Anlotinib suppresses the DNA damage response by disrupting SETD1A and inducing p53-dependent apoptosis in Transformed Follicular Lymphoma.

Purpose: The high tumor mutational burden (TMB) of transformed follicular lymphoma (tFL) leads to tumor heterogeneity and poor prognosis in follicular lymphoma, in which endogenous DNA damage and epigenetic modification are the key factors. This study aims to evaluate the efficacy of anlotinib in tFL and to investigate its potential therapeutic mechanism. Methods: Cell viability and apoptosis were tested with CCK-8 and annexin V/PI staining kits, respectively. The tumorigenicity test in mice was utilized to further confirm the efficacy of anlotinib in vivo. Western blotting was utilized to explore the molecular mechanisms. Results: Anlotinib induced G2/M phase arrest in tFL cells, inhibited the proliferation of tFL cells and promoted the apoptosis of tFL cells in a dose-dependent manner. Administration of anlotinib markedly reduced tumor mass and weight in an FL xenograft mouse model. The western blot and immunohistochemistry staining results confirmed that the mechanism by which anlotinib promoted tumor cell apoptosis was DNA damage. Further results showed that anlotinib significantly downregulated the expression of SETD1A, leading to its destruction. Anlotinib administration resulted in a significant dose-dependent increase in the level of p-p53. Furthermore, anlotinib greatly downregulated the antiapoptotic proteins Mcl-1 and in parallel upregulated the proapoptotic element BAX and Bak, accompanied by caspase-3 activation and PARP degradation. Conclusion: Anlotinib has a good proapoptotic effect on tumor cells in vitro and in vivo, and its possible mechanism is related to the inhibition of the DNA damage response by disrupting SETD1A.

Metastatic Lymph Node 64 (MLN64) Expression in Gastric Cancer: The Clinical and Molecular Implications in Drug Resistance.

BACKGROUND/AIM: Metastatic lymph node 64 (MLN64) is often co-amplified with ERBB2 (HER2) and plays a role in the progression of breast and prostate cancer. The present study explored the expression of MLN64 in clinical gastric cancer in association with the ERBB family and its impact on drug resistance in patients. MATERIALS AND METHODS: Two independent gastric cancer cohorts (n=324; n=87) were used to explore the expression profile of MLN64 in conjunction with ERBB family members in clinical gastric cancer and its association with neoadjuvant chemotherapy responses. Gastric cancer AGS and HCG27 cells with MLN64 knockdown were generated to determine the function of MLN64 in cell behavioural changes. RESULTS: Gastric tumor tissues expressed significantly higher levels of MLN64 compared with normal tissues (p<0.01); however, MLN64 alone was a weak prognostic indicator. An integrated co-expression of MLN64, ERBB4, and NRG4 was a significant factor in assessing overall survival in both cohorts. MLN64 was a profound indicator of patient response to neoadjuvant chemotherapy. In vitro studies indicated a significant contribution of MLN64 to the response of gastric cancer cells to chemodrugs and Her-2 inhibitors. MLN64 knockdown also contributed to the adhesion and migration and suggested a possible mechanism mediated by the interaction between MLN64 and ERBBs. CONCLUSION: MLN64 is an indicator of patient response to neoadjuvant chemotherapy in gastric cancer. Together with the expression pattern of ERBB4, MLN64 is a poor prognostic factor for patients with gastric cancer.

Expression of Claudin-9 (CLDN9) in Breast Cancer, the Clinical Significance in Connection with Its Subcoat Anchorage Proteins ZO-1 and ZO-3 and Impact on Drug Resistance.

