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: Porphyromonas gingivalis (P. gingivalis) is one of the major pathogens causing periodontitis and apical periodontitis (AP). Long noncoding RNA (lncRNA) can regulate cellular mineralization and inflammatory diseases. The aim of this study was to investigate the role and mechanism of lncRNA in P. gingivalis-stimulated cementoblast mineralization. In vivo, C57BL/6 mice were divided into the healthy, the AP, and AP + P. gingivalis groups (n = six mice per group). Micro computed tomography, immunohistochemistry staining, and fluorescence in situ hybridization were used to observe periapical tissue. In vitro, cementoblasts were treated with osteogenic medium or P. gingivalis. Pluripotency associated transcript 3 (Platr3), interleukin 1 beta (IL1B), and osteogenic markers were analyzed by quantitative real-time polymerase chain reaction and western blot. RNA pull-down and RNA immunoprecipitation assays were used to detect proteins that bind to Platr3. RNA sequencing was performed in Platr3-silenced cementoblasts. In vivo, P. gingivalis promoted periapical tissue destruction and IL1B expression, but inhibited Platr3 expression. In vitro, P. gingivalis facilitated IL1B expression (P < 0.001), whereas suppressed the expression of Platr3 (P < 0.001) and osteogenic markers (P < 0.01 or 0.001). In contrast, Platr3 overexpression alleviated the repressive effect of P. gingivalis on cementoblast mineralization (P < 0.01 or 0.001). Furthermore, Platr3 bound to nudix hydrolase 21 (NUDT21) and regulated the nuclear factor-κB (NF-κB) signaling pathway. Knocking down NUDT21 suppressed osteogenic marker expression and activated the above signaling pathway. Collectively, the results elucidated that Platr3 mediated P. gingivalis-suppressed cementoblast mineralization through the NF-κB signaling pathway by binding to NUDT21. [ABSTRACT FROM AUTHOR]

Summary: This paper presents a robust neural network–based control scheme to deal with the problem of tracking and stabilization simultaneously for a wheeled mobile robot subject to parametric uncertainties, external disturbances, and input saturation. At first, a new error‐state transformation scheme is designed by introducing some auxiliary variables as an additional virtual control signals to reduce the adverse effect caused by the underactuation. These variables can change their structures for different desired trajectories to be tracked. Then, a robust control law is proposed combining with a kinematic controller and a dynamic controller, while a three‐layer neural network system is applied to approximate model uncertainties. Stability analysis via the Lyapunov theory shows that the proposed controller can make tracking errors converge to bounded neighborhoods of the origin. Finally, some simulation results are illustrated to verify the effectiveness of the proposed control strategy. [ABSTRACT FROM AUTHOR]

This paper presents a cyber-physical management of smart buildings based on smart-gateway network with distributed and real-time energy data collection and analytics. We consider a building with multiple rooms supplied with one main electricity grid and one additional solar energy grid. Based on smart-gateway network, energy signatures of rooms are first extracted with consideration of uncertainty and further classified as different types of agents. Then, a multiagent minority-game (MG)-based demand-response management is introduced to reduce peak demand on the main electricity grid and also to fairly allocate solar energy on the additional grid. Experiment results show that compared to the traditional static and centralized energy-management system (EMS), and the recent multiagent EMS using price-demand competition, the proposed uncertainty-aware MG-EMS can achieve up to $50\times $ and $145\times $ utilization rate improvements, respectively, regarding to the fairness of solar energy resource allocation. More importantly, the peak load from the main electricity grid is reduced by 38.50% in summer and 15.83% in winter based on benchmarked energy data of building. Lastly, an average 23% uncertainty can be reduced with an according 37% balanced energy allocation improved comparing to the MG-EMS without consideration of uncertainty. [ABSTRACT FROM PUBLISHER]

The article presents the case -control study focused on obesity and cardiovascular risk. It mentions that Asia is a threat of metabolic disorders related to increased cardiovascular risk. It mentions that the consumption increment of fat in China as in North America. It mentions that the epidemic of metabolic disorders in Asia is related to the process from undernutrition.

