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Background: Circular RNAs (circRNAs) have important roles in human malignancies, including breast cancer (BC). In this study, we intended to explore the function of circRNA ribonuclease P RNA component H1 (circ_RPPH1) in BC development and clarify the mechanistic pathway. Methods: Expression of circ_RPPH1, microRNA-542-3p (miR-542-3p), and Rho GTPase-activating protein 1 (ARHGAP1) in BC tissues and cells was determined by quantitative real-time polymerase chain reaction or Western blot assay. The stability of circ_RPPH1 was confirmed by RNase R and actinomycin D treatment. Cell viability and colony formation ability were measured by methyl thiazolyl tetrazolium (MTT) assay and colony formation assay, respectively. Western blot analysis was also used to detect proliferation biomarker (Ki67) and epithelial-mesenchymal transition (EMT) biomarkers (E-cadherin, N-cadherin, and vimentin). Flow cytometry and Transwell assays were performed to monitor cell apoptosis, migration, and invasion. The binding potency between miR-542-3p and circ_RPPH1 or ARHGAP1 was validated by dual-luciferase reporter assay. Functional role of circ_RPPH1 in vivo was investigated by xenograft tumor reporter assay. Results: Upregulation of circ_RPPH1 and ARHGAP1, and downregulation of miR-542-3p were detected in BC tissues and cells. circ_RPPH1 knockdown or miR-542-3p introduction inhibited BC cell proliferation and metastasis, while promoted apoptosis in vitro. circ_RPPH1 sponged miR-542-3p to upregulate ARHGAP1 expression, thereby affecting BC progression. Moreover, depletion of circ_RPPH1 suppressed tumor growth in vivo. Conclusions: circ_RPPH1 contributed to BC tumorigenesis by sponging miR-542-3p and upregulating ARHGAP1, affording a novel mechanistic pathway in BC development.

Design of highly active and stable non-precious electrocatalysts towards hydrogen evolution reaction (HER) is a hot research topic in low cost, clean and sustainable hydrogen energy field, yet remaining the important challenge caused by the sluggish reaction kinetics for water-alkali electrolyzers. Herein, a robust electrocatalyst is proposed by designing a novel sub-nanometer of copper and ruthenium bimetallic phosphide nanoclusters (RuxCuyP2) supported on a graphited carbon nanofibers (CNF). Uniform RuxCuyP2 (~1.90 nm) on the surface of CNF are obtained by introducing the dispersed Ru, thereby improving the intrinsic activity for HER. On optimizing the Ru ratio, the (x = y = 1) RuCuP2/CNF catalyst exhibits an excellent HER electroactivity with an overpotential of 10 mV in 1.0 M NaOH electrolyte to produce 10 mA cm−2 current density, which is lower than commercial 20% Pt/C in alkaline solution. Moreover, the kinetic study demonstrated that electrochemical activation energies for HER of RuCuP2/CNF is 20.7 kJ mol−1 highest among different ratio bimetallic phosphide. This simple, cost-effective, and environmentally friendly methodology can pave the way for exploitation of bimetallic phosphide nanoclusters for catalyst design.

Abstact Cell migration proceeds in 3D matrices in vivo, which can naturally switch to distinct phenotypes for better invasion in confined microenvironments. The studies of important metabolites under confinement are extremely meaningful for comprehensive insights into cancer metastasis. The integration of cell confinement device and analytical techniques is a key point for in-situ analysis of significant metabolites in vitro. Herein, an electrochemiluminescence (ECL) sensing platform was designed for in-situ monitoring of cell-secreted lactate in highly confined microenvironments. The 3-μm confiner was exactly fabricated via microfabrication and microfluidics technique, and cells in high confinement and low adhesion tended to be round with contractile blebs on cell margins. Significantly, in-situ monitoring of lactate was successfully achieved on the ECL platform with the catalysis of lactate oxidase, in which the levels in different time intervals were acquired in the luminol-hydrogen peroxide system. Furthermore, the results were verified by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology, which showed similar fluctuations with the ECL platform. This system offered an available avenue for metabolites analysis in highly confined microenvironments, which may advance deeper insights into metabolic mechanisms of cancer metastasis

Solid lipid nanoparticles (SLN) have been intensively exploited as nanocarriers for pulmonary drug delivery. However, no consensus on the underlying mechanisms between particle sizes and cell uptake behaviors was attained owing to their unclear in vivo fate after inhalation, which hindered the further development of a novel nanoparticle delivery system. Recently, aggregation-caused quenching (ACQ) probes had been developed to monitor the integrity of nanocarriers. In this study, an ACQ probe, P4, was employed to clarify the effect of particle size on SLN cellular uptake. SLN (120, 240, and 480 nm in size), incubated with epithelium cells (A549) and macrophages (RAW 264.7), mainly localized in the cytoplasm in an integrated pattern, showing a positive correlation relationship between particle size and cellular intake. In conclusion, this study established a firm basis to understand the effect of particle size on cellular uptake of nanoparticle systems and promoted the development of novel pulmonary drug delivery systems.

Chemodynamic therapy (CDT) is an effective tumor treatment strategy in which FeII reacts with hydrogen peroxide (H2 O2 ) in tumor cells to produce highly toxic hydroxyl radical (. OH) through the Fenton reaction. However, the content of endogenous H2 O2 in cells is limited, and the reaction between FeIII and H2 O2 is inefficient, greatly limiting the efficiency of the Fenton reaction and reducing the effectiveness of tumor treatment. Therefore, in this work, we designed and synthesized a new type of nano-system (CaO2 @TA-FeIII ) for the enhanced CDT of tumors, in which the polyphenolic compound- tannic acid (TA) and FeIII formed a TA-Fe nano-coating on the surface of calcium peroxide (CaO2 ) nanospherical aggregates. When the CaO2 @TA-FeIII nanoconjugates reach the tumor site, the CaO2 contained in the nanoconjugates produces H2 O2 after disintegration in tumor cells, and the carried TA rapidly reduces FeIII to FeII , solving the two major shortcomings in CDT of (1) insufficient content of H2 O2 in cancer cells, and (2) low catalytic efficiency of the Fenton reaction. Additionally, the . OH produced in the Fenton reaction induces oxidative stress for the tumor cells, promoting the occurrence of the "calcium overload" process, and thereby accelerating the death of tumor cells. Experimental results in vitro and in vivo showed that CaO2 @TA-FeIII nanoconjugates can effectively kill cancer cells and display an excellent tumor therapeutic effect. We believe that the CaO2 @TA-FeIII nanoconjugates are a promising new nano-platform for highly effective tumor treatment.

