Chii-Wann Lin

Sympathetic Nerve Sprouting, Electrical Remodeling, and Increased Vulnerability to Ventricular Fibrillation in Hypercholesterolemic Rabbits

Abstract— Whether hypercholesterolemia (HC) can induce proarrhythmic neural and electrophysiological remodeling is unclear. We fed rabbits with either high cholesterol (HC, n=10) or standard (S, n=10) chows for 12 weeks (protocol 1), and with HC (n=12) or S (n=10) chows for 8 weeks (protocol 2). In protocol 3, 10 rabbits were fed with various protocols to observe the effects of different serum cholesterol levels. Results showed that the serum cholesterol levels were 2097±288 mg/dL in HC group and 59±9 mg/dL in S group for protocol 1 and were 1889±577 mg/dL in HC group and 50±21 mg/dL in S group for protocol 2. Density of growth-associated protein 43– (GAP43) and tyrosine hydroxylase– (TH) positive nerves in the heart was significantly higher in HC than S in protocol 1. Compared with S, HC rabbits had longer QTc intervals, more QTc dispersion, longer action potential duration, increased heterogeneity of repolarization and higher peak calcium current (ICa) density (14.0±3.1 versus 9.1±3.4 pA/pF;P <0.01) in protocol 1 and 2. Ventricular fibrillation was either induced or occurred spontaneously in 9/12 of hearts of HC group and 2/10 of hearts in S group in protocol 2. Protocol 3 showed a strong correlation between serum cholesterol level and nerve density for GAP43 (R2=0.94;P <0.001) and TH (R2=0.91;P <0.001). We conclude that HC resulted in nerve sprouting, sympathetic hyperinnervation, and increased ICa. The neural and electrophysiological remodeling was associated with prolonged action potential duration, longer QTc intervals, increased repolarization dispersion, and increased ventricular vulnerability to fibrillation.

High-sensitivity detection of carbohydrate antigen 15-3 using a gold/zinc oxide thin film surface plasmon resonance-based biosensor

We report that gold/zinc oxide (Au/ZnO) nanocomposite films were effectively employed to enhance the performance of surface plasmon resonance (SPR) for the detection of tumor markers. Carbohydrate antigen 15.3 (CA15-3), a tumor marker for breast cancer, was chosen as a model analyte. We analyzed intensity response to the samples at various concentrations (0.0125 U/mL to 160 U/mL) in pleural fluid to evaluate the detection capability of the SPR biosensor based on Au/ZnO thin films. The linear range extended from 1 to 40 U/mL with a correlation coefficient of R(2) = 0.991 and a limit of detection reaching 0.025 U/mL at a signal-to-noise ratio of 3:1. Compared with the degree of the shift in SPR intensity induced by the specific binding event between antibody and antigen, the change of intensity on the Au/ZnO layers was increased by at least 2 fold over that on the gold/chromium (Au/Cr) layers. In addition, we determined that the Au/ZnO layers allowed for a detection limit 4 times lower than the Au/Cr layers, which are in widespread use as the sensing interfaces in current SPR-based detectors. In conclusion, the use of Au/ZnO films greatly enhanced the SPR signal yield for this bimolecular interaction and showed high sensitivity.

Diagnostic Devices for Isothermal Nucleic Acid Amplification

Since the development of the polymerase chain reaction (PCR) technique, genomic information has been retrievable from lesser amounts of DNA than previously possible. PCR-based amplifications require high-precision instruments to perform temperature cycling reactions; further, they are cumbersome for routine clinical use. However, the use of isothermal approaches can eliminate many complications associated with thermocycling. The application of diagnostic devices for isothermal DNA amplification has recently been studied extensively. In this paper, we describe the basic concepts of several isothermal amplification approaches and review recent progress in diagnostic device development.

Aptamer-based colorimetric detection of platelet-derived growth factor using unmodified goldnanoparticles

We developed a simple method for the detection of platelet-derived growth factors (PDGFs) based on base stacking effect coupled with an unmodified gold nanoparticle (AuNP) indicator. In the absence of a target, an aptamer probe and a capture probe stably co-exist in a solution, as it is difficult to sustain an interaction between both these probes due to the short 8bp duplex. However, when a target protein binds to the aptamer probe, the strong base stacking effect can lead to a favorable and stable interaction between the aptamer and capture probes. Hence, the capture probe dissociates from the AuNP surfaces, inducing AuNP aggregation. Compared with other AuNP-based aptasensors for PDGFs, using this base stacking effect can overcome a structured-aptamer methods limitation of requiring thiolated-aptamer-modified AuNPs. Under optimal detection conditions, this label-free colorimetric sensor could detect PDGFs down to 6nM with high selectivity in the presence of other interferring proteins. This simple detection approach provides viable methods for a structured-aptamer sensing protocol.

