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As a new type of smart material, magnetic shape memory alloy has the advantages of a fast response frequency and outstanding strain capability in the field of microdrive and microposition actuators. The hysteresis nonlinearity in magnetic shape memory alloy actuators, however, limits system performance and further application. Here we propose a feedforward-feedback hybrid control method to improve control precision and mitigate the effects of the hysteresis nonlinearity of magnetic shape memory alloy actuators. First, hysteresis nonlinearity compensation for the magnetic shape memory alloy actuator is implemented by establishing a feedforward controller which is an inverse hysteresis model based on Krasnosel'skii-Pokrovskii operator. Secondly, the paper employs the classical Proportion Integration Differentiation feedback control with feedforward control to comprise the hybrid control system, and for further enhancing the adaptive performance of the system and improving the control accuracy, the Radial Basis Function neural network self-tuning Proportion Integration Differentiation feedback control replaces the classical Proportion Integration Differentiation feedback control. Utilizing self-learning ability of the Radial Basis Function neural network obtains Jacobian information of magnetic shape memory alloy actuator for the on-line adjustment of parameters in Proportion Integration Differentiation controller. Finally, simulation results show that the hybrid control method proposed in this paper can greatly improve the control precision of magnetic shape memory alloy actuator and the maximum tracking error is reduced from 1.1% in the open-loop system to 0.43% in the hybrid control system. [ABSTRACT FROM AUTHOR]

The evaluation of engineered nanomaterial safety has been hindered by conflicting reports demonstrating differential degrees of toxicity with the same nanoparticles. The unique properties of these materials increase the likelihood that they will interfere with analytical techniques, which may contribute to this phenomenon. We tested the potential for: 1) nanoparticle intrinsic fluorescence/absorbance, 2) interactions between nanoparticles and assay components, and 3) the effects of adding both nanoparticles and analytes to an assay, to interfere with the accurate assessment of toxicity. Silicon, cadmium selenide, titanium dioxide, and helical rosette nanotubes each affected at least one of the six assays tested, resulting in either substantial over- or under-estimations of toxicity. Simulation of realistic assay conditions revealed that interference could not be predicted solely by interactions between nanoparticles and assay components. Moreover, the nature and degree of interference cannot be predicted solely based on our current understanding of nanomaterial behaviour. A literature survey indicated that ca. 95% of papers from 2010 using biochemical techniques to assess nanotoxicity did not account for potential interference of nanoparticles, and this number had not substantially improved in 2012. We provide guidance on avoiding and/or controlling for such interference to improve the accuracy of nanotoxicity assessments. [ABSTRACT FROM AUTHOR]

In this paper, intercalation of nanoclay in the miscible polymer blend of poly(vinylidene fluoride) (PVDF) and acrylic rubber(ACM) was studied. X-ray diffraction was used to investigate the formation of nanoscale polymer blend/clay hybrid. Infrared spectroscopy and X-ray analysis revealed the coexistence of β and γ crystalline forms in PVDF/Clay nanocomposite while α crystalline form was found to be dominant in PVDF/ACM/Clay miscible hybrids. Flory-Huggins interaction parameter (B) was used to further explain the miscibility phenomenon observed. The B parameter was determined by combining the melting point depression and the binary interaction model. The estimated B values for the ternary PVDF/ACM/Clay and PVDF/ACM pairs were all negative, showing both proper intercalation of the polymer melt into the nanoclay galleries and the good miscibility of PVDF and ACM blend. The B value for the PVDF/ACM blend was almost the same as that measured for the PVDF/ACM/Clay hybrid, suggesting that PVDF chains in nanocomposite hybrids interact with ACM chains and that nanoclay in hybrid systems is wrapped by ACM molecules. [ABSTRACT FROM AUTHOR]

