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Background: The intriguing connection between selenium and cancer resembles a captivating puzzle that keeps researchers engaged and curious. While selenium has shown promise in reducing cancer risks through supplementation, its interaction with epigenetics in cervical cancer remains a fascinating yet largely unexplored realm. Unraveling the intricacies of selenium's role and its interaction with epigenetic factors could unlock valuable insights in the battle against this complex disease. Result: Selenium has shown remarkable inhibitory effects on cervical cancer cells in various ways. In in vitro studies, it effectively inhibits the proliferation, migration, and invasion of cervical cancer cells, while promoting apoptosis. Selenium also demonstrates significant inhibitory effects on human cervical cancer-derived organoids. Furthermore, in an in vivo study, the administration of selenium dioxide solution effectively suppresses the growth of cervical cancer tumors in mice. One of the mechanisms behind selenium's inhibitory effects is its ability to inhibit histone demethylases, specifically JMJD3 and UTX. This inhibition is observed both in vitro and in vivo. Notably, when JMJD3 and UTX are inhibited with GSK-J4, similar biological effects are observed in both in vitro and in vivo models, effectively inhibiting organoid models derived from cervical cancer patients. Inhibiting JMJD3 and UTX also induces G2/M phase arrest, promotes cellular apoptosis, and reverses epithelial-mesenchymal transition (EMT). ChIP-qPCR analysis confirms that JMJD3 and UTX inhibition increases the recruitment of a specific histone modification, H3K27me3, to the transcription start sites (TSS) of target genes in cervical cancer cells (HeLa and SiHa cells). Furthermore, the expressions of JMJD3 and UTX are found to be significantly higher in cervical cancer tissues compared to adjacent normal cervical tissues, suggesting their potential as therapeutic targets. Conclusions: Our study highlights the significant inhibitory effects of selenium on the growth, migration, and invasion of cervical cancer cells, promoting apoptosis and displaying promising potential as a therapeutic agent. We identified the histone demethylases JMJD3 and UTX as specific targets of selenium, and their inhibition replicates the observed effects on cancer cell behavior. These findings suggest that JMJD3 and UTX could be valuable targets for selenium-based treatments of cervical cancer. [ABSTRACT FROM AUTHOR]

Assessing the risk of water leakage within urban water distribution networks (UWDN) is crucial prior to implementing any control measures. Conducting a risk assessment facilitates the development of effective water leakage management plans. By comprehensively analyzing the probability and loss factors that contribute to the risk of leakage in UWDN, this paper presents an evaluation index system for pipeline leakage risk. This index system utilized both quantitative and qualitative data on influencing factors derived from an actual pipeline network. In order to determine the precise level of pipeline leakage risk, an index theory-based pipeline leakage risk evaluation model was established. This model consisted of a single-index measure function and a multi-index comprehensive measure vector. The combined weight of evaluation indices through game theory was used to determine the weight of each index, thereby minimizing the negative effects of a single weight determination method. A risk assessment model that evaluated the leakage risk of specific pipelines was constructed based on actual data from the water distribution network in a certain area of China. The analysis showed that the risk of pipeline leakage in this area was mainly classified as a third-level risk, which is consistent with the actual evaluation results obtained from field visits. [ABSTRACT FROM AUTHOR]

Introduction. Circadian rhythm is involved in multiple biological activities and implicated in cancer development. However, the role of circadian rhythm in head and neck squamous cell carcinoma (HNSCC) has not been fully interpreted yet. Herein, the present study set out to explore the significance of circadian regulator genes (CRGs) in HNSCC. Materials and Methods. The molecular landscape and clinical significance of 13 CRGs in HNSCC were explored based on The Cancer Genome Atlas (TCGA). The biological functions of PER3, a key CRG, were validated by cellular experiments. The correlation of CRGs with microenvironment, pathway activities, and prognosis was determined by bioinformatic algorithms. A novel circadian score was introduced to evaluate the circadian modification pattern of each patient and further validated in an independent cohort from the Gene Expression Omnibus (GEO) dataset. Results. CRGs presented high heterogeneity in HNSCC at both genomic and transcriptomic levels. Specifically, PER3 indicated a better prognosis and inhibited HNSCC cell proliferation. Moreover, HNSCC tissues displayed three circadian regulator patterns with distinct clinical outcomes, transcriptomic characteristics, and microenvironment features. Circadian score was an independent risk factor and exhibited excellent predictive efficiency in both the training cohort from the TCGA database and the validation cohort from the GEO database. Conclusions. CRGs played an indispensable role in HNSCC development. An in-depth exploration of circadian rhythm would improve the understanding of HNSCC carcinogenesis and confer novel insights for future clinical practices. [ABSTRACT FROM AUTHOR]

