Post-stroke angiogenesis facilitates neurovascular remodeling process and promotes neurological recovery. Proangiogenic effects of Salvianolic acids (Sals) have been reported in various ischemic disorders. However, the underlying mechanisms are still poorly understood. Previous studies of our laboratory have demonstrated that activating Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is involved in the protection against cerebral ischemia/reperfusion injury. In this study, we investigated the impacts of Sals on angiogenesis and long-term neurological recovery after ischemic stroke as well as the potential mechanisms. Male mice subjected to permanent distal middle cerebral artery occlusion were administrated with Sals, 5-bromo-2'-deoxyuridine, and JAK2 inhibitor AG490 once daily from day 1 to day 14 after distal middle cerebral artery occlusion. Compared with the control group, Sals treatment significantly improved neurological recovery at day 14 and 28 after ischemic stroke. Sals enhanced post-stroke angiogenesis, pericytes and astrocytic endfeet covered ratio in the peri-infarct area. The JAK2/STAT3 signaling pathway was activated by Sals in the angiogenesis process, and inhibition of JAK2/STAT3 signaling blocked the effects of Sals on post-stroke angiogenesis and neurological recovery as well as abolished the mediation of proangiogenic factors. In summary, these data suggest that Sals administration enhances cerebral angiogenesis and promotes neurological recovery after ischemic stroke, mediated by the activation of JAK2/STAT3 signaling pathway.

Left bundle branch block (LBBB) creates considerable regional differences in mechanical load within the left ventricle (LV). We investigated expression of selected microRNAs (miRs) in relation to regional hypertrophy and fibrosis in LBBB hearts and their reversibility upon cardiac resynchronization therapy (CRT).

Hypercholesterolemia confers susceptibility to cardiovascular disease (CVD). Both serum total cholesterol (TC) and LDL-cholesterol (LDL-C) exhibit a strong genetic component (heritability estimates 0.41-0.50). However, a large part of this heritability cannot be explained by the variants identified in recent extensive genome-wide association studies (GWAS) on lipids. Our aim was to find genetic causes leading to high LDL-C levels and ultimately CVD in a large Austrian family presenting with what appears to be autosomal dominant inheritance for familial hypercholesterolemia (FH).

The present study aimed to explore the underlying mechanisms of epicatechin-3-gallate-(4β→8, 2β→O→7)-epicatechin-3-gallate (A-type ECG dimer) and epigallocatechin-3-gallate-(4β→8, 2β→O→7)-epigallocatechin-3-gallate (A-type EGCG dimer) involved in their strong inhibitory effects on 3T3-L1 preadipocytes differentiation. In the synthetic "lipid raft-like" liposome, A-type ECG and EGCG dimers incorporated into the liposome with high affinity and decreased the fluidity of the liposome. In 3T3-L1 preadipocytes, A-type ECG and EGCG dimers possibly bonded to lipid rafts cholesterol and disrupted the integrity of lipid rafts, thus exerting their notable inhibitory effects on 3T3-L1 preadipocytes differentiation by suppressing mitotic clonal expansion process and mRNA levels of PPARγ, C/EBPα and SREBP1C. A highly positive correlation between the cholesterol binding capacity of the two dimers and their inhibitory effect on 3T3-L1 preadipocytes differentiation (R2=0.9328) was observed. Molecular dynamics simulation further verified that A-type ECG and EGCG dimers could bond to cholesterol via hydrogen bonding. The results of this study suggested that the disruption of A-type ECG and EGCG dimers on membrane lipid rafts by targeting cholesterol in the lipid rafts was involved in the underlying mechanisms of their strong inhibitory effects on 3T3-L1 preadipocytes differentiation. This broadens the understanding of the molecular mechanisms of polyphenols on modulating and controlling of metabolic dysregulation, particularly adipocyte differentiation, which is a significant risk factor associated with the development of cardiovascular disease.

