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Objective Residue risk assessment of pesticides in celery was conducted to provide a scientific basis for agricultural regulation policies and working procedures. Methods Three hundred samples from eight main growing regions in China were collected and pesticide residue analyses were performed using GC–MS/MS and LC-MS/MS methods. Both chronic and acute intake risk of pesticides were assessed. Furthermore, intake risk of each detected pesticide was ranked according to a predefined ranking matrix. Results (1) Out of these 300 samples, 175 were revealed to contain one or more pesticide residues. Twenty-five pesticides were identified in total, out of which, carbofuran was found to exceed the maximum residue limit. (2) Chronic and acute intake risks were evaluated and lie in between 0 and 1.80 and between 0.05 and 28.0 for these twenty-five pesticides, respectively. (3) Intake risk of individual pesticide was ranked; five pesticides, including avermectin, triazophos, chlorpyrifos, dimethoate oxygen, and carbofuran posed the highest risks. Conclusion Pesticide residues were detected in more than 58% celery samples in our study. Most pesticides have a residue level lower than their maximum residue limit and pose low chronic and acute dietary intake risk. However, usage of some pesticides like carbofuran should be closely monitored and regulated in the future. [ABSTRACT FROM AUTHOR]

Bitespiramycin is a novel antibiotic containing a number of 4″-acylated spiramycin derivatives (isovalerylspiramycins I–III, butanoylspiramycin III, propanoylspiramycin III and acetylspiramycin III) as major components. These spiramycin derivatives are susceptible to degradation in acid solution. Liquid chromatography–ion trap mass spectrometry (LC/MSn) was used to study the degradation of these spiramycin derivatives in simulated gastric fluid at 37°C. All derivatives degraded by first-order reactions for which rate constants (k) and half-lives (t1/2) were calculated. Acyl groups at position 3 had less effect on acid-stability of spiramycin derivatives than acyl groups at position 4″. The introduction of 4″-acyl groups enhanced the acid-stability of spiramycin derivatives and altered the degradation pathway in simulated gastric fluid such that loss of forosamine rather than loss of mycarose becomes the major degradation pathway. [Copyright &y& Elsevier]

Investigates the role of acetylcholine (Ach) on plant root-shoot communication using the root-split system of Vicia faba L. Decrease of Ach content in root tips and increase in the xylem sap transported per time unit, due to a slight osmotic stress; Probable function of Ach content decrease to regulate stomatal behavior.

Studies the effects and the relationship between salicylic acid (SA) and nitric oxide (NO) on Vicia faba L. stomatal movement. Evidence that exogenous SA and NO induced stomatal closure; Suggestion that both cGMP and cADPR might mediate the signal transduction of SA and NO-based stomatal closure.

Investigates the protein tyrosine phosphatase (PTPase) in relation to the cellular signaling of ABA accumulation in response to water deficit. Indication that protein phosphatases may be involved in the cellular signaling in response to water deficit; Evolution of plants to cope with water deficit and other environmental stresses.

Discusses the involvement of Ca2+/CaM in the signal transduction of acetylcholine regulating stomatal movement. How the neutrotransmitter acetylcholine (ACh) is able to regulate the movement of stomata in plants; Demonstration that Ca2+/CaM are also involved in the ACh regulated stomatal movement.

The unique roles of individual cells may be critical to the physiology of an organism. In such cases, micromethods are essential to elucidating the molecular biology, biochemistry and biophysics of the specialized cells or even subcellular compartments of the important cells. The great proliferation of micromethods testifies to their value and no single review can be comprehensive. This review therefore provides only a generalized overview of one approach, namely dissection that provides a pure sample for subsequent extraction and analysis by microdroplet chemistry. As a means of illustrating the utility of this approach, an application—study of the interaction of cytosolic malate concentration and guard-cell phosphoenolpyruvate carboxylase—is provided. [ABSTRACT FROM AUTHOR]

Implementing combination medication through crystal engineering technology receives increasing attention from researchers due to improvements in the clinical treatment effects as well as the physicochemical properties of the drug. Berberine (BER) is commonly used to treat gastroenteritis and bacterial diarrhea, with the problems of poor solubility and low oral bioavailability. Recently, it is found that gallic acid (GA) also has anti‐inflammatory and anti‐bacterial activities. Therefore, if the above‐mentioned two ingredients can be combined, it is possible to enhance the therapeutic effects and physicochemical properties of BER. Inspired by this, 8‐hydroxy‐7,8‐dihydroberberine (8H‐HBER) in this study is employed to react with gallic acid to yield BER gallate dihydrate (2BER‐2GA‐2 W). Furthermore, dissolution experiments demonstrate that the maximum apparent solubility (MAS) of 2BER‐2GA‐2 W in dilute hydrochloric acid solution medium (pH 1.2) has increased by 7 times compared to the commercial form of BER, because of avoiding the common‐ion effect. Moreover, 2BER‐2GA‐2 W has also obviously enhanced stability relative to the commercial form of BER. In addition, 2BER‐2GA‐2 W has a better inhibitory effect on Staphylococcus aureus (S. aureus) relative to the commercial form of BER. Hence, 2BER‐2GA‐2 W will be a promising solid‐state form of BER for its further development. [ABSTRACT FROM AUTHOR]

