OBJECTIVE

To estimate the cost-effectiveness ratio of highly-active antiretroviral therapy (HAART) in Canada.

METHODS

A before-and-after analysis to calculate incremental cost of life year gained (LYG) between 1991 and 1995 (pre-HAART period) and between 1997 and 2001 (HAART period) for non-AIDS and AIDS groups (CDC stage of HIV infection).

METHODS

For two Quebec HIV hospital clinics, mean inpatient (IP) days, outpatient (OP) visits and direct health care costs per patient-year (PPY) were calculated. Cox's proportional hazards models calculated disease progression, stratified by study periods and adjusted for gender, age at cohort entry, sexual orientation, injecting drug use and baseline CD4 cell count.

RESULTS

For non-AIDS patients, mean IP days was 1.6 (pre-HAART period) compared with 0.8 PPY (HAART period); mean OP visits increased from 2.8 to 5.5 PPY. Total cost was US$ 4265 (pre-HAART period) and US$ 9445 PPY (HAART period) of which 66 and 84%, respectively were spent on antiretroviral drugs. Median progression time was 6.3 years in the pre-HAART period compared with 12.5 years in HAART period (log rank chi = 270, P < 0.0001). Incremental cost per LYG between periods was US$ 14 587. For AIDS patients, mean IP days decreased from 13.3 to 4.4 PPY between periods; OP visits increased from 8.3 to 9.2 PPY. Total costs increased from US$ 9099 to US$ 11 754 PPY, while expenditure on antiretroviral drugs increased from 29 to 72% of total cost. Median progression time was 3.8 years in the pre-HAART period, which increased to 13.3 years in the HAART period (log rank chi = 158, P < 0.0001); incremental cost per LYG between periods was US$ 12 813.

CONCLUSIONS

HAART appeared a cost-effective intervention in Canada.

Cardiac tissue engineering (TE) is one of the most promising strategies to reconstruct infarct myocardium and the major challenge is to generate a bioactive substrate with suitable chemical, biological, and conductive properties, thus mimicking the extracellular matrix (ECM) both structurally and functionally. In this study, polypyrrole/poly(ε-caprolactone)/gelatin nanofibrous scaffolds were electrospun by incorporating different concentrations of polypyrrole (PPy) to PCL/gelatin (PG) solution. Morphological, chemical, mechanical, and biodegradation properties of the electrospun nanofibers were evaluated. Our data indicated that by increasing the concentration of PPy (0-30%) in the composite, the average fiber diameters reduced from 239 ± 37 nm to 191 ± 45 nm, and the tensile modulus increased from 7.9 ± 1.6 MPa to 50.3 ± 3.3 MPa. Conductive nanofibers containing 15% PPy (PPG15) exhibited the most balanced properties of conductivity, mechanical properties, and biodegradability, matching the requirements for regeneration of cardiac tissue. The cell proliferation assay, SEM, and immunostaining analysis showed that the PPG15 scaffold promote cell attachment, proliferation, interaction, and expression of cardiac-specific proteins better than PPG30. Electrospun PPG15 conductive nanofibrous scaffold could be desirable and promising substrates suitable for the regeneration of infarct myocardium and cardiac defects.

Thyroid cancer is one of the most common endocrine malignancies. Multiple evidences revealed that a large number of microRNAs and mRNAs were abnormally expressed in thyroid cancer tissues. These microRNAs and mRNAs play important roles in tumorigenesis. In the present study, we identified 72 microRNAs and 1,766 mRNAs differentially expressed between thyroid cancer tissues and normal thyroid tissues and evaluated their prognostic values using Kaplan-Meier survival curves by log-rank test. Seven microRNAs (miR-146b, miR-184, miR-767, miR-6730, miR-6860, miR-196a-2 and miR-509-3) were associated with the overall survival. Among them, three microRNAs were linked with six differentially expressed mRNAs (miR-767 was predicted to target COL10A1, PLAG1 and PPP1R1C; miR-146b was predicted to target MMP16; miR-196a-2 was predicted to target SYT9). To identify the key genes in the protein-protein interaction network , we screened out the top 10 hub genes (NPY, NMU, KNG1, LPAR5, CCR3, SST, PPY, GABBR2, ADCY8 and SAA1) with higher degrees. Only LPAR5 was associated with the overall survival. Multivariate analysis demonstrated that miR-184, miR-146b, miR-509-3 and LPAR5 were an independent risk factors for prognosis. Our results of the present study identified a series of prognostic microRNAs and mRNAs that have the potential to be the targets for treatment of thyroid cancer.

