Exploring causal relationships between inflammatory cytokines and allergic rhinitis, chronic rhinosinusitis, and nasal polyps: a Mendelian randomization study

ObjectivesPrevious research has suggested connections between specific inflammatory cytokines and nasal conditions, including Allergic Rhinitis (AR), Chronic Rhinosinusitis (CRS), and Nasal Polyps (NP). However, a lack of robust research establishing the causal underpinnings of them. This Mendelian Randomization (MR) study aims to evaluate the causal relationships between 41 inflammatory cytokines and the incidence of AR, CRS and NP.MethodsThis study employed a two-sample MR design, harnessing genetic variations derived from publicly accessible genome-wide association studies (GWAS) datasets. AR data was sourced from a GWAS with 25,486 cases and 87,097 controls (identifier: ukb-b-7178). CRS data originated from a GWAS encompassing 1,179 cases and 360,015 controls (identifier: ukb-d-J32). NP data was extracted from a GWAS involving 1,637 cases and 335,562 controls (identifier: ukb-a-541). The data for 41 inflammatory cytokines were obtained from an independent GWAS encompassing 8,293 participants. Inverse variance weighted (IVW), MR Egger regression and Weighted median were used to evaluate the causalities of exposures and outcomes. A range of sensitivity analyses were implemented to assess the robustness of the results.ResultsThe results revealed significant associations between elevated circulating levels of MIP-1α (odds ratio, OR: 1.01798, 95% confidence interval, CI: 1.00217–1.03404, p = 0.02570) and TNF-α (OR: 1.01478, 95% CI: 1.00225–1.02746, p = 0.02067) with an augmented risk of AR in the IVW approach. Heightened levels of circulating IL-2 exhibited a positive correlation with an increased susceptibility to NP in the IVW approach (OR: 1.00129, 95% CI: 1.00017–1.00242, p = 0.02434), whereas elevated levels of circulating PDGF-BB demonstrated a decreased risk of NP (OR: 0.99920, 95% CI: 0.99841–0.99999, p = 0.047610). The MR analysis between levels of 41 inflammatory cytokines and the incidence of CRS yielded no positive outcomes.ConclusionThis investigation proposes a potential causal association between elevated levels of MIP-1α and TNF-α with an elevated risk of AR, as well as an increased risk of NP linked to elevated IL-2 levels. Furthermore, there appears to be a potential association between increased levels of circulating PDGF-BB and a reduced risk of NP

Numerical study of the switching mechanism of a jet valve using the meshless method

This study numerically investigates fluid dynamics of a jet flow at supersonic speed. The meshless method and the overlapping point cloud method are used to handle the moving boundary problems. The interaction between the jet flow and a moving ball-shaped plug is numerically solved, which has been rarely done in the published literature. The switching mechanism of a novel designed jet valve in an attitude and orbit control system (AOCS) is analyzed. It is found out that applied pressure to the control inlets of the jet valve must be high enough in order to successfully drive the plug to move and subsequently change the force direction acting on the jet valve. Then the switching mechanism of AOCS can be triggered. The initial fluid condition also plays a vital role and it significantly influences the response time of the switch. This study explores the underlying physics of the jet flow on its deflection, wall attachment, and interaction with the ball-shaped plug. It contributes to the optimization design of the jet valve in the AOCS with a fast and efficient response.Published versionThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by National Natural Science Foundation of China (grant No. 11702134)

Effects of Mn and Zn solutes on grain refinement of commercial pure magnesium

The effects of Mn (peritectic system) and Zn (eutectic system) on the grain refinement of commercial pure Mg were investigated. Interdependence model and solute paradigm theory were applied to evaluate the grain nucleation and growth for these two alloy systems. Both Mn and Zn can refine the grain of pure Mg. Compared to Mg–Zn, the nucleant particles in Mg–Mn alloys are more potent, but the relatively activated number of nucleation sites is much fewer. Zn with relatively high value of growth restriction factor increases the initial rate of development of the constitutional supercooling (CS) zone at the earliest stage of grain growth, which plays a key role in determining the final grain size. Moreover, heavy segregation of Zn during solidification provides a driving-force to activate further nucleation in the CS zone, which may trigger some unknown native nucleation particles to sever as nuclei

