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.     

Engineering Bioactive M2 Macrophage-Polarized Anti-Inflammatory,Antioxidant, and Antibacterial Scaffolds for Rapid Angiogenesis and Diabetic Wound Repair

Diabetic wound healing still faces great challenges due to the excessive inflammation, easy infection, and impaired angiogenesis in wound beds. The immunoregulation of macrophages polarization toward M2 phenotype that facilitates the transition from inflammation to proliferation phase has been proved to be an effective way to improve diabetic wound healing. Herein, an M2 phenotype-enabled anti-inflammatory, antioxidant, and antibacterial conductive hydrogel scaffolds (GDFE) for producing rapid angiogenesis and diabetic wound repair are reported. The GDFE scaffolds are fabricated facilely through the dynamic crosslinking between polypeptide and polydopamine and graphene oxide. The GDFE scaffolds possess thermosensitivity, self-healing behavior, injectability, broad-spectrum antibacterial activity, antioxidant and anti-inflammatory ability, and electronic conductivity. GDFE effectively activates the polarization of macrophages toward M2 phenotype and significantly promotes the proliferation of dermal fibroblasts, the migration, and in vitro angiogenesis of endothelial cells through paracrine mechanisms. The in vivo results from a full-thickness diabetic wound model demonstrate that GDFE can rapidly promote the diabetic wound repair and skin regeneration, through fast anti-inflammation and angiogenesis and M2 macrophage polarization. This study provides highly efficient strategy for treating diabetic wound repair through designing the M2 polarization-enabled anti-inflammatory, antioxidant, and antibacterial bioactive materials.     

Microstructure and shear strength of Au-20wt%Sn solder joints fabricated by thermo-compression bonding for LED packages

Journal of Materials Science: Materials in Electronics - Solder joints of Au-20wt%Sn (Au-20Sn) between real light-emitting diode Si chips and AlN substrates were fabricated using thermo-compression...     

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.      

Effects of four multi-compound freezing medium on the quality of red drum (Sciaenops ocellatus) during frozen storage

Taking air freezing (AF) as the reference, the effects of four types of multi-compound freezing medium for cryogenic liquid quick-freezing (immersion freezing, IF) on the freezing rate, quality and myofibrillar protein (MP) denaturation of red drum (Sciaenops ocellatus) fillets during frozen storage (−18°C) from days 0 to 90 were studied. Samples were gathered on days 0, 15, 30, 45, 60 and 90 for analysis. The results showed that IF groups (IF-1: 20% ethanol, 30% propylene glycol, 10% sodium chloride aqueous solution; IF-2: 20% ethanol, 20% propylene glycol, 10% glycerol, 10% sodium chloride aqueous solution; IF-3: 20% ethanol, 20% propylene glycol, 10% polyethylene glycol, 10% sodium chloride aqueous solution; IF-4: 20% ethanol, 20% propylene glycol, 5% glycerol, 5% polyethylene glycol, 10% sodium chloride aqueous solution) significantly shortened the time to cross the formation zone of maximum ice crystals while the freezing rate was 6.13 times higher than the AF group after adding 30% propylene glycol as the freezing medium. Furthermore, compared with the AF group, the IF groups significantly reduced losses in the water-holding capacity, the myofibrillar fragmentation index, microstructure damage, texture characteristics, drip loss and water migration (P < 0.05). In addition, the MP of IF groups had higher maximum transition temperatures (T_max1 and T_max2), total sulfhydryl content, Ca²⁺-ATPase activity and relative α-helix content compared with the AF group. In conclusion, IF could significantly increase the freezing rate of red drum fillets, and slow down quality deterioration and denaturation of MP during frozen storage for 90 days (−18°C). In particular, IF-2 (20% ethanol, 20% propylene glycol, 10% glycerol, 10% sodium chloride aqueous solution) was found to be more suitable for the immersion freezing of marine fish among the four multi-compound freezing medium.     

Physicochemical analysis of non-fermented probiotic milk with probiotic Lactobacillus plantarum Ln1 isolated from Korea traditional fermented food

Food Science and Biotechnology - The objective of this study was to develop a non-fermented probiotic milk that maintains its physicochemical properties, microbial properties, antioxidant activity,...     

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer.     

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.