Rechargeable aqueous zinc-ion batteries (AZBs) are potentially considered as potential alternatives for large-scale stationary energy storage systems by taking advantage of their easy operating con...

A method for achieving the accurate measurement of the antiferroelectric-ferroelectric (AFE-FE) phase switching time based on the electrically induced light scattering effect was designed. The AFE-FE switching times of lanthanum-modified lead zirconate titanate (PLZT) transparent ceramics decreased with the increase of the applied electric fields, and the logarithm of the switching time was approximately proportional to the electric field reciprocal. The random orientation of the polycrystalline structures with dispersion-distributed mixed phases of the PLZT transparent ceramics was the intrinsic mechanism affecting the corresponding switching times in the applied electric field. The smaller electrode size samples switched faster than the larger samples in the same electric field. The size effect of the switching times occurred due to the higher dielectric constant of the ceramics and the parameters of the test circuit, and the larger capacitance of the samples resulted in a longer rising time of the applied electric field, which in turn slowed down the phase switching and prolonged the switching time.

The in vitro detection of low abundance biomolecules via nonenzymatic signal amplification is an attractive strategy. However, it remains a challenge to monitor targets of interest in situ in living cells by low-background interference and visualized enzyme-free signal amplification strategies. Taking advantage of the single-molecule imaging and dynamic DNA nanotechnologies, we have achieved the target-triggered self-assembly of nanostructure-based dual-color fluorescent probes (NDFPs) by an enzyme-free toehold-mediated strand displacement cascade. NDFPs will facilitate the simple and visualized monitoring of microRNA (miRNA) at the femtomolar level. The recycled miRNA can be considered as the catalyst for the assembly of multiple H1/H2 duplexes. This generated the fluorescence signal of the enhanced target expression, indicating both in vitro and in vivo signal-amplified imaging. Moreover, the NDFPs improved the measurement accuracy by dual-color colocalization imaging to greatly avoid false-positive signals and enabled the successful in situ imaging of miRNA in living cells in real time. This work provides a strategy to visually monitor and study the integration of signal amplification detection and single-molecule imaging. NDFPs may be an important step toward the enzyme-free amplified monitoring and imaging of various biomolecules in living cells at the single-molecule level.

Animal models, notably with non-competitive NMDA receptor antagonist MK801, are commonly used to investigate the mechanisms of schizophrenia and to pursue its mechanism-related drug discoveries. In the current study, we have extensively examined the protective effects of MogrosideV (MogV), a plant-derived three terpene glucoside known to exhibit anti-oxidative and anti-inflammatory activities. Here, we investigated its protective effects against neuronal damages elicited by MK-801 treatment. Our behavioral experimental results showed that MK-801-induced PPI deficits and social withdrawal were prevented by MogV treatment. Moreover, the cellular and neurochemical responses of MK-801 in medial prefrontal cortical cortex (mPFC) were also ameliorated by MogV treatment. Also, profiling metabolites assay through artificial intestinal microbiota was performed to identify bioactive components of MogV. An in vitro study of primary neuronal culture demonstrated that MogV and its metabolite 11-oxo-mogrol treatment prevented the MK-801-induced neuronal damages through the mechanisms of promoting neurite outgrowth, inhibiting cell apoptosis, and [Ca2+]i release. Additionally, 11-oxo-mogrol reversed inactivation of phosphorylation levels of AKT and mTOR induced by MK801. These results suggest therapeutic potential of MogV for schizophrenia.

The design of carbon anode materials with both high gravimetric and volumetric performances is one of the main limitations in the real applications of sodium-ion batteries (SIBs). Herein, we develop novel micro/nanostructure carbon microspheres (CMSs) assembled of onion-like carbons via an in situ pyrolysis approach. When used as anode materials for SIBs, the CMSs electrode possesses a high pressing density of 1.36 g cm−3. The CMSs exhibit a high reversible gravimetric capacity of 275 mAh g−1 and a reversible volumetric capacity of 374 mAh cm−3 at 100 mA g−1, which can be comparable to the volumetric capacity of graphite for lithium-ion batteries. At high current densities of 1, 2 and 5 A g−1, the reversible gravimetric capacities can still be maintained at 195, 165 and 115 mAh g−1 and the volumetric capacities can reach up to 265, 224 and 156 mAh cm−3. Such excellent electrochemical performances should be attributed to the special spherical micro/nanostructure of CMSs, which can not only guarantee a high density, but also provide void spaces to alleviate the volume variation and enhance Na ions diffusion kinetics. Accordingly, this study proposes a new strategy for the design of carbon materials with both high gravimetric and volumetric performances.

AntiSMASH analysis of genome DNA of Streptomyces CPCC 204980, a soil isolate with potent antibacterial activity, revealed a gene cluster for polycyclic xanthones. A subsequent chemical study confir...

Aqueous rechargeable zinc batteries (ARZBs) are desirable for energy storage devices owing to their low cost and abundance of the Zn anode, but their further development is limited by a dearth of ideal cathode materials that can simultaneously possess high capacity and stability. Herein, we employ a layered structure of ammonium vanadium bronze (NH4)0.5V2O5 as the cathode material for ARZBs. The large interlayer distance supported by the NH4+ insertion not only facilitates the Zn2+-ion intercalation/deintercalation but also improves the electrochemical stability in ARZBs. As a result, the layered structural (NH4)0.5V2O5 cathode delivers a high capacity up to 418.4 mA h g-1 at a current density of 0.1 A g-1. A reversible capacity of 248.8 mA h g-1 is still retained after 2000 cycles and a capacity retention of 91.4% was maintained at 5 A g-1. Furthermore, in comparison with previously reported Zn-ion batteries, the Zn/(NH4)0.5V2O5 battery achieves a prominent high energy density of 418.4 W h kg-1 while delivering a high power density of 100 W kg-1. The results would enlighten and push the ammonium vanadium compounds to a brand new stage for the application of aqueous batteries.

