VI-116, A Novel Potent Inhibitor of VRAC with Minimal Effect on ANO1

Volume-regulated anion channel (VRAC) is ubiquitously expressed and plays a pivotal role in vertebrate cell volume regulation. A heterologous complex of leucine-rich repeat containing 8A (LRRC8A) and LRRC8B-E constitutes the VRAC, which is involved in various processes such as cell proliferation, migration, differentiation, intercellular communication, and apoptosis. However, the lack of a potent and selective inhibitor of VRAC limits VRAC-related physiological and pathophysiological studies, and most previous VRAC inhibitors strongly blocked the calcium-activated chloride channel, anoctamin 1 (ANO1). In the present study, we performed a cell-based screening for the identification of potent and selective VRAC inhibitors. Screening of 55,000 drug-like small-molecules and subsequent chemical modification revealed 3,3′-((2-hydroxy-3-methoxyphenyl)methylene)bis(4-hydroxy-2H-chromen-2-one) (VI-116), a novel potent inhibitor of VRAC. VI-116 fully inhibited VRAC-mediated I⁻ quenching with an IC₅₀ of 1.27 ± 0.18 μM in LN215 cells and potently blocked endogenous VRAC activity in PC3, HT29 and HeLa cells in a dose-dependent manner. Notably, VI-116 had no effect on intracellular calcium signaling up to 10 μM, which completely inhibited VRAC, and showed high selectivity for VRAC compared to ANO1 and ANO2. However, DCPIB, a VRAC inhibitor, significantly affected ATP-induced increases in intracellular calcium levels and Eact-induced ANO1 activation. In addition, VI-116 showed minimal effect on hERG K⁺ channel activity up to 10 μM. These results indicate that VI-116 is a potent and selective VRAC inhibitor and a useful research tool for pharmacological dissection of VRAC.     

Red bean extract reduces inflammation and increases survival in a murine sepsis model

This study used in vitro and in vivo experimental models to investigate the anti-inflammatory potential of the butanol fraction of red bean ethanol extract (BF-RBEE), which contains the biologically active molecule catechin-7-β-d-glucopyranoside. Treatment with BF-RBEE inhibited nitric oxide production in lipopolysaccharide (LPS)-stimulated macrophages through suppression of extracellular signalregulated kinase and IκBα activation. In an in vivo murine sepsis model, oral administration of BF-RBEE improved mouse survival. Specifically, the survival rate of mice injected with LPS was 0 and 40% in ICR and BALB/c mice, respectively, whereas the survival of mice co-treated with BF-RBEE was 100% in both mouse types. This increase in survival with the BF-RBEE administration was correlated with decreased tumor-necrosis factor-α and interferon-γ and increased interleukin-10. Oral administration of BF-RBEE also inhibited total and ovalbumin-specific IgE production in experimental mice. These results suggest the possible usefulness of red beans in the treatment of inflammatory diseases.     

Efficiency improvement of polymer light-emitting diodes using a quantum dot interlayer between a hole transport layer and an emitting layer

The current efficiency of polymer light-emitting diodes (PLEDs) were improved using a quantum dot interlayer between a hole transport layer and an emitting layer. The quantum dot interlayer played a role of controlling the hole transport in the PLEDs and enhanced the charge balance in the emitting layer. The current efficiency of the PLEDs was increased by more than 20% by the quantum dot interlayer. In particular, the efficiency improvement was significant at high luminance due to reduced efficiency roll-off in the quantum dot-embedded PLEDs.     

Enhanced transformation of triclosan by laccase in the presence of redox mediators

Triclosan (TCS), an antimicrobial agent, is an emerging and persistent environmental pollutant that is often found as a contaminant in surface waters and sediments; hence, knowledge of its degradability is important. In this study we investigated laccase-mediated TCS transformation and detoxification, using laccase (from the fungus Ganoderma lucidum) in the presence and absence of redox mediators. Transformation products were identified using HPLC, ESI-MS and GC-MS, and transformation mechanisms were proposed. In the absence of redox mediator, 56.5% TCS removal was observed within 24 h, concomitant with formation of new products with molecular weights greater than that of TCS. These products were dimers and trimers of TCS, as confirmed by ESI-MS analysis. Among the various mediators tested, 1-hydroxybenzotriazole (HBT) and syringaldehyde (SYD) significantly enhanced TCS transformation (∼90%). The presence of these mediators resulted in products with lower molecular weights than TCS, including 2,4-dichlorophenol (2,4-DCP; confirmed by GC-MS) and dechlorinated forms of 2,4-DCP. When SYD was used as the mediator, dechlorination resulted in 2-chlorohydroquinone (2-CHQ). Bacterial growth inhibition studies revealed that laccase-mediated transformation of TCS effectively decreased its toxicity, with ultimate conversion to less toxic or nontoxic products. Our results confirmed the involvement of two mechanisms of laccase-catalyzed TCS removal: (i) oligomerization in the absence of redox mediators, and (ii) ether bond cleavage followed by dechlorination in the presence of redox mediators. These results suggest that laccase in combination with natural redox mediator systems may be a useful strategy for the detoxification and elimination of TCS from aqueous systems.     

Fabrication and performance of parallel-addressed InGaN micro-LED arrays

High-performance, two-dimensional arrays of parallel-addressed InGaN blue micro-light-emitting diodes (LEDs) with individual element diameters of 8, 12, and 20 /spl mu/m, respectively, and overall dimensions 490 /spl times/490 /spl mu/m, have been fabricated. In order to overcome the difficulty of interconnecting multiple device elements with sufficient step-height coverage for contact metallization, a novel scheme involving the etching of sloped-sidewalls has been developed. The devices have current-voltage (I-V) characteristics approaching those of broad-area reference LEDs fabricated from the same wafer, and give comparable (3-mW) light output in the forward direction to the reference LEDs, despite much lower active area. The external efficiencies of the micro-LED arrays improve as the dimensions of the individual elements are scaled down. This is attributed to scattering at the etched sidewalls of in-plane propagating photons into the forward direction.     

