Regulation of transforming growth factor ß2-induced epithelial-mesenchymal transition and autophagy in lens epithelial cells by the miR-492/NPM1 axis.

A cataract is a clinically common blinding disease closely related to the ageing of the eye cells, which has become a major health killer in the elderly. Our research seeks to analyze the primary targets linked to the pathogenesis of cataracts during the ageing process. We performed bioinformatics analyses on the GSE101727 dataset to discover genes linked with ageing and cataracts. To explore the impacts of Nucleophosmin 1 (NPM1) on cell apoptosis, proliferation, as well as epithelial-mesenchymal transition (EMT) processes, in vitro tests such as western blotting, flow cytometry, and MTT were carried out. Additionally, the study incorporated transforming growth factor ß2 (TGF-ß2) to examine its function in cellular responses, chloroquine (CQ) to regulate autophagic flow, and H2O2 therapy to mimic oxidative stress. Our study discovered seven ageing-related genes, including NPM1, that had substantial relationships with cataracts. NPM1 overexpression was shown to boost cell proliferation and prevent apoptosis in SRA01/04 cells. Notably, NPM1 modulated the TGF-ß signalling pathway, influencing cell proliferation and EMT processes. miR-429 was shown to be adversely regulating NPM1 and autophagy-related proteins, as demonstrated by changes in their expression in response to TGF-ß2 treatment. Furthermore, NPM1 knockdown restored autophagy activity suppressed by miR-429 mimics, indicating a complex interaction of miR-429, NPM1, and TGF-ß2 pathways in regulating autophagy and EMT. Lens epithelial cell proliferation and apoptosis were largely regulated by NPM1, as well as autophagy and EMT, which were significantly mediated by TGF-ß2 and the miR-429/NPM1 axis. These results imply new possible targets for prognosis and therapy of cataracts.

Changes in gut microbiota and cytokines following laparoscopic sleeve gastrectomy are associated with cognitive function improvement.

Purpose: Variations of cytokines and gut microbiota diversity with improved cognitive function in patients with obesity following bariatric surgery were poorly understood. The aim of this study was to testify the relationship among gut microbiota, cytokines and cognitive function in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG). Methods: Forty patients were enrolled in this study. Demographics, and serum and stool specimens were collected from all patients before and 3 months after LSG. The Montreal Cognitive Assessment (MoCA) scale, as well as assessment of immediate and delayed memory were used to evaluate self-perceived cognitive improvement after LSG. Results: LSG resulted in significant weight loss and improvement in cognitive functions, as measured by questionnaires. Bariatric surgery tended to increase gut microbiota relative abundance and diversity. The intestinal flora increased in the proportion of Bacteroidetes and Fusobacteria phyla, and decreased in the proportion of Firmicutes, Proteobacteria, and Actinobacteria phyla after LSG. Plasma IL-1ß and TNF-α levels were significantly decreased following LSG, while IL-4 was significantly increased. MoCA test scores were significant correlated with IL-4, TNF-α and IL-1ß. In addition, Firmicutes had a positive correlation with TNF-α, while Fuscobacteria had a negative correlation with IL-1ß. Bacteroidetes was negatively correlated with IL-4. Conclusion: Changes in gut microbiota were positive relationship with cognitive function improvement following LSG. Inflammation cytokines maybe played as a mediator between gut microbiota and cognitive function through gut-microbiota-brain axis.

A descriptive study on clinical department managers' cognition of the Plan-Do-Check-Act cycle and factors influencing their cognition.

BACKGROUND: The mastery and application of the "Plan-Do-Check-Act" (PDCA) cycle by hospital clinical department managers are essential for hospitals to carry out total quality management and continuously improve medical quality. This study investigated the degree of cognition of the PDCA cycle by clinical department managers and the factors affecting their cognition. METHODS: A self-designed questionnaire was used to evaluate the cognition of clinical department managers regarding the PDCA cycle in 11 municipal public Class III Grade A hospitals in Western China. RESULTS: More than 25% of clinical department managers in the surveyed hospitals are unaware or partially aware of the PDCA cycle. Logistic regression analysis showed that sex (P = 0.049), education (P < 0.001), duty (P < 0.001), and tenure (P = 0.002) had a significant influence on managers' cognition of PDCA. Participants who were female (P < 0.001), undergraduate (P < 0.001), head nurses, or deputy head nurses (P < 0.001), with a tenure of 5-10 years (P = 0.024) had a better cognition of the PDCA cycle. In the daily management of the department, the vast majority of managers do not implement the Check and Action steps. Among the trained managers, only 65.44% applied the complete PDCA cycle in daily management. Nearly a third of managers thought PDCA was a response to hospital demands; 82.83% of the managers need to receive PDCA cycle training, and half of them indicated a preference for online training. CONCLUSIONS: The cognition level of hospital clinical department managers regarding the PDCA cycle is relatively low, especially among the clinical department heads, and most of them are willing to accept PDCA cycle training.

