Objectives The aim of this study was to investigate the role of p75 neurotrophin receptor (p75NTR) in regulating the mouse alveolar bone development and the mineralization potential of murine ectomesenchymal stem cells (EMSCs). Moreover, we tried to explore the underlying mechanisms associated with the PI3K/Akt/β‐catenin pathway. Materials and methods p75NTR knockout (p75NTR−/−) mice and wild‐type (WT) littermates were used. E12.5d p75NTR−/− and WT EMSCs were isolated in the same pregnant p75NTR‐/+ mice from embryonic maxillofacial processes separately. Mouse alveolar bone mass was evaluated using micro‐CT. Differential osteogenic differentiation pathways between p75NTR−/− and WT EMSCs were analysed by RNA‐sequencing. The PI3K inhibitor LY294002 and PI3K agonist 740Y‐P were used to regulate the PI3K/Akt pathway in EMSCs. p75NTR overexpression lentiviruses, p75NTR knock‐down lentiviruses and recombined mouse NGF were used to transfect cells. Results The alveolar bone mass was found reduced in the p75NTR knockout mouse comparing to the WT mouse. During mineralization induction, p75NTR−/− EMSCs displayed decreased osteogenic capacity and downregulated PI3K/Akt/β‐catenin signalling. The PI3K/Akt/β‐catenin pathway positively regulates the potential of differential mineralization in EMSCs. The promotive effect of p75NTR overexpression can be attenuated by LY294002, while the inhibitory effect of p75NTR knock‐down on Runx2 and Col1 expression can be reversed by 740Y‐P. Conclusion Deletion of p75NTR reduced alveolar bone mass in mice. P75NTR positively regulated the osteogenic differentiation of EMSCs via enhancing the PI3K/Akt/β‐catenin pathway.

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B4C/TiB2 ceramic composites reinforced with three size scales (average particle size: 7 μm, 500 nm, and 50 nm) of TiB2 were prepared by using a pressureless sintering furnace at 2100 °C under Ar atmosphere for 60 min. The results demonstrated that during the sintering process, TiB2 located on the boundaries between different B4C grains could inhibit the grain growth which improved the mass transport mechanism and sintering driving force. A semi-coherent interface between B4C and SiC was found, which is supposed to help to reduce the interface energy and obtain good mechanical properties of the B4C/TiB2 ceramic composite. On sample cooling from sintering temperature to room temperature, the residual tensile stress fields formed at the TiB2 interfaces owning to the thermo-elastico properties mismatched, which might have contributed to increase the ability of the sample to resist crack propagation. The results showed that the relative density, Vickers hardness, and fracture toughness of the composite with 20 wt.% submicron and 10 wt.% nano-TiB2 were significantly improved, which were 98.6%, 30.2 GPa, and 5.47 MPa·m1/2, respectively.

BackgroundCell division cycle-associated protein 2 (CDCA2) is a member of cell cycle-related proteins. CDCA2 plays a role in the regulation of protein phosphatase 1(PP1) γ-dependent DNA damage response (DDR) and H3 phosphorylation. CDCA2 promotes the tumorigenesis and development of several types of cancers by promoting the proliferation of tumor cells. However, the relationship between CDCA2 expression and the clinicopathological characteristics of hepatocellular carcinoma (HCC) is unknown.MethodsGene expression information and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. The expression of CDCA2 and its correlation to clinical characteristics in HCC were analyzed. The expression level of CDCA2 was validated in HCC cell lines. The relationship between CDCA2 expression and the survival of patients with HCC was analyzed by using Kaplan–Meier method. The prognostic value of CDCA2 in HCC was estimated by Cox regression analysis. The expression difference of CDCA2 between HCC and normal tissues and its correlation to survival were verified in independent datasets. Gene set enrichment analysis (GSEA) was used to screen the CDCA2-related signaling pathways.ResultsCell division cycle-associated protein 2 expression was upregulated in HCC tissues (p < 0.001) and increased CDCA2 was correlated to increased T stage, pathologic stage, histologic grade, and alpha-fetoprotein (AFP) level (p < 0.001). In addition, CDCA2 was overexpressed in HCC cell lines HepG2 and LM3. High CDCA2 expression level was associated with poor overall survival [hazard ratio (HR) = 1.69; 95% CI, 1.20–1.40, p = 0.003], disease specific survival (HR = 1.73; 95% CI, 1.11–2.71, p = 0.016), and progress free interval (HR = 1.74; 95% CI, 1.30–2.34, p < 0.001). Overexpression of CDCA2 and its correlation to poor survival in HCC were verified in Gene Expression Omnibus (GEO) datasets and Kaplan–Meier plotter database. Increased CDCA2 expression was associated with upregulation of PD-L1 (Spearman's coefficient = 0.207, p < 0.001), PD-L2 (Spearman coefficient's = 0.118, p < 0.05), and CTLA4 (Spearman's coefficient = 0.355, p < 0.001). GSEA showed that homologous recombination pathway, insulin signaling pathway, mitogen-activated protein kinase (MAPK) pathway, mismatch repair pathway, mechanistic target of rapamycin (mTOR) pathway, Notch pathway, T cell receptor pathway, toll like receptor pathway, and WNT pathway were enriched in CDCA2 high expression phenotype.ConclusionCell division cycle-associated protein 2 may serve as an independent biomarker for poor prognosis in HCC and increased CDCA2 expression was associated with upregulation of immune checkpoints.

