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Scutellariae Radix (SR) and its bioactive flavones elicit a variety of effects in the brain. However, the brain uptake of individual SR flavones and its relationship to the elicited effects after SR administration remain unknown. Moreover, previous studies seldom measured pharmacokinetic and pharmacodynamic outcomes simultaneously. In the current study, the brain uptake of six major SR flavones and the anxiolytic behavior following oral administration of a SR extract at two clinically relevant doses (600 and 1200 mg/kg twice daily) were simultaneously investigated in mice (n = 18 per group). Brain and plasma concentrations of the flavones were measured by LC-MS/MS, while the anxiolytic effect was evaluated using the elevated plus maze. To further investigate the mechanism behind the differential brain uptake of the six SR flavones, these flavones were separately administered to mice at an equivalent molar oral dose (n = 6). The brain tissue bindings of the SR flavones were also measured with the in vitro brain slice method. Our results indicated that all six SR flavones including three aglycons (baicalein, wogonin, and oroxylin A) and three glucuronides (baicalin, wogonoside, and oroxyloside) could pass through the blood-brain barrier, with brain concentrations ranging from 7.9 to 224.0 pmol/g. It provided novel evidence that oroxylin A had the highest brain uptake among the six SR flavones regardless of its limited content in SR extract, in which 3.6-3.9% of the administered oroxylin A dose was present in the brain 6 h postdosing and with a brain-to-plasma ratio of 0.42-0.46. Although SR extract contains flavones that are positive modulators of the benzodiazepine binding site of GABA A receptors (baicalein, wogonin, and baicalin), our behavioral study for the first time indicated that SR extract (a mixture of six flavones) did not elicit significant anxiolytic effect at the studied doses. Oroxylin A also demonstrated the highest brain uptake when the six flavones were separately administered to mice, and the highest affinity to brain tissues in the in vitro tissue binding assay. The high brain uptake of oroxylin A, a GABA A antagonist which had been reported to antagonize diazepam-induced anxiolytic effect, might have suppressed the anxiolytic effects of the other flavones and account for the lack of overall anxiolytic effect of SR extract. The current study illustrates the importance of monitoring pharmacokinetics in a behavioral study, particularly for herbal medicines which consist of multiple components that might have different or even opposite pharmacological effects on the same target.

Electroosmotic flow (EOF) or electro-osmosis has been shown to exhibit a hysteresis effect under displacement flow involving two solutions with different concentrations, i.e. the flow velocity for a high-concentration solution displacing a low-concentration solution is faster than the flow velocity in the reverse direction involving the same solution pair. On the basis of our recent numerical analysis, a pH change initiated at the interface between the two solutions has been hypothesized as the cause for the observed anomalies. We report the first experimental evidence of EOF hysteresis induced by a pH change in the bulk solution. pH-sensitive dye was employed to quantify the pH changes in the microchannel during EOF. The electric-field gradient across the boundary of two solutions generates an accumulation or depletion of a minority of pH-governing ions such as hydronium (H 3 O + ) ions, thus inducing pH variations across the microchannel. When a high-concentration solution displaced a lower-concentration solution, a pH increase was observed, while the flow in the reverse direction induced a decrease in pH. This effect causes significant changes to the zeta potential and flow velocity. The experimental results show good quantitative agreement with numerical simulations. This work presents the experimental proof which validates the hypothesis of a pH change during electroomostic flow hysteresis as predicted by numerical analysis. The understanding of pH changes during EOF is crucial for accurate flow manipulation in microfluidic devices and maintenance of constant pH in biological and chemical systems under an electric field.

Electroosmotic flow (EOF) with two or more fluids is often encountered in various microfluidic applications. However, no investigation has hitherto been conducted to investigate the hysteretic or flow direction-dependent behavior during displacement flow of solutions with dissimilar anion species. In this investigation, EOF of dissimilar anionic solutions was studied experimentally through the current monitoring method and numerically through finite element simulations. As opposed to other conventional displacement flows, EOF involving dissimilar anionic solutions exhibits counterintuitive behavior, whereby the current-time curve does not reach the steady-state value of the displacing electrolyte. Two distinct mechanics have been identified as the causes for this observation: (a) ion concentration adjustment when the displacing anions migrate upstream against EOF due to competition between the gradients of electromigrative and convective fluxes and (b) ion concentration readjustment induced by the static diffusive interfacial region between the dissimilar fluids which can only be propagated throughout the entire microchannel with the presence of EOF. The resultant ion distributions lead to the flow rate to be directional-dependent, indicating that the flow conditions are asymmetric between these two different flow directions. The outcomes of this investigation contribute to the in-depth understanding of flow behavior in microfluidic systems involving inhomogeneous fluids, particularly dissimilar anionic solutions. The understanding of EOF hysteresis is fundamentally important for the accurate prediction of analytes transport in microfluidic devices under EOF.

