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1.
Anal Chim Acta ; 1101: 65-73, 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32029120

RESUMO

A facile strategy was developed for the fabrication of a magnetic covalent organic framework (COF) via grafting of the monomers, 2,5-dihydroxyterephthalaldehyde (Dt) and 1,3,5-tris(4-aminophenyl) benzene (Tb) onto surface-modified Fe3O4 nanoparticles. The magnetic COF, named as magnetic COF-DtTb, was readily fabricated without high temperature or harsh reaction conditions. The synthesized magnetic COF-DtTb nanoparticles were fully characterized, presenting a regular core-shell spherical structure, large specific surface area, superparamagnetism, and good thermal stability. Their potential as an enrichment adsorbent was investigated to establish an efficient magnetic solid-phase extraction method for the determination of organophosphorus pesticide residues in fruits. Systematic method validation revealed good linearity in the concentration range of 1-200 µg L-1 (correlation coefficient >0.9957). The method limits of detection were in the range of 0.002-0.063 µg kg-1, the method limit of quantification was 1.00 µg kg-1 and recoveries ranged from 72.8% to 111% with RSDs lower than 12.3%. The results indicated that magnetic COF-DtTb possesses superior trace enrichment properties for organophosphorus pesticides in fruits.

2.
J Sep Sci ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32074394

RESUMO

A high-throughput and environmentally friendly method based on 96-well plate thin-film microextraction was established to determine 14 fungicides in grapes and grape juice using liquid chromatography-tandem mass spectrometry. The thin-film microextraction optimized method consisted of 60 min of extraction at pH 6.0 with the addition of sodium chloride (2-5%). Acetonitrile/water in the ratio of 8:2 was used for desorption analytes for 60 min. Evaluation of different extractive phases showed that polyacrylonitrile-polystyrene-divinylbenzene was the optimum coating. The linearity of the method was good in the range of 0.01-0.5 µg/mL for 14 fungicides with determination coefficients (R2 ) from 0.990 to 0.999, which indicated good linearity for both the grape juice and grape matrixes. The limit of detection was in the range of 0.002-0.01 µg/mL. The limit of quantitation was in the range of 0.01 mg/kg according to the minimum fortified level. The average absolute recoveries of the 14 fungicides ranged from 75.0 to 118.3%. The intraday relative standard deviation (n = 4) and interday relative standard deviation (n = 4) were 5.6-13.0% and 1.6-6.4%, respectively. This study showed that this method can be used for analyzing 96 samples in parallel, and the sample preparation time was approximately 2.0 min per sample. In addition, this approach offers a green and low-cost sample pretreatment technique for future analyses.

3.
Environ Pollut ; 260: 114105, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32041085

RESUMO

Pesticides scarcely exist as individual compounds in the water ecosystem, but rather as mixtures of multiple chemicals at relatively low concentrations. In this study, we aimed to explore the mixture toxic effects of fludioxonil (FLU) and triadimefon (TRI) on zebrafish (Danio rerio) by employing different toxicological endpoints. Results revealed that the 96-h LC50 values of FLU to D. rerio at multiple developmental stages ranged from 0.055 (0.039-0.086) to 0.61 (0.33-0.83) mg L-1, which were less than those of TRI ranging from 3.08 (1.84-5.96) to 9.75 (5.99-14.78) mg L-1. Mixtures of FLU and TRI exerted synergistic effects on embryonic zebrafish. Activities of total superoxide dismutase (T-SOD) and catalase (CAT) were markedly altered in most of the individual and pesticide mixture treatments compared with the control. The expressions of 16 genes involved in oxidative stress, cellular apoptosis, immune system and endocrine system displayed that embryonic zebrafish were affected by the individual pesticides and their mixtures, and greater variations of four genes (ERɑ, Tnf, IL and bax) were found when exposed to pesticide mixtures compared with their individual compounds. Therefore, more studies on mixture toxicities among different pesticides should be taken as a priority when evaluating their ecological risk.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31950217

RESUMO

Although the carbendazim is widely used to manage spot blight in celery cultivation, information on residues identified is of interest. In this study, we examined the dissipation and residual amounts of carbendazim in celery and soil under different cultivation methods when using the suggested dose and ten times of that and the bioconcentration factor of carbendazim for celery. The results showed that when celery leaves were sprayed with the suggested dose, the half-lives in a celery field and greenhouse were 2.75 days and 3.29 days, respectively. When the soil matrix was sprayed with the recommended dose before cultivation, the half-lives of carbendazim residues were 16.86 days and 11.97 days. We also conducted a long-term dietary risk assessment using the corresponding criteria. The results showed that, in China, the use of carbendazim at a dose of 0.022 g/m2 is safer and more reasonable when the harvest interval is 28 days.

