Bisphosphonate inhibits the expression of cyclin A2 at the transcriptional level in normal human oral keratinocytes.

Nitrogen-containing bisphosphonates (N-BPs) are the most widely used anti-resorptive agents in the treatment of bone-related diseases. N-BPs inhibit bone resorption by specifically targeting osteoclasts, bone-resorbing cells. However, soft tissue toxicity, such as oral or gastrointestinal (GI) ulcerations has frequently been reported in N-BP users, suggesting that N-BPs may also directly target cells other than osteoclasts. Previously, we reported that BPs inhibit proliferation without inducing the apoptosis of normal human oral keratinocytes (NHOKs). However, the molecular mechanisms through which N-BPs inhibit the proliferation of NHOKs are not yet fully understood. In this study, we performed gene expression profiling in N-BP-treated NHOKs and identified cyclin A2 as one of the most commonly downregulated genes. When the NHOKs were treated with N-BPs, we found that the level of cyclin A2 was suppressed in a dose- and time-dependent manner. In addition, the protein level of cyclin A2 was also significantly lower in oral epithelial cells in N-BP-treated oral mucosal tissue constructs. Cyclin A2 promoter reporter assay revealed that N-BPs inhibited the luciferase activity, indicating that the inhibition of cyclin A2 expression occurs at the transcriptional level. Furthermore, N-BPs did not alter the expression of cyclin A2 in normal human oral fibroblasts (NHOFs), suggesting that the effect of N-BPs on cyclin A2 expression may be cell-type specific. Thus, the findings of our study demonstrate that the inhibition of NHOK proliferation by N-BPs is mediated, at least in part, by the suppression of cyclin A2 expression at the transcriptional level, which may explain the underlying mechanisms of soft tissue toxicity by N-BPs

Periodontitis-induced systemic inflammation exacerbates atherosclerosis partly via endothelial-mesenchymal transition in mice.

Growing evidence suggests close associations between periodontitis and atherosclerosis. To further understand the pathological relationships of these associations, we developed periodontitis with ligature placement around maxillary molars or ligature placement in conjunction with Porphyromonas gingivalis lipopolysaccharide injection at the ligature sites (ligature/P.g. LPS) in Apolipoprotein E knock out mice and studied the atherogenesis process in these animals. The mice were fed with high fat diet for 11 weeks and sacrificed for analyzing periodontitis, systemic inflammation, and atherosclerosis. Controls did not develop periodontitis or systemic inflammation and had minimal lipid deposition in the aortas, but mice receiving ligature or ligature/P.g. LPS showed severe periodontitis, systemic inflammation, and aortic plaque formation. The aortic plaque contained abundant macrophages and cells expressing both endothelial and mesenchymal cell markers. The severity of periodontitis was slightly higher in mice receiving ligature/P.g. LPS than ligature alone, and the magnitude of systemic inflammation and aortic plaque formation were also notably greater in the mice with ligature/P.g. LPS. These observations indicate that the development of atherosclerosis is due to systemic inflammation caused by severe periodontitis. In vitro, P.g. LPS enhanced the secretion of pro-inflammatory cytokines from macrophages and increased the adhesion of monocytes to endothelial cells by upregulating the expression of adhesion molecules from endothelial cells. Moreover, secretory proteins, such as TNF-α, from macrophages induced endothelial-mesenchymal transitions of the endothelial cells. Taken together, systemic inflammation induced by severe periodontitis might exacerbate atherosclerosis via, in part, causing aberrant functions of vascular endothelial cells and the activation of macrophages in mice

