RESUMEN
Oxidative stress and lipid metabolism disorder caused by estrogen deficiency are regarded as the main causes of postmenopausal atherosclerosis, but the underlying mechanisms remain still unclear. In this study, ovariectomized (OVX) female ApoE-/- mice fed with high-fat diet were used to imitate postmenopausal atherosclerosis. The atherosclerosis progression was significantly accelerated in OVX mice, accompanied by the upregulation of ferroptosis indicators, including increased lipid peroxidation and iron deposition in the plaque and the plasma. While both estradiol (E2) and ferroptosis inhibitor ferrostatin-1 alleviated atherosclerosis in OVX mice, with the inhibition of lipid peroxidation and iron deposition, as well as the upregulation of xCT and GPX4, especially in endothelial cells. We further investigated the effects of E2 on ferroptosis in endothelial cells induced by oxidized-low-density lipoprotein or ferroptosis inducer Erastin. It was found that E2 exhibited anti-ferroptosis effect through antioxidative functions, including improving mitochondrial dysfunction and upregulating GPX4 expression. Mechanistically, NRF2 inhibition attenuated the effect of E2 against ferroptosis as well as the upregulation of GPX4. Our findings revealed that endothelial cell ferroptosis played a pivotal role in postmenopausal atherosclerosis progression, and the NRF2/GPX4 pathway activation contributed to the protection of E2 against endothelial cell ferroptosis.
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Aterosclerosis , Factor 2 Relacionado con NF-E2 , Animales , Femenino , Ratones , Células Endoteliales , Estrógenos/deficiencia , Hierro , PosmenopausiaRESUMEN
BACKGROUND: Tar is the main toxic of cigarettes, and its effect on atherosclerosis progression and the underlying mechanisms remain largely unknown. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and plaque vulnerability. The present study sought to investigate the mechanism of atherosclerosis progression through tar-induced VSMC necroptosis, a recently described form of necrosis. METHODS: The effect of tar on atherosclerosis progression and VSMC necroptosis was examined in ApoE-/- mice and cultured VSMCs. The role of necroptosis in tar-induced plaque development was evaluated in RIPK3-deletion mice (ApoE-/-RIPK3-/-). The key proteins of necroptosis in carotid plaques of smokers and non-smokers were also examined. Quantitative proteomics of mice aortas was conducted to further investigate the underlying mechanism. Pharmacological approaches were then applied to modulate the expression of targets to verify the regulatory process of tar-induced necroptosis. RESULTS: Tar administration led to increased atherosclerotic plaque area and reduced collagen and VSMCs in ApoE-/- mice. The expression of RIPK1ãRIPK3ãand MLKL in VSMCs of plaques were all increased in tar-exposed mice and smokers. RIPK3 deletion protected against VSMC loss and plaque progression stimulated by tar. In mechanistic studies, quantitative proteomics analysis of ApoE-/- mice aortas suggested that tar triggered endoplasmic reticulum (ER) stress. PERK-eIF2α-CHOP axis was activated in tar-treated VSMCs and atherosclerotic plaque. Inhibition of ER stress using 4PBA significantly reduced plaque progression and VSMC necroptosis. Further study revealed that ER stress resulted in calcium (Ca2+) release into mitochondria and cytoplasm. Elevated Ca2+ levels lead to mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, which consequently promote RIPK3-dependent necroptosis. In addition, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated by cytosolic Ca2+ overload binds to RIPK3, accounting for necroptosis. CONCLUSION: The findings revealed that cigarette tar promoted atherosclerosis progression by inducing RIPK3-dependent VSMC necroptosis and identified novel avenues of ER stress and Ca2+ overload.
