5 mg/kg) required to exhibit comparable in vivo activity towards Huh-7 xenografts.  https://www.selleckchem.com/products/oicr-9429.html  Cellular events resulting from Hec1/Nek2 inhibition with T-1101 treatment include Nek2 degradation, chromosomal misalignment, and apoptotic cell death. A combination of T-1101 with either of doxorubicin, paclitaxel, and topotecan in select cancer cells also resulted in synergistic effects. Inactivity of T-1101 on non-cancerous cells, a panel of kinases, and hERG demonstrates cancer specificity, target specificity, and cardiac safety, respectively. Subsequent salt screening showed that T-1101 tosylate has good oral AUC (62.5 μM·h), bioavailability (F = 77.4%), and thermal stability. T-1101 tosylate is currently in phase I clinical trials as an orally administered drug for cancer therapy. Here, we formulated and investigated the structure-activity relationships of novel N-substituted carbazole sulfonamide derivatives with improved physicochemical properties. Most of these new compounds displayed good aqueous solubility. Certain molecules presented strong in vitro antiproliferative and in vivo antitumor activity. Relative to the control, 50 mg/kg compound 3v substantially reduced human HepG2 xenograft mouse tumor growth by 54.5% and its efficacy was comparable to that of CA-4P. Compound 3h demonstrated anticancer efficacy in both subcutaneous and orthotopic HepG2 xenograft mouse models. We also developed a novel synthetic method for 7-hydroxy-substituted carbazole sulfonamides. Compared with the control, 25 mg/kg compound 4c inhibited human HepG2 xenograft mouse tumor growth by 71.7% and was more potent than 50 mg/kg CA-4P with only 50% tumor shrinkage efficacy. Among the three water-soluble carbazole sulfonamide derivatives formulated in the present study, compound 4c displayed the most effective tumor growth inhibition in vivo and merit further investigation as potential antitumor agents for cancer therapy. China is facing the dual challenge of economic development and environment protection. Recently, Shanghai (tier-1 city) implemented the pilot project of household solid waste (HSW) management and expects to execute a similar project in 45 cities across China by 2020. The current research's aim is to examine the pilot project's progress by comparing it with existing HSW management practice in other cities. From a theoretical perspective, a socio-ecological framework is used to examine citizens' HSW sorting behavior (HSWSB), which is further mapped based on the theory of planned behavior to enrich the findings. A total of 1409 citizen responses are utilized to generalize the findings. The study concludes that replicating tier-1 practices in other cities could produce unsatisfactory results. The regulatory environment should focus on comparatively long-lasting citizen behavior change by designing a citizen-centric approach (i.e., awareness campaigns) related to ecological concerns (i.e., climate change) because it could define the future of HSWSB practice in Chinese society. Learning is important for honey bee fitness and the pollination services that they provide. Neonicotinoid pesticides impair learning, fitness, colony health, and pollination, but most studies on how they affect bee learning have focused on olfactory learning. We tested the effects of field realistic doses of 0.8 ng/bee and 1.34 ng/bee of the neonicotinoid pesticide, thiamethoxam (TMX), on bee visual learning. We adapted a T-maze bioassay and classically conditioned bees to associate sugar reward with a simulated flower color (blue or yellow light) in a choice assay. At 1.34 ng/bee, TMX significantly reduced correct choices in the final learning trial as compared to the control treatment. There was no TMX effect in our 1-h memory test. We found stronger effects on decision time and abnormal behaviors. TMX decreased bee decision times, a potential byproduct of induced hyperactivity since bees walked to make choices. Behaviors (falling, trembling, and rapid abnormal movements) were significantly increased by both TMX doses as compared to the control treatment. These results suggest that the effects of neonicotinoids on bee visual learning should be further studied and incorporated into Risk Assessment protocols. Amikacin (AMI) is an aminoglycoside antibiotic widely used in the treatment of severe infections caused by multi-resistant bacteria, with established exposition targets in therapeutic drug monitoring (TDM). The usual specimen for AMI concentration measurement is plasma or serum. The access to TDM of AMI in Developing Countries is constrained by the limited availability of laboratories performing the quantitation of this drug. In this context, the use of dried microsamples, such as dried plasma spots (DPS) could be an alternative to allow reduced specimen transportation and storage costs in resource-limited settings, increasing the access to TDM of AMI. This study aimed to develop and validate the first report of simultaneous determination of AMI and creatinine (CRE) in DPS, using UHPLC-MS/MS. Precision, accuracy and stability assays showed acceptable results. AMI was stable in DPS for 14 days at 6 °C, 2 days at 22 °C, and one day at 42 °C. CRE was stable during 14 days at all tested temperatures. AMI and CRE concentrations in DPS and plasma were compared by Passing-Bablok regression and Bland and Altmann plots and presented comparable results. Estimates of patient's clearance, volume of distribution and suggested doses of AMI were also similar using DPS or plasma concentrations. The assay provides a useful logistic alternative to allow more widespread access to dose individualization of AMI in limited resources settings. Two unknown impurities in roxithromycin were discovered and preliminarily characterized by two-dimensional liquid chromatography coupled with QTOF mass analyzer (2D LC-QTOF MS/MS). The column-switching technique of 2D LC made the chromatographic conditions in official standard of roxithromycin compatible with mass spectrometric detector. The complete MS/MS fragmentation patterns of the impurities were studied to obtain structural information of these impurities. Furthermore, these two impurities were separated and purified by preparative HPLC, and their structures were confirmed by 1D and 2D nuclear magnetic resonance (NMR). Structural elucidation of two impurities by 1H NMR, 13C NMR, the 1H-1H COSY, HSQC and HMBC NMR spectra has been discussed. Based on high resolution MS/MS and NMR data, the structures of these two impurities were elucidated respectively as 11-O-[(2-Methoxyethoxy) methyl] roxithromycin and de(N-methyl)-N-formyl roxithromycin. In addition, the mechanisms for formation of the impurities were also proposed.