Human periodontal ligament stem cells (hPDLSCs) are a promising source in regenerative medicine. Due to the complexity and heterogeneity of hPDLSCs, it is critical to isolate homogeneous hPDLSCs with high regenerative potential. In this study, p75 neurotrophin receptor (p75NTR) was used to isolate p75NTR + and p75NTR − hPDLSCs by fluorescence‐activated cell sorting. Differences in osteogenic differentiation among p75NTR + , p75NTR − and unsorted hPDLSCs were observed. Differential gene expression profiles between p75NTR + and p75NTR − hPDLSCs were analysed by RNA sequencing. α1 Integrin (ITGA1) small interfering RNA and ITGA1‐overexpressing adenovirus were used to transfect p75NTR + and p75NTR − hPDLSCs. The results showed that p75NTR + hPDLSCs demonstrated superior osteogenic capacity than p75NTR − and unsorted hPDLSCs. Differentially expressed genes between p75NTR + and p75NTR − hPDLSCs were highly involved in the extracellular matrix‐receptor interaction signalling pathway, and p75NTR + hPDLSCs expressed higher ITGA1 levels than p75NTR − hPDLSCs. ITGA1 silencing inhibited the osteogenic differentiation of p75NTR + hPDLSCs, while ITGA1 overexpression enhanced the osteogenic differentiation of p75NTR − hPDLSCs . These findings indicate that p75NTR optimizes the osteogenic potential of hPDLSCs by up‐regulating ITGA1 expression, suggesting that p75NTR can be used as a novel cell surface marker to identify and purify hPDLSCs to promote their applications in regenerative medicine.

In order to investigate the key attributes of casino hotel customer eWOM and their structural relationships, this study selects two casino hotels located in Las Vegas and Macao. Through big data analytics, online reviews of two casino hotels from Google Travel were utilized. The frequency and CONCOR analyses showed the top 50 high-frequency words for each hotel and divided them into groups. The results of the factor analysis and linear regression analysis show that four factors, namely “Physical Environment”, “Entertainment”, “Experience”, and “Amenity”, in Las Vegas have a significant impact on customer satisfaction, while two factors, namely “Value” and “Physical Environment”, do in Macao. Through the results, the study points out the general characteristics affecting customer satisfaction of casino hotels, as well as the distinctions in influencing factors of their customer satisfaction in different source markets.

The aim of this study was to evaluate the effects of protecting the facial nerve and reducing the scar visibility using a modified tragus edge and transmasseteric anteroparotid approach compared to classic preauricular approach for intracapsular and condylar neck fractures. This retrospective study included 64 patients (78 sides) who underwent surgical treatment for intracapsular or condylar neck fractures from January 2014 to June 2018. Patients were divided into the experimental group (treated via a modified tragus edge and transmasseteric anteroparotid approach), and the control group (treated via the classical preauricular approach). Therapeutic outcome assessment parameters included facial nerve injury, salivary fistulae, wound infection, restricted mouth opening, postoperative occlusion disorders, and scar visibility. In the control group, there were 3 cases of facial nerve injuries and 2 cases of salivary fistulae. One case of temporary facial nerve injury occurred in the experimental group, with complete recovery within 1 month. The scars were less visible in the experimental group than in the control group. These results suggest that a modified tragus edge and transmasseteric anteroparotid approach reduced the incidences of facial nerve injuries, minimized the scar visibility, improved exposure of the operative site and fixation of titanium screws or plates, and did not increase the frequency of other complications.

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