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Acquiring a highly efficient electrocatalyst capable of sustaining prolonged operation under high current density is of paramount importance for the process of electrocatalytic water splitting. Herein, Fe-doped phosphide (Fe-Ni5P4) derived from the NiFc metal-organic framework (NiFc-MOF) (Fc: 1,1'-ferrocene dicarboxylate) shows high catalytic activity for overall water splitting (OWS). Fe-Ni5P4||Fe-Ni5P4 exhibits a low voltage of 1.72 V for OWS at 0.5 A cm-2 and permits stable operation for 2700 h in 1.0 m KOH. Remarkably, Fe-Ni5P4||Fe-Ni5P4 can sustain robust water splitting at an extra-large current density of 1 A cm-2 for 1170 h even in alkaline seawater. Theoretical calculations confirm that Fe doping simultaneously reduces the reaction barriers of coupling and desorption (O*âOOH*, OOH*âO2 *) in the oxygen evolution reaction (OER) and regulates the adsorption strength of the intermediates (H2O*, H*) in the hydrogen evolution reaction (HER), enabling Fe-Ni5P4 to possess excellent dual functional activity. This study offers a valuable reference for the advancement of highly durable electrocatalysts through the regulation derived from coordination frameworks, with significant implications for industrial applications and energy conversion technologies.
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Background: Limited studies have explored the association between blood urea nitrogen (BUN) levels and in-hospital mortality in patients with acute myocardial infarction (AMI) and subsequent gastrointestinal bleeding (GIB). Our objective was to explore this correlation. Methods: 276 individuals with AMI and subsequent GIB were retrospectively included between January 2012 and April 2023. The predictive value of BUN for in-hospital mortality was assessed through receiver operating characteristic (ROC) curve. Logistic regression models were constructed to assess the relationship between BUN and in-hospital mortality. Propensity score weighting (PSW), sensitivity and subgroup analyses were used to further explore the association. Results: Fifty-three (19.2%) patients died in the hospital. BUN levels were higher in non-survivors compared with the survivors [(11.17 ± 6.17) vs (8.09 ± 4.24), p = 0.001]. The ROC curve suggested that the optimal cut-off for BUN levels to predict in-hospital mortality was 8.45 mmol/L (AUC [area under the ROC curve] 0.678, 95% confidence interval [CI] 0.595-0.761, p < 0.001). Multivariable logistic regression showed that elevated BUN levels ( ≥ 8.45 mmol/L) were positively association with in-hospital mortality (odds ratio [OR] 4.01, 95% CI 1.55-10.42, p = 0.004). After PSW, sensitivity and subgroup analyses, the association remained significant. Conclusions: Elevated BUN levels were associated with in-hospital mortality in patients with AMI and subsequent GIB.
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The development of cost-effective electrocatalysts with high efficiency and long durability for hydrogen evolution reaction (HER) remains a great challenge in the field of water splitting. Herein, we design an ultrafine and highly dispersed Ru nanoparticles stabilized on porous V8C7/C matrix via pyrolysis of the metal-organic frameworks V-BDC (BDC: 1,4-benzenedicarboxylate). The obtained Ru-V8C7/C composite exhibits excellent HER performance in all pH ranges. At the overpotential of 40 mV, its mass activity is about 1.9, 4.1 and 9.4 times higher than that of commercial Pt/C in acidic, neutral and alkaline media, respectively. Meanwhile, Ru-V8C7/C shows the remarkably high stability in all pH ranges which, in particular, can maintain the current density of 10 mA cm-2 for over 150 h in 1.0 mol L-1 phosphate buffer saline (PBS). This outstanding HER performance can be attributed to the high intrinsic activity of Ru species and their strong interface interactions to the V8C7/C substrate. The synergistic effect of abundant active sites on the surface and the formed Ru-C-V units at the interface promotes the adsorption of reaction intermediates and the release of active sites, contributing the fast HER kinetics. This work provides a reference for developing versatile and robust HER catalysts by surface and interface regulation for pH tolerance.
