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Urban flood risk assessment plays a crucial role in disaster prevention and mitigation. A scientifically accurate assessment and risk stratification method are of paramount importance for effective flood risk management. This study aims to propose a comprehensive urban flood risk assessment approach by coupling GeoDetector-Dematel and Clustering Method to enhance the accuracy of urban flood risk evaluation. Based on simulation results from hydraulic models and existing literature, the research established a set of urban flood risk assessment indicators comprising 10 metrics across two dimensions: hazard factors and vulnerability factors, among which vulnerability factors include exposure factors, sensitivity factors, and adaptability factors. Subsequently, the research introduced the GeoDetector-Dematel method to determine indicator weights, significantly enhancing the scientific rigor and precision of weight calculation. Finally, the research employed the K-means clustering method to risk zonation, providing a more scientifically rational depiction of the spatial distribution of urban flood risks. This novel comprehensive urban flood risk assessment method was applied in the Fangzhuang area of Beijing. The results demonstrated that this integrated approach effectively enhances the accuracy of urban flood risk assessment. In conclusion, this research offers a new methodology for urban flood risk assessment and contributes to decision-making in disaster prevention and control measures.
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Desastres , Inundaciones , Desastres/prevención & control , Medición de Riesgo/métodos , Beijing , Factores de RiesgoRESUMEN
Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/ß-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/ß-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.
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Berberina , Infarto del Miocardio , Ratones , Animales , Berberina/farmacología , beta Catenina/metabolismo , Miocardio , Infarto del Miocardio/tratamiento farmacológico , Miocitos Cardíacos , Macrófagos/metabolismoRESUMEN
A safe, biocompatible, and stimuli-responsive cucurbit[7]uril-mediated supramolecular bactericidal nanoparticle was fabricated by encapsulating a highly bioactive carbazole-decorated imidazolium salt (A1, EC50 = 0.647 µg/mL against phytopathogen Xanthomonas oryzae pv oryzae) into the host cucurbit[7]uril (CB[7]), thereby leading to self-assembled topographies from microsheets (A1) to nanospheroidal architectures (A1@CB[7]). The assembly behaviors were elucidated by acquired single-crystal structures, 1H NMR, ITC, and X-ray powder diffraction experiments. Complex A1@CB[7] displayed lower phytotoxicity and could efficiently switch on its potent antibacterial ability via introducing a simple competitor 1-adamantanamine hydrochloride (AD). In vivo antibacterial trials against rice bacterial blight revealed that A1@CB[7] could relieve the disease symptoms after being triggered by AD and provide a workable control efficiency of 42.6% at 100 µg/mL, which was superior to bismerthiazol (33.4%). These materials can provide a viable platform for fabricating diverse stimuli-responsive supramolecular bactericides for managing bacterial infections with improved safety.
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Infecciones Bacterianas , Nanopartículas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias , Preparaciones de Acción Retardada , Compuestos Heterocíclicos con 2 Anillos , Humanos , Imidazolidinas , Compuestos MacrocíclicosRESUMEN
High-fat diet (HFD)-induced insulin resistance (IR) in skeletal muscle is often accompanied by mitochondrial dysfunction and oxidative stress. Boosting nicotinamide adenine dinucleotide (NAD) using nicotinamide riboside (NR) can effectively decrease oxidative stress and increase mitochondrial function. However, whether NR can ameliorate IR in skeletal muscle is still inconclusive. We fed male C57BL/6J mice with an HFD (60% fat) ± 400 mg/kg·bw NR for 24 weeks. C2C12 myotube cells were treated with 0.25 mM palmitic acid (PA) ± 0.5 mM NR for 24 h. Indicators for IR and mitochondrial dysfunction were analyzed. NR treatment alleviated IR in HFD-fed mice with regard to improved glucose tolerance and a remarkable decrease in the levels of fasting blood glucose, fasting insulin and HOMA-IR index. NR-treated HFD-fed mice also showed improved metabolic status regarding a significant reduction in body weight and lipid contents in serum and the liver. NR activated AMPK in the skeletal muscle of HFD-fed mice and PA-treated C2C12 myotube cells and upregulated the expression of mitochondria-related transcriptional factors and coactivators, thereby improving mitochondrial function and alleviating oxidative stress. Upon inhibiting AMPK using Compound C, NR lost its ability in enhancing mitochondrial function and protection against IR induced by PA. In summary, improving mitochondrial function through the activation of AMPK pathway in skeletal muscle may play an important role in the amelioration of IR using NR.
