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The ingenious hierarchical structure of enamel composed of rods and protein produces excellent fracture resistance. However, the fracture resistance mechanism in the inner enamel is unknown. The micromechanical models of enamel are constructed to numerically analyze the mechanical behaviors of the inner enamel with different decussation angles and different decussation planes. The results show that the manner of crack propagation in the inner enamel, including crack bridging, crack deflection, and crack bifurcation, is determined by both the rod decussation angle and the decussation plane. In the case of the strong decussation plane, the fracture strength and the required energy dissipation with the decussation angles of 15° and 30° are much higher than those without decussation, demonstrating that decussation is an important mechanism in improving the fracture resistance of enamel. The maximum tensile stress of enamel with the decussation angle of 15° is slightly higher than that of enamel with the decussation angle of 30°, illustrating that an optimal decussation angle exists which balances the strength and toughness. The synergetic mechanism of the decussation angle and the decussation plane on the crack propagation provides a new design hint for bionic composites. [ABSTRACT FROM AUTHOR]

Introduction  Understanding the anatomic features of the zygomatic nerve is critical for performing the endoscopic transmaxillary approach properly. Injury to the zygomatic nerve can result in facial numbness and corneal problems. Objective  To evaluate the surgical anatomy of the zygomatic nerve and its segments from an endoscopic endonasal perspective for clinical implications of performing the endoscopic transmaxillary approach. Methods  The origin, course, length, and segments of the zygomatic nerve were studied in four specimens from an endonasal perspective. Results  The zygomatic nerve arises 4.1 ± 1.7 mm from the foramen rotundum of the maxillary nerve in the superolateral pterygopalatine fossa (PPF). According to its anatomic region in endonasal endoscopic surgery, we divided the zygomatic nerve into two segments: the PPF segment, from origin to the point of entry under Muller's muscle, which runs superolaterally to the inferior orbital fissure (IOF) (length, 4.6 ± 1.3 mm), and the IOF segment, starting at the entry point in Muller's muscle and terminating at the exit point in the IOF, which travels between Muller's muscle and the great wing of the sphenoid bone (length, 19.6 ± 3.6 mm). In the transmaxillary approach, the zygomatic nerve is a critical landmark in the superolateral PPF. Conclusion  The zygomatic nerve travels in the PPF and the IOF; better visualization and preservation of this nerve during endonasal endoscopic surgery are crucial for successful outcomes. [ABSTRACT FROM AUTHOR]

The axial vibration of the liquid-filled pipes can be represented with a four-equation fluid–structure interaction (FSI) model. When distributed friction was neglected, this model could be solved with an exact solution without computational grid, while the only weakness was the high time cost. A fast meshless solution (FMS) developed earlier used the time-line interpolation rather than the recursive algorithm, to speed the calculation. For the purpose of practical applications, the FMS for supports at pipe end and middle position is proposed, and series connection is also studied in this paper. The support is described by the complex constraint including elastic, damping and inertial effects. A numerical case of the double-pipe water hammer is employed to validate the series connection and end supports. The FMS for the middle support is validated by an existing experiment, where the support can be described by the dry friction. Both numerical and experimental cases indicate the effectiveness and the efficiency of the proposed solution method. • The fast meshless solution for the double pipe is proposed. • Complex constraints at pipe supports are incorporated and solved. • Calculation efficiency is improved significantly and high accuracy is achieved. [ABSTRACT FROM AUTHOR]

Objective: Kappa opioid receptor (KOR) signaling is involved in joint development and inflammation in Osteoarthritis (OA), while the biochemical mechanism remains unclarified. This study aims to investigate downstream molecular events of KOR activation, to provide novel perspectives in OA pathology. Methods: U50,488H, a selective KOR agonist, was intra-articularly injected in mice upon destabilization of the medial meniscus (DMM) as OA models, with PBS injection as control. The behavioral and histological evaluation was assessed by hot plate test and red solid green staining, respectively. Alterations in mRNA and protein expression were assessed by RNA-seq, RT-qPCR, immunohistochemistry and western blotting (WB) in chondrocytes treated with TNF-α or TNF-α + U50,488H. Proteins interacted with KOR were explored using proximity labeling followed by mass spectrometry and then testified by co-immunoprecipitation (Co-IP) assay and immunofluorescence (IF). Results: OA-induced pain was reduced and cartilage degeneration was alleviated upon KOR activation in DMM mice. In chondrocytes, activation of KOR reversed the upregulation of MMPs, IL-6, IL-1β and phosphorylated(p-) STAT3, stimulated by TNF-α, while the expression of NF-κB, MAPKs and AKT signaling weren't reversed. RNA-seq and IF results presented that KOR activation evidently reduced STAT3 nuclear translocation in chondrocytes upon TNF-α stimuli. The reduction may be resulted from the binding of KOR and STAT3 in the plasma membrane, revealed by proximity labeling and Co-IP results. Conclusions: KOR activation protects cartilage from OA, and this protective effect is mainly exerted via sequestering STAT3 on the plasma membrane, resulting in inactivation of STAT3-dependent immune responses which otherwise contributes to OA. [ABSTRACT FROM AUTHOR]

Pituitary adenomas (PAs), or pituitary neuroendocrine tumors (PitNETs), are commonly found in the anterior pituitary gland. Although the majority of PitNETs are benign and stable, several tumors have malignant characteristics. The tumor microenvironment (TME) plays an important role in the process of tumorigenesis and is composed of several types of cells. Various cells in the TME are significantly affected by oxidative stress. It has been reported that immunotherapeutic strategies have good effects in several cancers. However, the clinical potential of immunotherapies in PitNETs has not yet been fully discussed. Oxidative stress can regulate PitNET cells and immune cells in the TME, thus affecting the immune status of the TME of PitNETs. Therefore, modulation of oxidative stress‐regulated immune cells using a combination of several agents and the immune system to suppress PitNETs is a promising therapeutic direction. In this review, we systematically analyzed the oxidative stress process within PitNET cells and various immune cells to elucidate the potential value of immunotherapy. [ABSTRACT FROM AUTHOR]

