Structure-Based Discovery of mPGES-1 Inhibitors Suitable for Preclinical Testing in Wild-Type Mice as a New Generation of Anti-Inflammatory Drugs

Human mPGES-1 is recognized as a promising target for next generation of anti-inflammatory drugs without the side effects of currently available anti-inflammatory drugs, and various inhibitors have been reported in the literature. However, none of the reported potent inhibitors of human mPGES-1 has shown to be also a potent inhibitor of mouse or rat mPGES-1, which prevents using the well-established mouse/rat models of inflammation-related diseases for preclinical studies. Hence, despite of extensive efforts to design and discover various human mPGES-1 inhibitors, the promise of mPGES-1 as a target for the next generation of anti-inflammatory drugs has never been demonstrated in any wild-type mouse/rat model using an mPGES-1 inhibitor. Here we report discovery of a novel type of selective mPGES-1 inhibitors potent for both human and mouse mPGES-1 enzymes through structure-based rational design. Based on in vivo studies using wild-type mice, the lead compound is indeed non-toxic, orally bioavailable, and more potent in decreasing the PGE2 (an inflammatory marker) levels compared to the currently available drug celecoxib. This is the first demonstration in wild-type mice that mPGES-1 is truly a promising target for the next generation of anti-inflammatory drugs

Nebulization using ZnO/Si surface acoustic wave devices with focused interdigitated transducers

Propagation of surface acoustic waves (SAWs) on bulk piezoelectric substrates such as LiNbO3 and quartz, exhibits an in-plane anisotropic effect due to their crystal cut orientations. Thin film SAW devices, such as those based on ZnO or AlN, offer potential advantages, including isotropic wave velocities in all in-plane directions, higher power handling capability, and potentially lower failure rates. This paper reports experimental and simulation results of nebulization behaviour for water droplets using ZnO/Si surface acoustic wave devices with focused interdigital transducers (IDTs). Post-deposition annealing of the films at various temperatures was applied to improve the quality of the sputtering-deposited ZnO films, and 500 °C was found to be the optimal annealing temperature. Thin film ZnO/Si focused SAW devices were fabricated using the IDT designs with arc angles ranging from 30° to 90°. Nebulization was significantly enhanced with increasing the arc angles of the IDTs, e.g., increased nebulization rate, reduced critical powers required to initialise nebulization, and concentration of the nebulised plume into a narrower size of spray. Effects of applied RF power and droplet size have been systematically studied, and increased RF power and reduced droplet size significantly enhanced the nebulization phenomena

Film bulk acoustic resonator pressure sensor with self temperature reference

A novel film bulk acoustic resonator (FBAR) with two resonant frequencies which have opposite reactions to temperature changes has been designed. The two resonant modes respond differently to changes in temperature and pressure, with the frequency shift being linearly correlated with temperature and pressure changes. By utilizing the FBAR's sealed back trench as a cavity, an on-chip single FBAR sensor suitable for measuring pressure and temperature simultaneously is proposed and demonstrated. The experimental results show that the pressure coefficient of frequency for the lower frequency peak of the FBAR sensors is approximately −17.4 ppm kPa−1, while that for the second peak is approximately −6.1 ppm kPa−1, both of them being much more sensitive than other existing pressure sensors. This dual mode on-chip pressure sensor is simple in structure and operation, can be fabricated at very low cost, and yet requires no specific package, therefore has great potential for applications

Flexible surface acoustic wave resonators built on disposable plastic film for electronics and lab-on-a-chip applications

Flexible electronics are a very promising technology for various applications. Several types of flexible devices have been developed, but there has been limited research on flexible electromechanical systems (MEMS). Surface acoustic wave (SAW) devices are not only an essential electronic device, but also are the building blocks for sensors and MEMS. Here we report a method of making flexible SAW devices using ZnO nanocrystals deposited on a cheap and bendable plastic film. The flexible SAW devices exhibit two wave modes - the Rayleigh and Lamb waves with resonant frequencies of 198.1 MHz and 447.0 MHz respectively, and signal amplitudes of 18 dB. The flexible devices have a high temperature coefficient of frequency, and are thus useful as sensitive temperature sensors. Moreover, strong acoustic streaming with a velocity of 3.4 cm/s and particle concentration using the SAW have been achieved, demonstrating the great potential for applications in electronics and MEMS

Emulsion Electrospinning of Polytetrafluoroethylene (PTFE) Nanofibrous Membranes for High-Performance Triboelectric Nanogenerators