How to Mask in Error Correction Code Transformer: Systematic and Double Masking

In communication and storage systems, error correction codes (ECCs) are pivotal in ensuring data reliability. As deep learning's applicability has broadened across diverse domains, there is a growing research focus on neural network-based decoders that outperform traditional decoding algorithms. Among these neural decoders, Error Correction Code Transformer (ECCT) has achieved the state-of-the-art performance, outperforming other methods by large margins. To further enhance the performance of ECCT, we propose two novel methods. First, leveraging the systematic encoding technique of ECCs, we introduce a new masking matrix for ECCT, aiming to improve the performance and reduce the computational complexity. Second, we propose a novel transformer architecture of ECCT called a double-masked ECCT. This architecture employs two different mask matrices in a parallel manner to learn more diverse features of the relationship between codeword bits in the masked self-attention blocks. Extensive simulation results show that the proposed double-masked ECCT outperforms the conventional ECCT, achieving the state-of-the-art decoding performance with significant margins.Comment: 8 pages, 5 figure

Iterative Soft Decoding Algorithm for DNA Storage Using Quality Score and Redecoding

Ever since deoxyribonucleic acid (DNA) was considered as a next-generation data-storage medium, lots of research efforts have been made to correct errors occurred during the synthesis, storage, and sequencing processes using error correcting codes (ECCs). Previous works on recovering the data from the sequenced DNA pool with errors have utilized hard decoding algorithms based on a majority decision rule. To improve the correction capability of ECCs and robustness of the DNA storage system, we propose a new iterative soft decoding algorithm, where soft information is obtained from FASTQ files and channel statistics. In particular, we propose a new formula for log-likelihood ratio (LLR) calculation using quality scores (Q-scores) and a redecoding method which may be suitable for the error correction and detection in the DNA sequencing area. Based on the widely adopted encoding scheme of the fountain code structure proposed by Erlich et al., we use three different sets of sequenced data to show consistency for the performance evaluation. The proposed soft decoding algorithm gives 2.3% ~ 7.0% improvement of the reading number reduction compared to the state-of-the-art decoding method and it is shown that it can deal with erroneous sequenced oligo reads with insertion and deletion errors

Nanodiamond-Gutta Percha Composite Biomaterials for Root Canal Therapy.

Root canal therapy (RCT) represents a standard of treatment that addresses infected pulp tissue in teeth and protects against future infection. RCT involves removing dental pulp comprising blood vessels and nerve tissue, decontaminating residually infected tissue through biomechanical instrumentation, and root canal obturation using a filler material to replace the space that was previously composed of dental pulp. Gutta percha (GP) is typically used as the filler material, as it is malleable, inert, and biocompatible. While filling the root canal space with GP is the standard of care for endodontic therapies, it has exhibited limitations including leakage, root canal reinfection, and poor mechanical properties. To address these challenges, clinicians have explored the use of alternative root filling materials other than GP. Among the classes of materials that are being explored as novel endodontic therapy platforms, nanodiamonds (NDs) may offer unique advantages due to their favorable properties, particularly for dental applications. These include versatile faceted surface chemistry, biocompatibility, and their role in improving mechanical properties, among others. This study developed a ND-embedded GP (NDGP) that was functionalized with amoxicillin, a broad-spectrum antibiotic commonly used for endodontic infection. Comprehensive materials characterization confirmed improved mechanical properties of NDGP over unmodified GP. In addition, digital radiography and microcomputed tomography imaging demonstrated that obturation of root canals with NDGP could be achieved using clinically relevant techniques. Furthermore, bacterial growth inhibition assays confirmed drug functionality of NDGP functionalized with amoxicillin. This study demonstrates a promising path toward NDGP implementation in future endodontic therapy for improved treatment outcomes

Wnt4 Signaling Prevents Skeletal Aging and Inflammation by Inhibiting Nuclear Factor-κB

