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Nasal epithelium provides a physical barrier to potentially harmful stimuli. Cilia, which is on the apical side of the human nasal epithelial cells (HNEpCs), plays a critical role in removing inhaled harmful matter. Ciliary beat frequency (CBF) and ciliary beat pattern (CBP) are the two important indicators for ciliary beat function. However, impacts of the fine particulate matter (PM2.5) on CBF and CBP are still unknown. We aimed to evaluate the impact of PM2.5 on the ciliary beat function of the HNEpCs and its potential mechanisms. After exposed to PM2.5 for 12 h, cilia of HNEpCs were in disordered arrangement. The ciliary coverage rate was decreased after PM2.5 exposure of a series of concentration, while the proportion of basal cells was continuously increased and could be observed on the apical side of the HNEpCs which is hardly be observed without PM2.5 exposure. PM2.5 increased the CBF after 12 h exposure, while 24 h exposure increased the CBF at the relative lower dosage groups and then made a decrease at relative higher dosage groups. CBF were classified into two different types, which had different changes following PM2.5 exposure. CBP showed significant changes characterized as the increased dyskinesia index. Total levels of cellular ATP and the mitochondrial membrane potential were decreased following 12 h exposure of PM2.5, while no change was found in O2 consumption. In conclusion, PM2.5 impact the ciliary beat function of HNEpCs, and the mitochondrial dysfunction might play an important role in it.

We studied the concentrations, seasonal distributions, sources, exposures, and health risks of phthalates in indoor and outdoor PM2.5 in Beijing. The results showed that phthalate concentrations during haze periods were significantly higher than during non-haze periods both indoors and outdoors, with higher concentrations for the former, which reached a maximum of 1995.56 ng m–3. Phthalates are mainly derived from the use of indoor plasticized products, the outdoor plastic products industry, and other sources of fuel emissions. Lifelong exposure to fine (2-ethylhexyl) phthalate (DEHP) through inhalation and dermal absorption was calculated, and the results indicated a risk of cancer, with DEHP carcinogenic risk levels of 4.09 × 10–6 and 10.50 × 10–6 for adults and children, respectively. The highest DEHP carcinogenic risk group was 1–2-year-old children, and the risk decreased afterward with age.

As an increasing number of nanoproducts enter our daily life, their potential health risks have caused widespread concerns and have also promoted studies of nanotoxicity. Among these investigations, the genotoxicity of nanomaterials has attracted more attention. Engineered silver nanorod with gold core and silver shell (Au@Ag NR) was used in this study to investigate the possible genotoxicity and genotoxicity patterns in peripheral lymphocytes and hepatocytes introduced by released Ag+ and the nanoparticle itself by integrating the Pig-a gene, micronucleus, and comet assays. Most of the Au@Ag NR was rapidly cleared from the circulatory system of Sprague Dawley rats, and a small amount of Au@Ag NR was retained in the liver for at least 14 days. Our data confirmed that clastogenicity was the primary genotoxicity type induced by Au@Ag NR, and both NR particles containing Ag and the released Ag+ contribute to genotoxicity. Au@Ag NR was shown to be a clastogen through the introduction of increased %Tail DNA in peripheral lymphocytes (5.82%±0.25%) and hepatocytes (4.83%±0.17%) and promotion of the formation of micronuclei in hepatocytes (1.12%±0.13%) 3 days and 14 days after dosing, respectively (P < 0.05), which could be a result of both Ag+ and Ag shell of the Au@Ag NR. However, Au@Ag NR was not shown to be a mutagen, as the average RBCCD59- count was not changed significantly as compared with control. These data suggest the importance of adopting appropriate genotoxicity testing strategies in identifying the genotoxicity of nanoparticles in vivo.

Along with the increasing applications of nanomaterials in medical fields, to know the systemic distribution of nanomaterials in the body through a precise method is required for the biosafety assessment of nanomaterials. In this study, we firstly have established a reliable inductively coupled plasma mass spectrometry (ICP-MS) method for concentration measurement of silver (Ag) and gold (Au) in biological tissues. Then, based on this method, the Ag or Au distribution in rat blood and almost all of the organs were analyzed after an i.v. or s.c. administration of Au@Ag NRs. Both the time-dependent contents of Ag and Au in blood and two pharmacokinetic models confirmed the rapid clearance of Ag from blood. At 24 h after i.v. injection, there was the highest level of Ag in liver, followed by portal nodes, spleen, lung, bone marrow and pancreas. In addition, we also found there were gender-related distributions of Ag and Au in some organs, especially after s.c. injection. Therefore, these more comprehensive and important results would give fundamental information for the biological risk assessment of nanomaterials.

