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Microplastics have been identified as a potentially emerging threat to water environment and human health. Therefore, there is a pressing demand for effective strategies to remove microplastics from water. Hydrocyclone offers a rapid separation and low energy consumption alternative but require reduction of microparticle entrainment by short flow, which limits the effectiveness for small density differentials and ultralow concentrations separation. We proposed an enhanced mini-hydrocyclone with overflow microchannels (0.72 mm width) based on the active control of short flow in hydrocyclone for microplastic removal from water. The overflow microchannels effectively redirect the particles that would typically be entrained by the short flow, leading to higher separation efficiency. Simulation results show overflow microchannels effectively reduced short flow to 0.7 %, a reduction of up to 94 % compared to conventional hydrocyclones. The hydrocyclone with overflow microchannel demonstrated a removal efficiency exceeding 98 % for 8 µm plastic microbeads at ultralow concentrations (10 ppm), which is a 33.7 % improvement over conventional hydrocyclone. Compared with other methods (e.g., filtration, adsorption, coagulation) for microplastic removal, this work achieves rapid separation capability and long period operation, highlighting hydrocyclone as a promising approach for microplastic removal in industry-scale water treatment.
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This study analyzed the dissolved organic matter (DOM) released by adsorbent during wastewater treatment. It was found that the adsorption method resulted in an organic removal efficiency of over 97 % for coal-to-olefin (CTO) wastewater, with the lowest value of 15.7 mg/L. The Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) detected 4111 DOM in the wastewater, 4052 remaining DOM after first-stage anthracite (ANC) adsorption, and 1013 after second-stage macroporous adsorption resin (MAR). The removal degree of lipids in wastewater was the highest, followed by aliphatic/amino-acid/mini-peptides and lignin. During the adsorption process, the proportion of halogenated compounds (HCs) declined from 59.86 % to 38.63 % and 21.67 %. Additionally, freshly produced 2035 and 311 DOMs were found in the adsorption effluent of ANC and MAR, respectively, with HCs accounting for 34.71 % and 67.96 %. Upon flowing ultra-pure water through ANC and MAR, the effluent dissolved organic carbon (DOC) ranges were 1.118-3.574 mg/L and 1.014-2.557 mg/L, respectively. There were 159 and 131 species of DOM detected, respectively, with HCs content of 59.06 % and 45.02 %. Comparative experiments revealed the complex components of the wastewater promoting the release of organic matter on the adsorbent surface that further reacted to generate organic matter. However, fewer substances were released by the adsorbent.
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INTRODUCTION: Physical activity (PA) is believed to play an important part in many aspects during childhood and adolescence, especially cardiorespiratory fitness and cardiometabolic health. However, whether different levels of PA in daily life influence the structure or function of heart in school-aged children remains unknown. We aimed to investigate the association between PA and cardiovascular parameters in 7-year-old children. METHODS: Follow-up data from the Shanghai Prenatal Cohort Study and the Shanghai Birth Cohort was analyzed. Perinatal information including both maternal and offspring datum was recorded. A refined questionnaire was used to evaluate the frequency and duration of children's PA levels. Blood pressure, echocardiography, and anthropometry assessment were conducted during the follow-up of 7-year-old children. RESULTS: Overall, high PA level was associated with higher left ventricle posterior wall thickness in diastole (LVPWd, ß coefficient: 0.36, 95% CI: 0.12, 0.61), higher left ventricle mass index (LVMI, ß = 0.28, 95% CI: 0.07, 0.48), mitral E/a ratio (ß = 0.47, 95% CI: 0.22, 0.71) and slower heart rate (ß = -0.32, 95% CI: -0.57, -0.07), compared to low PA level. Medium PA level was associated with lower diastolic blood pressure (DBP, ß = -0.18, 95% CI: -0.35, -0.01). In subgroup analysis, increased relative wall thickness (RWT) was found in high PA level boys (ß = 0.36, 95% CI: 0.05, 0.67), and systolic blood pressure (SBP) showed a significant decrease in high PA level girls (ß = -0.42, 95% CI: -0.78, -0.06). CONCLUSIONS: This study suggested non-athlete children having higher PA level were associated with thicker left ventricle (LV) walls and better LV diastolic function, as well as slower heart rate and DBP at the age of 7. Furthermore, disparity in the association between PA level with morphological heart patterns and blood pressure existed in different sex category.
