34 research outputs found

    Characteristic gene expression in the liver monocyte-macrophage-DC system is associated with the progression of fibrosis in NASH

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    BackgroundThe monocyte-macrophage-dendritic cell (DC) (MMD) system exerts crucial functions that may modulate fibrogenesis in nonalcoholic steatohepatitis (NASH). In this study, we explored the cell characteristics, distribution and developmental trajectory of the liver MMD system in NASH mice with fibrosis and clarified characteristic genes of the MMD system involved in liver fibrosis progression in NASH mice and patients.MethodsSingle cells in liver tissue samples from NASH and normal mice were quantified using single-cell RNA sequencing (scRNA-seq) analysis. Differentially expressed genes (DEGs) in the MMD system by pseudotime analysis were validated by tyramide signal amplification (TSA)-immunohistochemical staining (IHC) and analyzed by second harmonic generation (SHG)/two-photon excitation fluorescence (TPEF).ResultsCompared with control mice, there were increased numbers of monocytes, Kupffer cells, and DCs in two NASH mouse models. From the transcriptional profiles of these single cells, we identified 8 monocyte subsets (Mono1-Mono8) with different molecular and functional properties. Furthermore, the pseudotime analysis showed that Mono5 and Mono6 were at the beginning of the trajectory path, whereas Mono2, Mono4, Kupffer cells and DCs were at a terminal state. Genes related to liver collagen production were at the late stage of this trajectory path. DEGs analysis revealed that the genes Fmnl1 and Myh9 in the MMD system were gradually upregulated during the trajectory. By TSA-IHC, the Fmnl1 and Myh9 expression levels were increased and associated with collagen production and fibrosis stage in NASH mice and patients.ConclusionsOur transcriptome data provide a novel landscape of the MMD system that is involved in advanced NASH disease status. Fmnl1 and Myh9 expression in the MMD system was associated with the progression of NASH fibrosis

    Molecular Dynamics Analysis Reveals Structural Insights into Mechanism of Nicotine N-Demethylation Catalyzed by Tobacco Cytochrome P450 Mono-Oxygenase

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    CYP82E4, a cytochrome P450 monooxygenase, has nicotine N-demethylase (NND) activity, which mediates the bioconversion of nicotine into nornicotine in senescing tobacco leaves. Nornicotine is a precursor of the carcinogen, tobacco-specific nitrosamine. CYP82E3 is an ortholog of CYP82E4 with 95% sequence identity, but it lacks NND activity. A recent site-directed mutagenesis study revealed that a single amino acid substitution, i.e., cysteine to tryptophan at the 330 position in the middle of protein, restores the NND activity of CYP82E3 entirely. However, the same amino acid change caused the loss of the NND activity of CYP82E4. To determine the mechanism of the functional turnover of the two molecules, four 3D structures, i.e., the two molecules and their corresponding cys–trp mutants were modeled. The resulting structures exhibited that the mutation site is far from the active site, which suggests that no direct interaction occurs between the two sites. Simulation studies in different biological scenarios revealed that the mutation introduces a conformation drift with the largest change at the F-G loop. The dynamics trajectories analysis using principal component analysis and covariance analysis suggests that the single amino acid change causes the opening and closing of the transfer channels of the substrates, products, and water by altering the motion of the F-G and B-C loops. The motion of helix I is also correlated with the motion of both the F-G loop and the B-C loop and; the single amino acid mutation resulted in the curvature of helix I. These results suggest that the single amino acid mutation outside the active site region may have indirectly mediated the flexibility of the F-G and B-C loops through helix I, causing a functional turnover of the P450 monooxygenase

    How do urban residents use energy for winter heating at home? A large-scale survey in the hot summer and cold winter climate zone in the Yangtze River region

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    The increasing demand for improving indoor thermal environment in the hot summer and cold winter climate zone (HSCW) in the Yangtze River region in China poses enormous challenges in terms of energy policy and design solutions for this unique region. A comprehensive understanding of people’s habits and behaviors involving winter heating is imperative for decision making for urban heating infrastructure investment strategies that significantly impact the decarbonization of heating. However, there are little studies of a large-scale survey to gain such knowledge acrose the region. The aim of this study is to develop a rigorous survey method in order to obtain reliable data for analysis. Five municipal/capital cities across the upper, middle and downstream Yangtze River were surveyed based on 30 randomly generated locations in each city. A total of 8481 valuable samples were obtained in the survey conducted in the winter from November 2017 to March 2018. It is revealed that air conditioning/air source heat pumps are the predominant systems, accounting for 63% and 58% for bedroom and living room heating respectively. The use patterns of heating are diverse featuring ‘part-time-part-space’ systems in accordance with the occupancy patterns. There is significant evidence of the habit of opening a window to provide a gap for fresh air irrespective of whether the heating is in use. Two-step cluster analysis is employed to subdivide occupants’ heating-related behaviors into three clusters to characterize households. This study fills the knowledge gap of winter-heating-related behaviors. The research outcomes will benefit building energy simulations for energy prediction and help policy makers making decisions on providing strategic guidance in terms of winter heating solutions in this region

    Dermoscopic characterization and clinical application of four facial erythematous inflammatory dermatoses