The aims of this study were to investigate the contamination status of chlorothalonil pesticide residues in vegetables from Shandong province, and to assess the potential risk of chlorothalonil to consumers based on vegetable consumption and body weight using an improved non-parameter probabilistic model. The results showed that Young children (8 months–6 years old) were more sensitive than General population(above 1year-old). In general, the health risk of chlorothalonil residues to 2 consumer groups via vegetable exposure was low, and the level of residual chlorothalonil was below the Acute Reference Dose (ARfD). This result would provide useful information for re-evaluating pesticides and for revising the chlorothalonil standard in vegetables. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) and Jasmonic acid (JA) are two key signaling molecules involved in many and diverse biological pathways in plants. Growing evidence suggested that NO signaling interacts with JA signaling. In this work, Our experiment showed that NO exists in guard cell of Vicia faba L., and NO is involved in signal transduction of JAinduced stomata closuring: ( i ) JA enhances NO synthesis in guard cell; ( ii ) both JA and NO induced stomatal closure, and had dose response to their effects; (iii) there are synergetic correlation between JA and lower NO concentration in regulation of stomatal movement; (iv) JA-induced stomatal closure was largely prevented by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), a specific NO scavenger. An inhibitor of NO synthase (NOS) in mammalian cells, NG-nitro-L-Arg-methyl eater (L-NAME) also inhibits plant NOS, repressing JA-induced NO generation and JA-induced stomatal closure. We presumed that NO mainly comes from NOS after JA treatment. [ABSTRACT FROM AUTHOR]

Acetylcholine (ACh) is an important neurochemical transmitter in animals; it also exists in plants and plays a significant role in various kinds of physiological functions in plants. ACh has been known to induce the stomatal opening. By monitoring the changes of cytosolic Ca2+ with fluorescent probe Fluo-3 AM under the confocal microscopy, we found that exogenous ACh increased cytosolic Ca2+ concentration of guard cells ofVicia faba L. Muscarine, an agonist of muscarine acetylcholine receptor (mAChR), could do so as well. In contrast, atropine, the antagonist of mAChR abolished the ability of ACh to increase Ca2+ in guard cells. This mechanism is similar to mAChR in animals. When EGTA was used to chelate Ca2+ or ruthenium red to block Ca2+ released from vacuole respectively, the results showed that the increased cytosolic Ca2+ mainly come from intracellular Ca2+ store. The evidence supports that Ca2+ is involved in guard-cell response to ACh and that Ca2+ signal is coupled to mAChRs in ACh signal transduction in guard cells. [ABSTRACT FROM AUTHOR]

Acetylcholine (ACh) is an important neurochemical transmitter in animals; it also exists in plants and plays a significant role in various kinds of physiological functions in plants. ACh has been known to induce the stomatal opening. By monitoring the changes of cytosolic Ca2+ with fluorescent probe Fluo-3 AM under the confocal microscopy, we found that exogenous ACh increased cytosolic Ca2+ concentration of guard cells of Vicia faba L. Muscarine, an agonist of muscarine acetylcholine receptor (mAChR), could do so as well. In contrast, atropine, the antagonist of mAChR abolished the ability of ACh to increase Ca2+ in guard cells. This mechanism is similar to mAChR in animals. When EGTA was used to chelate Ca2+ or ruthenium red to block Ca2+ released from vacuole respectively, the results showed that the increased cytosolic Ca2+ mainly come from intracellular Ca2+ store. The evidence supports that Ca2+ is involved in guard-cell response to ACh and that Ca2+ signal is coupled to mAChRs in ACh signal transduction in guard cells. [ABSTRACT FROM AUTHOR]

Currently, conjugation of artemisinin-derived dimers, trimers, and tetramers is a viable strategy for developing new effective antimalarial candidates. Furthermore, nanotechnology is an effective means to achieve intravenous administration of hydrophobic drugs. In this paper, an ester-linked dihydroartemisinin trimer (DHA3) was synthesized and further prepared as self-assembled nanoparticles (DHA3NPs) by a one-step nanoprecipitation method. The pharmacokinetics and antimalarial pharmacodynamics of DHA3NPs were studied in rats and mice infected with Plasmodium yoelii BY265 (PyBY265). DHA3NPs had a regular spherical shape with a uniform size distribution of 140.27 ± 3.59 nm, entrapment efficiency (EE) of 99.63 ± 0.17%, and drug loading efficiency (DL) of 79.62 ± 0.11%. The in vitro release characterization revealed that DHA3NPs were easily hydrolysed into DHA in an esterase environment. The pharmacokinetics study demonstrated that the area under the concentration–time curve (AUC0-t) of DHA in DHA3NPs group was 2070.52 ± 578.76 h×ng×mL−1, which was higher than that of DHA and artesunate (AS) control groups (AUC0-t values of 724.18 ± 94.32 and 448.40 ± 94.45 h×ng×mL−1, respectively) (P < 0.05). The antimalarial pharmacodynamics in vivo suggested that DHA3NPS (ED90 7.82 ± 1.16 μmol×(kg×day)−1) had a superior antimalarial effect compared with that of control groups (ED90 values of 14.68 ± 0.98 (DHA) and 14.34 ± 1.96 (AS) μmol×(kg×day)−1) (P < 0.05). In addition, DHA3NPS reduced the recurrence ratio and improved the cure ratio and survival time. In summary, DHA3NPs exhibited promising pharmacokinetic characteristics and antimalarial pharmacodynamics in vivo. [ABSTRACT FROM AUTHOR]

Features a study that used the fluorescent BODIPY FL-labeled 3-2'-aminobenzhydryloxy tropane to detect muscarinic acetylcholine receptors (mAChR) in plant guard cells. Localization of mAChR in the abaxial epidermis of Vicia faba L; Distribution of mAChR in the guard cell protoplasts of Vicia faba L; Localization of mAChR in the abaxial dermis of Pisum sativum L.