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Pressão Sanguínea , Ecocardiografia , Exercício Físico , Humanos , Feminino , Criança , Masculino , Estudos Transversais , China , Exercício Físico/fisiologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/anatomia & histologia , Seguimentos , Aptidão Cardiorrespiratória/fisiologia , População do Leste AsiáticoRESUMO
The environmental changes from climatic, terrestrial and anthropogenic drivers can significantly influence the groundwater quality that may pose a threat to human health. However, the driving mechanism of groundwater quality and potential health risk still remains to be studied. In this paper, 165 groundwater samples were analyzed to evaluate the groundwater quality, driving mechanism, and probabilistic health risk in the central Yinchuan Plain by applying fuzzy comprehensive evaluation method (FCEM), redundance analysis (RDA) and Monte Carlo simulation. The results showed that hydrochemical evolution of groundwater were strongly influenced by water-rock interaction, evaporation and human activities. While 55.2% of groundwater samples reached the drinking water quality standard (Class I, II and III), 44.8% of samples exceeded the standard limits of Class III water quality (Class IV and V), indicating a high pollution level of groundwater. Mn, TDS, NH4+, NO3-, Fe, F-, NO2-, As were among major indicators that influence the groundwater quality due to the natural and anthropogenic processes. The RDA analysis revealed that climatic factors (PE: 10.9%, PRE: 1.1%), GE chemical properties (ORP: 20.7%, DO: 2.4%), hydrogeological factors (BD: 16.5%, K: 4.1%), and terrestrial factors (elevation: 1.2%; distanced: 5.6%, distancerl: 1.5%, NDVI: 1.2%) were identified as major driving factors influencing the groundwater quality in the study area. The HHRA suggested that TCR values of arsenic in infants, children and teens greatly exceeded the acceptable risk threshold of 1E-4, indicating a high cancer risk with a basic trend: infants > children > teens, while TCR values of adults were within the acceptable risk level. THI values of four age groups in the RME scenario were nearly ten times higher than those in the CTE scenario, displaying a great health effect on all age groups (HQ > 1). The present study provides novel insights into the driving mechanism of groundwater quality and potential health hazard in arid and semi-arid regions.
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Água Subterrânea , Poluentes Químicos da Água , Qualidade da Água , Água Subterrânea/análise , Água Subterrânea/química , Humanos , China , Medição de Risco , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Criança , Adolescente , Adulto , Lactente , Pré-Escolar , Adulto Jovem , Água Potável/análise , Água Potável/químicaRESUMO
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection.
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Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Epitopos , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Phlebovirus/imunologia , Camundongos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/prevenção & controle , Humanos , Epitopos/imunologia , Feminino , Camundongos Endogâmicos BALB C , Proteínas do Envelope Viral/imunologia , Cristalografia por Raios X , Chlorocebus aethiops , Glicoproteínas/imunologia , Células VeroRESUMO
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne viral pathogen that causes severe fever with thrombocytopenia syndrome (SFTS). The disease was initially reported in central and eastern China, then later in Japan and South Korea, with a mortality rate of 13-30%. Currently, no vaccines or effective therapeutics are available for SFTS treatment. In this study, three monoclonal antibodies (mAbs) targeting the SFTSV envelope glycoprotein Gn were obtained using the hybridoma technique. Two mAbs recognized linear epitopes and did not neutralize SFTSV, while the mAb 40C10 can effectively neutralized SFTSV of different genotypes and also the SFTSV-related Guertu virus (GTV) and Heartland virus (HRTV) by targeting a spatial epitope of Gn. Additionally, the mAb 40C10 showed therapeutic effect in mice infected with different genotypes of SFTSV strains against death by preventing the development of lesions and by promoting virus clearance in tissues. The therapeutic effect could still be observed in mice infected with SFTSV which were administered with mAb 40C10 after infection even up to 4 days. These findings enhance our understanding of SFTSV immunogenicity and provide valuable information for designing detection methods and strategies targeting SFTSV antigens. The neutralizing mAb 40C10 possesses the potential to be further developed as a therapeutic monoclonal antibody against SFTSV and SFTSV-related viruses.
