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Male infertility has become a global health problem. Currently, the diagnosis of male infertility depends on the results of semen quality or requires invasive surgical intervention. The process is complex and time-consuming. Metabolomics is an emerging platform with unique advantages in disease diagnosis and pathological mechanism research. In this study, ultra-performance liquid chromatography-electrospray ionization-ion trap-time of flight mass spectrometry (UPLC-ESI-IT-TOFMS) combined with chemometrics methods was used to discover potential biomarkers of male infertility based on non-targeted plasma metabolomics. Plasma samples from healthy controls (HC, n = 43) and various types of infertile patients, i.e., patients having oligozoospermia (OS, n = 36), asthenospermia (AS, n = 56) and erectile dysfunction (ED, n = 45) were analyzed by UPLC-ESI-IT-TOFMS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed. The results of OPLS-DA showed that HCs could be discriminated from infertile patients including OS (R 2 = 0.903, Q 2 = 0.617, AUC = 0.992), AS (R 2 = 0.985, Q 2 = 0.658, AUC = 0.999) or ED (R 2 = 0.942, Q 2 = 0.500, AUC = 0.998). Some potential biomarkers were successfully discovered by variable selection methods and variable important in the projection (VIP) in combination with the T-test. Statistical significance was set at p < 0.05; the Benjamini-Hochberg false discovery rate was used to reduce type 1 errors resulting from multiple comparisons. The identified biomarkers were associated with energy consumption, hormone regulation and antioxidant defenses in spermatogenesis. To elucidate the pathophysiology of male infertility, relative metabolic pathways were studied. It was found that male infertility is closely related to disturbed phospholipid metabolism, amino acid metabolism, steroid hormone biosynthesis metabolism, metabolism of fatty acids and products of carnitine acylation, and purine and pyrimidine metabolisms. Plasma metabolomics provides a novel strategy for the diagnosis of male infertility and offers a new insight to study pathogenesis mechanism.

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Human skin contains multiple receptors, and is able to sense various stimuli such as temperature, pressure, force, corrosion etc, and to feel pains and the shape of objects. The development of skin-like sensors capable of sensing these stimuli is of great importance for various applications such as robots, touch detection, temperature monitoring, strain gauges etc. Great efforts have been made to develop high performance skin-like sensors, but they are far from perfect and much inferior to human skin as most of them can only sense one stimulus with focus on pressure (strain) or temperature, and are unable to visualize sensations and shape of objects. Here we report a skin-like sensor which imitates real skin with multiple receptors, and a new concept of pain sensation. The sensor with very high resolution not only has multiple sensations for touch, pressure, temperature, but also is able to sense various pains and reproduce the three dimensional shape of an object in contact.

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This paper reports high performance flexible Lamb wave humidity sensors with a graphene oxide sensing layer. The devices were fabricated on piezoelectric ZnO thin films deposited on flexible polyimide substrates. Two resonant peaks, namely the zero order antisymmetric (A0) and symmetric (S0) mode Lamb waves, were observed and fitted well with the theoretical analysis and modelling. With graphene oxide microflakes as the sensing layer, the sensing performance of both wave modes was investigated. The humidity sensitivity of the A0 mode is 145.83 ppm per %RH (at humidity 85%RH), higher than that of S0 mode of 89.35 ppm per %RH. For the first time, we have demonstrated that the flexible humidity sensors work as usual without noticeable deterioration in performance even under severe bending conditions up to 1500 µÎµ. Also the sensors showed an excellent stability upon repeated bending for thousand times. All the results demonstrated that the Lamb wave flexible humidity sensors have a great potential for application in flexible electronics.

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The film bulk acoustic resonator (FBAR) is a widely-used MEMS device which can be used as a filter, or as a gravimetric sensor for biochemical or physical sensing. Current device architectures require the use of an acoustic mirror or a freestanding membrane and are fabricated as discrete components. A new architecture is demonstrated which permits fabrication and integration of FBARs on arbitrary substrates. Wave confinement is achieved by fabricating the resonator on a polyimide support layer. Results show when the polymer thickness is greater than a critical value, d, the FBARs have similar performance to devices using alternative architectures. For ZnO FBARs operating at 1.3-2.2 GHz, d is ~9 µm, and the devices have a Q-factor of 470, comparable to 493 for the membrane architecture devices. The polymer support makes the resonators insensitive to the underlying substrate. Yields over 95% have been achieved on roughened silicon, copper and glass.

