Signaling by 4-hydroxy-2-nonenal: Exposure protocols, target selectivity and degradation.

4-hydroxy-2-nonenal (HNE), a major non-saturated aldehyde product of lipid peroxidation, has been extensively studied as a signaling messenger. In these studies a wide range of HNE concentrations have been used, ranging from the unstressed plasma concentration to far beyond what would be found in actual pathophysiological condition. In addition, accumulating evidence suggest that signaling protein modification by HNE is specific with only those proteins with cysteine, histidine, and lysine residues located in certain sequence or environments adducted by HNE. HNE-signaling is further regulated through the turnover of HNE-signaling protein adducts through proteolytic process that involve proteasomes, lysosomes and autophagy. This review discusses the HNE concentrations and exposure modes used in signaling studies, the selectivity of the HNE-adduction site, and the turnover of signaling protein adducts

ED-Dehaze Net: Encoder and Decoder Dehaze Network

The presence of haze will significantly reduce the quality of images, such as resulting in lower contrast and blurry details. This paper proposes a novel end-to-end dehazing method, called Encoder and Decoder Dehaze Network (ED-Dehaze Net), which contains a Generator and a Discriminator. In particular, the Generator uses an Encoder-Decoder structure to effectively extract the texture and semantic features of hazy images. Between the Encoder and Decoder we use Multi-Scale Convolution Block (MSCB) to enhance the process of feature extraction. The proposed ED-Dehaze Net is trained by combining Adversarial Loss, Perceptual Loss and Smooth L1 Loss. Quantitative and qualitative experimental results showed that our method can obtain the state-of-the-art dehazing performance

Knowledge-based clinical pathway for medical quality improvement

Clinical pathways have been adopted for various diseases in clinical departments for quality improvement as a result of standardization of medical activities in treatment process. Using knowledge-based decision support on the basis of clinical pathways is a promising strategy to improve medical quality effectively. However, the clinical pathway knowledge has not been fully integrated into treatment process and thus cannot provide comprehensive support to the actual work practice. Therefore this paper proposes a knowledgebased clinical pathway management method which contributes to make use of clinical knowledge to support and optimize medical practice. We have developed a knowledgebased clinical pathway management system to demonstrate how the clinical pathway knowledge comprehensively supports the treatment process. The experiences from the use of this system show that the treatment quality can be effectively improved by the extracted and classified clinical pathway knowledge, seamless integration of patient-specific clinical pathway recommendations with medical tasks and the evaluating pathway deviations for optimization

TGFβ1 rapidly activates Src through a non-canonical redox signaling mechanism.

Transforming growth factor-β1 (TGF-β) is involved in multiple cellular processes through Src activation. In the canonical pathway, Src activation is initiated by pTyr530 dephosphorylation followed by a conformational change allowing Tyr419 auto-phosphorylation. A non-canonical pathway in which oxidation of cysteine allows bypassing of pTyr530 dephosphorylation has been reported. Here, we examined how TGF-β activates Src in H358 cells, a small cell lung carcinoma cell line. TGF-β increased Src Tyr419 phosphorylation, but surprisingly, Tyr530 phosphorylation was increased rather than decreased. Vanadate, a protein tyrosine phosphatase inhibitor, stimulated Src activation itself, but rather than inhibiting Src activation by TGF-β, activation by vanadate was additive with TGF-β showing that pTyr530 dephosphorylation was not required. Thus, the involvement of the non-canonical oxidative activation was suspected. TGF-β increased extracellular H2O2 transiently while GSH-ester and catalase abrogated Src activation by TGF-β. Apocynin, a NADPH oxidase inhibitor, inhibited TGF-β-stimulated H2O2 production. Furthermore, mutation of cysteines to alanine, 248C/A, 277C/A, or 501C/A abrogated, while 490C/A significantly reduced, TGF-β-mediated Src activation. Taken together, the results indicate that TGF-β-mediated Src activation operates largely through a redox dependent mechanism, resulting from enhanced H2O2 production through an NADPH oxidase and that cysteines 248, 277, 490, and 501 are critical for this activation

Oxidative stress response and Nrf2 signaling in aging.

Increasing oxidative stress, a major characteristic of aging, has been implicated in a variety of age-related pathologies. In aging, oxidant production from several sources is increased, whereas antioxidant enzymes, the primary lines of defense, are decreased. Repair systems, including the proteasomal degradation of damaged proteins, also decline. Importantly, the adaptive response to oxidative stress declines with aging. Nrf2/EpRE signaling regulates the basal and inducible expression of many antioxidant enzymes and the proteasome. Nrf2/EpRE activity is regulated at several levels, including transcription, posttranslation, and interactions with other proteins. This review summarizes current studies on age-related impairment of Nrf2/EpRE function and discusses the changes in Nrf2 regulatory mechanisms with aging

Low dose inflammatory potential of silica particles in human-derived THP-1 macrophage cell culture studies - Mechanism and effects of particle size and iron.

