Color Stability Enhancement and Antioxidation Improvement of Sanhua Plum Wine under Circulating Ultrasound.

Anthocyanins contribute to the attractive color of fruit wine, and their excessive degradation is deleterious to quality, especially for wine with an inherently low anthocyanin content, such as Sanhua plum wine. Ultrasonic treatment is well recognized for wine color maintenance. In the present study, fresh Sanhua plum wine was ultrasonic-treated and aged in barrels for three months. Our results demonstrate that ultrasonic treatment at 28 and 40 kHz improves color performance, as expressed by an increase in a*, b*, and C* values and color intensity, which is highly related to copigmentation. This successful conservation was attributed to the inactivation of polyphenol oxidase and the corresponding reduction in anthocyanin degradation. Finally, the increased antioxidative ability was verified due to the hydrogen donating ability of the surviving anthocyanins. This study indicates the reliability of ultrasonic treatment for providing superior colorfastness during Sanhua plum wine aging, which is also of great potential in processing different fruit wines.

Gap-Mode Surface-Plasmon-Enhanced Photoluminescence and Photoresponse of MoS2.

2D materials hold great potential for designing novel electronic and optoelectronic devices. However, 2D material can only absorb limited incident light. As a representative 2D semiconductor, monolayer MoS2 can only absorb up to 10% of the incident light in the visible, which is not sufficient to achieve a high optical-to-electrical conversion efficiency. To overcome this shortcoming, a "gap-mode" plasmon-enhanced monolayer MoS2 fluorescent emitter and photodetector is designed by squeezing the light-field into Ag shell-isolated nanoparticles-Au film gap, where the confined electromagnetic field can interact with monolayer MoS2 . With this gap-mode plasmon-enhanced configuration, a 110-fold enhancement of photoluminescence intensity is achieved, exceeding values reached by other plasmon-enhanced MoS2 fluorescent emitters. In addition, a gap-mode plasmon-enhanced monolayer MoS2 photodetector with an 880% enhancement in photocurrent and a responsivity of 287.5 A W-1 is demonstrated, exceeding previously reported plasmon-enhanced monolayer MoS2 photodetectors.

Enhanced performance of a graphene/GaAs self-driven near-infrared photodetector with upconversion nanoparticles.

Near-infrared photodetectors (NIRPDs) have attracted great attention because of their wide range of applications in many fields. Herein, a novel self-driven NIRPD at the wavelength of 980 nm is reported based on the graphene/GaAs heterostructure. Extraordinarily, its sensitivity to light illumination (980 nm) is far beyond the absorption limitation of GaAs (874 nm). This means that the photocurrent originates from the separation of photo-induced carriers in graphene, which is caused by the vertically built-in electric field formed through the high quality van der Waals contact between graphene and GaAs. Moreover, after introducing NaYF4:Yb3+/Er3+ upconversion nanoparticles (UCNPs) onto the graphene/GaAs heterojunction, the responsivity increases to be as superior as 5.97 mA W-1 and the corresponding detectivity is 1.1 × 1011 cm Hz0.5 W-1 under self-driven conditions. This dramatic improvement is mainly ascribed to the radiative energy transfer from UCNPs to the graphene/GaAs heterostructure. The high-quality and self-driven UCNPs/graphene/GaAs heterostructure NIRPD holds significant potential for practical application in low-consumption and large-scale optoelectronic devices.

ZnO quantum dot-doped graphene/h-BN/GaN-heterostructure ultraviolet photodetector with extremely high responsivity.

A ZnO quantum dot  photo-doped graphene/h-BN/GaN-heterostructure ultraviolet photodetector with extremely high responsivity of more than 1915 A W-1 and detectivity of more than 1.02 × 1013 Jones (Jones = cm Hz1/2 W-1) has been demonstrated. The interfaced h-BN layer increases the barrier height at the graphene/GaN heterojunction, which decreases the dark current and improves the on/off current ratio of the device. The photo-doping effect increases the barrier height and carrier concentration at the graphene/h-BN/GaN heterojunction, thus the responsivity is improved from 1473 A W-1 to 1915 A W-1 and the detectivity is improved from 5.8 × 1012 to 1.0 × 1013 Jones. Moreover, all of the responsivity and detectivity values are the highest values among all the graphene-based ultraviolet photodetectors.