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Aterosclerosis , Placa Aterosclerótica , Breas , Ratones , Animales , Placa Aterosclerótica/metabolismo , Músculo Liso Vascular , Necroptosis , Aterosclerosis/metabolismo , Estrés del Retículo Endoplásmico , Apolipoproteínas E/metabolismo , Miocitos del Músculo Liso/metabolismoRESUMEN
BACKGROUND: Elevated plasma homocysteine levels, known as hyperhomocysteinemia, have been identified as an independent risk factor for atherosclerosis and related cardiovascular diseases. Macrophage pyroptosis-mediated inflammation is crucial in the development of atherosclerosis, but the underlying mechanisms remain unclear. METHODS: A hyperhomocysteinemia atherosclerotic model with ApoE-/- mice fed with a high-methionine diet was constructed to investigate the role of plasma homocysteine in atherosclerosis. THP-1-derived macrophages were used to investigate the mechanisms by which Hcy regulates pyroptosis. RESULTS: We found that hyperhomocysteinemia resulted in larger atherosclerotic plaques and more secretion of inflammatory cytokines, while these effects were attenuated in Caspase-1 knockdown mice. Likewise, in vitro experiments demonstrated that treatment of macrophages with homocysteine resulted in NLRP3 inflammasome activation and pyroptosis, as evidenced by cleavage of Caspase-1, production of downstream IL-1ß, elevation of lactate dehydrogenase activity, and extensive propidium iodide-positive staining of cells. These were all inhibited by Caspase-1 inhibitor. In addition, excessive generation of reactive oxygen species was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential and ATP synthesis. Moreover, further experiments revealed that homocysteine induced endoplasmic reticulum stress, enhanced communication between the endoplasmic reticulum and mitochondria, and consequently contributed to calcium disorder. Furthermore, the endoplasmic reticulum stress inhibitor, 4PBA, the calcium chelator, BAPTA, and calcium channel inhibitor, 2-APB significantly improved macrophage pyroptosis. CONCLUSION: Homocysteine accelerates atherosclerosis progression by enhancing macrophages pyroptosis via promoting endoplasmic reticulum stress, endoplasmic reticulum-mitochondria coupling, and disturbing of calcium disorder.
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Aterosclerosis , Hiperhomocisteinemia , Animales , Ratones , Piroptosis , Calcio , Caspasa 1 , Estrés del Retículo EndoplásmicoRESUMEN
Toxic trace elements (TEs) can pose serious risks to ecosystems and human health. However, a comprehensive understanding of atmospheric emission inventories for several concerning TEs has not yet been developed. In this study, we systematically reviewed the status and progress of existing research in developing atmospheric emission inventories of TEs focusing on global, regional, and sectoral scales. Multiple studies have strengthened our understanding of the global emission of TEs, despite attention being mainly focused on Hg and source classification in different studies showing large discrepancies. In contrast to those of developed countries and regions, the officially published emission inventory is still lacking in developing countries, despite the fact that studies on evaluating the emissions of TEs on a national scale or one specific source category have been numerous in recent years. Additionally, emissions of TEs emitted from waste incineration and traffic-related sources have produced growing concern with worldwide rapid urbanization. Although several studies attempt to estimate the emissions of TEs based on PM emissions and its source-specific chemical profiles, the emission factor approach is still the universal method. We call for more extensive and in-depth studies to establish a precise localization national emission inventory of TEs based on adequate field measurements and comprehensive investigation to reduce uncertainty.
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Contaminantes Atmosféricos , Mercurio , Oligoelementos , Humanos , Oligoelementos/análisis , Contaminantes Atmosféricos/análisis , Ecosistema , Monitoreo del Ambiente/métodos , Mercurio/análisisRESUMEN
Pyroptosis plays an important role in inflammatory diseases such as viral hepatitis and atherosclerosis. Apigenin exhibits various bioactivities, particularly anti-inflammation, but its effect on pyroptosis remains unclear. The aim of this study is to investigate the effect of apigenin on pyroptosis and explore its potential against inflammatory diseases. THP-1 macrophages treated by lipopolysaccharides/adenosine 5'-triphosphate were used as the in vitro pyroptosis model. Western blot was used to detect the expression of NLRP3 inflammasome components and key regulators. Immunofluorescence was used to observe ROS production and intracellular location of p65. The potential of apigenin against inflammatory diseases was evaluated using atherosclerotic mice. Plaque progression was observed by pathological staining. Immunofluorescence was used to observe the expression of NLRP3 inflammasome components in plaques. The results showed that apigenin inhibited NLRP3 inflammasome activation. Apigenin reduced ROS overproduction and inhibited p65 nuclear translocation. Additionally, apigenin decreased the expression of NLRP3 inflammasome components in the plaque. Plaque progression was inhibited by apigenin. In conclusion, apigenin exhibited a preventive effect on macrophage pyroptosis by reducing oxidative stress and inhibiting the NF-κB pathway. Apigenin may alleviate atherosclerosis at least partially by inhibiting macrophage pyroptosis. These findings suggest apigenin to be a promising therapeutic agent for inflammatory diseases.