Antibiotics are increasingly detected in groundwater, but little is known about their presence in deep underground sediments. In this study, underground sediment samples were collected from pig farms, chicken houses, fishponds and riverbanks in a small region of the Jianghan Plain. Sixteen antibiotics were detected in different layers of sediments in various animal-breeding areas, with the riverbank containing the most pollution, followed by the fishpond, then the pig farm and the least being the chicken house. Samples taken from different sections of the collection sites and tested for each antibiotic compound revealed significant pollution, with the riverbank containing the most pollution, followed by the fishpond, then the pig farm and the least being the chicken house. The concentrations of the targets did not decrease with depth, but increased between 0.6 m and 1.0 m, which was a significant fluctuation. The aquifer sediment analysis indicated that the greatest antibiotic retention was within 8 m, with a small increase between 12 and 16 m, consistent with the depth of sandy aquifer layers. None of the compounds were detected in the deep layer at 20 m but for sulfadiazine and chlorotetracycline. Tetracyclines and Fluoroquinolones were the two groups observed at higher concentrations in most sediment layers, although their residual levels no more than 20 ng g-1. This study revealed that antibiotics generally exist in the underground environment, along with groundwater migration and particle adsorption. The pollution of antibiotics in alluvial sediments is an immense challenge to groundwater remediation, and its environmental effects should be studied.

Antigen-specific treatments are highly desirable for autoimmune diseases in contrast to treatments which induce systemic immunosuppression. A novel antigen-specific therapy has been developed which, when administered semi-therapeutically, is highly efficacious in the treatment of the mouse model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). The treatment uses dual-sized, polymeric microparticles (dMPs) loaded with specific antigen and tolerizing factors for intra- and extra-cellular delivery, designed to recruit and modulate dendritic cells toward a tolerogenic phenotype without systemic release. This approach demonstrated robust efficacy and provided complete protection against disease. Therapeutic efficacy required encapsulation of the factors in controlled-release microparticles and was antigen-specific. Disease blocking was associated with a reduction of infiltrating CD4+ T cells, inflammatory cytokine-producing pathogenic CD4+ T cells, and activated macrophages and microglia in the central nervous system. Furthermore, CD4+ T cells isolated from dMP-treated mice were anergic in response to disease-specific, antigen-loaded splenocytes. Additionally, the frequency of CD86hiMHCIIhi dendritic cells in draining lymph nodes of EAE mice treated with Ag-specific dMPs was reduced. Our findings highlight the efficacy of microparticle-based drug delivery platform to mediate antigen-specific tolerance, and suggest that such a multi-factor combinatorial approach can act to block autoimmunity.

The aberrant activation of Wnt/β-catenin signaling is involved in the development of multiple myeloma; thus, this signaling pathway is a potential target for the development of therapeutics for this malignancy. Here, we performed cell-based chemical screening and found that CGK012, a pyranocoumarin compound, suppressed the Wnt3a-CM-mediated activation of β-catenin response transcription. CGK012 induced β-catenin phosphorylation at Ser33/Ser37/Thr41, leading to proteasomal degradation and reducing the level of intracellular β-catenin. Furthermore, CGK012 consistently decreased the amount of β-catenin and repressed the expression of cyclin D1, c-myc, and axin-2 (downstream target genes of β-catenin) in RPMI-8226 multiple myeloma cells. In addition, CGK012 inhibited the proliferation of RPMI-8226 cells and promoted apoptosis, as indicated by the increase in the population of Annexin V-FITC-stained cells and caspase-3/7 activity. These findings suggest that CGK012 could exert antiproliferative activity against multiple myeloma cells by attenuating the Wnt/β-catenin pathway; thus, it may have potential as a therapeutic agent for multiple myeloma treatment.

