Summary
Arsenic can be biomethylated to form a variety of organic arsenicals differing in toxicity and environmental mobility. Trivalent methylarsenite (MAs(III)) produced in the methylation process ...is more toxic than inorganic arsenite (As(III)). MAs(III) also serves as a primitive antibiotic and, consequently, some environmental microorganisms have evolved mechanisms to detoxify MAs(III). However, the mechanisms of MAs(III) detoxification are not well understood. In this study, we identified an arsenic resistance (ars) operon consisting of three genes, arsRVK, that contribute to MAs(III) resistance in Ensifer adhaerens ST2. ArsV is annotated as an NADPH‐dependent flavin monooxygenase with unknown function. Expression of arsV in the arsenic hypersensitive Escherichia coli strain AW3110Δars conferred resistance to MAs(III) and the ability to oxidize MAs(III) to MAs(V). In the presence of NADPH and either FAD or FMN, purified ArsV protein was able to oxidize both MAs(III) to MAs(V) and Sb(III) to Sb(V). Genes with arsV‐like sequences are widely present in soils and environmental bacteria. Metagenomic analysis of five paddy soils showed the abundance of arsV‐like sequences of 0.12–0.25 ppm. These results demonstrate that ArsV is a novel enzyme for the detoxification of MAs(III) and Sb(III) and the genes encoding ArsV are widely present in soil bacteria.
Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC ...through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined.
Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis.
MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies.
MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.
Lithium (Li) metal is promising in the next‐generation energy storage systems. However, its practical application is still hindered by the poor cycling performance and serious safety issues for the ...consequence of dendritic Li. Herein, a dendrite‐free Li/carbon nanotube (CNT) hybrid is proposed, which is fabricated by direct coating molten Li on CNTs, for Li‐metal batteries. The favorable thermodynamic and kinetic conditions are the powerful force to drive the rapid lift upwards and infusion of molten Li into CNTs network, which is the key to form a uniform metallic layer in Li/CNTs hybrid. The obtained hybrid indicates super‐stable functions even at an ultrahigh current density of 40 mA cm−2 for 2000 cycles with a stripping/plating capacity of 2 mAh cm−2 in symmetric cells. Subsequently, this hybrid also demonstrates a significantly decreased resistance, excellent cycling stability at high current density and flexibility in the full Li‐S battery. This work provides valuable concepts in fabricating Li anodes toward Li‐metal batteries and beyond for their high‐level services.
A dendrite‐free Li/carbon nanotube (CNT) hybrid is fabricated by direct coating of molten Li on CNTs for Li‐metal batteries. Favorable thermodynamic and kinetic conditions are a powerful force to drive the rapid lift upward and infusion of molten Li into CNTs network. The obtained hybrid exhibits superstable function even at an ultrahigh current density.
To explore the correlations between liver fat content and clinical index in patients with impaired glucose tolerance (IGT) and healthy subjects.
56 subjects were enrolled and each of them underwent ...upper-abdominal MRI examination that involved a T1 VIBE Dixon sequence. 14 was clinically diagnosed with IGT (collectively as IGT group ) while 42 showed normal glucose tolerance,(collectively as NGT group). NGT group was further divided into NGTFat (BMI≥25, 18 subjects) and NGTLean (BMI<25, 24 subjects). The total liver fat contents was measured and compared with clinical findings and laboratory results in order to determine statistical correlations between these parameters. Differences among IGT, NGTFat and NGTLean groups were evaluated.
For all the subjects, fat volume fractions (FVFs) ranged from 4.2% to 24.2%, positive correlations was observed with BMI, waist hip ratio(WHR), low density lipoprotein(LDL), fasting plasma insulin(FPI), homeostasis model assessment insulin resistance (HOMA-IR) and homeostasis model assessment β(HOMAβ). FVFs of IGT group (p = 0.004) and NGTFat group (p = 0.006) were significantly higher than those of NGTLean group.
People with higher BMI, WHR and LDL levels tend to have higher liver fat content. Patients with BMI≥25 are more likely to develop IGT. Patients with higher FVF showed higher resistance to insulin, thus obtained a higher risk of developing type 2 diabetes mellitus.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Silicon (Si) shows promise as an anode material in lithium-ion batteries due to its very high specific capacity. However, Si is highly brittle, and in an effort to prevent Si from fracturing, the ...research community has migrated from the use of Si films to Si nanoparticle based electrodes. However, such a strategy significantly reduces volumetric energy density due to the porosity of Si nanoparticle electrodes. Here we show that contrary to conventional wisdom, Si films can be stabilized by two strategies: (a) anchoring the Si films to a carbon nanotube macrofilm (CNM) current collector and (b) draping the films with a graphene monolayer. After electrochemical cycling, the graphene-coated Si films on CNM resembled a tough mud-cracked surface in which the graphene capping layer suppresses delamination and stabilizes the solid electrolyte interface. The graphene-draped Si films on CNM exhibit long cycle life (>1000 charge/discharge steps) with an average specific capacity of ∼806 mAh g–1. The volumetric capacity averaged over 1000 cycles of charge/discharge is ∼2821 mAh cm–3, which is 2 to 5 times higher than what is reported in the literature for Si nanoparticle based electrodes. The graphene-draped Si anode could also be successfully cycled against commercial cathodes in a full-cell configuration.
