Resolvin D1 Induces mTOR-independent and ATG5-dependent Autophagy in BV-2 Microglial Cells

Objective The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation.Autophagy is a catabolic process responsible for maintaining cellular homeostasis.In recent years,autophagy has been demonstrated to play an important role in neuroinflammation.Resolvin D1(RvD1)is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities.However,whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation.The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways.Methods Mouse microglial cells(BV-2)were cultured,treated with RvD1,and examined by Western blotting,confocal immunofluorescence microscopy,transmission electron microscopy,and flow cytometry.Results RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes.Importantly,RvD1 had no significant effect on the activation of mammalian target of rapamycin(mTOR)signaling.Furthermore,RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II(CaMK II)activation.Moreover,by downregulating ATG5,the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy.Conclusion The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy,highlighting its therapeutic potential against neuroinflammation.

The first power generation test of hot dry rock resources exploration and production demonstration project in the Gonghe Basin,Qinghai Province,China

Hot dry rock(HDR)is a kind of clean energy with significant potential.Since the 1970s,the United States,Japan,France,Australia,and other countries have attempted to conduct several HDR development research projects to extract thermal energy by breaking through key technologies.However,up to now,the development of HDR is still in the research,development,and demonstration stage.An HDR exploration borehole(with 236℃ at a depth of 3705 m)was drilled into Triassic granite in the Gonghe Basin in northwest China in 2017.Subsequently,China Geological Survey(CGS)launched the HDR resources exploration and production demonstration project in 2019.After three years of efforts,a sequence of significant technological breakthroughs have been made,including the genetic model of deep heat sources,directional drilling and well completion in high-temperature hard rock,large-scale reservoir stimulation,reservoir characterization,and productivity evaluation,reservoir connectivity and flow circulation,efficient thermoelectric conversion,monitoring,and geological risk assessment,etc.Then the whole-process technological system for HDR exploration and production has been preliminarily established accordingly.The first power generation test was completed in November 2021.The results of this project will provide scientific support for HDR development and utilization in the future.

FedIERF: Federated Incremental Extremely Random Forest for Wearable Health Monitoring

Wearable health monitoring is a crucial technical tool that offers early warning for chronic diseases due to its superior portability and low power consumption.However,most wearable health data is distributed across dfferent organizations,such as hospitals,research institutes,and companies,and can only be accessed by the owners of the data in compliance with data privacy regulations.The first challenge addressed in this paper is communicating in a privacy-preserving manner among different organizations.The second technical challenge is handling the dynamic expansion of the federation without model retraining.To address the first challenge,we propose a horizontal federated learning method called Federated Extremely Random Forest(FedERF).Its contribution-based splitting score computing mechanism significantly mitigates the impact of privacy protection constraints on model performance.Based on FedERF,we present a federated incremental learning method called Federated Incremental Extremely Random Forest(FedIERF)to address the second technical challenge.FedIERF introduces a hardness-driven weighting mechanism and an importance-based updating scheme to update the existing federated model incrementally.The experiments show that FedERF achieves comparable performance with non-federated methods,and FedIERF effectively addresses the dynamic expansion of the federation.This opens up opportunities for cooperation between different organizations in wearable health monitoring.

Protectin DX Exhibits Protective Effects in Mouse Model of Lipopolysaccharide-Induced Acute Lung Injury

Background：Acute lung injury （ALI） is a severe disease with high mortality and poor prognosis.Protectin DX （PDX）,a pro-resolving lipid mediator,exhibits protective effects in ALI.Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide （LPS）.Methods：BALB/c mice were randomly divided into five groups：sham,LPS,LPS plus 1 ng ofPDX （LPS ＋ PDX-1 ng）,LPS plus 10 ng ofPDX （LPS ＋ PDX-10 ng）,and LPS plus 100 ng ofPDX （LPS ＋ PDX-100 ng）.Bronchoalveolar lavage fluids （BALFs） were collected after 24 h,and total cells,polymorphonuclear leukocytes,monocyte-macrophages,and lymphocytes in BALF were enumerated.The concentration of interleukin （IL）-1 β3,IL-6,IL-10,tumor necrosis factor-alpha （TNF-α）,macrophage inflammatory protein （MIP）-1 cα,and MIP-2 in BALF was determined,and histopathological changes of the lung were observed.The concentration of protein in BALF and lung wet/dry weight ratios were detected to evaluate pulmonary edema.After determining the optimal dose of PDX,neutrophil-platelet interactions in whole blood were evaluated by flow cytometry.Results：The highest dose of PDX （100 ng/mouse） failed to provide pulmonary protective effects,whereas lower doses of PDX （1 ng/mouse and 10 ng/mouse）,especially 1 ng PDX,alleviated pulmonary histopathological changes,mitigated LPS-induced ALI and pulmonary edema,inhibited neutrophil infiltration,and reduced pro-inflammatory mediator （IL-1β,IL-6,TNF-α,and MIP-lα） levels.Meanwhile,1 ng PDX exhibited pro-resolving functions in ALI including upregulation of monocyte-macrophage numbers and anti-inflammatory mediator IL-l 0 levels.The flow cytometry results showed that PDX could inhibit neutrophil-platelet interactions in ALI.Conclusion：PDX exerts protective effects in LPS-inducedALI by mitigating pulmonary inflammation and abrogating neutrophil-platelet interactions.