In this paper, we describe the effects of the combination of topographical, mechanical, chemical and intracellular electrical stimuli on a co-culture of fibroblasts and skeletal muscle cells. The co-culture was anisotropically grown onto an engineered micro-grooved (10 µm-wide grooves) polyacrylamide substrate, showing a precisely tuned Young’s modulus (∼ 14 kPa) and a small thickness (∼ 12 µm). We enhanced the co-culture properties through intracellular stimulation produced by piezoelectric nanostructures (i.e., boron nitride nanotubes) activated by ultrasounds, thus exploiting the ability of boron nitride nanotubes to convert outer mechanical waves (such as ultrasounds) in intracellular electrical stimuli, by exploiting the direct piezoelectric effect. We demonstrated that nanotubes were internalized by muscle cells and localized in both early and late endosomes, while they were not internalized by the underneath fibroblast layer. Muscle cell differentiation benefited from the synergic combination of topographical, mechanical, chemical and nanoparticle-based stimuli, showing good myotube development and alignment towards a preferential direction, as well as high expression of genes encoding key proteins for muscle contraction (i.e., actin and myosin). We also clarified the possible role of fibroblasts in this process, highlighting their response to the above mentioned physical stimuli in terms of gene expression and cytokine production. Finally, calcium imaging-based experiments demonstrated a higher functionality of the stimulated co-cultures. [ABSTRACT FROM AUTHOR]

Peristaltic transport of copper-water nanofluid in an inclined channel is reported in the presence of mixed convection. Both velocity and thermal slip conditions are considered. Mathematical modelling has been carried out using the long wavelength and low Reynolds number approximations. Resulting coupled system of equations is solved numerically. Quantities of interest are analyzed through graphs. Numerical values of heat transfer rate at the wall for different parameters are obtained and examined. Results showed that addition of copper nanoparticles reduces the pressure gradient, axial velocity at the center of channel, trapping and temperature. Velocity slip parameter has a decreasing effect on the velocity near the center of channel. Temperature of nanofluid increases with increase in the Grashoff number and channel inclination angle. It is further concluded that the heat transfer rate at the wall increases considerably in the presence of copper nanoparticles. [ABSTRACT FROM AUTHOR]

The issue of single-cell control has recently attracted enormous interest. However, in spite of the presently achievable intracellular-level physiological probing through bio-photonics, nano-probe-based, and some other techniques, the issue of inducing selective, single-cell-precision apoptosis, without affecting neighbouring cells remains essentially open. Here we resolve this issue and report on the effective single-cell-precision cancer cell treatment using the reactive chemistry of the localized corona-type plasma discharge around a needle-like electrode with the spot size ∼1 µm. When the electrode is positioned with the micrometer precision against a selected cell, a focused and highly-localized micro-plasma discharge induces apoptosis in the selected individual HepG2 and HeLa cancer cells only, without affecting any surrounding cells, even in small cell clusters. This is confirmed by the real-time monitoring of the morphological and structural changes at the cellular and cell nucleus levels after the plasma exposure. [ABSTRACT FROM AUTHOR]

A reusable and mediator-free cholesterol biosensor based on cholesterol oxidase (ChOx) was fabricated based on self-assembled monolayer (SAM) of thioglycolic acid (TGA) (covalent enzyme immobilization by dropping method) using bio-chips. Cholesterol was detected with modified bio-chip (Gold/Thioglycolic-acid/Cholesterol-oxidase i.e., Au/TGA/ChOx) by reliable cyclic voltammetric (CV) technique at room conditions. The Au/TGA/ChOx modified bio-chip sensor demonstrates good linearity (1.0 nM to 1.0 mM; R = 0.9935), low-detection limit (∼0.42 nM, SNR∼3), and higher sensitivity (∼74.3 µAµM−1cm−2), lowest-small sample volume (50.0 μL), good stability, and reproducibility. To the best of our knowledge, this is the first statement with a very high sensitivity, low-detection limit, and low-sample volumes are required for cholesterol biosensor using Au/TGA/ChOx-chips assembly. The result of this facile approach was investigated for the biomedical applications for real samples at room conditions with significant assembly (Au/TGA/ChOx) towards the development of selected cholesterol biosensors, which can offer analytical access to a large group of enzymes for wide range of biomedical applications in health-care fields. [ABSTRACT FROM AUTHOR]

