[Metabonomic study of biochemical changes in serum of PCPA-induced insomnia rats after treatment with Suanzaoren Decoction].

Suanzaoren Decoction(SZRD) is a classical formula for the clinical treatment of insomnia. This study analyzed the effect of SZRD on endogenous metabolites in insomnia rats based on metabonomics and thereby explored the anti-insomnia mechanism of SZRD. To be specific, DL-4-chlorophenylalanine(PCPA) was used to induce insomnia in rats. Then pathological changes of the liver and brain were observed and biochemical indexes such as 5-hydroxytryptamine(5-HT), dopamine(DA), glutamate(Glu), γ-aminobutyric acid(GABA), and norepinephrine(NE) in the hippocampus and prostaglandin D2(PGD2), tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and IL-6 in the serum of rats were detected. On this basis, the effect of SZRD on PCPA-induced insomnia rats was preliminarily assessed. The metabolic profile of rat serum samples was further analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were combined with t-test and variable importance in projection(VIP) to identify differential metabolites, and MetaboAnalyst 5.0 was employed for pathway analysis. The results showed that SZRD could improve the pathological changes of brain and liver tissues, increase the levels of neurotransmitters 5-HT, DA, and GABA in hippocampus and the level of PGD2 in hypothalamic-pituitary-adrenal axis(HPA axis), and reduce the levels of IL-1ß and TNF-α in serum of insomnia rats. Metabonomics analysis yielded 12 significantly changed potential metabolites: 5-aminovaleric acid, N-acetylvaline, L-proline, L-glutamate, L-valine, DL-norvaline, D(-)-arginine, pyroglutamic acid, 1-methylguanine, L-isoleucine, 7-ethoxy-4-methylcoumarin, and phthalic acid mono-2-ethylhexyl ester(MEHP), which were related with multiple biochemical processes including metabolism of D-glutamine and D-glutamate, metabolism of alanine, aspartate, and glutamate, metabolism of arginine and proline, arginine biosynthesis, glutathione metabolism. These metabolic changes indicated that SZRD can improve the metabolism in insomnia rats by regulating amino acid metabolism.

Numerical Study of Customized Artificial Cornea Shape by Hydrogel Biomaterials on Imaging and Wavefront Aberration.

The blindness caused by cornea diseases has exacerbated many patients all over the world. The disadvantages of using donor corneas may cause challenges to recovering eye sight. Developing artificial corneas with biocompatibility may provide another option to recover blindness. The techniques of making individual artificial corneas that fit the biometric parameters for each person can be used to help these patients effectively. In this study, artificial corneas with different shapes (spherical, aspherical, and biconic shapes) are designed and they could be made by two different hydrogel polymers that form an interpenetrating polymer network for their excellent mechanical strength. Two designed cases for the artificial corneas are considered in the simulations: to optimize the artificial cornea for patients who still wear glasses and to assume that the patient does not wear glasses after transplanting with the optimized artificial cornea. The results show that the artificial corneas can efficiently decrease the imaging blur. Increasing asphericity of the current designed artificial corneas can be helpful for the imaging corrections. The differences in the optical performance of the optimized artificial corneas by using different materials are small. It is found that the optimized artificial cornea can reduce the high order aberrations for the second case.

Numerical Study of Tunable Photonic Nanojets Generated by Biocompatible Hydrogel Core-Shell Microspheres for Surface-Enhanced Raman Scattering Applications.

Core-shell microspheres have been applied in various research areas and, in particular, they are used in the generation of photonic nanojets with suitable design for photonic applications. The photonic nanojet is a narrow and focused high-intensity light beam emitting from the shadow-side of microspheres with tunable effective length, thus enabling its applications in biosensing technology. In this paper, we numerically studied the photonic nanojets brought about from biocompatible hydrogel core-shell microspheres with different optical properties. It was found that the presence of the shell layer can significantly affect the characteristics of the photonic nanojets, such as the focal distance, intensity, effective length, and focal size. Generally speaking, the larger the core-shell microspheres, the longer the focal distance, the stronger the intensity, the longer the effective length, and the larger the focal size of the generated photonic nanojets are. The numerical simulations of the photonic nanojets from the biocompatible core-shell microspheres on a Klarite substrate, which is a classical surface-enhancing Raman scattering substrate, showed that the Raman signals in the case of adding the core-shell microspheres in the system can be further enhanced 23 times in water and 108 times in air as compared in the case in which no core-shell microspheres are present. Our study of using tunable photonic nanojets produced from the biocompatible hydrogel core-shell microspheres shows potential in future biosensing applications.

