5-aminosalicylic acid suppresses osteoarthritis through the OSCAR-PPARγ axis.

Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone remodeling, and synovitis. Despite affecting millions of patients, effective and safe disease-modifying osteoarthritis drugs are lacking. Here we reveal an unexpected role for the small molecule 5-aminosalicylic acid (5-ASA), which is used as an anti-inflammatory drug in ulcerative colitis. We show that 5-ASA competes with extracellular-matrix collagen-II to bind to osteoclast-associated receptor (OSCAR) on chondrocytes. Intra-articular 5-ASA injections ameliorate OA generated by surgery-induced medial-meniscus destabilization in male mice. Significantly, this effect is also observed when 5-ASA was administered well after OA onset. Moreover, mice with DMM-induced OA that are treated with 5-ASA at weeks 8-11 and sacrificed at week 12 have thicker cartilage than untreated mice that were sacrificed at week 8. Mechanistically, 5-ASA reverses OSCAR-mediated transcriptional repression of PPARγ in articular chondrocytes, thereby suppressing COX-2-related inflammation. It also improves chondrogenesis, strongly downregulates ECM catabolism, and promotes ECM anabolism. Our results suggest that 5-ASA could serve as a DMOAD.

The Threat of Disruptive Jamming to Blockchain-Based Decentralized Federated Learning in Wireless Networks.

Machine learning techniques have attracted considerable attention for wireless networks because of their impressive performance in complicated scenarios and usefulness in various applications. However, training with and sharing raw data obtained locally from each wireless node does not guarantee privacy and requires a large communication overhead. To mitigate such issues, federated learning (FL), in which sharing parameters for model updates are shared instead of raw data, has been developed. FL has also been studied using blockchain techniques to efficiently perform learning in distributed wireless systems without having to deploy a centralized server. Although blockchain-based decentralized federated learning (BDFL) is a promising technique for various wireless sensor networks, malicious attacks can still occur, which result in performance degradation or malfunction. In this study, we analyze the impact of a jamming threats from malicious miners to BDFL in wireless networks. In a wireless BDFL system, it is possible for malicious miners with jamming capability to interfere with the collection of model parameters by normal miners, thus preventing the victim miner from generating a global model. By disrupting normal miners participating in BDFL systems, malicious miners with jamming capability can more easily add malicious data to the mainstream. Through various simulations, we evaluated the success probability performance of malicious block insertion and the participation rate of normal miners in a wireless BDFL system.

Stable maintenance of the Mre11-Rad50-Nbs1 complex is sufficient to restore the DNA double-strand break response in cells lacking RecQL4 helicase activity.

The proper cellular response to DNA double-strand breaks (DSBs) is critical for maintaining the integrity of the genome. RecQL4, a DNA helicase of which mutations are associated with Rothmund-Thomson syndrome (RTS), is required for the DNA DSB response. However, the mechanism by which RecQL4 performs these essential roles in the DSB response remains unknown. Here, we show that RecQL4 and its helicase activity are required for maintaining the stability of the Mre11-Rad50-Nbs1 (MRN) complex on DSB sites during a DSB response. We found using immunocytochemistry and live-cell imaging that the MRN complex is prematurely disassembled from DSB sites in a manner dependent upon Skp2-mediated ubiquitination of Nbs1 in RecQL4-defective cells. This early disassembly of the MRN complex could be prevented by altering the ubiquitination site of Nbs1 or by expressing a deubiquitinase, Usp28, which sufficiently restored homologous recombination repair and ATM, a major checkpoint kinase against DNA DSBs, activation abilities in RTS, and RecQL4-depleted cells. These results suggest that the essential role of RecQL4 in the DSB response is to maintain the stability of the MRN complex on DSB sites and that defects in the DSB response in cells of patients with RTS can be recovered by controlling the stability of the MRN complex.

Majority Voting-Based MAC Protocol for Exploiting Link-Layer Diversity in Wireless Networks.

In wireless local area networks (WLANs), the effect of interference signals between neighboring nodes increases as the number of wireless nodes using limited radio frequency resources in a limited space increases, which can significantly degrade the reliability of data transmission. In high-density WLANs, there can be several neighboring access points (APs) that can receive uplink transmission from a station. In conventional medium access control (MAC) protocols, uplink data frames containing errors or transmitted from a non-associated station are discarded at APs. Alternatively, we propose a MAC protocol using redundant wireless links between neighboring APs and the non-associated stations. In the proposed MAC protocol, we consider a centralized WLAN with a control node that performs error corrections of erroneous uplink data frames via a majority voting algorithm-based link-layer diversity scheme using uplink data received from multiple APs to increase the reliability of data transmission. In addition, we propose an adaptive carrier sensing ranging mechanism to improve the uplink network throughput in the proposed centralized WLAN system. Further, we conduct simulation studies and software-defined radio-based experiments to evaluate the performance of the proposed MAC protocol in various WLAN scenarios.