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Aterosclerosis , FN-kappa B , Ratones , Animales , FN-kappa B/metabolismo , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis/fisiología , Apigenina/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Estrés Oxidativo/fisiología , Macrófagos , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismoRESUMEN
To investigate the direct influence and mechanism of China's financial and manufacturing co-agglomeration on environmental pollution, we constructed a panel data regression model incorporating mediating and threshold effects with the panel data of 285 prefecture-level cities from 2009 to 2019. The results showed a higher co-agglomeration level significantly increased environmental pollution. The transmission and upgrading from secondary to tertiary industries exhibited a remarkable intermediary role, yet the credit scale formed a nonlinear threshold effect. Both industrial structure optimization and credit scale expansion contributed to environmental protection. Nevertheless, the path of "industrial co-agglomeration â technological progress â environmental protection" was not obvious, and the positive externalities of technology need to be strengthened. These findings provide viable insights for the implementation of financial and manufacturing integration and green development.
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Contaminación Ambiental , Industrias , Ciudades , China , ComercioRESUMEN
Cement production is a major contributor to carbon dioxide (CO2) and multiple hazardous air pollutant (HAP) emissions, threatening climate mitigation and urban/regional air quality improvement. In this study, we established a comprehensive emission inventory by coupling the unit-based bottom-up and mass balance methods, revealing that emissions of most HAPs have been remarkably controlled. However, an increasing 6.0% of atmospheric mercury emissions, as well as 14.1 and 23.7% of fuel-related and process-related CO2 emission growth were witnessed unexpectedly. Industrial adjustment policies have imposed a great impact on the spatiotemporal changes in emission characteristics. Monthly emissions of CO2 and multiple HAPs decreased from December to February due to the "staggered peak production," especially in northern China after implementing the intensified action plan for air pollution control in winter. Upgrading environmental technologies and adjusting capacity structures are identified as dominant driving forces for reducing HAP emissions. Besides, energy intensity improvement can help offset some of the impact caused by the increase in clinker/cement production. Furthermore, scenario analysis results show that ultra-low emission and low-carbon technology transformation constitute the keys to achieve the synergic reduction of CO2 and multiple HAP emissions in the future.
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Contaminantes Atmosféricos , Contaminación del Aire , Mercurio , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Dióxido de Carbono/análisis , ChinaRESUMEN
Particulate matter (i.e., PM1.0 and PM2.5), considered as the key atmospheric pollutants, exerts negative effects on visibility, global climate, and human health by associated chemical compositions. However, our understanding of PM and its chemical compositions in Beijing under the current atmospheric environment is still not complete after witnessing marked alleviation during 2013-2017. Continuous measurements can be crucial for further air quality improvement by better characterizing PM pollution and chemical compositions in Beijing. Here, we conducted simultaneous measurements on PM in Beijing during 2018-2019. Results indicate that annual mean PM1.0 and PM2.5 concentrations were 35.49 ± 18.61 µg/m3 and 66.58 ± 60.17 µg/m3, showing a positive response to emission controls. The contribution of sulfate, nitrate, and ammonium (SNA) played an enhanced role with elevated PM loading and acted as the main contributors to pollution episodes. Discrepancies observed among chemical species between PM1.0 and PM2.5 in spring suggest that sand particles trend to accumulate in the range of 1-2.5 µm. Pollution episodes occurred accompanied with southerly clusters and high formation of SNA by heterogeneous reactions in summer and winter, respectively. Results from positive matrix factorization (PMF) combined with potential source contribution function (PSCF) models showed that potential areas were seasonal dependent, secondary and vehicular sources became much more important compared with previous studies in Beijing. Our study presented a continuous investigation on PM and sources origins in Beijing, which provides a better understanding for further emission control as well as a reference for other cities in developing countries.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Beijing , Monitoreo del Ambiente , Humanos , Nitratos , Compuestos Orgánicos/análisis , Material Particulado/análisis , SulfatosRESUMEN
Vanadium is a strategically important metal in the world, although sustained exposure under high vanadium levels may lead to notable adverse impact on health. Here, we leverage a bottom-up approach to quantitatively evaluate vanadium emissions from both anthropogenic and natural sources during 1949-2017 in China for the first time. The results show that vanadium emissions increased by 86% from 1949 to 2005 to a historical peak value and then gradually decreased to 12.9 kt in 2017. With the effective implementation of air pollution control measures, vanadium emissions from anthropogenic sources decreased sharply after 2011. During 2011-2017, about half of vanadium emissions came from coal and oil combustion. In addition, industrial processes and natural sources also cannot be ignored, with the total contributions of more than 24%. The high levels of vanadium emissions were mainly distributed throughout the North China Plain and the eastern and coastal regions, especially in several urban agglomerations. Furthermore, the comprehensive evaluation by incorporating contrastive analysis, Monte Carlo approach, and GEOS-Chem simulation shows that vanadium emissions estimated in this study were reasonable and acceptable. The findings of our study provide not only a scientific foundation for investigating the health effects of vanadium but also useful information for formulating mitigation strategies.