Surface plasmons excited by multiple layer grating.

The surface plasmons that are excited by the multiple layer grating structures on the gold thin film are studied using the finite-difference time-domain method in this paper. The structure parameters' effects on the coupling enhancement of surface plasmons are examined, and the structure design guidelines are given. It is found that the distance between the grating layers and the distance between the gratings and gold thin film are the key structure parameters for better cavity resonances. To have the stronger field enhancements of the excited surface plasmons for the multilayer grating structures, it is found that the width of the gratings should be smaller for the lower grating layers. The multiple layer gratings with proper structure designs can have better performances than single layer grating structure because the cavity effects can enhance the light coupling and more light can be coupled into the surface plasmons by more layers of grating. It is found that the maximum electric field intensity for five layer grating structures can be 163% of the case of the single layer grating structure in our simulations.

Optical Properties of Au-based and Pt-based Alloys for Infrared Device Applications: A Combined First Principle and Electromagnetic Simulation Study.

Due to the rapid progress in MEMS-based infrared emitters and sensors, strong demand exists for suitable plasmonic materials for such microdevices. We examine the possibility of achieving this goal by alloying other metals with the noble metals Au and Pt, which have some drawbacks, such as low melting point, structural instability, and high costs. The six different metals (Ir, Mo, Ni, Pb, Ta, and W) which possess good properties for heat resistance, stability, and magnetism are mixed with noble metals to improve the properties. The optical properties are calculated by density functional theory and they are used for further investigations of the optical responses of alloy nanorods. The results show that the studied alloy nanorods have wavelength selective properties and can be useful for infrared devices and systems.

Vortex energy flows generated by core-shell nanospheres.

Investigated in this paper is the interaction of light and the nanospheres composed by a dielectric core with a gold-shell cladding that causes the optical vortices inside the core and the whirlpools around the shell. Different radius ratios, dimensions and the dielectric functions of nanospheres were studied using the finite-difference time-domain method. It was found that optical vortices were most likely to occur in the regions of increased absorption cross section and reduced scattering cross section. Two optical vortices of the opposite polarity, each centered in one of the particles of a dimer are created by a nanoshell dimer. The surrounding media of a nanoshell with different dielectric functions can be used to affect the energy flows generated by core-shell nanospheres.

Effects of the rotation angle on surface plasmon coupling of nanoprisms.

We studied the effects of relative orientation of bowtie nanostructures on the plasmon resonance both experimentally and theoretically in this work. Specifically, we fabricated gold bowtie nanoantennas with rotated nanoprisms, measured the near-field and the far-field resonance behaviors using Raman spectroscopy and scattering microspectroscopy, and simulated the effects of the rotation angle on the localized surface plasmonic resonance using finite-difference time-domain simulations. In addition to the widely-discussed dipolar resonance in regular bowtie nanostructures, defined as tip-mode resonance in the present study, the excitations of edge-mode resonance were discovered under certain rotation angles of nanoprisms. Because of the resonances of different modes at different wavelengths, two different incident laser sources were used to measure the Raman spectra to provide evidence for the evolution of different resonance modes. Also, both the tip-mode and edge-mode resonances were verified by the simulated charge density distribution and their trends were discussed. Based on the discovered trend, a plasmon protractor was created with a near-exponential decay relationship between the relative resonance wavelength shift and cosine of the rotation angle. A plasmon hybridization model was also proposed for rotated bowties to explain the coupling between nanoprisms during rotation.

Mitochondrial dysfunction induced by ultra-small silver nanoclusters with a distinct toxic mechanism.