Background: Cementoblasts on the tooth-root surface are responsible for cementum formation (cementogenesis) and sensitive to Porphyromonas gingivalis stimulation. We have previously proved transcription factor CXXC-type zinc finger protein 5 (CXXC5) participates in cementogenesis. Here, we aimed to elucidate the mechanism in which CXXC5 regulates P. gingivalis-inhibited cementogenesis from the perspective of mitochondrial biogenesis. Methods: In vivo, periapical lesions were induced in mouse mandibular first molars by pulp exposure, and P. gingivalis was applied into the root canals. In vitro, a cementoblast cell line (OCCM-30) was induced cementogenesis and submitted for RNA sequencing. These cells were co-cultured with P. gingivalis and examined for osteogenic ability and mitochondrial biogenesis. Cells with stable CXXC5 overexpression were constructed by lentivirus transduction, and PGC-1α (central inducer of mitochondrial biogenesis) was down-regulated by siRNA transfection. Results: Periapical lesions were enlarged, and PGC-1α expression was reduced by P. gingivalis treatment. Upon apical inflammation, Cxxc5 expression decreased with Il-6 upregulation. RNA sequencing showed enhanced expression of osteogenic markers, Cxxc5, and mitochondrial biogenesis markers during cementogenesis. P. gingivalis suppressed osteogenic capacities, mitochondrial biogenesis markers, mitochondrial (mt)DNA copy number, and cellular ATP content of cementoblasts, whereas CXXC5 overexpression rescued these effects. PGC-1α knockdown dramatically impaired cementoblast differentiation, confirming the role of mitochondrial biogenesis on cementogenesis. Conclusions: CXXC5 is a P. gingivalis-sensitive transcription factor that positively regulates cementogenesis by influencing PGC-1α-dependent mitochondrial biogenesis. A5vAuiTS6Tkq1RfziX_nr_ Video Abstract [ABSTRACT FROM AUTHOR]

Cementum, a constituent part of periodontal tissues, has important adaptive and reparative functions. It serves to attach the tooth to alveolar bone and acts as a barrier delimit epithelial growth and bacteria evasion. A dynamic and highly responsive cementum is essential for maintaining occlusal relationships and the integrity of the root surface. It is a thin layer of mineralized tissue mainly produced by cementoblasts. Cementoblasts are osteoblast‐like cells essential for the restoration of periodontal tissues. In recent years, glucose metabolism has been found to be critical in bone remodeling and osteoblast differentiation. However, the glucose metabolism of cementoblasts remains incompletely understood. First, immunohistochemistry staining and in vivo tracing with 18F‐fluorodeoxyglucose (18F‐FDG) revealed significantly higher glucose metabolism in cementum formation. To test the bioenergetic pathways of cementoblast differentiation, we compared the bioenergetic profiles of mineralized and unmineralized cementoblasts. As a result, we observed a significant increase in the consumption of glucose and production of lactate, coupled with the higher expression of glycolysis‐related genes. However, the expression of oxidative phosphorylation‐related genes was downregulated. The verified results were consistent with the RNA sequencing results. Likewise, targeted energy metabolomics shows that the levels of glycolytic metabolites were significantly higher in the mineralized cementoblasts. Seahorse assays identified an increase in glycolytic flux and reduced oxygen consumption during cementoblast mineralization. Apart from that, we also found that lactate dehydrogenase A (LDHA), a key glycolysis enzyme, positively regulates the mineralization of cementoblasts. In summary, cementoblasts mainly utilized glycolysis rather than oxidative phosphorylation during the mineralization process. [ABSTRACT FROM AUTHOR]

As a chronic inflammatory disease, periodontitis involves many biological processes including autophagy. At the same time, casein kinase 2 interacting protein-1 (CKIP-1) was reported to play a role in regulation of inflammation. But whether CKIP-1 and autophagy interact in periodontitis remains unclear. In this paper, our research team verified the levels of CKIP-1 expression and autophagy increase in the periodontal tissues of a ligature-induced periodontitis mouse model. And this result was also confirmed in Porphyromonas gingivalis (Pg)-induced human gingival fibroblasts (HGF) and human periodontal ligament cells (PDLC). We also showed the autophagy level in periodontal tissues is higher in Ckip-1 knockout (KO) mice than wild type (WT). At the same time, CKIP-1 knockdown lentivirus was used in PDLC and HGF, and it was found that silencing CKIP-1 significantly activated autophagy. Unfortunately, the regulatory role of autophagy in periodontitis is still unclear. Then, the autophagy agonist Rapamycin and inhibitor 3-MA were used in a periodontitis mouse model to investigate periodontal tissue destruction. We found the inflammation in periodontal tissue was reduced when autophagy activated. All these conclusions have been verified both in vivo and in vitro experiments. Finally, our research proved that silencing CKIP-1 reduces the expression of inflammatory cytokines in Pg-induced PDLC and HGF by regulating autophagy. Overall, a new role for CKIP-1 in regulating periodontal tissue inflammation was demonstrated in our study, and it is possible to treat periodontitis by targeting the CKIP-1 gene. [ABSTRACT FROM AUTHOR]

