CircRNA circRREB1 promotes tumorigenesis and progression of breast cancer by activating Erk1/2 signaling through interacting with GNB4.

Current investigations have illuminated the essential roles played by circular RNAs (circRNAs) in driving breast cancer (BC) tumorigenesis. However, the functional implications and molecular underpinnings of most circRNAs in BC are not well characterized. Here, Circular RNA (circRNA) expression profiles were analyzed in four surgically resected BC cases along with adjacent non-cancerous tissues applying RNA microarray analysis. The levels and prognostic implications of circRREB1 in BC were subjected to quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Experimental manipulation of circRREB1 levels in both in vivo and in vitro settings further delineated its role in BC cell growth, invasion, and metastasis. The mechanical verification of circRREB1's interaction with GNB4 was established through RNA pull-down, mass spectrometry, Western blot analysis, RNA immunoprecipitation assays (RIP), fluorescence ISH (FISH), and rescue experiments. We found that circRREB1 exhibited significant upregulation in BC tissues and cells, implicating its association with an unfavorable prognosis in BC patients. CircRREB1 knockdown elicited anti-proliferative, anti-migratory, anti-invasive, and pro-apoptotic effects in BC cells, whereas its upregulation exerted opposing influences. Follow-up mechanistic examinations suggested that circRREB1 might interact with GNB4 directly, inducing the activation of Erk1/2 signaling and driving BC progression. Our findings collectively indicate that the interplay of circRREB1 with GNB4 promotes Erk1/2 signaling, thereby fostering BC progression, and positioning circRREB1 as a candidate therapeutic target for intervention in BC.

Association of SGLT2is with cardiovascular and reproductive diseases: a meta-analysis based on 14 large-scale randomized trials.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) can improve long-term cardio-renal outcomes in patients with diabetes, heart failure (HF), or renal failure. We aimed to investigate the association of SGLT2is with the risks of various cardiovascular and reproductive diseases. METHODS: Large-scale randomized trials enrolling more than 1000 participants and assessing SGLT2is were included. Outcomes of interest were the various serious adverse events related to cardiovascular or reproductive diseases. Meta-analysis was done to generate pooled risk ratio (RR) and 95% confidence interval (CI). RESULTS: We included 14 large trials and evaluated 169 types of cardiovascular and reproductive diseases. SGLT2is were significantly associated with the lower risks of 13 types of cardiovascular diseases, e.g., cardiac failure chronic (RR 0.70, 95% CI 0.57-0.87), cardiac failure congestive (RR 0.74, 95% CI 0.66-0.83), acute cardiac failure (RR 0.72, 95% CI 0.60-0.86), coronary artery disease (RR 0.75, 95% CI 0.58-0.97), ischemic cardiomyopathy (RR 0.72, 95% CI 0.52-0.99), atrial fibrillation (RR 0.88, 95% CI 0.78-0.99), bradycardia (RR 0.72, 95% CI 0.53-0.99), and hypertension (RR 0.70, 95% CI 0.54-0.91). SGLT2is were not significantly associated with 18 types of reproductive diseases, e.g., adenomyosis, endometrial hyperplasia, and metrorrhagia. Although SGLT2is were observed to have a significant association with a higher risk of uterine prolapse, the 95% CI of RR for this outcome was relatively wide. CONCLUSION: This meta-analysis confirms the benefits of SGLT2is against chronic congestive HF again; reveals the possible benefits of SGLT2is against acute HF, myocardial infarction, arrhythmias, and hypertension; and identifies that SGLT2is are safe in general for the reproductive system.

Bacterial diversity and its correlation with sensory quality of two types of zha-chili from Shennongjia region, China.

In the Shennongjia region of China, two types of zha-chili with distinct flavors exist: the first type (P zha-chili) uses a significant amount of chili pepper but no potato, while the other (PP zha-chili) contains a smaller amount of chili pepper but a proportion of potato. In order to investigate the bacterial diversity and sensory properties of these two types of zha-chili, this study employed a combination of amplicon sequencing, culture-based methods, and sensory technology. The results of the study showed statistically significant differences (P < 0.05) in bacterial diversity and communities between the two types of zha-chili. In particular, four dominant lactic acid bacteria (LAB) genera - Lactiplantibacillus, Lactococcus, Leuconostoc, and Weissella - were significantly enriched in PP zha-chili. The findings suggest that the proportions of chili pepper and potato can influence the bacterial diversity and content of LAB, with a higher proportion of chili pepper potentially inhibiting the growth of harmful species within the Enterobacteriaceae family. The study also used culture-based methods to identify the most dominant bacteria in the zha-chili samples as Lactiplantibacillus plantarum group, Companilactobacillus alimentarius, and Lacticaseibacillus paracasei. Correlation analysis indicated that LAB likely plays a significant role in shaping the aroma profile of zha-chili, with Levilactobacillus, Leuconostoc, Lactiplantibacillus, and Lactococcus showing correlation with E-nose sensory indices. However, these LAB were not significantly correlated with the taste properties of zha-chili. The study provides new insights into the influence of chili pepper and potato on the microbial diversity and flavor properties of zha-chili, and also presents potential LAB isolates for future research on zha-chili.

