Extracellular Vesicles and Asthma—More Than Just a Co-Existence

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.     

并联旁侧支路风流逆转次序的实验研究

为研究上行通风网络火灾中并联旁侧支路风流逆转次序的问题,设计并制作了一个包含3条并联支路的小型模拟实验台.在其中1条支路中设置了燃烧器,用来模拟火灾支路;另两条模拟旁侧支路.取旁侧支路长度及初始风速(点火前的风速)的不同组合,分别进行模拟实验.利用热线风速仪和烟迹观测了两条旁侧支路中风流逆转的过程.结果表明:上行风流火灾中两条并联的旁侧支路可以在不同时刻发生风流逆转;风流逆转次序取决于两条支路长度与初始风速的乘积之比;长度与初始风速乘积较小的支路将较早发生风流逆转.     

基于CFD的新型风幕控尘装置的模拟研究及其应用

针对传统风幕控尘装置设备多、空间小、掘进机移动不便等诸多不足之处,⌒进行了优化设计。为确保新型风幕控尘装置的实际应用效果,指导现场防尘系统设计,确定抽出式风机风筒安设位置,依(山西某矿掘进巷道工作面1:1建立了物理几何模型,并利用计算流体动力学(CFD)进行模拟。根(湍流模型特性及流体运动特点,选取拉格朗日法离散相模型对掘进巷道粉尘浓度分布进行了模拟分析并进行现场实践。结果显示,所选物理几何模型参数设置合理,拟合精度达到预测要求;加装新型风幕控尘装置前后,粉尘浓度下降对比明显;距底板2.1 m处安设抽出式风机风筒时,系统降尘效果显著。     

Numerical simulation of particle deposition in obstructive human airways

To investigate airflow pattern and its impact on particle deposition, finite-volume based computational fluid dynamics (CFD) simulations were conducted in the diseased triple-bifurcation airways. Computations were carried out for twenty Reynolds numbers ranging from 100 to 2 000 in the step of 100. Particles in the size range of 1–10 μm were conducted. Two particle deposition mechanisms (gravitational sedimentation and inertial impaction) were considered. The results indicate that there are strong relationship between airflow structures and particle deposition patterns. Deposition efficiency is different for different particles in the whole range of the respiratory rates. Particles in different sizes can deposit at different sites. Smaller particles can be uniformly deposited at the inside wall of the considered model. Larger particles can be mainly deposited in the proximal bifurcations. Deposition fraction varies a lot for different inlet Reynolds numbers. For lower Reynolds numbers, deposition fraction is relatively small and varies a little with varying the diameters. For higher Reynolds numbers, there is a most efficient diameter for each Reynolds number to target the aerosols at the specific site.     

Lysophosphatidylserine Induces MUC5AC Production via the Feedforward Regulation of the TACE-EGFR-ERK Pathway in Airway Epithelial Cells in a Receptor-Independent Manner

Lysophosphatidylserine (LysoPS) is an amphipathic lysophospholipid that mediates a broad spectrum of inflammatory responses through a poorly characterized mechanism. Because LysoPS levels can rise in a variety of pathological conditions, we sought to investigate LysoPS’s potential role in airway epithelial cells that actively participate in lung homeostasis. Here, we report a previously unappreciated function of LysoPS in production of a mucin component, MUC5AC, in the airway epithelial cells. LysoPS stimulated lung epithelial cells to produce MUC5AC via signaling pathways involving TACE, EGFR, and ERK. Specifically, LysoPS- dependent biphasic activation of ERK resulted in TGF-α secretion and strong EGFR phosphorylation leading to MUC5AC production. Collectively, LysoPS induces the expression of MUC5AC via a feedback loop composed of proligand synthesis and its proteolysis by TACE and following autocrine EGFR activation. To our surprise, we were not able to find a role of GPCRs and TLR2, known LyoPS receptors in LysoPS-induced MUC5AC production in airway epithelial cells, suggesting a potential receptor-independent action of LysoPS during inflammation. This study provides new insight into the potential function and mechanism of LysoPS as an emerging lipid mediator in airway inflammation.     

Airway Delivery of Hydrogel-Encapsulated Niclosamide for the Treatment of Inflammatory Airway Disease

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl⁻ currents and intracellular Ca²⁺ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca²⁺ activated Cl⁻ channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca²⁺ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.     

基于苦味受体表达的多组织细胞传感器及其应用

非口腔组织中的苦味受体(TAS2Rs)可能成为相关疾病治疗的新靶点。 该研究将表达有 TAS2Rs 的细胞作为敏感元 件,根据其生理特性与不同的传感器耦合,探究了味觉受体异位表达及其在个性化药物筛选中的应用,构建了针对不同疾病模 型的个性化药物筛选平台。 首先,基于细胞阻抗传感器以及内源性表达 TAS2R38 受体的结肠癌细胞,开发了异硫氰酸酯类物 质特异性药物筛选平台,求得苯硫脲的 EC50 为 157. 6 μM;其次,结合微电极阵列检测系统,探究了 TAS2Rs 激动剂地芬尼多 (5~ 160 μM)和水杨苷(0. 001~ 100 μM)对心肌细胞收缩的抑制作用;此外,基于 3D 呼吸道平滑肌细胞 (ASMCs) 阵列,结合凝 胶成像系统,探究了 TAS2Rs 激动剂桔皮素(20 μM)对呼吸道平滑肌细胞的舒张作用。     

提高四气门气缸盖进气道一致性工艺措施浅析

进气道性能及其性能一致性偏差是四气门气缸盖的关键指标之一,其性能参数为进气涡流比和流量系数,涡流比大小代表进缸气流旋转程度,流量系数代表进气量多少,对柴油机燃油燃烧效果和排放有很大影响。因一般四气门气缸盖至少有一个是切向进气道,其气道性能参数对制造偏差非常敏感,本文通过总结试制中的各种方案,总结了三种对进气道一致性影响比较大的因素以及保证性能一致性的工艺措施。     

岳南煤业南翼回风大巷支护技术与实践

岳南煤业将南翼回风大巷地质条件与自然平衡拱理论结合,运用理论计算得出锚杆的主要支护参数,提出南翼回风大巷的支护设计方案,并设置监测点进行现场监测,结果表明顶底板移近量稳定在140 mm,两帮移近量稳定在150 mm,取得了较好的支护效果,实现了较好的技术和经济效益。     

人工气道内持续湿化护理观察

目的探讨气道内持续湿化方法对人工气道建立患者预防肺部感染的护理治疗效果。方法 35例进入急诊科和重症监护室的人工气道建立患者随机分成实验组20例和对照组15例,实验组患者采用微量注射泵持续湿化的方法对人工气道进行护理,对照组采用常规护理方法间断给予气道内湿化的方法对人工气道进行护理,分别观察记录2组患者体温、吸痰间隔时间、拔管时间并进行痰液细菌培养,主要以体温和痰液细菌培养结果判断是否有肺部感染的发生评价疗效,卡方检验方法对临床采集数据进行统计学处理。结果实验组与对照组比较,实验组发生肺部感染例数明显减少,统计学处理差异有显著性。结论与传统的间断气道湿化相比,采用微量注射泵持续气道湿化操作简单,安全可靠,效果确切,并发症少。