The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically revie...The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.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
In IPv6 based MANETs, the neighbor discovery enables nodes to self-configure and communicate with neighbor nodes through autoconfiguration. The Stateless address autoconfiguration(SLAAC) has proven to face several sec...In IPv6 based MANETs, the neighbor discovery enables nodes to self-configure and communicate with neighbor nodes through autoconfiguration. The Stateless address autoconfiguration(SLAAC) has proven to face several security issues. Even though the Secure Neighbor Discovery(SeND) uses Cryptographically Generated Addresses(CGA) to address these issues, it creates other concerns such as need for CA to authenticate hosts, exposure to CPU exhaustion attacks and high computational intensity. These issues are major concern for MANETs as it possesses limited bandwidth and processing power. The paper proposes empirically strong Light Weight Cryptographic Address Generation(LW-CGA) using entropy gathered from system states. Even the system users cannot monitor these system states; hence LW-CGA provides high security with minimal computational complexity and proves to be more suitable for MANETs. The LW-CGA and SeND are implemented and tested to study the performances. The evaluation shows that LW-CGA with good runtime throughput takes minimal address generation latency.展开更多
基金supported by Yuan Du Scholars,Clinical Research Center of Affiliated Hospital of Shandong Second Medical University,No.2022WYFYLCYJ02Weifang Key Laboratory,Weifang Science and Technology Development Plan Project Medical Category,No.2022YX093.
文摘The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.
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.
文摘In IPv6 based MANETs, the neighbor discovery enables nodes to self-configure and communicate with neighbor nodes through autoconfiguration. The Stateless address autoconfiguration(SLAAC) has proven to face several security issues. Even though the Secure Neighbor Discovery(SeND) uses Cryptographically Generated Addresses(CGA) to address these issues, it creates other concerns such as need for CA to authenticate hosts, exposure to CPU exhaustion attacks and high computational intensity. These issues are major concern for MANETs as it possesses limited bandwidth and processing power. The paper proposes empirically strong Light Weight Cryptographic Address Generation(LW-CGA) using entropy gathered from system states. Even the system users cannot monitor these system states; hence LW-CGA provides high security with minimal computational complexity and proves to be more suitable for MANETs. The LW-CGA and SeND are implemented and tested to study the performances. The evaluation shows that LW-CGA with good runtime throughput takes minimal address generation latency.
