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Find video protocols related to scientific articles indexed in Pubmed.
Plasmon-induced transparency in a single multimode stub resonator.
Opt Express
PUBLISHED: 11-18-2014
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We investigate electromagnetically induced transparency (EIT)-like effect in a metal-dielectric-metal (MDM) waveguide coupled to a single multimode stub resonator. Adjusting the geometrical parameters of the stub resonator, we can realize single or double plasmon-induced transparency (PIT) windows in the plasmonic structure. Moreover, the consistency between analytical results and finite difference time domain (FDTD) simulations reveals that the PIT results from the destructive interference between resonance modes in the stub resonator. Compared with previous EIT-like scheme based on MDM waveguide, the plasmonic system takes the advantages of easy fabrication and compactness. The results may open up avenues for the control of light in highly integrated optical circuits.
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Theoretical analysis and applications on nano-block loaded rectangular ring.
J Opt Soc Am A Opt Image Sci Vis
PUBLISHED: 11-18-2014
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We propose compact and switchable optical filters based on nano-block loaded rectangular rings, and investigate the selection property numerically and theoretically. A simple and convenient phase model is established for the theoretical analysis. The dependent factors, such as the number, size, and positions of the loaded blocks, are discussed in detail. It is found that a longer wavelength can be obtained without increasing the device dimension, and the selected wave is more sensitive to the length of the loaded blocks. The loading positions play key roles in the realization of separating the second-order modes. Finally, applications of this proposed structure are discussed simply. We find that the loaded filter device provides a more compact size than the unloaded one for the same properties, and a tunable plasmon induced transparency based switch effect is also achieved. These findings suggest potential applications in compact filters, tunable slow light devices, and sensor fields.
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Insulin-Like Growth Factor-1 Modulates Polycomb Cbx8 Expression and Inhibits Colon Cancer Cell Apoptosis.
Cell Biochem. Biophys.
PUBLISHED: 11-16-2014
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Colon cancer is one of the leading causes of death in human beings. The pathogenesis of colon cancer is unclear. Recent reports indicate that Chromobox protein homolog 8 (Cbx8) and insulin-like growth factor-1 (IGF1) are associated with the pathogenesis of cancer. This study aims to investigate the role of Cbx8 and IGF1 in facilitating colon cancer cell proliferation. In this study, human colon cancer cell line, HCT116 cells, was cultured using an in vitro study model. The expression of Cbx8 and IGF1R (IGF1 receptor) in HCT116 cells was observed with approaches of real-time RT-PCR, Western blotting, gene silencing, and gene overexpression. The results showed that HCT116 cells express both Cbx8 and IGF1R. Exposure of HCT116 cells to IGF1 increased the expression of Cbx8. Knockdown of Cbx8 induced HCT116 cell apoptosis. Overexpression of Cbx8 induced HCT116 cell proliferation. We conclude that IGF1 can promote the colon cancer cell line, HCT116 cell, proliferation via promoting Cbx8 expression.
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Combined theoretical analysis for plasmon-induced transparency in waveguide systems.
Opt Lett
PUBLISHED: 11-01-2014
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We propose a novel combination of a radiation field model and the transfer matrix method (TMM) to demonstrate plasmon-induced transparency (PIT) in bright-dark mode waveguide structures. This radiation field model is more effective and convenient for describing direct coupling in bright-dark mode resonators, and is promoted to describe transmission spectra and scattering parameters quantitatively in infinite element structures by combining it with the TMM. We verify the correctness of this novel combined method through numerical simulation of the metal-dielectric-metal (MDM) waveguide side-coupled with typical bright-dark mode, H-shaped resonators; the large group index can be achieved in these periodic H-shaped resonators. These results may provide a guideline for the control of light in highly integrated optical circuits.
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[Efficacy and safety of a combined oral contraceptive containing drospirenone 3 mg and ethinylestradiol 20 µg in the treatment of premenstrual dysphoric disorder: a randomized, double blind placebo-controlled study].
Zhonghua Fu Chan Ke Za Zhi
PUBLISHED: 10-21-2014
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To compare the efficacy and safety of a new low-dose oral contraceptive pill (YAZ) containing drospirenone 3 mg and ethinylestradiol 20 µg with placebo in reducing symptoms of premenstrual dysphoric disorder (PMDD).
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Graphene Nanoplatelets Prepared by Electric Heating Acid-Treated Graphite in a Vacuum Chamber and Their Use as Additives in Organic Semiconductors.
ACS Appl Mater Interfaces
PUBLISHED: 10-18-2014
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Graphene nanoplatelets (GNPs) were prepared from acid-treated expandable graphite using a novel method of electric heating the graphite in an evaporation chamber under high vacuum, followed by solvent exfoliation. Such prepared graphene nanoplatelets, the eGNPs, were compared to GNPs prepared from two conventional methods: thermal expansion in an isothermal oven followed by solvent exfoliation (oGNPs), and direct solvent exfoliation (sGNPs), using various characterization techniques including UV-vis spectroscopy, scanning electron microscopy, and atomic force microscopy. It was found that the eGNPs were very thin, with a thickness of 4-16 nm, and showed no oxidation. On the other hand, oGNPs exhibited much thicker sheets, upward of 40 nm, and the sGNPs showed a high degree of oxidation. Utilizing the high purity eGNPs as an additive in PQT-12 semiconductor layer has been shown to improve the mobility by a factor of 2 in thin-film transistor devices.
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Novel Rolling Circle Amplification and DNA Origami-Based DNA Belt-Involved Signal Amplification Assay for Highly Sensitive Detection of Prostate-Specific Antigen (PSA).
ACS Appl Mater Interfaces
PUBLISHED: 10-18-2014
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Prostate-specific antigen (PSA) is one of the most important biomarkers for the early diagnosis and prognosis of prostate cancer. Although many efforts have been made to achieve significant progress for the detection of PSA, challenges including relative low sensitivity, complicated operation, sophisticated instruments, and high cost remain unsolved. Here, we have developed a strategy combining rolling circle amplification (RCA)-based DNA belts and magnetic bead-based enzyme-linked immunosorbent assay (ELISA) for the highly sensitive and specific detection of PSA. At first, a 96-base circular DNA template was designed and prepared for the following RCA. Single stranded DNA (ssDNA) products from RCA were used as scaffold strand for DNA origami, which was hybridized with three staple strands of DNA. The resulting DNA belts were conjugated with multiple enzymes for signal amplification and then employed to magnetic bead based ELISA for PSA detection. Through our strategy, as low as 50 aM of PSA can be detected with excellent specificity.
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Acute brucellosis with typical hemophagocytic lymphohistiocytosis accompanying elevated tumor markers.
Arch Iran Med
PUBLISHED: 10-13-2014
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We reported a typical brucellosis, which was diagnosed as hemophagocytic lymphohistiocytosis (HLH). Although some tumor markers (CEA, CYFRA21-1, NSE, CA19-9) in the patient's serum were elevated, carcinomas were excluded by a variety of inspections including bone marrow aspirations, ultrasound examinations, and whole-body PET-CT scans. It was concluded that serum tumor markers are considered medically necessary as a screening test for brucellosis with HLH, however, detailed inspections were needed to make a final diagnosis. Moreover, combination of epidemiology investigations and laboratory inspections were helpful to determine the etiology of HLH and initiate the corresponding treatments.
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DNA nanostructure-based universal microarray platform for high-efficiency multiplex bioanalysis in biofluids.
ACS Appl Mater Interfaces
PUBLISHED: 10-09-2014
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Microarrays of biomolecules have greatly promoted the development of the fields of genomics, proteomics, and clinical assays because of their remarkably parallel and high-throughput assay capability. Immobilization strategies for biomolecules on a solid support surface play a crucial role in the fabrication of high-performance biological microarrays. In this study, rationally designed DNA tetrahedra carrying three amino groups and one single-stranded DNA extension were synthesized by the self-assembly of four oligonucleotides, followed by high-performance liquid chromatography purification. We fabricated DNA tetrahedron-based microarrays by covalently coupling the DNA tetrahedron onto glass substrates. After their biorecognition capability was evaluated, DNA tetrahedron microarrays were utilized for the analysis of different types of bioactive molecules. The gap hybridization strategy, the sandwich configuration, and the engineering aptamer strategy were employed for the assay of miRNA biomarkers, protein cancer biomarkers, and small molecules, respectively. The arrays showed good capability to anchor capture biomolecules for improving biorecognition. Addressable and high-throughput analysis with improved sensitivity and specificity had been achieved. The limit of detection for let-7a miRNA, prostate specific antigen, and cocaine were 10 fM, 40 pg/mL, and 100 nM, respectively. More importantly, we demonstrated that the microarray platform worked well with clinical serum samples and showed good relativity with conventional chemical luminescent immunoassay. We have developed a novel approach for the fabrication of DNA tetrahedron-based microarrays and a universal DNA tetrahedron-based microarray platform for the detection of different types of bioactive molecules. The microarray platform shows great potential for clinical diagnosis.
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A novel strategy to synthesize hierarchical, porous carbohydrate-derived carbon with tunable properties.