Purpose. Segmentation of hepatocellular carcinoma (HCC) is crucial; however, manual segmentation is subjective and time-consuming. Accurate and automatic lesion contouring for HCC is desirable in ...clinical practice. In response to this need, our study introduced a segmentation approach for HCC combining deep convolutional neural networks (DCNNs) and radiologist intervention in magnetic resonance imaging (MRI). We sought to design a segmentation method with a deep learning method that automatically segments using manual location information for moderately experienced radiologists. In addition, we verified the viability of this method to assist radiologists in accurate and fast lesion segmentation. Method. In our study, we developed a semiautomatic approach for segmenting HCC using DCNN in conjunction with radiologist intervention in dual-phase gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid- (Gd-EOB-DTPA-) enhanced MRI. We developed a DCNN and deep fusion network (DFN) trained on full-size images, namely, DCNN-F and DFN-F. Furthermore, DFN was applied to the image blocks containing tumor lesions that were roughly contoured by a radiologist with 10 years of experience in abdominal MRI, and this method was named DFN-R. Another radiologist with five years of experience (moderate experience) performed tumor lesion contouring for comparison with our proposed methods. The ground truth image was contoured by an experienced radiologist and reviewed by an independent experienced radiologist. Results. The mean DSC of DCNN-F, DFN-F, and DFN-R was 0.69±0.20 (median, 0.72), 0.74±0.21 (median, 0.77), and 0.83±0.13 (median, 0.88), respectively. The mean DSC of the segmentation by the radiologist with moderate experience was 0.79±0.11 (median, 0.83), which was lower than the performance of DFN-R. Conclusions. Deep learning using dual-phase MRI shows great potential for HCC lesion segmentation. The radiologist-aided semiautomated method (DFN-R) achieved improved performance compared to manual contouring by the radiologist with moderate experience, although the difference was not statistically significant.
Pancreatic cancer (PC) represents one of the most aggressive forms of cancer. The role of long non-coding RNAs (lncRNAs) has been highlighted in various malignancies including PC. The aim of the ...present study was to investigate the effects associated with actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) on the progression of PC and the underlying mechanism.
Microarray-based gene expression profiling of PC was performed to identify PC-related lncRNAs, after which the expression of AFAP1-AS1 and cancer stem cell (CSC) markers in PC tissues and cells were determined accordingly. The potential microRNA-384 (miR-384) capable of binding to AFAP1-AS1, in addition to its ability to regulate activin receptor A type I (ACVR1) were analyzed. In order to investigate the effect of the AFAP1-AS1/miR-384/ACVR1 axis on self-renewal ability, tumorigenicity, invasion, migration and stemness of PC cells, shRNA-AFAP1-AS1, miR-384 mimic and inhibitor were cloned into cells.
High expression of AFAP1-AS1 and ACVR1 with low expression of miR-384 were detected in PC tissues. ACVR1 was determined to be down-regulated when miR-384 was overexpressed, while the inhibition of AFAP1-AS1 decreased its ability to binding competitively to miR-384, resulting in the down-regulation of ACVR1 and enhancing miR-384 expression, ultimately inhibiting the progression of PC. The knockdown of AFAP1-AS1 or overexpression of miR-384 was confirmed to impair PC cell self-renewal ability, tumorigenicity, invasion, migration and stemness.
Taken together, AFAP1-AS1 functions as an endogenous RNA by competitively binding to miR-384 to regulate ACVR1, thus conferring inhibitory effects on PC cell stemness and tumorigenicity.
Flexible carbon nanotube macro-films (CMFs) are perfect current collectors for preparing foldable lithium-ion batteries (LIBs). However, selecting appropriate anodes for electrode is difficult ...because of the different potentials (vs. Li/Li+) of carbon nanotubes and traditional metallic current collector. This study demonstrated an additional reaction at potential below 0.9 V (vs. Li/Li+) caused by CMF, And Li+ will be constrained, which decreased capacity of anode/CMF electrode. Conversely, results changed when the anode potential exceeded 0.9 V (vs. Li/Li+) because Li+ passed the potential threshold, and the CMF retained its electrochemical inactivity. Consequently, the CMF-based foldable LIBs performed well. The potential threshold mechanism of anode is expected to provide new impetus to both academia and industry for exploring flexible or foldable LIBs.
