WHEN a mutinous band of the Democratic Republic of the Congo （DRC） military precipitated the latest eruption of war in June, it was hardly surprising given the fragile situation in Africa＇s second largest and natur...WHEN a mutinous band of the Democratic Republic of the Congo （DRC） military precipitated the latest eruption of war in June, it was hardly surprising given the fragile situation in Africa＇s second largest and natural resources endowed country. DRC has not known a continuous period of peace and tranquility since the mid-1990s.展开更多
Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrog...Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.展开更多
For decades,lignin-the rigid polymer that gives plants their structure-has been the“problem child”of green chemistry.When processed,its molecules tangle like stubborn knots,forming useless clumps.Then came 2024’s t...For decades,lignin-the rigid polymer that gives plants their structure-has been the“problem child”of green chemistry.When processed,its molecules tangle like stubborn knots,forming useless clumps.Then came 2024’s transformative solution-breaking lignin’s tangles at the molecular level.In that May,a team led by scientists from the Chinese Academy of Sciences(CAS)came up with an approach to make this“knotty problem”profitable by hacking lignin’s chemistry to spin it into bio-bisphenols.展开更多
BACKGROUND Alzheimer’s disease(AD)is a progressive neurodegenerative disorder currently lacking effective therapeutic interventions.Pathological hallmarks of AD include intracellular neurofibrillary tangles(NFTs)and ...BACKGROUND Alzheimer’s disease(AD)is a progressive neurodegenerative disorder currently lacking effective therapeutic interventions.Pathological hallmarks of AD include intracellular neurofibrillary tangles(NFTs)and extracellular amyloid beta(Aβ)plaques.Neuroplastin 65(NP65),highly expressed in the brain,has been previously shown to mitigate cognitive impairments and decrease Aβplaques in the AD mouse model,suggesting that NP65 is involved in AD neuropathology.However,direct evidence linking NP65 expression to AD pathogenesis in human brain remains absent.AIM To quantify NP65 isoform expression gradients across distinct neuroanatomical regions in the healthy brain and investigate the alterations of NP65 expression in the AD brain.METHODS Immunohistochemical,immunofluorescent and western blot analyses were used to investigate NP65 expression in 19 postmortem brains(AD=10,controls=9).Double immunostaining with 6E10 and or phosphorylated-microtubule-associated protein tau(AT-8,a marker for NFT)markers was performed to assess NP65 colocalization with Aβplaques and NFTs.RESULTS In controls,NP65 was highly expressed in a wide-range of brain areas.AD cases showed significantly increased NP65 immunoreactivity across multiple brain regions,including the frontal and temporal cortex,hippocampus,and cerebellum,compared to controls.Western blot analysis consistently confirmed significantly elevated NP65 expression in the hippocampus of AD patients relative to controls.Double immunostaining demonstrated partial colocalization of NP65 with NFTs and Aβplaques in AD brain tissue.CONCLUSION Our findings demonstrate a significant increase of NP65 protein,which colocalizes with NFTs and Aβplaques in AD brains,providing direct evidence supporting a critical role of NP65 expression in the neuropathological mechanisms of this disease.展开更多
Declining recognition of top university lists prompts China to look for new ways to evaluate its higher learning institutions Zhejiang University for the first time has overtaken Peking University and Tsinghua Univers...Declining recognition of top university lists prompts China to look for new ways to evaluate its higher learning institutions Zhejiang University for the first time has overtaken Peking University and Tsinghua University to rank No.1 on the latest list of Chinese college rankings.The rankings are an important part of the book Picking Your University展开更多
Syria’s ties to Russia and Iran make Western intervention unlikely After the fall of Muammar Gaddafi in Libya,Syria appeared to be the next target of Western powers.They have declared sanctions against Syria and publ...Syria’s ties to Russia and Iran make Western intervention unlikely After the fall of Muammar Gaddafi in Libya,Syria appeared to be the next target of Western powers.They have declared sanctions against Syria and publicly demanded Syrian President Bashar al-Assad step down.This Middle Eastern country now展开更多
How does it feel,to be sitting at a Bob Dylan concert in Beijing?I had to keep asking myself that question when the living legend sauntered on to the stage at the Beijing Worker’s Gymnasium.The troubadour who blew in...How does it feel,to be sitting at a Bob Dylan concert in Beijing?I had to keep asking myself that question when the living legend sauntered on to the stage at the Beijing Worker’s Gymnasium.The troubadour who blew in the wind like the pied piper all those years ago and has managed to roll展开更多
The Mao-era public radio speakers are disappearing from China’s villages,but not everyone is happy中国农村的“大喇叭”广播曾给一代人留下了难忘的记忆,而现在它正离我们远去Wake up at 7 a.m.in rural China and you’ll lik...The Mao-era public radio speakers are disappearing from China’s villages,but not everyone is happy中国农村的“大喇叭”广播曾给一代人留下了难忘的记忆,而现在它正离我们远去Wake up at 7 a.m.in rural China and you’ll likely hear the melodic strains of a love song,a popular talk show,or the local news wafting from an old speaker strung up on a telephone pole in the largest public space in the village.展开更多
Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau pro...Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein.Recent studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease neurodegeneration.Tau physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like characteristics.In addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner.This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.展开更多