Graphene/h-BN/GaAs sandwich diode as solar cell and photodetector.

In graphene/semiconductor heterojunction, the statistic charge transfer between graphene and semiconductor leads to decreased junction barrier height and limits the Fermi level tuning effect in graphene, which greatly affects the final performance of the device. In this work, we have designed a sandwich diode for solar cells and photodetectors through inserting 2D hexagonal boron nitride (h-BN) into graphene/GaAs heterostructure to suppress the static charge transfer. The barrier height of graphene/GaAs heterojunction can be increased from 0.88 eV to 1.02 eV by inserting h-BN. Based on the enhanced Fermi level tuning effect with interface h-BN, through adopting photo-induced doping into the device, power conversion efficiency (PCE) of 10.18% has been achieved for graphene/h-BN/GaAs compared with 8.63% of graphene/GaAs structure. The performance of graphene/h-BN/GaAs based photodetector is also improved with on/off ratio increased by one magnitude compared with graphene/GaAs structure.

Interface designed MoS2/GaAs heterostructure solar cell with sandwich stacked hexagonal boron nitride.

MoS2 is a layered two-dimensional semiconductor with a direct band gap of 1.8 eV. The MoS2/bulk semiconductor system offers a new platform for solar cell device design. Different from the conventional bulk p-n junctions, in the MoS2/bulk semiconductor heterostructure, static charge transfer shifts the Fermi level of MoS2 toward that of bulk semiconductor, lowering the barrier height of the formed junction. Herein, we introduce hexagonal boron nitride (h-BN) into MoS2/GaAs heterostructure to suppress the static charge transfer, and the obtained MoS2/h-BN/GaAs solar cell exhibits an improved power conversion efficiency of 5.42%. More importantly, the sandwiched h-BN makes the Fermi level tuning of MoS2 more effective. By employing chemical doping and electrical gating into the solar cell device, PCE of 9.03% is achieved, which is the highest among all the reported monolayer transition metal dichalcogenide based solar cells.

Graphene/h-BN/ZnO van der Waals tunneling heterostructure based ultraviolet photodetector.

We report a novel ultraviolet photodetector based on graphene/h-BN/ZnO van der Waals heterostructure. Graphene/ZnO heterostructure shows poor rectification behavior and almost no photoresponse. In comparison, graphene/h-BN/ZnO structure shows improved electrical rectified behavior and surprising high UV photoresponse (1350AW(-1)), which is two or three orders magnitude larger than reported GaN UV photodetector (0.2~20AW(-1)). Such high photoresponse mainly originates from the introduction of ultrathin two-dimensional (2D) insulating h-BN layer, which behaves as the tunneling layer for holes produced in ZnO and the blocking layer for holes in graphene. The graphene/h-BN/ZnO heterostructure should be a novel and representative 2D heterostructure for improving the performance of 2D materials/Semiconductor heterostructure based optoelectronic devices.

Dipeptidyl peptidase IV as a potential target for selective prodrug activation and chemotherapeutic action in cancers.

