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A large eddy simulation (LES) was conducted of turbulent flow in a channel with a rough wall on one side and a free surface on the other by adopting an anisotropy-resolving subgrid-scale (SGS) model. A shear Reynolds number of Reτ = 395 was used based on the mean friction velocity and channel height. To investigate the grid dependency of the LES results caused by the SGS model, three grid resolutions were tested under the same definition of a roughness shape by using the immersed boundary method. The results obtained were compared with direct numerical simulation data with and without thewall roughness and thosewithout the extra anisotropic term. The primary focus was on how the present anisotropic SGS model with coarser grid resolutions can properly provide the effects of roughness on the mean velocity and turbulent stresses, leading to a considerable reduction of the computational cost of LES. [ABSTRACT FROM AUTHOR]

Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of L-DOPA via the L-type amino acid transporter (LAT) at the plasma membrane. The uptake of L-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. L-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of L-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension. [ABSTRACT FROM AUTHOR]

Lack or downregulation of the dopamine D2 receptor (D2R) results in increased renal expression of injury markers and proinflammatory factors that is independent of a blood pressure increase. This study aimed to determine the mechanisms involved in the regulation of renal inflammation by D2Rs. Silencing D2Rs in mouse renal proximal tubule cells increased the expression of the proinflammatory TNF-α, monocyte chemoattractant protein-1 (MCP-1), and IL-6. D2R downregulation also increased Akt phosphorylation and activity, and glycogen synthase kinase-3β (GSK3β) phosphorylation and cyclin D1 expression, downstream targets of Akt; however. phosphatidylinositol 3-kinase (PI3K) activity was not affected. Conversely, D2R stimulation decreased Akt and GSK3β phosphorylation and cyclin D1 expression. Increased phospho-Akt, in the absence of increased PI3K activity, may result from decreased Akt dephosphorylation. Inhibition of protein phosphatase 2A (PP2A) with okadaic acid reproduced the effects of D2R downregulation on Akt, GSK3β, and cyclin D1. The PP2A catalytic subunit and regulatory subunit PPP2R2C coimmunoprecipitated with the D2R. Basal phosphatase activity and the expression of PPP2R2C were decreased by D2R silencing that also blunted the increase in phosphatase activity induced by D2R stimulation. Similarly, silencing PPP2R2C also increased the phosphorylation of Akt and GSK3β. Moreover, downregulation of PPP2R2C resulted in increased expression of TNF-α, MCP-1, and IL-6, indicating that decreased phosphatase activity may be responsible for the D2R effect on inflammatory factors. Indeed, the increase in NF-kB reporter activity induced by D2R silencing was blunted by increasing PP2A activity with protamine. Our results show that D2R controls renal inflammation, at least in part, by modulation of the Akt pathway through effects on PP2A activity/expression. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a noninvasive and light-activated method for cancer treatment. Two of the vital parameters that govern the efficiency of PDT are the light irradiation to the photosensitizer and visual detection of the selective accumulation of the photosensitizer in malignant cells. Herein, we prepared an integrated nanoplatform for targeted PDT and imaging of cancer cells using folic acid and horseradish peroxidase (HRP)-bifunctionalized semiconducting polymer dots (FH-Pdots). In the FH-Pdots, meta-tetra(hydroxyphenyl)-chlorin (m-THPC) was used as photosensitizer to produce cytotoxic reactive oxygen species (ROS); fluorescent semiconducting polymer poly[2-methoxy-5-((2-ethylhexyl)oxy)-p-phenylenevinylene] was used as light antenna and hydrophobic matrix for incorporating m-THPC, and amphiphilic Janus dendrimer was used as a surface functionalization agent to conjugate HRP and aminated folic acid onto the surface of FH-Pdots. Results indicated that the doped m-THPC can be simultaneously excited by the on-site luminol-H2O2-HRP chemiluminescence system through two paths. One is directly through chemiluminescence resonance energy transfer (CRET), and the other is through CRET and subsequent fluorescence resonance energy transfer. In vitro PDT and specificity studies of FH-Pdots using a standard transcriptional and translational assay against MCF-7 breast cancer cells, C6 glioma cells, and NIH 3T3 fibroblast cells demonstrated that cell viability decreased with increasing concentration of FH-Pdots. At the same concentration of FH-Pdots, the decrease in cell viability was positively relevant with increasing folate receptor expression. Results from in vitro fluorescence imaging exhibited that more FH-Pdots were internalized by cancerous MCF-7 and C6 cells than by noncancerous NIH 3T3 cells. All the results demonstrate that the designed semiconducting FH-Pdots can be used as an integrated nanoplatform for targeted PDT and on-site imaging of cancer cells. [ABSTRACT FROM AUTHOR]