5.
Nat Commun ; 11(1): 117, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913283

RESUMO

Increased expression of protein kinase ULK1 was reported to negatively correlate with breast cancer metastasis. Here we report that ULK1 suppresses the migration and invasion of human breast cancer cells. The suppressive effect is mediated through direct phosphorylation of Exo70, a key component of the exocyst complex. ULK1 phosphorylation inhibits Exo70 homo-oligomerization as well as its assembly to the exocyst complex, which are needed for cell protrusion formation and matrix metalloproteinases secretion during cell invasion. Reversely, upon growth factor stimulation, Exo70 is phosphorylated by ERK1/2, which in turn suppresses its phosphorylation by ULK1. Together, our study identifies Exo70 as a substrate of ULK1 that inhibits cancer metastasis, and demonstrates that two counteractive regulatory mechanisms are well orchestrated during tumor cell invasion.

6.
Sci Total Environ ; 708: 135221, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31806340

RESUMO

To achieve multi-pesticides residue analysis in seawater, hydrophilic-lipophilic-balanced magnetic particles were designed and fabricated by swelling polymerization of divinyl benzene (DVB) and N-vinyl pyrrolidone (NVP) on the surface of Fe3O4@SiO2 magnetic particles. The ratio of DVB to NVP was adjusted to achieve a proper balance in hydrophilicity and lipophilicity. The obtained magnetic particles were systematically characterized by TEM, SEM, FT-IR and vibrating sample magnetization. Based on the optimized magnetic nanoparticles, a sensitive magnetic solid-phase extraction method was developed for the simultaneous pre-concentration and determination of 96-pesticide residues from large-volume seawater samples prior to being detected by liquid chromatography-tandem mass spectrometry. Recoveries of pesticides in spiked seawater samples (0.001, 0.01, 0.1, 1.0 µg L-1) ranged from 62% to 112% with RSDs less than 21%. The method limits of detection of 96 pesticides ranged from 0.13 to 0.42 ng L-1, the method limits of quantification of 96 pesticides ranged from 1.0 to 10 ng L-1. The method was successfully applied to pesticide residue analysis in water samples from Jiulong River Estuary of China, demonstrating the prospects of this technique as a potential method for the rapid determination of trace levels of multi-pesticide residues in seawater.

7.
Environ Pollut ; 256: 113437, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672357

RESUMO

Pesticides often occur as mixtures of complex compounds in water environments, while most of studies only focus on the toxic effects of individual pesticides with little attention to the joint toxic effects. In the present study, we aimed to the mixture toxicity of beta-cypermethrin (BCY) and thiacloprid (THI) to zebrafish (Danio rerio) employing multiple toxicological endpoints. Results displayed that the 96-h LC50 values of BCY to D. rerio at various developmental stages ranged from 2.64 × 10 (1.97 × 10-3.37 × 10) to 6.03 × 103 (4.54 × 103-1.05 × 104) nM, which were lower than those of THI ranging from 2.97 × 104 (1.96 × 104-4.25 × 104) to 2.86 × 105 (2.19 × 105-5.87 × 105) nM. Mixtures of BCY and THI exhibited synergistic response in embryonic zebrafish. Meanwhile, the enzyme activities of antioxidants (CAT and SOD) and detoxification enzyme (CarE), endogenous T-GSH and MDA contents, as well as gene expressions (tsh, crh, cxcl and bax) involved in oxidative stress, cellular apoptosis, immune system and endocrine system were obviously changed in the mixture exposure compared with the respective BCY or THI treatment. Consequently, the increased toxicity of pesticide mixture suggested that the toxicological data acquired from individual pesticide tests might underrate the toxicity risk of pesticides that actually arise in the real environment. Taken together, our present study provided evidence that mixture exposure of BCY and THI could induce additional toxic effect compared with their respective individual pesticides on D. rerio, offering valuable insights into the toxic mechanism of pesticide mixture.