Appropriate control of substrate surface properties prior to inkjet printing could be employed to improve the printing quality of fine resolution structures. In this paper, novel methods to fabricate patterned surfaces with a combination of hydrophilic and hydrophobic properties are investigated. The results of inkjet printing of PEDOT/PSS conductive ink on these modified surfaces are presented. Selective wetting was achieved via a two-step hydrophilic-hydrophobic coating of 3-aminopropyl trimethoxysilane (APTMS) and 3M electronic grade chemical respectively on PET surfaces; this was followed by a selective hydrophilic treatment (either atmospheric O2/Ar plasma or UV/ozone surface treatment) with the aid of a Nickel stencil. Hydrophobic regions with water contact angle (WCA) of 105° and superhydrophilic regions with WCA <5° can be achieved on a single surface. During inkjet printing of the treated surfaces, PEDOT/PSS ink spread spontaneously along the hydrophilic areas while avoiding the hydrophobic regions. Fine features smaller than the inkjet droplet size (approximately 55 μm in diameter) can be successfully printed on the patterned surface with high wettability contrast.

In this study, we aim to identify the potential biomarkers in hTG pathogenesis in schisandrin B-induced hTG mouse model. To investigate whether these identified biomarkers are only specific to schisandrin B-induced hTG mouse model, we also measured these biomarkers in a high fat diet (HFD)-induced hTG mouse model. We employed a LC/MS/MS-based lipidomic approach for the study. Mouse liver and serum metabolites were separated by reversed phase liquid chromatography. Metabolite candidates were identified by matching with marker retention times, isotope distribution patterns, and high-resolution MS/MS fragmentation patterns. Subsequently, target candidates were quantified by quantitative MS. In the schisandrin B-induced hTG mice, we found that the plasma fatty acids, diglyceroids, and phospholipids were significantly increased. Palmitic acid and stearic acid were increased in the plasma; oleic acid, linoleic acid, linolenic acid, arachidonic acid, and docosahexaenoic acid were increased in both the plasma and the liver. Acetyl-CoA, malonyl-CoA, and succinyl-CoA were increased only in the liver. The changes in levels of these identified markers were also observed in HFD-induced hTG mouse model. The consistent results obtained from both hTG models not only suggest novel biomarkers in hTG pathogenesis, but they also provide insight into the underlying mechanism of the schisandrin B-induced hTG.

The study presents a dielectrophoretic cell separation method via three-dimensional (3D) nonuniform electric fields generated by employing a periodic array of discrete but locally asymmetric triangular bottom microelectrodes and a continuous top electrode. Traversing through the microelectrodes, heterogeneous cells are electrically polarized to experience different strengths of positive dielectrophoretic forces, in response to the 3D nonuniform electric fields. The cells that experience stronger positive dielectrophoresis are streamed further in the perpendicular direction to the fluid flow, leaving the cells that experience weak positive dielectrophoresis, which continue to traverse the microelectrode array essentially along the laminar flow streamlines. The proposed method has achieved 87.3% pure live cells harvesting efficiency from a live/dead NIH-3T3 cells mixture, and separation of MG-63 cells from erythrocytes with a separation efficiency of 82.8%. The demonstrated cell separation shows promising applications of the DEP separator for cell separation in a continuous mode.

