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The production of riboflavin with Bacillus subtilis, is an established process, however it is yet to be fully optimized. The aim of this study was to explore how riboflavin yields can be improved via in vitro and in vivo metabolic engineering modification of the pentose phosphate pathway (PPP). In vitro, glucose was replaced with sodium gluconate to enhance PPP. Flask tests showed that the riboflavin titer increased from 0.64 to 0.87 g/L. The results revealed that the direct use of sodium gluconate could benefit riboflavin production. In vivo, gntP (encoding gluconate permease) was overexpressed to improve sodium gluconate uptake. The riboflavin titer reached 1.00 g/L with the mutant B. subtilis RF01. Ultimately, the fermentation verification of the engineered strain was carried out in a 7-L fermenter, with the increased riboflavin titer validating this approach. The combination of metabolic engineering modifications in vitro and in vivo was confirmed to promote riboflavin production efficiently by increasing PPP and has great potential for industrial application. This work is aimed to explore how to improve the riboflavin yield by the rational renovation of the pentose phosphate pathway (PPP). In vitro, metabolic engineering mainly uses sodium gluconate as a carbon source instead of glucose, and in vivo, metabolic engineering mainly includes the overexpression of sodium gluconate utility-related genes. The effect of sodium gluconate on cell growth, riboflavin production was investigated in the flasks and fermenter scale.

Background Drug-eluting stents impair post-angioplasty re-endothelialization thus compromising restenosis prevention while heightening thrombotic risks. We recently found that inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) effectively mitigated both restenosis and thrombosis in rodent models. This motivated us to determine how PERK inhibition impacts re-endothelialization. Methods Re-endothelialization was evaluated in endothelial-denuded rat carotid arteries after balloon angioplasty and periadventitial administration of PERK inhibitor in a hydrogel. To study whether PERK in smooth muscle cells (SMCs) regulates re-endothelialization by paracrinally influencing endothelial cells (ECs), denuded arteries exposing SMCs were lentiviral-infected to silence PERK; in vitro, the extracellular vesicles isolated from the medium of PDGF-activated, PERK-upregulating human primary SMCs were transferred to human primary ECs. Results Treatment with PERK inhibitor versus vehicle control accelerated re-endothelialization in denuded arteries. PERK-specific silencing in the denuded arterial wall (mainly SMCs) also enhanced re-endothelialization compared to scrambled shRNA control. In vitro, while medium transfer from PDGF-activated SMCs impaired EC viability and increased the mRNA levels of dysfunctional EC markers, either PERK inhibition or silencing in donor SMCs mitigated these EC changes. Furthermore, CXCL10, a paracrine cytokine detrimental to ECs, was increased by PDGF activation and decreased after PERK inhibition or silencing in SMCs. Conclusions Attenuating PERK activity pharmacologically or genetically provides an approach to accelerating post-angioplasty re-endothelialization in rats. The mechanism may involve paracrine factors regulated by PERK in SMCs that impact neighboring ECs. This study rationalizes future development of PERK-targeted endothelium-friendly vascular interventions.

A miniaturized flow device has been developed to combine microfluidics technology and plasma process. In this microreactor, atmospheric pressure dielectric barrier discharges are generated in a gas in contact with a liquid phase. This study was conducted with plasma generated in ammonia in contact with a flow of liquid cyclohexane. Cyclohexylamine was synthesized with a good selectivity, and the process can be implemented to improve conversion and effectiveness. Numerical simulations confirmed that NH2 radicals are generated in the plasma and react with cyclohexyls radicals to achieve the reaction, giving a selectivity of 50% and a total molar conversion of 20% of cyclohexane. The effects of voltage and frequency on the selectivity and the experimental conversion rate were studied and discussed.

The assembly of nano- and micro-scale building blocks on surface has been the focus of intense interest in materials science for years. In this work, (3-aminopropyl)triethoxysilane (APTES) carrying one primary amino group was deposited on various substrate surfaces using the plasma polymerization method. The key plasma parameters i.e. pressure and power were varied to obtained the highest density of primary amino groups. The influence of such parameters on the characteristics of deposited layers (e.g. chemical structure, adhesion strength, growth rate, etc.) was systemically investigated using various characterization methods such as XPS, FTIR, ellipsometry and so on. Meanwhile, three types of particles (AuNPs, zeolites and gold@zeolites) with sizes from nano- to submicro-range were synthesized and further used as model building blocks. Subsequently, the prepared particles were deposited onto cyclic olefin copolymer (COC) substrate surfaces, which were pre-functionalized by deposition of the plasma polymer layer using the parameters of pressure = 1.0 mbar and power = 30 W. The results confirmed the formation of membrane structures consisting of highly packed particles on the COC surface, and such immobilized structures showed high stability against flowing water, evidencing the good immobilization ability of deposited APTES layers with amino groups.

To improve the removal efficiency of pharmaceutical antibiotics from water by adsorption technologies, it is vital to optimize the porous geometrical structure of carbonaceous adsorbents. In this study, a hierarchical porous carbon that possesses micro/meso bimodal pores (MMC) is synthesized and is employed in the adsorption of tetracycline in both batch mode and column mode. In comparison, microporous carbon, mesoporous carbon, and commercial activated carbon (AC) are induced as carbonaceous adsorbents. In batch mode adsorption, the maximum adsorbed amount of tetracycline on MMC reaches 701.31 mg/g, which is twice as much as that on AC. While in the column adsorption process, the treatment capacity and the total adsorbed amount of MMC toward tetracycline are found 10 times greater than those of AC. The porous geometrical structure of the adsorbent is revealed to play an important role in determining the adsorption efficiency in the column adsorption process with a limited contact time. The surface utiliz...

