Magnetically Guidable Proteinaceous Adhesive Microbots for Targeted Locoregional Therapeutics Delivery in the Highly Dynamic Environment of the Esophagus

The esophagus is a tubular-shaped muscular organ where swallowed fluids and muscular contractions constitute a highly dynamic environment. The turbulent, coordinated processes that occur through the oropharyngeal conduit can often compromise targeted administration of therapeutic drugs to a lesion, significantly reducing therapeutic efficacy. Here, magnetically guidable drug vehicles capable of strongly adhering to target sites using a bioengineered mussel adhesive protein (MAP) to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions are proposed. A suite of highly uniform microparticles embedded with iron oxide (IO) nanoparticles (MAP@IO MPs) is microfluidically fabricated using the genipin-mediated covalent cross-linking of bioengineered MAP. The MAP@IO MPs are successfully targeted to a specific region and prolongedly retained in the tubular-structured passageway. In particular, orally administered MAP@IO MPs are effectively captured in the esophagus in vivo in a magnetically guidable manner. Moreover, doxorubicin (DOX)-loaded MAP@IO MPs exhibit a sustainable DOX release profile, effective anticancer therapeutic activity, and excellent biocompatibility. Thus, the magnetically guidable locomotion and robust underwater adhesive properties of the proteinaceous soft microbots can provide an intelligent modular approach for targeted locoregional therapeutics delivery to a specific lesion site in dynamic fluid-associated tubular organs such as the esophagus.     

In-situ measurement of reflection coefficient and its application to predicting combustion instability in a gas turbine combustor

Journal of Mechanical Science and Technology - Here, a procedure that uses in-situ data recorded by two microphones placed inside an operating gas turbine combustor to determine the reflection...     

D-limonene Inhibits Pentylenetetrazole-Induced Seizure via Adenosine A2A Receptor Modulation on GABAergic Neuronal Activity

Background: Epilepsy is a chronic neurological disorder characterized by the recurrence of seizures. One-third of patients with epilepsy may not respond to antiseizure drugs. Purpose: We aimed to examine whether D-limonene, a cyclic monoterpene, exhibited any antiseizure activity in the pentylenetetrazole (PTZ)-induced kindling mouse model and in vitro. Methods: PTZ kindling mouse model was established by administering PTZ (30 mg/kg) intraperitoneally to mice once every 48 h. We performed immunoblot blots, immunohistochemistry (IHC), and high-performance liquid chromatography (HPLC) analysis after the behavioral study. Results: An acute injection of PTZ (60 mg/kg) induced seizure in mice, while pretreatment with D-limonene inhibited PTZ-induced seizure. Repeated administration of PTZ (30 mg/kg) increased the seizure score gradually in mice, which was reduced in D-limonene (10 mg/kg)-pretreated group. In addition, D-limonene treatment increased glutamate decarboxylase-67 (GAD-67) expression in the hippocampus. Axonal sprouting of hippocampal neurons after kindling was inhibited by D-limonene pretreatment. Moreover, D-limonene reduced the expression levels of Neuronal PAS Domain Protein 4 (Npas4)-induced by PTZ. Furthermore, the adenosine A2A antagonist {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261 and ZM241385 inhibited anticonvulsant activity and gamma-aminobutyric acid (GABA)ergic neurotransmission-induced by D-limonene. Conclusion: These results suggest that D-limonene exhibits anticonvulsant activity through modulation of adenosine A2A receptors on GABAergic neuronal function.     

Texturing behaviours of (K0.47Na0.51Li0.02)(Nb0.8Ta0.2)O3 piezoelectric ceramics produced using NaNb1-xTaxO3 templates

Textured (K_0.47Na_0.51Li_0.02)(Nb_0.8Ta_0.2)O₃ (KNLNT20) piezoelectric ceramics were prepared using NaNb_1?xTa_xO₃ templates. The highest degree of grain orientation (97%) and piezoelectric constant (342 pC/N) were obtained upon adding 3 wt% of the NaNb_0.8Ta_0.2O₃ (NNT20) template and sintering at 1150 °C for 1 h. Back-scattered scanning electron micrographs of the textured KNLNT20 samples sintered at 1150 °C for 1 h indicated the presence of templates similar in size to the original ones within the cores of the textured grains. The peak value of the dielectric constant corresponding to the NNT20 core decreased after prolonged holding at 1150 °C, owing to a decrease in the size of the NNT20 core because of the interdiffusion of K, Na, and Li ions between the NNT20 core and KNLNT20 shell. This interdiffusion also decreased the piezoelectric constant, d₃₃ value of the textured KNLNT20 samples by inducing a change in the chemical composition of the shell region.     

