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OBJECTIVE: Retinoblastoma (RB) is a prevalent type of eye cancer in youngsters. Prospero homeobox 1 (Prox1) is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic, hepatocyte, pancreatic, heart, lens, retinal, and cancer cells. The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance, as well as to explore the underlying Notch1 mechanism. METHODS: Human RB cell lines (SO-RB50 and Y79) and a primary human retinal microvascular endothelial cell line (ACBRI-181) were used in this study. The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction (RT-qPCR) and Western blotting. Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay. Drug-resistant cell lines (SO-RB50/vincristine) were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance. We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1. Finally, a xenograft model was constructed to assess the effect of Prox1 on RB in vivo. RESULTS: Prox1 was significantly downregulated in RB cells. Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine. Notch1 was involved in Prox1's regulatory effects. Notch1 was identified as a target gene of Prox1, which was found to be upregulated in RB cells and repressed by increased Prox1 expression. When pcDNA-Notch1 was transfected, the effect of Prox1 overexpression on RB was removed. Furthermore, by downregulating Notch1, Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo. CONCLUSION: These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1, implying that Prox1 could be a potential therapeutic target for RB.
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Neoplasias de la Retina , Retinoblastoma , Humanos , Línea Celular Tumoral , Proliferación Celular/genética , Resistencia a Medicamentos , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/genética , Neoplasias de la Retina/metabolismo , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/genética , Retinoblastoma/metabolismo , Vincristina/farmacologíaRESUMEN
BACKGROUND: Role ambiguity is recognized as a significant psychological risk stressor in nursing practice, which undermines the psychological well-being of nurses. Since the well-being of nurses plays a crucial role in ensuring positive patient outcomes, it becomes imperative to identify strategies for improving nurses' psychological well-being. OBJECTIVES: This study aimed to explore the effects of role ambiguity on anxiety in intensive care unit nurses and the mechanisms mediating emotional intelligence. METHODS: In April-June 2023, a convenience sampling method was used to collect data from 360 intensive care unit nurses in a total of 7 hospitals in Shaanxi Province, Hunan Province, Beijing, and Jiangsu Province, China. A linear regression model was used to verify the mediating effect. RESULTS: Role ambiguity was significantly and positively associated with anxiety in ICU nurses (p < 0.01). A mediating mechanism between role ambiguity and anxiety was established for emotional intelligence (p < 0.01). CONCLUSIONS: Role ambiguity has a significant impact on the mental health of intensive care nurses, and emotional intelligence plays a mediating role in reducing role ambiguity and anxiety in nurses. IMPLICATIONS FOR CLINICAL PRACTICE: This study highlights that role ambiguity in the intensive care unit setting increases nurses' anxiety, while emotional intelligence alleviates the anxiety associated with role ambiguity. Creating support systems and improving the environment is a top priority for nursing administrators. This includes, but is not limited to, clarifying the roles of nurses, conducting social-emotional training, and developing emotional intelligence to prevent and regulate nurses' anxiety and maintain mental health.
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Trastornos de Ansiedad , Ansiedad , Humanos , Ansiedad/complicaciones , Emociones , Inteligencia Emocional , Unidades de Cuidados IntensivosRESUMEN
BACKGROUND: work alienation is receiving increasing attention as a psychological risk at work, and little is known about the mechanisms of role ambiguity and work alienation in nurses in the context of the COVID-19 pandemic. This article aims to examine how role ambiguity affects work alienation among Chinese nurses during the two years after COVID-19 pandemic and verify emotional exhaustion as mediators. METHODS: A cross-sectional study design was used to recruit 281 Chinese nurses. Nurses completed online questionnaires containing demographic characteristics, role ambiguity, emotional exhaustion, and work alienation, and SPSS 26.0 and AMOS 24.0 were used for data analysis and structural equation modelling. RESULTS: work alienation scores were (34.64 ± 10.09), work alienation was correlated with role ambiguity and emotional exhaustion (r1 = 0.521, r2 = 0.755; p < .01), and role ambiguity was positively correlated with emotional exhaustion (r = 0.512; p < .01). A mediating effect of emotional exhaustion between role ambiguity and work alienation held (mediating effect of 0.288, 95% CI: 0.221-0.369, accounting for 74.8% of the total effect). CONCLUSION: Role ambiguity has a significant direct effect on nurses' feelings of alienation and exacerbates alienation through emotional exhaustion. Clarifying roles at work and being less emotionally drained are effective ways to reduce nurses' feelings of alienation.
