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1.
Risk Anal ; 43(8): 1539-1556, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36307897

RESUMO

As the decision-making basis for "safety" in risk management and risk assessment activities, acceptable risk has always been an important topic of risk-related research. Based on the records in the Science Citation Index Expanded database and Social Sciences Citation Index database via the Web of Science Core Collection, 1124 articles or reviews related to acceptable risk in engineering and operations research and management science were retrieved. These documents, published between 1961 and 2021, covered 3056 authors, 75 countries/territories, 1296 institutions, and 323 journals. In this study, bibliometric data such as annual growth trends were analyzed by using descriptive statistics. Through the co-occurrence maps created by CiteSpace and Gephi, the most productive and influential countries/territories, institutions, and authors as well as their cooperation networks were identified. Further analysis was conducted to determine the core publications and publication sources in this field through co-citation analysis. Insights into focus areas and research topics over time were obtained through keyword co-occurrence analysis. This study provides a macroscopic overview of acceptable risk research and may help researchers better understand this research field and predict its dynamic directions.

2.
Yi Chuan ; 43(10): 962-971, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702708

RESUMO

Microhaplotype loci (microhaplotype, MHs), defined by two or more closely linked single nucleotide polymorphisms, are a type of molecular marker within a short segment of DNA. As emerging forensic genetic markers, MHs have no stutter artefacts and higher polymorphism, and permit the design of smaller amplicons. In order to identify the markers from a genome wide perspective and explore their potential application further, we constructed the most comprehensive MH dataset to date, based on the whole genome sequencing data of 105 Han individuals in Southern China from 1000 Genomes Project. The results showed that there were 9,490,075 MH loci in the range of 350 bp in the human genome, and the distribution density of microhaplotypes suggests gene variation. Polymorphism analysis of MHs from various base spans showed that the polymorphism of MHs could reach or exceed common short tandem repeat sites. In addition, based on their flexible assembly, a scheme to build the public database of microhaplotypes was proposed.


Assuntos
Impressões Digitais de DNA , Sequenciamento de Nucleotídeos em Larga Escala , China , Genética Forense , Frequência do Gene , Genética Populacional , Genômica , Haplótipos , Humanos , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único/genética
3.
J Oncol Pharm Pract ; 26(4): 794-802, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31483750

RESUMO

OBJECTIVES: Despite safe handling guidelines published by several groups, health care worker exposure to hazardous drugs continues to occur due to suboptimal engineering controls and low use of protective equipment. Simple, multi-target and specific analytical methods are needed so that acute exposures to these drugs in the workplace can be assessed rapidly. Our aim was to develop an analytical method for simultaneous detection and quantification of widely used cancer drugs to rule out accidental acute chemotherapy exposures in health care workers. METHODS: We examined the feasibility of alternate high-performance liquid chromatographic-tandem mass spectrometry methods to simultaneously detect eighteen chemotherapy analytes in plasma and urine. The linear concentration ranges tested during assay development were 0.1-50 ng/mL. After development of a multi-analyte assay protocol, plasma samples (n = 743) from a multi-center cluster-randomized clinical trial (n = 12 sites) of an hazardous drug educational intervention were assayed. Confirmatory assays were performed based on the individual acute-spill case-histories. RESULTS: An innovative HPLC-multiple reaction monitoring-information dependent acquisition-enhanced production ion (MRM-IDA-EPI) analytical method was developed to simultaneously detect: cytarabine, gemcitabine, dacarbazine, methotrexate, topotecan, mitomycin, pemetrexed, irinotecan, doxorubicin, vincristine, vinblastine, ifosamide, cyclophosphamide, vinorelbine, bendamustine, etoposide, docetaxel, and paclitaxel. The retention times ranged from 4 min to 13 min for the analytical run. The limit of detection (MRM-IDA-EPI) and limit of quantitation (MRM) was 0.25 ng/mL and 0.1 ng/mL, respectively for most analytes. No detectable plasma concentrations were measured at baseline, post-intervention and in cases of documented acute spills. Use of a secondary tandem mass spectrometry approach was able to successfully rule out false positive results. CONCLUSIONS: Development of a sensitive high-throughput multi-analyte cancer chemotherapy assay is feasible using an MRM-IDA-EPI method. This method can be used to rapidly rule out systemic exposure to accidental acute chemotherapy spills in health care workers.