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Contaminantes Atmosféricos , Contaminantes Atmosféricos/análisis , Carbón Mineral/análisis , Monitoreo del Ambiente , Industrias , VanadioRESUMEN
Airborne trace elements (TEs) pose a notable threat to human health due to their toxicity and carcinogenicity, whereas their exposures and associated health risks in China remain unclear. Here, we present the first nationwide assessment of spatiotemporal exposure to 11 TEs in China by coupling a bottom-up emission inventory with a modified CMAQ model capable of TE simulation. Associated health risks of 11 TEs are then evaluated using a set of risk assessment models. Our results show that the CMAQ model could reasonably reproduce the spatiotemporal variations of 11 TEs in China compared to observations. We find significant but spatiotemporal-heterogeneous cancer risks associated with high-level exposure of TEs in China. Gridded cell concentrations of hexavalent chromium, arsenic, and nickel in eastern and central China usually exceed China's air quality standard limits, resulting in significant cancer risks that affected over 85% of the entire population in China in 2015. National annual mean population-weighted concentrations of 11 TEs decrease by 9.8-35.6% from 2012 to 2015, largely attributed to emission reduction from coal combustion. Our study provides critical insights for policymakers to implement stricter measures to alleviate health burdens and benefit relevant epidemiological research on airborne TEs.
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Contaminantes Atmosféricos , Contaminación del Aire , Oligoelementos , Contaminantes Atmosféricos/análisis , China , Carbón Mineral/análisis , Monitoreo del Ambiente , Humanos , Oligoelementos/análisisRESUMEN
To investigate the up-to-date migration and emission characteristics of NH3/NH4+ in coal-fired power plants (CFPPs) after implementing ultralow emission retrofitting, typical air pollution control devices (APCDs) in CFPPs, including flue gas denitrification, dust collectors, combined wet flue gas desulfurization (WFGD), and wet precipitators are involved in field measurements. The results show that most of the excessive injected and/or unreacted ammonia from the flue gas denitrification system, whether selective catalytic reduction (SCR) or selective noncatalytic reduction (SNCR), is converted into particle-bound NH4+ (>91%), and the rest (less than 9%) is carried by flue gas in the form of gaseous NH3, with a concentration value of 0.15-0.54 mg/(N m3) at the denitrification outlet. When passing through dust collectors, particle-bound NH4+ concentration decreases substantially along with the removal of particle matter. In WFGD, the dissolution and volatilization effects affect the gaseous ammonia concentration, which decreases when using limestone slurry and a 20% solution of ammonia as a desulfurization agent, while liquid ammonia solution with a high concentration (99.8%) may cause the flue gas NH3 concentration to increase considerably by 13 times. Particle-bound NH4+ concentration is mainly influenced by the relative strength of desulfurization slurry scouring and flue gas carrying effects and increases 2.84-116 times through ammonia-based WFGD. Furthermore, emission factors of NH3 for combinations of APCDs are discussed.
