RESUMEN
Geminiviruses constitute the largest group of known plant viruses and cause devastating diseases and economic losses in many crops worldwide. Due to limited naturally occurring resistance genes, understanding plant antiviral defense against geminiviruses is critical for finding host factors of geminiviruses and development of strategies for geminivirus control. Here we identified NbWRKY1 as a positive regulator of plant defense against geminivirus infection. Using tomato yellow leaf curl China virus/tomato yellow leaf curl China betasatellite (TYLCCNV/TYLCCNB) as a representative geminivirus, we found that NbWRKY1 was upregulated in response to TYLCCNV/TYLCCNB infection. Overexpression of NbWRKY1 attenuated TYLCCNV/TYLCCNB infection, whereas knockdown of NbWRKY1 enhanced plant susceptibility to TYLCCNV/TYLCCNB. We further revealed that NbWRKY1 bound to the promoter of the NbWHIRLY1 (NbWhy1) transcription factor and inhibited the transcription of NbWhy1. Consistently, NbWhy1 negatively regulates plant response against TYLCCNV/TYLCCNB. Overexpression of NbWhy1 significantly accelerated TYLCCNV/TYLCCNB infection. Conversely, knockdown of NbWhy1 led to impaired geminivirus infection. Furthermore, we demonstrated that NbWhy1 interfered with the antiviral RNAi defense and disrupted the interaction between calmodulin 3 and calmodulin-binding transcription activator-3. Moreover, the NbWRKY1-NbWhy1 also confers plant antiviral response toward tomato yellow leaf curl virus infection. Taken together, our findings suggest that NbWRKY1 positively regulates plant defense to geminivirus infection by repressing NbWhy1. We propose that the NbWRKY1-NbWhy1 cascade could be further employed to control geminiviruses.
Asunto(s)
Begomovirus , Geminiviridae , Geminiviridae/genética , Geminiviridae/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Calmodulina/metabolismo , Nicotiana , Begomovirus/metabolismo , Regulación de la Expresión Génica , Enfermedades de las Plantas/genéticaRESUMEN
OBJECTIVES: Adolescents and young adults are the main target population for human papillomavirus (HPV). The study aimed to investigate school students' HPV vaccination intentions and explore the contributing factors from a socio-ecological perspective. DESIGN: A questionnaire survey was conducted in three secondary schools and three colleges in China. SAMPLE: A total of 1756 students aged 14-22 years participated in this study. Among the 1756 participants, 182 students have received the HPV vaccine. For the remaining 1574 students, we analyzed their HPV vaccination intentions and the influencing factors. MEASUREMENTS: Survey items for sociodemographics, knowledge and awareness of HPV, sexual intercourse and sexual knowledge, subjective socioeconomic status, self-efficacy, eHealth literacy, perceived social support from family, and the availability of HPV vaccine information were measured. RESULTS: Only 182 (10.4%) had received the HPV vaccine among the 1756 participants. Among the remaining 1574 students, the majority of the students (1403, 89.1%) were willing to receive the HPV vaccine. Binary logistic regression analysis showed that students who were female, had lower self-efficacy, scored higher on sexual knowledge, believed vaccination preventing related diseases, worried about side effects after vaccination, thought oneself at risk of contracting HPV, had higher family support, knew the availability of the HPV vaccine in Mainland China from healthcare institutions, and with family residence in rural areas were more willing to receive the HPV vaccine. CONCLUSIONS: Students had high HPV vaccination intentions while had low vaccination rate. Intrapersonal, interpersonal and institutional or community factors predicted HPV vaccination intention. Public health nurses in communities and schools could target the modifiable factors to promote students' HPV vaccine uptake.
Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Adulto Joven , Adolescente , Masculino , Intención , Infecciones por Papillomavirus/prevención & control , Estudios Transversales , Neoplasias del Cuello Uterino/prevención & control , Aceptación de la Atención de Salud , Vacunas contra Papillomavirus/uso terapéutico , China , Encuestas y Cuestionarios , Vacunación , Virus del Papiloma Humano , Conocimientos, Actitudes y Práctica en SaludRESUMEN
PURPOSE: This study evaluated the association among the plasma concentration of ticagrelor, ARC124910XX, aspirin, and salicylic acid with the risk of recent bleeding in patients with the acute coronary syndrome. To this end, we developed an accurate model to predict bleeding. METHODS: A total of 84 patients included in this study cohort between May 2021 and November 2021. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic curve to verify the accuracy of the prediction model. RESULTS: Multivariable logistic analysis showed that ticagrelor concentration (odds ratio [OR]: 2.47, 95% confidence interval [CI], 1.51-4.75, P = 0.002), ST-segment elevation acute myocardial infarction (OR: 32.2, 95% CI, 2.37-780, P = 0.016), and lipid-lowering drugs (OR: 11.52, 95% CI, 1.91-110, P = 0.015) were positively correlated with bleeding. However, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (OR: 0.04, 95% CI, 0.004-0.213, P < 0.001) was negatively correlated with bleeding. The receiver operating characteristic curve analysis showed that ticagrelor concentration and these factors together predict the occurrence of bleeding (area under receiver operating characteristic curve = 0.945, 95% CI, 0.896-0.994) and that ticagrelor concentration >694.90 ng/mL is the threshold of bleeding concentration (area under receiver operating characteristic curve = 0.696, 95% CI, 0.558-0.834). CONCLUSION: In patients with acute coronary syndrome treated with dual antiplatelet therapy, ticagrelor concentration >694.90 ng/mL was an independent risk factor for bleeding (OR: 2.47, 95% CI, 1.51-4.75, P = 0.002), but ARC124910XX and salicylic acid concentration did not affect bleeding risk ( P > 0.05).
Asunto(s)
Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Ticagrelor/efectos adversos , Aspirina , Inhibidores de Agregación Plaquetaria , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , Pueblos del Este de Asia , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Ácido Salicílico/uso terapéutico , Intervención Coronaria Percutánea/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Children's injuries from traffic accidents have been identified as a global public health issue. Child restraint system (CRS) is a useful tool for lowering the risk of injury to children. Nevertheless, CRS usage is really low in China. The goal of the current study was to investigate the use of CRS after the legislation revised in China and to explore the influencing factors based on Information, Motivation, and Behavioral Skills model (IMB). METHODS: The study is a cross-sectional survey of parents who took their 0 to 6-year-old children for seeking primary care services at the Children Preventive Health Care Clinic of a tertiary hospital in Shandong Province, China. Parents were invited to complete the self-administered questionnaire between March and June 2022, including their knowledge, motivation, and behavioral skills, use behavior of CRS and socio-demographics. Ordinal logistic regression was used to explore the factors associated with CRS use by using SPSS software (version 26.0). RESULTS: In total, 442 parents participated in the study; 56.1% (n = 201) of the parents utilized CRS for their child passengers, however only 29.0% used CRS frequently. The result of logistic regression analysis show that parents with junior college (OR = 0.398, 95%CI: 0.185 ~ 0.857), possessing a high family economic status(OR = 0.225, 95%CI: 0.088 ~ 0.578), being trained on children's unintentional injuries(OR = 0.435,95%CI: 0.272 ~ 0.695), and having high scores on CRS riding mode cognition(OR = 0.476, 95%CI: 0.368 ~ 0.616), CRS type cognition(OR = 0.519, 95%CI: 0.392 ~ 0.689), CRS use motivation(OR = 0.392, 95%CI: 0.295 ~ 0.520) and installation skills(OR = 0.559, 95%CI:0.411 ~ 0.761) were the main factors promoting the usage of CRS. CONCLUSIONS: This study found that the use of CRS can be increased by improving parents' knowledge, motivation and behavior skills and hence related educational programs is necessary for increasing CRS use in China.
Asunto(s)
Sistemas de Retención Infantil , Motivación , Niño , Humanos , Estudios Transversales , Padres , Accidentes de Tránsito , ChinaRESUMEN
Fusarium head blight (FHB) is a global cereal disease caused by a complex of Fusarium species. Both Fusarium graminearum and F. asiaticum are the causal agents of FHB in China. F. asiaticum is the predominant species in the Middle-Lower Reaches of the Yangtze River (MLRYR) and southwest China. Therefore, detecting F. asiaticum in a timely manner is crucial for controlling the disease and preventing mycotoxins from entering the food chain. Here, we combined rapid genomic DNA extraction, recombinase polymerase amplification, Cas12a cleavage, and lateral flow detection techniques to develop a method for the rapid detection of F. asiaticum. The reaction conditions were optimized to provide a rapid, sensitive, and cost-effective method for F. asiaticum detection. The optimized method demonstrated exceptional specificity in detecting F. asiaticum while not detecting any of the 14 other Fusarium strains and 3 non-Fusarium species. Additionally, it could detect F. asiaticum DNA at concentrations as low as 20 ag/µL, allowing for the diagnosis of F. asiaticum infection in maize and wheat kernels even after 3 days of inoculation. The developed assay will provide an efficient and robust detection platform to accelerate plant pathogen detection.