Epidemiologic studies have shown a reduced risk of developing Parkinson's disease (PD) among cigarette smokers. Nicotine, as a key component in tobacco products, is thought as a possible candidate for action of smoking in neuroprotection. α7 nicotinic acetylcholine receptors (α7-nAChRs) is one of the most abundant nAChRs in the mammalian brain. Although nicotine is thought to exert this protective action by acting on nicotinic receptors, including the α7-nAChRs; the mechanisms underlying how α7-nAChRs protect against dopaminergic neuron loss are highly complex. Using nicotine and a selective α7-nAChR agonist PNU-282987, we first confirmed that their addition to SH-SY5Y cells challenged with 1-methyl-4-phenylpyridinium (MPP+ ) could afford neuroprotection and result in a reduction in apoptotic cell death. Then, we found that the pretreatment with nicotine and PNU-282987 showed the neuroprotective antiapoptotic effects via activating the α7-nAChRs/MAPK/p53 axis. Furthermore, we used RNA interference to silence the expression of α7-nAChRs in SH-SY5Y cells and found that suppressing α7-nAChR expression diminished the antiapoptotic effects of nicotine and PNU-282987, not the toxic effects of MPP+ . Moreover, α7-nAChR knockdown could only decrease the inhibitory effects of nicotine and PNU-282987 on the phosphorylated extracellular signal-regulated kinase (ERK), not c-Jun amino-terminal kinase and p38. Therefore, our findings indicate the important roles of ERK/MAPK signaling in the neuroprotective effects of α7-nAChRs and suggest that α7-nAChR agonists may be validated as novel treatments for PD.

The development of anode materials for both sodium-ion batteries (SIBs) and potassium-ion batteries (KIBs) with promising performance is of fundamental and technological significance. In this work, N-rich hollow carbon-onion-constructed nanosheets (HCONs) are developed from Co–hexamine coordination frameworks. Impressively, as anode materials for SIBs, the HCONs demonstrate an ultrastable Na-ion storage capability of 151 mA h g−1 at 5 A g−1 even after 10 000 cycles, with a capacity retention of 96%. For KIBs, the HCONs also deliver a high-rate capability of 105 mA h g−1 at 10 A g−1 and an excellent long-term cycling performance of 132 mA h g−1 at 2 A g−1 after 5000 cycles. The outstanding electrochemical performance can be ascribed to the interconnected carbon onions constructing a unique 2D nanosheet structure. On the one hand, the small graphitic layer size of carbon onions together with the abundance of N atoms can greatly enhance the ion diffusion and capacitive effects as supported by kinetic analysis. On the other hand, the hollow carbon onions possess highly stable structures that can mitigate the volume strain induced by the Na- and K-ion intercalation process. The results shed light on the further design of graphitic carbon towards favourable Na- and K-ion storage.

Electrochemical sensors have the high sensitivity, fast response, and simple operation for applications in biological, medical, and chemical detection, but limited by the poor stability and high cost of the electrode materials. In this work, we used PtNi lagged-like nanowire for caffeic acid (CA) electrochemical detection. The removal of outer layer Ni during reaction process contributed to the rehabilitation of active Pt sites at the surface, leading to the excellent electrocatalytic behavior of CA sensing. Carbon-supported PtNi-modified glassy carbon electrode (PtNi/C electrode) showed a broad CA detecting range (from 0.75 to 591.783 μM), a low detection limit (0.5 μM), and excellent stability. The electrode preserved high electrocatalytic performance with 86.98% of the initial oxidation peak current retained after 4000 potential cycles in 0.5 mM caffeic acid solution. It also demonstrates excellent anti-interference capability and is ready for use in the real sample analysis. Electronic supplementary material The online version of this article (10.1186/s11671-018-2839-0) contains supplementary material, which is available to authorized users.

Water-saturated column experiments were conducted to study the effect of nonwoven geotextiles on bacteria transport and deposition through two sandy porous media with grain sizes 1.05 and 3.25 mm. The breakthrough curves (BTCs) of tracer for the all porous media exhibited an asymmetrical shape with a substantial tailing, indicating that non-equilibrium and dispersive flow patterns in these porous media. The mass recovery of the bacteria from the effluent (Meff) increased with grain size. The retention profiles (RPs) exhibited hyper-exponential behavior, especially in the finer sand. The presence of the geotextiles increased bacteria retention rate. For a given geotextile, greater retention was observed in the surrounding region close to the geotextile. Moreover, the retention of bacteria became more significant in the geotextile with a lower porosity. Results demonstrated that model simulations of bacteria transport and fate need to accurately account for both observed BTC and RP behaviors and also the geotextile placement can impact mechanisms of retention.

The membrane proteins of microbes are at the forefront of host and parasite interactions. Having a general view of the functions of microbial membrane proteins is vital for many biomedical studies on microbiota. Nevertheless, due to the strong hydrophobicity and low concentration of membrane proteins, it is hard to efficiently enrich and digest the proteins for mass spectrometry analysis. Herein, we design an enzymatic nanoreactor for the digestion of membrane proteins using methylated well-ordered hexagonal mesoporous silica (Met-SBA-15). The material can efficiently extract hydrophobic membrane proteins and host the proteolysis in nanopores. The performance of the enzymatic nanoreactor is first demonstrated using standard hydrophobic proteins and then validated using membrane proteins extracted from Escherichia coli (E. coli) or a mixed bacterial sample of eight strains. Using the nanoreactor, 431 membrane proteins are identified from E. coli, accounting for 38.5% of all membrane proteins of the species, which is much more than that by the widely used in-solution digestion protocol. From the mixed bacterial sample of eight strains, 1395 membrane proteins are identified using the nanoreactor. On the contrary, the traditional in-solution proteolysis workflow only leads to the identification of 477 membrane proteins, demonstrating that the Met-SBA-15 can be offered as an excellent tool for microbial membrane proteome research and is expected to be used in human microbiota studies, e.g. host-microbe interactions.

Background Circular RNAs (circRNAs) have been demonstrated to play significant roles in regulating gene expression in tumorigenesis, including breast cancer (BC). This study was designed to explore the role and underlying molecular mechanisms of circMMP11 in BC. Methods The real-time quantitative polymerase chain reaction (RT-qPCR) assay was used for examining expression of circMMP11, microRNA-625-5p (miR-625-5p), and Zinc finger E-box binding homeobox-2 (ZEB2). The protein expression of ZEB2, Vimentin, and E-cadherin was assessed by western blot assay. The proliferation ability of BC cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and colony-forming assays. The transwell assay was used to measure migration and invasion of BC cells. The apoptotic cells were examined by flow cytometry assay. The interaction association among circMMP11, miR-625-5p, and ZEB2 was confirmed by RNA pull-down and dual-luciferase report assays. A xenograft experiment was established to clarify the role of circMMP11 silencing in vivo. Results We found that circMMP11 and ZEB2 were overexpressed in BC tissues and cells compared with controls. The suppression of circMMP11 or ZEB2 repressed proliferation, migration, and invasion while induced apoptosis of BC cells. Additionally, miR-625-5p, interacted with ZEB2, was a target of circMMP11 in BC cells. CircMMP11 regulated the expression of ZEB2 by targeting miR-625-5p. Knockdown of circMMP11-mediated effects on BC cells could be abolished by overexpression of ZEB2. Consistently, silencing of circMMP11 impeded the tumor growth in vivo. Conclusions CircMMP11/miR-625-5p/ZEB2 axis affected proliferation, migration, invasion, and apoptosis of BC cells through the mechanism of competing endogenous RNAs (ceRNA), indicating that circMMP11 was an oncogenic circRNA in BC.