CircDNAJC11 interacts with TAF15 to promote breast cancer progression via enhancing MAPK6 expression and activating the MAPK signaling pathway.

BACKGROUND: Breast cancer (BC) is a common malignant tumor in women worldwide. Circular RNA (circRNA) has been proven to play a critical role in BC progression. However, the exact biological functions and underlying mechanisms of circRNAs in BC remain largely unknown. METHODS: Here, we first screened for differentially expressed circRNAs in 4 pairs of BC tissues and adjacent non-tumor tissues using a circRNA microarray. Functionally, gain- and loss-of-function experiments in vitro and in vivo showed that circDNAJC11 promoted BC cell proliferation, migration, invasion, and tumor growth. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization assays, and rescue experiments were executed. RESULTS: We found that circDNAJC11 was significantly upregulated in triple-negative breast cancer tissues and cells. Clinical data revealed that the high expression of circDNAJC11 was closely correlated with a poor prognosis of BC patients and could be an independent risk factor for BC prognosis. Functionally, gain- and loss-of-function experiments in vitro and in vivo showed that circDNAJC11 promoted BC cell proliferation, migration, invasion, and tumor growth. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization assays, and rescue experiments were executed. We demonstrated that circDNAJC11 combined with TAF15 to promote BC progression via stabilizing MAPK6 mRNA and activating the MAPK signaling pathway. CONCLUSIONS: The circDNAJC11/TAF15/MAPK6 axis played a crucial role in the progression and development of BC, suggesting that circDNAJC11 might be a novel biomarker and therapeutical target for BC.

Hypoxia-inducible CircPFKFB4 Promotes Breast Cancer Progression by Facilitating the CRL4DDB2 E3 Ubiquitin Ligase-mediated p27 Degradation.

Hypoxic microenvironment and circular RNAs (circRNAs) have shown critical implications in breast cancer (BC) progression. However, the specific functions and underlying mechanisms of circRNAs in BC under hypoxia remain largely unknown. We first screened for differentially expressed circRNAs in normoxic and hypoxic MCF-7 cells using circRNA microarray. A novel hypoxia-induced circRNA, circPFKFB4, was identified. Clinical investigation showed that circPFKFB4 was highly expressed in BC tissues and cell lines, and its overexpression was positively correlated with the advanced clinical stage and poor prognosis of BC patients. Functionally, circPFKFB4 promoted the proliferation of BC cells both in vitro and in vivo. Mechanistically, HIF1α bound to hypoxia response elements in the promoter region of the PFKFB4 gene to facilitate the biogenesis of circPFKFB4 under hypoxia. Hypoxia-induced circPFKFB4 directly bound to both DDB1 and DDB2 and promoted the CRL4DDB2 E3 ubiquitin ligase assembly, resulting in p27 ubiquitination and BC progression under hypoxia. Our findings revealed a novel interaction between circPFKFB4 and the CRL4DDB2 E3 ubiquitin ligase, suggesting that circPFKFB4 might serve as a promising biomarker and therapeutic target for BC.

Effectiveness of the combination of workshops and flipped classroom model to improve tube fixation training for nursing students.