The efficacy of chemotherapeutic drugs is often offset by severe side effects attributable to poor selectivity and toxicity to normal cells. Recently, the enzyme dipeptidyl peptidase IV (DPPIV) was considered as a potential target for the delivery of chemotherapeutic drugs. The purpose of this study was to investigate the feasibility of targeting chemotherapeutic drugs to DPPIV as a strategy to enhance their specificity. The expression profile of DPPIV was obtained for seven cancer cell lines using DNA microarray data from the DTP database, and was validated by RT-PCR. A prodrug was then synthesized by linking the cytotoxic drug melphalan to a proline-glycine dipeptide moiety, followed by hydrolysis studies in the seven cell lines with a standard substrate, as well as the glycyl-prolyl-melphalan (GP-Mel). Lastly, cell proliferation studies were carried out to demonstrate enzyme-dependent activation of the candidate prodrug. The relative RT-PCR expression levels of DPPIV in the cancer cell lines exhibited linear correlation with U95Av2 Affymetrix data (r(2) = 0.94), and with specific activity of a standard substrate, glycine-proline-p-nitroanilide (r(2) = 0.96). The significantly higher antiproliferative activity of GP-Mel in Caco-2 cells (GI50 = 261 µM) compared to that in SK-MEL-5 cells (GI50 = 807 µM) was consistent with the 9-fold higher specific activity of the prodrug in Caco-2 cells (5.14 pmol/min/µg protein) compared to SK-MEL-5 cells (0.68 pmol/min/µg protein) and with DPPIV expression levels in these cells. Our results demonstrate the great potential to exploit DPPIV as a prodrug activating enzyme for efficient chemotherapeutic drug targeting.

Effects of traditional Chinese medicine on rats with Type II diabetes induced by high-fat diet and streptozotocin: a urine metabonomic study.

BACKGROUND: Type II diabetes has become a serious threat to human health in recent years. Among adults above 20 years old in China, the prevalence rate of diabetes is 9.7%. Thus, it is imperative to study the mechanisms underlying type II diabetes to develop effective therapeutic treatments. OBJECTIVE: To examine metabolic changes in a rat model of type II diabetes and explore mechanisms underlying the beneficial effects of traditional Chinese medicine (TCM) in this model. 120 rats were divided into four groups, including a control group, a high-fat diet group (high-fat diet and streptozotocin injection), a TCM group (high-fat diet, streptozotocin injection, followed by TCM administration), and a rosiglitazone maleate group (high-fat diet, streptozotocin injection, followed by rosiglitazone maleate administration). Metabolites in urine samples from 1-3 weeks (time point 1) and 4-6 weeks (time point 2) of drug administration were compared by gas chromatography-mass spectrometry (GC-MS). RESULTS: Our results showed that in the high-fat diet group, at time point 2, the levels of dihydroxybenzoic acid, L-ascorbic acid, D-gluconic acid, octadecanoic acid, and glutaric acid in urine were significantly higher than at time point 1. In the TCM group, at time point 2, the urine levels of L-ascorbic acid were markedly lower than at time point 1. CONCLUSION: Our studies demonstrated that examining urine metabolic changes provided important insights into the mechanisms underlying type II diabetes as well as the therapeutic effects of TCM.

Effects of Sini San used alone and in combination with fluoxetine on central and peripheral 5-HT levels in a rat model of depression.

OBJECTIVE: To investigate the effects of Sini San and fluoxetine on the levels of central and peripheral 5-HT in a rat model of depression, and provide new insight into the treatment of depression with integrated Chinese-Western Medicine. METHODS: A rat model of depression was established by chronic mild stress (CMS). Model rats received either Sini San, fluoxetine, a combination of the two drugs, or no drug treatment. Healthy naive rats were used as controls. Open field and sucrose preference tests were used to assess depression-like behavior. ELISA and immunohistochemistry were used to determine central and peripheral levels of 5-HT. RESULTS: In the group with no drug treatment, central 5-HT expression decreased while peripheral 5-HT concentrations increased as CMS continued. Four weeks after CMS, Sini San alone was less effective in reducing depression-like behavior than fluoxetine alone or in combination with Sini San, but combined use was more effective than fluoxetine alone. Eight weeks after CMS, Sini San alone or in combination with fluoxetine was more effective in reducing depression-like behavior than fluoxetine alone. Furthermore Sini San and fluoxetine used alone or in combination notably increased central 5-HT expression and decreased peripheral 5-HT levels in the rat model. CONCLUSION: The results of the present study indicate that there is a synergistic action between the two medicines in the treatment of depression. Sini San exhibited a relatively long lag before its effects were observed; however, by eight weeks the Traditional Chinese Medicine appeared at least as effective as fluoxetine. We suggest that Sini San can replace fluoxetine in the later stages of depression treatment to minimize side effects observed with long-term fluoxetine administration.