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How to transfer industrial exhaust gases of nitrogen oxides into high-values product is significantly important and challenging. Herein, we demonstrate an innovative method for artificial synthesis of essential α-amino acids from nitric oxide (NO) by reacting with α-keto acids through electrocatalytic process with atomically dispersed Fe supported on N-doped carbon matrix (AD-Fe/NC) as the catalyst. A yield of valine with 32.1â µmol mgcat -1 is delivered at -0.6â V vs. reversible hydrogen electrode, corresponding a selectivity of 11.3 %. In situ X-ray absorption fine structure and synchrotron radiation infrared spectroscopy analyses show that NO as nitrogen source converted to hydroxylamine that promptly nucleophilic attacked on the electrophilic carbon center of α-keto acid to form oxime and subsequent reductive hydrogenation occurred on the way to amino acid. Over 6 kinds of α-amino acids have been successfully synthesized and gaseous nitrogen source can be also replaced by liquid nitrogen source (NO3 - ). Our findings not only provide a creative method for converting nitrogen oxides into high-valued products, which is of epoch-making significance towards artificial synthesis of amino acids, but also benefit in deploying near-zero-emission technologies for global environmental and economic development.
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Aminoácidos Essenciais , Óxido Nítrico , Aminoácidos , Hidrogenação , Carbono , Gases , CetoácidosRESUMO
The construction of high-activity and low-cost electrocatalysts is critical for efficient hydrogen production by water electrolysis. Herein, we developed an advanced electrocatalyst by anchoring well-dispersed Ir nanoparticles on nickel metal-organic framework (MOF) Ni-NDC (NDC: 2,6-naphthalenedicarboxylic) nanosheets. Benefiting from the strong synergy between Ir and MOF through interfacial Ni-O-Ir bonds, the synthesized Ir@Ni-NDC showed exceptional electrocatalytic performance for hydrogen evolution reaction (HER), oxygen evolution reaction (OER) and overall water splitting in a wide pH range, superior to commercial benchmarks and most reported electrocatalysts. Theoretical calculations revealed that the charge redistribution of Ni-O-Ir bridge induced the optimization of H2 O, OH* and H* adsorption, thus leading to the accelerated electrochemical kinetics for HER and OER. This work provides a new clue to exploit bifunctional electrocatalysts for pH-universal overall water splitting.
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Metal-organic frameworks (MOFs), with diverse metal nodes and designable organic linkers, offer unique opportunities for the rational engineering of semiconducting properties. In this work, we report a mixed-linker conductive MOF system with both tetrathiafulvalene and Ni-bis(dithiolene) moieties, which allows the fine-tuning of electronic structures and semiconductive characteristics. By continuously increasing the molar ratio between tetrathiafulvalene and Ni-bis(dithiolene), the switching of the semiconducting behaviors from n-type to p-type was observed along with an increase in electrical conductivity by 3 orders of magnitude (from 2.88×10-7 â S m-1 to 9.26×10-5 â S m-1 ). Furthermore, mixed-linker MOFs were applied for the chemiresistive detection of volatile organic compounds (VOCs), where the sensing performance was modulated by the corresponding linker ratios, showing synergistic and nonlinear modulation effects.
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Precise understanding of interfacial metal-hydrogen interactions, especially under in operando conditions, is crucial to advancing the application of metal catalysts in clean energy technologies. To this end, while Pd-based catalysts are widely utilized for electrochemical hydrogen production and hydrogenation, the interaction of Pd with hydrogen during active electrochemical processes is complex, distinct from most other metals, and yet to be clarified. In this report, the hydrogen surface adsorption and sub-surface absorption (phase transition) features of Pd and its alloy nanocatalysts are identified and quantified under operando electrocatalytic conditions via on-chip electrical transport measurements, and the competitive relationship between electrochemical carbon dioxide reduction (CO2RR) and hydrogen sorption kinetics is investigated. Systematic dynamic and steady-state evaluations reveal the key impacts of local electrolyte environment (such as proton donors with different pKa) on the hydrogen sorption kinetics during CO2RR, which offer additional insights into the electrochemical interfaces and optimization of the catalytic systems.
