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Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.
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Válvulas Cardíacas , Hidrogeles , Ratas Sprague-Dawley , Ingeniería de Tejidos , Andamios del Tejido , Ingeniería de Tejidos/métodos , Animales , Andamios del Tejido/química , Anisotropía , Ratas , Hidrogeles/química , Materiales Biocompatibles/química , Prótesis Valvulares Cardíacas , Poliésteres/química , Células Cultivadas , Humanos , Matriz Extracelular/química , MasculinoRESUMEN
Increasing microRNAs are shown to be participate in polycystic ovarian syndrome (PCOS) pathogenesis. Nevertheless, the biological effects of miR-144-3p and its detailed mechanisms in PCOS are to be investigated. The purpose of our work was to study the function of miR-144-3p in PCOS. Currently, Expression of miR-144-3p was greatly reduced in PCOS patients and PCOS rat models. In addition, HSP-70 expression was greatly elevated PCOS. Cell proliferation assays and flow cytometry assay were carried out following the overexpression of miR-144-3p in ovarian granulosa cells from PCOS rat models. We observed that miR-144-3p overexpression induced the proliferation and repressed cell apoptosis while loss of miR-144-3p demonstrated an opposite process. Then, PCOS rat models were classified to four groups: LV-NC group, LV-miR-144-3p group, Anti-control group, and Anti-miR-144-3p group. In response to loss of miR-144-3p, we found E2, T, and LH serum levels were elevated and FSH serum level was inhibited. Upregulation of miR-144-3p exhibited an opposite process. Moreover, HSP-70 was a direct target of miR-144-3p. Furthermore, increased expression of HSP-70 rescued the effects of miR-144-3p on ovarian granulosa cell growth and apoptosis. In addition, knockdown of HSP-70 alleviated endocrine disorders and abnormal ovarian weight in vivo. To sum up, miR-144-3p might function as a novel target for PCOS treatment via targeting HSP-70.
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MicroARNs , Síndrome del Ovario Poliquístico , Animales , Apoptosis/genética , Proliferación Celular/genética , Femenino , Células de la Granulosa/metabolismo , Células de la Granulosa/patología , Proteínas HSP70 de Choque Térmico , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/terapia , RatasRESUMEN
Emerging drug resistance is generating an urgent need for novel and effective antibiotics. A promising target that has not yet been addressed by approved antibiotics is the bacterial DNA gyrase subunit B (GyrB), and GyrB inhibitors could be effective against drug-resistant bacteria, such as methicillin-resistant S. aureus (MRSA). Here, we used the 4-hydroxy-2-quinolone fragment to search the Specs database of purchasable compounds for potential inhibitors of GyrB and identified AG-690/11765367, or f1, as a novel and potent inhibitor of the target protein (IC50: 1.21 µM). Structural modification was used to further identify two more potent GyrB inhibitors: f4 (IC50: 0.31 µM) and f14 (IC50: 0.28 µM). Additional experiments indicated that compound f1 is more potent than the others in terms of antibacterial activity against MRSA (MICs: 4-8 µg/mL), non-toxic to HUVEC and HepG2 (CC50: approximately 50 µM), and metabolically stable (t1/2: > 372.8 min for plasma; 24.5 min for liver microsomes). In summary, this study showed that the discovered N-quinazolinone-4-hydroxy-2-quinolone-3-carboxamides are novel GyrB-targeted antibacterial agents; compound f1 is promising for further development.
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Girasa de ADN , Staphylococcus aureus Resistente a Meticilina , Girasa de ADN/metabolismo , Girasa de ADN/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Inhibidores de Topoisomerasa II/farmacología , Inhibidores de Topoisomerasa II/química , Quinazolinonas/farmacología , ADN Bacteriano , Pruebas de Sensibilidad Microbiana , BacteriasRESUMEN
S. aureus resistant to methicillin (MRSA) is one of the most-concerned multidrug resistant bacteria, due to its role in life-threatening infections. There is an urgent need to develop new antibiotics against MRSA. In this study, we firstly compiled a data set of 2,3-diaminoquinoxalines by chemical synthesis and antibacterial screening against S. aureus, and then performed cheminformatics modeling and virtual screening. The compound with the Specs ID of AG-205/33156020 was discovered as a new antibacterial agent, and was further identified as a Gyrase B (GyrB) inhibitor. In light of the common features, we hypothesized that the 6c as the representative of 2,3-diaminoquinoxalines also inhibited GyrB and eventually proved it. Via molecular docking and molecular dynamics simulations, we identified binding modes of AG-205/33156020 and 6c to the ATPase domain of GyrB. Importantly, these GyrB inhibitors inhibited the MRSA strains and showed selectivity to HepG2 and HUVEC. Taken together, this research work provides an effective ligand-based computational workflow for scaffold hopping in anti-MRSA drug discovery, and discovers two new GyrB inhibitors that are worthy of further development.
