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The photolysis of particulate nitrate (pNO3-) has been suggested to be an important source of nitrous acid (HONO) in the troposphere. However, determining the photolysis rate constant of pNO3- (jpNO3-) suffers from high uncertainty. Prior laboratory measurements of jpNO3- using aerosol filters have been complicated by the "shadow effect"âa phenomenon of light extinction within aerosol layers that potentially skews these measurements. We developed a method to correct the shadow effect on the photolysis rate constant of pNO3- for HONO production (jpNO3- â HONO) using aerosol filters with identical chemical compositions but different aerosol loadings. We applied the method to quantify jpNO3- â HONO over the North China Plain (NCP) during the winter haze period. After correcting for the shadow effect, the normalized average jpNO3- â HONO at 5 °C increased from 5.89 × 10-6 s-1 to 1.72 × 10-5 s-1. The jpNO3- â HONO decreased with increasing pH and nitrate proportions in PM2.5 and had no correlation with nitrate concentrations. A parametrization for jpNO3- â HONO was developed for model simulation of HONO production in NCP and similar environments.
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Poluentes Atmosféricos , Atmosfera , Nitratos , Ácido Nitroso , Fotólise , Nitratos/química , Atmosfera/química , Ácido Nitroso/química , Poluentes Atmosféricos/química , AerossóisRESUMO
The synthesis of a (phosphino)(stannyl)carbene is documented. The combination of phosphino and stannyl substituents imparts a highly ambiphilic nature to this carbene, enabling reactions with cyanide, isocyanide, and carbon monoxide. This leads to rare stannylketenimines and a stannylketene.
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This manuscript describes the synthesis of green long afterglow nanophosphors SrAl2O4:Eu2+, Nd3+ using the combustion process. The study encompassed the photoluminescence behavior, elemental composition, chemical valence, morphology, and phase purity of SrAl2O4:Eu2+, Nd3+ nanoparticles. The results demonstrate that after introducing Eu2+ into the matrix lattice, it exhibits an emission band centered at 508 nm when excited by 365 nm ultraviolet light, which is induced by the 4f65d1â4f7 transition of Eu2+ ions. The optimal doping concentrations of Eu2+ and Nd3+ were determined to be 2% and 1%, respectively. Based on X-ray diffraction (XRD) analysis, we have found that the physical phase was not altered by the doping of Eu2+ and Nd3+. Then, we analyzed and compared the quantum yield, fluorescence lifetime, and afterglow decay time of the samples; the co-doped ion Nd3+ itself does not emit light, but it can serve as an electron trap center to collect a portion of the electrons produced by the excitation of Eu2+, which gradually returns to the ground state after the excitation stops, generating an afterglow luminescence of about 15 s. The quantum yields of SrAl2O4:Eu2+ and SrAl2O4:Eu2+, Nd3+ phosphors were 41.59% and 10.10% and the fluorescence lifetimes were 404 ns and 76 ns, respectively. In addition, the Eg value of 4.98 eV was determined based on the diffuse reflectance spectra of the material, which closely matches the calculated bandgap value of SrAl2O4. The material can be combined with polyacrylic acid to create optical anti-counterfeiting ink, and the butterfly and ladybug patterns were effectively printed through screen printing; this demonstrates the potential use of phosphor in the realm of anti-counterfeiting printing.
