Paraquat-induced reactive oxygen species inhibit neutrophil apoptosis via a p38 MAPK/NF-κB-IL-6/TNF-α positive-feedback circuit.

Paraquat (PQ), a widely used herbicide and potent reactive oxygen species (ROS) inducer, can injure multiple tissues and organs, especially the lung. However, the underlying mechanism is still poorly understood. According to previous reports, neutrophil aggregation and excessive ROS production might play pivotal pathogenetic roles. In the present study, we found that PQ could prolong neutrophil lifespan and induce ROS generation in a concentration-independent manner. Activated nuclear factor-κB (NF-κB), p38 mitogen-activated kinase (p38 MAPK), and myeloid cell leukemia sequence 1 (Mcl-1) but not Akt signaling pathways were involved in this process, as well as increasing levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β. Furthermore, the proinflammatory mediators IL-6 and TNF-α could in turn promote ROS generation, creating a vicious cycle. The existence of such a feedback loop is supported by our finding that neutrophil apoptosis is attenuated by PQ in a concentration-independent manner and could partially explain the clinical dilemma why oxygen therapy will exacerbate PQ induced tissue injury

Research on Shape Changes in Cylinder Electrodes Incident to Micro-EDM

This paper discusses electrode wear changes under different operating conditions. A series of experiments were designed and conducted using an EDM machine tool with a rectangular pulse power supply. The phenomena of the cylinder electrode shape changes were abstracted from the experiments; the change mechanisms of the end face are discussed and verified by experimental data and interrelated theory. The results disclose that the shape of an electrode is subject to pulse-on time, discharge current density, and electrode polarity

TNF-α and IL-6, but not IL-1β, formed a positive-feedback circuit with ROS generation upon PQ stimulus.

<p>(A) TNF-α, IL-1β, and IL-6 production levels were remarkably promoted by PQ and significantly decreased by DPI. (B) PQ-induced ROS generation was decreased by preincubation with TNF-α or IL-6 antibody respectively, but not by IL-1β, which indicated a positive-feedback circuit between the regulation of ROS generation and TNF-α and IL-6 production under PQ stimulus. ROS contents were normalized to control. *<i>P</i><0.05.</p

INFLUENCING FACTOR ANALYSIS OF FATIGUE CRACK INITIATION LIFE ON CRANE LATTICE BOOM

The crane lattice boom is complex and the load is diversity,part of the structure may suffer plastic deformation because of the high stress concentration or poor weld quality under exceptional poor load conditions. So using strain analysis parameter is reasonable compared to stress parameter. The paper was focused on the fatigue crack initiation stage of crane lattice boom. The method of local stress strain was used combined with the correction Neuber method. A crane fatigue crack initiation life evaluation algorithm model was built. According to the model,three main factors which will influence the initiation life calculation were analyzed and compared. Fatigue tests were also carried out with K nodes of crane lattice boom. When the material was determined under certain circumstances,the stress concentration factor had the most impact result on the life. The mean stress on the material had the less impact but it cannot be ignored. According to the Factors,optimization suggestions to lattice boom spatial structure and work process improvement measures were proposed

p38 MAPK and NF-κB signaling pathways, but not Akt, were involved in PQ-induced ROS generation and reduced neutrophil apoptosis.

<p>(A, B) p-p38 MAPK and p-Mcl-1 production were predominantly induced by PQ and suppressed by DPI co-treatment. The specific p38 MAPK inhibitor SB203580 blocked both p-p38MAPK and p-Mcl-1 productions, whereas SC200137 suppressed p-Mcl-1 but not p-p38MAPK. (C) The Akt pathway was not affected by PQ. (D, E) Both p-IκBα and p-P65 were activated by PQ pretreatment and decreased by DPI. (F) PQ-mediated reduction in neutrophil apoptosis could be rescued by SB203580, SC200137, and PDTC but not SC221226, which indicated that p38MAPK, Mcl-1, and NF-κB pathways were involved in the PQ-regulated decrease in neutrophil apoptosis. *<i>P</i><0.05.</p

ROS were involved in PQ-induced neutrophil apoptosis delay.

<p>(A) ROS generation was assessed with DCFH-DA fluorescence intensity and was remarkably increased by all PQ concentration (5, 50, and 100 μM) at all time points (6, 12, 18, and 24 h) in a concentration-independent manner. (B) DPI or apocynin pretreatment suppressed PQ-induced ROS generation. (C) PQ-induced neutrophil apoptosis was also attenuated by DPI or apocynin pretreatment. ROS contents were normalized to control. *<i>P</i><0.05.</p

PQ delayed neutrophil apoptosis in a concentration-independent manner.

<p>Neutrophil apoptosis was assessed with annexin V-FITC and PI staining followed by flow cytometry. Compared with the control, the doses of PQ (5, 50, or 100 μM) significantly attenuated neutrophil apoptosis at all time points after treatment (6, 12, 18, and 24 h). No difference was found between different concentration groups. *<i>P</i><0.05 compared with control at the same time point.</p