Asunto(s)
Fusarium , Queratoconjuntivitis , Recombinasas , Fusarium/genética , Sistemas CRISPR-Cas , NucleotidiltransferasasRESUMEN
Polyelectrolyte has wide applications in biomedicine, agriculture and soft robotics. However, it is among one of the least understood physical systems because of the complex interplay of electrostatics and polymer nature. In this review, a comprehensive description is presented on experimental and theoretical studies of the activity coefficient, one of the most important thermodynamic properties of polyelectrolyte. Experimental methods to measure the activity coefficient were introduced, including direct potentiometric measurement and indirect methods such as isopiestic measurement and solubility measurement. Next, progress on the various theoretical approaches was presented, ranging from analytical, empirical and simulation methods. Finally, challenges for future development are proposed on this field.
RESUMEN
As a new member of the silica-derivative family, modified glass fiber (MGF) has attracted extensive attention because of its excellent properties and potential applications. Surface modification of glass fiber (GF) greatly changes its performance, resulting in a series of changes to its surface structure, wettability, electrical properties, mechanical properties, and stability. This article summarizes the latest research progress in MGF, including the different modification methods, the various properties, and their advanced applications in different fields. Finally, the challenges and possible solutions were provided for future investigations of MGF.
RESUMEN
BACKGROUND: Constipation is one of the common symptoms in childhood. The prevalence of FC is about 0.5% to 32% and still on the rise according to global statistics. The aim of this study is to explore the associations between family-related factors (e.g., parental conflict, parenting style, and parent-child relationship) and functional constipation of preschool children based on family system theory. METHODS: The study is a case-control survey of preschoolers in China. In total, 108 preschoolers with functional constipation diagnosed with pediatric Rome IV criteria and 324 healthy examination preschoolers without functional constipation were enrolled in the study. Parents completed the following 5 instruments: General information questionnaire, the Parental Conflict Scale, the Parenting Style Questionnaire, the Child-parent Relationship Scale and the Children's Emotional Adjustment Scale-Preschool Version. RESULTS: Nine categories of factors which significantly predicted functional constipation in preschoolers were retained in the final logistic regression model: Second child in birth order (OR = 0.456; 95% CI, 0.229 to 0.910), children picky eating (OR = 2.936; 95% CI, 1.133 to 7.611), bad bowel habits (OR = 2.896; 95% CI, 1.391 to 6.028), parental history of constipation (OR = 3.259; 95% CI, 1.600 to 6.639), parents blaming the child for having a bad bowel movement (OR = 3.788; 95% CI, 1.391 to 10.318), more than 3 h of fathers-child interaction time per day (OR = 0.137; 95% CI, 0.024 to 0.778), parental conflict (OR = 1.981; 95% CI, 0.950 to 3.831), doting or authoritarian parenting style (OR = 1.644; 95% CI, 1.067 to 2.534, OR = 2.481; 95% CI, 1.362 to 4.519), and anxiety control or temper control in children (OR = 0.492; 95% CI, 0.303 to 0.799, OR = 0.189; 95% CI, 0.103 to 0.348). CONCLUSIONS: This study identified the significant associations between family-related factors and functional constipation in preschool children, which provide implications for healthcare professionals to address functional constipation in early childhood using a preventive lens.
