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Abstract Objective Connexin 43 (Cx43) is a critical gene for maintaining myocardial homeostasis. Interestingly, Cx43 and stress‐induced phosphoprotein 1 (STIP1) were recorded to be lowly expressed in ischemia/reperfusion (I/R). However, their impacts on reperfusion arrhythmia (RA) remain to be explored. Our study aimed to find out the related underlying mechanisms. Methods After the establishment of an isolated heart model through Langendorff perfusion, the heart rate, conduction activation time, conduction velocity, and conduction direction of the left ventricle were evaluated, along with the apoptotic rate detection in the collected myocardial tissues. After the construction of a hypoxia/reoxygenation (H/R)‐induced cellular model, cell apoptosis, intercellular communication, cell viability, and the content of reactive oxygen species, superoxide dismutase, malondialdehyde, and lactic dehydrogenase were measured. The expression of Cx43 and STIP1 was determined in both rat heart and cell models. The bindings of STIP3 and Cx43 to heat shock protein 90 (HSP90) and heat shock protein 70 (HSP70) were verified. Results Relative to the corresponding controls, Cx43 and STIP1 were decreased in myocardial tissues of RA rats and H/R‐stimulated H9C2 cells, where Cx43‐binding HSP70 and HSP90 were respectively increased and decreased, and ubiquitination level of Cx43 was enhanced. STIP1 overexpression promoted protein expression of Cx43, intercellular communication, and cell viability, and reduced cell apoptosis and oxidative stress in H/R‐stimulated H9C2 cells. Conclusion STIP1 promoted Cx43 expression to improve intercellular communication and reduce oxidative stress in H/R‐stimulated H9C2 cells.

Epidermal growth factor receptor (EGFR) is often overexpressed in head and neck squamous cell carcinoma (HNSCC) and represents a top candidate for targeted HNSCC therapy. However, the clinical effectiveness of current Food and Drug Administration (FDA)‐approved drugs targeting EGFR is moderate, and the overall survival rate for HNSCC patients remains low. Therefore, more effective treatments are urgently needed. In this study, we generated a novel diphtheria toxin‐based bivalent human epidermal growth factor fusion toxin (bi‐EGF‐IT) to treat EGFR‐expressing HNSCC. Bi‐EGF‐IT was tested for in vitro binding affinity, cytotoxicity, and specificity using 14 human EGFR‐expressing HNSCC cell lines and three human EGFR‐negative cancer cell lines. Bi‐EGF‐IT had increased binding affinity for EGFR‐expressing HNSCC compared with the monovalent version (mono‐EGF‐IT), and both versions specifically depleted EGFR‐positive HNSCC, but not EGFR‐negative cell lines, in vitro. Bi‐EGF‐IT exhibited a comparable potency to that of the FDA‐approved EGFR inhibitor, erlotinib, for inhibiting HNSCC tumor growth in vivo using both subcutaneous and orthotopic HNSCC xenograft mouse models. When tested in an experimental metastasis model, survival was significantly longer in the bi‐EGF‐IT treatment group than the erlotinib treatment group, with a significantly reduced number of metastases compared with mono‐EGF‐IT. In addition, in vivo off‐target toxicities were significantly reduced in the bi‐EGF‐IT treatment group compared with the mono‐EGF‐IT group. These results demonstrate that bi‐EGF‐IT is more effective and markedly less toxic at inhibiting primary HNSCC tumor growth and metastasis than mono‐EGF‐IT and erlotinib. Thus, the novel bi‐EGF‐IT is a promising drug candidate for further development.

Objective. The aim of this study was to investigate the changes of syndecan-4 (SDC-4) during the hypertensive period in two kidney-two clip (2K2C) hypertension rats and compare them to brain natriuretic peptide (BNP) and the echocardiographic parameters for diastolic function evaluation in the rat model of 2K2C hypertension. Methods. A total of 36 Sprague–Dawley (SD) rats were used in this study. Hypertension was induced in 21 by 2K2C surgery, and 15 were sham-operated. Both the 2K2C hypertension group (n = 21) and the sham-operated group (n = 15) were equally divided into 3 subgroups according to the schedules (week 4, week 8, and week 12). Serum SDC-4 and BNP were detected by ELISA, and echocardiography indexes were acquired. Results. The level of SDC-4 and cardiac fibrosis increased gradually as the experiment was processed, and BNP, Tei index, and E/E′ followed to be raised as high blood pressure was maintained after four weeks in the 2K2C hypertension rats. In the earlier 4 weeks, only SDC-4 and cardiac fibrosis were significantly increased in 2K2C hypertensive rats in comparison with normotensive rats. And it was shown that SDC-4 was positively correlated with BNP level during the entire study (r = 0.762, p