Graphene-based field-effect transistors (FETs) have been developed rapidly and are currently considered as an alternative for postsilicon electronics. In this study, polypyrrole-converted nitrogen-doped few-layer graphene (PPy-NDFLG) was grown on Cu substrate by chemical vapor deposition combined with vapor deposition polymerization and then transferred onto a flexible substrate. Furthermore, antivascular endothelial growth factor (VEGF) RNA aptamer conjugated PPy-NDFLG was integrated into a liquid-ion gated FET geometry to fabricate a high-performance VEGF aptamer-based sensor. Field-induced high sensitivity was observed for the analyte-binding events, eventually leading to the recognition of the target molecules at an unprecedentedly low concentration (100 fM). Additionally, the aptasensor had excellent reusability, mechanical bendability, and durability in the flexible process. The developed methodology describes, for the first time, the fabrication of N-doped graphene using conducting polymers including heteroatoms in their structures as the carbonization precursor and demonstrates its use in a high-performance, flexible FET-type aptasensor to detect vascular endothelial growth factor as a cancer biomarker.

Previously, a single-stranded (ss) DNA element, polypyrimidine (PPy) element, was found to be important for the proximal promoter activity of mouse micro-opioid receptor (MOR) gene in a neuronal cell model. In this study, we identified the presence of unknown ssDNA binding proteins specifically bound to MOR ssPPy element in the mouse brain, implicating the physiological significance of these proteins. To identify the ssDNA binding proteins, yeast one-hybrid system with PPy element as the bait was used to screen a mouse brain cDNA library. The clone encoding poly C binding protein (PCBP) was obtained. Its full-length cDNA sequence and protein with molecular weight approximately 38 kDa were confirmed. Electrophoretic mobility shift analysis (EMSA) revealed that PCBP bound to ssPPy element, but not doubled-stranded, in a sequence-specific manner. EMSA with anti-PCBP antibody demonstrated the involvement of PCBP in MOR ssPPy/proteins complexes of mouse brain and MOR expressing neuroblastoma NMB cells. Functional analysis showed that PCBP trans-activated MOR promoter as well as a heterologous promoter containing MOR PPy element. Importantly, ectopic expression of PCBP in NMB cells up-regulated the expression level of endogenous MOR gene in vivo in a dose-dependent manner. Collectively, above results suggest that PCBP participates in neuronal MOR gene expression.

Polypyrrole nanoparticles (PPy NPs) exhibit strong absorption in the near infrared (NIR) region. With an excellent photothermal efficiency of ~45% at 808 nm, sub-100 nm PPy NPs are demonstrated to be a promising photothermal agent for in vivo cancer therapy using NIR irradiation.

The photophysical properties for a series of facial (fac) cyclometalated Ir(III) complexes (fac-Ir(C--N)(3) (C--N = 2-phenylpyridyl (ppy), 2-(4,6-difluorophenyl)pyridyl (F2ppy), 1-phenylpyrazolyl (ppz), 1-(2,4-difluorophenyl)pyrazolyl) (F2ppz), and 1-(2-(9,9'-dimethylfluorenyl))pyrazolyl (flz)), fac-Ir(C--N)(2)(C--N') (C--N = ppz or F2ppz and C--N' = ppy or F2ppy), and fac-Ir(C--C')(3) (C--C' = 1-phenyl-3-methylbenzimidazolyl (pmb)) have been studied in dilute 2-methyltetrahydrofuran (2-MeTHF) solution in a temperature range of 77-378 K. Photoluminescent quantum yields (Phi) for the 10 compounds at room temperature vary between near zero and unity, whereas all emit with high efficiency at low temperature (77 K). The quantum yield for fac-Ir(ppy)(3) (Phi = 0.97) is temperature-independent. For the other complexes, the temperature-dependent data indicates that the luminescent efficiency is primarily determined by thermal deactivation to a nonradiative state. Activation energies and rate constants for both radiative and nonradiative processes were obtained using a Boltzmann analysis of the temperature-dependent luminescent decay data. Activation energies to the nonradiative state are found to range between 1600 and 4800 cm(-1). The pre-exponential factors for deactivation are large for complexes with C--N ligands (10(11)-10(13) s(-1)) and significantly smaller for fac-Ir(pmb)(3) (10(9) s(-1)). The kinetic parameters for decay and results from density functional theory (DFT) calculations of the triplet state are consistent with a nonradiative process involving Ir-N (Ir-C for fac-Ir(pmb)(3)) bond rupture leading to a five-coordinate species that has triplet metal-centered ((3)MC) character. Linear correlations are observed between the activation energy and the energy difference calculated for the emissive and (3)MC states. The energy level for the (3)MC state is estimated to lie between 21,700 and 24,000 cm(-1) for the fac-Ir(C--N)(3) complexes and at 28,000 cm(-1) for fac-Ir(pmb)(3).

