Tetraspanin 7 regulates osteoclast function through association with the RANK/αvß3 integrin complex.

Actin rings are unique structures that facilitate the attachment of osteoclasts to the bone matrix during bone resorption. Previous studies have shown that tetraspanin7 (TSPAN7) plays an important role in the reorganization of the cytoskeleton necessary for the bone-resorbing activity of osteoclasts. However, questions remain as to the mechanisms by which TSPAN7 regulates this cytoskeletal rearrangement. In this study, we investigated the roles of TSPAN7 in osteoclasts by deleting the Tm4sf2 gene in mice, which encodes TSPAN7. The Tm4sf2 global knockout model showed protective effects on pathological bone loss, but no discernible changes in bone phenotypes under physiological conditions. In vitro study revealed that ablation of Tm4sf2 caused significant defects in integrin-mediated actin ring formation, thereby leading to significantly decreased bone resorption. Additionally, we demonstrated an association between TSPAN7 and the receptor activator of nuclear factor-кB/αvß3 integrin. Overall, our findings suggest that TSPAN7 acts as a novel modulator regulating the bone-resorbing function of osteoclasts.

BaroTac: Barometric Three-Axis Tactile Sensor with Slip Detection Capability.

Tactile sensors for robotic applications enhance the performance of robotic end-effectors as they ca n provide tactile information to operate various tasks. In particular, tactile sensors can measure multi-axial force and detect slip can aid the end-effectors in grasping diverse objects in an unstructured environment. We propose BaroTac, which measures three-axial forces and detects slip with a barometric pressure sensor chip (BPSC) for robotic applications. A BPSC is an off-the-shelf commercial sensor that is inexpensive, easy to customize, robust, and simple to use. While a single BPSC-based tactile sensor can measure pressure, an array of BPSC-based tactile sensors can measure multi-axial force through the reactivity of each sensor and detect slip by observing high frequency due to slip vibration. We first experiment with defining the fundamental characteristics of a single-cell BPSC-based sensor to set the design parameters of our proposed sensor. Thereafter, we suggest the sensing method of BaroTac: calibration matrix for three-axis force measurement and discrete wavelet transform (DWT) for slip detection. Subsequently, we validate the three-axis force measuring ability and slip detectability of the fabricated multi-cell BPSC-based tactile sensor. The sensor measures three-axis force with low error (0.14, 0.18, and 0.3% in the X-, Y- and Z-axis, respectively) and discriminates slip in the high-frequency range (75-150 Hz). We finally show the practical applicability of BaroTac by installing them on the commercial robotic gripper and controlling the gripper to grasp common objects based on our sensor feedback.

Micro-Current Stimulation Suppresses Inflammatory Responses in Peptidoglycan-Treated Raw 264.7 Macrophages and Propionibacterium acnes-Induced Skin Inflammation via TLR2/NF-κB Signaling Pathway.

Acne is a common inflammatory disorder of the human skin and a multifactorial disease caused by the sebaceous gland and Propionibacterium acnes (P. acnes). This study aimed to evaluate the anti-inflammatory effect of micro-current stimulation (MC) on peptidoglycan (PGN)-treated raw 264.7 macrophages and P. acnes-induced skin inflammation. To specify the intensity with anti-inflammatory effects, nitric oxide (NO) production was compared according to various levels of MC. As the lowest NO production was shown at an intensity of 50 µA, subsequent experiments used this intensity. The changes of expression of the proteins related to TLR2/NF-κB signaling were examined by immunoblotting. Also, immunofluorescence analysis was performed for observing NF-κB p65 localization. All of the expression levels of proteins regarding TLR2/NF-κB signaling were decreased by the application of MC. Moreover, the application of MC to PGN-treated raw 264.7 cells showed a significant decrease in the amount of nuclear p65-protein. In the case of animal models with P. acnes-induced skin inflammation, various pro-inflammatory cytokines and mediators significantly decreased in MC-applied mice. In particular, the concentration of IL-1ß in serum decreased, and the area of acne lesions, decreased from the histological analysis. We suggest for the first time that MC can be a novel treatment for acne.

Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis.

Cinchonine (CN) has been known to exert antimalarial, antiplatelet, and antiobesity effects. It was also recently reported to inhibit transforming growth factor ß-activated kinase 1 (TAK1) and protein kinase B (AKT) through binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). However, its role in bone metabolism remains largely unknown. Here, we showed that CN inhibits osteoclast differentiation with decreased expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key determinant of osteoclastogenesis. Immunoblot and quantitative real-time polymerase chain reaction analysis as well as the reporter assay revealed that CN inhibits nuclear factor-κB and activator protein-1 by regulating TAK1. CN also attenuated the activation of AKT, cyclic AMP response element-binding protein, and peroxisome proliferator-activated receptor-γ coactivator 1ß (PGC1ß), an essential regulator of mitochondrial biogenesis. Collectively, these results suggested that CN may inhibit TRAF6-mediated TAK1 and AKT activation, which leads to downregulation of NFATc1 and PGC1ß resulting in the suppression of osteoclast differentiation. Interestingly, CN not only inhibited the maturation and resorption function of differentiated osteoclasts but also promoted osteoblast differentiation. Furthermore, CN protected lipopolysaccharide- and ovariectomy-induced bone destruction in mouse models, suggesting its therapeutic potential for treating inflammation-induced bone diseases and postmenopausal osteoporosis.

Micro-Current Stimulation Has Potential Effects of Hair Growth-Promotion on Human Hair Follicle-Derived Papilla Cells and Animal Model.

Recently, a variety of safe and effective non-pharmacological methods have been introduced as new treatments of alopecia. Micro-current electrical stimulation (MCS) is one of them. It is generally known to facilitate cell proliferation and differentiation and promote cell migration and ATP synthesis. This study aimed to investigate the hair growth-promoting effect of MCS on human hair follicle-derived papilla cells (HFDPC) and a telogenic mice model. We examined changes in cell proliferation, migration, and cell cycle progression with MCS-applied HFDPC. The changes of expression of the cell cycle regulatory proteins, molecules related to the PI3K/AKT/mTOR/Fox01 pathway and Wnt/ß-catenin pathway were also examined by immunoblotting. Subsequently, we evaluated the various growth factors in developing hair follicles by RT-PCR in MCS-applied (MCS) mice model. From the results, the MCS-applied groups with specific levels showed effects on HFDPC proliferation and migration and promoted cell cycle progression and the expression of cell cycle-related proteins. Moreover, these levels significantly activated the Wnt/ß-catenin pathway and PI3K/AKT/mTOR/Fox01 pathway. Various growth factors in developing hair follicles, including Wnts, FGFs, IGF-1, and VEGF-B except for VEGF-A, significantly increased in MCS-applied mice. Our results may confirm that MCS has hair growth-promoting effect on HFDPC as well as telogenic mice model, suggesting a potential treatment strategy for alopecia.

Dehydrocostus lactone suppresses osteoclast differentiation by regulating NFATc1 and inhibits osteoclast activation through modulating migration and lysosome function.

Excessive osteoclast activity can lead to an imbalance between the synthesis and breakdown of bone, with pathologic consequences that include osteoporosis and periodontitis. Thus, controlling osteoclast differentiation and function has significant therapeutic implications. In this study, we investigated the effects of dehydrocostus lactone (DL) on osteoclast differentiation and activation and elucidated the possible mechanisms underlying these processes. DL suppressed osteoclast differentiation by reducing the expression of the nuclear factor of activated T-cells, cytoplasmic 1. When used to challenge differentiated osteoclasts, DL also effectively inhibited their enlargement and resorption activity, and biochemical approaches revealed that DL attenuates osteoclast activation by inhibiting the migration and lysosome biogenesis and secretion via the down-regulation of integrin ß3, PKC-ß, and autophagy related 5 expression. Furthermore, DL prevented bone destruction in inflammation- and ovariectomy-induced osteolytic mouse models. These results indicate that DL has therapeutic potential to treat bone diseases caused by excessive or hyperactive osteoclasts.-Lee, H. I., Lee, J., Hwang, D., Lee, G.-R., Kim, N., Kwon, M., Lee, H., Piao, D., Kim, H. J., Kim, N. Y., Kim, H. S., Seo, E. K., Kang, D., Jeong, W. Dehydrocostus lactone suppresses osteoclast differentiation by regulating NFATc1 and inhibits osteoclast activation through modulating migration and lysosome function.

