The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Alzheimer's disease(AD),a degenerative disease of the central nervous system,is characterized by progressive cognitive dysfunction and behavioral impairment.AD has been linked to the formation of amyloid-β(Aβ)pl...Alzheimer's disease(AD),a degenerative disease of the central nervous system,is characterized by progressive cognitive dysfunction and behavioral impairment.AD has been linked to the formation of amyloid-β(Aβ)plaque deposits and neurofibrillary tangles(NFTs)in the brain[1].The aggregation of Aβmay repress the signal transmission of synapses between neurons,while tau tangles,the main components of NFTs,hinder the trafficking of nutrients and other molecules that are critical to normal function and neuronal survival.It has been reported that the deposition of Aβand the tangles of tau protein can activate microglia in the brain,during which balance cannot be maintained,chronic inflammation occurs,and the brain function of AD patients may be further impaired[2].As the mainstream theories,Aβand tau protein continue to be studied.Although researchers have mainly focused on the toxic effects of pathological factors such as Aβ,tau protein,and inflammatory factors,the physiological significance in pathological states and generative processes have rarely been considered.展开更多
Ischemic stroke accounts for~85%of all strokes and generally occurs when blood flow is severely reduced due to clots or masses blocking blood vessels and cutting off blood flow to brain cells.The death or damage to ne...Ischemic stroke accounts for~85%of all strokes and generally occurs when blood flow is severely reduced due to clots or masses blocking blood vessels and cutting off blood flow to brain cells.The death or damage to neurons caused by a stroke lead to corresponding symptoms such as weakness,paralysis,and numbness in the part of the body controlled by the affected area.展开更多
The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia ...The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.展开更多
Yttria-stabilized zirconia(YSZ)fiber composites are highly efficient thermal insulating materials;however,the poor thermal shock resistance limits their versatile applications.In the present study,YSZ fiber was mixed ...Yttria-stabilized zirconia(YSZ)fiber composites are highly efficient thermal insulating materials;however,the poor thermal shock resistance limits their versatile applications.In the present study,YSZ fiber was mixed directly with Al_(2)TiO_(5)fiber,which had an extremely low thermal expansion coefficient,to prepare YSZ–Al_(2)TiO_(5)(ZAT)fiber composites by compression molding and heat treatment.The minimum thermal expansion coefficient of the prepared ZAT fiber composites was measured to be 7.74×10^(−6)K^(−1),which was 26%lower than that of the YSZ fiber composites(10.42×10^(−6)K^(−1)).It was shown that the prepared ZAT fiber composites maintain the integrity after undergoing 51 thermal shock cycles between 1100℃and room temperature.Whereas,YSZ fiber composites burst immediately after only one thermal shock cycle under the same condition.In addition,the ZAT fiber composites also exhibit considerable mechanical and thermal insulating performance.展开更多
Astrocytes,the most abundant cells in the central nervous system(CNS),have a variety of functions such as providing nutrients for neurons,facilitating the formation and functioning of synapses,pruning synapses through...Astrocytes,the most abundant cells in the central nervous system(CNS),have a variety of functions such as providing nutrients for neurons,facilitating the formation and functioning of synapses,pruning synapses through phagocytosis,and maintaining homeostasis[1].As a response to CNS injury and disease,quiescent astrocytes are transformed into reactive astrocytes,which usually can be divided into two types:Al and A2[2].Al astrocytes help to drive the death of neurons and oligodendrocytes in neurodegenerative disorders by producing a large number of inflammatory factors and secreted toxins,while A2 astrocytes protect neurons via releasing many neurotrophic factors[3].展开更多
Objective:To identify risk factors for anastomotic leakage after gastrectomy in patients with Siewert type II/III adenocarcinoma(AEG)of the esophagogastric junction.Methods:This was a retrospective case-control study ...Objective:To identify risk factors for anastomotic leakage after gastrectomy in patients with Siewert type II/III adenocarcinoma(AEG)of the esophagogastric junction.Methods:This was a retrospective case-control study of 903 patients with Siewert type II/III AEG treated from January 2012 to January 2015 at the Shanxi Cancer Hospital in China.All patients underwent gastrectomy,and their clinical characteristics were analyzed to identify associations with anastomotic leakage.Independent risk factors were identified by binary logistic regression.The 2-year disease-free survival was calculated and compared between patients with anastomotic leakage and control patients.The study was approved by the Institutional Review Board of Shanxi Medical University(approval No.2014-09-39)on September 19,2014.Results:Out of the 903 patients were included in the study,80(8.86%,80/903)experienced anastomotic leakage.The mortality rate attributed to anastomotic leakage was 8.75%(7/80).Logistic regression analysis revealed that preoperative hypoalbuminemia(odds ratio(OR)=3.249,95%confidence interval(CI):1.569-6.725,P=0.002),type of reconstruction(OR=1.795,95%CI:1.026-3.142,P=0.040),and combined organ resection(OR=1.807,95%CI:1.069-3.055,P=0.027)were independent risk factors for anastomotic leakage.Conclusion:Preoperative hypoalbuminemia,type of reconstruction,and combined organ resection were identified as risk factors for anastomotic leakage in patients undergoing gastrectomy for Siewert type Ⅱ/Ⅲ AEG.展开更多
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by the National Natural Science Foundation of China(92049104)the Research Startup Project by Hangzhou Normal University(4125C5021920435 and 4125C5021920453)the General Scientific Research Project of Zhejiang Provincial Department of Education in 2021(Y202147589).