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Resistencia a la Insulina , Masculino , Ratones , Animales , Resistencia a la Insulina/fisiología , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones Endogámicos C57BL , Mitocondrias , Músculo Esquelético/metabolismo , Insulina/metabolismo , Ácido Palmítico/farmacología , Ácido Palmítico/metabolismo , Dieta Alta en Grasa/efectos adversosRESUMEN
BACKGROUND: Many endangered species exist in small, genetically depauperate, or inbred populations, hence promoting genetic differentiation and reducing long-term population viability. Forest Musk Deer (Moschus berezovskii) has been subject to illegal hunting for hundreds of years due to the medical and commercial values of musk, resulting in a significant decline in population size. However, it is still unclear to what extent the genetic exchange and inbreeding levels are between geographically isolated populations. By using whole-genome data, we reconstructed the demographic history, evaluated genetic diversity, and characterized the population genetic structure of Forest Musk Deer from one wild population in Sichuan Province and two captive populations from two ex-situ centers in Shaanxi Province. RESULTS: SNP calling by GATK resulted in a total of 44,008,662 SNPs. Principal component analysis (PCA), phylogenetic tree (NJ tree), ancestral component analysis (ADMIXTURE) and the ABBA-BABA test separated Sichuan and Shaanxi Forest Musk Deer as two genetic clusters, but no obvious genetic differentiation was observed between the two captive populations. The average pairwise FST value between the populations in Sichuan and Shaanxi ranged from 0.05-0.07, suggesting a low to moderate genetic differentiation. The mean heterozygous SNPs rate was 0.14% (0.11%-0.15%) for Forest Musk Deer at the genomic scale, and varied significantly among three populations (Chi-square = 1.22, p < 0.05, Kruskal-Wallis Test), with the Sichuan population having the lowest (0.11%). The nucleotide diversity of three populations varied significantly (p < 0.05, Kruskal-Wallis Test), with the Sichuan population having the lowest genetic θπ (1.69 × 10-3). CONCLUSIONS: Genetic diversity of Forest Musk Deer was moderate at the genomic scale compared with other endangered species. Genetic differentiation between populations in Sichuan and Shaanxi may not only result from historical biogeographical factors but also be associated with contemporary human disturbances. Our findings provide scientific aid for the conservation and management of Forest Musk Deer. They can extend the proposed measures at the genomic level to apply to other musk deer species worldwide.
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Ciervos , Especies en Peligro de Extinción , Genética de Población , Animales , China , Ciervos/genética , Bosques , Metagenómica , Nucleótidos , FilogeniaRESUMEN
BACKGROUND: The antecubital fossa is a main perforator cluster region located beside the anterior elbow defect, rendering it crucial to harvest the perforator pedicled flaps for the anterior elbow defects. PATIENTS AND METHODS: A total of 30 preserved cadaveric forearms were dissected in order to describe the perforator anatomy in the antecubital fossa. For each perforator, the number, the site of origin, the diameter at its origin, and the trajectory were recorded. In addition, all the patients treated for anterior elbow defects using inferior cubital artery (ICA) perforator pedicled flaps between June 2013 and June 2018 were reviewed in this retrospective study. RESULTS: A total of 85 perforators were dissected in the antecubital fossa area from the 30 specimens. Among these, 65 perforators originated from the radial artery, 6 from the recurrent radial artery, 13 from the brachial artery, and 1 from the ulnar artery. Each forearm specimen had a constant and large ICA perforator. All perforators originated from source vessels 2-5 cm distal from the interepicondylar line and could be harvested as perforator pedicled flap for anterior elbow reconstruction. In the clinical study, 11 patients with anterior elbow defects were treated with ICA perforator pedicled flaps with satisfactory functional and aesthetic outcomes. CONCLUSION: The antecubital fossa has a constant and dominant ICA perforator and many other perforators. The pedicled antecubital fossa perforator flaps could be harvested flexibly with a reliable blood supply for anterior elbow reconstruction.