Assuntos
Antineoplásicos/análise , Cromatografia Líquida de Alta Pressão/métodos , Pessoal de Saúde , Espectrometria de Massas em Tandem/métodos , Humanos , Local de Trabalho
5.
Int J Mol Sci ; 19(7)2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30041403

RESUMO

Neuroglobin is an endogenous neuroprotective protein, but the underlying neuroprotective mechanisms remain to be elucidated. Our previous yeast two-hybrid screening study identified that Dishevelled-1, a key hub protein of Wnt/ß-Catenin signaling, is an interaction partner of Neuroglobin. In this study, we further examined the role of Neuroglobin in regulating Dishevelled-1 and the downstream Wnt/ß-Catenin and NFκB signaling pathway. We found that Neuroglobin directly interacts with Dishevelled-1 by co-immunoprecipitation, and the two proteins are co-localized in both cytoplasma and nucleus of SK-N-SH cells. Moreover, the ectopic expression of Neuroglobin promotes the degradation of exogenous and endogenous Dishevelled-1 through the proteasomal degradation pathway. Furthermore, our results showed that Neuroglobin significantly inhibits the luciferase activity of Topflash reporter and the expression of ß-Catenin mediated by Dishevelled-1 in SK-N-SH cells. In addition, we also documented that Neuroglobin enhances TNF-α-induced NFκB activation via down-regulating Dishevelled-1. Finally, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assays showed that Neuroglobin is an important neuroprotectant that protects SK-N-SH cells from TNF-α-induced decrease in cell viability. Taken together, these findings demonstrated that Neuroglobin functions as an important modulator of the Wnt/ß-Catenin and NFκB signaling pathway through regulating Dishevelled-1.


Assuntos
Globinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Proteínas Desgrenhadas/metabolismo , Globinas/genética , Humanos , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/genética , Neuroglobina , Ligação Proteica , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
6.
J Sci Food Agric ; 98(10): 3815-3822, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29352462

RESUMO

BACKGROUND: Postharvest diseases result in major losses in fruits. Tomato is susceptible to postharvest rot caused by Botrytis cinerea and is regarded as a good model system to study postharvest disease and quality deterioration in fruit. To develop a safe and effective technique to alleviate disease and maintain fruit quality, the effects of methyl salicylate (MeSA) and 1-methylcyclopropene (1-MCP) either separately or combined on quality and gray mold caused by B. cinerea in tomato fruit were investigated. RESULTS: The results showed that application of MeSA (0.05 mmol L-1 ) delayed fruit ripening and reduced gray mold. Compared with MeSA treatment, 1-MCP (0.5 µL L-1 ) effectively delayed fruit ripening. Further, MeSA combined with 1-MCP treatment was more effective in inhibiting fungal decay during storage than MeSA treatment alone. The combined treatment not only enhanced pathogenesis-related protein 1 (PR1) expression, activities of defense enzymes and total phenolic content but also inhibited the increase in electrical conductivity and malondialdehyde content. The combined treatment was also more effective in retaining firmness, color change and titratable acidity content than MeSA treatment alone. CONCLUSION: MeSA combined with 1-MCP treatment was a useful technique to maintain quality and alleviate gray mold in postharvest tomato fruit during storage. © 2018 Society of Chemical Industry.


Assuntos
Botrytis/efeitos dos fármacos , Ciclopropanos/farmacologia , Conservação de Alimentos/métodos , Conservantes de Alimentos/farmacologia , Frutas/microbiologia , Salicilatos/farmacologia , Solanum lycopersicum/química , Botrytis/fisiologia , Frutas/química , Solanum lycopersicum/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle
7.
Drug Metab Dispos ; 42(5): 839-43, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24595680

