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We thank Dr. Yang and colleagues for their attention to our article1,2 . And we appreciate their meaningful suggestions, which we highly agree with. With the purpose of letting the public know the overall situation of the clinical trials of new coronary pneumonia in China as soon as possible, we completed the data collection and brief analysis in a very short time. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Coronaviruses are common human viruses and include the severe acute respiratory syndrome coronavirus (SARS-CoV), the middle east respiratory syndrome coronavirus and the SARS-CoV-2. Coronaviruses mainly bind to transmembrane receptor proteins on the human cell membrane through spike proteins (S-proteins), thus releasing the RNA of the virus into the interior of the host cell to cause an infection. In this article, we discuss the mechanism and production of cyclodextrin-soluble angiotensin-converting enzyme 2 (CD-sACE2) inclusion compounds in the treatment of SARS-CoV-2 infections by blocking S-proteins. On the basis of the current research evidence, we believe that CD-sACE2 inclusion compounds have the potential to treat COVID-19. We hope that our article can provide a theoretical basis for later experiments. © 2020 Wiley Periodicals, Inc.Immune checkpoint inhibitors (ICIs) are nowadays widely used in clinical oncology treatment, and significantly improve the prognosis of cancer patients. However, overactivation of T cells and related signaling pathways caused by ICIs can also induce immune-related adverse effects (irAEs). Renal immune side-effects are relatively rare, but some are serious and fatal. Acute kidney injury (AKI), diagnosed mainly by percentage increases in serum creatinine (sCr), is the most common clinical manifestation, while acute tubulointerstitial nephritis (ATIN) is the main cause of ICI-related AKI. Urinalysis analysis and sediment evaluation, 24 hour urine protein and sCr are helpful in screening and monitoring renal irAEs. Multiple potential causes for AKI are involved during cancer therapy, and should be differentiated from the immune mechanisms of ICIs. Under these circumstances, a renal biopsy should be considered which is essential for clinical decision-making. Steroids are an effective treatment option for renal irAEs. Most patients who experience ICI-related ATIN achieve a partial or complete renal recovery with prompt diagnosis and treatment. Multidisciplinary collaborations of different specialists will improve the effectiveness and outcome in the management of ICI irAEs. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.Androgen deprivation therapy (ADT) is the main treatment strategy for men with metastatic prostate cancer (PC). However, ADT is associated with various metabolic disturbances, including impaired glucose tolerance, insulin resistance and weight gain, increasing risk of diabetes and cardiovascular death. Much remains unknown about the metabolic pathways and disturbances altered by ADT and the mechanisms. We assessed the metabolomic effects of ADT in the serum of 20 men receiving ADT. Sera collected before (baseline), 3 and 6 months after initiation of ADT was used for the metabolomics and lipidomics analyses. The ADT-associated metabolic changes were identified by univariable and multivariable statistical analysis, ANOVA, and Pearson correlation. We found multiple key changes. First, ADT treatments reduced the steroid synthesis as reflected by the lower androgen sulfate and other steroid hormones. Greater androgen reduction was correlated with higher serum glucose levels, supporting the diabetogenic role of ADT. Second, ADT consistently decreased the 3-hydroxybutyric acid and ketogenesis. https://www.selleckchem.com/products/Temsirolimus.html Third, many acyl-carnitines were reduced, indicating the effects on the fatty acid metabolism. Fourth, ADT was associated with a corresponding reduction in 3-formyl indole (a.k.a. indole-3-carboxaldehyde), a microbiota-derived metabolite from the dietary tryptophan. Indole-3-carboxaldehyde is an agonist for the aryl hydrocarbon receptor and regulates the mucosal reactivity and inflammation. Together, these ADT-associated metabolomic analyses identified reduction in steroid synthesis and ketogenesis as prominent features, suggesting therapeutic potential of restricted ketogenic diets, though this requires formal testing. ADT may also impact the microbial production of indoles related to the immune pathways. Future research is needed to determine the functional impact and underlying mechanisms to prevent ADT-linked comorbidities and diabetes risk. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.The polo-box domain (PBD) of PLK1 determines mitotic substrate recognition and subcellular localization. Compounds that target PLK1 selectively are required due to the tumor suppressor roles of PLK3. A structure-activity analysis of the PBD phosphopeptide binding motif has identified potent peptides that delineate the determinants required for mimicry by non-peptidic inhibitors and provide insights into the structural basis for the selectivity of inhibitors for the PLK1 PBD. Fragment-ligated inhibitory peptides (FLIPs) obtained through REPLACE have been optimized to enhance in vitro binding and a systematic analysis of selectivity for PLK1 vs 3 has been carried out for peptides and peptidomimetics. Furthermore, these more drug-like non-ATP competitive inhibitors had on target engagement in a cellular context as evidenced by stabilization of PLK1 in a thermal shift assay and by inhibition of the phosphorylation of TCTP, a target of PLK1. Investigation in cells expressing a mutant PLK1 showed that these are sensitive to PBD inhibitors but dramatically resistant to clinically investigated ATP competitive compounds. These results provide further validity of targeting the PBD binding site and progress towards PBD-inhibitors active against tumors resistant to ATP-inhibitors. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Serum lipid abnormalities (dyslipidemias) are major risk factors for cardiovascular disease in type 2 diabetes. The features of diabetic dyslipidemia are elevated plasma concentrations of triglyceride (TG)-rich lipoproteins (TRLs), small dense low-density lipoprotein cholesterol (sdLDL-C) and decreased plasma high-density lipoprotein cholesterol (HDL-C) concentration. This article is protected by copyright. All rights reserved.
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