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Anticorpos Monoclonais , Anticorpos Antivirais , Camundongos Endogâmicos BALB C , Phlebovirus , Phlebovirus/imunologia , Phlebovirus/genética , Animais , Anticorpos Monoclonais/imunologia , Camundongos , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Feminino , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Epitopos/imunologia , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genética , Glicoproteínas/imunologia , Glicoproteínas/genética , Infecções por Bunyaviridae/imunologia , Infecções por Bunyaviridae/virologia , Infecções por Bunyaviridae/prevenção & controle , HumanosRESUMO
BACKGROUND: The incongruity between dietary patterns and the circadian clock poses an elevated risk for metabolic health issues, particularly obesity and associated metabolic disorders. The intestinal microflora engages in regulating various physiological functions of the host through its metabolites. OBJECTIVES: This study aimed to investigate the impact of reversed feeding schedules during the day and night on intestinal flora and lipid metabolism in high-fat diet-induced obese mice. METHODS: Mice aged 8-10 wk were subjected to either daytime or nighttime feeding and were administered a control or high-fat diet for 18 wk. At the end of the experiment, various assessments were conducted, including analysis of serum biochemic indices, histologic examination, evaluation of gene and protein expression in adipose tissue, and scrutiny of changes in intestinal microbial composition. RESULTS: The results showed that day-night reversed feeding caused an increase in fasting blood glucose and exacerbated the high-fat diet-induced weight gain and lipid abnormalities. The mRNA expression levels of Leptin and Dgat1 were increased by day-night reversed feeding, which also reduced the expression level of adiponectin under the high-fat diet. Additionally, there was a significant increase in the protein concentrations of PPARγ, SREBP1c, and CD36. Inverted feeding schedules led to a reduction in intestinal microbial diversity, an increase in the abundance of inflammation-related bacteria, such as Coriobacteriaceae_UCG-002, and a suppression of beneficial bacteria, including Akkermansia, Candidatus_Saccharimonas, Anaeroplasma, Bifidobacterium, Carnobacterium, and Odoribacter. Acinetobacter exhibited a significant negative correlation with Leptin and Fasn, suggesting potential involvement in the regulation of lipid metabolism. CONCLUSIONS: The results elucidated the abnormalities of lipid metabolism and intestinal flora caused by day-night reversed feeding, which exacerbates the adverse effects of a high-fat diet on lipid metabolism and intestinal microflora. This reversal in feeding patterns may disrupt both intestinal and lipid metabolism homeostasis by altering the composition and abundance of intestinal microflora in mice.
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Tecido Adiposo , Dieta Hiperlipídica , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Tecido Adiposo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Ritmo Circadiano , Obesidade/metabolismo , Obesidade/etiologia , Obesidade/microbiologia , Aumento de PesoRESUMO
In addition to controlling smooth muscle tone in coronary vessels, endothelial cells also influence subjacent cardiomyocyte growth. Because heparanase, with exclusive expression in endothelial cells, enables extracellular matrix remodeling, angiogenesis, metabolic reprogramming, and cell survival, it is conceivable that it could also encourage development of cardiac hypertrophy. Global heparanase overexpression resulted in physiologic cardiac hypertrophy, likely an outcome of HSPG clustering and activation of hypertrophic signaling. The heparanase autocrine effect of releasing neuregulin-1 could have also contributed to this overexpression. Hyperglycemia induced by streptozotocin-induced diabetes sensitized the heart to flow-induced release of heparanase and neuregulin-1. Despite this excess secretion, progression of diabetes caused significant gene expression changes related to mitochondrial metabolism and cell death that led to development of pathologic hypertrophy and heart dysfunction. Physiologic cardiac hypertrophy was also observed in rats with cardiomyocyte-specific vascular endothelial growth factor B overexpression. When perfused, hearts from these animals released significantly higher amounts of both heparanase and neuregulin-1. However, subjecting these animals to diabetes triggered robust transcriptome changes related to metabolism and a transition to pathologic hypertrophy. Our data suggest that in the absence of mechanisms that support cardiac energy generation and prevention of cell death, as seen after diabetes, there is a transition from physiologic to pathologic cardiac hypertrophy and a decline in cardiac function.