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A new type of ultraviolet (UV) light sensor based on film bulk acoustic wave resonator (FBAR) is proposed. The new sensor uses gold and a thin n-type ZnO layer deposited on the top of piezoelectric layer of FBAR to form a Schottky barrier. The Schottky barrier's capacitance can be changed with UV light, resulting in an enhanced shift in the entire FBAR's resonant frequency. The fabricated UV sensor has a 50 nm thick n-ZnO semiconductor layer with a carrier concentration of ~ 10(17) cm(-3). A large frequency downshift is observed when UV light irradiates the FBAR. With 365 nm UV light of intensity 1.7 mW/cm(2), the FBAR with n-ZnO/Au Schottky diode has 250 kHz frequency downshift, much larger than the 60 kHz frequency downshift in a conventional FBAR without the n-ZnO layer. The shift in the new FBAR's resonant frequency is due to the junction formed between Au and n-ZnO semiconductor and its properties changes with UV light. The experimental results are in agreement with the theoretical analysis using an equivalent circuit model of the new FBAR structure.

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Graphene (Gr) nanosheets with multilayer structures were dispersed in a nickel (Ni) plating solution by using a surfactant with a magnetic stirring method. Gr nanosheets were incorporated into a Ni matrix through a plating process to form Ni-Gr composites on a target substrate. Gr nanosheets were uniformly dispersed in the Ni matrix, and the oxygen radicals present in the Gr were reduced during the electro-deposition process. The incorporation of Gr in the Ni matrix increases both the inter-planar spacing and the degree of preferred orientation of crystalline Ni. With the addition of Gr content as low as 0.05 g L(-1), the elastic modulus and hardness of the Ni-Gr composites reach 240 GPa and 4.6 GPa, respectively, which are about 1.7 and 1.2 times that of the pure Ni deposited under the same condition. The enhancement in mechanical properties of the composites is attributed to the preferred formation of the Ni crystalline phases in its (111) plane, the high interaction between Ni and Gr and the prevention of the dislocation sliding in the Ni matrix by the Gr. The results suggest that the method of using Gr directly instead of graphene oxide (GO) is efficient and scalable.

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We report ZnO/glass surface acoustic wave (SAW) humidity sensors with high sensitivity and fast response using graphene oxide sensing layer. The frequency shift of the sensors is exponentially correlated to the humidity change, induced mainly by mass loading effect rather than the complex impedance change of the sensing layer. The SAW sensors show high sensitivity at a broad humidity range from 0.5%RH to 85%RH with < 1 sec rise time. The simple design and excellent stability of our GO-based SAW humidity sensors, complemented with full humidity range measurement, highlights their potential in a wide range of applications.

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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.

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Smooth and continuous ZnO films consisting of densely packed ZnO nanorods (NRs), which can be used for electronic device fabrication, were synthesized using a hydro-thermo-chemical solution deposition method. Such devices would have the novelty of high performance, benefiting from the inherited unique properties of the nanomaterials, and can be fabricated on these smooth films using a conventional, low cost planar process. Photoluminescence measurements showed that the NR films have much stronger shallow donor to valence band emissions than those from discrete ZnO NRs, and hence have the potential for the development of ZnO light emission diodes and lasers, etc. The NR films have been used to fabricate large area surface acoustic wave devices by conventional photolithography. These demonstrated two well-defined resonant peaks and their potential for large area device applications. The chemical solution deposition method is simple, reproducible, scalable and economic. These NR films are suitable for large scale production on cost-effective substrates and are promising for various fields such as sensing systems, renewable energy and optoelectronic applications.

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Thin film bulk acoustic wave resonator (FBAR) devices supporting simultaneously multiple resonance modes have been designed for gravimetric sensing. The mechanism for dual-mode generation within a single device has been discussed, and theoretical calculations based on finite element analysis allowed the fabrication of FBARs whose resonance modes have opposite reactions to temperature changes; one of the modes exhibiting a positive frequency shift for a rise of temperature whilst the other mode exhibits a negative shift. Both modes exhibit negative frequency shift for a mass load and hence by monitoring simultaneously both modes it is possible to distinguish whether a change in the resonance frequency is due to a mass load or temperature variation (or a combination of both), avoiding false positive/negative responses in gravimetric sensing without the need of additional reference devices or complex electronics.

