Physiologically stable F127-GO supramolecular hydrogel with sustained drug release characteristic for chemotherapy and photothermal therapy

A synthetic method for preparing a Pluronic F127 (F127)-stabilized graphene (GO) supramolecular hydrogel as a safe nanovehicle for combination treatment has been studied. Doxorubicin (DOX) as a model drug is non-covalently bound on the great surface area of GO due to strong π–π interaction, hydrophobic interaction, and the strongest hydrogen bonding. In vitro drug release experiments revealed that this F127-stabilized GO supramolecular hydrogel has a sustained drug release characteristic. Furthermore, the supramolecular hydrogel showed better in vitro antitumor ability under NIR (near infrared) laser irradiation because of the excellent photothermal effect of GO. Moreover, we evaluated its antitumor ability in vivo and the results show that the hydrogel system can also markedly inhibit the growth of a tumor when administered individually, especially under laser irradiation. All these findings make the supramolecular hydrogel system promising for combination therapy with good bioavailability and minimal side effects.

The F127-GO-DOX supramolecular hydrogel system with sustained drug release characteristic for chemotherapy and photothermal therapy.     

N-Acetyl-l-leucine-polyethylenimine-mediated miR-34a delivery improves osteogenesis and bone formation in vitro and in vivo

Oral bone defects are difficult to treat. Recently, endogenous miR-34a was shown to be involved in bone anabolism. Clinical application of such microRNAs requires the inherent instability of microRNAs to be overcome by an efficient delivery system. In this study, we employed N-acetyl-l-leucine-modified polyethylenimine (N-Ac-l-Leu-PEI) as an miR-34a carrier and evaluated its delivery ability, transfection efficiency, cytotoxicity and whether it enhanced osteogenic differentiation and bone formation in vitro and in vivo. Stable N-Ac-l-Leu-PEI/miR-34a nanocomplexes were synthesized at a mass ratio of 4 and had a small size (190.34 nm), a low zeta potential (21.1 mV), a high transfection efficiency (69.39%) and no cytotoxicity in MG63 cells. N-Ac-l-Leu-PEI-mediated miR-34a delivery in vitro promoted ALP activity and expression of osteogenic differentiation markers, Runx2, SP7 and ColI to higher levels than those produced by Lipofectamine 2000-mediated delivery. N-Ac-l-Leu-PEI also achieved delivery of miR-34a in vivo to a local cranial bone defect area with miR-34a retaining the ability to initiate significant new bone formation 12 weeks post-implantation. This demonstrates the potential for N-Ac-l-Leu-PEI as a gene therapy vehicle for the regeneration of bone defects.

We employ N-acetyl-l-leucine-modified polyethylenimine as an miR-34a carrier and evaluate its delivery ability, transfection efficiency, cytotoxicity and whether it enhances osteogenic differentiation and bone formation in vitro and in vivo.     

Electrolytic extraction of dysprosium and thermodynamic evaluation of Cu–Dy intermetallic compound in eutectic LiCl–KCl

The electrochemical reduction of dysprosium(iii) was studied on W and Cu electrodes in eutectic LiCl–KCl by transient electrochemical methods. Cyclic voltammogram and current reversal chronopotentiogram results demonstrated that dysprosium(iii) was directly reduced to dysprosium (0) on the W electrode through a single-step process with the transfer of three electrons. Electrochemical measurements on the Cu electrode showed that different Cu–Dy intermetallics are formed. Moreover, the thermodynamic properties of Cu–Dy intermetallic compounds were estimated by open circuit chronopotentiometry in a temperature range of 773–863 K. Using the linear polarization method, the exchange current density (j₀) of dysprosium in eutectic LiCl–KCl on the Cu electrode was estimated, and the temperature dependence of j₀ was studied to estimate the activation energies associated with Dy(iii)/Cu₅Dy and Dy(iii)/Cu_9/2Dy couples. In addition, potentiostatic electrolysis was conducted to extract dysprosium on the Cu electrode, and five Cu–Dy intermetallic compounds, CuDy, Cu₂Dy, Cu_9/2Dy, Cu₅Dy and Cu_0.99Dy_0.01 were identified by X-ray diffraction, scanning electron microscopy and energy dispersive spectrometry. Meanwhile, the change of dysprosium(iii) concentration was monitored using inductively coupled plasma-atomic emission spectrometry, and the maximum extraction efficiency of dysprosium was found to reach 99.2%.

The electrochemical reduction of dysprosium(iii) was studied on W and Cu electrodes in eutectic LiCl–KCl by transient electrochemical methods.     

