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Background Coumarin and 3,4-dihydroquinolinone nuclei are two heterocyclic rings that are important and widely exploited for the development of bioactive molecules. Here, we designed and synthesized a series of 3,4-dihydroquinolinone and coumarin derivatives (Compounds 8, 9, 11, 14, 15, 18-20, 23, 24 and 28 are new compounds) and studied their antidepressant activities. Methods Forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant activity of the target compounds. The most active compound was used to evaluate the exploratory activity of the animals by the open-field test. 5-HT concentration was estimated to evaluate if the compound has an effect on the mouse brain, by using ELISA. A 5-HT1A binding assay was also performed. The biological activities of the compounds were verified by molecular docking studies. The physicochemical and pharmacokinetic properties of the target compounds were predicted by Discovery Studio and ChemBioDraw Ultra. Results Of all the compounds tested, compound 7 showed the best antidepressant activity, which decreased the immobility time by 65.52 s in FST. However, in the open-field test, compound 7 did not affect spontaneous activity. The results of 5-HT concentration estimation in vivo showed that compound 7 may have an effect on the mouse brain. Molecular docking results indicated that compound 7 showed significant interactions with residues at the 5-HT1A receptor using homology modeling. The results show that compound 7 exhibits good affinity for the 5-HT1A receptor. Conclusion Coumarin and 3,4-dihydroquinolinone derivatives synthesized in this study have a significant antidepressant activity. These findings can be useful in the design and synthesis of novel antidepressants.

Targeting neddylation pathway has been recognized as an attractive anticancer therapeutic strategy, thus discovering potent and selective neddylation inhibitors is highly desirable. Our work reported the discovery of novel cinnamyl piperidine compounds and their antitumor activity in vitro and in vivo. Among these compounds, compound 4g was identified as a novel neddylation inhibitor and decreased the neddylation levels of cullin 1, cullin 3 and cullin 5. Mechanistic studies demonstrated that compound 4g could inhibit the migration ability of gastric cancer cells and induce apoptosis partly mediated by the Nrf2-Keap1 pathway. Furthermore, in vivo anti-tumor studies showed that 4g effectively inhibited tumor growth without obvious toxicity. Collectively, the cinnamyl piperidine derivatives could serve as new lead compounds for developing highly effective neddylation inhibitors for gastric cancer therapy.

AIM: To investigate the relationship between semaphorin 7a expression and cell proliferation and migration in pterygium fibroblasts. METHODS: Twenty-six patients with surgically diagnosed pterygium were enrolled, including 15 cases of primary pterygium and 11 cases of recurrent pterygium. In addition, 12 cases of normal conjunctival tissue were collected. The expression of semaphorin 7a in normal conjunctival tissue, primary pterygium and recurrent pterygium was detected by real-time polymerase chain reaction. Recurrent pterygium fibroblasts were isolated and cultured, and the expression of semaphorin 7a was silenced by small interfering RNA (siRNA) interference technique. Furthermore, the effects of si-semaphorin 7a interference on the mRNA and protein levels of β1-integrin, vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor (VEGFR), and on fibroblast proliferation were analyzed. Transwell assay was used to detect the effect of semaphorin 7a interference on fibroblast migration. RESULTS: Semaphorin 7a was highly expressed in the primary pterygium and recurrent pterygium samples than that of the normal conjunctival tissue. Compared with the primary pterygium, the expression of semaphoring 7a in the recurrent pterygium samples was significantly increased (P

Two series of furo[3,2-f]quinoline-2-carboxylate were obtained via a three-component reaction of aldehydes, 5-aminobenzofuran-2-carboxylate, and 4-hydroxy-2H-chromen-2-one or cyclopentane-1,3-dione in DMF under catalyst-free condition in high yields. This one-pot three-component reaction provided an efficient method for the synthesis of fused polycyclic heterocycles for bioactive screening.

A series of 7-phenyl-4,5,6,7-tetrahydrothieno[3,2-b]pyridine derivatives containing triazole and other heterocycle substituents (methyltriazole, tetrazole, and triazolone) is described. Two experimental methods, maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ), were used to evaluate the anticonvulsant activity of the target compounds. Moreover, the neurotoxicity (NT) was tested using the Rotarod test. 5-(4-Chlorophenyl)-4,5-dihydrothieno[2,3-e][1,2,4]triazolo[4,3-a]pyridine (6c) showed the best anticonvulsant activity. In the MES and PTZ experiments, the 50% effective dose (ED50 ) values of compound 6c were 9.5 and 20.5 mg/kg, respectively. From the therapeutic index (PI) values, 6c (MES and PTZ with PI values of 48.0 and 22.2, respectively) showed better safety than the clinical drugs carbamazepine (MES with PI value of 6.4) and ethosuximide (PTZ with PI value of 3.2). The biological activities of the compounds were verified by using molecular docking studies. Compound 6c showed significant interactions with residues at the benzodiazepine-binding site on gamma-aminobutyric acid A (GABAA ) receptors. The results of in vivo GABA estimation and bicuculline-induced seizures showed that 6c may have an effect on the GABA system. The physicochemical and pharmacokinetic properties of the target compounds were predicted.