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Colgajo Perforante , Procedimientos de Cirugía Plástica , Arterias/cirugía , Codo/cirugía , Humanos , Colgajo Perforante/irrigación sanguínea , Estudios RetrospectivosRESUMEN
Wu-tou decoction has been used as a traditional Chinese medicine prescription for thousands of years. It comprises five herbs, namely Radix Aconiti Preparata, Ephedrae Herba, Astragali Radix, Glycyrrhiza Radix, and Paeoniae Radix Alba. In addition, the original prescription contains honey, but in modern research, the existence of honey is commonly ignored. The aim was to investigate the effect of absorption in rats after oral wu-tou decoction with or without honey. In this research, a rapid and sensitive UPLC-MS/MS method was investigated for the quantitative analysis of ephedrine, pseudoephedrine, paeoniflorin, calycosin-7-glucoside, glycyrrhizic acid, liquiritin, and benzoylmesaconine in rat plasma after single and continuous oral decoctions. The results of the pharmacokinetic parameters showed that Cmax , CL/F, AUC0-t , and AUC0-∞ in the honey group were significantly increased than those in the non-honey group except for ephedrine and pseudoephedrine. The same trend was observed regardless of single or continuous oral administrations. Research studies showed that honey could promote the absorption of some effective components in wu-tou decoction in rats, enhance bioavailability, and provide a theoretical basis for the scientific and rational compatibility of the original prescription.
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Medicamentos Herbarios Chinos , Miel , Animales , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida , Medicamentos Herbarios Chinos/farmacocinética , Ratas , Espectrometría de Masas en Tándem/métodosRESUMEN
A series of new thiazole-based stilbene analogs were designed, synthesized and evaluated for DNA topoisomerase IB (Top1) inhibitory activity. Top1-mediated relaxation assays showed that the synthesized compounds possessed variable Top1 inhibitory activity. Among them, (E)-2-(3-methylstyryl)-4-(4-fluorophenyl)thiazole (8) acted as a potent Top1 inhibitor with high Top1 inhibition of ++++ which is comparable to that of CPT. A possible binding mode of compound 8 with Top1-DNA complex was further provided by molecular docking. An MTT assay against human breast cancer (MCF-7) and human colon cancer (HCT116) cell lines revealed that the majority of these compounds showed high cytotoxicity, with IC50 values at micromolar concentrations. Compounds 8 and (E)-2-(4-tert-butylstyryl)-4-(4-fluorophenyl)thiazole (11) exhibited the most potent cytotoxicity with IC50 values of 0.78 and 0.62 µM against MCF-7 and HCT116, respectively. Moreover, the preliminary structure-activity relationships of thiazole-based stilbene analogs was also discussed.
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Antineoplásicos/química , Estilbenos/química , Tiazoles/química , Inhibidores de Topoisomerasa/química , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Diseño de Fármacos , Células HCT116 , Humanos , Células MCF-7 , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Estilbenos/síntesis química , Estilbenos/farmacología , Tiazoles/síntesis química , Tiazoles/farmacología , Inhibidores de Topoisomerasa/síntesis química , Inhibidores de Topoisomerasa/farmacologíaRESUMEN
ABSTRACT: We explored the protective effect of spironolactone on cardiac function in the patients undergoing coronary artery bypass grafting (CABG) by determining serum hypoxia-inducible factor-1α (HIF-1α) before and after CABG. We used the propensity score matching method retrospectively to select 174 patients undergoing CABG in our hospital from March 2018 to December 2019. Of the 174 patients, 87 patients taking spironolactone for more than 3 months before CABG were used as a test group and other 87 patients who were not taking spironolactone as a control group. In all patients, serum HIF-1α and troponin I levels were determined before as well as 24 hours and 7 days after CABG, serum N-terminal probrain natriuretic peptide (NT-proBNP) level was determined before as well as 12, 24, and 36 hours after CABG, and electrocardiographic monitoring was performed within 36 hours after CABG. The results indicated that there were no significant differences in the HIF-1α level between the test group and the control group before and 7 days after CABG, but the HIF-1α level was significantly lower in the test group than that in the control group 24 hours after CABG (P < 0.01). The 2 groups were not significantly different in the troponin I level at any time point. There was no significant difference in the serum NT-proBNP level between the test group and the control group before CABG, but NT-proBNP (BNP) levels were all significantly lower in the test group than those in the control group at postoperative 12, 24, and 36 hour time points (all P <0.05). The incidence of postoperative atrial fibrillation was also significantly lower in the test group than that in the control group (P = 0.035). Spironolactone protects cardiac function probably by improving myocardial hypoxia and inhibiting myocardial remodeling.