Background: Advanced glycation end product receptor (RAGE) acts as a receptor of pro-inflammatory ligands and is highly expressed in alveolar epithelial cells (AECs). Autophagy in AECs has received much attention recently. However, the roles of autophagy and RAGE in the pathogenesis of acute lung injury remain unclear. Therefore, this study aimed to explore whether RAGE activation signals take part in the dysfunction of alveolar epithelial barrier through autophagic death. Methods: Acute lung injury animal models were established using C57BL/6 and Ager gene knockout (Ager−/− mice) mice in this study. A549 cells and primary type II alveolar epithelial (ATII) cells were treated with siRNA to reduce Ager gene expression. Autophagy was inhibited by 3-methyladenine (3-MA). Lung injury was assessed by histopathological examination. Cell viability was estimated by cell counting kit-8 (CCK-8) assay. The serum and bronchoalveolar lavage fluid (BALF) levels of interleukin (IL)-6, IL-8 and soluble RAGE (sRAGE) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The involvement of RAGE signals, autophagy and apoptosis was assessed using western blots, immunohistochemistry, immunofluorescence, transmission electron microscopy and TUNEL test. Results: The expression of RAGE was promoted by lipopolysaccharide (LPS), which was associated with activation of autophagy both in mice lung tissues and A549 cells as well as primary ATII cells. sRAGE in BALF was positively correlated with IL-6 and IL-8 levels. Compared with the wild-type mice, inflammation and apoptosis in lung tissues were alleviated in Ager−/− mice. Persistently activated autophagy contributed to cell apoptosis, whereas the inhibition of autophagy by 3-MA protected lungs from damage. In addition, Ager knockdown inhibited LPS-induced autophagy activation and attenuated lung injury. In vitro, knockdown of RAGE significantly suppressed the activation of LPS-induced autophagy and apoptosis of A549 and primary ATII cells. Furthermore, RAGE activated the downstream STAT3 signaling pathway. Conclusion: RAGE plays an essential role in the pathogenesis of ATII cells injury. Our results suggested that RAGE inhibition alleviated LPS-induced lung injury by directly suppressing autophagic apoptosis of alveolar epithelial cells. [ABSTRACT FROM AUTHOR]

The p16INK4A is a multifunction gene that includes regulation of the cell cycle, apoptosis, senescence and tumor development. However, the effects of p16 in hydroquinone‐induced malignant transformation of TK6 cells remain unclear. The present study aimed to explore whether p16 loss facilitate malignant transformation in TK6 cells. The results demonstrated that p16/Rb signal pathway was suppressed in hydroquinone‐induced malignant transformation of TK6 cells. We further confirmed that p16 loss stimulated cell proliferation, and accelerated cell cycle progression in vitro and in vivo. The immunoblotting analysis indicated that p16 regulated cell cycle progression via Rb and p53. Therefore, we conclude that p16 is involved in HQ‐induced malignant transformation associated with suppressing Rb and p53 which resulting in accelerating the cell cycle progression. [ABSTRACT FROM AUTHOR]

Background. Sepsis induces the release of lipid mediators, which control both lipid metabolism and inflammation. However, the role of serum apolipoprotein A-V (ApoA5) in sepsis is poorly understood in pediatric patients. Methods. ApoA5 was screened from serum proteomics profile in lipopolysaccharide- (LPS-) treated mice for 2 h, 24 h, and controls. Then, we conducted a prospective pilot study, and patients with sepsis admitted to a pediatric intensive care unit (PICU) were enrolled from January 2018 to December 2018. Serum ApoA5 levels on PICU admission were determined using enzyme-linked immunosorbent assays (ELISA). Blood samples from 30 healthy children were used as control. The correlation of ApoA5 with the clinical and laboratory parameters was analyzed. Logistic regression analyses and receiver operating characteristic curve (ROC) analysis were used to investigate the potential role of serum ApoA5 as a prognostic predictor for PICU mortality in pediatric patients with sepsis. Results. A total of 101 patients with sepsis were enrolled in this study. The PICU mortality rate was 10.9% (11/101). Serum ApoA5 levels on PICU admission were significantly lower in nonsurvivors with sepsis compared with survivors (P = 0.009). In subgroup analysis, serum levels of ApoA5 were significantly correlated with sepsis-associated multiple organ dysfunction syndrome (MODS) (P < 0.001), shock (P = 0.002), acute kidney injury (AKI) (P < 0.001), acute liver injury (ALI) (P = 0.002), and gastrointestinal (GI) dysfunction (P = 0.012), but not respiratory failure, brain injury, and pathogenic species (all P > 0.05). Correlation analyses revealed significant correlations of serum ApoA5 with Ca2+ concentration. Remarkably, the area under ROC curve (AUC) for serum ApoA5 levels on PICU admission was 0.789 for prediction of PICU mortality with a sensitivity of 75% and a specificity of 84.5% at a threshold value of 822 ng/mL. Conclusions. Serum ApoA5 level is associated with sepsis-associated shock, AKI, ALI, GI dysfunction, or MODS in children. Moreover, the findings of the present study suggest a prognostic value of ApoA5 in children with sepsis, and lower serum ApoA5 than 822 ng/mL predicts worse outcome in pediatric sepsis. [ABSTRACT FROM AUTHOR]

Research interest in Chinese businesses in Africa has surged in recent years. While state-owned firms have attracted considerable attention regarding the motives of their investment, relatively few studies have examined the strategy of the state-owned Chinese firms and human resource management (HRM) implications. Similarly, the causes underlying the expansion of Chinese mining firms internationally and the effects of management are yet to be adequately addressed in the international management literature. This study fills these research gaps through the investigation of the international expansion motives of four state-owned mining firms, the strategy adopted to facilitate this expansion and the HRM implications. Drawing on institutional theory and data from 39 interviews with government officials, managers and Chinese expatriates, factors such as why and how different institutional actors interact with each other at the strategic and operational levels to shape the Chinese mining firms’ business opportunities and constraints are examined. The study shows the Chinese mining firms’ flexible and pragmatic approaches to building connections with various institutional actors in the host country. They also develop organizational capacity through joint ventures and acquiring human resources from the international market. The study contributes to the knowledge in the international management area, a field that has been dominated by the study of private firms, by revealing the strategies and management practices of the Chinese state-owned multinational firms in the mining sector. [ABSTRACT FROM PUBLISHER]