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Abstract Ischemic stroke leads to white matter damage and neurological deficits. However, the characteristics of white matter injury and repair after stroke are unclear. Additionally, the precise molecular communications between microglia and white matter repair during the stroke rehabilitation phase remain elusive. In this current study, MRI DTI scan and immunofluorescence staining were performed to trace white matter and microglia in the mouse transient middle cerebral artery occlusion (tMCAO) stroke model. We found that the most serious white matter damage was on Day 7 after the ischemic stroke, then it recovered gradually from Day 7 to Day 30. Parallel to white matter recovery, we observed that microglia centered around the damaged myelin sheath and swallowed myelin debris in the ischemic areas. Then, microglia of the ischemic hemisphere were sorted by flow cytometry for RNA sequencing and subpopulation analysis. We found that CD11c+ microglia increased from Day 7 to Day 30, demonstrating high phagocytotic capabilities, myelin-supportive genes, and lipid metabolism associated genes. CD11c+ microglia population was partly depleted by the stereotactic injecting of rAAV2/6M-taCasp3 (rAAV2/6M-CMV-DIO-taCasp3-TEVp) into CD11c-cre mice. Selective depletion of CD11c+ microglia disrupted white matter repair, oligodendrocyte maturation, and functional recovery after stroke by Rotarod test, Adhesive Removal test, and Morris Water Maze test. These findings suggest that spontaneous white matter repair occurs after ischemic stroke, while CD11c+ microglia play critical roles in this white matter restorative progress.

Abstract Background Vascular dementia (VAD) is the second most common type of dementia lacking effective treatments. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, displays protective effects in multiple cerebral diseases. In this study, we aimed to investigate the therapeutic effects and potential mechanisms of PTX in VAD. Methods Bilateral common carotid artery stenosis (BCAS) mouse model was established to mimic VAD. Mouse behavior was tested by open field test, novel object recognition test, Y-maze and Morris water maze (MWM) tests. Histological staining, magnetic resonance imaging (MRI) and electron microscopy were used to define white matter integrity. The impact of PTX on microglia phagocytosis, peroxisome proliferator-activated receptors-γ (PPAR-γ) activation and Mer receptor tyrosine kinase (Mertk) expression was assessed by immunofluorescence, western blotting and flow cytometry with the application of microglia-specific Mertk knockout mice, Mertk inhibitor and PPAR-γ inhibitor. Results Here, we found that PTX treatment alleviated cognitive impairment in novel object recognition test, Y-maze and Morris water maze tests. Furthermore, PTX alleviated white matter injury in corpus callosum (CC) and internal capsule (IC) areas as shown by histological staining and MRI analysis. PTX-treatment group presented thicker myelin sheath than vehicle group by electron microscopy. Mechanistically, PTX facilitated microglial phagocytosis of myelin debris by up-regulating the expression of Mertk in BCAS model and primary cultured microglia. Importantly, microglia-specific Mertk knockout blocked the therapeutic effects of PTX in BCAS model. Moreover, Mertk expression was regulated by the nuclear translocation of PPAR-γ. Through modulating PPAR-γ, PTX enhanced Mertk expression. Conclusions Collectively, our results demonstrated that PTX showed therapeutic potentials in VAD and alleviated ischemic white matter injury via modulating Mertk-mediated myelin clearance in microglia.

Microglia are the resident immune cells of the central nervous system that exert diverse roles in the pathogenesis of ischemic stroke. During the past decades, microglial polarization and chemotactic properties have been well-studied, whereas less attention has been paid to phagocytic phenotypes of microglia in stroke. Generally, whether phagocytosis mediated by microglia plays a beneficial or detrimental role in stroke remains controversial, which calls for further investigations. Most researchers are in favor of the former proposal currently since efficient clearance of tissue debris promotes tissue reconstruction and neuronal network reorganization in part. Other scholars propose that excessively activated microglia engulf live or stressed neuronal cells, which results in neurological deficits and brain atrophy. Upon ischemia challenge, the microglia infiltrate injured brain tissue and engulf live/dead neurons, myelin debris, apoptotic cell debris, endothelial cells, and leukocytes. Cell phagocytosis is provoked by the exposure of “eat-me” signals or the loss of “don’t eat-me” signals. We supposed that microglial phagocytosis could be initiated by the specific “eat-me” signal and its corresponding receptor on the specific cell type under pathological circumstances. In this review, we will summarize phagocytic characterizations of microglia after stroke and the potential receptors responsible for this programmed biological progress. Understanding these questions precisely may help to develop appropriate phagocytic regulatory molecules, which are promoting self-limiting inflammation without damaging functional cells.

High levels of toxic organic pollutants commonly detected during domestic/industrial wastewater treatment have been attracting research attention globally because they seriously threaten human health. Sulfate-radical-based advanced oxidation processes (SR-AOPs) have been successfully used in wastewater treatment, such as that containing antibiotics, pesticides, and persistent organic pollutants, for refractory contaminant degradation. This review summarizes activation methods, including physical, chemical, and other coupling approaches, for efficient generation of sulfate radicals and evaluates their applications and economic feasibility. The degradation behavior as well as the efficiency of the generated sulfate radicals of typical domestic and industrial wastewater treatment is investigated. The categories and characteristics of the intermediates are also evaluated. The role of sulfate radicals, their kinetic characteristics, and possible mechanisms for organic elimination are assessed. In the last section, current difficulties and future perspectives of SR-AOPs for wastewater treatment are summarized.

This study statistically reported the current state of sludge treatment/disposal in China from the aspects of sources, technical routes, geographical distribution, and development by using observational data after 1978. By the end of 2019, 5476 municipal wastewater treatment plants were operating in China, leading to an annual sludge productivity of 39.04 million tons (80% water content). Overall, 29.3% of the sludge in China was disposed via land application, followed by incineration (26.7%) and sanitary landfills (20.1%). Incineration, compost, thermal hydrolysis and anerobic digestion were the mainstream technologies for sludge treatment in China, with capacities of 27,122, 11,250, 8342 and 6944 t/d in 2019, respectively. Incineration and drying were preferentially constructed in East China. In contrast, sludge compost was most frequently used in Northeast China (46.5%), East China (22.4%) and Central China (12.8%), while anaerobic digestion in East China, North China and Central China. The capacities of sludge facilities exhibited a sharp increase in 2009–2019, with an overall greenhouse gas emissions in China in 2019 reached 108.18 × 108 kg CO2-equivaient emissions, and the four main technical routes contributed as: incineration (45.11%) > sanitary landfills (23.04%) > land utilization (17.64%) > building materials (14.21%). Challenges and existing problems of sludge disposal in China, including high CO2 emissions, unbalanced regional development, low stabilization and land utilization levels, were discussed. Finally, suggestions regarding potential technical and administrative measures in China, and sustainable sludge management for developing countries, were also given.