Asunto(s)
Relaciones Padres-Hijo , Responsabilidad Parental , Estudios de Casos y Controles , Niño , Preescolar , Estreñimiento/diagnóstico , Estreñimiento/epidemiología , Estreñimiento/etiología , Humanos , Responsabilidad Parental/psicología , Padres/psicología , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Ultrasound-targeted microbubble destruction (UTMD) is an effective technology for microRNA (miRNA) delivery. miR-1228 plays a crucial role and acts as an oncogenic role in several types of cancers. This study aimed to investigate the functional effect of UTMD-mediated miR-1228 knockdown in cervical-cancer cells. DESIGN: A total of 131 patients who were diagnosed with cervical cancer by histopathological examination were enrolled in this study at the Third Affiliated Hospital of Qiqihar Medical University from February 2018 to January 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: miR-1228 expression was tested by reverse-transcription quantitative PCR assay. miR-1228 inhibitors were transfected into cervical-cancer cells using the UTMD method. Then, Cell Counting Kit-8 and transwell assays were carried out to explore the cell proliferation, migration, and invasion potentials, respectively. RESULTS: The results revealed that miR-1228 expression was high in human cervical-cancer tissues and cell lines. Knockdown of miR-1228 suppressed tumor cell proliferation abilities, migration, and invasion capacities. Moreover, UTMD-mediated mIR-1228 inhibitor delivery enhanced the transfection efficiency of miR-1228 inhibitor alone. The UTMD-mediated miR-1228 inhibition enhanced the suppressive role of miR-1228 downregulation on cell proliferation capacity, migration, and invasion abilities in tumor cells, compared to miR-1228 knockdown alone. LIMITATIONS: The experiments were carried out only in SiHa and HeLa cells in vitro, and the results were not verified in animals. CONCLUSIONS: These results indicated that the delivery of the UTMD-mediated miR-1228 inhibitor might be a potential therapeutic method for the treatment of cervical cancer through suppressing cellular activities.
Asunto(s)
MicroARNs , Neoplasias del Cuello Uterino , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Regulación hacia Abajo , Femenino , Células HeLa , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Microburbujas , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapiaRESUMEN
OBJECTIVE: To perform therapeutic drug monitoring of total and free plasma valproic acid (VPA) concentrations in clinical samples and to analyze the related factors. METHODS: The total VPA concentration in plasma was determined by ultrahigh-performance liquid chromatography with precolumn derivatization with α-bromoacetophenone, and the free VPA concentration was determined by liquid chromatography-tandem mass spectrometry after the plasma was treated by hollow fiber centrifugal ultrafiltration. Regression analysis was performed to examine the associations between free plasma VPA, total plasma VPA, and the plasma protein binding rate. The impact of individual situations, outpatient or inpatient factors, and drug combinations on VPA concentrations were examined. RESULTS: Of the 569 clinical samples, 268 were inpatients and 301 were outpatients, and the total VPA concentration in 138 cases (24.2%) was lower than the effective treatment concentration range; the total and free VPA concentrations in outpatient samples were 11.0% and 26.1% higher than those of inpatients, respectively. There was no linear relationship between the free and total VPA concentrations. The relationship equation between the plasma protein binding rate and free VPA concentrations was as follows: Y = 0.0255X2 - 1.1357X + 97.429 (r = 0.8011). The total and free VPA concentrations were significantly decreased after the coadministration of phenobarbital (83.7% and 64.3% of the control group, P < 0.05) or carbapenem antibiotics (32.0% and 32.7% of the control group, P < 0.05). CONCLUSIONS: The total VPA concentrations in patients with epilepsy at our hospital was lower than the effective treatment concentration range, which was inadequate for epilepsy control; the total VPA concentrations of outpatients were higher than those of inpatients; as phenobarbital affects VPA metabolism, therapeutic drug monitoring is recommended. Carbapenem antibiotic coadministration with VPA should be avoided because carbapenem antibiotics can lead to the failure of VPA antiepileptic treatment.