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    Use dermoscope to identify inflammatory dermatoses with facial erythema as the main feature and other atypical clinical manifestations. By reviewing the clinical data and dermoscopic images of outpatients in our hospital, four diseases of rosacea, seborrheic dermatitis, contact dermatitis and atopic dermatitis were screened out, and their dermoscopic characteristics were obtained: Rosacea is a diffuse distribution of polygonal blood vessels on a red or purple background; SD is an atypical vascularity on a yellow-red background with an oil-drop reddish halo around the hair follicle. Contact dermatitis is linear blood vessels and pleomorphic blood vessels in a light red background; AD is punctate blood vessels and spherical blood vessels under a light red background with a visible scaly distribution. Honeycomb pigmentation can be seen in seborrheic dermatitis and contact dermatitis. Combined with relevant clinical reports, the application of dermoscope in clinical diagnosis and treatment are discussed

    Dermoscopic characterization and clinical application of four facial erythematous inflammatory dermatoses

    Get PDF
    Use dermoscope to identify inflammatory dermatoses with facial erythema as the main feature and other atypical clinical manifestations. By reviewing the clinical data and dermoscopic images of outpatients in our hospital, four diseases of rosacea, seborrheic dermatitis, contact dermatitis and atopic dermatitis were screened out, and their dermoscopic characteristics were obtained: Rosacea is a diffuse distribution of polygonal blood vessels on a red or purple background; SD is an atypical vascularity on a yellow-red background with an oil-drop reddish halo around the hair follicle. Contact dermatitis is linear blood vessels and pleomorphic blood vessels in a light red background; AD is punctate blood vessels and spherical blood vessels under a light red background with a visible scaly distribution. Honeycomb pigmentation can be seen in seborrheic dermatitis and contact dermatitis. Combined with relevant clinical reports, the application of dermoscope in clinical diagnosis and treatment are discussed

    Temperature-regulation liquid gating membrane with controllable gas/liquid separation

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    Membrane separation technology with the ability to regulate gas/liquid transport and separation is critical for environmental fields, such as sewerage treatment, multiphase separation, and desalination. Although numerous membranes can dynamically control liquid-phase fluids transport via external stimuli, the transport and separation of gas-phase fluids remains a challenge. Here, we show a temperature-regulation liquid gating membrane that allows in-situ dynamically controllable gas/liquid transfer and multiphase separation by integrating a thermo-wettability responsive porous membrane with functional gating liquid. Experiments and theoretical analysis have demonstrated the temperature-regulation mechanism of this liquid gating system, which is based on thermo-responsive changes of porous membrane surface polarity, leading to changes in affinity between the porous membrane and the gating liquid. In addition, the sandwich configuration with dense Au-coated surfaces and heterogeneous internal components by a bistable interface design enables the liquid gating system to enhance response sensitivity and maintain working stability. This temperature-regulation gas/liquid transfer strategy expands the application range of liquid gating membranes, which are promising in environmental governance, water treatment and multiphase separation

    Properties of Dietary Flavone Glycosides, Aglycones, and Metabolites on the Catalysis of Human Endoplasmic Reticulum Uridine Diphosphate Glucuronosyltransferase 2B7 (UGT2B7)

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    Flavone glycosides, their aglycones, and metabolites are the major phytochemicals in dietary intake. However, there are still many unknowns about the cellular utilization and active sites of these natural products. Uridine diphosphate glucuronosyltransferases (UGTs) in the endoplasmic reticulum have gene polymorphism distribution in the population and widely mediate the absorption and metabolism of endogenous and exogenous compounds by catalyzing the covalent addition of glucuronic acid and various lipophilic chemicals. Firstly, we found that rutin, a typical flavone O-glycoside, has a stronger UGT2B7 binding effect than its metabolites. After testing a larger number of flavonoids with different aglycones, their aglycones, and metabolites, we demonstrated that typical dietary flavone O-glycosides generally have high binding affinities towards UGT2B7 protein, but the flavone C-glycosides and the phenolic acid metabolites of flavones had no significant effect on this. With the disposition of 4-methylumbelliferone examined by HPLC assay, we determined that 10 ÎŒM rutin and nicotifiorin could significantly inhibit the activity of recombinant UGT2B7 protein, which is stronger than isovitexin, vitexin, 3-hydroxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid. In addition, in vitro experiments showed that in normal and doxorubicin-induced lipid composition, both flavone O-glycosides rutin and flavone C-glycosides isovitexin at 10 ÎŒM had no significant effect on the expression of UGT1A1, UGT2B4, UGT2B7, and UGT2B15 genes for 24 h exposure. The obtained results enrich the regulatory properties of dietary flavone glycosides, aglycones, and metabolites towards the catalysis of UGTs and will contribute to the establishment of a precise nutritional intervention system based on lipid bilayers and theories of nutrients on endoplasmic reticulum and mitochondria communication

    Photothermally induced liquid gate with navigation control of the fluid transport

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    The ability to control multiphase flows is essential for applications such as microvalves, chemical analyses, microreactors, and multiphase separators. Furthermore, more specific controls, including the positional navigation control of fluids under steady-state pressures, will improve the development of these applications. Here, we present a fundamentally new photothermally induced liquid gating system that allows light-controlled contactless fluid transport and gas/liquid separations at designated locations, with seconds response times, under constant pressures. Experiments and theoretical calculations demonstrate the stability of our system and its novel regulation mechanism, which is based on a photothermally induced liquid-reconfigurable gate with a change in the surface/interfacial tension and Marangoni flow redistribution of the gating liquid at the illuminated location. This regulation mechanism with positional navigation properties requires neither mechanical parts nor complex accessories and can further enable the miniaturization and integration of various engineering processes. Our application demonstrations confirm the potential of this system in fields of smart valves, multiphase separations, multiphase microreactors, and beyond
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