Subtypes of Maxillomandibular Advancement Surgery for Patients With Obstructive Sleep Apnea.

Maxillomandibular advancement (MMA) surgery, which is the most effective treatment modality for patients with moderate-to-severe obstructive sleep apnea with apparent skeletal discrepancies, has been modified in conjunction with segmental osteotomies, counterclockwise rotation of maxillomandibular complex, and other adjunctive procedures. However, any single type of MMA could not treat or cure all the patients with obstructive sleep apnea showing different dentofacial and pharyngeal patterns. We aimed to suggest critical decision factors for the selective application of MMA subtypes, categorized as straight MMA with genioplasty, rotational MMA, segmental MMA, and segmental-rotational MMA, in the surgical treatment objective process: anteroposterior position of maxilla, upper lip projection, overjet, lower incisor inclination as sagittal factors, and upper incisor exposure and occlusal plane angle as vertical factors. This case series deserves a clinical basis on the way of case-by-case application of the optimal MMA subtype based on the successful treatment outcomes with short-term stability.

Effect of Annealing Temperature on the Structural and Electrochemical Properties of Hydrothermally Synthesized NiCo2O4 Electrodes.

In this study, a porous Ni-foam support was employed to enhance the capacitance of nickel cobaltite (NiCo2O4) electrodes designed for supercapacitors. The hydrothermal synthesis method was employed to grow NiCo2O4 as an active material on Ni-foam. The NiCo2O4 sample derived from hydrothermal synthesis underwent subsequent post-heat treatment at temperatures of 250 °C, 300 °C, and 350 °C. Thermogravimetric analysis of the NiCo2O4 showed that weight loss due to water evaporation occurs after 100 °C and enters the stabilization phase at temperatures above 400 °C. The XRD pattern indicated that NiCo2O4 grew into a spinel structure, and the TEM results demonstrated that the diffraction spots (DSs) on the (111) plane of the sample annealed at 350 °C were more pronounced than those of other samples. The specific capacitance of the NiCo2O4 electrodes exhibited a decrease with increasing current density across all samples, irrespective of the annealing temperature. The electrode annealed at 350 °C recorded the highest specific capacitance value. However, the capacity retention rate of the NiCo2O4 electrode revealed a deteriorating trend, declining to 88% at 250 °C, 75% at 300 °C, and 63% at 350 °C, as the annealing temperature increased.

Micro-Current Stimulation Can Modulate the Adipogenesis Process by Regulating the Insulin Signaling Pathway in 3T3-L1 Cells and ob/ob Mice.

Obesity is a disease in which fat is abnormally or excessively accumulated in the body, and many studies have been conducted to overcome it with various techniques. In this study, we evaluated whether micro-current stimulation (MCS) can be applied to prevent obesity by regulating the adipogenesis through 3T3-L1 cells and ob/ob mice. To specify the intensity of MCS, Oil Red O staining was conducted with various intensities of MCS. Based on these, subsequent experiments used 200 and 400 µA for the intensity of MCS. The expressions of insulin signaling pathway-related proteins, including phosphorylation of IGF-1 and IR, were decreased in all MCS groups, and in turn, downstream signals such as Akt and ERK were decreased. In addition, MCS reduced the nucleus translocation of PPAR-γ and decreased the protein expression of C/EBP-α. In the ob/ob mouse model, MCS reduced body weight gain and abdominal adipose tissue volume. In particular, the concentration of triglycerides in serum was also decreased. Taken together, our findings showed that MCS inhibited lipid accumulation by regulating insulin signaling in 3T3-L1, and it was effective at reducing body weight and adipose tissue volume in ob/ob mice. These suggest that MCS may be a useful treatment approach for obesity.