This study was conducted to identify the brain regions corresponding to mechanical noxious stimulation in cats using functional magnetic resonance imaging (fMRI) and to investigate the modulatory effect of remifentanil on the activation of these regions. Six healthy cats were anesthetized using a constant-rate infusion of alfaxalone. Cats were allocated to one of three treatment groups: remifentanil 0 (saline), 0.25, and 0.5μg/kg/min. A 3.0-T MRI unit was used to collect fMRI data. During the fMRI scanning, mechanical noxious stimulation was applied by tail clamping. The brain regions activated by the stimulation were identified based on blood oxygenation level-dependent (BOLD) responses. The modulatory effects of remifentanil were evaluated using a region of interest (ROI) analysis comparing signal changes in each brain region. Increased activity from noxious stimulation was observed in the somatosensory area (the postcruciatus gyrus, the anterior part of the marginalis gyrus, and the anterior part of the ectomarginalis gyrus), the parietal association area (the middle part of the marginalis gyrus and the middle part of the ectomarginalis gyrus), the cingulate cortex, the hippocampus, and the cerebellum. The results of the ROI analysis indicated that activations in the somatosensory area, the cingulate cortex, the hippocampus, and the cerebellum were significantly modulated (P<0.05) by remifentanil. In cats, activation patterns evoked by mechanical noxious stimulation were observed in several brain regions thought to be involved in various aspects of pain processing, including sensory discrimination and integration, affect, and motor response. These brain responses were modulated by remifentanil.

Matrix metalloproteinase-8 (MMP-8) has oncosuppressive properties in various cancers. We attempted to assess MMP-8 function in oral tongue squamous cell carcinoma (OTSCC).

Glass-ionomer-cement (GIC) is helpful in Minimal Intervention Dentistry because it releases fluoride ions and is highly biocompatible. The aim of this study is to investigate the mechanisms by which hydroxyapatite (HAp) improves the mechanical strength and bioactive functioning of GIC when these materials are combined to make apatite ionomer cement (AIC). A conventional GIC powder was mixed with porous, spherical-HAp particles (HApS), crystalline HAp (HAp200) or one of two types of cellulose. The micro-compressive strengths of the additive particles were measured, and various specimens were evaluated with regard to their compressive strengths (CS), fluoride release concentrations (fluoride electrode) and multi-element release concentrations. The AIC was found to release higher concentrations of fluoride (1.2 times) and strontium ions (1.5 times) compared to the control GIC. It was detected the more release of calcium originated from HApS than HAp200 in AIC. The CS of the AIC incorporating an optimum level of HAp was also significantly higher than that of the GIC. These results suggest that adding HAp can increase the release concentration of ions required for remineralization while maintaining the CS of the GIC. This effect does not result from a physical phenomenon, but rather from chemical reactions between the HAp and polyacrylic acid of GIC.

Both laser-arc hybrid welding and narrow gap welding have potential for the fabrication of thick sections, but their combination has been seldom studied. In this research, 40 mm thick mild steel was welded by narrow gap laser-arc hybrid welding. A weld with smooth layer transition, free of visible defects, was obtained by nine passes at a 6 mm width narrow gap. The lower part of the weld has the lowest mechanical properties because of the lowest amount of acicular ferrite, but its ultimate tensile strength and impact absorbing energy is still 49% and 60% higher than those of base metal, respectively. The microhardness deviation of all filler layers along weld thickness direction is no more than 15 HV0.2, indicating that no temper softening appeared during multiple heat cycles. The results provide an alternative technique for improving the efficiency and quality of welding thick sections.

This study evaluated epigallocatechin-3-gallate (EGCG) and epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG-3Me) modified etch-and-rinse adhesives (Single Bond 2, SB 2) for their antibacterial effect and bonding stability to dentin. EGCG-3Me was isolated and purified with column chromatography and preparative high performance liquid chromatography. EGCG and EGCG-3Me were incorporated separately into the adhesive SB 2 at concentrations of 200, 400, and 600 µg/mL. The effect of cured adhesives on the growth of Streptococcus mutans (S. mutans) was determined with scanning electron microscopy and confocal laser scanning microscopy; the biofilm of bacteria was further quantified via optical density 600 values. The inhibition of EGCG and EGCG-3Me on dentin-originated collagen proteases activities was evaluated with a proteases fluorometric assay kit. The degree of conversion (DC) of the adhesives was tested with micro-Raman spectrum. The immediate and post-thermocycling (5000 cycles) bond strength was assessed through Microtensile Bond Strength (MTBS) test. Cured EGCG/EGCG-3Me modified adhesives inhibit the growth of S. mutans in a concentration-dependent manner. The immediate MTBS of SB 2 was not compromised by EGCG/EGCG-3Me modification. EGCG/EGCG-3Me modified adhesive had higher MTBS than SB 2 after thermocycling, showing no correlation with concentration. The DC of the adhesive system was affected depending on the concentration of EGCG/EGCG-3Me and the depth of the hybrid layer. EGCG/EGCG-3Me modified adhesives could inhibit S. mutans adhesion to dentin-resin interface, and maintain the bonding stability. The adhesive modified with 400 µg/mL EGCG-3Me showed antibacterial effect and enhanced bonding stability without affect the DC of adhesive.