Artemisinin (ART) drugs showed declining plasma concentrations after repeated oral dosing, known as time-dependent pharmacokinetics (PK). ART and dihydroartemisinin (DHA) were adopted as representatives to evaluate the roles of first-pass effects and systemic metabolism in time-dependent PK by comparison of oral versus intravenous administration and 1 dose versus 5 consecutive doses PK in rats and dogs, respectively. The hepatic extraction ratio (ER h) and the intestinal elimination changes were further investigated in rats to distinguish the roles of hepatic first-pass effect or intestinal first-pass effect. The induction capacities of ARTs to cytochrome P450 (CYP450) in rats and human cells were evaluated as well. For ART, only the oral groups showed time-dependent PK. A fairly high ER h that obtained for ART was not sensitive to multiple oral doses. An increased elimination and CYP450 expression have also been found in the intestine. For DHA, though a significant CYP450 induction was observed, neither time-dependent PK nor changes in the first-pass effects was found. In conclusion, time-dependent PK of ART was mainly caused by the increased intestinal first-pass effect rather than hepatic first-pass effect or systemic metabolism. DHA was not involved in auto-induction elimination, thus showing no time-dependent PK. [ABSTRACT FROM AUTHOR]

As a quinazolinocarboline alkaloid, dehydroevodiamine (DHED) derived from Evodia rutaecarpa has recently gained attention because it improves memory failure in Alzheimer's mice. However, its solid forms, which have not yet been elucidated, could be a vital factor affecting its bioactivity and dosage form design. In this study, five DHED-related crystals, including DHED, its hydrochloride anhydrate (DHED·HCl), methanol solvate (DHED·HCl·CH3OH), dihydrate (DHED·HCl·2H2O) and trihydrate (DHED·HCl·3H2O), were obtained via re-crystallization. The five crystals fell into four distinct structural types based on the analysis of their similarities, and DHED·HCl·CH3OH and DHED·HCl·2H2O were proven to be isostructural. The water or solvent molecules incorporated into the crystal lattices via hydrogen bonds and π–π interactions were the main causes of formation of the distinct solid DHED hydrochloride forms. After dehydration at a high temperature, DHED·HCl·3H2O was transformed into an amorphous form (DHED·HCl-AM). Stability tests showed that the two isostructural crystals exhibited the same solid forms under all investigated conditions, and the humidity-induced phase transformation of DHED·HCl was closely tied to the moisture content. Solubility experiments showed that DHED achieved the highest solubility of approximately 3.6 μg ml−1, because of the loose molecular arrangements in DHED with the smallest packing coefficient and lack of π–π interactions. Additionally, transformations among evodiamine (EVO), DHED, DHED·HCl·2H2O and rutaecarpine (RUT) were also revealed: EVO was transformed into DHED·HCl·2H2O in hydrochloric acid-acidified acetone, and all of the solid forms of DHED hydrochloride were converted to RUT at 523 K. The transformations provided a novel and reliable approach to prepare these compounds. [ABSTRACT FROM AUTHOR]

Five novel crystals of acotiamide hydrochloride (AH) with solvates dimethyl formide (DMF), dimethyl sulfoxide (DMSO), ethyl acetate (EA) and water (W) [1AH‐1W‐1DMF, 1AH‐1DMSO‐I, 1AH‐1DMSO‐II, 1AH‐1W‐1DMSO and 2AH‐2DMSO‐1EA] were characterized using single‐crystal X‐ray diffraction, powder X‐ray diffraction, thermal analysis and Fourier transform infrared spectroscopy. The five crystals can be divided into four distinct structural types based on analysis of their similarities; 1AH‐1W‐1DMF and 1AH‐1W‐1DMSO are isostructural. The benzene rings in 1AH‐1DMSO‐I, 1AH‐1DMSO‐II and 2AH‐2DMSO‐1EA can rotate 180°, and the intramolecular hydrogen bond changes from an OH...C=O bond to an NH...OH bond relative to what is seen in 1AH‐1W‐1DMF and 1AH‐1W‐1DMSO. Phase transformation experiments show that a humidity‐induced phase transformation is closely tied to moisture content. [ABSTRACT FROM AUTHOR]

Provides information on a study which showed that agonists of muscarinic receptor could induce stomatal opening, while the antagonists could block stomatal opening induced by acetylcholine. Materials and methods; Results and discussion.