Asunto(s)
Ultrafiltración , Ácido Valproico , Anticonvulsivantes , Cromatografía Liquida , Humanos , Espectrometría de Masas en Tándem/métodos , Ultrafiltración/métodosRESUMEN
BACKGROUND: With the outbreak of COVID-19, it has become very important to improve biosafety measures taken by medical staff. Fewer pretreatment steps correspond to lower chances of infection. The authors established a direct injection technique to analyze levetiracetam (LEV) concentrations in human serum and studied its application in therapeutic drug monitoring. METHODS: Serum samples were prepared by hollow fiber centrifugal ultrafiltration and the filtrate was directly injected into a ultra-high performance liquid chromatography apparatus (Waters UPLC BEH C18 column: 50 × 2.1 mm, 1.7 µm) for analysis. The mobile phase consisted of acetonitrile and water (8:92) at a flow rate of 1.0 mL/min. The column temperature was maintained at 30°C. The detected wavelength was 210 nm. RESULTS: A linear relationship was obtained for LEV from 0.625 to 80 mcg/mL (r2 = 0.999). The limit of detection for the analysis of LEV was 0.125 mcg/mL. The analysis time was shortened to 4 minutes. The recovery rate of LEV based on the current method was 96.6%-100.1%, whereas the absolute recovery rate was 93.2%-96.8%. The relative SD of intraday and interday precision was <7.3%. Stability was achieved at room temperature for 24 hours after 3 freeze-thaw cycles and at -80°C for 21 days. The method was successfully applied to determine LEV concentrations in the serum of 19 patients. CONCLUSIONS: The present method is simple, accurate, and sensitive, and can improve biosafety with the direct injection technique. It is suitable for the analysis of LEV concentrations in therapeutic drug monitoring.
Asunto(s)
Recolección de Muestras de Sangre/métodos , COVID-19/epidemiología , Monitoreo de Drogas/métodos , Levetiracetam/sangre , Cromatografía Líquida de Alta Presión , Humanos , Reproducibilidad de los Resultados , SARS-CoV-2 , Factores de TiempoRESUMEN
The whitefly-transmitted geminiviruses induce severe developmental abnormalities in plants. Geminivirus-encoded C4 protein functions as one of viral symptom determinants that could induce abnormal cell division. However, the molecular mechanism by which C4 contributes to cell division induction remains unclear. Here we report that tomato leaf curl Yunnan virus (TLCYnV) C4 interacts with a glycogen synthase kinase 3 (GSK3)/SHAGGY-like kinase, designed NbSKη, in Nicotiana benthamiana. Pro32, Asn34 and Thr35 of TLCYnV C4 are critical for its interaction with NbSKη and required for C4-induced typical symptoms. Interestingly, TLCYnV C4 directs NbSKη to the membrane and reduces the nuclear-accumulation of NbSKη. The relocalization of NbSKη impairs phosphorylation dependent degradation on its substrate-Cyclin D1.1 (NbCycD1;1), thereby increasing the accumulation level of NbCycD1;1 and inducing the cell division. Moreover, NbSKη-RNAi, 35S::NbCycD1;1 transgenic N. benthamiana plants have the similar phenotype as 35S::C4 transgenic N. benthamiana plants on callus-like tissue formation resulted from abnormal cell division induction. Thus, this study provides new insights into mechanism of how a viral protein hijacks NbSKη to induce abnormal cell division in plants.
Asunto(s)
Begomovirus/metabolismo , Ciclina D1/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Nicotiana/metabolismo , Proteínas de Plantas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Virales/metabolismo , Agrobacterium tumefaciens/fisiología , Begomovirus/patogenicidad , División Celular , Ciclina D1/química , Eliminación de Gen , Proteínas Luminiscentes/química , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Fosforilación , Filogenia , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/microbiología , Hojas de la Planta/ultraestructura , Proteínas de Plantas/antagonistas & inhibidores , Proteínas de Plantas/química , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Plantas Modificadas Genéticamente/microbiología , Plantas Modificadas Genéticamente/ultraestructura , Mutación Puntual , Complejo de la Endopetidasa Proteasomal/metabolismo , Complejo de la Endopetidasa Proteasomal/ultraestructura , Dominios y Motivos de Interacción de Proteínas , Procesamiento Proteico-Postraduccional , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/genética , Estabilidad Proteica , Transporte de Proteínas , Proteolisis , Interferencia de ARN , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Nicotiana/genética , Nicotiana/microbiología , Nicotiana/ultraestructura , Proteínas Virales/químicaRESUMEN
Most of undergraduate healthcare students will become future health professionals committing to promoting people's health in practice. They often service as coaches to improve clients' healthy lifestyle behaviors. However, relatively little is known about their health behaviors and health status. The study was conducted to investigate health behaviors and health status among undergraduate healthcare students and the associated factors in China by drawing an ecological perspective. A total of 430 students aged 18-20 years participated in the study between October 2017 and March 2018. Questionnaires on health behavior, health status, peer influence, family environment, and social support were employed. Overall, the healthcare students reported poor health behaviors and an intermediate level of health status. Regression analyses indicate that peers and family environment were significant predictors of health behavior, yet only explained 6.7% of the variance. Social support was the most significant predictor of self-rated health, followed by family environment, health behavior and peers, which together explained 31.5% of the total variance. Peers and social support were the major predictors of health behavior and health status compared to demographics among undergraduate healthcare students. Intervention targeting the predictive factors is needed to improve healthcare students' health.