Nanoscale
PUBLISHED: 10-01-2014
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Hydrothermal carbonization (HTC) of carbohydrate is an interesting candidate for the preparation of carbon materials, as it provides an easy, inexpensive and environmental friendly route. However, it is difficult to prepare porous carbon materials by a straight HTC process. Herein, the solubilising technology of micelles was introduced to direct the HTC of fructose by using an amphiphilic block copolymer, poly-(4-vinylpyridine)-block-poly-(ethylene glycol) (P4VP-PEG), as a structure-directing agent. By this strategy, hierarchical porous carbon materials with tunable properties were prepared. It was found that P4VP-PEG micelles could solubilize fructose and confine the formation of primary carbon domains during a sol-gel process. And the micelle size could be adjusted easily by changing the preparation conditions. Accordingly, the particle size of the obtained carbon materials was effectively tuned from 20 to 100 nm by the direction of the primary micelle size. After calcination, the hierarchical porous carbon materials were evidenced as effective electrode materials for supercapacitor with a capacitance of ?197 F at 1 A g(-1), which was almost four times higher than the carbon materials prepared by a straight HTC process.
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Gold nanoparticle-based enzyme-linked antibody-aptamer sandwich assay for detection of salmonella typhimurium.
ACS Appl Mater Interfaces
PUBLISHED: 09-19-2014
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Enzyme-linked immunosorbent assay (ELISA) provides a convenient means for the detection of Salmonella enterica serovar Typhimurium (STM), which is important for rapid diagnosis of foodborne pathogens. However, conventional ELISA is limited by antibody-antigen immunoreactions and suffers from poor sensitivity and tedious sample pretreatment. Therefore, development of novel ELISA remains challenging. Herein, we designed a comprehensive strategy for rapid, sensitive, and quantitative detection of STM with high specificity by gold nanoparticle-based enzyme-linked antibody-aptamer sandwich (nano-ELAAS) method. STM was captured and preconcentrated from samples with aptamer-modified magnetic particles, followed by binding with detector antibodies. Then nanoprobes carrying a large amount of reporter antibodies and horseradish peroxidase molecules were used for colorimetric signal amplification. Under the optimized reaction conditions, the nano-ELAAS assay had a quantitative detection range from 1 × 10(3) to 1 × 10(8) CFU mL(-1), a limit of detection of 1 × 10(3) CFU mL(-1), and a selectivity of >10-fold for STM in samples containing other bacteria at higher concentration with an assay time less than 3 h. In addition, the developed nanoprobes were improved in terms of detection range and/or sensitivity when compared with two commercial enzyme-labeled antibody signal reporters. Finally, the nano-ELAAS method was demonstrated to work well in milk samples, a common source of STM contamination.
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A More Than Six Orders of Magnitude UV-Responsive Organic Field-Effect Transistor Utilizing a Benzothiophene Semiconductor and Disperse Red 1 for Enhanced Charge Separation.
Adv. Mater. Weinheim
PUBLISHED: 09-10-2014
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A more than six orders of magnitude UV-responsive organic field-effect transistor is developed using a benzothiophene (BTBT) semiconductor and strong donor-acceptor Disperse Red 1 as the traps to enhance charge separation. The device can be returned to its low drain current state by applying a short gate bias, and is completely reversible with excellent stability under ambient conditions.
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PEGylated nickel carbide nanocrystals as efficient near-infrared laser induced photothermal therapy for treatment of cancer cells in vivo.
Nanoscale
PUBLISHED: 09-04-2014
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Photothermal therapy has attracted significant attention as a minimally invasive therapy methodology. In this work, we report PEGylated nickel carbide nanocrystals (Ni3C NCs) as an efficient photothermal agent for the first time. The nanoparticles exhibit a broad absorption from the visible to the near-infrared regions and a rapid rise in temperature when irradiated by an 808 nm laser even at a concentration of 100 ?g mL(-1). In vitro and in vivo cytotoxicity assays demonstrate they have good biocompatibility, which lays an important foundation for their biological application. In vitro studies reveal the efficient damage of cancer cells by the exposure of 808 nm laser with a power density of 0.50 W cm(-2). Furthermore, hematoxylin and eosin (H & E) and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining of tumor slices confirmed the obvious destruction of cancer cells in vivo by an 808 nm laser (0.50 W cm(-2)) after only a 5 min application. Our work may open up a new application domain for transition metal carbides for biomedicine.
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Oxygen-nitrogen switchable copolymers of 2,2,2-trifluoroethyl methacrylate and n,n-dimethylaminoethyl methacrylate.
Macromol Rapid Commun
PUBLISHED: 09-01-2014
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In this work, a novel class of O2 /N2 switchable polymers is reported, which is prepared by atom transfer radical copolymerization (ATRcoP) of commercially available 2,2,2-trifluoroethyl methacrylate (FMA) and N,N-dimethylaminoethyl methacrylate (DMA). The copolymer is random and contains 10 FMA units and 85 DMA units. Its aqueous solution becomes transparent with O2 bubbling and turns to turbid with N2 purging. This O2 /N2 -responsive switchability between the transparent and turbid states is reversible. The FMA-DMA copolymer is thermosensitive and has a lower critical solution temperature (LCST) of 24.5 °C. O2 molecules interact with fluorinated groups of the copolymer and increase the LCST to 55 °C. Purging N2 removes O2 and returns the polymer thermosensitivity back to its initial state. The switchability occurs in the whole temperature range (24.5-55 °C).
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Highly CO2/N2-switchable zwitterionic surfactant for pickering emulsions at ambient temperature.
Langmuir
PUBLISHED: 08-18-2014
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Cross-linked polymer particles were prepared via surfactant-free emulsion copolymerization of 2-(diethylamino)ethyl methacrylate (DEAEMA) and sodium methacrylate (SMA) using N,N'-methylenebis(acrylamide) (MBA) as a cross-linker. Generated particles are zwitterionic, possessing unique isoelectric points in the pH range of 7.5-8.0, which is readily tunable through CO2/N2 bubbling. The particles were found to be highly responsive to CO2/N2 switching, dissolving in water with CO2 bubbling and precipitating with N2 bubbling at room temperature. Pickering emulsions of n-dodecane were prepared using these particles as the sole emulsifier. These emulsions can be rapidly demulsified with CO2 bubbling, resulting in complete oil/water phase separations. Nitrogen bubbling efficiently re-emulsifies the oil with the aid of homogenization. The rapid emulsification/demulsification using CO2/N2 bubbling at room temperature provides these cross-linked zwitterionic particles with distinct advantages as functional Pickering surfactants.
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Phosphorescent Polymeric Nanoparticles by Coordination Cross-Linking as a Platform for Luminescence Imaging and Photodynamic Therapy.
Chemistry
PUBLISHED: 07-10-2014
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Water-soluble phosphorescent polymeric nanoparticles with an average diameter of approximately 100?nm were synthesized by a coordination cross-linking reaction. The pyridine blocks in poly(4-vinyl pyridine-b-ethylene oxide) (P4VP-b-PEO) were cross-linked by the iridium chloride-bridged dimer in DMF solution. Owing to the presence of an iridium complex with different ligands in the core of the polymeric nanoparticles, NP-1, NP-2, and NP-3 showed bright green, yellow, and red phosphorescence, respectively. PEG chains in the shell gave the polymeric nanoparticles solubility and biocompatibility, which was confirmed by an MTT assay using HeLa cells as a model cancer cell line. The flow cytometry and laser confocal fluorescence microscopy results revealed NP-2, as an example, could be effectively uptaken by HeLa cells. Therefore, these polymeric nanoparticles can be used as luminescent probes for living cells. In addition, (1) O2 could be effectively generated in the presence of NP-2 upon irradiation with visible light (?>400?nm, 300?mW?cm(-2) ), which was confirmed by a clear decrease in the fluorescence intensity of 9,10-dimethylanthracene (DMA). After incubation with NP-2 at a concentration of 200??g?mL(-1) for 6?h, approximately 90?% of HeLa cells were effectively ablated upon irradiation with visible light for only 10?min, indicating the potential for photodynamic therapy with polymeric nanoparticles.
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A peptide probe for the detection of neurokinin-1 receptor by disaggregation enhanced fluorescence and magnetic resonance signals.
Sci Rep
PUBLISHED: 07-09-2014
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We report a novel peptide probe for the detection of neurokinin-1 receptor using disaggregation-caused signal enhancement. The probe was obtained via the aggregation of a modified substance P in a terpyridine-Fe (II) complex with Gd (III)-DOTA into well-defined nanostructures, which effectively weaken ligand fluorescence and slow the exchange rate of inner-sphere water molecules. This probe disaggregates upon binding to the neurokinin-1 receptor and activates the contrast agents to generate a fluorescent signal that positively enhances magnetic resonance imaging contrast and allows for the detection of overexpressed receptors on tumor cells and the identification of lung cancer using serum samples.
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Isolation and purification of a polysaccharide from the caterpillar medicinal mushroom Cordyceps militaris (Ascomycetes) fruit bodies and its immunomodulation of RAW 264.7 macrophages.
Int J Med Mushrooms
PUBLISHED: 06-19-2014
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A novel polysaccharide (CP2-S) was purified from Cordyceps militaris fruit bodies by hot water extraction, ethanol precipitation, DEAE-Sepharose Fast Flow and Sephacryl S-400 high-resolution chromatography. The polysaccharide had a molecular weight of 5.938 × 10(6) g/mol and was mainly composed of glucose. CP2-S had carbohydrate content estimated to be 100% using the phenol-sulfuric acid method. Immunostimulating experiments in vitro indicated that CP2-S could stimulate nitric oxide production, phagocytosis, respiratory burst activity, and secretion of interleukin-1? and interleukin-2 of macrophages, suggesting that this water-soluble polysaccharide from the fruit body of C. militaris is a natural immunostimulating polysaccharide with potential for further application.
