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1.
Environ Monit Assess ; 196(4): 390, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517576

RESUMO

Atmospheric aerosols affect surface ozone concentrations by influencing radiation, but the mechanism and dominant factors are unclear. Therefore, this paper analyses the changes in aerosol-radiative-surface ozone in China's arid and semi-arid regions with the help of the Atmospheric Radiative Transfer (SBDART) model. The results suggest that Aerosol Optical Depth (AOD) and coarse Particulate Matter (PM10) have the same trend, with high values in spring and winter and low values in summer and autumn. Surface ozone is high in spring and summer and low in autumn and winter. Surface ozone is higher in spring and summer and lower in autumn and winter. In winter, mainly secondary pollutants are dominated by high pollution levels. In the rest of the seasons, a mixture of dust, motor vehicle exhaust, and soot is dominated by low pollution levels. Surface ozone is positively correlated with fine particles and negatively correlated with coarse particles. Temperature is positively correlated with surface ozone in all seasons and negatively correlated with PM10 in summer, autumn, and winter. Precipitation negatively correlates with PM10 each season and surface ozone in winter and spring. Analysis of surface ozone and PM10 sources in the more polluted city of Hohhot based on the back-line trajectory model showed that airflow trajectories mainly transported surface ozone and PM10 pollution from northwestern Inner Mongolia and western Mongolia. During dusty solid weather, the decrease in radiation reaching the Earth's surface and the cooling effect of aerosols lead to lower temperatures, which slows down the rate of chemical reactions of precursors of surface ozone, resulting in lower ozone concentrations at the surface. This study can provide a theoretical reference for aerosol and surface ozone control in arid and semi-arid areas of China.


Assuntos
Poluentes Atmosféricos , Ozônio , Poluentes Atmosféricos/análise , Ozônio/análise , Monitoramento Ambiental/métodos , Material Particulado/análise , Estações do Ano , China , Poeira/análise , Aerossóis/análise
2.
Angew Chem Int Ed Engl ; 63(7): e202318850, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38169147

RESUMO

Due to the demanding depolymerization conditions and limited catalytic efficiency, enhancing lignin valorization remains challenging. Therefore, lowering the bond dissociation energy (BDE) has emerged as a viable strategy for achieving mild yet highly effective cleavage of bonds. In this study, a photocatalytic semi-hydrogenation/reduction strategy utilizing CsPbBr3 quantum dots (CPB-QDs) and Hantzsch ester (HEH2 ) as a synergistic catalytic system was introduced to reduce the BDE of Cß -O-Ar, achieving effective cleavage of the Cß -O-Ar bond. This strategy offers a wide substrate scope encompassing various ß-O-4 model lignin dimers, preoxidized ß-O-4 polymers, and native oxidized lignin, resulting in the production of corresponding ketones and phenols. Notably, this approach attained a turnover frequency (TOF) that is 17 times higher than that of the reported Ir-catalytic system in the photocatalytic depolymerization of the lignin model dimers. It has been observed via meticulous experimentation that HEH2 can be activated by CPB-QDs via single electron transfer (SET), generating HEH2 ⋅+ as a hydrogen donor while also serving as a hole quencher. Moreover, HEH2 ⋅+ readily forms an active transition state with the substrates via hydrogen bonding. Subsequently, the proton-coupled electron transfer (PCET) from HEH2 ⋅+ to the carbonyl group of the substrate generates a Cα ⋅ intermediate.

3.
Vox Sang ; 118(8): 647-655, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37322810

RESUMO

BACKGROUND AND OBJECTIVES: Cryopreserved platelets (cPLTs) can be stored for years and are mainly used in military settings. However, the commonly used cryoprotectant dimethyl sulphoxide (DMSO) has toxic side effects when utilized in high quantities. We developed a novel method to aseptically remove DMSO from thawed cPLTs by dialysis. MATERIALS AND METHODS: One unit of platelets (N = 6) was mixed with 75 mL of 27% DMSO within 4 days after collection and stored at -80°C for 1 week. The platelet counts, platelet distribution width, mean platelet volume (MPV), platelet activity, platelet release, platelet aggregation, platelet metabolism indicators and platelet ultrastructural features (determined by electron microscopy) of the samples at the pre-freeze, post-thaw wash (post-TW) and 24 h post-thaw wash (24-PTW) stages were determined and compared. RESULTS: The DMSO clearance rate from the post-TW platelets was 95.56 ± 1.3%, and the platelet recovery rate after washing was 74.66 ± 6.34%. The total count, activity, release factors, aggregation and thrombolytic ability of the post-TW platelets were lower, whereas the MPV and apoptosis rates were higher compared with those of the pre-freeze platelets. The lactic acid, glucose and potassium ions released from the platelets during washing were filtered away by the dialyser, which significantly reduced their concentration. However, 24-PTW platelets were metabolically active, resulting in a decrease in pH and glucose content and an increase in lactic acid content. The level of potassium ions remained low after 24 h of storage and washing. The pre-freeze platelets maintained their normal disc shape and exhibited an open canalicular system (OCS) and a dense tubular system. The cPLTs appeared irregular after washing, with protruding pseudopodia and an extensive OCS, which increased the release of their contents. CONCLUSION: We developed a novel dialysis method to effectively remove DMSO from cPLTs under aseptic conditions and maintain platelet quality. The clinical efficacy of our method remains to be determined. However, the function of the platelets declined 24 h after washing, making them unsuitable for transfusion.