Seven genes and two anonymous markers were mapped to a single linkage group on rat chromosome 10 using progeny of an F2 intercross of Fischer (F344/N) and Lewis (LEW/N) inbred rats. Two genes, the neu oncogene or cellular homologue of the viral oncogene erbb2 (ERBB2) and growth hormone (GH) were mapped by Southern blot analysis of restriction fragment length polymorphisms. Five genes, embryonic skeletal myosin heavy chain (MYH3), androgen binding protein/sex hormone binding globulin (SHBG), asialoglycoprotein receptor (hepatic lectin)-1 (ASGR1), ATP citrate lysase (CLATP), and pancreatic polypeptide (PPY), and two anonymous markers, F16F2 and F10F1, were mapped using PCR amplification techniques. The PCR-typable polymorphic markers for the five genes were also highly polymorphic in 10 other inbred rat strains (SHR/N, WKY/N, MNR/N, MR/N, LOU/MN, BN/SsN, BUF/N, WBB1/N, WBB2/N, and ACI/N). These markers should be useful in genetic analysis of traits described in inbred rat strains, as well as in genetic monitoring of such strains. The loci in this linkage group covered 50 cM of rat chromosome 10 with the following order: MYH3, SHBG/ASGR1 (no recombinants detected), F16F2, ERBB2, CLATP, PPY, GH, and F10F1. Comparative gene mapping analysis indicated that this region of rat chromosome 10 exhibits linkage conservation with regions of human chromosome 17 and mouse chromosome 11.

A series of novel carbazole compounds was synthesized and tested for their suitability as host for triplet emitters in an organic-light emitting diode (OLED). In these compounds, a carbazole unit is either connected to other carbazole units to form carbazole dimers and trimers or to fluorene and oxadiazole derivatives to form mixed compounds. The HOMO level of carbazole compounds can be tuned by substitution at the 3, 6, and/or 9 positions. Making oligomers by connecting carbazole molecules via their 3 (3') positions shifts the HOMO level to higher energy, while replacing alkyl groups at the 9 (9') positions by aryl groups shifts the HOMO level to lower energy. Furthermore, it has been found that the triplet energy of these compounds is determined by the presence of poly(p-phenyl) chains in the molecular structure. By identifying the longest poly(p-phenyl) chain, one can predict whether a compound will be a suitable host for a high-energy triplet emitter. An overview of HOMO levels, singlet and triplet levels, and exchange energies is given for all carbazole compounds synthesized. Finally, OLEDs employing two selected carbazole compounds as host and fac-tris(2-phenylpyridine)-iridium (Ir(ppy)(3)) as guest were constructed and characterized electrically.

Electroactive polymers such as polypyrrole (PPy) are highly attractive for a number of biomedical applications, including their use as coatings for electrodes or neural probes and as scaffolds to induce tissue regeneration. Surface modification of these materials with biological moieties is desired to enhance the biomaterial-tissue interface and to promote desired tissue responses. Here, we present the synthesis and physicochemical characterization of poly(1-(2-carboxyethyl)pyrrole) (PPyCOOH), a PPy derivative that contains a chemical group that can be easily modified with biological moieties at the N-position of the polymer backbone. FTIR, XPS, and fluorescence microscopy were used to demonstrate the successful incorporation of carboxylic acid (-COOH) functionality into PPy materials, and a four-point probe analysis was used to demonstrate electrical conductivity in the semiconductor range. Human umbilical vascular endothelial cells (HUVECs) cultured on PPyCOOH films surface-modified with the cell-adhesive Arg-Gly-Asp (RGD) motif demonstrated improved attachment and spreading. Thus, PPyCOOH could be useful in developing PPy composites that contain a variety of biological molecules as bioactive conducting platforms for specific biomedical purposes.