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Design, synthesis and biological activity of piperlongumine derivatives as selective anticancer agents.
Eur J Med Chem
PUBLISHED: 05-26-2014
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In an effort to expand the structure-activity relationship of the natural anticancer compound piperlongumine, we have prepared sixteen novel piperlongumine derivatives with halogen or morpholine substituents at C2 and alkyl substituents at C7. Most of 2-halogenated piperlongumines showed potent in vitro activity against four cancer cells and modest selectivity for lung normal cells. The highly active anticancer compound 11h exhibited obvious ROS elevation and excellent in vivo antitumor potency with suppressed tumor growth by 48.58% at the dose of 2 mg/kg. The results indicated that halogen substituents as electrophilic group at C2 played an important role in increasing cytotoxicity.
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Pinellia pedatisecta agglutinin-based lectin blot analysis distinguishes between glycosylation patterns in various cancer cell lines.
Oncol Lett
PUBLISHED: 05-13-2014
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The analysis of altered glycosylation patterns may provide biomarkers for various types of cancer. The present study developed a Pinellia pedatisecta agglutinin (PPA)-based lectin blot analysis technique, which was used to analyze the glycosylation patterns in various types of cancer cells. Results showed that a typical band located between 47 and 85 kDa was obtained in the HL60 leukemia cells, whereas three typical bands located between 20 and 47 kDa were observed in the Kasumi-1 leukemia cells. For the PLC, BEL-7404, Huh7 and H1299 solid tumor cell lines, different band patterns were detected, with bands typically located between 55 and 100 kDa. The findings of the present study show that PPA-based lectin blot analysis is capable of distinguishing between glycosylation patterns in leukemia and solid tumor cell lines. The glycofiles detected using PPA-based lectin blot analysis may provide a 'glycosylation fingerprint' for a variety of cancer cells, which may be valuable for cancer prognosis and diagnosis.
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Efficacy and safety of aripiprazole in Chinese Han schizophrenia subjects: a randomized, double-blind, active parallel-controlled, multicenter clinical trial.
Schizophr. Res.
PUBLISHED: 05-04-2014
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Antipsychotics, such as aripiprazole and risperidone, are often used to treat individuals with schizophrenia. The efficacy as well as safety of aripiprazole in Western populations has been described. The objective of this study is to investigate the efficacy, safety, and tolerability of aripiprazole and risperidone in Chinese Han schizophrenia subjects in mainland China.
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Cu-catalyzed direct amidation of aromatic C-H bonds: an access to arylamines.
J. Org. Chem.
PUBLISHED: 04-30-2014
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A Cu-catalyzed aromatic C-H amidation with phthalimide under oxygen as a terminal oxidant without using additional additives has been achieved. This reaction has the broad substrate scope and shows moderate to good yields in most cases. This method is complementary to the previously reported metal-catalyzed C-H amination systems.
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General protocol for the synthesis of functionalized magnetic nanoparticles for magnetic resonance imaging from protected metal-organic precursors.
Chemistry
PUBLISHED: 04-25-2014
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The development of magnetic nanoparticles (MNPs) with functional groups has been intensively pursued in recent years. Herein, a simple, versatile, and cost-effective strategy to synthesize water-soluble and amino-functionalized MNPs, based on the thermal decomposition of phthalimide-protected metal-organic precursors followed by deprotection, was developed. The resulting amino-functionalized Fe3O4, MnFe2O4, and Mn3O4 MNPs with particle sizes of about 14.3, 7.5, and 6.6?nm, respectively, had narrow size distributions and good dispersibility in water. These MNPs also exhibited high magnetism and relaxivities of r2 = 107.25?mM(-1) ?s(-1) for Fe3O4, r2 = 245.75?mM(-1) ?s(-1) for MnFe2O4, and r1 = 2.74?mM(-1) ?s(-1) for Mn3O4. The amino-functionalized MNPs were further conjugated with a fluorescent dye (rhodamine?B) and a targeting ligand (folic acid: FA) and used as multifunctional probes. Magnetic resonance imaging and flow-cytometric studies showed that these probes could specifically target cancer cells overexpressing FA receptors. This new protocol opens a new way for the synthesis and design of water-soluble and amino-functionalized MNPs by an easy and versatile route.
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[An alternative model of composite tissue transplantation in rat: the femur osteomyocutaneous flap].
Zhonghua Zheng Xing Wai Ke Za Zhi
PUBLISHED: 04-24-2014
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To reconstruct a simpler and reliable composite tissue transplantation model-the femur osteomyocutaneous flap for the replacement of hindlimb transplantation.
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Genetic variations of TAP1 gene exon 3 affects gene expression and Escherichia coli F18 resistance in piglets.
Int J Mol Sci
PUBLISHED: 04-12-2014
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Firstly, our research group identified Sutai pigs' phenotypes that exhibited extreme resistance and susceptibility to the Escherichia coli F18 respectively, and then eight ETEC (Enterotoxigenic Escherichia coli) F18-resistant piglets and eight ETEC F18-sensitive piglets were selected. Then, the TAP1 (Transporter associated with antigen processing) mRNA relative expression levels were analyzed in 11 tissues of the resistant and susceptible phenotypes. Simultaneously, we detected the genetic variations in exon 3 of the TAP1 gene and evaluated the TAP1 mRNA expression levels among the different genotype pigs to study the effects of the genetic variation on gene expression, and the E. coli F18 resistance. The results revealed higher expression levels in the resistant genotypes than that in the susceptible genotypes in 11 tissues, with significant differences in the spleen, lymph node, lung, thymus, duodenum and jejunum. Furthermore, a G729A mutation was identified in the TAP1 gene exon 3, and this mutation deviates from Hardy-Weinberg equilibrium (p < 0.01). The TAP1 mRNA levels in GG genotype were significantly higher than that in the other two genotypes, with significant differences in the liver, lung, kidney, thymus, lymph node, duodenum and jejunum tissues. We speculated that high expression of the TAP1 gene might confer resistance against the E. coli F18, the G729A mutation had a significant effect on the mRNA expression, and individuals with the GG genotype possessed a stronger ability to resist the E. coli F18 infection.
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(-)-Menthol based thixotropic hydrogel and its application as a universal antibacterial carrier.
Soft Matter
PUBLISHED: 04-04-2014
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A kind of novel hydrogelator based on (-)-menthol, a traditional cooling compound, tailed by an amino acid derivate through an alkyl chain, has been designed and synthesized. The hydrogelator containing an l-lysine can form a stable hydrogel with thixotropic character in a large pH range. An interesting feature is that the viscoelastic character of the hydrogel can be enhanced by mechanical force. The mechanism of the self-assembly process was investigated by means of IR, SEM, AFM and X-ray diffraction. The formation of three dimensional multiporous networks through acid base interactions and strong double hydrogen bonding between amino acids is proposed to be the driving force for the construction of the stable hydrogel. As a result, the hydrogelator can further gelate aqueous solutions of some confirmed antibacterial agents such as Zn(2+) and a series of water soluble organic antibiotic medicines like lincomycin, amoxicillin, etc., in such a unique way that the concentration of the antibacterial agents loaded into the hydrogel can be tuned to a large extent. The antimicrobial susceptibility of the hydrogels loaded with Zn(2+) or lincomycin is much more effective than that of the corresponding aqueous solution tested by the Oxford cup method. Furthermore, the hydrogelator is completely innoxious to living cells by measurement of MTT assay. Thus, the hydrogel can be developed as a universal carrier for antibacterial agents and may also be widely used in the fields of cell culture, tissue engineering, or drug delivery systems.
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Discovery of 1-arylpyrrolidone derivatives as potent p53-MDM2 inhibitors based on molecule fusing strategy.
Bioorg. Med. Chem. Lett.
PUBLISHED: 04-02-2014
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Introducing an aryl moiety to our previous pyrrolidone scaffold by molecule fusing strategy afforded two sets of isopropylether-pyrrolidone and ?-phenylethylamine-pyrrolidone derivatives. Two novel compounds 8b and 8g of the latter serial showed potent p53-MDM2 inhibitory activities with Ki values of 90nM which were three-time higher than that of the parent compound. We also confirmed compound 8b can activate p53 proteins in lung cancer A549 cells. The results offered us valuable information for further lead optimization.
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The transcription factor CUTL1 is associated with proliferation and prognosis in malignant melanoma.
Melanoma Res.
PUBLISHED: 04-02-2014
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The transcription factor CUTL1 (CCAAT displacement protein 1) has been reported to participate in the proliferation of diverse types of cancer. In the present study, we investigated the potential involvement of CUTL1 in the proliferation of malignant melanoma. We found that CUTL1 expression was upregulated in malignant melanoma tissues and cell lines, and CUTL1 expression was selected as a prognostic predictor for malignant melanoma patients by both univariate and multivariate analysis. Knockdown of CUTL1 by short hairpin RNA significantly reduced the colony-forming ability of malignant melanoma cells in vitro and reduced tumor growth in vivo, whereas forced overexpression of CUTL1 produced the opposite results. Consistently, cell cycle progression was impaired upon downregulation of CUTL1 and enhanced when CUTL1 was upregulated. Additional experiments suggested that CUTL1 may regulate the proliferation of malignant melanoma by modulating the expression of cell cycle-related proteins.
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Iron/iron oxide core/shell nanoparticles for magnetic targeting MRI and near-infrared photothermal therapy.
