Nrf2/HO-1 Alleviates Disulfiram/Copper-Induced Ferroptosis in Oral Squamous Cell Carcinoma.

Accumulating evidence indicates that the disulfiram/copper complex (DSF/Cu) has been shown to have potent antitumor activity against various cancers. This research evaluated the effects and probable mechanisms of DSF/Cu on oral squamous cell carcinoma (OSCC). In this study, we report the toxicity of the DSF/Cu to OSCC both in vitro and in vivo. Our study showed that DSF/Cu reduced the proliferation and clonogenicity of OSCC cells. DSF/Cu also induced ferroptosis. Importantly, we confirmed that DSF/Cu could increase the free iron pool, enhance lipid peroxidation, and eventually result in ferroptosis cell death. Inhibition of NRF2 or HO-1 enhances the sensitivity of OSCC cells to DSF/Cu-induced ferroptosis. DSF/Cu inhibited the xenograft growth of OSCC cells by suppressing the expression of Nrf2/HO-1. In conclusion, these results provide experimental evidence that Nrf2/HO-1 alleviates DSF/Cu-induced ferroptosis in OSCC. We propose that this therapy could be a novel strategy for treating OSCC.

Prognostic value of microRNA-100 in esophageal squamous cell carcinoma.

BACKGROUND: MicroRNA-100 (miR-100) has been demonstrated to be implicated in tumorigenesis and tumor progression of human esophageal squamous cell carcinoma (ESCC). However, its expression patterns in ESCC are controversial and its prognostic value in this malignancy has not been fully elucidated. The aim of this study was to investigate the expression and clinical significance of miR-100 in ESCC. MATERIALS AND METHODS: Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to detect expression levels of miR-100 in 120 self-paired specimens of ESCC and adjacent normal esophageal tissues. The associations of miR-100 expression with clinicopathologic features, locoregional progression-free survival (LPFS), distant progression-free survival (DPFS), and overall survival (OS) of patients with ESCC were statistically analyzed. RESULTS: Compared with adjacent normal esophageal tissues, the expression levels of miR-100 in ESCC were significantly decreased (normal versus ESCC: 3.53 ± 1.22 versus 1.89 ± 0.38, P <0.001). Additionally, low miR-100 expression in ESCC tissues was significantly associated with the advanced clinical stage (P = 0.008), the presence of distant metastasis (P = 0.008), and the great depth of invasion (P = 0.02). Moreover, univariate analysis revealed that low miR-100 expression was associated with poor LPFS, DPFS, and OS. In multivariate analysis, miR-100 expression was identified as an independent prognostic factor for all LPFS, DPFS, and OS. CONCLUSIONS: These findings show the reduced expression of miR-100 in human ESCC tissues and suggest a crucial role of its downregulation in ESCC progression and prognosis. More interestingly, the detection of miR-100 expression may be used to efficiently screen those ESCC patients who would benefit from radiotherapy.

Disulfiram/Copper Activates ER Stress to Promote Immunogenic Cell Death of Oral Squamous Cell Carcinoma.

Disulfiram/copper complex (DSF/Cu) was found to have anti-tumor effects in a range of malignancies, including oral squamous cell carcinoma (OSCC), yet its precise mechanism remains unknown. It has been shown that ER stress enhances immunogenic cell death (ICD) in tumor cells, as it can influence the anti-cancer immune system favorably. In this study, we reported that DSF/Cu exhibited a marked inhibitory effect on the growth of OSCC cells, accompanied by cell apoptosis. OSCC cells treated with DSF/Cu showed the hallmarks of immunogenic cell death (ICD), including surface expression of calreticulin (CRT), heat shock protein 70 (HSP70), high mobility-group box 1 (HMGB-1) and adenosine triphosphate (ATP), thus, eliciting the maturation and activation of dendritic cells. Furthermore, we showed DSF/Cu-induced endoplasmic reticulum (ER) stress in OSCC cells. In vivo, results demonstrate that DSF/Cu inhibits tumor growth locally and alters the intratumoral immune cell infiltration and response. In conclusion, DSF/Cu suppresses OSCC development by inducing ICD and ER stress. DSF/Cu has the potential to be a new anti-tumor immunotherapy concept because of its ability to elicit ICD.

A theoretical model for predicting the startup performance of pumps as turbines.

Using the unsteady Bernoulli equation for the piping system and the angular momentum equation for the rotor, derives here a theoretical model to predict the startup performance of a pump as turbine (PAT). This model is effective for predicting the instantaneous evolution characteristics of the main performance parameters of PAT during startup, and these changings are initially faster and then slowly as a whole. The effect of the rotor moment of inertia and the final stabilized rotational speed of PAT on evolution characteristics of parameters is opposite. The rotational speed, head, hydraulic power, and conversion efficiency show a upward rising trend with the startup time, whereas the flow rate and hydraulic head loss display a downward trend.