The preformulation stability studies of a proline prodrug of methotrexate.

In order to reduce toxicity of methotrexate and improve bioavailability, permeability, and explore other delivery routes, a proline prodrug of methotrexate was synthesized and preformulation stability studies were conducted under accelerated conditions to assess compound liability and possible conversion to the parent drug. Forced degradation studies showed that the prodrug will degrade in the presence of water, acid, and heat (70 °C), generating the parent compound methotrexate. It was also found that this conversion is temperature dependent. In addition, the prodrug is extremely light and oxidative labile. Therefore, future formulation studies should be light protected and stabilized by a suitable antioxidant. It was also found that the prodrug is stable in the HPLC diluent, consisting of water and acetonitrile; stored bench-top and protected from light for up to two weeks.

Recent advances of siRNA delivery by nanoparticles.

INTRODUCTION: The field of RNA interference technology has been researched extensively in recent years. However, the development of clinically suitable, safe and effective drug delivery vehicles is still required. AREAS COVERED: This paper reviews the recent advances of non-viral delivery of small interfering RNA (siRNA) by nanoparticles, including biodegradable nanoparticles, liposomes, polyplex, lipoplex and dendrimers. The characteristics, composition, preparation, applications and advantages of different nanoparticle delivery strategies are also discussed in detail, along with the recent progress of non-viral nanoparticle carrier systems for siRNA delivery in preclinical and clinical studies. EXPERT OPINION: Non-viral carrier systems, especially nanoparticles, have been investigated extensively for siRNA delivery, and may be utilized in clinical applications in the future. So far, a few preliminary clinical trials of nanoparticles have produced promising results. However, further research is still required to pave the way to successful clinical applications. The most important issues that need to be focused on include encapsulation efficiency, formulation stability of siRNA, degradation in circulation, endosomal escape and delivery efficiency, targeting, toxicity and off-target effects. Pharmacology and pharmacokinetic studies also present another great challenge for nanoparticle delivery systems, owing to the unique nature of siRNA oligonucleotides compared with small molecules.

Analytical methods for heavy metals in herbal medicines.

INTRODUCTION: It is estimated that about 70-80% of the world's population relies on non-conventional medicine, mainly of herbal origin. However, owing to the nature and sources of herbal medicines, they are sometimes contaminated with toxic heavy metals such as lead, arsenic, mercury and cadmium, which impose serious health risks to consumers. It is critical to analyse source materials for heavy metals in order to ensure that their concentrations meet the related standards or regulations limiting their concentrations in herbal medicines. In this review, different analytical methods for analysis of heavy metals in herbal medicines are discussed. OBJECTIVE: To provide a comprehensive review of the current state of the art in analytical methods used to detect heavy metals in herbal medicines. METHODOLOGY: We systematically searched and reviewed the research articles regarding analytical methods for heavy metals in herbal medicine from various databases, such as Medline/PubMed, ScienceDirect, SciFinder, Google Scholar, EBSCO, Gale InfoTrac, Ingenta, Ovid, ProQuest and ISI Web of Knowledge. RESULTS: In this review, we discuss in detail several commonly used and sensitive analytical techniques, including atomic absorption spectrometry, inductively coupled plasma optical emission spectrometry or mass spectrometry, X-ray fluorescence spectrometry, high-performance liquid chromatography, differential pulse polarography, neutron activation analysis and anodic stripping voltammetry. We also provide some application examples of these analytical techniques for heavy metals in herbal medicines.

Development of methotrexate proline prodrug to overcome resistance by MDA-MB-231 cells.