Direct automatic determination of the methanol content in red wines based on the temperature effect of the KMnO4/K2S2O5/fuchsin sodium sulfite reaction system

The standard method for methanol assay in wine is based on a methanol/KMnO₄/H₂C₂O₄/fuchsin sodium sulfite (FSS) reaction system. However, it is difficult to control the degree of colour and the temperature of the reaction product in this assay, and its repeatability is also poor due to the generation of CO and CO₂ in the reaction. Therefore, to solve these problems, potassium metabisulfite was selected to replace H₂C₂O₄, and an automatic analysis method was developed which can realize rapid and accurate determination of methanol and can be used to make an online analyzer. It was discovered that the reactions of methanol/KMnO₄ and acetaldehyde/FSS are exothermic, while the reactions of methanol/KMnO₄ and formaldehyde/FSS are endothermic. Consequently, based on the temperature effect, not only was the interference of ethanol eliminated in detecting methanol in wines, the purpose of the research was achieved to directly and accurately determine methanol without sample pretreatment. By optimizing the system, the obtained conditions for determining methanol in wines were as follows: 20 g L⁻¹ concentration for KMnO₄; 3 g L⁻¹ concentration for FSS; 40 cm length for the first reaction coil (RC₁); 100 cm length for RC₂; 700 cm (I.D.: 0.8 mm) length for RC₃; 50 °C for RC₃; about 20 °C for RC₁ and RC₂; 330 μL for the sample volume. The method showed a linear response in the range 25–1000 mg L⁻¹, with a 0.6% RSD, 8.8 mg L⁻¹ detection limit and 25 samples per h, and was successfully used for testing representative wine samples. It also obtained better accuracy than previous methods. Due to its superiority in automated operation, reproducibility, analysis speed and test cost, this method and system can serve as a supplementary standard for methanol assay, and for the quality control of the winemaking process and the final wine-product, as well as for low-alcohol drinks.

We found that methanol/KMnO₄ and acetaldehyde/FSS are exothermic, formaldehyde/FSS is endothermic, so based on the temperature effect, eliminated ethanol interference in detecting methanol in wines, also realized automatic analysis for methanol without sample pretreatment.     

3D Pd/Co core–shell nanoneedle arrays as a high-performance cathode catalyst layer for AAEMFCs

A novel cathode architecture using vertically aligned Co nanoneedle arrays as an ordered support for application in alkaline anion-exchange membrane fuel cells (AAEMFCs) has been developed. The Co nanoneedle arrays were directly grown on a stainless steel sheet via a hydrothermal reaction and then a Pd layer was deposited on the surface of the Co nanoneedle arrays using a vacuum sputter-deposition method to form Pd/Co nanoneedle arrays. After transferring the Pd/Co nanoneedle arrays to an AAEM, a cathode catalyst layer was formed. Without the use of an alkaline ionomer, the AAEMFC with the prepared cathode catalyst layer showed an enhanced performance with ultra-low Pd loading of down to 33.5 μg cm⁻², which is much higher than the conventionally used cathode electrode with a Pt loading of 100 μg cm⁻². This is the first report where three-dimensional Co nanoneedle arrays have been used as the cathode support in an AAEMFC, which is able to deliver a higher power density without an alkaline ionomer than that of conventional membrane electrode assembly (MEA).

A novel ordered Pd/Co nanoneedle array was used as a cathode in an AAEMFC and delivered a higher power density than that of conventional MEA.     

Membrane adaptation limitations in Enterococcus faecalis underlie sensitivity and the inability to develop significant resistance to conjugated oligoelectrolytes

The growing problem of antibiotic resistant bacteria, along with a dearth of new antibiotics, has redirected attention to the search for alternative antimicrobial agents. Conjugated oligoelectrolytes (COEs) are an emerging class of antimicrobial agents which insert into bacterial cell membranes and are inhibitory against a range of Gram-positive and Gram-negative bacteria. In this study, the extent of COE resistance that Enterococcus faecalis could achieve was studied. Enterococci are able to grow in hostile environments and develop resistance to membrane targeting antibiotics such as daptomycin in clinical settings. Herein we expand our knowledge of the antimicrobial mechanism of action of COEs by developing COE-resistant strains of E. faecalis OG1RF. Evolution studies yielded strains with a moderate 4–16 fold increase in antimicrobial resistance relative to the wild type. The resistant isolates accumulated agent-specific mutations associated with the liaFSR operon, which is a cell envelope-associated stress-response sensing and regulating system. The COE resistant isolates displayed significantly altered membrane fatty acid composition. Subsequent, exogenous supplementation with single fatty acids, which were chosen based on those dominating the fatty acid profiles of the mutants, increased resistance of the wild-type E. faecalis to COEs. In combination, genetic, fatty acid, and uptake studies support the hypothesis that COEs function through insertion into and disruption of membranes and that the mechanism by which this occurs is specific to the disrupting agent. These results were validated by a series of biophysical experiments showing the tendency of COEs to accumulate in and perturb adapted membrane extracts. Collectively, the data support that COEs are promising antimicrobial agents for targeting E. faecalis, and that there is a high barrier to the emergence of severely resistant strains constrained by biological limits of membrane remodeling that can occur in E. faecalis.