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Agotamiento Profesional , COVID-19 , Enfermeras y Enfermeros , Personal de Enfermería en Hospital , Humanos , Estudios Transversales , Pueblos del Este de Asia , Pandemias , Agotamiento Profesional/psicología , Personal de Enfermería en Hospital/psicología , Emociones , Encuestas y CuestionariosRESUMEN
BACKGROUND: COVID-19 infection continues all over the world, causing serious physical and psychological impacts to patients. Patients with COVID-19 infection suffer from various negative emotional experiences such as anxiety, depression, mania, and alienation, which seriously affect their normal life and is detrimental to the prognosis. Our study is aimed to investigate the effect of psychological capital on alienation among patients with COVID-19 and the mediating role of social support in this relationship. METHODS: The data were collected in China by the convenient sampling. A sample of 259 COVID-19 patients completed the psychological capital, social support and social alienation scale and the structural equation model was adopted to verify the research hypotheses. RESULTS: Psychological capital was significantly and negatively related to the COVID-19 patients' social alienation (p < .01). And social support partially mediated the correlation between psychological capital and patients' social alienation (p < .01). CONCLUSION: Psychological capital is critical to predicting COVID-19 patients' social alienation. Social support plays an intermediary role and explains how psychological capital alleviates the sense of social alienation among patients with COVID-19 infection.
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COVID-19 , Capital Social , Aislamiento Social , Apoyo Social , COVID-19/psicología , Humanos , China , Análisis de Mediación , Modelos Psicológicos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Reproducibilidad de los Resultados , Intervalos de ConfianzaRESUMEN
Introduction: Aptamers are valuable for bioassays, but aptamer-target binding is susceptible to reaction conditions. In this study, we combined thermofluorimetric analysis (TFA) and molecular dynamics (MD) simulations to optimize aptamer-target binding, explore underlying mechanisms and select preferred aptamer. Methods: Alpha-fetoprotein (AFP) aptamer AP273 (as the model) was incubated with AFP under various experimental conditions, and melting curves were measured in a real-time PCR system to select the optimal binding conditions. The intermolecular interactions of AP273-AFP were analysed by MD simulations with these conditions to reveal the underlying mechanisms. A comparative study between AP273 and control aptamer AP-L3-4 was performed to validate the value of combined TFA and MD simulation in selecting preferred aptamers. Results: The optimal aptamer concentration and buffer system were easily determined from the dF/dT peak characteristics and the melting temperature (Tm) values on the melting curves of related TFA experiments, respectively. A high Tm value was found in TFA experiments performed in buffer systems with low metal ion strength. The molecular docking and MD simulation analyses revealed the underlying mechanisms of the TFA results, i.e., the binding force and stability of AP273 to AFP were affected by the number of binding sites, frequency and distance of hydrogen bonds, and binding free energies; these factors varied in different buffer and metal ion conditions. The comparative study showed that AP273 was superior to the homologous aptamer AP-L3-4. Conclusion: Combining TFA and MD simulation is efficient for optimizing the reaction conditions, exploring underlying mechanisms, and selecting aptamers in aptamer-target bioassays.