Silica and iron are major constituents in ambient particulate matter, and iron is a common impurity in many engineered nanomaterials. The purpose of this work was to determine the pro-inflammatory and other biological effects and mechanism of particle size and iron presence under low dose, non-cytotoxic conditions that are likely to approximate actual exposure levels, in contrast with higher dose studies in which cytotoxicity occurs. Specifically, human-derived THP-1 macrophages were exposed to 1 μg/ml of pristine and iron-coated 50 nm and 2 μm engineered silica nanoparticles. Particles were first characterized for size, size distribution, surface area, iron concentration, phase and aggregation in cell culture media. Then, biological assays were conducted to determine a non-lethal dose used in subsequent experiments. Superoxide production, lipid peroxidation, and increased pro-inflammatory cytokine (TNF-α and IL-1β) mRNA expression were measured as a function of particle size and iron presence. Smaller particle size and the presence of iron increased superoxide production, lipid peroxidation, and the induction of pro-inflammatory cytokine mRNA expression. Separate addition of an iron-chelator, a scavenger of superoxide and hydrogen peroxide, and an inhibitor of phosphatidylcholine specific phospholipase C (PC-PLC), suppressed the increase in cytokine mRNA expression. Furthermore, free iron itself showed none of the aforementioned effects. The results highlight the importance of particle size and iron in lung inflammation for both natural and engineered nanomaterials, under low dose, non-toxic conditions, and support the role of an oxidant, lipid peroxidation and PC-PLC dependent inflammatory mechanism

Delayed Nrf2-regulated antioxidant gene induction in response to silica nanoparticles.

Silica nanoparticles with iron on their surface cause the production of oxidants and stimulate an inflammatory response in macrophages. Nuclear factor erythroid-derived 2 - like factor 2 (Nrf2) signaling and its regulated antioxidant genes play critical roles in maintaining redox homeostasis. In this study we investigated the regulation of four representative Nrf2-regulated antioxidant genes; i.e., glutamate cysteine ligase (GCL) catalytic subunit (GCLC), GCL modifier subunit (GCLM), heme oxygenase 1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1), by iron-coated silica nanoparticles (SiO2-Fe) in human THP-1 macrophages. We found that the expression of these four antioxidant genes was modified by SiO2-Fe in a time-dependent manner. At 6h, their expression was unchanged except for GCLC, which was reduced compared with controls. At 18h, the expression of these antioxidant genes was significantly increased compared with controls. In contrast, the Nrf2 activator sulforaphane induced all antioxidant genes at as early as 3h. The nuclear translocation of Nrf2 occurred later than that for NF-κB p65 protein and the induction of proinflammatory cytokines (TNFα and IL-1β). NF-κB inhibitor SN50 prevented the reduction of GCLC at 6h and abolished the induction of antioxidant genes at 18h by SiO2-Fe, but did not affect the basal and sulforaphane-induced expression of antioxidant genes, suggesting that NF-κB signaling plays a key role in the induction of Nrf2-mediated genes in response to SiO2-Fe. Consistently, SN50 inhibited the nuclear translocation of Nrf2 caused by SiO2-Fe. In addition, Nrf2 silencing decreased the basal and SiO2-induced expression of the four reprehensive antioxidant genes. Taken together, these data indicated that SiO2-Fe induced a delayed response of Nrf2-regulated antioxidant genes, likely through NF-κB-Nrf2 interactions

Statistical characteristics of ionospheric backscatter observed by SuperDARN Zhongshan radar in Antarctica

Zhongshan HF radar, as one component of SuperDARN, has been established and in operation since April, 2010. Using data from the first two years of its operation, this paper investigates the radar’s performance, the diurnal and seasonal variations of ionospheric echoes, and their dependence on geomagnetic activity. Statistical studies show that the occurrence of echoes in different beams varies at different frequencies, which arises from the direction of the beam and the area over which the beam can achieve the orthogonality condition between the wave vector and the Earth’s magnetic field. The diurnal variation is obvious with double peak structures both in the occurrence rate and average power at 04–08 UT and 16–17 UT. The line-of-sight velocities are mainly positive on the dayside and negative on the nightside for Beam 0, which is the opposite of the trend for Beam 15. The spectral widths on the dayside are often higher than those on the nightside owing to the high energy particle precipitation in the cusp region. The seasonal variations are more obvious for those beams with larger numbers. The occurrence, the average power, the line-of-sight velocity, and the spectral widths are generally larger in the winter months than in the summer months. The influence of geomagnetic activity on radar echoes is significant. The peak echo occurrence appears on the dayside during geomagnetically quiet times, and shifts toward the nightside and exhibits an obvious decrease with increasing Kp. With increasing geomagnetic activity, the line-of-sight velocities increase, whereas the spectral widths decrease. The frequency dependence is investigated and it is found that in the operating frequency bands in 2010, 9–10 MHz is the most appropriate band for the SuperDARN Zhongshan radar

Ecosystem health towards sustainability

Ecosystems are becoming damaged or degraded as a result of stresses especially associated with human activities. A healthy ecosystem is essential to provide the services that humans and the natural environment require and has tremendous social and economic value. Exploration of the definition of ecosystem health includes what constitutes health and what it means to be healthy. To evaluate ecosystem health, it is necessary to quantify ecosystem conditions using a variety of indicators. In this paper, the main principles and criteria for indicator selection, classification of indicators for different kinds of ecosystems, the most appropriate indicators for measuring ecosystem sustainability, and various methods and models for the assessment of ecosystem health are presented. Drivers, sustainability, and resilience are considered to be critical factors for ecosystem health and its assessment. Effective integration of ecological understanding with socioeconomic, biophysical, biogeochemical, and public-policy dimensions is still the primary challenge in this field, and devising workable strategies to achieve and maintain ecosystem health is a key future challenge