(1) Introduction: Claudin-9 (CLDN9) is a member of the claudin protein family, a critical transmembrane protein family for tight junctions that are implemented in the progression of numerous cancer types. The present study investigated the role that CLDN9, along with the subcoat proteins, Zonula Occludens (ZOs), plays in clinical breast cancer and subsequent impact on drug response of patients. (2) Methods: CLDN9 protein and CLDN9 transcript were determined and correlated with clinical and pathological indicators, together with the status of hormonal receptors. The levels of CLDN9 transcript were also assessed against the therapeutic responses of the patients to chemotherapies by using a dataset from the TCGA database. Breast cancer cell models, representing different molecular subtypes of breast cancer, with differential expression of CLDN9 were created and used to assess the biological impact and response to chemotherapeutic drugs. (3) Results: Breast cancer tissues expressed significantly higher levels of the CLDN9, with the high levels being associated with shorter survival. CLDN9 was significantly correlated with its anchorage proteins ZO-1 and ZO-3. Integrated expression of CLDN9, ZO-1 and ZO-3 formed a signature that was significantly linked to overall survival (OS) (p = 0.013) and relapse-free survival (RFS) (p = 0.024) in an independent matter. CLDN9 transcript was significantly higher in patients who were resistant to chemotherapies (p < 0.000001). CLDN9 connection to chemoresistance was particularly prominent in patients of ER-positive (ER(+)), Her-2-negative((Her-2(-)), ER(+)/Her-2(-) and triple-negative breast cancers (TNBCs), but not in patients with HER-2-positive tumors. In Her-2-negative MCF7 and MDA-MB-231 cancer cells, loss of CLDN9 significantly increased sensitivity to several chemotherapeutic drugs including paclitaxel, gemcitabine and methotrexate, which was not seen in Her-2(+) SKBR3 cells. However, suppressing Her-2 using neratinib, a permanent Her-2 inhibitor, sensitized cellular response to these chemodrugs in cells with CLDN9 knockdown. (4) Conclusions: CLDN9 is an important prognostic indicator for patients with breast cancer and also a pivotal factor in assessing patient responses to chemotherapies. Her-2 is a negating factor for the treatment response prediction value by CLDN9 and negating Her-2 and CLDN9 may enhance breast cancer cellular response to chemotherapeutic drugs.

Claudin-10 in the Blood Brain Barrier Function of Cerebral Endothelial Cells and Transendothelial Invasion of Breast Cancer Cells.

BACKGROUND/AIM: Claudin-10 (CLDN10) is a membrane integral protein. It is one of the widely expressed tight junctional claudins with functions not well defined. In the present study, the expression profile and its role in cerebral endothelial cells and in the interaction between breast cancer and endothelial cells were investigated. MATERIALS AND METHODS: CLDN10 expression was examined in a wide range of cell types. Brain endothelial cell models with or without CLDN10 expression were generated using the hCMEC/D3 cell line and used to test the barrier and permeability functions. Transendothelial drug delivery and invasion were also evaluated. RESULTS: hCMEC/D3 cells express high levels of CLDN10, compared with peripheral endothelial cells, mesothelial cells, fibroblasts, and breast cancer cells, which were either negative or expressed low levels of CLDN10. Knockdown of CLDN10 in hCMEC/D3 cells resulted in impaired tight junctions as seen by reduced transendothelial electric resistance and paracellular permeability. It also accelerated invasion of breast cancer cells through the endothelial cell layer. CLDN10 knockdown in hCMEC/D3 cells led to an increase in transendothelial chemodrug delivery. Furthermore, the SRC kinase inhibitor (AZM475271) was able to decrease the impedance and increase the paracellular permeability in cerebral endothelial cells. CONCLUSION: Cerebral endothelial cells express high levels of CLDN10, a protein regulating barrier function and thereby drug permeability and cancer invasiveness in brain endothelial cells, suggesting that it is a novel therapeutic target for the treatment of brain metastasis-related diseases.

Preclinical Evaluation of the Multiple Tyrosine Kinases Inhibitor Anlotinib in Leukemia Stem Cells.

Leukemia stem cells (LSCs) constitute the critical barrier to the cure of acute myeloid leukemia (AML) due to their chemoresistance and immune evasion property. Herein, the role of anlotinib, a multiple tyrosine kinase inhibitor, in killing LSCs and regulating chemoresistance and immune evasion was explored. Anlotinib treatment induced apoptosis of LSC-like cells as well as primary AML LSCs, while sparing the normal mononuclear cells in vitro. Moreover, anlotinib could impair the regeneration capacity of LSCs in the patient-derived leukemia xenograft mouse model. Mechanistically, anlotinib inhibited phosphorylation of c-kit, JAK2/STAT3, and STAT5, and downregulated STAT3 and STAT5 expression. In addition, anlotinib downregulated the anti-apoptotic proteins Bcl-2 and Bcl-xL, and upregulated Bax, thereby enhancing the sensitivity of LSCs to idarubicin in vitro. Intriguingly, anlotinib could also partially rescue the interferon-g production of T cells cocultured with LSCs by downregulating PD-L1 expression. In conclusion, anlotinib showed anti-LSC activity and the potential to enhance the sensitivity to idarubicin and inhibit the immunosuppressive feature of LSCs via JAK2/STAT signaling pathway downregulation in the preclinical study. Our results provided a rational basis for combinatory strategies involving anlotinib and chemotherapy or immunotherapy.