Renal dopamine receptors participate in the regulation of blood pressure. Genetic factors, including polymorphisms of the dopamine D2 receptor gene (DRD2) are associated with essential hypertension, but the mechanisms of their contribution are incompletely understood. Mice lacking Drd2 (D2-/-) have elevated blood pressure, increased renal expression of inflammatory factors, and renal injury. We tested the hypothesis that decreased dopamine D2 receptor (D2R) function increases vulnerability to renal inflammation independently of blood pressure, is an immediate cause of renal injury, and contributes to the subsequent development of hypertension. In D2-/- mice, treatment with apocynin normalized blood pressure and decreased oxidative stress, but did not affect the expression of inflammatory factors. In mouse RPTCs Drd2 silencing increased the expression of TNFa and MCP-1, while treatment with a D2R agonist abolished the angiotensin IIinduced increase in TNF-α and MCP-1. In uni-nephrectomized wild-type mice, selective Drd2 silencing by subcapsular infusion of Drd2 siRNA into the remaining kidney produced the same increase in renal cytokines/chemokines that occurs after Drd2 deletion, increased the expression of markers of renal injury, and increased blood pressure. Moreover, in mice with two intact kidneys, short-term Drd2 silencing in one kidney, leaving the other kidney undisturbed, induced inflammatory factors and markers of renal injury in the treated kidney without increasing blood pressure. Our results demonstrate that the impact of decreased D2R function on renal inflammation is a primary effect, not necessarily associated with enhanced oxidant activity, or blood pressure; renal damage is the cause, not the result, of hypertension. Deficient renal D2R function may be of clinical relevance since common polymorphisms of the human DRD2 gene result in decreased D2R expression and function. [ABSTRACT FROM AUTHOR]

On the basis of the host-guest interactions between azobenzenes and cyclodextrins, a new strategy for the preparation of a dually functionalized poly(dimethylsiloxane) (PDMS) surface was investigated using surface--initiated atom--transfer radical polymerization (SI--ATRP) and click chemistry. The PDMS substrates were first oxidized in a H2SO4/H2O2 solution to transform the surface Si-CH3 groups into Si-OH groups. Then, the SI--ATRP initiator 3--(2--bromoisobutyramido)propyl(trime--thoxy)silane was grafted onto the substrates through a silanization reaction. Sequentially, the poly(ethylene glycol) (PEG) units were introduced onto the PDMS-Br surfaces via SI--ATRP reaction using oligo(ethylene glycol) methacrylate. Afterward, the bromide groups on the surface were converted to azido groups via nucleophilic substitution reaction with NaN3. Finally, the azido--grafted PDMS surfaces were subjected to a click reaction with alkynyl and PEG--modified β--cyclodextrins, resulting in the grafting of cyclodextrins onto the PDMS surfaces. The composition and chemical state of the modified surfaces were characterized via X--ray photoelectron spectroscopy, and the stability and dynamic characteristics of the cyclodextrin--modified PDMS substrates were investigated via attenuated total reflection--Fourier transform infrared spectroscopy and temporal contact angle experiments. The surface morphology of the modified PDMS surfaces was characterized through imaging using a multimode atomic force microscope. A protein adsorption assay using Alexa Fluor594--labeled bovine serum albumin, Alexa Fluor594--labeled chicken egg albumin, and FITC--labeled lysozyme shows that the prepared PDMS surfaces possess good protein--repelling properties. On--surface studies on the interactions between azobenzenes and the cyclodextrin--modified surfaces reveal that the reversible binding of azobenzene to the cyclodextrin--modified PDMS surfaces and its subsequent release can be reversibly controlled using UV irradiation. Sandwich fluoroimmunoassay of the cardiac markers myoglobin and fatty acid--binding protein demonstrates that the cyclodextrin--modified PDMS surfaces can be repeatedly utilized in disease biomarker analysis. [ABSTRACT FROM AUTHOR]

The article cites a study that evaluated the resistance and susceptibility of cowpea after an induced infection with Fusarium wilt. The researches made use of fifty seedlings that were soaked with a solution of fungal spores for 15 minutes before being transplanted into a sterilized sandy soil. Results of the study indicated an involvement of several enzymes, including chitinase in the resistance of cowpea to infection of fusarium wilt.