The cullin-RING ubiquitin ligases (CRLs) are responsible for about 20% of cellular protein degradation and regulate diverse cellular processes, and the dysfunction of CRLs is implicated in human diseases. Targeting the CRLs has become an emerging strategy for the treatment of human diseases. Herein, we describe the discovery of a hit compound from our in-house library and further structure-based optimizations, which have enabled the identification of new triazolo[1,5-a]pyrimidine-based inhibitors targeting the DCN1–UBC12 interaction. Compound WS-383 blocks the DCN1–UBC12 interaction (IC50 = 11 nM) reversibly and shows selectivity over selected kinases. WS-383 exhibits cellular target engagement to DCN1 in MGC-803 cells. WS-383 inhibits Cul3/1 neddylation selectively over other cullins and also induces accumulation of p21, p27, and NRF2. Collectively, targeting the DCN1–UBC12 interaction would be a viable strategy for selective neddylation inhibition of Cul3/1 and may be of therapeutic potential for diseas...

In this paper, an atmospheric pressure polyethylene terephthalate dielectric barrier discharge is produced in a helium–argon mixture. The influences of the electrode voltage on the discharge mode are experimentally investigated. The results show that, at a fixed argon content of 50%, the discharge transits from local uniform, through the isolated pattern, to whole uniform with the increase in the electrode voltage. Both the peak value of current pulse and argon spectra (696.54, 763.13, 772.09, 811.17, and 911.81 nm) intensities are captured to clarify the characteristics of the discharge mode transition. The different discharge characteristic regions are obtained by varying the argon content. In addition, the influence of the argon content on the above-mentioned argon spectra intensities is also researched. The spectra intensities enhance at 696.54, 763.13, and 772.09 nm but weaken at 811.17 and 911.81 nm with the increase in the argon content when the discharge operates in the whole uniform mode. The physical reasons for these results are discussed.

Alkaline phosphatase (ALP) is an important biomarker for diagnosis, and the abnormal level of serum ALP is closely related to a variety of diseases. In present work, a ratiometric fluorescence probe based on hybrid nanoparticles CDs@YVO4: Dy3+ nanoparticle is introduced for alkaline phosphatase (ALP) activity determination. The CDs@YVO4: Dy3+ probe is constructed by the carbon dots (CDs) and YVO4: Dy3+ through a simple mixing method, in which the blue emission of CDs at 405 nm acts as the calibrated signal, the green emission of YVO4: Dy3+ at 574 nm decreased with the increasing targets ALP, and used as the output signal. In addition, the Cu2+ and pyrophosphate (PPi) were also employed in this strategy to utilize the excellent fluorescnece quenching efficiency of Cu2+ to the Dy3+ ions emission of CDs@YVO4: Dy3+, as well as the strong affinity of PPi for Cu2+. In the presence of analyts ALP, ALP catalyzes the hydrolysis of PPi, causing the release of Cu2+, resulting in the Dy3+ ions emission quenched, while the CDs emission at 405 nm retained unchanged, based on this, we designed the off-on-off ratiometric fluorescence platform for ALP sensing. The experiment result shows that the ratio of F574/F405 is linear to the concentration of ALP in arange of 0.05∼3000 U/L with a detection limit of 0.04 U/L, which is comparable or better than those reported fluorescence probe, especially the calibrated signal introduction of CDs can eliminate the background interference, improve the accuracy of proposed probe greatly. Furthermore, the discrimination of ALP enzyme inhibitor with the IC50 of 26 μM, and ALP concentration in real human serum sample has also demonstrated the applicability of CDs@YVO4: Dy3+ fluorescence sensor well.

Ischemia–reperfusion (I/R) injury after a liver transplant is a major cause of severe complications that lead to graft dysfunction. Fucoidan, a complex of sulfated polysaccharides derived from marine brown algae, demonstrated antiapoptotic as well as potential anti-inflammatory properties in previous studies. Fucoidan has also shown protective effects on I/R-injured kidney and heart. However, whether fucoidan can attenuate hepatic I/R injury has not been examined. To clarify the role of fucoidan in hepatic I/R injury, Sprague–Dawley rats were subjected to sham operation or ischemia followed by reperfusion with treatment of saline or fucoidan (50, 100, or 200 mg·(kg body mass)−1·d−1). The fucoidan-treated group showed decreased levels of alanine aminotransferase and aspartate aminotransferase compared with the control group. Myeloperoxidase and malondialdehyde activities and mRNA levels of CD11b in the fucoidan-treated group were significantly decreased. Hepatocellular swelling/necrosis, sinusoidal/vascular congestion, and inflammatory cell infiltration were also attenuated in the fucoidan group. The expression of TNF-α, IL-6, IL-1β, CXCL-10, VCAM-1, and ICAM-1 were markedly decreased in the samples from the fucoidan-treated group. Fucoidan largely prevented activation of the inflammatory signaling pathway, compared with the control group. In summary, fucoidan can protect the liver from I/R injury through suppressing activation of the inflammatory signaling pathway, as well as the expression of inflammatory mediators, and inflammatory cell infiltration.

A simple and green method for the determination of trace bisphenol A (BPA) was established by coupling supported ionic liquid solid-phase extraction to β -cyclodextrin modified ionic liquids carbon paste electrode-based electrochemical detection (SILs-SPE-ED). The synthesized imidazolium ionic liquids modified styrene type macroporous resin was used as adsorbent for SPE of BPA. The experimental parameters that affected the extraction efficiency were investigated and optimized. Dynamic adsorption test showed that the maximum adsorption capacity of BPA on the SILs-SPE cartridge was 10.1 mg g −1 , and the enrichment factor was 40. The calibration curve showed a good linearity between the anodic current and the BPA concentration in the range of 1.0 × 10 −8 −1.0 × 10 −6 M. The detection limit was 4.16 nM (equal to 0.95 μg L −1 ). The SILs-SPE-ED method, with the advantages including high sensitivity and good practicability, was applied to the analysis of real water and plastic samples, and the results agreed well with HPLC method.

