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

The effect of solute segregation on stability and strength of Cu symmetrical tilt grain boundaries from the first-principles study

Grain boundary (GB) stability and strength are two essential points for nanocrystalline materials. In this study, the effects and underlying mechanisms of segregation-induced GB stabilization and GB strengthening in various Cu GBs for selected 8 alloying elements (Mg, Ca, Cr, Ni, Zn, Zr, Ag and Sn) were investigated through first-principles total energy calculations. The segregation energy results show that all other elements excluding Ni can segregate to GB thus improving the GB stability. The segregation driving force is associated with the volume of Voronoi cell of solute, in the trend that increases along with the volume of Voronoi cell growth. The stabilizing mechanism should attribute to the decrease in the number of antibonding electrons. As to GB strength, the embrittling potency results show that Mg, Cr, Zr and Ag are enhancers in Σ5 [001](310) GB, while for Σ5 [001](210) and Σ11 [110](113) GBs, only Cr and Zr are enhancers. The embrittling potency is concerned with segregation energy and the volume of Voronoi cell of solute, in a trend that increases with the segregation energy decline and the volume of Voronoi cell growth. The enhancing mechanism lies in the formation of covalent-like bonds between solute and matrix atoms. Furthermore, by comparing the stabilizing and strengthening effectiveness of alloying elements in various Cu GBs. The trend that the worse the stability and strength of GBs, the better the stabilizing and strengthening effects of alloying elements were revealed

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

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

Study on Long-Term Dynamic Mechanical Properties and Degradation Law of Sandstone under Freeze-Thaw Cycle

This study is based on the tunnel-face slope engineering of Dongfeng tunnel in Shanxi section of China’s Shuozhou-Huanghua Railway. The sandstone specimens in the perennial freeze-thaw zone of the slope were collected to carry out freeze-thaw cycle static physical mechanics test and split Hopkinson pressure bar (SHPB) dynamic mechanical test. Thus, the damage process of sandstone under freeze-thaw cycle and impact load is studied. Also, the dynamic compressive strength and dynamic elastic modulus of sandstone are analysed under different loading strain rates and freeze-thaw cycle based on LS-DYNA, a dynamic finite element program. The results showed that the dynamic compressive strength of sandstone subjected to multiple freeze-thaw cycles under 0.04 MPa air pressure has a greater damage ratio than that under 0.055 MPa and 0.07 MPa air pressure, which was more likely to cause damage to slope sandstone than in actual engineering; the dynamic compressive strength and elastic modulus of sandstone decrease greatly within a certain range of freeze-thaw cycles and loading strain rate, leading to significant deterioration. When the freeze-thaw cycle exceeded 200 times and the strain rate was greater than 200 s−1, the physical and mechanical properties of sandstone gradually tended to be stable

Tunable crystallographic grain orientation and Raman fingerprints of polycrystalline SnO thin films

In this study, (001) and (101)-orientated polycrystalline SnO films were respectively fabricated. The preferred orientation conversion was observed by modifying the stoichiometry of the SnO films. It was revealed that the O-rich and Sn-rich SnO films favor (001) and (101) grain orientations, respectively. Moreover, based on the Raman selection rule and our experimental results, the 110 cm(-1) Raman peak is assigned to the low-frequency E-g mode of SnO. The Raman intensity ratio between the 110 cm(-1) and 210 cm(-1) peak of SnO increases with the relative texture coefficient of the (101) grain orientation but decreases with that of the (001) one, demonstrating that the Raman characteristic information could be used as fingerprint recognition to mutually predict the crystallographic texture of SnO films

Repressive effects of TET on the expression of COX-1 and COX-2 in LPS-induced hyperalgesia.

<p>(A) Western blotting of COX-1 and COX-2 in brain tissues and the quantified comparison of relative densities are shown. (B) COX-1 and COX-2 mRNA expression were tested by qRT-PCR in brain tissues. (C) COX-1 and COX-2 mRNA expression were tested by qRT-PCR in cultured astroglia. Values are shown as M±SD, and normalized to the NS groups. *, <i>P</i><0.05.</p

Induction of hyperalgesia by LPS in BALB/C mice.

<p>(A) Molecular structure of TET. (B) Latency time of hind-paw licking in the hot-plate test in mice that were treated with LPS at different concentrations and time points. (C) Writhing counts obtained from the acetic acid-induced abdominal constriction test in mice that were treated with LPS at different concentrations and time points. (D and E) Percentages of protection by TET (15, 30, 45 mg/kg) at 6 h after LPS (100 μg/kg) stimulus, as indicated by the hot-plate test (D) or acetic acid-induced abdominal constriction test (E). Indomethacin (5 mg/kg) and morphine (10 mg/kg) were applied as the positive controls. Values are shown as M±SD. *, <i>P</i><0.05.</p