Assuntos
Plaquetas , Dimetil Sulfóxido , Humanos , Plaquetas/metabolismo , Preservação de Sangue/métodos , Diálise Renal , Criopreservação/métodos , Glucose/metabolismo , Ácido Láctico/metabolismo
4.
Microb Ecol ; 85(4): 1179-1189, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35355087

RESUMO

Core microbiota is shared microbial taxa within the same habitat, which is important for understanding the stable and consistent components of the complex microbial assembly. However, information on the microplastic core bacteria from the river ecosystems is poor. Here, we investigated the composition and function of microplastic core bacteria from the Three Gorges Reservoir area along the approximate 662 km of the Yangtze River via full-length 16S rRNA gene sequencing, compared with those in water, sediment, and soil. The results showed that the spatial turnover of bacterial communities in four habitats supported deterministic processes dominated by niche differentiation, which shaped their core bacteria. The composition and function of microplastic core bacteria were significantly different from those in the other three habitats. Rhodobacteraceae was the main component of microplastic core bacteria, while the main component of core bacteria in water, sediment, and soil were Burkholderiaceae (21.90%), Burkholderiaceae (5.01%), Nitrosomonadaceae (4.61%), respectively. Furthermore, microplastic core bacteria had stronger geographic limitations along the Yangtze River in the Three Gorges Reservoir area. Stronger geographic limitations shaped the rapid community turnover and a potentially more connected network for the microplastic core bacteria than water, sediment, and soil. More importantly, microplastic core bacteria had strong potential functions of drug resistance and could cause risks to ecosystems and human health. Microplastic core bacteria were mainly influenced by sediment core bacteria, although the bacteria colonizing on microplastics could be from all the contact environments and original sources. These findings provide important insights into the composition, function, and association of microplastic core bacteria with their surrounding environment.


Assuntos
Microbiota , Microplásticos , Humanos , Plásticos , RNA Ribossômico 16S/genética , Bactérias/genética , Solo , Água
5.
Environ Monit Assess ; 195(8): 932, 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37432491

RESUMO

Afforestation can improve soil erosion in the ecologically fragile areas of the Loess Plateau; however, the amount of water and phosphorus fertilizer that can promote vegetation survival is unclear, which hinders the improvement of the local ecological environment and the waste of water and fertilizer. In this study, based on field surveys, water and fertilizer control tests on Robinia pseudoacacia L. seedlings in experimental fields, and fitting CO2 response curves to R. pseudoacacia seedlings using a Li-6400 portable photosynthesizer, we measured their leaf nutrient contents and calculated resource use efficiency. The results showed that (1) under the same moisture gradient, except for photosynthetic phosphorus utilization efficiency (PPUE), light use efficiency (LUE), water use efficiency (WUE), carbon utilization efficiency (CUE), and photosynthetic nitrogen use efficiency (PNUE) all increased with increasing phosphorus fertilizer application. Under the same phosphorus fertilizer gradient, WUE increased with decreasing water application, and LUE, CUE, PNUE, and PPUE all reached the maximum at 55-60% of field water holding capacity. (2) Net photosynthetic rate (Pn) of R. pseudoacacia seedlings increased with increasing intercellular carbon dioxide concentration (Ci), and as Ci continued to increase, the increase in Pn became slower, but no maximal electron transport rate (TPU) occurred. Under the same CO2 concentration, Pn reached a maximum at 55-60% of field water holding capacity and phosphorus fertilizer at 30 gPm-2·a-1. (3) Leaf maximum carboxylation rate (Vcmax), maximum electron transport rate (Jmax), daily respiration (Rd), stomatal conductance (Gs), and mesophyll conductance (Gm) reached their maximum at 30 gPm-2·a-1 of phosphorus fertilizer. Vcmax, Jmax, and Rd reached their maximum at 55-60% of field water holding capacity; Gs and Gm reached their maximum at 75-80% of field water holding capacity. (4) The higher the soil phosphorus content, the lower the biochemical (lb), stomatal (ls), and mesophyll (lm). With the increase of soil moisture, lb and ls are higher, and lm is lower. (5) Structural equation modeling showed that water-phosphorus coupling had a less direct effect on Rd and a more direct impact on Gs and Gm. Relative photosynthetic limitation directly affected the photosynthetic rate, indicating that water and phosphorus affected the photosynthetic rate through relative plant limitation. It was concluded that the resource use efficiency and photosynthetic capacity reached the maximum when 55-60% of field water holding capacity was maintained, and phosphorus fertilization was at 30 gP m-2·a-1. Therefore, maintaining suitable soil moisture and phosphorus fertilizer levels in the semi-arid zone of the Loess Plateau can improve the photosynthetic capacity of R. pseudoacacia seedlings.