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Surface acoustic wave (SAW) devices with 64 µm wavelength were fabricated on a zinc oxide (ZnO) film deposited on top of an ultra-smooth nanocrystalline diamond (UNCD) layer. The smooth surface of the UNCD film allowed the growth of the ZnO film with excellent c-axis orientation and low surface roughness, suitable for SAW fabrication, and could restrain the wave from significantly dissipating into the substrate. The frequency response of the fabricated devices was characterized and a Rayleigh mode was observed at ∼65.4 MHz. This mode was utilised to demonstrate that the ZnO/UNCD SAW device can be successfully used for microfluidic applications. Streaming, pumping, and jetting using microdroplets of 0.5 and 20 µl were achieved and characterized under different powers applied to the SAW device, focusing more on the jetting behaviors induced by the ZnO SAW.

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Significant surface morphology evolution between relief and wrinkling was observed on a 3.5 microm thick TiNiCu film sputter-deposited on a silicon substrate. At room temperature, variation in surface relief morphology (from separated martensite crystals embedded in amorphous matrix to fully interweaved martensite plates) was observed with slight change in film composition. The phenomenon was attributed to variations in crystallization temperatures of as-deposited amorphous films during annealing because of the compositional difference. During thermal cycling between room temperature and 100 degrees C, reversible surface morphology changes can be observed between surface relief and wrinkling patterns. The formation of the surface wrinkling is attributed to the large compressive stress in the film during high temperature post-annealing and crystallization, whereas surface relief is caused by the martensitic transformation to relieve the large tensile stress in the film. Compositional effect on this surface morphology evolution is discussed. Results also indicate that there is a critical dimension for the wrinkling to occur, and a small circular island can only relax by in-plane expansion.

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Nanocrystalline Si films were prepared with a RF-PECVD system using different SiH4/H2 ratios, plasma powers, substrate temperatures and annealing conditions. The film's intrinsic stress was characterized in relation to the crystallization fraction. Results show that an increasing H2 gas ratio, plasma power or substrate temperature can shift the growth mechanism across a transition point, past which nanocrystalline Si is dominant in the film structure. The film's intrinsic stress normally peaks during this transition region. Different mechanisms of stress formation and relaxation during film growth were discussed, including ion bombardment effects, hydrogen induced bond-reconstruction and nanocomposite effects (nanocrystals embedded in an amorphous Si matrix). A three-parameter schematic plot has been proposed which is based on the results obtained. The film structure and stress are presented in relation to SiH4 gas ratio, plasma power and temperature.

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The conformational stabilities of two homodimeric class mu glutathione transferases (GSTM1-1 and GSTM2-2) were studied by urea- and guanidinium chloride-induced denaturation. Unfolding is reversible and structural changes were followed with far-ultraviolet circular dichroism, tryptophan fluorescence, enzyme activity, chemical cross-linking, and size-exclusion chromatography. Disruption of secondary structure occurs as a monophasic transition and is independent of protein concentration. Changes in tertiary structure occur as two transitions; the first is protein concentration dependent, while the second is weakly dependent (GSTM1-1) or independent (GSTM2-2). The second transition corresponds with the secondary structure transition. Loss in catalytic activity occurs as two transitions for GSTM1-1 and as one transition for GSTM2-2. These transitions are dependent upon protein concentration. The first deactivation transition coincides with the first tertiary structure transition. Dimer dissociation occurs prior to disruption of secondary structure. The data suggest that the equilibrium unfolding/refolding of the class mu glutathione transferases M1-1 and M2-2 proceed via a three-state process: N(2) <--> 2I <--> 2U. Although GSTM1-1 and GSTM2-2 are homologous (78% identity/94% homology), their N(2) tertiary structures are not identical. Dissociation of the GSTM1-1 dimer to structured monomers (I) occurs at lower denaturant concentrations than for GSTM2-2. The monomeric intermediate for GSTM1-1 is, however, more stable than the intermediate for GSTM2-2. The intermediates are catalytically inactive and display nativelike secondary structure. Guanidinium chloride-induced denaturation yields monomeric intermediates, which have a more loosely packed tertiary structure displaying enhanced solvent exposure of its tryptophans and enhanced ANS binding. The three-state model for the class mu enzymes is in contrast to the equilibrium two-state models previously proposed for representatives of classes alpha/pi/Sj26 GSTs. Class mu subunits appear to be intrinsically more stable than those of the other GST classes.

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The synthesis of 6-amino-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (3,7-dideazaguanine, 2) has been accomplished from 3-(ethoxycarbonyl)pyrrole-2-acetonitrile. In contrast to 3-deazaguanine, compound 2 did not show any antitumor, antiviral, or antibacterial properties. Furthermore, it was not a substrate for hypoxanthine-guanine phosphoribosyltransferase or purine nucleoside phosphorylase.

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