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Prostate cancer (PCa) constitutes a highly common and lethal disease that impacts males globally. However, the specific molecular pathways responsible for its development are still unknown. Therefore, revealing the molecular regulators that contributed to the progression of PCa is pivotal for developing unique management strategies. Through comprehensive bioinformatics analysis of multiple public gene databases, we thoroughly investigated COL10A1 expression level, clinical significance, co‐expressed genes and signalling pathways in PCa. COL10A1 and INHBA expression level was assessed in clinical PCa specimens using RT‐qPCR, Western blotting and immunohistochemistry. A combination of experimental techniques, including CCK‐8 assay, colony formation, flow cytometry, Transwell, wound‐healing, immunoprecipitation assays and rescue study, was utilised to examine the fundamental molecular pathways of COL10A1's action across PCa. The COL10A1 expression was significantly elevated in PCa, and its upregulation has been connected with tumour aggressiveness and a weak predictive outcome in subjects. The current investigation revealed that regulation of COL10A1 expression, either by upregulation or downregulation, resulted in sequential augmentation or suppression of PCa cell progression, migration and invasion. Mechanistically, COL10A1 was manifested to directly interact with INHBA and facilitate PI3K and AKT phosphorylation pathways within PCa cells and mouse models. The results of our study offer new perspectives on the tumorigenic role of COL10A1 in PCa and its interactions with INHBA may play important roles in PCa progression. [ABSTRACT FROM AUTHOR]

With increasing criticism on measuring executive performance based primarily on Total Shareholder Return (TSR), some academics and practitioners have revived discussions on using Economic Value Added (EVA) as an alternative. But if EVA failed to gain traction over the past two decades, is there any new evidence for it or different approaches to better implement it in corporate settings? In this study, we start by confirming EVA‐related metrics' significant positive relationships with long‐term TSR in the Australian market. Our empirical findings also address EVA's major drawback – too much complexity arising from accounting adjustments. Our results suggest that accounting adjustments are generally not necessary, and efforts should be re‐directed to designing direct and intuitive plan mechanisms. In addition, we develop a pseudo environment to illustrate EVA's managerial benefits and potential to cultivate sustainable growth. To study this influence, we leverage capital‐based simulation techniques and mimic executive decision making under different performance measurement conditions, which was typically only discussed in a qualitative or theoretical sense. We find that EVA‐related metrics naturally induce long‐term, strategic and sustainable decision making without limiting executives to overly focus on short‐term profitability. This simulation approach not only provides quantitative evidence, but also gives practitioners in different market environments an expandable and scalable pseudo framework to test the effect of different incentive plans and inform performance target setting, a useful but often overlooked feature in, for instance, the Australian market, where data is relatively scarce. [ABSTRACT FROM AUTHOR]

Background: Glycyrrhiza is one of the most widely used traditional Chinese medicines in China. Its main bioactive ingredient glycyrrhizic acid (GA) has the potential to be used as a treatment for atopic dermatitis (AD) because it has similar actions to steroids, but with relatively few side effects. Aims: The objective of this study was to explore the potential mechanisms of GA on AD mice model. Methods: Calcipotriol, a vitamin D3 analogue (MC903) was applied topically to establish AD mouse model. Mice were intraperitoneally administrated with 2 mg/kg dexamethasone (DEX), 25 or 50 mg/kg GA for 15 days. After mice were executed, skin tissues were collected and detected the expression levels of IL‐4, IFN‐γ, TNF‐α and thymic stromal lymphopoietin (TSLP). The percentages of Th1, Th2, Th17, langerhans cells (LCs) in draining lymph nodes (dLNs) were measured by flow cytometry. Results: Our data demonstrated that GA improved the symptoms of AD by exerting anti‐inflammatory and anti‐allergic functions in vivo. We found that GA treatment decreased the level of total IgE in serum, suppressed ear swelling, reduced the infiltration of mast cells in skin lesions and decreased expressions of IL‐4, IFN‐γ, TNF‐α and TSLP in skin lesions. Furthermore, our experimental results demonstrated that GA suppressed the Th1/Th2/Th17‐immune responses in the dLNs, inhibited the migration of LCs in dLNs. Conclusions: In conclusion, our findings suggested potential therapeutic effects of GA against MC903‐induced AD‐like skin lesions in mice. [ABSTRACT FROM AUTHOR]

