ACP-5862 suppresses esophageal squamous cell carcinoma growth through inducing apoptosis via activation of endoplasmic reticulum stress and ROS production.

Esophageal squamous cell carcinoma (ESCC) is a common type of human oral malignancy with poor survival. Presently, it is necessary to find new and effective drugs for clinical therapy. This study aimed to identify the potential anti-tumor effects of ACP-5862, a major metabolite of acalabrutinib, on human ESCC progression, and to reveal the underlying mechanisms. Our findings suggested that ACP-5862 treatments markedly reduced the cell proliferation of ESCC cell lines in a time- and dose-dependent manner, while had no significant cytotoxicity to normal cells. Cell cycle arrest in G2/M phase was markedly induced by ACP-5862 in ESCC cells. Furthermore, apoptosis and endoplasmic reticulum (ER) stress were detected in ESCC cells treated with ACP-5862. Intriguingly, ACP-5862-induced apoptotic cell death was partly dependent on ER stress. Moreover, reactive oxygen species (ROS) was greatly triggered in ACP-5862-incubated ESCC cells, which was closely involved in apoptosis and ER stress mediated by ACP-5862. In addition, we showed that the expression of nuclear factor-erythroid 2-related factor-2 (Nrf-2) was considerably reduced in ACP-5862-treated cells. Importantly, ACP-5862 combined with Nrf-2 knockdown could further induce apoptosis and ER stress in ESCC cells compared with the ACP-5862 single group. Animal studies confirmed that repressing Nrf-2 promoted the anti-tumor effect of ACP-5862 on ESCC growth. Taken together, these findings demonstrated that ACP-5862 exerted anti-cancer effects on ESCC through inducing ER stress-mediated apoptosis via the ROS production. Meanwhile, ACP-5862 co-treated with Nrf-2 inhibitors may supply new and effective therapeutic strategies for ESCC treatment in future.

Research on the drag reduction property of puffer (Takifugu flavidus) spinal nonsmooth structure surface.

Puffers show good drag reduction performance during migration. It is worth noting that spines which are different from ordinary fish scales are densely distributed on the puffer skin. Here, the special morphological structure of puffer spines was observed using microscopy techniques, accurate contour models were established based on image processing techniques and curve fitting, then feature sizes were obtained. Based on the results, the nonsmooth surface was established by orthogonal test to simulate the flow field. In addition, the influence of spinal structure on boundary layer flow field and the drag reduction property of nonsmooth surface were further analyzed. The nonsmooth surface formed by spinal structure elements can effectively reduce the wall shear stress and Reynolds stress, and there was a special "climbing vortex" phenomenon, so as to reduce the surface viscous friction resistance and achieve drag reduction. Compared with the smooth surface, the drag reduction rate of the nonsmooth surface was 12.94% when the inflow velocity was 5 m/s, which revealed and verified the drag reduction performance of the spines of puffer skin. The results lay a foundation for further research and optimization of drag reduction ability of nonsmooth surface of bionic spines. HIGHLIGHTS: The contour of the spinous process was accurately reflected by the Fourier function. The spines of puffer skin have good drag reduction effect. There was a special "climbing vortex" phenomenon to explain the drag reduction property.

Evaluation of microRNA expression profiling in highly metastatic laryngocarcinoma cells.

BACKGROUND: Until now, little is known about the role of miRNAs in the invasion and metastasis of Laryngeal squamous cell carcinoma (LSCC). OBJECTIVES: This study aimed to explore the relationship between microRNA and the invasion and metastasis of LSCC. MATERIAL AND METHODS: The highly metastatic laryngocarcinoma cells were obtained from the established animal model with spontaneous lymph node metastasis of LSCC in our previous study. MicroRNA expression profiling and bioinformatic analysis were performed to analyze the microRNA expression changes in the highly metastatic laryngocarcinoma cells and the parental tumor cells (HEP-2). RT-PCR was performed for further validation of the result of microarray. RESULTS: A total of 40 microRNAs were found to be significantly altered in the highly metastatic laryngocarcinoma cells compared to controls. Bioinformatic analysis identified that 19 key microRNAs might involve in LSCC development. Moreover, RT-PCR confirmed that miR-25, miR-100, miR-125b-5p and let-7g were differentially expressed in different laryngocarcinoma cells and human tumor specimens. CONCLUSIONS AND SIGNIFICANCE: Our findings suggest that microRNA play an important role in the invasion and metastasis of LSCC, and provide the clues for studying the function of microRNA as well as opportunities to analyze the complex molecular abnormalities driving LSCC progression.

Clinical observation on hearing conditions of centenarians in northern district of China.

CONCLUSION: The hearing conditions of the centenarians were quite poor as regards hearing thresholds and speech detection ability. OBJECTIVE: To investigate hearing conditions of centenarians. METHODS: A total of 54 centenarians in Rizhao and Linyi Districts in Shandong Province were investigated to assess hearing conditions of centenerians comprehensively by questionnaire investigation, pure-tone audiometry, acoustic immitance, intelligence evaluation, and speech detection scores. Also, 135 individuals were recruited as controls and divided into four groups according to their age: 45-59 years, 60-69 years, 70-79 years, and 80-89 years. RESULTS: The hearing thresholds of the centenarians were dramatically higher than those of the control group (p < 0.05) and all centenarians suffered moderate to profound hearing loss according to the World Health Organization (WHO) criteria. Few centenarians had normal level of speech detection scores. All centenarians showed descending hearing curve, and the hearing threshold of the male centenarians at 8000 Hz was higher than that of the females (p = 0.047). There was a significant air-bone conduction gap in the centenarians (p < 0.05).