Hypertrophic scar (HS) is an undesirable skin abnormality following deep burns or operations. Although intralesional multi-injection with the suspension of triamcinolone acetonide (TA) and 5-fluorouracil (5-Fu) has exhibited great promise to HS treatment in clinical, the difference of metabolic behavior between TA and 5-Fu remarkably compromised the treatment efficacy. Besides, the traditional injection with great pain is highly dependent on the skill of the experts, which results in poor compliance. Herein, a bilayer dissolving microneedle (BMN) containing TA and 5-Fu (TA-5-Fu-BMN) with biphasic release profile was designed for HS therapy. Equipped with several micro-scale needle tips, the BMN could be self-pressed into the HS with uniform drug distribution and less pain. Both in vitro permeation and in vivo HS retention tests revealed that TA and 5-Fu could coexist in the scar tissue for a sufficient time period due to the well-designed biphasic release property. Subsequently, the rabbit ear HS model was established to assess therapeutic efficacy. The histological analysis showed that TA-5-Fu-BMN could significantly reduce abnormal fibroblast proliferation and collagen fiber deposition. It was also found that the value of scar elevation index was ameliorated to a basal level, together with the downregulation of mRNA and protein expression of Collagen I (Col I) and transforming growth factor-β1 (TGF-β1) after application of TA-5-Fu-BMN. In conclusion, the BMN with biphasic release profiles could serve as a potential strategy for HS treatment providing both convenient administrations as well as controlled drug release behavior., Graphical abstract Image 1, Highlights • A bilayer microneedle co-delivery system was designed for hypertrophic scar therapy. • The system contained rapid release triamcinolone and sustained-release 5- Fluorouracil. • The system was constructed to control the intralesional retention of different drugs. • The co-delivery system showed a superior therapeutic effect in hypertrophic scar.

Volatile organic compounds (VOCs) are the most harmful contaminants that have been identified, most of which are gaseous organic pollutants. In this study, TiO2@diatomite catalysts with various loading amounts of TiO2 were fabricated using a facile solvothermal method with anhydrous ethanol as a solvent for the removal of VOCs. X-ray diffraction analysis revealed that TiO2 has an anatase phase and the introduction of diatomite has no negative effect. The catalysts were characterized using scanning electron microscopy and transmittance electron microscopy techniques. The results indicate that after introducing diatomite, TiO2 nanoparticles are mostly square-like and intact, and are uniformly immobilized in the diatomite. Finally, their photocatalytic performance was investigated using liquid ultraviolet spectrometry and gas chromatography-mass spectrometry. Among the catalysts tested, 0.35TiO2@diatomite (with a mass ratio of TiO2 to diatomite of 0.35) exhibited higher photocatalytic activity than the other samples, i.e., pure TiO2 and diatomite, and could effectively remove acetone and benzene, demonstrating its potential market application and practical significance.

Visceral pain is one of the leading causes for abdominal pain in gastroenterological diseases and is still hard to treat effectively. Bulleyaconitine A (BAA) is an aconitine analog and has been used for the treatment of pain. Our previous work suggested that BAA exerted analgesic effects on neuropathic pain through stimulating the expression of dynorphin A in spinal microglia. Here, we investigated the inhibitory effect of BAA on visceral pain and examined whether the expression of dynorphin A in spinal microglia was responsible for its effects. We found that BAA produced significant antivisceral pain effect induced by acetic acid through stimulating dynorphin A expression in spinal microglia. In addition, anxiety and chronic visceral pain are highly prevalent comorbid conditions in clinical research, which is still a problem to be solved. We also aimed to evaluate the effects of BAA on anxiety. A comorbidity model with characteristics of both chronic visceral pain and anxiety was developed by colorectal injection of 2,4,6-trinitrobenzene sulfonic acid and the induction of heterotypic intermittent chronic stress protocol. In comorbid animals, BAA exerted great antianxiety effects. Meanwhile, the antianxiety mechanism of BAA was different with the antivisceral pain mechanism of BAA. In conclusion, our study demonstrated, for the first time, that BAA exerted marked antivisceral pain and antianxiety effects, which expands the analgesic spectrum and clinical application of BAA. Furthermore, it also it provides a better guidance for the clinical use of BAA.

An electrochemical immunosensor for sensitive detection of thyroid stimulating hormone (TSH) has been developed by using an inkjet printed microchip and based on a double signal amplification strategy using magnetic beads (MBs), alkaline phosphatase (ALP) and p-aminophenyl phosphate (pAPP) reaction. Differential pulse voltammetry (DPV), cyclic voltammogram (CV) and amperometric i–t curve (i–t) were employed to characterize the immunosensor. High sensitivity and good selectivity were observed. The detection linear range was from 0.01 μIU/mL to 10 μIU/mL, in which the peak currents increased along with the concentration. The detection limit was 0.005 μIU/mL at S/N = 3. The immunosensor was also applied for TSH detection in human serum with recoveries from 98.0% to 101.8% and relative standard deviations from 1.3% to 3.1%, demonstrating potential value in clinical diagnosis.

Na-ion storage in graphitic carbons is a kinetically unfavorable process. It is envisioned that decreasing the size of graphitic layers can efficiently enhance Na-ion storage by shortening the diffusion pathway. However, because of the lack of model graphitic carbons, investigation on the effect of decreasing the graphitic layer size on Na-ion storage has not yet been carried out. In this work, quadrangular carbon nanotubes (q-CNTs) with herringbone-like graphitic walls are employed as model materials to exhibit the idea above. The q-CNTs show reduced dependence on the electrolytes. They deliver high capacity, excellent rate performance, and ultralong cyclic stability in both ether-based and ester-based electrolytes. Typically, the q-CNTs-600 exhibits high reversible capacities of 212 and 200 mA h g–1 at 0.1 A g–1 in ether-based and ester-based electrolytes, respectively. Even at 5 A g–1, the reversible capacity of 132 mA h g–1 can still be maintained in the ether-based electrolyte. The excellent Na-ion s...