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Puente de Arteria Coronaria , Estenosis Coronaria/cirugía , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Espironolactona/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/etiología , Fibrilación Atrial/prevención & control , Biomarcadores/sangre , Puente de Arteria Coronaria/efectos adversos , Estenosis Coronaria/sangre , Estenosis Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Estudios Retrospectivos , Factores de Riesgo , Espironolactona/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Troponina I/sangreRESUMEN
Based on our previous study on the development of the furoquinolinedione and isoxazoloquinolinedione TDP2 inhibitors, the further structure-activity relationship (SAR) was studied in this work. A series of furoquinolinedione and isoxazoloquinolinedione derivatives were synthesized and tested for enzyme inhibitions. Enzyme-based assays indicated that isoxazoloquinolinedione derivatives selectively showed high TDP2 inhibitory activity at sub-micromolar range, as well as furoquinolinedione derivatives at low micromolar range. The most potent 3-(3,4-dimethoxyphenyl)isoxazolo[4,5-g]quinoline-4,9-dione (70) showed TDP2 inhibitory activity with IC50 of 0.46 ± 0.15 µM. This work will facilitate future efforts for the discovery of isoxazoloquinolinedione TDP2 selective inhibitors.
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Proteínas de Unión al ADN/antagonistas & inhibidores , Inhibidores de Fosfodiesterasa/farmacología , Quinolonas/farmacología , Animales , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Ratones , Modelos Moleculares , Estructura Molecular , Inhibidores de Fosfodiesterasa/síntesis química , Inhibidores de Fosfodiesterasa/química , Hidrolasas Diéster Fosfóricas/metabolismo , Quinolonas/síntesis química , Quinolonas/química , Relación Estructura-ActividadRESUMEN
OBJECTIVES: To enhance detection of the products of hyperpolarized [2-13C]dihydroxyacetone metabolism for assessment of three metabolic pathways in the liver in vivo. Hyperpolarized [2-13C]DHAc emerged as a promising substrate to follow gluconeogenesis, glycolysis and the glycerol pathways. However, the use of [2-13C]DHAc in vivo has not taken off because (i) the chemical shift range of [2-13C]DHAc and its metabolic products span over 144 ppm, and (ii) 1H decoupling is required to increase spectral resolution and sensitivity. While these issues are trivial for high-field vertical-bore NMR spectrometers, horizontal-bore small-animal MR scanners are seldom equipped for such experiments. METHODS: Real-time hepatic metabolism of three fed mice was probed by 1H-decoupled 13C-MR following injection of hyperpolarized [2-13C]DHAc. The spectra of [2-13C]DHAc and its metabolic products were acquired in a 7 T small-animal MR scanner using three purpose-designed spectral-spatial radiofrequency pulses that excited a spatial bandwidth of 8 mm with varying spectral bandwidths and central frequencies (chemical shifts). RESULTS: The metabolic products detected in vivo include glycerol 3-phosphate, glycerol, phosphoenolpyruvate, lactate, alanine, glyceraldehyde 3-phosphate and glucose 6-phosphate. The metabolite-to-substrate ratios were comparable to those reported previously in perfused liver. DISCUSSION: Three metabolic pathways can be probed simultaneously in the mouse liver in vivo, in real time, using hyperpolarized DHAc.
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Dihidroxiacetona/química , Animales , Isótopos de Carbono , Gluconeogénesis , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Ratones , ProtonesRESUMEN
BACKGROUND: This study aimed to explore the trend and risk indicators for dental caries of children aged 12 years in China based on national oral health survey data in 2005 and 2015. METHODS: Research data were from the two latest national oral health surveys conducted in mainland China, including 30 and 31 provinces, autonomous regions, and municipalities in 2005 and 2015, respectively. Children aged 12 years were clinically examined for dental caries and dental fluorosis according to the World Health Organization criteria. Sociodemographic characteristics and oral health-related behaviours were collected using questionnaires. Multilevel zero-inflated negative binomial regression model was used to investigate the association between dental caries severity and dental fluorosis, sociodemographic characteristics, and oral health-related behaviours. RESULTS: The final analyses included 12,350 and 27,818 children surveyed in 2005 and 2015, respectively. The standardized prevalence of dental caries increased from 27.05% (95% confidence interval [CI], 24.25-28.85) in 2005 to 37.92% (95% CI, 34.94-40.90) in 2015, and the respective standardized mean decayed, missing, filled teeth (DMFT) index scores increased from 0.50 (standard deviation [SD], 1.04) to 0.83 (SD, 1.45) (P < 0.001). Fujian province had the highest increase in dental caries, followed by Liaoning, Heilongjiang, Hainan, and Yunnan. Results revealed that children who were girls, more frequently experienced dental pain, and had more recent dental visits, had significantly higher DMFT scores after adjusting for the survey year and other variables (all P < 0.05). CONCLUSIONS: Dental caries of 12-year-old children in China deteriorated from 2005 to 2015, particularly in the northeast and southwest regions. Dental caries was associated with sex, dental pain, and dental service utilization.
