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In cases with low eGFR (eGFR≥30 less then 60), ipragliflozin has the possibility of increasing eGFR in cases with low eGFR and exerting a renoprotective effect. This article is protected by copyright. All rights reserved.Invited for this month’s cover is the group of Robert A. W. Dryfe at the University of Manchester in collaboration with William Blythe Ltd. (Lancashire). The image shows bees building a graphene-containing battery that powers an external circuit, depicted by a purple curve. This curve represents a cyclic voltammogram, specifically of copper oxide during a charge/discharge cycle in a Li-ion half-cell, as presented in the article. The use of bees has both scientific and geographic significance. For the former, bees are assisting in building the honeycomb-like hexagonal graphene lattice, just as they do in nature. Geographically, bees are symbolic to the locations of both collaborators on this project, the University of Manchester and William Blythe (Lancashire). The Full Paper itself is available at 10.1002/cssc.201902784. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Two series of carbazole analogs of 8-methoxy- N -substituted-9 H -carbazole-3-carboxamides (series-1) and carbazolyl substituted rhodanines (series-2) were synthesized through facile synthetic routes. All the final compounds from these two series were evaluated for their preliminary in vitro antifungal and antibacterial activity against four fungal ( Candida albicans , Cryptococcus neoformans , Cryptococcus tropicalis and Aspergillus niger ) and four bacterial ( Staphylococcus aureus , Bacillus subtilis , Escherichia coli and Pseudomonas aeruginosa ) strains, respectively. Among the tested compounds, 6d , 6e and 6f (series-1) displayed promising antifungal and antibacterial activity, especially against C. neoformans and S. aureus. In addition, compound 6f displayed notable antimicrobial activity (MIC 6.25 µg/mL) against clinical isolates of C. albicans and C. neoformans (MIC 12.5 µg/mL). From the second series, 15f , 15g , 15i and 16f exhibited significant antifungal and antibacterial activity, especially against C. neoformans and S. aureus . The most active compound 15i displayed a prominent antimicrobial activity against C. neoformans (MIC 3.125 µg/mL) and S. aureus (MIC 1.56 µg/mL), respectively. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The cytochrome P450 family is composed of hemeproteins involved in the metabolic transformation of endogenous and exogenous substances. The CYP2D6 enzyme is responsible for the metabolism of approximately 25% of clinically used drugs and is mainly expressed in the liver. The CYP2D6 gene is known to have a large number of Single Nucleotide Polymorphisms (SNPs) and the majority of them do not present clinical consequences. Nevertheless, these variations could modify the CYP2D6 enzyme’s function, resulting in poor metabolizing or ultra-extensive metabolizing phenotypes, when metabolism is slower or accelerated, respectively. Currently, there are several computational tools for predicting functional changes caused by genetic variations. Here we evaluated the predictive power of 20 web servers using a data set of 37 CYP2D6 missense SNPs (2 neutral and 35 deleterious) previously reported in literature with enzymatic assays with the purified protein. The results suggest that the most appropriate tools for CYP2D6 SNP prediction are SDM and PoPMuSiC, which could aid in the classification of novel missense SNPs in this gene, providing the identification of mutations potentially associated with drug metabolism and pointing new directions for precise medicine. This article is protected by copyright. All rights reserved.Glioblastomas are the most aggressive type of brain tumour, with poor prognosis even after standard treatment such as surgical resection, temozolomide and radiation therapy. The overexpression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in glioblastomas is recognized as an important treatment target. Thus, an urgent need regarding glioblastomas is the development of a new, suitable agent that may show potential for the inhibition of extracellular signal-regulated kinase (ERK)/NF-κB-mediated glioblastoma progression. Imipramine, a tricyclic antidepressant, has anti-inflammatory actions against inflamed glial cells; additionally, imipramine can induce glioblastoma toxicity via the activation of autophagy. However, whether imipramine can suppress glioblastoma progression via the induction of apoptosis and blockage of ERK/NF-κB signalling remains unclear. The main purpose of this study was to investigate the effects of imipramine on apoptotic signalling and ERK/NF-κB-mediated gline and John Wiley & Sons Ltd.INTRODUCTION Hyperthyroidism (HT) has been associated with not insignificant rates of thyroid malignancy. There are no current specific guidelines that suggest routine pre-operative imaging for thyroid nodules in patients with Grave’s disease. We therefore performed a systematic review assessing rates of thyroid malignancy in patients undergoing surgery for different causes of HT Grave’s disease (GD), toxic adenoma (TA) and toxic multinodular goitre (TMNG). METHODS Major databases (MEDLINE, PubMed and the Cochrane library) were searched to identify eligible studies. RESULTS After searching and appraising, 33 papers were found to be eligible for analysis. The mean overall rate of malignancy was 8.5% (range 0.8% to 32.4%). The mean rates based upon histological subtype were as follows papillary thyroid cancer (PTC) 3.1% (range 0% to 13.2%), micro-papillary carcinoma (mPTC) 5.1% (range 0% to 16.9%) and follicular thyroid cancer (FTC) 0.8% (range 0% to 4.4%). In those patients who had pre-operative imaging, mean malignancy rates were higher in patients with pre-identified nodules (19.8%) compared to those without any nodules (8.7%). selleck compound Mean rates were lower in patients with GD/ diffuse goitre (5.9%) compared to patients with TA (6.5%) and TMNG (12%). CONCLUSION HT is associated with notable rates of thyroid cancer, although the mechanisms for this are not clear. The presence of nodules increases this risk. This review raises the question for considering pre-operative assessment of nodules in all patients undergoing surgery for HT, in order to correctly assess and evaluate any patients with suspected concurrent thyroid malignancy, before proceeding with surgery. 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