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The on-chip electrocatalytic microdevice (OCEM) is an emerging platform specialized in the electrochemical investigation of single-entity nanomaterials, which is ideal for probing the intrinsic catalytic properties, optimizing performance, and exploring exotic mechanisms. However, the current catalytic applications of OCEMs are almost exclusively in electrocatalytic hydrogen/oxygen evolution reactions with minimized influence from the mass transfer. Here, an OCEM platform specially tailored to investigate the electrocatalytic oxygen reduction reaction (ORR) at a microscopic level by introducing electrolyte convection through a microfluidic flow cell is reported. The setup is established on gold microelectrodes and later successfully applied to investigate how Ar-plasma treatment affects the ORR activities of 2H MoS2 . This study finds that Ar-plasma treatment significantly enhances the ORR performance of MoS2 nanosheets owing to the introduction of surface defects. This study paves the way for highly efficient microscopic investigation of diffusion-controlled electrocatalytic reactions.
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Molibdênio , Nanoestruturas , Molibdênio/química , Catálise , Nanoestruturas/química , Ouro/química , Oxigênio/químicaRESUMO
Operando reconstruction of solid catalyst into a distinct active state frequently occurs during electrocatalytic processes. The correlation between initial and operando states, if ever existing, is critical for the understanding and precise design of a catalytic system. Inspired by recently established intermediate metallic state of Bi-based catalysts during electrocatalytic carbon dioxide reduction (CO2RR), here we investigate a series of Bi oxide catalysts (Bi, Bi2O3, BiO2) and demonstrate that the operando surface/subsurface oxygen loading, positively correlated to the initial oxygen content, plays a critical role in determining Bi-based CO2RR performance. Higher initial oxygen loading indicates a better electrocatalytic efficiency. Further analysis shows that this conclusion generally applies to all Bi-based electrocatalysts reported up to date. Following this principle, cost-effective BiO2 nanocrystals demonstrated the highest formate Faradaic efficiency (FE) and current density compared to Bi/Bi2O3, further allowing a pair-electrolysis system with 800 mA/cm2 current density and an overall 175% FE for formate production.
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Single-atom catalysts represent a unique catalytic system with high atomic utilization and tunable reaction pathway. Despite current successes in their optimization and tailoring through structural and synthetic innovations, there is a lack of dynamic modulation approach for the single-atom catalysis. Inspired by the electrostatic interaction within specific natural enzymes, here we show the performance of model single-atom catalysts anchored on two-dimensional atomic crystals can be systematically and efficiently tuned by oriented external electric fields. Superior electrocatalytic performance have been achieved in single-atom catalysts under electrostatic modulations. Theoretical investigations suggest a universal "onsite electrostatic polarization" mechanism, in which electrostatic fields significantly polarize charge distributions at the single-atom sites and alter the kinetics of the rate determining steps, leading to boosted reaction performances. Such field-induced on-site polarization offers a unique strategy for simulating the catalytic processes in natural enzyme systems with quantitative, precise and dynamic external electric fields.
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Eletricidade , Catálise , Eletricidade EstáticaRESUMO
OBJECTIVE: To evaluate the association between proton pump inhibitor (PPI) use and in-hospital gastrointestinal (GI) bleeding in patients with acute coronary syndrome (ACS) taking dual antiplatelet therapy (DAPT). PATIENTS AND METHODS: This study is based on the Improving Care for Cardiovascular Disease in China-ACS project, an ongoing collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. A total of 25,567 patients with ACS taking DAPT from 172 hospitals from July 1, 2017, through December 31, 2018, were included. Multivariable Cox regression and propensity score-matched analyses were used to evaluate the association between PPI use and in-hospital GI bleeding. RESULTS: Of these patients with ACS, 63.9% (n=16,332) were prescribed PPIs within 24 hours of admission. Patients using PPIs had a higher rate of GI bleeding compared with those not using PPIs (1.0% vs 0.5%; P<.001). In the multivariable Cox regression analysis, early PPI use was associated with a 58% higher risk of GI bleeding (hazard ratio, 1.58; 95% CI, 1.15 to 2.18; P=.005). Further propensity score matching attenuated the association but still showed that patients using PPIs had a higher rate of GI bleeding (0.8% vs 0.6%; P=.04). CONCLUSION: In China, PPIs are widely used within 24 hours of admission in patients with ACS taking DAPT. An increased risk of GI bleeding is observed in inpatients with early PPI use. Randomized trials on early use of PPIs in patients with ACS receiving DAPT are warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02306616.