As noble metal nanoclusters (NCs) are widely employed in nanotechnology, their potential threats to human and environment are relatively less understood. Herein, the biological effects of ultra-small silver NCs coated by bovine serum albumin (BSA) (Ag-BSA NCs) on isolated rat liver mitochondria were investigated by testing mitochondrial swelling, membrane permeability, ROS generation, lipid peroxidation and respiration. It was found that Ag-BSA NCs induced mitochondrial dysfunction via synergistic effects of two different ways: (1) inducing mitochondrial membrane permeability transition (MPT) by interacting with the phospholipid bilayer of the mitochondrial membrane (not with specific MPT pore proteins); (2) damaging mitochondrial respiration by the generation of reactive oxygen species (ROS). As far as we know, this is the first report on the biological effects of ultra-small size nanoparticles (∼2 nm) at the sub-cellular level, which provides significant insights into the potential risks brought by the applications of NCs. It would inspire us to evaluate the potential threats of nanomaterials more comprehensively, even though they showed no obvious toxicity to cells or in vivo animal models. Noteworthy, a distinct toxic mechanism to mitochondria caused by Ag-BSA NCs was proposed and elucidated.

Effects of exchange correlation functional on optical permittivity of gold and electromagnetic responses.

Understanding the optical properties of nanometer-scale noble metals is important for the nanoplasmonic devices. The bulk gold and thin film are calculated by density functional theory (DFT) with LDA, PBE, and GLLBSC functionals, respectively. The GLLBSC results for bulk gold are closer to the experimental data because the GLLBSC functional has better descriptions of transition energy. The Im(ε) of thin film calculated by LDA and PBE are overestimated. The effects of DFT-based optical properties are performed by conducting electromagnetic simulations. The transmission for the gold thin film by GLLBSC is blue-shifted. The gold grating structure with the GLLBSC-based optical permittivity has strong localized streamlines of Poynting vector in the corner edges at the resonance condition.

Electric field enhancement and far-field radiation pattern of the nanoantenna with concentric rings.

The optical antennas have the potential in various applications because of their field enhancement and directivity control. The directivity of a dipole antenna can be improved by directivity-enhanced Raman scattering structure, which is a combination of a dipole antenna and a ring reflector layer on a ground plane. The concentric rings can collect the light into the center hole. Depending upon the geometry of the antenna inside the hole, different electric field enhancements can be achieved. In this paper, we propose to combine the concentric rings with the directivity-enhanced Raman scattering structure in order to study its electric field enhancement and the far-field radiation pattern by finite-difference time-domain simulations. Compared with the structure without the concentric rings over the ground plane, it is found that our proposed structure can obtain stronger electric field enhancements and narrower radiation beams because the gold rings can help to couple the light into the nanoantenna and they also scatter light into the far field and modify the far-field radiation pattern. The designed structures were fabricated and the chemical molecules of thiophenol were attached on the structures for surface-enhanced Raman scattering (SERS) measurements. The measured results show that the structure with concentric rings can have stronger SERS signals. The effects of the dielectric layer thickness in our proposed structure on the near-field enhancements and far-field radiation are also investigated. The proposed structure can be useful for several nanoantenna applications, such as sensing or detecting.

Self-assembled monolayer immobilized gold nanoparticles for plasmonic effects in small molecule organic photovoltaic.

The aim of this study was to investigate the effect of gold nanoparticle (Au NP)-induced surface plasmons on the performance of organic photovoltaics (OPVs) that consist of copper phthalocyanine and fullerene as the active materials. The photon absorption can be enhanced by immobilization of surfactant-stabilized Au NPs on a self-assembled monolayer-modified indium tin oxide (ITO) electrode, and thus, the photocurrent as well as the power conversion efficiency (PCE) of these OPVs can be improved. Varying the density of the immobilized Au NPs in the devices provided no significant variation in the charge mobility but it did enhance the photocurrent. In addition, device simulation results demonstrated that the improvement in photocurrent was due to the enhancement of light absorption and the increase in charge separation, which was facilitated by the Au NPs. Overall, we attributed the improvement in PCE of OPVs to a localized surface plasmon resonance effect generated by the Au NPs.

Mitochondrial permeability transition induced by different concentrations of zinc.

Zinc is one of the required trace elements in animals, and it serves an important role in biological systems. However, high levels of zinc are poisonous to organisms. So far, there exist conflicting reports about zinc ions-induced mitochondrial permeability transition (MPT). We analyzed the effects of Zn²âº on MPT by monitoring mitochondrial swelling with the ultraviolet-visible light absorption spectrum, characterizing the fluidity of the membrane with fluorescence anisotropy, detecting the transmembrane potential (Δψ) with fluorescence intensity, and observing mitochondrial ultrastructure with transmission electron microscopy. Data reveal that low concentrations of zinc ions can trigger MPT while high levels of zinc ions cannot, which implies that zinc ions' toxicity cannot be the result of a single simple mechanism.

