MicroRNA-4443 regulates monocyte activation by targeting tumor necrosis factor receptor associated factor 4 in stroke-induced immunosuppression.

BACKGROUND AND PURPOSE: MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the early stage of acute ischaemic stroke (AIS). The purpose of this study was to investigate the expression patterns of miRNAs in peripheral blood mononuclear cells (PBMCs) from AIS patients and further explore related molecular mechanisms in stroke-induced immunodeficiency syndrome (SIDS). METHODS: The miRNA expression patterns of PBMCs were detected by miRNA microarray and validated by quantitative real-time polymerase chain reaction (qRT-PCR) in AIS patients and healthy controls. Bioinformatics methods and luciferase reporter assays were used to detect the downstream target genes. Following stimulation with lipopolysaccharide and interleukin-4, the expression of miR-4443, tumor necrosis factor receptor associated factor 4 (TRAF4) and the nuclear factor kappa B (NF-κB) pathway were evaluated. Furthermore, transfection with miR-4443 mimic or inhibitor in the monocytes was carried out to gain insight into the mechanisms in SIDS. RESULTS: Interleukin-10 in AIS patients was significantly higher than that of healthy controls. The miRNA microarray analysis and qRTPCR validation showed that only miR-4443 was upregulated expressed in PBMCs from AIS patients, especially in monocytes. miR-4443 was shown to directly interact with the 3' untranslated regions of TRAF4, resulting in suppression of TRAF4 protein expression. Furthermore, the expression of miR-4443 and TRAF4 was regulated by stimulation with lipopolysaccharide or interleukin-4. Additionally, overexpression of miR-4443 suppressed the TRAF4/Iκα/NF-κB signaling pathway to activate the expression of anti-inflammatory cytokines in monocytes. CONCLUSIONS: The increased expression of miR-4443 induced monocyte dysfunction by targeting TRAF4, which may function as a crucial mediator in SIDS.

AADS: Augmented autonomous driving simulation using data-driven algorithms.

Simulation systems have become essential to the development and validation of autonomous driving (AD) technologies. The prevailing state-of-the-art approach for simulation uses game engines or high-fidelity computer graphics (CG) models to create driving scenarios. However, creating CG models and vehicle movements (the assets for simulation) remain manual tasks that can be costly and time consuming. In addition, CG images still lack the richness and authenticity of real-world images, and using CG images for training leads to degraded performance. Here, we present our augmented autonomous driving simulation (AADS). Our formulation augmented real-world pictures with a simulated traffic flow to create photorealistic simulation images and renderings. More specifically, we used LiDAR and cameras to scan street scenes. From the acquired trajectory data, we generated plausible traffic flows for cars and pedestrians and composed them into the background. The composite images could be resynthesized with different viewpoints and sensor models (camera or LiDAR). The resulting images are photorealistic, fully annotated, and ready for training and testing of AD systems from perception to planning. We explain our system design and validate our algorithms with a number of AD tasks from detection to segmentation and predictions. Compared with traditional approaches, our method offers scalability and realism. Scalability is particularly important for AD simulations, and we believe that real-world complexity and diversity cannot be realistically captured in a virtual environment. Our augmented approach combines the flexibility of a virtual environment (e.g., vehicle movements) with the richness of the real world to allow effective simulation.

Triglyceride to high-density lipoprotein cholesterol ratio predicts worse outcomes after acute ischaemic stroke.

BACKGROUND AND PURPOSE: The effect of the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) on clinical outcomes of acute ischaemic stroke (AIS) patients is unclear. This study sought to determine whether the TG/HDL-C ratio in AIS patients is associated with worse outcomes at 3 months. METHODS: Acute ischaemic stroke patients who were admitted from 2011 to 2014 were enrolled in this study. TG, total cholesterol (TC), HDL-C and low-density lipoprotein cholesterol (LDL-C) were collected on admission. Three end-points were defined according to the modified Rankin scale (mRS) score at 3 months after symptom onset (excellent outcome, mRS 0-1; good outcome, mRS 0-2; and death, mRS 6). RESULTS: In all, 1006 patients were included (median age 68.5 years; 58.2% male). Higher TG, non-HDL-C and TG/HDL-C were strongly associated with the three end-points after adjustments: excellent [odds ratio (OR) = 1.39, OR 1.89 and OR 2.34, respectively] and good (OR 1.48, OR 2.90 and OR 4.12) outcomes, and death (OR 0.59, OR 0.29 and OR 0.26). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a TG/HDL-C ≥ 0.87 for excellent outcomes [area under the ROC curve (AUC) 0.596; sensitivity 73.3%; specificity 42.7%] and non-death (AUC 0.674; sensitivity 67.8%; specificity 60.6%) as well as a TG/HDL-C ≥ 1.01 for a good outcome (AUC 0.652; sensitivity 61.6%; specificity 63.2%). Patients with a TG/HDL-C < 0.87 had a 2.94-fold increased risk of death (95% confidence interval 1.89-4.55) compared with patients with a TG/HDL-C ≥ 0.87. CONCLUSIONS: A lower TG/HDL-C was independently associated with death and worse outcome at 3 months in AIS.

