Crosstalk between GABAA receptors in astrocytes and neurons triggered by general anesthetic drugs.

General anesthetic drugs cause cognitive deficits that persist after the drugs have been eliminated. Astrocytes may contribute to such cognition-impairing effects through the release of one or more paracrine factors that increase a tonic inhibitory conductance generated by extrasynaptic γ-aminobutyric acid type A (GABAA) receptors in hippocampal neurons. The mechanisms underlying this astrocyte-to-neuron crosstalk remain unknown. Interestingly, astrocytes express anesthetic-sensitive GABAA receptors. Here, we tested the hypothesis that anesthetic drugs activate astrocytic GABAA receptors to initiate crosstalk leading to a persistent increase in extrasynaptic GABAA receptor function in neurons. We also investigated the signaling pathways in neurons and aimed to identify the paracrine factors released from astrocytes. Astrocytes and neurons from mice were grown in primary cell cultures and studied using in vitro electrophysiological and biochemical assays. We discovered that the commonly used anesthetics etomidate (injectable) and sevoflurane (inhaled) stimulated astrocytic GABAA receptors, which in turn promoted the release paracrine factors, that increased the tonic current in neurons via a p38 MAPK-dependent signaling pathway. The increase in tonic current was mimicked by exogenous IL-1ß and abolished by blocking IL-1 receptors; however, unexpectedly, IL-1ß and other cytokines were not detected in astrocyte-conditioned media. In summary, we have identified a novel form of crosstalk between GABAA receptors in astrocytes and neurons that engages a p38 MAPK-dependent pathway. Brief commentary BACKGROUND: Many older patients experience cognitive deficits after surgery. Anesthetic drugs may be a contributing factor as they cause a sustained increase in the function of "memory blocking" extrasynaptic GABAA receptors in neurons. Interestingly, astrocytes are required for this increase; however, the mechanisms underlying the astrocyte-to-neuron crosstalk remain unknown. TRANSLATIONAL SIGNIFICANCE: We discovered that commonly used general anesthetic drugs stimulate GABAA receptors in astrocytes, which in turn release paracrine factors that trigger a persistent increase in extrasynaptic GABAA receptor function in neurons via p38 MAPK. This novel form of crosstalk may contribute to persistent cognitive deficits after general anesthesia and surgery.

Novel Surrogates for Membrane Fouling and the Application of Support Vector Machine in Analyzing Fouling Mechanism.

It is difficult to recognize specific fouling mechanisms due to the complexity of practical feed water, thus the current studies usually employ foulant surrogates to carry out research, such as alginate and xanthan gum. However, the representativeness of these surrogates is questionable. In this work, the classical surrogates (i.e., alginate and xanthan gum) were systematically studied, and results showed that they behaved differently during filtration. For the mixture of alginate and xanthan gum, both filtration behaviors and adsorption tests performed by quartz-crystal microbalance with dissipation monitoring (QCM-D) indicated that alginate plays a leading role in fouling development. Furthermore, by examining the filtration behaviors of extracellular polymeric substances (EPS) extracted from practical source water, it turns out that the gel layer formation is responsible for EPS fouling, and the properties of gel layer formed by EPS share more similarities with that formed from pectin instead of alginate. In addition, with the use of experimental data sets extracted from this study and our previous studies, a modeling method was established and tested by the support vector machine (SVM) to predict complex filtration behaviors. Results showed that the small differences of fouling mechanisms lying between alginate and pectin cannot be recognized by Hermia's models, and SVM can show a discrimination as high as 76.92%. As such, SVM may be a powerful tool to predict complex filtration behaviors.

Huaxian Sanjie compound granule improves silicosis fibrosis in rats throughPI3K/Akt/NF-κB signaling pathway / 中国职业医学

@#Abstract: Objective To study the effect and mechanism of Huaxian Sanjie compound granule on silicosis fibrosis in rats. Methods The specific pathogen free male SD rats were randomly divided into control group, silicosis model group and - interventiongroup,withsixratsineachgroup.Disposableventilatorcombinedwithnon exposedintratrachealdripwasused,the ratsinthesilicosismodelgroupandinterventiongroupweretreatedwith 1.0mLsilica suspensionwithamassconcentrationof 50.0 g/L to establish silicon dust rat model, while the rats in the control group were treated with equal volume of 0.9% sodium chloride solution. After 24 hours of dust exposure, the rats in the intervention group were given 10 mL/kg body weight of Huaxian Sanjie compound granule suspension with a mass concentration of 212.5 g/L by gavage, while the rats in the control group and silicosis model group were given the same amount of 0.9% sodium chloride solution, once a day. Three rats in each groupweresacrificedonthe14thand28thday,respectively,andtheirlungtissueswereseparatedforpathologicalexamination.----Thelevelsofinterleukin6(IL6)andtransforminggrowthfactorβ