High temperature superconductivity at FeSe/LaFeO3 interface.

Enormous enhancement of superconducting pairing temperature (Tg) to 65 K in FeSe/SrTiO3 has made it a spotlight. Despite the effort of interfacial engineering, FeSe interfaced with TiOx remains the unique case in hosting high Tg, hindering a decisive understanding on the general mechanism and ways to further improving Tg. Here we constructed a new high-Tg interface, single-layer FeSe interfaced with FeOx-terminated LaFeO3. Large superconducting gap and diamagnetic response evidence that the superconducting pairing can emerge near 80 K, highest amongst all-known interfacial superconductors. Combining various techniques, we reveal interfacial charge transfer and strong interfacial electron-phonon coupling (EPC) in FeSe/LaFeO3, showing that the cooperative pairing mechanism works beyond FeSe-TiOx. Intriguingly, the stronger interfacial EPC than that in FeSe/SrTiO3 is likely induced by the stronger interfacial bonding in FeSe/LaFeO3, and can explain the higher Tg according to recent theoretical calculations, pointing out a workable route in designing new interfaces to achieve higher Tg.

Novel folic acid conjugated Fe3O4-ZnO hybrid nanoparticles for targeted photodynamic therapy.

A novel folic acid conjugated core-shell hybrid iron oxide-zinc oxide nanoparticle was developed for applications as a photosensitier (PS) in photodynamic therapy. Photodegradation studies on methylene blue demonstrated significantly enhanced photophysical properties of the produced nano-PSs, due to the charge recombination via electron trapping by dissolved Fe3+. A time and dose dependant toxicity associated with the nano-PSs was observed upon exposure to human epithelial colorectal adenocarcinoma (Caco-2) cells in the dark. UV irradiation of the synthesised nano-PSs resulted in a significant photo-killing effect with drastic reduction in Caco-2 cell viability to as low as 6%. Reduction in viability upon exposure was due fundamentally to cellular interactions with light irradiated PSs as the influence of radiation alone was subtracted. FA conjugation further enhanced the photo-killing effect.

Cytotoxicity of folic acid conjugated hollow silica nanoparticles toward Caco2 and 3T3 cells, with and without encapsulated DOX.

Hollow silica nanoparticles of two sizes with and without a folic acid targeting ligand were synthesized. Fickian diffusion of the antitumor drug doxorubicin hydrochloride (DOX) was demonstrated by the produced nanoparticles, achieving a cumulative release of 73% and 45% for 215 nm and 430 nm particles respectively over a period of 500 h. The hollow silica nanoparticles presented a time and dose dependent toxicity, selective to human epithelial colorectal adenocarcinoma (Caco2) cells, over mouse embryonic fibroblast (3T3) cells. At 24h Caco2 cell viability was reduced to 66% using pure hollow silica at a concentration of 50 µg mL(-1), while that of 3T3 cells remained at 94% under the same conditions. The selective cytotoxicity of hollow silica nanoparticles was further enhanced by conjugation of folic acid and incorporation of DOX: at 24h and an equivalent DOX concentration of 0.5 µg mL(-1), viable Caco2 cells were reduced to 45% while 3T3 cells were reduced to 83%. Interestingly the equivalent dose of free DOX was more toxic to 3T3 than to Caco2 cells, reducing the 3T3 viability to 72% and the Caco2 viability to 80%, which is likely due to the presence of the p-glycoprotein pumps in Caco2 cells. Folic acid conjugation served to enhance the viability of both cell lines in this work. Careful optimization of the folate content should further improve the cell specificity of the hollow silica nanoparticles, thus providing a viable targeting platform for cancer therapy.

High-Throughput Cancer Cell Sphere Formation for Characterizing the Efficacy of Photo Dynamic Therapy in 3D Cell Cultures.

Photodynamic therapy (PDT), wherein light sensitive non-toxic agents are locally and selectively activated using light, has emerged as an appealing alternative to traditional cancer chemotherapy. Yet to date, PDT efficacy has been mostly characterized using 2D cultures. Compared to 2D cultures, 3D sphere culture generates unique spatial distributions of nutrients and oxygen for the cells that better mimics the in-vivo conditions. Using a novel polyHEMA (non-adherent polymer) fabrication process, we developed a microfluidic sphere formation platform that can (1) generate 1,024 uniform (size variation <10%) cancer spheres within a 2 cm by 2 cm core area, (2) culture spheres for more than 2 weeks, and (3) allow the retrieval of spheres. Using the presented platform, we have successfully characterized the different responses in 2D and 3D cell culture to PDT. Furthermore, we investigated the treatment resistance effect in cancer cells induced by tumor associated fibroblasts (CAF). Although the CAFs can enhance the resistance to traditional chemotherapy agents, no significant difference in PDT was observed. The preliminary results suggest that the PDT can be an attractive alternative cancer therapy, which is less affected by the therapeutic resistance induced by cancer associated cells.

