Shean-Jen Chen

Nitrogen-Doped Graphene Oxide Quantum Dots as Photocatalysts for Overall Water-Splitting under Visible Light Illumination

Nitrogen-doped graphene oxide quantum dots exhibit both p- and n-type conductivities and catalyze overall water-splitting under visible-light irradiation. The quantum dots contain p-n type photochemical diodes, in which the carbon sp(2) clusters serve as the interfacial junction. The active sites for H2 and O2 evolution are the p- and n-domains, respectively, and the reaction mimics biological photosynthesis.

Gold Nanorods in Photodynamic Therapy, as Hyperthermia Agents, and in Near‐Infrared Optical Imaging

Decreasing the size of a material to the nanometer scale makes it sensitive to a further decrease in size or a change in shape. Among the nanomaterials that are currently being developed, gold nanoparticles are extensively exploited in organisms because of their good stability and biocompatibility. However, in biomedical applications that require a considerably deeper penetration of near-infrared (NIR) light, in which both blood and soft tissues are highly penetrable, a different type of gold nanostructure is required. Surface plasmon resonance (SPR) is a phenomenon in which free electrons in the nanostructures collectively oscillate and scatter or absorb the incident electromagnetic wave. Previous studies have demonstrated various methods of shifting the SPR of gold nanomaterials to the NIR region and shown their potential in biological applications. In the NIR region, tissue transmission is optimal owing to low scattering and energy absorption, thus providing maximum irradiation penetration through tissue and minimizing the autofluorescence of the non-target tissue. There are many applications for NIR-absorbing gold nanostructures in biology, and in particular gold nanorods. For example, gold nanorods can be applied in plasmon resonance light scattering, Rayleigh elastic scattering, surface-enhanced Raman inelastic scattering, optical coherent tomography scattering, twophoton luminescent non-linear imaging, and photothermal therapy. Gold nanorods have also received significant attention for their emerging potential in photothermal therapy. However, little attention has been paid to the use of nanorods combined with photosensitizers in photodynamic therapy (PDT), which is the destruction of cancer cells by the highly reactive singlet oxygen of the reactive oxygen species (ROS) produced by a photosensitizing compound and light of an appropriate wavelength. Gold nanorods couple a hydrophilic and anionic photosensitizer, indocyanine green (ICG) (Supporting Information, Figure S1), with light from an NIR laser emitting in the NIR region on the surface of the nanorods to produce PDT. Furthermore, the excitation and emission maxima of ICG are similar to NIR wavelengths, thus enabling ICG-conjugated gold nanorods to be utilized as an effective contrast agent in biomedical imaging. Practical applications in the early detection and destruction of cancer cells using nanomaterials have emerged in recent years, and the development of multifunctional nanomaterials is currently being pursued. Herein, we propose a medical diagnosis method that uses a lethal photochemical destruction reaction and shows that multifunctional ICGconjugated gold nanorods can simultaneously serve as photodynamic and photothermal therapeutic agents to destroy cancer cells. Furthermore, combined PDT and hyperthermia can more efficiently extinguish cancer cells than PDT or hyperthermia treatment alone, and the system can also serve as an effective bioimaging probe in the NIR region. Gold nanorods with a cetyltrimethylammonium bromide (CTAB) surfactant coating were synthesized using the seedless growth method. To conjugate ICG on the surface, CTAB was coated on the nanorods with poly(styrene-altmaleic acid) (PSMA) and ICG in sequence by an electrostatic interaction. A TEM image (Figure 1) depicts gold nanorods with an aspect ratio of approximately 3.8 (length: 35 nm, width: 9.3 nm). Owing to CTAB, the surface charge of the nanorods revealed a zeta potential of approximately 39.2 mV. PSMA polymer was then first hydrolyzed by NaOH to expose the carboxyl group and then adsorbed on the nanorods by electrostatic interactions (Supporting Information, Figure S2). Figure 1 b shows Au-PSMA nanorods with negatively charged PSMA; the Au-PSMA nanorods have a surface charge of approximately 10.7 mV. By the p–p stacking

Gold nanomaterials conjugated with indocyanine green for dual-modality photodynamic and photothermal therapy