The impact of silver nanoparticles (NPs) and microparticles (MPs) on bacterial and fungal assemblages was studied in soils collected from a low arctic site. Two different concentrations (0.066% and 6.6%) of Ag NPs and Ag MPs were tested in microcosms that were exposed to temperatures mimicking a winter to summer transition. Toxicity was monitored by differential respiration, phospholipid fatty acid analysis, polymerase chain reaction-denaturing gradient gel electrophoresis and DNA sequencing. Notwithstanding the effect of Ag MPs, nanosilver had an obvious, additional impact on the microbial community, underscoring the importance of particle size in toxicity. This impact was evidenced by levels of differential respiration in 0.066% Ag NP-treated soil that were only half that of control soils, a decrease in signature bacterial fatty acids, and changes in both richness and evenness in bacterial and fungal DNA sequence assemblages. Prominent after Ag NP-treatment were Hypocreales fungi, which increased to 70%, from only 1% of fungal sequences under control conditions. Genera within this Order known for their antioxidant properties (Cordyceps/Isaria) dominated the fungal assemblage after NP addition. In contrast, sequences attributed to the nitrogen-fixing Rhizobiales bacteria appeared vulnerable to Ag NP-mediated toxicity. This combination of physiological, biochemical and molecular studies clearly demonstrate that Ag NPs can severely disrupt the natural seasonal progression of tundra assemblages. [ABSTRACT FROM AUTHOR]

Traction forces exerted by adherent cells on their microenvironment can mediate many critical cellular functions. Accurate quantification of these forces is essential for mechanistic understanding of mechanotransduction. However, most existing methods of quantifying cellular forces are limited to single cells in isolation, whereas most physiological processes are inherently multi-cellular in nature where cell-cell and cell-microenvironment interactions determine the emergent properties of cell clusters. In the present study, a robust finite-element-method-based cell traction force microscopy technique is developed to estimate the traction forces produced by multiple isolated cells as well as cell clusters on soft substrates. The method accounts for the finite thickness of the substrate. Hence, cell cluster size can be larger than substrate thickness. The method allows computing the traction field from the substrate displacements within the cells' and clusters' boundaries. The displacement data outside these boundaries are not necessary. The utility of the method is demonstrated by computing the traction generated by multiple monkey kidney fibroblasts (MKF) and human colon cancerous (HCT-8) cells in close proximity, as well as by large clusters. It is found that cells act as individual contractile groups within clusters for generating traction. There may be multiple of such groups in the cluster, or the entire cluster may behave a single group. Individual cells do not form dipoles, but serve as a conduit of force (transmission lines) over long distances in the cluster. The cell-cell force can be either tensile or compressive depending on the cell-microenvironment interactions. [ABSTRACT FROM AUTHOR]

Novel hybrid magnetic cross-linked enzyme aggregates of phenylalanine ammonia lyase (HM-PAL-CLEAs) were developed by co-aggregation of enzyme aggregates with magnetite nanoparticles and subsequent crosslinking with glutaraldehyde. The HM-PAL-CLEAs can be easily separated from the reaction mixture by using an external magnetic field. Analysis by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) indicated that PAL-CLEAs were inlayed in nanoparticle aggregates. The HM-PAL-CLEAs revealed a broader limit in optimal pH compared to free enzyme and PAL-CLEAs. Although there is no big difference in Km of enzyme in CLEAs and HM-PAL-CLEAs, Vmax of HM-PAL-CLEAs is about 1.75 times higher than that of CLEAs. Compared with free enzyme and PAL-CLEAs, the HM-PAL-CLEAs also exhibited the highest thermal stability, denaturant stability and storage stability. The HM-PAL-CLEAs retained 30% initial activity even after 11 cycles of reuse, whereas PAL-CLEAs retained 35% of its initial activity only after 7 cycles. These results indicated that hybrid magnetic CLEAs technology might be used as a feasible and efficient solution for improving properties of immobilized enzyme in industrial application. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to fabricate a TiO2 nanotubular surface, which could maintain hydrophilicity over time (resist aging). In order to achieve non-aging hydrophilic surfaces, anodization and annealing conditions were optimized. This is the first study to show that anodization and annealing condition affect the stability of surface hydrophilicity. Our results indicate that maintenance of hydrophilicity of the obtained TiO2 nanotubes was affected by anodization voltage and annealing temperature. Annealing sharply decreased the water contact angle (WCA) of the as-synthesized TiO2 nanotubular surface, which was correlated to improved hydrophilicity. TiO2 nanotubular surfaces are transformed to hydrophilic surfaces after annealing, regardless of annealing and anodization conditions; however, WCA measurements during aging demonstrate that surface hydrophilicity of non-anodized and 20 V anodized samples decreased after only 11 days of aging, while the 60 V anodized samples maintained their hydrophilicity over the same time period. The nanotubes obtained by 60 V anodization followed by 600 °C annealing maintained their hydrophilicity significantly longer than nanotubes which were obtained by 60 V anodization followed by 300 °C annealing. [ABSTRACT FROM AUTHOR]