Assuntos
Robinia , Solo , Plântula , Dióxido de Carbono , Fertilizantes , Monitoramento Ambiental , China , Nitrogênio , Fósforo
6.
Environ Monit Assess ; 195(3): 433, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36856933

RESUMO

Microplastics (MPs) are ubiquitous in the aquatic environment and have received widespread attention worldwide as emerging pollutants. Urbanization and anthropogenic activities are the main sources of MPs in rivers; however, the MPs in plateau rivers with less human activities are not well understood. In this study, the pollution of MPs in the surface water and shore sediment of the Lhasa River from the Qinghai-Tibet Plateau was investigated, and a risk assessment was conducted. The abundance of MPs in the surface water and shore sediment of Lhasa River were 0.63 n/L and 0.37 n/g, respectively. MPs in surface water were mainly dominated by films (43.23%) and fibers (31.12%) in shape, transparent (54.25%) in color, and 0-0.5 mm (75.83%) in size, while MPs in the shore sediment were mainly fibers (43.69%) and fragments (36.53%), transparent (71.91%), and 0-0.5 mm (60.18%). PP and PE were the predominant polymer types, accounting for 44.55% and 30.79% respectively in the surface water and 32.51% and 36.01% respectively in the shore sediment. More notably, the polymer pollution index (H) of MPs in the Lhasa River was at hazard level III due to the high risk caused by PVC, but the pollution load index (PLI) was low at hazard level I. This study reveals that the remote river in the Qinghai-Tibet Plateau are polluted by MPs, and their potential risks to the vulnerable ecosystem deserve attention.


Assuntos
Microplásticos , Plásticos , Humanos , Tibet , Ecossistema , Rios , Monitoramento Ambiental , China , Medição de Risco , Polímeros , Água
7.
Environ Monit Assess ; 195(9): 1048, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37589897

RESUMO

Air pollution is considered one of the greatest threats to human health. This study combines a land use regression (LUR) model with satellite measurements and a distributed-lagged non-linear model (DLNM). It aims to predict high-resolution ground-level concentrations of nitrogen dioxide (NO2) and particulate matter 2.5 (PM2.5) in the Yangtze River Delta (YRD) and reveal the mechanisms of influence between NO2 and PM2.5 and precursors and meteorological factors. Results showed that the annual average NO2 and PM2.5 in the YRD urban agglomeration 2019 were 39.5 µg/m3 and 37.5 µg/m3, respectively. The seasonal variation of NO2 and PM2.5 showed winter > spring > autumn > summer. There is a compelling and complex relationship between NO2 and PM2.5. Predictors indicate that latitude (Y), surface pressure (P), ozone (O3), carbon monoxide (CO), aerosol optical depth (AOD), residential, and rangeland have positive impacts on NO2 and PM2.5. In contrast, temperature (T), precipitation (PRE), and industrial trees hurt NO2 and PM2.5. DLNM model results show that NO2 and PM2.5 had significant associations with the included precursors and meteorological elements, with lagged and non-linear effects observed. Satellite data could help significantly increase the accuracy of LUR models; the R2 of tenfold cross-validation was enhanced by 0.18-0.22. In 2019, PM2.5 will be the dominant pollutant in the YRD, and NO2 showed a high value in the central and eastern parts of the YRD. High concentrations of NO2 and PM2.5 are present in 86% of the YRD, meaning that residents will have difficulty avoiding exposure to these two high pollution levels.