Variations in the Physical Properties of RF-Sputtered CdS Thin Films Observed at Substrate Temperatures Ranging from 25 °C to 500 °C.

CdS films with a wide range of substrate temperatures as deposition parameters were fabricated on Corning Eagle 2000 glass substrates using RF magnetron sputtering. The crystallographic structure, microscopic surface texture, and stoichiometric and optical properties of each CdS film deposited at various substrate temperatures were observed to be highly temperature-dependent. The grown CdS thin films revealed a polycrystalline structure in which a cubic phase was mixed based on a hexagonal wurtzite phase. The relative intensity of the H(002)/C(111) peak, which represents the direction of the preferential growth plane, enhanced as the temperatures climbed from 25 °C to 350 °C. On the contrary, the intensity of the main growth peak at the higher temperatures of 450 °C and 500 °C was significantly reduced and exhibited amorphous-like behavior. The sharp absorption edge revealed in the transmission spectrum shifted from the long wavelength to the short wavelength region with the rise in the substrate temperature. The bandgap showed a tendency to widen from 2.38 eV to 2.97 eV when the temperatures increased from 25 °C to 350 °C. The CdS films grown at the temperatures of 450 °C and 500 °C exhibited glass-like transmittance with almost no interference fringes of light, which resulted in wide bandgap values of 3.09 eV and 4.19 eV, respectively.

In Vivo Cellular-Level 3D Imaging of Peripheral Nerves Using a Dual-Focusing Technique for Intra-Neural Interface Implantation.

In vivo volumetric imaging of the microstructural changes of peripheral nerves with an inserted electrode could be key for solving the chronic implantation failure of an intra-neural interface necessary to provide amputated patients with natural motion and sensation. Thus far, no imaging devices can provide a cellular-level three-dimensional (3D) structural images of a peripheral nerve in vivo. In this study, an optical coherence tomography-based peripheral nerve imaging platform that employs a newly proposed depth of focus extension technique is reported. A point spread function with the finest transverse resolution of 1.27 µm enables the cellular-level volumetric visualization of the metal wire and microstructural changes in a rat sciatic nerve with the metal wire inserted in vivo. Further, the feasibility of applying the imaging platform to large animals for a preclinical study is confirmed through in vivo rabbit sciatic nerve imaging. It is expected that new possibilities for the successful chronic implantation of an intra-neural interface will open up by providing the 3D microstructural changes of nerves around the inserted electrode.

Effect of 2.5D haptic feedback on virtual object perception via a stylus.

As touch screen technologies advanced, a digital stylus has become one of the essential accessories for a smart device. However, most of the digital styluses so far provide limited tactile feedback to a user. Therefore we focused on the limitation and noted the potential that a digital stylus may offer the sensation of realistic interaction with virtual environments on a touch screen using a 2.5D haptic system. Thus, we developed a haptic stylus with SMA (Shape Memory Alloy) and a 2.5D haptic rendering algorithm to provide lateral skin-stretch feedback to mimic the interaction force between fingertip and a stylus probing over a bumpy surface. We conducted two psychophysical experiments to evaluate the effect of 2.5D haptic feedback on the perception of virtual object geometry. Experiment 1 investigated the human perception of virtual bump size felt via the proposed lateral skin-stretch stylus and a vibrotactile stylus as reference. Experiment 2 tested the participants' ability to count the number of virtual bumps rendered via the two types of haptic styluses. The results of Experiment 1 indicate that the participants felt the size of virtual bumps rendered with lateral skin-stretch stylus significantly sensitively than the vibrotactile stylus. Similarly, the participants counted the number of virtual bumps rendered with the lateral skin-stretch stylus significantly better than with the vibrotactile stylus. A common result of the two experiments is a significantly longer mean trial time for the skin-stretch stylus than the vibrotactile stylus.