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Síndrome Coronariana Aguda , Inibidores da Bomba de Prótons , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Quimioterapia Combinada , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/complicações , Hospitais , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Helicobacter pylori infection rates are high in China and worldwide, and maintaining good hygiene is effective in preventing H. pylori infection. Childhood is a critical stage for developing good hygiene practices. Therefore, in this study, we aimed to explore whether a comprehensive hygiene intervention can prevent H. pylori infection in primary schools in China. METHODS AND ANALYSIS: The School-based Hygiene Intervention to Prevent HelicObacter Pylori infection among childrEn study is a cluster-randomised controlled trial, which will include approximately 2400 children in grades 2-4 from 60 classes in 10 primary schools of Linqu County, Shandong Province. Schools will be randomly assigned (1:1) via a computer-generated list, to receive either comprehensive hygiene intervention (intervention) or the usual health education lessons (control), with stratification by area (urban or rural). The interventions will include the following: (1) Children's education: lessons and cartoon books designed to provide basic knowledge about hygiene, H. pylori, hand hygiene, diet and oral hygiene will be provided to children; (2) Caregiver's education: children will be empowered to share hygiene-related knowledge with their caregivers as homework; caregivers will be also invited to the school for hygiene lessons; (3) School hygiene promotion: suggestions will be provided for improving the hygienic environment. Children in control schools will receive usual health education lessons according to the arrangements of each school. The primary outcome is the prevalence and incidence of H. pylori infection among children at 1-year follow-up. The secondary outcomes are H. pylori and hygiene knowledge, family eating customs and hygiene practices among children and their caregivers, as well as school absences owing to diarrhoea. Additionally, growth in children is set as an exploratory outcome. General linear mixed models will be used to analyse differences between the intervention and control schools. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Institution Review Board of Tsinghua University (No: 20220020). Written informed consent will be obtained from each child and one of their caregivers. The findings of this study will be actively disseminated through scientific publications and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200056191.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Criança , Infecções por Helicobacter/prevenção & controle , Higiene , Educação em Saúde , Instituições Acadêmicas , Serviços de Saúde Escolar , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Accurately regulating the selectivity of the oxygen reduction reaction (ORR) is crucial to renewable energy storage and utilization, but challenging. A flexible alteration of ORR pathways on atomically dispersed Zn sites towards high selectivity ORR can be achieved by tailoring the coordination environment of the catalytic centers. The atomically dispersed Zn catalysts with unique O- and C-coordination structure (ZnO3 C) or N-coordination structure (ZnN4 ) can be prepared by varying the functional groups of corresponding MOF precursors. The coordination environment of as-prepared atomically dispersed Zn catalysts was confirmed by X-ray absorption fine structure (XAFs). Notably, the ZnN4 catalyst processes a 4â e- ORR pathway to generate H2 O. However, controllably tailoring the coordination environment of atomically dispersed Zn sites, ZnO3 C catalyst processes a 2â e- ORR pathway to generate H2 O2 with a near zero overpotential and high selectivity in 0.1â M KOH. Calculations reveal that decreased electron density around Zn in ZnO3 C lowers the d-band center of Zn, thus changing the intermediate adsorption and contributing to the high selectivity towards 2â e- ORR.