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To explore the potential significance of the reverberation of calcification by comparing both intravascular ultrasound (IVUS) and optical coherence tomography (OCT) measurement post manual coregistration. The reverberation phenomenon is often detected by IVUS for severe calcified lesions post rotational atherectomy (RA), which is thought to be due to the glassy and smooth inner surfaces of calcifications. Because of the poor penetration of IVUS, it is impossible to measure the thickness of calcifications, and the relationship between multiple reverberations and the thickness of calcification lesions has not been reported before. A total of forty-nine patients with severe calcified coronary lesions that were detected by IVUS and OCT simultaneously were enrolled in our retrospective study. If reverberation phenomena were detected by IVUS, intravascular imaging (IVI) data (including distance between the IVUS catheter center and the inner surface of the reverberation signal, the intervals between all adjacent reverberation signals, the number of layers of reverberation in IVUS, and the thickness of the calcification in OCT) were measured at the same position and same direction (each cross-section had 4 mutually perpendicular directions) at 1-mm intervals. The correlation between each reverberation observational value and OCT data was the primary target in this retrospective study, and the correlation between reverberation and calcium crack post predilatation was analyzed in other 15 patients. Four hundred twenty-eight valid observational points were analyzed simultaneously by IVUS and OCT; among them, 300 points had a single layer of reverberation, 83 had double layers of reverberation and 42 had multiple layers (≥ 3 layers) of reverberation by IVUS detection post-RA. Multivariate logistic regression analysis showed that the number of layers of reverberation by IVUS was significantly related to the thickness of calcifications by OCT at the same point and in the same direction (p < 0.001). Single, double, and multiple layers of reverberation in IVUS correspond to median calcification thicknesses (interquartile ranges (IQRs)) of 0.620 mm (0.520-0.720), 0.950 mm (0.840-1.040) and 1.185 mm (1.068-1.373), respectively, by OCT detection. Another 100 points in other 15 patients with integrated IVUS data pre- and post-predilatation showed that only single layer of reverberation was related to calcium crack (p < 0.001). The number of layers of reverberation signal detected by IVUS is positively correlated with the thickness of calcifications measured by OCT post-RA and single layer of reverberation is correlated to calcium crack post-predilatation.
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Enfermedad de la Arteria Coronaria , Calcificación Vascular , Humanos , Enfermedad de la Arteria Coronaria/patología , Estudios Retrospectivos , Calcio , Ultrasonografía Intervencional , Valor Predictivo de las Pruebas , Vasos Coronarios/diagnóstico por imagen , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy of RIC for acute moderate ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). Main Outcomes and Measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. Conclusions and Relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03740971.
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Poscondicionamiento Isquémico , Accidente Cerebrovascular Isquémico , Anciano , China , Femenino , Humanos , Poscondicionamiento Isquémico/métodos , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/terapia , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/prevención & control , Enfermedades del Sistema Nervioso/terapia , Recuperación de la Función , Resultado del Tratamiento , Extremidad Superior/irrigación sanguíneaRESUMEN
In order to investigate the characteristics of soil microbial community structure and their relationships with environmental factors in the surrounding farmlands of a mercury mining region, we analyzed soil physical and chemical properties, Hg pollution, enzyme activity, and microbial community structure characteristics in the surrounding farmlands of a mercury mining region in Tong Ren (Bahuang Town, Bijiang District; Huaqiao Town, Shiqian County; Kaide Town, Jiangkou County; and Chuantong town, Bijiang District; referred to as BJ, SQ, JK, and TR, respectively). The relationships between the characteristics of soil microbial community structure and environmental factors were determined using redundancy analysis (RDA) and correlation network analysis. The results showed that the degree of soil Hg contamination varied depending on the sampling locations in the study region. The soils in JK and TR were categorized as having light-level Hg contamination, whereas those in SQ and BJ were at moderate-level Hg contamination. The potential ecological risk indicated that the soil suffered different degrees of Hg contamination (TR was at a medium level, BJ and JK were at a serious level, and SQ was at a high severe level of pollution). The dominant bacteria flora were Proteobacteria, Actinobacteria, Acidobacteria, and Chloroflexi, whereas the dominant flora of fungi included Ascomycota, Basidiomycota, and Mortierellomycota. RDA analysis showed that pH, sucrase (SC), and catalase (CAT) activities were the key environmental factors of soil bacterial community structure. Soil pH, available nitrogen (AN), available potassium (AK), HCl-Hg, acid phosphatase (ACP), and urease (URE) activities were the key environmental factors that affected soil fungal community structure. Correlation network analysis indicated that pH, available phosphorus (AP), HCl-Hg, SC, ACP, and CAT were the key environmental factors affecting soil bacterial community structure, including Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Firmicutes, Rokubacteria, and Planctomycetes. AK, pH, total nitrogen (TN), AP, AN, ACP, URE, and SC activities were the key environmental factors affecting soil fungal community structure, such as Ascomycota, Basidiomycota, Mortierellomycota, Glomeromycota, Chytridiomycota, Rozellomycota, Kickxellomycota, and Mucoromycota.