Background: The E3 ligase SIAH1 is deregulated in human cancers and correlated with poor prognosis, but its contributions to chemoresistance in epithelial ovarian cancer (EOC) are not evident. Methods: SIAHI, RPS3, NF-κB (P65), FLAG and GFP protein levels were assessed by western blotting (WB) or immunohistochemistry (IHC). The mRNA levels were revealed by qRT-PCR. Colocalization of RPS3 and SIAH1 was detected by confocal microscopy and co-immunoprecipitation (CO-IP). RPS3 ubiquitination levels were detected by immunoprecipitation (IP). Cell functional experiments were performed and A2780 xenograft models were employed to expose the latent mechanisms of the SIAH1-RPS3-NF-κB axis as well as the role of SIAH1 in inhibiting chemoresistance in vitro and in vivo.Results: We show that SIAH1 is decreased in EOC tumour tissues and cell lines and negatively correlated with RPS3 level. SIAH1 overexpression suppresses tumour cell growth, colony formation, invasion, metastasis, and cisplatin resistance in vivo and in vitro. SIAH1 promoted RPS3 ubiquitination and degradation using the RING-finger domain, which was required for RPS3 localization to the cytoplasm for subsequent NF-κB inactivation, thereby conferring chemosensitivity. Moreover, ectopic expression of RPS3 or depletion of RPS3 ubiquitination mediated by SIAH1 via the K214R mutant significantly impaired cisplatin-induced tumour suppression in cells stably expressing SIAH1. Conclusions: Our findings reveal a tumour suppressor function of SIAH1 and provide evidence that the SIAH1-RPS3-NF-κB axis may act as an appealing strategy to tackle treatment resistance in EOC.

Polymer membranes represent a low cost, low energy solution to separating biologically derived chemicals from fermentation. However, the performance of these membranes is commonly limited by fouling caused by biological components, but additives are also included in typical fermentation broths that can interact with the polymer membrane. Here, we examine how a common polyol antifoam agent (Antifoam 204) dramatically swells and plasticizes a high performing biobutanol membrane copolymer of hydroxyhexafluoroisopropyl and n-butyl substituted norbornene. When equilibrated against 1 wt % (aq) butanol, the solvent in the copolymer increases from 40 vol % at 1 ppm of antifoam and >80 vol % at 100 ppm of antifoam. The effect of the antifoam on the properties of the copolymer as determined by QCM-D is much more significant than that of the butanol concentration. Even with 4 wt % butanol (greater than typically viable for biobutanol), the copolymer swells

To overcome the fast or burst release of hydrophilic drugs from hydrophilic alginate-based carriers, hydrophobic molecule (vinyl acetate, VAc) was grafted on alginate (Alg), which was further used to prepare drug carriers. Amphiphilic Alg-g-PVAc hydrogel beads were firstly prepared by emulsification/internal gelation technique for the loading of bovine serum albumin (BSA). Then, chitosan was coated on the surface of beads to form novel amphiphilic Alg-g-PVAc/chitosan (Alg-g-PVAc/CS) microcapsules. The BSA-loading amphiphilic Alg-g-PVAc/chitosan (Alg-g-PVAc/CS) microcapsules display similar morphology and size to the hydrophilic alginate/chitosan (AC) microcapsules. However, the drug loading and loading efficiency of BSA in Alg-g-PVAc/CS microcapsules are higher, and the release rate of BSA from Alg-g-PVAc/CS microcapsules is slower. The results demonstrate that the introduction of hydrophobic PVAc on alginate can effectively help retard the release of BSA, and the higher degree of substitution is, the slower the release rate is. In addition, the complex membrane can also be adjusted to delay the release of BSA. As a whole, amphiphilic sodium alginate-vinyl acetate/CS microparticles could be developed for macromolecular drug delivery.

We have previously demonstrated that the rate of fluid shear stress (ΔSS) can manipulate the fate of mesenchymal stem cells (MSCs) to osteogenic or chondrogenic cells. However, whether ΔSS is comparable to other two means of induction medium and substrate stiffness that have been proven to be potent in differentiation control is unknown. In this study, we subjected MSCs to 1-7 days of osteogenic or chondrogenic chemical induction, or 1-4 days of 37 or 86 kPa of substrate stiffness induction, followed by 20 min of Fast ΔSS (0-0') or Slow ΔSS (0-2'), which is a laminar FSS that linearly increased from 0 to 10 dyn/cm 2 in 0 (Fast) or 2 min (Slow) and maintained at 10 dyn/cm 2 for a total of 20 min. We found that 20 min of ΔSS could compete with 5 days' chemical and 2 days' substrate stiffness inductions. Our study confirmed that ΔSS is a powerful tool to control the differentiation of MSCs, which stressed the possible application in MSCs linage specification.

International audience; Nematic liquid crystal elastomer (LCE) micropillars with reversible thermomechanical deformations and photo luminescence (PL) intensity variations were successfully fabricated by introducing a cyano-oligo(p-phenylene vinylene) dye as a chemical crosslinker. The PL intensity of the micropillars decreased and increased reversibly during the thermal-deformation process. We studied in detail the possible factors that influence the PL intensity variations of the micropillars, including temperature variation, contraction/extension and phase transition. The dye molecules mainly kept the “monomer” state in the micropillars during the thermo-activated deformation. It was found that the phase transition from nematic to isotropic of the LCEs played the major role in the PL intensity variations. This kind of micropillar may have potential application in fluorescent soft sensors and actuators.

International audience; Photoredox/Nickel dual catalysis using easy oxydized bis-catecholato hypercoordinated silicon derivatives as radical sources and acylchlorides as electrophile allows a new method of formation of dialkyl and alkyl-aryl ketones as well as dibenzyl ketones which are less easily accessed. Flow chemistry can be used

Visual Abstract, Highlights • Distinct from other histone deacetylases, HDAC6 primarily resides in the cytosol. • Unexpectedly, HDAC6-selective inhibition (or silencing) enhances the nuclear activity of SRF. • HDAC6 inhibition elevates acetylation and protein levels of myocardin-related transcription factor A, a cytoplasmic-nuclear shuttling co-activator of SRF. Myocardin-related transcription factor A/SRF are known to critically regulate vascular smooth muscle cell phenotypic stability. • HDAC6 inhibition prevents smooth muscle cell dedifferentiation in vitro and reduces neointima and restenosis in vivo., Summary Cellular plasticity is fundamental in biology and disease. Vascular smooth muscle cell (SMC) dedifferentiation (loss of contractile proteins) initiates and perpetrates vascular pathologies such as restenosis. Contractile gene expression is governed by the master transcription factor, serum response factor (SRF). Unlike other histone deacetylases, histone deacetylase 6 (HDAC6) primarily resides in the cytosol. Whether HDAC6 regulates SRF nuclear activity was previously unknown in any cell type. This study found that selective inhibition of HDAC6 with tubastatin A preserved the contractile protein (alpha-smooth muscle actin) that was otherwise diminished by platelet-derived growth factor-BB. Tubastatin A also enhanced SRF transcriptional (luciferase) activity, and this effect was confirmed by HDAC6 knockdown. Interestingly, HDAC6 inhibition increased acetylation and total protein of myocardin-related transcription factor A (MRTF-A), a transcription co-activator known to translocate from the cytosol to the nucleus, thereby activating SRF. Consistently, HDAC6 co-immunoprecipitated with MRTF-A. In vivo studies showed that tubastatin A treatment of injured rat carotid arteries mitigated neointimal lesion, which is known to be formed largely by dedifferentiated SMCs. This report is the first to show HDAC6 regulation of the MRTF-A/SRF axis and SMC plasticity, thus opening a new perspective for interventions of vascular pathologies.