Asunto(s)
Conductas Relacionadas con la Salud , Estado de Salud , Apoyo Social , Estudiantes del Área de la Salud/estadística & datos numéricos , Adolescente , Adulto , Familia , Humanos , Adulto JovenRESUMEN
The aim of this study was to investigate the function of Cystic fibrosis transmembrane conductance regulator (CFTR) in human glioblastoma (GBM) cells. Data dining results of the Human Protein Atlas showed that low CFTR expression was associated with poor prognosis for GBM patients. We found that CFTR protein expression was lower in U87 and U251 GBM cells than that in normal humane astrocyte cells. CFTR activation significantly reduced GBM cell proliferation. In addition, CFTR activation significantly abrogated migration and invasion of GBM cells. Besides, CFTR activator Forskolin treatment markedly reduced MMP-2 protein expression. These effects of CFTR activation were significantly inhibited by CFTR inhibitor CFTRinh-172 pretreatment. Our findings suggested that JAK2/STAT3 signaling was involved in the anti-glioblastoma effects of CFTR activation. Moreover, CFTR overexpression in combination with Forskolin induced a synergistic anti-proliferative response in U87â¯cells. Overall, our findings demonstrated that CFTR activation suppressed GBM cell proliferation, migration and invasion likely through the inhibition of JAK2/STAT3 signaling.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Movimiento Celular , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patología , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Colforsina/farmacología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Humanos , Janus Quinasa 2 , Antígeno Ki-67/metabolismo , Invasividad Neoplásica , Pronóstico , Antígeno Nuclear de Célula en Proliferación/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Ensayo de Tumor de Célula MadreAsunto(s)
Resistencia a la Enfermedad , Oryza , Enfermedades de las Plantas , Virus de Plantas , Plantas Modificadas Genéticamente , Oryza/genética , Oryza/virología , Plantas Modificadas Genéticamente/genética , Virus de Plantas/genética , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismoRESUMEN
Cytosine DNA methylation is a conserved epigenetic silencing mechanism that defends against biotic stresses such as geminivirus infection. As a countermeasure, geminiviruses encode proteins that inhibit methylation and transcriptional gene silencing (TGS). Previous studies showed that V2 protein of Tomato yellow leaf curl virus (TYLCV) functions as a TGS suppressor. However, how V2 mediates TGS suppression remains unknown. Here we show that V2 interacts directly with a Nicotiana benthamiana histone deacetylase 6 (NbHDA6), a homolog of Arabidopsis HDA6 (AtHDA6), known to be involved in gene silencing in cooperation with methyltransferase 1 (MET1). NbHDA6 genetically complemented a late-flowering phenotype and restored histone deacetylation of an AtHDA6 mutant. Furthermore, our investigation showed that NbHDA6 displayed histone deacetylase enzymatic activity, which was not inhibited by V2. Genetic analysis revealed that silencing of NbHDA6 expression resulted in enhanced susceptibility to TYLCV infection. In addition, methylation-sensitive PCR and bisulfite sequencing analysis showed that silencing of NbHDA6 expression caused reduced DNA methylation of the viral genome in infected plants. HDA6 was previously shown to recruit and physically interact with MET1 to function in gene silencing. Using competitive pulldown and coimmunoprecipitation assays, we demonstrated that V2 did not interact but competed with NbMET1 for direct binding to NbHDA6. These findings suggest that V2 interacts with host HDA6 and interferes with the recruitment of MET1 by HDA6, resulting in decreased methylation of the viral DNA genome by TGS with a concomitant increase in host susceptibility to TYLCV infection.IMPORTANCE Plants employ repressive viral genome methylation as an epigenetic defense against geminiviruses. In turn, geminiviruses encode proteins that inhibit methylation by TGS. Previous studies showed that TYLCV V2 can efficiently suppress TGS, but the mechanism remains unknown. We showed that V2 interacted with NbHDA6 but did not inhibit its enzymatic activity. As HDA6 is known to be involved in gene silencing in cooperation with MET1, we explored the relationship between V2, NbMET1, and NbHDA6. Our investigation showed that V2 did not interact but competed with NbMET1 for direct binding to NbHDA6. To our knowledge, this is the first report that viral proteins inhibit TGS by interacting with histone deacetylase but not by blocking the methyl cycle. This work provides an additional mechanism for TGS suppression by geminiviruses.