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Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Quinoxalinas/farmacología , Antibacterianos/síntesis química , Antibacterianos/metabolismo , Antibacterianos/toxicidad , Girasa de ADN/metabolismo , Evaluación Preclínica de Medicamentos , Células Hep G2 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ligandos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Unión Proteica , Quinoxalinas/síntesis química , Quinoxalinas/metabolismo , Quinoxalinas/toxicidad , Inhibidores de Topoisomerasa II/síntesis química , Inhibidores de Topoisomerasa II/metabolismo , Inhibidores de Topoisomerasa II/farmacología , Inhibidores de Topoisomerasa II/toxicidadRESUMEN
Diesel-fired combustion is one of the main sources of air pollution in the world. In this study, to better understand the energy consumption and main air pollutant emissions of diesel-fired combustion, a practical investigation and historical data analyses were conducted to determine the variations and driving forces of diesel consumption, the distribution of diesel consumption, and the contribution of emissions among various industries. Based on the results of this study, future control measures can be proposed for diesel-fired combustion. The results show that economic development led to an increase in the total volume of passengers and freight transportation, and the number of diesel vehicles increased from 0.16 million in 2009 to 0.25 million in 2018. However, diesel consumption in Beijing decreased from 2.4 Mt in 2009 to 1.8 Mt in 2018 due to the dominant driving forces, such as structural optimization of the diesel vehicle fleet and stricter limit standards for single-vehicle fuel consumption. The use of diesel vehicles in the logistics and transportation industries and the use of diesel-fired machinery in the construction industry were the two main sources of diesel consumption, accounting for 55% and 23% of the total, respectively. The main air pollutant emissions from diesel-fired combustion from 2009 to 2018 first increased and then decreased, while the NOX emissions peaked at 74,800 tons in 2014, which was affected by the structural optimization of the vehicle fleet and the elimination of old diesel trucks. The emissions finally decreased to 54,000 tons in 2018, which was approximately 89% of the amount in 2009. However, the continuously increasing contribution of diesel combustion to the total emissions requires more attention. The electrification of diesel vehicles and the structural upgrading of diesel vehicles have played important roles in mitigating the emissions of diesel combustion. Our study suggests that consumption control targets should be set, reduction plans for key industries such as the logistics and transportation, construction, and tourism industries should be developed, and low-emission zones should be created to promote the elimination and updating of low-emission diesel vehicles and machinery.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Ambientales , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Beijing , China , Monitoreo del Ambiente , Gasolina , Vehículos a Motor , Emisiones de Vehículos/análisisRESUMEN
Aggregation of C60, as an important process governing its mobility and toxicity, has been quantitatively investigated. However, effects of sunlight and agitation intensity on the aggregation behavior of aqu/nC60 produced via extended mixing, have not been clarified. Therefore, in the present study, the aggregation behavior of aqu/nC60 produced at 500 and 800 rpm in the absence and presence of sunlight was investigated. Aggregation with increasing concentrations could be accelerated, while changes of Zave and zeta potential were not obvious. Critical coagulation concentrations (CCCs) of aqu/nC60 obtained at 800 rpm in the absence/presence of sunlight and that at 500 rpm under sunlight were 330, 205 and 170 mM NaCl, and 10.0, 2.6 and 3.1 mM CaCl2, respectively. These CCCs indicated that the aqu/nC60 prepared by the extended mixing were more stable than those produced by other methods. Salt-induced aggregation occurred more easily for aqu/nC60 formed under sunlight than that formed in the dark. Extra surface oxidation induced by high agitation intensity remarkably increased the stability of aqu/nC60 in NaCl solutions. In contrast, in CaCl2 solutions, aqu/nC60 formed at high agitation intensity had similar stability or even inadequate stability to that obtained at low agitation intensity due to the charge neutralization and cross-link bridging.