International audience; The recovery of metals from WEEE, Waste from Electrical and Electronic Equipment, is a major challenge to preserve natural resources. Hydrometallurgy, which consists in leaching metals is a promising method but generates large amounts of polluting effluents. In this study we design aqueous leaching foams, composed of 90% v/v of gas and 10% v/v of HCl solution to oxidize and dissolve copper. We take advantage of the oxidizing power of the dioxygen (O2) present in the air bubbles whose fast transfer through the foams enables an efficient oxidation of copper. We then extend the concept of leaching foams to another gas, ozone, to oxidize silver (Ag). We finally show that using an anionic surfactant to complex cupric ions helps improving the dissolution of the metal. These promising results open new recycling routes for metals contained in WEEE, with a lower environmental footprint.

Refereed/Peer-reviewed Hierarchical porous carbon (HPC) materials have found advanced applications in energy storage, adsorption, and catalysis in recent years. The HPC can be synthesized from a vast range of inexpensive carbon precursors, and contain unique structural features, such as nano-scale dimension, high porosity, high surface area, and tunable pore surfaces. These materials hold immense potential for removing contaminants from water and wastewater. However, this area is severely under-explored yet. In this review, we have discussed the recent advances of synthesis, modification, and application of HPC for the removal of pollutants from water, especially focusing on organic pollutants. Owing to their intrinsic hydrophobic nature and unique interconnected porous structure, HPC demonstrates a high affinity to hydrophobic organic contaminants, which can be enhanced many folds by target-specific chemical activation. Successful high-performance removal of contaminants by pristine and modified HPC includes plastic-derived (e.g. bisphenol A), pharmaceutical (e.g. antibiotics), dye (e.g. methylene blue) and pesticide micro-pollutants. Future research is warranted to find optimal and effective HPC synthesis and modification methods for further improving their ability to remove aqueous organic contaminants as a low-cost and energy-inexpensive remediation technology.

Caryolanes, known as β-caryophyllene alcohols, are widely occurring sesquiterpenes in plants. From the cultures of marine Streptomyces sp. AH25, two new caryolane sesquiterpenes, micaryolanes A and B (1 and 2), together with caryolan-1,9β-diol (3) were isolated. Their structures were elucidated by extensive analyses of HR-MS and NMR spectroscopic data. The absolute configurations were assigned via the CD data of the in situ formed [Rh2 (OCOCF3 )4 ] complex and supported by comparison of experimental and calculated specific rotation values. Compounds 1-3 exhibited no activities against Hep3B or MG-63 cell lines or against Gram-positive and Gram-negative bacteria. The results not only enriched the caryolane family, but also proved bacteria as a productive source of terpene metabolites.

International audience; The research on soft actuators including liquid crystal elastomers (LCEs) becomes more and more appealing at a time when the expansion of artificial systems is blooming. Among the various LCE actuators, the bending deformation is often in the origin of many actuation modes. Here, a new strategy with plasma technology is developed to prepare single‐layer main‐chain LCEs with thermally actuated bending and contraction deformations. Two distinct reactions, plasma polymerization and plasma‐induced photopolymerization, are used to polymerize in one step the nematic monomer mixture aligned by magnetic field. The plasma polymerization forms cross‐linked but disoriented structures at the surface of the LCE film, while the plasma‐induced photopolymerization produces aligned LCE structure in the bulk. The actuation behaviors (bending and/or contraction) of LCE films can be adjusted by plasma power, reaction time, and sample thickness. Soft robots like crawling walker and flower mimic are built by LCE films with bending actuation.

Bromodomain protein BRD4 reads histone acetylation (H3K27ac), an epigenomic mark of transcription enhancers. CCAAT enhancer binding protein delta (CEBPD) is a transcription factor typically studied in metabolism. While both are potent effectors and potential therapeutic targets, their relationship was previously unknown. Here we investigated their interplay in vascular smooth muscle cell (SMC) inflammation. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) revealed H3K27ac/BRD4 enrichment at Cebpd in injured rat carotid arteries. While genomic deletion of BRD4-associated enhancer in SMCs in vitro decreased Cebpd transcripts, BRD4 gene silencing also diminished Cebpd mRNA and protein, indicative of a BRD4 control over CEBPD expression. Bromodomain-1, but not bromodomain-2, accounted for this BRD4 function. Moreover, endogenous BRD4 protein co-immunoprecipitated with CEBPD, and both proteins co-immunoprecipitated the Cebpd promoter and enhancer DNA fragments. These co-immunoprecipitations (coIPs) were all abolished by the BRD4-bromodomain blocker JQ1, suggesting a BRD4/CEBPD /promoter/enhancer complex. While BRD4 and CEBPD were both upregulated upon tumor necrosis factor alpha (TNF-α) stimulation of SMC inflammation (increased interleukin [IL]-1b, IL-6, and MCP-1), they mediated this stimulation via preferentially elevated expression of platelet-derived growth factor receptor alpha (PDGFRα, versus PDGFRβ), as indicated by loss- and gain-of-function experiments. Taken together, our study unravels a hierarchical yet collaborative BRD4/CEBPD relationship, a previously unrecognized mechanism that prompts SMC inflammation and may underlie other pathophysiological processes as well., Graphical abstract, The inflammatory smooth muscle cell state is a common etiology in vascular diseases. Unraveling its underlying mechanism, this study reveals a novel interplay between an epigenetic reader of chromatin bookmarks and a master transcription factor, through in vivo and in vitro analyses of epigenomic remodeling and molecular interactions.