Assuntos
Poluentes Ambientais , Humanos , Dióxido de Nitrogênio , Rios , Monitoramento Ambiental , China , Material Particulado
8.
Cancer Sci ; 113(6): 2022-2033, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35381120

RESUMO

Metastasis is the main cause of cancer patients' death despite tremendous efforts invested in developing the related molecular mechanisms. During cancer cell migration, cells undergo dynamic regulation of filopodia, focal adhesion, and endosome trafficking. Cdc42 is imperative for maintaining cell morphology and filopodia, regulating cell movement. Integrin beta1 activates on the endosome, the majority of which distributes itself on the plasma membrane, indicating that endocytic trafficking is essential for this activity. In cancers, high expression of lysosome-associated protein transmembrane 4B (LAPTM4B) is associated with poor prognosis. LAPTM4B-35 has been reported as displaying plasma membrane distribution and being associated with cancer cell migration. However, the detailed mechanism of its isoform-specific distribution and whether it relates to cell migration remain unknown. Here, we first report and quantify the filopodia localization of LAPTM4B-35: mechanically, that specific interaction with Cdc42 promoted its localization to the filopodia. Furthermore, our data show that LAPTM4B-35 stabilized filopodia and regulated integrin beta1 recycling via interaction and cotrafficking on the endosome. In our zebrafish xenograft model, LAPTM4B-35 stimulated the formation and dynamics of focal adhesion, further promoting cancer cell dissemination, whereas in skin cancer patients, LAPTM4B level correlated with poor prognosis. In short, this study establishes an insight into the mechanism of LAPTM4B-35 filopodia distribution, as well as into its biological effects and its clinical significance, providing a novel target for cancer therapeutics development.


Assuntos
Integrina beta1 , Neoplasias , Animais , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Adesões Focais/metabolismo , Humanos , Integrina beta1/metabolismo , Lisossomos/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias/metabolismo , Proteínas Oncogênicas/metabolismo , Peixe-Zebra/metabolismo
9.
Exp Cell Res ; 400(2): 112495, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33524362

RESUMO

Pulpitis refers to inflammation of the inner pulp by invading microbes, and tissue repair occurs due to odontogenic differentiation of human dental pulp cells (hDPCs) with multidifferentiation potential. Long noncoding RNAs (lncRNAs) can modulate numerous pathological and biological processes; however, the role of lncRNAs in the inflammation and regeneration of the dentin-pulp complex in pulpitis is unclear. Here, we performed high-throughput sequencing to identify differentially expressed lncRNAs between human normal and inflamed pulp and concluded that lncMEG3 (lncRNA maternally expressed gene 3, MEG3) was significantly upregulated in both inflamed pulp and LPS-treated hDPCs. MEG3 expression in the pulp tissue was detected using the RNAscope® technique. RNA pulldown assays identified the MEG3-interacting proteins and the potential mechanisms. With MEG3 knockdown, we investigated the role of MEG3 in the secretion of inflammatory cytokines in LPS-treated hDPCs and odontogenic differentiation of hDPCs. MEG3 downregulation inhibited the secretion of TNF-α, IL-1ß and IL-6 in LPS-treated hDPCs, and the p38/MAPK signaling pathway may be related to this effect. MEG3 knockdown promoted odontogenic differentiation of hDPCs by regulating the Wnt/ß-catenin signaling pathway. Our study suggested that MEG3 has a negative effect on inflammation and regeneration of the dentin-pulp complex in pulpitis.


Assuntos
Diferenciação Celular , Polpa Dentária/citologia , Inflamação/patologia , Lipopolissacarídeos/efeitos adversos , Odontogênese , Pulpite/patologia , RNA Longo não Codificante/genética , Adolescente , Adulto , Apoptose , Biomarcadores/metabolismo , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Polpa Dentária/metabolismo , Regulação da Expressão Gênica , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Pulpite/genética , Pulpite/metabolismo , Adulto Jovem
10.
Environ Monit Assess ; 195(1): 169, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36451005

