Prediction of Proppant Settling Velocity in Fiber-Containing Fracturing Fluids.

Hydraulic fracturing is the main stimulation method in the development of oil and gas fields. It is helpful to predict the fracture support effect during fracturing by calculating the settling velocity of particles in the fracturing fluid. Experimental research shows that fibers mixed into the fracturing fluid can improve the performance of suspended sand. In this study, fiber was considered a solvent in the fracturing fluid, and the constitutive model of the fiber-containing fracturing fluid was modified according to the fluid rheology. From the analysis of the mechanical behavior in the fiber-containing fluid, the settling velocity of particles slowed down because of some reasons. First, the viscosity of the fiber-containing fracturing fluid increased significantly. The other mechanism is the resistance mechanism of the fiber acting on the particle. The apparent viscosity was fitted based on the rheological model and the measurements. Then, the drag coefficient model of the settling particles was built according to the rheological data of the fibrous fluid. A semi-empirical model was developed to predict the terminal settling velocity through research on dynamics. By characteristic analysis of the results, we found that the fiber on the settling velocity is closely related to the concentration of the base fluid. This prediction model is suitable for the base fluid and fiber-containing fracturing fluid, and the average relative difference between the prediction model and measurements was acceptable.

Outcome effects of enalapril with or without bisoprolol in patients with acute myocardial infarction.

OBJECTIVE: This study was designed to determine the effects of enalapril combined with bisoprolol on patients with acute myocardial infarction (AMI) and their prognosis. METHODS: This study retrospectively analyzed data of 104 patients receiving AMI treatment in the First People's Hospital of Shanghai from May 2019 to October 2021, including 48 patients treated with enalapril alone (control group) and 56 patients treated with enalapril combined with bisoprolol (observation group). The efficacy, adverse reactions, cardiac function [left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVED), left ventricular end-systolic diameter (LVES) and left ventricular mass (LVM)] of the two groups were measured and analyzed. The patients were followed up for one year to compare their prognosis. RESULTS: The observation group showed a significantly higher total response rate than the control group (P < 0.05), but the incidence of adverse reactions was not different significantly between the two groups (P > 0.05). After treatment, LVES, LVED and LVEF increased significantly in both groups (P < 0.05), and the observation group showed significantly lower LVES and LVM levels and had a higher LVEF level than the control group (P < 0.05). The follow-up results revealed no significant difference in prognosis and survival between the two groups (P > 0.05). CONCLUSION: Enalapril combined with bisoprolol is effective and safe in the treatment of AMI, because this regimen can effectively improve patients' cardiac function.

ERCC5, HES6 and RORA are potential diagnostic markers of coronary artery disease.

The mortality rate of patients with coronary artery disease (CAD) increases year by year, and the age of onset is decreasing, primarily because of the lack of an efficient and convenient diagnostic method for CAD. In the present study, we aimed to detect CAD-correlated biomarkers and the regulatory pathways involved through weighted co-expression network analysis. The microarray data originated from 93 CAD patients and 48 controls within the Gene Expression Omnibus (GEO) database. The gene network was implemented by weighted gene co-expression network analysis, and the genes were observed to fall into a range of modules. We took the intersection of genes in the modules most correlated with CAD with the differentially expressed genes of CAD, which were identified by applying the limma package. Lasso regression and support vector machine recursive feature elimination algorithms were used to determine CAD candidate signature genes. The biomarkers for diagnosing CAD were detected by validating candidate signature gene diagnostic capabilities (receiver operating characteristic curves) based on data sets from GEO. Three modules were selected, and 26 vital genes were identified. Eight of these genes were reported as the optimal candidate features in terms of CAD diagnosis. Through receiver operating characteristic curve analysis, we identified three genes (ERCC5, HES6 and RORA; area under the curve > 0.8) capable of distinguishing CAD from the control, and observed that these genes are correlated with the immune response. In summary, ERCC5, HES6 and RORA may have potential for diagnosis of CAD.