International audience; Carbon-11 is undoubtedly an attractive PET radiolabeling synthon because carbon is present in all biological molecules. It is mainly found under 11CO2, but the latter being not very reactive, it is necessary to convert it into a secondary precursor. 11CO is an attractive precursor for labeling the carbonyl position through transition-metal mediated carbonylation because of its access to a wide range of functional groups (e.g., amides, ureas, ketones, esters, and carboxylic acids) present in most PET tracer molecules. However, the main limitations of 11CO labeling are the very short half-life of the radioisotope carbon-11 and its low concentration, and the low reactivity and poor solubility of 11CO in commonly used organic solvents. In this work, we show that a possible solution to these limitations is to use microfluidic reactor technology to perform carbonylation reactions, whilst a novel approach to generate CO from CO2 by plasma is described. The methodology consists of the decomposition of CO2 into CO by non-thermal DBD plasma at room temperature and atmospheric pressure, followed by the total incorporation of CO thus formed in the gas phase by carbonylation reaction, in less than 2 min of residence time. This “proof of principle” developed in carbon-12 would be further applied in carbon-11. Although considerable advances in 11CO chemistry have been reported in recent years, its application in PET tracer development is still an area of work in progress, because of the lack of commercially available synthesis instruments designed for 11C-carbonylations. To the best of our knowledge, such an innovative and efficient process, combining microfluidics and plasma, allowing the very fast organic synthesis of carbonyl molecules from CO2 with high yield, in mild conditions, has never been studied.

Hydrophobically modified copolymers provide a versatile platform of hydrogel materials for diverse applications, but the influence of salts on the swelling and material properties of this class of hydrogels has not been extensively studied. Here, we investigate model hydrogels with three different sodium salts with anions chosen from the classic Hofmeister series to determine how these counterions influence the swelling and mechanical properties of neutral hydrogels. The gel chosen was based on a statistical copolymer of dimethylacrylamide and 2-(

Uterine contractions during normal pregnancy and preterm birth are an important physiological activity. Although the cause of preterm labor is usually unknown, preterm birth creates very serious health concerns in many cases. Therefore, understanding normal birth and predicting preterm birth can help both newborn babies and their families. In our previous work, we developed a multiscale dynamic electrophysiology model of uterine contractions. In this paper, we mainly focus on the cellular level and use electromyography (EMG) and cell force generation methods to construct a new ionic channel model and a corresponding mechanical force model. Specifically, the ionic channel model takes into consideration the knowledge of individual ionic channels, which include the electrochemical and bioelectrical characteristics of individual myocytes. We develop a new sodium channel and a new potassium channel based on the experimental data from the human myometrium and the average correlations are 0.9946 and 0.9945, respectively. The model is able to generate the single spike, plateau type and bursting type of action potentials. Moreover, we incorporate the effect of oxytocin on changing the properties of the L-type and T-type calcium channels and further influencing the output action potentials. In addition, we develop a mechanical force model based on the new ionic channel model that describes the detailed ionic dynamics. Our model produces cellular mechanical force that propagates to the tissue level. We illustrate the relationship between the cellular mechanical force and the intracellular ionic dynamics and discuss the relationship between the application of oxytocin and the output mechanical force. We also propose a simplified version of the model to enable large scale simulations using sensitivity analysis method. Our results show that the model is able to reproduce the bioelectrical and electromechanical characteristics of uterine contractions during pregnancy.

A novel method was proposed in this study to increase the stability of tooeleite, which is a ferric arsenite sulfate mineral, by synthesizing pure and well-crystallized tooeleite using the hydrothermal method. The effects of temperature, pH and Fe/As were systematically studied; the optimized tooeleite can be obtained under the conditions of pH 1.6, Fe/As 1.5, and 120 °C. Mossbauer spectrum was employed, which proved that the acquired tooeleite was pure and did not contain amorphous phases. The short-term stability of tooeleite was tested using Toxicity Characteristic Leaching Procedure, which exhibited relatively good stability compared with that synthesized by the currently existing method. A silica coating method was further utilized to help the tooeleite successfully reach the standard. Finally, the competitive formation of tooeleite and natrojarosite that occured during the hydrothermal process was researched and the preferential formation range of tooeleite was acquired. This study suggests that tooeleite has the potential to be used in the fixation of arsenite.

The oxidation of fatty acids affects the aroma of foxtail millet porridge. However, the relationship between volatile compounds and fatty acid precursors is still unclear. Gas chromatography-mass spectrometry was used to detect the volatiles of foxtail millet porridge. The results showed that 23 volatiles were detected, and the content of most aldehydes increased after cooking. The free fatty acid content increased 0.8–1.2-fold, while the total fatty acid content decreased 0.1–0.4-fold. Modeling experiments showed that palmitic acid had no contribution to the formation of volatile compounds, whereas stearic acid produced heptadecane by decarboxylation. Moreover, oleic acid produced octanal, nonanal, nonane, and decanal. Linoleic acid produced hexanal, (Z)-2-heptenal, (E)-2-octenal, 2-pentyl-furan, 3-ethyl-2-methyl-1,3-hexadienal, (E,E)-2,4-decadienal, N-phenyl-benzenamine, 2-n-butylfuran, and benzaldehyde. Linolenic acid produced (E,E)-2,4-decadienal, decanal, benzaldehyde, tetradecane, hexadecane, 2,6,10-trimethyl-pentadecane, and heptadecane. Unsaturated fatty acids play important roles in the formation of the volatiles of foxtail millet porridge.

Pharmaceutical antibiotics have recently become emerging environmental contaminants. To enhance the removal efficiency of antibiotics in water, hierarchically porous carbons (HPCs) with designed porous patterns are used in both batch and column mode adsorption processes in this study, and the role of their nanoporous geometry in the adsorption dynamics are explored. THPC (HPC with trimodal pores) and DHPC (HPC with bimodal pores) exhibit remarkably superior adsorption performances to the selected antibiotics than those of commercial activated carbon (AC) with similar surface area, especially in column mode adsorption. The effective treatment volumes of the HPC-columns remain up to 8–10 times those of the AC-columns for the removal of tetracycline and 4–6 times for the removal of tylosin. The mass transfer rates of the carbon-based columns present the order of THPC > DHPC > AC. As comparison, the columns based on monomodal mesoporous carbon (MEC) and microporous carbon (MAC) exhibit low effective treatment volumes although their high mass transfer speed. The interconnected meso/macropores in HPCs benefit the intraparticle mass transfer of guest molecules and the accessibility of adsorption sites. The micropores linking to the meso/macropores not only provide adsorption sites but also facilitate adsorption affinity.

