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By integrated magnetic sensors and microfluidic system, a microfluidic magnetic bioprocessor was developed for the rapid detection of multi-target biomarkers. Three digestive system tumor makers, α-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were simultaneously detected in immune reactions in the microchannel as a model system to evaluate this multi-target detection system performance. The experiment parameters including injecting flow velocity, immune reaction time and rinsing rate for each step were optimized. The standard curves were established for three tumor markers detection in serum samples, with the detection limits of 0.1 ng mL −1 (CEA), 0.1 ng mL −1 (AFP), 30 U mL −1 (CA19-9) and the dynamic ranges spanning four orders of magnitude. Multi-biomarker analysis could be completed within 30 min, and good linear relations were obtained between the results of magnetic bioprocessor and ELISA method, otherwise, the former had the advantages such as fast detection and high sensitivity.

We sought to investigate the antifibrotic effects of an artificial microRNA (miRNA) targeting connective tissue growth factor (CTGF) using the ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system. Cationic liposomes were conjugated with microbubbles using a biotin-avidin system. Plasmids carrying the most effective artificial miRNA sequences were delivered by ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system to rats with hepatic fibrosis. The results show that this method of gene delivery effectively transported the plasmids to the rat liver. The artificial miRNA reduced hepatic fibrosis pathological alterations as well as the protein and mRNA expressions of CTGF and transforming growth factor β1. Furthermore, the CTGF gene silencing decreased the levels of type I collagen and α-smooth muscle actin (P

Transcutaneous immunization (TCI) has many advantages compared with needle-based administrations. But the conventional TCI shows poor permeation of antigens across the skin barrier. In this study, Functional MicroArray (FMA) system was used to poke the skin and increase the permeability, and the hydrogel patch formulation was used as the carrier for transdermal delivery of hepatitis B surface antigen (HBsAg) and cholera toxin B (CTB) as an adjuvant. In vitro permeation of antigen was studied using porcine ear skin and rat abdominal skin. The results showed that FMA system could significantly increase the permeation of HBsAg across skin compared with conventional TCI. HBsAg loaded hydrogel formulation exhibited better antigenic thermostability than the liquid formulation. In vivo immunization studies were performed in mice, and the serum IgG titer, IgG2a/IgG1 ratio were measured. The results showed that TCI with FMA induced more potent immune responses than the groups without FMA pretreatment. CTB adjuvanted TCI group could induce higher IgG titers compared with the group without CTB. Furthermore, TCI group can maintain a longer duration of stable IgG titers compared with the intramuscular injection (IM) group. In conclusion, the FMA/hydrogel system was proved to be a potential vaccination strategy against hepatitis B virus.

The BaFe12O19/multiwall carbon nanotubes/poly(3-methyl-thiophene) (BaFe12O19/MCNTs/P(3MT)) composites were synthesized through an in situ chemical polymerization of 3-methyl-thiophene (3MT) in the presence of BaFe12O19/MCNTs composite powders. The BaFe12O19/MCNTs/P(3MT) composites were characterized by the fourier transform infrared spectrometry (FTIR) and X-ray diffraction (XRD). The morphologies of the composites were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The electric conductive properties were tested by a four-probe conductivity tester and the magnetic properties were measured by vibrating sample magnetometer (VSM). The electromagnetic performance tests showed that when the mass ratio of BaFe12O19 to MCNTs was 0.4, and the BaFe12O19/MCNTs to P(3MT) was 0.15, the conductivity, saturation magnetization (Ms) and residual magnetization (Mr) of the BaFe12O19/MCNTs/P(3MT) composites achieved 166.740 S/m, 29.884 emu/g, and 17.581 emu/g, respectively. POLYM. COMPOS., 34:1801–1808, 2013. © 2013 Society of Plastics Engineers

La/Sm-doped strontium-ferrite/poly-m-toluidine) (PMT) composites were synthesized by in-situ chemical polymerization of m-toluidine in the presence of La/Sm-doped strontium-ferrite particles. Structural, morphological and electro-magnetic properties of nanocomposites were performed by Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), four-probe conductivity tester and vibrating sample magnetometer (VSM). The results of XRD indicated that La3+ and Sm3+ had entered into the lattice of strontium ferrite. FTIR spectra demonstrated that there were interactions between ferrite particles and PMT. SEM studies showed that the composites presented the core-shell structure. Under applied magnetic field, nanocomposite exhibited the hystereric loops of the ferromagnetic behavior. The saturation magnetization and coercivity of nanocomposites varied with the content of (LaSm)(0.06)SrFe(11.88)O(19)particles.

Ultrasound-targeted microbubble (MB) destruction (UTMD) has been shown to increase the glomerular permeability, providing a potential novel therapeutic approach in targeted drug release for kidney diseases. Therefore, we investigated the impact of UTMD on renal interstitial permeability using MB-mediated diagnostic ultrasound (DUS). The left kidney of Sprague-Dawley (SD) rat was insonated by UTMD with either continuous or intermittent mode for 5 min. Evans blue (EB) revealed that both modes induced renal vascular permeability increase after DUS but recovered after 24 h. Intermittent insonation caused more severe injury than continuous mode. Red blood cells leaked out of the capillaries into interstitium without glomerular capillary hemorrhage (GCH) by hematoxylin and eosin (HE) staining. Electronic microscopy revealed the disruption of focal capillary wall in interstitial tissues. Morphological results confirmed capillary wall recovered in 24 h post-treatment. Results from fluorescence-labeled MBs showed that MBs were mainly localized in the interstitial portion of the tubular region and retained at 24 h. Intriguingly, urinalysis showed no clinical proteinuria after treatment. Our results indicated that MB plus DUS specifically and reversibly enhanced the interstitial permeability without affecting glomerulus, which may be developed into a therapeutic approach for targeting drug release to individual renal compartments.