Chemical Speciation and Leaching Behavior of Hazardous Trace Elements in Coal Combustion Products from Coal-Fired Power Stations in China.

This paper reports on the chemical speciation and leaching behavior of a selected group of hazardous trace pollutants in lignite and lignite-petcoke blend co-combustion products from three power stations in China. The evaluation of speciation results showed that, during combustion, oxidizable elements, mainly As and Mo, bound to organic matter and sulfides in coals were mostly transferred to easily water-soluble forms or to slightly acidic states in the ashes. This manner was the most readily bioavailable condition for such an environment. The evaluation of the leaching results shows that the use of petroleum coke as co-fuel has an impact on the ash composition and on the leaching behavior of some inorganic trace pollutants such as Mo and V. The leaching results compared to the European waste acceptance criteria for landfills reveal that the Mo and As' leaching yield brand the coal combustion products as materials that necessitate preventative measures to reduce their potential leaching. Future work will be focused on the application of our novel chemical stabilization method to these coal ashes to reduce the mobility of elements such as Mo and As, and other potentially leachable elements, and on the use of the resulting ash with aggregate products as a substitute for concrete production.

Identification of serum metabolites enhancing inflammatory responses in COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a strong production of inflammatory cytokines such as TNF and IL-6, which underlie the severity of the disease. However, the molecular mechanisms responsible for such a strong immune response remains unclear. Here, utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages, we identified that 611 metabolites (of 1,039) were significantly altered in COVID-19 patients. Among them, two metabolites, agmatine and putrescine, were prominently elevated in the serum of patients; and 2-quinolinecarboxylate was changed in a biphasic manner, elevated during early COVID-19 infection but levelled off. When tested in mouse embryonic fibroblasts (MEFs) and macrophages, these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production. Importantly, these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice, but not in the mice lacking NF-κB. Intriguingly, these metabolites have little effects on the activation of interferon regulatory factors (IRFs) for the production of type I interferons (IFNs) for antiviral defenses. These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses, exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons. Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients.

Geochemistry and oxidative potential of the respirable fraction of powdered mined Chinese coals.

This study evaluates geochemical and oxidative potential (OP) properties of the respirable (finer than 4 µm) fractions of 22 powdered coal samples from channel profiles (CP4) in Chinese mined coals. The CP4 fractions extracted from milled samples of 22 different coals were mineralogically and geochemically analysed and the relationships with the OP evaluated. The evaluation between CP4/CP demonstrated that CP4 increased concentrations of anatase, Cs, W, Zn and Zr, whereas sulphates, Fe, S, Mo, Mn, Hf and Ge decreased their CP4 concentrations. OP results from ascorbic acid (AA), glutathione (GSH) and dithiothreitol (DTT) tests evidenced a clear link between specific inorganic components of CP4 with OPAA and the organic fraction of OPGSH and OPDTT. Correlation analyses were performed for OP indicators and the geochemical patterns of CP4. These were compared with respirable dust samples from prior studies. They indicate that Fe (r = 0.83), pyrite (r = 0.66) and sulphate minerals (r = 0.42) (tracing acidic species from pyrite oxidation), followed by S (r = 0.50) and ash yield (r = 0.46), and, to a much lesser extent, Ti, anatase, U, Mo, V and Pb, are clearly linked with OPAA. Moreover, OPGSH correlation was identified by organic matter, as moisture (r = 0.73), Na (r = 0.56) and B (r = 0.51), and to a lesser extent by the coarse particle size, Ca and carbonate minerals. In addition, Mg (r = 0.70), B (r = 0.47), Na (r = 0.59), Mn, Ba, quartz, particle size and Sr regulate OPDTT correlations. These became more noticeable when the analysis was done for samples of the same type of coal rank, in this case, bituminous.

Geochemical controls on the enrichment of fluoride in the mine water of the Shendong mining area, China.