The key to the commercialization of sustainable energy conversion technologies is the development of high-performance catalysts. The discovery of a stable, efficient, and low-cost multi-function catalysts is the key. We used a simple green precipitation method to load nanozinc oxide particles onto a diatomite substrate. The ZnO is nano-sized. This precipitation method produces ZnO nanoparticles in situ on diatomite. The catalysts degraded 90% of Methylene blue solution and also degraded gaseous benzene and gaseous acetone. Not only can the catalysts be used for the organic degradation of wastewater, but it also has the potential to degrade volatile organic compounds. Photocatalytic efficiency is closely related to the generation and separation of photogenerated electrons and holes. The effective suppression of the recombination rate of photoliving carriers and thus improvement of the photocatalytic activity, has become a key research area. At present, photocatalysis is an effective technology to inhibit photogenerated carrier recombination, which is often studied in sewage treatment. Photoelectrochemical decomposition of water reduces the recombination of photogenerated electrons and holes by applying an external bias, thus improving the quantum efficiency for the complete mineralization of organic pollutants. The composite catalysts were used for oxygen and hydrogen extraction reactions, and a comparison of the catalysts with various loading ratios showed that the photoelectrochemical decomposition of water activity of the composite catalysts are due to pure ZnO, and the efficiency is highest when the loading ratio is 10%. This work provides new methods for the design and further optimization of the preparation of photoelectrochemical decomposition of water catalysts.

In this paper, deep eutectic solvents (DESs) were firstly used as new and green solvents for the preparation of polymer-grafted silica stationary phases. 1-Vinylimidazole and acrylic acid were homopolymerized and copolymerized on silica via surface radical chain-transfer reaction in the DESs. Three stationary phases including poly(1-vinylimidazole)-, poly(acrylic acid)-, poly(1-vinylimidazole-co-acrylic acid)-grafted silica were obtained and characterized by elemental analysis and Fourier transform infrared spectroscopy. Their hydrophilic interaction chromatographic properties were investigated for separation of nucleosides, nucleobases, saccharides and amino acids. The retention changes of nucleosides and nucleobases on these columns were investigated under different chromatographic conditions including acetonitrile content, salt concentration, pH of mobile phase and column temperature. The repeatability of these columns was also investigated. The results demonstrate that DESs can be used as new media for the synthesis of silica-based stationary phases by homopolymerization and copolymerization on the surface of porous silica particles.

The effect of normal force on fretting corrosion behaviors of Inconel 690 in 3.5% sodium chloride was investigated. The results indicated that fretting corrosion behaviors strongly depended on fretting regime and normal force. In gross slip regime, the wear volume increased but coefficient of friction (COF) decreased with increasing normal force. The damage mechanism was nanostructures and delamination cracks, and the tribologically transformed structure was separated into Ni-rich/Cr-rich oxide zones. The wear mechanism was delamination/oxidation wear. In partial slip regime, wear volume and COF decreased with increasing normal force. The main damage mechanism was fatigue cracks and asperity corrosion. The fatigue cracks propagated along the direction of 40–50° to the surface. The wear mechanism was oxidation/abrasive wear.

A cubic Pd and reduced graphene oxide modified glassy carbon electrode (Pd/RGO/GCE) was fabricated to simultaneously detect dopamine (DA) and uric acid (UA) by cyclic voltammetry (CV) and different pulse voltammetry (DPV) methods. Compared with Pd/GCE and RGO/GCE, the Pd/RGO/GCE exhibited excellent electrochemical activity in electrocatalytic behaviors. Performing the Pd/RGO/GCE in CV measurement, the well-defined oxidation peak potentials separation between DA and UA reached to 145mV. By using the differential pulse voltammetry (DPV) technique, the calibration curves for DA and UA were found linear with the concentration range of 0.45-421μM and 6-469.5μM and the detection limit (S/N =3) were calculated to be 0.18μM and 1.6μM, respectively. Furthermore, the Pd/RGO/GCE displayed high selectivity when it was applied into the determination of DA and UA even though in presence of high concentration of interferents. Additionally, the prepared electrochemical sensor of Pd/RGO/GCE demonstrated a practical feasibility in rat urine and serum samples determination.

Microstructural characteristics of Alloy 690TT subjected to fretting corrosion in high temperature water were investigated. The results indicated that there were oxide, tribologically transformed structure (TTS) and deformation layers in worn subsurface. Oxide layer had a multilayered structure: the outer part consisted of Fe-rich spinel oxides and tribolayer which was composed of Fe 3 O 4 and Cr 2 O 3 ; the inner part contained local amorphous Cr-rich oxides. TTS layer consisted of equiaxed nanograins which formed due to dynamic recrystallization of deformed structure. Internal oxidation occurred within TTS layer because the nanograins provided the short-circuits for oxygen diffusion, resulting in the ellipsoid and stripe-like Cr 2 O 3 .

Rutin has a broad range of physiological activities and often used clinically as therapeutic medicine on humans, and it is important to develop sensitive analytical methods for rutin determination. The nanocomposites, consisting of Cu2O, Au nanoparticles and nitrogen-doped graphene (denoted as Cu2O-Au/NG), were successfully fabricated by a facile and green method and used for highly sensitive detection of rutin. The electrochemical methods, such as cyclic voltammetry (CV) and differential pulse voltammetry (DPV) have been used to investigate the electrochemical properties of the fabricated sensors for rutin detection. The results showed that under optimal conditions, Cu2O-Au/NG/GCE exhibited highest sensitivity of 114.94 μA·mM− 1 than the other modified electrodes, and a low detection limit of 30 nM could be achieved with a linear concentration response range from 0.06 to 512.90 μM. The enhanced electrochemical performances could be attributed to the synergistic effect between Cu2O-Au and NG and the outstanding catalytic effect of the Cu2O-Au nanoparticles. Finally, the sensor was successfully used to analyze rutin tablets, showing high potential for practical applications.

