Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain ischemic stroke by suppressing ARF1 lactylation.

Low-density lipoprotein receptor-related protein-1 (LRP1) is an endocytic/signaling cell-surface receptor that regulates diverse cellular functions, including cell survival, differentiation, and proliferation. LRP1 has been previously implicated in the pathogenesis of neurodegenerative disorders, but there are inconsistencies in its functions. Therefore, whether and how LRP1 maintains brain homeostasis remains to be clarified. Here, we report that astrocytic LRP1 promotes astrocyte-to-neuron mitochondria transfer by reducing lactate production and ADP-ribosylation factor 1 (ARF1) lactylation. In astrocytes, LRP1 suppressed glucose uptake, glycolysis, and lactate production, leading to reduced lactylation of ARF1. Suppression of astrocytic LRP1 reduced mitochondria transfer into damaged neurons and worsened ischemia-reperfusion injury in a mouse model of ischemic stroke. Furthermore, we examined lactate levels in human patients with stroke. Cerebrospinal fluid (CSF) lactate was elevated in stroke patients and inversely correlated with astrocytic mitochondria. These findings reveal a protective role of LRP1 in brain ischemic stroke by enabling mitochondria-mediated astrocyte-neuron crosstalk.

Omeprazole activates aryl hydrocarbon receptor to reduce hyperoxia-induced oxidative stress in the peripheral blood mononuclear cells from premature infants.

OBJECTIVE: To investigate the correlation between the aryl hydrocarbon receptor (AhR) and reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) of premature infants, to demonstrate the protective role of AhR against hyperoxia-induced oxidative stress in premature infants and to provide a rational basis for the use of omeprazole (OM) as a new treatment for bronchopulmonary dysplasia (BPD). METHODS: From January 2021 to June 2021, 1-3 ml of discarded peripheral blood was collected from premature infants of gestational age less than 32 weeks who were not taking inhaled oxygen and were admitted to the Department of Neonatology of the Affiliated Hospital of Southwest Medical University. Using a random number table, the PBMCs were randomly assigned to each of the following groups: the control group, air + OM group, hyperoxia group, and hyperoxia + OM group. After 48 h of in vitro modeling and culture, PBMCs and the culture medium of each group were collected. Immunofluorescence analysis was used to examine ROS levels in PBMCs. A full-spectrum spectrophotometer was used to examine malondialdehyde (MDA) levels in the culture medium. Enzyme-linked immunosorbent assay (ELISA) was used to examine monocyte chemotactic protein 1 (MCP-1) levels in culture medium. Immunofluorescence analysis was used to examine the intracellular localization of AhR. Western blotting was used to examine the expression level of AhR in PBMCs. RESULTS: Compared with those in the control group, the levels of ROS, MDA, and MCP-1 and the cytoplasm-nuclear translocation rate of AhR in the air + OM group did not change significantly (p > 0.05), but the expression level of AhR increased significantly (p < 0.05). The levels of ROS, MDA, and MCP-1 and the cytoplasm-nuclear translocation rate of AhR significantly increased in the hyperoxia group (p < 0.05), and the expression level of AhR was significantly reduced (p < 0.05). Compared with those in the hyperoxia group, the levels of ROS, MDA, and MCP-1 in the hyperoxia + OM group were significantly reduced (p < 0.05), and the cytoplasm-nuclear translocation rate of AhR and the expression level of AhR were significantly increased (p < 0.05), but did not reach the level of the control group (p < 0.05). CONCLUSION: OM can activate AhR to inhibit hyperoxia-induced oxidative stress in the PBMCs from premature infants.

TSPO ligand Ro5-4864 modulates microglia/macrophages polarization after subarachnoid hemorrhage in mice.

Brain injury after subarachnoid hemorrhage (SAH) is closely related to microglia/macrophages-induced neuroinflammation. Translocator protein (TSPO) is a hall marker of activated microglia/macrophages, and the TSPO ligands have been proved to be beneficial for controlling neuroinflammation. Ro5-4864, one of the TSPO ligands, has been reported to be able to regulate inflammation in neurological diseases. Here, we investigated the effects of Ro5-4864 on microglia/macrophages polarization in a SAH mice model, which was induced by endovascular perforation. Ro5-4864 was administered intraperitoneally dissolved in DMSO-saline. Post-SAH assessments included neurological tests, SAH grade, western blotting, ELISA assay and immunohistochemistry. The results showed that brain injury was accompanied by the accumulation of TNF-α and IL-1ß, as well as the increase of iNOS protein levels. Finally, we found that Ro5-4864 improved neurological function, increased the expression of anti-inflammatory factors, and influenced phenotypes of M2 microglia/macrophages after SAH. Together, these data reveal a protective role of TSPO ligand Ro5-4864 in inflammatory processes of SAH as well as a potential alternative for SAH treatment.

[A Novel and Fast P Wave Detection Algorithm in ECG Signals].

This paper presents a new, simple and fast algorithm of automated P wave detection in multi-lead ECG Signals. Range of QRS-T complex is detected firstly. Then QRS-T complex is eliminated. Final y, P wave's onset and offset are detected by using the average of low-pass difference method and tangent method. Tangent method is always used to locate the offset of T Wave but it wil firstly be used to locate the P wave onset and offset in this paper. The proposed algorithm is tested by the annotated CSE database. Result shows that algorithm test result has a good consistency with BIS CSE annotation. Compared with the mean and standard deviation of P wave onset and offset, our algorithm and CSE annotation is-2.01 ms, 3.94 ms and 4.96 ms, 5.86 ms.

[Design and Application of Portable Micro Sleep Monitoring System].

Through the study of the pathology of sleep apnea-hypopnea syndrome, evaluation indexes, diagnosis requirements and so on, a portable sleep monitoring system was designed, which had the characteristics of convenience, wireless transmission and no disturbance. The system can be assessed by respiration monitoring and pulse oximetry, which is based on the pressure variation in miniature air-bag and spectral absorption method. It provides the value of the apnea-hypopnea index (AHI), which is used to evaluate OSAHS severity. The experiment of the system's stability and accuracy is done, which exhibits good performance, it can diagnose OSAHS effectively and provide convenience for home monitoring.

[Performance of Novel Macromolecule Flocculant in the Treatment of Wastewater Containing Cr (VI) Ions].

A novel macromolecule flocculant, polyethyleneimine-sodium xanthogenate (PEX), was applied in the treatment of wastewater containing Cr(VI) ions. The trapping performance of PEX for Cr(VI) ions was studied, and effects of selective important factors, such as initial Cr(VI) concentration, pH value, coexisting inorganic substance and turbidity etc., on the removal of chromium by PEX were investigated. The experimental results indicated that PEX could efficiently remove different concentrations of chromium in strong acidic media. The maximum removal rate of Cr(VI) and total Cr reached 99.1% and 96.6% at pH 2.0, respectively. The existence of influencing substance (e. g. NaCl, NaF, Na2SO4, CaCl2 and turbidity) would inhibit the removal of Cr(VI) ions, and promote the removal of total Cr to some extent. Fourier transform infrared spectroscopy (FTIR) analysis showed that the behaviors in the removal of Cr(VI) ions included reduction and chelation. Cr(VI) ions were reduced to Cr(III) ions by dithiocarboxylic acid groups on the PEX molecule, and then chelating reactions existed between Cr(III) ions and dithiocarboxylic acid groups and amino groups of PEX.