Underground coal mining produces large amounts of mine water annually in the Shendong mining area of China. Due to the severe scarcity of water resources, mine water is extensively used for productive, domestic, and ecological demands. However, mine water exhibits high fluoride levels. For water-use security, reduction of fluoride exposure and environmental protection, knowledge of sources and geochemical controls of fluoride enrichment in mine water is required. The results showed that F- concentrations of mine waters vary from 0.05 to 11.65 mg/L, with a mean value of 1.96 mg/L, and 51% of the mine waters contain F- concentrations exceeding the Chinese drinking water standard (1 mg/L). The overall mine water quality is influenced by cation exchange, mineral dissolution, pyrite oxidation, silicate weathering and so on. The high-fluoride mine waters are all associated with Na-type, with a remarkable cation composition feature of higher Na+ and lower Ca2+ and Mg2+ concentrations. Overall, the high-fluoride mine waters are well-matched with the water environment with higher pH, TDS, and EC levels. PCA reveals that the geochemical controls on the enrichment of F- in mine waters include dissolution of fluoride-bearing minerals and F--OH- ion exchange; the former process is mainly caused by the decrease in Ca2+ concentrations resulting from Na + -Ca2+ cation exchange and mineral precipitation, and the latter process benefits from a highly alkaline water environment, facilitating the substitution of OH- in the mine water for F- within or absorbed on the minerals. Evaporation also controls F- enrichment in local areas.

Role of rgsA in Oxidative Stress Resistance in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a common opportunistic pathogen that causes infections in vulnerable patients including those with metabolic disorders, hematologic diseases, and malignancies, and in those who have undergone surgery. In addition, P. aeruginosa exhibits high intrinsic resistance to numerous antibiotics and tends to form biofilms rendering it even more refractory to treatment. Among the mechanisms used by P. aeruginosa to adapt to environmental stresses are those involving small regulatory RNAs (sRNAs), which are 40-500 nucleotides long and are ubiquitous in bacteria. sRNAs play important regulatory roles in various vital processes in diverse bacteria, with their quantity and diversity of regulatory functions exceeding those of proteins. In this study, we show that deletion of the sRNA, rgsA, decreased the growth rate of P. aeruginosa. Furthermore, ΔrgsA P. aeruginosa exhibited decreased ability to resist the stress induced by exposure to different concentrations and durations of peroxides in both planktonic and biofilm growth modes compared with the wild-type strain. These results highlight the role of rgsA in the defense of P. aeruginosa against oxidative stress.

Integrated Analysis to Obtain Potential Prognostic Signature in Glioblastoma.

Glioblastoma multiforme (GBM) is the most malignant and multiple tumors of the central nervous system. The survival rate for GBM patients is less than 15 months. We aimed to uncover the potential mechanism of GBM in tumor microenvironment and provide several candidate biomarkers for GBM prognosis. In this study, ESTIMATE analysis was used to divide the GBM patients into high and low immune or stromal score groups. Microenvironment associated genes were filtered through differential analysis. Weighted gene co-expression network analysis (WGCNA) was performed to correlate the genes and clinical traits. The candidate genes' functions were annotated by enrichment analyses. The potential prognostic biomarkers were assessed by survival analysis. We obtained 81 immune associated differentially expressed genes (DEGs) for subsequent WGCNA analysis. Ten out of these DEGs were significantly associated with targeted molecular therapy of GBM patients. Three genes (S100A4, FCGR2B, and BIRC3) out of these genes were associated with overall survival and the independent test set testified the result. Here, we obtained three crucial genes that had good prognostic efficacy of GBM and may help to improve the prognostic prediction of GBM.

Mineralogy, geochemistry and toxicity of size-segregated respirable deposited dust in underground coal mines.

We focus on a comparison of the geochemistry and mineralogy patterns found in coal, deposited dust (DD), respirable deposited dust (RDD) and inhalable suspended dust (PM10) from a number of underground mines located in China, with an emphasis on potential occupational health relevance. After obtaining the RDD from DD, a toxicological analysis (oxidative potential, OP) was carried out and compared with their geochemical patterns. The results demonstrate: i) a dependence of RDD/DD on the moisture content for high rank coals that does not exist for low rank coals; ii) RDD enrichment in a number of minerals and/or elements related to the parent coal, the wear on mining machinery, lime gunited walls and acid mine drainage; and iii) the geochemical patterns of RDD obtained from DD can be compared with PM10 with relatively good agreement, demonstrating that the characterization of DD and RDD can be used as a proxy to help evaluate the geochemical patterns of suspended PM10. With regards to the toxicological properties of RDD, the Fe content and other by-products of pyrite oxidation, as well as that of anatase, along with Si, Mn and Ba, and particle size (among others), were highly correlated with Ascorbic Acid and/or Glutathione OP.