A plasma microreactor dedicated to chemical synthesis has been conceived and developed using soft-lithography techniques. In this study, we propose to use highly reactive species created by the plasma discharge to replace traditionally used chemical initiators. A dielectric barrier discharge plasma was generated under atmospheric pressure and then dispersed into a continuous liquid phase with a T-junction geometry. Injected metal electrodes made it possible for in situ optical observations with an intensified charge-coupled device camera. No signal was detected when analyzing the exhaust liquid by electron spin resonance (ESR) spectroscopy. Numerical simulations confirmed that only low quantities of hydroxyl radicals could diffuse into the liquid phase, giving a concentration of DMPO-OH of 10−6 mol/l, below the detection limit of ESR.

Traditionally a pharmacologic target for antipsychotic treatment, the sigma-2 receptor (S2R) was recently implicated in cholesterol homeostasis. Here we investigated the transcriptional regulation of S2R by the Bromo/ExtraTerminal epigenetic reader family (BETs, including BRD2, 3, 4) upon cholesterol perturbation.Cytosolic cholesterol deprivation was induced using an export blocker of lysosomal cholesterol in ARPE19 cells. This condition upregulated mRNA and protein levels of S2R, and of SREBP2 but not SREBP1, transcription factors key to cholesterol/fatty acid metabolism. Silencing BRD2 but not BRD4 (though widely deemed as a master regulator) or BRD3 prevented S2R upregulation induced by cholesterol deprivation. Silencing SREBP2 but not SREBP1 diminished S2R expression. Furthermore, BRD2 co-immunoprecipitated with the SREBP2 transcription-active N-terminal domain, and chromatin immunoprecipitation-qPCR showed a BRD2 occupancy at the S2R gene promoter.In summary, this study reveals a novel BRD2/SREBP2 cooperative regulation of S2R transcription in response to cytosolic cholesterol deprivation, thus shedding new light on epigenetic control of cholesterol biology.

Background Vein-graft bypass is commonly performed to overcome atherosclerosis but is limited by high failure rates, principally due to neointimal wall thickening. Recent studies reveal that endothelial-mesenchymal transition (EndoMT) is critical for vein-graft neointima formation. BETs are a family of Bromo/ExtraTerminal domains-containing epigenetic reader proteins (BRD2, BRD3, BRD4). They bind acetylated histones through their unique tandem bromodomains (BD1, BD2), facilitating transcriptional complex formation and cell-state transitions. The role for BETs, including individual BRDs and their unique BDs, is not well understood in EndoMT and neointimal formation. Methods and results Repression of BRD4 expression abrogated TGFβ1-induced EndoMT, with greater effects than BRD2 or BRD3 knockdown. An inhibitor selective for BD2 in all BETs, but not that for BD1, blocked EndoMT. Moreover, expression of a dominant-negative BRD4-specific BD2 fully abolished EndoMT. Concordantly, BRD4 knockdown repressed TGFβ1-stimulated increase of ZEB1 protein – a transcription factor integral in EndoMT. In vivo, lentiviral gene transfer of either BRD4 shRNA or dominant negative BRD4-specific BD2 mitigated neointimal development in rat jugular veins grafted to carotid arteries. Conclusions Our data reveal the BD2 domain of BRD4 as a determinant driving EndoMT in vitro and neointimal formation in vivo. These findings provide new insight into BET biology, while offering prospects of specific BET domain targeting as an approach to limiting neointima and extending vein graft patency.

A divergent member of the polo-like kinase family, PLK4 is known for its canonical role in centriole duplication. Its non-canonical function and regulators are poorly defined. Here we investigated PLK4’s activation and expression and regulations thereof in rat adventitial fibroblast cell-type transition induced by platelet-derived growth factor (PDGF-AA).Experiments using siRNA and selective inhibitor (centrinone-B) revealed a role for PLK4 not only in AA-induced proliferation/migration, but also in serum response factor (SRF) activation and smooth muscle α-actin expression. PDGFR (receptor) inhibition abrogated AA-stimulated PLK4 activation (phosphorylation) and expression; P38 inhibition (siRNA, inhibitor) downstream of PDGFR also mitigated PLK4 activation. Furthermore, transcription of PLK4 (and PDGFRα) was repressed by pan-inhibition of the bromodomain/extraterminal family of chromatin-bookmark readers (BRD2, BRD3, BRD4), an effect determined herein as mainly mediated by BRD4. In vivo, periadventitial administration of centrinone-B reduced collagen content and thickness of the adventitia in a rat model of carotid artery injury.In summary, we have identified a non-canonical role for PLK4 in SRF activation and its regulations by BRD4/PDGFRα-dominated pathways. Results in this study suggest PLK4 inhibition as a potential anti-fibrotic intervention.

Background Pneumonia is a common respiratory disease in pediatrics. Quercetin is a natural flavonoid widely distributed in many foods and drinks. Herein, we focused our investigation on the possible protective activity of quercetin in lipopolysaccharide (LPS)-caused inflammatory damage of WI-38 lung fibroblasts. Methods Viability and apoptosis of WI-38 were respectively tested using CCK-8 assay and Annexin V-FITC/PI staining. qRT-PCR was used to measure the expression levels of microRNA-221 (miR-221), IL-6 and TNF-a in WI-38. ELISA was conducted to determine the concentrations of IL-6 and TNF-a in culture supernatant of WI-38. miR-221 mimic was transfected to increase miR-221 expression. The protein levels of key molecules involving in cell apoptosis, inflammation, NF-κB and JNK pathways were assessed using western blotting. Results LPS stimulation caused inflammatory damage of WI-38 lung fibroblasts via suppressing cell viability, inducing cell apoptosis and enhancing the production of inflammatory cytokines IL-6 and TNF-a. Quercetin treatment mitigated the LPS-caused inflammatory damage of WI-38 lung fibroblasts via enhancing cell viability, inhibiting cell apoptosis and reducing the production of inflammatory cytokines IL-6 and TNF-a. Moreover, quercetin ameliorated LPS-caused up-regulation of miR-221 in WI-38. The effects of quercetin on LPS-caused inflammatory damage of WI-38 were reversed by miR-221 overexpression. Furthermore, quercetin inactivated NF-κB and JNK pathways in LPS-treated WI-38 via down-regulation of miR-221. Conclusion This research verified the protective effects of quercetin on lung fibroblasts inflammatory damage. We revealed that quercetin ameliorated LPS-caused inflammatory damage of WI-38 lung fibroblasts might be through down-regulation of miR-221 and inactivation of NF-κB and JNK pathways.

