There is an increasing international focus to understand and quantify the potential ecological risks of low-frequency underwater sounds produced from anthropogenic activities (e.g., commercial shipping, dredging, construction, and offshore energy production). For dredge operations, a risk-based approach has been proposed for identifying, assessing, and managing risks; however, specific details of the framework and demonstration of the approach are lacking. Thus, the goal of this study was to provide a practical, concise, and reliable framework for assessing the effects of dredging sounds on aquatic life. The specific objectives were to 1) further specify a risk-assessment approach for assessing underwater sounds from dredging operations, 2) demonstrate the utility of the approach in practice using a case study, and 3) document the strengths and challenges of the approach. The risk framework was adapted for underwater sounds to include a project formulation step, an analysis step to analyze and assess exposureght. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. METHOD This was an investigator-initiated multicenter prospective intervention study in which ipragliflozin (50 mg) was administered once daily and glycemic control, estimated glomerular filtration rate (eGFR) and adverse events were evaluated after 4, 12-108 weeks of treatment. RESULT There were 407 cases subject to analysis. In the estimated glomerular filtration rate (eGFR) ≥ 90 group and eGFR ≥60 300 group, and the eGFR less then 60, UACR less then 300 group, revealed a greater reduction in eGFR in the former (-5.4 ± 2.4 vs 3.3 ± 1.1) at 12 weeks and maintained to 104 weeks. In any group, eGFR did not significantly decrease until 104 weeks compared to 4 weeks. UACR after 52 weeks and after 104 weeks was significantly decreased compared to baseline in the eGFR ≥ 90 group. CONCLUSIONS Ipragliflozin lowers eGFR and corrects hyperfiltration in cases with high eGFR (eGFR ≥60). 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%). 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. This article is protected by copyright. All rights reserved.The role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137-modified ECs (CD137-Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti-CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo. CD137-Exo efficiently induced the progression of AS in ApoE-/- mice. CD137-Exo increased the proportion of Th17 cells both in vitro and vivo. The IL-6 contained in CD137-Exo which is regulated by Akt and NF-КB pathway was verified to activate Th17 cell differentiation. IL-17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1) and E-selectin in the supernatants of ECs after IL-17 treatment was dramatically increased. CD137-Exo promoted the progression of AS and Th17 cell differentiation via NF-КB pathway mediated IL-6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.Although the enemy release hypothesis forms the theoretical basis for classical (=importation) biological control of invasive pests, its core assumptions are not always examined. This could contribute to unrealistic expectations for some biological control programs. In this paper we examine the assumptions that (i) enemy release has contributed to the invasive nature of four exotic pentatomids in North America; and (ii) classical biological control with egg parasitoids has been or will be successful in reducing populations of these pests below economically significant levels. First, we review the history of biological control programs against invasive stink bugs to highlight the variable and controversial levels of success of introducing egg parasitoids against stink bugs. Then, we use simple stage-structured matrix models to demonstrate that it may be easy to overestimate the contribution of egg parasitism alone to a reduction in stink bug population growth. Finally, we discuss what realistic expectations might be for success of biological control against invasive stink bugs using egg parasitoids in the context of integrated pest management programs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.