Structure, Luminescence, and Magnetic Properties of Crystalline Manganese Tungstate Doped with Rare Earth Ion.

The precursor prepared by co-precipitation method was sintered at various temperatures to synthesize crystalline manganese tungstate (MnWO4). Sintered MnWO4 showed the best crystallinity at a sintering temperature of 800 °C. Rare earth ion (Dysprosium; Dy3+) was added when preparing the precursor to enhance the magnetic and luminescent properties of crystalline MnWO4 based on these sintering temperature conditions. As the amount of rare earth ions was changed, the magnetic and luminescent characteristics were enhanced; however, after 0.1 mol.%, the luminescent characteristics decreased due to the concentration quenching phenomenon. In addition, a composite was prepared by mixing MnWO4 powder, with enhanced magnetism and luminescence properties due to the addition of dysprosium, with epoxy. To one of the two prepared composites a magnetic field was applied to induce alignment of the MnWO4 particles. Aligned particles showed stronger luminescence than the composite sample prepared with unsorted particles. As a result of this, it was suggested that it can be used as phosphor and a photosensitizer by utilizing the magnetic and luminescent properties of the synthesized MnWO4 powder with the addition of rare earth ions.

Enhanced Crystallinity and Luminescence Characteristics of Hexagonal Boron Nitride Doped with Cerium Ions According to Tempering Temperatures.

Hexagonal boron nitride was synthesized by pyrolysis using boric acid and melamine. At this time, to impart luminescence, rare earth cerium ions were added to synthesize hexagonal boron nitride nanophosphor particles exhibiting deep blue emission. To investigate the changes in crystallinity and luminescence according to the re-heating temperature, samples which had been subjected to pyrolysis at 900 °C were subjected to re-heating from 1100 °C to 1400 °C. Crystallinity and luminescence were enhanced according to changes in the reheating temperature. The synthesized cerium ion-doped hexagonal boron nitride nanoparticle phosphor was applied to the anti-counterfeiting field to prepare an ink that can only be identified under UV light.

Structure and Photoluminescence Properties of Rare-Earth (Dy3+, Tb3+, Sm3+)-Doped BaWO4 Phosphors Synthesized via Co-Precipitation for Anti-Counterfeiting.

Barium tungstate (BaWO4) powders with various sintering temperatures, and BaWO4:Dy3+ phosphor samples with concentrations of different rare-earth (RE) activator ions (Dy3+, Sm3+, Tb3+) were prepared through co-precipitation. The structural, morphological, and photoluminescent characteristics of barium tungstate phosphors depend on the concentration of RE ions. The crystallographic characteristics of the synthesized BaWO4 were analyzed using X-ray diffraction (XRD) patterns. The size and shape of the crystalline particles were estimated based on images measured with a field emission scanning electron microscope (FE-SEM). As the sintering temperature of the BaWO4 particles increased from 400 °C to 1000 °C, the size of the particles gradually increased and showed a tendency to clump together. In the sample doped with 7 mol % Dy3+ ions, the intensity of all emission bands reached their maximum. The emission spectra of the RE3+-doped BaWO4 powders by excitation at 325 nm were composed of yellow (Dy3+), red (Sm3+), and green (Tb3+) band at 572, 640, and 544 nm. This indicates that most of the RE3+ ions absorbed the position without reversal symmetry in the BaWO4 lattice. These results propose that strong emission intensity and tunable color for the phosphors can be accomplished by rare-earth doped host with an suitable quantity. In addition, the phosphor thin films, having high transparency from aqueous colloidal solutions, were deposited on banknotes, and it is considered whether it is suitable for anti-counterfeiting applications.

One-step Implantation of a 3D Neural Microelectrode Array.