Aims Positive associations between periodontitis (PD) and atherosclerosis have been established, but the causality and mechanisms are not clear. We aimed to explore the causal roles of PD in atherosclerosis and dissect the underlying mechanisms. Methods and results A mouse model of PD was established by ligation of molars in combination with application of subgingival plaques collected from PD patients and then combined with atherosclerosis model induced by treating atheroprone mice with a high-cholesterol diet (HCD). PD significantly aggravated atherosclerosis in HCD-fed atheroprone mice, including increased en face plaque areas in whole aortas and lesion size at aortic roots. PD also increased circulating levels of triglycerides and cholesterol, hepatic levels of cholesterol, and hepatic expression of rate-limiting enzymes for lipogenesis. Using 16S ribosomal RNA (rRNA) gene sequencing, Fusobacterium nucleatum was identified as the most enriched PD-associated pathobiont that is present in both the oral cavity and livers. Co-culture experiments demonstrated that F. nucleatum directly stimulated lipid biosynthesis in primary mouse hepatocytes. Moreover, oral inoculation of F. nucleatum markedly elevated plasma levels of triglycerides and cholesterol and promoted atherogenesis in HCD-fed ApoE −/− mice. Results of RNA-seq and Seahorse assay indicated that F. nucleatum activated glycolysis, inhibition of which by 2-deoxyglucose in turn suppressed F. nucleatum -induced lipogenesis in hepatocytes. Finally, interrogation of the molecular mechanisms revealed that F. nucleatum -induced glycolysis and lipogenesis by activating PI3K/Akt/mTOR signalling pathway in hepatocytes. Conclusions PD exacerbates atherosclerosis and impairs lipid metabolism in mice, which may be mediated by F. nucleatum -promoted glycolysis and lipogenesis through PI3K/Akt/mTOR signalling in hepatocytes. Treatment of PD and specific targeting of F. nucleatum are promising strategies to improve therapeutic effectiveness of hyperlipidaemia and atherosclerosis. [ABSTRACT FROM AUTHOR]

(1) Background: glioma is the most prevalent primary tumor of the human central nervous system and accompanies extremely poor prognosis in patients. The transient receptor potential (TRP) channels family consists of six different families, which are closely associated with cancer cell proliferation, differentiation, migration, and invasion. TRP family genes play an essential role in the development of tumors. Nevertheless, the function of these genes in gliomas is not fully understood. (2) Methods: we analyze the gene expression data of 28 TRP family genes in glioma patients through bioinformatic analysis. (3) Results: the study showed the aberrations of TRP family genes were correlated to prognosis in glioma. Then, we set enrichment analysis and selected 10 hub genes that may play an important role in glioma. Meanwhile, the expression of 10 hub genes was further established according to different grades, survival time, IDH mutation status, and 1p/19q codeletion status. We found that TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, MCOLN1, MCOLN2, and MCOLN3 were significantly correlated to the prognosis in glioma patients. Furthermore, we illustrated that the expression of hub genes was associated with immune activation and immunoregulators (immunoinhibitors, immunostimulators, and MHC molecules) in glioma. (4) Conclusions: we proved that TRP family genes are promising immunotherapeutic targets and potential clinical biomarkers in patients with glioma. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer among females. Dachshund Homolog 1 (DACH1) gene is regarded as an important tumor suppressor gene in breast cancer which plays an important regulatory role in the development disease progression, particularly in carcinomas. Circular RNAs (circRNAs) and microRNA (miRNA), regarded as a novel group of noncoding RNAs, are always involved in regulating gene expression. In this work, hsa_circ_0047604 expressed lower in breast cancer tissue and played the role of sponge of miR-548o. By this way, hsa_circ_0047604 could upregulate DACH1 to inhibit breast cancer. In conclusion, this study revealed that hsa_circ_0047604 acted as a tumor suppressor and regulated breast cancer progression via hsa_circ_0047604–miR-548o–DACH1 axis, which might provide a therapeutic method for breast cancer. [ABSTRACT FROM AUTHOR]

Aim: To demonstrate the clinical value of epithelial membrane protein 3 (EMP3) with bioinformatic analysis and clinical data, and then to establish a practical nomogram predictive model with bicenter validation. Methods: The data from CGGA and TCGA database were used to analyze the expression of EMP3 and its correlation with clinical prognosis. Then, we analyzed EMP3 expression in samples from 179 glioma patients from 2013 to 2017. Univariate and multivariate cox regression were used to predict the prognosis with multiple factors. Finally, a nomogram to predict poor outcomes was formulated. The accuracy and discrimination of nomograms were determined with ROC curve and calibration curve in training and validation cohorts. Results: EMP3 was significantly higher in higher‐grade glioma and predicted poor prognosis. In multivariate analysis, high expression of EMP3 (HR = 2.842, 95% CI 1.984–4.071), WHO grade (HR = 1.991, 95% CI 1.235–3.212), and IDH1 mutant (HR = 0.503, 95% CI 0.344–0.737) were included. The nomogram was constructed based on the above features, which represented great predictive value in clinical outcomes. Conclusion: This study demonstrated EMP3 as a novel predictor for clinical progression and clinical outcomes in glioma. Moreover, the nomogram with EMP3 expression represented a practical approach to provide individualized risk assessment for glioma patients. [ABSTRACT FROM AUTHOR]