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BACKGROUND: The global research on pandemics or epidemics and mental health has been growing exponentially recently, which cannot be integrated through traditional systematic review. Our study aims to systematically synthesize the evidence using natural language processing (NLP) techniques. METHODS: Multiple databases were searched using titles, abstracts, and keywords. We systematically identified relevant literature published prior to Dec 31, 2023, using NLP techniques such as text classification, topic modelling and geoparsing methods. Relevant articles were categorized by content, date, and geographic location, outputting evidence heat maps, geographical maps, and narrative synthesis of trends in related publications. RESULTS: Our NLP analysis identified 77,915 studies in the area of pandemics or epidemics and mental health published before Dec 31, 2023. The Covid pandemic was the most common, followed by SARS and HIV/AIDS; Anxiety and stress were the most frequently studied mental health outcomes; Social support and healthcare were the most common way of coping. Geographically, the evidence base was dominated by studies from high-income countries, with scant evidence from low-income counties. Co-occurrence of pandemics or epidemics and fear, depression, stress was common. Anxiety was one of the three most common topics in all continents except North America. CONCLUSION: Our findings suggest the importance and feasibility of using NLP to comprehensively map pandemics or epidemics and mental health in the age of big literature. The review identifies clear themes for future clinical and public health research, and is critical for designing evidence-based approaches to reduce the negative mental health impacts of pandemics or epidemics.
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BACKGROUND: Early childhood caries (ECC) is a challenge for pediatric dentists all over the world, and dietary factor is an important factor affecting the occurrence of ECC. Currently, there is limited research on the impact of dietary nutrient intake from Chinese diets on ECC. The purpose of this study is to explore the correlation of dietary nutrients intake with ECC and caries activity (CA) among children aged 3-5 years, and to provide dietary guidance to slow down the occurrence and development of ECC. METHODS: A cross-sectional study was conducted in 2022. A total of 155 children were divided into three groups: caries-free group, ECC group and Severe early childhood caries (SECC) group according to the caries statues. And according to the caries activity test (CAT) value, they were also divided into three group: low CA group (L-CA), middle CA group (M-CA) and high CA group (H-CA). The 24-hour dietary intake information was collected by mobile phone application (APP). The intake of children's daily dietary nutrients were calculated referring to "China Food Composition Tables". RESULTS: In this study, 17, 39,and 99 children were diagnosed with caries-free, ECC, and SECC. There were 33, 36, and 86 children diagnosed with L-CA, M-CA, and H-CA. The risk of ECC was increased with the intake of cholesterol(OR = 1.005) and magnesium (OR = 1.026) and decreased with the intake of iron (OR = 0.770). The risk of SECC was increased with the intake of cholesterol (OR = 1.003). The risk of high CA was increased with the intake of cholesterol (OR = 1.002). The combined application of dietary total calories, carbohydrate, cholesterol, sodium, magnesium and selenium in the diagnosis of ECC had an area under ROC curve of 0.741. CONCLUSIONS: The increased dietary cholesterol intake may be a common risk factor for ECC and high CA in children aged 3-5. The combined application of dietary intake of total calories, carbohydrate, cholesterol, sodium, magnesium and selenium has a higher predictive value for the occurrence of ECC.
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Cárie Dentária , Humanos , Estudos Transversais , Pré-Escolar , Cárie Dentária/epidemiologia , Cárie Dentária/etiologia , Cárie Dentária/prevenção & controle , Masculino , Feminino , China/epidemiologia , Dieta , Nutrientes/administração & dosagem , Ingestão de EnergiaRESUMO
Airborne trace elements (TEs) present in atmospheric fine particulate matter (PM2.5) exert notable threats to human health and ecosystems. To explore the impact of meteorological conditions on shaping the pollution characteristics of TEs and the associated health risks, we quantified the variations in pollution characteristics and health risks of TEs due to meteorological impacts using weather normalization and health risk assessment models, and analyzed the source-specific contributions and potential sources of primary TEs affecting health risks using source apportionment approaches at four sites in Shandong Province from September to December 2021. Our results indicated that TEs experience dual effects from meteorological conditions, with a tendency towards higher TE concentrations and related health risks during polluted period, while the opposite occurred during clean period. The total non-carcinogenic and carcinogenic risks of TEs during polluted period increased approximately by factors of 0.53-1.74 and 0.44-1.92, respectively. Selenium (Se), manganese (Mn), and lead (Pb) were found to be the most meteorologically influenced TEs, while chromium (Cr) and manganese (Mn) were identified as the dominant TEs posing health risks. Enhanced emissions of multiple sources for Cr and Mn were found during polluted period. Depending on specific wind speeds, industrialized and urbanized centers, as well as nearby road dusts, could be key sources for TEs. This study suggested that attentions should be paid to not only the TEs from primary emissions but also the meteorology impact on TEs especially during pollution episodes to reduce health risks in the future.