The poly(3-octyl-thiophene)/BaFe 11.92 (LaNd) 0.04 O 19 -titanium dioxide/multiwalled carbon nanotubes (P(3OT)/BF–TD/MCNTs) nanocomposites were synthesized through in situ chemical polymerization of 3-octyl-thiophene in the presence of the BF–TD nanocomposites and MCNTs. Nanocomposites were characterized by thermogravimetry (TG), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), vibrating sample magnetometer (VSM). TG, FT-IR and XRD images indicated the formation of P(3OT)/BF–TD/MCNTs nanocomposites. SEM and TEM observations showed the particles size of the BF–TD nanocomposites was less than 50 nm and lots of MCNTs were absorbed by BF–TD nanocomposites. Under applied magnetic field, the nanocomposites exhibited the ferromagnetic behavior. The saturation magnetization, remanent magnetization and coercivity of nanocomposites varied with the content of Ba(LaNd) 0.09 Fe 11.82 O 19 particles. A scheme for the formation of the nanocomposites was proposed. When the BF and TD mass ratio was 6:5, P(3OT)/BF–TD/MCNTs nanocomposites possessed the best magnetic parameter.

This work investigated the effect of diagnostic ultrasound-targeted microbubble destruction (UTMD) on the permeability of normal liver tissue and the safety of this technique. One hundred and four rats were divided into four groups: the control group, the microbubble-only (MB) group, the ultrasound-only (US) group, and the ultrasound-targeted microbubble destruction group (UTMD). The permeabilities of capillaries and cell membranes were determined using Evans blue and lanthanum nitrate as tracers, respectively. The amount of Evans blue was approximately fourfold higher in the UTMD group than in the control, MB-only, and US-only groups (all P

The aims of this study were to investigate and compare the left ventricular (LV) geometry and function in elderly nonhypertensive type 2 diabetic patients with normal (NPP,60 mm Hg) and with high (HPP, ≥60 mmHg) 24-hour pulse pressure, and to explore the independent predictors of LV strain values in these patients.A total of 76 elderly nonhypertensive type 2 diabetic patients with normal (≥55%) LV ejection fraction (LVEF) were included, 36 of whom had HPP. The control group included 40 age- and sex-matched healthy volunteers with normal NPP. Conventional echocardiography and three-dimensional speckle-tracking echocardiography (3DSTE) were performed and LV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were measured.Significant differences in the two-dimensional LV geometry were found among the three groups (p = 0.015), and concentric geometry was most prevalent in the diabetic patients with HPP. The diabetic patients with NPP only showed significantly lower GLS than the controls (p0.05). However, the diabetic patients with HPP showed significantly lower LVEF and severely lower strain values in all directions than the controls and the diabetic patients with NPP (p0.01or p0.05 or p0.001). Fasting plasma glucose, HPP, and body mass index were independently associated with all strain parameters in diabetic patients.The combination of conventional echocardiography and 3DSTE could detect LV subclinical abnormalities in nonhypertensive type 2 diabetic patients with NPP and HPP. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:416-425, 2017.

DNA vaccines are simple to produce and can generate strong cellular and humoral immune response, making them attractive vaccine candidates. However, a major shortcoming of DNA vaccines is their poor immunogenicity when administered intramuscularly. Transcutaneous immunization (TCI) via microneedles is a promising alternative delivery route to enhance the vaccination efficacy. A novel dissolving microneedle array (DMA)-based TCI system loaded with cationic liposomes encapsulated with hepatitis B DNA vaccine and adjuvant CpG ODN was developed and characterized. The pGFP expression in mouse skin using DMA was imaged over time. In vivo immunity tests in mice were performed to observe the capability of DMA to induce immune response after delivery of DNA. The results showed that pGFP could be delivered into skin by DMA and expressed in skin. Further, the amount of expressed GFP was likely to peak at day 4. The immunity tests showed that the DMA-based DNA vaccination could induce effective immune response. CpG ODN significantly improved the immune response and achieved the shift of immune type from predominate Th2 type to a balance Th1/Th2 type. The cationic liposomes could further improve the immunogenicity of DNA vaccine. In conclusion, the novel DMA-based TCI system can effectively deliver hepatitis B DNA vaccine into skin, inducing effective immune response and change the immune type by adjuvant CpG ODN.

Our objective is to investigate the promoting effect of hypoxic preconditioning combined with microbubble (MB)-mediated ultrasound (US) on the SDF-1/CXCR4 expression and the migration ability of mesenchymal stem cells (MSCs). Based on the uniform design, the parameters of MB-mediated US, such as the total treatment time (T), acoustic intensity (Q), and the dosage of MBs, were optimized firstly. The results were assessed by regression analysis. Using the optimum irradiation parameters, the concentration of SDF-1 in the supernatant, the expression levels of membrane CXCR4, and the cell viability of hypoxic MSCs or normoxic MSCs were compared. The in vitro transwell migration assay was performed as well. The best combination of parameters for more SDF-1 secretion and less MSCs death was T = 30 s, A = 0.6 W/cm(2), and MB = 10(6)/ml. After 24 h of hypoxic preconditioning, the expression of SDF-1 and surface CXCR4 was increased in the hypoxic MSC group as compared to the normoxic MSC group (P

Although meloxicam (MX) is relatively safer than other NSAIDs, adverse effects relating to the gastro-intestinal tract are still a problem when administrated MX at high doses and on the long-term treatment. Drug delivery via skin provides an attractive alternative to oral administration, but is limited by the first layer of the skin-stratum corneum. Studies have been focused on developing effective methods to break the barrier of stratum corneum for enhancing delivery of MX to and across the skin. Strategies including formulation optimizing, chemical modification and physical enhancements to transiently reduce stratum corneum barrier function have been introduced. This article reviews the current state of the techniques in the delivery of MX to and across the skin, and it also includes the profiles of pharmacokinetic and safety related with skin delivery of MX.