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The occurrences, distributions, and risks of 55 target volatile organic compounds (VOCs) in water, sediment, sludge, and soil samples taken from a chemical industrial park and the adjacent area were investigated in this study. The Σ55-VOCs concentrations in the water, sediment, sludge, and soil samples were 1.22-5449.21 µg L-1, ND-52.20 ng g-1, 21.53 ng g-1, and ND-11.58 ng g-1, respectively. The main products in this park are medicines, pesticides, and novel materials. As for the species of VOCs, aromatic hydrocarbons were the dominant VOCs in the soil samples, whereas halogenated aliphatic hydrocarbons were the dominant VOCs in the water samples. The VOCs concentrations in water samples collected at different locations varied by 1-3 orders of magnitude, and the average concentration in river water inside the park was obviously higher than that in river water outside the park. However, the risk quotients for most of the VOCs indicated a low risk to the relevant, sensitive aquatic organisms in the river water. The average VOCs concentration in soil from the park was slightly higher than that from the adjacent area. This result showed that the chemical industrial park had a limited impact on the surrounding soil, while the use of pesticides, incomplete combustion of coal and biomass, and automobile exhaust emissions are all potential sources of the VOCs in the environmental soil. The results of this study could be used to evaluate the effects of VOCs emitted from chemical production and transportation in the park on the surrounding environment.
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Motivated by in silico predictions that Co, Rh, and Ir dopants would lead to low overpotentials to improve OER activity of Ni-based hydroxides, we report here an experimental confirmation on the altered OER activities for a series of metals (Mo, W, Fe, Ru, Co, Rh, Ir) doped into γ-NiOOH. The in situ electrical conductivity for metal doped γ-NiOOH correlates well with the trend in enhanced OER activities. Density functional theory (DFT) calculations were used to rationalize the in situ conductivity of the key intermediate states of metal doped γ-NiOOH during OER. The simultaneous increase of OER activity with intermediate conductivity was later rationalized by their intrinsic connections to the double exchange (DE) interaction between adjacent metal ions with various d orbital occupancies, serving as an indicator for the key metal-oxo radical character, and an effective descriptor for the mechanistic evaluation and theoretical guidance in design and screening of efficient OER catalysts.
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Developing high-performance electrocatalysts toward hydrogen evolution reaction is important for clean and sustainable hydrogen energy, yet still challenging. Herein, we report a single-atom strategy to construct excellent metal-organic frameworks (MOFs) hydrogen evolution reaction electrocatalyst (NiRu0.13-BDC) by introducing atomically dispersed Ru. Significantly, the obtained NiRu0.13-BDC exhibits outstanding hydrogen evolution activity in all pH, especially with a low overpotential of 36 mV at a current density of 10 mA cm-2 in 1 M phosphate buffered saline solution, which is comparable to commercial Pt/C. X-ray absorption fine structures and the density functional theory calculations reveal that introducing Ru single-atom can modulate electronic structure of metal center in the MOF, leading to the optimization of binding strength for H2O and H*, and the enhancement of HER performance. This work establishes single-atom strategy as an efficient approach to modulate electronic structure of MOFs for catalyst design.
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Air pollution control has become one of the top priorities of China's "Ecological Civilization" development. As a quick response to the 2013 PM2.5 episodes, the Chinese Government issued the "Air Pollution Prevention and Control Action Plan" as the national strategy and roadmap for air quality improvements consisting of phased quantitative targets and concrete measures. Taking this into account, this study explores the spatiotemporal variations of the five conventional pollutants-PM2.5, PM10, SO2, NO2, and O3-as well as the Air Quality Index and primary pollutants in 338 Chinese cities from 2013 to 2017 in order to comprehensively understand China's current air pollution situation and evaluate the effectiveness of the Action Plan. The results indicate that: (1) the overall air quality has been significantly improved, with the concentrations of PM2.5, PM10, and SO2 decreasing noticeably, although the still high PM level, the dramatically increasing O3 concentration, and the stagnant amounts of NO2 present further challenges, along with the intensification of regional compound air pollution problems; (2) in contrast to the three key regions under the Action Plan exhibiting significant decreases in PM and SO2, the Fen-Wei Plain (FWP) is suffering from serious compound pollution, suggesting that there is an urgent need for the development of a regional joint prevention and control mechanism in the FWP and similar areas; (3) with the exception of the common pollution hot spots mainly concentrated in the FWP as well as Beijing-Tianjin-Hebei (BTH) and its surrounding regions, the distribution of each pollutant exhibited remarkable spatial heterogeneity due to their distinctive emission sources, a finding that strongly indicates the need for regionally differentiated management; and (4) the most frequent primary pollutant at the national level was O3, followed by PM2.5 and PM10. In the Wuhan Metropolitan Area (WHM), Changsha-Zhuzhou-Xiangtan Metropolitan Area (CZT), and Sichuan-Chongqing Region (CY), PM2.5 pollution is playing the dominant role, while in the FWP, BTH, Yangtze River Delta region (YRD), and Pearl River Delta region (PRD), the synergistic control of PM2.5 and O3 pollutants is urgently needed as soon as possible, which will require that more attention be paid to emission mitigation in the transportation sector, as well as the synergistic control of NOx and VOC emissions.
