NOX2 inhibition stabilizes vulnerable plaques by enhancing macrophage efferocytosis via MertK/PI3K/AKT pathway.

NADPH oxidases 2 (NOX2) is the main source of ROS in macrophages, which plays a critical role in the formation of atherosclerosis. However, effects of NOX2 inhibition on established vulnerable plaques and the potential role involved remain unclear. The purpose of this study is to investigate the latent mechanism of NOX2-triggered vulnerable plaque development. We generated a vulnerable carotid plaque model induced by carotid branch ligation and renal artery constriction, combined with a high-fat diet in ApoE-/- mice. NOX2 specific inhibitor, GSK2795039 (10 mg/kg/day by intragastric administration for 8 weeks) significantly prevented vulnerable plaque, evaluated by micro-ultrasound imaging parameters. A profile of less intraplaque hemorrhage detection, increased collagen-lipid ratio, fibrous cap thickness and less necrotic core formation were also found in GSK2795039 treated group. Mechanistically, reduced 4-HNE, in situ lesional apoptosis and enhanced efferocytosis were involved in mice treated with NOX2 inhibitor. Further analysis in mouse macrophages confirmed the role of NOX2 inhibition in enhancing macrophage efferocytosis by regulating the MertK/PI3K/AKT pathway. In summary, our data defined previously few recognized roles of NOX2 in vulnerable plaque pathogenesis and an undescribed NOX2-ROS-MerTK axis acts involved in regulating macrophage efferocytosis in the formation of rupture-prone vulnerable plaques.

Manipulative experiments networks on response and adaptation of terrestrial ecosystems to environmental changes: Building the research methods and technology system.

The feedback relationship between organisms or ecosystems and environment has been a key issue in ecological research. Manipulative experiments with changing biological or environmental factors and large-scale field experiment networks were regarded as effective approaches to understand and accurately quantify the process and mechanisms underlying ecosystem response and adaptation to environmental changes. In recent years, a few networks have been developed, including large-scale networks of field physics simulation experiment (i.e., ECOTRON), ecosystem analysis and experiment platform (AnaEE), international Drought Network, Nutrient Network, and experiment networks based on regional ecological observation stations (i.e., USA-ILTER) at global scale. The development of continent-scale experiment network platform is attracting more attention from the academic community, and will play a more important role in understanding the process and mechanism underlying ecosystem responses to environmental change. We reviewed the development of method and experiment system of ecosystem manipulative experiments, and clearly pointed out that different experiments should form a joint collaborative system to answer fundamental scientific questions about the response and adaptation of ecosystem to global environment change. Manipulative experiments could be classified into four types: 1) Physiological and ecological experiments in closed laboratory equipment; 2) semi-open experiments with changing environmental factors in the field; 3) near-natural field experiments; 4) experiment networks based on field ecological station. Furthermore, we discussed the trends in network design of manipulative experiments focusing on ecosystem response and adaptation to environmental changes and the advantages of large-scale experiments based on natural environmental gradients. We put forward a proposal of integrating the technical advantages of different types of experiments and developing a new generation of field experiment network system. The study discussed the research system based on field experiment network, demonstrated the possibility to understand the patterns and mechanisms of the ecosystem short-term response and long-term adaptation to environmental changes, and proposed some equations to quantify the environmental response of ecosystems. The application of the design plan of the manipulative experiments network proposed here will greatly promote the scientific research level of ecosystems and environmental changes in China and even over the whole world, which has important scientific significance for the national response to climate change and ecological environmental construction.

[Spermine attenuates high glucose-induced myocardial fibrosis by regulating the cell cycle].

Objective: To investigate the protective effect of spermine (Sp) on diabetic cardiomyopathy (DCM) and high glucose-induced cardiac fibroblasts (CFs), and to explore its mechanism.Methods: ①Animal experiments: 24 male Wistar rats were randomly divided into control group, type 1 diabetes group (TID) and spermine group (TID+Sp, each group n=8). TID rats were induced by streptozocin (STZ, 60 mg/kg), and TID+Sp rat were pretreated with spermine (Sp, 5 mg/(kg·d)) for 2 weeks before STZ injection. After 12 weeks of modeling, blood glucose, insulin levels, ejection fraction (EF) and shortening fraction (FS) were measured, and Masson staining and Sirius red staining were performed in the rat cardiac tissues. ②Cell experiments: primary CFs were extracted from newborn (1-3 d) Wistar rat hearts, and were randomly divided into control group, high-glucose group (HG) and HG+Sp group (n=6 per group). HG group was treated with 40 mmol/L glucose, and the HG+Sp group was pretreated with 5 µmol/L Sp for 30 min before HG treatment. The cell viability of CFs was detected by CCK8, the content of collagen in culture medium was analyzed by ELISA, and protein expressions of cell cycle related proteins (PCNA, CyclinD1 and P27) were detected by Western blot. Results: Compared with control group, the blood glucose and collagen content were increased, and the insulin level and heart function were decreased in the T1D group. Meanwhile, HG induced an increasing of the cell viability, the collagen content in the medium and the expressions of PCNA and CyclinD1, while the expression of P27 was down-regulated. Spermine could reduce the above changes, manifested as improving the cardiac function, regulating the expression of cyclin and reducing the level of myocardial fibrosis. Conclusion: Spermine can alleviate myocardial fibrosis in diabetic cardiomyopathy, which mechanism is related to the regulation of cell cycle.