A lyophilized hydrogel patch system was developed for microneedle-mediated insulin delivery. The matrix of Cross-linked poly(acrylamide-co-acrylic acid) were synthesized by precipitation polymerization. Recombinant human Insulin was loaded into the lyophilized polymer matrix, which can be rehydrated by water. After the hydrated patch was applied to the abdominal skin of diabetic rats after microneedle pretreatment, pharmacodynamics and pharmacokinetics evaluation was performed. The blood samples were collected to monitor blood glucose and serum insulin levels for 12 h. Blood glucose was lowered in proportion to the concentration of insulin loaded in lyophilized hydrogel patches (R(2)=0.99), with a longer duration of action compared to subcutaneous injection. Stability study confirmed more than 90% of insulin activity was retained in lyophilized hydrogel after 6 months of storage at 4 °C. In conclusion, hydrogel patches were demonstrated to be appropriate drug reservoir for sustained release of insulin with microneedle mediated transdermal delivery.

La-doped barium-ferrite/polythiophene (LB/PTh) composites have been successfully synthesized by in situ chemical polymerization with ferric chloride (FeCl3) as an initiator. Crystal structure was investigated by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Morphology was investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Electromagnetic of composites was tested by four-probe conductivity tester and vibrating sample magnetometer (VSM). The results of XRD indicated that La3+ had entered into the lattice of barium ferrite. FTIR spectra demonstrated that there were interactions between ferrite particles and PTh. TEM and SEM studies showed that the composites presented the core–shell structure. The electrical conductivity of the composites decreases with the ferrite particles content increase. Under applied magnetic field, nanocomposite exhibited the hysteretic loops of the ferromagnetic behavior. The saturation magnetization and coercivity of nanocomposites varied with the content of ferrite particles.

La/Nd-doped barium-ferrite/polypyrrole nanocomposites were synthesized by in situ chemical polymerization of pyrrole in the presence of La/Nd-doped barium-ferrite particles. Structural, morphological and electro-magnetic properties of the nanocomposites were performed by Fourier transform infrared (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), four-probe conductivity tester and vibrating sample magnetometer (VSM). The results of XRD indicated that La 3+ and Nd 3+ had entered into the lattice of barium ferrite. FTIR spectra demonstrated that there were interactions between ferrite particles and PPy. The TEM and SEM studies showed that the composites presented the core–shell structure. Under applied magnetic field, nanocomposites exhibited the hysteresis loops of the ferromagnetic behavior. The saturation magnetization and coercivity of nanocomposites varied with the content of Ba(LaNd) 0.09 Fe 11.82 O 19 particles.

Insulin delivery relies on subcutaneous or intravascular injection, leading to reduced patient compliance. Transdermal delivery of insulin has been successfully demonstrated but dose accuracy and skin irritation are problematic in addition to the complex basal-bolus delivery profile required by insulin therapy. Here we present a novel intraepidermal delivery technology (delivered site at epidermis layer,150 μm) by combining skin pretreatment with short microneedles (150 μm in length) and iontophoresis transdermal patch (enhanced transport via electrical field) that can provide a continuous basal dose and on-demand bolus dosing for mealtime insulin needs. To our knowledge, this is the first demonstration of therapeutic equivalence between fast-acting human regular insulin and long-acting insulin with possibilities for on-demand dose adjustment. This new intraepidermal delivery technology is likely to change the therapy regimen of patients suffering from insulin-dependent diabetes mellitus and provide a way to lower cost in comparison with insulin pumps and improve patient compliance.The authors present a novel intraepidermal insulin delivery technology by combining skin pretreatment with short microneedles and iontophoresis transdermal patch to provide a continuous basal dose and on-demand bolus dosing. This new method is has the potentials to replace insulin pumps by offering a cost effective alternative with less inconvenience and improved compliance.

Dissolving microneedles (DMNs) based transdermal delivery is an attractive drug delivery approach with minimal invasion. However, it is still challenging to load poorly water-soluble drugs in DMNs for systemic delivery. The aim of the study was to develop DMNs loaded with artemether (ARM) as a model drug, to enable efficient drug penetration through skin for systemic absorption and distribution. The micro-conduits created by microneedles were imaged by confocal laser scanning microscopy (CLSM), and the insertion depth was suggested to be about 270μm. The maximum amount of ARM delivered into skin was 72.67±2.69% of the initial dose loaded on DMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma ARM concentrations, after ARM-loaded DMNs treatment. In contrast to intramuscular injection, DMNs application resulted in lower peak plasma levels, but higher plasma ARM concentration at 8h after administration. There were no significant difference in area under the curve and bioavailability between DMNs group and intramuscular group (P>0.05). Pharmacodynamics studies performed in collagen-induced arthritis (CIA) rats showed that ARM-loaded DMNs could reverse paw edema, similar to ARM intramuscular injection. In conclusion, developed DMNs provided a potential minimally invasive route for systemic delivery of poorly water-soluble drugs.