Wogonin Improves Histological and Functional Outcomes, and Reduces Activation of TLR4/NF-κB Signaling after Experimental Traumatic Brain Injury

Background Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. This study was undertaken to investigate the effects of wogonin, a flavonoid with potent anti-inflammatory properties, on functional and histological outcomes, brain edema, and toll-like receptor 4 (TLR4)- and nuclear factor kappa B (NF-κB)-related signaling pathways in mice following TBI. Methodology/Principal Findings Mice subjected to controlled cortical impact injury were injected with wogonin (20, 40, or 50 mg·kg−1) or vehicle 10 min after injury. Behavioral studies, histology analysis, and measurement of blood-brain barrier (BBB) permeability and brain water content were carried out to assess the effects of wogonin. Levels of TLR4/NF-κB-related inflammatory mediators were also examined. Treatment with 40 mg·kg−1 wogonin significantly improved functional recovery and reduced contusion volumes up to post-injury day 28. Wogonin also significantly reduced neuronal death, BBB permeability, and brain edema beginning at day 1. These changes were associated with a marked reduction in leukocyte infiltration, microglial activation, TLR4 expression, NF-κB translocation to nucleus and its DNA binding activity, matrix metalloproteinase-9 activity, and expression of inflammatory mediators, including interleukin-1β, interleukin-6, macrophage inflammatory protein-2, and cyclooxygenase-2. Conclusions/Significance Our results show that post-injury wogonin treatment improved long-term functional and histological outcomes, reduced brain edema, and attenuated the TLR4/NF-κB-mediated inflammatory response in mouse TBI. The neuroprotective effects of wogonin may be related to modulation of the TLR4/NF-κB signaling pathway.

The Soreness and Numbness Effect of Acupuncture on Skin Blood Flow

The purpose of this study was to investigate the effect of the De-Qi sensations of acupuncture (sourness-distension and distension-numbness) stimulation. Fifty-two healthy medical student volunteers were given acupuncture at the Hoku (LI-4) acupoint as they were resting. During a test that lasted 30 minutes, their skin blood flow was measured at the Quchi (LI-11) acupoint and their palm temperature was measured. Our results indicated that acupuncture increased blood flow when the De-Qi sensation occurred. If the needle was twirled a few minutes thereafter and the De-Qi feeling again occurred, the same blood flow increase was seen again. If the needle was not twirled, but the test person felt soreness, numbness and heat sensation within a few minutes after needle insertion, the same blood flow increase was also seen. After acupuncture, Quchi did not show continuous increase of blood flow as did Hoku. Hoku acupuncture also increased palm temperature suggesting that the blood flow increased from cutaneous vessel vasodilation. In conclusion, when the test person felt the sore and numb De-Qi sensation, there was an increase of blood flow at the acupuncture points. Thus, our results suggest that increased flow may be one of the mechanisms accounting for meridian system responses during acupuncture.

Surface plasmon effects on two photon luminescence of gold nanorods

Gold nanorods emit strong photoluminescence under two photon excitation; the efficient two photon lumininescence (TPL) arises from the local field enhancement assisted by surface plasmons. The surface plasmon effects on the TPL efficiency and spectrum are investigated by measuring the TPL of gold nanorods with various aspect ratios. A large TPL efficiency is found when incident light wavelength coincides with the longitudinal surface plasmon mode of the gold nanorods. However, the emission spectra of nanorods with various aspect ratios look similar and exhibit modest surface plasmon features, which implies a major non-radiative decay of excited surface plasmons.

Amplified surface plasmon resonance immunosensor for interferon-Gamma based on a streptavidin-incorporated aptamer

Interferon-gamma (IFN-γ) is associated with susceptibility to tuberculosis, which is a major public health problem worldwide. Although significant progress has been made with regard to the design of enzyme immunoassays for IFN-γ, this assay is still labor-intensive and time-consuming. We therefore designed a DNA aptamer hairpin structure for the detection of IFN-γ with high sensitivity and selectivity. A streptavidin DNA aptamer was incorporated into the IFN-γ binding aptamer probe for the amplified detection of the target molecules. Initially, the probe remained in the inactive configuration. The addition of IFN-γ induced the rearrangement of the aptamer structure, allowing the self-assembly of the active streptavidin aptamer conformation for the streptavidin molecular recognition. Under optimized conditions, the detection limit was determined to be 33 pM, with a dynamic range from 0.3 to 333 nM, both of which were superior to those of corresponding optical sensors. Because combined aptamers are composed of nucleic acids, this optical aptasensor provided the advantages of high sensitivity, simplicity, reusability, and no further labeling or sample pre-treatment.

Electrical properties of single and multiple poly(3,4-ethylenedioxythiophene) nanowires for sensing nitric oxide gas

The electrical properties of conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), nanowires were studied to develop nitric oxide (NO) gas sensors with low working temperatures. A nanowire with a diameter of 300 nm was fabricated using dip-pen nanolithography (DPN) across a 55 microm gap between a pair of electrodes. The electrical properties of single or multiple PEDOT nanowires were examined by plotting the current-voltage (I-V) curves in the range -3 V to +3 V at temperatures between 298 K and 393 K. The conductance of parallel wires was normalized with respect to the dimensions of the fabricated nanowires. The single nanowire exhibited nonlinear conductance associated with hysteresis but multiple wires did not. The currents increased with the temperature and the I-V characteristics were consistent with the power law G(T)alphaT(alpha) with alpha approximately 5.14 and 5.43. The responses to NO were highly linear and reproducible, indicating that sensing using PEDOT nanowires was reliable with a minimal concentration of NO of 10 ppm.

Emission characteristics of organic light-emitting diodes and organic thin-films with planar and corrugated structures.

In this paper, we review the emission characteristics from organic light-emitting diodes (OLEDs) and organic molecular thin films with planar and corrugated structures. In a planar thin film structure, light emission from OLEDs was strongly influenced by the interference effect. With suitable design of microcavity structure and layer thicknesses adjustment, optical characteristics can be engineered to achieve high optical intensity, suitable emission wavelength, and broad viewing angles. To increase the extraction efficiency from OLEDs and organic thin-films, corrugated structure with micro- and nano-scale were applied. Microstructures can effectively redirects the waveguiding light in the substrate outside the device. For nanostructures, it is also possible to couple out the organic and plasmonic modes, not only the substrate mode.