Iron oxides nanoparticles tailored for magnetic particle imaging (MPI) have been synthesized, and their MPI signal intensity is three-times that of commercial MPI contrast (Ferucarbotran, also called Vivotrax) and seven-times that of MRI contrast (Feraheme) at the same Fe concentration. MPI tailored iron oxide nanoparticles were encapsulated with semiconducting polymers to produce Janus nanoparticles that possessed optical and magnetic properties for MPI and fluorescence imaging. Janus particles were applied to cancer cell labeling and in vivo tracking, and as few as 250 cells were imaged by MPI after implantation, corresponding to an amount of 7.8 ng of Fe. Comparison with MRI and fluorescence imaging further demonstrated the advantages of our Janus particles for MPI-super sensitivity, unlimited tissue penetration, and linear quantitativity. [ABSTRACT FROM AUTHOR]

Static and dynamic mechanical properties of cement-asphalt composites with various contents of asphalt incorporated were studied. Uniaxial compressive stress-strain curves of different cement-asphalt mortars (CAMs) with cement mass ratio (A/C) in the range of 0.2 to 1.0 were obtained by the Materials Testing System (MTS) under different testing temperatures ranging from to 80°C. Two typical CAMs, one with A/C of 0.2 denoted by LAC and the other with A/C of 0.9 denoted by HAC, were chosen to be tested at varied deformation rates over a range of 0.3 to 30 mm/min at room temperature. The correlation between mechanical properties, e.g., peak stress or elastic modulus, and temperature or loading rate was, respectively, acquired. As a result, temperature sensitivity and loading rate dependence for mechanical behavior of different CAMs were analyzed. Dynamic mechanical analysis (DMA) on three cement-asphalt binders (CABs) with A/Cs from 0.2 to 1.0 was carried out, and temperature spectra and frequency spectra were obtained. The Burger model was used to simulate the viscoelastic mechanical behaviors of CABs. Results indicate that peak stress and elastic modulus of CAMs decline with the increasing A/C and temperature. The temperature sensitivity and the loading rate dependence for mechanical properties of CAMs with higher A/Cs are greater than those of CAMs with lower A/Cs. To quantify the dependence of mechanical properties on temperature and loading rate, temperature-sensitive factor and rate-influencing factor are defined separately. The two factors increase with the A/C, implying that CAMs with higher A/Cs have greater dependence on temperature and loading rate. Furthermore, the two factors for peak stress are bigger than those for elastic modulus for a given CAM. Dynamic modulus of CABs descends with the increase of A/C or temperature but ascends with the loading frequency. As the temperature rises or A/C increases, the viscoelasticity becomes more remarkable. The dependence of dynamic modulus of CABs with varied A/Cs on loading frequency is successfully simulated by using the Burger model. [ABSTRACT FROM AUTHOR]

Background: The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is widely used as a complementary screening tool for dementia. However, there are few studies concerning the efficacy of the IQCODE for assessing the severity of cognitive impairments in patients with Alzheimer's disease (AD). We aimed to evaluate the efficacy of the IQCODE for assessing the severity of dementia in patients with AD. Methods: According to the clinical dementia rating (CDR), 394 patients with AD were enrolled and classified into three groups: mild, moderate and severe groups. The IQCODE scores of each group were determined by interviewing the informants with the short version of the 16-item IQCODE. The correlations of the IQCODE score with the Mini- Mental State Examination (MMSE), the Mattis Dementia Rating Scale (DRS) and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) were analysed. Statistical analyses were conducted to examine the differences in the IQCODE scores among the three groups. Results: The validity coefficients of the IQCODE with the MMSE, DRS and ADAS-Cog were - 0.528, - 0.436, and 0.477, respectively. The sensitivity was 66.1%, and the specificity was 59.8% when using a cut-off score of 65 to discriminate between mild-moderate dementia. When 75 was used as the threshold between moderate-severe dementia, the sensitivity and the specificity were 73.9 and 67.7%, respectively. Conclusions: The IQCODE is moderately effective for assessing the severity of cognitive impairment in patients with AD. [ABSTRACT FROM AUTHOR]