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Fulerenos/química , Nanopartículas/química , Luz Solar , Fulerenos/efectos de la radiación , Nanopartículas/efectos de la radiación , Cloruro de Sodio/químicaRESUMEN
End Stage Renal Disease (ESRD) is a highly heterogeneous disease with significant differences in prevalence, mortality, complications, and treatment modalities across age, sex, race, and ethnicity. An improved knowledge of disease characteristics results from the use of a data-driven phenotypic classification strategy to identify patients of different subtypes and expose the clinical traits of different subtypes. This study used topic models and process mining techniques to perform subtyping of ESRD patients on hemodialysis based on real-world longitudinal electronic health record data. The mined subtypes are interpretable and clinically significant, and they can reflect differences in the progression of the disease state and clinical outcomes.
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Registros Electrónicos de Salud , Fallo Renal Crónico , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Diálisis Renal , Etnicidad , ConocimientoRESUMEN
Hemodialysis (HD) is the main treatment for end-stage renal disease with high mortality and heavy economic burdens. Predicting the mortality risk in patients undergoing maintenance HD and identifying high-risk patients are critical to enable early intervention and improve quality of life. In this study, we proposed a two-stage protocol based on electronic health record (EHR) data to predict mortality risk of maintenance HD patients. First, we developed a multilayer perceptron (MLP) model to predict mortality risk. Second, an Active Contrastive Learning (ACL) method was proposed to select sample pairs and optimize the representation space to improve the prediction performance of the MLP model. Our ACL method outperforms other methods and has an average F1-score of 0.820 and an average area under the receiver operating characteristic curve of 0.853. This work is generalizable to analyses of cross-sectional EHR data, while this two-stage approach can be applied to other diseases as well.
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Fallo Renal Crónico , Calidad de Vida , Humanos , Estudios Transversales , Diálisis Renal , Aprendizaje Basado en Problemas , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/terapiaRESUMEN
OBJECTIVE: To identify the vaginal microbial signature in women with chronic endometritis (CE) and investigate the potential of vaginal microbiome characterization as a novel diagnostic tools for CE. METHODS: A cross-sectional study was conducted to compare the characteristics of the vaginal microbiome in 98 women who underwent endometrial biopsy for routine clinical inspection of infertility (49 women diagnosed with CE and 49 with non-CE). The vaginal microbiome was analyzed using 16S ribosomal RNA gene amplicon sequencing. The study included an analysis of diversity, bacterial abundance, and microbial function. In addition, microbial markers were identified, and a CE classifier was developed. RESULTS: The relative abundances of genera, including Bifidobacterium, Prevotella and Gardnerella, were found to be different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways reported differential expression in metabolism-related pathways in the two groups. We identified four microbial markers of CE (Enterobacter, Prevotella, Faecalibacterium, and Phascolarctobacterium) and developed a predictive classifier for diagnosing CE, achieving an area under the curve of 83.26%. CONCLUSION: The results of the current study revealed that, compared with the non-CE controls, patients with CE have a different vaginal microbiota, highlighting the diagnostic significance of the vaginal microbiome as a promising noninvasive biomarker in detecting CE.
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Quantitative nuclear magnetic resonance (qNMR) has a potential risk of inaccurate quantification of complex organic compounds with low purity due to incomplete separation of the impurity signals and the target component signals. The high performance liquid chromatography-qNMR (HPLC-qNMR) method removes impurities from the sample by HPLC and accurately determines the purity of the sample by qNMR, avoiding the laborious, time-consuming, and costly step of qualitative and quantitative determination of impurities in conventional mass balance methods. An improved method, named post-collection purity correction for internal standard correction-HPLC-qNMR (ISC-HPLC-qNMR), was developed and demonstrated on a complex compound oxytetracycline with low purity. In this method, a correction factor was introduced to compensate for the inability to achieve 100% purity through the HPLC purification procedure. The purity value with standard deviation of the oxytetracycline study material using this method was 82.00% ± 0.82%, while that obtained from the conventional qNMR with deconvolution was 81.70% ± 0.35%. The consistency of these results demonstrated that the improved method extends the applicability to the samples where HPLC is not capable of purifying complex compounds with low purity to near 100%, especially containing highly similar structural-related impurities. Furthermore, this method allows purification and quantification without the need to identify impurities in the sample, resulting in significant savings of time and cost. Additionally, it effectively compensates for the limitations of qNMR deconvolution in handling peak overlap in the sample.