As a widely applied nanomaterial, silver nanomaterials (AgNMs) have increased public concern about their potential adverse biological effects. However, there are few related researches on the long-term toxicity, especially on the reversibility of AgNMs in vivo. In the current study, this issue was tackled by exploring liver damage after an intravenous injection of silver nanorods with golden cores (Au@AgNRs) and its potential recovery in a relatively long term (8 w). After the administration of Au@AgNRs into rats, Ag was found to be rapidly cleared from blood within 10 min and mainly accumulated in liver as well as spleen until 8 w. All detected parameters almost displayed a two-stage response to Au@AgNRs administration, including biological markers, histological changes and metabolic variations. For the short-term (2 w) responses, some toxicological parameters (hematological changes, cytokines, liver damages etc.) significantly changed compared to control and AuNRs group. However, after a 6-week recovery, all abovementioned changes mostly returned to the normal levels in the Au@AgNRs group. These indicated that after a lengthy period, acute bioeffects elicited by AgNMs could be followed by the adaptive recovery, which will provide a novel and valuable toxicity mechanism of AgNMs for potential biomedical applications of AgNMs.

This study presents the mass concentrations of PM2.5, O3, SO2 and NOx at one urban, one suburban and two rural locations in the Changchun region from September 25 to October 27 2013. Major chemical components of PM2.5 at the four sites were daily sampled and analyzed. Most of daily concentrations of SO2 (7–82 μg/m3), O3 (27–171 μg/m3) and NOx (14–213 μg/m3) were below the limits of the National Ambient Air Quality Standard (NAAQS) in China. However, PM2.5 concentrations (143–168 μg/m3) were 2-fold higher than NAAQS. Higher PM2.5 concentrations (~ 150 μg/m3) were measured during the pre-harvest and harvest at the urban site, while PM2.5 concentrations significantly increased from 250 to 400 μg m− 3 at suburban and rural sites with widespread biomass burning. At all sites, PM2.5 components were dominated by organic carbon (OC) and followed by soluble component sulfate (SO42 −), ammonium (NH4+) and nitrate (NO3−). Compared with rural sites, urban site had a higher mineral contribution and lower potassium (K+ and K) contribution to PM2.5. Severe atmospheric haze events that occurred from October 21 to 23 were attributed to strong source emissions (e.g., biomass burning) and unfavorable air diffusion conditions. Furthermore, coal burning originating from winter heating supply beginning on October 18 increased the atmospheric pollutant emissions. For entire crop harvest period, the Positive Matrix Factorization (PMF) analysis indicated five important emission contributors in the Changchun region, as follows: secondary aerosol (39%), biomass burning (20%), supply heating (18%), soil/road dust (14%) and traffic (9%).

This study presents the observations of PM10 and PM2.5 concentrations at an agricultural site from April to October 2012 in Dehui city, China. Ambient air was sampled by filter-based samplers and online PM monitors. The filter samples were analyzed to determine the abundance of ionic/inorganic elements, organic carbon (OC) and elemental carbon (EC). The daily PM10 concentrations varied significantly over the monitoring period, with an average of 168±63 (in the range of 52-277)μg/m(3) during the land preparation/planting period (26 April-15 June), 85±65 (36-228)μg/m(3) during the growing season (16 June-25 September), and 207±88 (103-310)μg/m(3) during the harvest period (26 September-31 October). PM2.5 accounted for 44%, 56% and 66% of atmospheric PM10 during these periods, respectively. The PM10 diurnal variation showed a distinct peak from 16:00 to 21:00 (LST) during the growing and harvesting seasons, while a gradual increase throughout the daytime until 17:00 was observed during tilling season. Mineral dust elements (Al, Ca, Fe, and Mg) dominated the PM10 chemical composition during the tilling season; OC, NO3(-), SO4(2-) and NH4(+) during the growing season; and carbonaceous species (i.e., OC and EC) during the harvesting season. Our results indicate that the soil particles emitted by farm tillage and organic matter released from straw burning are the two most significant sources of PM10 emissions contributing to the recurring high pollution events in this region. Therefore, development of agricultural PM inventories from soil tillage and straw burning is prioritized to support air quality modeling.