RESUMO

It has been proposed that in humans 4ß-hydroxycholesterol is formed mainly by CYP3A-catalyzed metabolism of cholesterol and thus may serve as an endogenous marker for CYP3A activity. The cynomolgus monkey is widely used as one of the nonrodent preclinical safety species in pharmaceutical research. In the current study, the potential application of 4ß-hydroxycholesterol as an endogenous biomarker of CYP3A in response to drug treatment was evaluated in cynomolgus monkeys. Following multiple oral administration of rifampicin (a known CYP3A inducer) at 15 mg/kg/d in cynomolgus monkeys, the mean serum 4ß-hydroxycholesterol levels increased 4-fold from the baseline of 55.3 ± 21.7 to 221 ± 53.4 ng/ml. The mean concentration ratios of 4ß-hydroxycholesterol to cholesterol increased 5-fold. The data suggest that 4ß-hydroxycholesterol formation from cholesterol metabolism was induced by rifampicin treatment in monkeys. This observation correlated with the metabolism of midazolam (a probe substrate of CYP3A activity) monitored in the same study. The serum exposure (area under the curve) of midazolam was markedly decreased by ∼95%, confirming the induction of CYP3A catalytic activity by rifampicin treatment in monkeys. The formation of 4ß-hydroxycholesterol from cholesterol was specifically mediated by recombinant cynomolgus CYP3A8 and CYP3A5. The Km values of CYP3A8 and CYP3A5 for 4ß-hydroxycholesterol formation from cholesterol were 204 and 104 µM, respectively, and Vmax values were 0.600 and 0.310 pg/pmol/min, respectively. The results suggest that 4ß-hydroxycholesterol can be used as an endogenous biomarker to identify strong CYP3A inducers in cynomolgus monkeys, which may help to evaluate drug-drug interaction potential of drug candidates in preclinical settings.


Assuntos
Citocromo P-450 CYP3A/metabolismo , Hidroxicolesteróis/sangue , Administração Oral , Animais , Biomarcadores/sangue , Biotransformação , Colesterol/metabolismo , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP3A/biossíntese , Citocromo P-450 CYP3A/genética , Avaliação Pré-Clínica de Medicamentos , Indução Enzimática , Feminino , Macaca fascicularis , Masculino , Midazolam/sangue , Midazolam/farmacocinética , Rifampina/farmacologia , Especificidade por Substrato , Espectrometria de Massas em Tandem
8.
Patient Prefer Adherence ; 18: 1373-1383, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38953017

RESUMO

Aim: The aim of this study is to describe the readiness of hospital discharge of patients with coronary heart disease (CHD) who have undergone coronary stent implantation and explore its influencing factors. Methods: This is a cross sectional single center study. Convenient sampling was used to select patients who underwent coronary stent implantation in the Cardiovascular Department of a tertiary hospital in Chengdu from October 2021 to April 2022 as the research subjects. Data were collected using the General Information Questionnaire, which included domains such as uncertainty in illness, the quality of discharge teaching, perceived social support, and health locus of control. The Readiness for Hospital Discharge Scale (RHDS) was used to assess readiness for hospital discharge. Multiple regression adjusted for relevant confounders was used to determine the associations. Results: A total of 276 questionnaires were distributed, and 263 valid questionnaires were collected. The average item score of RHDS is 7.66 ± 1.13. Multiple regression analysis indicated that the influential factors of RHDS of patients who underwent coronary stent implantation included: deliver skill (ß = 0.43), marital status (ß = 0.12), living alone (ß = -0.14), inconsistency (ß = -0.22) and household income per capita (ß = -0.12) (all P<0.05). The RHDS score of patients with CHD after coronary stent implantation were at a moderate level. Conclusion: Discharge readiness was significantly associated with delivery skill, marital status, living alone, inconsistency of information, and household income per capita. The present study highlights the need for improved educational interventions and tailored discharge planning.

9.
J Agric Food Chem ; 72(10): 5185-5196, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38427575

RESUMO

Mitogen-activated protein kinase (MAPK) cascades and raffinose have been observed to increase in plants exposed to cold. However, it remains elusive whether and how MAPK regulates raffinose synthesis under cold stress. Here, overexpression of SlMAPK3 promoted the accumulation of galactinol and raffinose under cold stress, while CRISPR/Cas9-mediated mutants showed the opposite results. Moreover, SlMAPK3 promoted the expression of SlWRKY46 at low temperatures and interacted with SlWRKY46 protein. Overexpression of SlWRKY46 enhanced cold resistance. Furthermore, SlWRKY46 directly bound to the promoter of SlGols1 to enhance its expression and promoted the accumulation of raffinose. Virus-induced gene-silencing (VIGS)-mediated knockdown of SlGols1 remarkably elevated cold sensitivity and reduced raffinose content. Meanwhile, exogenous supplementation of raffinose could improve the cold tolerance of tomato plants. Thus, our data indicates that SlMAPK3 modulates cold resistance by regulating raffinose content and SlWRKY46 expression. SlWRKY46 also promotes the accumulation of raffinose by inducing the expression of SlGols1.