Recurrence and metastasis are the major causes of mortality in head and neck squamous cell carcinoma (HNSCC). It is suggested that cancer stem cells (CSCs) play pivotal roles in recurrence and metastasis. Thus, a greater understanding of the mechanisms of CSC regulation may provide opportunities to develop novel therapies for improving survival by controlling recurrence or metastasis. Here, we report that overexpression of the gene encoding the catalytic subunit of PI3K (PIK3CA), the most frequently amplified oncogene in HNSCC, promotes epithelial‐to‐mesenchymal transition and enriches the CSC population. However, PIK3CA is not required to maintain these traits and inhibition of the phosphatidylinositol 3‐kinase (PI3K) signaling pathway paradoxically promotes CSC population. Molecular analysis revealed that overexpression of PIK3CA activates multiple receptor tyrosine kinases (RTKs), in which ephrin receptors (Ephs), tropomyosin receptor kinases (TRK) and mast/stem cell growth factor receptor (c‐Kit) contribute to maintain CSC population. Accordingly, simultaneous inhibition of these RTKs using a multi‐kinase inhibitor ponatinib has a superior effect at eliminating the CSC population and reduces metastasis of PIK3CA‐overexpressing HNSCC cells. Our result suggests that co‐targeting of Ephs, TRKs and the c‐Kit pathway may be effective at eliminating the PI3K‐independent CSC population, thereby providing potential targets for future development of a novel anti‐CSC therapeutic approach for HNSCC patients, particularly for patients with PIK3CA amplification.

Abstract Aims/Introduction Recently, some data have supported the concept that diabetes is negatively associated with aortic aneurysm. In the present study, we aimed to investigate the relationship between diabetes and cardiac structural and functional characteristics, in particular, aortic root dimensions, in end‐stage renal disease (ESRD) patients. Methods ESRD patients receiving peritoneal dialysis for >3 months were consecutively enrolled. Clinical features and echocardiographic parameters were analyzed according to the presence of diabetes history. Correlation analyses were carried out for diabetes mellitus and aortic root dilatation. Multiple logistic regression analysis was carried out to identify variables correlated with aortic root dilatation. Results A total of 218 ESRD patients receiving peritoneal dialysis were enrolled. Patients with diabetes showed lower left ventricular internal measurements in end‐diastole, left ventricular internal measurements in end‐systole and aortic root diameter (ARD)/body surface area (BSA). Worse cardiac diastolic function was also observed in these patients. In addition, the age‐related increase of ARD/BSA and ARD/height was attenuated in patients with diabetes. With the increase of ARD/BSA, lower levels of serum creatinine, phosphorus and serum glucose, as well as higher serum high‐density lipoprotein cholesterol and apolipoprotein A‐1 were also observed. Increased normalized left ventricular internal measurements were shown in patients with greater ARD/BSA. Multiple regression analysis showed that diabetes (odds ratio 0.353, P = 0.015) was an independent correlate of aortic root dilatation, even after correction for age, sex and other clinical confounders in the enrolled patients. Conclusions The present findings shown an inverse association between diabetes and age‐related aortic root dilatation in ESRD patients. Diabetes remained to be independently correlated with aortic root dilatation even after adjustment for age, sex and other clinical confounders in ESRD patients.

A large‐scale multi‐projector display system offers high‐resolution, high‐brightness and immersive visualisation for realistic experience to end users. It has been demonstrated to be effective tackling the conflict between the increasing demands of super‐resolution display and the resolution limitation of a single display system. However, there is still no standardisation method for curved‐surface projection screen. In this study, we propose a novel approach for calibrating multi‐projector display systems, which have curved surfaces. First, based on a detailed analysis on arbitrarily curved surfaces, we present a three‐dimensional reconstruction algorithm based on Bezier surface models. Then, for fully utilising the projection area of each projector, we propose a novel curved‐surface stitching algorithm to achieve geometry seamlessness of multi‐projector display systems. Experimental results show that by constructing local Bessel models for the curved screen, the proposed method performs better than traditional approaches, i.e. the new method achieves geometric calibration with higher accuracy. The proposed method of modelling projection screen and the corresponding automatic geometric correction scheme effectively increase the utilisation ratio of the original projection area of each projector and improve the calibration accuracy of multi‐projector system with continuous curved surface.

The Fourth Party Logistics (4PL) network faces disruptions of various sorts under the dynamic and complex environment. In order to explore the robustness of the network, the 4PL network design with consideration of random disruptions is studied. The purpose of the research is to construct a 4PL network that can provide satisfactory service to customers at a lower cost when disruptions strike. Based on the definition of β-robustness, a robust optimization model of 4PL network design under disruptions is established. Based on the NP-hard characteristic of the problem, the artificial fish swarm algorithm (AFSA) and the genetic algorithm (GA) are developed. The effectiveness of the algorithms is tested and compared by simulation examples. By comparing the optimal solutions of the 4PL network for different robustness level, it is indicated that the robust optimization model can evade the market risks effectively and save the cost in the maximum limit when it is applied to 4PL network design.