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Caries Dental , Niño , China/epidemiología , Estudios Transversales , Índice CPO , Caries Dental/epidemiología , Femenino , Humanos , Análisis Multinivel , PrevalenciaRESUMEN
BACKGROUND: The relationship between dental caries and periodontal disease is still controversial. The objective of this study was to explore the relationship between different types of caries and periodontal disease severity in middle-aged and elderly people in China. METHODS: The study population consisted of 4407 middle-aged and 4117 elderly subjects. Caries were divided into the following three types: type A, crown caries; type B, lesions involving both the crown and root, representing mixed-type caries; and type C, root caries. These three types together represent the overall caries situation, which we call type ABC. Caries were quantitated by decayed and filled teeth (DFT index). Periodontitis was evaluated by clinical attachment loss. RESULTS: Middle-aged people with periodontitis had a significant association with DFT type B (OR: 1.21, 95% CI 1.17-1.25) and type C (OR: 1.40, 95% CI 1.24-1.56). Elderly people with periodontitis had a significant association with DFT type C (OR: 1.28, 95% CI 1.21-1.35). CONCLUSIONS: In China, caries types B/C were positively correlated with periodontitis in the middle-aged group, and only caries type C was positively correlated with periodontitis in the elderly group.
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Caries Dental , Enfermedades Periodontales , Anciano , China/epidemiología , Índice CPO , Caries Dental/epidemiología , Susceptibilidad a Caries Dentarias , Encuestas de Salud Bucal , Humanos , Persona de Mediana Edad , Salud Bucal , Enfermedades Periodontales/complicaciones , Enfermedades Periodontales/epidemiologíaRESUMEN
Background Tumor cells frequently show high rates of aerobic glycolysis, which provides the glycolytic intermediates needed for the increased biosynthetic demands of rapid cell growth and proliferation. Existing clinical methods (fluorodeoxyglucose PET and carbon 13 MRI and spectroscopy) do not allow quantitative images of glycolytic flux. Purpose To evaluate the use of deuterium (hydrogen 2 [2H]) MR spectroscopic imaging for quantitative mapping of tumor glycolytic flux and to assess response to chemotherapy. Materials and Methods A fast three-dimensional 2H MR spectroscopic imaging pulse sequence, with a time resolution of 10 minutes, was used to image glycolytic flux in a murine tumor model after bolus injection of D-[6,6'-2H2]glucose before and 48 hours after treatment with a chemotherapeutic agent. Tumor lactate labeling, expressed as the lactate-to-water and lactate-to-glucose signal ratios, was also assessed in localized 2H MR spectra. Statistical significance was tested with a one-sided paired t test. Results 2H MR spectroscopic imaging showed heterogeneity in glycolytic flux across the tumor and an early decrease in flux following treatment with a chemotherapeutic drug. Spectroscopy measurements on five animals showed a decrease in the lactate-to-water signal ratio, from 0.33 ± 0.10 to 0.089 ± 0.039 (P = .005), and in the lactate-to-glucose ratio, from 0.27 ± 0.12 to 0.12 ± 0.06 (P = .04), following drug treatment. Conclusion Rapidly acquired deuterium (hydrogen 2) MR spectroscopic images can provide quantitative and spatially resolved measurements of glycolytic flux in tumors that can be used to assess treatment response. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Ouwerkerk in this issue.
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Glucólisis , Imagenología Tridimensional/métodos , Linfoma/diagnóstico por imagen , Espectroscopía de Resonancia Magnética/métodos , Animales , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Deuterio , Modelos Animales de Enfermedad , Linfoma/tratamiento farmacológico , Ratones , TiempoRESUMEN
A series of novel indole-pyrazoline hybrid derivatives were designed, synthesized, and evaluated for topoisomerase 1 (Top1) inhibitory activity. Top1-mediated relaxation assays showed that our synthesized compounds had variable Top1 inhibitory activity. Among these compounds, 3-(5-(naphthalen-1-yl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-1-(phenylsulfonyl)-1H-indole (6n) was found to be a strong Top1 inhibitor with better inhibitory activity than CPT and hit compounds. Our further experiments rationalized the mode of action for this new type of inhibitors, which showed no significant binding to supercoiled DNA.