Assuntos
Solanum lycopersicum , Rafinose/metabolismo , Proteínas de Plantas/metabolismo , Temperatura Baixa , Proteínas Quinases Ativadas por Mitógeno/genética , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/metabolismo
10.
J Agric Food Chem ; 72(9): 4552-4563, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38379128

RESUMO

Pathogens influence the growth and development of plants, resulting in detrimental damage to their yields and quality. Ethylene, a gaseous phytohormone, serves a pivotal function in modulating diverse physiological processes in plants, including defense mechanisms against pathogen invasion. Ethylene biosynthesis is involved in both plants and pathogens. Recent empirical research elucidates the intricate interactions and regulatory mechanisms between ethylene and pathogens across various plant species. In this review, we provide a comprehensive overview of the latest findings concerning ethylene's role and its regulatory networks in host-pathogen interactions. Additionally, we explore the crosstalk between ethylene and other phytohormones. Points regarding ethylene emission and its modulation by pathogens are also emphasized. Moreover, we also discuss potential unresolved issues in the field that warrant further investigation.


Assuntos
Etilenos , Reguladores de Crescimento de Plantas , Plantas/genética
11.
Environ Sci Pollut Res Int ; 31(30): 43351-43368, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38900404

RESUMO

To solve the problem of unclear targeted inhibition of key free radicals by antioxidants, this paper took the hydroxyl radical with the highest oxidation activity of coal as the inhibition target and selected five antioxidants such as ethylene diamine tetraacetic acid, tea polyphenol, citric acid, vitamin C, and proanthocyanidins. Based on the theory of quantum chemistry, the characteristics and oxidation pathway of antioxidants inhibiting coal oxidation of hydroxyl radical were analyzed. Analyze the influence characteristics of antioxidants on the evolution of free radicals in coal through an electron paramagnetic resonance experiment (ESR). The results showed that the electron density of antioxidants was mainly distributed in the functional groups of carboxyl and hydroxyl, which played a key inhibitory role, and the vicinity of carboxyl and hydroxyl and other functional groups was positive potential, which was the active site of inhibiting hydroxyl radical. The order of inhibitory capacity of the five antioxidants was determined as GTP > PC > EDTA > CA > VC. It is concluded that the energy barrier of hydroxyl radical inhibition by citric acid is much lower than that of EDTA. For the hydrogen extraction reaction, VC inhibited the hydroxyl radical pathway with a higher energy barrier than the other three antioxidants. The mechanism of five antioxidants inhibiting •OH reaction was comprehensively analyzed. It was found that tea polyphenols have more active sites that can react with •OH to quench it, so the inhibition of tea polyphenols should be the most significant. When antioxidants inhibit coal spontaneous combustion, the type, complexity, concentration, and linewidth of free radicals in coal molecules are lower than those in raw coal, with GTP antioxidants having the best inhibitory effect. The research results have important theoretical and practical significance for revealing the mechanism of coal spontaneous combustion inhibition and developing directional coal spontaneous combustion inhibition technology.


Assuntos
Antioxidantes , Carvão Mineral , Radical Hidroxila , Oxirredução , Radical Hidroxila/química , Antioxidantes/química , Antioxidantes/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica
12.
J Agric Food Chem ; 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37023258