Objective: Epidemiological studies have shown that women of reproductive age have much less possibility of developing Parkinson disease (PD) than men. The beneficial effect of estrogen also has been well-described in both culture and animal models of PD. G protein-coupled estrogen receptor (GPER) is a membrane-associated estrogen receptor, and displayed a neuroprotective role in a mouse model of PD. Since GPER is highly expressed in microglia, we speculate that GPER mediates the neuroprotective function of estradiol through suppressing the neuroinflammation of PD. Methods: We investigated the effects of GPER agonist G1 and GPER antagonist G15 on the neurodegeneration of dopaminergic neuron, the activation of microglia, and the production of IL-1β, TNF-α, and IL-6 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of parkinsonism. Furthermore, we confirmed the effects of GPER activation on the production of IL-1β, TNF-α, and IL-6 in an in vitro MPP+ model in BV2 microglial cells. Results: After 12-day treatment with G1, mice showed an increase in the number of tyrosine hydroxylase-immunoreactive cells, reduced activation of microglia, and the abatement of proinflammatory cytokines, and the anti-inflammatory effect of G1 was abolished by G15. Meanwhile, in vitro studies demonstrated that GPER activation also reduced the release of proinflammatory cytokines from BV2 microglial cells after MPP+ stimulation. Conclusion: Our data suggest that GPER mediates the anti-neuroinflammatory effect of estrogen in experimental PD progression.

The objective of this study was to develop a novel anhydrous reverse micelle nanoparticles (ARM-NPs) system to overcome the sedimentation instability of peptide-containing pressurized metered-dose inhalers (pMDIs). A bottom-up method was utilized to fabricate ARM-NPs. Tertiary butyl alcohol (TBA)/water system, freeze-drying and lipid inversion method were successively used to produce the ARM-NPs for pMDI. Various characteristics of ARM-NPs were investigated including particle size, morphology, secondary structure of the peptide drug, aerosolization properties and storage stability. As revealed by the results, ARM-NPs with spherical shape possessed 147.7 ± 2.0 nm of particle size with 0.152 ± 0.021 PdI. The ARM-NPs for pMDI had satisfactory fine particle fraction (FPF) value of 46.99 ± 1.33%, while the secondary structure of the peptide drug was unchanged. Stability tests showed no pronounced sedimentation instability for over 12 weeks at 4–6 °C. Furthermore, a hypothesis was raised to explain the formation mechanism of ARM-NPs, which was verified by the differential scanning calorimetry analysis. The lecithin employed in the reverse micelle vesicles could serve as a steric barrier between peptide drugs and bulk propellant, which prevented the instability of peptide drugs in hydrophobic environment. Homogenous particle size could avoid Ostwald ripening phenomenon of particles in pMDIs. It was concluded that the ARM-NPs for pMDI could successfully overcome sedimentation instability by the steric barrier effect and homogeneous particle size.

Astrocytes, as the largest population of glial subtype, play crucial roles in normal brain function and pathological conditions, such as Parkinson’s disease (PD). Restoring the functions of astrocyte is a promising new therapeutic target for PD. Astrocytes can express multiple types of neurotransmitter receptors, including functional α7 nicotinic acetylcholine receptor (α7nAChR). Previously, we found that a non-selective α7nAChR agonist nicotine exerted a protective effect against H2O2-induced astrocyte apoptosis via an α7nAChR-dependent pathway. However, the molecular mechanism of the antiapoptotic response of astroglial α7nAChR has not been studied. In the present study, using pharmacological inhibition and genetic knockout of α7nAChR, we assessed the antiapoptotic effects of an α7nAChR agonist PNU-282987 in primary cultured astrocytes treated with 1-methyl-4-phenylpyridinium (MPP+). PNU-282987 promoted the viability of astrocytes, alleviated MPP+ induced apoptosis, and decreased the number of GFAP+/TUNEL+ cells. Meanwhile, PNU-282987 upregulated the expression of the antiapoptotic protein Bcl-2 and downregulated the expression of the apoptotic protein Bax and cleaved-caspase-3. Moreover, the suppression of the JNK-p53-caspase-3 signaling may underlie the neuroprotective property of PNU-282987. Therefore, PNU-282987 ameliorates astroglial apoptosis induced by MPP+ through α7nAChR-JNK-p53 signaling. Our findings suggest that PNU-282987 may be a potential drug for restoring astroglial functions in the treatment of PD.

Frameshift mutations frequently occur in colorectal cancer (CRC) with microsatellite instability (MSI), but the nature and biological function of many MSI‐associated mutations remain elusive. Here, an MSI frameshift mutation is identified in glioma tumor suppressor candidate region gene 1 (GLTSCR1) that produces two C‐terminal‐truncated proteins. Additionally, GLTSCR1 is verified as a tumor suppressor that inhibits CRC metastasis. Through binding to bromodomains and the phosphorylation‐dependent interaction domain of bromodomain protein 4 (BRD4) via the C‐terminus, GLTSCR1 blocks oncogenic transcriptional elongation. However, truncated GLTSCR1 translocates into the cytoplasm and loses BRD4 binding domain, which induces the phosphorylation of RNA Pol II at Ser2 and dephosphorylation at Ser5, then increases oncogenic transcriptional elongation. Importantly, GLTSCR1 deficiency decreases sensitivity to bromodomain and extra terminal domain inhibitors. This study highlights the molecular mechanism of the GLTSCR1‐BRD4 interaction, which is a potential therapeutic target for CRC., This study reports a microsatellite instability‐selected frameshift mutation in glioma tumor suppressor candidate region gene 1 (GLTSCR1) that converts GLTSCR1 from an antimetastatic gene to a prometastatic gene. A bromodomain protein 4‐GLTSCR1‐DNA model is proposed in which the truncated GLTSCR1 coregulates the oncogenic transcriptional elongation and these findings provide a strong rationale for targeting GLTSCR1 in colorectal cancer.

It was well-known that Berberine, a major bioactive compound extracted from natural plants Coptis chinensis, has anti-diabetic effects for decades in china. Other types of pharmacological activities, such as anti-inflammatory, antimicrobial, hypolipidemic, and anti-cancer effects, have also been examined. At cellular level, these pharmacological activities were mostly an inhibitory effect. However, the cytoprotective effect of berberine was also observed in various types of cells, such as neurons, endothelial cells, fibroblasts, and β-cells. The paradoxical result may be closely associated with characteristics and distribution of berberine within cells, and they can be explained mechanically by mitohormesis, one particular form of hormesis. Here, we reviewed the mitohormetic response and assessed the berberine-induced effects and the possible signaling pathway involved. These findings may contribute to better clinical applications of berberine and indicate that some mitochondria-targeted conventional drugs should be considered carefully in clinical application.

