SciCombinator

Discover the most talked about and latest scientific content & concepts.

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Fluoroalkylated quinoxlines with various groups were efficiently synthesized via a one-pot tandem Michael addition / azidation / cycloamination process. Under the mild and metal-free conditions, a bis-imine intermediate (4a) was detected and isolated for the first time. KI played a crucial role in this reaction. The mechanism was described.

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Multi-parameter phenotypic profiling of small molecules is a powerful approach to their toxicity assessment and identifying potential mechanisms of actions. The present study demonstrates the application of image-based multi-parameter phenotypic profiling in MCF-7 cells to assess the overall toxicity and estrogenic activity of whole environmental water. Phenotypic profiling of 30 reference compounds and their complex mixtures was evaluated to investigate the cellular morphological outcomes to targeted biological pathways. Overall toxicity and estrogenic activity of environmental water samples were then evaluated by phenotypic analysis comparing with conventional bioassays and chemical analysis by multivariate analysis. The phenotypic analysis for reference compounds demonstrated that size and structure of cells related to biological processes like cell growth, death, and communication. The phenotypic alteration and nuclei intensity were selected as potential biomarkers to evaluate overall toxicity and estrogenic activities, respectively. The phenotypic profiles were associated with the chemical structure profiles in environmental water samples.Since the phenotypic parameters revealed multiple toxicity endpoints, it could provide more information that is relevant to assessing the toxicity of environmental water samples in compare with conventional bioassays. In conclusion, the image-based multi-parameters phenotypic analysis with MCF-7 cells provides a rapid and information-rich tool for toxicity evaluation and identification in whole water samples.

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While preclinical studies suggest the breast cancer (BC) chemopreventive effects of dietary polyphenols, the human evidence is still very weak. The huge existing in vitro-in vivo gap is mainly due to the plethora of potential effects reported by in vitro studies that usually assay polyphenols as occurring in the food (beverages, extracts, foods) and/or derived aglycone metabolites with doubtful physiological relevance. Since Phase-II metabolites can reach systemic tissues such as malignant breast tumors, we aimed here to compare for the first time the antiproliferative and estrogenic/antiestrogenic effects of dietary polyphenols and microbiota-derived metabolites, i.e. resveratrol, dihydroresveratrol, urolithins (A, B, and isourolithin-A), and the flavanone hesperetin, with those effects exerted by their physiologically relevant glucuronides and sulfates on human BC cell lines (MDA-MB-231 and MCF-7). Results showed that aglycones exerted dose-dependent antiproliferative and estrogenic/antiestrogenic activities but both their glucuronide and sulfate conjugates lacked these activities. In addition, aglycones underwent Phase-II metabolism in BC cells, mainly via sulfation, which determined the cell-dependent differences in the effects observed. Therefore, phase-II metabolism limits the antiproliferative, estrogenic and antiestrogenic activities of dietary polyphenols on BC cells. Likewise, as a call of caution, enthusiasm should be limited for publishing effects that are not physiologically relevant.

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Dienyl derivatives of 6,8-dioxabicyclo[3.2.1]octanes, closely related to naturally abundant molecules, have been synthesized from 2-acetyl-3,4-dihydropyrans (readily available from ketones and acetylene in two steps), which further add to aryl(hetaryl)acetylenes in the KOBut/DMSO superbase system (105 oC, 1.5 h) to stereoselectively give the corresponding E-styryl adducts. The latter undergo ring closure (NH4Cl/H2O, acetonitrile, reflux, 8 h) to form 6,8-dioxabicyclo[3.2.1]octane core decorated with (1Z, 3E)-diene substituent.

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A periodic layer structure consisting of sol-gel SrTiO3 and anodized Al2O3 has been designed and fabricated by interface engineering. Utilizing the anodized Al2O3 to be the blocking layer, not only the local high electric field of hole and crack defects could be significantly reduced but also, and equally important, the blocking layer undertaking higher electric field could effectively decrease the breakdown probability of SrTiO3 layer based on the finite element analysis. As the sample has been modified, the barrier height of the charge carrier was increased through fitting the conductance activation energy (Hc). In addition, the space charge limited conductance (SCLC) conductance mechanism was almost eliminated according to the fitted results in the LnE - LnJ diagram, indicating that most of the charge carrier released from traps were blocked or isolated by the Al2O3 layer. As a result of the periodic interface modification, the leakage current was decreased two orders of magnitude and breakdown strength was enhanced from 144.13MV m-1 to 754.23 MV m-1. More importantly, the ultimate energy density is up to 39.49 J cm-3, which is 1505% greater than the the sample without interface modification.

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Hierachical Fe3O4 microspheres with superparamagnetic property are attractive for their superior structural, water-dispersible and magnetic separation merits. Here self-template etching route was developed to create optimal porous structure in superparamagnetic Fe3O4 microspheres by using the oxalic acid (H2C2O4) as etching agent. A plausible formation mechanism of the urchin-like Fe3O4 microspheres was proposed based on systematic investigation of the etching process, which involved two stages including pore-forming step based on size-selective etching and pore-expanding step based on further etching. The as-synthesized Fe3O4 microspheres exhibited urchin-like structure with specific surface area and pore-size tunable, water-dispersible and superparamagnetic properties. The optimal urchin-like Fe3O4 microspheres demonstrated superior performance including fast magnetic separation and high removal capabilities for the heavy metals ions like Pb2+ (112.8 mg g-1) and Cr(VI) (68.7 mg g-1). This work will shed new light on the synthesis of urchin-like microspheres for superior performance.

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A novel C-H functionalization enabled multicomponent reaction involving N-heterocycles, dinucleophile and dipolarophile has been developed. Direct α- and more challenging β-C(sp3)-H functionalization of aliphatic N-heterocycles was achieved without the use of metallic reagents and oxidants either under conventional or microwave aided heating conditions. In a single operation, up to five carbon-carbon and carbon-heteroatom bonds are formed in a highly diastereoselective manner providing the expeditious access to the complex heteropolycycles.

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Amyloid formation of α-synuclein (α-Syn) and its familial mutations are directly linked with Parkinson’s disease (PD) pathogenesis. Recently, a new familial α-Syn mutation (A53E) was discovered, associated with an early-onset aggressive form of PD, which delays the α-Syn aggregation. When we overexpressed WT and A53E proteins in cells, neither of them showed toxicity or aggregate formation, suggesting merely overexpression may not recapitulate the PD phenotype in cell models. We hypothesized that cell expressing A53E mutant might possess enhanced susceptibility to PD associated toxicants compared to WT. When cells were treated with PD toxicants (dopamine and rotenone), cells expressing A53E showed more susceptibility to cell death along with compromised mitochondrial potential and increased generation of reactive oxygen species. The higher toxicity of A53E could be due to more oligomers load in cells as confirmed by dot blot assay using amyloid specific OC and A11 antibody and using in vitro aggregation study. The present cellular model suggests that along with familial mutation, environmental and other cellular factors might play a crucial role in dictating PD pathogenesis.

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A very sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the quantitation of the most common neonicotinoids (thiamethoxam, clothianidin, imidacloprid, acetamiprid, and thiacloprid) at trace levels in milk. Using fast and selective liquid-liquid extraction (LLE) starting from 0.5 mL of milk, lowest limits of quantitation (LLOQ) equal or lower than 10 pg/mL for all analytes were achieved. Precision and accuracy were evaluated at four different concentrations (5, 10, 500 and 10000 pg/mL) and ranged between 2-16% (RSD) and 77-125%, respectively. Extraction recoveries and matrix effects ranged between 64-76% and 88-98%, respectively. The method was applied to measure neonicotinoid levels in a series of conventional and organic Swiss milks as well as in human breast milk and commercial powdered milk. More than 90% of the samples tested positive for at least one neonicotinoid. However, all animal samples were far below the maximum residue limits authorized for human consumption with average total neonicotinoid levels of 16.1 ± 13.1 pg/mL. Human breast milks and powdered milks contained similar amounts of neonicotinoids. Taken together, our results demonstrate the high prevalence of neonicotinoids in milk from all origins, albeit at levels considered to be safe for human consumption.

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Langmuir-Blodgett deposition is a popular route to produce thin films of graphene oxide for applications such as transparent conductors and biosensors. Unfortunately, film morphologies vary from sample to sample, often with undesirable characteristics such as folded sheets and patch-wise depositions. In conventional Langmuir-Blodgett deposition of graphene oxide, alcohol (typically methanol) is used to spread the graphene oxide sheets onto an air-water interface before deposition onto substrates. Here we show that methanol gives rise to Marangoni flow, which fundamentally limits control over Langmuir-Blodgett depositions of graphene oxide. We directly identified the presence of Marangoni flow by using photography, and we evaluated depositions with atomic force microscopy and scanning electron microscopy. The disruptive effect of Marangoni flow was demonstrated by comparing conventional Langmuir-Blodgett depositions to depositions where Marangoni flow was suppressed by a surfactant. Because methanol is the standard spreading solvent for conventional Langmuir-Blodgett deposition of graphene oxide, Marangoni flow is a general problem and may partly explain the wide variety of undesirable film morphologies reported in the literature.