Polypyrrole multi-walled carbon nanotube composite layers were used to modify the gold layer to measure heavy metal ions using the surface plasmon resonance technique. The new sensor was fabricated to detect trace amounts of mercury (Hg), lead (Pb), and iron (Fe) ions. In the present research, the sensitivity of a polypyrrole multi-walled carbon nanotube composite layer and a polypyrrole layer were compared. The application of polypyrrole multi-walled carbon nanotubes enhanced the sensitivity and accuracy of the sensor for detecting ions in an aqueous solution due to the binding of mercury, lead, and iron ions to the sensing layer. The Hg ion bonded to the sensing layer more strongly than did the Pb and Fe ions. The limitation of the sensor was calculated to be about 0.1 ppm, which produced an angle shift in the region of 0.3° to 0.6°. [ABSTRACT FROM AUTHOR]

In this letter we present the “Egg of Columbus” for making fibres with unprecedented toughness: a slider, in the simplest form just a knot, is introduced as frictional element to dissipate additional energy and thus demonstrating the existence of a previously “hidden” toughness. The proof of concept is experimentally realized making the world's toughest fibre, increasing the toughness modulus of a commercial Endumax macroscopic fibre from 44 J/g up to 1070 J/g (and of a zylon microfiber from 20 J/g up to 1400 J/g). The ideal upperbound toughness is expected for graphene, with a theoretical value of ∼105 J/g. This new concept, able of maximizing (one fold increment) the structural robustness, could explain the mysterious abundance of knot formations, in spite of their incremental energy cost and topological difficulty, in biological evolved structures, such as DNA strands and proteins. [ABSTRACT FROM AUTHOR]

Current medically relevant metals for prosthetic reconstructions enjoy a relatively good success rate, but their performance drops significantly in patients with compromised health status, and post-surgical infections still remain an important challenge. To address these problems, different nanotechnology-based strategies have been exploited to create implantable metals with an enhanced bioactivity and antibacterial capacities. Among these, oxidative nanopatterning has emerged as a very effective approach to engender nanoporous surfaces that stimulate and guide the activity of adhering cells. The resulting nanoporosity is also attractive because it offers nanoconfined volumes that can be exploited to load bioactive compounds and modulate their release over time. Such extended elution is needed since a single exposure to growth factors and/or antibiotics, for instance, may not be adequate to further sustain bone regeneration and/or to counteract bacterial colonization. In this article, we assessed the capacities of nanoporous titanium surfaces generated by oxidative nanopatterning to provide controlled and sustained elution of proteins and antibiotic molecules. To this end, we have selected bovine serum albumin (BSA) and vancomycin to reflect commonly used compounds, and investigated their adsorption and elution by Fourier-transform infrared (FT-IR) and ultraviolet–visible (UV-VIS) spectroscopy. Our results demonstrate that while the elution of albumin is not significantly affected by the nanoporosity, in the case of vancomycin, nanoporous surfaces provided an extended release. These findings were successively correlated to the establishment of interactions with the surface and physical-entrapment effects exerted by the nanopores, ultimately highlighting their synergistic contribution to the release profiles and thus their importance in the design of nanostructured eluting platforms for applications in medicine. [ABSTRACT FROM AUTHOR]

Purpose: To investigate gold nanorods (GNRs) as a contrast agent to enhance Doppler optical coherence tomography (OCT) imaging of the intrascleral aqueous humor outflow. Methods: A serial dilution of GNRs was scanned with a spectral-domain OCT device (Bioptigen, Durham, NC) to visualize Doppler signal. Doppler measurements using GNRs were validated using a controlled flow system. To demonstrate an application of GNR enhanced Doppler, porcine eyes were perfused at constant pressure with mock aqueous alone or 1.0×1012 GNR/mL mixed with mock aqueous. Twelve Doppler and volumetric SD-OCT scans were obtained from the limbus in a radial fashion incremented by 30°, forming a circular scan pattern. Volumetric flow was computed by integrating flow inside non-connected vessels throughout all 12 scans around the limbus. Results: At the GNR concentration of 0.7×1012 GNRs/mL, Doppler signal was present through the entire depth of the testing tube without substantial attenuation. A well-defined laminar flow profile was observed for Doppler images of GNRs flowing through the glass capillary tube. The Doppler OCT measured flow profile was not statistically different from the expected flow profile based upon an autoregressive moving average model, with an error of −0.025 to 0.037 mm/s (p = 0.6435). Cross-sectional slices demonstrated the ability to view anterior chamber outflow ex-vivo using GNR-enhanced Doppler OCT. Doppler volumetric flow measurements were comparable to flow recorded by the perfusion system. Conclusions: GNRs created a measureable Doppler signal within otherwise silent flow fields in OCT Doppler scans. Practical application of this technique was confirmed in a constant pressure ex-vivo aqueous humor outflow model in porcine eyes. [ABSTRACT FROM AUTHOR]