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Poluentes Atmosféricos , Poluição do Ar , Pequim , China , Cidades , Monitoramento Ambiental , Material Particulado , Melhoria de QualidadeRESUMO
DDX21 regulates the biogenesis of rRNA and transcription of ribonucleoprotein genes. Recently, it has been reported that DDX21 regulates the growth of some RNA viruses through various mechanisms, such as inhibiting viral genome replication, suppressing virion assembly and release, and modulating antiviral immune responses (Chen et al., Cell Host Microbe 15:484-493, 2014, https://doi.org/10.1016/j.chom.2014.03.002; Dong et al., Biophys Res Commun, 473:648-653, 2016, https://doi.org/10.1016/j.bbrc.2016.03.120; and Watanabe et al., PLoS Pathog 5:e1000654, 2009, https://doi.org/10.1371/journal.ppat.1000654). The relationship between DDX21 and DNA viruses has not yet been explored. In this study, we used human cytomegalovirus (HCMV), a large human DNA virus, to investigate the potential role of DDX21 in DNA virus replication. We found that HCMV infection prevented the repression of DDX21 at protein and mRNA levels. Knockdown of DDX21 inhibited HCMV growth in human fibroblast cells (MRC5). Immunofluorescence and quantitative PCR (qPCR) results showed that knockdown of DDX21 did not affect viral DNA replication or the formation of the viral replication compartment but did significantly inhibit viral late gene transcription. Some studies have reported that DDX21 knockdown promotes the accumulation of R-loops that could restrain RNA polymerase II elongation and inhibit the transcription of certain genes. Thus, we used the DNA-RNA hybrid-specific S9.6 antibody to stain R-loops and observed that more R-loops formed in DDX21-knockdown cells than in control cells. Moreover, an DNA-RNA immunoprecipitation assay showed that more R-loops accumulated on a viral late gene in DDX21-knockdown cells. Altogether, these results suggest that DDX21 knockdown promotes the accumulation of R-loops, which prevents viral late gene transcription and consequently results in the suppression of HCMV growth. This finding provides new insight into the relationship between DDX21 and DNA virus replication.IMPORTANCE Previous studies have confirmed that DDX21 is vital for the regulation of various aspects of RNA virus replication. Our research is the first report on the role of DDX21 in HCMV DNA virus replication. We identified that DDX21 knockdown affected HCMV growth and viral late gene transcription. In order to elucidate how DDX21 regulated this transcription, we applied DNA-RNA immunoprecipitation by using the DNA-RNA hybrid-specific S9.6 antibody to test whether more R-loops accumulated on the viral late gene. Consistent with our expectation, more R-loops were detected on the viral late gene at late HCMV infection time points, which demonstrated that the accumulation of R-loops caused by DDX21 knockdown prevented viral late gene transcription and consequently impaired HCMV replication. These results reveal that DDX21 plays an important role in regulating HCMV replication and also provide a basis for investigating the role of DDX21 in regulating other DNA viruses.
