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Abstract Background C-Myc is a short-lived oncoprotein that is destroyed by ubiquitin-mediated proteolysis. Dysregulated accumulation of c-Myc commonly occurs in human cancers. Some of those cases with the dysregulated c-Myc protein accumulation are attributed to gene amplification or increased mRNA expression. However, the abnormal accumulation of c-Myc protein is also a common finding in human cancers with normal copy number and transcription level of c-Myc gene. It seems that the mechanistic dysregulation in the control of c-Myc protein stabilization is another important hallmark associated with c-Myc accumulation in cancer cells. Here we report a novel mechanistic pathway through which DNA-dependent protein kinase catalytic subunit (DNA-PKcs) modulates the stability of c-Myc protein. Results Firstly, siRNA-mediated silencing of DNA-PKcs strikingly downregulated c-Myc protein levels in HeLa and HepG2 cells, and simultaneously decreased cell proliferation. The c-Myc protein level in DNA-PKcs deficient human glioma M059J cells was also found much lower than that in DNA-PKcs efficient M059K cells. ATM deficiency does not affect c-Myc expression level. Silencing of DNA-PKcs in HeLa cells resulted in a decreased stability of c-Myc protein, which was associated the increasing of c-Myc phosphorylation on Thr58/Ser62 and ubiquitination level. Phosphorylation of Akt on Ser473, a substrate of DNA-PKcs was found decreased in DNA-PKcs deficient cells. As the consequence, the phosphorylation of GSK3 β on Ser9, a negatively regulated target of Akt, was also decreased, and which led to activation of GSK 3β and in turn phosphorylation of c-Myc on Thr58. Moreover, inhibition of GSK3 activity by LiCl or specific siRNA molecules rescued the downregulation of c-Myc mediated by silencing DNA-PKcs. Consistent with this depressed DNA-PKcs cell model, overexpressing DNA-PKcs in normal human liver L02 cells, by sub-chronically exposing to very low dose of carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), increased c-Myc protein level, the phosphorylation of Akt and GSK3 β, as well as cell proliferation. siRNA-mediated silencing of DNA-PKcs in this cell model reversed above alterations to the original levels of L02 cells. Conclusion A suitable DNA-PKcs level in cells is necessary for maintaining genomic stability, while abnormal overexpression of DNA-PKcs may contribute to cell proliferation and even oncogenic transformation by stabilizing the c-Myc oncoprotein via at least the Akt/GSK3 pathway. Our results suggest DNA-PKcs a novel biological role beyond its DNA repair function.

The microbiological transformation of the triterpene nigranoic acid (3,4-secocycloarta-4(28),24(Z)-diene-3,26-dioic acid) (1) to 3,4-secocycloarta-4(28),17(20),24(Z)-triene-7β-hydroxy-16β,26-lactone-3-oic acid (2) and 3,4-secocycloarta-4(28),17(20)(Z),24(Z)-triene-7β-hydroxy-16β-methoxy-3,26-dioic acid (3) by the freshwater fungus Dictyosporium heptasporum YMF1.01213 has been demonstrated. The structures of the biotransformation products were determined by spectroscopic and MS analyses. Compound 2, characterized by the presence of a formed C-16/C-26 ester bridge, provided a novel nine-membered lactone ring structural skeleton for 3,4-secocycloartane triterpenoid derivatives. In addition, Compounds 1–3 exhibited weak anti-HIV activity in vitro. Compounds 2 and 3 were reported for the first time as natural product derivatives. [ABSTRACT FROM AUTHOR]

Based on the concentrations of 21 inorganic elements in particulate matter with diameters less than 10 μm (PM 10 ) in 2004, and PM 2.5 in 2004 and 2013 of representative road dust in Beijing, the pollution characteristics and potential ecological risks of heavy metals in this dust were analyzed and discussed. The results showed that the six main elements in road dust in Beijing were Si, Ca, Al, Fe, Mg, and K, and the proportions of the total content of the six elements in PM 10 in 2004, PM 2.5 in 2004, and PM 2.5 in 2013 accounted for 96.51%, 96.42%, and 96.53% of the total content of all elements tested, respectively. The elemental enrichment level and the pollution degree and the potential ecological risk of heavy metal in road dust in Beijing in 2004 were PM 2.5 >PM 10 . Se, a characteristic element of coal dust, was highly enriched in PM 2.5 in 2004, and Cd was high in PM 10 and PM 2.5 in 2004 with enrichment factors of 1024.03, 68.15, and 871.55, respectively. Co, Zn, Ca, and Cu were significantly enriched in PM 10 and PM 2.5 in 2004 with enrichment factors of 12.93, 12.33, 8.30, and 8.07 in PM 10 and 17.41, 21.80, 12.83, and 19.73 in PM 2.5 , respectively; Na and Si were not enriched in the road dust. The pollution load index (PLI) of heavy metals was 3.95 in PM 10 and 7.71 in PM 2.5 in 2004. Owing to the implementation of dust, motor vehicles, and combustion source control measures in Beijing and the relocation of the Shougang corporation, the elemental enrichment level, pollution degree, and potential ecological risk of heavy metals in road dust PM 2.5 in 2013 were significantly lower than those in 2004. The enrichment factors of Cd and Se in PM 2.5 in 2013 decreased to 98.47 and 0.95, respectively; those of Cu, Ca, and Zn decreased to 11.90, 8.84, and 8.20, respectively; and PLI decreased to 2.56. The results showed that the total potential ecological risk of heavy metals in road dust in Beijing was extremely strong. Heavy metal Cd was the most significant pollution factor and the main potential ecological risk source; its potential ecological risk index (RI) contribution to the total RI of heavy metals was more than 85%. In 2004, the pollution degree of heavy metals in road dust of main roads was significantly higher than that for other road types. The pollution degree of heavy metals in PM 10 was main road > expressway entrance to Beijing > secondary main road > ring road; that for PM 2.5 was main road > ring road > expressway entrance to Beijing > secondary main road. For PM 2.5 in 2013, however, the order was expressway entrance to Beijing > main road > ring road > secondary main road. The pollution degree of heavy metals in road dust of secondary main roads was significantly lower than that for other road types. In 2013, for road dust PM 2.5 in Beijing, the correlation of heavy metals Ti, Zn, V, Cr, Cu, Pb, and Ni was significant owing mainly to traffic-related emissions.

