259 research outputs found

    DABCO-Catalyzed Michael/Alkylation Cascade Reactions Involving α‑Substituted Ammonium Ylides for the Construction of Spirocyclopropyl Oxindoles: Access to the Powerful Chemical Leads against HIV‑1

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    A novel Michael/alkylation cascade reaction of N-unprotected 3-bromooxindoles with α,β-unsaturated acyl phosphonates using DABCO as a robust catalyst followed by the derivatization of the acyl phosphonate intermediates in situ has been developed. This scenario enables rapid access to a diverse set of highly functionalized spirocyclopropyl oxindoles in moderate yields with good to excellent diastereoselectivities, which are analogues of a high active non-nucleoside reverse transcriptase inhibitor against HIV-1. The synthetic potential of this tactic has been highlighted by a gram-scale reaction and Suzuki cross-coupling reactions of the product. Moreover, the reaction mechanism has been tentatively elucidated by control experiments and dynamic high-resolution mass spectrometry studies, which indicates that the Michael/alkylation cascade reaction involves DABCO-derived α-substituted ammonium ylides

    Efficacy and safety of metformin in pregnant women with polycystic ovary syndrome: a systematic review with meta-analysis of randomized and non-randomized controlled trials

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    To evaluate the efficacy and safety of using metformin in pregnant women with polycystic ovarian syndrome (PCOS) and to explore the most effective and safe protocol by using a meta-analysis method. Medline, EMBASE, Cochrane Library, and other databases were searched for randomized controlled trials and prospective cohort studies enrolling pregnant women with PCOS on receiving metformin or placebo or nothing. Subgroup analyses were undertaken. A total of 17 studies involving 2899 patients were included. Compared with control group, the use of metformin significantly reduced the incidence of preterm delivery (cumulative rate 3.86% vs 9.19%, relative risk (RR), 0.42 [95% confidence interval (CI), 0.25–0.71,]; p = .001), early miscarriage (cumulative rate 6.58% vs 18.35%, RR, 0.40 [95% CI, 0.20–0.78]; p = .007), gestational diabetes (cumulative rate 12.86% vs 22.91%, RR, 0.48 [95% CI, 0.26–0.89]; p = .02), and pre-eclampsia (cumulative rate 4.95% vs 7.72%, RR, 0.61 [95% CI, 0.40–0.93]; p = .02), the need for insulin treatment throughout pregnancy (cumulative rate 2.14% vs 5.12%, RR, 0.43 [95% CI, 0.22–0.85]; p = .01), and weight gain of pregnant women (mean difference, −2.45, [95% CI, −3.04 to −1.85]; p  The use of metformin in pregnant women with PCOS can significantly reduce maternal complications. No significant difference was observed in serious maternal adverse events. The efficacy and safety of metformin are worthy of recognition.</p

    On the Mechanism of Negative Differential Resistance in Ferrocenylundecanethiol Self-Assembled Monolayers

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    Negative differential resistance (NDR) peaks in the current−voltage characteristics of ferrocenylundecanethiol self-assembled monolayers are not reversible. The peaks turn to smoothly increasing currents as oxygen is removed from the system, indicating that NDR arises from the reaction of an energetic charged species with ambient oxygen

    Formation of Molecular Junctions by Single-Entity Collision Electrochemistry

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    Controlling and understanding the chemistry of molecular junctions is one of the major themes in various fields ranging from chemistry and nanotechnology to biotechnology and biology. Stochastic single-entity collision electrochemistry (SECE) provides powerful tools to study a single entity, such as single cells, single particles, and even single molecules, in a nanoconfined space. Molecular junctions formed by SECE collision show various potential applications in monitoring molecular dynamics with high spatial resolution and high temporal resolution and in feasible combination with hybrid techniques. This Perspective highlights the new breakthroughs, seminal studies, and trends in the area that have been most recently reported. In addition, future challenges for the study of molecular junction dynamics with SECE are discussed

    Video_1_Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain.MP4

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    ASH1L is one of the highest risk genes associated with autism spectrum disorder (ASD) and intellectual disability (ID). Our recent studies demonstrate that loss of Ash1l in the mouse brain is sufficient to induce ASD/ID-like behavioral and cognitive deficits, suggesting that disruptive ASH1L mutations are likely to have a positive correlation with ASD/ID genesis. However, the core pathophysiological changes in the Ash1l-deficient brain remain largely unknown. Here we show that loss of Ash1l in the mouse brain causes locomotor hyperactivity, high metabolic activity, and hyperactivity-related disturbed sleep and lipid metabolic changes. In addition, the mutant mice display lower thresholds for the convulsant reagent-induced epilepsy and increased neuronal activities in multiple brain regions. Thus, our current study reveals that neural hyperactivity is a core pathophysiological change in the Ash1l-deficient mouse brain, which may function as a brain-level mechanism leading to the Ash1l-deletion-induced brain functional abnormalities and autistic-like behavioral deficits.</p

    Thermochemical Study of the Solid Complexes Ln[(CH<sub>3</sub>)<sub>2</sub>NCS<sub>2</sub>)]<sub>3</sub>(C<sub>12</sub>H<sub>8</sub>N<sub>2</sub>) (Ln = Eu, Gd, Tb, Dy)

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    Four solid complexes Ln(Me2dtc)3(phen) (Ln = Eu, Gd, Tb, Dy) have been prepared from the reactions of hydrous lanthanide chloride, sodium dimethyldithiocarbamate (NaMe2dtc), and 1,10-phenanthroline (phen·H2O) in anhydrous ethanol. The title complexes were characterized by elemental analysis, IR spectroscopy, TG−DTG−DSC, and X-ray diffraction analysis. Their enthalpy changes of liquid-phase reactions of formation, ΔrHmθ(l), were determined at 298.15 K by a microcalorimeter, and the enthalpy changes of the solid-phase reactions of formation, ΔrHmθ(s), were calculated on the basis of a thermochemical cycle. The thermodynamics of reactions of formation of the complexes were studied via the reactions in solution. Combining the thermochemical data of the reactions and kinetic equations with the data of thermokinetic experiments, fundamental thermodynamic and kinetic parameters were achieved. The molar heat capacities of the title complexes were determined using an improved RD496-III type microcalorimeter at 298.15 K

    Video_2_Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain.MP4

    No full text
    ASH1L is one of the highest risk genes associated with autism spectrum disorder (ASD) and intellectual disability (ID). Our recent studies demonstrate that loss of Ash1l in the mouse brain is sufficient to induce ASD/ID-like behavioral and cognitive deficits, suggesting that disruptive ASH1L mutations are likely to have a positive correlation with ASD/ID genesis. However, the core pathophysiological changes in the Ash1l-deficient brain remain largely unknown. Here we show that loss of Ash1l in the mouse brain causes locomotor hyperactivity, high metabolic activity, and hyperactivity-related disturbed sleep and lipid metabolic changes. In addition, the mutant mice display lower thresholds for the convulsant reagent-induced epilepsy and increased neuronal activities in multiple brain regions. Thus, our current study reveals that neural hyperactivity is a core pathophysiological change in the Ash1l-deficient mouse brain, which may function as a brain-level mechanism leading to the Ash1l-deletion-induced brain functional abnormalities and autistic-like behavioral deficits.</p

    Forest plot of the residual rate of HPV after LEEP with negative margins.

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    Forest plot of the residual rate of HPV after LEEP with negative margins.</p
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