RESUMO

Mitogen-activated protein kinase (MAPK) cascades and ethylene are crucial for plant growth, development, and stress responses, but their potential mechanisms in cold resistance remain unclear. We revealed that SlMAPK3 transcript levels were dramatically induced by cold treatment in an ethylene-dependent manner. Under cold stress, the proline content of SlMAPK3-overexpression fruit was 96.5 and 115.9% higher than that of wild-type fruit (WT), respectively, while the ion leakage was 37.3 and 32.5% lower than that of WT. RNA sequencing revealed that overexpression of SlMAPK3 caused upregulation of genes that are enriched in the ethylene-activated signaling pathway (GO:0009873), cold signaling pathway (GO:0009409), and heat signaling pathway (GO:0009408). RT-qPCR demonstrated that the expression levels of SlACS2, SlACS4, SlSAHH, SlCBF1, SlDREB, SlGolS1, and SlHSP17.7 in the OE.MAPK3 fruits were consistent with the RNA sequencing results. Meanwhile, the knockout of SlMAPK3 reduced the ethylene content, ACC content, and ACS activity. Moreover, the knockout of SlMAPK3 reduced the positive effect of ethylene in cold stress, while suppressing the expression of SlICE1 and SlCBF1. In conclusion, our study demonstrated a novel mechanism by which SlMAPK3 positively regulates the ethylene production of postharvest tomato fruits and is involved in ethylene-mediated cold tolerance.

13.
Foods ; 12(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37509842

RESUMO

Tomato fruit is highly susceptible to infection by Botrytis cinerea (B. cinerea), a dominant pathogen, during storage. Recent studies have shown that autophagy is essential for plant defense against biotic and abiotic stresses. Autophagy-related gene 5 (ATG5) plays a key role in autophagosome completion and maturation, and is rapidly induced by B. cinerea, but the potential mechanisms of ATG5 in Solanum lycopersicum (SlATG5) in postharvest tomato fruit resistance to B. cinerea remain unclear. To elucidate the role of SlATG5 in tomato fruit resistant to B. cinerea, CRISPR/Cas9-mediated knockout of SlATG5 was used in this study. The results showed that slatg5 mutants were more vulnerable to B. cinerea and exhibited more severe disease symptoms and lower activities of disease-resistant enzymes, such as chitinase (CHI), ß-1,3-glucanase (GLU), phenylalanine ammonia-lyase (PAL), and polyphenol oxidase (PPO), than the wild type (WT). Furthermore, the study observed that after inoculation with B. cinerea, the relative expression levels of genes related to salicylic acid (SA) signaling, such as SlPR1, SlEDS1, SlPAD4, and SlNPR1, were higher in slatg5 mutants than in WT. Conversely, the relative expression levels of jasmonic acid (JA) signaling-related genes SlLoxD and SlMYC2 were lower in slatg5 mutants than in WT. These findings suggested that SlATG5 positively regulated the resistance response of tomato fruit to B. cinerea by inhibiting the SA signaling pathway and activating the JA signaling pathway.

14.
Environ Sci Pollut Res Int ; 30(41): 94865-94877, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37542016

RESUMO

The intrinsic reaction of coal with oxygen in the process of low-temperature oxidation is the main reaction path leading to self-heating and spontaneous combustion of coal. Most of the existing studies regard the coal oxidation as an overall reaction, ignoring the multi-path characteristics of coal low-temperature oxidation, and it is difficult to accurately explore the intrinsic reaction characteristics between coal with oxygen. Therefore, the low-temperature oxidation process of coal was studied by using a C80 microcalorimeter and in situ FTIR technology from the macro and micro levels. The "profile subtraction method" was used to study the coal-oxygen intrinsic reaction process, and the reaction heat effect and the change characteristics of key functional groups in the process were analyzed. Furthermore, the gray correlation analysis method was used to study the relevant characteristic parameters in the reaction process and grasp the essential structure-activity relationship. The experimental results show that, compared with the overall reaction process in air atmosphere, the change in the heat release of the coal-oxygen intrinsic reaction path has changed to different degrees, and the change in the slow oxidation stage is the most significant (the heat absorption decreases by 70.1-90.9%). In addition, the characteristic temperature points show different degrees of advance, of which the initial exothermic temperature point is the largest (about 21-46 °C), which directly leads to a significant shortening of the slow oxidation stage (30.1-47.4%). The changes of functional groups in the intrinsic reaction path are more regular. With the increase of temperature, the oxygen-containing functional groups -C=O and the aliphatic hydrocarbon functional groups -CH2- and -CH3 showed a fluctuating trend of increasing and decreasing, respectively. The oxidation heat-contributing functional groups of coal are mainly related to the degree of metamorphism and the functional group reaction characteristics during the reaction. With the deepening of coalification degree, the main heat-contributing functional groups as a whole showed the change rule of oxygen-containing functional groups → aliphatic hydrocarbon functional groups → aromatic hydrocarbon functional groups. In addition, the change of -OH content in the three coal samples has a high correlation with the change of the total heat release of coal.