Downregulation of secreted frizzled-related protein 4 inhibits hypoxia/reoxygenation injury in diabetic cardiomyocytes by protein tyrosine phosphatase nonreceptor type 12.

Myocardial ischemia-reperfusion injury in diabetic patients leads to an increased incidence of complications and mortality. Secreted frizzled-related protein 4 (SFRP4) plays a critical role in diabetic myocardial ischemia-reperfusion. This paper aims to uncover the underlying mechanisms of SFRP4 in hypoxia/reoxygenation (H/R) injury of diabetic myocardial cells. An in vitro ischemia/reperfusion (I/R) injury model was established using high glucose-induced H9c2 cardiomyocytes. Expression of SFRP4 was detected by real-time reverse transcriptase-polymerase chain reaction and Western blotting. After transfection of SFRP4, the binding of SFRP4 to protein tyrosine phosphatase nonreceptor type 12 (PTPN12) was predicted by database and verified by co-immunoprecipitation assay. P13 K/AKT protein levels were examined by Western blotting. PTPN12 levels were tested by RT-qPCR and Western blotting, cell viability by Cell Counting Kit-8, lactose dehydrogenase kit, terminal dUTP nick-end labeling assay, and cell inflammation and oxidative stress by Western blotting and enzyme linked immunosorbent assay. After overexpression of PTPN12, the experiments for cell viability, inflammation and oxidative stress were repeated once more. SFRP4 expression was upregulated in a high-glucose-stimulated H/R cardiomyocyte model. The interference of SFRP4 promoted cell viability, inhibited the inflammatory and oxidative stress response of H/R cardiomyocytes induced by high glucose. SFRP4 interacted with PTPN12 and inhibited the PI3K/AKT signaling pathway. PTPN12 overexpression reversed the inhibitory effect of sh-SFRP4 on H/R cardiomyocyte damage induced by high glucose. Downregulation of SFRP4 inhibited H/R cell damage in diabetic cardiomyocytes by binding to PTPN12.

MKNK2 enhances chemoresistance of ovarian cancer by suppressing autophagy via miR-125b.

Chemoresistance is a major cause for high mortality and poor survival in patients with ovarian cancer. Changes of cellular autophagy is associated with tumor cell chemoresistance. MAP kinase interacting serine/threonine kinase 2 (MKNK2) belongs to the protein kinase superfamily mediating cell cycle, apoptosis and angiogenesis. However, its effects on chemoresistance during ovarian cancer development remain unclear. In this study, we found that MKNK2 expression levels were markedly up-regulated in chemoresistant ovarian cancer cells compared with the sensitive cells. In addition, significantly increased expression of MKNK2 was detected in clinical ovarian cancer tissues, particularly in tumor samples from patients with drug resistance, and high MKNK2 expression is closely associated with poor prognosis. Our in vitro experiments subsequently showed that MKNK2 knockdown markedly reduced the proliferation of chemoresistant ovarian cancer cells, which was confirmed in SKOV3/DDP xenograft mouse models. Importantly, MKNK2 knockdown considerably induced autophagy in ovarian cancer cells with drug resistance, which was involved in the suppression of cell proliferation. Of note, we showed that miR-125b directly targeted MKNK2, and a negative correlation was observed between the expression of them in clinical tumor tissues. MKNK2 silence also increased miR-125b expression levels in drug-resistant ovarian cancer cells. Intriguingly, MKNK2 knockdown-suppressed cell proliferation and -induced autophagy were almost abrogated by miR-125b inhibition in chemoresistant ovarian cancer cells. Together, these findings demonstrated that MNKN2 is responsible for chemoresistance in ovarian cancer through modulating autophagy by targeting miR-125b, which may be a promising therapeutic target to develop strategies against ovarian cancer with drug resistance.

Antitumor activity and structure-activity relationship of heparanase inhibitors: Recent advances.