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ADN-Topoisomerasas de Tipo I/química , Indoles/química , Pirazoles/química , Inhibidores de Topoisomerasa I/síntesis química , Sitios de Unión , ADN-Topoisomerasas de Tipo I/metabolismo , ADN Superhelicoidal/química , ADN Superhelicoidal/metabolismo , Diseño de Fármacos , Humanos , Simulación de Dinámica Molecular , Relación Estructura-Actividad , Inhibidores de Topoisomerasa I/metabolismoRESUMEN
Based on DNA topoisomerase IB (TOP1) and tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibition of the ethanol extract of the roots of Isodon ternifolius (D. Don) Kudo (Labiatae), its secondary metabolites has been studied. Two new compounds, an ent-abietane diterpenoid isodopene A (1) and a 2,3-seco-triterpene isodopene B (13), along with 25 known compounds were isolated. Their structures were elucidated by spectroscopic analysis and theoretical calculations. The enzyme-based assays indicated that 1 and 13 showed strong (+++) and moderate (++) TOP1 inhibition, respectively. Two chalcone derivatives 11 and 12 were firstly found as dual TDP1 and TOP1 natural inhibitors, and showed synergistic effect with the clinical TOP1 inhibitors topotecan in MCF-7 cells. Compounds 8, 16, and 22 acted as TOP1 catalytic inhibitors with equipotent TOP1 inhibition to camptothecin (++++). Compounds 7 and 8 exhibited significant cytotoxicity against MCF-7, A549, and HCT116 cells with GI50 values in the range of 2.2-4.8 µM. This work would provide valuable information that secondary metabolites from I. ternifolius could be developed as anticancer agents.
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Antineoplásicos Fitogénicos/farmacología , ADN-Topoisomerasas de Tipo I/metabolismo , Isodon/química , Inhibidores de Fosfodiesterasa/farmacología , Hidrolasas Diéster Fosfóricas/metabolismo , Inhibidores de Topoisomerasa I/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Bovinos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Isodon/metabolismo , Estructura Molecular , Inhibidores de Fosfodiesterasa/química , Inhibidores de Fosfodiesterasa/aislamiento & purificación , Relación Estructura-Actividad , Inhibidores de Topoisomerasa I/química , Inhibidores de Topoisomerasa I/aislamiento & purificación , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To explore the experiences of front-line nurses combating the coronavirus disease-2019 epidemic. DESIGN AND SAMPLE: Fifteen front-line nurses caring for COVID-19 patients were recruited from two hospitals in Wuhan, China from January 26 to February 5, 2020. Data were collected through semi-structured individual interviews and analyzed using standard qualitative methods. RESULTS: Four theme categories emerged from the data analysis: (a) "Facing tremendous new challenges and danger"; (b) "Strong pressure because of fear of infection, exhaustion by heavy workloads and stress of nursing seriously ill COVID-19 patients"; (c) "Strong sense of duty and identity as a healthcare provider"; (d) "Rational understanding of the epidemic-the nurses believed that the epidemic would soon be overcome and would like to receive disaster rescue training." CONCLUSIONS: Although the intensive rescue work drained front-line nurses, both physically and emotionally, they showed a spirit of dedication and felt a responsibility to overcome this epidemic. Their experiences provide useful insights into implementing a safer public health emergency rescue system in preparation for future outbreaks of infectious diseases. Specifically, psychological support and humanistic care should be provided to front-line nurses to maintain their well-being, and nationwide emergency rescue training and disaster education should be implemented.