Silver nanoparticles (Ag-NPs) can enter the brain and subsequently induce neurotoxicity. However, the toxicity of Ag-NPs on the blood-brain barrier (BBB) and the underlying mechanism(s) of action on the hippocampus in vivo are not well understood. To investigate Ag-NP suspension (Ag-NPS)-induced toxicity on the BBB and neurons, Sprague-Dawley rats were randomly divided into 3 groups, and Ag-NPS, Ag-ion, and 5% sucrose solution (vehicle control) were administrated intravenously, respectively. After 24 h exposure to Ag-NPS, the BBB permeability was not significantly changed. However, the Ag concentrations in the brain tissues were only detected in the Ag-NPS group. Gene expression results indicated that the expression of Claudin 4 (tight junction protein) was significantly decreased. Furthermore, astrocyte foot swelling, neuron shrinkage and Ag-NP like particles were observed under transmission electron microscopy. Global gene expression analysis showed that 502 genes were up-regulated and 703 genes were down-regulated in the hippocampi treated with Ag-NPS. In the Ag-NPS-treated group, 78 biological functions were changed based on gene ontology (GO) and 34 signaling pathways were significantly changed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, which were associated with the neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, calcium signaling pathway and MAPK signaling pathway. In comparison, 27 GO and 9 KEGG pathways were changed in the released Ag-ion-treated group. Ag-NPS decreased C1qtnf3 expression and increased Adra1d expression to affect MAPK signaling pathway, which promoted inflammation and apoptosis in the hippocampus. Moreover, Ag-NPS significantly increased Spp1, Cacna1s and Tacr3 mRNAs expression, which may result in intracellular calcium increasing and initiate cell death. Furthermore, Ag-NPS affected calcium signaling pathway and neuroactive ligand-receptor (Grin2a, Drd2, and Adra1d), which are crucial in diverse cellular functions in the brain including cognition and neurodevelopment. These results draw our attention to the importance of Ag-NP-induced toxicity in the rat hippocampus and provide a better understanding of its toxicological mechanisms in vivo.

Mineral dust is one of the most important aerosol in mass over the world, affecting health and dynamics. This aerosol is mainly emitted over arid areas but may be long-range transported, impacting the local budget of air quality in many cities. While models were extensively used to study a single specific event, or making a global analysis at coarse resolution, the goal of our study is to simultaneously focus on several areas - Europe, North America, Central Asia, East China and the Caribbean area - for a one month period, March 2014, avoiding any parameter fitting to better simulate a given dust outbreak. The simulation is performed for the first time with the hemispheric version of the CHIMERE model, with a horizontal resolution of 10km. In this study, an overview of several simultaneous dust outbreaks over the north hemisphere is proposed to assess the capability of such modelling tools to predict dust pollution events. A quantitative and qualitative evaluation of the most striking episodes is presented with comparisons to satellite data, ground based Particulate Matter and calcium measurements. Despite some overestimation of dust concentrations far from emission areas, the model is able to simulate the timing of the arrival of dust outbreaks on observational sites. For instance, several spectacular dust storms in the US and China are perfectly captured by the models. The high resolution allows to better describe and understand the orographic effects and the long-range transport of dust plumes.

Superparamagnetic iron oxide nanoparticles (IONPs) are being investigated for brain cancer therapy because alternating magnetic field (AMF) activates them to produce hyperthermia. For central nervous system applications, brain entry of diagnostic and therapeutic agents is usually essential. We hypothesized that AMF-induced hyperthermia significantly increases IONP blood-brain barrier (BBB) association/uptake and flux.Cross-linked nanoassemblies loaded with IONPs (CNA-IONPs) and conventional citrate-coated IONPs (citrate-IONPs) were synthesized and characterized in house. CNA-IONP and citrate-IONP BBB cell association/uptake and flux were studied using two BBB Transwell(®) models (bEnd.3 and MDCKII cells) after conventional and AMF-induced hyperthermia exposure.AMF-induced hyperthermia for 0.5 h did not alter CNA-IONP size but accelerated citrate-IONP agglomeration. AMF-induced hyperthermia for 0.5 h enhanced CNA-IONP and citrate-IONP BBB cell association/uptake. It also enhanced the flux of CNA-IONPs across the two in vitro BBB models compared to conventional hyperthermia and normothermia, in the absence of cell death. Citrate-IONP flux was not observed under these conditions. AMF-induced hyperthermia also significantly enhanced paracellular pathway flux. The mechanism appears to involve more than the increased temperature surrounding the CNA-IONPs.Hyperthermia induced by AMF activation of CNA-IONPs has potential to increase the BBB permeability of therapeutics for the diagnosis and therapy of various brain diseases.