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Actinobacteria , Mercurio , Microbiota , Acidobacteria , Bacterias , Granjas , Hongos , Minería , Nitrógeno , Proteobacteria , Suelo/química , Microbiología del SueloRESUMEN
OBJECTIVE: To analyze the relationship between serum miR-34a level and thrombocytopenia after chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 69 eligible DLBCL patients who received chemotherapy in our hospital from January 2018 to January 2020 were prospectively included as the research subjects, all patients received R-CHOP 21 regimen (rituximab + cyclophosphamide + adriamycin + vincristine + prednisone) for chemotherapy, 3 weeks was 1 cycle, and 2 cycles of chemotherapy were used. The patients were divided into a reduction group and a non reduction group according to whether there was thrombocytopenia after chemotherapy, the general data and laboratory indexes of the two groups were investigated and compared, the relationship between serum miR-34a before chemotherapy and thrombocytopenia after chemotherapy in patients was analyzed. RESULTS: Among the 69 DLBCL patients, 36 patients developed thrombocytopenia after 2 cycles of R-CHOP 21 regimen for chemotherapy, the incidence was 52.17%; the level of serum IL-11 and the relative expression of miR-34a mRNA in the reduction group were significantly lower than the non reduction group (P<0.05), compared other data between groups, there was no statistical significant difference (P>0.05); after Logistic regression analysis, the results showed that the level of serum IL-11 and the relative expression of miR-34a mRNA were related to thrombocytopenia after chemotherapy in DLBCL patients, low expression of each index may be a risk factor of thrombocytopenia after chemotherapy in DLBCL patients (OR>1, P<0.05); ROC curve was drawn, and the results showed that the AUC of serum IL-11 level and miR-34a mRNA relative expression before chemotherapy alone and in combination predicted the risk of thrombocytopenia after chemotherapy in DLBCL patients were all >0.80, and the predictive value was ideal, when the cut-off value of serum IL-11 level before chemotherapy was 42.094 pg/ml, and the cut-off value of miR-34a mRNA relative expression was 3.894, the combined prediction value was the best. CONCLUSION: The relative expression of miR-34a mRNA is associated with thrombocytopenia after chemotherapy in DLBCL patients, which may be a risk factor for thrombocytopenia in patients after chemotherapy, has certain value in predicting the risk of thrombocytopenia of patients after chemotherapy.
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Linfoma de Células B Grandes Difuso , MicroARNs , Trombocitopenia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida , Doxorrubicina , Humanos , Interleucina-11/uso terapéutico , Linfoma de Células B Grandes Difuso/genética , MicroARNs/genética , Prednisona/uso terapéutico , Pronóstico , ARN Mensajero , Rituximab/uso terapéutico , VincristinaRESUMEN
Background and Aims: Aptamers are artificial ligands that bind to biological targets with high specificity and affinity. We previously selected a group of aptamers against the serum of primary hepatic carcinoma (PHC) via systematic evolution of ligands by exponential and enrichment (SELEX) method, and some of the aptamers were valuable for PHC diagnosis in polyacrylamide gel electrophoresis (PAGE) analysis. Here, we used aptamers to develop a novel method suitable for the clinical diagnosis of PHC. Methods: The intensities of serum autofluorescence, cell-free DNA (cfDNA)-related fluorescence and aptamer-related fluorescence, named the aptamer-based triple serum fluorescence intensity (ATSFI), were sequentially measured at 8 °C and 37 °C in one tube by using a real-time polymerase chain reaction (PCR) system as a fluorimeter in patients with PHC (n=346) or liver cirrhosis (n=321). The diagnostic performances of ATSFI indicators alone and in combination were evaluated by area under the receiver operator characteristic curve (AUROC), and the underlying clinical mechanisms were analyzed by bivariate correlation. Results: The measurement of ATSFI was high throughput, rapid, convenient, and low cost. The aptamer-related fluorescence indicator SEA-SE37 was the most valuable for PHC diagnosis among all fluorescence indicators and superior to alpha-fetoprotein (AFP) (AUROC 0.879 vs. 0.836). The logistic model of ATSFI indicators exhibited excellent diagnostic performance for PHC, including AFP-negative, early and small PHCs, with AUROCs of 0.935-0.950 and accuracies of 86.8-88.3%. The diagnostic performance was further improved when ATSFI indicators were combined with AFP, with AUROCs of approximately 0.95 and accuracies of approximately 90%, suggesting ATSFI was independent of but complementary to AFP in PHC diagnosis. ATSFI models were highly valuable in clinical decision-making. The aptamer-related fluorescence intensity was generally independent of the clinicopathological characteristics of PHC but correlated with laboratory characteristics of PHC serum. Conclusions: The ATSFI assay is a novel, robust and feasible method for the clinical diagnosis of PHC.