Heparanase (HPSE)-directed tumor progression plays a crucial role in mediating tumor-host crosstalk and priming the tumor microenvironment, leading to tumor growth, metastasis and chemo-resistance. HPSE-mediated breakdown of structural heparan sulfate (HS) networks in the extracellular matrix (ECM) and basement membranes (BM) directly facilitates tumor growth and metastasis. Lysosome HPSE also induces multi-drug resistance via enhanced autophagy. Therefore, HPSE inhibitors development has become an attractive topic to block tumor growth and metastasis or eliminate drug resistance. In this review, we summarize HPSE inhibitors applied experimentally and clinically according to interaction with the binding sites of HPSE and participation of growth factors. The antitumor activity and structure-activity relationship (SAR) are also emphasized.

Genistein protects against doxorubicin-induced cardiotoxicity through Nrf-2/HO-1 signaling in mice model.

Doxorubicin (DOX)-induced cardiomyopathy is a lethal disease. DOX-induced cardiotoxic effects are attributed towards increased redox status and apoptotic signaling. In this study, we show that genistein offers protection against DOX-induced cardio toxicity in the mice model. DOX-mediated increase in serum cardiac troponin and redox markers (ROS, LPO, 4-hydroxynonenal-protein adducts [HNE] levels) was significantly reduced by genistein treatment. Significantly increased TNF-α, IL-6, IL-8 expressions during DOX-induced inflammatory responses were down regulated by genistein treatment. Further, we found that genistein regulated antioxidant response through increased Nrf-2, HO-1, NQO1 protein expressions. In addition, DOX downregulated survival proteins (p-Akt, Bcl-2) with concomitant upregulation in Erk (1/2), Bax and cleaved caspase-3 expressions. The apoptotic activation was significantly downregulated by genistein treatment through suppression of apoptosis. Altogether, these findings show that genistein protects against DOX-induced cardiotoxic effects through activation of Nrf-2/HO-1 signaling.

The DPP-4 inhibitor saxagliptin ameliorates ox-LDL-induced endothelial dysfunction by regulating AP-1 and NF-κB.

Diabetes-associated cardiovascular complications are the leading cause of death for diabetic patients. Dipeptidyl peptidase 4 (DPP-4) inhibitor agents, known as gliptins, are a class of potent anti-glycemic agents developed to treat diabetes. Recently, gliptins have been shown to have independent cardiovascular benefits. In this study, we revealed the protective role of saxagliptin in vascular endothelial cells. Our data show that saxagliptin suppresses oxidized low-density lipoprotein cholesterol (ox-LDL)-induced expression of its receptor lectin-like ox-LDL receptor-1 (LOX-1). Saxagliptin treatment reduces ox-LDL-induced production of cytokines and vascular adhesion molecules including tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), vascular cell adhesion molecule 1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1). The presence of saxagliptin suppressed ox-LDL-induced adhesion of monocytes to endothelial cells in co-culture adhesion experiments. Moreover, saxagliptin mitigated ox-LDL-induced production of reactive oxygen species and suppressed elevated expression of endothelial nicotinamide adenine dinucleotide phosphate oxidase subunit (NOX-4) induced by ox-LDL. Mechanistically, saxagliptin exerted inhibitory effects against ox-LDL-induced phosphorylation of JNK kinase, expression of the activator protein 1 (AP-1) subunits c-Jun/c-fos, and AP-1 promoter activity. Saxagliptin also suppressed nuclear factor κB (NF-κB) p65 accumulation and inhibited its promoter activity. Our data elaborate the molecular mechanism of saxagliptin-mediated endothelial protection and indicate that saxagliptin could have vascular benefits independent on its anti-glycemic function.

Effects of microrna-93 on mouse cardiac microvascular endothelial cells injury and inflammatory response by mediating SPP1 through the NF-ΚB pathway.