This paper presents a neurosurgical device called NEIT 2 (Nerve Electrode Insertion Tool) to implant a 3D microelectrode array into a peripheral nervous system. Using an elastomer-made nerve holder, the device is able to stable target a flexible nerve, and then safely inserts an electrode array into the fixed nerve. Finally, a nerve containment assembly is made at once. We conducted animal experiments to evaluate the proposed scenario using a 3D printed prototype and commercial microelectrodes. The results show that microelectrodes are successfully implanted into sciatic nerves of rats and neural signals are recorded through the chronically implanted electrodes.

Osteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation.

Osteoarthritis (OA), primarily characterized by articular cartilage destruction, is the most common form of age-related degenerative whole-joint disease. No disease-modifying treatments for OA are currently available. Although OA is primarily characterized by cartilage destruction, our understanding of the processes controlling OA progression is poor. Here, we report the association of OA with increased levels of osteoclast-associated receptor (OSCAR), an immunoglobulin-like collagen-recognition receptor. In mice, OSCAR deletion abrogates OA manifestations, such as articular cartilage destruction, subchondral bone sclerosis, and hyaline cartilage loss. These effects are a result of decreased chondrocyte apoptosis, which is caused by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in induced OA. Treatments with human OSCAR-Fc fusion protein attenuates OA pathogenesis caused by experimental OA. Thus, this work highlights the function of OSCAR as a catabolic regulator of OA pathogenesis, indicating that OSCAR blockade is a potential therapy for OA.

A Pilot Study On The Novel Non-Invasive Nerve-Holder With Negative-Pressure Suctions.

In performing neurosurgical operation on peripheral nervous system, the most important first step is to robustly hold the target nerve, since the nerve-holding stability and reliability significantly affect the result of surgical operation. However it is not straightforward to robustly hold peripheral nerve during the surgical operation, because the peripheral nerve is too flexible and slippery. In this study, we design a novel peripheral nerve-holder that can be used for the neurosurgical operation. Considering the anatomical characteristics of the peripheral nerve that small bundles of nerve fibers (i.e., fascicles) are structured inside the outermost layer of the nerve bundle (i.e., epineurium), we aim to develop a non-clamping and non-invasive type nerve-holder to protect the nerve fibers. For the aim, the negative-pressure suction method is applied to the proposed holder. And, in order to hold the nerve more robustly, micro-bump structure is fabricated on the suction surface contacting with the nerve. This paper introduces the concept, working principle, characteristics, and in-vitro experimental results on feasibility evaluation of the proposed holder.

Three-dimensional alteration of constricted alveolar ridge affected by root thrusting with and without open-flap decortication.

OBJECTIVE: To investigate the morphometric and histological alterations of the constricted alveolar ridge when affected by root thrusting with and without open-flap decortication. MATERIALS AND METHODS: Eight beagles were divided into three groups: C, control without root thrusting; R, root thrusting only; RD, root thrusting with alveolar decortication. The ridge constriction model was prepared in 16 mandibular quadrants after extraction of the third premolars. Reciprocal root thrusting of the second and fourth premolars was performed toward the constricted ridge for 10 weeks, having a moment of 900 g-mm. Open-flap decortication was conducted on the constricted bone surface in group RD. Micro-CT-based histomorphometric analysis and trichrome-staining-based tissue fractional analysis were performed to evaluate morphometric and microstructural changes on the ridge. RESULTS: Group R revealed a higher percentage of bone volume (P < .001), lower bone mineral density (P < .01), and higher trabecular number (P < .001) than did group C, which was supported by a higher bone fraction woven to lamellar bone (P < .05) resulting from histologic fractional analysis. However, group RD showed no significant difference from group C. CONCLUSIONS: Root thrusting toward the constricted ridge induced hypertrophic bone modeling with a high trabecular fraction on the ridge. However, combined open-flap decortication with root thrusting did not improve the volume or quality of the constricted ridge.