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Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Aprendizado de Máquina , Material Particulado , Oligoelementos , Poluentes Atmosféricos/análise , Material Particulado/análise , Poluição do Ar/estatística & dados numéricos , Oligoelementos/análise , China , Medição de RiscoRESUMO
China implemented the Targeted Poverty Alleviation (TPA) policy in 2015 to fight against poverty. In order to assess the health performance of the TPA policy, this study aims to evaluate the impact of the TPA policy on healthcare utilization among older adults who normally have higher vulnerability to poverty and diseases. Drawing on data from four waves of the China Health and Retirement Longitudinal Study (CHARLS), we investigated the impact of the TPA policy on older individuals' outpatient and inpatient utilization using the difference-in-differences (DID) approach. In total, 5285 older respondents were incorporated into a final sample. The results indicated that the implementation of the TPA policy had a significantly positive impact on increasing inpatient care utilization for poor older adults. However, its impact on outpatient service utilization was not significant. To ensure that the increased level of inpatient care utilization was not caused by deteriorating health status, we further analyzed the impact of the TPA policy on poor older adults' health outcomes. Results indicated that the TPA policy improved self-rated health and reduced the number of ADL limitations among older adults in registered poor households. The positive impact of the TPA policy on inpatient care utilization was found to be most beneficial for older adults in poor households who were female, coupled, and aged 70 years and above. The TPA policy in China improved healthcare access for economically disadvantaged older adults and contributed to the enhancement of their health outcomes. This evidence may have broad implications for other low- and middle-income countries aiming to reduce poverty and achieve health equity.
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Aceitação pelo Paciente de Cuidados de Saúde , Pobreza , Humanos , China , Idoso , Feminino , Masculino , Pobreza/estatística & dados numéricos , Estudos Longitudinais , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Política de SaúdeRESUMO
The synthesis of heteronuclear alkyne analogues incorporating heavier group 14 elements (R1-C≡E-R2, E = Si, Ge, Sn, Pb) has posed a long-standing challenge. Neutral silynes (R1-C≡Si(L)-R2) and germynes (R1-C≡Ge(L)-R2) stabilized by a Lewis base have achieved sufficient stability for structural characterization at low temperatures. Here we show the isolation of a base-free stannyne (R1-C≡Sn-R2) at room temperature, achieved through the strategic use of a bulky cyclic phosphino ligand in combination with a bulky terphenyl substituent. Despite an allenic structure with strong delocalization of π-electrons, this compound exhibits adjacent ambiphilic carbon and tin centres, forming a carbon-tin multiple bond with ionic character. The stannyne demonstrates reactivity similar to carbenes or stannylenes, reacting with 1-adamantyl isocyanide and 2,3-dimethyl-1,3-butadiene. Additionally, its carbon-tin bond can be saturated by Et3N·HCl or cleaved by isopropyl isocyanate.
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Phosphagermylenylidenes (R-PâGe), as heavier analogs of isonitriles, whether in their free state or as complexes with a Lewis base, have not been previously identified as isolable entities. In this study, we report the synthesis of a stable monomeric phosphagermylenylidene within the coordination sphere of a Lewis base under ambient conditions. This species was synthesized by Lewis base-induced dedimerization of a cyclic phosphagermylenylidene dimer or via Me3SiCl elimination from a phosphinochlorogermylene framework. The deliberate integration of a bulky, electropositive N-heterocyclic boryl group at the phosphorus site, combined with coordination stabilization by a cyclic (alkyl)(amino)carbene at the low-valent germanium site, effectively mitigated its natural tendency toward oligomerization. Structural analyses and theoretical calculations have demonstrated that this unprecedented species features a PâGe double bond, characterized by conventional electron-sharing π and σ bonds, complemented by lone pairs at both the phosphorus and germanium atoms. Preliminary reactivity studies show that this base-stabilized phosphagermylenylidene demonstrates facile release of ligands at the Ge atom, coordination to silver through the lone pair on P, and versatile reactivity including both (cyclo)addition and cleavage of the PâGe double bond.