BACKGROUND: This study aims to investigate the regulative role of microRNA-93 (miR-93) in mouse cardiac microvascular endothelial cells (CMECs) injury and inflammatory response by negatively targeting SPP1 gene via the NF-κB signaling pathway. METHODS: Healthy Balb/c mice were recruited to establish a mouse model with myocarditis using the CVB3 virus. Mice were grouped into normal, blank, negative control (NC), miR-93 inhibitor, miR-93 mimic, SPP1 short hairpin RNA (shRNA), and miR-93 mimic+SPP1 shRNA groups. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were applied to determine the expressions of miR-93, SPP1, VEGFA, p50, p65, Bax, and Bcl-2. MTT assay was conducted to evaluate cell viability, annexin V-fluorescein isothiocyanate/propidium iodide double staining was conducted to examine cell apoptosis, enzyme-linked immunosorbent assay was conducted to measure secretion of inflammatory factors, and chemical colorimetry was conducted to determine NO secretion. RESULTS: SPP1 was a target gene of miR-93. Compared with the normal group, other six groups showed increased expressions of SPP1, p50, p65, VEGFA, and Bax, as well as cell apoptosis rate and secretion of cell inflammatory factors, and decreased expression of Bcl-2, cell viability, and NO secretion. Compared with the blank group, the miR-93 inhibitor group showed elevated expressions of SPP1, p50, p65, VEGFA, and Bax, as well as cell apoptosis rate and secretion of cell inflammatory factors, and reduced Bcl-2, cell viability, and NO secretion. While the miR-93 mimic and SPP1 shRNA groups displayed opposite results. CONCLUSION: Taking our results together, we conclude that upregulation of miR-93 reduces CMECs injury and inflammatory response by negatively targeting SPP1 via inactivating the NF-κB signaling pathway.

Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats.

OBJECTIVES: Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats. METHODS: The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot. RESULTS: After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom. CONCLUSION: It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

Controlled Release of Antimicrobial ClO2 Gas from a Two-Layer Polymeric Film System.

We report a two-component label system comprising a chlorite-containing polymer film and an acid-containing polymer film that can release antimicrobial ClO2 gas upon adhering the two films together to enable a reaction of the chlorite and acid under moisture exposure. The chlorite-containing film comprises a commercial acrylate-based pressure-sensitive adhesive polymer impregnated with sodium chlorite. The acid-containing film comprises a commercial poly(vinyl alcohol) polymer loaded with tartaric acid. Both of the films were prepared on low ClO2-absorbing substrate films from stable aqueous systems of the polymers with high reagent loading. Rapid and sustained releases of significant amounts of ClO2 gas from the label system were observed in an in situ quantification system using UV-vis spectroscopy. It was found that the ClO2 release is slower at a lower temperature and can be accelerated by moisture in the atmosphere and the films. Controlled release of ClO2 gas from the label system was demonstrated by tailoring film composition and thickness. A model was developed to extract release kinetics and revealed good conversions of the label system. This two-component system can potentially be applied as a two-part label without premature release for applications in food packaging.

Thermoreversible partitioning of poly(ethylene oxide)s between water and a hydrophobic ionic liquid.

We describe a poly(ethylene oxide) (PEO) homopolymer "shuttle" between water and a hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][TFSI]). PEO homopolymers with varying molecular weight transferred reversibly and quantitatively between water at room temperature and [EMIM][TFSI] at an elevated temperature. The temperature of the transfer from water to [EMIM][TFSI] shows a linear dependence on PEO molecular weight and a dependence on polymer concentration consistent with expectation based on Flory-Huggins theory. These results are also consistent with the previously observed lower critical solution temperature (LCST) behavior of PEO in water. Dynamic light scattering study of the concentration and temperature dependence of the swelling degree of PEO corona of polybutadiene (PB)-PEO block copolymer micelles indicates that the solvent quality of [EMIM][TFSI] for PEO remains essentially the same as a good solvent over the temperature range of the PEO shuttle. Fundamental understanding of the PEO shuttle is of significance in development of systems for phase transfer of reagents and reaction products between ionic liquids and water.