Montmorillonite (Mt) plays a very important role in controlling drug delivery. In this paper, the hydrochloric acid (HCl) treated Mt. was exploited to obtain composites, which were able to enhance dexibuprofen (IBU) loading and achieve to sustain release drug. The textural properties of the Mt. were strongly dependent on the treatment of HCl. The drug loading of pristine Mt. was 190 mg/g, while it was increased to 298 mg/g for Acid-Mt. In vitro release showed that the IBU was released about 92% from IBU/Acid-Mt within 12 h, while the pure IBU was released all within 4 h in simulated intestinal fluid, which meant that the IBU/Acid-Mt were able to retard the drug release with a controlled manner. The release profiles of IBU from composites were fitted by Higuchi and Korsmeyer-Peppas equations, which manifested that diffusion sustained release dominated the main mechanism. Meanwhile, in vivo pharmacokinetics studies in rats displayed that the IBU/Acid-Mt exhibited better gradual drug release than the commercial IBU suspension. For the IBU/Acid-Mt composites, the area under the plasma concentration-time curve from 0 to 24 h ( AUC 0–24 ) and mean residence time ( MRT 0–24 ) were 644.49 ± 73.26 μg/h/mL and 7.65 ± 0.48 h, both of which were significantly larger than commercial IBU suspension ( AUC 0–24 of 439.88 ± 84.41 μg/h/mL and MRT 0–24 of 3.10 ± 0.38 h), respectively ( P  < 0.05). The relative bioavailability of IBU/Acid-Mt was 154.11% ± 27.41% compared to commercial IBU suspension. As a result, the IBU/Acid-Mt is expected to achieve sustained release and extend residence time in plasma. [ABSTRACT FROM AUTHOR]

The dihydroartemisinin-derived dimer (DHA dimer) was synthesized, and its antimalarial activities were evaluated both in vitro and in vivo. The dimer IC50 value of 0.51 ± 0.12 nM in vitro was significantly lower than that of DHA at 1.81 ± 0.70 nM. The dimer ED50 values were 0.44 ± 0.03 and 0.18 ± 0.03 mg/(kg·day) in vivo for intragastric (i.g.) and intravenous (i.v.) groups, respectively, to Plasmodium yoelii rodent malaria. It also performed better relative to those of DHA which had ED50 values of 0.76 ± 0.03 mg/(kg·day) (i.g.) and 0.32 ± 0.03 mg/(kg·day) (i.v.). Moreover, the recrudescence rate, negative conversion rate, and cure rate of the dimer showed superior performance. Furthermore, the metabolites and major metabolic pathways of the dimer in rats were preliminarily investigated using the HPLC-HRMSn method. Twenty-seven metabolites, including DHA, 11 metabolites of DHA, and 15 other novel metabolites, were detected in rats after i.g. administration of dimer. The metabolic pathways of the 15 novel metabolites were inferred: deoxygenation, hydroxylation, and hydroxylation with dehydration. [ABSTRACT FROM AUTHOR]

An ultrahigh-performance liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of sterigmatocystin, verruculogen, enniatin A, fusarenon-X, fumonisins B1, B2, B3, aflatoxins B1, B2, G1, G2, ochratoxin A, deoxynivalenol, 3-acetyldeoxynivalenol, 5-acetyldeoxynivalenol, and zearalenone. The mycotoxins were extracted and cleaned up using a multitoxin column, separated on a C18 column, and then detected on a triple-quadrupole mass spectrometer. The limits of detection and quantification ranged within 0.2–2 µg/kg and 1–10 µg/kg, respectively. The recoveries ranged from 70.8 to 118.4%, with relative standard deviations below 15%. The method was used to analyze 80 samples obtained from Shandong Province in China. Fifty-eight samples were contaminated with 10 mycotoxins at concentrations ranging from 1.4 to 6566.1 µg/kg. Some samples exceeded the maximum limits in China and in European regulations for mycotoxins in unprocessed maize. [ABSTRACT FROM PUBLISHER]

Doxorubicin (DOX) is used as a first-line chemotherapeutic drug, whereas dihydroartemisinin (DHA) also shows a certain degree of antitumor activity. Disulfide bonds (-SS-) in prodrug molecules can be degraded in highly reducing environments. Thus, heterodimer prodrugs of DOX and DHA linked by a disulfide bond was designed and subsequently prepared as reduction-responsive self-assembled nanoparticles (DOX-SS-DHA NPs). In an in vitro release study, DOX-SS-DHA NPs exhibited reduction-responsive activity. Upon cellular evaluation, DOX-SS-DHA NPs were found to have better selectivity toward tumor cells and less cytotoxicity to normal cells. Compared to free DiR, DOX-SS-DHA NPs showed improved accumulation at the tumor site and even had a longer clearance half-life. More importantly, DOX-SS-DHA NPs possessed a much higher tumor inhibition efficacy than DOX-sol and MIX-sol in 4T1 tumor-bearing mice. Our results suggested the superior antitumor efficacy of DOX-SS-DHA NPs with less cytotoxicity. [Display omitted] • A novel heterodimer prodrug (DOX-SS-DHA) was synthesized to take advantages of the combination therapy. • In vitro efficacy studies of the designed DOX-SS-DHA NPs showed enhanced tumor suppression and improved survival time. • DOX-SS-DHA NPs prepared here had better security to mice and better selectivity to the tumor sites of mice. [ABSTRACT FROM AUTHOR]