Biomaterials
PUBLISHED: 03-22-2014
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The development of photothermal agents (PTAs) with good stability, low toxicity, highly targeting ability and photothermal conversion efficiency is an essential pre-requisite to near-infrared photothermal therapy (PTT) in vivo. Herein, we report the readily available PEGylated Fe@Fe3O4 NPs, which possess triple functional properties in one entity - targeting, PTT, and imaging. Compared to Au nanorods, they exhibit comparable photothermal conversion efficiency (?20%), and much higher photothermal stability. They also show a high magnetization value and transverse relaxivity (?156 mm(-1) s(-1)), which should be applied for magnetic targeting MRI. With the Nd-Fe-B magnet (0.5 T) beside the tumour for 12 h on the xenograft HeLa tumour model, PEGylated Fe@Fe3O4 NPs exhibit an obvious accumulation. In tumour, the intensity of MRI signal is ? three folds and the increased temperature is ? two times than those without magnetic targeting, indicating the good magnetic targeting ability. Notably, the intrinsic high photothermal conversion efficiency and selective magnetic targeting effect of the NPs in tumour play synergistically in highly efficient ablation of cancer cells in vitro and in vivo.
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Sound management may sequester methane in grazed rangeland ecosystems.
Sci Rep
PUBLISHED: 03-07-2014
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Considering their contribution to global warming, the sources and sinks of methane (CH4) should be accounted when undertaking a greenhouse gas inventory for grazed rangeland ecosystems. The aim of this study was to evaluate the mitigation potential of current ecological management programs implemented in the main rangeland regions of China. The influences of rangeland improvement, utilization and livestock production on CH4 flux/emission were assessed to estimate CH4 reduction potential. Results indicate that the grazed rangeland ecosystem is currently a net source of atmospheric CH4. However, there is potential to convert the ecosystem to a net sink by improving management practices. Previous assessments of capacity for CH4 uptake in grazed rangeland ecosystems have not considered improved livestock management practices and thus underestimated potential for CH4 uptake. Optimal fertilization, rest and light grazing, and intensification of livestock management contribute mitigation potential significantly.
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Autophagy activated by Toxoplasma gondii infection in turn facilitates Toxoplasma gondii proliferation.
Parasitol. Res.
PUBLISHED: 03-05-2014
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Autophagy was found to play an antimicrobial or antiparasitic role in the activation of host cells to defend against intracellular pathogens, at the same time, pathogens could compete with host cell and take advantage of autophagy to provide access for its proliferation, but there are few articles for studying the outcome of this competition between host cell and pathogens. Therefore, the aim of our study was to investigate the relationship between autophagy activated by Toxoplasma gondii (T. gondii) and proliferation of T. gondii affected by autophagy in vitro. Firstly, human embryonic fibroblasts (HEF) cells were infected with T. gondii for different times. The monodansylcadaverine (MDC) staining, acridine orange (AO) staining, punctuate GFP-LC3 distribution, and transmission electron microscopy (TEM) assays were conducted, and the results were consistent in showing that gondii infection could induce autophagy. Secondly, HEF cells were infected with T. gondii and treated with autophagy inhibitor bafilomycin A1 or inducer lithium chloride for different times. Giemsa staining was conducted, and the results exhibited that T. gondii infection-induced autophagy could in turn promote T. gondii proliferation. Simultaneously, the results of Giemsa staining also revealed that autophagy inhibitor could reduce the number of each cell infected with T. gondii and inhibit T. gondii proliferation. In contrast, autophagy inducer could increase the number of each cell infected with T. gondii and encourage T. gondii proliferation. Therefore, our study suggests that T. gondii infection could activate autophagy, and this autophagy could in turn facilitate T. gondii proliferation in HEF cells for limiting nutrients.
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Dynamic and quantitative control of the DNA-mediated growth of gold plasmonic nanostructures.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-03-2014
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Reproducible and controllable growth of nanostructures with well-defined physical and chemical properties is a longstanding problem in nanoscience. A key step to address this issue is to understand their underlying growth mechanism, which is often entangled in the complexity of growth environments and obscured by rapid reaction speeds. Herein, we demonstrate that the evolution of size, surface morphology, and the optical properties of gold plasmonic nanostructures could be quantitatively intercepted by dynamic and stoichiometric control of the DNA-mediated growth. By combining synchrotron-based small-angle X-ray scattering (SAXS) with transmission electron microscopy (TEM), we reliably obtained quantitative structural parameters for these fine nanostructures that correlate well with their optical properties as identified by UV/Vis absorption and dark-field scattering spectroscopy. Through this comprehensive study, we report a growth mechanism for gold plasmonic nanostructures, and the first semiquantitative revelation of the remarkable interplay between their morphology and unique plasmonic properties.
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CMOS-compatible silicon nanowire field-effect transistors for ultrasensitive and label-free microRNAs sensing.
Small
PUBLISHED: 02-27-2014
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MicroRNAs (miRNAs) have been regarded as promising biomarkers for the diagnosis and prognosis of early-stage cancer as their expression levels are associated with different types of human cancers. However, it is a challenge to produce low-cost miRNA sensors, as well as retain a high sensitivity, both of which are essential factors that must be considered in fabricating nanoscale biosensors and in future biomedical applications. To address such challenges, we develop a complementary metal oxide semiconductor (CMOS)-compatible SiNW-FET biosensor fabricated by an anisotropic wet etching technology with self-limitation which provides a much lower manufacturing cost and an ultrahigh sensitivity. This nanosensor shows a rapid (< 1 minute) detection of miR-21 and miR-205, with a low limit of detection (LOD) of 1 zeptomole (ca. 600 copies), as well as an excellent discrimination for single-nucleotide mismatched sequences of tumor-associated miRNAs. To investigate its applicability in real settings, we have detected miRNAs in total RNA extracted from lung cancer cells as well as human serum samples using the nanosensors, which demonstrates their potential use in identifying clinical samples for early diagnosis of cancer.
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Uniform theoretical description of plasmon-induced transparency in plasmonic stub waveguide.
Opt Lett
PUBLISHED: 02-25-2014
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We investigate a classic analog of electromagnetically induced transparency (EIT) in a metal-dielectric-metal (MDM) bus waveguide coupled to two stub resonators. A uniform theoretical model, for both direct and indirect couplings between the two stubs, is established to study spectral features in the plasmonic stub waveguide, and the theoretical results agree well with the finite difference time domain simulations. Adjusting phase difference and coupling strength of the interaction, one can realize the EIT-like phenomena and achieve the required slow light effect. The theoretical results may provide a guideline for the control of light in highly integrated optical circuits.
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Paramagnetic hollow silica nanospheres for in vivo targeted ultrasound and magnetic resonance imaging.
Biomaterials
PUBLISHED: 02-20-2014
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A series of hollow silica nanospheres (HSNSs) with sizes ranging from 100 to 400 nm were synthesized and used for primary ultrasound imaging (US) efficiency assessment. The 400 nm HSNSs were chosen as platform for conjugation with Gd-DTPA and cyclo-arginine-glycine-aspartic acid c(RGD) peptide to construct US and magnetic resonance imaging (MRI) dual-modal contrast agents (CAs): [HSNSs@(DTPA-Gd)-RGD]. The obtained CAs displayed good physiological stability, low cytotoxicity and negligible hemolytic activity in vitro. Furthermore, the passive accumulation and active-targeting of the HSNSs in the tumor site of mice was demonstrated by US and MR imaging, respectively. The qualitative and quantitative biodistribution of the HSNSs showed that they mainly accumulated in the tissues of liver, lung, tumor after intravenous administration and then be excreted from feces. In addition, histological, hematological, blood and biochemical analysis were used to further study toxicity of the HSNSs, and all results indicated that there were no covert toxicity of HSNSs in mice after long exposure times. Findings from this study indicated that the silica-based paramagnetic HSNSs can be used as a platform for long-term targeted imaging and therapy studies safely in vivo.
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Gold-catalyzed C(sp3)-H/C(sp)H coupling/cyclization/oxidative alkynylation sequence: a powerful strategy for the synthesis of 3-alkynyl polysubstituted furans.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 02-15-2014
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In sharp contrast to the gold-catalyzed reactions of alkynes/allenes with nucleophiles, gold-catalyzed oxidative cross-couplings and especially C-H/C-H cross-coupling have been under represented. By taking advantage of the unique redox property and carbophilic ??acidity of gold, this work realizes the first gold-catalyzed direct C(sp(3))-H alkynylation of 1,3-dicarbonyl compounds with terminal alkynes under mild reaction conditions, with subsequent cyclization and in situ oxidative alkynylation. A variety of terminal alkynes including aryl, heteroaryl, alkenyl, alkynyl, alkyl, and cyclopropyl alkynes all successfully participate in the domino reaction. The protocol offers a simple and region-defined approach to 3-alkynyl polysubstituted furans.
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Interferon-? suppresses invasion and enhances cisplatin-mediated apoptosis and autophagy in human osteosarcoma cells.
Oncol Lett
PUBLISHED: 02-15-2014
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Interferon (IFN)-? is generated in response to viral infections and is used clinically in the therapy of a variety of viral infections and cancers. The present study investigated whether IFN-? could inhibit the invasive ability of osteosarcoma cells using a Matrigel invasion assay. In addition, the osteosarcoma cells were treated with cisplatin and/or IFN-?. Apoptosis and autophagy were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Hoechst 33258 staining, flow cytometry assay, acridine orange staining, green fluorescent protein-LC3 dot assay and transmission electron microscopy. Further analysis revealed that the efficacy of cisplatin was enhanced by the addition of the cytokine, IFN-?. These results indicate that the combination therapy of chemotherapeutics and IFN-? is a new approach for osteosarcoma, which requires validation by experiments in vivo.