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Cardiomegalia , Diabetes Mellitus Experimental , Glucuronidase , Remodelação Ventricular , Animais , Masculino , Ratos , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Diabetes Mellitus Experimental/metabolismo , Glucuronidase/metabolismo , Glucuronidase/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Neuregulina-1/metabolismo , Neuregulina-1/genética , Remodelação Ventricular/fisiologia , FemininoRESUMO
Heartland virus (HRTV), an emerging tick-borne pathogenic bunyavirus, has been a concern since 2012, with an increasing incidence, expanding geographical distribution, and high pathogenicity in the United States. Infection from HRTV results in fever, thrombocytopenia, and leucopenia in humans, and in some cases, symptoms can progress to severe outcomes, including haemorrhagic disease, multi-organ failure, and even death. Currently, no vaccines or antiviral drugs are available for treatment of the HRTV disease. Moreover, little is known about HRTV-host interactions, viral replication mechanisms, pathogenesis and virulence, further hampering the development of vaccines and antiviral interventions. Here, we aimed to provide a brief review of HRTV epidemiology, molecular biology, pathogenesis and virulence on the basis of published article data to better understand this virus and provide clues for further study.
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Bunyaviridae , Replicação Viral , Humanos , Virulência , Animais , Infecções por Bunyaviridae/virologia , Thogotovirus/patogenicidade , Thogotovirus/genética , Thogotovirus/fisiologia , Estados Unidos/epidemiologia , Interações Hospedeiro-PatógenoRESUMO
As a natural pH-sensing colorant, purple sweet potato anthocyanins (PSPAs) have demonstrated great potential in colorimetric film for freshness monitoring. However, the photothermal instability of PSPAs is still a challengeable issue. Herein, γ-cyclodextrin metal-organic framework (CD-MOF) loaded with PSPAs (PSPAs@CD-MOF, i.e., PM) and eugenol (EUG) were incorporated in cellulose acetate (CA) matrix for developing a smart active colorimetric film of CA/PM/EUG, where PM and EUG were hydrogen-bonded with CA. Attentions were focused on the photothermal colorimetric stability, colorimetric response, and antibacterial activity of the films. The presence of PM and EUG endowed the film outstanding UV-blocking performance and enhanced the barrier against water vapor and oxygen. Target film of CA/PM15/EUG10 had good photothermal colorimetric stability due to the protection of CD-MOF on PSPAs and the color changes with pH-stimuli were sensitive and reversible. In addition to antioxidant activity, CA/PM15/EUG10 had antibacterial activity against Escherichia coli and Staphylococcus aureus. The application trial results indicated that the CA/PM15/EUG10 was valid to indicate pork freshness and extended the shelf-life by 100 % at 25 °C, which has demonstrated a good perspective on smart active packaging for freshness monitoring and shelf-life extension.
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Celulose/análogos & derivados , Ciclodextrinas , Ipomoea batatas , Estruturas Metalorgânicas , Carne de Porco , Carne Vermelha , Suínos , Animais , Antocianinas/farmacologia , Colorimetria , Eugenol , Antibacterianos/farmacologia , Escherichia coli , Embalagem de Alimentos , Concentração de Íons de HidrogênioRESUMO
Previous research investigating the correlation between prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and subsequent blood pressure (BP) in offspring has yielded limited and contradictory findings. This study was conducted to investigate the potential relationship between maternal PFAS levels during pregnancy and subsequent BP in early childhood. A total of 129 expectant mothers from the Shanghai Birth Cohort were included in the study. Using high-performance liquid chromatography/tandem mass spectrometry, we measured ten PFAS compounds in maternal plasma throughout the pregnancy. When the children reached the age of 4, we examined their systolic BP (SBP) and diastolic BP (DBP), along with mean arterial pressure (MAP) and pulse pressure (PP). Data interpretation employed multiple linear and logistic regression models, complemented by Bayesian kernel machine regression (BKMR).We found that the majority of PFAS concentrations remained