High efficiency red phosphorescent organic light-emitting diodes using a spirobenzofluorene type phosphine oxide as a host material

High efficiency red phosphorescent organic light-emitting diodes have been developed using a spirobenzofluorene type phosphine oxide (SPPO2) as a host material. The SPPO2 had a high glass transition temperature of 119 °C and a smooth surface morphology with a surface roughness less than 1 nm. The red device with the SPPO2 as a host showed a quantum efficiency of 14.3% with a current efficiency of 20.4 cd/A.     

Dynamic spectrum access based on interruptible spectrum leasing

Dynamic spectrum access (DSA) based on interruptible spectrum leasing allows secondary users (SUs) to lease a licensed, but idle, spectrum that is owned by primary users (PUs) on condition that the PUs preempt the access to the leased spectrum. This paper considers a DSA scenario where the SUs opportunistically use the primary spectrum in addition to their own band and the PUs use their own band regardless of the opportunistic access. This operating scenario can contribute to leverage the spectrum utilization by exploiting underutilized spectrum resources, but involves a problem that the SUs may be forced to interrupt on-going services in response to the PUs?? reclamation of the leased spectrum. In this paper, we address the optimal call admission control (CAC) problem in order to coordinate the DSA based on interruptible spectrum leasing by considering the tradeoff between the additional spectrum use and the penalty on the service interruption. To this end, we adopt the profit of the secondary wireless service provider as a cost function of the CAC policy in a market mechanism manner. The optimization problem is modeled as a profit maximization problem, and a linear programming (LP) formulation of the semi-Markov decision process approach is provided. Through the simulation results, we analyze the LP solution of the optimal CAC for the leasing based DSA and demonstrate that the proposed CAC policy judiciously uses the access opportunities of the SUs considering the service interruption.     

Mucoadhesive Phenolic Pectin Hydrogels for Saliva Substitute and Oral Patch

Oral disease is one of the most common conditions worldwide, negatively affecting general health, reducing the quality of life, and often developing into systemic illness. However, the design of therapeutic agents for oral diseases is challenging due to various unique features of the oral cavity, including its wet and dynamic environment and curved shape. Herein, the development of highly biocompatible mucoadhesive functional hydrogels for oral applications is reported, generated by introducing bio-inspired phenolic moieties into a pectin polymer. Pyrogallol-functionalized pectin (Pec-PG) can be crosslinked in situ via autoxidation without chemical agents and readily fabricated as various formulations. Sprayable Pec-PG hydrogel exhibits strong mucoadhesion and outstanding hydration ability ex vivo and in vivo, thus displaying significant potential as a novel saliva substitute for dry mouth. The authors further show that topical application of mucoadhesive Pec-PG patches pre-loaded with corticosteroid significantly promotes the repair of diabetic oral ulcer tissue via prolonged drug release, free radical scavenging, and physical barrier effects. Moreover, similar applications for oral ulcer treatment using a pectin hydrogel modified with catechol (Pec-CA), another phenolic moiety are demonstrated. Together, these findings suggest that mucoadhesive phenolic pectin derivatives can provide highly biocompatible, convenient, and effective hydrogel platforms for treating oral diseases.     

Regulation of Stem Cell Fate in a Three‐Dimensional Micropatterned Dual‐Crosslinked Hydrogel System

Micropatterning technology is a powerful tool for controlling the cellular microenvironment and investigating the effects of physical parameters on cell behaviors, such as migration, proliferation, apoptosis, and differentiation. Although there have been significant developments in regulating the spatial and temporal distribution of physical properties in various materials, little is known about the role of the size of micropatterned regions of hydrogels with different crosslinking densities on the response of encapsulated cells. In this study, a novel alginate hydrogel system that can be micropatterned three‐dimensionally is engineered to create regions that are crosslinked by a single mechanism or dual mechanisms. By manipulating micropattern size while keeping the overall ratio of single‐ to dual‐crosslinked hydrogel volume constant, the physical properties of the micropatterned alginate hydrogels are spatially tunable. When human adipose‐derived stem cells (hASCs) are photoencapsulated within micropatterned hydrogels, their proliferation rate is a function of micropattern size. Additionally, micropattern size dictates the extent of osteogenic and chondrogenic differentiation of photoencapsulated hASC. The size of 3D micropatterned physical properties in this new hydrogel system introduces a new design parameter for regulating various cellular behaviors, and this dual‐crosslinked hydrogel system provides a new platform for studying proliferation and differentiation of stem cells in a spatially controlled manner for tissue engineering and regenerative medicine applications.     

Interactive plant simulation modeling for developing an operator training system in a natural gas pressure-regulating station

This study proposes a method of interactive plant simulation modeling which delivers the online simulated results to the field operators and induces them to take proper actions in the case of pre-identified accident scenarios in a chemical plant. The developed model integrates the real-time process dynamic simulation with 3DCFD accident simulation in a designed interface using object linking and embedding technology so that it can convey to trainees the online information of the accident which is not available in existing operator training systems. The model encompasses the whole process of data transfer till the end of the training at which a trainee operates an emergency shutdown system in a programmed model. In this work, an overall scenario is simulated which is from an abnormal increase in the main valve discharge (second) pressure due to valve malfunction to accidental gas release through the crack of a pressure recorder, and the magnitude of the accident with respect to the lead time of each trainee’s emergency response is analyzed. The model can improve the effectiveness of the operator training system through interactively linking the trainee actions with the simulation model resulting in different accident scenarios with respect to each trainee’s competence when facing an accident.