According to the practice of city gas odorization, the technological thought that the diffusion behavior of natural gas in soil was indirectly reflected by the adsorption capacity of tetrahydrothiophene (THT) as an odorant of natural gas in soil was put forward and explored. The adsorbed amount of THT in soil samples by gas chromatography-mass spectrometry (GS-MS) with purge and trap was determined. The impact of four parameters (namely gas leakage, water content, particle size and texture of the soil) on the adsorption properties of soil was then quantitatively analyzed. The experimental results showed that at initial stage of adsorption, the adsorption capacity of THT in soil sample was linear positively correlated with gas leakage and was negatively correlated with water content of the soil and there were no significant differences between particle size and texture of the soil and the amount of THT.

Ethnopharmacological relevance: Kangqianling decoction (KQL), the modified formulation of a classical Chinese prescription named Taohongsiwu decoction, was clinically employed to treat renal fibrosis in chronic renal failure. Aim of the study: The present study was designed to examine whether KQL has a protective effect on renal function in association with transforming growth factor-s (TGF-s), angiotensin II (Ang II), tumor necrosis factor-a (TNF-a), nuclear factor-?B (NF-?B) in rats with 5/6 renal ablation (Nx)-induced chronic renal failure. Results: In renal function deterioration progression, the high expression of serum creatinine (Scr), 24-h urine protein and systolic blood pressure were markedly (P < 0.05 or P < 0.01) restored by KQL, respectively, at 4 and 8 weeks. The increasing expressions of renal Ang II (P < 0.05), angiotensin II1-receptor (AT1R) (P < 0.05), TNF-a (P < 0.05), NF-?B (P < 0.001) and urine TGF-s1 (P < 0.05) were reduced by the treatment of KQL. Immunohistochemical study further confirmed the nephro-protective activity of KQL as compared to the control and Sham group. Conclusions: The results indicate that KQL is able to protect renal function via ameliorating experimental rat renal failure as found in these renal functional parameters.

A simple and rapid ultra-performance liquid chromatography-electrospray ionization mass spectrometry method for the simultaneous determination of thirteen free fatty acids (FFAs) in Pheretima has been developed and validated. Measurements for each FFA were linear over a wide range (0.05–3.95 μg mL−1) with good correlation coefficients (>0.99). The limit of detection and limit of quantification for all the fatty acids were below 26 and 78 ng mL−1, respectively. The intra- and inter-assay precision and accuracy for the thirteen FFAs fell well within the predefined limits of acceptability. Satisfactory recoveries were in the range of 96–103%.

Introduction Saponins are bioactive compounds employed in the prevention and treatment of cardiovascular and cerebrovascular diseases. The adventitious roots of Panax notoginseng may offer an alternative source of saponins. Identification and determination of saponins in the crude extract is challenging owing to their similar structures and the lack of standards. Objective To develop a rapid, sensitive and accurate method based on solid-phase extraction followed by ultra-performance liquid chromatography–electrospray ionisation mass spectrometry (UPLC-ESI-MS) for the identification and quantification of saponins in P. notoginseng. Methodology Following extraction using Waters OasisTM HLB cartridges, the analytes were subjected to a UPLC system with a Waters Acquity BEH C18 chromatographic column and a binary mobile phase system consisting of 0.05% formic acid in water and acetonitrile under gradient elution conditions, with final detection by ESI-MS in the positive ion mode. Results The UPLC-ESI-MS method gave limits of detection and quantification within the range 0.015–0.382 and 0.052–1.124 µg/mL, respectively, for 15 studied saponins. The instrumentation/injection precision (RSD) was 4.5% for a low concentration and 3.2% for an intermediate concentration sample. The intra- and inter-day repeatability was less than 2.65% (RSD). The method described was validated using spiked samples with different amounts of saponin standards. Conclusion This UPLC-ESI-MS assay provides a suitable quality control method for the tentative identification and determination of major biological active constituents in adventitious and native roots of P. notoginseng. Copyright © 2008 John Wiley & Sons, Ltd.

