ology. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of genes whose products defend our cells for toxic and oxidative insults. Although NRF2 activation may reduce cancer risk by suppressing oxidative stress and tumor promoting inflammation, many cancers exhibit elevated NRF2 activity either due to mutations that disrupt the negative control of NRF2 activity or other factors. Importantly, NRF2 activation is associated with poor prognosis and NRF2 has turned out to be a key activator of cancer supportive anabolic metabolism. In this review, we summarize the diverse roles played by NRF2 in cancer focusing on metabolic reprogramming and tumor-promoting inflammation. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.OBJECTIVE To observe the restraining effect of IL-38 on inflammatory response in collagen-induced arthritis rats (CIA), and to explore the regulatory mechanism of SIRT1/HIF-1α signaling pathway. METHODS 40 SD rats were randomly divided into Control group, CIA group, CLL group and CLH group, with 10 rats in each group; CIA rat model was established; The effects of IL-38 on arthritis index, inflammatory response, osteogenic factor and angiogenic factor were observed by methods including  HE staining, ELISA, Immunohistochemical and immunofluorescence. Human synoviocytes were cultured in vitro, and SIRT1 inhibitors were added to detect the expression for relating factors of SIRT1/HIF-1α signaling pathway by Western blot. RESULTS IL-38 could alleviate CIA joint damage and restrain inflammatory response, up-regulate the expression of OPG in CIA rats and down-regulate the expression of RANKL and RANK; IL-38 could restrain the expression of VEGF, VEGFR1, VEGFR2 and HIF. Moreover, we found that IL-38 could upregulate the SIRT1 expression and down-regulate the HIF-1α, TLR4 and NF-KB p65 expression in CLL group and CLH group. The treatment of synoviocytes to simulate the CIA model and the treatment of SIRT1 inhibitors, we demonstrated that the inhibitory effect of IL38 on inflammatory factors as well as regulation of SIRT1/HIF-1α signaling pathway-related proteins were inhibited. CONCLUSION IL-38 can restrain the inflammatory response of CIA rats, promote the expression of osteogenic factors, inhibit neovascularization, and alleviate joint damage in rats. The mechanism may be related to the regulation of SIRT1/HIF-1α signaling pathway. Copyright 2020 The Author(s).BACKGROUND The increasing incidence of skin cancers poses a burden to health care systems. General practitioners (GPs) play an important role in triaging these diseases and referring relevant patients to specialists. It is challenging to distinguish benign from malignant skin lesions, and GPs may benefit from diagnostic support from teledermoscopy (TD). OBJECTIVES To assess whether the introduction of TD in general practice was feasible and might reduce the number of unnecessary referrals to specialists and to assess the diagnostic accuracy and confidence of participating GPs. METHODS Fifty general practices in Southern Denmark participated. Adult patients presenting to their GP with suspected skin cancer could be included. Images including dermoscopy were taken by the GP and sent for evaluation by specialized dermatologists at a university hospital. Patients were simultaneously referred for a face-to-face evaluation at the university hospital. Diagnoses proposed by the GPs and by TD were compared to the final diagnoses obtained by histopathology or, if not available, face-to-face evaluation. RESULTS Five hundred and nineteen patients with 600 suspected skin cancers were included. The final diagnosis was benign in 72.3%. The photo quality was good or fair in 90.5%. GPs reported uncertainty about their diagnoses in 41.5% of cases. The GPs’ positive predictive values for any malignancy and for malignant melanoma were 49.5% and 26.3%, respectively. On evaluation by TD, 31.5% of lesions did not need further in-person assessment. CONCLUSION Useful images of suspicious skin lesions were obtained from general practice, and GPs could benefit from TD to improve their diagnostic accuracy and confidence. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.The disease risk score (DRS) can be used to summarize a potentially large vector of covariates with a single variable. The DRS can be used to control for confounding by the covariates that went into estimation of the DRS and obtain a standardized estimate of an exposure’s effect on disease. However, to-date, literature on the DRS has not addressed analyses that focus on estimation of survival or hazard functions, which are common in epidemiological analyses of cohort data. Here, we propose a method for standardization of hazard ratios using the DRS in longitudinal analyses of the association between a binary exposure and outcome. This approach to handling a potentially large set of covariates through a model-based approach to standardization may provide a useful tool for cohort analyses of hazard ratios, and may particularly well-suited to settings where an exposure propensity score is difficult to model. Simulations are used to illustrate the approach, and an empirical example is provided. © The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Rearrangements involving the mixed lineage leukemia (MLL) gene are common adverse prognostic factors of pediatric acute lymphoblastic leukemia (ALL). Even allogeneic hematopoietic stem cell transplantation does not improve the outcome of ALL cases with some types of MLL rearrangements. The aim of the present study was to identify the co-expressed genes that related to MLL rearrangement (MLL-r) and elucidate the potential mechanisms of how MLL-r and their partner genes lead to leukemogenesis. Gene co-expression networks were constructed using the gene expression data and sample traits of 204 pretreated pediatric ALL patients, and co-expression modules significantly related to the MLL-r were screened out. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis of the module genes were performed. Hub genes were identified and their expression levels were analyzed in samples with or without MLL-r and the results were validated by an independent investigation. Furthermore, the relationships between the hub genes and sample traits were analyzed. In total, 21 co-expression modules were identified. The green module was positively correlated with MLL-r. PROM1, LGALS1, CD44, FUT4 and HOXA10 were identified as hub genes, which were involved in focal adhesion, calcium-dependent phospholipid binding, connective tissue development and transcriptional misregulation in cancer. The expression levels of the five hub genes were significantly increased in MLL-r samples, and the results were further validated. PROM1, LGALS1, CD44 and HOXA10 were positively related to the leukocyte count. These findings might provide novel insight regarding the mechanisms and potential therapeutic targets for pediatric ALL with MLL-r. © 2020 The Author(s).Ischemic heart disease is the main cardiovascular complication of diabetes patients which mainly caused by oxidative stress. DJ-1 is the key regulator for myocardial protection through inhibiting PTEN and activating Akt. This research is to investigate whether the antioxidant N-acetylcysteine (NAC) could alleviating diabetic myocardial ischemia reperfusion (I/R) injury by the protective molecule DJ-1. DJ-1 in rat myocardial H9c2 cells and cardiac tissue was respectively knocked down by siRNA and adeno-associated virus (AAV). From this study, it could be found that compared with high glucose (HG)-normal (N)/DM group, hypoxia reoxygenation (H/R) or I/R injury can aggravate oxidative stress injury and apoptosis rate of myocardial cells, inhibit the expression of Bcl-2, activate the BAX and cleaved caspase-3(c-caspase-3) protein and PTEN/Akt pathway. However, in the groups of HG-N, DM, HG-N+I/R and DM+I/R, NAC can significantly reduce oxidative stress injury and apoptosis rate of myocytes, promote the Bcl-2 and DJ-1 molecules, inhibit BAX and c-caspase-3 protein and PTEN/Akt pathway. Compared with HG-N+I/R+NAC and DM+I/R+NAC groups, the oxidative stress injury, apoptosis rate of myocardial cells and heart tissues increased after the knockdown of DJ-1, the expression of Bcl-2 and DJ-1 were inhibited, the BAX and c-caspase-3 expression was increased, and PTEN/Akt pathway was activated. Taken together, the findings suggest that NAC can reduce ischemia reperfusion injury in diabetic myocardium by up-regulating the PTEN/Akt pathway through the level of DJ-1. Copyright 2020 The Author(s).The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr kinase that comprises two complexes, termed mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1 phosphorylates S6K1 at Thr 389, whereas mTORC2 phosphorylates AKT at Ser 473 to promote cell growth. As the mTOR name implies it is the target of natural product called rapamycin, a clinically approved drug used to treat human disease. Short-term rapamycin treatment inhibits the kinase activity of mTORC1 but not mTORC2. However, ATP-competitive catalytic mTOR inhibitor Torin1 was identified to inhibit the kinase activity of both mTORC1 and mTORC2. Here, we report that H89 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide), a well-characterized ATP-mimetic kinase inhibitor, renders the phosphorylation of S6K1 and AKT resistant to mTOR inhibitors across multiple cell lines. Moreover, H89 prevented the dephosphorylation of AKT and S6K1 under nutrient depleted conditions. PKA and other known H89-targeted kinases do not alter the phosphorylation status of S6K1 and AKT. Pharmacological inhibition of some phosphatases also enhanced S6K1 and AKT phosphorylation. These findings suggest a new target for H89 by which it sustains the phosphorylation status of S6K1 and AKT, resulting in mTOR signaling. Copyright 2020 The Author(s).Host-defense antimicrobial peptides (AMPs) from amphibians are usually considered as one of the most promising next-generation antibiotics because of their excellent antimicrobial properties and low cytotoxicity. In the present study, one novel Brevinin-1 type peptide, Brevinin-1GHd, was isolated and characterized from the skin secretion of the frog, Hylarana guentheri. Brevinin-1GHd was found to possess a wide range of antimicrobial activity through penetrating the bacterial membrane within a short time while showing low hemolysis at bactericidal concentrations, even against the resistant strains. It also inhibited and eradicated biofilms that are thought to be closely related to the rise in resistance. Meanwhile, Brevinin-1GHd exhibited wide-spectrum anti-proliferation activity toward human cancer lines. Taken together, these results indicate that Brevinin-1GHd with its excellent antimicrobial and anticancer activities is a promising candidate for a novel antibiotic agent, and study of its structure-activity relationships also provided a rational template for further research and peptide analog design.