Electrically conductive polypyrrole is very attractive for tissue engineering because of its potential to modulate cellular activities through electrical stimulation. However, its in vivo behaviors have not been fully studied. This paper investigates the in vivo biocompatibility and biostability of PPy-coated polyester fabrics. Three PPy-coated fabrics were prepared using phosphonylation (PPy-Phos), plasma activation (PPy-Plas), and plasma activation plus heparin treatment (PPy-Plas-HE). Virgin and fluoropassivated fabrics (F-PET) were controls. The specimens were implanted subcutaneously in the back of rats for 3-90 days, then harvested and processed for enzymatic, histological, and morphological analyses. A noninvasive MRI method was used to continuously monitor the inflammation. The level of acid and alkaline phosphatase showed a similar or a less intensive cellular reaction by the PPy-coated fabrics, when compared to the controls. Histology supported the enzymatic results and showed a fast collagen infiltration at 28 days for the PPy-Phos fabric. MRI reported an overall decrease of inflammation over time, with the PPy-coated fabrics showing a similar or mild inflammation in contrast to the non-coated fabrics. PPy clusters and excessive PPy laminary coating on the PPy-Plas and PPy-Plas-HE were lost with the implantation. This experiment suggests a similar in vivo biocompatibility of the PPy-coated and noncoated polyester fabrics and the importance of achieving a thin, uniform PPy coating.

Up to today, several techniques have been used to maintain cells in culture for studying many aspects of cell biology and physiology. More often, cell culture is dependent on proper anchorage of cells to the growth surface. Poly-l-lysine is commonly used as adhesive molecule. In this study, we present, as an alternative to poly-l-lysine, new polymer film substrates, realized by electropolymerization of different monomers on fluorine-doped tin oxide (FTO) surfaces since electropolymerization is a good method to coat selectively metallic or semiconducting electrodes with polymer films. So, the adhesion, proliferation and morphology of rat neuronal cell lines were investigated on polymer treated surfaces. Several amine-based biocompatible polymers were tested: polyethyleneimine (PEI), polypropyleneimine (PPI), polypyrrole (PPy) and poly(p-phenylenediamine) (PPPD). These polymer films were coated on FTO surfaces by electrochemical oxidation. After 8 h in a culture medium, a high percentage of cells was found to be attached to PEI and PPI compared to the other polymers and to the reference surfaces (glass and FTO uncovered). After 24 and 72 h in the culture medium, cells were found to proliferate faster on PEI and PPI than on other polymers and reference surfaces. Consequently, cells have a greater fold expansion on PEI and PPI than on PPPD, PPy or glass and FTO uncoated. From these results, we deduce that PEI and PPI can be useful as coating surface to cultivate neuronal cells.

Fe(3)O(4) coated polypyrrole (PPy) magnetic nanocomposite was prepared via in situ polymerization of pyrrole monomer for the removal of highly toxic Cr(VI). Structure and morphology of the prepared nanocomposite were characterized by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction pattern, Field emission scanning electron microscopy (FE-SEM) and high resolution transmission electron microscopy (HR-TEM). Electron spin resonance (ESR) studies confirmed that the nanocomposite is magnetic in nature. Up to 100% adsorption was found with 200mg/L Cr(VI) aqueous solution at pH 2. Adsorption of Cr(VI) on the surface of the adsorbent was confirmed by the ATR-FTIR and X-ray photoelectron spectroscopy (XPS). XPS studies also suggested that ion exchange and reduction on the surface of the nanocomposite may be the possible mechanism for Cr(VI) removal by the PPy/Fe(3)O(4) nanocomposite. Adsorption results showed that Cr(VI) removal efficiency by the nanocomposite decreased with an increase in pH. Adsorption kinetics was best described by the pseudo-second-order rate model. Isotherm data fitted well to the Langmuir isotherm model. Thermodynamic study revealed that the adsorption process is endothermic and spontaneous in nature. Desorption experiment showed that in spite of the very poor recovery of the adsorbed Cr(VI); the regenerated adsorbent can be reused successfully for two successive adsorption-desorption cycles without appreciable loss of its original capacity.