stable during pregnancy. The linear and BKMR models indicated a positive relationship between the PFAS mixture in maternal plasma and offspring's DBP and MAP, with perfluorohexanesulphonic acid (PFHxS) having the most significant influence (PFHxS and DBP [first trimester:ß=3.03, 95%CI: (1.01,5.05); second trimester: ß=2.35, 95%CI: (0.94,3.75); third trimester: ß=2.57, 95%CI:(0.80,4.34)]; MAP [first trimester:ß=2.55, 95%CI: (0.64,4.45); second trimester: ß=2.28, 95%CI: (0.95,3.61); third trimester: ß=2.35, 95%CI:(0.68,4.01)]). Logistic regression highlighted an increased risk of prehypertension and hypertension in offspring with higher maternal PFHxS concentrations during all three trimesters [first trimester: OR=2.53, 95%CI:(1.11,5.79), second trimester: OR=2.05, 95%CI:(1.11,3.78), third trimester: OR=3.08, 95%CI:(1.40,6.79)]. A positive correlation was identified between the half-lives of PFAS and the odds ratio (OR) of prehypertension and hypertension in childhood (ß=0.139, P=0.010). In conclusion, this research found maternal plasma PFAS concentrations to be positively associated with BP in offspring, with PFHxS showing the most significant influence. This correlation remained consistent throughout pregnancy, and this effect was proportional to the half-lives of PFAS.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Hipertensão , Pré-Hipertensão , Criança , Gravidez , Feminino , Humanos , Pré-Escolar , Pressão Sanguínea , Pré-Hipertensão/induzido quimicamente , Teorema de Bayes , Poluentes Ambientais/toxicidade , Fluorocarbonos/toxicidade , China , Hipertensão/induzido quimicamente , Ácidos Alcanossulfônicos/toxicidadeRESUMO
Using novel active food packaging has gradually become a daily necessity in terms of impeding microbial contamination. Here, an antimicrobial photodynamic inactivation (PDI) pH-responsive film is developed by incorporating aloe-emodin (AE) into a vehicle of gelatin/chitosan (GC). Besides enhancement in hydrophobicity, the well-dispersed crystals of AE in the GC matrix by hydrogen bonding can upgrade the film's mechanical strength and barrier. The matrix is capable of regulating the release of AE in response to acidic stimuli by a combination mechanism of diffusion and polymer relaxation. Being benefitted from the inherent bioactivity of AE and the PDI activity under visible light irradiation (i.e., 456 nm), the target film of GC-AE2 has excellent antibacterial effect towards Staphylococcus aureus and Escherichia coli, showing bacterial viability of 9.93 ± 1.33 % and 14.85 ± 1.16 %, respectively. Furthermore, the film can effectively thwart Botrytis cinerea infection in cherry tomatoes, demonstrating its potential in preventing the microbial spoilage of postharvest fruits.
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Aloe , Anti-Infecciosos , Quitosana , Emodina , Quitosana/farmacologia , Quitosana/química , Gelatina/química , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Embalagem de Alimentos , Concentração de Íons de HidrogênioRESUMO
Ethylene (C2H4) and pathogenic microorganisms are the two major causes of the deterioration of postharvest fruits and vegetables (F&V). Hence, the development of active packaging with C2H4 scavenging and bactericidal activities is urgently desirable. Herein, a novel photocatalytic active film (CS-PC-AC) is developed for banana preservation by incorporating WO3/AgBr/Ag photocatalyst (PC) and activated carbon (AC) into chitosan (CS). The fabricated PC is a ternary Z-scheme heterojunction and its high photocatalytic activity is achieved by the bridge of Ag between WO3 and AgBr through rapid transfer and separation of photogenerated electrons and holes. AC plays an indispensable role in the photocatalytic reaction through molecule adsorption and transport. PC and AC are hydrogen bonded with chitosan and their incorporation has slight effect on film's thermal stability but decreases the film's mechanical and barrier properties to some extent. CS-PC-AC exhibits strong bactericidal activity (killing ~100 % of Escherichia coli and Staphylococcus aureus within 3 h) and good C2H4 scavenging activity (C2H4 scavenging rate of 49 ± 2 %) under visible light irradiation, which can extend the banana shelf-life by at least 50 % at 25 °C. These results indicate the good perspective of CS-PC-AC in the delay of the deterioration of postharvest F&V.