A novel sonophotochemical Fenton-like system was investigated in this study for degradation of antibiotic sulfamethazine (SMZ). In the presence of oxalic acid (Ox), the heterogeneous Fe3O4-catalyzed system (US/UV/Fe3O4/Ox) could induce in-situ generation of H2O2 and also Fenton-like reaction. A Significant synergistic SMZ degradation including significantly enhanced SMZ mineralization and detoxification was achieved in the system, as compared to its corresponding individual systems. Ultrasound (US) treatment could eliminate the initial lag period of SMZ degradation which appeared in UV/Fe3O4/Ox system without the pre-dissolution phase. This phenomenon was evidenced by significant enhancements in the initial dissolution rate of the iron oxides as well as production rate of the reactive oxygen species (ROS). A reaction mechanism involving a heterogeneous/homogenous iron cycle and a series of homogenous radical reactions was proposed. The promotional role of US could be mostly ascribed to the sonochemcial cavitation effect in both heterogeneous solid--liquid interphase reactions and homogenous radical reactions. The cleavage of SN bond via *OH attack would be the main SMZ decomposition pathway. The solution pH and [Fe3O4Ox] ratio were the two important factors for SMZ degradation. The repeating SMZ degradation tests of the US/UV/Fe3O4/Ox system also suggested that Fe3O4 was a favorable catalyst for application of the system in wastewater treatment. [ABSTRACT FROM AUTHOR]

A quaternized poly(dimethylaminoethyl methacrylate)-grafted poly(dimethylsiloxane) (PDMS) surface (PDMS-QPDMAEMA) was successfully prepared in this study via solution-phase oxidation reaction and surface-initiated atom transfer radical polymerization (SI-ATRP) using dimethylaminoethyl methacrylate (DMAEMA) as initial monomer. PDMS substrates were first oxidized in H2SO4/H2O2 solution to transform the Si-CH3 groups on their surfaces into Si-OH groups. Subsequently, a surface initiator for ATRP was immobilized onto the PDMS surface, and DMAEMA was then grafted onto the PDMS surface via copper-mediated ATRP. Finally, the tertiary amino groups of PolyDMAEMA (PDMAEMA) were quaternized by ethyl bromide to provide a cationic polymer brush-modified PDMS surface. Various characterization techniques, including contact angle measurements, attenuated total reflection infrared spectroscopy, and X-ray photoelectron spectroscopy, were used to ascertain the successful grafting of the quaternized PDMAEMA brush onto the PDMS surface. Furthermore, the wettability and stability of the PDMS-QPDMAEMA surface were examined by contact angle measurements. Antifouling properties were investigated via protein adsorption, as well as bacterial and cell adhesion studies. The results suggest that the PDMS-QPDMAEMA surface exhibited durable wettability and stability, as well as significant antifouling properties, compared with the native PDMS and PDMS-PDMAEMA surfaces. In addition, our results present possible uses for the PDMS-QPDMAEMA surface as adhesion barriers and antifouling or functional surfaces in PDMS microfluidics-based biomedical applications. [Copyright &y& Elsevier]

Studies on the degeneration and regeneration of neurons as individual compartments of axons or somata can provide critical information for the clinical therapy of nervous system diseases. A controllable in vitro platform for multiple purposes is key to such studies. In the present study, we describe an integrated microfluidic device designed for achieving localized stimulation to neuronal axons or somata. We observed neuronal compartment degeneration after localized chemical stimulation and regeneration under the accessorial function of an interesting compound treatment or coculture with desired cells in controllable chambers. In a spatiotemporally controlled manner, this device was used to investigate hippocampal neuronal soma and axon degeneration after acrylamide stimulation, as well as subsequent regeneration after treatment with the monosialoganglioside GM1 or with cocultured glial cells (astrocytes or Schwann cells). To gain insight into the molecular mechanisms that mediate neuronal injury and regeneration, as well as to investigate whether acrylamide stimulation to neurons induces changes in Ca(2+) concentrations, the related neuronal genes and real-time Ca(2+) signal in neurons were also analyzed. The results showed that neuronal axons were more resistant to acrylamide injury than neuronal somata. Under localized stimulation, axons had self-destruct programs different from somata, and somatic injury caused the secondary response of axon collapse. This study provides a foundation for future in-depth analyses of spatiotemporally controlled and multifactor neuronal compartment regeneration after various injuries. The microfluidic device is also useful in evaluating potential therapeutic strategies to treat chemical injuries involving the central nervous system. [ABSTRACT FROM AUTHOR]