A dichromate digestion and spectrophotometric procedure is proposed for estimating soil microbial biomass carbon (C) in association with fumigation–extraction. The recommended procedure uses a volume (1.6 ml) of 0.5 M potassium sulfate (K2SO4) soil extracts and oxidant solution (dichromate–sulfuric acid, 2.4 mL), mixed with a volume (4 mL) for digestion at 140 °C for 30 min. The digested solution is then directly read for absorbance at 350 nm using a spectrophotometer, and the C in the digested soil extracts is measured against glucose standards. The KEC (indicating the extractable part of microbial biomass C after fumigation) value is estimated as 0.33 for the proposed method. There are good correlations between soil microbial biomass C measured by the proposed method, the dichromate digestion titration, and oven oxidation by total organic C (TOC) analytical method. This method is a simple, rapid, and economical procedure associated with fumigation–extraction for biomass C analysis.

This work investigated the effect of infusion of a self-made ultrasound contrast agent with long persistence (named ZHIFUXIAN) on rat right ventricular pressure and made a preliminary evaluation on the relative safety of the novel microbubbles. Normal saline, SonoVue and ZHIFUXIAN were injected through caudal vein at the total volume of 0.5ml for each injection. The right ventricular systolic pressure (RVSP) and end-diastolic pressure (RVEDP) were monitored and the changes of the pressure were compared with baseline readings. RVSP increased when saline, SonoVue or ZHIFUXIAN were injected, the greatest change being after SonoVue (about 2mmHg), but there was no statistical significance compared with baseline (P>0.05). There was no significant difference in RVSP between saline, SonoVue and ZHIFUXIAN at any time point. Also, there was no significant difference in RVEDP between groups at each time point and between different time points in each group. The results indicate that the self-made microbubbles effect on right ventricular hemodynamics is equivalent to that of normal saline at the same volume needed for effective enhanced imaging, demonstrating that it does not produce changes in right ventricular blood pressure under the study conditions. Pathological examination also showed it had no obvious influence on lung, liver and kidney.

Celery was found to provoke human allergenic response in some countries. Labeling of celery ingredients was required by the European Union, and the threshold set at 10 mg/kg (0.001%). In our study, a celery mannitol transporter (Mat3) gene-based detection method was established by means of SYBR Green real-time PCR technique. No cross-reactivity was found between celery and the other food materials. Absolute detection limit (LODa), relative detection limit (LODr), and practical detection limit (LODp) of the method were determined through experiments on pure celery DNA, DNA mix, and spiked food samples. The method was able to detect 0.001 raw food sample and 0.01 heated food sample. The utility of the method was confirmed by the investigation of 13 commercial foods.

Objective The purpose of the present study is to prepare a nanoscale ultrasound contrast agent and to investigate its characterization and ultrasonic imaging in vivo. Methods Nanoscale ultrasound contrast agent was prepared by machine vibration and low speed centrifugation, and the appearance, distribution, diameter, and zeta potential of the nanoscale ultrasound contrast agent were measured. Contrast-enhanced ultrasonography was performed on normal rabbit liver to observe the duration and intensity of enhancement. Results The nanoscale ultrasound contrast agent had a good shape and uniform distribution by light microscope and transmission electron microscope, with average diameters of 623.4 nm and average zeta potential of 1.3 mV. The contrast imaging study in vivo showed that the nanoscale ultrasound contrast agent could significantly enhance the duration and echo intensity of the vessels and parenchyma in rabbit livers, and there were no obvious difference with micro-scale microbubbles. Conclusions The nanoscale ultrasound contrast agent is stable and effective for the enhancement of ultrasound imaging. This study provides an important platform for miniaturizing and improving the targeting performance of ultrasound contrast agents.

An intradermal microdelivery system comprising a wafer having 150-mum long microneedles and an applicator was used for controlled release of insulin. Insulin was topically applied on microneedle-pretreated skin. In vitro percutaneous studies showed that the penetration amount of FITC-Insulin following microneedle pretreatment was enhanced significantly and continued to increase for several hours after the removal of donor phase. In vivo studies on diabetic rats confirmed that the pharmacodynamic profile of percutaneously administrated regular insulin was smooth, with the duration of action comparable to that of subcutaneously injected biphasic insulin. The effects of insulin concentration, duration and area of microneedle treatment on blood glucose lowering were studied in vivo. The results indicated that the duration of microneedle treatment and insulin concentration were key influencing factors to optimize blood glucose control. The extent of blood glucose lowering was in proportion to the area of microneedle treatment.

Methods to facilitate topical anesthesia for venipuncture are characterized by substantial limitations. This randomized double-blind study was undertaken to assess whether use of a quickly and painlessly applied microneedle system (functional microarray, FMA) to create punctures in the stratum corneum facilitates topical anesthesia in healthy adults. In 25 volunteers receiving topical dyclonine, FMA was applied to one forearm and a sham device in the other, followed by assessment of pain levels associated with application of a standardized stimulus at 5-minute intervals over an hour. Analysis of the primary end point, time required to achieve a significant degree of pain reduction (13 mm on a 100-mm scale), revealed that FMA significantly sped time to pain reduction (log-rank P = .007). Functional microarray also resulted in a greater degree of pain reduction (Kruskal-Wallis P < .0001). Functional microarray application had no adverse effects, and the device shows promise for facilitation of topical anesthesia.

