Notes

C-H Electrophilic (phenylsulfonyl)difluoromethylation regarding (hetero)arenes having a recently made reagent.
We conclude that intravenous ketamine dosing in rats should not use the same mg-kg-1-hr-1 dose for all rats, but take into account the strong allometric relationship between dose and rat weight. There is an advantage in using smaller doses in order to prevent unnecessary depression of neural responses.Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders which affects the hippocampus and cortical neurons leading to impairment of cognitive ability. Treatment of AD depends mainly on acetylcholinesterase inhibitors, however, a novel therapeutic approach is introduced based on the maintenance of neuronal viability and functionality exerted through neurotrophic factors. In the current study, Ulmus pumila L. leaves alcoholic extract was investigated for its neuroprotective activity in AlCl3-induced AD in rats. Rats were orally treated with AlCl3 (17 mg/kg) for 4 weeks followed by U. pumila extract (150 mg/kg b.wt.) for another 6 weeks. Treatment of neuro-intoxicated rats with U. pumila extract resulted in a significant regulation in neurotrophic factors; brain derived neurotrophic factor and transforming growth factor-β and pro-inflammatory cytokine; TNF. It also induced an elevation in serum levels of monoamine neurotransmitters; norepinephrine, dopamine and serotonin and a decline in brain acetlycholinesterase activity. U. pumila extract also showed potent antioxidant activity as indicated by the declined malondialdehyde and elevated reduced glutathione, catalase and super oxide dismutase levels in AD rats' brains. Histological improvement was detected in the cerebral cortex, the hippocampus and striatum of the treated rats. The phytochemical analysis of U. pumila extract revealed high contents of flavonoids and phenolics and the major compounds were isolated and chemically characterized. Additionally, U. pumila extract and the isolated compounds exerted a prominent activity in in-vitro acetylcholinesterase inhibition assay with kaempferol-3-O-β-glucoside being the most potent compound showing IC50 of 29.03 ± 0.0155 μM. A molecular docking study indicated high affinity of kaempferol-3-O-β-robinobioside on acetylcholine esterase binding site with estimated binding free energy of -8.26 kcal/mol.Linalool and 1,8-cineole are plant-derived isoprenoids with anticancer activities in lung cancer cells, nevertheless, the cellular and molecular mechanisms of action remain poorly understood. The purpose of this study was to determine the anticancer mechanisms of action of linalool and 1,8-cineole in lung adenocarcinoma A549 cells. Linalool (0-2.0 mM) and 1,8-cineole (0-8.0 mM) inhibited cell proliferation by inducing G0/G1 and/or G2/M cell cycle arrest without affecting cell viability of normal lung WI-38 cells. None of the two monoterpenes were able to induce apoptosis, as observed by the lack of caspase-3 and caspase-9 activation, PARP cleavage, and DNA fragmentation. Linalool, but not 1,8-cineole, increased reactive oxygen species production and mitochondrial membrane potential depolarization. Reactive oxygen species were involved in cell growth inhibition and mitochondrial depolarization induced by linalool since the antioxidant N-acetyl-L-cysteine prevented both effects. Besides, linalool (2.0 mM) and 1,8-cineole (8.0 mM) inhibited A549 cell migration. The combination of each monoterpene with simvastatin increased the G0/G1 cell cycle arrest and sensitized cells to apoptosis compared with simvastatin alone. Our results showed that both monoterpenes might be promising anticancer agents with antiproliferative, anti-metastatic, and sensitizer properties for lung cancer therapy.The purpose of this research is to examine the effect of voluntary integrated reporting on information asymmetry in European and Asian firms and investigate size as a moderator variable to this relationship. Pyrrolidinedithiocarbamate ammonium inhibitor Using a final sample of 94 firms in Europe and Asia that published integrated reports in 2016, the Ordinary Least Square is then performed to analyze the data on quarterly basis. The quarterly analysis is used to look at the relevance of accounting information decline as the time lag increases. The results show that there is an insignificant relationship between integrated reporting quality and information asymmetry which is captured by spread. In addition, the insignificant effect of size to moderate this relationship is also found. These results are supported by additional analysis. This research contributes to the existing debate about whether integrated reporting affects the market, particularly information asymmetry. To the best of the authors' knowledge, this is the first study to examine the effect of integrated reporting quality on the market on a quarterly basis.
To describe the baseline and serial tumor microbiome in HPV-associated oropharynx cancer (OPC) over the course of radiotherapy (RT).

Patients with newly diagnosed HPV-associated OPC treated with definitive radiotherapy +/- concurrent chemotherapy were enrolled in this prospective study. Using 16S rRNA gene sequencing, dynamic changes in the tumor site microbiome during RT were investigated. Surface tumor samples were obtained before RT and at week 1, 3 and 5 of RT. Radiological primary tumor response at mid-treatment was categorized as complete (CR) or partial (PR).

Ten patients were enrolled, but 9 patients were included in the final analysis. Mean age was 62years (range 51-71). As per AJCC 8th Ed, 56%, 22% and 22% of patients had stage I, II and III, respectively. At 4-weeks, 6 patients had CR and 3 patients had PR; at follow-up imaging post treatment, all patients had CR. The baseline diversity of the tumoral versus buccal microbiome was not statistically different. For the entire cohort, alpha diver exhibits reduced alpha diversity and altered taxa abundance over the course of radiotherapy. The baseline bacterial profiles of smokers vs. non-smokers were inherently different. Baseline tumor alpha diversity of patients with CR was higher than patients with PR, suggesting that the microbiome deserves further investigation as a biomarker of radiation response.
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