In this study, folate-functionalized hybrid polymeric nanoparticles (NPs) were prepared as carriers of low water solubility paclitaxel for tumor targeting, which were composed of monomethoxy-poly(ethylene glycol)-b-poly(lactide)-paclitaxel (MPEG-PLA-paclitaxel) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-folate (TPGS-FOL). NPs with various weight ratios of MPEG-PLA-paclitaxel and TPGS-FOL were prepared using a solvent extraction/evaporation method, which can also physically encapsulate paclitaxel. The size, size distribution, surface charge, and morphology of the drug-loaded NPs were characterized using a Zetasizer Nano ZS, scanning electron microscope (SEM), and atomic force microscopy (AFM). The encapsulation and drug loading efficiencies of these polymeric NPs are analyzed using high-performance liquid chromatography (HPLC) at 227 nm. The combination of covalent coupling and physical encapsulation is found to improve the loading of paclitaxel in NPs greatly. The in vitro antitumor activity of the drug-loaded NPs is assessed using a standard method of transcriptional and translational (MTT) assays against HeLa and glioma C6 cells. When the cells were exposed to NPs with the same paclitaxel weights, cell viability decreases in relation to the increase in TPGS-FOL in drug-loaded NPs. To investigate drug-loaded NP cellular uptake, the fluorescent dye coumarin-6 is utilized as a model drug and enveloped in NPs with 0 or 50% TPGS-FOL. Confocal laser scanning microscopy (CLSM) analysis shows that cellular uptake is lower for coumarin-6-loaded NPs with 0% TPGS-FOL than those with 50% TPGS-FOL. However, no difference for NIH 3T3 cells with normally expressed folate receptors is found. Results from in vitro antitumor activity and cellular uptake assay demonstrate that folic acid promotes drug-loaded NP cellular uptake through folate receptor-mediated endocytosis (RME). All of these results demonstrate that folate-decorated hybrid polymeric NPs are potential carriers for tumor-targeted drug delivery. [ABSTRACT FROM AUTHOR]

To develop more potent therapeutic agents with therapeutic efficacy for ischemia/reperfusion (I/R) injury, we linked an antiinflammatory moiety (1,3-dioxane derivative) to the key pharmacophoric moiety of melatonin. We hypothesized that the resulting new indole derivatives might induce a synergistic protection against oxidative damage associated with I/R injury. Our results indicate that one of these indole derivatives (7) manifests potent antiinflammatory antioxidant effects and exerts a protective effect against skeletal muscle injury and associated lung injury following limb I/R in rats. [ABSTRACT FROM AUTHOR]

An improved approach for the surface modification of poly(dimethylsiloxane) (PDMS) using carboxymethyl cellulose (CMC), carboxymethyl β-1,3-dextran (CMD), and alginic acid (AA) was investigated. The PDMS substrates were first oxidized in a H2SO4/H2O2 solution to transform the Si-CH3 groups on their surfaces into Si-OH groups. Then methacrylate groups were grafted onto the substrates through a silanization reaction using 3-(trimethoxysilyl)propyl methacrylate. Sequentially, cysteamine was conjugated onto the silanized surfaces by the reaction between the thiol and methacrylate groups under 254 nm UV exposure. Afterward, the amino-terminated PDMS substrates were sequentially reacted with CMC, CMD, and AA in the presence of N-hydroxysuccinimide and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide, resulting in the grafting of polysaccharides onto PDMS surfaces. The composition and chemical state of the modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS). In addition, the stability and dynamic characteristics of the polysaccharide-grafted PDMS substrates were investigated by XPS and temporal contact angle experiments. A protein adsorption assay using bovine serum albumin (BSA), chicken egg albumin, lysozyme, and RNase-A showed that the introduction of CMD and AA can reduce the adsorption of negatively charged BSA and chicken egg albumin, but increase the adsorption of the positively charged lysozyme and RNase-A. However, CMC-modified PDMS surfaces showed protein-repelling properties, regardless of whether the protein was positively or negatively charged. A cell culture and migration study of glioma C6, MKN-45, MCF-7, and HepG-2 cells revealed that the polysaccharide-modified PDMS greatly improved the cytocompatibility of native PDMS. [ABSTRACT FROM AUTHOR]

Abstract: High-yield synthesis (>90%) of two dimeric diphenyl cyclopentadienyl–phenoxyoxochlorotitanium(IV) complexes 3, and 4 has been achieved by hydrolysis of the monomeric 2-(3,4-diphenyl-cyclopentadienyl)-4,6-di-tert-butyl phenoxytitanium dichloride (1) and 2-(3,4-diphenyl-cyclopentadienyl)-6-tert-butyl phenoxytitanium dichloride (2). The molecular structure of 3 has been determined by single-crystal X-ray analysis. Both complexes have been characterized by 1H and 13C NMR spectroscopy. When activated with i Bu3Al and , complexes 3 and 4 exhibit reasonable catalytic activity for ethene polymerization, producing polyethylenes with moderate molecular weights and melting temperatures. [Copyright &y& Elsevier]