Organic matter pollution and heavy metal pollution have become one of the main problems in water recycling, and the strategy to simultaneously remove soluble organic matter and metal ions is crucial for sewage treatment. In this study, multilayer calcium Alginate beads (n-Alg-DBs-Bas) containing Diatom Biosilica (DBs) and Bacillus subtilis (Bas) were designed as microecologics for sewage treatment. The introduction of DBs in beads and the multilayer structure could promote Bas growth, prolong the stability of the beads, and enhance the adsorption of beads, further improve the sewage treatment efficiency. The organic matter degradation of 3 layered Alg-DBs-Bas reached to 68.23 ± 0.95 % of COD and 58.88 ± 0.84 % of NH4+-N, and the metal ion adsorption was up to 119.31 mg/g for Fe3+, 110.81 mg/g for Zn2+ and 141.34 mg/g for Cu2+. The prepared multilayer calcium alginate beads combined organic matter degradation and metal ions absorption, which is significant for environmental applications.

Background: Traditional Chinese medicine involves complex ingredients and mixtures of ingredients that often exhibit low bioavailability, and excipients are often lacking to increase the absorption-enhancing effects. This study modified the generation 4 polyamidoamine dendrimer with polyethylene glycol of different molecular weights (5000, 2000, 1000) to form a series of polyamidoamine-co-polyethylene glycol (PAMAM-co-PEG) as a novel class of oral absorption enhancers. Evodiamine, the major alkaloid found in the traditional Chinese medicine Wu Zhu Yu (Fructus Evodiae), was used as a model drug to verify the absorption-enhancing effects and the safety of this alkaloid. Methods: This study utilized the solubility determination method documented in the Pharmacopoeia of the People’s Republic of China (2015 edition) and the D0 values recommended in the US FDA guidelines to comprehensively evaluate the solubility of evodiamine. The permeability of evodiamine was assessed using the apparent permeability coefficient in experiments based on in vitro cell models. Multiple aspects of the biological safety of PAMAM-co-PEG were explored using the MTT assay, LDH assay, and total protein release of the rat intestinal tract. Moreover, the absorption-enhancing effects of PAMAM-co-PEG at different molecular weights on evodiamine were verified via the use of in vitro cell models and in vivo intestinal loop circulation experiments with rats. Results: Evodiamine exhibited low solubility and permeability and was classified into class IV compounds using the biopharmaceutical classification system. PAMAM-co-PEG 2000 demonstrated improvement in the biosafety and absorption-enhancement effect of evodiamine at a specific concentration. This study showed that 0.05% (w/v) of PAMAM-co-PEG 2000 increased the cumulative penetration of evodiamine via cell transport by 1.32 times, and 0.10% (w/v) of PAMAM-co-PEG 2000 increased the area under curve value of evodiamine by 1.31 times. Conclusion: Evodiamine possesses low solubility and permeability and leads to poor oral bioavailability and a certain degree of cytotoxicity. PAMAM-co-PEG 2000 was found to be a potentially safe and efficient oral absorption enhancer. The results of this study might create a foundation for the development of novel excipients suitable for the complex active ingredients of traditional Chinese medicine.

International audience; Amorphous Ge33As12Se55 films have been deposited by electron beam physical vapor deposition and their optical properties have been studied using reverse engineering on spectrophotometric measurements. Definition of the different optical constants were made by Tauc-Lorentz model allowing simultaneous characterization in high and low absorption area. Moreover an investigation of the layer's photosensitivity with an exposure wavelength at ~808 nm has been carried out and reveals a photo-bleaching effect generating up to 0.04 refractive index variation at 1µm. Finally the stability of the fabricated layers is studied.

Background Intimal hyperplasia is a common cause of many vasculopathies. There has been a recent surge of interest in the bromo and extra-terminal (BET) epigenetic “readers” including BRD4 since the serendipitous discovery of JQ1(+), an inhibitor specific to the seemingly undruggable BET bromodomains. The role of the BET family in the development of intimal hyperplasia is not known. Methods We investigated the effect of BET inhibition on intimal hyperplasia using a rat balloon angioplasty model. Results While BRD4 was dramatically up-regulated in the rat and human hyperplastic neointima, blocking BET bromodomains with JQ1(+) diminished neointima in rats. Knocking down BRD4 with siRNA, or treatment with JQ1(+) but not the inactive enantiomer JQ1(−), abrogated platelet-derived growth factor (PDGF-BB)-stimulated proliferation and migration of primary rat aortic smooth muscle cells. This inhibitory effect of JQ1(+) was reproducible in primary human aortic smooth muscle cells. In human aortic endothelial cells, JQ1(+) prevented cytokine-induced apoptosis and impairment of cell migration. Furthermore, either BRD4 siRNA or JQ1(+) but not JQ1(−), substantially down-regulated PDGF receptor-α which, in JQ1(+)-treated arteries versus vehicle control, was also reduced. Conclusions Blocking BET bromodomains mitigates neointima formation, suggesting an epigenetic approach for effective prevention of intimal hyperplasia and associated vascular diseases., Highlights • Blocking BET epigenetic readers with JQ1(+) mitigates neointimal proliferation in balloon-injured rat carotid arteries. • JQ1(+) or BRD4 knockdown inhibits vascular smooth muscle cell proliferation, migration, and PDGF receptor expression. • JQ1(+) prevents inflammatory dysfunction of vascular endothelial cells. The transition of vascular smooth muscle cells to a migratory proliferative state produces a new thick layer of tissue on the inner vessel wall obstructing blood flow. Epigenetic control of this transition is poorly understood. We find that inhibiting a family of epigenetic regulators called “readers” halts this disease-prone process. Our study may open fresh opportunities for epigenetic interventions to prevent smooth muscle cell instability and associated occlusive vascular diseases that pose a great threat to public health.