Hypoxia often occurs in inflammatory tissues, such as tissues affected by periodontitis and apical periodontitis lesions. Mitochondrial biogenesis can be disrupted in hypoxia. Peroxisome proliferator‐activated receptor gamma coactivator‐1 alpha (PGC‐1α) is a core factor required for mitochondrial biogenesis. Cementoblasts are root surface lining cells that play an integral role in cementum formation. There is a dearth of research on the effect of hypoxia on cementoblasts and underlying mechanisms, particularly in relation to mitochondrial biogenesis during the hypoxic process. In this study, we found that the expression of hypoxia inducible factor‐1α was elevated in apical periodontitis tissues in vivo. In contrast, periapical lesions exhibited a reduction of PGC‐1α expression. For in vitro experiments, cobalt chloride (CoCl2) was used to induce hypoxia. We observed that CoCl2‐induced hypoxia suppressed the mineralization ability and mitochondrial biogenesis of cementoblasts, accompanied by abnormal mitochondria morphology. Furthermore, we found that CoCl2 blocked the p38 pathway, while it activated the Erk1/2 pathway, with the former upregulating the expression of PGC‐1α, while the latter reversed the effects. Overall, our findings demonstrate that mitochondrial biogenesis, especially via PGC‐1α, is impaired during cementogenesis in the context of CoCl2‐induced hypoxia, dependent on the mitogen‐activated protein kinase signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Catch‐up fat in adults (CUFA) caused by rapid nutrition promotion after undernutrition plays an important role in the epidemic of insulin resistance (IR)‐related diseases in developing societies. Insulin resistance is considered to be closely associated with reduced testosterone levels and cognitive function. However, the effects of CUFA on testosterone levels and cognitive function are unclear in males. Objectives: To investigate the changes in testosterone levels and cognitive function in CUFA in male humans and rats, and explore their probable relationship and mechanisms in rats. Materials and methods: The blood testosterone levels, fasting glucose, and blood insulin (FINS) were measured in subpopulation 1 (27 CUFA individuals, 61 controls without CUFA) aged 40–50 years to show the characteristics of sex hormone levels and the metabolic status in CUFA men. Cognitive Flexibility Inventory was conducted in subpopulation 2 (54 CUFA individuals, 214 controls) over 20 years to investigate the associations between sex hormone levels, cognitive function, and CUFA. Male rats (n = 27) were randomly allocated to the NC group (normal chow controls), RN group (CUFA, refeeding after caloric restriction), and RT group (RN with testosterone intramuscular injected while refeeding). The blood testosterone levels, intraperitoneal insulin tolerance test (IPITT), and FINS were measured, and the attentional set‐shifting task test (ASST) for the assessment of cognitive function was performed in these animals. Insulin signaling pathway, N‐methyl‐d‐aspartate receptors subtype 2A (NR2A) and 2B (NR2B) expression levels were determined in the rat cerebral cortex. Results: The total testosterone levels decreased (medium [inter‐quartile ranges], 13.43 [9.87–18.96] vs. 15.58 [13.37–24.96], p = 0.036), and HOMA‐IR (Homeostatic Model Assessment for Insulin Resistance) elevated (1.61 [1.08–2.33] vs. 1.24 [0.87–1.87], P = 0.037) in CUFA men in subpopulation 1. Additionally, cognitive impairment was observed in CUFA men in subpopulation 2. Moreover, our results indicated decreases in total and free testosterone levels, elevations in visceral lipid accumulation, FINS, HOMA‐IR, blood glucose, and the area under the curve after IPITT, increases in the number of trials required to achieve the criterion of the first reversal of discrimination (R1) in ASST, and downregulation of IRS‐1 mRNA expression, AKT phosphorylation, and the NR2A and NR2B expression in brain tissue in male CUFA rats. Notably, testosterone supplementation improved visceral lipid accumulation and IR‐related metabolic disorders, cognitive dysfunction, decreases in IRS‐1 mRNA expression, Akt phosphorylation, and NR2A and NR2B expression in brain tissue in male CUFA rodents. Discussion and Conclusion: CUFA was characterized by reduced testosterone levels, metabolic abnormalities, and cognitive dysfunction in males, and testosterone supplementation attenuated these changes, as well as the alteration in insulin signaling and NR2A and NR2B expression in male CUFA rodents. Herein, we tentatively put forward that CUFA in males induces low testosterone, consequently promoting metabolic abnormalities and cognitive impairment probably mediated by defects in insulin signaling and NR2A, NR2B pathway in brain tissue. [ABSTRACT FROM AUTHOR]