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Multiple phytohormones and phytoalexins are involved in disease resistance to Magnaporthe oryzae invaded from roots in rice.
Physiol Plant
PUBLISHED: 02-13-2014
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Blast, caused by the fungus Magnaporthe oryzae, is one of the most devastating diseases of rice worldwide. Phenylalanine ammonia lyase (PAL) is a key enzyme in the phenylpropanoid pathway, which leads to the biosynthesis of defense-related phytohormone salicylic acid (SA) and flavonoid-type phytoalexins sakuranetin and naringenin. However, the roles and biochemical features of individual rice PALs in defense responses to pathogens remain unclear. Here, we report that rice OsPAL06, which can catalyze the formation of trans-cinnamate using l-phenylalanine, is involved in rice root-M. oryzae interaction. OsPAL06-knockout mutant showed increased susceptibility to M. oryzae invaded from roots and developed typical leaf blast symptoms, accompanied by nearly complete disappearance of sakuranetin and naringenin and a two-third reduction of the SA level in roots. This mutant also showed compensatively induced expression of chalcone synthase, which is involved in flavonoid biosynthesis, isochorismate synthase 1, which is putatively involved in SA synthesis via another pathway, reduced jasmonate content and increased ethylene content. These results suggest that OsPAL06 is a positive regulator in preventing M. oryzae infection from roots. It may regulate defense by promoting both phytoalexin accumulation and SA signaling that synergistically and antagonistically interacts with jasmonate- and ethylene-dependent signaling, respectively.
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Comprehensive analysis of VQ motif-containing gene expression in rice defense responses to three pathogens.
Plant Cell Rep.
PUBLISHED: 02-09-2014
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Expression levels of rice VQ motif-containing genes in response to pathogen infection vary among pathogens, and some of the genes are co-expressed with defense-response WRKY genes. Recent studies have revealed that some VQ (FxxxVQxLTG) motif-containing proteins in plants partner with WRKY transcription factors to participate in their functions. Accumulating information suggests that WRKY proteins play important roles in the response of rice plants to pathogen infection. However, the functions of rice VQ motif-containing proteins are unknown. To explore whether VQ motif-containing proteins are involved in defense against pathogens in rice, we performed a comprehensive expression analysis of the genes for these proteins. The rice VQ motif-containing family consists of 40 genes, all of which encode proteins harboring a 21-amino acid VQ-containing motif, which in turn contains the known VQ motif. On the basis of their phylogenetic relationships and tissue-specific and developmental stage-specific expression characteristics, we transcriptionally analyzed 13 representative genes in rice responses to three pathogens: Xanthomonas oryzae pv. oryzae, which causes bacterial blight disease; X. oryzae pv. oryzicola, which causes bacterial streak disease; and Magnaporthe oryzae, which causes fungal blast disease. The expression of some of the genes changed markedly in response to infection by at least one of the pathogen species, and some of the genes also showed markedly different expression in resistant and susceptible reactions. In addition, some defense-responsive VQ motif-containing genes were co-expressed with defense-response WRKY genes. These results provide a new perspective on the putative roles of rice VQ motif-containing proteins and their putative WRKY partners in rice-pathogen interactions.
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Ethanol extract of Forsythia suspensa root induces apoptosis of esophageal carcinoma cells via the mitochondrial apoptotic pathway.
Mol Med Rep
PUBLISHED: 02-03-2014
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Forsythia suspensa root is used in the treatment of fever and jaundice in Traditional Chinese Medicine. In the present study, the anti-tumor activity of the ethanolic extract of Forsythia suspensa root (FSREE) against esophageal carcinoma cells was investigated in vitro and in vivo and its anti-cancer mechanism was examined. The results revealed that FSREE, rather than Forsythia suspensa ethanolic extracts from the leaf (FSLEE) and fruit (FSFEE) exhibited marked anti-tumor activity towards human esophageal cancer cells. FSREE induced cancer cell apoptosis and growth arrest by downregulating B?cell lymphoma (Bcl)?2, Bcl?extra large and myeloid cell leukemia 1, while upregulating Bcl?2?associated X protein, Bcl?2 antagonist of cell death and phorbol?12?myristate?13?acetate?induced protein 1. This led to the activation of poly(ADP ribose) polymerase, caspase?3 and caspase?9, but not caspase?8. Furthermore, the anti-cancer activity of FSREE was associated with a decreased level of phosphorylated Janus kinase/signal transducer and activator of transcription 3 and extracellular?signal?regulated kinase signaling activity. It was also observed that the levels of cytochrome c were elevated in the cytoplasm, accounting for the loss of mitochondrial membrane potential in the TE?13 cells upon treatment with FSEER. In addition, FSEER inhibited the growth of esophageal cancer cells in xenograft models and no detectable toxicity was present in the lung or liver tissues. These observations provided further evidence of the anti-tumor effect of FSEER and may be of importance to further examine the potential role of Forsythia suspensa root as a therapeutic agent in esophageal carcinoma therapy.
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A bubble-mediated intelligent microscale electrochemical device for single-step quantitative bioassays.
Adv. Mater. Weinheim
PUBLISHED: 01-28-2014
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An intelligent microscale electrochemical device (iMED) for one-step, quantitative and multiplexed electrochemical detection of biomarkers for infectious diseases and tumors is developed. A "plug-in-cartridge" technology is introduced and adapted for use in screen-printed electrodes (SPEs) in electrochemical devices. Using this iMED, biomarkers for two types of tumors and one infectious disease are detected at sub-ng/mL levels in less than 30 min.
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Molecular logic gates on DNA origami nanostructures for microRNA diagnostics.
Anal. Chem.
PUBLISHED: 01-27-2014
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Molecular computing holds great promise for diagnosis and treatment of diseases at the molecular level; nevertheless, designing molecular logic gates to operate programmably and autonomously for molecular diagnostics still remains challenging. We designed logic gates on DNA Origami for microRNA analysis. As a demonstration, two indicators of heart failure, microRNA-21 and microRNA-195, were selected as the logic inputs. The logic gates contain two main modules: computation module and output module, performing in a single DNA Origami nanostructure. The computation module recognizes disease indicators, while the output module display different nanoscale symbols, "+" (positive) or "-" (negative), depending on the computing results. We demonstrated that the molecular logic gates worked well with single and two input combinations.
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Prostate stem cell antigen antibody-conjugated multiwalled carbon nanotubes for targeted ultrasound imaging and drug delivery.
Biomaterials
PUBLISHED: 01-17-2014
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Multiwalled carbon nanotubes (MWCNTs) are cut short and grafted with polyethylenimine (PEI) for further covalent conjugation to fluorescein isothiocyanate (FITC) and prostate stem cell antigen (PSCA) monoclonal antibody (mAb). The in vitro and in vivo toxicity data reveal that the as-prepared CNT-PEI(FITC)-mAb has good biocompatibility. Combined flow cytometry and confocal luminescence imaging experiments confirm that the CNT-PEI(FITC)-mAb can specifically target the cancer cells which overexpress PSCA. The results of in vitro and in vivo ultrasound (US) imaging indicate that CNT-PEI(FITC)-mAb has great potential to be used as a targeted US contrast agent. The in vivo anti-cancer efficacy testing using PC-3 tumor-bearing mice as animal models demonstrates that CNT-PEI(FITC)-mAb can targetedly deliver drug to the tumors and suppress tumor growth. Findings from this study suggest that the CNT-PEI(FITC)-mAb could be used as a multifunctional platform for simultaneous US imaging and drug delivery applications.
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Tungsten oxide nanorods: an efficient nanoplatform for tumor CT imaging and photothermal therapy.
Sci Rep
PUBLISHED: 01-14-2014
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We report here a facile thermal decomposition approach to creating tungsten oxide nanorods (WO2.9 NRs) with a length of 13.1 ± 3.6 nm and a diameter of 4.4 ± 1.5 nm for tumor theranostic applications. The formed WO2.9 NRs were modified with methoxypoly(ethylene glycol) (PEG) carboxyl acid via ligand exchange to have good water dispersability and biocompatibility. With the high photothermal conversion efficiency irradiated by a 980 nm laser and the better X-ray attenuation property than clinically used computed tomography (CT) contrast agent Iohexol, the formed PEGylated WO2.9 NRs are able to inhibit the growth of the model cancer cells in vitro and the corresponding tumor model in vivo, and enable effective CT imaging of the tumor model in vivo. Our "killing two birds with one stone" strategy could be extended for fabricating other nanoplatforms for efficient tumor theranostic applications.
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Rice OsPAD4 functions differently from Arabidopsis AtPAD4 in host-pathogen interactions.
Plant J.