Simultaneous measurements of precursor gases NH 3 ,NO,NO 2 ,SO 2 and the main water-soluble ions in PM 2.5 such as sulphate (SO 4 2- ),nitrate (NO 3 - ) and ammonium (NH 4 + ) (collectively called SNA)were carried out in the urban area of Beijing during 2015-01 to 2015-12,which obtained 325 groups of samples. PTFE membrane filters were used to collect particulate NH 4 + , NO 3 - and SO 4 2- , followed by the online instruments to collect precursor gases. The pollution characteristics of the precursor gases and SNA were analyzed and their correlation was studied. The mean concentrations of NH 3 , NO, NO 2 , SO 2 , NH 4 + ,NO 3 - and SO 4 2- were 21.5, 17.7, 54.3, 14.2, 8.1, 13.5 and 12.7 μg·m -3 respectively during the period of monitoring, and SNA accounted for 43.4% of PM 2.5 . The concentrations of SO 2 ,NO x and SNA declined compared to 2014. The concentrations of NO,NO 2 and SO 2 were highest in winter and lowest in summer. The concentration of NH 3 was higher in summer and lower in autumn; The concentration and the percentage of NH 4 + were stable during the four seasons,both the concentrations and the percentage of NO 3 - were lowest in summer. The concentrations of SO 4 2- was highest in winter and the percentage was lowest in summer. The ratio of ([NO 3 - ]+2[SO 4 2- ]) and NH 4 + was 0.97 during the whole year, showing that anions mainly existed in the form of NO 3 - and SO 4 2- . In summer, the ratio of[NO 3 - ]+2[SO 4 2- ] and[NH 4 + ] was slightly higher than 1.0, which was the reason why NO 3 - was bound to Ca 2+ , Mg 2+ and Na + besides NH 4 + . With the increase of pollution, the mass concentration of precursor gases and SNA increased dramatically, among which NO x increased most rapidly, and SO 2 decreased from severe pollution to serious pollution. The contribution rate of NH 4 + was maintained at a relatively stable level. SO 4 2- had a higher contribution when the pollution level was lower, whereas the concentration of NO 3 - was higher than others and contributed most to PM 2.5 in heavy pollution. Heterogeneous transformation on the surface of particulate matter played a more important role in the formation of SO 4 2- and NO 3 - . The correlations between NO 3 - , NO 2 and NO,NH 4 + and NH 3 ,SO 4 2- and SO 2 were significant at the confidence level of 0.01. SO 4 2- had negative correlation with SO 2 , and NO 3 - had positive correlation with NO 2 . Compared with NH 3 , the NH 4 + concentration was more obviously affected by acid gases NO 2 , SO 2 .

Concentrations of water-soluble ions were measured in Beijing during 2014 for comparison of URG online monitoring systems and filter-based manual methods. The differences of four main ions components in spring, summer, autumn and winter were compared. The total concentrations of eight ions measured by URG online were higher than those of filter-based manual method. There was no significant differences among the annual concentrations of Cl - ,NO 3 - ,Mg 2+ and Ca 2+ obtained by the two methods, while the concentrations of SO 4 2- ,NH 4 + ,Na + ,K + from online were higher than those from filter. NO 3 - ,SO 4 2- ,Cl - had good correlations in autumn and winter, and NH 4 + only had better fitting performance in winter.

The mass concentration of PM₂.₅ associated with its online and off-line water-soluble ions were obtained during 2014- 10- 2014-11. Secondary inorganic species NO₃⁻, SO₄²⁻ and NH₄⁺ were the major components of PM₂.₅ during different observation periods. The total concentration of NO₃⁻, SO₄²⁻ and NH₄⁺ was (26.8 ± 22.5) µg · m⁻³, which contributed (41.7 ± 8.5)% to PM₂.₅. The concentration of NO₃⁻ was higher than those of others and contributed most to PM₂.₅. The ions of NO₃⁻, SO₄²⁻ NH₄⁺ and Cl⁻ all showed three different periods during 2014 Beijing APEC, besides the different meteorological condition, the cumulative effect caused by local emissions and regional pollution could also not be ignored. Although the characteristics of water-soluble ions was different during different observation periods, there was no obvious acidification of PM₂.₅ in Beijing at the end of autumn and beginning of winter.