Porous carbons (PCs) for super capacitors were prepared from coal tar pitch by a one-step microwave-assisted KOH activation with low KOH consumption. The surface area of the PC (PC 2− M ) made at a KOH/pitch mass ratio of 2 with microwave heating for 30 min reaches 1786 m 2 /g. The electrochemical performance of the PC electrode for super capacitors was evaluated in different electrolytes including KOH, K 2 SO 4 , Na 2 SO 4 , Li 2 SO 4 in water, and tetraethylammonia tetrafluoroborate in propylene carbonate. The super capacitors have a high specific capacitance of 267 F/g in 6 M KOH aqueous electrolyte at 0.1 A/g and a high energy density of 12.0 W/kg at 1318 W/kg in a 0.5 M K 2 SO 4 neutral electrolyte. The one-step microwave-assisted KOH activation is a simple, efficient and low energy-consumption approach for the preparation of high performance PCs for super capacitors. [New Carbon Materials 2014, 29(6): 493–502]

This work presents a theoretical demonstration of the Aharonov-Bohm (AB) effect in monolayer phosphorene nanorings (PNRs). Atomistic quantum transport simulations of PNRs are employed to investigate the impact of multiple modulation sources on the sample conductance. In the presence of a perpendicular magnetic field, we find that the conductance of both armchair and zigzag PNRs oscillate periodically in a low-energy window as a manifestation of the AB effect. Our numerical results reveal a giant magnetoresistance (MR) in zigzag PNRs (with a maximum magnitude approaching 2000%). It is attributed to the AB-effect-induced destructive interference phase over a wide energy range below the bottom of the second subband. We also demonstrate that PNR conductance is highly anisotropic, offering an additional way to modulate MR. The giant MR in PNRs is maintained at room temperature in the presence of the thermal broadening effect.

Molecularly imprinted polymers for dimethoate recognition were synthesized by the precipitation polymerization technique using methyl methacrylate (MMA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker. The morphology, adsorption and recognition properties were investigated by scanning electron microscopy (SEM), static adsorption test, and competitive adsorption test. To obtain the best selectivity and binding performance, the synthesis and adsorption conditions of MIPs were optimized through single factor experiments. Under the optimized conditions, the resultant polymers exhibited uniform size, satisfactory binding capacity and significant selectivity. Furthermore, the imprinted polymers were successfully applied as a specific solid-phase extractants combined with high performance liquid chromatography (HPLC) for determination of dimethoate residues in the cucumber samples. The average recoveries of three spiked samples ranged from 78.5% to 87.9% with the relative standard deviations (RSDs) less than 4.4% and the limit of detection (LOD) obtained for dimethoate as low as 2.3 μg/mL. Keywords: Molecularly imprinted polymer, Precipitation polymerization, Dimethoate, Cucumber, HPLC

Poly (aspartic acid-co-leucine) (PL) synthesized with aspartic acid and leucine was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) by ethylenediamine. Then the compound obtained was chelated with gadolinium (III) to form PL-A 2 -DOTA-Gd. The structure of PL-A 2 -DOTA-Gd was characterized by nuclear magnetic resonance and gel chromatography and its performance was evaluated by cytotoxicity test, heamolysis test, in vitro relaxivity determination and animal in vivo magnetic resonance characterization. PL-A 2 -DOTA-Gd exhibited much lower cytotoxicity than Gd-DOTA. The T1-relaxivity of PL-A 2 -DOTA-Gd (15.3 mM −1 s −1 ) was 2.6 times than that of Gd-DOTA (5.8 mM −1 s −1 ) in D 2 O. The results of magnetic resonance imaging (MRI) experiments showed a significant enhancement in the rat liver imaging after the intravenous administration of PL-A 2 -DOTA-Gd. In addition, the imaging time persisted by using PL-A 2 -DOTA-Gd than that of Gd-DOTA and the imaging effect of liver tissue was enhanced by an average of 65.1% ± 5.2% and 21.3% ± 4.9% for PL-A 2 -DOTA-Gd and Gd-DOTA, respectively.

A catalytic diastereo- and enantiocontrolled preparation of cis -β-fluorocyclopropane carboxylates through the Rh-catalyzed cyclopropanation of alkenyl fluorides with diazoarylacetates has been realized. Rh 2 ( S -DOSP) 4 and benzyl diazoarylacetates were found to be beneficial to the cyclopropanation with high diastereoselectivity. Thirteen cis -β-fluorocyclopropane carboxylates were prepared in hexane at 0 °C with good to excellent yields. The enantiomeric excess was up to 97%, and the diastereomer ratio was up to 95:5.

The influences of coagulant species, dose, water turbidity, and pollution situation of raw water on the results of enhanced coagulation have been investigated targeted at water contaminated by chemical agent. Ferric trichloride and polymeric aluminum ferric chloride (PAFC) acted as coagulant, poly dimethyl diallyl ammonium chloride (HCA) worked as coagulant aid and paraoxon acted as simulation agent of chemical agent VX in this process. The results show that: enhanced coagulation process cannot remove effectively chemical agent (paraoxon) in raw water; the result of treatment by PAFC and PAFC+HCA is better than that by FeCl3 and FeCl3+HCA; the addition of certain amount of HCA based on the condition that coagulant has been added will improve removal rate of both chemical agent and turbidity; the bigger the turbidity of raw water is, the higher the removal rate of paraoxon will be.

Super-hard tool material is a main research point of mechanical engineering because of excellent performance. The development of technology for high-speed cutting process could enhance the machining quality and surface precision. It is a difficulty thing to get higher finished surface for traditional machining process. However, the super-hard cutter material could enhance the finished performance of tool material. For example, the wearing resistance, high stability of PCD (polycrystalline diamond) and PCBN (poly cubic boron nitride) can get more information for obtaining higher finished surface quality. The author introduces super-hard cutters materials (PCD and PCBN) development, and discusses several material properties. The features of materials used in different cutting fields are discussed.