Assuntos
Carvão Mineral , Temperatura Alta , Carvão Mineral/análise , Oxigênio/análise , Temperatura , Hidrocarbonetos
15.
Expert Opin Investig Drugs ; 32(5): 441-450, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37183631

RESUMO

BACKGROUND: SIM0295, a novel inhibitor of human uric acid transporter 1 (hURAT1), is used to treat patients with gout and hyperuricemia. This study aimed to develop population pharmacokinetics and pharmacodynamics (popPK/PD) models of SIM0295 and explore potential covariates to inform clinical drug development. RESEARCH DESIGN AND METHODS: Data were obtained from four phase I studies conducted in healthy Korean and Chinese subjects and two phase II studies conducted in Korean patients with gout and hyperuricemia. The popPK/PD model of SIM0295 was developed using nonlinear mixed effects modeling. RESULTS: SIM0295 pharmacokinetics was described using a two-compartment model with the absorption of four transit compartments and first-order elimination. PK parameters were normalized to weight via allometric scaling. Food was identified as a factor significantly affecting the absorption rate, with no clinical relevance. The sigmoid Emax model with a semi-mechanism of inhibition of serum uric acid (sUA) reabsorption was used to describe the exposure-response relationship. Additionally, Monte Carlo simulations demonstrated that approimately 9 mg/day of SIM0295 for 7 days could achieve the maximum decrease in sUA. CONCLUSION: The established popPK/PD model characterized the dose-exposure-response relationship for SIM0295 in healthy subjects and patients with gout and hyperuricemia and could be used to inform the drug development.


Assuntos
Gota , Hiperuricemia , Humanos , Hiperuricemia/tratamento farmacológico , Ácido Úrico , Voluntários Saudáveis , Gota/tratamento farmacológico , Supressores da Gota/farmacologia
16.
Eur J Pharm Sci ; 191: 106598, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37783378

RESUMO

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.


Assuntos
COVID-19 , Inibidores de Proteases , Adulto , Humanos , Antivirais/efeitos adversos , Inibidores Enzimáticos , Voluntários Saudáveis , Inibidores de Proteases/efeitos adversos , Ritonavir/uso terapêutico , SARS-CoV-2
17.
Phytochem Anal ; 23(3): 197-207, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21800386

RESUMO

INTRODUCTION: The rhizome of Iris dichotoma Pall., a traditional Chinese herbal medicine that contains (iso) flavonoids as the main bioactive compound, has been used to treat several disorders such as inflammation, throat disorders, asthma and coughs. However, there is a lack of suitable methods for its qualitative and quantitative analysis as well as quality control. OBJECTIVES: To establish an HPLC method for the simultaneous determination of phenolic constituents, the identification of characteristic metabolites in the rhizomes of I. dichotoma and to compare their contents in samples from different areas of China. METHODOLOGY: HPLC coupled with diode-array detection (DAD) and electrospray ionisation multistage mass spectrometry (ESI-MS(n) ), and principal component analysis (PCA) were used for the qualitative and quantitative analysis of phenolic compounds in I. dichotoma samples. RESULTS: Twenty characteristic compounds were identified or tentatively characterised. A quantitative HPLC-UV method allowing the simultaneous quantification of 10 phenolic compounds was optimised and validated in terms of linearity, precision, accuracy, and limits of detection and quantification. CONCLUSION: The methodology developed proved to be effective for the identification and quantification of phenolic compounds in the rhizomes of I. dichotoma. Samples were classified into three groups according to their geographical origin based on their phenolic composition using principal component analysis.