Schisandra chinensis (Turcz.) Baill. is a rich source of lignans with diverse biological activities. Quantitative analysis and chromatographic fingerprinting of the fruitlets of the plant by liquid chromatography (LC) were performed in order to characterize and evaluate the region-related variation. Using the optimized LC method, satisfactory linearity and repeatability were obtained for all the test standards. This method was subsequently applied for the identification and quantitation of six lignans in fruitlets of Schisandra chinensis by comparing the retention time with that of authentic standards available. Principal component analysis (PCA) was also employed to assess the similarity and dissimilarity of the fingerprint profiles from different origins encompassing eleven areas from China and two samples from Japan. The work suggested that the fruitlets of Schisandra chinensis from Japan exhibited great difference with those from China as evidenced by the clear separation in the PCA scores plot as well as quantitative analysis e.g., schisandrin and deoxyschisandrin are 5.50 μg mg−1 $$ (\overline{X} ) $$ and 0.90 μg mg−1 $$ (\overline{X} ) $$ in the materials from China and 3.40 μg mg−1 $$ (\overline{X} ) $$ and 1.90 μg mg−1 $$ (\overline{X} ) $$ in the materials from Japan, respectively. Such a reliable method potentially provides an effective and convenient method for quality control of herbal medicine from different regions.

The flower buds of Panax notoginseng have been commonly used for the treatment of hypertension, vertigo, tinnitus and acute faucitis in China. The amount of total saponins in the flower buds is higher than in any other parts of P. notoginseng. However, the compositions of flower buds have not been quantified clearly until now. A sensitive and efficient high-performance liquid chromatography-ultraviolet (HPLC-UV) method was developed for the first time to simultaneously quantify eight active saponins in the flower buds of P. notoginseng, including notoginsenoside R(1) and ginsenosides Rg(1), Re, Rb(1), Rb(2), Rb(3), Rd and F(2). The analysis was performed on a reversed-phase C(18) column with gradient elution of acetonitrile and 0.01% aqueous formic acid. The proposed method provided good linearity, reproducibility and sensitivity for the simultaneous quantification of the investigated saponins with overall intra- and inter-day precision and accuracy of better than 4.1% (RSD) and higher than 95% (accuracy), respectively. The recoveries for all the saponins determined were in the range 94.7-104.8% with RSD better than 3.1%. Using the optimized method, we were able to analyze samples from different villages of Wenshan Prefecture, China, which is helpful for quality control of flower buds of P. notoginseng.

A rapid analytical method for quantifying 17 ginsenosides in rat urine by ultra performance liquid chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) is described. All analytes were extracted by solid-phase extraction optimized to obtain good recovery and quantified using digoxin as an internal standard. ESI-MS was optimized for different cone voltages at positive ionization mode to allow simultaneous analysis of all analytes in a relatively short time. Qualitative methodological considerations, including the linear range, precision, limit of quantification, limit of detection, recovery and sensitivity are also provided.

PM2.5 and PM10 samples were simultaneously collected monthly at a downtown site in Beijing from May 2002 to April 2003 and analyzed by instrumental neutron activation analysis (INAA) combined with organic solvent extraction method for the concentrations and distributions of extractable organohalogens (EOX), including extractable organochlorinated (EOCl), organobrominated (EOBr) and organoiodinated compounds (EOI). The concentrations of EOCl, EOBr and EOI were 10.5-79.2 ng/m(3), ND-8.2 ng/m(3) and 1.6-8.2 ng/m(3) in PM2.5, respectively, and 37.0-73.3 ng/m(3), 1.6-12.8 ng/m(3) and 1.6-8.5 ng/m(3) in PM10, respectively, which were increasing in the order of EOCl >> EOBr similar to EOI. EOCl accounted for 73-88% and 69-91% of EOX in PM2.5 and PM10, respectively, which showed that EOCl was the major component of the organohalogens. There was a significant difference of EOCl concentrations in PM2.5 and PM10 in different seasons, which suggested that the concentrations of EOCl in the atmosphere were significantly affected by the meteorologic conditions and anthropogenic activities.