The first method for the kinetic resolution of indolines through catalytic N-acylation is described. To improve the selectivity factor, new planar-chiral PPY-derived catalysts were synthesized, wherein the chiral environment was systematically modified. This work provides a rare example of a nonenzyme-based acylation catalyst for the kinetic resolution of amines.

Engineered scaffolds simultaneously exhibiting multiple cues are highly desirable for neural tissue regeneration. To this end, we developed a neural tissue engineering scaffold that displays submicrometer-scale features, electrical conductivity, and neurotrophic activity. Specifically, electrospun poly(lactic acid-co-glycolic acid) (PLGA) nanofibers were layered with a nanometer thick coating of electrically conducting polypyrrole (PPy) presenting carboxylic groups. Then, nerve growth factor (NGF) was chemically immobilized onto the surface of the fibers. These NGF-immobilized PPy-coated PLGA (NGF-PPyPLGA) fibers supported PC12 neurite formation ( 28.0±3.0% of the cells) and neurite outgrowth (14.2 μm median length), which were comparable to that observed with NGF (50 ng/mL) in culture medium ( 29.0±1.3%, 14.4 μm). Electrical stimulation of PC12 cells on NGF-immobilized PPyPLGA fiber scaffolds was found to further improve neurite development and neurite length by 18% and 17%, respectively, compared to unstimulated cells on the NGF-immobilized fibers. Hence, submicrometer-scale fibrous scaffolds that incorporate neurotrophic and electroconducting activities may serve as promising neural tissue engineering scaffolds such as nerve guidance conduits.

In this study the synergistic effect of delivering two neurotrophins simultaneously to encourage neuron survival and neurite elongation was explored. Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) were incorporated into polypyrrole (PPy) during electrosynthesis and the amounts incorporated and released were determined using iodine-125 ((125)I) radio-labelled neurotrophins. Neurite outgrowth from cochlear neural explants grown on the conducting polymer was equivalent to that on tissue culture plastic but significantly improved with the incorporation of NT-3 and BDNF. Neurite outgrowth from explants grown on polymers containing both NT-3 and BDNF showed significant improvement over PPy doped only with NT-3, due to the synergistic effect of both neurotrophins. Neurite outgrowth was significantly improved when the polymer containing both neurotrophins was electrically stimulated. It is envisaged that when applied to the cochlear implant, these conducting and novel polymer films will provide a biocompatible substrate for storage and release of neurotrophins to help protect auditory neurons from degradation after sensorineural hearing loss and encourage neurite outgrowth towards the electrodes.

The mechanical and electrical properties of polycaprolactone fumarate-polypyrrole (PCLF-PPy) scaffolds were studied under physiological conditions to evaluate their ability to maintain the material properties necessary for application as conductive nerve conduits. PC12 cells cultured on PCLF-PPy scaffolds were stimulated with regimens of 10 μA of either a constant or a 20 Hz frequency current passed through the scaffolds for 1h per day. PC12 cellular morphologies were analyzed by fluorescence microscopy after 48 h. PCLF-PPy scaffolds exhibited excellent mechanical properties at 37 °C which would allow suturing and flexibility. The surface resistivity of the scaffolds was 2 kΩ and the scaffolds were electrically stable during the application of electrical stimulation (ES). In vitro studies showed significant increases in the percentage of neurite bearing cells, number of neurites per cell and neurite length in the presence of ES compared with no ES. Additionally, extending neurites were observed to align in the direction of the applied current. This study shows that electrically conductive PCLF-PPy scaffolds possess the material properties necessary for application as nerve conduits. Additionally, the capability to significantly enhance and direct neurite extension by passing an electrical current through PCLF-PPy scaffolds renders them even more promising as future therapeutic treatments for severe nerve injuries.

