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Glass fiber reinforced polymer (GFRP) concrete beams reinforced by carbon fiber reinforced polymer (CFRP) grid reinforced engineering cementitious composite (ECC) have excellent flexural performance and corrosion resistance in marine environments. However, the lack of a reliable theoretical model for predicting the flexural behavior of the hybrid beams makes it challenging apply them in the practical engineering. To address this issue, a series of numerical models were established to investigate the effects of key parameters on the flexural behavior of the hybrid beams, including the peak load, the neutral axis height, and the sectional stress distribution. Subsequently, based on the influence of the failures of different materials on the flexural performance of the hybrid beam, the loads of four feature points were calculated in the theoretical model to predict the entire load–displacement curve. Finally, the application range of the theoretical model was given based on the neutral axis height. The results showed that the cover thickness of the ECC, the GFRP reinforcement ratio and the cross‐sectional area of the CFRP grid were the key factors affecting the flexural performance of the hybrid beams. The theoretical model established in this study can predict the load–displacement curve accurately and can provide a reference for the subsequent design of the hybrid beams. [ABSTRACT FROM AUTHOR]

Summary: Claddings are susceptible to damage due to underestimation of extreme wind‐induced surface pressures. Commonly accepted methods for estimating the peak factor (an input used to determine cladding design loads) involve complex calculation‐intensive procedures. This research develops a four‐parameter unified auto‐spectral model of wind pressure to simplify peak factor estimation of wind‐induced surface pressure via analysis of wind tunnel wind load data on tri‐centered cylindrical roofs. Values of the model parameters were identified via statistical analysis of wind tunnel wind pressure measurement on two long‐span tri‐centered cylindrical roof structures with different curvatures. The study identified roof regions with non‐Gaussian features by inspecting probabilistic density functions of the standardized wind‐induced roof pressures and the third‐ and fourth‐order statistical moments of wind pressure time histories. The paper ultimately proposed and evaluated a simplified method for estimating the peak factors in the non‐Gaussian regions, the Three‐parameter Hermite Model, derived through the moment‐based Hermite Model, the Revised Hermite Model, and the parameter simplification accomplished in this study. The results show that the auto‐spectral model of wind‐induced roof pressures can accurately estimate the zero‐ and second‐order spectral moments, which reflects the wind pressure fluctuating characteristics and geometric features of spectral curves. Compared with the peak factors of the moment‐based Hermite Model and the Revised Hermite Model, the peak factor errors estimated by the Three‐parameter Hermite Model are all less than 10%. These results suggest that the Three‐parameter Hermite Model simplifies the calculation with acceptable accuracy. [ABSTRACT FROM AUTHOR]

Summary: This paper comprehensively presents the results of a wind tunnel experiment of the wind pressure fluctuating characteristics of a long‐span roof structure, namely the fluctuating wind pressure coefficient (FWPC), wind pressure power spectrum, and wind pressure coherence. The variation trend of FWPCs in the wind directions of 0°, 45°, and 90° were analyzed in sealed and open conditions, as well as the fluctuating wind pressure coefficients of lateral and longitudinal profiles of roof. Subsequently, the models of wind pressure spectrum in different zones and the spatial coherence of fluctuating wind pressure at different wind angles were discussed. The zone values of wind load shape factors of envelope structure with sealed, open, and pile of coal in open were calculated by area weighted averaging. The results indicate that the sealed condition significantly influences the fluctuating characteristics on the roof surface more than the open condition, suggesting that the maximum varied gradient of FWPCs is achieved in the 45° wind direction. Further, different forms and peak frequencies of the wind pressure spectrum in the roof region developed three zones, revealing that the peak frequency in energy‐preserved, inertia, and energy‐dissipated regions show an increasing trend for the different directions. The spatial correlations of wind pressure between measurement taps decrease with the increase in the frequency and spatial distance. Moreover, the correlation coefficients are lower than 0.2 when the frequency was higher than 35 Hz, and a modified three‐dimensional spatial coherence function of wind pressure is proposed. In contrast to the sealed case, the zone values of wind load shape factors of envelope structure with open and pile of coal in open are alleviated due to the separation flows. [ABSTRACT FROM AUTHOR]