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HLA-B*15:659 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.
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Alelos , Povo Asiático , Sequência de Bases , Éxons , Teste de Histocompatibilidade , Análise de Sequência de DNA , Humanos , Povo Asiático/genética , Análise de Sequência de DNA/métodos , Antígeno HLA-B15/genética , Antígeno HLA-B15/imunologia , Alinhamento de Sequência , Códon , Doadores de Tecidos , População do Leste AsiáticoRESUMO
Correction for 'Recent advances in the chemistry of isolable carbene analogues with group 13-15 elements' by Mian He et al., Chem. Soc. Rev., 2024, https://doi.org/10.1039/D3CS00784G.
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The relaxation of restrictions on Chinese Spring Festival (SF) firework displays in certain regions has raised concerns due to intensive emissions exacerbating air quality deterioration. To evaluate the impacts of fireworks on air quality, a comparative investigation was conducted in a city between 2022 (restricted fireworks) and 2023 SF (unrestricted), utilizing high time-resolution field observations of particle chemical components and air quality model simulations. We observed two severe PM2.5 pollution episodes primarily triggered by firework emissions and exacerbated by static meteorology (contributing approximately 30%) during 2023 SF, contrasting with its absence in 2022. During firework displays, freshly emitted particles containing more primary inorganics (such as chloride and metals like Al, Mg, and Ba), elemental carbon, and organic compounds (including polycyclic aromatic hydrocarbons) were predominant; subsequently, aged particles with more secondary components became prevalent and continued to worsen air quality. The primary emissions from fireworks constituted 54% of the observed high PM2.5 during the displays, contributing a peak hourly PM2.5 concentration of 188 µg/m3 and representing over 70% of the ambient PM2.5. This study underscores that caution should be exercised when igniting substantial fireworks under stable meteorological conditions, considering both the primary and potential secondary effects.
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Poluentes Atmosféricos , Poluição do Ar , Material Particulado , Material Particulado/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Férias e Feriados , Hidrocarbonetos Policíclicos Aromáticos/análiseRESUMO
Neuroendocrine carcinomas (NECs) are extremely lethal malignancies that can arise at almost any anatomic site. Characterization of NECs is hindered by their rarity and significant inter- and intra-tissue heterogeneity. Herein, through an integrative analysis of over 1,000 NECs originating from 31 various tissues, we reveal their tissue-independent convergence and further unveil molecular divergence driven by distinct transcriptional regulators. Pan-tissue NECs are therefore categorized into five intrinsic subtypes defined by ASCL1, NEUROD1, HNF4A, POU2F3, and YAP1. A comprehensive portrait of these subtypes is depicted, highlighting subtype-specific transcriptional programs, genomic alterations, evolution trajectories, therapeutic vulnerabilities, and clinicopathological presentations. Notably, the newly discovered HNF4A-dominated subtype-H exhibits a gastrointestinal-like signature, wild-type RB1, unique neuroendocrine differentiation, poor chemotherapeutic response, and prevalent large-cell morphology. The proposal of uniform classification paradigm illuminates transcriptional basis of NEC heterogeneity and bridges the gap across different lineages and cytomorphological variants, in which context-dependent prevalence of subtypes underlies their phenotypic disparities.