Light-exposure-mediated higher temperatures that markedly accelerate the degradation of indocyanine green (ICG) in aqueous solutions by thermal decomposition have been a serious medical problem. In this work, we present the example of using gold nanorods (Au NRs) and gold nanoparticles (Au NPs) simultaneously serving as photodynamic and photothermal agents to destroy malignant cells. Au NRs and Au NPs were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and photothermal therapy (PTT). We also demonstrated that Au NRs and Au NPs conjugated with ICG displayed high chemical stability and acted as a promising diagnostic probe. Moreover, the photochemical destruction ability would have a gradually increase depending on different sizes of Au NPs. Due to its stability even via higher temperatures mediated by laser irradiation, the combination of PTT and PDT proved to be efficiently killing cancer cells as compared to PTT or PDT treatment alone and enhanced the effectiveness of photodestruction and was demonstrated to enhance its photostability. As a result, the preparation of Au-based nanomaterials conjugated with ICG as well as their use in biomedical applications is valuable developments in multifunctional nanomaterials.

Common-path phase-shift interferometry surface plasmon resonance imaging system

Surface plasmon resonance (SPR) and common-path phase-shift interferometry (PSI) techniques are integrated in a biosensing imaging system for measuring the two-dimensional spatial phase variation caused by biomolecular interactions on a sensing chip without the need for additional labeling. The common-path PSI technique has the advantage of long-term stability, even when it is subjected to external disturbances. Hence the system meets the requirements of the real-time kinetic studies involved in biomolecular interaction analysis. The proposed SPR-PSI imaging system demonstrates a detection limit of a 2 x 10(-7) refractive-index change, a long-term phase stability of 2.5 x 10(-4) pi rms for 4 h, and a spatial phase resolution of 10(-3) pi with a lateral resolution of 100 microm.

Complement C1q Activates Tumor Suppressor WWOX to Induce Apoptosis in Prostate Cancer Cells

Background Tissue exudates contain low levels of serum complement proteins, and their regulatory effects on prostate cancer progression are largely unknown. We examined specific serum complement components in coordinating the activation of tumor suppressors p53 and WWOX (also named FOR or WOX1) and kinases ERK, JNK1 and STAT3 in human prostate DU145 cells. Methodology/Principal Findings DU145 cells were cultured overnight in 1% normal human serum, or in human serum depleted of an indicated complement protein. Under complement C1q- or C6-free conditions, WOX1 and ERK were mainly present in the cytoplasm without phosphorylation, whereas phosphorylated JNK1 was greatly accumulated in the nuclei. Exogenous C1q rapidly restored the WOX1 activation (with Tyr33 phosphorylation) in less than 2 hr. Without serum complement C9, p53 became activated, and hyaluronan (HA) reversed the effect. Under C6-free conditions, HA induced activation of STAT3, an enhancer of metastasis. Notably, exogenous C1q significantly induced apoptosis of WOX1-overexpressing DU145 cells, but not vehicle-expressing cells. A dominant negative and Y33R mutant of WOX1 blocked the apoptotic effect. C1q did not enhance p53-mediated apoptosis. By total internal reflection fluorescence (TIRF) microscopy, it was determined that C1q destabilized adherence of WOX1-expressing DU145 cells by partial detaching and inducing formation of clustered microvilli for focal adhesion particularly in between cells. These cells then underwent shrinkage, membrane blebbing and death. Remarkably, as determined by immunostaining, benign prostatic hyperplasia and prostate cancer were shown to have a significantly reduced expression of tissue C1q, compared to age-matched normal prostate tissues. Conclusions/Significance We conclude that complement C1q may induce apoptosis of prostate cancer cells by activating WOX1 and destabilizing cell adhesion. Downregulation of C1q enhances prostate hyperplasia and cancerous formation due to failure of WOX1 activation.

Enhancement of the resolution of surface plasmon resonance biosensors by control of the size and distribution of nanoparticles

A new resolution-enhanced surface plasmon resonance (SPR) biosensor offers a tenfold improvement in resolution compared with conventional SPR biosensors in the detection of the surface coverage of biomaterials. The proposed optical biosensor, based on the attenuated total-reflection method, excites both the surface plasmons and particle plasmons to enhance the local electromagnetic field by control of the size and volume fraction of embedded Au nanoparticles to increase the resolution of the device. The SPR biosensor design is based on the Maxwell-Garnett model and the Fresnel equations, and the device is fabricated with a cosputtering deposition system.