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Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/enfermería , Epidemias , Personal de Enfermería en Hospital/psicología , Neumonía Viral/epidemiología , Neumonía Viral/enfermería , Adulto , COVID-19 , China/epidemiología , Femenino , Humanos , Masculino , Personal de Enfermería en Hospital/estadística & datos numéricos , Pandemias , Investigación Cualitativa , Adulto JovenRESUMEN
OBJECTIVE: Benzodiazepines and benzodiazepine-related drugs (BZRDs) are used to treat various psychiatric diseases. However, there are concerns that BZRDs increase the risk of pneumonia. METHODS: We performed a systematic review and meta-analysis of observational studies to determine whether BZRD use affects the risk of pneumonia. Our analysis included all observational studies that compared pneumonia development among patients receiving BZRD vs those with no treatment. RESULTS: In total, 12 citations of 10 studies involving more than 120,000 pneumonia cases were included in our meta-analysis. After pooling the estimates, the odds for developing pneumonia were 1.25-fold higher (odd ratio, OR = 1.25; 95% confidence interval (CI), 1.09-1.44) in BZRD users compared with individuals who had not taken BZRD. On the basis of exposure window, we found an increased risk of pneumonia among current (OR = 1.4; 95%CI, 1.22-1.6) and recent (OR = 1.38; 95%CI, 1.06-1.8) users, but not with the past users (OR = 1.11; 95%CI, 0.96-1.27). CONCLUSION: Current or recent exposure to BZRD is associated with an increased pneumonia risk. Clinicians need to weight the benefit-risk balance of BZRD use, especially those with other risk factors for pneumonia.
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Benzodiazepinas , Hipnóticos y Sedantes , Neumonía , Benzodiazepinas/efectos adversos , Peso Corporal , Humanos , Hipnóticos y Sedantes/efectos adversos , Trastornos Mentales/tratamiento farmacológico , Oportunidad Relativa , Neumonía/inducido químicamente , Medición de Riesgo , Factores de RiesgoRESUMEN
A modified quick, easy, cheap, effective, rugged and safe (QuEChERS) method was developed for the determination of thiamethoxam and its metabolite clothianidin in citrus (including the whole citrus, peel and pulp) and soil samples by liquid chromatography-tandem mass spectrometry. The sample was extracted with acetonitrile and purified with octadecylsilane. The detection limits of both compounds were 0.0001-0.0002 mg kg-1, while the limit of quantification of thiamethoxam was 0.002 mg kg-1 and the limit of quantitation of metabolites was 0.001 mg kg-1. The recovery was 70.37%-109.76%, with inter-day relative standard deviations (RSD) (n = 15) values ≤9.46% for the two compounds in the four matrices. The degradation curve of thiamethoxam in whole citrus and soil was plotted using the first-order kinetic model. The half-life of the whole citrus was 1.9-6.2 days, and the half-life of the soil was 3.9-4.2 days. The terminal residue of thiamethoxam (the sum of thiamethoxam and clothianidin, expressed as thiamethoxam) was found to be concentrated on the peel. The final residual amount of thiamethoxam in the edible portion (pulp) was less than 0.061 mg kg-1. The risk quotient values were all below 1, indicating that thiamethoxam as a citrus insecticide does not pose a health risk to humans at the recommended dosage.
Asunto(s)
Citrus/química , Contaminación de Alimentos/análisis , Guanidinas/análisis , Neonicotinoides/análisis , Contaminantes del Suelo/análisis , Tiametoxam/análisis , Tiazoles/análisis , China , Cromatografía Liquida/métodos , Exposición Dietética/análisis , Guanidinas/toxicidad , Semivida , Humanos , Insecticidas/análisis , Límite de Detección , Neonicotinoides/toxicidad , Medición de Riesgo , Espectrometría de Masas en Tándem/métodos , Tiametoxam/toxicidad , Tiazoles/toxicidadRESUMEN
This study evaluated the hydrolysis and photolysis kinetics of pyraclostrobin in an aqueous solution using ultra-high-performance liquid chromatography-photodiode array detection and identified the resulting metabolites of pyraclostrobin by hydrolysis and photolysis in paddy water using high-resolution mass spectrometry coupled with liquid chromatography. The effect of solution pH, metal ions and surfactants on the hydrolysis of pyraclostrobin was explored. The hydrolysis half-lives of pyraclostrobin were 23.1-115.5 days and were stable in buffer solution at pH 5.0. The degradation rate of pyraclostrobin in an aqueous solution under sunlight was slower than that under UV photolysis reaction. The half-lives of pyraclostrobin in a buffer solution at pH 5.0, 7.0, 9.0 and in paddy water were less than 12 h under the two light irradiation types. The metabolites of the two processes were identified and compared to further understand the mechanisms underlying hydrolysis and photolysis of pyraclostrobin in natural water. The extracted ions obtained from paddy water were automatically annotated by Compound Discoverer software with manual confirmation of their fragments. Two metabolites were detected and identified in the pyraclostrobin hydrolysis, whereas three metabolites were detected and identified in the photolysis in paddy water.