We describe the existence and structure of large fullerenes in terms of symmetry breaking of the molecule. Specifically, we describe the existence of in terms of breaking of the icosahedral symmetry of by the insertion into its middle of an additional decagon. The surface of is formed by 12 regular pentagons and 25 regular hexagons. All 105 edges of are of the same length. It should be noted that the structure of the molecules is described in exact coordinates relative to the non-orthogonal icosahedral bases. This symmetry breaking process can be readily applied, and could account for and describe other larger cage cluster fullerene molecules, as well as more complex higher structures such as nanotubes. [ABSTRACT FROM AUTHOR]

Effective point-of-use devices for providing safe drinking water are urgently needed to reduce the global burden of waterborne disease. Here we show that plant xylem from the sapwood of coniferous trees – a readily available, inexpensive, biodegradable, and disposable material – can remove bacteria from water by simple pressure-driven filtration. Approximately 3 cm3 of sapwood can filter water at the rate of several liters per day, sufficient to meet the clean drinking water needs of one person. The results demonstrate the potential of plant xylem to address the need for pathogen-free drinking water in developing countries and resource-limited settings. [ABSTRACT FROM AUTHOR]

In this study, we demonstrate closed-loop motion control of self-propelled microjets under the influence of external magnetic fields. We control the orientation of the microjets using external magnetic torque, whereas the linear motion towards a reference position is accomplished by the thrust and pulling magnetic forces generated by the ejecting oxygen bubbles and field gradients, respectively. The magnetic dipole moment of the microjets is characterized using the U-turn technique, and its average is calculated to be 1.310−10 A.m2 at magnetic field and linear velocity of 2 mT and 100 µm/s, respectively. The characterized magnetic dipole moment is used in the realization of the magnetic force-current map of the microjets. This map in turn is used for the design of a closed-loop control system that does not depend on the exact dynamical model of the microjets and the accurate knowledge of the parameters of the magnetic system. The motion control characteristics in the transient- and steady-states depend on the concentration of the surrounding fluid (hydrogen peroxide solution) and the strength of the applied magnetic field. Our control system allows us to position microjets at an average velocity of 115 m/s, and within an average region-of-convergence of 365 m. [ABSTRACT FROM AUTHOR]

Mixed morphologies of Ga-doped Zinc Oxide (ZnO) nanostructures are synthesized by vapor transport method. Systematic scanning electron microscope (SEM) studies of different morphologies, after periodic heat treatments, gives direct evidence of sublimation. SEM micrographs give direct evidence that morphological defects of nanostructures can be removed by annealing. Ultra Violet (UV) and visible emission depends strongly on the annealing temperatures and luminescent efficiency of UV emission is enhanced significantly with each subsequent heat treatment. X-Ray diffraction (XRD) results suggest that crystal quality improved by annealing and phase separation may occur at high temperatures. [ABSTRACT FROM AUTHOR]

Cancer can be easily treated when found early. A probe capable of detecting cell transformation may increase the success rate of early diagnosis of cancer. In this report we have tested the ability of a fluorescent, quadruplex DNA binding probe, 3,6-bis(1-methyl-4- vinylpyridinium) carbazole diiodide (BMVC), to detect cell transformation in vitro. BMVC was applied to living cells in several different models of cell transformation, and the fluorescence signals of BMVC were measured. The degrees of cell transformation in these models were characterized by alterations in cellular morphological phenotype and subcellular organization. When BMVC probes were applied, the number of BMVC-positive cells increased in accordance with the degree of transformation. BMVC was capable of significantly detecting formation of foci, increased cellular motility, cell proliferation, cell apoptosis, anchorage-independent growth, and increased invasiveness of transformed cells. These results demonstrate the ability of BMVC probes to detect cell transformation and indicate that BMVC is of promise for use as a probe in early cancer detection. [ABSTRACT FROM AUTHOR]