Bilayer membrane permeability of ionic liquid-filled block copolymer vesicles in aqueous solution.

The bilayer membrane permeability of block copolymer vesicles ("polymersomes") with ionic liquid interiors dispersed in water is quantified using fluorescence quenching. Poly((1,2-butadiene)-b-ethylene oxide) (PB-PEO) block copolymer vesicles in water with their interiors filled with a common hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide, were prepared containing a hydrophobic dye, Nile Red, by intact migration of dye-encapsulated vesicles from the ionic liquid to water at room temperature. A small quencher molecule, dichloroacetamide, was added to the aqueous solution of the dye-loaded vesicles, and the permeation of the quencher passing through the membrane into the interior was determined from the fluorescence quenching kinetics. Rapid permeation of the quencher across the nanoscale membrane was observed, consistent with the high fluidity of the liquid polybutadiene membrane. Two different PB-PEO copolymers were employed, in order to vary the thickness of the solvophobic membrane. A significant increase in membrane permeability was also observed with decreasing membrane thickness, which is tentatively attributable to differences in quencher solubility in the membranes. Quantitative migration of the vesicles from the aqueous phase back to an ionic liquid phase was achieved upon heating. These microscopically heterogeneous and thermoresponsive vesicles with permeable and robust membranes have potential as recyclable nanoreactors, in which the high viscosity and capital expense of an ionic liquid reaction medium can be mitigated, while retaining the desirable features of ionic liquids as reaction media, and facile catalyst recovery.

Temperature- and pH-triggered reversible transfer of doubly responsive hairy particles between water and a hydrophobic ionic liquid.

This article reports on the synthesis of thermo- and pH-sensitive polymer-brush-grafted silica particles ("hairy" particles) and the study of their phase-transfer behavior between water and a hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ([EMIM][TFSA]), in response to temperature and pH changes. The hairy particles were made by the surface-initiated atom transfer radical polymerization of methoxytri(ethylene glycol) methacrylate (TEGMMA) and tert-butyl methacrylate with a molar ratio of 100:11 in the presence of a free initiator and the subsequent removal of tert-butyl groups. The cloud points (CPs) of poly(TEGMMA-co-methacrylic acid), obtained after the treatment of the free polymer with trifluoroacetic acid, in both water and [EMIM][TFSA]-saturated water increased with the increase in pH and can be tuned over a wide temperature range. The hairy particles moved spontaneously from the aqueous phase to the [EMIM][TFSA] phase upon heating at 80 °C and returned to the aqueous layer upon cooling at 10 °C. This process can be repeated many times regardless of whether the pH of the aqueous phase is 2.99, 5.00, or 7.02. UV-vis absorbance measurements showed that the transfer temperature (T(tr)) of hairy particles from water to [EMIM][TFSA] increased with the increase in the pH of the aqueous phase. A linear relationship was observed between the T(tr) of hairy particles and the CP of the corresponding free polymer. By taking advantage of the tunability of the T(tr) of hairy particles, we demonstrated the pH-driven reversible transfer of hairy particles at a fixed temperature by changing the pH of the aqueous phase and multiple phase-transfer processes by controlling both the temperature and pH.

Spontaneous phase transfer of thermosensitive hairy particles between water and an ionic liquid.