A fluorescence magnetic biosensor for the DNA methyltransferase activity was developed based on the cooperative amplification by combining the magnetic nanoparticles synergistic exonuclease III (Exo III)-assisted circular exponential amplification and a supramolecular structure ZnPPIX/G-quadruplex. First, a duplex DNA probe, which was constructed by the hybridization of a quadruplex-forming oligomer with a molecular beacon, was assembled on the magnetic nanoparticles (MNPs) as a reporter. A hairpin probe (HP)-containing sequence of GATC was used as the methylation substrate of DNA adenine methyltransferase (DAM). Once HP was methylated by DAM, it could be recognized and cleaved by Dpn I, which allows the release of a single-stranded DNA. The DNA (tDNA1) then hybridizes to the MNP probe, which then triggers the exonuclease III-mediated target exponential recycling reaction. Simultaneously, numerous quadruplex forming oligomers are liberated and folded into the G-quadruplex-ZnPPIX complexes with the help of zinc(ii)-protoporphyrin IX(ZnPPIX) on the MNP surface to give a remarkable fluorescence response. In the developed sensor, a small amount of target DAM can be converted to a large number of stable DNA triggers, leading to remarkable amplification of the target. Moreover, using MNPs as a vector of the sensor may reduce the interference from the real samples, which increases the anti-interference of the sensing system. Based on this unique amplification strategy, a very low detection limit down to 2.0 × 10−4 U mL−1 was obtained. Furthermore, the sensor could be used to evaluate the DAM activity in different growth stages of E. coli cells and screen Dam MTase inhibitors. Therefore, the strategy proposed here provides a promising platform for monitoring the activity and inhibition of DNA MTases and has great potential to be applied further in early clinical diagnostics and medical research. [ABSTRACT FROM AUTHOR]

Site-specific identification of DNA methylation and assay of MTase activity are imperative for determining specific cancer types, provide insights into the mechanism of gene repression, and develop novel drugs to treat methylation-related diseases. Herein, we developed a highly sensitive fluorescence assay of DNA methyltransferase by methylation-sensitive cleavage-based primer generation exponential isothermal amplification (PG-EXPA) coupled with supramolecular fluorescent Zinc(II)-protoporphyrin IX (ZnPPIX)/G-quadruplex. In the presence of DNA adenine methylation (Dam) MTase, the methylation-responsive sequence of hairpin probe is methylated and cleaved by the methylation-sensitive restriction endonuclease Dpn I. The cleaved hairpin probe then functions as a signal primer to initiate the exponential isothermal amplification reaction (EXPAR) by hybridizing with a unimolecular DNA containing three functional domains as the amplification template, producing a large number of G-quadruplex nanostructures by utilizing polymerases and nicking enzymes as mechanical activators. The G-quadruplex nanostructures act as host for ZnPPIX that lead to supramolecular complexes ZnPPIX/G-quadruplex, which provides optical labels for amplified fluorescence detection of Dam MTase. While in the absence of Dam MTase, neither methylation/cleavage nor PG-EXPA reaction can be initiated and no fluorescence signal is observed. The proposed method exhibits a wide dynamic range from 0.0002 to 20 U/mL and an extremely low detection limit of 8.6×10 −5 U/mL, which is superior to most conventional approaches for the MTase assay. Owing to the specific site recognition of MTase toward its substrate, the proposed sensing system was able to readily discriminate Dam MTase from other MTase such as M.SssI and even detect the target in a complex biological matrix. Furthermore, the application of the proposed sensing strategy for screening Dam MTase inhibitors was also demonstrated with satisfactory results. This novel method not only provides a promising platform for monitoring activity and inhibition of DNA MTases, but also shows great potentials in biological process researches, drugs discovery and clinical diagnostics. [ABSTRACT FROM AUTHOR]

An autonomous DNA nanomachine based on rolling circle amplification (RCA)-bridged two-stage exonuclease III (Exo III)-induced recycling amplification (Exo III-RCA-Exo III) was developed for label-free and highly sensitive homogeneous multi-amplified detection of DNA combined with sensitive fluorescence detection technique. According to the configuration, the analysis of DNA is accomplished by recognizing the target to a unlabeled molecular beacon (UMB) that integrates target-binding and signal transducer within one multifunctional design, followed by the target-binding of UMB in duplex DNA removed stepwise by Exo III accompanied by the releasing of target DNA for the successive hybridization and cleavage process and autonomous generation of the primer that initiate RCA process with a rational designed padlock DNA. The RCA products containing thousands of repeated catalytic sequences catalytically hybridize with a hairpin reporter probe that includes a “caged” inactive G-quadruplex sequence (HGP) and were then detected by Exo III-assisted recycling amplification, liberating the active G-quadruplex and generating remarkable ZnPPIX/G-quadruplex fluorescence signals with the help of zinc(II)-protoporphyrin IX (ZnPPIX). The proposed strategy showed a wide dynamic range over 7 orders of magnitude with a low limit of detection of 0.51 aM. In addition, this designed protocol can discriminate mismatched DNA from perfectly matched target DNA, and holds a great potential for early diagnosis in gene-related diseases. [ABSTRACT FROM AUTHOR]