The resistance to methotrexate by a number of cancer cells such as breast cancer cell-line MDA-MB-231 due to poor permeability renders it less effective as an anticancer agent for these cells. Proline prodrug of methotrexate (Pro-MTX) was designed as a substrate of prolidase which is specific for imido bond of dipeptide containing proline and expected to penetrate MDA-MB-231 cells more efficiently. The prodrug was synthesized by solid-phase peptide synthesis method and examined as a substrate of pure prolidase as well as cell homogenate. The cytotoxicity against MDA-MB-231 and non-methotrexate resistant breast cancer cell line, MCF-7 was also examined by XTT assay. The results showed that Pro-MTX was a substrate of prolidase. It was also shown that the prodrug could be converted to parent drug methotrexate in Caco-2 and HeLa cell homogenate. When tested with Caco-2 and MCF-7 cells, Pro-MTX showed weaker cytotoxicity compared with methotrexate. But for methotrexate resistant MDA-MB-231 cells, Pro-MTX showed stronger activity than methotrexate. The results indicated that the proline prodrug of methotrexate may overcome the resistance of human breast cancer cells in culture.

Development of acetaminophen proline prodrug.

In this research work, proline ester prodrug of acetaminophen (Pro-APAP) was synthesized and evaluated for its stability in PBS buffer at various pH and Caco-2 cell homogenate. The Pro-APAP is more stable at lower pH than higher pH, with half-life of 120min in PBS buffer at pH 2.0, half-life of 65min at pH 5.0, and half life of 3.5min at pH 7.4, respectively. The half-life of Pro-APAP in Caco-2 cell homogenate is about 1min, much shorter than the half-life in PBS buffer at pH 7.4, indicating enzymes in the cell homogenate contribute to the hydrolysis of the ester bond. Carboxypeptidase A was incubated with Pro-APAP at pH 7.4 with half-life of 3.8min which is very close to the half life in buffer itself. This clearly indicates carboxypeptidase A is not one of the enzymes contributing to the hydrolysis of the prodrug. Physicochemical characteristics such as melting point and stability of newly synthesized prodrug were determined by MDSC technique.

The development and mechanism studies of cationic chitosan-modified biodegradable PLGA nanoparticles for efficient siRNA drug delivery.

PURPOSE: In order to improve siRNA delivery for possible clinical applications, we developed biodegradable chitosan-modified poly(D,L-lactide-co-glycolide) (CHT-PLGA) nanoparticles with positive surface charge, high siRNA loading, high transfection efficiency and low toxicity. METHODS: CHT-PLGA nanoparticles were prepared, and siRNA was loaded by emulsion evaporation method with poly(vinyl alcohol) (PVA) as emulsifier. siRNA loading efficiency, particle size, and Zeta potential of nanoparticles were measured. Gel retardation and protection assays were conducted to determine the loading and binding of siRNA in the formulation. Cell transfection was performed to study in vitro siRNA silencing efficiency. XTT assay was used to evaluate the cytotoxicity. RESULTS: It was found that the nanoparticle diameter and positive Zeta potential increase as the chitosan coating concentration increases. CHT-PLGA nanoparticles showed excellent siRNA binding ability and effective protection of oligos from RNase degradation. siRNA-loaded nanoparticles were successfully delivered into the HEK 293 T cell line, and the silencing of green fluorescence protein (GFP) expression was observed using fluorescent microscopy and flow cytometry. In addition, the cytotoxicity assay revealed that CHT-PLGA nanoparticles had relatively low cytotoxicity. CONCLUSION: This study suggests that biodegradable cationic CHT-PLGA nanoparticles possess great potential for efficient and safer siRNA delivery in future clinical applications.

Targeting the transcriptional machinery with unique artificial transcriptional activators.

The link between a growing number of human diseases and misregulation of gene expression has spurred intense interest in artificial transcriptional activators that could be used to restore controlled expression of affected genes. To expand the repertoire of activation domains available for the construction of artificial transcriptional regulators, a selection strategy was used to identify two unique activation domain motifs. These activation domains bear little sequence homology to endogenous counterparts and bind to unique sites within the transcriptional machinery. A comparison with two well-characterized activation domains, VP2 and P201, demonstrated for the first time that functional potency is not solely dictated by binding affinity. Finally, the selection strategy described is readily applicable to the identification of small molecule activation domains.