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Electrical stimulation (ES) has shown beneficial effects in repairing injured tissues. However, current ES techniques that use tissue-traversing leads and bulky external power suppliers have significant limitations in translational medicine. Hence, exploring noninvasive in vivo ES to provide controllable electrical cues in tissue engineering is an imminent necessity. Herein, a conductive hydrogel with in situ electrical generation capability as a biodegradable regeneration scaffold and wireless ES platform for spinal cord injury (SCI) repair is demonstrated. When a soft insulated metal plate is placed on top of the injury site as a wireless power transmitter, the conductive hydrogel implanted at the injury site can serve as a wireless power receiver, and the capacitive coupling between the receiver and transmitter can generate an alternating current in the hydrogel scaffold owing to electrostatic induction effect. In a complete transection model of SCI rats, the implanted conductive hydrogels with capacitive-coupling in situ ES enhance functional recovery and neural tissue repair by promoting remyelination, accelerating axon regeneration, and facilitating endogenous neural stem cell differentiation. This facile wireless-powered electroactive-hydrogel strategy thus offers on-demand in vivo ES with an adjustable timeline, duration, and strength and holds great promise in translational medicine.
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Regeneración Nerviosa , Traumatismos de la Médula Espinal , Ratas , Animales , Axones , Hidrogeles/farmacología , Traumatismos de la Médula Espinal/terapia , Estimulación Eléctrica , Andamios del TejidoRESUMEN
There is overwhelming evidence indicating that the use of measurable residual disease (MRD) as a biomarker provides critical prognostic information and that MRD may have a role in directing postremission decisions. There are a variety of assays for MRD assessment, such as multiparameter flow cytometry and molecular assessment of MRD, which present different characteristics in patients older than 60 years of age. Due to multiple reasons related to age, the progress of older adult AML patients is rarely investigated, especially with respect to MRD. In this review, we will clarify the characteristics of different assays for assessing MRD, focusing on its role as a risk-stratification biomarker to predict prognostic information and its role in optimal postremission therapy among older adult AML patients. These characteristics also provide guidance regarding the potential to apply personalized medicine in older adult AML patients.
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Leucemia Mieloide Aguda , Humanos , Anciano , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Citometría de FlujoRESUMEN
It has great potential to integrate medical knowledge and electronic health record data for diagnosis prediction. However, present studies only utilized information from knowledge graphs, omitting potentially significant global graph structural features. In this study, we proposed a knowledge and data integrating modeling approach to reconstruct patient electronic health record data with graph structure and use medical knowledge as internal information of patient data to build a risk prediction model for acute kidney injury in patients with heart failure based on graph neural networks. Experimental results based on the MIMIC III data showed that the method proposed was superior to other baseline models in predicting the risk of acute kidney injury in heart failure patients, with an accuracy of 0.725 and an F1 score of 0.755. This study provides a novel approach to the disease risk prediction models that integrates medical knowledge and data.
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Lesión Renal Aguda , Insuficiencia Cardíaca , Humanos , Redes Neurales de la Computación , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Registros Electrónicos de SaludRESUMEN
Construction machinery (CM) is considered to be a significant source of air pollution. The estimation of emissions from CM is essential for policy-makers to control air pollution and reduce carbon emissions. In this study, air pollutant emissions from CM with four emissions standards (Beijing I-IV) in Beijing from 2015 to 2019 were estimated by combining data from the Non-road Mobile Source Emissions Inventory Compiled Technical Guidelines, Motor Vehicle Emission Simulator (MOVES) and actual measurements. Taking an example for 2019, emissions of hydrocarbons (HCs), carbon monoxide (CO), nitrogen oxides (NOx), particulate matter (PM) and carbon dioxide (CO2) were estimated to be 4.80 Gg, 16.51 Gg, 27.77 Gg, 1.35 Gg and 5.09 Tg, respectively, representing annual mean decreases of 13.2%, 13.1%, 10.8%, 15.2% and 3.5%, respectively, over the five-year period. Tongzhou, Shunyi and Changping Districts contributed 53-67% of total CM emissions in 2019. Among the ten types of CM considered, loaders were the largest contributors to total emissions, accounting for 41-54% of total CM emissions in Beijing from 2015 to 2019. Machinery with a mean power above 75 kW accounted for the largest share (67-78%) of total CM emissions in Beijing from 2015 to 2019. Our results contribute to the limited data of estimated CM emissions and can help develop control strategies to improve air quality and alleviate climate change.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Beijing , Monitoreo del Ambiente/métodos , Contaminación del Aire/análisis , Emisiones de Vehículos/análisis , Material Particulado/análisisRESUMEN