Numerical investigation of flow characteristics in the front and rear chambers of centrifugal pump and pump as turbine.

To investigate the flow characteristics in front chamber and rear chamber in pump mode and pump as turbine mode, a 3D computational model of a centrifugal pump was established, including the front and rear chamber. Based on Realizable k-ε turbulence model, numerical calculations of incompressible flow were carried out for internal viscous flow in two operating modes. Further analysis was conducted on the flow stability and hydraulic losses under two modes using energy gradient theory and entropy production theory. The numerical simulation results are within reasonable error compared to the experimental results in pump operation mode, which ensures the reliability of the numerical calculation method. The results indicate that the volumetric efficiency in both two modes is on an upward trend with increasing flow, but the volumetric efficiency of the pump mode is more significantly affected by changes in flow; the distribution patterns of dimensionless circumferential velocity and dimensionless radial velocity in the front and rear chambers under two operating modes are similar, but the distribution pattern of dimensionless radial velocity in the front chamber in turbine mode is significantly different from other operating conditions; flow instability is most likely to occur at the outlet of impeller, and the energy loss in clearance of wear-rings is greater than that in the pump chamber.

Study on the integrated self-priming process of a vehicle-mounted self-priming pump.

In order to explore the self-priming characteristics of the self-priming pump at the mobile pump truck, this paper established a complete three-dimensional circulatory piping system including the self-priming pump, tank, valves, inlet pipe and outlet pipe. The UDF(User Defined Functions) was used to realize the acceleration-constant speed operation process of the impeller, thus reflecting the actual changing state of the rotational speed. Based on the VOF(Volume Of Fluid) multiphase flow model and the Realizable k-ε turbulence model, a coupled numerical calculation of unsteady incompressible viscous flow was conducted for its self-priming process. The results show that the self-priming process of the pump can be roughly divided into four stages: the rapid suction stage, the shock exhaust stage, the rapid exhaust period and the pump residual gas discharge stage. The proportion of each stage in the total self-priming time showed an increasing trend. During the rapid suction stage, the water level in the vertical section of the inlet pipe showed a slow and then fast-rising pattern. During the shock exhaust stage, the average gas-phase volume fraction in the volute is lower than that of the impeller, and the gas content at the volute outlet is lower than that of the impeller inlet. The region at the inlet and outer edge of the impeller consistently experience significant energy losses.

Hydraulic loss experiment of straight-through Tesla valve in forward and reverse directions.

Tesla valves are widely used in the field of fluid control. To study the hydraulic performance of straight-through Tesla valves in forward and reverse flow, 16 straight-through Tesla valves with diverse blade parameters were designed in this paper, and hydraulic loss tests were carried out in forward and reverse flow under different working conditions. The results show that the hydraulic loss increases with the increasing working flow rate in forward and reverse flow; at the identical flow rate, the reverse loss is higher than the forward loss. Both the hydraulic loss through the valve and the unidirectional conductivity of the valve increase with increasing blade length, pitch, and number of blades, but too long of a length results in weakened unidirectional conductivity. The hydraulic loss increases with the increase of blade angle, and the unidirectional conductivity decreases with the increase of blade angle. When the blades are arranged in perfect symmetry, the hydraulic loss through the valve is maximum, and the valve has the best unidirectional conductivity.

Prenatal ethanol exposure induced disorder of hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programming alteration and dysfunction of glucose and lipid metabolism in 40-week-old female offspring rats.

This study was designed to demonstrate disorder of hypothalamic-pituitary-adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration and dysfunction of glucose and lipid metabolism induced by prenatal ethanol exposure (PEE) in postnatal week 40 (PW40) female offspring rats. Pregnant Wistar rats were administrated 4  g/kg·d ethanol intragastrically from gestational day 11 until term delivery. After weaning, the female offspring were fed with high-fat diet until PW24, and suffered to unpredictable chronic stress (UCS) during PW38-40. Animal serum was collected to examine the changes in hypothalamic-pituitary-adrenal (HPA) axis activity, glucose and lipid metabolic phenotypes before and after UCS. We found that pups in the PEE group manifested a low birthweight at PW1 and an early catch-up growth pattern. Furthermore, a low basal activity of HPA axis continued to PW38 in the PEE group. On the basal condition, serum low-density lipoprotein-cholesterol (LDL-C) level was significantly increased and high-density lipoprotein-cholesterol (HDL-C) level was significantly decreased in the PEE group, while serum triglyceride, total cholesterol (TCH), glucose and insulin levels were not significantly changed. Under unpredictable chronic stress, serum insulin in the PEE group was significantly decreased, while the levels of serum triglyceride, TCH, LDL-C, and the ratio of LDL-C/HDL-C were significantly higher than those in the control. These results suggest that PEE increases the dysfunction of glucose and lipid metabolism in PW40 female offspring, which is related to the disorder of HPA axis-associated neuroendocrine metabolic programming alteration.