To enhance the removal efficiency of bulky dyes from water and wastewater, a hierarchical porous carbon (HPC) is developed and evaluated as a superior adsorbent in this study. Characterization of the prepared HPC demonstrates that it adopts an interconnected hierarchical porous structure. Macropores with 800–1000 nm diameters interconnect each other via inner windows, and mesopores with an average diameter of 8.1 nm locate in the interwalls of the macropores. The Brunauer-Emmett-Teller (BET) surface area and the pore volume of the HPC reach 1058 m2/g and 2.16 cm3/g, respectively. The adsorption kinetics and isotherms of HPC towards selected dyes are investigated and analyzed by theoretical models. Compared to the commercial activated carbon (AC) and mesoporous carbon (MC), HPC exhibits superior adsorption rate and capacity towards bulky dyes. For the adsorption of all the selected dyes in this study, the intraparticle diffusion rates of HPC keep 2–4 times as high as those of AC and 1.5–2 times as high as those of MC. The interconnected hierarchical porous framework of HPC strongly improves the diffusion rate of guest molecules through the porous network, and consequently accelerates the adsorption rate. A maximum adsorbed amount of 584.32 mg/g of brilliant yellow is achieved by HPC, which is nearly 6 times the capacity of AC. The opened macro/meso porous structure of HPC is assumed to enhance the accessibility of the inner surface to bulky molecules.

Background: Cardiovascular diseases remain the leading cause of death in developed countries. Endovascular surgical interventions trigger uncontrolled proliferation of smooth muscle cells (SMCs) in the intima (intimal hyperplasia) leading to lumen re-narrowing (restenosis). Despite extensive efforts devoted to therapeutic methods with a focus on inhibiting SMC proliferation, restenosis persists at a significant rate. In recent years, a growing body of knowledge has underscored a crucial role for endothelium damage in the pathophysiology of restenosis, suggesting that preservation of the endothelium would provide an effective approach for effectively curbing restenosis. Methods and Results: We utilized high-throughput screening methods to search for small molecules that could inhibit the proliferation of human aortic SMCs without damaging human aortic endothelial cells (ECs). We identified such a lead compound in Prestwick Library; i.e. Parthenolide, a sesquiterpene lactone extracted from feverfew. Treatment with a low dose (1 μM) of Parthenolide for 96h inhibited SMC but not EC proliferation. When the cells were stimulated with inflammatory cytokines (TNF-α or IL-1β), Parthenolide mitigated cytokine-induced proliferation and MCP-1 production of SMCs, but rescued cytokine-induced endothelial dysfunction, including apoptosis, proliferation, decrease of eNOS, and increase of inflammatory markers. Mechanistic studies showed that while Parthenolide treatment in both SMCs and ECs induced NRF-2 activation (nuclear translocation), NRF-2 knockdown with siRNA diminished the aforementioned beneficial effects of Parthenolide in both cell types. In contrast, NFkB activation was not significantly affected by Parthenolide. In a rat balloon angioplasty model, perivascular delivery of Parthenolide in Pluronic gel effectively inhibited intimal hyperplasia and restenosis 14 days after surgery. Conclusion: These results indicate that the natural compound Parthenolide differentially attenuates pathological behaviors of both human vascular SMCs and ECs, whereas known agents as such are scarce. Thus Parthenolide may serve as a promising lead compound for future development of next-generation anti-restenotic therapeutics.

International audience; The present paper relates the integration of nonthermal plasma inside a biphasic gas-liquid mi-crofluidic chip. It evaluates the ability of plasma activation to become a synthetic tool in organic chemistry, operating in mild conditions (room temperature, atmospheric pressure) and without catalyst. Few preceding works on plasma chemistry involved a liquid phase and none of them was able to handle the high reactivity of plasma to achieve both high conversion rate and selective reactions. We fabricated a glass-polymer microfluidic chip comprising a one metre long serpentine channel, in which a parallel gas-liquid flow was stabilized thanks to a specific step-like cross-sectional shape. Transparent ITO electrodes, deposited on both sides of the chip and linked to a AC high voltage source, produced a dielectric barrier discharge all along the channel. We assessed the behaviour of the flow through optical observations and characterized the discharge through electrical measurements and real time intensified-CCD monitoring. We report the successful treatment of liquid cyclohexane with an oxygen plasma inside our chip. The GC analysis of the outflowing liquid revealed only a partial oxidation of cyclohexane into a mixture of cyclohexanol, cyclohexanone (both industrially known as "KA oil") and cyclohexyl hydroperoxide, with a total selectivity above 70% and conversion up to 30%. This indicates that alkanes can be activated and functionalized by means of plasma discharges, in a controlled way. In that respect, we claim to have successfully overcome some of the barriers to an industrially relevant plasma chemistry. We believe that the combined use of plasma and microfluidic technologies is essential to the development of this new field of research.

As linear polymers, alginate, carrageenan, and agar have excellent film-forming properties that can be used in the development of edible coatings and microcapsules for functional food products. These seaweed-derived hydrocolloids can enhance the functional benefits of food products through their protection of bioactive food ingredients from environmental damage and ensure stability and controlled release during consumption. This chapter reviewed the applications of seaweed-derived hydrocolloids as food coating and encapsulation agents and summarized the many methods, techniques, systems, and applications in this field.

In this work, we develop a simple and low-cost synthetic strategy to prepare BCN hybrid nanosheets. The conversion of graphene oxide (GO) into BCN hybrid nanosheets is accomplished through a reaction with boric acid and melamine at 600 °C, during which boron and nitrogen atoms are incorporated into the graphene atomic sheets. In the absence of metal ions, the BCN exhibits high fluorescence. However, the addition of metal ions causes fluorescence quenching, this property making application of BCN possible as a fluorosensor to detect metal ions quantitatively. Because of its high selectivity towards Ag+, the BCN can be used as a facile sensing platform for label-free sensitive and selective detection of Ag+ in aqueous solution. The whole detection process can be completed within 2 min with a detection limit as low as 16 nM.