A cascadic sensing system was developed for detection of DNA target at ultralow concentration by a combination of magnetic nanoparticles (MNPs) and exonuclease III (Exo III)-induced cascade two-stage isothermal amplification in the study. An ingeniously designed capture hairpin probe (CHP) that integrates target-binding and signal transduction sequences within one multifunctional design was assembled on MNPs. Upon sensing of the analyte nucleic acid, the hairpin probe on MNPs could be opened and stepwise removed by Exo III accompanied by the releasing of target DNA for the successive hybridization and cleavage process and the generation of bare signal transduction sequences of CHP as a new trigger for next circular reaction. The new DNA triggers initiate hybridizing with hairpin DNA probe that contains a partially "caged" G-quadruplex sequence (GHP), forming a duplex structure and liberating the active G-quadruplex structure. Then, Exo III digests the resulting duplex domain, leading to the recycling of new DNA trigger and simultaneously generating numerous ZnPPIX/G-quadruplex supramolecular complexes with the help of the zinc (II)-protoporphyrin IX (ZnPPIX), as an optical label for amplified fluorescence sensing event. Finally, numerous liberated cascade ZnPPIX/G-quadruplex supramolecular complexes give a remarkable fluorescence response. Because of two-stage autocatalytic recycling amplification and the specifically catalyzed formation of ZnPPIX/G-quadruplex supramolecular complexes, this newly designed protocol provides a high sensitivity with a detection limit of 0.75 fM, can discriminate mismatched DNA from perfectly matched target DNA, and gives low matrix effect due to using MNPs as the separation and amplification elements in the real samples. Therefore, it holds great potential for early diagnosis in gene-related diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] Targeting delivery and prolonging action duration of artemisinin drugs are effective strategies for improving antimalarial treatment outcomes. Here, dihydroartemisinin (DHA) loaded poly (lactic- co -glycolic acid) (PLGA) nanoparticles (PDNs) were prepared and further cloaked with red blood cell (RBC) membranes via electrostatic interactions to yield RBC membrane-cloaked PDNs (RPDNs). The prepared RPDNs displayed a notable "core-shell" structure, with a negative surface charge of −29.2 ± 4.19 mV, a relatively uniform size distribution (86.4 ± 2.54 nm, polydispersity index of 0.179 ± 0.011), an average encapsulation efficiency (70.1 ± 0.79%), and a 24-h sustained-release behavior in vitro. Compared with PDNs, RPDNs showed markedly decreased phagocytic activity by RAW 264.7 cells and had prolonged blood circulation duration. The Pearson correlation coefficient of RPDNs distribution in infected red blood cells (iRBCs) was 0.7173, suggesting that RPDNs could effectively target Plasmodium -iRBCs. In Py By265-infected mice, RPDNs showed a higher inhibition ratio (88.39 ± 2.69%) than PDNs (83.13 ± 2.12%) or DHA (58.74 ± 3.78%), at the same dose of 8.8 μmol/kg. The ED 90 of RPDNs (8.13 ± 0.18 μmol/kg) was substantially lower than that of PDNs (14.48 ± 0.23 μmol/kg) and DHA (17.67 ± 3.38 μmol/kg). Furthermore, no apparent abnormalities were detected in routine blood examination, liver function indexes, and pathological analysis of tissue sections of Py By265-infected mice following RPDNs treatment. In conclusion, the prepared RPDNs exhibited enhanced antimalarial efficacy, prolonged circulation, targeted delivery to Plasmodium -iRBCs, and satisfactory biocompatibility. [ABSTRACT FROM AUTHOR]

Abstract: A new aptamer biosensor was presented for the detection of thrombin in this work, which was based on fluorescence polarization (FP) using silica nanoparticles as enhancement probe. The silica nanoparticles covered by streptavidin were tagged with a thrombin aptamer (5'-biotin-GGTTGGTGTGGTTGG-3'), which was bound to the surface of silica nanoparticle through the specific interaction between streptavidin and biotin. In the presence of thrombin, it induced the aptamer to form quadruplex structure. When the other thrombin aptamer labeled with fluorescein (5'-FAM-AGTCCGTGGTAGGGCAGGTTGGGGTGACT-3') was added to the above system, a sandwich structure can form at the surface of silica nanoparticles. The fluorescence polarization was therefore enhanced and quantification between fluorescence polarization signal and concentration of thrombin was built. The sensor provided a linear range from 0.6 to 100nM for thrombin with a detection limit of 0.20nM (3.29S B/m, according to the recent recommendation of IUPAC) in a homogeneous media. The same linear range was obtained in spiked human serum samples with a slightly higher detection limit (0.26nM), demonstrating high anti-interference of the sensor in a complex biological sample matrix. And the sensor can be used to monitor spiked concentration of thrombin level in real human plasma with satisfactory results obtained. [Copyright &y& Elsevier]

A simple, label-free and sensitive fluorescence protein assay has been developed on the basis of aptamer exonuclease protection and exonuclease III (Exo III)-assisted recycling amplification-responsive cascade ZnPPIX/G-quadruplex supramolecular fluorescent labels. In the sensing system, a special aptamer probe containing the aptamer sequence at the 3′-terminus and the DNAzyme sequence at the 5′-terminus was applied, which has the capacity to recognize a protein target with high affinity and specificity. Exonuclease I (Exo I) can efficiently catalyze the degradation of free single stranded DNA probes in the 3′ to 5′ direction. In the presence of the target protein, the strong binding between the target protein and its aptamer can protect aptamer probes from degradation. Subsequently, the protected aptamer probes act as catalysators to trigger hybridization with the hairpin DNA probe that contains a partially “caged” G-quadruplex sequence. Upon interaction with the protected aptamer probes, the hairpin opens to yield the active G-quadruplex structure. In the presence of exonuclease III (Exo III), Exo III-assisted recycling amplification occurs generating numerous G-quadruplex supramolecular structures. The zinc(ii)-protoporphyrin IX (ZnPPIX) fluorophore binds to the G-quadruplexes and this results in the enhanced fluorescence of the fluorophore. The resulting fluorescence of the ZnPPIX/G-quadruplex provides the readout signal for the sensing event. Thrombin is used as the model analyte in the current proof-of-concept. The developed method was demonstrated to have very high sensitivity for the detection of proteins with a limit of detection of 0.2 pM without using washes or separations. In addition, this new method for protein detection is simple and inherits all the advantages of aptamers. The mechanism, moreover, may be generalized and used for other forms of protein analysis. [ABSTRACT FROM AUTHOR]