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OBJECTIVE: To identify and utilize gene signatures for the prognostic evaluation of postoperative patients with hepatocellular carcinoma (HCC). METHODS: The gene mRNA expression profiles and corresponding clinicopathological data of postoperative patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Highly differentially expressed genes (DEGs) in tumor tissues compared to adjacent tissues were identified, and their associations with the overall survival (OS) of HCC patients were analyzed. The strongly associated genes were used to develop a prognostic score for the survival stratification of HCC, and the underlying mechanisms were analyzed using bioinformatics. RESULTS: A total of 376 DEGs were identified and four DEGs (ADH4, COL15A1, RET and KCNJ16) were independently associated with OS. A prognostic score derived from the four genes could effectively stratify HCC patients with different OS outcomes, independent of clinical parameters. Patients with high scores exhibited poorer OS than patients with low scores (HR 5.526, 95% CI: 2.451-12.461, p < .001). The four genes were involved in cancer-related biological processes and were independent of each other in bioinformatics analyses. CONCLUSION: Four genes strongly associated with the prognosis of postoperative patients with HCC were identified, and the derived prognostic score was simple and valuable for overall survival prediction.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirugía , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Pronóstico , ARN MensajeroRESUMEN
In the present study, we aimed to evaluate the cardioprotective effect of neoandrographolide (Neo) on myocardial ischemia/reperfusion injury (I/R) models and explore its possible mechanism. We randomly and equally divided male mice into sham-operation, I/R, and I/R + Neo groups. H9C2 cell line and primary neonatal rat cardiomyocytes were induced into the simulated I/R's status and used to further validate the Neo's role in vitro. Heart systolic function, indexes of myocardial injury (IMI), infarct size, pathological change, cell apoptosis, inflammatory cytokines, and indexes related to apoptotic and NF-κB signaling pathways were analyzed in vivo or in vitro after the Neo treatment. Compared to the I/R group, Neo significantly suppressed IMI, infarct size, inflammatory cell infiltration, cell apoptosis, inflammatory cytokines, bax, cleaved caspase-3, P-IKBa, and P-NF-κB protein expressions, and the translocation of NF-kB subunit p65 from the cytoplasm to the nucleus in vivo or in vitro. Still, ejected fraction, fractional shortening, and the bcl-2 protein expression were notably increased after the Neo treatment. Neo could be developed into a new drug for treating myocardial I/R by inhibiting myocardial inflammation and apoptosis, which was closely related to suppressing the activation of bax/bcl-2 and NF-κB signaling pathways.
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Diterpenos , Daño por Reperfusión Miocárdica , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Apoptosis , Diterpenos/farmacología , Glucósidos , Masculino , Ratones , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos , FN-kappa B/genética , Ratas , TetrahidronaftalenosRESUMEN
Fragaria orientalis Lozinsk. is valuable germplasm material for cross breeding in Fragaria. In this study, we assembled the complete mitochondrial genome of F. orientalis using a combination of Illumina data and Nanopore data. The mitochondrial genome was 275,143 bp in length, including 29 protein-coding genes, 20 tRNA genes, and three rRNA genes, with a total GC content 45.23%. Seven protein-coding genes contained introns, and three were trans-spliced. Phylogenetic analysis indicated that F. orientalis is making a sister clade to the Amygdaloideae species. The complete mitochondrial genome of F. orientalis reported in this study will improve our understanding of Fragaria evolution.
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Spiroconyone A (1), the first rearranged phytosterol featuring an unusual spiro [5,6] ring system, and nine known compounds (2-10) were isolated from the aerial parts of Conyza japonica. The structure of 1 was elucidated through spectroscopic methods, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Enzyme-based assay revealed that spiroconyone A showed weak TDP1 inhibition and compounds 7 and 10 showed TDP1 inhibition with IC50 values of 36 µM and 16 µM, respectively. MTT assay indicated that 7 and 10 showed a strong synergistic effect with the clinical TOP1 inhibitor topotecan in MCF-7 cells. Compound 5 displayed the most potent cytotoxicity against MCF-7 cells with a GI50 value of 3.3 µM. Furthermore, a hypothetical biosynthetic pathway for 1 was proposed. This work provides valuable information that the secondary metabolites from Conyza japonica could be developed as anticancer agents.