PM2.5 and PM10 samples were simultaneously collected at a downtown site in Beijing from May 2002 to April 2003 and analyzed by instrumental neutron activation analysis (INAA) and gas chromatography (GC) combined with organic solvent extraction method for the concentrations and distributions of extractable organohalogens (EOX), including extractable organo-chlorine (EOCl), -bromine (EOBr) and -iodine compounds (EOI), and organochlorinated pesticides (OCPs) and polychlorinated biphenyls (PCBs). The concentrations of EOX were increasing in the order of EOCl⪢EOBr∼EOI. EOCl accounted for 73–88% and 69–91% of EOX in PM2.5 and PM10, respectively, suggesting that EOCl was the major component of the organohalogens in the atmosphere. The relative proportions of the known organochlorines (such as HCHs, DDTs, chlordanes, and PCBs) to total EOCl were 0.04–0.7% and 0.06–0.3% in PM2.5 and PM10, respectively, which implied that most of EOCl measured in aerosol was unknown. The ratios of α / γ -HCH (0.9–1.5) and p,p′-DDE+DDD/p,p′-DDT (0.2–0.5) revealed the presence of the recent use of lindane and DDTs or impure dicofol in Beijing. In the plots of the logarithm of the OCPs concentrations versus reciprocal temperature ( 1 / T ) , their linear relations were observed for PM2.5, which could be partly explained by temperature differences, but poor linearity for PM10.

Intercalation of 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, or 3,5-pyridinedicarboxylate into the layered double hydroxide (LDH), [Mg0.73Al0.27(OH)2](CO3)0.14·1.34H2O was carried out by the reconstruction method in the molar ratio of organic acid:calcined LDH=3:8, in 80% alcoholic aqueous solution at 70 °C. Selective reaction was observed in competitive experiments involving an equal concentration pairs of acids. The preference order of the organic acids intercalated into the Mg-Al-LDH was found to be in the order of 2,3-pyridinedicarboxylate>2,5-pyridinedicarboxyate>2,4-pyridinedicarboxylate>3,5-pyridinedicarboxylate>3,4-pyridinedicarboxylate>2,6-pyridinedicarboxylate. The structures of the intercalates formed by the reaction of six guests with Mg-Al-LDH were characterized by X-ray diffraction, infrared and thermogravimetry techniques. And the charge density on the oxygens of each of the carboxylate groups for the six anions was investigated utilizing ab initio (HF/6-31G) method by G98w. From the X-ray diffraction data, the guest size and the charge density of the oxygens of the guest, the orientation of 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, or 3,5-pyridinedicarboxylate anions between the layers was determined and the preferential intercalation mechanism was discussed. These results indicate the possibility of a molecular recognition ability of LDH and it would be exploited for the chemical separation of some anions from solution.

Aerosol samples of PM2.5 and PM10 were collected in both summer and winter seasons from 2002 to 2003 synchronously at a traffic site, an industrial site, and a residential site in Beijing, which could basically be the representatives over Beijing. Twenty-three elements and 15 ions together with organic carbon and elemental carbon were analyzed systematically for characterization of Beijing aerosol. PM2.5 was the major part of the inhalable particles (PM10), as the ratios of PM2.5/PM10 were 0.45-0.48 in summer and 0.52-0.73 in winter. SO42-, NO3-, NH4+, organic matter, crustal matter, and element carbon were the six dominant species, which totally accounted for 85.8-97.7% of Secondary aerosol, (SO42-, NO3-, and NH4+), road dust or/and long-range transported dust from outside Beijing, industry and motor vehicles emission, coal burning were the major contributors to the air-borne particulate pollution in Beijing. Overall, coal burning and the traffic exhausts, plus the dust from the long-range transport, could be the major sources of the aerosol pollution at Beijing. A relatively even spatial distribution of chemical species in PM2.5 was found while in PM10 a significant variation with the highest concentrations at the industrial site in summer and at the residential site in winter was observed. The concentrations of PM10, PM2.5 as well as various chemical species were higher in winter than in summer. The contributions of mineral aerosol from outside Beijing were first estimated with a newly developed element tracer technique, which accounted for 79% and 37% of the total mineral in PM10 and PM2.5 in winter, and 19% and 20% in summer, respectively. During the dust storm period from 20 to 22 March, it reached up to 97% in TSP, 79% in PM10 and 76% in PM2.5. This is the technique, firstly, developed for estimating the relative contributions of sources from inside and outside Beijing to the total mineral aerosol and it could provide the basic information in controlling the air-borne particulate pollution at Beijing. (C) 2004 Elsevier Ltd. All rights reserved.