PUBLISHED: 01-11-2014
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The extensively studied Arabidopsis phytoalexin deficient 4 (AtPAD4) gene plays an important role in Arabidopsis disease resistance; however, the function of its sequence ortholog in rice is unknown. Here, we show that rice OsPAD4 appears not to be the functional ortholog of AtPAD4 in host-pathogen interactions, and that the OsPAD4 encodes a plasma membrane protein but that AtPAD4 encodes a cytoplasmic and nuclear protein. Suppression of OsPAD4 by RNA interference (RNAi) increased rice susceptibility to the biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo), which causes bacteria blight disease in local tissue. OsPAD4-RNAi plants also show compromised wound-induced systemic resistance to Xoo. The increased susceptibility to Xoo was associated with reduced accumulation of jasmonic acid (JA) and phytoalexin momilactone A (MOA). Exogenous application of JA complemented the phenotype of OsPAD4-RNAi plants in response to Xoo. The following results suggest that OsPAD4 functions differently than AtPAD4 in response to pathogen infection. First, OsPAD4 plays an important role in wound-induced systemic resistance, whereas AtPAD4 mediates systemic acquired resistance. Second, OsPAD4-involved defense signaling against Xoo is JA-dependent, but AtPAD4-involved defense signaling against biotrophic pathogens is salicylic acid-dependent. Finally, OsPAD4 is required for the accumulation of terpenoid-type phytoalexin MOA in rice-bacterium interactions, but AtPAD4-mediated resistance is associated with the accumulation of indole-type phytoalexin camalexin.
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Contrasting soil microbial community functional structures in two major landscapes of the Tibetan alpine meadow.
Microbiologyopen
PUBLISHED: 01-06-2014
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The grassland and shrubland are two major landscapes of the Tibetan alpine meadow, a region very sensitive to the impact of global warming and anthropogenic perturbation. Herein, we report a study showing that a majority of differences in soil microbial community functional structures, measured by a functional gene array named GeoChip 4.0, in two adjacent shrubland and grassland areas, were explainable by environmental properties, suggesting that the harsh environments in the alpine grassland rendered niche adaptation important. Furthermore, genes involved in labile carbon degradation were more abundant in the shrubland than those of the grassland but genes involved in recalcitrant carbon degradation were less abundant, which was conducive to long-term carbon storage and sequestration in the shrubland despite low soil organic carbon content. In addition, genes of anerobic nitrogen cycling processes such as denitrification and dissimilatory nitrogen reduction were more abundant, shifting soil nitrogen cycling toward ammonium biosynthesis and consequently leading to higher soil ammonium contents. We also noted higher abundances of stress genes responsive to nitrogen limitation and oxygen limitation, which might be attributed to low total nitrogen and higher water contents in the shrubland. Together, these results provide mechanistic knowledge about microbial linkages to soil carbon and nitrogen storage and potential consequences of vegetation shifts in the Tibetan alpine meadow.
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Rice MtN3/saliva/SWEET gene family: Evolution, expression profiling, and sugar transport.
J Integr Plant Biol
PUBLISHED: 01-06-2014
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The rice MtN3/saliva/SWEET gene family consists of 21 paralogs. However, their functions in physiological processes are largely unknown, although at least three of the 21 paralogs are used by pathogenic bacteria to infect rice. Here, we report the evolutionary features, transcriptional characteristics, and putative functions in sugar transport of this gene family. The wild rice accessions in this study included those with AA, BB, CC, BBCC, CCDD, EE, and GG genomes, which appeared approximately 0.58-14.6 million years ago. The structures, chromosomal locations, phylogenetic relationships, and homologous distribution among the accessions suggest that the number of rice MtN3/saliva/SWEET paralogs gradually increased as the Oryza genus evolved, and one third of the paralogs may have originated recently. These paralogs are differentially expressed in vegetative and reproductive tissues, in the leaf senescence process, and in signaling dependent on gibberellic acid, cytokinin, or 1-naphthalene acetic acid (an analog of auxin), suggesting that they may be associated with multiple physiological processes. Four paralogs could transport galactose in yeast, which suggests that they may have a similar function in rice. These results will help to elucidate their roles and biochemical functions in rice development, adaptation to environment, host-pathogen interaction, and so forth.
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Alpine grassland soil organic carbon stock and its uncertainty in the three rivers source region of the Tibetan Plateau.
PLoS ONE
PUBLISHED: 01-01-2014
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Alpine grassland of the Tibetan Plateau is an important component of global soil organic carbon (SOC) stocks, but insufficient field observations and large spatial heterogeneity leads to great uncertainty in their estimation. In the Three Rivers Source Region (TRSR), alpine grasslands account for more than 75% of the total area. However, the regional carbon (C) stock estimate and their uncertainty have seldom been tested. Here we quantified the regional SOC stock and its uncertainty using 298 soil profiles surveyed from 35 sites across the TRSR during 2006-2008. We showed that the upper soil (0-30 cm depth) in alpine grasslands of the TRSR stores 2.03 Pg C, with a 95% confidence interval ranging from 1.25 to 2.81 Pg C. Alpine meadow soils comprised 73% (i.e. 1.48 Pg C) of the regional SOC estimate, but had the greatest uncertainty at 51%. The statistical power to detect a deviation of 10% uncertainty in grassland C stock was less than 0.50. The required sample size to detect this deviation at a power of 90% was about 6-7 times more than the number of sample sites surveyed. Comparison of our observed SOC density with the corresponding values from the dataset of Yang et al. indicates that these two datasets are comparable. The combined dataset did not reduce the uncertainty in the estimate of the regional grassland soil C stock. This result could be mainly explained by the underrepresentation of sampling sites in large areas with poor accessibility. Further research to improve the regional SOC stock estimate should optimize sampling strategy by considering the number of samples and their spatial distribution.
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Functional nanoprobes for ultrasensitive detection of biomolecules: an update.
Chem Soc Rev
PUBLISHED: 12-17-2013
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With the rapidly increasing demands for ultrasensitive biodetection, the design and applications of functional nanoprobes have attracted substantial interest for biosensing with optical, electrochemical, and various other means. In particular, given the comparable sizes of nanomaterials and biomolecules, there exists plenty of opportunities to develop functional nanoprobes with biomolecules for highly sensitive and selective biosensing. Over the past decade, numerous nanoprobes have been developed for ultrasensitive bioaffinity sensing of proteins and nucleic acids in both laboratory and clinical applications. In this review, we provide an update on the recent advances in this direction, particularly in the past two years, which reflects new progress since the publication of our last review on the same topic in Chem. Soc. Rev. The types of probes under discussion include: (i) nanoamplifier probes: one nanomaterial loaded with multiple biomolecules; (ii) quantum dots probes: fluorescent nanomaterials with high brightness; (iii) superquenching nanoprobes: fluorescent background suppression; (iv) nanoscale Raman probes: nanoscale surface-enhanced Raman resonance scattering; (v) nanoFETs: nanomaterial-based electrical detection; and (vi) nanoscale enhancers: nanomaterial-induced metal deposition.
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Facile adsorption-dry process to incorporate Cu into TiO2 nanotube for highly efficient photocatalytic hydrogen production.
J Nanosci Nanotechnol
PUBLISHED: 11-20-2013
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Cu species was introduced into TiO2 nanotube prepared by hydrothermal method via a facile adsorption-dry process. The fabricated sample exhibited excellent H2 generation activity (76.3 mmol h(-1) g(-1)(catalyst)), which was higher than most of the reported Cu incorporated TiO2 samples, even superior to some Pt/Pd/Au/Ni incorporated TiO2. Compared to wet impregnation and in-situ photo-deposition methods, the facile adsorption-dry process was much simpler but more efficient to introduce Cu species into TiO2 for H2 production. To fully understand the adsorption-dry process, characterizations of the samples were carried out by high-resolution transmission electron microscope, X-ray diffractometer, energy dispersive X-ray spectrometer, BET surface area analysis, UV-visible spectrophotometer and X-ray photoelectron spectroscopy. It was found that the facile adsorption-dry process could well maintain the morphology of TiO2 support, for instance, 1-D tubular structure and large BET surface area of TiO2 nanotube; moreover, the introduced Cu species was highly dispersed and intensively bonded with TiO2. All of these contributed to the high H2 generation activity.
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Synthesis of HCV Replicase Inhibitors: Base-Catalyzed Synthesis of Protected ?-Hydrazino Esters and Selective Aerobic Oxidation with Catalytic Pt/Bi/C for Synthesis of Imidazole-4,5-dicarbaldehyde.
J. Org. Chem.
PUBLISHED: 11-13-2013
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A robust convergent synthesis of the prodrugs of HCV replicase inhibitors 1-5 is described. The central 5H-imidazo[4,5-d]pyridazine core was formed from acid-catalyzed cyclocondensation of an imidazole-4,5-dicarbaldehyde (20) and a ?-hydrazino ester, generated in situ from the bis-BOC-protected precursors 25 and 33. The acidic conditions not only released the otherwise unstable ?-hydrazino esters but also were the key to avoid facile decarboxylation to the parent drugs from the carboxylic ester prodrugs 1-5. The bis-BOC ?-hydrazino esters 25 and 33 were prepared by addition of ester enolates (from 23 and 32) to di-tert-butyl azodicarboxylate via catalysis with mild inorganic bases, such as Li2CO3. A selective aerobic oxidation with catalytic 5% Pt-Bi/C in aqueous KOH was developed to provide the dicarbaldehyde 20 from the diol 27.
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Asymmetric synthesis of chiral dihydrothiopyrans via an organocatalytic enantioselective formal thio [3 + 3] cycloaddition reaction with binucleophilic bisketone thioethers.
Org. Lett.