The proinflammatory property of cisplatin is potentially destructive and contributes to the pathogenesis of acute kidney injury (AKI). The role and upstream regulatory mechanism of histone acetyltransferase 1 (HAT1) in acute kidney inflammation are still unknown. We performed RNA sequencing to filter differentially expressed microRNAs (miRNAs) in the kidney tissue of mice with AKI induced by cisplatin and ischemia‐reperfusion. Here, we found that miR‐486‐5p was upregulated and that the expression of HAT1 was reduced in AKI mouse models and injured human renal proximal tubular epithelial cell (HK‐2) model induced by cisplatin. miR‐486‐5p is implicated in cisplatin‐induced kidney damage in vivo. Bioinformatics analysis predicted a potential binding site between miR‐486‐5p and HAT1. The Luciferase reporter assay and Western blot confirmed that miR‐486‐5p directly targeted the 3′‐untranslated region of HAT1 mRNA and inhibited its expression in the cytoplasm of HK‐2 cells. In the in vitro study, inhibiting miR‐486‐5p reduced apoptosis, and the expression of proinflammatory mediators was induced by cisplatin in HK‐2 cells. Simultaneously, the downregulation of miR‐486‐5p inhibited the activation of the toll‐like receptor 4 (TLR4) and nuclear factor‐kappa B (NF‐κB). We further found that HAT1 could inhibit apoptosis and the activation of cisplatin on the TLR4/NF‐κB pathway and that the upregulation of miR‐486‐5p reversed this effect. Therefore, the upregulation of miR‐486‐5p targeting HAT1 promoted the cisplatin‐induced apoptosis and acute inflammation response of renal tubular epithelial cells by activating the TLR4/NF‐κB pathway, providing a new basis to highlight the potential intervention of regulating the miR‐486‐5p/HAT1 axis. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common form of kidney cancer, with a high recurrence rate and metastasis capacity. Circular RNAs (circRNAs) have been suggested to act as the critical regulator in several diseases. This study is designed to investigate the role of circCSNK1G3 on RCC progression. We observed a highly expression of circCSNK1G3 in RCC tissues compared with normal tissues. The aberrantly circCSNK1G3 promoted the tumour growth and metastasis in RCC. In the subsequent mechanism investigation, we discovered that the tumour-promoting effects of circCSNK1G3 were, at least partly, achieved by up-regulating miR-181b. Increased miR-181b inhibits several tumour suppressor gene, including CYLD, LATS2, NDRG2 and TIMP3. Furthermore, the decreased TIMP3 leads to the enhanced epithelial to mesenchymal transition (EMT) process, thus promoting the cancer metastasis. In conclusion, we identified the oncogenic role of circCSNK1G3 in RCC progression and demonstrated the regulatory role of circCSNK1G3 induced miR-181b expression, which leads to TIMP3-mediated EMT process, thus resulting in tumour growth and metastasis in RCC. This study reveals the promise of circCSNK1G3 to be developed as a potential diagnostic and prognostic biomarker in the clinic. And the roles of circ-CSNK1G3 in cancer research deserve further investigation. [ABSTRACT FROM AUTHOR]

The objective of this paper is to propose a novel deep learning methodology to gain pragmatic insights into the behavior of an insured person using unsupervised variable importance. It lays the groundwork for understanding how insights can be gained into the fraudulent behavior of an insured person with minimum effort. Starting with a preliminary investigation of the limitations of the existing fraud detection models, we propose a new variable importance methodology incorporated with two prominent unsupervised deep learning models, namely, the autoencoder and the variational autoencoder. Each model's dynamics is discussed to inform the reader on how models can be adapted for fraud detection and how results can be perceived appropriately. Both qualitative and quantitative performance evaluations are conducted, although a greater emphasis is placed on qualitative evaluation. To broaden the scope of reference of fraud detection setting, various metrics are used in the qualitative evaluation. [ABSTRACT FROM AUTHOR]