Assuntos
Neonicotinoides/toxicidade , Praguicidas/toxicidade , Piretrinas/toxicidade , Tiazinas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Embrião não Mamífero/metabolismo , Embrião não Mamífero/fisiologia , Expressão Gênica/efeitos dos fármacos , Larva/metabolismo , Estresse Oxidativo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
8.
Methods Mol Biol ; 2099: 39-50, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31883086

RESUMO

Three-dimensional structures of the receptor-binding domain (RBD) of MERS-CoV spike glycoprotein bound to cellular receptor and monoclonal antibodies (mAbs) have been determined by X-ray crystallography, providing structural information about receptor recognition and neutralizing mechanisms of mAbs at the atomic level. In this chapter, we describe the purification, crystallization, and structure determination of the MERS-CoV RBD.

9.
Sci Total Environ ; 706: 136039, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31846872

RESUMO

Cis-epoxiconazole is a widely used triazole fungicide for control and prevention of a series of fungal diseases in fruits, vegetables, teas and grains. The present work aimed at exploring enantioselective behavior of cis-epoxiconazole in the vegetable-soil-earthworm system. Firstly, the absolute configuration of cis-epoxiconazole enantiomers was ascertained. Secondly, enantioselective degradation of cis-epoxiconazole in cabbage, pakchoi and pepper were performed under field trials, which has not been previously reported. Enantioselective degradation occurred in cabbage and pepper samples. 2R, 3S-(+)-cis-epoxiconazole was degraded faster than 2S, 3R-(-)-cis-epoxiconazole in cabbage, while the reversed results were obtained in pepper. No enantioselective degradation was observed in pakchoi. Finally, soil is the principal reservoir of environmental pesticides, so the enantioselective behaviors of cis-epoxiconazole in soil and soil organism (earthworm, Eisenia fetida) were evaluated. Similar bioaccumulation curves in earthworms and degradation curves in soil were observed under the exposure levels of 1 and 10 mg/kg. Accumulation factors (AFs) indicated earthworms had weak bioaccumulation potential to cis-epoxiconazole in the contaminated soil, and no obvious enantioselectivity was observed. The different enantioselectivities in different vegetables illuminated that preferentially enriched enantiomer might impose higher risk on human health than the other one, and the high risk enantiomer required further assessment. These results may reduce the uncertainty of cis-epoxiconazole to the environmental risk assessment.

10.
Chemosphere ; 239: 124802, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31521933

RESUMO

Pesticides are usually present as mixtures in water environments. Evaluating the toxic effects of individual pesticide may not be enough for protecting ecological environment due to interactions among substances. In this study, we aimed to examine the lethal doses and gene expression changes in zebrafish (Danio rerio) upon exposure to individual and mixture pesticides [malathion (MAL), chlorpyrifos (CHL) and lambda-cyhalothrin (LCY)]. Individual pesticide toxicity evaluation manifested that the toxicity of the three pesticides to D. rerio at various developmental stages (embryonic, larval, juvenile and adult stages) followed the order of LCY > CHL > MAL. On the contrary, the least toxicity to the animals was discovered from MAL. Most of the tested pesticides displayed lower toxicities to the embryonic stage compared with other life stages of zebrafish. Synergistic effects were monitored from two binary mixtures of LCY in combination with MAL or CHL and ternary mixture of MAL + CHL + LCY. The expressions of 16 genes involved in oxidative stress, immunity system, cell apoptosis and endocrine disruption at the mRNA level revealed that embryonic zebrafish were influenced by the individual or mixture pesticides. The expressions of Tnf, P53, TRα, Crh and Cyp19a exerted greater variations upon exposure to pesticide mixtures compared with their individual compounds. Collectively, the transcriptional responses of these genes might afford early warning biomarkers for identifying pollutant exposure, and the data acquired from this study provided valuable insights into the comprehensive toxicity of pesticide mixtures to zebrafish.