Effects of the tip shape on the localized field enhancement and far field radiation pattern of the plasmonic inverted pyramidal nanostructures with the tips for surface-enhanced Raman scattering.

The plasmonic 2D W-shape and 3D inverted pyramidal nanostructures with and without the tips are studied. The effects of the tip height and tip tilt angle on the near field enhancement and far field radiation pattern are discussed in this paper. The localized hot spots are found around the pits and the radiation pattern can be affected by the tip structures. The inverted pyramidal nanostructures with and without the tips were fabricated and their reflection spectra and surface-enhanced Raman scattering (SERS) signals for the chemical molecules thiophenol were measured. The simulation according to the geometry parameters of the fabricated structures is demonstrated. We found that the SERS of our proposed structures with the tips can have stronger light field enhancements than the inverted pyramidal nanostructures without the tips, and the far field radiation pattern can be varied by changing the tip height and tip tilt angle. The study of surface plasmon modes and charge distributions can help the understanding of how to arrange the plasmonic structures to achieve high field enhancement and preferred far field radiation pattern. Our study can be useful for the design of the strong field enhancement SERS substrate with specific far field radiation properties. It can be also applied to the portable Raman detectors for in situ and remote measurements in specific applications.

Resonance modes, cavity field enhancements, and long-range collective photonic effects in periodic bowtie nanostructures.

The discovery of single-molecule sensitivity via surface-enhanced Raman scattering on resonantly excited noble metal nanoparticles has brought an increasing interest in its applications to the molecule detection and identification. Periodic gold bowtie nanostructures have recently been shown to give a large enhancement factor sufficient for single molecule detection. In this work, we simulate the plasmon resonance for periodic gold bowtie nanostructures. The difference between the dipole and the quadrupole resonances is described by examining the magnitude and phase of electric field, the bound surface charge, and the polarization. The gap size dependence of the field enhancement can be interpreted by considering cavity field enhancement. Also, additional enhancement is obtained through the long-range collective photonic effect when the bowtie array periodicity matches the resonance wavelength.

A novel pH-sensitive (±)-α-tocopherol-5-fluorouracil adduct with antioxidant and anticancer properties.

A novel pH-sensitive (±)-α-tocopherol-5-fluorouracil (VE-5-FU) adduct with antioxidant and anticancer properties for antioxidant-based cancer chemoprevention was synthesized and utilized for selective drug release in the stomach.

Spectroscopic and microscopic studies on the mechanisms of mitochondrial toxicity induced by different concentrations of cadmium.

The deleterious action of Cd2+ on rat liver mitochondria was investigated in this work using spectroscopic and microscopic methods. The concentration dependence of Cd2+ on mitochondrial swelling, membrane potential and membrane fluidity was studied. Our aim was to detect the active sites of Cd2+ in the mitochondrial membrane treatments with cyclosporin A (CsA) and EGTA on the mitochondrial permeability transition (MPT) induced by low and high concentrations of Cd2+. The protective effects of dithiothreitol, human serum albumin and monobromobimane+ on Cd2+-induced MPT were also monitored. All of these investigations indicated that Cd2+ can directly affect MPT at two separate localization sites at different concentrations: the classic Ca2+ triggering site and the thiol (-SH) groups of membrane proteins matched by MPT pore opening (defined as "S" site). At the high concentration of Cd2+, other free -SH groups in the mitochondrial matrix may be involved in this process. These findings were supported by transmission electron microscopy and shed light on the toxic mechanism of Cd2+ on mitochondria.

Enhancement of the optical transmission by mixing the metallic and dielectric nanoparticles atop the silicon substrate.

We propose a structure with the metallic and dielectric nanoparticles on the surface of the silicon material and study its optical transmission properties. The structure with the radiuses of the silver and silica nanoparticles as 50 nm and 100 nm, respectively, with the gap as 8 nm between silver and silica nanoparticles is found to have the largest optical transmission into the silicon material in our simulations. The largest field intensities are on the bottom of the silver nanoparticles and these can result strong field scattering into the silicon material. From the plotting of the average power densities around the gaps and the air regions between the silver and silica nanoparticles, the light power can go thorough these regions and flow downward to the silicon material. It is also found that the light energy rotates around the bottom of the silver nanoparticles due to the strong localized surface plasmons. The rectangular arrangement of the nanoparticle structures with mixing metallic and dielectric nanoparticles are studied, and the cases for the structures with only the metallic nanoparticles or only the dielectric nanoparticles are also simulated and compared. The rectangular or hexagonal structures with mixing metallic and dielectric nanoparticles on the surface of the silicon substrate can have better optical transmission than the cases of the rectangular arrangement with only metallic or dielectric nanoparticles.