Concentrations of organic carbon (OC) and element carbon (EC) in PM2.5 in the urban and rural areas of Beijing were determined and their sources were qualitatively discussed.PM2. 5 samples were collected at five sites of Beijing during summers and winters of 2001 and 2002 and spring of 2003.Daily average 10. 7 73.6 and 5.772.9m gm � 3 in summer and 36.7719.4 and 15.2711.1m gm � 3 in winter of 2002 for OC and EC, respectively, were observed in Beijing urban area.The concentrations of carbonaceous species contributed 18.4 73.5% and 37.2712.7% of PM2.5 in summer and winter, respectively, of which OC accounted for 70% or more of the total carbon (TC).OC and EC concentrations and their mass percentages in PM2.5 were higher in winter than in summer, which could be attributed to the coal consumption of heating period.Organic aerosols would constitute up to 42% of PM2. 5 in winter based on the evaluation of 1.6 for the ratio of OC to organic particulates. Secondary organic carbon (SOC) were estimated to be more than 50% and up to 95% of total OC in summer based on the minimum OC/EC ratio of 0.9. Comparisons of OC and EC with trace elements, As, Zn, K and Pb, at various sites demonstrated that coal combustion was a dominant source of carbonaceous species of PM2.5 in the urban area of Beijing during winter, and biomass burning, traffic and/or industry emission were the major sources of OC and EC in the summer. r 2004 Published by Elsevier Ltd.

Objective: Characterize the flux of platelet-endothelial cell adhesion molecule (PECAM-1) antibody-coated superparamagnetic iron oxide nanoparticles (IONPs) across the blood-brain barrier (BBB) and its biodistribution in vitro and in vivo. Methods: Anti-PECAM-1 IONPs and IgG IONPs were prepared and characterized in house. The binding affinity of these nanoparticles was investigated using human cortical microvascular endothelial cells (hCMEC/D3). Flux assays were performed using a hCMEC/D3 BBB model. To test their immunospecificity index and biodistribution, nanoparticles were given to Sprague Dawley rats by intra-carotid infusion. The capillary depletion method was used to elucidate their distribution between the BBB and brain parenchyma. Results: Anti-PECAM-1 IONPs were ,130 nm. The extent of nanoparticle antibody surface coverage was 63.668.4%. Only 6.3961.22% of labeled antibody dissociated from IONPs in heparin-treated whole blood over 4 h. The binding affinity of PECAM-1 antibody (KD) was 32 nM with a maximal binding (Bmax )o f 17610 5 antibody molecules/cell. Anti-PECAM-1 IONP flux across a hCMEC/D3 monolayer was significantly higher than IgG IONP’s with 31% of anti-PECAM-1 IONPs in the receiving chamber after 6 h. Anti-PECAM-1 IONPs showed higher concentrations in lung and brain, but not liver or spleen, than IgG IONPs after infusion. The capillary depletion method showed that 17612% of the anti-PECAM-1 IONPs crossed the BBB into the brain ten minutes after infusion. Conclusions: PECAM-1 antibody coating significantly increased IONP flux across the hCMEC/D3 monolayer. In vivo results showed that the PECAM-1 antibody enhanced BBB association and brain parenchymal accumulation of IONPs compared to IgG. This research demonstrates the benefit of anti-PECAM-1 IONPs for association and flux across the BBB into the brain in relation to its biodistribution in peripheral organs. The results provide insight into potential application and toxicity concerns of anti-PECAM-1 IONPs in the central nervous system.

Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit manufacture, and is being pursued as an antioxidant therapeutic. Our objective is to extend previous findings showing that there were no reductions of cerium in organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days after a single nanoscale ceria administration. An ~5% aqueous dispersion of citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside observations were obtained daily, body weight weekly. Daily urinary and fecal cerium outputs were quantified for 2 weeks. Nine organs were weighed and samples collected from 14 tissues/organs/systems, blood and cerebrospinal fluid for cerium determination. Histology and oxidative stress were assessed. Less than 1% of the nanoceria was excreted in the first 2 weeks, 98% in feces. Body weight gain was initially impaired. Spleen weight was significantly increased in some ceria-treated groups, associated with abnormalities. Ceria was primarily retained in the spleen, liver, and bone marrow. There was little decrease of ceria in any tissue over the 90 days. Granulomas were observed in the liver. Time-dependent oxidative stress changes were seen in the liver and spleen. Nanoscale ceria was persistently retained by organs of the mononuclear phagocyte system, associated with adverse changes. The results support concern about the long-term fate and adverse effects of inert nanoscale metal oxides that distribute throughout the body, are persistently retained, and produce adverse changes.