This study develops a numerical method to find optimal ergodic (long‐run average) dividend strategies in a regime‐switching model. The surplus process is modelled by a regime‐switching process subject to liability constraints. The regime‐switching process is modelled by a finite‐time continuous‐time Markov chain. Using the dynamic programming principle, the optimal long‐term average dividend payment is a solution to the coupled system of Hamilton–Jacobi–Bellman equations. Under suitable conditions, the optimal value of the long‐term average dividend payment can be determined by using an invariant measure. However, due to the regime switching, getting the invariant measure is very difficult. The objective is to design a numerical algorithm to approximate the optimal ergodic dividend payment strategy. By using the Markov chain approximation techniques, the authors construct a discrete‐time controlled Markov chain for the approximation, and prove the convergence of the approximating sequences. A numerical example is presented to demonstrate the applicability of the algorithm. [ABSTRACT FROM AUTHOR]

In white spruce (Picea glauca) protoplasts, abscisic acid (ABA) and optically pure ABA analogs induced expression of a reporter gene under regulation of a wheat ABA‐responsive promoter. A fusion of a 650 bp promoter fragment from the wheat Em gene promoter and the Escherichia coli uidA sequence encoding β‐glucuronidase (GUS) was linked in the plasmid pBM 113Kp. Expression of the Em‐uidA fusion varied among 6 white spruce genotypes. Protoplasts from 4‐day‐old embryogenic suspension cultures gave the highest GUS activity relative 10 other stages in the 7‐day growth cycle of suspension cultures. Racemic ABA [R.S‐(±)‐ABA] induced a significant increase of protoplast GUS activity over background at a concentration of 1 × 10−5M, but maximum GUS activity was found at 1 × 10−3M, ABA stereochemistry had a significant effect on gene expression. The natural isomer of ABA [S‐(+)‐ABA] was an effective inducer at a concentration as low as 1 × 10−7M, but a concentration of greater than 1 × 10−4M was required for induction by [R‐(—)‐ABA]. Moreover, analogs with the same configuration at C‐l1 as that of natural ABA were more effective for induction of expression from the Em‐uidA. insert at 1 × 10−4M than were their enamiomers. Plasnud pBI511. carrying the chloramphenicol acety] transferase (CAT) gene driven by the constitutively expressed, tandemly duplicated cauliflower mosaic virus 35S promoter, was co‐electroporated with pBM113Kp for monitoring Ihe influence of addition of exogenous ABA or ABA analogs on heterologous gene expression in protoplasts. CAT activity was not significantly affected by the presence or absence of ABA or the analogs used. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common form of kidney cancer, with a high recurrence rate and metastasis capacity. Circular RNAs (circRNAs) have been suggested to act as the critical regulator in several diseases. This study is designed to investigate the role of circCSNK1G3 on RCC progression. We observed a highly expression of circCSNK1G3 in RCC tissues compared with normal tissues. The aberrantly circCSNK1G3 promoted the tumour growth and metastasis in RCC. In the subsequent mechanism investigation, we discovered that the tumour-promoting effects of circCSNK1G3 were, at least partly, achieved by up-regulating miR-181b. Increased miR-181b inhibits several tumour suppressor gene, including CYLD, LATS2, NDRG2 and TIMP3. Furthermore, the decreased TIMP3 leads to the enhanced epithelial to mesenchymal transition (EMT) process, thus promoting the cancer metastasis. In conclusion, we identified the oncogenic role of circCSNK1G3 in RCC progression and demonstrated the regulatory role of circCSNK1G3 induced miR-181b expression, which leads to TIMP3-mediated EMT process, thus resulting in tumour growth and metastasis in RCC. This study reveals the promise of circCSNK1G3 to be developed as a potential diagnostic and prognostic biomarker in the clinic. And the roles of circCSNK1G3 in cancer research deserve further investigation., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)