Isarubrolones are bioactive polycyclic tropoloalkaloids from Streptomyces. Three new isarubrolones (2-4), together with the known isarubrolone C (1) and isatropolones A (5) and C (6, 3( R)-hydroxyisatropolone A), were identified from Streptomyces sp. CPCC 204095. The structures of these compounds were determined using a combination of mass spectrometry, 1D and 2D NMR spectroscopy, and ECD. Compounds 3 and 4 feature a pyridooxazinium unit, which is rarely seen in natural products. Compound 6 could conjugate with amino acids or amines to expand the structural diversity of isarubrolones with a pentacyclic or hexacyclic core. Importantly, 1 and 3-6 were found to induce complete autophagy.

A single-particle enumeration method based on phosphorylation-directed in situ assembly of gold nanoparticles is developed for the ultrasensitive sensing of cellular protein kinase A activity. In comparison to existing strategies, the proposed new method demonstrates five orders of linear range and improves the detection limit up to 10-to-1000 fold without the involvement of target amplification.

The objective of this study was to develop a novel delivery system for recombinant human epidermal growth factor (rhEGF) for chronic wound treatment. Such a delivery system should be of good cargo stability and system mechanical properties in order to guarantee a satisfactory wound-healing effect. rhEGF-containing lyotropic liquid crystalline precursors (rhEGF-LLCPs) with in situ gelation capability were considered as a promising candidate to achieve this aim. Various properties of the optimal formulations (rhEGF-LLCP1 and rhEGF-LLCP2) were characterized, including apparent viscosity, gelation time, in vitro release and phase behavior. The stability of rhEGF and system mechanical properties (i.e. mechanical rigidity and bioadhesive force) were verified. Interestingly, rhEGF-LLCP2 with a larger internal water channel diameter exhibited faster release rate in vitro and then better bioactivity in Balb/c 3T3 and HaCaT cell models. Moreover, rhEGF-LLCP2 showed distinct promotion effects on wound closure, inflammatory recovery and re-epithelization process in Sprague-Dawley rat models. In conclusion, rhEGF-LLCP emerged as a prospective candidate to preserve the stability and enhance the wound-healing effect of rhEGF, which might serve as a new delivery system for chronic wound therapies.

Heteroatom-doping is an effective way to regulate the electronic structure of carbon so as to improve their Na-ion storage capability. In all kinds of heteroatoms, selenium (Se)-doping has rarely been investigated even though Se has unique physicochemical properties. Herein, we report a facile fabrication of Se/N-codoped carbon nanosheets (N/Se-CNs) with 10 at% N and 2 at% Se by an oxidation-selenization process. The synchrotron X-ray photoelectron spectroscopy (XPS) measurements indicate that Se doping can significantly change the electronic structures of carbon nanosheets, because Se can act as stronger electron-withdrawing units for Na storage compared with C and N. Therefore, Se can better play the role of improving the conductivity and wettability of the carbon materials. And Se atoms effectively enlarge the interlayer distance of carbon nanosheets to enhance the Na-ion diffusion kinetics and also generate extra active sites for Na-ion storage. Served as anode materials for SIBs, the N/Se-CNs delivers higher specific capacity and better rate capability compared with only N-doped carbon nanosheets. Therefore, Se-doping is an effective way for improvement of Na-storage capability of carbon materials. Moreover, this work should provide a new pathway for design of carbons doped by heteroatoms with large atomic size towards excellent Na-ion storage.

Transition metallic phosphides (TMPs) have attracted considerable attention for use as efficient and durable electrocatalysts for the hydrogen evolution reaction (HER). However, it is still challenging for TMPs to achieve HER performance similar to that of the state-of-the-art platinum (Pt) catalysts. Herein, we report new amorphous phosphatized ruthenium-iron bimetallic nanoclusters (RuxFeyP-NCs) supported on graphitized carbon nanofibers (CNF), synthesized through a facile two-step method, which combine the merits of several catalyst design strategies. The amorphous structure allows more catalytically active sites to be exposed, and the synergy between Ru and Fe may boost the intrinsic catalytic activity. Moreover, the conductive CNF support facilitates electron transport and firmly immobilizes RuxFeyP-NCs enabling a long-term stability. The resulting RuxFeyP-NCs/CNF with optimal equimolar Ru and Fe (i.e. RuFeP-NCs/CNF) exhibits outstanding Pt-like HER performance, requiring low overpotentials of 65.8 and 16.0 mV to deliver a current density of 10 mA cm−2 in acidic and alkaline solutions, respectively, and showing a long-term stability of 100 h. The density functional theory (DFT) calculations demonstrate that RuFeP-NCs/CNF shows Gibbs free energy of hydrogen adsorption close to that of Pt and much smaller than that of FeP-NCs/CNF and RuxFey-NCs/CNF controls with non-equimolar Ru/Fe, which rationally explains the experimentally observed prominent HER performance of RuFeP-NCs/CNF.

An electrochemiluminescence (ECL) resonance energy transfer system is constructed for 17β-estradiol (E2) detection using α-FeOOH@CdS nanospheres as the ECL-active substrates and Ag NCs as an efficient quencher. CdS QDs loaded onto three-dimensional (3D) urchin-like α-FeOOH nanospheres (α-FeOOH@CdS nanospheres) exhibited excellent ECL responses, which is attributed to dual-amplification of α-FeOOH frameworks. The 3D hierarchical structure of the α-FeOOH nanospheres provided abundant sites for loading ECL-active species, thus significantly improving the ECL performance of substrates; While Fe3+ presented on surface of α-FeOOH nanospheres could be reduced to Fe2+ in negative potentials, after which might activate persulfate in a Fenton-like process, resulting in more sulfate free radicals for more effective ECL responses via electron transfer reactions. Additionally, Ag nanoclusters (Ag NCs) stabilized by single stranded oligonucleotide were introduced as quenching probes for CdS QDs owing to the well-matched donor-acceptor spectrum for efficient energy transfer, which makes them appropriate for detection of E2. The proposed strategy displayed a desirable dynamic range from 0.01 to 10 pg mL−1 with a limit of detection of 0.003 pg mL−1. The proposed strategy based on the ECL-RET strategy offered an ideal way for E2 detection, and also revealed an alternative platform for detection of other small molecules.

A method based on the Stokes vectors was developed for the measurement of electro-optical (EO) coefficients, and the detailed test principle, experimental apparatus and data processing were described. The practicability of this method was illustrated by the determination of the EO coefficient of lanthanum-modified lead zirconate titanate (PLZT) transparent ceramics, and the measurement results indicated that the standard deviation values of the EO coefficients obtained by the Stokes vector method was almost half of that of the values measured using the Senarmont compensator method. The apparatus used for the Stokes vector method consists of only a few optical elements and was easy to adjust and calibrate, thereby enabling scientific, accurate, and efficient EO coefficient measurements for the development of EO materials and devices.