A novel folic acid-conjugated TiO2-SiO2 photosensitizer for cancer targeting in photodynamic therapy.

In this paper, a novel folic acid-conjugated silica-coated titanium dioxide (TiO2-SiO2) photosensitizer was synthesized and characterized using various analytical instruments. The photosensitizer was further assessed with regards to its photoreactivity, cellular and hemocompatibility, cell internalization, and phototoxicity. Conjugating folic acid with TiO2-SiO2 has shown a significantly improved compatibility of the nanoparticles with the mouse fibroblast cells (L929) at 24 h. An improved compatibility with the human nasopharyngeal epidermoid cancer (KB) cells was also demonstrated, but to a slightly reduced degree. Enhanced cell internalization was well demonstrated in the TiO2-SiO2 folate nanoparticles. Upon exposure to UV light, TiO2-SiO2 folate nanoparticles maintained a high level photodynamic reactivity and yielded a 38-43% photo-killing of KB cells. The photo-killing effect increased with increasing dosage in the investigated concentration range of 50-100 µg ml(-1).

Nano-photosensitizers Engineered to Generate a Tunable Mix of Reactive Oxygen Species, for Optimizing Photodynamic Therapy, Using a Microfluidic Device.

This work is aimed at engineering photosensitizer embedded nanoparticles (NPs) that produce optimal amount of reactive oxygen species (ROS) for photodynamic therapy (PDT). A revised synthetic approach, coupled with improved analytical tools, resulted in more efficient PDT. Specifically, methylene blue (MB) conjugated polyacrylamide nanoparticles (PAA NPs), with a polyethylene glycol dimethacrylate (PEGDMA, Mn 550) cross-linker, were synthesized so as to improve the efficacy of cancer PDT. The long cross-linker chain, PEGDMA, increases the distance between the conjugated MB molecules so as to avoid self-quenching of the excited states or species, and also enhances the oxygen permeability of the NP matrix, when compared to the previously used shorter cross-linker. The overall ROS production from the MB-PEGDMA PAA NPs was evaluated using the traditional way of monitoring the oxidation rate kinetics of anthracence-9,10-dipropionic acid (ADPA). We also applied singlet oxygen sensor green (SOSG) so as to selectively derive the singlet oxygen (1O2) production rate. This analysis enabled us to investigate the ROS composition mix based on varied MB loading. To effectively obtain the correlation between the ROS productivity and the cell killing efficacy, a microfluidic chip device was employed to provide homogeneous light illumination from an LED for rapid PDT efficacy tests, enabling simultaneous multiple measurements while using only small amounts of NPs sample. This provided multiplexed, comprehensive PDT efficacy assays, leading to the determination of a near optimal loading of MB in a PAA matrix for high PDT efficacy by measuring the light-dose-dependent cell killing effects of the various MB-PEGDMA PAA NPs using C6 glioma cancer cells.

A high-throughput photodynamic therapy screening platform with on-chip control of multiple microenvironmental factors.

We present a novel high-throughput microfluidic platform that enables the evaluation of the anticancer efficacy of photodynamic therapy (PDT) drugs over multiple microenvironmental factors. PDT is uniquely complex, originating from its dependence on three separate but essential elements: drug (also called photosensitizer), oxygen, and light. Thus, obtaining a reliable evaluation of PDT efficacy is highly challenging, requiring considerable effort and time to evaluate all three interdependent parameters. In this paper, we report a high-throughput efficacy screening platform that we implemented by developing microfluidic components that individually control basic PDT elements (photosensitizer concentrations, oxygen levels, and light fluence) and then integrating them into a single triple-layer device. The integrated microfluidic chip consists of an array of small compartments, each corresponding to a specific combination of these three variables. This allows for more than 1000 different conditions being tested in parallel. Cancer cells are cultured within the device, exposed to different PDT conditions, and then monitored for their viability using live/dead fluorescence staining. The entire screening assay takes only 1 hour, and the collected PDT outcomes (cell viability) for combinatorial screening are analysed and reported as traditional dose-response curves or 3D bubble charts using custom software. As a proof of concept, methylene blue is adopted as a photosensitizer and its drug efficacy on C6 glioma cells has been successfully evaluated for a total of 324 PDT conditions using the fabricated chip. This platform can facilitate not only the development of new photosensitizers but also the optimization of current PDT protocols.

Controlling silica coating thickness on TiO2 nanoparticles for effective photodynamic therapy.

