Improved gliotransmission by increasing intracellular Ca2+ via TRPV1 on multi-walled carbon nanotube platforms.

BACKGROUND: Astrocyte is a key regulator of neuronal activity and excitatory/inhibitory balance via gliotransmission. Recently, gliotransmission has been identified as a novel target for neurological diseases. However, using the properties of nanomaterials to modulate gliotransmission has not been uncovered. RESULTS: We prepared non-invasive CNT platforms for cells with different nanotopography and properties such as hydrophilicity and conductivity. Using CNT platforms, we investigated the effect of CNT on astrocyte functions participating in synaptic transmission by releasing gliotransmitters. Astrocytes on CNT platforms showed improved cell adhesion and proliferation with upregulated integrin and GFAP expression. In addition, intracellular GABA and glutamate in astrocytes were augmented on CNT platforms. We also demonstrated that gliotransmitters in brain slices were increased by ex vivo incubation with CNT. Additionally, intracellular resting Ca2+ level, which is important for gliotransmission, was also increased via TRPV1 on CNT platforms. CONCLUSION: CNT can improve astrocyte function including adhesion, proliferation and gliotransmission by increasing resting Ca2+ level. Therefore, our study suggests that CNT would be utilized as a new therapeutic platform for central nervous system diseases by modulating gliotransmission.

Continuous-wave operation of DFB laser diodes based on GaN using 10$

Single longitudinal mode continuous-wave operation of distributed-feedback (DFB) laser diodes based on GaN is demonstrated using laterally coupled 10th-order surface Bragg gratings. The gratings consist of V-shaped grooves alongside a 1.5 µm wide p-contact stripe fabricated by using electron-beam lithography and plasma etching. By varying the period of the Bragg grating, the lasing wavelength could be adjusted between 404.8 and 408.5 nm. The feasibility of this device concept was confirmed by mode-hop-free operation up to an optical output power of 90 mW, a low temperature sensitivity of the lasing wavelength, and a Gaussian lateral far-field distribution.

Colorimetric detection of iron and fluorescence detection of zinc and cadmium by a chemosensor containing a bio-friendly octopamine.

Chemosensor 1 was synthesized by the reaction of octopamine with 2,3-dihydroxybenzaldehyde. Sensor 1 determined iron with an obvious color change from pale yellow to brown in nearly-pure water. The detection limits (0.55 and 0.25 µM) for Fe2+ and Fe3+, respectively, were far lower than the EPA (Environmental Protection Agency) guideline concentration for drinking water (5.37 µM). In addition, 1 could be employed to quantify iron in environmental water samples. Moreover, sensor 1 exhibited different fluorescence emissions in response to zinc (green) and cadmium (blue). The binding structures and sensing mechanisms of 1 for iron, zinc and cadmium were proposed from various spectroscopic studies and theoretical calculations.

A multifunctional selective "turn-on" fluorescent chemosensor for detection of Group IIIA ions Al3+, Ga3+ and In3.

A versatile chemosensor 1 (E)-2-(((8-hydroxy-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)methylene)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione, based on naphthalimide and julolidine moieties, was developed for highly distinguishable and selective recognition of Group IIIA metal ions (Al3+, Ga3+ and In3+). Sensor 1 exhibited significant 'off-on' fluorescence responses at 488 nm in the presence of Al3+ and at 570 nm in the presence of Ga3+ and In3+. The same emission of Ga3+ and In3+ could be distinguished through different color changes (from colorless to yellow for Ga3+ and no color change for In3+). Binding constants of 1 for Ga3+ and In3+ are the highest reported to date for an organic chemosensor. A 2 : 1 binding mode between 1 with Al3+, Ga3+ and In3+ is proposed based on electrospray ionization mass spectrometry, Job plot analysis, and theoretical calculations.

A Multi-Responsive Naphthalimide-Based "Turn-on" Fluorescent Chemosensor for Sensitive Detection of Trivalent Cations Ga3+, Al3+ and Cr3.

A new multifunctional chemosensor 1, (E)-2-(((2-hydroxynaphthalen-1-yl)methylene)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione, based on naphtalimide and naphthaldehyde was developed, which showed the fluorescence responses to trivalent metal ions (Ga3+, Al3+ and Cr3+). Sensor 1 detected and differentiated selectively trivalent metal ions Ga3+, Al3+ and Cr3+ by fluorescence enhancement at different emissions. The association constant of Ga3+-2∙1 complex is the highest one among those of the organic chemosensors reported, to date. The sensing mechanisms for Ga3+, Al3+ and Cr3+ were explained by UV-vis titrations, Job plots, ESI-mass analyses and theoretical calculations.