Guided bone regeneration (GBR) is one such treatment that reconstructs neo-bone tissue by using a barrier membrane to prevent the invasion of soft tissue and to create a space for guiding new bone growth into the bone defect. Herein, we report a novel functionally graded bilayer membrane (FGBM) for GBR application. To fabricate the novel membrane, the composites of poly(lactic-co-glycolic acid) and nano-hydroxyapatite were prepared by phase inversion for the dense layer and by electrospinning for another porous layer, and their corresponding properties were evaluated including surface morphology, mechanics, degradability, cell barrier function, and in vitro osteogenic bioactivity. The results showed that PLGA with 5% nHA in dense layer could meet the requirement of mechanical strength and have excellent barrier function even on condition of post-degradation. Furthermore, PLGA with 30% nHA in porous layer could achieve the good physical and chemical properties. In addition, 30% nHA incorporation would enhance the in vitro mineralization, and have superior capabilities of cell adhesion, proliferation and differentiation compared to other groups. Therefore, the designed FGBM could potentially serve as a barrier for preferential tissue ingrowth and achieve a desirable therapeutic result for bone tissue regeneration.

Gold nanoparticles, capped by 3-mercapto propane sulfonate (Au-3MPS), were synthesized inside a swollen sulfonated poly(ether ether ketone) membrane (sPEEK). The formation of the Au-3MPS nanoparticles in the swollen sPEEK membrane was observed by spectroscopic and microscopic techniques. The nanocomposite containing the gold nanoparticles grown in the sPEEK membrane, showed the plasmon resonance λmax at about 520 nm, which remained stable over a testing period of three months. The size distribution of the nanoparticles was assessed, and the sPEEK membrane roughness, both before and after the synthesis of nanoparticles, was studied by AFM. The XPS measurements confirm Au-3MPS formation in the sPEEK membrane. Moreover, AFM experiments recorded in fluid allowed the production of images of the Au-3MPS@sPEEK composite in water at different pH levels, achieving a better understanding of the membrane behavior in a water environment; the dynamic hydration process of the Au-3MPS@sPEEK membrane was investigated. These preliminary results suggest that the newly developed nanocomposite membranes could be promising materials for fuel cell applications.

LiV₃O₈/polytriphenylamine composites are synthesized by a chemical oxidative polymerization process and applied as cathode materials for rechargeable lithium batteries (RLB). The structure, morphology, and electrochemical performances of the composites are characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, galvanostatic discharge/charge tests, and electrochemical impedance spectroscopy. It was found that the polytriphenylamine particles were composited with LiV₃O₈ nanorods which acted as a protective barrier against the side reaction of LiV₃O₈, as well as a conductive network to reduce the reaction resistance among the LiV₃O₈ particles. Among the LiV₃O₈/polytriphenylamine composites, the 17 wt % LVO/PTPAn composite showed the largest d100 spacing. The electrochemical results showed that the 17 wt % LVO/PTPAn composite maintained a discharge capacity of 271 mAh·g-1 at a current density of 60 mA·g-1, as well as maintaining 236 mAh·g-1 at 240 mA·g-1 after 50 cycles, while the bare LiV₃O₈ sample retained only 169 and 148 mAh·g-1, respectively. Electrochemical impedance spectra (EIS) results implied that the 17 wt % LVO/PTPAn composite demonstrated a decreased charge transfer resistance and increased Li⁺ ion diffusion ability, therefore manifesting better rate capability and cycling performance compared to the bare LiV₃O₈ sample.