Aging-related bone loss and osteoporosis affect millions of people worldwide. Chronic inflammation associated with aging promotes bone resorption and impairs bone formation. Here we show that Wnt4 attenuates bone loss in osteoporosis and skeletal aging mouse models by inhibiting nuclear factor-κB (NF-κB) via noncanonical Wnt signaling. Transgenic mice expressing Wnt4 from osteoblasts were significantly protected from bone loss and chronic inflammation induced by ovariectomy, tumor necrosis factor or natural aging. In addition to promoting bone formation, Wnt4 inhibited osteoclast formation and bone resorption. Mechanistically, Wnt4 inhibited NF-κB activation mediated by transforming growth factor-β–activated kinase-1 (Tak1) in macrophages and osteoclast precursors independently of β-catenin. Moreover, recombinant Wnt4 alleviated bone loss and inflammation by inhibiting NF-κB in vivo in mouse models of bone disease. Given its dual role in promoting bone formation and inhibiting bone resorption, our results suggest that Wnt4 signaling could be an attractive therapeutic target for treating osteoporosis and preventing skeletal aging

Effects of exercise on obesity-induced mitochondrial dysfunction in skeletal muscle

Obesity is known to induce inhibition of glucose uptake, reduction of lipid metabolism, and progressive loss of skeletal muscle function, which are all as- sociated with mitochondrial dysfunction in skeletal muscle. Mitochondria are dy- namic organelles that regulate cellular metabolism and bioenergetics, including ATP production via oxidative phosphorylation. Due to these critical roles of mitochon- dria, mitochondrial dysfunction results in various diseases such as obesity and type 2 diabetes. Obesity is associated with impairment of mitochondrial function (e.g., decrease in O2 respiration and increase in oxidative stress) in skeletal muscle. The bal- ance between mitochondrial fusion and fission is critical to maintain mitochondrial homeostasis in skeletal muscle. Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion and fission by favorably shifting fission or reducing fusion proteins. Mitophagy is the catabolic process of damaged or unnecessary mito- chondria. Obesity reduces mitochondrial biogenesis in skeletal muscle and increases accumulation of dysfunctional cellular organelles, suggesting that mitophagy does not work properly in obesity. Mitochondrial dysfunction and oxidative stress are reported to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in skeletal muscle. It is well known that exercise is the most effective intervention to protect against obesity. Although the cellular and molecular mechanisms by which exercise protects against obesity-induced mitochondrial dysfunction in skeletal mus- cle are not clearly elucidated, exercise training attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in obese skeletal muscle

The effects of wearing KF94 masks on cardiorespiratory function and hemorheological response during moderate intensity exercise in adult males

The purpose of this study was to examine the effect of wearing a Korea filter 94 (KF94) mask on cardiorespiratory function and hemorheological responses during moderate intensity exercise in men during the Coronavirus disease 2019 (COVID-19) pandemic. 12 healthy males aged 20 to 29 years (28.3 ± 3.6 yr) were recruited for this study. The exercise intensity corresponding to the anaerobic threshold level was determined following a maximum graded exercise test, and exercise was performed for 40 minutes with a cycle ergometer at the target exercise intensity. Cardiorespiratory function, blood pressure, and hemorheological responses were measured every 10 minutes at rest and during exercise. Our results indicated no differences between conditions in respiratory frequency (Rf), tidal volume (TV), minute ventilation (VE), carbon dioxide production (V̇CO2), and partial pressure of arterial oxygen (PaO2). However, oxygen consumption (V̇O2) was significantly lower in the KF94 mask group compared to the control. There were no differences in systolic blood pressure (SBP), diastolic blood pressure (DBP), rate pressure product (RPP), aggregation index (AI), and blood critical stress (BCS) between the two groups. The mask group had a significant respiratory exchange ratio (R) at rest and during 10 minutes exercise compared to the control. The elongation index was higher at rest, 10 minutes, and 30 minutes in the mask group than control group (p < 0.05). Overall, our results suggest that although V̇O2 was decreased and R values were increased, the effects of other physiological parameters and hemorheological responses imposed by face masks during moderate intensity exercise are small. Thus, although negative effects of using face masks affect exercise capacity (i.e., exercise tolerance), our findings suggest that individuals wearing KF94 could safely exercise and get some health benefits from physical activities during the COVID-19 pandemic