Differences in two-point discrimination and sensory threshold in the blind between braille and text reading: a pilot study.

[Purpose] This study investigated two-point discrimination (TPD) and the electrical sensory threshold of the blind to define the effect of using Braille on the tactile and electrical senses. [Subjects and Methods] Twenty-eight blind participants were divided equally into a text-reading and a Braille-reading group. We measured tactile sensory and electrical thresholds using the TPD method and a transcutaneous electrical nerve stimulator. [Results] The left palm TPD values were significantly different between the groups. The values of the electrical sensory threshold in the left hand, the electrical pain threshold in the left hand, and the electrical pain threshold in the right hand were significantly lower in the Braille group than in the text group. [Conclusion] These findings make it difficult to explain the difference in tactility between groups, excluding both palms. However, our data show that using Braille can enhance development of the sensory median nerve in the blind, particularly in terms of the electrical sensory and pain thresholds.

MicroRNA Regulation for Inflammasomes in High Glucose-Treated ARPE-19 Cells.

Purpose: This study aimed to evaluate the expression of microRNAs (miRNAs) and inflammasomes in diabetes-induced retinal cells and to determine their role in the pathogenesis of diabetic retinopathy (DR). Methods: To establish diabetes-induced cell models, ARPE-19 cells were treated with high glucose. The expression levels of five miRNAs (miR-185, miR-17, miR-20a, miR-15a, and miR-15b) were measured in high glucose-treated ARPE-19 cells using real-time quantitative polymerase chain reaction. Western blotting was performed to measure inflammasome expression in cellular models. miR-17 was selected as the target miRNA, and inflammasome expression was measured following the transfection of an miR-17 mimic into high glucose-treated ARPE-19 cells. Results: In high glucose-treated ARPE-19 cells, miRNA expression was substantially downregulated, whereas that of inflammasome components was significantly increased. Following the transfection of the miR-17 mimic into high glucose-treated ARPE-19 cells, the levels of inflammasome components were significantly decreased. Conclusions: This study investigated the relationship between miRNAs and inflammasomes in diabetes-induced cells using high glucose-treated ARPE-19 cells. These findings suggested that miR-17 suppresses inflammasomes, thereby reducing the subsequent inflammatory response and indicating that miRNAs and inflammasomes could serve as new therapeutic targets for DR.

Expression of microRNAs related to apoptosis in the aqueous humor and lens capsule of patients with glaucoma.

Background: The aim of this study is to investigate the expression profiles of microRNAs (miRNAs) related to apoptosis in the aqueous humor (AH) and lens capsule (LC) of patients with glaucoma. Methods: AH and LC samples were collected from patients with open-angle glaucoma and control participants who were scheduled for cataract surgery. A miRNA PCR array comprising 84 miRNAs was used to analyze the AH (glaucoma, n = 3; control, n = 3) and LC samples (glaucoma, n = 3; control, n = 4). Additionally, the AH and LC samples (glaucoma, n = 3; control, n = 4) were subjected to quantitative real-time PCR to validate the differentially expressed miRNAs determined using the PCR array. Bioinformatics analysis was performed to identify the interactions between miRNAs and diseases. Additionally, the differential expression of these miRNAs and the target gene was validated through in vitro experiments using a retinal ganglion cell (RGC) model. Results: Expression levels of 19 and 3 miRNAs were significantly upregulated in the AH and LC samples of the glaucoma group, respectively (p < 0.05). Of these, the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p showed significant differences in both AH and LC samples. Bioinformatics analysis showed experimentally validated 8 miRNA:gene pairs. Among them, PTEN was selected to analyze the expression level in AH and LC from separate cohort (glaucoma, n = 5; control, n = 4). The result showed downregulation of PTEN concurrent with upregulation of the two miRNAs in LC samples of glaucoma group. In vitro experiments validated that the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p were significantly upregulated, and that of PTEN was significantly downregulated in the H2O2-treated RGC, while the level of PTEN was recovered through co-treatment with miR-193a inhibitor or miR-222 inhibitor. Conclusion: This is the first study to investigate the differential expression of apoptosis-related miRNAs in the AH and LC of patients with glaucoma. Hsa-miR-193a-5p and hsa-miR-222-3p, which were upregulated in both AH and LC, may be considered potential biomarkers for glaucoma.