GaN surface acoustic wave filter with low insertion loss.

Surface acoustic wave (SAW) filter with a low insertion loss (IL) of 4.415 dB has been demonstrated on Carbon-doped semi-insulating c-plane bulk GaN without external lumped element matching. The center frequency, 3 dB bandwidth, out-of-band attenuation, return loss of the filter are 477.05 MHz, 0.308 MHz, 32.5 dB, and -9.72 dB, respectively. The electromechanical coupling coefficient (Kt2), and temperature coefficient of frequency (TCF) of the filter are 0.21 % and -26.0 ppm/°C, respectively. The impact of the number of interdigital transducers (NIDT) and acoustic propagation direction on filter performance has been studied. The IL of filters reduces from 16.07 dB to 4.415 dB with the increase of NIDT from 50 to 150 due to the enhanced acoustic superposition. The numerical distribution of elastic stiffness ([cij]), and piezoelectric constants ([eik]) of GaN has been calculated in Euler angle space, indicating that they are isotropic on c-plane. The small performance difference of filters along the m- and a-direction on c-plane bulk GaN can be attributed to the small offset angle of 0.5° of the bulk GaN wafer or IDT quality variation.

FOXA2 suppresses PKM2 transcription and affects the Wnt/ß-catenin activity to block aerobic glycolysis in thyroid carcinoma.

Aerobic glycolysis is critical for the energy metabolism of cancer cells. This study focuses on the regulation of forkhead box A2 (FOXA2) on pyruvate kinase M2 (PKM2) and their effects on the glycolytic activity and malignant phenotype of thyroid carcinoma (THCA) cells. By analysing four Gene Expression Omnibus datasets and querying bioinformatics systems, we obtained FOXA2 as a poorly expressed transcription factor in THCA. Later, we validated decreased mRNA and protein levels of FOXA2 in THCA cells by quantitative polymerase chain reaction and western blot assays. FOXA2 upregulation in THCA cells suppressed the glucose uptake and lactate production, and it reduced the extracellular acidification rate, but increased the oxygen consumption rate of cells. Meanwhile, the FOXA2 overexpression blocked the proliferation and mobility, and the tumourigenic activity of cancer cells. The chromatin immunoprecipitation and luciferase assays showed that FOXA2 bound to PKM2 promoter and suppressed the transcription of PKM2, which was highly expressed in THCA cells. Further upregulation of PKM2 elevated the ß-catenin, c-Myc and cyclin D1 levels and restored the glycolytic activity as well as the malignant properties of cancer cells. Collectively, this work reveals that FOXA2 suppresses aerobic glycolysis and progression of THCA by blocking PKM2 transcription and inactivating the Wnt/ß-catenin pathway.

The Interaction Between SMAD1 and YAP1 Is Correlated with Increased Resistance of Gastric Cancer Cells to Cisplatin.

Drug resistance is a major obstacle leading to treating failure and poor outcome in gastric cancer (GC). This study explores the interaction between SMAD family member 1 (SMAD1) and Yes1-associated transcriptional regulator (YAP1) and their roles in cisplatin (DDP) resistance in GC. Transcriptome analysis predicted that SMAD1 is highly expressed in DDP-resistant cells. Elevated SMAD1 expression was detected in GC tissue and cells, especially in DDP-resistant cells (MKN-45/DDP and AGS/DDP). SMAD1 downregulation in cells decreased 50% inhibition value of DDP, reduced proliferation, migration, and invasion, and promoted cell cycle arrest and apoptosis. A protein-protein interaction network suggested a possible SMAD1 and YAP1 interaction in GC. The SMAD1 and YAP1 interaction was validated by chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP), and luciferase assays. SMAD1 bound to YAP1 and activated its transcription. SMAD1 formed complexes with YAP1 in nucleus, and YAP1 upregulation enhanced SMAD1 activity as well. Upregulation of YAP1 restored the malignant behaviors of GC cells suppressed by SMAD1 silencing. In vivo, SMAD1 silencing suppressed growth and DDP resistance of xenograft tumors in nude mice, and this suppression was blocked by YAP1 overexpression again. In conclusion, this study demonstrates that SMAD1 can interact with YAP1 to enhance the DDP resistance of GC cells.