文摘Alzheimer's disease(AD),a degenerative disease of the central nervous system,is characterized by progressive cognitive dysfunction and behavioral impairment.AD has been linked to the formation of amyloid-β(Aβ)plaque deposits and neurofibrillary tangles(NFTs)in the brain[1].The aggregation of Aβmay repress the signal transmission of synapses between neurons,while tau tangles,the main components of NFTs,hinder the trafficking of nutrients and other molecules that are critical to normal function and neuronal survival.It has been reported that the deposition of Aβand the tangles of tau protein can activate microglia in the brain,during which balance cannot be maintained,chronic inflammation occurs,and the brain function of AD patients may be further impaired[2].As the mainstream theories,Aβand tau protein continue to be studied.Although researchers have mainly focused on the toxic effects of pathological factors such as Aβ,tau protein,and inflammatory factors,the physiological significance in pathological states and generative processes have rarely been considered.
基金supported by grants from the Research Start-up Project by Hangzhou Normal University(4125C5021920435 and 4125C5021920453).
文摘Ischemic stroke accounts for~85%of all strokes and generally occurs when blood flow is severely reduced due to clots or masses blocking blood vessels and cutting off blood flow to brain cells.The death or damage to neurons caused by a stroke lead to corresponding symptoms such as weakness,paralysis,and numbness in the part of the body controlled by the affected area.
基金supported by the National Natural Science Foundation of China,Nos.82071387(to HT),81971172(to YW)the Natural Science Foundation of Zhejiang Province,China,No.LY22H090012(to HT)the Basic Research Project of Wenzhou City,China,No.Y20220923(to MZ)。
文摘The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.
基金This work was supported by the National Natural Science Foundation of China(Grant No.51472144)the Shandong University Young Scholars Program(Grant No.2016WLJH27)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.2082019014)Shandong Provincial Natural Science Foundation(Grant No.ZR2020ME023)for financial support.
文摘Yttria-stabilized zirconia(YSZ)fiber composites are highly efficient thermal insulating materials;however,the poor thermal shock resistance limits their versatile applications.In the present study,YSZ fiber was mixed directly with Al_(2)TiO_(5)fiber,which had an extremely low thermal expansion coefficient,to prepare YSZ–Al_(2)TiO_(5)(ZAT)fiber composites by compression molding and heat treatment.The minimum thermal expansion coefficient of the prepared ZAT fiber composites was measured to be 7.74×10^(−6)K^(−1),which was 26%lower than that of the YSZ fiber composites(10.42×10^(−6)K^(−1)).It was shown that the prepared ZAT fiber composites maintain the integrity after undergoing 51 thermal shock cycles between 1100℃and room temperature.Whereas,YSZ fiber composites burst immediately after only one thermal shock cycle under the same condition.In addition,the ZAT fiber composites also exhibit considerable mechanical and thermal insulating performance.
基金supported by the National Natural Science Foundation of China(92049104 and 82103210)a Research Start-up Project by Hangzhou Normal University(4125C5021920453 and 4125C50220204106).
文摘Astrocytes,the most abundant cells in the central nervous system(CNS),have a variety of functions such as providing nutrients for neurons,facilitating the formation and functioning of synapses,pruning synapses through phagocytosis,and maintaining homeostasis[1].As a response to CNS injury and disease,quiescent astrocytes are transformed into reactive astrocytes,which usually can be divided into two types:Al and A2[2].Al astrocytes help to drive the death of neurons and oligodendrocytes in neurodegenerative disorders by producing a large number of inflammatory factors and secreted toxins,while A2 astrocytes protect neurons via releasing many neurotrophic factors[3].
基金the Wu Jieping Medical Foundation(Nos.320.6750.2020-11-5 and 320.6750.2020-11-6)Key Research and Development(R&D)Projects of Shanxi Province(No.201703D321008).
文摘Objective:To identify risk factors for anastomotic leakage after gastrectomy in patients with Siewert type II/III adenocarcinoma(AEG)of the esophagogastric junction.Methods:This was a retrospective case-control study of 903 patients with Siewert type II/III AEG treated from January 2012 to January 2015 at the Shanxi Cancer Hospital in China.All patients underwent gastrectomy,and their clinical characteristics were analyzed to identify associations with anastomotic leakage.Independent risk factors were identified by binary logistic regression.The 2-year disease-free survival was calculated and compared between patients with anastomotic leakage and control patients.The study was approved by the Institutional Review Board of Shanxi Medical University(approval No.2014-09-39)on September 19,2014.Results:Out of the 903 patients were included in the study,80(8.86%,80/903)experienced anastomotic leakage.The mortality rate attributed to anastomotic leakage was 8.75%(7/80).Logistic regression analysis revealed that preoperative hypoalbuminemia(odds ratio(OR)=3.249,95%confidence interval(CI):1.569-6.725,P=0.002),type of reconstruction(OR=1.795,95%CI:1.026-3.142,P=0.040),and combined organ resection(OR=1.807,95%CI:1.069-3.055,P=0.027)were independent risk factors for anastomotic leakage.Conclusion:Preoperative hypoalbuminemia,type of reconstruction,and combined organ resection were identified as risk factors for anastomotic leakage in patients undergoing gastrectomy for Siewert type Ⅱ/Ⅲ AEG.