A method based on reversed-phase liquid chromatography-tandem mass spectrometry (LC/MS/MS) combined with solid phase extraction (SPE) was developed and validated for qualitative and quantitative detection of eight parabens in three types of water-based food simulants including distilled water, 3% acetic acid, 10% alcohol. Detection limits of eight parabens after SPE procedure were 0.005-0.010 μg/L in distilled water, 0.006-0.015 μg/L in 3% acetic acid and 0.005-0.017 μg/L in 10% alcohol. The relative standard deviations (RSDs) were in the range of 1.90-8.48% for distilled wsater, 1.01-3.73% for 3% acetic acid and 5.78-12.97% for 10% alcohol. The method could make a complement for detecting parabens migrated to food and feeds.

We developed a novel type of azobenzene-containing photoresponsive molecule-imprinted silica microspheres. Ibuprofen and activated silica particles were used as template molecules and substrates, respectively. Pre-synthesized azobenzene-based monomers were chemically bonded on the surface of silica particles. Template–monomer complexes were formed relying on hydrogen bonding. Then skin layer was formed by graft polymerization of azobenzene-based monomers. After that, ibuprofen molecules were removed from their embedded spaces. The vacant spaces on the surface of particles were easily accessible for the template molecules. Furthermore, photoinduced trans–cis isomerization of azobenzene chromophores within imprinted vacant spaces was able to regulate their substrate affinity. The results demonstrated that the imprinted silica microspheres possessed obvious molecular imprinting effects towards the template ibuprofen, rather fast template rebinding kinetics, and appreciate selectivity over structurally related compounds.

Hypertrophic scar (HS) is a refractory skin disease caused by major physical damage or other inflammation. Some reports found that botulinum toxin type A (BTXA) could be an alternative treatment of the HS. Therefore, the authors studied the effects of BTXA on the treatment of HS and the dose response of BTXA. Hypertrophic scars were harvested from the ears of 18 young adult New Zealand big-eared rabbits and treated with BTXA or triamcinolone acetonide (TAC) in vivo experiment. The hypertrophic index (HI) was measured by histological examination. Collagen fibrils were checked by sirius red straining, and the cell nucleuses of fibroblasts were checked by Ki67. The HI of hypertrophic scars with BTXA treatment was lower than that with phosphate-buffered saline treatment (P

Glycosylation plays a major role in the diversity in the chemical compositions of flavonoids. In this study, we performed biochemical and molecular assays to identify a glucosyltransferase gene responsible for the anthocyanin composition in litchi. Cyanidin-3-glucoside and cyanidin-3-rutinoside were predominant anthocyanins in the red pericarp and young leaf of litchi. Anthocyanin composition varied among litchi varieties. Anthocyanin profile was primarily determined by genetic factors. Higher activities of UDP-rhamnose: cyanidin-3-glucoside rhamnosyltransferase (CGRT) were detected in the pericarps of the cyanidin-3-rutinoside predominant varieties. Three full-length putative UDP-rhamnose: flavonoid glycoside 2″-O-beta-l-rhamnosyltransferase-like genes were isolated and designated as LcFGRT2, LcFGRT4, and LcFGRT5. Phylogenetic analysis showed that these genes were clustered with other glucoside-glycosyltransferases. Notable activities in catalyzing cyanidin-3-rutinoside formation were observed in extracts of tobacco leaves and yeast with heterologous expression of LcFGRT4. However, the expression pattern of LcFGRT4 did not agree with the CGRT activity. This result suggests that the difference in CGRT among varieties occurred post-transcriptionally. Nucleotide variation in LcFGRT4 was surveyed by sequencing 30 litchi accessions with different anthocyanin profiles. Eight non-synonymous single-nucleotide polymorphisms were detected. Type A LcFGRT4 sequence (LcFGRT4A) was observed in cyanidin-3-glucoside-dominant varieties, whereas type B LcFGRT4 sequence (LcFGRT4B) was detected in cyanidin-3-glucoside-dominant varieties. A mutant in 343 C/G polymorphism was targeted as the critical point responsible for the CGRT activity. Results indicated that a single-point mutation in LcFGRT4 could alter the activity of CGRT and may contribute to the diverse anthocyanin profile of litchi.

Background Genetic manipulation of brassinosteroid (BR) biosynthesis or signaling is a promising strategy to improve crop yield and quality. However, the relationships between the BR-promoted growth and photosynthesis and the exact mechanism of BR-regulated photosynthetic capacity are not clear. Here, we generated transgenic tomato plants by overexpressing Dwarf, a BR biosynthetic gene that encodes the CYP85A1, and compared the photosynthetic capacity with the BR biosynthetic mutant dim and wild type. Results Overexpression of Dwarf promoted net photosynthetic rate (PN), whereas BR deficiency in dim led to a significant inhibition in PN as compared with WT. The activation status of RuBisCO, and the protein content and activity of RuBisCO activase, but not the total content and transcripts of RuBisCO were closely related to the endogenous BR levels in different genotypes. However, endogenous BR positively regulated the expression and activity of fructose-1,6-bisphosphatase. Dwarf overexpression enhanced the activity of dehydroascorbate reductase and glutathione reductase, leading to a reduced redox status, whereas BR deficiency had the contrasting effects. In addition, BR induced a reduction of 2-cystein peroxiredoxin without altering the protein content. Conclusions BR plays a role in the regulation of photosynthesis. BR can increase the photosynthetic capacity by inducing a reduced redox status that maintains the activation states of Calvin cycle enzymes. Electronic supplementary material The online version of this article (doi:10.1186/s12870-016-0715-6) contains supplementary material, which is available to authorized users.

