Fine-tuning of microglia polarization prevents diabetes-associated cerebral atherosclerosis

Diabetes increases the occurrence and severity of atherosclerosis. When plaques form in brain vessels, cerebral atherosclerosis causes thickness, rigidity, and unstableness of cerebral artery walls, leading to severe complications like stroke and contributing to cognitive impairment. So far, the molecular mechanism underlying cerebral atherosclerosis is not determined. Moreover, effective intervention strategies are lacking. In this study, we showed that polarization of microglia, the resident macrophage in the central nervous system, appeared to play a critical role in the pathological progression of cerebral atherosclerosis. Microglia likely underwent an M2c-like polarization in an environment long exposed to high glucose. Experimental suppression of microglia M2c polarization was achieved through transduction of microglia with an adeno-associated virus (serotype AAV-PHP.B) carrying siRNA for interleukin-10 (IL-10) under the control of a microglia-specific TMEM119 promoter, which significantly attenuated diabetes-associated cerebral atherosclerosis in a mouse model. Thus, our study suggests a novel translational strategy to prevent diabetes-associated cerebral atherosclerosis through in vivo control of microglia polarization

Spatial heterogeneity of cyanobacteria-inoculated sand dunes significantly influences artificial biological soil crusts in the Hopq Desert (China)

Artificial biological soil crusts (ABSCs), formed by inoculating Microcoleus vaginatus Gom. and Scytonema javanicum Born. et Flah. onto the topsoil of desert dunes, proved to be effective tools for the stabilization of moving dunes and promotion of soil fertility. As dominant driving forces in arid habitats, the abiotic environmental conditions of undulating dunes produce a gradient of abiotic stresses on cyanobacteria. Cyanobacteria are considered pioneering phototrophs in early soil crust communities in deserts. In this study, the development of ABSCs under various environmental site conditions was investigated using 16S rRNA-based polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and soil property measurements. After inoculation in 2002 and long-term development, patchy moss crusts were observed on the dunes. All of the available sequenced bands in the DGGE gels belonged to Oscillatoriales and Nostocales. The dominant Nostocales genus in the ABSCs was still Scytonema; however, more Oscillatoriales genera were identified, which belonged to Microcoleus and Phormidium. The cyanobacterial compositions of different slope types were significantly distinct (p&nbsp;&lt;&nbsp;0.05), particularly those from windward slopes. The crusts of the top-dune slopes were more heterogeneous. In addition, the soil physicochemical properties and richness indices of the windward slopes were significantly lower than those of the leeward and interdune slopes (p&nbsp;&lt;&nbsp;0.05). Compared with uninoculated control dunes, all of the inoculated dunes had far higher biodiversities. &copy; 2013 Springer-Verlag Berlin Heidelberg.Artificial biological soil crusts (ABSCs), formed by inoculating Microcoleus vaginatus Gom. and Scytonema javanicum Born. et Flah. onto the topsoil of desert dunes, proved to be effective tools for the stabilization of moving dunes and promotion of soil fertility. As dominant driving forces in arid habitats, the abiotic environmental conditions of undulating dunes produce a gradient of abiotic stresses on cyanobacteria. Cyanobacteria are considered pioneering phototrophs in early soil crust communities in deserts. In this study, the development of ABSCs under various environmental site conditions was investigated using 16S rRNA-based polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and soil property measurements. After inoculation in 2002 and long-term development, patchy moss crusts were observed on the dunes. All of the available sequenced bands in the DGGE gels belonged to Oscillatoriales and Nostocales. The dominant Nostocales genus in the ABSCs was still Scytonema; however, more Oscillatoriales genera were identified, which belonged to Microcoleus and Phormidium. The cyanobacterial compositions of different slope types were significantly distinct (p < 0.05), particularly those from windward slopes. The crusts of the top-dune slopes were more heterogeneous. In addition, the soil physicochemical properties and richness indices of the windward slopes were significantly lower than those of the leeward and interdune slopes (p < 0.05). Compared with uninoculated control dunes, all of the inoculated dunes had far higher biodiversities