[Seasonal variations of soil enzyme activities in typical plant communities in the Ebinur Lake wetland, China]. / è‰¾æ¯”æ¹–æ¹¿åœ°å ¸åž‹æ¤ç‰©ç¾¤è½åœŸå£¤é ¶æ´»æ€§å­£èŠ‚å˜åŒ–ç‰¹å¾.

In this study, the soil catalase, phosphatase and urease activities of typical plant communities of reed (Phragmites australis) and tamarisk (Tamarix ramosissima) and their influencing factors were investigated in Ebinur Lake wetland. The results showed that three soil enzyme activities of reed and tamarisk had seasonal dynamic characteristics during different growth periods. For the reed community, the peak concentrations of soil catalase, phosphatase and urease appeared at vigorous stage with 3.26, 0.60 and 0.33 mg·g-1, respectively, and the minimum value occurred at budding stage and leaf-expansion stage. For the tamarisk community, the peak values of three soil enzyme activities appeared at withered stage with values of 6.33, 0.58 and 0.21 mg·g-1, respectively, and the valley values were observed at flowering and vigorous stages. Urease was stable during different growth periods, and it could be used as an indicator to identify the differences of soil enzyme activities in the wetlands. The enzyme activities of reed and tamarisk had significant positive correlation with soil organic matter and total P in all growth periods, while there was no significant relationship between enzyme activities and soil water content. The enzyme activities of reed had significant positive correlation with ammonium nitrogen in the rapid growth period. There were no significant relationships between enzyme activities and soil salinity in both communities. The soil enzyme activities of reed and tamarisk were controlled by many factors. Soil organic matter, soil water and soil temperature were the main factors influencing the enzyme activities in the Ebinur Lake wetland.

[Distribution and health risk assessment of heavy metals of groundwaters in the irrigation district of the lower reaches of Yellow River].

In order to investigate the contamination levels of groundwater in the irrigation districts of the lower reaches of Yellow River, fifty-nine groundwater samples collected from the irrigation districts of Henan and Shandong provinces, were analyzed. Health risks associated with eleven metals (Ba, Cd, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se and Zn) were assessed using water pollution index and USEPA health risk assessment model. The average concentrations of Fe with 0.496 mg x L(-1) and Zn with 0.445 mg x L(-1) were higher than the concentrations of other heavy metals. Concentrations of Fe, Mn, Se and Zn exceeded the relevant standards and the over-standard rates by 27.12%, 27.12%, 15.25% and 5.09%, respectively. Inverse distance weighted method was applied to estimate the unobserved points and their distribution maps were obtained, which indicated that areas of over-standard heavy metals were Wucheng country, Fan country, Dong'e country, Yucheng city and Guan country. Health risks of ingestion of water for all non-carcinogenic metals are higher than those of dermal absorption, while health risks of ingestion of water for carcinogenic metals is lower than those of dermal absorption. Among the health risks caused by the carcinogenic metals in drinking water and dermal absorption, the highest risks associated with Cr, are seven times and twenty-eight times as that of Cd, respectively, but both were significantly lower than the maximum allowance levels recommended by ICRP (5 x 10(-5) a (-1)). The non-carcinogenic metal risks( Ba, Cu, Fe, Mn, Mo, Ni, Pb, Se and Zn), ranging from 1.73 x 10(-13) to 3.46 x 10(-10) a(-1) in dermal absorption and from 1.13 x 10(-9) to 6.06 x 10(-8) a(-1) in drinking water, were much lower than the maximum allowance levels.

Behavior and fate of alkylphenols in surface water of the Jialu River, Henan Province, China.

The behavior and fate of alkylphenols (APs) were studied in surface water from the Jialu River, Henan Province, China. Located at its upper stream, Zhengzhou city is regarded as the major discharge source to this river with its annual effluents containing 726 kg for nonylphenol (NP) and 30.2 kg for octylphenol (OP). The concentrations of NP and OP in surface water ranged from 75.2 to 1520 ngL(-1) and from 20.9 to 63.2 ngL(-1), respectively. To assess the behavior of APs along the river, a mass balance equation based on chloride was adopted, due to its relative conservation. The results showed that dilution effect was prevailing in determining the APs concentrations in surface water along the river. The effect of potential biodegradation was also estimated with an assumption of the optimized biodegradation. The contributions of dilution and biodegradation to the decline of APs concentrations were 38.8%, 23.7% for NP and 57.8%, 24.3% for OP, respectively. The other contribution to the decline of APs concentrations along the river was considered as an integrated effect of adsorption and air-water exchange with the values of 37.5% for NP and 17.9% for OP. The decay half-lives of NP and OP from surface water bodies were 1.6 and 2.4d, respectively. About 70.2% of total NP and 24.1% of total OP were finally eliminated from water phase to surrounding matrix in the downstream. The results suggested that the downstream river channel served as the net sink of APs in the study area.