To date, there is no periadventitial drug delivery method available in the clinic to prevent restenotic failure of open vascular reconstructions. Resveratrol is a promising anti-restenotic natural drug but subject to low bioavailability when systemically administered. In order to reconcile these two prominent issues, we tested effects of periadventitial delivery of resveratrol on all three major pro-restenotic pathologies including intimal hyperplasia (IH), endothelium impairment, and vessel shrinkage. In a rat carotid injury model, periadventitial delivery of resveratrol either via Pluronic gel (2-week), or polymer sheath (3-month), effectively reduced IH without causing endothelium impairment and vessel shrinkage. In an in vitro model, primary smooth muscle cells (SMCs) were stimulated with elevated transforming growth factor (TGFβ) and its signaling protein Smad3, known contributors to IH. TGFβ/Smad3 up-regulated Kruppel-like factor (KLF5) protein, and SMC de-differentiation which was reversed by KLF5 siRNA. Furthermore, TGFβ/Smad3-stimulated KLF5 production and SMC de-differentiation were blocked by resveratrol via its inhibition of the Akt-mTOR pathway. Concordantly, resveratrol attenuated Akt phosphorylation in injured arteries. Taken together, periadventitial delivery of resveratrol produces durable inhibition of all three pro-restenotic pathologies — a rare feat among existing anti-restenotic methods. Our study suggests a potential anti-restenotic modality of resveratrol application suitable for open surgery.

This work presents quantitative measurements of the mixing performance inside the liquid slugs of the gas–liquid Taylor flow in a Y-shaped microchannel in comparison with the mixing of liquids in conventional single-phase laminar flow microchannels by using μ-LIF technique at low and medium Reynolds numbers. First, stratified flow and vortex flow for water–ethanol system were obtained in the single-phase laminar flow system in a Y-shaped micro-contactor. Then, the fundamentals of steady intermittent flow pattern with independent bubbles and slugs in a gas–liquid Taylor flow system were investigated in the same microchannel. It turns out that with the introduced gas phase, the parallel symmetric flow of the liquid in the stratified and vortex flow regime is rigorously disarranged, which enhances the liquid mixing performance inside the individual slugs. This enhancement is due to the squeezing effect as well as the recirculation flow in the slugs. Then we applied these two systems to study the mixing sensitive process, i.e., the anti-solvent precipitation of the curcumin nano-particles. Nano-particles with good appearance and a narrow size distribution were prepared in the gas–liquid microchannel reactors at low Re numbers.

The mixing process of highly viscous liquids in a small stirred tank for High Throughput Experimentation (HTE) apparatus was investigated using a visualization approach, i.e., the Planar Laser-Induced Fluorescence (PLIF) technique. Segregated regions were detected despite a long period of agitation, indicating that the mixing homogeneity can be hardly attained for the mixing of highly viscous liquid. Based on the image analysis of PLIF results, we defined a desegregating time to quantify the mixing process of viscous liquids and to compare the mixing performances under different operating conditions. Eccentric agitation proved to be an efficient way to intensify the mixing of viscous liquid for the fact of significantly reduced desegregating time under the same stirring rate.

This work presented a multi-component LBM approach to model the scalar mixing process with the chemical reactions in a liquid system. Two-dimensional simulation was applied to investigate the enhancement of the mixing performance at the laminar flow regime with very low Re numbers. The mixing degree measured with both IOS (intensity of segregation, characterized by the pure mixing without reaction) and X S (segregation index, characterized by the chemical reaction) was used to quantify the mixing performance. The investigation in both pure mixing process and the reacting flow system showed that the flow-focusing effect with the simple geometry could significantly enhance the mixing as well as the subsequent chemical reactions at very low Re numbers. We expected the theoretical approach described in our study to provide an effective method for micro-device design and optimization.

Three-dimensional multiphase/multicomponent Lattice Boltzmann model (LBM) was developed to simulate the complex hydrodynamics inside micro-droplets generated in micro-channels. Special attention was paid to the ways to generate droplets, which determined the initial liquid concentration and velocity distribution inside the droplets and accordingly made a remarkable contribution to the following mixing performance along the flow development in the micro-channels. Flow characteristics and mixing performance under different geometries and how the differences in configuration influenced the initial status of droplets were illustrated by LBM simulations. The results showed that the effective way to intensify the mixing process was to break up the bilateral symmetric fluid distribution as well as to take full advantage of the internal recirculation inside the droplet during its generation process. It is expected that general guidelines to manipulate the droplet formation and its inside mixing can be brought up through this work. Furthermore, flexible solutions can be simply provided to control the mixing process more precisely by just changing the key geometry of the microchannel.

Introduction: Intimal hyperplasia (IH) occurs primarily due to vascular smooth muscle cell (SMC) transformation from quiescent to pathogenic phenotypes (e.g. proliferation and inflammation). Identification and effective targeting of key epigenetic factors governing SMC pathogenic transformation may lead to novel therapeutic methods for prevention of IH. We previously found that globally blocking the bromo- and extra-terminal (BET) epigenetic “reader” family abrogated SMC phenotype transformation and IH. We further investigated the functions of the two BET bromodomains (Bromo1 and Bromo2). Hypothesis: Bromo1 and Bromo2 play different roles in SMC pathogenic transformation. Methods and Results: We pre-treated rat primary aortic SMCs (for 2h) with Olinone or RVX208, inhibitors specific for Bromo1 and Bromo2 respectively, and then stimulated SMC phenotype transformation. Whereas RVX208 abrogated PDGF-BB-stimulated SMC proliferation (BrdU assay) in a dose dependent manner, Olinone enhanced SMC proliferation at high concentrations (>20 μM). RVX208 at 50 μM reduced TNFα-induced SMC inflammation (MCP-1 ELISA) by 80%,but Olinone at the same concentration slightly increased MCP-1. Furthermore, whereas RVX208 abolished PDGF-BB or TNFα-induced STAT3 phosphorylation (Western blotting), Olinone slightly increased phospho-STAT3. Conclusions: Our results reveal that blocking two BET bromodomains respectively produces distinct effects on SMC phenotype transformation, suggesting their differential epigenetic functions. Further elucidation of the underlying molecular mechanisms should contribute to precise targeting of the BET family for optimal mitigation of IH.