Ordered conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) was electrochemically fabricated using a self-assembled medium of surfactant molecules as a template. The morphology and microstructure were extensively investigated by optical and electron microscopy, and results show that the coated films were composed of anisotropic domains having a characteristic size of 15-150 nm. The surfactant-templated ordered PEDOT films were electrochemically deposited on microfabricated neural probes with an electrode site area of 1,256 microm(2). The electrical properties were studied by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). EIS showed a lowered magnitude of 35 kOmega (from an initial approximately 800 kOmega) at the biologically relevant frequency of 1 kHz. CV results show that the film has higher charge capacity and is more electrochemically stable than either nodular PEDOT or PPy. Furthermore, we have begun to probe the biological response to such a material intended to define the tissue-material interface. Results show that minute concentrations of the non-ionic surfactant are enough to kill all nearby cells in culture. It is possible however, to create surfactant-templated ordered PEDOT such that SH-SY5Y survive on the conductive polymer.

The cellular behavior and toxicity effect of organometallic complexes depend largely on their peripheral ligands. In this study, we have synthesized a series of novel luminescent cationic iridium(III) complexes by tuning the ancillary N(∧)N ligand based on a structure [Ir(ppy)2(N(∧)N)](+) (ppy = 1-phenyl-pyridine; N(∧)N = 2,2'-bipyridine (bpy, 1) or phenanthroline (phen, 2) or 4,7-diphenyl-1,10- phenanthroline (DIP, 3)). As the size of coordinated N(∧)N ligand increases, absorbance/emission efficiency, quantum yields, lipophilicity, and cell uptake rates of the complexes also increase, in a general order: 3>> 2>> 1. All three complexes display anticancer activity, with 3 exhibiting the highest cellular uptake efficiency and the greatest cytotoxic activities in several cancer cell lines with IC50s lower than that of cisplatin. Because of its strong hydrophobic nature, the death inducer 3 was found to accumulate favorably to endoplasmic reticulum (ER) and to cause ER stress in cells. The fast cytosolic release of calcium from stressed ER disturbed the morphology and function of mitochondria, initiating an intrinsic apoptotic pathway. Understanding of the cell death mechanism would help further structure-activity optimization on these novel Ir(III) complexes as emerging cancer therapeutics.

Conjugated polymers with strong absorbance in the near-infrared (NIR) region have been widely explored as photothermal therapy agents due to their excellent photostability and high photothermal conversion efficiency. Herein, polypyrrole (PPy) nanoparticles are fabricated by using bovine serum albumin (BSA) as the stabilizing agent, which if preconjugated with photosensitizer chlorin e6 (Ce6) could offer additional functionalities in both imaging and therapy. The obtained PPy@BSA-Ce6 nanoparticles exhibit little dark toxicity to cells, and are able to trigger both photodynamic therapy (PDT) and photothermal therapy (PTT). As a fluorescent molecule that in the meantime could form chelate complex with Gd(3+), Ce6 in PPy@BSA-Ce6 nanoparticles after being labeled with Gd(3+) enables dual-modal fluorescence and magnetic resonance (MR) imaging, which illustrate strong tumor uptake of those nanoparticles after intravenous injection into tumor-bearing mice. In vivo combined PDT and PTT treatment is then carried out after systemic administration of PPy@BSA-Ce6, achieving a remarkably improved synergistic therapeutic effect compared to PDT or PTT alone. Hence, a rather simple one-step approach to fabricate multifunctional nanoparticles based on conjugated polymers, which appear to be promising in cancer imaging and combination therapy, is presented.

Photoacoustic imaging has emerged as a highly promising tool to visualize molecular events with deep tissue penetration. Like most other modalities, however, image contrast under in vivo conditions is far from optimal due to background signals from tissue. Using iron oxide-gold core-shell nanoparticles, we have previously demonstrated the concept of magnetomotive photoacoustic (mmPA) imaging, which is capable of dramatically reducing the influence of background signals and producing high-contrast molecular images. Here, we report two significant advances toward clinical translation of this technology. First, we introduce a new class of compact, uniform, magneto-optically coupled core-shell nanoparticles, prepared through localized copolymerization of polypyrrole (PPy) on an iron oxide nanoparticle surface. The resulting iron oxide-PPy nanoparticles feature high colloidal stability and solve the photoinstability and small-scale synthesis problems previously encountered by the gold coating approach. In parallel, we have developed a new generation of mmPA featuring cyclic magnetic motion and ultrasound speckle tracking (USST), whose imaging capture frame rate is several hundred times faster than the photoacoustic speckle tracking (PAST) method we demonstrated previously. These advances enable robust artifact elimination caused by physiologic motions and demonstrate the application of the mmPA technology for in vivo sensitive tumor imaging.