This article describes the temperature-induced phase transfer behavior of a series of thermosensitive polymer brush-grafted particles between water and a hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][TFSI]). Six samples were made by surface-initiated atom transfer radical polymerization: silica particles grafted with poly(methoxypoly(ethylene glycol) methacrylate) (PPEGMMA) with two different molecular weights, poly(methoxytri(ethylene glycol) methacrylate) (PTEGMMA), poly(methoxydi(ethylene glycol) methacrylate) (PDEGMMA), and two copolymers of PEGMMA and TEGMMA with different compositions (P(PEGMMA-co-TEGMMA)-82 and P(PEGMMA-co-TEGMMA)-74). The cloud points of free PPEGMMA with M(n,SEC) of 23 and 40 kDa, P(PEGMMA-co-TEGMMA)-82, P(PEGMMA-co-TEGMMA)-74, and PTEGMMA in [EMIM][TFSI]-saturated water were 95, 94, 80, 72, and 43 °C, respectively. PDEGMMA was not soluble in the ionic liquid-saturated water. PPEGMMA brush-grafted particles moved spontaneously and completely from water to the [EMIM][TFSI] phase upon heating at 80 °C. When cooled to 22 °C, all particles returned to the water layer. From UV-vis absorbance measurements, the transfer temperature (T(tr)) of PPEGMMA-grafted particles from water to the ionic liquid was 42 °C. Thermodynamic analysis showed that the particle transfer was an entropically driven process. P(PEGMMA-co-TEGMMA)-82, P(PEGMMA-co-TEGMMA)-74, and PTEGMMA brush-grafted particles also underwent reversible and quantitative transfer between the two phases upon heating at 70 °C and cooling at 0 °C; their transfer temperatures from water to [EMIM][TFSI] were 36, 30, and 16 °C, respectively. T(tr) was a linear function of the cloud point of the corresponding free polymer in ionic liquid-saturated water. In contrast, PDEGMMA-grafted particles moved spontaneously to the ionic liquid layer upon heating but did not return to water even after prolonged stirring at 0 °C.

Polymersomes with ionic liquid interiors dispersed in water.

We describe polymersomes with ionic liquid interiors dispersed in water. The vesicles are prepared via a simple and spontaneous migration of poly(butadiene-b-ethylene oxide) (PB-PEO) block copolymer vesicles from a hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][TFSI]), to water at room temperature. As PB is insoluble in both water and [EMIM][TFSI] and PEO is well solvated in both media, the vesicles feature a PB membrane with PEO brushes forming both interior and exterior coronas. The robust and stable PB-PEO vesicles migrate across the liquid-liquid interface with their ionic liquid interiors intact and form a stabilized aqueous dispersion of vesicles enclosing microscopic ionic liquid pools. The nanostructure of the vesicles with ionic liquid interiors dispersed in water is characterized by direct visualization using cryogenic transmission electron microscopy. Upon heating, the vesicles can be quantitatively transferred back to [EMIM][TFSI], thus enabling facile recovery. The reversible transport capability of the shuttle system is demonstrated by the use of distinct hydrophobic dyes, which are selectively and simultaneously loaded in the vesicle membrane and interior. Furthermore, the fluorescence of the loaded dyes in the vesicles enables probing of the microenvironment of the vesicular ionic liquid interior through solvatochromism and direct imaging of the vesicles using laser scanning confocal microscopy. This vesicle system is of particular interest as a nanocarrier or nanoreactor for reactions, catalysis, and separations using ionic liquids.

Pluronic micelle shuttle between water and an ionic liquid.

We demonstrate an effective micelle shuttle between water and a hydrophobic ionic liquid and its application in transportation in the biphasic system, using a commercially available and inexpensive Pluronic block copolymer. The poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) (P123) block copolymer self-assembles into micelles in both water and the ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate, as characterized by dynamic light scattering. The poly(ethylene oxide) blocks provide the well-solvated corona, whereas the poly(propylene oxide) blocks form the solvophobic core. The micelles can spontaneously transfer between the two phases upon a simple temperature stimulus; the transfer is reversible and repeatable, and (1)H NMR analysis indicates quantitative transfer. The micelle nanocarriers are used to transport various cargoes in the biphasic system: fully reversible transport of hydrophobic small organic dyes into and out of water and facile extraction of an ionic liquid-phobic polymer from the ionic liquid. This simple round-trip delivery system may be used in delivery, separations, and extraction in synthesis and biphasic catalysis involving ionic liquids.