Chronic endometritis (CE) has been considered to reduce uterine receptivity and negatively affect reproductive outcomes for in vitro fertilization-embryo transfer (IVF-ET) patients, especially for people undergoing recurrent implantation failure (RIF). To investigate the effects of antibiotic and platelet-rich plasma (PRP) therapy on pregnancy outcomes following frozen-thawed embryo transfer (FET) in RIF patients with CE, endometrial specimens of 327 patients with RIF obtained by endometrial scratching during mid-luteal phase were immunostained by multiple myeloma oncogene-1 (Mum-1)/syndecan-1 (CD138). RIF patients with CE were given antibiotics and PRP treatment. According to the Mum-1+/CD138+ plasmacytes after treatment, patients were divided into persistent weak positive CE (+) group, CE (-) group and non-CE group. FET was performed and the basic characteristics and pregnancy outcomes of patients in three groups were compared. Among 327 RIF patients, 117 patients were complicated with CE, the prevalence was 35.78%. The prevalence of strong positive was 27.22% and that of weak positive was 8.56%. 70.94% patients with CE converted to negative after treatment. There was no significant difference in the basic characteristics, including age, BMI, AMH, AFC, infertility years, infertility types, number of previous transplant cycles, endometrial thickness on transplantation day and number of transplanted embryos (p > 0.05); The positive rate of hCG, clinical pregnancy rate and implantation rate in CE (-) group were significantly increased compared with the weak CE (+) group and non-CE group (p < .01), and the live birth rate also improved (p < .05). Whereas, the rate of early abortion in CE (-) group was 12.70%, which was higher than that in weak CE (+) group and non-CE group (p < .05). After multivariate analysis, number of previous failed cycles and CE remained independent factors associated with live birth rate, while only CE remained to be the independent factor of clinical pregnancy rate. It is recommended to perform CE-related examination for patients with RIF. Antibiotic and PRP treatment can significantly improve pregnancy outcomes of patients with CE negative conversion in FET cycle.
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Diabetic retinopathy (DR) is one of the most common retinal microvascular diseases in diabetic patients. Therefore, elucidating the underlying molecular mechanism of DR is of great significance for its clinical treatment. This study explores the effects of the upregulated circFTO in DR patients in terms of cell apoptosis and viability. Several molecular assays are employed to explore these molecular mechanistic aspects, such as luciferase reporter, RNA pull-down, RT-qPCR, Western blot, and ELISA assays. miR-148a-3p is downregulated in DR patients. The expression of circFTO promoted ARPE-19 cells apoptosis and inhibited proliferation, reflecting the regulatory effect of circFTO/miR-148a-3p on retinal epithelial cells injury. In addition, the absence of circFTO could reduce ARPE-19 cells injury caused by HG by inhibiting oxidative stress and inflammation. Further, the investigations at the molecular level showed that circFTO could regulate the level of miR-148a-3p and TGFA in vitro. As the molecular sponge of miR-148a-3p, circFTO regulated cell viability and apoptosis and promoted the progression of DR through regulating the expression of TGFA. Together, this study provides new targets and markers for early diagnosis and therapy of DR.
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MicroARNs , Apoptosis/genética , Proliferación Celular/genética , Supervivencia Celular/genética , Glucosa/toxicidad , Humanos , MicroARNs/metabolismoRESUMEN
Vehicle exhaust, an important source of air pollution, is affected by many factors, including driving conditions, combustion efficiencies, and the usage of emission control devices. In this study, the Portable Emission Measurement System (PEMS) was used to test the emissions from China V and China VI heavy-duty diesel vehicles to evaluate the integrated effects of Selective Catalytic Reduction (SCR), velocity, and air-fuel ratio on carbon dioxide (CO2) and nitrogen oxide (NOx) emissions. Our results reveal that the average distance-based CO2 and CO emission factors at high velocities (50-90 km/h) are 25% and 61% lower than those at low velocities (less than 50 km/h). The use of SCR increases CO2 emissions in the range of 70-90 km/h (an average increase of 10.9%). In addition, SCR leads to a 55% NOx emission reduction at low velocities and 89% at high velocities, with an overall average reduction of 84%. We also find that SCR leads to a significant reduction in the correlation between NOx emissions and air-fuel ratio (0.76 vs 0.47 for China V truck; 0.72 vs 0.05 for China VI truck), but it does not cause a drastic reduction in the correlation coefficients between CO2 emissions and air-fuel ratio, which can be used to detect whether SCR is working effectively.