Therapeutic ultrasound-mediated microbubble destruction has been applied in the targeted delivery of genes, drugs and stem cells. We intended to study whether diagnostic US irradiating lipid-coated microbubble destruction combined with bone-marrow derived MSC infusion could enable the targeted delivery of MSCs into the myocardium and improve cardiac function of the myocardial infarction of New Zealand rabbits.Diagnostic ultrasound was applied to the anterior chest for 10 min after intravenous injection of lipid-coated microbubble followed by infusion of BM-MSCs. Echocardiography, histological examination, and western blotting were performed 4 weeks after cell transplantation.The cardiac function (assessed by fractional shortening and ejection fraction) was markedly improved by US+Microbubble+MSC treatment. The number of capillaries stained by HE in US+Microbubble+MSC group (47+/-23) was much greater than that of the MSCs infusion group (26+/-7), US+Microbubble group(22+/-5) and PBS infusion group (19+/-10), P0.01. US+Microbubble stimulation induced the expression of adhesion molecule (VCAM-1) in capillaries and enhanced the myocardial permeability of microvessels. US+Microbubble-mediated supply of MSCs increased the level of VEGF in ischemic myocardium. Area of cardiac fibrosis in the US+Microbubble+MSC group was significantly decreased by 25.6%,40.1% and 46.8% when compared with MSC infusion group, US+Microbubble group and PBS infusion group, respectively.This non-invasive cell delivery system may be useful as a novel and efficient approach for angiogenic cell therapy to the infarcted myocardium.

Various methods have been developed for quantitative analysis of DNA methylation. However, there is currently no reference analysis system regarding DNA methylation with which other analytical approaches can be compared and evaluated. A standard measurement system that includes reference methods and reference materials may improve comparability and credibility of data obtained from different analytical environments. In an effort to establish a standard system for measurement of DNA methylation, the Korea Research Institute of Standards and Science (KRISS) coordinated an international comparison study among different national metrology institutes. An initial stage of the study involved an intercomparison regarding quantitative measurement of total methyl cytosine contents in artificially constructed DNA samples. The measurement principle involved measurement of dNMP contents following enzymatic hydrolysis of DNA samples. Results of the study showed good comparability among four of five participants and close agreement with reference values assigned by the coordinating laboratory. Conflicting data from one participant may have resulted from incomplete hydrolysis of samples due to use of insufficient amounts of enzymes. These results indicate that comparable and accurate results can be obtained from different measurement environments if digestion conditions are controlled appropriately and valid calibration systems are employed.

There is a significant interest in the application of microneedles in intradermal drug delivery systems. Previous studies have demonstrated that skin permeation of drugs can be increased by orders of magnitude with microneedle insertion. In this study, emphasis is placed on the development of low cost, painless intradermal microneedle systems that can enhance the percutaneous drug permeation. Microneedles of octagonal pyramidal shape with the length of 150 mum were employed, and the capabilities of skin permeation enhancement under different delivery conditions were examined. The delivery parameters taken into account included the insertion time and the area of insertion. It was found that when solid microneedle arrays of 150 mum in length were pierced into human dermatomed skin for 5 to 60 s, microconduits with the depth of 50 to 80 mum were created to facilitate the percutaneous permeation of drugs. In percutaneous tests, it was demonstrated that the permeability coefficient of calcein (MW = 622.55) was significantly increased by 10(4) to 10(5) times compared to that on intact skin. In terms of biocompatibility, biological evaluation indicated a broad spectrum of safety for the microneedle system. These results suggest that the octagonal pyramidal microneedles can be an effective tool in developing novel intradermal drug delivery system.

Phenylalanine molecularly imprinted polymer was synthesized in the presence of triflouroacetic acid. HPLC‐MS evaluation showed it had good affinity toward its template among 16 amino acid mixtures. It was used for quantification of phenylalanine in protein hydrolysis solution and in serum without sample pre‐treatment. Further study revealed the molecular recognition mechanism involved size exclusion, hydrophobic interaction, and hydrogen bonding interaction. The molecularly imprinted polymer presented here can be used for actual sample analysis and the well characterized recognition mechanism can benefit the design, synthesis, and application of MIP.

A new chelating resin using chitosan as a base material was synthesized. Functional moiety of 2-amino-5-hydroxy benzoic acid (AHBA) was chemically bonded to the amino group of cross-linked chitosan (CCTS) through the arm of chloromethyloxirane (CCTS-AHBA resin). Several elements, such as Ag, Be, Cd, Co, Cu, Ni, Ph, U, V, and rare earth elements (REEs), could be adsorbed on the resin. To use the resin for on-line pretreatment, the resin was packed in a mini-column and installed into a sequential-injection/automated pretreatment system (Auto-Pret System) coupled with inductively coupled plasma-atomic emission spectrometry (ICP-AES). The sequential-injection/automated pretreatment system was a laboratory-assembled, and the program was written using Visual Basic software. This system can provide easy operation procedures, less reagent consumption, as well as less waste production. Experimental variables considered as effective factors in the improvement sensitivity, such as an eluent concentration, a sample and an eluent flow rate, pH of samples, and air-sandwiched eluent were carefully optimized. The proposed system provides excellent on-line collection efficiency, as well as high concentration factors of analytes in water samples, which results in highly sensitive detection of ultra-trace and trace analysis. Under the optimal conditions, the detection limits of 24 elements examined are in the range from ppt to sub-ppb levels. The proposed method was validated by using the standard reference material of a river water, SLRS-4, and the applicability was further demonstrated to the on-line collection/concentration of trace elements, such as Ag, Be, Cd, Co, Cu, Ni, Ph, U, V, and REEs in water samples.

A novel photochromic Schiff base derivative, 5,17-N,N′-(5,5′-di-methoxyl-benzlaldehyde)diimine-25,27-dipropoxy-calix[4]arene has been synthesized through incorporation of two imine groups into the upper rims of calix[4]arene. The experiments showed that the addition of Dy3+ or Er3+ ions to compound 4 results in the solution color change, but other metal ions caused less change. It indicated that the synthetic receptor can selectively recognize Dy3+ and Er3+ ion by naked eye over other lanthanide cations. Thus, these systems can be applied as chemosensor for Dy3+ and Er3+ ion in analytical chemistry.