Dissolution kinetics of alumina in molten CaO–Al2O3–FetO–MgO–SiO2 oxide representing the RH slag in steelmaking process

In order to effectively remove alumina inclusions suspending in ultra-low C steel during RH process, the dissolution kinetics of alumina in molten CaO–Al₂O₃–Fe_tO–MgO–SiO₂ oxide was investigated. A crucible dissolution technique was used where the alumina crucible was allowed to dissolve in the slag of various conditions ((% CaO)/(% Al₂O₃), (% Fe_tO), temperature). The obtained data were interpreted using a kinetic mass transport equation to obtain the mass transport coefficient (k_m) in each condition. Increasing (% CaO)/(% Al₂O₃), (% Fe_tO), and temperature increased the dissolution rate as well as the k_m provided that the slag composition is not close to its saturation composition by alumina. In order to simulate the dissolution of alumina inclusion in the RH slag, which cannot be measured by a confocal scanning laser microscopy (CSLM) at present due to the opaqueness of the slag, the modified invariant interface approximation was employed. Along with the obtained k_m, the viscosity of slag, and a reference experiment using the CSLM, the dissolution kinetics of alumina inclusion in the Fe_tO-containing RH slag was predicted. The time required for the dissolution of alumina inclusions from liquid steel to RH slag was discussed.     

Quick high-temperature hydrothermal synthesis of mesoporous materials with 3D cubic structure for the adsorption of lysozyme

Three-dimensional cage-like mesoporous FDU-12 materials with large tuneable pore sizes ranging from 9.9 to 15.6 nm were prepared by varying the synthesis temperature from 100 to 200 °C for the aging time of just 2 h using a tri-block copolymer F-127(EO₁₀₆PO₇₀EO₁₀₆) as the surfactant and 1,3,5-trimethyl benzene as the swelling agent in an acidic condition. The mesoporous structure and textural features of FDU-12-HX (where H denotes the hydrothermal method and X denotes the synthesis temperature) samples were elucidated and probed using x-ray diffraction, N₂ adsorption, ²⁹Si magic angle spinning nuclear magnetic resonance, scanning electron microscopy and transmission electron microscopy. It has been demonstrated that the aging time can be significantly reduced from 72 to 2 h without affecting the structural order of the FDU-12 materials with a simple adjustment of the synthesis temperature from 100 to 200 °C. Among the materials prepared, the samples prepared at 200 °C had the highest pore volume and the largest pore diameter. Lysozyme adsorption experiments were conducted over FDU-12 samples prepared at different temperatures in order to understand their biomolecule adsorption capacity, where the FDU-12-HX samples displayed high adsorption performance of 29 μmol g⁻¹ in spite of shortening the actual synthesis time from 72 to 2 h. Further, the influence of surface area, pore volume and pore diameter on the adsorption capacity of FDU-12-HX samples has been investigated and results are discussed in correlation with the textural parameters of the FDU-12-HX and other mesoporous adsorbents including SBA-15, MCM-41, KIT-5, KIT-6 and CMK-3.     

Effect of nanoparticle surface functionality on microdomain orientation in block copolymer thin films under electric field

The electric field induced microdomain orientations has been an interesting research topic. In this article, the effect of nanoparticle surface functionality on microdomain alignments in block copolymer/nanoparticle hybrid thin films was investigated with transmission electron microscopy experiments. The presence of gold nanoparticles influenced the microdomain orientation behaviors of block copolymer/nanoparticle thin films. The possibility for complete alignment normal to the substrate was illustrated by controlling electric field strength, concentration, and surface ligands of nanoparticles. This work provides basic and essential data to understand the properties and behaviors of emerging block copolymer/nanoparticle hybrid thin films.     

Simvastatin Attenuates the Oxidative Stress,Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure

Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF), and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI)-induced heart failure (HF) rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group) and underwent echocardiography, AF induction studies and left atrial (LA) fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (I_NCX), sarcoplasmic reticulum calcium ATPase (SERCA), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham), which were significantly reduced by simvastatin (p < 0.05 vs. MI). The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, I_NCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.     

Development of a Multiplex and Cost-Effective Genotype Test toward More Personalized Medicine for the Antiplatelet Drug Clopidogrel

There has been a wide range of inter-individual variations in platelet responses to clopidogrel. The variations in response to clopidogrel can be driven by genetic polymorphisms involved in the pathway of absorption, distribution, metabolism, excretion, and the target receptor P2Y12. A set of genetic variants known for causing variations in clopidogrel responses was selected, which included CYP2C19*2, *3, *17, CYP2B6*4, *6, *9, CYP3A4*18, CYP3A5*3, MDR1 2677G > T/A, 3435C > T, and P2Y12 H2 (742T > C). The simultaneous detection of these 10 variants was developed by using a multiplex PCR and single-base extension (MSSE) methodology. The newly developed genotyping test was confirmed by direct DNA sequencing in the representative positive control samples and validated in an extended set of 100 healthy Korean subjects. Genotyping results from the developed MSSE exhibited a perfect concordance with the direct DNA sequencing data and all of variants tested in 100 healthy Korean subjects were in agreement with Hardy-Weinberg equilibrium (p > 0.05). The present molecular diagnostic studies provide an accurate, convenient, and fast genotyping method for the detection of multiple variants. This would be helpful for researchers, as well as clinicians, to use genetic information toward more personalized medicine of clopidogrel and other antiplatelet drugs in the future.