Molecular basis for failure of "atypical" C1 domain of Vav1 to bind diacylglycerol/phorbol ester.

C1 domains, the recognition motif of the second messenger diacylglycerol and of the phorbol esters, are classified as typical (ligand-responsive) or atypical (not ligand-responsive). The C1 domain of Vav1, a guanine nucleotide exchange factor, plays a critical role in regulation of Vav activity through stabilization of the Dbl homology domain, which is responsible for exchange activity of Vav. Although the C1 domain of Vav1 is classified as atypical, it retains a binding pocket geometry homologous to that of the typical C1 domains of PKCs. This study clarifies the basis for its failure to bind ligands. Substituting Vav1-specific residues into the C1b domain of PKCδ, we identified five crucial residues (Glu(9), Glu(10), Thr(11), Thr(24), and Tyr(26)) along the rim of the binding cleft that weaken binding potency in a cumulative fashion. Reciprocally, replacing these incompatible residues in the Vav1 C1 domain with the corresponding residues from PKCδ C1b (δC1b) conferred high potency for phorbol ester binding. Computer modeling predicts that these unique residues in Vav1 increase the hydrophilicity of the rim of the binding pocket, impairing membrane association and thereby preventing formation of the ternary C1-ligand-membrane binding complex. The initial design of diacylglycerol-lactones to exploit these Vav1 unique residues showed enhanced selectivity for C1 domains incorporating these residues, suggesting a strategy for the development of ligands targeting Vav1.

Air-ring microstructure arrays for enhanced light extraction from a face-up light-emitting diode.

In this Letter, a light-emitting diode (LED) with prism-shaped-air-ring microstructures (PSAMs) formed on flat sapphire substrate is demonstrated as an alternative design to face-up LEDs on patterned sapphire substrate (PSS) for enhanced light extraction efficiency. In this LED design, the emitted photons can be deflected to the top of the chip for its effective extraction, contrary to the PSS-LED wherein photons are guided to sapphire and get absorbed by packaging materials. The PSAM-LED showed an enhancement in the radiometric power as high as 10% with a low far-field angle of 129° over that of a PSS-LED under an injection current of 20 mA.

Dual stimuli-responsive mesoporous silica nanoparticles for efficient loading and smart delivery of doxorubicin to cancer with RGD-integrin targeting.

The recent progress in nanoparticle applications, such as tumor-targeting, has enabled specific delivery of chemotherapeutics to malignant tissues with enhanced local efficacy while limiting side effects. However, existing delivery systems leave much room for improvement in terms of achieving enhanced colloidal stability in fluid medium, efficient targeting of intended sites, and effective release of therapeutic drugs into diseased cells. Here, an efficient stimuli-responsive nanocarrier for mammalian cells, termed RGD-NAMs, was developed, which enabled temperature- and pH-sensitive release of drug loads. The RGD-NAMs comprise two parts: a stimuli-responsive copolymer shell (NIBIm-AA-RGD) and drug-container core (MSNs). The RGD-NAMs have a stable drug-loading capacity with a marked difference in the release rate depending on the temperature and pH conditions. The RGD-NAMs also exhibit high colloidal stability in SBF (Stimulated body fluid) solutions and minimal toxicity in skeletal myoblasts (C2C12) and bovine arterial endothelial cells (BAEC). The doxorubicin-loaded RGD-NAMs induced a cytotoxic effect in a dose-dependent manner, which was furthered by an increase in temperature from 37 to 40 °C. Moreover, significant control of the release rate and the amount were achieved through pH change. This novel, smart drug-delivery system with high responsiveness to temperature and pH changes has wide application prospects in biomedical fields, including the theragnosis of tumors and vascular diseases.

High performance of InGaN light-emitting diodes by air-gap/GaN distributed Bragg reflectors.

The effect of air-gap/GaN DBR structure, fabricated by selective lateral wet-etching, on InGaN light-emitting diodes (LEDs) is investigated. The air-gap/GaN DBR structures in LED acts as a light reflector, and thereby improve the light output power due to the redirection of light into escape cones on both front and back sides of the LED. At an injection current of 20 mA, the enhancement in the radiometric power as high as 1.91 times as compared to a conventional LED having no DBR structure and a far-field angle as low as 128.2° are realized with air-gap/GaN DBR structures.