Investigating the interactions between nanoscale materials and microorganisms is crucial to provide a comprehensive, proactive understanding of nanomaterial toxicity and explore the potential for novel applications. It is well known that nanomaterial behavior is governed by the size and composition of the particles, though the effects of small differences in size toward biological cells have not been well investigated. Palladium nanoparticles (Pd NPs) have gained significant interest as catalysts for important carbon-carbon and carbon-heteroatom reactions and are increasingly used in the chemical industry, however, few other applications of Pd NPs have been investigated. In the present study, we examined the antimicrobial capacity of Pd NPs, which provides both an indication of their usefulness as target antimicrobial compounds, as well as their potency as potential environmental pollutants. We synthesized Pd NPs of three different well-constrained sizes, 2.0±0.1 nm, 2.5±0.2 nm and 3.1±0.2 nm. We examined the inhibitory effects of the Pd NPs and Pd2+ ions toward gram negative Escherichia coli (E. coli) and gram positive Staphylococcus aureus (S. aureus) bacterial cultures throughout a 24 hour period. Inhibitory growth effects of six concentrations of Pd NPs and Pd2+ ions (2.5×10−4, 10−5, 10−6, 10−7, 10−8, and 10−9 M) were examined. Our results indicate that Pd NPs are generally much more inhibitory toward S. aureus than toward E. coli, though all sizes are toxic at ≥10−5 M to both organisms. We observed a significant difference in size-dependence of antimicrobial activity, which differed based on the microorganism tested. Our work shows that Pd NPs are highly antimicrobial, and that fine-scale (<1 nm) differences in size can alter antimicrobial activity. [ABSTRACT FROM AUTHOR]

We have studied in vitro toxicity of iron oxide nanoparticles (NPs) coated with a thin silica shell (Fe3O4/SiO2 NPs) on A549 and HeLa cells. We compared bare and surface passivated Fe3O4/SiO2 NPs to evaluate the effects of the coating on the particle stability and toxicity. NPs cytotoxicity was investigated by cell viability, membrane integrity, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) assays, and their genotoxicity by comet assay. Our results show that NPs surface passivation reduces the oxidative stress and alteration of iron homeostasis and, consequently, the overall toxicity, despite bare and passivated NPs show similar cell internalization efficiency. We found that the higher toxicity of bare NPs is due to their stronger in-situ degradation, with larger intracellular release of iron ions, as compared to surface passivated NPs. Our results indicate that surface engineering of Fe3O4/SiO2 NPs plays a key role in improving particles stability in biological environments reducing both cytotoxic and genotoxic effects. [ABSTRACT FROM AUTHOR]

With increasing production and applications of nanostructured zinc oxide, e.g., for biomedical and consumer products, the question of safety is getting more and more important. Different morphologies of zinc oxide structures have been synthesized and accordingly investigated. In this study, we have particularly focused on nano-micro ZnO tetrapods (ZnO-T), because their large scale fabrication has been made possible by a newly introduced flame transport synthesis approach which will probably lead to several new applications. Moreover, ZnO-T provide a completely different morphology then classical spherical ZnO nanoparticles. To get a better understanding of parameters that affect the interactions between ZnO-T and mammalian cells, and thus their biocompatibility, we have examined the impact of cell culture conditions as well as of material properties on cytotoxicity. Our results demonstrate that the cell density of fibroblasts in culture along with their age, i.e., the number of preceding cell divisions, strongly affect the cytotoxic potency of ZnO-T. Concerning the material properties, the toxic potency of ZnO-T is found to be significantly lower than that of spherical ZnO nanoparticles. Furthermore, the morphology of the ZnO-T influenced cellular toxicity in contrast to surface charges modified by UV illumination or O2 treatment and to the material age. Finally, we have observed that direct contact between tetrapods and cells increases their toxicity compared to transwell culture models which allow only an indirect effect via released zinc ions. The results reveal several parameters that can be of importance for the assessment of ZnO-T toxicity in cell cultures and for particle development. [ABSTRACT FROM AUTHOR]