Characteristics of Dust in Coal Mines in Central North China and Its Research Significance.

The identification of the dust characteristics in coal mine working faces is essential for preventing coal dust explosion and occupational diseases. In this paper, dust samples from the coal mines in southern Shanxi province and Henan province, central North China, were selected as the research objects. The results show that the dust contains primarily organic matter, as well as considerable amounts of minerals. The chemical composition of dust at the working faces is the most complex. According to the proportion of PM10, the dust composition can be divided into three types: symmetrical, fine-dominated, and coarse-dominated. The wettability of dust increases with the increase of the oxygen-carbon ratio on its surface, increase of ash content, decrease of fixed carbon content, and decrease of particle size. In addition, the great variety of harmful elements in dust, some with a high content, can harm the human body. An explosion index is proposed to evaluate the likeliness tendency of coal dust explosion based on several key affecting factors. The surfactant (0.05% AN solution) adopted in this paper can significantly increase the wettability of coal dust and inhibit the generation of dust greatly, showing good ability in preventing coal dust explosion and occupational diseases.

Hydrogeochemistry signatures of produced waters associated with coalbed methane production in the Southern Junggar Basin, NW China.

The Southern Junggar Basin (SJB) in China is an emerging coalbed methane (CBM) development area with abundant low-rank CBM resources. CBM development is accomplished by pumping significant volumes of water from the aquifer, and this water is commonly termed as produced water, which has great utilization values for the water-deficient areas like SJB. Geochemistry signatures are prerequisites in the management of the produced water. Meanwhile, geochemistry surveys of this produced water could also help study the basin hydrogeology and then serve the CBM development. In this study, geochemical compositions of the produced waters, including major ions, stable isotopic compositions, trace elements, and rare earth elements, were analyzed. Results show that produced waters from CBM wells in the SJB are of Na-HCO3 type and have wide total dissolved solid (TDS) ranges from 963 to 11,916 mg/L (avg. 7417 mg/L). Cl-, Na+, and HCO3- are the principal determinates of the TDS contents of the produced waters, and their concentrations all increase with greater depth of the produced waters. Overall, the net results of groundwater-aquifer mineral-bacteria interactions with groundwater flowing along the flow path are to deplete Ca2+, Mg2+, and SO42- and increase Na+, Cl-, HCO3-, and TDS. Stable isotopic values of the CBM produced waters (δDH2O and δ18OH2O) cluster along or below the local meteoric water line (LMWL), and the shift of stable isotopic values to the right side of LMWL was affected by a joint effect of evaporation and mixing with near-surface water. Trace elements that exceed the regulated concentrations for drinking water of China include As, Fe, Mn, Ba, and Ni, among which Ba and Fe need to be most concerned because over 50% of the CBM produced waters exceed the regulated values. Through principal component analysis, the trace element associations in the CBM produced waters and their potential origins were analyzed. The ∑REY concentrations of the CBM produced waters increase exponentially with the increase of pH and present a certain correlation with TDS. The relationship between ∑REY concentrations and TDS reflects different water-rock reaction degrees and hydrogeological backgrounds.

Conditioned medium mimicking the tumor microenvironment augments chemotherapeutic resistance via ataxia­telangiectasia mutated and nuclear factor­κB pathways in gastric cancer cells.

The tumor microenvironment affects the processes involved in the development of gastric cancer and contributes to multidrug resistance (MDR). Although the metabolism of gastric cancer cells is known to be associated with the development of the tumor microenvironment, the exact role of metabolism in microenvironment­induced MDR formation remains unclear. In the present study, conditioned medium (CM) formed through the metabolism of SGC­7901 gastric carcinoma cells was used to mimic the tumor microenvironment. The effects of CM on drug resistance were evaluated in gastric carcinoma cells. The results revealed that CM was not only able to upregulate the expression levels of ATP­binding cassette subfamily G member 2 (ABCG2) and MDR­associated protein 2 (MRP2), but also upregulated the expression of certain anti­apoptotic proteins in SGC­7901 cells. In addition, CM activated the ataxia­telangiectasia mutated (ATM) and NF­κB pathways, while CM­induced ABCG2, MRP2 and anti­apoptotic protein upregulation was impaired by ATM and NF­κB inhibitors. The results of the present study indicated that CM augmented chemotherapeutic resistance by activating the ATM and NF­κB pathways in gastric cancer cells, and that these pathways may be potential therapeutic targets for cases of chemotherapeutic resistance in gastric cancer.

