BackgroundMacrophage infiltration and polarization are crucial for the pathogenesis of intracranial aneurysm (IA) rupture. Axl, a receptor tyrosine kinase, is involved in inflammation and efferocytosis in multiple organs. Upregulated soluble Axl in cerebrospinal fluid (CSF) and plasma is correlated with intracranial aneurysm rupture. This study aimed to investigate the role of Axl in IA rupture and macrophage polarization.MethodsMale C57BL/6J mice were used to induce IA. The level of Axl from control vessels and unruptured and ruptured IA samples was detected. In addition, the relationship between Axl and macrophages was confirmed. The pathway of Axl-mediated macrophage polarization was explored after IA induction in vivo and in bone marrow-derived macrophages (BMDMs) stimulated by LPS/IFN-γ in vitro. The animals were randomized into three groups and treated intraperitoneally with the vehicle, selective AXL antagonist R428, and recombinant mouse growth arrest-specific 6 (rmGas6) for 21 consecutive days. Then, we evaluated the influence of Axl on IA rupture by administrating R428 to inhibit or rmGas6 to activate the Axl receptor in vivo.ResultsCompared with that in normal vessels, Axl expression was significantly upregulated in unruptured IA samples. The ruptured IA tissue exhibited significantly higher expression of Axl than the unruptured IA tissue. Axl and F4/80 were coexpressed in IA tissue and LPS/IFN-γ-stimulated BMDMs. R428 treatment significantly reduced the rate of M1-like macrophage infiltration and IA rupture. In contrast, rmGas6 treatment promoted M1 macrophage infiltration and IA rupture. Mechanistically, R428 inhibited the phosphorylation of Axl and STAT1 and the expression of hypoxia-inducible factor-1α (HIF-1α) and decreased the levels of IL-1β, NOS2, and MMP9 in LPS/IFN-γ-stimulated BMDMs. rmGas6 promoted the phosphorylation of Axl and STAT1 and the expression of HIF-1α. In addition, STAT1 knockdown abolished Axl-mediated M1 macrophage polarization.ConclusionThe inhibition of Axl reduced macrophage polarization toward the M1 phenotype via the STAT1/HIF-1α signaling pathway and prevented IA rupture in mice. This finding suggests that pharmacological inhibition of Axl might be used to prevent the progression and rupture of IA.

No abstract

Curcumin could be used as a modulator of gut microbiota for intestinal health improvement and immunity homeostasis via modulation of the BA-FXR pathway and ILC3s function.

No abstract

No abstract

No abstract

This article presents the application of a computational fluid dynamics (CFD) finite volume method (FVM) model for a thermo-mechanical coupling simulation of the weld pool used in variable polarity plasma arc welding (VPPAW). Based on the mechanism of the additional pressure produced through self-magnetic arc compression and the jet generated from mechanical plasma arc compression, and considering the influence of arc height and keyhole secondary compression on arc pressure, a three-dimensional transient model of variable polarity plasma arc (VPPA) arc pressure was established. The material flow behaviors of the perforated weld pools were studied. The results show that three kinds of flow behavior existed in the perforation weld pools and it is feasible to predict the weld pool stability by the material flow behaviors of the perforated weld pools. The weld pools can exist stably if the material flow in the bottom of the perforated weld pools can form confluences with moderate flow velocities of 0.45 m/s, 0.55 m/s and 0.60 m/s. The weld pools were cut when the material flowed downward and outward with the maximum velocity of 0.70 m/s, 0.80 m/s. When the maximum material flow velocity was 0.40 m/s, the weld pool collapsed downward under the action of larger gravity. The thermo-mechanical coupling model was verified by the comparison of the simulation and experimental results.

A 7075 aluminum alloy was successfully welded by pulsed variable polarity plasma arc welding (PVPPAW) and the single-stage aging behavior of the 7075 aluminum alloy PVPPAW joint was systematically investigated. The results demonstrated that the tensile strength of the welded joints initially increased and then decreased with the increase of the single-stage aging temperature and time. After single-stage aging at 490 °C for 80 min and at 130 °C for 24 h, the tensile strength of the welded joint was 551 MPa, which was increased by 38.5% compared to the as-welded joint. Moreover, the conductivity was 25% international annealed copper standard (IACS) at room temperature, and the resistance to stress corrosion was improved. The main strengthening phases of the weld center were η′ and η phase. The average precipitate size slightly increased with the increase of the single-stage aging temperature, but no obvious change was observed with the increase of the single-stage aging time. The area fraction was initially increased and then decreased with the increase of the single-stage aging temperature and time.