Assuntos
Medicamentos de Ervas Chinesas/análise , Gênero Iris/química , Fenóis/análise , Rizoma/química , Calibragem , China , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/normas , Geografia , Glicosídeos/análise , Glicosídeos/química , Isoflavonas/análise , Isoflavonas/química , Estrutura Molecular , Fenóis/química , Fenóis/normas , Análise de Componente Principal , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray/métodos
18.
Sci Total Environ ; 843: 157072, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35780872

RESUMO

To explore the thermal behavior and hazard during the spontaneous combustion fires (SCFs) of coal and coal gangue (CG), the characteristics of heat release and thermal transfer during the SCFs of coal and CG were tested. The results indicate that coal contains more combustibles and aromatic hydrocarbons, while CG possesses higher contents of ash and inorganic silicate. Coal has a stronger heat release capacity, while CG owns a smaller specific heat capacity, a larger thermal diffusivity and a greater thermal conductivity. Thus, CG performs better with respect to heat transfer. The apparent activation energy of coal is larger in the endothermic stage, whereas that of CG is more notable in the exothermic stage. Based on heat release and heat transfer performance, hazardous zones during the SCFs of coal and CG were identified, and the combustion growth index was established to quantify the hazard of SCF disasters. The results show that the hazard is determined by both heat release and thermal transfer capacities. Coal or CG with a combustible component of 31.3 %, which not only releases massive heat but also transfers heat quickly, corresponds to the most considerable hazard of SCF disasters.


Assuntos
Incêndios , Combustão Espontânea , Carvão Mineral
19.
Hu Li Za Zhi ; 58(6): 82-9, 2011 Dec.
Artigo em Zh | MEDLINE | ID: mdl-22113637

RESUMO

BACKGROUNDS: Inappropriate patient positioning during surgery causes respiratory pattern changes, inadequate gaseous exchange, tissue hypoperfusion and disruption of skin integrity. Inadvertent loosening of positioning devices on a patient in our ward during surgery caused surgical field contamination. We thus proposed a project to promote patient positioning accuracy in operating rooms to improve patient safety. PURPOSES: This project was intended to promote accurate patient positioning by operating room nurses, raise nursing professionalism, ensure patient safety, and avoid unnecessary patient injury. RESOLUTIONS: Under the project, we held educational training programs, developed patient positioning standard operating procedures (SOPs) and check lists, inspected all positioning assistance devices, purchased additional belt restraint straps, and conducted periodic monitoring. RESULTS: Patient positioning execution accuracy increased from 80% to 100%; cognition of patient positioning increased from 88% to 100%. CONCLUSIONS: The operating room committee adopted the proposed procedures and they are now SOPs in all operating rooms at our hospital. We suggest including the SOPs developed in this project in continuous education programs and urge making well-designed positioning assistance devices available to protect patient safety during surgery.


Assuntos
Enfermagem de Centro Cirúrgico , Posicionamento do Paciente , Segurança do Paciente , Humanos
20.
Plant Physiol Biochem ; 166: 1-9, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34087740

RESUMO

WRKY, as one of the largest families of transcription factors (TFs), binds to cis-acting elements of downstream genes to regulate biotic and abiotic stress. However, the role of SlWRKY46 in fungal disease response induced by Botrytis cinerea (B.cinerea) and potential mechanism remains obscure. To ascertain the role of SlWRKY46 in response to B.cinerea, we constructed SlWRKY46-overexpression plants, which were then inoculated with B.cinerea. SlWRKY46-overexpression plants were more susceptible to B.cinerea and accompanied by the inhibited activities of phenylalanine ammonialyase (PAL), polyphenol oxidase (PPO), chitinase (CHI), and ß-1,3-glucanase (GLU). Additionally, SlWRKY46-overexpression plants showed the decreased activities of ascorbate peroxidase (APX), superoxide dismutase (SOD) and the content of H2O2, and the increased content of O2•-. Moreover, over-expression of SlWRKY46 suppressed the salicylic acid (SA) and jasmonic acid (JA) marker genes, pathogenesis related protein (PR1), and proteinase inhibitors (PI Ⅰ and PI Ⅱ) and consequently aggravated the disease symptoms. Therefore, we speculated that SlWRKY46 played negative regulatory roles in B. cinerea infection probably by inhibiting the activities of antioxidants and disease resistance enzymes, regulating SA and JA signaling pathways and modulating reactive oxygen (ROS) homeostasis.


Assuntos
Botrytis , Solanum lycopersicum , Botrytis/metabolismo , Ciclopentanos , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Homeostase , Peróxido de Hidrogênio , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Oxilipinas , Doenças das Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico
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