COEs are emerging antimicrobials to combat drug resistant infections and to which bacteria develop only limited resistance.     

Shunaoxin dropping pill,a Chinese herb compound preparation,attenuates memory impairment in d-galactose-induced aging mice

The Shunaoxin dropping pill (SNX) is derived from a traditional recipe. It has been used to treat cerebrovascular diseases in China since 2005 (approval number Z20050041). In this study, we used an in vitro H₂O₂-induced PC12 cell oxidative damage model and an in vivod-gal-induced mouse memory impairment model to investigate whether SNX had neuroprotective effects. In vitro, prior to exposure to 100 μM H₂O₂ for 2 h, PC12 cells were pre-treated with SNX 50 μg mL⁻¹ for 24 h. Hoechst 33258 staining was used to confirm the effect of SNX on apoptosis in the PC12 cells. Our results demonstrate that H₂O₂ suppresses the proliferation of PC12 cells and induces cell death. Pretreatment with SNX attenuates H₂O₂-induced apoptosis in PC12 cells. In vivo, d-gal was administered (100 mg kg⁻¹, subcutaneously (s.c.)) once daily for 8 weeks to induce memory deficit and neurotoxicity in the brain of an aging mouse. Then, SNX (320 mg kg⁻¹) was simultaneously administered orally. The present study demonstrates that SNX can alleviate aging in the mouse brain induced by d-gal via improving behavioral performance, alleviating oxidative stress, inhibiting neuroinflammation, and reducing brain cell damage in the hippocampus. Overall, these data clearly demonstrate the neuroprotective effect of SNX from the in vitro and in vivo results. SNX may be considered a novel agent for easing aging and/or age-related neurodegenerative diseases.

The Shunaoxin dropping pill (SNX) is derived from a traditional recipe.     

Large-area perovskite solar cells – a review of recent progress and issues

In recent years, perovskite solar cells (PSCs) have attracted great attention in the photovoltaic research field, because of their high-efficiency (certified 22.1%) and low-cost. In this review paper, we briefly introduce the history of efficiency development for PSCs, and discuss some of the major problems for large-area (≥1 cm²) PSC devices. In addition, we summarize the recent progress in the aspects of fabrication methods for large-area perovskite films, and improving the efficiency and stability of the large-area PSC devices. Finally, we give a short summary and outlook of large-area PSC devices. This article is mainly organized into three parts. The first part focuses on the main fabricating technologies for large-area perovskite films. The second section discusses some methods that are used to improve the efficiency of PSCs. In the last part, different approaches are used to improve the stability of PSCs.

In this review, we summarize the recent progress in the aspects of the fabrication methods for large-area perovskite films, improving the efficiency and stability of the large-area PSC devices.     

Local application of lactoferrin promotes bone regeneration in a rat critical‐sized calvarial defect model as demonstrated by micro‐CT and histological analysis

Lactoferrin is a multifunctional glycoprotein with therapeutic potential for bone tissue engineering. The aim of this study was to assess the efficacy of local application of lactoferrin on bone regeneration. Five‐millimetre critical‐sized defects were created over the right parietal bone in 64 Sprague–Dawley rats. The rats were randomized into four groups: group 1 (n  =  20) had empty defects; group 2 (n  =  20) had defects grafted with collagen gels (3 mg/ml); group 3 (n  =  20) had defects grafted with collagen gels impregnated with bovine lactoferrin (10 μg/gel); and group 4 (n  =  4) had sham surgeries (skin and periosteal incisions only). The rats were sacrificed at 4 or 12 weeks post‐operatively, and the calvaria were excised and evaluated with micro‐CT (Skyscan 1172) followed by histology. The bone volume fraction (BV/TV) was higher in lactoferrin‐treated animals at both timepoints, with groups 1, 2, 3 and 4 measuring 10.5  ±  1.1%, 8.6  ±  1.4%, 16.5  ±  0.6% and 24.27  ±  2.6%, respectively, at 4 weeks (P  <  0.05); and 12.2  ±  1.3%, 13.6  ±  1.5%, 21.9  ±  1.2% and 29.3  ±  0.8%, respectively, at 12 weeks (P  <  0.05). Histological analysis revealed that the newly formed bone within the calvarial defects of all groups was a mixture of woven and lamellar bone, with more bone in the group treated with lactoferrin at both timepoints. Our study demonstrated that local application of lactoferrin significantly increased bone regeneration in a rat critical‐sized calvarial defect model. The profound effect of lactoferrin on bone regeneration has therapeutic potential to improve the poor clinical outcomes associated with bony non‐union. LF In Vivo JTERM Authors Contributions. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons, Ltd.     

Acupressure Therapy for Acute Ankle Sprains: A Randomized Clinical Trial

Background

Ankle sprains occur frequently among young and active people, accounting for almost 2 million injuries per year. Previous reports suggest that acupressure therapy for acute ankle sprains may shorten the recovery time.