Assuntos
Misturas Complexas/toxicidade , Larva/efeitos dos fármacos , Praguicidas/toxicidade , Animais , Clorpirifos/toxicidade , Interações de Medicamentos , Disruptores Endócrinos/toxicidade , Estágios do Ciclo de Vida/efeitos dos fármacos , Malation/toxicidade , Nitrilos/toxicidade , Piretrinas/toxicidade , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
11.
J Agric Food Chem ; 67(40): 10997-11004, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31487170

RESUMO

The enantioselective bioactivity, toxicity, and environmental behaviors of isocarbophos (ICP) were investigated. The order of the bioactivity and toxicity was S-(+) ≥ rac > R-(-), and the difference of R-(-) and S-(+) was up to 232 times. The usage of S-(+)-ICP may efficiently reduce the usage amount of rac-ICP by 35% under the same effect, and the toxicity was not increased. Based on the toxic unit analysis, the additive effect and synergistic effect of ICP enantiomers were found in the four nontarget organisms, and R-(-)-ICP might cooperate the side-effects of S-(+)-ICP. The accumulation of rac-ICP in earthworms was enantioselective with an enantioenrichment of R-(-)-ICP, so the usage of racemic ICP might increase the exposure risk of R-(-)-ICP to earthworms. From the comprehensive results, the production of enantiomer enriched S-(+)-ICP might increase bioactivity and reduce environmental pollution, while the toxicity of S-(+)-ICP to other nontarget organisms needs to be further assessed.


Assuntos
Inseticidas/química , Inseticidas/toxicidade , Malation/análogos & derivados , Animais , Malation/química , Malation/toxicidade , Oligoquetos/efeitos dos fármacos , Oligoquetos/crescimento & desenvolvimento , Estereoisomerismo , Relação Estrutura-Atividade
12.
Structure ; 27(8): 1296-1307.e5, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31257107

RESUMO

The interleukin 1 (IL-1) receptor family, whose members contain three immunoglobulin-like domains (D1-D3) in the extracellular region, is responsible for transmitting pleiotropic signals of IL-1 cytokines. The inter-domain flexibility of IL-1 receptors and its functional roles have not been fully elucidated. In this study, we used small-angle X-ray scattering to show that ligand-binding primary receptors and co-receptors in the family all have inherent inter-domain flexibility due to the D2/D3 linker. Variants of the IL-1RAcP and IL-18Rß co-receptors with mutated D2/D3 linkers cannot form a cytokine-receptor complex and mediate signaling. Our analysis further revealed that these mutated co-receptors exhibited a changed conformational ensemble, suggesting that loss of function is due to the alteration of receptor dynamics. Taken together, our results demonstrate that the D2/D3 linker is a critical functional determinant of IL-1 receptor and underscore the important roles of the inter-domain flexibility in cytokine/receptor binding and signaling.

13.
Nat Commun ; 10(1): 3068, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296843

RESUMO

Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/metabolismo , Anticorpos Neutralizantes/ultraestrutura , Anticorpos Antivirais/sangue , Anticorpos Antivirais/metabolismo , Anticorpos Antivirais/ultraestrutura , Linhagem Celular Tumoral , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Cristalografia por Raios X , Dipeptidil Peptidase 4/metabolismo , Modelos Animais de Doenças , Mapeamento de Epitopos , Epitopos/imunologia , Feminino , Células HEK293 , Humanos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Testes de Neutralização , Ligação Proteica/imunologia , Domínios Proteicos/imunologia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestrutura , Glicoproteína da Espícula de Coronavírus/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Células Vero , Internalização do Vírus
14.
ACS Appl Mater Interfaces ; 11(29): 26250-26260, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31251555

RESUMO

Metal-organic frameworks (MOFs) have shown considerable prospects for sensing pesticide residues. However, the low stability of MOFs in water hinders them from testing food and environmental samples. Herein, we report an easy and cost-efficient synthesis of a water-stable zirconium luminescent MOF (Zr-LMOF) and its application for rapid, sensitive, and in situ detection of organophosphorous pesticides (OPPs). The Zr-MOF is prepared using Zr(IV) and 1,2,4,5-tetrakis(4-carboxyphenyl)benzene. The synthesized Zr-LMOF rapidly absorbs trace amounts of OPP parathion-methyl and indicates its presence. A low limit of detection of 0.115 µg kg-1 (0.438 nM) with a wide linear range from 70 µg kg-1 to 5.0 mg kg-1 was achieved. Satisfactory recoveries ranging from 78% to 107% were obtained for spiked food and environmental samples. Further, the Zr-LMOF was applied to imitate rapid and in situ imaging detection of pesticide residue on fresh produce nondestructively; visual signals appeared under ultraviolet light within 5 min. These results suggest that the Zr-LMOF has the potential for low-cost, rapid, and in situ imaging detection of OPPs contamination via easy-to-read visual signal.