Improving the optical performance of InGaN light-emitting diodes by altering light reflection and refraction with triangular air prism arrays.

The effect of triangular air prism (TAP) arrays with different distance-to-width (d/w) ratios on the enhancement of light extraction efficiency (LEE) of InGaN light-emitting diodes (LEDs) is investigated. The TAP arrays embedded at the sapphire/GaN interface act as light reflectors and refractors, and thereby improve the light output power due to the redirection of light into escape cones on both the front and back sides of the LED. Enhancement in radiometric power as high as 117% and far-field angle as low as 129° are realized with a compact arrangement of TAP arrays compared with that of a conventional LED made without TAP arrays under an injection current of 20 mA.

Wearable CNTs-based humidity sensors with high sensitivity and flexibility for real-time multiple respiratory monitoring.

Sensors, such as optical, chemical, and electrical sensors, play an important role in our lives. While these sensors already have widespread applications, such as humidity sensors, most are generally incompatible with flexible/inactive substrates and rely on conventional hard materials and complex manufacturing processes. To overcome this, we develop a CNT-based, low-resistance, and flexible humidity sensor. The core-shell structured CNT@CPM is prepared with Chit and PAMAM to achieve reliability, accuracy, consistency, and durability, resulting in a highly sensitive humidity sensor. The average response/recovery time of optimized sensor is only less than 20 s, with high sensitivity, consistent responsiveness, good linearity according to humidity rates, and low hysteresis (- 0.29 to 0.30 %RH). Moreover, it is highly reliable for long-term (at least 1 month), repeated bending (over 15,000 times), and provides accurate humidity measurement results. We apply the sensor to smart-wear, such as masks, that could conduct multi-respiratory monitoring in real-time through automatic ventilation systems. Several multi-respiratory monitoring results demonstrate its high responsiveness (less than 1.2 s) and consistent performance, indicating highly desirable for healthcare monitoring. Finally, these automatic ventilation systems paired with flexible sensors and applied to smart-wear can not only provide comfort but also enable stable and accurate healthcare in all environments.

Electrical and thermal stimulus-responsive nanocarbon-based 3D hydrogel sponge for switchable drug delivery.

Smart hydrogels that are responsive to various external (e.g. electrical and/or thermal) stimulation have become increasingly popular in recent years for simple, rapid, and precise drug delivery that can be controlled and turned on or off with external stimuli. For such a switchable drug delivery material, highly homogeneous dispersion and distribution of the hydrophobic, electrically conductive nanomaterials throughout a hydrophilic three-dimensional (3D) hydrogel network remains a challenge and is essential for achieving well-connected electrical and thermal conducting paths. Herein we developed electrical and thermal stimulus-responsive 3D hydrogels based on (i) carbon nanotubes (CNTs) as the core unit and an electrical/thermal conductor, (ii) chitosan (Chit) as the shell unit and a hydrophilic dispersant, and (iii) poly(NIPAAm-co-BBVIm) (pNIBBIm) as the drug carrier and a temperature-responsive copolymer. By formulating the CNT-core and Chit-shell units and constructing a CNT sponge framework, uniform distribution and 3D connectivity of the CNTs were improved. The 3D hydrogel based on the CNT sponge, namely the 3D frame CNT-Chit/pNIBBIm hydrogel, delivered approximately 37% of a drug, ketoprofen used for the treatment of musculoskeletal pain, during about 30% shrinkage after electrical and thermal switches on/off and exhibited the best potential for future use in a smart transdermal drug delivery system. The physicochemical, mechanical, electrical, thermal, and biocompatible characteristics of this nanocarbon-based 3D frame hydrogel led to remarkable electrical and thermal stimulus-responsive properties capable of developing an excellent controllable and switchable drug delivery platform for biomedical engineering and medicine applications.

Comparison of various surface textured layer in InGaN LEDs for high light extraction efficiency.