PUBLISHED: 10-23-2013
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An unprecedented organocatalytic highly enantioselective approach to a 3,4-dihydro-2H-thiopyran scaffold with two contiguous stereogenic centers has been implemented through a formal thio [3 + 3] cycloaddition process involving a Michael-aldol condensation cascade sequence. Notably, a new class of binucleophilic bisketone thioethers is designed for the process. Furthermore, the fine-tuning of their reactivity enables the cascade process to proceed with highly regioselectively.
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Rice WRKY13 Regulates Cross Talk between Abiotic and Biotic Stress Signaling Pathways by Selective Binding to Different cis-Elements.
Plant Physiol.
PUBLISHED: 10-15-2013
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Plants use a complex signal transduction network to regulate their adaptation to the ever-changing environment. Rice (Oryza sativa) WRKY13 plays a vital role in the cross talk between abiotic and biotic stress signaling pathways by suppressing abiotic stress resistance and activating disease resistance. However, it is not clear how WRKY13 directly regulates this cross talk. Here, we show that WRKY13 is a transcriptional repressor. During the rice responses to drought stress and bacterial infection, WRKY13 selectively bound to certain site- and sequence-specific cis-elements on the promoters of SNAC1 (for STRESS RESPONSIVE NO APICAL MERISTEM, ARABIDOPSIS TRANSCRIPTION ACTIVATION FACTOR1/2, CUP-SHAPED COTYLEDON), the overexpression of which increases drought resistance, and WRKY45-1, the knockout of which increases both bacterial disease and drought resistance. WRKY13 also bound to two cis-elements of its native promoter to autoregulate the balance of its gene expression in different physiological activities. WRKY13 was induced in leaf vascular tissue, where bacteria proliferate, during infection, and in guard cells, where the transcriptional factor SNAC1 enhances drought resistance, during both bacterial infection and drought stress. These results suggest that WRKY13 regulates the antagonistic cross talk between drought and disease resistance pathways by directly suppressing SNAC1 and WRKY45-1 and autoregulating its own expression via site- and sequence-specific cis-elements on the promoters of these genes in vascular tissue where bacteria proliferate and guard cells where the transcriptional factor SNAC1 mediates drought resistance by promoting stomatal closure.
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Effect of nonionic compound emulsifiers Tween80 and Span80 on the properties of microencapsulated phase change materials.
J Microencapsul
PUBLISHED: 10-14-2013
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Abstract In this article, the nonionic compound emulsifiers Tween80 and Span80 were used to prepare microcapsules containing phase change materials (microPCMs) with melamine-formaldehyde (MF) shells by in situ polymerization method. The effects of compound emulsifiers Tween80 and Span80 on the structure, morphologies and properties of microPCMs containing paraffin were studied. SEM morphological investigation suggests that a complex of Tween80 and Span80 as emulsifiers are optimal for the fabrication of microPCMs in this study compared to Tween60 or OP-10. The diameter distributions of microPCMs synthesized with different amounts of compound emulsifiers are uniform, whereas compound emulsifiers amount affect the mean diameter of microPCMs decreasing from 5.34 to 3.05?µm. These microPCMs with the core/shell weight ratio 3/1 have smoother surface and a higher core content of 68.7% than other core/shell ratio. Anti-osmosis measurements indicate that microPCMs have good compactness and stable performance compared to those synthesized by one type of emulsifier.
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A New Strategy To Improve the Metabolic Stability of Lactone: Discovery of (20S,21S)-21-Fluorocamptothecins as Novel, Hydrolytically Stable Topoisomerase I Inhibitors.
J. Med. Chem.
PUBLISHED: 10-09-2013
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Lactone is a common structural motif in biologically active natural products. However, the metabolic instability of lactone significantly reduces their in vivo potency. In the present investigation, a new strategy to improve the metabolic stability of lactone was provided by the design of ?-fluoro ether as a novel bioisostere of lactone. The effectiveness of the ?-fluoro ether/lactone replacement was validated by the discovery of (20S,21S)-21-fluorocamptothecins as hydrolytically stable topoisomerase I inhibitors. A highly potent camptothecin derivative, 8l, was successfully identified, which showed excellent in vitro and in vivo antitumor activities and represents a promising lead for the discovery of novel antitumor agents. Interestingly, this study also provided a new structure-activity relationship for the C21-carbonyl group of camptothecin, which has been regarded as an essential pharmacophore. Our results revealed that the conserved C21-carbonyl group can be replaced by a fluorine substituent. ?-Fluoro ether may have general application in improving the metabolic stability of lactone.
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Aptamer-conjugated Mn3O4@SiO2 core-shell nanoprobes for targeted magnetic resonance imaging.
Nanoscale
PUBLISHED: 09-13-2013
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The objective of this study was to evaluate the targeted T1-magnetic resonance imaging (MRI), quantitative biodistribution and toxicity of aptamer (AS411) conjugated Mn3O4@SiO2 core-shell nanoprobes (NPs) in human cervical carcinoma tumor-bearing mice. The NPs were firstly prepared by encapsulating a hydrophobic Mn3O4 core within an amino functionalized silica shell. The fluorophore rhodamine (RB) was doped into the silica shell and the amphiphilic polymer poly(ethylene glycol) (PEG) was modified on the surface of the shell to improve its biocompatibility, then the aptamer AS411 was conjugated onto the end of the PEG chains as targeting ligands. The final NPs were abbreviated as Mn3O4@SiO2(RB)-PEG-Apt. By means of in vitro fluorescence confocal imaging and in vivo MRI, the NPs have been demonstrated to target cancer cells and prominent tumor aggregation effectively. The imaging results were further confirmed by a quantitative biodistribution study. In addition, histological, hematological and biochemistry analysis also proved the low toxicity of NPs in vivo. Our results showed the great potential of the Mn3O4@SiO2(RB)-PEG-Apt NPs could be used as a multifunctional nanoplatform for long-term targeted imaging and therapy of cancer.
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Unsorted single walled carbon nanotubes enabled the fabrication of high performance organic thin film transistors with low cost metal electrodes.
Chem. Commun. (Camb.)
PUBLISHED: 08-21-2013
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Transistors with a diketopyrrolopyrrole-quarterthiophene (DPP-QT) semiconductor and low-cost Al or Cu electrodes were studied. Albeit a large charge injection resistance exists between DPP-QT and Al or Cu, the resistance was dramatically reduced when unsorted single walled carbon nanotubes (SWCNTs) were blended into the DPP-QT film. This led to a high mobility of 0.64 and 1.1 cm(2) V(-1) s(-1), respectively, for Al and Cu devices, which is similar or even better than the device using gold electrodes (0.78 cm(2) V(-1) s(-1)).
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Aerobic Ru-catalyzed direct C2-olefination of N-heteroarenes with alkenes directed by a removable N-dimethylcarbamoyl group.
Chem. Commun. (Camb.)
PUBLISHED: 08-21-2013
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A highly efficient and selective Ru-catalyzed direct C2-olefination of indoles, pyrroles, and carbazoles assisted by a removable N-dimethylcarbamoyl group has been developed by using O2 as the terminal oxidant. Both electron-deficient and unactivated alkenes are applicable to the protocol.
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Asymmetric effects of daytime and night-time warming on Northern Hemisphere vegetation.
Nature
PUBLISHED: 07-04-2013
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Temperature data over the past five decades show faster warming of the global land surface during the night than during the day. This asymmetric warming is expected to affect carbon assimilation and consumption in plants, because photosynthesis in most plants occurs during daytime and is more sensitive to the maximum daily temperature, Tmax, whereas plant respiration occurs throughout the day and is therefore influenced by both Tmax and the minimum daily temperature, Tmin. Most studies of the response of terrestrial ecosystems to climate warming, however, ignore this asymmetric forcing effect on vegetation growth and carbon dioxide (CO2) fluxes. Here we analyse the interannual covariations of the satellite-derived normalized difference vegetation index (NDVI, an indicator of vegetation greenness) with Tmax and Tmin over the Northern Hemisphere. After removing the correlation between Tmax and Tmin, we find that the partial correlation between Tmax and NDVI is positive in most wet and cool ecosystems over boreal regions, but negative in dry temperate regions. In contrast, the partial correlation between Tmin and NDVI is negative in boreal regions, and exhibits a more complex behaviour in dry temperate regions. We detect similar patterns in terrestrial net CO2 exchange maps obtained from a global atmospheric inversion model. Additional analysis of the long-term atmospheric CO2 concentration record of the station Point Barrow in Alaska suggests that the peak-to-peak amplitude of CO2 increased by 23?±?11% for a +1?°C anomaly in Tmax from May to September over lands north of 51°?N, but decreased by 28?±?14% for a +1?°C anomaly in Tmin. These lines of evidence suggest that asymmetric diurnal warming, a process that is currently not taken into account in many global carbon cycle models, leads to a divergent response of Northern Hemisphere vegetation growth and carbon sequestration to rising temperatures.
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Multifunctional Polypyrrole@Fe3 O4 Nanoparticles for Dual-Modal Imaging and In Vivo Photothermal Cancer Therapy.
Small
PUBLISHED: 07-02-2013
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Magnetic Fe3 O4 crystals are produced in situ on preformed polypyrrole (PPY) nanoparticles by rationally converting the residual Fe species in the synthetic system. The obtained PPY@Fe3 O4 composite nanoparticles exhibit good photostability and biocompatibility, and they can be used as multifunctional probes for MRI, thermal imaging, and photothermal ablation of cancer cells.
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Numerical simulation of bubble dynamics in an elastic vessel.