BACKGROUND: Tube indwelling is a key procedure in modern medicine. Careful tube setup is necessary to prevent unplanned extubation. The training for tube fixation is time- and resource-consuming, and optimal modes of training are currently being sought. Previous studies have compared workshops and flipped classroom models separately using conventional teaching strategies, but no study has examined a combination of both teaching models in nursing training. AIM: To compare the effectiveness of workshops vs workshops combined with the flipped classroom model for improving tube fixation training for nursing students. METHODS: This was a prospective cohort study. In this study, 149 nurses who joined our hospital in 2019 underwent training using workshops combined with the flipped classroom model (experimental group), while 159 nurses who joined the hospital in 2018 received only workshop-based training (control group). The combination of workshops with the flipped classroom training model was divided into two modules: pre-class and in-class training. The participation of nurses in the training activities, on-site assessment of training, nurses' evaluation of their training, and related indicators of tube quality management were evaluated. RESULTS: The average age of nurses in the control group was 22.94 ± 0.94 years and that of nurses in the experimental group was 25.42 ± 3.23 years (P < 0.01). The qualified rate of after-class assessments for the experimental and control groups was 100.00% (average score: 94.01 ± 2.78 points) and 91.82% (average score: 84.24 ± 2.94 points), respectively (P < 0.01). Most nurses in the experimental group completely agreed that the combined training was helpful to cultivate clinical thinking and independent learning ability and to master knowledge of tube fixation. In addition, the training content within the pre-class teaching video, pre-class tube atlas, pre-class main instructor guidance, in-class demonstration, and in-class practice was very informative. The experimental group had higher evaluation scores than the control group (4.88 ± 0.38 vs 4.67 ± 0.64; P < 0.01). Comparison of tube quality management before and after training in 2018 to 2019 revealed that the unplanned ureteral tube removal rate dropped from 0.25‰ to 0.06‰, the unplanned chest tube removal rate dropped from 1.07‰ to 0.78‰, and the unplanned gastric tube removal rate dropped from 0.36‰ to 0.17‰. The incidence rate of pressure ulcers caused by the tube decreased from 0.78‰ to 0.45‰. CONCLUSION: The combination of workshop and flipped classroom training is effective in improving tube fixation training of nurses, cultivating nurses' active learning abilities and clinical thinking, and improving the safety of the procedure.

Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10.

BACKGROUND: Hypoxia has long been considered as a hallmark of solid tumors and is closely associated with tumor progression. Circular RNAs (circRNAs) have been identified as a critical modulator in various cancers. However, the connections between hypoxia and circRNAs are largely unknown. METHODS: Here, we investigated the expression profile of circRNAs in breast cancer (BC) MCF-7 cells under hypoxia and normoxia using microarray. We identified a novel hypoxia-responsive circRNA named circWSB1, whose expression pattern, potential diagnostic value and prognostic significance were assessed by qRT-PCR and in situ hybridization. Loss- and gain-of-function investigations in vivo and in vitro were performed to determine the biological functions of circWSB1. Mechanistically, chromatin immunoprecipitation and dual luciferase reporter assays were carried out to analyze the biogenesis of circWSB1. Furthermore, biotin-labeled RNA pull-down, mass spectrometry, RNA immunoprecipitation, fluorescent in situ hybridization, RNA electrophoretic mobility shift, deletion-mapping, co-immunoprecipitation assays and rescue experiments were applied to investigate the interaction between circWSB1 and Ubiquitin-specific peptidase 10 (USP10) as well as the relationship between USP10 and p53. RESULTS: We found that the expression of circWSB1 was significantly upregulated in BC tissues and correlated with poor clinical outcomes, which might serve as an independent prognostic factor for BC patients. Ectopic expression of circWSB1 promoted the proliferation of BC cell in vitro and in vivo. Mechanistically, circWSB1 was transcriptionally upregulated by HIF1α in response to hypoxia and could competitively bind to deubiquitinase USP10 to prevent the access of p53 to USP10 in BC cells, leading to degradation of p53 and tumor progression of BC. CONCLUSIONS: Taken together, our findings disclose a novel mechanism that hypoxia-inducible circWSB1 could interact with USP10 to attenuate USP10 mediated p53 stabilization and promote the progression of BC, providing an alternative prognostic biomarker and therapeutic target for BC.

Adsorption performance of antimony by modified iron powder.

Antimony pollution resulting from industrial production is a great threat to the environment, ecology and the human body. Zero-valent iron powder is low-cost and easy to obtain. Nevertheless, the lower adsorption capacity limits its application when it is used as an adsorbent. In the present study, ball-milling and acid modification were developed to change its surface characteristics and γ-Fe2O3, γ-FeOOH and Fe3O4 were obtained after treatment, which promoted its adsorption capacity. Compared with the raw iron powder, the adsorption capacities for Sb(iii) and Sb(v) using the modified material were increased from 12.93 mg g-1 and 5.47 mg g-1 to 17.96 mg g-1 and 10.58 mg g-1, respectively. The study showed that the experimental data fitted the Langmuir model and the pseudo-first-order kinetic model better; the adsorption process was monolayer and chemically controlled at pH 5.0 ± 0.2. XPS and FT-IR analysis showed that Fe-O-Sb bonds arose during the adsorption process. The effect of pH on the adsorption capacity was also studied and the pH affected the adsorption of Sb(v) more than the adsorption of Sb(iii). In addition, the modified iron powder presented better efficiency when applied to the removal of low levels of antimony in drinking water. Based on the increase of adsorption capacity and low cost, iron powder should be a promising adsorbent for aqueous antimony removal.