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Contaminantes Atmosféricos , Contaminantes Ambientales , Contaminantes Atmosféricos/análisis , Dióxido de Carbono/análisis , China , Gases , Gasolina , Vehículos a Motor , Emisiones de Vehículos/análisisRESUMEN
The effect of pathogenic fungal infestation on berry quality and volatile organic compounds (VOCs) of Cabernet Sauvignon (CS) and Petit Manseng (PM) were investigated by using biochemical assays and gas chromatography-ion mobility spectrometry. No significant difference in diseases-affected grapes for 100-berry weight. The content of tannins and vitamin C decreased significantly in disease-affected grapes, mostly in white rot-affected PM, which decreased by 71.67% and 66.29%. The reduced total flavonoid content in diseases-affected grape, among which the least and most were anthracnose-affected PM (1.61%) and white rot-affected CS (44.74%). All diseases-affected CS had much higher titratable acid, a maximum (18.86 g/100 ml) was observed in the gray mold-affected grapes, while only anthracnose-affected grapes with a higher titratable acid level (21.8 g/100 mL) were observed in PM. A total of 61 VOCs were identified, including 14 alcohols, 13 esters, 12 aldehydes, 4 acids, 4 ketones, 1 ether, and 13 unknown compounds, which were discussed from different functional groups, such as C6-VOCs, alcohols, ester acetates, aldehydes, and acids. The VOCs of CS changed more than that of Petit Manseng's after infection, while gray mold-affected Cabernet Sauvignon had the most change. C6-VOCs, including hexanal and (E)-2-hexenal were decreased in all affected grapes. Some unique VOCs may serve as hypothetical biomarkers to help us identify specific varieties of pathogenic fungal infestation.
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A method for the simultaneous determination of 19 succinate dehydrogenase inhibitor (SDHI) fungicide residues in 8 kinds of cereals was established by combining UHPLC-MS/MS with the improved QuEChERS method. MgSO4 and octadecylsilane (C18) were used as the dispersive-solid phase extraction sorbent. The proposed method had good linearity in the range of 10-100 µg/L with correlation coefficients (R2 > 0.99). The limit of quantification of 19 fungicides was 10 µg/L, which is the minimum addition level of the method. The fortified recoveries of 19 SDHI fungicides at three levels were ranged from 79.57 % to 126.25 %. The developed method was utilized for the analysis of 45 real cereal samples, only 5 samples were detected with SDHI fungicides. The contents of the fungicides detected in the real samples are far lower than the MRL. The results indicated that the proposed method is reliable for detecting SDHI fungicides in cereals.
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Fungicidas Industriales , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión , Cromatografía Liquida/métodos , Grano Comestible/química , Fungicidas Industriales/análisis , Succinato Deshidrogenasa/análisis , Ácido Succínico/análisis , Espectrometría de Masas en Tándem/métodosRESUMEN
AIMS/INTRODUCTION: Emerging evidence has indicated that long non-coding ribonucleic acids play important roles in the development and progression of diabetic retinopathy (DR). It is reported that urothelial carcinoma-associated 1 (UCA1) is highly expressed in diabetic lymphoendothelial cells and influences glucose metabolism in rats with DR. The aim of the present study was to explore the role of UCA1 in the mechanism of DR. MATERIALS AND METHODS: Gene expression analyses in fibrovascular membranes excised from patients with DR using public microarray datasets (GSE60436). Reverse transcription polymerase chain reaction was carried out to detect UCA1, micro-ribonucleic acid (miR)-624-3p and vascular endothelial growth factor C (VEGF-C) expressions in the blood of patients and human retinal endothelial cells (HRECs). Furthermore, Cell Counting kit-8, Transwell assay, and tube formation assay were used to identify biological effects of UCA1 on HRECs proliferation, migration ability and angiogenesis in vitro. RESULTS: UCA1 and VEGF-C were elevated in DR patients and high glucose-induced HRECs cell lines, whereas miR-624-3p was decreased. UCA1 inhibition inhibited proliferation, angiogenesis and migration of HRECs cells under high-glucose condition. Luciferase reporter assay showed that UCA1 could sponge with miR-624-3p, which could directly target VEGF-C. Finally, we proved a pathway that UCA1 promoted cell proliferation, migration and angiogenesis through sponging with miR-624-3p, thereby upregulating VEGF-C in high-glucose-induced HRECs. CONCLUSIONS: We identified UCA1 as an important factor associated with DR, which could regulate the expression of VEGF-C by sponging miR-624-3p in human retinal endothelial cells. Our results pave the way for further studies on diagnostic and therapeutic studies related to UCA1 in DR patients.