Background: We evaluated the outcome of esophageal reconstructions using tissue‐engineered scaffolds. Method: Partial esophageal defects were reconstructed with the following scaffolds; animals were grouped (n = 7 per group) as follows: (a) normal rats; (b) rats implanted with three‐dimensional printing (3DP) polycaprolactone (PCL) scaffolds; (c) with human adipose‐derived mesenchymal stem cell (ADSC)‐seeded 3DP PCL scaffolds; (d) with polyurethane (PU)‐nanofiber(Nf) scaffolds; and (e) with ADSC‐seeded PU‐Nf scaffolds. Results: The esophageal defects were successfully repaired; however, muscle regeneration was greater in the 3DP PCL + ADSC groups than in the PU‐Nf + ADSC groups (P <.001). Regeneration of the epithelium was greater in PU‐Nf and PU‐Nf + ADSC groups than in the 3DP PCL and 3DP PCL + ADSC groups (P <.001). Conclusion: A tendency for more re‐epithelization was observed with the PU‐Nf scaffolds, while more muscle regeneration was achieved with the 3DP PCL scaffolds. [ABSTRACT FROM AUTHOR]

Yes‐associated protein 1 (YAP1), the core downstream effector of the Hippo signaling cascade, was involved in the regulation of osteoblast and osteoclast differentiation and in bone metabolism. However, the regulatory effects and mechanisms of YAP1 on bone‐remodeling molecules in osteoblasts under inflammation remain unknown. In this study, YAP1 expression level was downregulated after treatment with inflammatory cytokine tumor necrosis factor‐α (TNF‐α) in MC3T3‐E1 cells. The key osteoclastogenic molecules induced by TNF‐α, namely, interleukin‐6 and receptor activator of nuclear factor‐κB (NF‐κB) ligand, were suppressed after lentivirus‐induced YAP1 overexpression, which dramatically increased the expression level of osteoprotegerin. Conversely, the expression levels of the above factors showed opposite trends in the YAP1 small interfering RNA and YAP1 inhibitor (verteporfin) group. Mechanistically, YAP1 attenuated the TNF‐α‐induced activation of the NF‐κB signaling pathway as revealed by the reduced expression of phosphorylated‐p65 and NF‐κB reporter activity and the nuclear translocation of p65. Moreover, the expression level of YAP1 suppressed by TNF‐α was reversed by berberine in concentration‐dependent manner. Taken together, our study suggests that YAP1 plays a critical role in the regulation of bone metabolism and is a potential therapeutic target for treating inflammatory bone resorption. [ABSTRACT FROM AUTHOR]

Yes‐associated protein 1 (YAP1) transcriptional coactivator has recently been identified to regulate skeletal lineage cell differentiation and bone development. However, the role and molecular mechanisms of YAP1 in the regulation of osteoblastic differentiation remains to be elucidated. In this study, we demonstrated that YAP1 expression was increased during osteogenic differentiation of rat bone mesenchymal stem cells and MC3T3‐E1. YAP1 overexpression MC3T3‐E1 showed increased expression of osteogenesis markers, such as runt‐related transcription factor 2, osteocalcin, and osteopontin, as well as alkaline phosphatase and alizarin red staining. Conversely, YAP1 knockdown significantly suppressed MC3T3‐E1 osteoblastic differentiation. Mechanistically, we found that YAP1 overexpression upregulated the mRNA and protein expression of the inhibitor of differentiation/DNA binding 1 (ID1), which was contrary to the results of YAP1‐knockdown group. Moreover, the early osteogenic differentiation of MC3T3‐E1 cells was enhanced by ID1 overexpression. Furthermore, transient transfection with exogenous ID1 overexpression plasmid completely recaptured the decreased effects of YAP1 knockdown on MC3T3‐E1 cell differentiation. In addition, β‐catenin and AMP‐activated protein kinase signaling pathways participated in YAP1 regulation processes. Taken together, our study suggests that YAP1 is a crucial modulator of osteoblast differentiation in vitro, and provides insight into the mechanism by which YAP1 regulates osteoblast differentiation. [ABSTRACT FROM AUTHOR]