A novel fluorescent chemosensor with two 5-nitro-salicylaldehyde groups at the upper rim of calix[4]arene has been synthesized. The chemosensor can effectively recognize copper(II) ion. This system could be considered as a molecular switch. By alternating the light irradiation of mixed solution formed by the host and Cu 2+ , off–on–off fluorescent switching is carried out.

Objective This study aims to compare the diagnostic accuracy of combined two-dimensional (2D) and real time three-dimensional (RT3D) transesophageal echocardiogram (TEE) imaging with the anatomic findings during surgery in adults with aorto-left ventricular tunnel (ALVT). Background ALVT has typically been reported in infants rather than in adults. TEE appears to be a promising method of recognizing the spatial relationship of intracardiac structures. Methods Patients underwent comprehensive 2D and RT3DTEE within 1 week preoperative and intraoperative. The TEE images were compared with the surgical findings. Results Nine patients diagnosed with ALVT using TEE were selected. The operations were successfully performed in 8 patients. The origin of the tunnels diagnosed by TEE was superior to the right coronary sinus (RCS) in 3 patients, superior to the commissure of the left coronary sinus (LCS) and the RCS in 3 patients, inferior to the junction of the LCS and noncoronary sinus (NCS) in 2 patients, and superior to the NCS in 1 patient. The surgical findings confirmed ALVT in 8 patients. The average diameter of the tunnel orifices in the LV or in the aorta measured by TEE versus surgery was 6.15 ± 3.21 mm versus 6.80 ± 3.91 mm (correlation displayed as r = 0.99, P

The article focuses on the self-drying curing characteristics of energy-saving and environmental friendly water-based self-drying / fast-drying foundry coating. Through check experiment, the differences of strength, humidity resistance and influence on the strength of resin sand when respectively using new water-based foundry coating, common water-based and alcohol-based coating are compared and studied. The results show that the coating strength of new water-based coating is significantly higher than that of common water-based coating and is almost the same as alcohol-based coating. The coating has a minimal impact on the strength of resin sand, and its humidity resistance is obviously better than that of common water-based and alcohol-based coating, for the residual water content of the coating is only about 1.4% after self-drying.

Factors affected drying speed of energy saving and environment friendly water-based self-drying / fast-drying foundry coatings and its regularity changing were analyzed. The results show that the self-drying speed of coating is improved significantly with the decrease of humidity and the increase of temperature, the coating is able to naturally dry in about 2 hours under the condition of 25 and 80% RH °C , the self-drying speed of coating increases in an approximately linear manner with the decreasing of its thickness, the hot air quick drying time of the water-based self-drying / fast-drying coating is 3.5~7.0min when the thickness of coatings is 0.3~0.8 mm and the hot air temperature is 80 ±5 °C °C.

Mesenchymal stem cell (MSC) therapy shows considerable promise for the treatment of myocardial infarction (MI). However, the inefficient migration and homing of MSCs after systemic infusion have limited their therapeutic applications. Ultrasound-targeted microbubble destruction (UTMD) has proven to be promising to improve the homing of MSCs to the ischemic myocardium, but the concrete mechanism remains unclear. We hypothesize that UTMD promotes MSC homing by upregulating SDF-1/CXCR4, and this study was aimed at exploring this potential mechanism. We analyzed SDF-1/CXCR4 expression after UTMD treatment in vitro and in vivo and counted the number of homing MSCs in MI areas. The in vitro results demonstrated that UTMD not only led to elevated secretion of SDF-1 but also resulted in an increased proportion of MSCs that expressed surface CXCR4. The in vivo findings show an increase in the number of homing MSCs and higher expression of SDF-1/CXCR4 in the UTMD combined with MSCs infusion group compared to other groups. In conclusion, UTMD can increase SDF-1 expression in the ischemic myocardium and upregulate the expression of surface CXCR4 on MSCs, which provides a molecular mechanism for the homing of MSCs assisted by UTMD via SDF-1/CXCR4 axis.

Multi-tube rocket projectiles scattered in a considerable number of cases is mainly caused by the initial disturbance. Monte Carlo method is based on probability and mathematical statistics, based on probabilistic models do a mathematical simulation method to approximate calculation. It is a random sampling method as a means of reliability prediction system based on reliability block diagram. MATLAB simulation analysis using the deviation caused by the placement of the main error sources can save the development expenditure, but also shorten the development cycle.

Transdermal drug delivery is generally limited by the extraordinary barrier properties of the stratum corneum, the outer 10–15 µm layer of skin. A conventional needle inserted across this barrier and into deeper tissues could effectively deliver drugs. However, it would lead to infection and cause pain, thereby reducing patient compliance. In order to administer a frequent injection of insulin and other therapeutic agents more efficiently, integrated arrays with very short microneedles were recently proposed as very good candidates for painless injection or extraction. A variety of microneedle designs have thus been made available by employing the fabrication tools of the microelectronics industry and using materials such as silicon, metals, polymers and glass with feature sizes ranging from sub-micron to nanometers. At the same time, experiments were also made to test the capability of the microneedles to inject drugs into tissues. However, due to the difficulty encountered in measurement, a detailed understanding of the spatial and transient drug delivery process still remains unclear up to now. To better grasp the mechanisms involved, quantitative theoretical models were developed in this paper to simultaneously characterize the flow and drug transport, and numerical solutions were performed to predict the kinetics of dispersed drugs injected into the skin from a microneedle array. Calculations indicated that increasing the initial injection velocity and accelerating the blood circulation in skin tissue with high porosity are helpful to enhance the transdermal drug delivery. This study provides the first quantitative simulation of fluid injection through a microneedle array and drug species transport inside the skin. The modeling strategy can also possibly be extended to deal with a wider range of clinical issues such as targeted nanoparticle delivery for therapeutics or molecular imaging.