Continuing our search for natural product-based compounds for the control of B. longissima Larvae, 25 stilbene analogs were synthesized and evaluated for insect antifeedant activity against third-instar larvae of B. longissima for the first time. Among all the tested compounds, especially compounds 3a, 3c, and 6 showed pronounced antifeedant activities with AFC50 values of 0.218, 0.327, and 0.226 mg/mL, respectively. The different antifeedant activity ranges of these compounds indicated that variation of chemical structures in the stilbene skeleton markedly affected the activity profiles of this compound class, and some important SAR information has been revealed from it. In addition, to understand the structural requirements for antifeedant activities of the 25 synthesized stilbene analogs, a comparative molecular field analysis (CoMFA) model, which yielded the leave-one-out (LOO) cross-validated correlation coefficient (q2) of 0.533 and a non-cross-validated correlation coefficient (r2) of 0.929, was constructed. Together, these preliminary results may be useful in guiding further modification of stilbenes in the development of potential new antifeedants.

Four novel spin-labelled combretastatin A-4 (CA-4) analogues were first synthesised in quantitative yield by reacting CA-4 with the corresponding nitroxyl radical. Their cytotoxic activities against A-549 (human lung cancer) and HePG-2 (human liver cancer) in vitro were evaluated, and the results indicated that these derivatives were more cytotoxic than the clinical drug irinotecan.

Nanometer titanium dioxide films supported on glass, quartz, molybdenum, and aluminum were prepared by sol-gel method. The loaded titanium dioxide films were characterized by atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and photocatalytic degradation of aqueous crystal violet. The titanium dioxide films supported on different substrates were all composed of polycrystalline nanoparticles, which belonged to single-phase anatase, and displayed different morphology after sintering at 773 K for 1 h. Some elements in the substrate made of noncrystal appeared on the surface of titanium dioxide films. The experiment about basic crystal violet degradation displayed the photocatalysis activity of titanium oxide films supported on the molybdenum was better.

The CIMS development and the high-speed cutting has given a higher demands on cutter performance. It is an tremendous tendency of studying excellent wearing resistance and high stability. PCD (polycrystalline diamond) and PCBN (poly cubic boron nitride) can obtain more higher finished surface quality, which cannot acquire by regular cutting process. This study introduces super-hard cutters materials (PCD and PCBN) development, and discusses two kinds of material properties, The features of them used in different cutting fields are given.

Magnetic resonance imaging (MRI) is one of the most useful diagnostic techniques in clinical medicine and more than 30% of all MRI examinations are accompanied by administration of a contrast agent which has become a class of pharmaceuticals. The principles, characterization and classification and recent developments of MRI contrast agents are presented in this review. The primary focus of such research is to study the MRI contrast agents with organ-selectivity, high relaxivity and safety.

Graft copolymerization of acrylic acid(AA) and acrylamide(AM) on cellulose to prepare super absorbent resin (SAR) under microwave irradiation were investigated using N,N-methylene bis-acrylamide as crosslinking agent, and potassium persulfate/sodium thiosulfate as initiator. The results indicated that it only needed 5min under the microwave level of 320W to obtain the resin with the maximum absorption amount of 1388g•g-1 , under the conditions that the ratio of acrylic acid to cellulose of 14:1, 0.25wt% initiator to AA, 0.25wt% crosslinking agent, 70% neutralization degree of AA. Under microwave irradiation, the preparation of SAR could be completed without the protection of nitrogen. Compared to conventional heating method, the methods had the striking advantages of short reaction time, simple process and low cost.

The biochemical effects of gadolinium chloride were studied using high-resolution H-1 nuclear magnetic resonance (NMR) spectroscopy to investigate the biochemical composition of tissue (liver and kidney) aqueous extracts obtained from control and gadolinium chloride (GdCl3) (10 and 50 mg/kg body weight, intraperitoneal injection. i.p.) treated rats. Tissue samples were collected at 48, 96 and 168 h p.d. after exposure to GdCl3, and extracted using methanol/chloroform solvent system. H-1 NMR spectra of tissue extracts were analyzed by pattern recognition using principal components analysis. The liver damages caused by GdCl3 were characterized by increased succinate and decreased glycogen level and elevated lactate, alanine and betaine concentration in liver. Furthermore, the increase of creatine and lactate, and decrease of glutamate, alanine, phosphocholine, glycophosphocholine (GPC), betaine, myo-inositol and trimethylamine N-oxide (TMAO) levels in kidney illustrated kidney disturbance induced by GdCl3.

Online sampling experiments were carried out to investigate the development of immiscible polymer blend morphology along a single screw extruder using specially designed sampling devices. The morphology of molten blend samples collected at different locations was observed by scanning electron microscopy (SEM) and evaluated both qualitatively and quantitatively. Two polypropylene/polyamide-6 blends with different viscosity ratios, one about 0.1 and the other about 1.0, were selected to investigate the influence of the viscosity ratio on the morphology development. Experimentally observed results showed that, for the blend with a smaller viscosity ratio, major morphological changes occurred during the initial softening stage of blending. For the blend with a larger viscosity ratio, the extended striations are transformed to a droplet morphology gradually along the screw. It was demonstrated that it is possible to detect the morphology development along the extruder screw nearly in real time with the sampling device assembled in a single screw extruder. Information about the dynamics of morphology development in the extruder can be obtained.