Current development of creep-resistant magnesium cast alloys: a review

The low creep resistance has been one of the major issues of Mg alloys, which limited their wider industrial applications in the past decades. It has been reported that the inherent creep resistance of Mg should be higher than that Al. Hence, it is highly likely that the low creep resistance of Mg alloys was attributed to the effects of alloying elements rather than Mg itself. In order to systematically understand the effects of alloying elements on the creep behaviours of cast Mg alloys and therefore to develop new alloys with higher creep resistance, the present work reviews the major creep-resistant Mg systems that were developed and successfully commercialized for applications at different temperatures. Because the majority of commercial Mg alloys are used as cast, this review focuses on cast alloys. (C) 2018 Elsevier Ltd. All rights reserved

Development and prospects of degradable magnesium alloys for structural and functional applications in the fields of environment and energy

Magnesium and its alloys have such advantages with lightweight, high specific strength, good damping, high castability and machinability, which make them an attractive choice for applications where weight reduction is important, such as in the aerospace and automotive industries. However, their practical applications are still limited because of their poor corrosion resistance, low high temperature strength and ambient formability. Based on such their property shortcomings, recently degradable magnesium alloys were developed for broadening their potential applications. Considering the degradable Mg alloys for medical applications were well reviewed, the present review put an emphasis on such degradable magnesium alloys for structural and functional applications, especially the applications in the environmental and energy fields. Their applications as fracture ball in fossil energy, sacrificial anode, washing ball, and as battery anodes, transient electronics, were summarized. The roles of alloying elements in magnesium and the design concept of such degradable magnesium alloys were discussed. The existing challenges for extending their future applications are explored

Roles of Nd and Mn in a new creep-resistant magnesium alloy

Modification of the recently developed creep-resistant Mg-3Gd-2Ca (wt.%) magnesium alloy using Nd and Mn remarkably improved the creep resistance at both 180 °C and 210 °C. The modified Mg-2Gd-1Nd-2Ca-0.5Mn alloy after solid solution treatment exhibited outstanding creep resistance that is superior to the commercial creep-resistant Mg alloy, EV31, but contained less RE addition. The microstructural observations revealed that partial replacement of Gd with 1 wt% Nd did not enhance the effect of dynamic precipitates significantly. But further analysis by atom probe tomography verified the stronger co-segregation between Nd solute atoms and other solute atoms than that of Gd and Ca in the Mg solid solutions, leading to a higher solid solution strengthening effect on the creep resistance. The addition of 0.5 wt% Mn led to the formation of polygonal-shape α-Mn precipitates, which served as heterogeneous nucleants for dynamic precipitates, refining their size and increasing the number densities. As a result, the creep properties of newly developed Mg alloys were strengthened by a combination of improved solid solution strengthening by Nd and increased precipitation hardening by Mn addition

Understanding solid solution strengthening at elevated temperatures in a creep-resistant Mg-Gd-Ca alloy

The present work studies the strengthening mechanisms of a creep-resistant Mg-0.5Gd-1.2Ca (at.%) alloy at both room and elevated temperatures. Although peak-ageing (T6) at 180 °C for 32 h led to a significant increase in room temperature strength due to the precipitation strengthening by three types of precipitates (MgCa, MgGd on prismatic planes and a new type of Mg–Gd–Ca intermetallic compound on the basal plane), the as-solid solution treated (T4) alloy exhibited better resistance to temperature softening during compression and to stress relaxation at 180 °C and better creep resistance at 210 °C/100 MPa. The Gd–Ca co-clusters with short-range order in the Mg solid solution, which was verified, at the first time, by atom probe tomography (APT) analysis and atomic-resolution high angle annular dark field-scanning transmission electron microscopy (HAADF-STEM), were responsible for the solid solution hardening, offering a more effective strengthening effect through local order-strengthening. Such solid solution strengthening increased the thermal stability of the alloy structure at elevated temperatures, at least at early stage of the creep. Subsequently, dynamic precipitation started contributing to the creep resistance due to the formation of higher density of precipitates. However, in the T6 alloy, creep testing at elevated temperatures, particularly at 210 °C that was higher than the ageing temperature, led to coarsening of the precipitates, which acted as over ageing. As a result of such over ageing, the resistance of the T6 alloy to heat-induced softening was weakened, leading to lower creep resistance than the T4 alloy