Asunto(s)
Begomovirus/genética , Metilación de ADN , Silenciador del Gen , Histona Desacetilasa 6/genética , Nicotiana/virología , Proteínas Virales/genética , Begomovirus/metabolismo , Genoma Viral , Histona Desacetilasa 6/metabolismo , Interacciones Huésped-Patógeno/genética , Nicotiana/enzimología , Nicotiana/genética , Proteínas Virales/metabolismoRESUMEN
A recently characterized calmodulin-like protein is an endogenous RNA silencing suppressor that suppresses sense-RNA induced post-transcriptional gene silencing (S-PTGS) and enhances virus infection, but the mechanism underlying calmodulin-like protein-mediated S-PTGS suppression is obscure. Here, we show that a calmodulin-like protein from Nicotiana benthamiana (NbCaM) interacts with Suppressor of Gene Silencing 3 (NbSGS3). Deletion analyses showed that domains essential for the interaction between NbSGS3 and NbCaM are also required for the subcellular localization of NbSGS3 and NbCaM suppressor activity. Overexpression of NbCaM reduced the number of NbSGS3-associated granules by degrading NbSGS3 protein accumulation in the cytoplasm. This NbCaM-mediated NbSGS3 degradation was sensitive to the autophagy inhibitors 3-methyladenine and E64d, and was compromised when key autophagy genes of the phosphatidylinositol 3-kinase (PI3K) complex were knocked down. Meanwhile, silencing of key autophagy genes within the PI3K complex inhibited geminivirus infection. Taken together these data suggest that NbCaM acts as a suppressor of RNA silencing by degrading NbSGS3 through the autophagy pathway.
Asunto(s)
Calmodulina/metabolismo , Geminiviridae , Regulación de la Expresión Génica de las Plantas/fisiología , Nicotiana/virología , Enfermedades de las Plantas/virología , Autofagia , Immunoblotting , Enfermedades de las Plantas/genética , Proteínas de Plantas/metabolismo , Reacción en Cadena de la Polimerasa , Interferencia de ARN/fisiologíaRESUMEN
Two sequencing batch reactors (SBRs) were operated for 100days under aerobic conditions, with one being fed with unsterilized municipal wastewater (USBR), and the other fed with sterilized municipal wastewater (SSBR). Respirometric assays and fluorescence in situ hybridization (FISH) results show that active nitrifiers were present in the unsterilized influent municipal wastewater. The maximum ammonia utilization rate (AUR) and nitrite utilization rate (NUR) of the unsterilized influent were 0.32±0.12mg NH4+-N/(L·hr) and 0.71±0.18mg NO2--N/(L·hr). Based on the maximum utilization rates, the estimated seeding intensity for the ammonia oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) of the USBR was 0.08g AOB/(g AOB·day) and 0.20g NOB/(g NOB·day) respectively. The fraction of nitrifiers/total bacteria in the influent was 5.35%±2.1%, the dominant AOB was Nitrosomonas spp., Nitrosococcus mobilis hybridizated with Nsm156, and the dominant NOB was Nitrospira hybridizated with Ntspa662. The influent nitrifiers potentially seeded the activated sludge of the bioreactor and hence demonstrated a mitigation of the acclimatization times and instability during start-up and early operation. The AUR and NUR in the USBR was 15% and 13% higher than the SSBR respectively during the stable stage, FISH results showed that nitrifiers population especially the Nitrospira in the USBR was higher than that in the SSBR. These results indicate that the natural continuous immigration of nitrifiers from municipal influent streams may have some repercussions on the modeling and design of bioreactors.