Electrical stimulation (ES) has long been used as an alternative clinical treatment and an effective approach to modulate cellular behaviours. In this work we investigated the effects of ES on human skin fibroblast activity, myofibroblast transdifferentiation and the consequence on wound healing. Normal human fibroblasts were seeded on heparin-bioactivated PPy/PLLA conductive membranes, cultured for 24 h, and then exposed to ES of 50 or 200 mV/mm for 2, 4, or 6 h. Following ES, the cells were either subjected to various analyses or re-seeded to investigate their healing capacity. Our findings show that ES had no cytotoxic effect on the fibroblasts, as demonstrated by the similar LDH activity levels in the ES-exposed and non-exposed cultures, and by the comparable cell viability under both conditions. Furthermore, the number of viable fibroblasts was higher following exposure to 6 h of ES than in the non-exposed culture. This enhanced cell growth was likely due to the ES up-regulated secretion of FGF-1 and FGF-2. In an in vitro scratch-wound assay where cell monolayer was used as a healing model, the electrically stimulated dermal fibroblasts migrated faster following exposure to ES and recorded a high contractile behaviour toward the collagen gel matrix. This enhanced contraction was supported by the high level of α-smooth muscle actin expressed by the fibroblasts following exposure to ES, indicating the characteristics of myofibroblasts. Remarkably, the modulation of fibroblast growth continued long after ES. In conclusion, this work demonstrates for the first time that exposure to ES promoted skin fibroblast growth and migration, increased growth factor secretion, and promoted fibroblast to myofibroblast transdifferentiation, thus promoting wound healing.

The solar-driven reduction of carbon dioxide to value-added chemical fuels is a longstanding challenge in the fields of catalysis, energy science, and green chemistry. In order to develop effective CO2 fixation, several key considerations must be balanced, including (1) catalyst selectivity for promoting CO2 reduction over competing hydrogen generation from proton reduction, (2) visible-light harvesting that matches the solar spectrum, and (3) the use of cheap and earth-abundant catalytic components. In this report, we present the synthesis and characterization of a new family of earth-abundant nickel complexes supported by N-heterocyclic carbene-amine ligands that exhibit high selectivity and activity for the electrocatalytic and photocatalytic conversion of CO2 to CO. Systematic changes in the carbene and amine donors of the ligand have been surveyed, and [Ni((Pr)bimiq1)](2+) (1c, where (Pr)bimiq1 = bis(3-(imidazolyl)isoquinolinyl)propane) emerges as a catalyst for electrochemical reduction of CO2 with the lowest cathodic onset potential (E(cat) = -1.2 V vs SCE). Using this earth-abundant catalyst with Ir(ppy)3 (where ppy = 2-phenylpyridine) and an electron donor, we have developed a visible-light photoredox system for the catalytic conversion of CO2 to CO that proceeds with high selectivity and activity and achieves turnover numbers and turnover frequencies reaching 98,000 and 3.9 s(-1), respectively. Further studies reveal that the overall efficiency of this solar-to-fuel cycle may be limited by the formation of the active Ni catalyst and/or the chemical reduction of CO2 to CO at the reduced nickel center and provide a starting point for improved photoredox systems for sustainable carbon-neutral energy conversion.

We report on the fabrication of electrically responsive nanoporous membrane based on polypyrrole doped with dodecylbenzenesulfonate anion (PPy/DBS) that was electropolymerized on the upper part of anodized aluminum oxide membrane. The membrane has regular pore size and very high pore density. Utilizing a large volume change of PPy/DBS depending on electrochemical state, the pore size was acutated electrically. The actuation of the pores was experimentally confirmed by in situ atomic force microscopy and in situ flux measurement. We also demonstrated successfully pulsatile (or on-demand) drug release by using fluorescently labeled protein as a model drug. Because of a fast switching time (less than 10 s) and high flux of the drugs, this membrane could be used for emergency therapy of angina pectoris and migraine, which requires acute and on-demand drug delivery, and hormone-related disease and metabolic syndrome.