TWIST1-EP300 Expedites Gastric Cancer Cell Resistance to Apatinib by Activating the Expression of COL1A2.

The association between collagen type I alpha (COL1A) and chemoresistance has been verified in cancers. However, the specific role of COL1A2 in gastric cancer (GC) cell resistance to apatinib, a highly selective small-molecule inhibitor of vascular endothelial growth factor receptor 2, has not been investigated before. The purpose of this study was to explore the potential factors associated with COL1A2 regulation on GC cell apatinib resistance in vitro. With the aid of the Oncomine database and integrated bioinformatics methods, we identified COL1A2 overexpression in GC and its prognostic value. Mechanistically, the COL1A2 promoter has a distinct H3K27ac modification site and that E1A binding protein p300 (EP300) and twist family bHLH transcription factor 1 (TWIST1) can bind to the COL1A2 promoter, which in turn transcriptionally activated COL1A2 expression. In addition, overexpression of COL1A2 significantly promoted resistance to apatinib in GC cells, but knockdown of EP300 or TWIST1 remarkably inhibited COL1A2 expression and promoted sensitivity of GC cells to apatinib. Our findings demonstrated that the combination of EP300 and TWIST1 has a synergistically regulatory effect on COL1A2 expression, thus contributing to apatinib resistance in GC cells.

Development and Validation of Prognostic Nomogram in Patients With WHO Grade III Meningioma: A Retrospective Cohort Study Based on SEER Database.

INTRODUCTION: World Health Organization (WHO) Grade III meningioma is a central nervous system tumor with a poor prognosis. In this retrospective cohort study, the authors constructed a nomogram for predicting the prognosis of WHO Grade III meningioma. METHODS: The patients of this nomogram were based on the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018. All patients were randomly divided into a development cohort (964 patients) and a validation cohort (410 patients) in a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression was used to screen the predictors. The Cox hazards regression model was constructed and the prognosis was visualized by nomogram. The performance of the prognostic nomogram was determined by consistency index (C-index), clinical net benefit, and calibration. RESULTS: Eight variables were included in the nomogram: gender, race, age at diagnosis, histology, tumor site, tumor size, laterality, and surgical method. The C-index of the training set and verification set were 0.654 and 0.628. The calibration plots showed that the nomogram was in good agreement with the actual observation. The clinical decision curve indicates that the nomogram has a good clinical net benefit in WHO Grade III meningioma. CONCLUSIONS: A prognostic nomogram of a large cohort of WHO Grade III meningioma was established and verified based on the SEER database. The nomogram we established may help clinicians provide personalized treatment services and clinical decisions for patients.

Development and validation of prognostic nomogram in ependymoma: A retrospective analysis of the SEER database.

BACKGROUND: The prognostic factors for survival in patients with ependymoma (EPN) remain controversial. The aim of this study was to establish a prognostic model for 5- and 10-year survival probability nomograms for patients with EPN. METHODS: Clinical data from the Surveillance, Epidemiology, and End Results (SEER) database were used for patients diagnosed with ependymoma between 2000 and 2018 and were randomized 7:3 into a development set and a validation set. Factors significantly associated with prognosis were screened out using the least absolute shrinkage and selection operator (LASSO) regression. The calibration chart and consistency index (C-index) are used to evaluate the discrimination and consistency of the prediction model. Decision curve analysis (DCA) was used to further evaluate the established model. Finally, prognostic factors selected by LASSO regression were evaluated using Kaplan-Meier (KM) survival curves. RESULTS: A total of 3820 patients were included in the prognostic model. Seven survival predictors were obtained by LASSO regression screening, including age, gender, morphology, location, size, laterality, and resection. The prognostic model of the nomogram showed moderate discriminative ability in the development group and the validation group, with a C-index of 0.642 and 0.615, respectively. In the development set and validation set survival curves, the prognosis index of high risk was less effective than low risk (p < 0.001). CONCLUSIONS: Our nomograms may play an important role in predicting 5 and 10-year outcomes for patients with ependymoma. This will help assist clinicians in personalized medicine.