Micro/nanofluidic transport by special fibers deposited by electrohydrodynamic direct-writing

Recently micro/nanofluidic transportation is important in many natural and engineering processes, such as water collection, fluid patterning and microfluidic chip. But the natural microstructures for fluid transportation are usually difficult to manufacture and adjust. Here we find that some fibers (the diameters < 10 μm) deposited by electrohydrodynamic direct-writing(EDW) can be directly used for micro/nanofluidic transportation due to the geometries of fibers. The liquid paraffin (its minimum width < 100 nm) can transport along the circular fiber because of the wedge microcavities formed by circular fiber and substrate. Ultrafast directional water transport (about 22 mm/s) has been achieved by oblique elliptic fiber array which has been placed at a distance of 300 μm above the substrate. Moreover, we found that the contact angles of the test liquids on the substrates and on the fiber materials also play a crucial role in this structure. So electrowetting has been used to change the contact angles of water on the substrate to fast switch (response time < 0.4 s) direction of water transport. We think electrohydrodynamic direct-writing the fibers with various geometries opens up new low-cost, high efficiency, fast and accurate pathways to realize fabric-based wearable microfluidic device

Medium Optimization for Exopolysaccharide Production in Liquid Culture of Endophytic Fungus Berkleasmium sp. Dzf12

Abstract: Berkleasmium sp. Dzf12, an endophytic fungus from Dioscorea zingiberensis, is a high producer of spirobisnaphthalenes with various bioactivities. The exopolysaccharide (EPS) produced by this fungus also shows excellent antioxidant activity. In this study, the experimental designs based on statistics were employed to evaluate and optimize the medium for EPS production in liquid culture of Berkleasmium sp. Dzf12. For increasing EPS yield, the concentrations of glucose, peptone, KH2PO4, MgSO4·7H2O and FeSO4·7H2O in medium were optimized using response surface methodology (RSM). Both the fractional factorial design (FFD) and central composite design (CCD) were applied to optimize the main factors which significantly affected EPS production. The concentrations of glucose, peptone and MgSO4·7H2O were found to be the main effective factors for EPS production by FFD experimental analysis. Based on the further CCD optimization and RSM analysis, a quadratic polynomial regression equation was derived from the EPS yield and three variables. Statistical analysis showed the polynomial regression model was in good agreement with the experimental results with the determination coefficient (adj-R 2) as 0.9434. By solving the quadratic regression equation, the optimal concentrations of glucose

EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma (UM). Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular functions. In search of genetic vulnerability for UM, we found that inhibition of euchromatic histone lysine methyltransferase 2 (EHMT2) expression or activity significantly reduced the proliferation and migration capacity of cancer cells. Notably, elevated expression of EHMT2 had been validated in UM samples. Furthermore, Kaplan–Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T stage. Chromatin immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of EHMT2. Its transcription was suppressed by EHMT2 in a methyltransferase-dependent pattern in GNAQ/11-mutant UM cells, leading to elevated RhoA activity. Rescuing constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic phenotypes. Simultaneously blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth, suggesting the driver role of these two key molecules. In summary, our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM

Total Flavonoids of <i>Rhizoma Drynariae</i> Mitigates Aflatoxin B1-Induced Liver Toxicity in Chickens via Microbiota-Gut-Liver Axis Interaction Mechanisms

Aflatoxin B1 (AFB1) is a common mycotoxin that widely occurs in feed and has severe hepatotoxic effects both in humans and animals. Total flavonoids of Rhizoma Drynaria (TFRD), a traditional Chinese medicinal herb, have multiple biological activities and potential hepatoprotective activity. This study investigated the protective effects and potential mechanisms of TFRD against AFB1-induced liver injury. The results revealed that supplementation with TFRD markedly lessened broiler intestinal permeability by increasing the expression of intestinal tight junction proteins, as well as correcting the changes in gut microbiota and liver damage induced by AFB1. Metabolomics analysis revealed that the alterations in plasma metabolites, especially taurolithocholic acid, were significantly improved by TFRD treatment in AFB1-exposed chickens. In addition, these metabolites were closely associated with [Ruminococcus], ACC, and GPX1, indicating that AFB1 may cause liver injury by inducing bile acid metabolism involving the microbiota–gut–liver axis. We further found that TFRD treatment markedly suppressed oxidative stress and hepatic lipid deposition, increased plasma glutathione (GSH) concentrations, and reversed hepatic ferroptosis gene expression. Collectively, these findings indicate that ferroptosis might contribute to the hepatotoxicity of AFB1-exposed chickens through the microbiota–gut–liver axis interaction mechanisms; furthermore, TFRD was confirmed as an herbal extract that could potentially antagonize mycotoxins detrimental effects