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Carcinoma Neuroendócrino , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/classificação , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Sinalização YAP , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
Background: Acute myeloid leukemia (AML) is the most common form of leukemia among adults and is characterized by uncontrolled proliferation and clonal expansion of hematopoietic cells. There has been a significant improvement in the treatment of younger patients, however, prognosis in the elderly AML patients remains poor. Methods: We used computational methods and machine learning (ML) techniques to identify and explore the differential high-risk genes (DHRGs) in AML. The DHRGs were explored through multiple in silico approaches including genomic and functional analysis, survival analysis, immune infiltration, miRNA co-expression and stemness features analyses to reveal their prognostic importance in AML. Furthermore, using different ML algorithms, prognostic models were constructed and validated using the DHRGs. At the end molecular docking studies were performed to identify potential drug candidates targeting the selected DHRGs. Results: We identified a total of 80 DHRGs by comparing the differentially expressed genes derived between AML patients and normal controls and high-risk AML genes identified by Cox regression. Genetic and epigenetic alteration analyses of the DHRGs revealed a significant association of their copy number variations and methylation status with overall survival (OS) of AML patients. Out of the 137 models constructed using different ML algorithms, the combination of Ridge and plsRcox maintained the highest mean C-index and was used to build the final model. When AML patients were classified into low- and high-risk groups based on DHRGs, the low-risk group had significantly longer OS in the AML training and validation cohorts. Furthermore, immune infiltration, miRNA coexpression, stemness feature and hallmark pathway analyses revealed significant differences in the prognosis of the low- and high-risk AML groups. Drug sensitivity and molecular docking studies revealed top 5 drugs, including carboplatin and austocystin-D that may significantly affect the DHRGs in AML. Conclusion: The findings from the current study identified a set of high-risk genes that may be used as prognostic and therapeutic markers for AML patients. In addition, significant use of the ML algorithms in constructing and validating the prognostic models in AML was demonstrated. Although our study used extensive bioinformatics and machine learning methods to identify the hub genes in AML, their experimental validations using knock-out/-in methods would strengthen our findings.
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Developing a gradient porous scaffold similar to bone structure is gaining increasing attention in bone tissue engineering. The GelMA/HAP hydrogel has demonstrated potential in bone repair. Although 3D printing can build GelMA/HAP with porous structure, fabricating porous GelMA/HAP with gradient porosity and pore size in one step remains challenging. In this paper, a gradient porous structure with controllable pore size, based on gelatin methacryloyl (GelMA) and hydxroxyapatite (HAP), was engineered and printed using stereolithography. Firstly, the GelMA and HAP were mixed to prepare a hydrogel with a solid content ranging from 10 wt% to 50 wt% for stereolithography. Taking advantage of the sol-gel characteristics of GelMA/HAP hydrogel, GelMA/HAP was fed on the workbench through a combination of extrusion and paving to form a thin layer. During the curing of each layer, the hydrogel exposed to the curing of a single UV beam immediately solidified, forming a highly interconnected porous structure. Additionally, the hydrogel outside the scanning range could be further polymerized to form a relatively dense structure due to the residual laser energy. Finally, without gradient structural design or changing printing parameters, the gradient porous structure of bone-like could be printed in a single-step process. By adjusting the curing parameters of the single UV beam and the concentration and size of ceramic in the hydrogel, the printed pore diameter of the spongy structure could be controlled within the range of 50-260 µm, while the thickness of the compact area could be adjusted within 130-670 µm.
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Materiais Biocompatíveis , Durapatita , Gelatina , Metacrilatos , Impressão Tridimensional , Porosidade , Gelatina/química , Materiais Biocompatíveis/química , Durapatita/química , Metacrilatos/química , Alicerces Teciduais/química , Hidrogéis/química , Engenharia TecidualRESUMO
Topography of a place has a significant impact on soil characteristics that ultimately influence soil iodine levels. Lower Himalayan region (LHR) in Pakistan has a wide range of climatic and geological variations. Hence, an investigation was conducted to analyze the iodine concentration and other physicochemical properties of soils in two LHR districts, Haripur and Mansehra. Spatial analysis indicated a decrease in iodine levels in the mountainous regions in comparison to the flat portions of LHR. Soil samples obtained from different locations across Haripur had a stronger affinity for iodine due to variations in solubility and adsorption of iodine to soil clay components, which can be attributed to lower pH, higher organic matter, and a higher cation exchange capacity (CEC). In contrast to the plains of Haripur, elevated locations in the Mansehra district had decreased levels of iodine, along with a higher soil pH and reduced soil organic matter. The soil erosion and depletion of soil micronutrients in the hilly region of Mansehra may be attributed to the unfavorable soil conditions and excessive precipitation. Presence of clay, iron (Fe), and aluminum (Al) in the soil led to a rise in iodine levels. Iodine concentrations exhibited an inverse relationship with soil acidity. Study revealed a direct correlation between soil iodine levels and their cation exchange capacity (CEC) and clay content. This study aims to gather fundamental data for the chosen regions of LHR to address illnesses caused by iodine deficiency.