In this study, galvanic replacement provides a simple route for the synthesis of PdAg hollow nanoflower structures by using the Ag-seeds as sacrificial templates in the presence of l-ascorbic acid (reductant) and CTAC (capping agent). Transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and EDS mapping were used to characterize the as-prepared PdAg hollow nanoflower catalysts, where they were alloyed nanoflower structures with hollow interiors. By maneuvering the Pd/Ag ratio, we found that the as-prepared Pd1 Ag3 hollow nanoflower catalysts had the optimized performance for catalytic activity toward ethanol oxidation reaction. Moreover, these as-prepared PdAg hollow nanoflower catalysts exhibited noticeably higher electrocatalytic activity as compared to pure Pd and commercial Pd/C catalysts due to the alloyed Ag-Pd composition as well as the hollow nanoflower structures. It is anticipated that this work provides a rational design of other architecturally controlled bimetallic nanocrystals for application in fuel cells.

Parkinson's disease (PD) is primarily due to the progressive, selective and irreversible loss of dopaminergic (DA) neurons in the substantia nigra (SN). Interestingly, DA neurons in the ventral and lateral SN are much more susceptible than adjacent dopamine neurons in the ventral tegmental area (VTA) not only in human PD but in many PD model systems. However, the molecular causes of regional vulnerability in PD remain unknown. In our previous studies, we established acute PD animal models by administration of MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine), and found that AQP4 knockout mice were significantly more prone to MPTP-induced neurotoxicity. Here, we further observe that AQP4 deficiency resulted in the same susceptible to MPTP between SN DA neuron and VTA neurons both in acute and chronic PD model. Moreover, we show that AQP4 deficiency increased the numbers of reactive astrocytes and microglias not only in the SN and but also in the VTA under basal and MPTP-induced situations. Meanwhile, AQP4 deficiency disrupted the balance of the pro-inflammatory cytokine/neurotrophin in midbrain. Taken together, these results demonstrate that glial AQP4 is involved in the susceptibility differences of DA neurons between SN and VTA, although the precise mechanism of AQP4 remains to be explored. Moreover, these findings also suggest that these susceptibility differences are not only due to intrinsic neuronal factors, but also attribute to differences in astrocytes of these regions.

In this article, a nonenzymatic electrochemical sensor based on chemically reduced graphene oxide (RGO) and a Pt nanoparticles (PtNPs) modified glassy carbon electrode has been fabricated and used to determine rutin. The nanocomposites of PtNPs/RGO were characterized by transmission electron microscopy and X-ray diffraction, and the electrochemical behaviors of rutin on PtNPs/RGO were demonstrated by cyclic voltammetry and differential pulse voltammetry. The as-fabricated electrochemical sensor for rutin exhibited a wide linear range from 0.057 to 102.59 μM with a detection limit of 0.02 μM (S/N = 3). Additionally, the as-prepared electrode displayed a good reproducibility, stability and anti-interference ability for the detection of rutin. Finally, the electrode was successfully applied for the determination of rutin in pharmaceutical tablets.

The EGFR-targeting cancer therapies are commonly facing drug resistance, mostly due to mutations. Gene therapy with artificial microRNA targeting EGFR conserved sequence may avoid such problem. In this study, we constructed a recombinant adenovirus expressing EGFR-targeting artificial microRNA and active revCASP3 (Ad-EC), under the control of tumor-specific SLPI promoter, and evaluated its inhibitory effect on HEP-2 cancer cells both in vitro and in vivo. MTT assay showed that cell growth inhibition rate at 72h was 44.0% in Ad-EC group at MOI 50, while the rate was 7.7% in the control virus Ad-GFP group and 3.6% in Cetuximab (500 μg/ml) group respectively. Flow cytometry analysis revealed the late apoptotic cells rate was 36.1% in Ad-EC group, significantly higher than 6.5% of Ad-GFP group (p < 0.001). When Ad-EC (MOI 50) was combined with CDDP (0.25 μg/ml), late apoptotic cells rate increased to 61.2%, significantly higher than each monotherapy group (P < 0.001). The real-time xCELLigence system recorded an effective cell growth inhibition in Ad-EC and CDDP groups, and more enhanced effect in Ad-EC plus CDDP group. Western blot revealed that Ad-EC could inhibit the activation of AKT pathway and ERK1/2 pathway, while Cetuximab had the AKT pathway over-activated. In vivo experiments with HEP-2 xenograft in nude mice confirmed the tumor inhibition in Ad-EC, CDDP and Ad-EC plus CDDP groups compared with PBS group (P < 0.01). Collectively, these data support the effective inhibition of cancer cells by this novel gene therapy strategy.

The epithelial cell adhesion molecule (EpCAM) is a known biomarker of circulating tumor cells that plays an important role in tumor metastasis. The detection of EpCAM is vital for personalized diagnosis and therapy but is challenging because of its extremely low concentration in peripheral blood. In our work, an electrochemical aptasensor has been developed to quantitatively detect EpCAM at low concentrations. A gold electrode modified with an aptamer can capture EpCAM, which can then be further recognized by a second aptamer acting as a signal reporter. To amplify the signal, a silica nanoparticle/CdSe complex has been designed to enhance the detection system. First, silica nanoparticles were synthesized to act as carriers for loading many CdSe quantum dots which are capable of binding with the second aptamer by biotin-streptavidin interactions. A molecule of EpCAM can bind with numerous CdSe quantum dots (QDs) to realize significant signal amplification. By stripping square wave voltammetry (SSWV), concentrations down to 10 aM EpCAM can be successfully detected and quantified based on the newly developed aptasensor. The detection linear range is from 10 aM to 100 pM. This principle can also be extended to other biomarkers when a suitable aptamer or antibody is available. This aptasensor is expected to be a potential tool for the diagnosis, therapeutic evaluation and personalized medical care of cancer patients.

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1&mdash, a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (25 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% &plusmn, 2.2%, and low-density lipoprotein-cholesterol by 31.6% &plusmn, 3.2%, which was more effective than that of the resveratrol (8.4% &plusmn, 2.3%, 6.6% &plusmn, 2.1%) or berberine (10.5% &plusmn, 1.95%, 9.8% &plusmn, 2.58%) monotherapy (p &lt, 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 &micro, mol/L or 20 &micro, mol/L berberine combined with 25 &micro, mol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.