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Quitosana , Musa , Quitosana/farmacologia , Carvão Vegetal , Catálise , Antibacterianos/farmacologia , Escherichia coli , EtilenosRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high case mortality rates, which is caused by Dabie bandavirus (DBV), a novel pathogen also termed as SFTS virus (SFTSV). Currently, no specific therapeutic drugs or vaccines are available for SFTS. Myxovirus resistance protein A (MxA) has been shown to inhibit multiple viral pathogens; however, the role of MxA in DBV infection is unknown. Here, we demonstrated that DBV stimulates MxA expression which, in turn, restricts DBV infection. Mechanistic target analysis revealed that MxA specifically interacts with the viral nucleocapsid protein (NP) in a manner independent of RNA. Minigenome reporter assay showed that in agreement with its targeting of NP, MxA inhibits DBV ribonucleoprotein (RNP) activity. In detail, MxA interacts with the NP N-terminal and disrupts the interaction of NP with the viral RNA-dependent RNA polymerase (RdRp) but not NP multimerization, the critical activities of NP for RNP formation and function. Furthermore, MxA N-terminal domain was identified as the functional domain inhibiting DBV infection, and, consistently, then was shown to interact with NP and obstruct the NP-RdRp interaction. Additionally, threonine 103 within the N-terminal domain is important for MxA inhibition to DBV, and its mutation (T103A) attenuates MxA binding to NP and obstruction of the NP-RdRp interaction. This study uncovers MxA inhibition of DBV with a series of functional and mechanistical analyses, providing insights into the virus-host interactions and probably helping inform the development of antiviral agents in the future.IMPORTANCEDBV/SFTSV is an emerging high-pathogenic virus. Since its first identification in China in 2009, cases of DBV infection have been reported in many other countries, posing a significant threat to public health. Uncovering the mechanisms of DBV-host interactions is necessary to understand the viral pathogenesis and host response and may advance the development of antiviral therapeutics. Here, we found that host factor MxA whose expression is induced by DBV restricts the virus infection. Mechanistically, MxA specifically interacts with the viral NP and blocks the NP-RdRp interaction, inhibiting the viral RNP activity. Further studies identified the key domain and amino acid residue required for MxA inhibition to DBV. Consistently, they were then shown to be important for MxA targeting of NP and obstruction of the NP-RdRp association. These findings unravel the restrictive role of MxA in DBV infection and the underlying mechanism, expanding our knowledge of the virus-host interactions.
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Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Humanos , Proteínas do Nucleocapsídeo , Ribonucleoproteínas/metabolismo , RNA Polimerase Dependente de RNA , Febre Grave com Síndrome de Trombocitopenia/metabolismo , Febre Grave com Síndrome de Trombocitopenia/virologia , Phlebovirus/fisiologia , Interações Hospedeiro-PatógenoRESUMO
BACKGROUND: The heart relies heavily on external fatty acid (FA) for energy production. VEGFB (vascular endothelial growth factor B) has been shown to promote endothelial FA uptake by upregulating FA transporters. However, its impact on LPL (lipoprotein lipase)-mediated lipolysis of lipoproteins, a major source of FA for cardiac use, is unknown. METHODS: VEGFB transgenic (Tg) rats were generated by using the α-myosin heavy chain promoter to drive cardiomyocyte-specific overexpression. To measure coronary LPL activity, Langendorff hearts were perfused with heparin. In vivo positron emission tomography imaging with [18F]-triglyceride-fluoro-6-thia-heptadecanoic acid and [11C]-palmitate was used to determine cardiac FA uptake. Mitochondrial FA oxidation was evaluated by high-resolution respirometry. Streptozotocin was used to induce diabetes, and cardiac function was monitored using echocardiography. RESULTS: In Tg hearts, the vectorial transfer of LPL to the vascular lumen is obstructed, resulting in LPL buildup within cardiomyocytes, an effect likely due to coronary vascular development with its associated augmentation of insulin action. With insulin insufficiency following fasting, VEGFB acted unimpeded to facilitate LPL movement and increase its activity at the coronary lumen. In vivo PET imaging following fasting confirmed that VEGFB induced a greater FA uptake to the heart from circulating lipoproteins as compared with plasma-free FAs. As this was associated with augmented mitochondrial oxidation, lipid accumulation in the heart was prevented. We further examined whether this property of VEGFB on cardiac metabolism could be useful following diabetes and its associated cardiac dysfunction, with attendant loss of metabolic flexibility. In Tg hearts, diabetes inhibited myocyte VEGFB gene expression and protein secretion together with its downstream receptor signaling, effects that could explain its lack of cardioprotection. CONCLUSIONS: Our study highlights the novel role of VEGFB in LPL-derived FA supply and utilization. In diabetes, loss of VEGFB action may contribute toward metabolic inflexibility, lipotoxicity, and development of diabetic cardiomyopathy.