The synthesis and complexing properties of a calix[4]arene derivate ( 6 ) carrying two spirobenzopyran moieties are described. The addition of lanthanide ions resulted in significant UV–vis spectral shifts (68–84 nm) in visible region. It indicates that the synthetic receptor can recognize lanthanide ions by naked eyes over other cations including Na + , K + , Mg 2+ , Ca 2+ , Fe 3+ , Cu 2+ and Zn 2+ . The mechanism of recognition was studied with 1 H NMR, UV–vis spectra and emission spectra. The receptor may be applied to sense lanthanide ions.

Shengzheng Wu,1 Lu Li,1 Gong Wang,1 Weiwei Shen,2 Yali Xu,1 Zheng Liu,1 Zhongxiong Zhuo,1 Hongmei Xia,1 Yunhua Gao,1 Kaibin Tan1 1Department of Ultrasound, 2Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MBSDF-1) via covalent conjugation. The characterization and bioactivity of MBSDF-1 were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MBSDF-1. The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8µg/mL. MBSDF-1 remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MBSDF-1 destruction could promote the homing of MSCs to early DNkidneys and provide a novel potential therapeutic approach for DN kidney repair. Keywords: mesenchymal stem cell, ultrasound, microbubbles, homing, stromal cell-derived factor-1, diabetic nephropathy

A novel spiropyran derivative carrying a calix[4]arene group has been synthesized through incorporating two spirobenzopyran groups into one 1,3-substituent calix[4]arene derivative. Photochromic properties were studied under alternate irradiation of ultraviolet light and visible light in acetonitrile. Addition of metal ions (such as Mg 2+ , Ca 2+ , Eu 3+ ) decreased the first-order thermal decoloration rate constants to different extent. The colored forms of the compound are more stable than the parent 1′,3′,3-trimethyl-6-nitro-8-methanolspirobenzopyran. It provides a method of increasing stability of the merocyanine forms which are of high importance for applications of photochromic materials, especially in the presence of Eu 3+ . The compound may be applied as photochromic materials for its high thermal stability of colored forms.

The objective of the present study is to compare the immunogenicity of insulin by microneedle-mediated intradermal delivery or subcutaneous injection. Female and male rats were treated with insulin by either microneedle-mediated intradermal delivery or subcutaneous injection twice a week for 4 weeks. A control group without insulin administration was also studied. Human anti-insulin antibody (AIA) levels were measured by radioimmunoassay (RIA) before starting insulin treatment and after that within 20 weeks. The male rats did not induce positive AIA levels, and there was no significant difference between all male groups. In contrast, in female rats the AIA levels were significantly higher in microneedle group compared with injection group, and lasted from 6 to 20 weeks after starting insulin treatment. The increased immunogenicity of insulin delivery by microneedle might be due to the large number of immune cells in skin.

An extracellular β-glucosidase was extracted from the culture filtrate of Aspergillus niger No. 5.1 and purified to homogeneity by using ammonium sulfate precipitation, Chitopearl-DEAE chromatography, and Sephadex G-100 chromatography. The specific activity of the enzyme was enriched 6.33-fold, with a recovery of 11.67%. The enzyme was a monomer and the molecular mass was 67.5 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis and 66.5 kDa by gel-filtration chromatography. The enzyme had optimum activity at pH 6.0 and 60°C and was stable over the pH range of 3.0–9.0. It showed specificity of hydrolysis for p-nitrophenyl-β-d-glucoside and cellobiose. The K m and V max values of the enzyme for cellobiose and salicin were 5.34 mM, 2.57 µmol/(mL·s), and 3.09 mM, 1.34 µmol/(mL·s), respectively. Both amino acid composition and N-terminal amino acid sequence of the enzyme were determined, which provides useful information for cloning of this enzyme.

An improved fabrication of poly(methyl methacrylate) (PMMA)-based capillary electrophoresis microchips has been demonstrated. The microchannel structures on PMMA substrates were generated by one-step hot embossing procedure using a stainless steel template. Hundreds of patterned PMMA substrates have been successfully obtained using the single metal template. Sequent microchannel enclosure with high yield up to 90% was accomplished by a vacuum-assisted thermal bonding method. The results of profilometric scanning of separated substrates showed the dimensions of the channels were well preserved during the bonding process. Finally, analytical functionalities of these PMMA microchips were demonstrated by performing fast electrophoretic separations and high sensitive end-column amperometric detections of dopamine and catechol. The entire fabrication methodology may also be useful for preparation of other thermoplastic microfluidic systems.

In the present work, chemiluminescence detection was integrated with capillary electrophoresis microchip. The microchip was designed on the principle of flow-injection chemiluminescence system and capillary electrophoresis. It has three main channels, five reservoirs and a detection cell. As model samples, dopamine and catechol were separated and detected using a permanganate chemiluminescent system on the prepared microchip. The samples were electrokinetically injected into the double-T cross section, separated in the separation channel, and then oxidized by chemiluminescent reagent delivered by a home-made micropump to produce light in the detection cell. The electroosmotic flow could be smoothly coupled with the micropump flow. The detection limits for dopamine and catechol were 20.0 and 10.0 μM, respectively. Successful separation and detection of dopamine and catechol demonstrated the distinct advantages of integration of chemiluminescent detection on a microchip for rapid and sensitive analysis.

