Notes

Functionality involving β-Phosphinolactams via Phosphenes as well as Imines.
We have designed and synthesized anthraquinone containing compounds which have oligopyrrole side chains of varying lengths. These compounds stabilized the G-quadruplex DNA formed in the promoter regions of c-MYC oncogenes selectively over the duplex DNA. These observations were recorded using UV-vis spectroscopic titrations, fluorescence measurements and circular dichroism (CD) spectral titrations. The potency of the compounds to stabilize the G4 DNA has been shown from the thermal denaturation experiments. The compound interacts with c-MYC G-quadruplex DNA through stacking mode as obtained from ethidium bromide displacement assay, cyclic voltammetric titration, and docking experiments. Molecular modeling studies suggested that the stacking of the anthraquinone moiety over the G-tetrad of the G4 structures are responsible for the stability of such quadruplex secondary structure. Furthermore, polymerase stop assay also supported the formation of stable G4 structures in the presence of the above-mentioned compounds. The compounds have shown selective cancer cell (HeLa and HEK293T) cytotoxicity over normal cells (NIH3T3 and HDFa) under in vitro conditions as determined from MTT based cell viability assay. Apoptosis was found to be the mechanistic pathway underlying the cancer cell cytotoxicity as obtained from Annexin V-FITC and PI dual staining assay which was further substantiated by nuclear morphological changes as observed by AO/EB dual staining assay. Cellular morphological changes, as well as nuclear condensation and fragmentation upon treatment with these compounds, were observed under bright field and confocal microscopy. Research related to boronic acids, from synthetic development to materials to drug discovery, has skyrocketed in the past 20 years. In terms of drug discovery, the incorporation of boronic acids into medicinal chemistry endeavours has seen a steady increase in recent years. In fact, the Food and Drug Administration (FDA) and Health Canada have thus far approved five boronic acid drugs, three of which were approved in the past four years, and several others are in clinical trials. Boronic acids have several desirable properties that has led to their increased use, including potentially enhancing potency of drugs and/or improving their pharmacokinetics profile. This review explores discovery processes of boronic acid drugs. It begins with a brief scope of boron in natural products and in current drugs, followed by an investigation into the various rationalizations for boronic acid incorporation and the synthetic developments that focused on facilitating their addition into organic compounds. We hope that the knowledge we have assembled in this literature review will encourage medicinal chemists to consider the potential benefits of incorporating boronic acids into their future drug discovery endeavours. Carbapenemase-producing Enterobacteriaceae (CPE) confer resistance to antibiotics that are of critical importance to human medicine. There have only been a few reported cases of CPEs in the European food chain. We report the first detection of a carbapenemase-producing Escherichia coli (ST 5869) in the Belgian food chain. Our aim was to characterize the origin of the carbapenem resistance in the E. coli isolate. The isolate was detected during the screening of 178 minced pork samples and was shown to contain the carbapenemase gene blaVIM-1 by PCR and Sanger sequencing. Whole genome short and long read sequencing (MiSeq and MinION) was performed to characterize the isolate. With a hybrid assembly we reconstructed a 190,205 bp IncA/C2 plasmid containing blaVIM-1 (S15FP06257_p), in addition to other critically important resistance genes. This plasmid showed only low similarity to plasmids containing blaVIM-1 previously reported in Germany. Moreover, no sequences existed in the NCBI nucleotide database that completely covered S15FP06257_p. Analysis of the blaVIM-1 gene cassette demonstrated that it likely originated from an integron of a Klebsiella plasmid reported previously in a clinical isolate in Europe, suggesting that the meat could have been contaminated by human handling in one of the steps of the food chain. This study shows the relevance of fully reconstructing plasmids to characterize their genetic content and to allow source attribution. This is especially important in view of the potential risk of antimicrobial resistance gene transmission through mobile elements as was reported here for the of public health concern blaVIM-1. The introduction of new psychoactive substances (NPS) on the illicit drug market has led to major challenges for the analytical laboratories. Keeping screening methods up to date with all relevant drugs is hard to achieve and the risk of missing important findings in biological samples is a matter of concern. Aiming for an extended retrospective data analysis, diagnostic fragment ions from synthetic cannabinoids (n=251), synthetic opioids (n=88) and designer benzodiazepines (n=26) not included in our original analytical method were obtained from the crowdsourced database HighResNPS.com and converted to a personalized library in a format compatible with the analytical instrumentation. Data files from the analysis of 1314 forensic post mortem samples with an Agilent 6540 ultra high pressure liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) performed in our laboratory from January 2014 to December 2018 were retrieved and retrospectively processed with the new personalized library.Owing to the production and use of chemicals in chemical industry parks (CIPs), these areas are considered to be highly polluted. However, the type of pollutants presents in the wastewater from CIPs and the risk posed to the environment due to the release of these pollutants remains unclear. In this study, suspect screening was combined