The various surface texturing effects of InGaN light emitting diodes (LEDs) have been investigated by comparison of experimented data and simulated data. The single-layer and double-layer texturing were performed with the help of ITO nanospheres using wet etching, where the ITO ohmic contact layer and the p-GaN layer are textured using ITO nanospheres as an etch mask. In case of single-layer texturing, p-type GaN layer texturing was more effective than ITO ohmic contact layer texturing. The maximum enhancement of wall-plug efficiency of double-layered textured LEDs is 40% more than conventional LEDs, after packaging at an injected current of 20 mA. The increase of light scattering at the textured GaN surfaces is a major reason for increasing the light extraction efficiency of LEDs.

Enhanced light emission in blue light-emitting diodes by multiple Mie scattering from embedded silica nanosphere stacking layers.

We demonstrate enhanced light emission in blue light-emitting diodes (LEDs) by multiple Mie scattering from embedded silica nanosphere stacking layers (SNSL). A honeycomb cone structure is introduced in the GaN epilayer to confine a maximum number of silica nanospheres (SNs). We found that the light is predominantly directed vertically by scattering and geometrical effect in SNSL embedded LEDs. Consequently, the light output power is enhanced by 2.7 times, which we attribute to the improvement in light extraction efficiency due to the multiple Mie scattering of light from the embedded SNSL. The experimental results are verified by simulation using finite difference time domain method (FDTD).

Effect of embedded silica nanospheres on improving the performance of InGaN/GaN light-emitting diodes.

We report on the effect of embedded silica nanospheres on improving the performance of InGaN/GaN light-emitting diodes (LEDs). The silica nanospehres were coated on the selectively etched GaN using a spin-coating method. With the embedded silica nanospheres structures, we achieved a smaller reverse leakage current due to the selective defect blocking-induced crystal quality improvement. Moreover, the reflectance spectra show strong reflectance modulations due to the different refractive indices between the GaN and silica nanospheres. By using confocal scanning electroluminescence microscopy, a strong light emission from silica nanospheres demonstrates that the silica nanospheres acted as a reflector. We found that the optimized embedded silica nanospheres structure, whose the average size of the etched pits was about 3.5 µm and EPD was 3 x 10(7) cm(-2), could enhance light output power by a factor of 2.23 due to enhanced the probability of light scattering at silica nanospheres.

Potential involvement of CCL23 in atherosclerotic lesion formation/progression by the enhancement of chemotaxis, adhesion molecule expression, and MMP-2 release from monocytes.

OBJECTIVE: CCL23 [Ckß8-1/myeloid progenitor inhibitory factor 1 (MPIF1)/macrophage inflammatory protein-3 (MIP3)], a member of the CC chemokine family, is involved in leukocyte trafficking, and implicated in inflammatory diseases. In the present study, we investigated the role of CCL23 in the development of human atherosclerosis, which is characterized by an inflammatory disease. METHODS: CCL23 transcripts were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and CCL23 protein by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Expression of adhesion molecules was determined by flow cytometry, and matrix metalloproteinase-2 (MMP-2) levels by zymography. RESULTS: Proatherogenic factors such as oxidized low-density lipoprotein (oxLDL) and oxidative stress markedly enhanced CCL23 release from human THP-1 macrophages. CCL23 stimulated chemotaxis of human THP-1 monocytes in a dose-dependent manner and enhanced the expression of adhesion molecule CD11c, as well as release of MMP-2 from the THP-1 monocytes. Moreover, CCL23 expression at the mRNA level was significantly higher in human atherosclerotic lesions than in normal arteries, and CCL23 protein was co-expressed with CD68, a specific marker for macrophages. Circulating levels of plasma CCL23 were higher in atherosclerotic patients than in normal subjects. CONCLUSION: These findings suggest that CCL23 plays a role in the development of human atherosclerosis. CCL23 may be a useful target for the development of antiatherogenic agents.

Bilateral Cerebral Ptosis in a Patient with Subdural Hemorrhage: a Case Report.

Although cerebral ptosis is rare, it is commonly associated with unilateral right cerebral hemisphere lesions. We report a case of a 79-year-old woman who presented with bilateral complete ptosis after a traumatic right fronto-temporo-parietal subdural hemorrhage (SDH). Bilateral ptosis was the primary manifestation of the acute right SDH, and the patient had no parenchymal lesion. Her prognosis was good, and she made a complete recovery. Right hemispheric hypoperfusion, as demonstrated on brain perfusion single-photon emission computed tomography, implied that the lateralization of eyelid control was in the right hemisphere, in line with previous reports.