Asunto(s)
Reactores Biológicos/microbiología , Nitrificación , Aguas del Alcantarillado/microbiologíaRESUMEN
OBJECTIVE: Biocompatible polymer everolimus-eluting stents (EES) are associated with risk of stent thrombosis (ST); biodegradable polymer drug-eluting stents (BP-DES) were designed to reduce these risks. However, the long-term benefits are not completely clear. METHOD: We undertook a meta-analysis of randomized studies identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Primary outcome was the risk of ST. RESULTS: Twelve studies (11,692 patients) were included. Overall, compared with EES, BP-DES were associated with a broadly equivalent risk of definite and probable ST (OR, 0.91; 95% CI, 0.55 to 1.50; P = 0.71; I2 = 0.0%), early ST (OR, 2.25; 95% CI, 0.78 to 6.47; P = 0.13; I2 = 0.0%), late ST (OR, 3.57; 95% CI, 0.42 to 30.58; P = 0.25; I2 = 0.0%) and very late ST (OR, 0.50; 95% CI, 0.05 to 5.52; P = 0.57). Meanwhile, there was no significant difference in all-cause mortality (OR, 1.07; 95% CI, 0.86 to 1.32; P = 0.54; I2 = 0.0%), myocardial infarction (OR, 1.07; 95% CI, 0.88 to 1.30; P = 0.47; I2 = 0.0%), target vessel revascularization (OR, 1.02; 95% CI, 0.86 to 1.21; P = 0.80; I2 = 12.0%), and major adverse cardiac events (OR, 1.04; 95% CI, 0.93 to 1.16; P = 0.53; I2 = 0.0%). Furthermore, angiographic data showed that in-stent and in-segment late luminal loss were similar between the two groups. CONCLUSIONS: Compared with biocompatible polymer EES, biodegradable polymer stents appear to have equivalent clinical benefits.
Asunto(s)
Materiales Biocompatibles , Plásticos Biodegradables , Enfermedad de la Arteria Coronaria/cirugía , Reestenosis Coronaria/prevención & control , Stents Liberadores de Fármacos , Everolimus/farmacología , Intervención Coronaria Percutánea/métodos , Humanos , Inmunosupresores/farmacología , PolímerosRESUMEN
BACKGROUND: The begomoviruses are the largest and most economically important group of plant viruses exclusively vectored by whitefly (Bemisia tabaci) in a circulative, persistent manner. During this process, begomoviruses and whitefly vectors have developed close relationships and complex interactions. However, the molecular mechanisms underlying these interactions remain largely unknown, and the microRNA profiles for viruliferous and nonviruliferous whiteflies have not been studied. METHODS: Sequences of Argonaute 1(Ago1) and Dicer 1 (Dcr1) genes were cloned from B. tabaci MEAM1 cDNAs. Subsequently, deep sequencing of small RNA libraries from uninfected and Tomato yellow leaf curl China virus (TYLCCNV)-infected whiteflies was performed. The conserved and novel miRNAs were identified using the release of miRBase Version 19.0 and the prediction software miRDeep2, respectively. The sequencing results of selected deregulated and novel miRNAs were further confirmed using quantitative reverse transcription-PCR. Moreover, the previously published B. tabaci MEAM1 transcriptome database and the miRNA target prediction algorithm miRanda 3.1 were utilized to predict potential targets for miRNAs. Gene Ontology (GO) analysis was also used to classify the potential enriched functional groups of their putative targets. RESULTS: Ago1 and Dcr1orthologs with conserved domains were identified from B. tabaci MEAM1. BLASTn searches and sequence analysis identified 112 and 136 conserved miRNAs from nonviruliferous and viruliferous whitefly libraries respectively, and a comparison of the conserved miRNAs of viruliferous and nonviruliferous whiteflies revealed 15 up- and 9 down-regulated conserved miRNAs. 7 novel miRNA candidates with secondary pre-miRNA hairpin structures were also identified. Potential targets of conserved and novel miRNAs were predicted using GO analysis, for the targets of up- and down-regulated miRNAs, eight and nine GO terms were significantly enriched. CONCLUSIONS: We identified Ago1 and Dcr1 orthologs from whiteflies, which indicated that miRNA-mediated silencing is present in whiteflies. Our comparative analysis of miRNAs from TYLCCNV viruliferous and nonviruliferous whiteflies revealed the relevance of deregulated miRNAs for the post-transcriptional gene regulation in these whiteflies. The potential targets of all expressed miRNAs were also predicted. These results will help to acquire a better understanding of the molecular mechanism underlying the complex interactions between begomoviruses and whiteflies.