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Iodo , Solo , Solo/química , Iodo/análise , Iodo/química , Paquistão , Concentração de Íons de HidrogênioRESUMO
Carbenes (R2C:), compounds with a divalent carbon atom containing only six valence shell electrons, have evolved into a broader class with the replacement of the carbene carbon or the RC moiety with main group elements, leading to the creation of main group carbene analogues. These analogues, mirroring the electronic structure of carbenes (a lone pair of electrons and an empty orbital), demonstrate unique reactivity. Over the last three decades, this area has seen substantial advancements, paralleling the innovations in carbene chemistry. Recent studies have revealed a spectrum of unique carbene analogues, such as monocoordinate aluminylenes, nitrenes, and bismuthinidenes, notable for their extraordinary properties and diverse reactivity, offering promising applications in small molecule activation. This review delves into the isolable main group carbene analogues that are in the forefront from 2010 and beyond, spanning elements from group 13 (B, Al, Ga, In, and Tl), group 14 (Si, Ge, Sn, and Pb) and group 15 (N, P, As, Sb, and Bi). Specifically, this review focuses on the potential amphiphilic species that possess both lone pairs of electrons and vacant orbitals. We detail their comprehensive synthesis and stabilization strategies, outlining the reactivity arising from their distinct structural characteristics.
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Particulate organic nitrates (pONs) have drawn growing interests due to their effects on nitrogen cycling, air pollution, and regional climate. While secondary formation is typically considered as the major source of pONs, direct emissions from various sources remain poorly explored. Ship exhausts have been known as an important source of reactive nitrogen species, yet pONs emissions from ship have been rarely characterized. In this study, we conducted atmospheric measurement of pONs during a ship-based cruise measurement campaign in the East China Sea and also emission measurement of pONs from ship exhausts. During the ship-based cruise, total five typical kinds of pONs were determined and the average total concentrations of five pONs were 479 ± 193 and 250 ± 139 ng m-3 when sampling was influenced by ship emissions or not, respectively, indicating the notable impact of ship exhaust plumes on ambient pONs. Further, five typical pONs were successfully identified and quantified from ship exhausts, with the average total concentration of 1123 ± 406 µg m-3. The much higher pONs levels in ship exhausts than in ambient particulate matters demonstrated ship emission as an important source for pONs. Additionally, their emission factors from ship exhausts were determined as at a range of 0.1-12.6 mg kWh-1. The chemical transport model simulations indicate that direct pONs emissions from ship exert a significant contribution to atmospheric pONs, especially in the clean marine atmosphere. These findings provide compelling evidence for direct emission of pONs from ship and its considerable effects. We call for further studies to better characterize the direct pONs emissions from ship and other potential sources, which should be incorporated into global and regional models.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Navios , Monitoramento Ambiental , Material Particulado/análise , Poluição do Ar/análise , Emissões de Veículos/análise , Poeira , Carvão Mineral , ChinaRESUMO
The emissions and exposure limits for airborne PM0.1 are lacking, with limited scientific data for toxicity. Therefore, we continuously monitored and calculated the number and mass concentrations of airborne PM0.1 in December 2017, January 2018 and March 2018 during the high pollution period in Guangzhou. We collected PM0.1 from the same period and analyzed their chemical components. A549, THP-1 and A549/THP-1 co-cultured cells were selected for exposure to PM0.1, and evaluated for toxicological responses. Our aims are to 1) measure and analyze the number and mass concentrations, and chemical components of PM0.1; 2) evaluate and compare PM0.1 toxicity to different airway cells models at different time points. Guangzhou