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Contaminantes Atmosféricos , Contaminación del Aire , Compuestos de Amonio , Amoníaco , China , Carbón Mineral , Centrales EléctricasRESUMEN
In this study, we investigated the emission characteristics of condensable particulate matter (CPM) and sulfur trioxide (SO3) simultaneously through ammonia-based/limestone-based wet flue gas desulfurization (WFGD) from four typical coal-fired power plants (CFPPs) by conducting field measurements. Stack emissions of filterable particulate matter (FPM) all meet the Chinese ultralow emission (ULE) standards, whereas CPM concentrations are prominent (even exceed 10 mg/Nm3 from two CFPPs). We find that NH4+ and Cl- increase markedly through the ammonia-based WFGD, and SO42- is generally the main ionic component, both in CPM and FPM. Notably, the occurrence of elemental Se in FPM and CPM is significantly affected by WFGD. Furthermore, the established chemical profiles in FPM and CPM show a distinct discrepancy. In CPM, the elemental S mainly exists as a sulfate, and the metallic elements of Na, K, Mg, and Ca mainly exist as ionic species. Our results may indicate that not all SO3 are included in CPM and they co-exist in stack plume. With the substantial reduction of sulfur dioxide (SO2), S distributed in SO3, CPM, and FPM becomes non-negligible. Finally, the emission factors of CPM and SO3 under typical ULE technical routes fall in the ranges of 74.33-167.83 and 48.76-86.30 g/(t of coal) accordingly.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , China , Carbón Mineral , Material Particulado/análisis , Centrales Eléctricas , Óxidos de AzufreRESUMEN
Large areas of mainland China have been suffering frequently from heavy haze pollution during the past years, which feature high concentrations of fine particulate matter (PM2.5, particulate matters with aerodynamic diameters less than 2.5 µm) and low visibility. Moreover, these areas manifested strong regional complex pollution characteristics, particularly in North China including Beijing and the five surrounding provinces (BSFP). In this study, by using the localized comprehensive emission inventory of BSFP region in 2012 as an input, the Comprehensive Air Quality Model with Extensions-Particulate Matter Source Apportionment Technology (CAMx/PSAT) was used to assess the seasonal variations and source apportionment of PM2.5 in the highly polluted BSFP region, with a specific focus on the sectoral and sub-regional contributions to PM2.5 in Beijing during winter and summer. Results showed that the PM2.5 concentrations of BSFP region was higher in winter than that in summer. And the heavily polluted area in BSFP region shrinked noticeably in summer, compared with winter. As for source apportionment of PM2.5, residential and remaining industrial sectors constituted the top two sources of PM2.5 mass concentrations in Beijing. In addition, agricultural source represented a major contributor to ammonium, whereas transportation and power sectors constituted major sources to nitrates. In terms of contributions from sub-regions, the local sources ranked as the dominant contributors to PM2.5 in Beijing, while the main external contributions originated from the surrounding areas, such as Hebei and Shandong. Results of daily source apportionment to PM2.5 in Beijing showed that sub-regional long-distance transport became stronger when haze pollution was severe, in which contribution from remaining industrial sector would be higher than that of other periods. The results will allow for an improved understanding of the causes and origins of heavy regional PM2.5 pollution, and thus will benefit the development of effective joint control policies and identification of key polluting emission categories in North China and ultimately serve as references for other highly polluted megacities in the world.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China , Monitoreo del Ambiente , Material Particulado/análisis , Estaciones del AñoRESUMEN
To achieve ultralow-emission (ULE) standards, wet electrostatic precipitators (WESP) installed downstream from wet flue gas desulfurization (WFGD) have been widely used in Chinese coal-fired power plants (CFPPs). We conducted a comprehensive field test study at four 300 MW level ULE CFPPs, to explore the impact of wet clean processing (WFGD and WESP) on emission characteristics of three size fractions of particulate matter (PM: PM2.5, PM10-2.5, and PM>10) and their ionic compositions. All these CFPPs are installed with limestone-based/magnesium-based WFGD and followed by WESP as the end control device. Our results indicate that particle size distribution, mass concentration of PM, and ionic compositions in flue gas change significantly after passing WFGD and WESP. PM mass concentrations through WFGD are significantly affected by the relative strength between desulfur slurry scouring and flue gas carrying effects. Concentrations of ions in PM increase greatly after passing WFGD; especially, SO42- in PM2.5, PM10-2.5, and PM>10 increase on average by about 1.4, 3.9, and 8.3 times, respectively. However, WESP before the stack can effectively reduce final PM emissions and their major ionic compositions. Furthermore, emission factors (kg/(t of coal)) of PM for different combinations of air pollution control devices are presented and discussed.
