Synthesis and Photodynamic Activity of Peri-xanthenoxanthene Derivatives.

Photodynamic therapy (PDT) is a modern cancer therapy. But it is still difficult to obtain ideal photosensitizers. We synthesized six new peri-xanthenoxanthene derivatives rapidly and efficiently using solid-phase carbon-bath microwave irradiation technology, and investigated their in vitro photodynamic antitumor activity with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Our results showed that all compounds exhibited extremely low dark cytotoxicity and good phototoxicity against four human cancer cell lines. In particular, compound 3c showed the best in vitro PDT activity against Hela cells and Bel-7402 cells with IC50 values of 91 and 74 nmol/L, respectively. Its value of 1-octanol/water partition coefficient (log Kow) was 0.5309, suggesting that it is a promising photosensitizer for PDT due to its low dark cytotoxicity, high phototoxicity, and potential water solubility.

Persistency of Enlarged Autolysosomes Underscores Nanoparticle-Induced Autophagy in Hepatocytes.

The diverse biological effects of nanomaterials form the basis for their applications in biomedicine but also cause safety issues. Induction of autophagy is a cellular response after nanoparticles exposure. It may be beneficial in some circumstances, yet autophagy-mediated toxicity raises an alarming concern. Previously, it has been reported that upconversion nanoparticles (UCNs) elicit liver damage, with autophagy contributing most of this toxicity. However, the detailed mechanism is unclear. This study reveals persistent presence of enlarged autolysosomes in hepatocytes after exposure to UCNs and SiO2 nanoparticles both in vitro and in vivo. This phenomenon is due to anomaly in the autophagy termination process named autophagic lysosome reformation (ALR). Phosphatidylinositol 4-phosphate (PI(4)P) relocates onto autolysosome membrane, which is a key event of ALR. PI(4)P is then converted into phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 ) by phosphatidylinositol-4-phosphate 5-kinase. Clathrin is subsequently recruited by PI(4,5)P2 and leads to tubule budding of ALR. Yet it is observed that PI(4)P cannot be converted in nanoparticle-treated hepatocytes cells. Exogenous supplement of PI(4,5)P2 suppresses the enlarged autolysosomes in vitro. Abolishment of these enlarged autolysosomes by autophagy inhibitor relieves the hepatotoxicity of UCNs in vivo. The results provide evidence for disrupted ALR in nanoparticle-treated hepatocytes, suggesting that the termination of nanoparticle-induced autophagy is of equal importance as the initiation.

[Exposure Level of Population and Economy in Zhejiang Province Considering the Background of PM2.5 in East China].

Using the satellite-derived Fine Particulate Matter (PM2.5) data of global high-precision products during 1998-2012, detailed characteristics of PM2.5 distribution over East China and its change are given, and the PM2.5 exposure levels for population and economy in Zhejiang is further analyzed in this context. The results show that the overall variability of the regional average value of PM2.5 concentration exhibits an increasing trend followed by a decrease during 1998-2012, which is consistent in both the East China and Zhejiang provinces; the turning point occurs around 2007-2009. In the initial years (1998-2000), annual average PM2.5 concentrations are below 50 µg·m-3 in the southern part of East China and eastern part of Shandong, while it is 50-75 µg·m-3 in other areas. During this period, 51.8% of the area in East China and 21.1% of the area in Zhejiang have PM2.5 concentrations larger than 35 µg·m-3 (Air quality standard value in China). The rising trend in PM2.5 concentration is extremely obvious in 1998-2009; the mean linear trend over East China is 2.58 µg·(m3·a)-1, while it is 1.43 µg·(m3·a)-1 over Zhejiang province. PM2.5 concentration reaches its maximum during 2007-2009. The area where PM2.5 concentration is larger than 35 µg·m-3 reaches 82.1% in East China and 65.9% in Zhejiang province. After that, the PM2.5 concentration begins to decrease in each region, and the average change trend in East China and Zhejiang are -1.75 µg·(m3·a)-1 and -1.58 µg·(m3·a)-1, respectively. The regional area in which PM2.5concentrations aregreater than 35 µg·m-3 displays a slight decline during 2010-2012, which suggests that the energy conservation and emission reduction plan proposed by the Chinese government and associated measures may play a vital role in improving air quality of East China. In 2010, the proportion of the population and GDP for which the PM2.5 exposure level exceeded 35 µg·m-3 were 74.0% and 70.8%, respectively, of which 38.1% of the population lives in an environment where annual average PM2.5 concentrations are more than 50 µg·m-3. In addition, 38.9% of the GDP is produced in an environment with annual average PM2.5 concentrations more than 50 µg·m-3.

In vitro anti-HCV activities of Saxifraga melanocentra and its related polyphenolic compounds.

The aim of this study was to search for new natural anti-HCV agents from Chinese herbal medicine. Bioactivity-guided extraction and isolation methods were used. Active part and pure compounds were obtained from ethanolic extract of Saxifraga melanocentra Franch. and their in vitro inhibitory activities (IC50) against HCV NS3 serine protease were tested by enzyme-linked immunosorbent assay. Results showed that the polyphenolic ethyl acetate part of the herbal extract was the most active, and from this 18 polyphenols representing active compounds were isolated and identified. IC50 values of these compounds and five related ones were obtained. A broad-degree of anti-HCV activity was observed among them in the following order: gallated esters of D-glucose and rutin (0.68-4.86 microM)> flavonoids (33.11-370.37 microM)> gallic acid and its methyl and ethyl esters, Bergenin and others (over 1000 microM). The most active compound was 1,2,3,4,6-penta-O-galloyl-beta-D-glucoside (0.68 microM). In conclusion, polyphenols were responsible for the anti-HCV constitution of S. melanocentra, and multigallated esters of D-glucose possessed the strongest inhibition against HCV NS3 serine protease and little cytotoxic effect, suggesting the potential use of these compounds for designing and developing drugs for treatment of the viral infection.

[Analysis of acid rain characteristics of Lin'an Regional Background Station using long-term observation data].

Using long-term observation data of acid rain at Lin'an Regional Background Station (Lin'an RBS), this paper studied the interannual and monthly variations of acid rain, the reasons for the variations, and the relationships between acid rain and meteorological factors. The results showed that interannual variation of acid rain at Lin'an RBS had a general increasing trend in which there were two obvious intensifying processes and two distinct weakening processes, during the period ranging from 1985 to 2012. In last two decades, the monthly variation of acid rain at Lin'an RBS indicated that rain acidity and frequency of severe acid rain were increasing but the frequency of weak acid rain was decreasing when moving towards bilateral side months of July. Acid rain occurrence was affected by rainfall intensity, wind speed and wind direction. High frequency of severe acid rain and low frequency of weak acid rain were on days with drizzle, but high frequency of weak acid rain and low frequency of severe acid rain occurred on rainstorm days. With wind speed upgrading, the frequency of acid rain and the proportion of severe acid rain were declining, the pH value of precipitation was reducing too. Another character is that daily dominant wind direction of weak acid rain majorly converged in S-W section ,however that of severe acid rain was more likely distributed in N-E section. The monthly variation of acid rain at Lin'an RBS was mainly attributed to precipitation variation, the increasing and decreasing of monthly incoming wind from SSE-WSW and NWN-ENE sections of wind direction. The interannual variation of acid rain could be due to the effects of energy consumption raising and significant green policies conducted in Zhejiang, Jiangsu and Shanghai.