Biophysical studies on the interactions of a classic mitochondrial uncoupler with bovine serum albumin by spectroscopic, isothermal titration calorimetric and molecular modeling methods.

The interaction between a classic uncoupler (2,4-dinitrophenol, DNP) and bovine serum albumin (BSA) was investigated by fluorescence spectroscopy under the physiological conditions. The fluorescence quenching constants were calculated by the Stern-Volmer equation, and based upon the temperature dependence of quenching constants, it was proved that DNP caused a static quenching of the intrinsic fluorescence of BSA. Owing to the static quenching mechanism, different associative binding constants at various temperatures were determined and thus the thermodynamic parameters, namely enthalpy (ΔH=-21.12 kJ mol(-1)) and entropy changes (ΔS=23.51 J mol(-1) K(-1)) could be calculated based on the binding constants. Moreover, the enthalpy and entropy changes are consistent with the "Enthalpy-Entropy Compensation" equation obtained from our previous work. The negative enthalpy and positive entropy indicated that the electrostatic interactions played a major role in DNP-BSA binding process. Site marker competitive displacement experiments were carried out by using fluorescence and isothermal titration calorimetry (ITC) methods. These results showed that DNP bound with high affinity to Sudlow's site I (subdomain IIA) of BSA. The distance (r=3.78 nm) between donor (BSA) and acceptor (DNP) was obtained according to the mechanism of fluorescence resonance energy transfer (FRET). Furthermore, the results of synchronous fluorescence and circular dichroism (CD) spectroscopic studies indicated that the microenvironment and the secondary conformation of BSA were altered. The above results were supported by theoretical molecular modeling methods.

Modulation of optical focusing by using optimized zone plate structures.

The focusing properties of the optimized zone plate structures which have upper and lower zones with different thicknesses are studied by the three-dimensional finite-difference time-domain method. Two kinds of materials are chosen, including silver representing metal and BK7 glass representing dielectric. An optimization algorithm is applied to tune the parameters of zone plate structures. Several optimized zone plate structures with smaller circular-shape focus are presented. By using the angular spectrum representation method, we found that the cases with smaller focal sizes have larger high-k components; however, the intensities of side lobes also become larger in comparison with the main beam. It is also found that the phase differences between different spatial field components can have the influences on focusing properties. A special case with two focuses is shown by changing the cost function of the same optimization algorithm. Our findings suggest that the optimized zone plate structures can reconstruct the light intensity distribution and have a great potential for the applications in imaging, lithography, and data storage.

Synthesis of a novel hydrazone derivative and biophysical studies of its interactions with bovine serum albumin by spectroscopic, electrochemical, and molecular docking methods.

Hydrazone derivatives possess potential antitumor activities based on modulation of the iron metabolism in cancer cell. A novel hydrazone, N'-(2,4-dimethoxybenzylidene)-2-hydroxybenzohydrazide (DBH), has been synthesized and characterized, which is an analogue of 311 possessing potent anticancer activity. The interactions between DBH and bovine serum albumin (BSA) have been investigated systematically by fluorescence, molecular docking, circular dichroism (CD), UV-vis absorption, and electrochemical impedance spectroscopy (EIS) methods under physiological conditions. The fluorescence quenching observed is attributed to the formation of a complex between BSA and DBH, and the reverse temperature effect of the fluorescence quenching has been found and discussed. The primary binding pattern is determined by hydrophobic interaction occurring in Sudlow's site I of BSA. DBH could slightly change the secondary structure and induce unfolding of the polypeptides of protein. An average binding distance of ~4.0 nm has been determined on the basis of the Förster resonance energy theory (FRET). The effects of iron on the system of DBH-BSA have also been investigated. It is found that iron could compete against BSA to bind DBH. All of these results are supported by a docking study using a BSA crystal model. It is shown that DBH can efficiently bind with BSA and be transported to the focuses needed. Subsequent antitumor test and detailed anticancer mechanism are undergoing in our lab.