Thermodynamics and mechanism of the block copolymer micelle shuttle between water and an ionic liquid.

The micelle shuttle utilizing block copolymer micelles as nanocarriers for transportation between water and a hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][TFSI]), is examined in detail. Rhodamine B, a dye with a high molar absorptivity and fluorescence quantum yield, is conjugated to a short poly(1,2-butadiene) homopolymer and then loaded in amphiphilic poly((1,2-butadiene)-block-ethylene oxide) (PB-PEO) block copolymer micelles. The round-trip transportation of the micelles between water and the ionic liquid is simply triggered by temperature; it is fully reversible, quantitative, and without leakage. Quantitative fluorescence analysis reveals that the micelle distribution in the biphasic system has a very strong temperature dependence, which is favorable for control of the transportation. The standard Gibbs free energy change (DeltaG(o)), standard enthalpy change (DeltaH(o)), and standard entropy change (DeltaS(o)) of the micelle shuttle are extracted from the temperature dependence of the micelle distribution. Both DeltaH(o) and DeltaS(o) are positive, indicating an entropy-driven process. The slow yet spontaneous micelle shuttle is explored under quiescent conditions to understand the transfer kinetics. Both of the two-way transfers involve three steps, formation of micelle-concentrated [EMIM][TFSI]/water droplets in the initial phase, sedimentation/creaming of the droplets to the interface, and diffusion of the micelles to the destination phase. A detailed mechanism for the transfer is therefore proposed.

Block copolymer micelle shuttles with tunable transfer temperatures between ionic liquids and aqueous solutions.

Four poly((1,2-butadiene)- block-ethylene oxide) (PB-PEO) diblock copolymers were shown to self-assemble into micelles with PB cores and PEO coronas (including spheres, cylinders, and vesicles) in the ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][TFSI]). All four systems exhibited the "micelle shuttle" (He, Y.; Lodge, T. P. J. Am. Chem. Soc. 2006, 128, 12666-12667), whereby PB-PEO micelles transferred, reversibly and with preservation of micelle structure, from an aqueous phase at room temperature to a hydrophobic ionic liquid at high temperature. The micelle size (both mean and distribution) depends on whether it was initially dissolved in water or in the ionic liquid, but the initial micelle structures in the ionic liquid were shown by dynamic light scattering to be preserved during the transfer and persist essentially unchanged for months in both the ionic liquid and water. The transfer was shown to be driven by the deteriorating solvent quality of water for PEO at high temperature, while the ionic liquid remains a good solvent. The transfer temperature could be tuned by adding ionic or nonionic additives to the aqueous phase to change the solvent quality of water for PEO, and by using ionic liquids with different polarity.

Mechanisms of increased expression of toll-like receptor-4 in human monocyte/macrophage-derived foam cells.

The mechanisms of increased expression of toll-like receptor 4 (TLR-4) during the formation of foam cells were explored. Low density lipoprotein (LDL) was prepared by density gradient ultracentrifugation and oxidized by incubation with CuCl2. The human monocytic leukemia cell line (THP-1) was cultured in RPMI1640. The differentiation of THP-1 cells into macrophages (MPs) was induced by using myristate acetate (PMA) for 48 h. The macrophages were then incubated with oxidized LDL (ox-LDL) to generate foam cells (FCs). The mRNA and protein expression levels of human TLR-4 were detected by immunocytochemistry, Western blotting and reverse transcription polymerase chain reaction (RT-PCR). The results showed that the TLR-4 mRNA and the protein expression levels were significantly increased during the differentiation of monocytes into macrophages (P < 0.05) as well as during the formation of lipid-laden foam cells (P < 0.05). It was concluded that the upregulation of human TLR-4 gene expression during the differentiation of monocytes into macrophages and the differentiation of macrophages into foam cells could increase TLR-4 protein synthesis dramatically, which may enhance the ability of foam cells inflammation reaction in atherosclerosis.