Obstructive sleep apnea aggravates neuroinflammation and pyroptosis in early brain injury following subarachnoid hemorrhage via ASC/HIF-1α pathway

Obstructive sleep apnea can worsen the prognosis of subarachnoid hemorrhage.Howeve r,the underlying mechanism remains unclear.In this study,we established a mouse model of subarachnoid hemorrhage using the endovascular perforation method and exposed the mice to intermittent hypoxia for 8 hours daily for 2 consecutive days to simulate sleep apnea.We found that sleep apnea aggravated brain edema,increased hippocampal neuron apoptosis,and worsened neurological function in this mouse model of subarachnoid hemorrhage.Then,we established an in vitro HT-22 cell model of hemin-induced subarachnoid hemorrhage/intermittent hypoxia and found that the cells died,and lactate dehydrogenase release increased,after 48 hours.We further investigated the underlying mechanism and found that sleep apnea increased the expression of hippocampal neuroinflammatory factors interleukin-1β,interleukin-18,inte rleukin-6,nuclear factorκB,pyro ptosis-related protein caspase-1,pro-caspase-1,and NLRP3,promoted the prolife ration of astrocytes,and increased the expression of hypoxia-inducible factor 1αand apoptosis-associated speck-like protein containing a CARD,which are the key proteins in the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.We also found that knockdown of hypoxia-inducible factor 1αexpression in vitro greatly reduced the damage to HY22 cells.These findings suggest that sleep apnea aggravates early brain injury after subarachnoid hemorrhage by aggravating neuroinflammation and pyroptosis,at least in part through the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.

Tetracysteine as a Reporter for Gene Therapy

Objective To study the feasibility of using tetracysteine （TC） reporter in gene therapy. Methods Effects of TC reporter and conventional reporter genes encoding green fluorescence protein （GFP） and luciferase （Luc） on expression and function of the therapeutic gene MGMT^P140K were compared. Cytotoxicity and drug resistance were studied by Western blot. TC reporter used in therapy was analyzed by flow cytometry （FCM）. Results The TC reporter had no toxicity to cells and neither affected the expression or activity of therapeutic gene as compared to GFP and Luc. TC could be used in blood sample detection. Conclusion TC is a new kind of reporter gene for lentiviral vector in future gene therapy.

Identification of low-resistivity-low-contrast pay zones in the feature space with a multi-layer perceptron based on conventional well log data

In the early exploration of many oilfields,low-resistivity-low-contrast(LRLC)pay zones are easily overlooked due to the resistivity similarity to the water zones.Existing identification methods are model-driven and cannot yield satisfactory results when the causes of LRLC pay zones are complicated.In this study,after analyzing a large number of core samples,main causes of LRLC pay zones in the study area are discerned,which include complex distribution of formation water salinity,high irreducible water saturation due to micropores,and high shale volume.Moreover,different oil testing layers may have different causes of LRLC pay zones.As a result,in addition to the well log data of oil testing layers,well log data of adjacent shale layers are also added to the original dataset as reference data.The densitybased spatial clustering algorithm with noise(DBSCAN)is used to cluster the original dataset into 49 clusters.A new dataset is ultimately projected into a feature space with 49 dimensions.The new dataset and oil testing results are respectively treated as input and output to train the multi-layer perceptron(MLP).A total of 3192 samples are used for stratified 8-fold cross-validation,and the accuracy of the MLP is found to be 85.53%.