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Contaminantes Atmosféricos , Material Particulado , Carbón Mineral , Iones , Centrales EléctricasRESUMEN
Volatile organic compounds (VOCs) are key precursors for secondary organic aerosols (SOA) and ozone, imposing severe impacts on human health and environment. Considering the massive coal consumption, coal fired power plants (CFPPs) in China are non-negligible VOCs contributors, whose emission characteristics remain inadequately understood. Here, we investigated emission characteristics of 117 VOCs by field tests in four typical CFPPs, and a latest localized CFPPs source profile was compiled by integrating literature reviews. Then speciated-VOCs emission inventories for 2018-2022 were established based on dynamic emission factors and unit-level activity data. The results suggested that oxygenated VOCs (OVOCs) constituted the dominant group (76.5 %), with propionaldehyde (32.0 %) and formaldehyde (24.5 %) being the predominant species. OVOCs (93.2 %) and aromatics (77.4 %) were identified as the primary contributors to ozone and SOA, respectively. Driven by both the rise in coal consumption and technological advancements, nationwide VOCs emissions decreased from 83,393 t in 2018 to 53,251 t in 2022. Regional disparities and varying rates of decline in provincial emissions were evident, with VOCs emissions predominantly concentrated in northern and eastern provinces. Neimenggu, Shandong, Shanxi, Jiangsu, and Guangdong were identified as the top five provinces with the highest emissions. We believe this study would be conducive to a more comprehensive understanding and effective control of VOCs emissions from CFPPs in China.
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Green mold is a common postharvest disease infected by Penicillium digitatum that causes citrus fruit decay, and severely affects fruit storage quality. This work aimed to investigate the antifungal activity of Sanxiapeptin against P. digitatum, and elucidate the possible mechanisms involved. Sanxiapeptin was capable of inhibiting spore germination, germ tube length and mycelial growth. The SYTOX green staining assay revealed that Sanxiapeptin targeted the fungal membrane, and changed the membrane permeability, leading to the leakage of cell constituents. Meanwhile, Sanxiapeptin could influence the cell wall permeability and integrity by increasing the activities of chitinase and glucanase, resulting in abnormal chitin consumption and the decrease of glucan. Intriguingly, Sanxiapeptin could effectively control postharvest decay in citrus fruits, and activate the host resistance responses by regulating the phenylpropanoid pathway. In conclusion, Sanxiapeptin exhibits multiphasic antifungal mechanisms of action to control green mold in citrus fruits, shows great potential as novel food preservatives.
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Citrus , Conservantes de Alimentos , Frutas , Penicillium , Enfermedades de las Plantas , Citrus/microbiología , Citrus/química , Penicillium/crecimiento & desarrollo , Penicillium/efectos de los fármacos , Enfermedades de las Plantas/microbiología , Frutas/microbiología , Frutas/química , Frutas/crecimiento & desarrollo , Frutas/efectos de los fármacos , Conservantes de Alimentos/farmacología , Antifúngicos/farmacología , Antifúngicos/química , Conservación de Alimentos/métodos , Fungicidas Industriales/farmacología , Fungicidas Industriales/químicaRESUMEN
BACKGROUND: Micheliolide (MCL), which is the active metabolite of parthenolide, has demonstrated promising clinical application potential. However, the effects and underlying mechanisms of MCL on atherosclerosis are still unclear. METHOD: ApoE-/- mice were fed with high fat diet, with or without MCL oral administration, then the plaque area, lipid deposition and collagen content were determined. In vitro, MCL was used to pretreat macrophages combined by ox-LDL, the levels of ferroptosis related proteins, NRF2 activation, mitochondrial function and oxidative stress were detected. RESULTS: MCL administration significantly attenuated atherosclerotic plaque progress, which characteristics with decreased plaque area, less lipid deposition and increased collagen. Compared with HD group, the level of GPX4 and xCT in atherosclerotic root macrophages were increased in MCL group obviously. In vitro experiment demonstrated that MCL increased GPX4 and xCT level, improved mitochondrial function, attenuated oxidative stress and inhibited lipid peroxidation to suppress macrophage ferroptosis induced with ox-LDL. Moreover, MCL inhibited KEAP1/NRF2 complex formation and enhanced NRF2 nucleus translocation, while the protective effect of MCL on macrophage ferroptosis was abolished by NRF2 inhibition. Additionally, molecular docking suggests that MCL may bind to the Arg483 site of KEAP1, which also contributes to KEAP1/NRF2 binding. Furthermore, Transfection Arg483 (KEAP1-R483S) mutant plasmid can abrogate the anti-ferroptosis and anti-oxidative effects of MC in macrophages. KEAP1-R483S mutation also limited the protective effect of MCL on atherosclerosis progress and macrophage ferroptosis in ApoE-/- mice. CONCLUSION: MCL suppressed atherosclerosis by inhibiting macrophage ferroptosis via activating NRF2 pathway, the related mechanism is through binding to the Arg483 site of KEAP1 competitively.
