Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

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.     

Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.     

Effects of surface roughness of substrates on the c-axis preferred orientation of ZnO films deposited by r.f. magnetron sputtering

The c-axis preferred orientation of ZnO film is the most important factor for its successful application in piezoelectric devices. The effects of surface roughness of the substrate on the c-axis preferred orientation of ZnO thin films, deposited by radio frequency magnetron sputtering, were investigated. During sputtering, the oxygen content in the argon environment used was varied from 0 to 70% at a total sputtering pressure of 10 mTorr. Very smooth Si, smooth evaporated Au/Si, smooth evaporated-Al/Si, and rough sputtered-Al/Si were used as substrates. Their r.m.s. roughnesses, as measured by atomic force microscopy, were 1.27, 17.1, 21.1 and 65-118 Å, respectively. The crystalline structure and the angular spread of the (0 0* 2) plane normal to the ZnO films were determined using X-ray diffraction and X-ray rocking curves, respectively. The crystallinity and the preferred c-axis orientation of the ZnO films were strongly dependent on the surface roughness of the substrates rather than on the oxygen content of the working environment or on the chemical nature of the substrate.     

Solid phase crystallization of amorphous silicon on glass by thin film heater for thin film transistor (TFT) application

A new process for solid phase crystallization (SPC) of amorphous silicon (a-Si) using thin film heater is reported. With this localized Ti silicide thin film heater, we successfully crystallized 500 Å-thick a-Si in a few minutes without any thermal deformation of glass substrate. The size of crystallized silicon grain was abnormally big (30-40 μm). Polycrystalline thin film transistors (TFT) fabricated using this unique thin film heater showed better mobility than those of conventional ones by furnace annealing.     

Measurement and numerical simulation of three‐dimensional fiber orientation states in injection‐molded short‐fiber‐reinforced plastics

To determine three‐dimensional fiber orientation states in injection‐molded short‐fiber composites, a confocal laser scanning microscope (CLSM) is used. Since the CLSM optically sections the specimen, more than two images of the cross sections on and below the surface of the composite can be obtained. Three‐dimensional fiber orientation states can be determined by using geometric parameters of fiber images obtained from two parallel cross sections. For experiments, carbon‐fiber‐reinforced polystyrene is examined by the CLSM and geometric parameters of fibers on each cross‐sectional plane are measured by an image analysis. In order to describe fiber orientation states compactly, orientation tensors are determined at different positions of the prepared specimen. Three‐dimensional orientation states are obtained without any difficulty by determining the out‐of‐plane angles utilizing fiber images on two parallel planes acquired by the CLSM. Orientation states are different at different positions and show the shell–core structure along the thickness of the specimen. Fiber orientation tensors are predicted by a numerical analysis and the numerically predicted orientation states show good agreement with measured ones. However, some differences are found at the end of cavity. They may result from the fountain flow effects, which are not considered in the numerical analysis. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 500–509, 2003     

Wireless-adaptive fair scheduling for multimedia stream

As packet cellular networks are expected to support multimedia services, the authors incorporate the multimedia QoS requirements into the design of a new scheduling algorithm. The proposed wireless-adaptive fair scheduling tries to allocate time slots for each user with fair share by considering the varying channel condition while reflecting the stream requirements and achieving high throughput.     

A critical heat flux model based on mass, energy, and momentum balance for upflow boiling at low qualities

A mechanistic modeling of critical heat flux (CHF) in upflow boiling at low qualities is performed. The developed model is based on a physical criterion of CHF occurrence and a mechanism limiting the thermal transport between a stagnant bubbly layer and bulk stream. The mechanism can be mathematically formulated by coupling the equation of limiting mixing mass flux, which is derived from momentum balance equations in two regions, with local mass and energy balance equations on the bubbly layer. The resulting form of the model is represented by a general and straightforward CHF formula involving two empirical constants related to the void fraction and the thickness of the bubbly layer. The predictions agree well with the extensive CHF data of water in uniformly heated tubes.