A gecko's superb ability to adhere to surfaces is widely credited to the large attachment area of the hierarchical and fibrillar structure on its feet. The combination of these two features provides the necessary compliance for the gecko toe-pad to effectively engage a high percentage of the spatulae at each step to any kind of surface topography. With the use of multi-tiered porous anodic alumina template and capillary force assisted nanoimprinting, we have successfully fabricated a gecko-inspired hierarchical topography of branched nanopillars on a stiff polymer. We also demonstrated that the hierarchical topography improved the shear adhesion force over a topography of linear structures by 150%. A systematic analysis to understand the phenomenon was performed. It was determined that the effective stiffness of the hierarchical branched structure was lower than that of the linear structure. The reduction in effective stiffness favored a more efficient bending of the branched topography and a better compliance to a test surface, hence resulting in a higher area of residual deformation. As the area of residual deformation increased, the shear adhesion force emulated. The branched pillar topography also showed a marked increase in hydrophobicity, which is an essential property in the practical applications of these structures for good self-cleaning in dry adhesion conditions.

Moving dielectrophoresis has been recently developed by the authors as an alternative method to achieve simultaneous cell fractionation and transportation. With an array of independently excitable microelectrodes, this method generates a moving electric field to sequentially fractionate and transport cells across a microchannel. Due to the peculiarity of this method, the motion of the cells is unsteady and there are interesting and distinct differences between cells experiencing positive or negative dielectrophoresis. For a proper understanding and design of a microdevice utilizing this methodology, this study presents a model for the equation of motion for a polarized cell and its unsteady motion under moving dielectrophoresis. The model considers the basic module to generate a moving electric field, where there is a finite-width top electrode and an infinite-width bottom electrode, in a parallel-plate configuration. The forces considered include dielectrophoretic force, fluid drag, buoyancy, and gravitational force. These forces are modeled as equivalent point forces acting at the center of mass of the cell. A parallel-plate wall correction factor is employed to account for the effect of the large cell size to microchannel height ratio. Various parameters are examined including the initial position of the cell relative to the electrodes, cell's Clausius-Mossotti factor, cell size, applied voltage, electrode width, interelectrode gap, microchannel height, number of energized electrodes, and types of electrode configurations. Reasonable agreements were obtained between simulated and experimental results. As the solution of the unsteady motion is rather tedious, a MATLAB algorithm, with all the associated files, for the prediction of the cell trajectory, is available on request.

This study presents a new cell manipulation method using a moving dielectrophoretic force to transport or fractionate cells along a microfluidic channel. The proposed moving dielectrophoresis (mDEP) is generated by sequentially energizing a single electrode or an array of electrodes to form an electric field that moves cells continuously along the microchannel. Cell fractionation is controlled by the applied electrical frequency, and cell transportation is controlled by the interelectrode activation time. The applicability of this method was demonstrated to simultaneously fractionate and transport Saccharomyces cerevisiae yeast cells, both viable and nonviable, by operating at conditions under which the cells were subjected to positive and negative dielectrophoresis, respectively. Compared to the conventional dielectrophoresis (cDEP and traveling wave dielectrophoresis (twDEP), moving dielectrophoresis allows cells to be separated on the basis of the real part of the Clausius-Mossotti factor, as in cDEP, but yet allows the direct transportation of separated cells without using fluid flow, as in twDEP. This dielectrophoresis technique provides a new way to manipulate cells and can be readily implemented on programmable multielectrode devices.

The effects of a salt mixture consisting of a salt-out salt (NaCl) and a salt-in salt (NaI) on the sol-gel transition of methylcellulose (MC) in aqueous solution have been studied by means of micro differential scanning calorimetry and rheometry. The salt mixture was found to have a combined effect from the salt-out and salt-in salts in the mixture, and the salt effect was dependent on the water hydration abilities of the component ions and ion concentration. At a fixed total salt concentration, the sol-gel transition temperature nicely followed a rule of mixing: Tp = m1Tp1 + m2Tp2 where Tp, Tp1, and Tp2 are the gelation peak temperatures for the MC solutions with a salt mixture, NaCl, and NaI, respectively, and mi is the molar fraction of the salt component i in the salt mixture. The linear rule of mixing proved that the effects of NaCl and NaI on the sol-gel transition of MC are completely independent. In addition, the presence of a single salt or a salt mixture in a MC solution does not change the essential mechanism of MC gelation. Therefore, the sol-gel transition of MC can be simply controlled by a salt mixture consisting of a salt-out salt and a salt-in salt. The rheological results supported the micro thermal results excellently. But the gel strength of MC containing salts was influenced by both salt type and salt concentration., (Copyright 2004 American Chemical Society)