operations play an important role in the manufacturing industry. This paper proposes a method using an adaptive neuro-fuzzy inference system (ANFIS) to accurately establish the relationship between the features of surface image and the actual surface roughness, and consequently can effectively predict surface roughness using cutting parameters (cutting speed, feed rate, and depth of cut) and gray level of the surface image. Experimental results show that the proposed ANFIS-based method outperforms the existing polynomial network-based method in terms of modeling and prediction accuracy.     

High performance hydraulic design techniques of mixed-flow pump impeller and diffuser

In this paper, we describe a numerical study about the performance improvement of a mixed-flow pump by optimizing the design of the impeller and diffuser using a commercial computational fluid dynamics (CFD) code and design-of-experiments (DOE). The design variables of impeller and diffuser in the vane plane development were defined with a fixed meridional plane. The design variables were defined by the vane plane development, which indicates the blade-angle distributions and length of the impeller and diffuser. The vane plane development was controlled using the blade-angle in a fixed meridional plane. The blade shape of the impeller and diffuser were designed using a traditional method in which the inlet and exit angles are connected smoothly. First, the impeller optimum design was performed with impeller design variables. The diffuser optimum design was performed with diffuser design variables while the optimally designed impeller shape was fixed. The importance of the impeller and diffuser design variables was analyzed using 2^k factorial designs, and the design optimization of the impeller and diffuser design variables was determined using the response surface method (RSM). The objective functions were defined as the total head (Ht) and the total efficiency (?t) at the design flow rate. The optimally designed model was verified using numerical analysis, and the numerical analysis results for both the optimum model and the reference model were compared to determine the reasons for the improved pump performance. A pump performance test was carried out for the optimum model, and its reliability was proved by a comparative analysis of the results of the numerical analysis and an experiment using the optimum model.     

Fabrication of protective-coated SiC reinforced tungsten matrix composites with reduced reaction phases by spark plasma sintering

SiC reinforced tungsten matrix composites were fabricated via the spark plasma sintering process. In order to prevent an interfacial reaction between the SiC and tungsten during sintering, TiOx coated SiC particles were synthesized by a solution-based process. TiOx layer coated SiC particles were treated in high temperature nitriding conditions or annealed in a high temperature vacuum to form TiN or TiC coated SiC particles, respectively. The TiC layers coated on SiC particles successfully prevented tungsten from reacting with SiC; hence the proposed process resulted in successful fabrication of the SiC/W composites. The mechanical properties such as compressive strength and flexural strength of the composites were measured. Additionally, the effect of SiC on the high temperature oxidative ablation of tungsten was also investigated. The addition of SiC resulted in an improved oxidative ablation resistance of the tungsten-based composites.     

First-principles study on the thermal expansion of Ni-X binary alloys based on the quasi-harmonic Debye model

In this study, we use the quasi-harmonic Debye model to predict the coefficient of thermal expansion of Ni- X binary alloys. The method bridges between the macroscopic elastic behavior and thermodynamic properties of materials without an expensive calculation of the volume dependence of the phonon density of states. Furthermore, the Grüneisen parameter is derived from the volume dependence of the Debye temperature, which is calculated from the first-principles elastic stiffness constants. The experimental coefficient of thermal expansion (CTE) of pure nickel is well reproduced, especially in the low temperature region. Among the few alloying elements tested, Al is predicted to slightly decrease the CTE whereas Mo and W are more effective in reducing the CTE. For the cases of Ni-X binary alloy systems, where the variation in the CTE is relatively small, the method used here appears to perform better than certain other formulations that rely entirely on the energy vs. volume relationship.     

High-temperature thermo-mechanical behavior of functionally graded materials produced by plasma sprayed coating: Experimental and modeling results

Thermal barrier coatings are widely used in aerospace industries to protect exterior surfaces from harsh environments. In this study, functionally graded materials (FGMs) were investigated with the aim to optimize their high temperature resistance and strength characteristics. NiCrAlY bond coats were deposited on Inconel-617 superalloy substrate specimens by the low vacuum plasma spraying technique. Functionally graded Ni-yttria-stabilized zirconia (YSZ) coatings with gradually varying amounts of YSZ (20%-100%) were fabricated from composite powders by vacuum plasma spraying. Heat shield performance tests were conducted using a high- temperature plasma torch. The temperature distributions were measured using thermocouples at the interfaces of the FGM layers during the tests. A model for predicting the temperature at the bond coating–substrate interface was established. The temperature distributions simulated using the finite element method agreed well with the experimental results.     

Effects of environmental factors on corrosion behavior of aluminum

Aluminum, used as a material for heat exchangers in air conditioners, often has problems of leakage of refrigerant on the Al surface due to corrosion. The problems originate from pitting corrosion of the Al in an external environment. To understand corrosion problems, it is necessary to study the corrosion behavior of Al in various environments. In this study, the effects of environmental factors on the corrosion behavior of Al were studied by the surface analysis and electrochemical testing in 3.5 wt% NaCl solutions, with changes of dissolved oxygen, temperature, and concentration of Cl⁻ and S ions. Among the external environmental factors, the presence of oxygen and the increase of Cl⁻ ion concentration do not significantly affect the corrosion potential of Al, leading to an increase of only 1.1 and 6 times, respectively. There was a significant decrease in the corrosion resistance of Al, approximately 40 and 800 times, respectively, with the increase of concentration of S and temperature.     

Enhancement of Mechanical Properties of Extruded Mg–9Al–1Zn–1MM–0.7CaO–0.3Mn Alloy Through Pre-aging Treatment

The effect of pre-aging treatment before extrusion has been investigated in Mg–9.0Al–1.0Zn–1MM–0.7CaO–0.3Mn alloy. The as-cast microstructure consists of α-Mg dendrite with secondary solidification phase particles, (Mg, Al)₂Ca, β-Mg₁₇Al₁₂ and Al₁₁RE₃ at the inter-dendritic region. After extrusion, β-Mg₁₇Al₁₂ precipitates are present, but higher density and more homogeneous distribution in pre-aged alloy. In addition, μm-scale banded bulk β-Mg₁₇Al₁₂ particles are generated during extrusion. Al₁₁RE₃ particles are broken into small particles, and are aligned along the extrusion direction. (Mg, Al)₂Ca particles are only slightly elongated along the extrusion direction, providing stronger particle stimulated nucleation (PSN) effect by severe deformation during extrusion. The mechanical properties can be significantly enhanced by introducing pre-aging treatment, i.e. β-Mg₁₇Al₁₂ precipitates provide grain refining and strengthening effects and (Mg, Al)₂Ca particles provide PSN effect.