Abstract: In this work, we developed a sensitive and selective sensor technique for total mercury (Hg) detection in canned fish samples based on the fluorescence polarization (FP) method. The detection principle was that ssDNA containing thymine (T) bases was modified on magnetic nanoparticles (MNPs), which were used as enhancement probe. In the presence of Hg2+, the ssDNA on MNPs can hybridize with the fluorophore labeled aptamer owing to the specific interaction between T bases and Hg2+. The formation of thymine–Hg2+–thymine (T–Hg2+–T) complexes leads to the molar mass increase of fluorophore molecules, resulting in the enhancement of FP signal. The increase of FP was in a good linearity with the concentration of Hg2+ in range of 2.0nM–1.0mM and the limit of detection was 0.49nM (3.29 S B /m, according to the recent recommendation of IUPAC). Moreover, the proposed biosensor can be reused for 6 cycling times and was successfully applied in monitoring Hg2+ in real samples. [Copyright &y& Elsevier]

In this work, ZnO nano-needles were electrochemically deposited onto the surface of single carbon fiber. The influence of deposition condition on the surface morphology of ZnO nanostructures was investigated. A growth mechanism was suggested to elucidate the deposition process. Electrochemiluminescence conducted in 0.1 M KOH solution containing 0.1 M K2S2O8 and 0.1 M KCl displayed the stable and sensitive luminescent property of as-prepared ZnO nano-needles. The electrochemiluminescence intensity per projection area from ZnO nano-needles deposited on single carbon fiber was almost five orders of magnitude larger than that from ZnO nanostructures deposited on ITO and ZnO dip-coated on ITO. It demonstrated the high electrochemiluminescence efficiency of ZnO nano-needles deposited on single carbon fiber and the remarkable electrical conductivity of carbon fiber. This work presented a new strategy to deposit oxides on carbon fiber with tunable coverage and nanostructure. Furthermore, the excellent electrochemiluminescence property of ZnO nano-needles on carbon fiber highlights the importance and potential utility of such nanostructures in the development of optoelectronic and biomedical devices. [ABSTRACT FROM AUTHOR]

In the present work, gold nanocluster (GNC) induced by bovine serum albumin (BSA) was synthesized as a novel fluorescence probe to detect nitrite (NO) sensitively and selectively. The fluorescence of GNC was found to be quenched effectively by NO. Under the optimum conditions, it was found that the change of fluorescence intensity was proportional with the concentration of NO in the linear range of 0.1-50 μM ( R = 0.9990), with a detection limit (S/N = 3) of 30 nM. The absorption spectroscopy, circular dichroism (CD), and X-ray photoelectron spectroscopy (XPS) studies were employed to discuss the quenching mechanism. In addition, the present approach was successfully applied in real water samples. [ABSTRACT FROM AUTHOR]

Novel three-dimensional Ag nanoflowers (3DAN) were successfully synthesized through a facile Cu2+ mediated solution method using N,N-dimethylformamide (DMF), which serves as both a reducing agent and a solvent at room temperature. It was found that the introduction of a trace amount of Cu2+ could greatly slow the rate of the Ag+ reaction and thus this process effectively reduced the growth speed of Ag nanoparticles allowing 3DAN to be formed. The mechanism underlying the self-assembly process and shape evolution of 3DAN were systematically investigated by varying reaction time. X-Ray powder diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM) were used to characterize the structure and morphology of the obtained products. X-Ray photoelectron spectroscopy (XPS) was used to assess the chemical state and surface composition of the 3DAN. UV-vis absorption spectra of the products collected from the reaction solution at various stages were taken to study their optical properties. In the measurement of surface-enhanced Raman scattering using rhodamine 6G (R6G) as the probe, the 3DAN exhibited a significant enhancement factor, indicating their potential applications in biosensing and nanodevices. [ABSTRACT FROM AUTHOR]

Abstract: To improve the skin permeation of naproxen with larger dosage, microemulsion with high content of naproxen was investigated for transdermal delivery and its solubilization mechanism was studied. Naproxen micoremulsions composed of 4% isopropyl myristate, 18% Tween 80, 18% ethanol and water were prepared and phase inversion temperature (PIT) method was used to increase drug content. The using of PIT method resulted in the maximum content of naproxen in microemulsion increased from 1.98±0.13% to 4.12±0.07%, accordingly the permeation rate of naproxen from microemulsion through excised mice skin increased from 135.13±5.50 to 214.46±7.53μgcm−2 h−1. The analyses of Natural Bond Orbital and interaction energy using the B3LYP and MP2 (fc) methods suggested that the solubilization mechanism of microemulsion for naproxen mainly might be the formation of complex between the hydrogen atom of hydroxyl in Tween 80 and the oxygen atom of carbonyl group in naproxen, as is in accordance with the result from 1H NMR experiments. The change of thermodynamic function with temperature confirmed that, because the complex was easy to be formed in high temperature and that formed at PIT became more stable when the temperature decreased to below PIT, the solubilization ability of microemulsion for naproxen could be improved by the PIT method. The powerful permeation enhancing ability of microemulsion induced by the solubilization of PIT method makes it a promising vehicle for the transdermal delivery of naproxen. [Copyright &y& Elsevier]

