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1.
Yuria Jang Hong Moon Sohn Young Jong Ko Hoon Hyun Wonbong Lim 《International journal of molecular sciences》2021,22(1)
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. 相似文献
2.
Hyun Sun Choi Yun Kee Jo Gwang-Noh Ahn Kye Il Joo Dong-Pyo Kim Hyung Joon Cha 《Advanced functional materials》2021,31(46):2104602
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. 相似文献
3.
Wonje Jang Junhyuk Hyun Jhonghyun An Minho Cho Euntai Kim 《IEEE/CAA Journal of Automatica Sinica》2022,9(1):187-204
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. 相似文献
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Novel reddish-orange-emitting Ca2GdNbO6:Sm3+ phosphors based on the emission of 4G5/2 → 6H9/2 transition at 651 nm with the chromatic coordinate of (0.633, 0.366) were synthesized. The crystal structure and chemical purity were identified in detail. Under the 407 nm excitation, the optimum concentration of Sm3+ ion was found to be 5 mol% dominated by the dipole-dipole interaction in the Ca2GdNbO6 host material. The color purity of the sample with optimum doping was estimated to be about 78.38%. Besides, the thermal stability was also studied, and it was further found that the emission intensity remained 65.32% at 423 K. The packaged white LED device exhibited excellent CRI and CCT values of 92.43 and 4896 K. Finally, the polydimethylsiloxane film with a stable structure and flexible property was prepared. These above results reveal that novel reddish-orange-emitting Ca2GdNbO6:Sm3+ phosphors can be applied in high CRI white communication and flexible display applications. 相似文献
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Dr. Ala Jo Mingi Kim Dr. Jong In Kim Jaeyoung Ha Yoon Soo Hwang Hyunsung Nam Dr. Injae Hwang Dr. Jae Bum Kim Prof. Seung Bum Park 《ChemMedChem》2021,16(7):1104-1115
Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α–UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities. 相似文献
9.
Ha-Nul Lee Joo-Hee Choi Ji-Yeon Park Jae-Hun Ahn Da Eun Jang Jae Gun Shim Jong-Hwan Park Young-Min Kim 《Food science and biotechnology》2021,30(4):583
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. 相似文献
10.
Trinh Nguyen Thi Phuoc Cao Van Duc Duong Viet Viet Dong Quoc Hayeong Ahn Viet Anh Cao Min-Gu Kang Junghyo Nah Byong-Guk Park Jong-Ryul Jeong 《Ceramics International》2021,47(12):16770-16775
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 (VSSE) 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. 相似文献