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Cardiomiopatias Diabéticas , Insulina , Ratos , Animais , Insulina/farmacologia , Fator B de Crescimento do Endotélio Vascular/genética , Fator B de Crescimento do Endotélio Vascular/metabolismo , Ratos Wistar , Miócitos Cardíacos/metabolismo , Ácidos Graxos/metabolismo , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Triglicerídeos/metabolismo , Lipase Lipoproteica/metabolismo , Miocárdio/metabolismoRESUMO
In order to reveal the dynamic response characteristic of thin film thermocouples (TFTCs), the nichrome/nisil (NiCr/NiSi) TFTCs are prepared onto the glass substrate. With short pulse infrared laser system, NiCr/NiSi TFTCs are dynamically calibrated. The thermoelectric electromotive force (TEF) curves of NiCr/NiSi TFTCs are recorded by the memory hicorder system, which could reflect TEF signals with resolution ratio in nanosecond and microvolt, simultaneously. With increasing laser energy from 15.49 to 29.59 mJ, TEF curves display more and more violent oscillation, even negative value. The results show that the bounce of thermal energy happens between two interfaces of TFTCs because the thermal conductivity of glass and air is significantly lower than that of NiSi/NiCr TFTCs. The bounce of thermal energy results in the obvious decrease of nNiCr and nNiSi , as well as oscillation of TEF. For laser energy in 29.59 mJ, the bounce of thermal energy in NiCr film could result in nNiCr < nNiSi . Then, TEF value appears abnormal negative value. Based on the results, the complex thermal energy transport process in TFTCs dynamic calibration is revealed, which results in the oscillation of thermal energy and TEF signal.
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Nickel peroxides are a class of stoichiometric oxidants that can selectively oxidize various organic compounds, but their molecular level structure remained elusive until now. Herein, we utilized structural prediction using the Stochastic Surface Walking method based on a neural network potential energy surface and advanced characterization using the as-synthesized nickel peroxide to unravel its chemical identity as the bridging superoxide containing nickel hydroxide, or nickel superoxyhydroxide. Superoxide incorporation tunes the local chemical environment of nickel and oxygen beyond the conventional Bode plot, offering a 6.4-fold increase in the electrocatalytic activity of urea oxidation. A volcanic dependence of the activity on the oxygen equivalents leads to the proposed active site of the Ni(OO)(OH)Ni five-membered ring. This work not only unveils the possible structures of nickel peroxides but also emphasizes the significance of tailoring the oxygen environment for advanced catalysis.
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Severe fever with thrombocytopenia syndrome virus (SFTSV), Heartland virus (HRTV) and Guertu virus (GTV) belong to the severe fever with thrombocytopenia syndrome/Heartland group of genus Bandavirus in the family Phenuiviridae of order Bunyavirales. Severe fever with thrombocytopenia syndrome virus and HRTV, identified from ticks from Asia and America, respectively, are important pathogens causing severe febrile diseases in humans. Guertu virus, closely related to these two viruses, is a potential pathogen, but no confirmed infection has been identified. So far, human-derived neutralizing monoclonal antibodies (mAbs) against SFTSV have been identified as having a great potential to be developed as antivirals; however, there is still a lack of neutralizing mAbs to GTV and HRTV. In this study, five neutralizing the mAbs against GTV and HRTV were obtained by hybridoma screening technology, four of which (14B4, 14D8, and 20D4 derived from GTV, and 27C8 derived from HRTV) showed cross reactivity and neutralization to all three viruses, and one derived from HRTV (10D6) neutralized HRTV specifically. The possible mechanisms of mAbs cross neutralization among the three viruses are discussed by analyzing their glycoprotein (GP) sequences and structures. Generating these neutralizing mAbs provides important antiviral candidates against GTV, HRTV, and SFTSV despite their differential activities, and their protective effect could be further evaluated in virus-infected mice. Their differential neutralizing efficiency and specificity further suggested that the three viruses share common mechanisms on the basis of GP functioning, and that HRTV poses a unique mechanism that differs from the other viruses. These findings shed light on developing broad-spectrum antiviral strategies against bandaviruses and promoting an understanding of the bandavirus infection process.