15.
Anal Chim Acta ; 1074: 108-116, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159930

RESUMO

As an important "food and drug dual-use" product, chrysanthemums are widely used in both botanical medicine and food applications. However, the misuse of pesticides during chrysanthemum cultivation makes pesticide residue monitoring crucial. The aim of the present work was to address this practical demand for the simultaneous determination of multiple pesticide residues in various species of chrysanthemums. Both the sample pre-treatment and instrumental methods were systematically investigated. Seven chrysanthemum samples were extracted using acetonitrile and purified by dispersive solid-phase extraction with amino-modified multi-walled carbon nanotubes (MWCNTs-NH2) and C18 as the cleanup co-adsorbents. After optimizing the amounts of MWCNTs-NH2 and C18, matrix effects could not be avoided during LC-MS/MS analysis of 112 pesticides, although satisfactory recoveries were obtained. The use of SFC-MS/MS was evaluated, which demonstrated the significant positive role of SFC-MS/MS in reducing the matrix effects during pesticide residue analysis. In addition, the use of SFC-MS/MS permitted a shorter run time and afforded greater analytical efficiency. Method validation was further performed to evaluate the linearity, sensitivity, recovery, and precision of the developed method. Good linearity was observed for 92% of the analytes in the concentration range of 2-250 µg L-1 for all seven of the chrysanthemum samples. The LODs of the 112 pesticides ranged from 0.01 to 31.41 µg L-1, depending on the sample, while the mean recoveries of all of the spiked pesticides ranged from 81.8% to 102% for concentrations of 20, 50, and 200 µg kg-1. These results clearly demonstrate the applicability of the developed method for the simultaneous determination of multi-pesticides in various chrysanthemum samples.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Chrysanthemum/química , Resíduos de Praguicidas/análise , Espectrometria de Massas em Tandem/métodos , Acetonitrilos/química , Adsorção , Contaminação de Medicamentos/prevenção & controle , Contaminação de Alimentos/análise , Limite de Detecção , Nanotubos de Carbono/química , Extração em Fase Sólida/métodos
16.
Emerg Microbes Infect ; 8(1): 841-856, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31169078

RESUMO

The Middle East respiratory syndrome coronavirus (MERS-CoV) has spread through 27 countries and infected more than 2,200 people since its first outbreak in Saudi Arabia in 2012. The high fatality rate (35.4%) of this novel coronavirus and its persistent wide spread infectiousness in animal reservoirs have generated tremendous global public health concern. However, no licensed therapeutic agents or vaccines against MERS-CoV are currently available and only a limited few have entered clinical trials. Among all the potential targets of MERS-CoV, the spike glycoprotein (S) has been the most well-studied due to its critical role in mediating viral entry and in inducing a protective antibody response in infected individuals. The most notable studies include the recent discoveries of monoclonal antibodies and development of candidate vaccines against the S glycoprotein. Structural characterization of MERS-CoV S protein bound with these monoclonal antibodies has provided insights into the mechanisms of humoral immune responses against MERS-CoV infection. The current review aims to highlight these developments and discuss possible hurdles and strategies to translate these discoveries into ultimate medical interventions against MERS-CoV infection.


Assuntos
Anticorpos Antivirais/imunologia , Infecções por Coronavirus/prevenção & controle , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vacinas Virais/imunologia , Animais , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Glicoproteína da Espícula de Coronavírus/administração & dosagem , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
17.
J Hazard Mater ; 375: 305-311, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31082719

RESUMO

The enantioselective bioactivity and acute toxicity to target and non-target model species, and environmental fate of isocarbophos (ICP) in rice cultivation were investigated systematically. Bioactivity and toxicity of S-(+)-ICP was significantly greater than R-(-)-ICP, and the difference was 2.9-101 times. Based on the toxic unit analysis, the toxic interaction of ICP enantiomers for target pests was synergistic effect, while for non-target fish was concentration addition or antagonistic effect. Rac-ICP displayed equivalent bioactivity to S-(+)-ICP under the equal dosage, but the toxicity of rac-ICP to the tested fishes reduced at least 2 times. Rac-ICP is more suitable than optically pure S-(+)-ICP for rice cultivation based on the toxicity and bioactivity results. In environmental behavior experiments, the main metabolite of ICP, isocarbophos oxon (ICPO) was detected in rice plants, water, rice and rice hull samples. S-(+)-ICP and S-(+)-ICPO were more persistent than the R-form in these matrices. The comprehensive data of ICP enantiomers in rice cultivation will improve environmental and ecological risk assessment, and using racemate may be more safe and reasonable in rice cultivation system.

