Pepsin enhances glycolysis to promote malignant transformation of vocal fold leukoplakia epithelial cells with dysplasia.

PURPOSE: The mechanism underlying malignant transformation of vocal fold leukoplakia (VFL) and the precise role of the expression of pepsin in VFL remain unclear. This study aimed to investigate the effects of acidified pepsin on VFL epithelial cell growth and migration, and also identify pertinent molecular mechanisms. METHODS: Immunochemistry and Western blotting were performed to measure glucose transporter type 1 (GLUT1), monocarboxylate transporters 4 (MCT4), and Hexokinase-II (HK-II) expressions. Cell viability, cell cycle, apoptosis, and migration were investigated by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. Glycolysis-related contents were determined using the corresponding kits. Mitochondrial HK-II was photographed under a confocal microscope using Mito-Tracker Red. RESULTS: It was found: the expression of pepsin and proportion of pepsin+ cells in VFL increased with the increased dysplasia grade; acidified pepsin enhanced cell growth and migration capabilities of VFL epithelial cells, reduced mitochondrial respiratory chain complex I activity and oxidative phosphorylation, and enhanced aerobic glycolysis and GLUT1 expression in VFL epithelial cells; along with the transfection of GLUT1 overexpression plasmid, 18FFDG uptake, lactate secretion and growth and migration capabilities of VFL epithelial cell were increased; this effect was partially blocked by the glycolysis inhibitor 2-deoxy-glucose; acidified pepsin increased the expression of HK-II and enhanced its distribution in mitochondria of VFL epithelial cells. CONCLUSION: It was concluded that acidified pepsin enhances VFL epithelial cell growth and migration abilities by reducing mitochondrial respiratory complex I activity and promoting metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis.

Development of Impurity-Detection System for Tracked Rice Combine Harvester Based on DEM and Mask R-CNN.

Impurity rate is one of the key performance indicators of the rice combine harvester and is also the main basis for parameter regulation. At present, the tracked rice combine harvester impurity rates cannot be monitored in real time. Due to the lack of parameter regulation basis, the harvest working parameters are set according to the operator's experience and not adjusted during the operation, which leads to the harvest quality fluctuating greatly in a complex environment. In this paper, an impurity-detection system, including a grain-sampling device and machine vision system, was developed. Sampling device structure and impurity extraction algorithm were studied to enhance the impurity identification accuracy. To reduce the effect of impurity occlusion on visual recognition, an infusion-type sampling device was designed. The sampling device light source form was determined based on the brightness histogram analysis of a captured image under different light irradiations. The effect of sampling device structures on impurity visualization, grain distribution, and mass flow rate was investigated by the discrete element method (DEM). The impurity recognition algorithm was proposed based on Mask R-CNN, which mainly includes an impurity feature extraction network, an ROI generation network, and a target segmentation network. The test set experiment showed that the precision rate, recall rate, average precision, and comprehensive evaluation indicator of the impurity recognition model were 92.49%, 88.63%, 81.47%, and 90.52%, respectively. The conversion between impurity pixel number and its actual mass was realized according to the pixel density calibration test and impurity rate correction factor. The bench test result showed that the designed system has a good detection accuracy of 91.15~97.26% for the five varieties. The result relative error was in a range of 5.71~11.72% between the impurity-detection system and manual method in field conditions. The impurity-detection system could be applied to tracked rice combine harvesters to provide a reference for the adjustment of operating parameters.

[Surgical management of 27 cases with temporal bone cerebrospinal fluid leakage].