with traceability analysis to determine the type of pollutants present in wastewaters at 9 chemical enterprises and wastewater treatment plants (WWTPs) in the CIPs. Selleck 2-APV Additionally, the distribution of nine pollutants from the WWTPs' effluent stage and the risk they posed to the surrounding river was examined through target analysis. Upon conducting suspect analysis, the presence of 65 and 64 chemicals in the 9 chemical enterprises' wastewaters and WWTPs, respectively, was tentatively identified. Traceability analysis of the compounds screened in the effluent from the WWTPs determined that 41 substances were identified as characteristic pollutants of the chemical enterprises, indicating that the suspect screening strategy enabled relatively more efficient identification of the characteristic pollutants compared to traditional quantitative analysis. Targeting analysis combined with ecological risk assessment showed that metolachlor, carbendazim, atrazine, diuron, and chlorpyrifos posed relatively higher risks to aquatic organisms in the surrounding river. Therefore, the refined management of the wastewater treatment plant in the CIPs is necessary. BACKGROUND AND OBJECTIVE Chemotherapy is useful to many breast cancer patients, however, it is not therapeutic for some patients. Pathologic complete response (pCR) is an indicator to good response in Neoadjuvant chemotherapy (NAC). In this study, we aimed to develop a way to predict pCR before NAC. METHODS We retrospectively collected 287 stage II-III breast cancer cases either to a training set (N = 197) or to a test set (N = 90). Fourteen candidate genes were selected from four public microarray data sets. A prediction model was built, by using these fourteen candidate genes and three reference genes expression which were tested by TaqMan probe-based quantitative polymerase chain reaction, after selecting a better algorithm. RESULTS The Naive Bayes algorithm had a relatively higher predictive value, compared with random forest, support vector machine (SVM), and k-nearest neighbor (knn) algorithms (P less then 0.05). This 17-gene prediction model showed a high positive correlation with pCR (odds ratio, 8.914, 95% confidence interval, 4.430-17.934, P less then 0.001). By using this model, the enrolled patients were classified into sensitive (SE) and insensitive (INS) groups. The pCR rates between the SE and INS groups were highly different (42.3% vs.7.6%, P less then 0.001). The sensitivity and specificity of this prediction model were 84.5% and 62.0%. CONCLUSIONS Instead of whole transcriptome-based technologies, panel gene expression with tens of essential genes implemented in a machine learning model has predictive potential for chemosensitivity in breast cancers. V.Allosteric regulation of protein functions is ubiquitous in organismal biology, but the principles governing its evolution are not well understood. Here we discuss recent studies supporting the large-scale existence of latent allostery in ancestor proteins of superfamilies. As suggested, the evolution of allostery could be driven by the need for specificity in paralogs of slow evolving protein complexes with conserved active sites. The same slow evolution is displayed by purifying selection exhibited in allosteric proteins with somatic mutations involved in cancer, where disease-associated mutations are enriched in both orthosteric and allosteric sites. Consequently, disease-associated variants can be used to identify druggable allosteric sites that are specific for paralogs in protein superfamilies with otherwise similar functions. Grape pomace (GP) management has been a challenge worldwide. We have previously demonstrated a biorefinery process to recover oil and polyphenols, and produce biofuels from GP sequentially, although over 50% of GP solid waste remains post-processing. To approach zero solid waste during GP processing, herein a pyrolysis process was designed for converting GP and its secondary processing wastes to biochars, which were then evaluated for lead (Pb) adsorption from water. GP lignin pyrolyzed at 700 °C (GPL2700 biochar) with specific surface area of 485 m2/g showed the highest Pb adsorption capacity, and achieved 66.5% of Pb removal from an initially high concentration of 300 mg/L within 30 min. At low initial Pb concentrations (50-3000 μg/L), GPL2700 biochar could reduce Pb concentrations to 0.208-77.2 μg/L. In addition, experimental and modeling results revealed that both physisorption and chemisorption mechanisms were involved in the adsorption process of GPL2700 biochar. Inspired by fish scales, this study prepares a thermo-responsive underwater oleophobic PNIPAM/PAN/TiO2 nanofibrous membranes by traditional electrospinning technique using poly-N-isopropylacrylamide (PNIPAM) and polyacrylonitrile (PAN). Thermal properties, mechanical properties, surface chemical composition, wettability, photocatalysis, and oil/water separation of PNIPAM/PAN/TiO2 membrane are explored compared to pure PNIPAM membrane. Result reveals that PAN/TiO2 compounds make PNIPAM membrane with a smaller fiber diameter of 141 nm and high tensile stress of 7.4 MPa, and also decompose 98% of rhodamine B after UV light radiation. This bioinspired design structure endows the membrane with superhydrophilicity with a low water contact angle, and underwater superoleophobicity with a high oil contact angle of 157° (petroleum ether) and 151° (dichloromethane). This membrane can efficiency separate oil/water mixture with a high separation efficiency. Moreover, the resultant PNIPAM/PAN/TiO2 membrane has the bionic fish scale structure, and has wettability respond at lower critical solution temperature making the water flux decreased from 10013 ± 367 L m-2·h-1 to 7713 ± 324 L m-2·h-1, and thus has a potential to be used in purification of reclaimed water and separation of oil from water.
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