Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, ...pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
Orthopantomogram (OPG) is important for primary diagnosis of temporomandibular joint osteoarthritis (TMJOA), because of cost and the radiation associated with computed tomograms (CT). The aims of ...this study were to develop an artificial intelligence (AI) model and compare its TMJOA diagnostic performance from OPGs with that of an oromaxillofacial radiology (OMFR) expert. An AI model was developed using Karas' ResNet model and trained to classify images into three categories: normal, indeterminate OA, and OA. This study included 1189 OPG images confirmed by cone-beam CT and evaluated the results by model (accuracy, precision, recall, and F1 score) and diagnostic performance (accuracy, sensitivity, and specificity). The model performance was unsatisfying when AI was developed with 3 categories. After the indeterminate OA images were reclassified as normal, OA, or omission, the AI diagnosed TMJOA in a similar manner to an expert and was in most accord with CBCT when the indeterminate OA category was omitted (accuracy: 0.78, sensitivity: 0.73, and specificity: 0.82). Our deep learning model showed a sensitivity equivalent to that of an expert, with a better balance between sensitivity and specificity, which implies that AI can play an important role in primary diagnosis of TMJOA from OPGs in most general practice clinics where OMFR experts or CT are not available.
Determining the exact positional relationship between mandibular third molar (M3) and inferior alveolar nerve (IAN) is important for surgical extractions. Panoramic radiography is the most common ...dental imaging test. The purposes of this study were to develop an artificial intelligence (AI) model to determine two positional relationships (true contact and bucco-lingual position) between M3 and IAN when they were overlapped in panoramic radiographs and compare its performance with that of oral and maxillofacial surgery (OMFS) specialists. A total of 571 panoramic images of M3 from 394 patients was used for this study. Among the images, 202 were classified as true contact, 246 as intimate, 61 as IAN buccal position, and 62 as IAN lingual position. A deep convolutional neural network model with ResNet-50 architecture was trained for each task. We randomly split the dataset into 75% for training and validation and 25% for testing. Model performance was superior in bucco-lingual position determination (accuracy 0.76, precision 0.83, recall 0.67, and F1 score 0.73) to true contact position determination (accuracy 0.63, precision 0.62, recall 0.63, and F1 score 0.61). AI exhibited much higher accuracy in both position determinations compared to OMFS specialists. In determining true contact position, OMFS specialists demonstrated an accuracy of 52.68% to 69.64%, while the AI showed an accuracy of 72.32%. In determining bucco-lingual position, OMFS specialists showed an accuracy of 32.26% to 48.39%, and the AI showed an accuracy of 80.65%. Moreover, Cohen's kappa exhibited a substantial level of agreement for the AI (0.61) and poor agreements for OMFS specialists in bucco-lingual position determination. Determining the position relationship between M3 and IAN is possible using AI, especially in bucco-lingual positioning. The model could be used to support clinicians in the decision-making process for M3 treatment.
Transposable elements are major evolutionary forces which can cause new genome structure and species diversification. The role of transposable elements in the expansion of nucleotide-binding and ...leucine-rich-repeat proteins (NLRs), the major disease-resistance gene families, has been unexplored in plants.
We report two high-quality de novo genomes (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum) for peppers. Dynamic genome rearrangements involving translocations among chromosomes 3, 5, and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs are abundant across the angiosperms and, in most cases, are lineage-specific.
Our study reveals that retroduplication has played key roles for the massive emergence of NLR genes including functional disease-resistance genes in pepper plants.
Summary
Plants possess hundreds of intracellular immune receptors encoding nucleotide‐binding domain leucine‐rich repeat (NLR) proteins. Full‐length NLRs or a specific domain of NLRs often induce ...plant cell death in the absence of pathogen infection.
In this study we used genome‐wide transient expression analysis to identify a group of NLRs (ANLs; ancient and autonomous NLRs) carrying autoactive coiled‐coil (CCA) domains in pepper (Capsicum annuum). CCA‐mediated cell death mimics hypersensitive cell death triggered by the interaction between NLRs and pathogen effectors.
Sequence alignment and mutagenesis analyses revealed that the intact α1 helix of CCAs is critical for both CCA‐ and ANL‐mediated cell death. Cell death induced by CCAs does not require NRG1/ADR1 or NRC type helper NLRs, suggesting ANLs may function as singleton NLRs. We also found that CCAs localize to the plasma membrane, as demonstrated for Arabidopsis singleton NLR ZAR1. Extended studies revealed that autoactive CCAs are well conserved in other Solanaceae plants as well as in rice, a monocot plant. Further phylogenetic analyses revealed that ANLs are present in all tested seed plants (spermatophytes).
Our study not only uncovers the autonomous NLR clade in plants but also provides powerful resources for dissecting the underlying molecular mechanism of NLR‐mediated cell death in plants.