Photosensitive nanoparticles are useful in developing phototherapeutic agents for targeted cancer therapy. In this paper, core-shell structured titanium dioxide-silica (TiO2-SiO2) nanoparticles, with varying shell thickness, were synthesized. The influence of the silica shell thickness on the photoreactivity, cytotoxicity and photo-killing ability of the TiO2 nanoparticles was investigated. Silica coating reduced the photocatalytic reactivity but improved the cytocompatibility of the TiO2 nanoparticles. This effect was amplified with increasing silica shell thickness. When the silica thickness was about 5.5 nm, the coated TiO2 not only retained a high level photodynamic reactivity, comparable to the non-coated TiO2 nanoparticles, but also demonstrated an improved cell compatibility and effective photo-killing ability upon the mouse fibroblast cells (L929).

Isolation and characterization of microsatellite DNA markers for the Oriental White stork, Ciconia boyciana.

Following FIASCO protocol and across-amplification approach, we present eleven microsatellite primers of the Oriental White stork, Ciconia boyciana in this article. All loci were polymorphic, except for locus Cbo235, which possessed two alleles but was homozygous in all 23 individuals of C. boyciana used in this study. The number of the alleles per locus ranged from two to eight, and the observed heterozygosity (H(o)) and expected heterozygosity (H(E)) ranged from 0 to 0.857 and 0.222 to 0.851, respectively. These markers are proved useful in genetic study of C. boyciana.

Cell responses and hemocompatibility of g-HA/PLA composites.

The objective of this study was to investigate the hemocompatibility and cell responses to some novel poly(L-lactide) (PLA) composites containing surface modified hydroxyapatite particles for potential applications as a bone substitute material. The surface of hydroxyapatite (HA) particles was first grafted with L-lactic acid oligomers to form grafted HA (g-HA) particles. The g-HA particles were further blended with PLA to prepare g-HA/PLA composites. Our previous study has shown significant improvement in tensile properties of these materials due to the enhanced interfacial adhesion between the polymer matrix and HA particles. To further investigate the potential applications of these composites in bone repair and other orthopedic surgeries, a series of in vitro and in vivo experiments were conducted to examine the cell responses and hemocompatibility of the materials. In vitro experiments showed that the g-HA/PLA composites were well tolerated by the L-929 cells. Hemolysis of the composites was lower than that of pure PLA. Subcutaneous implantation demonstrated that the g-HA/PLA composites were more favorable than the control materials for soft tissue responses. The results suggested that the g-HA/PLA composites are promising and safe materials with potential applications in tissue engineering.

A novel gold-catalyzed chemoselective reduction of alpha,beta-unsaturated aldehydes using CO and H2O as the hydrogen source.

Chemoselective reduction of alpha,beta-unsaturated aldehydes in the presence of CO and H(2)O proceeds effectively over a ceria-supported gold catalyst system, providing a novel, efficient and clean approach to produce useful primary allyl alcohols with excellent activity and selectivity.

Calcification capacity of porous pHEMA-TiO2 composite hydrogels.

Many investigations have been attempted to promote calcification of synthetic polymers for applications as orthopaedic and dental implants. In this study, novel titanium dioxide (TiO(2)) reinforced porous poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels were synthesized. Calcification capacity of the composite polymers was examined using light microscopy, scanning electron microscopy and Fourier transform infrared spectroscopy after incubation of the materials in a simulated body fluid up to 53 days. Mechanical strength, porosity and in vitro cytotoxicity were also investigated. Calcification capacity of porous pHEMA was significantly enhanced by the addition of TiO(2) particulates. Infiltration of calcium phosphate, up to 1000 mum, was observed. The diffusion capacity of calcium ions was affected by the porosity and the interconnectivity of pores in the hydrogel polymers which were influenced by the presence of TiO(2) and the monomer concentration. Cell viability tests indicated that porous hydrogels containing 7.5% TiO(2) were not toxic to 3T3 fibroblast cells. These results demonstrate that incorporating TiO(2) nanoparticulates can promote enhanced formation of calcium phosphate whilst maintaining the porosity and interconnectivity of the hydrogel polymers and would be very useful for the development of orthopaedic tissue engineering scaffolds.

Orbital implants: potential new directions.