From August 2012 to July 2013, 220 groups of PM2.5 samples were continuously collected at four locations in the urban area of Beijing (Shijingshan, Chegongzhuang, Dongsi, and Tongzhou), and the primary chemical species of PM2.5 were analysed by the chemical mass balance method. It was found that the mass of PM2.5 obtained from chemical mass balance method agreed well with the value from gravimetric measurement, with a good correlation of 0. 95 in spring, autumn, and winter. However, the correlation seasonally changed in summer, with a relatively lower correlation coefficient of 0. 77. The concentrations of OM, EC, SO(4)2-, NO3-, NH4+, Cl-, crustal matter, and trace species were 31. 4, 3. 8, 19. 9, 21. 6, 14. 4, 4. 0, 15. 4, and 2. 9 µg.m-3, which accounted for 25. 1%, 3. 0% , 15. 9%, 17. 2%, 11. 5%, 3. 2%, 12. 3%, and 2. 3% of PM2, , respectively. Besides crustal matter, concentrations of the primary chemical species in PM2.5 from the west to the east gradually increased. The most serious PM pollution occurred between 11 and 14 February 2013, during which concentrations of OM, SO2-, NO3-, NH4+ were 1. 9, 5. 0, 3.2 and 4. 2 times as high as the annual average. SO(4)2- was recognized as the most important species for the pollution in the process. OM was the largest component of urban PM2.5 during both heating and non-heating periods. Comparing to non-heating period, the concentrations of OM, NH4+, NO3-, and SO(4)2- all increased during the heating period, except for the component of crust and EC. The biggest difference between the two periods was the component of Cl- (4. 4 fold), which can be attributed to the burning of coal. For unknown components, the main component was moisture, which accounted for about 6.0% in urban PM2.5. The highest moisture appeared in summer (6. 5%), followed by spring and winter, and the least appeared in fall (3. 7% ).

A total of 486 daily PM2.5 samples were collected at a background site, 3 urban sites, 4 suburban sites and a boundary transfer site during August 2012-July 2013. Mass concentrations of 9 water-soluble ions were obtained. The average mass concentration of the 9 ions was 60.5 μg x m(-3), and the order of concentration of ions was NO3- > SO4(2-) > NH4(+)- > Cl- > Na+ > K+ > Ca2+ > F- > Mg2+; Secondary inorganic species NO3-, SO4(2-) and NH4+ were the major components of water-soluble ions in PM2.5, with a contribution of 88% to the total ions of PM2.5. NO3- was the most fluctuated anion during the sampling period. With the increase of pollution level, the accumulation of SNA was obvious, the components that contained nitrogen, NO3- and NH4+, occupied the dominant position in the formation of the secondary components. NO3- had a relatively higher contribution to the accumulation of heavy pollution.

Based on the environment monitoring data and the ambient air quality data during the period of 1997-2011 from Beijing municipal environmental monitoring center, the correlations between primary pre-cursors of acid deposition, acidic materials and precipitation in Beijing area were analyzed in detail by taking economic development and energy mix into account. These results will be helpful for assessing the performance of environment quality improvement, as well as supplying scientific supporting information to make policies for national and local environment protection authorities. The main findings included as follows: there are significant correlations between the concentrations of NO2, NOx, and SO2 in the atmosphere, which indicated that both N and S in ambient air of Beijing came from fossil fuels combustion; acidic pollutants in the air are mainly discharged from local emission sources in Beijing, while there is no obvious correlation between S and N in wet deposition and concentrations of SO2, NO2 and NOx in the atmosphere, which demonstrated that concentrations of different ions in the acid deposition were influenced by both local sources as well as the inputs from other surrounding districts. Besides, the concentration of NO3- appeared to be correlative with the amount of motor vehicles, implying that the NOx from motor vehicles have contributed the increase of NO3- concentration of substantially.

Characteristics of chemical compositions of precipitation in Beijing were analyzed. The average value of pH was 5.19 from 2005 to 2009, showing stable characteristics of acidification with precipitation. The lowest annual average pH was 4. 87 in 2008 with the highest acidification frequency of 42% and 23% in Chegongzhuang and Daxing districts respectively. The inorganic ion concentrations declined in 5a, indicating an increasing improvement of air quality in Beijing. The concentrations of NH4+ and NO3- were found to increase and contributed to the high nitrogen amount in precipitation. Different seasons have influence on composition concentrations. Generally speaking, the ion concentrations in winter were higher that that in summer. SO4(2-) was the main factor responsible for the acidification of snow in winter, SO4(2-) and NO3- had similar contributions to the acidification of precipitation in summer. It was also found that the local pollutants of SO2, NO(x) and NH3 were major contributors to the acidification of precipitation in Beijing area, local geological conditions and long-distance transfers have important effects on the neutralization of the precipitation.