Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.     

Magnetically Guidable Proteinaceous Adhesive Microbots for Targeted Locoregional Therapeutics Delivery in the Highly Dynamic Environment of the Esophagus

The esophagus is a tubular-shaped muscular organ where swallowed fluids and muscular contractions constitute a highly dynamic environment. The turbulent, coordinated processes that occur through the oropharyngeal conduit can often compromise targeted administration of therapeutic drugs to a lesion, significantly reducing therapeutic efficacy. Here, magnetically guidable drug vehicles capable of strongly adhering to target sites using a bioengineered mussel adhesive protein (MAP) to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions are proposed. A suite of highly uniform microparticles embedded with iron oxide (IO) nanoparticles (MAP@IO MPs) is microfluidically fabricated using the genipin-mediated covalent cross-linking of bioengineered MAP. The MAP@IO MPs are successfully targeted to a specific region and prolongedly retained in the tubular-structured passageway. In particular, orally administered MAP@IO MPs are effectively captured in the esophagus in vivo in a magnetically guidable manner. Moreover, doxorubicin (DOX)-loaded MAP@IO MPs exhibit a sustainable DOX release profile, effective anticancer therapeutic activity, and excellent biocompatibility. Thus, the magnetically guidable locomotion and robust underwater adhesive properties of the proteinaceous soft microbots can provide an intelligent modular approach for targeted locoregional therapeutics delivery to a specific lesion site in dynamic fluid-associated tubular organs such as the esophagus.     

A Lane-Level Road Marking Map Using a Monocular Camera

The essential requirement for precise localization of a self-driving car is a lane-level map which includes road markings (RMs). Obviously, we can build the lane-level map by running a mobile mapping system (MMS) which is equipped with a high-end 3D LiDAR and a number of high-cost sensors. This approach, however, is highly expensive and ineffective since a single high-end MMS must visit every place for mapping. In this paper, a lane-level RM mapping system using a monocular camera is developed. The developed system can be considered as an alternative to expensive high-end MMS. The developed RM map includes the information of road lanes (RLs) and symbolic road markings (SRMs). First, to build a lane-level RM map, the RMs are segmented at pixel level through the deep learning network. The network is named RMNet. The segmented RMs are then gathered to build a lane-level RM map. Second, the lane-level map is improved through loop-closure detection and graph optimization. To train the RMNet and build a lane-level RM map, a new dataset named SeRM set is developed. The set is a large dataset for lane-level RM mapping and it includes a total of 25157 pixel-wise annotated images and 21000 position labeled images. Finally, the proposed lane-level map building method is applied to SeRM set and its validity is demonstrated through experimentation.      

Combination of vegetable soup and glucan demonstrates synergistic effects on macrophage-mediated immune responses

Vegetable soup (VS), a plant-based functional food, has been used as a traditional folk medicine and is attracting attention for its ability to enhance the immune response. β-Glucan, a well-established and effective immunomodulator, has synergistic effects when used in combination with some bioactive compounds. In the present study, we aimed to evaluate the synergistic immunomodulatory effects of the combination of VS and β-glucan on macrophage-mediated immune responses. β-Glucan was demonstrated to synergistically enhance the VS-stimulated immune response, including the production of interleukin-6, tumor necrosis factor-α, and nitric oxide, mainly through the mitogen-activated protein kinase pathway in macrophages. In addition, this combination has the potential for further development in functional foods with immune-enhancing activity.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10068-021-00888-x.     

Morphology-dependent spin Seebeck effect in yttrium iron garnet thin films prepared by metal-organic decomposition

In this study, we examined the dependence of surface morphology and spin Seebeck effect (SSE) voltages on the poly[vinylpyrrolidone] (PVP) concentration in polycrystalline Y₃Fe₅O₁₂ (YIG) ultrathin films on a silicon substrate synthesized by metal-organic decomposition followed by a crystallization process. During fabrication, PVP concentrations of 0.5–2 g were used while all other conditions remained fixed. Atomic force microscopy and grazing incidence X-ray diffraction (XRD) measurements revealed a strong dependence of crystallinity and sample morphology on PVP concentration. The 1-g PVP sample had the smoothest surface, with a root mean square roughness of 0.2 nm, as well as superior bulk uniformity with respect to the shape and intensity of XRD reflection peaks. This was confirmed by scanning electron microscopy measurements of a cross-section of the sample that revealed a uniform film without pores. SSE measurements were performed to obtain the output SSE voltages (V_SSE) of all samples, to which a platinum layer was added as a spin-detection layer. Repeatedly, the 1-g PVP sample had the best performance, demonstrating the importance of film crystallinity and morphology in the spin-to-charge conversion efficiency of YIG films.     

Stabilization of 6H-Hexagonal SrMnO3 Polymorph by Al2O3 insertion

We demonstrate the structural evolution of polymorphic phases in Al₂O₃-inserted SrMnO₃ ceramics synthesized by solid state reaction. While the 4H-hexagonal phase is predominant in pure SrMnO₃ ceramics, a small amount of 6H-hexagonal polymorph is identified in addition to the primary 4H-hexagonal SrMnO₃ and the secondary hexagonal SrAl₂O₄ phases in the as-sintered ceramics, evidenced by x-ray diffraction and subsequent Rietveld refinement analyses. The existence of the 6H-hexagonal SrMnO₃ phase is corroborated using Raman spectroscopy. The chemical compositions and electronic structures of the Al₂O₃-inserted SrMnO₃ compounds are also examined using energy dispersive spectroscopy and x-ray photoelectron spectroscopy, respectively. The first-principles calculations reveal that there is no clear difference between the total energies of 4H- and 6H-hexagonal polymorphs regardless of the presence/absence of Sr and oxygen vacancies. Possible origins are discussed with the estimation of actual strain based on the refined lattice parameter of 6H SrMnO₃.     

Aqueous dispersion of 1D van der Waals Mo6S3I6 crystal using biocompatible tri-block copolymer

To achieve the stable dispersion of 1D van der Waals crystal Mo₆S₃I₆ in aqueous media, the tri-block copolymer (Poloxamer) is used as dispersant. The head group of Poloxamer, hydrophobic polypropylene oxide parts can be adsorbed to Mo₆S₃I₆ surface by hydrophobic interaction and the tail group with hydrophilic polyethylene oxide exposed to the outside of the Mo₆S₃I₆ is soluble in water and can form sufficient steric hindrance, resulting in stable aqueous dispersion in nm scale. The excellent biocompatibility of aqueous dispersed nm scale 1D Mo₆S₃I₆ was demonstrated by effective proliferation of C2C12 cells.     

An Intelligent Product Recommendation Model to Reflect the Recent Purchasing Patterns of Customers

Mobile Networks and Applications - This study suggests a new product recommendation model to reflect the recent purchasing patterns of customers. There are many methods to measure the similarity...     

Solution‐Processable Photonic Inks of Mie‐Resonant Hollow Carbon–Silica Nanospheres

Hollow carbon–silica nanospheres that exhibit angle‐independent structural color with high saturation and minimal absorption are made. Through scattering calculations, it is shown that the structural color arises from Mie resonances that are tuned precisely by varying the thickness of the shells. Since the color does not depend on the spatial arrangement of the particles, the coloration is angle independent and vibrant in powders and liquid suspensions. These properties make hollow carbon–silica nanospheres ideal for applications, and their potential in making flexible, angle‐independent films and 3D printed films is explored.