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•CMF can be used for loading most of the present cathode materials.•CMF based foldable LIBs cannot be obtained as anode potential lower than 0.9 V.•A potential threshold exists for anode materials to match CMF current collector.•Foldable full LIBs can be prepared if its working voltage avoids dangerous region.
Euphorbia humifusa Willd., known as Di-Jin-Cao in Chinese, has long been utilized as a traditional herb for the treatment of furuncles and carbuncles mainly caused by Staphylococcus aureus infection. ...Despite extensive chemical and pharmacological studies reported previously for E. humifusa, the antibacterial and antibiofilm activities against S. aureus as well as the related mechanism of action (MoA) remain largely obscure.
To investigate the antibacterial and antibiofilm activities of the preferred fractions and compounds from E. humifusa against S. aureus and assess the associated MoA.
The bioactive fractions and compounds were obtained from the 75% ethanol extract of E. humifusa (75%-EEEH) with the assistance of the related antibacterial and antibiofilm screening. Their antibacterial activities were determined using the broth microdilution method, whilst the inhibition of biofilm formation and the disruption of preformed biofilm were assessed by crystal violet staining and confocal laser scanning microscopy (CLSM). To achieve more effective therapies, the combinatory effects of different components were also studied. The biofilm metabolic activities of isolated compounds were evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. The scanning electron microscopy (SEM) and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to explore the antibiofilm mechanism.
Fractions DJC06 and DJC07 collected from the ethyl acetate extract of the 75%-EEEH exhibited antibacterial activity (MIC = 256 μg/mL) against S. aureus and further separation of these two fractions led to the isolation and characterization of 22 compounds. Among the isolates, luteolin (LU), quercetin (QU), and kaempferol (KA) are the verified components associated with the antibacterial and antibiofilm activities by displaying individual or combinational MIC values of 8–128 μg/mL and 70.9–99.7% inhibition for biofilm formation. Importantly, QU and KA can work in synergy with LU to significantly enhance the efficacy via destroying cell integrity, increasing membrane permeability, and down-regulating the biofilm-related gene expression.
The preferred fractions and compounds from E. humifusa exerted desired antibacterial and antibiofilm efficacy against S. aureus via a MoA involving cell morphology disruption and altered genes expression. The findings herein not only support its traditional use in the treatment of furuncles and carbuncles, but reveal E. humifusa is a potential source for producing promising antibiofilm alternatives against S. aureus and highlight the isolated components (LU, QU, KA) that can potentiate the efficacy when used in synergy.
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•Fractions and compounds from Euphorbia humifusa exerted desired antibiofilm activity.•Luteolin (LU), quercetin (QU) and kaempferol (KA) represent the bioactive components.•QU and KA can work in synergy with LU to enhance the bioactivities against S. aureus.•QU + LU could down-regulate fnbA expression at the biofilm adhesion/attachment stage.
The corosolic acid (CA), also known as plant insulin, is a pentacyclic triterpenoid extracted from plants such as Lagerstroemia speciosa. It has been shown to have anti-diabetic, anti-inflammatory ...and anti-tumor effects. Its structural analogs ursolic acid (UA), oleanolic acid (OA), maslinic acid (MA), asiatic acid (AA) and betulinic acid (BA) display similar individual pharmacological activities to those of CA. However, there is no systematic review documenting pharmacological activities of CA and its structural analogues. This study aims to fill this gap in literature.
This systematic review aims to summarize the medical applications of CA and its analogues.
A systematic review summarizes and compares the extraction techniques, pharmacokinetic parameters, and pharmacological effects of CA and its structural analogs. Hypoglycemic effect is one of the key inclusion criteria for searching Web of Science, PubMed, Embase and Cochrane databases up to October 2020 without language restrictions. ‘corosolic acid’, ‘ursolic acid’, ‘oleanolic acid’, ‘maslinic acid’, ‘asiatic acid’, ‘betulinic acid’, ‘extraction’, ‘pharmacokinetic’, ‘pharmacological’ were used to extract relevant literature. The PRISMA guidelines were followed.
At the end of the searching process, 140 articles were selected for the systematic review. Information of CA and five of its structural analogs including UA, OA, MA, AA and BA were included in this review. CA and its structural analogs are pentacyclic triterpenes extracted from plants and they have low solubilities in water due to their rigid scaffold and hydrophobic properties. The introduction of water-soluble groups such as sugar or amino groups could increase the solubility of CA and its structural analogs. Their biological activities and underlying mechanism of action are reviewed and compared.
CA and its structural analogs UA, OA, MA, AA and BA are demonstrated to show activities in lowering blood sugar, anti-inflammation and anti-tumor. Their oral absorption and bioavailability can be improved through structural modification and formulation design. CA and its structural analogs are promising natural product-based lead compounds for further development and mechanistic studies.
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