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Citomegalovirus/fisiologia , RNA Helicases DEAD-box/fisiologia , Replicação Viral/fisiologia , Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , DNA Viral/metabolismo , Fibroblastos/virologia , Expressão Gênica , Técnicas de Silenciamento de Genes , Genes Virais , Células HEK293 , Humanos , Imunoprecipitação , RNA Polimerase II/metabolismo , Transcrição Gênica , Montagem de VírusRESUMO
Viral gene expression is tightly regulated during cytomegalovirus (CMV) lytic replication, but the detailed mechanism of late gene transcription remains to be fully understood. Previous studies reported that six viral proteins (named viral transactivation factors [vTFs]) supporting late gene expression were conserved in beta- and gammaherpesviruses but not in alphaherpesviruses. Here, we performed coimmunoprecipitation experiments to elucidate the organization of these six proteins in murine CMV. Our results showed that these proteins formed a complex by both direct and indirect interactions. Specifically, pM91 strongly bound to pM79 even in the absence of other vTFs. Similar to pM79, pM91 exhibited early-late expression kinetics and localized within nuclear viral replication compartments during infection. Functional analysis was also performed using the pM91-deficient virus. Real-time PCR results revealed that abrogation of M91 expression markedly reduced viral late gene expression and progeny virus production without affecting viral DNA synthesis. Using mutagenesis, we found that residues E61, D62, D89, and D96 in pM91 were required for the pM91-pM79 interaction. Disruption of the interaction via E61A/D62A or D89A/D96A double mutation in the context of virus infection inhibited progeny virus production. Our data indicate that pM91 is a component of the viral late gene transcription factor complex and that the pM91-pM79 interaction is essential for viral late gene expression.IMPORTANCE Cytomegalovirus (CMV) infection is the leading cause of birth defects and causes morbidity and mortality in immunocompromised patients. The regulation of viral late gene transcription is not well elucidated, and understanding of this process benefits the development of novel therapeutics against CMV infection. This study (i) identified that six viral transactivation factors encoded by murine CMV form a complex, (ii) demonstrated that pM91 interacts with pM79 and that pM91 and pM79 colocalize in the nuclear viral replication compartments, (iii) confirmed that pM91 is critical for viral late gene expression but dispensable for viral DNA replication, and (iv) revealed that the pM91-pM79 interaction is required for progeny virus production. These findings give an explanation of how CMV regulates late gene expression and have important implications for the design of antiviral strategies.
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Muromegalovirus/fisiologia , Proteínas Virais/química , Proteínas Virais/metabolismo , Sítios de Ligação , Regulação Viral da Expressão Gênica , Células HEK293 , Humanos , Muromegalovirus/metabolismo , Ligação Proteica , Multimerização Proteica , Proteínas Virais/genética , Replicação ViralRESUMO
RATIONALE: Small cell carcinoma of the ovary (SCCO) is a rare and aggressive extra-pulmonary variant of small cell tumors of uncertain histogenesis. The pathogenesis and optimal treatment of SCCO is unclear. We present a very rare case of a synchronous primary ovarian small cell carcinoma and endometrioid adenocarcinoma of the uterus in a patient after 2 years of tamoxifen treatment for breast cancer. This is the first such report in the English literature. PATIENT CONCERNS: A 46-year-old woman had a history of left breast cancer that was treated with a simple mastectomy and sentinel lymph node biopsy in 2013. The post-operative pathology was invasive ductal carcinoma of the left breast. she had been taking tamoxifen for 2 years. The patient underwent an exploratory laparotomy to reduce the tumor burden, improve bowel compression symptoms, and promote defecation in 2015. The post-operative pathology revealed a rare, simultaneous occurrence of two tumors (endometrial adenocarcinoma and SCCO [pulmonary type]). DIAGNOSES: Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient. INTERVENTIONS: The patient received 3 courses of chemotherapy after operation. The effect was not apparent and the general health status was poor. OUTCOMES: The patient died of progressive disease 7 months post-operatively. LESSONS: The present case suggests that tamoxifen use might be among many etiologic factors in SCCO development. Despite its rarity, SCCO requires a high degree of attention in clinical work because it is an aggressive tumor that has a poor prognosis.