Different types of exercise induce differential effects on neuronal adaptations and memory performance.

Different exercise paradigms show differential effects on various forms of memory. We hypothesize that the differential effects of exercises on memory performance are caused by different neuroplasticity changes in relevant brain regions in response to different exercise trainings. We examined the effects of treadmill running (TR) and wheel running (WR) on the Pavlovian fear conditioning task that assesses learning and memory performance associated with the amygdala (cued conditioning) and both the amygdala and hippocampus (contextual conditioning). The skeletal muscle citrate synthase activity, an indicator of aerobic capacity, was elevated in rats received 4 w of TR, but not WR. While both TR and WR elevated the contextual conditional response, only TR facilitated the cued conditional response. Using a single-neuron labeling technique, we found that while both TR and MR enlarged the dendritic field and increased the spine density in hippocampal CA3 neurons, only TR showed these effects in basolateral amygdalar neurons. Moreover, both types of exercise upregulated synaptic proteins (i.e., TrkB and SNAP-25) in the hippocampus; however only TR showed similar effects in the amygdala. Injection of K252a, a TrkB kinase inhibitor, in the dorsal hippocampus or basolateral amygdala abolished the exercise-facilitated contextual or cued fear learning and memory performance, respectively, regardless of the types of exercise. In summary, our results supported that different types of exercise affect the performance of learning and memory via BDNF-TrkB signaling and neuroplasticity in specific brain regions. The brain region-specific neuronal adaptations are possibly induced by various levels of intensity/stress elicited by different types of exercise.

Spatiotemporal focusing-based widefield multiphoton microscopy for fast optical sectioning

In this study, a microscope based on spatiotemporal focusing offering widefield multiphoton excitation has been developed to provide fast optical sectioning images. Key features of this microscope are the integrations of a 10 kHz repetition rate ultrafast amplifier featuring high instantaneous peak power (maximum 400 μJ/pulse at a 90 fs pulse width) and a TE-cooled, ultra-sensitive photon detecting, electron multiplying charge-coupled camera into a spatiotemporal focusing microscope. This configuration can produce multiphoton images with an excitation area larger than 200 × 100 μm² at a frame rate greater than 100 Hz (current maximum of 200 Hz). Brownian motions of fluorescent microbeads as small as 0.5 μm were observed in real-time with a lateral spatial resolution of less than 0.5 μm and an axial resolution of approximately 3.5 μm. Furthermore, second harmonic images of chicken tendons demonstrate that the developed widefield multiphoton microscope can provide high resolution z-sectioning for bioimaging.

One-step fabrication of nanostructures by femtosecond laser for surface-enhanced Raman scattering

This paper reports an efficient fabrication of nanostructures on silicon substrates for surface-enhanced Raman scattering (SERS). Silicon wafer substrates in the aqueous solution of silver nitrate were machined by the femtosecond laser direct writing to achieve simultaneously in one-step the generation of grating-like nanostructures on the surface of the substrate and the formation of silver nanoparticles on the surface of the nanostructures via the laser-induced photoreduction effect. Parametric studies were conducted for the different concentrations of aqueous silver nitrate solutions and scanning speeds. The enhancement factor of the SERS is found to be higher than 10(9). The patterning technique provides an opportunity to incorporate the SERS capability in a functional microchip.

Measurements of multiphoton action cross sections for multiphoton microscopy

We report quantitative measurements of two-, three-, and four-photon excitation action cross sections of several commonly used fluorophores and fluorescent proteins at three different excitation wavelengths of 800 nm, 1300 nm, and 1680 nm. The measured cross section values are consistent with simple quantum mechanic estimations. These values indicate that the optimum repetition rate for deep tissue 3-photon microscopy is approximately 1 to 2 MHz. We further demonstrate that it is feasible to perform 4-photon fluorescence microscopy of GFP labeled microglia in mouse brain in vivo at 1700 nm. 4-photon excitation increases the accessibility of fluorophores at the long wavelength spectral window of 1700 nm.