The solid-phase photocatalytic degradation of poly (vinyl chloride) (PVC) films was investigated in ambient air. The photodegradation of the PVC and PVC-TiO2 was compared with that of plasma-treated PVC and plasma-treated PVC-TiO2 performing a weight loss monitoring and scanning electron microscopic (SEM) analysis. The SEM of the PVC-TiO2 film treated by plasma showed many cracks on the surface after photodegradation. Furthermore, the surface wettability and surface structure of PVC after nitrogen plasma treatment was characterized by contact angle, surface tension, and electron spin resonance (ESR). The experiment indicated that the surface free energy and wettability of PVC treated by plasma increased greatly. ESR revealed that the signal of radicals on the surface of the plasma-treated PVC film was enhanced after treatment. The free radicals on the surface of plasma-treated PVC possibly decreased the activating energy of photocatalytic reaction, which belongs to the free radicals reaction, because the chemical activity of the free radicals was high. According to these findings, a mechanism on the photodegradation of plasma-treated PVC-TiO2 is proposed.

Anthocyanins generate the red color in the pericarp of Litchi chinensis. UDP-glucose: flavonoid 3-O-glycosyltransferase (UFGT, EC. 2.4.1.91) stabilizes anthocyanidin by attaching sugar moieties to the anthocyanin aglycone. In this study, the function of an UFGT gene involved in the biosynthesis of anthocyanin was verified through heterologous expression and virus-induced gene silencing assays. A strong positive correlation between UFGT activity and anthocyanin accumulation capacity was observed in the pericarp of 15 cultivars. Four putative flavonoid 3-O-glycosyltransferase-like genes, designated as LcUFGT1 to LcUFGT4, were identified in the pericarp of litchi. Among the four UFGT gene members, only LcUFGT1 can use cyanidin as its substrate. The expression of LcUFGT1 was parallel with developmental anthocyanin accumulation, and the heterologously expressed protein of LcUFGT1 displayed catalytic activities in the formation of anthocyanin. The LcUFGT1 over-expression tobacco had darker petals and pigmented filaments and calyxes resulting from higher anthocyanin accumulations compared with non-transformed tobacco. In the pericarp with LcUFGT1 suppressed by virus-induced gene silencing, pigmentation was retarded, which was well correlated with the reduced-LcUFGT1 transcriptional activity. These results suggested that the glycosylation-related gene LcUFGT1 plays a critical role in red color formation in the pericarp of litchi.

The effects of copolymer composition, drug structure and initial drug feed on drug loading of polymeric micelles based on amphiphilic polyphosphazenes were investigated. It was found that the drug loading capacity of micelles based on this type of amphiphilic copolymers was mainly determined by copolymer composition and the chemical structure of drug. In addition to the compatibility between drug and micellar core, hydrogen bonding interaction between drug and hydrophilic corona may significantly influence drug loading as well. In vitro drug release in 0.1 M PBS (pH 7.4) suggested that indomethacin (IND) in the micelles was released through Fickian diffusion, and no significant difference in release rate was observed for micelles based on copolymers with various EtTrp content. Compared with in vitro IND release profile, in vivo pharmacokinetic study after subcutaneous administration provides a more sustained release behavior. Additionally, in comparison with free drug solution at the same dose, IND concentration in rat plasma showed a prolonged retention when the drug was delivered through polymeric micelles. In vivo pharmacodynamic study based on both carrageenan-induced acute and complete Freund's adjuvant-induced adjuvant arthritis model indicated that sustained therapeutic efficacy could be achieved through intraarticular injection of IND-loaded micelles. Most importantly, local delivery of IND can avoid the severe gastrointestinal stimulation, which was frequently associated with oral administration.

[Ni(L−1)(HL)(H2O)2].ClO4 with a Schiff base ligand L (HL = 3-p-tolylimino-2-butanone oxime) was prepared and structurally characterized by IR, cyclic voltammetry and X-ray diffraction methods. The nickel atom has distorted octahedral coordination consisting of four nitrogen atoms and two oxygen atoms. The equatorial plane is formed by two oxime nitrogen atoms and two imine nitrogen atoms of two Schiff base ligand (L−1 and HL) with Ni‐ N bond distances between 2.01(1) and 2.11(1)A. Water oxygen atoms occupy axial positions with Ni‐ O bond distances of 2.06(1) and 2.15(1) A. The oxime groups in the Schiff base ligands are coordinated to Ni atom through their nitrogen atoms. One asymmetric intramolecular hydrogen bridge between the two oxime groups is found in the title complex.

Decreased Na(+) /K(+) -ATPase activity, and both sirtuin 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) have been reported to be involved in the development of diabetic cardiomyopathy (DCM). The present study aimed to investigate the advanced glycation end-products (AGE) that impair Na(+) /K(+) -ATPase stability by regulating the AMPK/SIRT1 pathway during progression of DCM. To study type 1 diabetic mellitus (T1DM), a disease model in rats was established by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg), and neonatal rat cardiomyocytes were also cultured. Heart function was detected by Doppler, and SIRT1 and AMPK protein expression were detected by immunohistochemistry and western blotting. Na(+) /K(+) -ATPase activity was also monitored. Using in vivo rat models of DCM, we showed that Na(+) /K(+) -ATPase activity decreased when both AMPK and SIRT1 expression were downregulated. In vitro, AGE impaired Na(+) /K(+) -ATPase activity and decreased the AMPK and SIRT1 expression. Sirtuin 1 overexpression increased Na(+) /K(+) -ATPase activity. 5-aminoimidazole-4-carboxamide-3-ribonucleoside (AICAR) upregulated SIRT1 expression and increased Na(+) /K(+) -ATPase activity, which could be partially abolished by splitomicin. Our results suggest that the dysfunction of DCM is related to AGE-induced Na(+) /K(+) -ATPase activity impairment through a mechanism involving the AMPK/SIRT1 pathway.