DDIT3 is of great importance in endoplasmic reticulum stress and is involved in many inflammatory diseases and mineralization processes. The cementum protects teeth from periodontitis and provides attachment for Sharpey's fibers of the periodontal ligament. However, the effect of DDIT3 on cementoblast differentiation remains largely unknown. In this study, we found that DDIT3 was suppressed during cementoblast differentiation. Knockdown of DDIT3 increased the messenger RNA (mRNA) and protein levels of several key osteogenic markers in vitro, including alkaline phosphatase, runt‐related transcription factor 2, and osteocalcin (OCN). In addition, isocitrate dehydrogenase 1 (IDH1) was increased during cementoblast differentiation, and knockdown of DDIT3 increased the protein and mRNA levels of IDH1. Furthermore, inhibition of IDH1 could partially reduce the effect of DDIT3 on cementoblast differentiation. The DDIT3 knockdown activated nuclear factor‐κB (NF‐κB) transcriptional activity and upregulated the expression of p‐p65 and p‐IκBα. The increased osteogenic differentiation ability and IDH1 expression, as induced by the DDIT3 knockdown, could be partially turned over by the addition of NF‐κB inhibitor BAY 11–7082. Overall, our data clarified that DDIT3 suppresses cementoblast differentiation through IDH1, via the NF‐κB pathway. In this study, we reported the decreased expression of DDIT3 during cementogenic mineralization, as well as the inhibitory effect of DDIT3 to cementogenic mineralization. In addition, we showed that DDIT3 can regulate isocitrate dehydrogenase 1 through the nuclear factor‐κB pathway. [ABSTRACT FROM AUTHOR]

Even the efficacy of substrate and mechanical stimuli in addition to biochemical cues have been recognized in many studies of stem cell differentiation, few studies have been reported on the differentiation into esophageal epithelial cells. Therefore, the aim of this study was set to propose a method of differentiating stem cells into esophageal epithelial cells according to biochemical reagent concentration, substrate properties, and mechanical forces. After the concentration of all‐trans retinoic acid was determined as 5 μM by a baseline experiment, the degree of differentiation was compared in three different kinds of substrates: cover glass, polyurethane (PU) membrane, and electrospun PU sheet (ePU). Then, on the substrate showing the more positive results, that is, ePU, two types of mechanical forces, intermittent hydrostatic pressure (IHP), and shear stress (SS), were applied individually at different magnitudes for the latter 7 days of an overall incubation period of 14 days. Following various biological assays, the lower IHP (50 mmHg) resulted in greater positive effects than the others. Even with cessation of the mechanical force, the relevant markers were remarkably increased. Although the range of factors regulating differentiation was limited, this study nonetheless demonstrated the combinational effects of mechanical force along with substrate type for the first time in related studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 552–560, 2019. [ABSTRACT FROM AUTHOR]

Yes-associated protein 1 (YAP1) transcriptional coactivator is a mediator of mechanosensitive signaling. Cementum, which covers the tooth root surface, continuously senses external mechanical stimulation. Cementoblasts are responsible for the mineralization and maturation of the cementum. However, the effect of YAP1 on cementoblast differentiation remains largely unknown. In this study, we initially demonstrated that YAP1 overexpression enhanced the mineralization ability of cementoblasts. YAP1 upregulated the mRNA and protein expression of several cementogenesis markers, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and dentin matrix acidic phosphoprotein 1 (DMP1). The YAP1 overexpression group showed higher intensities of ALP and Alizarin red stain than the YAP1-knockdown group. Unexpectedly, a sharp increase in the expression of dentin sialophosphoprotein (DSPP) was induced by the overexpression of YAP1. Knockdown of YAP1 suppressed DSPP transcriptional activity. YAP1 overexpression activated Smad-dependent BMP signaling and slightly inhibited Erk1/2 signaling pathway activity. Treatment with specific BMP antagonist (LDN193189) prevented the upregulation of the mRNA levels of ALP, RUNX2, and OCN, as well as intensity of ALP-stained and mineralized nodules in cementoblasts. The Erk1/2 signaling pathway inhibitor (PD 98,059) upregulated these cementogenesis markers. Thus, our study suggested that YAP1 enhanced cementoblast mineralization in vitro. YAP1 exerted its effect on the cementoblast partly by regulating the Smad-dependent BMP and Erk1/2 signaling pathways. [ABSTRACT FROM AUTHOR]