This study was compared and characterized two different alkali (potassium carbonate (PC) and potassium acetate (PA))-catalyzed acetylations of slicewood with vinyl acetate (VA) by a vapor phase reaction. The results revealed that the esterification reaction between VA and the hydroxyl groups of slicewood could be improved by using PC or PA as a catalyst. Additionally, a significant weight percent gain was obtained after VA acetylation with 5% of catalyst. Furthermore, the reactivity of the cellulose hydroxyl groups for VA acetylation was more pronounced at the C2 reactive site compared to acetylation with acetic anhydride. On the other hand, the apparent activation energy of thermal decomposition between 10% and 70% conversion is 174-183, 194-200, and 183-186 kJ/mol for unmodified slicewood and VA-acetylated slicewood with PC and PA, respectively. Accordingly, the thermal stability of the slicewood could be effectively enhanced by VA acetylation, especially for using the PC as a catalyst.

Vacuum-induced surface freezing of colloidal alumina was used to produce membranes that have elongated, aligned channels and, hence, are tortuous in the direction perpendicular to ice crystal growth. The effective tortuosity of the membranes was measured by steady-state diffusion of a solute, methylene blue. The resulting diffusion profiles show an initial step-increase in amount of dye reaching the acceptor that is caused by capillarity drawing the donor solution through any non-wetted channels in the membrane. This is followed by a linear steady-state phase whose flux is proportional to dye concentration in the donor and inversely proportional to the colloid's volume fraction of dispersed phase. From the steady-state flux, the effective tortuosity, τ* = (α/τ)-1, was calculated. This is the reciprocal quotient of the reduced available area for diffusion within the membrane, α = A*/A, where A* is the available area and A is the cross-sectional area of the membrane, and the increased mean diffusional path length, i.e., tortuosity = L * / L , where L* is the mean path length and L is the membrane thickness. The values of τ* lie in the range of 2-38 and increase as the volume fraction of dispersed phase is larger. This latter effect indicates that τ* > 1 results, to a larger extent, from the reduced available diffusion area, α, than from the lengthened pathway, τ, in these aligned porous membranes.

The thermoelectric properties of a poly(3-hexylthiophene) (P3HT) nanofiber mat which has higher crystallinity-and thus exhibits larger carrier mobility-than a non-fibrous P3HT film, were investigated. No significant difference was observed in the maximum values of the power factor between the P3HT nanofiber mat and the P3HT film. However, the thermal conductivity of the nanofiber mat was less than half that of the film despite having almost the same electrical conductivity. This higher thermoelectric property of the nanofiber mat than the film is attributed to the existence of highly effective conducting pathways and a large void fraction, and the result means that the nanofiber mat was a good candidate for use as a thermoelectric material.

In this work, the reflectance, optical absorption, and band gap have been determined for CdTe thin films grown on planar and microstructured substrates. The treated surface was prepared by laser ablation of a silicon wafer, forming holes in a periodic arrangement. Thin films were grown by pulsed laser ablation on silicon samples kept at 200 °C inside a vacuum chamber. The presence of CdTe was verified with X-ray diffraction and Raman spectroscopy indicating a nanocrystalline zinc blended structure. The optical absorption of thin films was calculated by using the Fresnel laws and the experimental reflectance spectrum. Results show that reflectance of 245 nm films deposited on modified substrates is reduced by up to a factor of two than the obtained on unchanged silicon and the optical absorption is 16% higher at ~456 nm. Additionally, it was determined that the band gap energy for planar and microstructured films is about 1.44 eV for both cases.

Although titanium remains as the prevalent material in dental implant manufacturing new zirconia-based materials that overcome the major drawbacks of the standard 3Y-yttria partially-stabilized zirconia (Y-TZP) are now emerging. In this study, a new ceramic nanocomposite made of alumina and ceria-stabilized TZP (ZCe-A) has been used to produce dental implants with the mechanic and topographic characteristics of a pilot implant design to evaluate bone and soft tissue integration in a dog model (n = 5). Histological cross-section analysis of the implanted ceramic fixations (n = 15) showed not only perfect biocompatibility, but also a high rate of osseous integration (defined as the percentage of bone to implant contact) and soft tissue attachment. This clinical success, in combination with the superior mechanical properties achieved by this Al₂O₃/Ce-TZP nanocomposite, may place this material as an improved alternative of traditional 3Y-TZP dental implants.