Unilateral Mastication Evaluated Using Asymmetric Functional Tooth Units as a Risk Indicator for Hearing Loss.

BACKGROUND: Some previous studies reported hearing ability can be reduced by impaired masticatory ability, but there has been little evidence reported of an association between hearing loss and unilateral mastication. Therefore, this study aimed to investigate the relationship between unilateral mastication (UM), estimated from individual functional tooth units (FTUs), and hearing loss in a representative sample of Korean adults. METHODS: The analyzed data were obtained from 1,773 adults aged 40-89 years who participated in Korean national survey. Hearing loss was defined as a pure-tone average of >25 dB at frequencies of 0.5, 1, 2, and 4 kHz in either ear. In each subject, UM was calculated as the difference in the sums of the FTU scores, which is an index of posterior tooth occlusion, on the two sides of the oral cavity. The scores were used to classify the UM into low, moderate, and high. The adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) were calculated in multivariable logistic regression analyses. RESULTS: When controlling for sociodemographic factors, the aOR for hearing loss was 3.12 (95% CI, 1.21-8.03) for high UM relative to low UM. This association remained in a fully-adjusted model containing factors related to noise exposure (aOR 2.88; 95% CI, 1.12-7.46). CONCLUSION: Adults with high UM as measured using FTUs showed a higher occurrence of hearing loss than those with low UM.

Detection of residual resin-based orthodontic adhesive based on light-induced fluorescence.

INTRODUCTION: This study evaluated the fluorescence of orthodontic adhesives using quantitative light-induced fluorescence-digital (QLF-D) images, and compared differences in the color characteristics of the fluorescence between adhesive and the adjacent tooth with that under white-light illumination in specimens containing residual adhesive of various thicknesses. METHODS: Disc-shaped adhesive samples and samples comprising adhesive attached to extracted human teeth were prepared using Transbond XT, Blugloo, and Enlight, and they were ground to thicknesses ranging from 800 to 20 µm. Fluorescence and white-light images of the two types of specimens were taken with a QLF-D system. The color parameters for the fluorescence from the discs and the color difference (ΔE) between residual adhesive and the adjacent tooth were quantified in images using the CIE L*a*b* system. RESULTS: The fluorescence color values of the discs differed significantly among the three adhesive products (P < 0.05). The ΔE values in fluorescence (ΔEF) and white-light (ΔEW) images for all three adhesives were lower for thinner residual adhesive specimens. The thickness of the adhesive could be perceived over a range of 50-100 µm for fluorescence images and 400-800 µm for white-light images (ΔE > 3.3). ΔEF was significantly larger than ΔEW for all of the residual adhesives, Blugloo specimens thicker than 100 µm, and Transbond XT and Enlight specimens thicker than 50 µm (P < 0.05). CONCLUSIONS: Detecting and analyzing fluorescence signals can improve the ability to detect residual adhesive on a tooth and also provide thickness information.

Differences in the intensity of light-induced fluorescence emitted by resin composites.

BACKGROUND: The aims of this study were to compare the intensities of fluorescence emitted by different resin composites as detected using quantitative light-induced fluorescence (QLF) technology, and to compare the fluorescence intensity contrast with the color contrast between a restored composite and the adjacent region of the tooth. METHODS: Six brands of light-cured resin composites (shade A2) were investigated. The composites were used to prepare composite discs, and fill holes that had been prepared in extracted human teeth. White-light and fluorescence images of all specimens were obtained using a fluorescence camera based on QLF technology (QLF-D) and converted into 8-bit grayscale images. The fluorescence intensity of the discs as well as the fluorescence intensity contrast and the color contrast between the composite restoration and adjacent tooth region were calculated as grayscale levels. RESULTS: The grayscale levels for the composite discs differed significantly with the brand (p<0.001): DenFil (10.84±0.35, mean±SD), Filtek Z350 (58.28±1.37), Premisa (156.94±1.58), Grandio (177.20±0.81), Charisma (207.05±0.77), and Gradia direct posterior (211.52±1.66). The difference in grayscale levels between a resin restoration and the adjacent tooth was significantly greater in fluorescence images for each brand than in white-light images, except for the Filtek Z350 (p<0.05). However, the Filtek Z350 restoration was distinguishable from the adjacent tooth in a fluorescence image. CONCLUSIONS: The intensities of fluorescence detected from the resin composites varied. The differences between the composite and adjacent tooth were greater for the fluorescence intensity contrast than for the colors observed in the white-light images.