The development of safe and efficient gene carriers is the key to the clinical success of gene therapy. The present study was designed to develop and evaluate the chitosan-graft-polyethylenimine (CP)/DNA nanoparticles as novel non-viral gene vectors for gene therapy of osteoarthritis. The CP/DNA nanoparticles were produced through a complex coacervation of the cationic polymers with pEGFP after grafting chitosan (CS) with a low molecular weight (Mw) PEI (Mw = 1.8 kDa). Particle size and zeta potential were related to the weight ratio of CP:DNA, where decreases in nanoparticle size and increases in surface charge were observed as CP content increased. The buffering capacity of CP was significantly greater than that of CS. The transfection efficiency of CP/DNA nanoparticles was similar with that of the Lipofectamine™ 2000, and significantly higher than that of CS/DNA and PEI (25 kDa)/DNA nanoparticles. The transfection efficiency of the CP/DNA nanoparticles was dependent on the weight ratio of CP:DNA (w/w). The average cell viability after the treatment with CP/DNA nanoparticles was over 90% in both chondrocytes and synoviocytes, which was much higher than that of PEI (25 kDa)/DNA nanoparticles. The CP copolymers efficiently carried the pDNA inside chondrocytes and synoviocytes, and the pDNA was detected entering into nucleus. These results suggest that CP/DNA nanoparticles with improved transfection efficiency and low cytotoxicity might be a safe and efficient non-viral vector for gene delivery to both chondrocytes and synoviocytes. [ABSTRACT FROM AUTHOR]

A novel supersaturated self-emulsifying drug delivery system (Super-SEDDS) loaded with scutellarin-phospholipid complex (SPC) was developed. The system aimed to address the limitations presented by conventional SEDDS as delivery carriers for drugs with poor water-solubility, low liposolubility and high dose. As an intermediate, SPC was first prepared based on the response surface design. The presence of amorphous scutellarin was demonstrated through differential scanning calorimetry (DSC) and X-ray diffraction (XRD), while enhanced liposolubility was confirmed through comparison with scutellarin powder via an octanol/water distribution test. On the basis of the solubility study and ternary phase diagram, Super-SEDDS containing SPC of up to 200% equilibrium solubility (Seq) was designed, which composed of ethyl oleate, Cremophor RH40 and Transcutol HP with a ratio of 60∶25∶15 (w/w%). The subsequent in vitro lipolysis study and ex vivo intestinal absorption test indicated that Super-SEDDS enhanced the cumulative dissolution from 70% to 100% and improved the intestinal absorption from 0.04 to 0.12 µg/cm2 compared with scutellarin powder. Furthermore, an in vivo study demonstrated that Super-SEDDS achieved the AUC0-t of scutellarin up to approximate 1.7-fold as scutellarin powder. It was also proved superior to SPC and the conventional SEDDS. Super-SEDDS showed great potential for expanding the usage of SEDDS and could act as an alternative to conventional SEDDS. [ABSTRACT FROM AUTHOR]

The energy mitigation properties of buckyballs are investigated using molecular dynamics (MD) simulations. A one dimensional buckyball long chain is employed as a unit cell of granular fullerene particles. Two types of buckyballs i.e. C60 and C720 with recoverable and non-recoverable behaviors are chosen respectively. For C60 whose deformation is relatively small, a dissipative contact model is proposed. Over 90% of the total impact energy is proven to be mitigated through interfacial reflection of wave propagation, the van der Waals interaction, covalent potential energy and atomistic kinetic energy evidenced by the decent force attenuation and elongation of transmitted impact. Further, the C720 system is found to outperform its C60 counterpart and is able to mitigate over 99% of the total kinetic energy by using a much shorter chain thanks to its non-recoverable deformation which enhances the four energy dissipation terms. Systematic studies are carried out to elucidate the effects of impactor speed and mass, as well as buckyball size and number on the system energy mitigation performance. This one dimensional buckyball system is especially helpful to deal with the impactor of high impact speed but small mass. The results may shed some lights on the research of high-efficiency energy mitigation material selections and structure designs. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the acute toxicity of intravenously administrated amorphous silica nanoparticles (SNPs) in mice. The lethal dose, 50 (LD50), of intravenously administrated SNPs was calculated in mice using Dixon's up-and-down method (262.45±33.78 mg/kg). The acute toxicity was evaluated at 14 d after intravenous injection of SNPs at 29.5, 103.5 and 177.5 mg/kg in mice. A silicon content analysis using ICP-OES found that SNPs mainly distributed in the resident macrophages of the liver (10.24%ID/g), spleen (34.78%ID/g) and lung (1.96%ID/g). TEM imaging showed only a small amount in the hepatocytes of the liver and in the capillary endothelial cells of the lung and kidney. The levels of serum LDH, AST and ALT were all elevated in the SNP treated groups. A histological examination showed lymphocytic infiltration, granuloma formation, and hydropic degeneration in liver hepatocytes; megakaryocyte hyperplasia in the spleen; and pneumonemia and pulmonary interstitial thickening in the lung of the SNP treated groups. A CD68 immunohistochemistry stain indicated SNPs induced macrophage proliferation in the liver and spleen. The results suggest injuries induced by the SNPs in the liver, spleen and lungs. Mononuclear phagocytic cells played an important role in the injury process. [ABSTRACT FROM AUTHOR]