Sulforaphane and sulforaphene are isothiocyanate compounds derived from cruciferous vegetables that have demonstrated antiproliferative properties against colon cancer. However, the underlying mechanism of action of these two compounds has yet to be elucidated. The aim of the present study was to examine the effects of sulforaphane and sulforaphene on colon cancer using next-generation sequencing (NGS). The SW480 colon cancer cell line was cultured with 25 µmol/l sulforaphane or sulforaphene. Total RNA was extracted from the cells following 48 h of incubation with these compounds, and NGS was performed. Pearson's correlation and principal component analyses were performed on the NGS data in order to determine sample homogeneity followed by hierarchical clustering, chromosomal location, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A total of 873 probes in the sulforaphene group were differentially expressed compared with the control group. Similarly, 959 probes in the sulforaphane group were differentially expressed compared with the control group. The differentially expressed genes were dispersed on the chromosomes, across 22 pairs of autosomes, as well as the X and Y chromosomes. GO and KEGG analyses demonstrated that both drugs affected the 'p53 signaling pathway', 'MAPK signaling pathway', 'FOXO signaling pathway' and 'estrogen signaling pathway', while 'Wnt signaling pathway' was enriched in the sulforaphane group, and 'ubiquitin mediated proteolysis' and 'estrogen signaling pathway' in the sulforaphene group. Thus, sulforaphane and sulforaphene exhibited similar biological activities on colon cancer cells. Sulforaphane and sulforaphene may be associated with Wnt and estrogen signaling, respectively. [ABSTRACT FROM AUTHOR]

Although protein tyrosine phosphatases (PTPases) play an important role in signal transduction in animal cells, little is known about the function of PTPases in higher plants. Hydrogen peroxide (H2O2) and mitogen-activated protein kinases (MAPKs) are the critical components of ABA signaling pathway in guard cells. PTPase is an important regulator of MAPK, which is believed to mediate ABA-induced H2O2 generation in guard cells of Vicia faba L. Here, we investigate the possible role of PTPases in stomatal movement process. Phenylarsine oxide (PAO), a specific inhibitor of PTPases, could prevent ABA or H2O2-induced stomatal closure of Vicia faba L; furthermore, it could promote opening of the stomata closed by ABA or H2O2. The activity of PTPases can be effectively inhibited by PAO and H2O2. DTT had no effect on the PAO-induced inhibition of PTPases activity, but it could relieve the inhibition of H2O2 on PTPases activity. PAO could also inhibit the ABA-induced H2O2 generation in guard cells of Vicia faba L. These results suggested that PTPases is a critical signaling component in ABA-induced stomatal closure, and serve as targets for H2O2 lying on the signaling pathways downstream of ABA induced H2O2 generation. [ABSTRACT FROM AUTHOR]

• DTX-S-S-DHA conjugates were synthesized using two-step reaction and furtherly assembled to nanoparticles (DSDNs). • Reductive sensitive release of the DSDNs. • Nanoconjugates enhanced synergistic effect on tumor cells. • Nanoconjugates protected healthy tissues from drugs toxicity. Co-delivery of anti-tumor agents with outstanding stimulus-triggered drug release in tumor cells, especially with the aid of nanotechnology, provided the possibility to enhance delivery efficiency for targeting tumor cells and antitumor efficacy. In this paper, docetaxel-dihydroartemisinin nanoconjugates linked by disulfide bond were designed to increase co-delivery and anti-tumor efficacy. Docetaxel and dihydroartemisinin were synthesized using two-step reaction and furtherly assembled to nanoconjugates. Nanoprescription was optimized to evaluate its physicochemical properties. In vitro anti-tumor activities of nanoformulation were assessed by MTT. The flow cytometry was adopted to analyze cell apoptosis and cell cycle arrest. The wound healing assay was used to evaluate antimigratory-property. In vivo pharmacokinetic and pharmacodynamic studies were investigated in rats and 4T1 bearing Balb/c mice model after intravenous injection, respectively. The chemical structure of conjugate was confirmed. The prepared nanoparticles possessed uniform size distribution (172.10 ± 1.70 nm, PDI 0.05 ± 0.01), was stable during storage period, sustained release profiles and sensitive reduction responsiveness. MTT assay indicated that the toxicity of nanoconjugates was slightly weak. Flow cytometry studies showed that nanoconjugates could promote early apoptosis significantly and mainly arose from G 0 /G 1 phase. The wound healing assay provided an obvious antimetastatic potential of nanoparticles in 4T1 cells. The result of pharmacokinetic study suggested that nanoconjugates exhibited higher exposure levels. In vivo pharmacodynamic research showed that mice treated with docetaxel-dihydroartemisinin nanoconjugates had lower systemic toxicity and higher survival ratio than those of control groups. This potential of nanoconjugates was developed as a novel nanoplateform to treat tumor. [ABSTRACT FROM AUTHOR]