Eur Phys J E Soft Matter
PUBLISHED: 06-08-2013
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The nonlinear evolution of a gas bubble in the middle of an elastic vessel is investigated numerically. The fluids inside and outside the vessel are assumed to be incompressible and potential. A boundary element method (BEM) is adopted to solve the Laplace equation for the velocity potential. The gas inside the bubble is described by the Boyle Law. The fluid outside the vessel is assumed to contain the elasticity. The dynamic boundary condition on the vessel interface i is obtained from the derived Bernoulli Equation. This numerical model is validated through the comparisons with both the analytic solution of Rayleigh-Plesset equation and spark bubble experiment. The bubble dynamic behavior with different elastic parameters and vessel inner radius is further discussed.
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Sub-10 nm Fe3O4@Cu(2-x)S core-shell nanoparticles for dual-modal imaging and photothermal therapy.
J. Am. Chem. Soc.
PUBLISHED: 05-30-2013
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Photothermal nanomaterials have recently attracted significant research interest due to their potential applications in biological imaging and therapeutics. However, the development of small-sized photothermal nanomaterials with high thermal stability remains a formidable challenge. Here, we report the rational design and synthesis of ultrasmall (<10 nm) Fe3O4@Cu2-xS core-shell nanoparticles, which offer both high photothermal stability and superparamagnetic properties. Specifically, these core-shell nanoparticles have proven effective as probes for T2-weighted magnetic resonance imaging and infrared thermal imaging because of their strong absorption at the near-infrared region centered around 960 nm. Importantly, the photothermal effect of the nanoparticles can be precisely controlled by varying the Cu content in the core-shell structure. Furthermore, we demonstrate in vitro and in vivo photothermal ablation of cancer cells using these multifunctional nanoparticles. The results should provide improved understanding of synergistic effect resulting from the integration of magnetism with photothermal phenomenon, important for developing multimode nanoparticle probes for biomedical applications.
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Facile construction of structurally diverse thiazolidinedione-derived compounds via divergent stereoselective cascade organocatalysis and their biological exploratory studies.
ACS Comb Sci
PUBLISHED: 05-08-2013
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In this article, we present a new approach by merging two powerful synthetic tactics, divergent synthesis and cascade organocatalysis, to create a divergent cascade organocatalysis strategy for the facile construction of new "privileged" substructure-based DOS (pDOS) library. As demonstrated, notably 5 distinct molecular architectures are produced facilely from readily available simple synthons thiazolidinedione and its analogues and ?,?-unsaturated aldehydes in 1-3 steps with the powerful strategy. The beauty of the chemistry is highlighted by the efficient formation of structurally new and diverse products from structurally close reactants under the similar reaction conditions. Notably, structurally diverse spiro-thiazolidinediones and -rhodanines are produced from organocatalytic enantioselective 3-component Michael-Michael-aldol cascade reactions of respective thiazolidinediones and rhodanines with enals. Nevertheless, under the similar reaction conditions, reactions of isorhodanine via a Michael-cyclization cascade lead to structurally different fused thiopyranoid scaffolds. This strategy significantly minimizes time- and cost-consuming synthetic works. Furthermore, these molecules possess high structural complexity and functional, stereochemical, and skeletal diversity with similarity to natural scaffolds. In the preliminary biological studies of these molecules, compounds 4f, 8a, and 10a exhibit inhibitory activity against the human breast cancer cells, while compounds 8a, 9a, and 9b display good antifungal activities against Candida albicans and Cryptococcus neoformans. Notably, their structures are different from clinically used triazole antifungal drugs. Therefore, they could serve as good lead compounds for the development of new generation of antifungal agents.
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Formation and evolution mechanisms of plasmon-induced transparency in MDM waveguide with two stub resonators.
Opt Express
PUBLISHED: 04-24-2013
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We demonstrate the realization of plasmonic analog of electromagnetically induced transparency (EIT) in a system composing of two stub resonators side-coupled to metal-dielectric-metal (MDM) waveguide. Based on the coupled mode theory (CMT) and Fabry-Perot (FP) model, respectively, the formation and evolution mechanisms of plasmon-induced transparency by direct and indirect couplings are exactly analyzed. For the direct coupling between the two stub resonators, the FWHM and group index of transparent window to the inter-space are more sensitive than to the width of one cut, and the high group index of up to 60 can be achieved. For the indirect coupling, the formation of transparency window is determined by the resonance detuning, but the evolution of transparency is mainly attributed to the change of coupling distance. The consistence between the analytical solution and finite-difference time-domain (FDTD) simulations verifies the feasibility of the plasmon-induced transparency system. It is also interesting to notice that the scheme is easy to be fabricated and may pave the way to highly integrated optical circuits.
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Graphene-based nanoprobes and a prototype optical biosensing platform.
Biosens Bioelectron
PUBLISHED: 04-11-2013
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Biochemical and biomedical applications of graphene are critically dependent on the interaction between biomolecules and the nanomaterial. In this work, we developed a graphene-based signal-amplification nanoprobe by combining anti-immunoglobulin G (anti-IgG) and horseradish peroxidase (HRP) with graphene oxide (GO). The structure and function of HRP in the nano-interface of GO were firstly investigated, which demonstrated that the enzyme retained 78% of its native activity and 77% of its native ?-helix content. HRP and anti-IgG were then co-adsorbed onto GO to form bifunctional nanoprobes. The nanoprobes provide both improved binding ability and signal-amplification ability. Comparing with conventional bioconjugates such as enzyme-linked antibody, co-adsorption could avoid chemical conjugation between biomolecules, keeping their bioactivity well. As an example for their application, the nanoprobes were used to obtain amplified signals in a sandwich-type immunoassay for cancer marker, instead of conventional colorimetric conjugates. This approach provided a detection limit of 10 pg/mL alpha-fetoprotein (AFP), which was much more sensitive than conventional enzyme-linked immunosorbent assay (ELISA) methods. The easily fabricated GO-based nanoprobes have the potential to become universal probes for molecular diagnostics.
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Corticotropin releasing hormone is correlated with tumorigenesis of gastric cancer.
Cancer Invest.
PUBLISHED: 03-13-2013
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The etiology of gastric cancer is unclear; its therapeutic effect is poor; the anatomical factor and lack of specific diagnostic markers are part of the reason. Recent reports indicate corticotropin releasing hormone (CRH) is associated with the pathogenesis of cancer. This study is designed to assess the levels of CRH in gastric tissue of a group of patients with gastric cancer and gastric chronic inflammation.
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A power-free microfluidic chip for SNP genotyping using graphene oxide and a DNA intercalating dye.
Chem. Commun. (Camb.)
PUBLISHED: 03-08-2013
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We herein report a power-free microfluidic chip for fluorescent DNA detection with high single-nucleotide polymorphism discrimination, using a DNA intercalator and graphene oxide.
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The microbial gene diversity along an elevation gradient of the Tibetan grassland.
ISME J
PUBLISHED: 03-05-2013
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Tibet is one of the most threatened regions by climate warming, thus understanding how its microbial communities function may be of high importance for predicting microbial responses to climate changes. Here, we report a study to profile soil microbial structural genes, which infers functional roles of microbial communities, along four sites/elevations of a Tibetan mountainous grassland, aiming to explore the potential microbial responses to climate changes via a strategy of space-for-time substitution. Using a microarray-based metagenomics tool named GeoChip 4.0, we showed that microbial communities were distinct for most but not all of the sites. Substantial variations were apparent in stress, N and C-cycling genes, but they were in line with the functional roles of these genes. Cold shock genes were more abundant at higher elevations. Also, gdh converting ammonium into urea was more abundant at higher elevations, whereas ureC converting urea into ammonium was less abundant, which was consistent with soil ammonium contents. Significant correlations were observed between N-cycling genes (ureC, gdh and amoA) and nitrous oxide flux, suggesting that they contributed to community metabolism. Lastly, we found by Canonical correspondence analysis, Mantel tests and the similarity tests that soil pH, temperature, NH4(+)-N and vegetation diversity accounted for the majority (81.4%) of microbial community variations, suggesting that these four attributes were major factors affecting soil microbial communities. On the basis of these observations, we predict that climate changes in the Tibetan grasslands are very likely to change soil microbial community functional structure, with particular impacts on microbial N-cycling genes and consequently microbe-mediated soil N dynamics.The ISME Journal advance online publication, 29 August 2013; doi:10.1038/ismej.2013.146.
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Guest induced morphological transformation from nanospheres to nanowires by hydrogen bond self-assembly.
Dalton Trans
PUBLISHED: 03-02-2013
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Phosphorescent nanospheres of a carboxyl-functionalized iridium complex ([Ir(ppy)2(Hdcbpy)], ppy: 2-phenylpyridine; Hdcbpy: 4-carboxy-2,2-bipyridyl-4-carboxylate) were prepared by a conventional precipitation method. Driven by hydrogen bond interaction between carboxylic groups of the complex and the guest molecule tris(imidazoline), these nanospheres can be transformed into 1-dimensional nanowires in the presence of tris(imidazoline) at the concentration of the iridium complex higher than 4.8 mM, while nanowires change back to nanospheres with the diameter obviously smaller than that of the sole complex of [Ir(ppy)2(Hdcbpy)]. The interaction between carboxylic groups and tris(imidazoline) molecules was confirmed by FT-IR spectra. The structures of the nanowires and nanospheres were further studied by XRD diffraction analysis. With the morphological transformation from nanospheres to nanowires, the phosphorescence of nanostructures was blue shifted from 590 to 564 nm.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.