Heptaplex PCR melting curve analysis for rapid detection of plasmid-mediated AmpC ß-lactamase genes.

Antimicrobial resistance mediated by plasmid-borne AmpC ß-lactamase in Gram-negative bacteria is an emerging event of significant clinical importance. Rapid and reliable detection of ampC is in urgent need for appropriate infection control. We described the development and evaluation of a heptaplex PCR melting curve analysis that could identify six groups of ampC, i.e., CIT, EBC, DHA, ACC, MOX and FOX, through predefined melting temperatures. The entire analysis could be finished within 2h for 96 samples after template DNA was prepared. We first evaluated the assay with 176 AmpC-producing isolates of Escherichia coli and Klebsiella pneumoniae, and the results showed that 36 isolates were positive for ampC, including 18 positive for DHA, 12 for CIT, 5 for EBC, and one for both DHA and EBC. These results were fully concordant with sequencing analysis whereas the comparison method, an electrophoresis-based singleplex PCR assay, missed four isolates. The assay was also used to analyze 429 randomly selected clinically relevant Gram-negative isolates involving 22 different species, and 34 isolates were found to be ampC-positive. The results again fully agreed with the sequencing analysis. We conclude that the established assay could be used for rapid and reliable detection of ampC.

Synthesis of merlinoite from Chinese coal fly ashes and its potential utilization as slow release K-fertilizer.

This study focuses on the synthesis of merlinoite from Chinese coal fly ashes by KOH direct conversion method, with special emphasis on the application of synthetic merlinoite as fertilizer. These fly ashes were collected from two pulverized-coal combustion (PCC) power plants in Xinjiang, Northwest China. The synthesis results are influenced by fly ash characteristics and different synthesis conditions (KOH solution concentrations, activation temperature, time, and KOH/fly ash ratios). A high quality merlinoite-rich product was synthesized under optimal activation conditions (KOH concentration of 5M, activation temperature of 150°C, activation time of 8h and KOH/fly ash ratio of 2l/kg), with a cation exchange capacity (CEC) of 160cmolkg(-1). The synthetic merlinoite is proved to be an efficient slow release K-fertilizer for plant growth, indicating that it can be widely used for high-nutrient demanding crops growing in nutrient-limited soils and for large-area poor soil amendment in opencast coal mine areas around the power plants that will substantially grow with the increasing coal combustion in Xinjiang in the near future.

Speciation and sources of atmospheric aerosols in a highly industrialised emerging mega-city in central China.

Monitoring air quality in large urban agglomerations is the key to the prevention of air pollution-related problems in emerging mega-cities. The city of Wuhan is a highly industrialised city with >9 million inhabitants in Central China. Simultaneous PM10 sampling was performed during 1 year at one urban and one industrial site. Mean PM10 daily levels (156 microg m(-3) at the urban site and 197 microg m(-3) at the industrial hotspot) exceed the US-EPA or EU annual limit values by 3-4 times. A detailed study of daily speciation showed that the mean chemical composition of PM10 presents minimal differences between peak and low PM episodes. This implies that PM10 aerosols in the study area result from local emissions, and air quality management and abatement strategies in Wuhan should thus focus on local anthropogenic sources. The levels of some elements of environmental concern are relatively high (409-615 ngPb m(-3), 66-70 ngAs m(-3), 116-227 ngMn m(-3), 10-12 ngCd m(-3)) due to industrial, but also urban emissions. Principal component analysis identified a mineral source (probably cement and steel manufacture) and smelting as the main contributors to PM10 levels at the industrial site (34%), followed by a coal fired power plant (20%) and the anthropogenic regional background (16%). At the urban site the major PM10 source is a mixed coal combustion source (31%), followed by the anthropogenic regional background (28%) and traffic (16%).