Sample Grating Distributed Feedback Quantum Cascade Laser Array.

A sample grating distributed feedback quantum cascade laser array aim at broad tunability and enhanced side mode suppression ratios is presented. Utilizing a sample grating dependence on emission wavelength and epitaxial side down bonding technique, the array of laser ridges exhibited three separated single mode emissions centered at 4.760, 4.721, and 4.711 µm respectively, in continuous wave at room temperature. Side mode suppression ratios of >35 dB and continuous wave output powers of >10 mW per laser ridge were obtained.

Influence of lactuside B on the expression of AQP4 and TRPM7 mRNAs in the cerebral cortex after cerebral ischemia injury.

AIM: This study aimed to determine the effect of Lactuside B isolated from Pterocypsela alata on the expression of AQP4 and TRPM7 mRNAs after cerebral ischemic injury. MATERIALS AND METHODS: Brain ischemia injury was established by occluding the MCA (middle cerebral artery) for 2 h, followed by reperfusion in rats. The neurologic deficit scores were used to determine the success of the model. All drugs were intraperitoneally administered once a day (5 ml/kg). Eight animals from each group were investigated for the Na+ level, and the others were examined for AQP4 and TRPM7 mRNA changes. RESULTS: Compared with the model group, the neurologic deficit scores and Na+ levels decreased in the lactuside B groups (p < 0.05 vs. p < 0.01). All lactuside B groups had significantly decreased AQP4 and TRPM7 mRNA expression compared with the model group (p < 0.05 vs. < 0.01). Dose dependence was observed between low and medium doses. CONCLUSIONS: Lactuside B protected against cerebral edema and nerve cell damage caused by cerebral ischemic injury by decreasing the expression of AQP4 and TRPM7 mRNAs in the cerebral cortex of rats.

A decrease of human leucocyte antigen-DR expression on monocytes in peripheral blood predicts stroke-associated infection in critically-ill patients with acute stroke.

BACKGROUND AND PURPOSE: To investigate changes in human leucocyte antigen (HLA)-DR expression on peripheral monocytes, determine the value of predicting the development of stroke-associated infection (SAI), and determine the correlation with other conditions in critically-ill patients in the neurological intensive care unit (NICU) who suffered an acute stroke. METHODS: All patients were enrolled consecutively and admitted to NICU within 24 h after the onset of symptoms. Patients were followed in order to identify whether infection developed and determine survival status within 2 weeks after the stroke. Patients were divided into stroke or control group by study design, infection or non-infection group by whether or not they had an infection, survival or death group by prognosis and cerebral infarction or cerebral haemorrhage group by stroke type. Patients in which acute stroke was excluded by head CT or MRI were admitted to general ward and were used as a control group. Blood samples were collected serially on days 1, 2, 4, 6 and 14 after stroke, then monocyte human leucocyte antigen-DR (HLA-DR) expression was determined by flow cytometry. The National Institute of Health Stroke Scale (NIHSS), Acute Physiology and Chronic Health Evaluation II (APACHEII) and Glasgow Coma Scale (GCS) scores were recorded over the course of observation. RESULTS: Fifty-three subjects and 39 controls were enrolled in the study. On days 1, 2, 4, 6 and 14, there was a significant difference in monocyte HLA-DR expression between stroke group and control group (all P < 0.001), but no difference was found between ischaemic stroke group and haemorrhagic stroke group (all P > 0.05). The infection group compared with non-infection group did not exhibit a significant difference in HLA-DR expression on days 1 and 2 (all P > 0.05), but significant differences emerged on days 4, 6 and 14 (all P < 0.01). On days 1 and 2 the HLA-DR expression in the survival group compared with death group, was not significantly different (all P > 0.05), but differences became significant on days 4 and 6 (P < 0.01). On day 1, HLA-DR expression <62.80% had the predictive value to SAI (sensitivity 83.3%, specificity 55.2%, AUC = 0.661, P = 0.031) and on day 2, HLA-DR expression <57.83% had the predictive value to SAI (sensitivity 95.8%, specificity 79.3%, AUC = 0.907, P = 0.000) in acute stroke patients. A statistically significant inverse correlation was found between NIHSS and HLA-DR on days 2 and 4 during the observation period (all P < 0.01), but there was no statistically significant negative correlation on days 1, 6 or 14 (all P > 0.05). HLA-DR expression did not correlate with APACHEII (all P > 0.05) or GCS (all P > 0.05) during the measurement period. CONCLUSIONS: Human leucocyte antigen-DR (HLA-DR) expression decreases and sustains a dynamic change and it also relates to the severity of patient's condition in the critically-ill patients with stroke. Progressively persistent low monocyte HLA-DR expression is associated with a poor prognosis. The decline in HLA-DR expression contributes to infection in critically-acute stroke patients. Monitoring of monocyte HLA-DR expression may be useful for identifying patients suffering from acute stroke who are at high risk for infection.