RESUMO

High-load carbonaceous and dust aerosols can significantly reduce direct radiation (DIRR), which would affect photosynthesis in terrestrial ecosystems, thereby further affecting the productivity of vegetation. Based on this, a variety of remote sensing data were used to study the spatiotemporal distributions and changing tendencies of the absorbing aerosols, CO, DIRR, and gross primary productivity (GPP) in China during 2005-2019; then, the relationships were analyzed between different types of absorbing aerosols and DIRR as well as GPP. The results showed that the annual mean absorbing aerosols index (AAI) in China during 2005-2019 was 0.39, with a slow growth rate of 0.02 year-1, and the emission of CO showed a decreasing trend with each passing year, especially in North China Plain and Sichuan Basin. Carbonaceous and dust aerosols were predominantly bounded by Hu line. The east of Hu line was the dominant area of carbonaceous aerosols, and the west of Hu line was the topographical region of dust aerosols. Near the Hu line was the dominant area of carbonaceous-dust aerosols. However, the Karamay-Urumqi-Hami area and Northeast China Plain were exceptional. During the vegetation growing season, different types of absorbing aerosols significantly negatively affected GPP. From a perspective of regional scale variation pattern, the negative effect of absorbing aerosols on vegetation productivity was the most significant in Northeast China; from the perspective of the effects of different vegetation types, the negative effect of absorbing aerosols on grasslands was greater than that of woodlands; from the perspective of the composition characteristics of aerosols, the negative effect of dust aerosols on GPP was greater than that of carbonaceous aerosols.


Assuntos
Ecossistema , Monitoramento Ambiental , Aerossóis , China , Poeira
11.
Phys Chem Chem Phys ; 23(6): 3963-3973, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33544113

RESUMO

The structural, electronic and optical properties of a new van der Waals heterostructure, C2N/g-ZnO, composed of C2N and g-ZnO monolayers with an intrinsic type-II band alignment and a direct bandgap of 0.89 eV at the Γ point, are extensively studied using first-principles density functional theory calculations. The results indicate that the special optoelectronic properties of the constructed heterostructure mainly originate from the interlayer coupling and electron transfer between the C2N and g-ZnO monolayers, and the photogenerated electrons and holes are located on the C2N and g-ZnO layers, respectively, which reduces the recombination probability of the electron-hole pairs. According to Bader charge analysis, there are 0.029 electrons transferred from g-ZnO to C2N to form a built-in electric field of ∼9.5 eV at the interface. Furthermore, the tunability of the electronic properties of the C2N/g-ZnO heterostructure under vertical strain and electric field is explored. Under different strains, the type-II band alignment properties of the heterostructure are retained and the vertical compressive strain has a greater influence on the bandgap modulation than the vertical stretching strain. The implemented electric field also does not change the type-II band alignment but changes the bandgap of the heterostructure from 1.30 to 0.58 eV when the electric field strength varies from -0.6 to 0.6 V Å-1. In addition, the absorption spectrum of the C2N/g-ZnO heterostructure under solar light is also studied. The absorption range of the heterostructure varies from the ultraviolet to near-infrared region with the absorption intensity in the order of 105 cm-1. All of these studies indicate that the C2N/g-ZnO heterostructure has excellent electronic and optical properties and promising applications in nanoelectronics and optoelectronics.

12.
Ecotoxicol Environ Saf ; 215: 112150, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33756290

RESUMO

To estimate spatial distribution, source analysis and uncertainty of heavy metals (Pb, Cd, Cr, Hg, As, Cu, Zn, and Ni) based on geographic information system (GIS), positive matrix factorization model (PMF) and bootstrap (BS) using 382 soil samples collected from cultivated soils in Lanzhou. The mean contents of Cd, Hg, Cu, Zn and Ni were high as 1.7,1.7, 2.1, 1.5 and 1.3 times local background values, mean contents of Pb, Cr and As were lower than local background values. However, the mean contents of eight heavy metals were lower environmental quality risk control standard for soil contamination of agricultural soil. Proportions of four sources were identified: Cr was predominantly contributed by natural sources (29.14%), Cu, Zn and Ni was primarily from industrial sources (25.26%), Hg and As were mainly of agricultural sources (27.49%), Pb and Cd mainly came from traffic source and smelting-related activities (18.09%). Uncertainties analysis contained three aspects: bootstrap runs, factor contributions in the PMF solution, and coefficient of variation (CV) values. By combining the four pollution source factors with bootstrap runs, the accuracy of the four pollution source factors were reliable based on PMF model. The median values in the BS runs was considered the most true factor contribution, and the 5th-95th quartile interval represents the variability of each factor, Factor 4 (traffic source) R2 was 0.70 and lower variability. The highest CV value usually means a significantly deviation degree. In this study, the CV values of Cr in Factor 1, Cu, Zn, and Ni in Factor 2, Hg, and As in Factor 3, Pb, and Cd in Factor 4 were lower, indicates a lower deviation degree. and with the lowest content among heavy metals usually was also with the greatest uncertainties. In this study improves understanding of the reduction of heavy metal pollution in cultivated soil, and also serves as reference for pollution source apportionment in other regions.