Electrospinning is a simple, versatile technique for fabricating fibrous nanomaterials with the desirable features of extremely high porosities and large surface areas. Using emulsion electrospinning, polytetrafluoro­ethylene/polyethene oxide (PTFE/PEO) membranes were fabricated, followed by a sintering process to obtain pure PTFE fibrous membranes, which were further utilized against a polyamide 6 (PA6) membrane for vertical contact-mode triboelectric nanogenerators (TENGs). Electrostatic force microscopy (EFM) measurements of the sintered electrospun PTFE membranes revealed the presence of both positive and negative surface charges owing to the transfer of positive charge from PEO which was further corroborated by FTIR measurements. To enhance the ensuing triboelectric surface charge, a facile negative charge-injection process was carried out onto the electrospun (ES) PTFE subsequently. The fabricated TENG gave a stabilized peak-to-peak open-circuit voltage (<i>V</i>_oc) of up to ∼900 V, a short-circuit current density (<i>J</i>_sc) of ∼20 mA m^–2, and a corresponding charge density of ∼149 μC m^–2, which are ∼12, 14, and 11 times higher than the corresponding values prior to the ion-injection treatment. This increase in the surface charge density is caused by the inversion of positive surface charges with the simultaneous increase in the negative surface charge on the PTFE surface, which was confirmed by using EFM measurements. The negative charge injection led to an enhanced power output density of ∼9 W m^–2 with high stability as confirmed from the continuous operation of the ion-injected PTFE/PA6 TENG for 30 000 operation cycles, without any significant reduction in the output. The work thus introduces a relatively simple, cost-effective, and environmentally friendly technique for fabricating fibrous fluoropolymer polymer membranes with high thermal/chemical resistance in TENG field and a direct ion-injection method which is able to dramatically improve the surface negative charge density of the PTFE fibrous membranes

The Effect of Positive Interactions on Temporal Turnover of Community Composition along an Environmental Gradient

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Acoustofluidics along inclined surfaces based on AlN/Si Rayleigh surface acoustic waves

Conventional acoustofluidics are restricted to manipulation of droplets on a flat surface, and there is an increasing demand for acoustofluidic devices to be performed at inclined surfaces to facilitate multilayered microfluidic device design and enhance system compactness. This paper reports theoretical and experimental studies of acoustofluidic behaviors (including transportation/pumping and jetting) along inclined surfaces using AlN/Si Rayleigh surface acoustic waves (SAWs). It has been demonstrated that for droplets with volume smaller than 3 μL, they could be efficiently transported on arbitrary inclined surfaces. The gravity effect would play a more and more important role in uphill climbing with the increased inclination angle. When the inclination angle was increased up to 90°, a higher threshold power was needed to transport the droplet and the maximum droplet volume which can be pumped also reached its minimum value. Effects of surface inclination angle on droplet jetting angles could be neglected for their volumes less than 2 μL. Moreover, microfluidic and acoustic heating performances of AlN/Si SAWs were further studied and compared with those conventional ZnO/Si SAWs with the same electrode configurations

Flexible thin-film acoustic wave devices with off-axis bending characteristics for multisensing applications

Flexible surface acoustic wave (SAW) devices have recently attracted tremendous attention for their widespread applications in sensing and microfluidics. However, for these applications, the SAW devices often need to be bent into off-axis deformations between the acoustic-wave propagation direction and bending direction. Currently there are few studies on this topic, and the bending mechanisms under off-axis bending deformations have remained unexplored for multi-sensing applications. Herein, we fabricated aluminum nitride (AlN) flexible SAW devices by using high quality AlN films deposited on flexible glass substrates and systematically investigated their complex deformation behaviors. A theoretical model was firstly developed using coupling wave equations and boundary condition method to analyze the device’s characteristics with bending and off-axis deformation under elastic strains. The relationships between frequency shifts of the SAW device with bending strain and off-axis angle were obtained which showed the identical results with those from the theoretical calculations. Finally, we performed proof-of-concept demonstrations of multi-sensing applications by monitoring human wrist movements at various off-axis angles and detecting UV light intensities on a curved surface, thus paving the ways for versatile flexible electronics applications

Preparation and optimization of poly (lactic-co-glycolic acid) rod-shaped particles in nano size range for paclitaxel delivery

Nanoparticle shape has been acknowledged as an important design parameter due to its influence on nanoparticle interaction with biological systems. However, there is lacking of simple and scalable preparation technique for drug loaded non-spherical polymeric nanoparticles for a long time, thus hindering the potential applications. Although our previous research has modified the traditional emulsion solvent evaporation technique by adding guest molecules to prepare non-spherical poly (lactic-co-glycolic acid) (PLGA) particles, it is difficult to obtain nano-sized rods with minor axis less than 200 nm, which may have great potential in cancer therapy. Herein, in present research, the two-step ESE method was used and optimized to prepare poly (lactic-co-glycolic acid) nanorods for paclitaxel delivery. Firstly, the single-factor experiment was used to screen the influence of multi-factors including type of guest molecules, concentration of guest molecules, emulsification method, surfactant concentration, oil volume, poly (lactic-co-glycolic acid) concentration on the size and shape to determine the range of variables; based on the above range, a multi-factor and multi-level orthogonal experiment was designed. The formula is evaluated by the rod fabrication yield and the aspect ratio of major axis to minor axis. The results showed that the yield of nanorods in the optimal formula was 99% and the aspect ratio was 5.35 ± 2.05 with the minor axis of 135.49 ± 72.66 nm, and major axis of 657.77 ± 307.63 nm. In addition, the anti-cancer drug paclitaxel was successfully encapsulated in PLGA nanorods by the same technique. Our results not only enrich the ESE technique for preparing small sized poly (lactic-co-glycolic acid) nanorods, but also envision the potential application of nanorods for targeted cancer therapy with the delivery of paclitaxel