Two series (14a-d and 21a-h) of novel spin-labeled combretastatin derivatives were synthesized and evaluated for cytotoxicity against four tumor cell lines (K562, SGC-7901, Hela and HepG-2). Simultaneously, a representative compound 21a was selected to investigate the antitumor mechanisms of these synthetic compounds. The results indicated that some of the compounds showed significant cytotoxicity against four tumor cell lines in vitro and were more active than etoposide, a clinically available anticancer drug. Among the newly synthesized compounds, 21a, 21b and 21c displayed the greatest cytotoxicity against three tested tumor cell lines (HEPG-2, BGC-832 and Hela), with IC50 values ranging from 0.15 to 1.05 mu M, compared with values of 0.014-0.403 mu M for 3-amino-deoxycombretastatin A-4 (3). In addition, the mechanistic analysis revealed that compound 21a effectively interfered with tubulin dynamics to prevent mitosis in cancer cells, leading to cell cycle arrest and, eventually, dose dependent apoptosis. (C) 2013 Elsevier Ltd. All rights reserved.

Objective To establish the quality standards of the herbs of Peganum harmala. Method According to the Chinese Pharmacopoeia (2010 version, volume 1) and its appendix method, the water, total ash, acid insoluble ash, water-soluble extractives, and heavy metal were analyzed for herbs of P. harmala. TLC method was used to separate harmaline, harmine and vasicine from the herb samples by mixture of ethyl acetate-methanol-ammonia (10: 1.5: 0.5) as a developing solvent on high performance silica gel precoated plate (HSGF254) and to identify them inspected under UV 366 nm, visualized by spraying with both Dragendorff reagent, and by bioautographic assay. In the HPLC method, vasicine was separated on a C18 (4.6 mm x 250 mm, 5 microm) column with metnanol-0.1% trifluoroacetic acid (15:85) as the mobile phase and detected at at 280 nm. Result In the TLC procedures, 254 nm fluorescent and bioautographic assay for the detection of acetylcholinesterase inhibitor can be used for the qualitative identification of the active ingredients. For the HPLC quantitation method, the calibration curve of vasicine displayed ideal linearity over the range of 0.7923-792.3 mg x L(-1) with the regression equation of Y = 18,227X - 24.879 (r = 0.9999). The average recovery of vasicine was 101.6% with a RSD of 1.9%. The RSD values of intra-day and inter-day precision were less than 2%. The content of vasicine in 10 batches of herbs of P. harmala fluctuates between 0.23% and 1.47%. Conclusion The results indicated that the limit of vasicine was not lower than 0.6%, and the water, total ash, acid insoluble ash, and water-soluble extractives were not more than 10.0%, 20.0%, 1.7%, and 30.0%, respectively. The heavy metal of plumbum, cadmium, arsenic, mercury, and copper were not more than 5, 3, 2, 2, and 20 mg x kg(-1), respectively. The qualitative and quantitative method established was suitable for the quality evaluation and assessment of herbs of P. harmala.

Litchi has diverse fruit color phenotypes, yet no research reflects the biochemical background of this diversity. In this study, we evaluated 12 litchi cultivars for chromatic parameters and pigments, and investigated the effects of abscisic acid, forchlorofenron (CPPU), bagging and debagging treatments on fruit coloration in cv. Feizixiao, an unevenly red cultivar. Six genes encoding chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), anthocyanidin synthase (ANS) and UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT) were isolated from the pericarp of the fully red litchi cv. Nuomici, and their expression was analyzed in different cultivars and under the above mentioned treatments. Pericarp anthocyanin concentration varied from none to 734 mg m(-2) among the 12 litchi cultivars, which were divided into three coloration types, i.e. non-red ('Kuixingqingpitian', 'Xingqiumili', 'Yamulong'and 'Yongxing No. 2'), unevenly red ('Feizixiao' and 'Sanyuehong') and fully red ('Meiguili', 'Baila', Baitangying' 'Guiwei', 'Nuomici' and 'Guinuo'). The fully red type cultivars had different levels of anthocyanin but with the same composition. The expression of the six genes, especially LcF3H, LcDFR, LcANS and LcUFGT, in the pericarp of non-red cultivars was much weaker as compared to those red cultivars. Their expression, LcDFR and LcUFGT in particular, was positively correlated with anthocyanin concentrations in the pericarp. These results suggest the late genes in the anthocyanin biosynthetic pathway were coordinately expressed during red coloration of litchi fruits. Low expression of these genes resulted in absence or extremely low anthocyanin accumulation in non-red cultivars. Zero-red pericarp from either immature or CPPU treated fruits appeared to be lacking in anthocyanins due to the absence of UFGT expression. Among these six genes, only the expression of UFGT was found significantly correlated with the pericarp anthocyanin concentration (r = 0.84). These results suggest that UFGT played a predominant role in the anthocyanin accumulation in litchi as well as pericarp coloration of a given cultivar.