Objective:To study the clinical manifestations and surgical treatment of temporal bone cerebrospinal fluid leakage. Methods:The clinical data of twenty seven cases with temporal bone cerebrospinal fluid leakage were analyzed retrospectively. Different surgical procedures were adopted according to the location of the leak and the hearing status of the affected ear.If the leakage location was clear before surgery, direct repair was performed via mastoid path or middle cranial fossa path with or without mastoid abdominal fat packing.For patients with unclear leak, large lesion or intractable CEREBROspinal fluid leakage of temporal bone, subtotal petrosal resection and abdominal fat packing were performed.Subtotal temporal bone resection and abdominal fat packing were performed for patients with cochlear involvement. Results:In this study, cases of temporal bone CSF leakage including 13 cases of inner ear malformation; 5 cases secondary to head trauma or previous surgery,5 cases of idiopathic intracranial hypertension or meningocele, 2 cases of langerhans histiocytosis in the temporal bone and 2 cases of inner ear inflammation. High resolution CT （HRCT） of temporal bone showed bone defect of inner auditory canal with vestibular communication in 13 patients with inner ear malformation.The temporal bone HRCT of the remaining 14 patients showed bone defects in the middle cranial fossa or posterior cranial fossa, while MRI of the temporal bone showed meningeal continuity interruption with cerebrospinal fluid inflow into the temporal bone or meningoencephalocele in 12 patients. The 26 patients were followed up from 6 months to 6 years. 1 patient lost follow-up.Meningitis recurred in only 1 patient with inner ear malformation, and subtotal resection of rock bone plus abdominal fat packing was performed.Postoperative hearing was preserved or improved in 7 patients.None of the patients had serious complications, and only 1 patient developed HB Grade Ⅱ facial paralysis after vestibular obliteration, and the facial paralysis recovered within one week. Conclusion:Temporal bone cerebrospinal fluid leakage is relatively rare. Surgical intervention should be taken as early as possible when conservative treatment is failure. Preoperative HRCT and MRI examination are necessary for the localization of the leakage, and individualized surgical approaches can be adopted according to the location of the leakage and the features of the lesion.

WWP2 regulates proliferation of gastric cancer cells in a PTEN-dependent manner.

WW domain containing E3 Ub-protein ligase 2 (WWP2) plays an important role in tumor progression as an E3 ligase of PTEN. Here, we investigated the role of WWP2 in gastric cancer (GC). We found that WWP2 is overexpressed in GC tissues, which is closely related to poor prognosis of GC patients. Using a WWP2-shRNA lentivirus expressing system, we established WWP2 stable-knockdown GC cell lines and found that knockdown of WWP2 inhibits the proliferation of GC cells both in vitro and in vivo. Also, WWP2 silencing induced the up-regulation of PTEN protein level and down-regulation of AKT phosphorylation level. We further investigated the role of PTEN in this regulating process by performing rescue assay and found that PTEN is essential for WWP2-mediated regulation of GC cells proliferation. Taken together, our results demonstrated that WWP2 promotes proliferation of GC cells by downregulating PTEN, which may provide new therapeutic targets for GC.

A novel FoxM1-PSMB4 axis contributes to proliferation and progression of cervical cancer.

The abnormally high activity of the proteasome system is closely related to the occurrence and development of various tumors. PSMB4 is a non-catalytic subunit for the proteasome assembly. Although the reports from genetic screening have demonstrated it's a driver gene for cell growth in several types of solid tumor, its expression pattern and regulatory mechanisms in malignant diseases are still elusive. Here, we found that PSMB4 is overexpressed in cervical cancer tissues. And knockdown of PSMB4 significantly inhibited cervical cancer cell proliferation. The mechanistic study revealed that FoxM1, a master regulator of cell division, binds directly to the promoter region of PSMB4 and regulates the PSMB4 expression in the mRNA level. In addition, the data analysis from TCGA showed a positive correlation between FxoM1 and PSMB4 in cervical cancer. Furthermore, the loss of functional and rescue experiments confirmed that PSMB4 is required for FoxM1-driven cervical cancer cell proliferation. Collectively, our study explains the phenomenon of dysregulated expression of PSMB4 in cervical cancer tissues and verifies its driver effect on cancer cell proliferation. More importantly, it highlights a FoxM1-PSMB4 axis could be a potential target for the treatment of cervical cancer.

Disturbance characteristics of half-selected cells in a cross-point resistive switching memory array.

Disturbance characteristics of cross-point resistive random access memory (RRAM) arrays are comprehensively studied in this paper. An analytical model is developed to quantify the number of pulses (#Pulse) the cell can bear before disturbance occurs under various sub-switching voltage stresses based on physical understanding. An evaluation methodology is proposed to assess the disturb behavior of half-selected (HS) cells in cross-point RRAM arrays by combining the analytical model and SPICE simulation. The characteristics of cross-point RRAM arrays such as energy consumption, reliable operating cycles and total error bits are evaluated by the methodology. A possible solution to mitigate disturbance is proposed.