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Aterosclerosis , Ferroptosis , Placa Aterosclerótica , Sesquiterpenos de Guayano , Animales , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Simulación del Acoplamiento Molecular , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/genética , Aterosclerosis/metabolismo , Placa Aterosclerótica/metabolismo , Macrófagos/metabolismo , Apolipoproteínas E/genética , Colágeno/metabolismoRESUMEN
Continued urbanization requires a deep understanding of how urbanization affects residents' health risks. This study used regression analysis of Chinese provincial-level panel data from 2004 to 2019 and empirically analyzed the nonlinear effects of urbanization on health risks and regional differences using STIRPAT model. Health risks were assessed by the average number of residents' visits to medical facilities and population mortality. We also examined the moderating effect of income and environmental factors. The results show that (1) urbanization increases the average number of residents' visits and reduces population mortality. The positive effect of urbanization in increasing the average number of visits is reinforced by an increase in income level and environmental pollution, whereas the negative effect of urbanization in reducing population mortality is weakened by environmental pollution. (2) Regarding long-term trends, urbanization has an N-shaped relationship with the average number of residents' visits, and a U-shaped relationship with population mortality; (3) Urbanization has an N-shaped relationship with the average number of residents' visits in the eastern, central, and western regions and an inverted N-shaped relationship with population mortality in the eastern region. Urbanization has significant effects on residents' health risks in areas with high levels of infrastructure. According to the results, suggestions are proposed, such as developing new-type urbanization, improving infrastructure, focusing on green urbanization, and promoting national fitness programs.
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Contaminación Ambiental , Urbanización , Humanos , Población Urbana , Ejercicio Físico , China/epidemiologíaRESUMEN
Correlating aroma expression with volatile compounds has long been an ambition in researches of flavor chemistry. To propose a reliable methodology to depict wine aroma, 76 oak barrel-aged dry red wines were investigated through the combination of machine learning algorithm and multivariate analysis. Aromatic characteristic was evaluated by quantitative descriptive analysis (QDA), while non- or oak derived volatiles were detected by HS-SPME-GC-MS and targeted SPE-GC-QqQ-MS/MS, respectively. Results showed that variable importance for projection values (VIPs) from partial least-squares regression (PLSR) and mean decrease accuracy (MDA) from random forest were efficient parameters for feature selection. The correlating accuracy of the optimal PLSR model to predict intensities of different aroma characteristics through selected volatile compounds could achieve 0.754 to 0.943, representing potential application to manage wine aroma by chemical assay in winemaking. From the perspective of mathematical modeling in the real wine matrix, the network analysis between aroma characteristics and key volatile compounds indicated that the expression of oak aroma was not only directly contributed by volatiles derived from oak wood, but also influenced by ethyl esters, including ethyl acetate, ethyl butanoate, ethyl hexanoate, ethyl decanoate, and ethyl nonanoate.
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Quercus , Compuestos Orgánicos Volátiles , Vino , Vino/análisis , Quercus/química , Espectrometría de Masas en Tándem , Compuestos Orgánicos Volátiles/análisisRESUMEN
Metals emitted from brake linings wear have adverse effects on air quality and human health due to their toxicity and reactivity. However, complexities of factors affecting brake like conditions of vehicles and roads hinder the accurate quantification. Here, we established a comprehensive emission inventory for multi-metals from brake linings wear in China during 1980-2020, based on metals contents in well-representative samples, the wear of brake linings before replacement, vehicle populations, fleet composition, and vehicle-kilometers travelled (VKT). We show that with the boom of vehicle population, the total emissions of studied metals have surged from 3.7 × 106 g in 1980 to 4.9 × 1010 g in 2020, which mainly concentrated in coastal and eastern urban areas while grown significantly in the central and western urban areas in recent years. Therein, Ca, Fe, Mg, Al, Cu, and Ba were the top six metals emitted, together responsible for >94 % of the mass total. Jointly determined by brake linings especially metals contents thereof, VKTs, and vehicle populations, heavy-duty trucks, light-duty passenger vehicles, and heavy-duty passenger vehicles were the top three contributors in metals emissions, together accounting about 90 % of the total. Moreover, more precise description on real-world metals emissions from brake linings wear are still urgently needed, considering the increasingly significant role it has been playing on worsening air quality and public health.