Main Ustilaginoidins and Their Distribution in Rice False Smut Balls

Rice false smut has become an increasingly serious fungal disease in rice (Oryza sativa L.) production worldwide. Ustilaginoidins are bis-naphtho-γ-pyrone mycotoxins previously isolated from the rice false smut balls (FSBs) infected by the pathogen Villosiclava virens in rice spikelets on panicles. To investigate the main ustilaginoidins and their distribution in rice FSBs, five main bis-naphtho-γ-pyrones, namely ustilaginoidins A (1), G (2), B (3), I (4) and C (5), were isolated and identified by NMR and high-resolution mass spectrometry as well as by comparison with the data in the literature. The rice FSBs at early, middle and late maturity stages were divided into their different parts and the contents of five main ustilaginoidins for each part were determined by HPLC analysis. The results revealed that the highest levels of ustilaginoidins were in late stage rice FSBs, followed by those at middle stage. Most ustilaginoidins, 96.4% of the total quantity, were distributed in the middle layer at early stage. However, ustilaginoidins were mainly distributed in the outer and middle layers at middle and late stages. Small amounts of ustilaginoidins A (1) and G (2) were found in the inner part of rice FSBs at each maturity stage. The contents of ustilaginoidins A (1) and G (2) without hydroxymethyl groups at C-2 and C-2’ of the γ-pyrone rings in rice FSBs were relatively high at early stage, while the contents of ustilaginoidins B (3), I (4), and C (5) with hydroxymethyl groups at C-2 or C-2’ were relatively high at late stage

HIV-1 Tat-Mediated Apoptosis in Human Blood-Retinal Barrier-Associated Cells

<div><p>HIV-1-associated ocular complications, such as microvasculopathies, can lead to the loss of vision in HIV-1-infected patients. Even in patients under highly active antiretroviral therapy, ocular lesions are unavoidable. Ocular complications have been demonstrated to be closely related to the breakdown of the blood-retinal-barrier (BRB); however, the underlying mechanism is not clear. The data from this study indicated that the HIV-1 Tat protein induced the apoptosis of human retinal microvascular endothelial cells (HRMECs) and retinal pigmen epithelium (RPE) cells, which compose the inner BRB and the outer BRB, respectively. In addition, this study found that the activation of N-methyl-D-aspartate receptors (NMDARs) was involved in the apoptosis of RPE cells, but it caused no changes in HRMECs. Furthermore, both cell types exhibited enhanced expression of Bak, Bax and Cytochrome c. The inhibition of Tat activity protected against the apoptosis induced by NMDAR activation and prevented the dysregulation of Bak, Bax and Cytochrome c, revealing an important role for the mitochondrial pathway in HIV-1 Tat-induced apoptosis. Together, these findings suggest a possible mechanism and may identify a potential therapeutic strategy for HIV-1-associated ocular complications.</p></div

HIV-1 Tat induces apoptosis in RPE cells.

<p>ARPE-19 cells were incubated with or without 200 ng/ml Tat for 48 hours. Representative flow cytometry images are shown, which indicate the percentage of cells in early apoptosis using Annexin V-FITC staining (<b>A</b>). Immunofluorescence micrographs showing apoptosis using Annexin V-FITC staining (green); the nuclei were counterstained with PI (red). Scale bar: 50 µm (<b>B</b>). Both the flow cytometric analysis and immunofluorescence showed that Tat induced the apoptosis of RPE cells. The expression levels of NMDAR, Bax, Bak and Cytochrome c were quantitatively analyzed using qPCR (*, P<0.05 vs. control) (<b>C</b>) (<b>D</b>) and Western blotting (<b>E</b>) after ARPE-19 cells were treated with Tat for 0, 6, 24 or 48 h. The corresponding graphs show the quantification of 3 independent experiments performed in duplicate; the data were normalized to cells without Tat treatment (<b>#</b>, P<0.05 vs. control) (<b>F</b>).</p

Neutralizing Tat attenuates Tat-induced HRMEC apoptosis.

<p>An anti-Tat antibody was added to HRMECs and incubated for 24 hours. The cells were then incubated with 0, 200, 400, or 600 ng/ml Tat for 48 hours. Representative phase-contrast microscopic images show the morphology of the cells (<b>A</b>). Immunofluorescence micrographs showing apoptosis using Annexin V-FITC staining (green). Scale bar: 50 µm (<b>B</b>). The levels of Bcl-2, Bax, Bak and Cytochrome c expression were quantitatively analyzed using qPCR (*, P<0.05 vs. control).</p

HIV-1 Tat induces apoptosis of HRMECs.

<p>HRMECs were incubated with 0, 200, 400, or 600/ml Tat for 48 hours. Representative phase-contrast microscopic images are shown, indicating the loss and swelling of HRMECs at different degrees (<b>A</b>). Immunofluorescence micrographs showing apoptosis using Annexin V-FITC staining (green). Scale bar: 50 µm (<b>B</b>). Quantitative analysis of Bcl-2, Bax, Bak and Cytochrome c expression using qPCR (*, P<0.05 vs. control) after HRMECs were treated with Tat at different concentrations for 48 h.</p