had the highest mass concentration of PM0.1 in December 2017, while the number concentration was the lowest. Chemical components in PM0.1 vary significantly at different time periods, and the correlation between the chemical composition or source of PM0.1 and the mass and number concentration of PM0.1 was dissimilar. Exposure to PM0.1 disrupted cell membranes, impaired mitochondrial function, promoted the expression of inflammatory mediators, and interfered with DNA replication in the cell cycle. The damage caused by exposure to PM0.1 at different times exhibited variations across different types of cells. PM0.1 in March 2018 stimulated co-cultured cells to secrete more inflammatory mediators, and CMA was significantly related to the expression of them. Our study indicates that it is essential to monitor both the mass and number concentrations of PM0.1 throughout all seasons annually, as conventional toxicological experiments and the internal components of PM0.1 may not effectively reveal the health damages caused by elevated number levels of PM0.1.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Material Particulado/toxicidade , Material Particulado/análise , China , Mediadores da Inflamação , Tamanho da Partícula , Monitoramento AmbientalRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucopyranoside (TSG) as the primary constituent of Polygonum multiflorum Thumb. (PM) possesses anti-oxidative, antihypercholesterolemic, anti-tumor and many more biological activities. The root of PM has been used as a tonic medicine for thousands of years. However, cases of PM-induced liver injury are occasionally reported, and considered to be related to the host immune status. AIM OF THE STUDY: The primary toxic elements and specific mechanisms PM causing liver damage are still not thoroughly clear. Our study aimed to investigate the influences of TSG on the immune response in idiosyncratic hepatotoxicity of PM. MATERIALS AND METHODS: The male C57BL/6 mice were treated with different doses of TSG and the alterations in liver histology, serum liver enzyme levels, proportions of T cells and cytokines secretion were evaluated by hematoxylin and eosin (HE), RNA sequencing, quantitative real time polymerase chain reaction (qRT-PCR), Flow cytometry (FCM), and enzyme-linked immunosorbent assay (ELISA), respectively. Then, primary spleen cells from drug-naive mice were isolated and cultured with TSG in vitro. T cell subsets proliferation and cytokines secretion after treated with TSG were assessed by CCK8, FCM and ELISA. In addition, mice were pre-treated with anti-CD25 for depleting regulatory T cells (Tregs), and then administered with TSG. Liver functions and immunological alterations were analyzed to evaluate liver injury. RESULTS: Data showed that TSG induced liver damage, and immune cells infiltration in the liver tissues. FCM results showed that TSG could activate CD4+T and CD8+T in the liver. Results further confirmed that TSG notably up-regulated the levels of inflammatory cytokines including TNF-α, IFN-γ, IL-18, perforin and granzyme B in the liver tissues. Furthermore, based on transcriptomics profiles, some immune system-related pathways including leukocyte activation involved in inflammatory response, leukocyte cell-cell adhesion, regulation of interleukin-1 beta production, mononuclear cell migration, antigen processing and presentation were altered in TSG treated mice. CD8+T/CD4+T cells were also stimulated by TSG in vitro. Interestingly, increased proportion of Tregs was observed after TSG treatment in vitro and in vivo. Foxp3 and TGF-ß1 mRNA expressions were up-regulated in the liver tissues. Depletion of Tregs moderately enhanced TSG induced the secretion of inflammatory cytokines in serum. CONCLUSIONS: Our findings showed that TSG could trigger CD4+T and CD8+T cells proliferation, promote cytokines secretion, which revealed that adaptive immune response associated with the mild liver injury cause by TSG administration. Regulatory T cells (Tregs) mainly sustain immunological tolerance, and in this study, the progression of TSG induced liver injury was limited by Tregs. The results of our investigations allow us to preliminarily understand the mechanisms of PM related idiosyncratic hepatotoxicity.