The objective of this study was to determine the residual pro-or anti-oxidant effects in rat brain 30 days after systemic administration of a 5 nm citrate-stabilized ceria dispersion. A ∼4% aqueous ceria dispersion was iv-infused (0 or 85 mg/kg) into rats which were terminated 30 days later. Ceria concentration, localization, and chemical speciation in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS), light and electron microscopy (EM), and electron energy loss spectroscopy (EELS), respectively. Pro- or anti-oxidant effects were evaluated by measuring levels of protein carbonyls (PC), 3-nitrotyrosine (3NT), and protein-bound-4-hydroxy-2-trans-nonenal (HNE) in the hippocampus, cortex, and cerebellum. Glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase levels and activity were measured in addition to levels of inducible nitric oxide (iNOS), and heat shock protein-70 (Hsp70). The blood brain barrier (BBB) was visibly intact and no ceria was seen in the brain cells. Ceria elevated PC and Hsp70 levels in hippocampus and cerebellum, while 3NT and iNOS levels were elevated in the cortex. Whereas glutathione peroxidase and catalase activity were decreased in the hippocampus, GR levels were decreased in the cortex, and GPx and catalase levels were decreased in the cerebellum. The GSH:GSSG ratio, an index of cellular redox status, was decreased in the hippocampus and cerebellum. The results are in accordance with the observation that this nanoscale material remains in this mammal model up to 30 days after its administration and the hypothesis that it exerts pro-oxidant effects on the brain without crossing the BBB. These results have important implications on the potential use of ceria ENM as therapeutic agents.

Aims: Characterize different sized ceria-engineered nanomaterial (ENM) distribution in, and clearance from, blood (compared to the cerium ion) following intravenous infusion. Materials & Methods: Cerium (Ce) was quantified in whole blood, serum and clot (the formed elements) up to 720 h. Results: Traditional pharmacokinetic modeling showed best fit for 5 nm ceria ENM and the cerium ion. Ceria ENMs larger than 5 nm were rapidly cleared from blood. After initially declining, whole blood 15 and 30 nm ceria increased (results that have not been well-described by traditional pharmacokinetic modeling). The cerium ion and 5 and 55 nm ceria did not preferentially distribute into serum or clot, a mixture of cubic and rod shaped ceria was predominantly in the clot, and 15 and 30 nm ceria migrated into the clot over 4 h. Conclusion: Reticuloendothelial organs may not readily recognize five nm ceria. Increased ceria distribution into the clot over time may be due to opsonization. Traditional pharmacokinetic analysis was not very informative. Ceria ENM pharmacokinetics are quite different from the cerium ion.

Engineered nanoscale ceria is used as a diesel fuel catalyst. Little is known about its mammalian central nervous system effects. The objective of this paper is to characterize the biodistribution of a 5-nm citrate-stabilized ceria dispersion from blood into brain and its pro- or antioxidant effects. An approximately 4% aqueous ceria dispersion was iv infused into rats (0, 100, and up to 250 mg/kg), which were terminated after 1 or 20 h. Ceria concentration, localization, and chemical speciation in the brain were assessed by inductively coupled plasma mass spectrometry, light and electron microscopy (EM), and electron energy loss spectroscopy (EELS). Pro- or antioxidative stress effects were assessed as protein carbonyls, 3-nitrotyrosine, and protein-bound 4-hydroxy-2-trans-nonenal in hippocampus, cortex, and cerebellum. Glutathione reductase, glutathione peroxidase, manganese superoxide dismutase, and catalase levels and activities were measured in hippocampus. Catalase levels and activities were also measured in cortex and cerebellum. Na fluorescein and horseradish peroxidase (HRP) were given iv as blood-brain barrier (BBB) integrity markers. Mortality was seen after administration of 175-250 mg ceria/kg. Twenty hours after infusion of 100 mg ceria/kg, brain HRP was marginally elevated. EM and EELS revealed mixed Ce(III) and Ce(IV) valence in the freshly synthesized ceria in vitro and in ceria agglomerates in the brain vascular compartment. Ceria was not seen in microvascular endothelial or brain cells. Ceria elevated catalase levels at 1 h and increased catalase activity at 20 h in hippocampus and decreased catalase activity at 1 h in cerebellum. Compared with a previously studied approximately 30-nm ceria, this ceria was more toxic, was not seen in the brain, and produced little oxidative stress effect to the hippocampus and cerebellum. The results are contrary to the hypothesis that a smaller engineered nanomaterial would more readily permeate the BBB.