18.
Emerg Microbes Infect ; 8(1): 760-772, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130102

RESUMO

The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.


Assuntos
Infecções por Coronavirus/prevenção & controle , Portadores de Fármacos/administração & dosagem , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Adenoviridae/genética , Administração Intranasal , Animais , Animais Geneticamente Modificados , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Humanos , Imunização Passiva , Camundongos Endogâmicos BALB C , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Glicoproteína da Espícula de Coronavírus/genética , Análise de Sobrevida , Linfócitos T/imunologia , Resultado do Tratamento , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
19.
Physiol Rep ; 7(8): e14071, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31033205

RESUMO

Growing evidence suggests that redox-sensitive proteins including glutaredoxins (Grxs) can protect cardiac muscle cells from oxidative stress-induced damage. Mammalian Grx3 has been shown to be critical in regulating cellular redox states. However, how Grx3 affects cardiac function by modulating reactive oxygen species (ROS) signaling remains unknown. In this study, we found that the expression of Grx3 in the heart is decreased during aging. To assess the physiological role of Grx3 in the heart, we generated mice in which Grx3 was conditionally deleted in cardiomyocytes (Grx3 conditional knockout (CKO) mice). Grx3 CKO mice were viable and grew indistinguishably from their littermates at young age. No difference in cardiac function was found comparing Grx3 CKO mice and littermate controls at this age. However, by the age of 12 months, Grx3 CKO mice exhibited left ventricular hypertrophy with a significant decrease in ejection fraction and fractional shortening along with a significant increase of ROS production in cardiomyocytes compared to controls. Deletion of Grx3 also impaired Ca2+ handling, caused enhanced sarcoplasmic reticulum (SR) calcium (Ca2+ ) leak, and decreased SR Ca2+ uptake. Furthermore, enhanced ROS production and alteration of Ca2+ handling in cardiomyocytes occurred, prior to cardiac dysfunction in young mice. Therefore, our findings demonstrate that Grx3 is an important factor in regulating cardiac hypertrophy and heart failure by modulating both cellular redox homeostasis and Ca2+ handling in the heart.

20.
Chemosphere ; 227: 489-495, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31005669

RESUMO

The contaminants, instead of single contaminants, are usually found as chemical mixtures in terrestrial environment. However, little information is now available about the joint effects of heavy metals and farm chemicals on the soil organism. Our current study aimed to assess the combined toxicity of cadmium (Cd) and four pesticides (atrazine, chlorpyrifos, lambda-cyhalothrin and abamectin) to the earthworm (Eisenia fetida) with binary, ternary, quaternary and quinquenary mixtures. Two distinct kinds of bioassay systems were applied in this study, including contact filter paper test and artificial soil test. Synergistic effects were observed from two quaternary mixtures (Cd-Atrazine-Chlorpyrifos-Lambda-cyhalothrin and Cd-Chlorpyrifos-Lambda-cyhalothrin-Abamectin) and one quinquenary mixture (Cd-Atrazine-Chlorpyrifos-Lambda-cyhalothrin-Abamectin) in both bioassay systems. Besides, two binary mixtures (Cd-Atrazine and Cd-Lambda-cyhalothrin) and three ternary mixtures (Cd-Atrazine-Chlorpyrifos, Cd-Atrazine-Lambda-cyhalothrin and Cd-Chlorpyrifos-Lambda-cyhalothrin) also exhibited synergistic effects on E. fetida by the soil toxicity test. It is more practical to evaluate the contaminant toxicities to earthworm by soil toxicity test. Therefore, the effects of chemical mixtures on soil invertebrates might be underestimated by data obtained from single toxicant. Our findings would offer a better understanding of the complex effects of chemical mixtures on non-target living creatures, and these findings provided valuable insights into the interplay of different chemicals in natural environment.


Assuntos
Cádmio/toxicidade , Misturas Complexas/farmacologia , Oligoquetos/efeitos dos fármacos , Praguicidas/toxicidade , Poluentes do Solo/toxicidade , Testes de Toxicidade , Animais , Inseticidas/toxicidade , Metais Pesados/toxicidade
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