Convolutional squeeze-and-excitation network for ECG arrhythmia detection

International audienceAutomatic detection of arrhythmia through an electrocardiogram (ECG) is of great significance for the prevention and treatment of cardiovascular diseases. In Convolutional neural network, the ECG signal is converted into multiple feature channels with equal weights through the convolution operation. Multiple feature channels can provide richer and more comprehensive information, but also contain redundant information, which will affect the diagnosis of arrhythmia, so feature channels that contain arrhythmia information should be paid attention to and given larger weight. In this paper, we introduced the Squeeze-and-Excitation (SE) block for the first time for the automatic detection of multiple types of arrhythmias with ECG. Our algorithm combines the residual convolutional module and the SE block to extract features from the original ECG signal. The SE block adaptively enhances the discriminative features and suppresses noise by explicitly modeling the interdependence between the channels, which can adaptively integrate information from different feature channels of ECG. The one-dimensional convolution operation over the time dimension is used to extract temporal information and the shortcut connection of the Se-Residual convolutional module in the proposed model makes the network easier to optimize. Thanks to the powerful feature extraction capabilities of the network, which can effectively extract discriminative arrhythmia features in multiple feature channels, so that no extra data preprocessing including denoising in other methods are need for our framework. It thus improves the working efficiency and keeps the collected biological information without loss. Experiments conducted with the 12-lead ECG dataset of the China Physiological Signal Challenge (CPSC) 2018 and the dataset of PhysioNet/Computing in Cardiology (CinC) Challenge 2017. The experiment results show that our model gains great performance and has great potential in clinical

Spatial heterogeneity of cyanobacteria-inoculated sand dunes significantly influences artificial biological soil crusts in the Hopq Desert (China).

Artificial biological soil crusts (ABSCs), formed by inoculating Microcoleus vaginatus Gom. and Scytonema javanicum Born. et Flah. onto the topsoil of desert dunes, proved to be effective tools for the stabilization of moving dunes and promotion of soil fertility. As dominant driving forces in arid habitats, the abiotic environmental conditions of undulating dunes produce a gradient of abiotic stresses on cyanobacteria. Cyanobacteria are considered pioneering phototrophs in early soil crust communities in deserts. In this study, the development of ABSCs under various environmental site conditions was investigated using 16S rRNA-based polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and soil property measurements. After inoculation in 2002 and long-term development, patchy moss crusts were observed on the dunes. All of the available sequenced bands in the DGGE gels belonged to Oscillatoriales and Nostocales. The dominant Nostocales genus in the ABSCs was still Scytonema; however, more Oscillatoriales genera were identified, which belonged to Microcoleus and Phormidium. The cyanobacterial compositions of different slope types were significantly distinct (p &lt; 0.05), particularly those from windward slopes. The crusts of the top-dune slopes were more heterogeneous. In addition, the soil physicochemical properties and richness indices of the windward slopes were significantly lower than those of the leeward and interdune slopes (p &lt; 0.05). Compared with uninoculated control dunes, all of the inoculated dunes had far higher biodiversities

PGC-1α Protects against Hepatic Ischemia Reperfusion Injury by Activating PPARα and PPARγ and Regulating ROS Production

Peroxisome proliferator-activated receptors (PPARs) α and γ have been shown to be protective in hepatic ischemia/reperfusion (I/R) injury. However, the precise role of PPARγ coactivator-1α (PGC-1α), which can coactivate both of these receptors, in hepatic I/R injury, remains largely unknown. This study was designed to test our hypothesis that PGC-1α is protective during hepatic I/R injury in vitro and in vivo. Our results show that endogenous PGC-1α is basally expressed in normal livers and is moderately increased by I/R. Ectopic PGC-1α protects against hepatic I/R and hepatocyte anoxia/reoxygenation (A/R) injuries, whereas knockdown of endogenous PGC-1α aggravates such injuries, as evidenced by assessment of the levels of serum aminotransferases and inflammatory cytokines, necrosis, apoptosis, cell viability, and histological examination. The EMSA assay shows that the activation of PPARα and PPARγ is increased or decreased by the overexpression or knockdown of PGC-1α, respectively, during hepatic I/R and hepatocyte A/R injuries. In addition, the administration of specific antagonists of either PPARα (MK886) or PPARγ (GW9662) can effectively decrease the protective effect of PGC-1α against hepatic I/R and hepatocyte A/R injuries. We also demonstrate an important regulatory role of PGC-1α in reactive oxygen species (ROS) metabolism during hepatic I/R, which is correlated with the induction of ROS-detoxifying enzymes and is also dependent on the activations of PPARα and PPARγ. These data demonstrate that PGC-1α protects against hepatic I/R injury, mainly by regulating the activation of PPARα and PPARγ. Thus, PGC-1α may be a promising therapeutic target for the protection of the liver against I/R injury

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial

Background: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. Methods: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140–180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. Findings: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07–1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18–1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47–2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. Interpretation: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. Funding: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra