Engelhawley5623

Indanocine, a potent anticancer investigational drug of National Cancer Institute-USA, has been much discussed in recent years. Present communication aimed at total synthesis of indanocine and its close analogues. Total synthesis was improved by double yields than previously reported yields. Some of the benzylidene and 2-benzyl derivatives with free rotation at C2 position exhibited potential cytotoxicities against various human cancer cell lines. Five such analogues exhibited potential antiproliferative effect against HCT-116 and MIA PACA-2 cell lines. Benzylindanocine 12i induced microtubule destabilization by occupying colchicine binding pocket of β-tubulin. It also exhibited anti-inflammatory activity by down-regulating IL-6 and TNF-α. In Ehrlich ascites carcinoma model, 12i reduced 78.4% of EAC tumour in Swiss albino mice at 90 mg/kg (i.p.) dose. Further, in in vivo safety studies, 12i was found to be safe to rodents up to 1,000 mg/kg dose. Concomitant anticancer and anti-inflammatory activity of benzylindanocine is distinctive, which suggests its further optimization for better efficacy and druggability.Since the discovery of recurrent mutations in histone H3 variants in paediatric brain tumours, so-called 'oncohistones' have been identified in various cancers. While their mechanism of action remains under active investigation, several studies have shed light on how they promote genome-wide epigenetic perturbations. These findings converge on altered post-translational modifications on two key lysine (K) residues of the H3 tail, K27 and K36, which regulate several cellular processes, including those linked to cell differentiation during development. We will review how these oncohistones affect the methylation of cognate residues, but also disrupt the distribution of opposing chromatin marks, creating genome-wide epigenetic changes which participate in the oncogenic process. Ultimately, tumorigenesis is promoted through the maintenance of a progenitor state at the expense of differentiation in defined cellular and developmental contexts. As these epigenetic disruptions are reversible, improved understanding of oncohistone pathogenicity can result in needed alternative therapies.Aglycone isoflavones are estrogen-like bioactive compounds found in low amounts in soybean, which are increased by biotransformation processes. This study investigated two biotransformation processes of soybean extracts with Aspergillus awamori fungus, evaluating aglycone content and capability of stimulation of collagen-I deposition. Isoflavones were quantified via HPLC; cytotoxicity of biotransformed extracts toward mouse and human fibroblasts was evaluated via NRU and apoptosis/necrosis assays; and collagen-I deposition was measured through Western blot, immunofluorescence, and immunoassay. BSE-2 was the biotransformed soybean extract with the highest aglycone content and did not decrease viability or demonstrated cytotoxicity to either L929 or HDFa cells. BSE-2, at the optimal concentration of 1.33 μg/mL, increased substantially collagen-I amount in HDFa intracellular matrix compared to non-biotransformed soybean extract (NBSE) and immunoassay demonstrated that the extracellular deposition was mostly inhibited by BSE-2 concentrations, except at 1.33 μg/mL. Hence, biotransformed soybean extract by the enzymatic filtrate of Aspergillus awamori fungus demonstrated a high nutricosmetic potential, showing safeness and effective collagen-I augmentation.In this study, as system-level photodetectors, light-to-frequency conversion circuits (LFCs) are realized by i) photosensitive ring oscillators (ROs) composed of amorphous indium-gallium-zinc-oxide/single-walled carbon nanotube (a-IGZO/SWNT) thin film transistors (TFTs) and ii) phase-locked-loop Si circuits built with frequency-to-digital converters (PFDC). The 3-stage ROs and logic gates based on a-IGZO/SWNT TFTs successfully demonstrate its performance on flexible substrates. Herein, along with the advantage of scalability, a-IGZO films are used as photosensitive n-type TFTs and SWNTs are employed as photo-insensitive p-type TFTs for better photosensitivity in circuit level. Through the controlling a post-annealing condition of a-IGZO film, responsivities and detectivities of a-IGZO TFTs are obtained as 36 AW-1 and 0.3 × 1012 Jones for red, 93 AW-1 and 3.1 × 1012 Jones for green, and 194 AW-1 and 11.7 × 1012 Jones for blue. Furthermore, as an advanced demonstration for practical application of LFCs, a unique circuit (i.e., PFDC) is designed to analyze the generated oscillation frequency (fosc ) from the LFC device and convert it to a digital code. As a result, the designed PFDC can exactly count the generated fosc from the flexible a-IGZO/SWNT ROs under light illumination with an outstanding sensitivity and assign input frequencies to respective digital code.A series of novel mandelic acid derivatives containing a 1,3,4-oxadiazothioether moiety were designed and synthesized. CCT251545 ic50 Bioassay results showed that some target compounds exhibited certain antifungal activity against six kinds of pathogenic fungi in vitro. Among the compounds, the EC50 values of T41 against Gibberella saubinetii, Verticillium dahlia and Sclerotinia sclerotiorum were 31.0, 27.0 and 32.1 μg/ml, respectively, and the EC50 value of T14 against S. sclerotiorum was 14.7 μg/ml. The antifungal activity against the resistant fungus S. sclerotiorum indicated that this series of target compounds may have the similar action modes or sites as the commercialized succinate dehydrogenase inhibitor carboxin. A morphological study with fluorescence microscope demonstrated that T41 can significantly destroy the membrane integrity of G. saubinetii.

In response to high rates of burnout among trainees, educators in obstetrics and gynaecology introduced a six-session wellness curriculum that improved professional fulfilment and resident burnout in participants with greater attendance. The implementation of the curriculum varied based on local variables and contextual factors.

To analyse the reactions of participants and curriculum leaders across the diverse settings of the pilot experience in order to identify the best practices for implementation of a wellness curriculum.

Twenty-five US OBGYN residency programmes completed the curriculum in the 2017-2018 academic year. OBGYN residents in all the years of training participated. Faculty members and fellows were workshop facilitators and course leaders. All participants completed post-intervention surveys. A qualitative, descriptive thematic analysis explored free-text responses from residents and workshop facilitators.

Among 592 eligible resident participants, 387 (65%) responded to the post-intervention survey.