Assuntos
Monitoramento Ambiental , Metais Pesados/análise , Poluentes do Solo/análise , Agricultura , China , Correlação de Dados , Poluição Ambiental/análise , Sistemas de Informação Geográfica , Indústrias , Mercúrio/análise , Medição de Risco , Solo , Incerteza
13.
Bull Environ Contam Toxicol ; 104(4): 532-537, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32232507

RESUMO

Accumulation, bioavailability and potential ecological risk of seven heavy metals - chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd) and lead (Pb) - have been analyzed in agricultural soil aggregates with particle size of > 1 mm, 0.25-1 mm, 0.05-0.25 mm, and < 0.05 mm from the Fenhe River Basin (FRB). Accumulation factor (AF) analysis demonstrated that heavy metals tend to be enriched in < 0.05 mm soil aggregate. The bioavailability to plants of Cu, Zn, and Cd was higher than that of other metals and increased with the decrease in soil aggregate particle sizes. Risk assessment code (RAC) of Ni, Cu, Zn and Cd were 13.84%-21.08%, 7.13%-13.74%, 32.08%-51.82% and 29.38%-43.82%, indicating that Cu, Zn, Cd and Ni had a low to very high risk to other ecosystems, and the smaller the particle size (0.05-0.25 mm and < 0.05 mm), the greater ecological risk.


Assuntos
Monitoramento Ambiental/métodos , Metais Pesados/análise , Rios/química , Poluentes do Solo/análise , Solo/química , Agricultura , Disponibilidade Biológica , China , Ecologia , Ecossistema , Medição de Risco
14.
Blood ; 130(6): 789-802, 2017 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-28619982

RESUMO

The bone marrow (BM) provides a protective microenvironment to support the survival of leukemic cells and influence their response to therapeutic agents. In acute myeloid leukemia (AML), the high rate of relapse may in part be a result of the inability of current treatment to effectively overcome the protective influence of the BM niche. To better understand the effect of the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhibitors, including approved and investigational agents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture conditions. In the stroma-based conditions, the AML patient cells exhibited significantly reduced sensitivity to 12% of the tested compounds, including topoisomerase II, B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL2), and many tyrosine kinase inhibitors (TKIs). The loss of TKI sensitivity was most pronounced in patient samples harboring FLT3 or PDGFRB alterations. In contrast, the stroma-derived conditions enhanced sensitivity to Janus kinase (JAK) inhibitors. Increased cell viability and resistance to specific drug classes in the BM stroma-derived conditions was a result of activation of alternative signaling pathways mediated by factors secreted by BM stromal cells and involved a switch from BCL2 to BCLXL-dependent cell survival. Moreover, the JAK1/2 inhibitor ruxolitinib restored sensitivity to the BCL2 inhibitor venetoclax in AML patient cells ex vivo in different model systems and in vivo in an AML xenograft mouse model. These findings highlight the potential of JAK inhibitors to counteract stroma-induced resistance to BCL2 inhibitors in AML.


Assuntos
Antineoplásicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 2/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Linhagem Celular , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Janus Quinase 1/metabolismo , Janus Quinase 2/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Camundongos , Nitrilas , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Pirazóis/farmacologia , Pirimidinas , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia , Sulfonamidas/farmacologia , Células Tumorais Cultivadas
15.
Int J Mol Sci ; 17(10)2016 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-27681722

RESUMO

MicroRNAs (miRNAs) have critical roles in lung tumorigenesis and development. To determine aberrantly expressed miRNAs involved in non-small cell lung cancer (NSCLC) and investigate pathophysiological functions and mechanisms, we firstly carried out small RNA deep sequencing in NSCLC cell lines (EPLC-32M1, A549 and 801D) and a human immortalized cell line 16HBE, we then studied miRNA function by cell proliferation and apoptosis. cDNA microarray, luciferase reporter assay and miRNA transfection were used to investigate interaction between the miRNA and target gene. miR-944 was significantly down-regulated in NSCLC and had many putative targets. Moreover, the forced expression of miR-944 significantly inhibited the proliferation of NSCLC cells in vitro. By integrating mRNA expression data and miR-944-target prediction, we disclosed that EPHA7 was a potential target of miR-944, which was further verified by luciferase reporter assay and microRNA transfection. Our data indicated that miR-944 targets EPHA7 in NSCLC and regulates NSCLC cell proliferation, which may offer a new mechanism underlying the development and progression of NSCLC.