The Hedgehog (Hh) pathway inhibitors have shown great promise in cancer therapeutics. SANT75, a novel compound we previously designed to specially inhibit the Smoothened (SMO) protein in the Hh pathway, has greater inhibitory potency than many of commonly used Hh inhibitors. However, preclinical studies of SANT75 revealed water insolubility and acute toxicity. To overcome these limitations, we developed a liposomal formulation of SANT75 and investigated its antitumor efficacy in vitro and in vivo. We encapsulated SANT75 into PEGylated liposome and the mean particle size distribution and zeta-potential (ZP) of liposomes were optimized. Using the Shh-light2 cell and Gli-GFP or Flk-GFP transgenic reporter zebrafish, we confirmed that liposome-encapsulated SANT75 inhibited Hh activity with similar potency as the original SANT75. SANT75 encapsulated into liposome exerted strong tumor growth-inhibiting effects in vitro and in vivo. In addition, the liposomal SANT75 therapy efficiently improved the survival time of tumor-bearing mice without obvious systemic toxicity. The pathological morphology and immunohistochemistry staining revealed that liposomal SANT75 induced tumor cell apoptosis, inhibited tumor angiogenesis as assessed by CD31 and down-regulated the expression of Hh target protein Gli-1 in tumor tissues. Our findings suggest that liposomal formulated SANT75 has improved solubility and bioavailability and should be further developed as a drug candidate for treating tumors with abnormally high Hh activity. [ABSTRACT FROM AUTHOR]

Radiative heat exchange at the nanoscale presents a challenge for several areas due to its scope and nature. Here, we provide a thermokinetic description of microscale radiative energy transfer including phonon-photon coupling manifested through a non-Debye relaxation behavior. We show that a lognormal-like distribution of modes of relaxation accounts for this non-Debye relaxation behavior leading to the thermal conductance. We also discuss the validity of the fluctuation-dissipation theorem. The general expression for the thermal conductance we obtain fits existing experimental results with remarkable accuracy. Accordingly, our approach offers an overall explanation of radiative energy transfer through micrometric gaps regardless of geometrical configurations and distances. [ABSTRACT FROM AUTHOR]

Micro/nanoparticle induced near-field laser ultra-focusing and heating has been widely used in laser-assisted nanopatterning and nanolithography to pattern nanoscale features on a large-area substrate. Knowledge of the temperature and stress in the nanoscale near-field heating region is critical for process control and optimization. At present, probing of the nanoscale temperature, stress, and optical fields remains a great challenge since the heating area is very small (∼100 nm or less) and not immediately accessible for sensing. In this work, we report the first experimental study on nanoscale mapping of particle-induced thermal, stress, and optical fields by using a single laser for both near-field excitation and Raman probing. The mapping results based on Raman intensity variation, wavenumber shift, and linewidth broadening all give consistent conjugated thermal, stress, and near-field focusing effects at a 20 nm resolution (<λ/26, λ = 32 nm). Nanoscale mapping of near-field effects of particles from 1210 down to 160 nm demonstrates the strong capacity of such a technique. By developing a new strategy for physical analysis, we have de-conjugated the effects of temperature, stress, and near-field focusing from the Raman mapping. The temperature rise and stress in the nanoscale heating region is evaluated at different energy levels. High-fidelity electromagnetic and temperature field simulation is conducted to accurately interpret the experimental results. [ABSTRACT FROM AUTHOR]

Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH). The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA) showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs) up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM) formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs. [ABSTRACT FROM AUTHOR]