This study aimed to develop an artificial intelligence (AI) model using deep learning techniques to diagnose dens evaginatus (DE) on periapical radiography (PA) and compare its performance with ...endodontist evaluations. In total, 402 PA images (138 DE and 264 normal cases) were used. A pre-trained ResNet model, which had the highest AUC of 0.878, was selected due to the small number of data. The PA images were handled in both the full (F model) and cropped (C model) models. There were no significant statistical differences between the C and F model in AI, while there were in endodontists (p = 0.753 and 0.04 in AUC, respectively). The AI model exhibited superior AUC in both the F and C models compared to endodontists. Cohen's kappa demonstrated a substantial level of agreement for the AI model (0.774 in the F model and 0.684 in C) and fair agreement for specialists. The AI's judgment was also based on the coronal pulp area on full PA, as shown by the class activation map. Therefore, these findings suggest that the AI model can improve diagnostic accuracy and support clinicians in diagnosing DE on PA, improving the long-term prognosis of the tooth.
Mental health problems in childhood and adolescence (e. g., attention deficits, problems in emotional understanding and subclinical levels of anxiety) are reported to develop further in adulthood ...and/or to increase the risk of developing mental health disorders in adulthood. Although it is important to provide treatment or prevention interventions for children and adolescents in order to reduce the risk of the further development of mental health problems, the pharmacological and behavioral treatments for this age group have limitations (e.g., limited access, unsustainable treatment effects and the lack of engagement in intervention). In order to overcome the limitations of conventional treatments, the use of digital technology, especially video games for this age group, is suggested. In order to be accepted as clinical interventions, objective evidence for the therapeutic effects of digital therapeutic that used video games to treat or prevent targeted mental health problems are required. Thus, this review aims to explore whether game-based digital therapeutics (DTx) for children and adolescents showed therapeutic effects on targeted mental health problems. As game-based DTx are suggested to show sustained therapeutic effects and the transfer of cognitive functions, it also reviews the maintenance of the therapeutic effects of DTx and the extent of the transfer of cognitive functions. Game-based DTx that are developed to treat or prevent mental health problems (e.g., attention deficit, depression) in children and adolescents are found to show therapeutic effects on targeted mental health problems despite the limitations (e.g., small sample size, limited investigation of the sustainability). This review would contribute to the understanding of whether there is objective evidence of the therapeutic effects of digital therapeutics using video games that deliver treatment or prevention interventions for mental health problems in children and adolescents.
Unlike the emphasis on negative results of video games such as the impulsive engagement in video games, cognitive training studies in individuals with cognitive deficits showed that characteristics ...of video game elements were helpful to train cognitive functions. Thus, this study aimed to have a more balanced view toward the video game playing by reviewing genres of commercial video games and the association of video games with cognitive functions and modulating factors. Literatures were searched with search terms (e.g. genres of video games, cognitive training) on database and Google scholar.
video games, of which purpose is players' entertainment, were found to be positively associated with cognitive functions (e.g. attention, problem solving skills) despite some discrepancy between studies. However, the enhancement of cognitive functions through video gaming was limited to the task or performance requiring the same cognitive functions. Moreover, as several factors (e.g. age, gender) were identified to modulate cognitive enhancement, the individual difference in the association between video game playing and cognitive function was found.
Commercial video games are suggested to have the potential for cognitive function enhancement. As understanding the association between video gaming and cognitive function in a more balanced view is essential to evaluate the potential outcomes of commercial video games that more people reported to engage, this review contributes to provide more objective evidence for commercial video gaming.
CJLP55 has anti-pathogenic bacterial and anti-inflammatory activities in vitro. We investigated the dietary effect of CJLP55 supplement in patients with acne vulgaris, a prevalent inflammatory skin ...condition. Subjects ingested CJLP55 or placebo (
= 14 per group) supplements for 12 weeks in this double-blind, placebo-controlled randomized study. Acne lesion count and grade, skin sebum, hydration, pH and surface lipids were assessed. Metagenomic DNA analysis was performed on urine extracellular vesicles (EV), which indirectly reflect systemic bacterial flora. Compared to the placebo supplement, CJLP55 supplement improved acne lesion count and grade, decreased sebum triglycerides (TG), and increased hydration and ceramide 2, the major ceramide species that maintains the epidermal lipid barrier for hydration. In addition, CJLP55 supplement decreased the prevalence of
and increased
, which were correlated with decreased TG, the major skin surface lipid of sebum origin. CJLP55 supplement further decreased the
:
ratio, a relevant marker of bacterial dysbiosis. No differences in skin pH, other skin surface lipids or urine bacterial EV phylum were noted between CJLP55 and placebo supplements. Dietary
CJLP55 was beneficial to clinical state, skin sebum, and hydration and urine bacterial EV phylum flora in patients with acne vulgaris.
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