A chitosan resin possessing the leucine moiety (leucine-type chitosan) was newly synthesized by using the chitosan cross-linked with ethylene glycol diglycidyl ether (EGDE) as a basic material. The adsorption behavior of trace amounts of metal ions on the leucine-type chitosan was systematically examined by packing it in a mini-column by ICP-MS (inductively coupled plasma mass spectrometry). Molybdenum was adsorbed on the resin quantitatively and was easily eluted with 1 M nitric acid. The optimized pH range was from 1 to 5, and Mo was collected by the chelation mechanism and/or the anion-exchange mechanism. The method was applied to the determination of Mo in sea and river water samples. A pretreatment with the resin could remove the matrix components in seawater. Preconcentration by 100-fold was accomplished by a column treatment, which had a sufficient concentration to measure trace Mo in river water samples by ICP-AES (inductively coupled plasma atomic emission spectrometry) and GFAAS (graphite furnac...

A chitosan resin derivatized with serine moiety (serine-type chitosan) was newly developed by using the cross-linked chitosan as a base material. The adsorption behavior of trace amounts of metal ions on the serine-type chitosan resin was systematically examined by packing it in a mini-column, passing a metal solution through it and measuring metal ions in the effluent by ICP-MS. The resin could adsorb a number of metal cations at pH from neutral to alkaline region, and several oxoanionic metals at acidic pH region by an anion exchange mechanism. Uranium and Cu could be adsorbed selectively at pH from acidic to alkaline region by a chelating mechanism; U could be adsorbed quantitatively even at pH 3–4. Uranium adsorbed on the resin was easily eluted with 1 M nitric acid: the preconcentration (5-, 10-, 50- and 100-fold) of U was possible. The column treatment method was used prior to the ICP-MS measurement of U in natural river, sea and tap waters; R.S.D. were 2.63, 1.13 and 1.37%, respectively. Uranium in tap water could be determined by 10-fold preconcentration: analytical result was 1.46±0.02 ppt. The resin also was applied to the recovery of U in sea water: the recovery tests for artificial and natural sea water were 97.1 and 93.0%, respectively.

Chelating resins, two kinds of iminodiacetate derivatives (IDA) of cross-linked chitosan (CCS) were synthesized and investigated for adsorption capacity, matrix elimination and collection/concentration of analytes by a column pretreatment in a multi-element ICP-MS determination method. The adsorption behavior of 54 elements at the 10 ng ml−1 level on chitosan derivatives in a packed mini-column was systematically examined. Almost 30 kinds of metal ions were recovered quantitatively at pH 5 with CCS–HP/IDA (cross-linked chitosan possessing N-2-hydroxypropyl iminodiacetic acid groups) column. Compared with available chitosan–iminodiacetate resin, CHITOPEARL CI-03, the recovery of the metal ions such as Cu, Pb and La is satisfactory with CCS–IDA (cross-linked chitosan possessing N,N-iminodiacetic acid groups) and CCS–HP/IDA using 2 M nitric acid as an eluent, which may be attributed to the difference of cross-linking and macroporous structure. Compared with Chelex-100, the adsorption efficiency is in the order: Chelex-100 > CCS–IDA > CCS–HP/IDA, especially in the chelating ability for alkaline earth metals. The resin with a longer spacer (CCS–HP/IDA) showed higher adsorption selectivity between heavy metal ions and alkaline earth metals at pH < 7. The separation efficiency of the major matrix cations in seawater (Na, K, Mg, Ca) has also been investigated, and matrix interference was negligible even in a seawater sample at pH 5 with CCS–HP/IDA. The recoveries of Mn at pH 5 with CCS–HP/IDA or Chelex-100 were almost 100%. However, those of Mg with each resin were 4 or 98%, respectively. The adsorption capacities of synthesized CCS–HP/IDA for Cu(II), Pb(II) and La(III) were 0.90, 0.65 and 0.34 mmol g−1, respectively. Therefore, the chelating chitosan resins developed are applicable to the pretreatment of trace amounts of elements in various kinds of water samples.

Xiang Wang,1 Ping Liu,1 Weixiao Yang,1 Lu Li,1 Peijing Li,2 Zheng Liu,1 Zhongxiong Zhuo,1 Yunhua Gao1 1Department of Ultrasound, Xinqiao Hospital of the Third Military Medical University, Chongqing, 2Department ofUltrasound, General Hospital ofthe Jinan Military Area, Jinan, People’s Republic of China Abstract: Methotrexate (MTX) is the single most effective agent for the treatment of primary central nervous system lymphoma. Currently, the delivery of MTX to the brain is achieved by high systemic doses, which cause severe long-term neurotoxicity, or intrathecal administration, which is highly invasive and may lead to infections or hemorrhagic complications. Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to MTX-loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. MTX-liposome-coupled microbubbles had a high drug-loading capacity of 8.91%±0.86%, and their size (2.64±0.93 µm in diameter) was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 cancer cells than MTX alone or MTX-loaded liposomes. When Sprague-Dawley rats were exposed to sonication, administration of these MTX-liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood–brain barrier without noticeable tissue or capillary damage. High-performance liquid chromatography analysis of the brain MTX concentration showed that MTX delivery to the brain followed the order of MTX-liposome-coupled microbubbles + ultrasound (25.3±2.4 µg/g) > unmodified ZHIFUXIAN + MTX + ultrasound (18.6±2.2 µg/g) > MTX alone (6.97±0.75 µg/g) > MTX-liposome-coupled microbubbles (2.92±0.39 µg/g). Therefore, treatment with MTX-liposome-coupled microbubbles and ultrasound resulted in a significantly higher brain MTX concentration than all other treatments (P