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Conyza/química , Fitosteroles/química , Células A549 , Animales , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Espectrometría de Masas/métodos , Ratones , Estructura Molecular , Hidrolasas Diéster Fosfóricas/efectos de los fármacos , Espectroscopía de Protones por Resonancia Magnética , Espectrofotometría UltravioletaRESUMEN
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
Four new sesquiterpenoids, conyterpenols A - D (1-4), along with nineteen known analogues (5-23) were isolated from the aerial parts of Conyza japonica. The structures of 1-4 were determined through spectroscopic analysis, while their absolute configurations were determined by comparison of calculated and experimental electronic circular dichroism (ECD) spectra. Conyterpenol D (4) was a new type of sesquiterpenoid with a seven-membered lactone ring. Compounds 1-23 were evaluated for their inhibitory activity against LPS-induced nitric oxide production in RAW264.7 macrophages and cytotoxicity against human hepatoma cell line (HepG2) and human breast adenocarcinoma cell line (MCF-7). Compounds 3, 4, and 12 displayed moderate inhibition against NO production with IC50 values in the range of 26.4-33.6 µM. And all compounds showed no obvious cytotoxicity against these two cancer cell lines at 100 µM.
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Conyza/química , Óxido Nítrico/metabolismo , Componentes Aéreos de las Plantas/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Animales , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Lipopolisacáridos/toxicidad , Ratones , Modelos Moleculares , Estructura Molecular , Células RAW 264.7RESUMEN
Considerable efforts are being made to develop new materials and technologies for the efficient and fast removal of toxic ions in drinking water. In this work, we developed a sulfur-complexed strategy to enhance the removal capability of heavy metal ions using the polyamide nanofiltration membrane by the covalent anchoring of l-cystine and l-cysteine. The sulfur-functionalized polyamide nanofiltration membrane exhibits superior complexation of heavy metal ions and can efficiently remove them from high-concentration wastewater. As a result, the sulfur-functionalized nanofiltration membrane not only showed excellent desalination performance but also achieved a record removal rate of heavy metal ions (99.99%), which can effectively reduce Hg(ii) concentration from 10 ppm to an extremely low level of 0.18 ppb, well below the acceptable limits in drinking water (2 ppb). Moreover, the sulfur-functionalized nanofiltration membrane showed an exciting long-term stability and can be easily regenerated without significant loss of Hg(ii) removal efficiency even after six cycles. Such outstanding performances were attributed to the synthetic effect of Hg-S coordinative interaction, electrostatic repulsion, and the sieving action of nanopores. These results highlight the tremendous potential of thiol/disulfide-functionalized NF active layer as an appealing platform for removing heavy metal ions from polluted water with high performance in environmental remediation.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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The original version of this Article contained errors in the symbols displayed in the eighteenth sentence of the third paragraph of the 'Determination of Hab and kET data for the Mo2 dimers' section of the Results, and the third sentence of the Discussion. This has been corrected in both the PDF and HTML versions of the Article.
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Thermal electron transfer through hydrogen bonds remains largely unexplored. Here we report the study of electron transfer through amide-amide hydrogen bonded interfaces in mixed-valence complexes with covalently bonded Mo2 units as the electron donor and acceptor. The rate constants for electron transfer through the dual hydrogen bonds across a distance of 12.5 Å are on the order of â¼ 1010 s-1, as determined by optical analysis based on Marcus-Hush theory and simulation of ν(NH) vibrational band broadening, with the electron transfer efficiencies comparable to that of π conjugated bridges. This work demonstrates that electron transfer across a hydrogen bond may proceed via the known proton-coupled pathway, as well as an overlooked proton-uncoupled pathway that does not involve proton transfer. A mechanistic switch between the two pathways can be achieved by manipulation of the strengths of electronic coupling and hydrogen bonding. The knowledge of the non-proton coupled pathway has shed light on charge and energy transport in biological systems.