Assuntos
Phlebovirus , Vírus de RNA , Febre Grave com Síndrome de Trombocitopenia , Animais , Humanos , Camundongos , Anticorpos Neutralizantes , Anticorpos Monoclonais , Glicoproteínas , Antivirais/farmacologia , Antivirais/uso terapêuticoRESUMO
Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 pathogen requiring urgent research and development efforts. The glycoproteins of CCHFV, Gn and Gc, are considered to play multiple roles in the viral life cycle by interactions with host cells; however, these interactions remain largely unclear to date. Here, we analyzed the cellular interactomes of CCHFV glycoproteins and identified 45 host proteins as high-confidence Gn/Gc interactors. These host molecules are involved in multiple cellular biological processes potentially associated with the physiological actions of the viral glycoproteins. Then, we elucidated the role of a representative cellular protein, HAX1. HAX1 interacts with Gn by its C-terminus, while its N-terminal region leads to mitochondrial localization. By the strong interaction, HAX1 sequestrates Gn to mitochondria, thus depriving Gn of its normal Golgi localization that is required for functional glycoprotein-mediated progeny virion packaging. Consistently, the inhibitory activity of HAX1 against viral packaging and hence propagation was further elucidated in the contexts of pseudotyped and authentic CCHFV infections in cellular and animal models. Together, the findings provide a systematic CCHFV Gn/Gc-cell protein-protein interaction map, but also unravel a HAX1/mitochondrion-associated host antiviral mechanism, which may facilitate further studies on CCHFV biology and therapeutic approaches.
Assuntos
Vírus da Febre Hemorrágica da Crimeia-Congo , Febre Hemorrágica da Crimeia , Animais , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Vírus da Febre Hemorrágica da Crimeia-Congo/metabolismo , Febre Hemorrágica da Crimeia/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismoRESUMO
BACKGROUND: Humans are widely exposed to perfluoroalkyl substances (PFAS), which have been found to be associated with various adverse birth outcomes. As blood pressure (BP) is an important parameter reflecting cardiovascular health in early life, it is necessary to investigate the association of PFAS exposure during early lifetime and BP in childhood. Therefore, we investigated the potential association between PFAS levels in umbilical cord blood and BP of the offspring at 4 years of age in a prospective cohort study. METHODS: PFAS in umbilical cord blood samples after birth were measured with high-performance liquid chromatography/tandem mass spectrometry in the Shanghai Birth Cohort. BP was measured at 4 years of age in the offspring. Multiple linear regression model was used to investigate the association between individual PFAS level and BP of the offspring. Bayesian kernel machine regression (BKMR) was used to analyze the relationship between the PFAS mixture and BP of the offspring, while weighted quantile sum (WQS) regression was utilized for sensitivity analysis. RESULTS: A total of 129 mother-child pairs were included in our analysis. In multiple linear regressions, we observed that long-chain PFAS, mainly including perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUA), was negatively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP). BKMR showed that an increase in umbilical cord blood PFAS mixture levels was significantly associated with a decrease in SBP, DBP and MAP [Estimated differences (SD): -0.433 (0.161); -0.437 (0.176); -0.382 (0.179), respectively]. The most important component in the association with SBP, DBP, and MAP was PFUA. PFDoA was found to be positively associated with SBP, DBP and MAP in both models. Sensitivity analysis with WQS regression showed consistent results. CONCLUSION: Our findings suggested that umbilical blood PFAS exposure was negatively associated with BP in offspring at 4 years of age, including SBP, DBP, and MAP.