16.
Cancer Sci ; 106(10): 1463-73, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26177443

RESUMO

In a previous study, we found that ERGIC3 was a novel lung cancer-related gene by screening libraries of differentially expressed genes. In this study, we developed a new murine monoclonal antibody (mAb) against ERGIC3. This avid antibody (6-C4) is well suited for immunohistochemistry, immunoblotting and solid-phase immunoassays. Furthermore, we systematically investigated expressions of ERGIC3 in a broad variety of normal human tissues and various types of tumors by immunohistochemistry. In normal human tissues, 6-C4 reacted only in some epithelial cells, such as hepatocytes, gastrointestinal epithelium, ducts and acini of the pancreas, proximal and distal tubules of the kidney, and mammary epithelial cells; however, most normal human tissues were not stained. Moreover, almost all carcinomas that originated from the epithelial cells were positive for 6-C4, whereas all sarcomas were negative. Notably, 6-C4 strongly stained non-small cell lung cancer (NSCLC) cells but did not react with normal lung tissues. Hence, ERGIC3 mAb could be used in histopathological diagnosis and cytopathological testing to detect early-stage NSCLC. We also studied the mechanisms of ERGIC3 regulation in vitro and in vivo by means of bioinformatics analysis, luciferase reporter assay, miRNA expression profiling and miRNA transfection. Results showed that miR-203a downregulation induced ERGIC3 overexpression in NSCLC cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Anticorpos Monoclonais/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Regulação para Baixo/genética , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , MicroRNAs/genética
17.
Ecotoxicology ; 24(1): 172-80, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25336043

RESUMO

The concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in surface sediment samples collected from the East Lake, China in winter 2012 and summer 2013 were analyzed in this study. The total PCB and PBDE concentrations ranged from not detected to 107.1 ng g(-1) dw and from 9.7 to 151.3 ng g(-1) dw, respectively. PCB-28, 101 and 180 were dominant congeners in both winter and summer. BDE-28 (44 %) was the dominant congener in winter and summer, followed by BDE-99 (28 %) and BDE-47 (26 %). The concentrations of PCBs in the sediment samples collected in summer were higher than those in winter, while the concentrations of PBDEs did not show much seasonal variations. Source analysis showed that the PCBs probably originated from urban runoff, industrial pollution and atmospheric deposition, and the PBDEs probably originated from historical usage of penta-BDE mixtures. Potential eco-toxicological risks caused by PCBs were found in about 5 % of the sampling sites; PBDEs had moderate eco-toxicological risk in 80 % sampling sites in the East Lake, China.


Assuntos
Monitoramento Ambiental , Sedimentos Geológicos/química , Éteres Difenil Halogenados/análise , Lagos/química , Bifenilos Policlorados/análise , Poluentes Químicos da Água/análise , China , Bifenil Polibromatos/análise , Medição de Risco , Estações do Ano , Análise Espacial
18.
Environ Monit Assess ; 187(3): 147, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25716527

RESUMO

Concentrations, distribution, sources, and ecological risk of seven heavy metals including chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), and mercury (Hg) in agricultural topsoil samples of the Three Gorges Dam region, China were investigated in this study. Among seven heavy metals, Zn had the highest mean concentration (149 mg kg(-1)) in the agricultural topsoil, followed by Cr (66 mg kg(-1)), Cu (52.2 mg kg(-1)), Pb (13.0 mg kg(-1)), Ni (8.5 mg kg(-1)), Cd (0.29 mg kg(-1)), and Hg (0.08 mg kg(-1)). Enrichment factor (EF) values of Zn, Cu, Cd, and Hg were higher than 1.5, indicating that Zn, Cu, Cd, and Hg were the major pollutants in this study area. The average potential ecological risk index (RI) value was 147, suggesting that heavy metals in the agricultural topsoil in the study area had a low ecological risk. The result of factor analysis (FA) and correlation analysis showed that long-term use of chemical fertilizer and pesticides, natural rock weathering, and atmospheric deposition were the several main sources of seven heavy metals in agricultural topsoil of the Three Gorges Dam region. Factor analysis-multiple linear regression (FA-MLR) results indicated that the most important source in this area was long-term use of chemical fertilizer and pesticides, which contributed 70 % for Cu and Zn, 62 % for Cd, and 72 % for Hg. More attention must be paid to the extensive use of chemical fertilizers and pesticides containing heavy metals which have been accumulated in the agricultural soil.