This article reviews orbital implants used to replace an eye after enucleation or evisceration. Advantages of implant placement are described, with discussion of implant and wrap material, and design features that affect clinical outcomes. Implants may be porous or nonporous, pegged for linkage with a cosmetic shell or unpegged, and may be wrapped with a covering material or tissue or unwrapped. Device shape, volume and material qualities affect tissue tolerance and the risk of exposure or extrusion. Limitations of currently available devices are discussed, with factors affecting surgeon and patient choice. Ideally, a device should be easy to insert, avoid the need for wrapping or adjunctive tissues, be light, biointegratable, comfortable after implantation and provide satisfactory orbital volume replacement, movement and cosmesis without requiring further surgery or pegging. This review briefly discusses developments in implant design and aspects of design that affect function, but is not a detailed clinical review; rather, it aims to stimulate thought on optimal design and discusses recent developments. Novel technology in the form of a prototype device with a soft, biointegratable anterior surface is described as an example of newer approaches.

Morphological and topographic effects on calcification tendency of pHEMA hydrogels.

Poly(2-hydroxyethyl methacrylate) hydrogels were prepared in the presence of varying concentrations of water, or a co-monomer ethoxyethyl methacrylate at different strengths of crosslinking agent ethylene glycol dimethacrylate. Calcification tendency and its correlation with monomer mixture composition, topography and porosity of these materials were investigated. Scanning (SEM) and transmission electron microscopy (TEM) was used to study topography and porosity respectively. Calcification and calcium diffusion ability in to the hydrogels were investigated by light microscopy, SEM and energy dispersive analysis of X-rays (EDAX) after incubation of the materials in a metastable calcifying solution for 48 days. Polymer and solvent volume fractions were also studied to determine if a correlation existed between porosity and calcification. Most of the series of hydrogels showed surface irregularities. Internal structure showed evidence of a porous structure in one of the series. Calcification studies indicated diffusion of calcium ions in some of the series. The diffusion of calcium is limited to 30-40 microm in most calcified specimens. For hydrogels that exhibited substantial surface irregularities and micro channels, the infiltration of calcium up to 200 microm was observed. Attempts to detect porosity by electron microscopy failed in some of the hydrogels due to difficulty in sample processing and sectioning. However, collaboration of the results with different techniques used, indicated that surface defects are the major contributors to calcium deposition. Decrease in porosity reduces the amount of calcium deposits and infiltration with decreasing solvent volume fraction which is associated with crosslinking concentration and initial water content of the polymer.

Drug release characteristics of phase separation pHEMA sponge materials.

A number of phase separation pHEMA sponge hydrogels have been prepared based on variations in monomer contents, concentration of cross-linking agent, solvent mixture and temperature of polymerization. The loading levels and release profiles of the anti-inflammatory drug prednisolone were examined for each of the pHEMA sponge materials. An effective diffusion coefficient determined by an optimization approach based on the experimental data was used to measure their release characteristics. The effect of morphological variations, revealed by the environmental scanning electron microscopy, and polymer/solvent volume fractions on these properties were discussed.

The Chirila Keratoprosthesis: phase I human clinical trial.

OBJECTIVE: To undertake a preliminary safety and performance evaluation of an artificial cornea, the Chirila Keratoprosthesis, in human patients. DESIGN: A prospective, interventional case series. PARTICIPANTS: Fourteen consecutive patients with blindness of corneal origin not treatable by repeated standard penetrating keratoplasty. METHODS: Keratoprostheses were manufactured and implanted. The patients, all with preoperative visual acuity of light perception to count fingers (CF), were followed clinically in adherence to a protocol. MAIN OUTCOME MEASURES: Safety (keratoprosthesis retention, incidence of serious complications) and performance (visual acuity, comfort, appearance). RESULTS: Ninety-three percent of keratoprostheses were retained to the date of reporting, up to 2.5 years. One keratoprosthesis (7%) was removed in a manner that restored the patient's preoperative condition. All but one patient maintained their preoperative level of visual acuity or improved on it, with most achieving their estimated full potential visual acuity, (range, count fingers - 20/20). CONCLUSIONS: This keratoprosthesis is acceptably safe and has demonstrated an ability to restore vision in cases in which alternative management would have had a poor prognosis. More extensive trials are warranted.

The use of synthetic polymers for delivery of therapeutic antisense oligodeoxynucleotides.

Developed over the past two decades, the antisense strategy has become a technology of recognised therapeutic potential, and many of the problems raised earlier in its application have been solved to varying extents. However, the adequate delivery of antisense oligodeoxynucleotides to individual cells remains an important and inordinately difficult challenge. Synthetic polymers appeared on this scene in the middle 1980s, and there is a surprisingly large variety used or proposed so far as agents for delivery of oligodeoxynucleotides. After discussing the principles of antisense strategy, certain aspects of the ingestion of macromolecules by cells, and the present situation of delivery procedures, this article analyses in detail the attempts to use synthetic polymers as carrier matrices and or cell membrane permeabilisation agents for delivery of antisense oligodeoxynucleotides. Structural aspects of various polymers, as well as the results, promises and limitations of their use are critically evaluated.