Spatial and temporal distribution of toxic compounds in sediments and potential ecological effects on macrobenthic faunal species in Hangzhou Bay from 2003 to 2015.

The development of toxic compounds in sediment and macrobenthos species in Hangzhou bay (2003-2015) was evaluated. Concentrations were compared to Chinese sediment quality guidelines (CN-SQG) and risk assessed by the ecological risk index (ERI) and t-Distributed Stochastic Neighbour Embedding (t-SNE). To study seafood contamination, sediment and swimming crabs were collected. Chromium, copper, and arsenic exceeded CN-SQG. Organic contaminants did not exceed CN-SQG; however, t-SNE revealed a negative relationship with benthic species numbers. Since 2003, half of the benthic species have disappeared. Species sensitive to contamination were not observed after 2003-2007, while crustacea species are more tolerant: cadmium levels in crabs were 5-17 times those in the sediment, demonstrating strong bioaccumulation. These results suggest that metals and organic pollutants pose ecological and seafood risks. For good environmental management in HZB, it is important to analyze sediment, benthic biota, and seafood species for compounds known to pose toxic risks.

NRF2 deficiency sensitizes human keratinocytes to zinc oxide nanoparticles-induced autophagy and cytotoxicity.

Zinc oxide nanoparticles (ZnO NPs) are one of the most commonly used metal oxide particles in many industrial fields. Many studies have shown that ZnO NPs induce harmful effects to human skin, but the mechanisms remain poorly understood. Our results showed that ZnO NPs concentration-dependently induced cytotoxicity, ROS accumulation, and mitochondrial dysfunction in HaCaT cells. The expressions of adaptive antioxidant response transcriptional factor NRF2 and autophagy-related proteins P62 and LC3 II/I were increased by ZnO NPs. Knock-down of NRF2 (NRF2-KD) sensitized the cells to ZnO NPs-induced autophagy and cytotoxicity while an autophagy inhibitor, 3-methyladenine, protected the cells from ZnO NPs-induced cell death. These results demonstrated that NRF2 deficiency sensitizes human keratinocytes to ZnO NPs induced autophagy and cytotoxicity, and proposed a key role of NRF2 in protecting skin cells against ZnO NPs through regulation of antioxidants and autophagy.

Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis: Involvement of reduced PPARγ expression.

Non-alcoholic fatty liver disease (NAFLD) is an emerging global disease with increasing prevalence. However, the mechanism of NAFLD development is not fully understood. To elucidate the cell-specific role of nuclear factor erythroid-derived 2-like 2 (NRF2) in the pathogenesis of NAFLD, we utilized hepatocyte- and macrophage-specific Nrf2-knockout [Nrf2(L)-KO and Nrf2(Mϕ)-KO] mice to examine the progress of NAFLD induced by high-fat diet (HFD). Compared to Nrf2-LoxP littermates, Nrf2(L)-KO mice showed less liver enlargement, milder inflammation and less hepatic steatosis after HFD feeding. In contrast, Nrf2(Mϕ)-KO mice displayed no significant difference in HFD-induced hepatic steatosis from Nrf2-LoxP control mice. Mechanistic investigations revealed that Nrf2 deficiency in hepatocytes dampens the expression of peroxisome proliferator-activated receptor γ (PPARγ) and its downstream lipogenic genes in the liver and/or primary hepatocytes induced by HFD and palmitate exposure, respectively. While PPARγ agonists augmented PPARγ expression and its transcriptional activity in primary hepatocytes in a NRF2-dependent manner, forced overexpression of PPARγ1 or γ2 distinctively reversed the decreased expression of their downstream genes fatty acid binding protein 4, lipoprotein lipase and/or fatty acid synthase caused by Nrf2 deficiency. We conclude that NRF2-dependent expression of PPARγ in hepatocytes is a critical initiating process in the development of NAFLD, suggesting that inhibition of NRF2 specifically in hepatocytes may be a valuable approach to prevent the disease.

[Distribution, sources and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in surface sediments of Yangtze estuary and Zhejiang coastal areas].

PAHs contents of surface sediments were tested from 62 sampling sites of the Yangtze River estuary and Zhejiang coastal zone in 2013. The results showed that: 16 kinds of PAHs, which are listed as priority pollutants by EPA, were found in all the samples. The total PAHs level (dry weight) reached 31. 8-384 µg x kg(-1) and the average amount was 131.1 µg x kg(-1). The distribution of PAHs was affected by terrigenous input and point source pollution, the high-value zones were found at 2# sampling site of the Yangtze River estuary and 21# sampling site of Ningbo. Compared with other sea areas, the survey sea area was at a low PAHs pollution level. PAHs were primarily tetracyclic or tricyclic, and source analysis showed that most of PAHs were originated from combustion of wood and coal. Based on the Sediment Quality Guidelines (SQGs), the assessment result showed that the PAHs content of surface sediments from survey sea area was at a relatively low level of ecological risk; While according to the assessment result of the Sediment Quality Standards (SQSs), PAHs pollution of surface sediments from survey sea area displayed an "Obviously negative ecological effect" to some extent, and some countermeasures are required to control and eliminate pollutions.