Assuntos
Agricultura , Monitoramento Ambiental , Metais Pesados/análise , Poluentes do Solo/análise , Solo/química , Cádmio/análise , China , Cromo/análise , Cobre/análise , Ecologia , Mercúrio/análise , Praguicidas/análise , Medição de Risco
19.
Mol Cancer ; 13: 245, 2014 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-25373388

RESUMO

BACKGROUND: Although tumor invasion and metastasis are both classical hallmarks of cancer malignancy and the major causes of poor clinical outcomes among cancer patients, the underlying master regulators of invasion and metastasis remain largely unknown. In this study, we observed that an overexpression of microspherule protein 1 (MCRS1) promotes the invasion and metastasis of non-small cell lung cancer (NSCLC) cells. Furthermore, we sought to systematically investigate the pathophysiological functions and related mechanisms of MCRS1. METHODS: Retrovirus-mediated RNA interference was employed to knockdown MCRS1 expression in NSCLC cell lines. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot respectively were used to measure levels of mRNA and protein. Further cell permeability assessment, invasion and proliferation assays were conducted to evaluate MCRS1 functions in vitro while nude mice experiments were performed to examine metastatic capability in vivo. Microarray analysis and microRNA (miRNA) sequencing were respectively carried out for mRNA and miRNA expression profiling, while chromatin immunoprecipitation (ChIP), luciferase reporter assay, and miRNA transfection were used to investigate the interaction between MCRS1 and miRNAs. RESULTS: MCRS1 knockdown induced morphological alterations, increased monolayer integrity, decreased cellular invasion and metastasis, and attenuated stemness and drug resistance among tested NSCLC cells. The levels of MCRS1 expression were likewise correlated with tumor metastasis among NSCLC patients. We identified differentially expressed genes after MCRS1 silencing, which included cell junction molecules, such as ZO-1, Occludin, E-cadherin, and DSG2. However, these differentially expressed genes were not directly recognized by a transcriptional complex containing MCRS1. Furthermore, we found that MCRS1 binds to the miR-155 promoter and regulates its expression, as well as MCRS1 promotes epithelial-mesenchymal transition (EMT), invasion, and metastasis through the up-regulation of miR-155. Systematic investigations ultimately showed that MCRS1 was directly and negatively regulated by the binding of miR-129* to its 3'-UTR, with miR-129* overexpression suppressing the growth and invasion of NSCLC cells. CONCLUSIONS: MiR-129* down-regulation induced MCRS1 overexpression, which promotes EMT and invasion/metastasis of NSCLC cells through both the up-regulation of miR-155 and down-regulation of cell junction molecules. This miR-129*/MCRS1/miR-155 axis provides a new angle in understanding the basis for the invasion and metastasis of lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Metástase Neoplásica/genética , Proteínas Nucleares/genética , Proteínas de Ligação a RNA/genética , Regiões 3' não Traduzidas , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , Regulação para Cima/genética
20.
Ecotoxicology ; 23(6): 978-87, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24748369

RESUMO

Distributions, potential sources and ecotoxicological risks of PCBs and PBDEs in surface water of the Three Gorges Dam (TGD) region (Yangtze River, China) were investigated. Samples were collected from 18 sites from upstream (UTGD) and downstream (DTGD) of the TGD. Thirty-two PCBs and ten PBDEs were analyzed. ΣPCBs from the UTGD and DTGD ranged from 10.6 to 26.1 and 1.7 to 29.8 ng L(-1), respectively. ΣPBDEs from the UTGD and DTGD ranged from 2.0 to 17.6 and 0.8 to 11.1 ng L(-1), respectively. The total concentrations of PCBs and PBDEs showed a declining trend from the UTGD to DTGD. Independent-samples t test analysis showed no statistical significance of ΣPCBs and ΣPBDEs between the UTGD and DTGD samples. Principal component analysis indicated the difference of potential sources and levels of PCBs and PBDEs in the study area. The potential eco-toxicological risk of PCBs in surface water of the TGD region is very low, whereas special attention needs to be paid to PBDEs in the study area.


Assuntos
Monitoramento Ambiental , Éteres Difenil Halogenados/análise , Bifenilos Policlorados/análise , Rios/química , Poluentes Químicos da Água/análise , China , Análise de Componente Principal , Medição de Risco
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