Copolymeric nanocarriers assembled by amphiphilic polyphosphazene bearing poly(N-isopropylacrylamide) (PNIPAAm) and ethyl glycinate (EtGly) as substitutes, were investigated as drug vehicles for indomethacin (IND). The physicochemical characteristics of the novel nanocontainers were studied, including lower critical solution temperature (LCST), critical micelle concentration (CMC) and drug loading capacity. LCST measurements revealed that copolymer is more sensitive to the introduction of salts into aqueous solution compared with homopolymer. A significant decrease in CMC was observed when the temperature increased above LCST. As evidenced by transmission electron microscopy (TEM) measurement, morphological transformation from multicompartment into spherical nanoparticles was observed when nanocarriers with higher IND content were concerned. In vitro release tests suggested that IND-loaded nanocontainers exhibited pH dependent release profiles. In vivo pharmacokinetic study after subcutaneous administration provided a relatively sustained release behavior. Additionally, compared with free drug solution at the same dose, IND concentration in rat plasma showed a prolonged retention in experimental group treated with IND-loaded micelles. In vivo pharmacodynamic study based on both carrageenan-induced acute and complete Freund's adjuvant (CFA) induced adjuvant-arthritis models indicated that sustained therapeutic efficacy could be achieved through intraarticular injection of IND-loaded micelles. Most importantly, local delivery of IND can avoid the severe gastrointestinal stimulation, which is frequently associated with oral administration.

AIM: To observe the protective effect of glucagon-like peptide-2 (GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect. METHODS: Thirty-six Sprague-Dawley rats were randomly divided into a sham operation group, an obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats. The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the other two groups were treated with the same concentration of normal saline. Alanine aminotransferase (ALT), total bilirubin, and endotoxin levels were recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14th day, body weight, the wet weight of the small intestine, pathological changes of the small intestine and the immunoglobulin A (IgA) expressed by plasma cells located in the small intestinal lamina propria were recorded for each group. RESULTS: In the rat model, jaundice was obvious, and the rats’ activity decreased 4-6 d post bile duct ligation. Compared with the sham operation group, the obstructive jaundice group displayed increased yellow staining of abdominal visceral serosa, decreased small intestine wet weight, thinning of the intestinal muscle layer and villi, villous atrophy, uneven height, fusion, partial villous epithelial cell shedding, substantial inflammatory cell infiltration and significantly reduced IgA expression. However, no significant gross changes were noted between the GLP-2 and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP-2 group were significantly increased compared with the sham group (P < 0.01). The increasing levels of the aforementioned markers were more significant in the obstructive jaundice group than in the GLP-2 group (P < 0.01). CONCLUSION: GLP-2 reduces intestinal mucosal injuries in obstructive jaundice rats, which might be attributed to increased intestinal IgA and reduced bilirubin and endotoxin.

The properties of polymer blends are largely determined by their morphology. So it is significant to investigate the morphology development of polymer blends during processing. In this work the morphology development of polymer blend was studied during flow along a single screw extruder. The polymer blend used incorporated polypropylene (PP) as its matrix phase and a high-viscosity or low-viscosity polyamide-6 (PA6) as the disperse phase. The samples of blends were taken from different positions using specially designed sampling device along the extruder online during the processing and were then examined using scanning electron microscopy (SEM). The morphology of the dispersed phase was quantitatively analyzed using image analysis software. The morphology evolution of blends along the melt conveying zone of screw was simulated. Theoretically predicted morphology evolution is in reasonable agreement with the experimental results. The aim of this work is to provide a better insight in the morphology development of blend during processing.Copyright © 2006 by ASME

The metabolic impact of redirection electron flow to high coupling efficiency of terminal oxidases on riboflavin biosynthetic ability was quantitatively assessed during batch culture in this paper. While disruption of the low coupling bd oxidase of the riboflavin overproducing B. subtilis PK, the apparent phenotype with more rapid specific growth rate and higher biomass yield was achieved. Compared to by-products formation, a discernible shift to less acetate and more acetoin in cyd mutant was observed. As the overflow metabolism was decreased in B. subtilis PK cyd, more carbon source was directed to biomass and riboflavin biosynthetic pathway, which resulted in higher biomass and about 30% improvement of riboflavin biosynthetic ability. The higher product-corrected biomass yield in mutant showed that the efficient energy generation is an important factor for exponential growth of riboflavin overproducing B. subtilis strain in batch culture.

The red coloration of litchi fruit depends on the accumulation of anthocyanins. The anthocyanins level in litchi fruit varies widely among cultivars, developmental stages and environmental stimuli. Previous studies on various plant species demonstrate that anthocyanin biosynthesis is controlled at the transcriptional level. Here, we describe a litchi R2R3-MYB transcription factor gene, LcMYB1, which demonstrates a similar sequence as other known anthocyanin regulators. The transcription levels of the LcMYB1 and anthocyanin biosynthetic genes were investigated in samples with different anthocyanin levels. The expression of LcMYB1 was strongly associated with tissue anthocyanin content. LcMYB1 transcripts were only detected in anthocyanin-accumulating tissues and were positively correlated with anthocyanin accumulation in the pericarps of 12 genotypes. ABA and sunlight exposure promoted, whereas CPPU and bagging inhibited the expression of LcMYB1 and anthocyanin accumulation in the pericarp. Cis-elements associated with light responsiveness and abscisic acid responsiveness were identified in the promoter region of LcMYB1. Among the 6 structural genes tested, only LcUFGT was highly correlated with LcMYB1. These results suggest that LcMYB1 controls anthocyanin biosynthesis in litchi and LcUFGT might be the structural gene that is targeted and regulated by LcMYB1. Furthermore, the overexpression of LcMYB1 induced anthocyanin accumulation in all tissues in tobacco, confirming the function of LcMYB1 in the regulation of anthocyanin biosynthesis. The upregulation of NtAn1b in response to LcMYB1 overexpression seems to be essential for anthocyanin accumulation in the leaf and pedicel. In the reproductive tissues of transgenic tobacco, however, increased anthocyanin accumulation is independent of tobacco's endogenous MYB and bHLH transcriptional factors, but associated with the upregulation of specific structural genes.