Wireless Sensor Network(WSN)is a distributed sensor network composed a large number of nodes with low cost,low performance and self-management.The special structure of WSN brings both convenience and vulnerability.For...Wireless Sensor Network(WSN)is a distributed sensor network composed a large number of nodes with low cost,low performance and self-management.The special structure of WSN brings both convenience and vulnerability.For example,a malicious participant can launch attacks by capturing a physical device.Therefore,node authentication that can resist malicious attacks is very important to network security.Recently,blockchain technology has shown the potential to enhance the security of the Internet of Things(IoT).In this paper,we propose a Blockchain-empowered Authentication Scheme(BAS)for WSN.In our scheme,all nodes are managed by utilizing the identity information stored on the blockchain.Besides,the simulation experiment about worm detection is executed on BAS,and the security is evaluated from detection and infection rate.The experiment results indicate that the proposed scheme can effectively inhibit the spread and infection of worms in the network.展开更多
Objective The production of neurotoxic β-amyloid and the formation of hyperphosphorylated tau are thought to be critical steps contributing to the neuropathological mechanisms in Alzheimer’s disease （AD）. However,...Objective The production of neurotoxic β-amyloid and the formation of hyperphosphorylated tau are thought to be critical steps contributing to the neuropathological mechanisms in Alzheimer’s disease （AD）. However, there remains an argument as to their importance in the onset of AD.Recent studies have shown that axonopathy is considered as an early stage of AD. However, the exact relationship between axonopathy and the origin and development of classic neuropathological changes such as senile plaques （SPs） and neurofibrillary tangles （NFTs） is unclear. The present study aimed to investigate this relationship. Methods Postmortem tracing, combined with the immunohistochemical or immunofluo-rescence staining, was used to detect axonopathy and the formation of SPs and NFTs. Results ＂Axonal leakage＂–a novel type of axonopathy, was usually accompanied with the extensive swollen axons and varicosities, and was associated with the origin and development of Aβ plaques and hyperphosphorylated tau in the brains of AD patients. Conclusion Axonopathy, particularly axonal leakage, might be a key event in the initiation of the neuropathological processes in AD.展开更多
We evaluate the monogamy inequality for symmetric, non-symmetric pure states of importance in terms of squared concurrence, squared entanglement of formation, squared negativity of partial transpose and compare the co...We evaluate the monogamy inequality for symmetric, non-symmetric pure states of importance in terms of squared concurrence, squared entanglement of formation, squared negativity of partial transpose and compare the corresponding tangles. We show that though concurrence and concurrence tangle are zero for two special classes of mixed entangled states, both negativity tangle and entanglement of formation（EOF） tangle turn out to be non-zero. A comparison of different tangles is carried out in each case and it is shown that while the concurrence tangle captures the genuine multiqubit entanglement in N-qubit pure states with N distinct spinors（containing GHZ and superposition of W-, obverse W states）either negativity tangle or EOF tangle is to be used as a better measure of entanglement in the W-class of states with two distinct spinors and in the special classes of mixed multiqubit states.展开更多
All retinoids, which can be natural and synthetic, are chemically related to vitamin A. Both natural and synthetic retinoids use specific nuclear receptors such as retinoic acid receptors and retinoid X receptors to a...All retinoids, which can be natural and synthetic, are chemically related to vitamin A. Both natural and synthetic retinoids use specific nuclear receptors such as retinoic acid receptors and retinoid X receptors to activate specific signaling pathways in the cells. Retinoic acid signaling is extremely important in the central nervous system. Impairment of retinoic acid signaling pathways causes severe pathological processes in the central nervous system, especially in the adult brain. Retinoids have major roles in neural patterning, differentiation, axon outgrowth in normal development, and function of the brain. Impaired retinoic acid signaling results in neuroinflammation, oxidative stress, mitochondrial malfunction, and neurodegeneration leading to progressive Alzheimer’s disease, which is pathologically characterized by extra-neuronal accumulation of amyloid plaques(aggregated amyloid-beta) and intra-neurofibrillary tangles(hyperphosphorylated tau protein) in the temporal lobe of the brain. Alzheimer’s disease is the most common cause of dementia and loss of memory in old adults. Inactive cholinergic neurotransmission is responsible for cognitive deficits in Alzheimer’s disease patients. Deficiency or deprivation of retinoic acid in mice is associated with loss of spatial learning and memory. Retinoids inhibit expression of chemokines and neuroinflammatory cytokines in microglia and astrocytes, which are activated in Alzheimer’s disease. Stimulation of retinoic acid receptors and retinoid X receptors slows down accumulation of amyloids, reduces neurodegeneration, and thereby prevents pathogenesis of Alzheimer’s disease in mice. In this review, we described chemistry and biochemistry of some natural and synthetic retinoids and potentials of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer’s disease.展开更多
Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofib...Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles.Most of the Alzheimer’s drugs targeting amyloidβhave been failed in clinical trials.Particularly,tau pathology connects greatly in the pathogenesis of Alzheimer’s disease.Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron.Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved.The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its conformation and structural state.Therefore,aberrant phosphorylation,as well as truncation of tau protein,has come into focus as significant mechanisms that make tau protein in a pathological entity.Furthermore,the shape-shifting nature of tau advocates to comprehend the progression of Alzheimer’s disease precisely.In this review,we emphasize the recent studies about the toxic and shape-shifting nature of tau in the pathogenesis of Alzheimer’s disease.展开更多
Hydrogen exhibits the potential to treat Alzheimer's disease. Stereotactic injection has been previously used as an invasive method of administering active hydrogen, but this method has limitations in clinical pra...Hydrogen exhibits the potential to treat Alzheimer's disease. Stereotactic injection has been previously used as an invasive method of administering active hydrogen, but this method has limitations in clinical practice. In this study, triple transgenic(3×Tg) Alzheimer's disease mice were treated with hydrogen-rich water for 7 months. The results showed that hydrogen-rich water prevented synaptic loss and neuronal death, inhibited senile plaques, and reduced hyperphosphorylated tau and neurofibrillary tangles in 3×Tg Alzheimer's disease mice. In addition, hydrogen-rich water improved brain energy metabolism disorders and intestinal flora imbalances and reduced inflammatory reactions. These findings suggest that hydrogen-rich water is an effective hydrogen donor that can treat Alzheimer's disease. This study was approved by the Animal Ethics and Welfare Committee of Shenzhen University, China(approval No. AEWC-20140615-002) on June 15, 2014.展开更多
Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangl...Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles （NFTs）; these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone （TIB） have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB （0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks） on the content of total and hyperphosphorylated Tau （PHF-1） proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB： it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.展开更多
Alzheimer＇s disease （AD） is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflam- mation in the brain, as well as impaired cognitive behavio...Alzheimer＇s disease （AD） is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflam- mation in the brain, as well as impaired cognitive behaviors. A sex difference in the prevalence of AD has been noted, while sex differences in the cerebral pathology and relevant molecular mechanisms are not well clarified. In the present study, we systematically investigated the sex differences in pathological characteristics and cognitive behavior in 12-month-old male and female APP/PSI/tau triple-trans- genic AD mice （3xTg-AD mice） and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofib- rillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expres- sion levels of hippocampal protein kinase A-cAMP response element-binding protein （PKA-CREB） and p38- mitogen-activated protein kinases （MAPK） also showed sex difference in the AD mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in the p-p38 in female, but not male, 3×Tg-AD mice. We suggest that an estrogen deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3×Tg-AD mice might be involved in the serious pathological and cognitive damage in these mice. Therefore, sex differences should be taken into account in investigating AD biomarkers and related target molecules, and estrogen supplementation or PKA-CREB- MAPK stabilization could be beneficial in relieving the pathological damage in AD and improving the cognitive behavior of reproductively-senescent females.展开更多
文摘WHEN a mutinous band of the Democratic Republic of the Congo （DRC） military precipitated the latest eruption of war in June, it was hardly surprising given the fragile situation in Africa＇s second largest and natural resources endowed country. DRC has not known a continuous period of peace and tranquility since the mid-1990s.
基金supported by the National Research Foundation of Korea (NRF)funded by the Ministry of Science,ICT&Future Planning (2022R1A2C2006229,2022R1A6A3A01086868)Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea (RS-2024-00345328)KIST Institutional Grant (2E32851)。
文摘Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.
文摘For decades,lignin-the rigid polymer that gives plants their structure-has been the“problem child”of green chemistry.When processed,its molecules tangle like stubborn knots,forming useless clumps.Then came 2024’s transformative solution-breaking lignin’s tangles at the molecular level.In that May,a team led by scientists from the Chinese Academy of Sciences(CAS)came up with an approach to make this“knotty problem”profitable by hacking lignin’s chemistry to spin it into bio-bisphenols.
基金the National Natural Science Foundation of China,No.81771441 and No.81371213the Natural Science Foundation of Shanghai,No.21ZR1468400.
文摘BACKGROUND Alzheimer’s disease(AD)is a progressive neurodegenerative disorder currently lacking effective therapeutic interventions.Pathological hallmarks of AD include intracellular neurofibrillary tangles(NFTs)and extracellular amyloid beta(Aβ)plaques.Neuroplastin 65(NP65),highly expressed in the brain,has been previously shown to mitigate cognitive impairments and decrease Aβplaques in the AD mouse model,suggesting that NP65 is involved in AD neuropathology.However,direct evidence linking NP65 expression to AD pathogenesis in human brain remains absent.AIM To quantify NP65 isoform expression gradients across distinct neuroanatomical regions in the healthy brain and investigate the alterations of NP65 expression in the AD brain.METHODS Immunohistochemical,immunofluorescent and western blot analyses were used to investigate NP65 expression in 19 postmortem brains(AD=10,controls=9).Double immunostaining with 6E10 and or phosphorylated-microtubule-associated protein tau(AT-8,a marker for NFT)markers was performed to assess NP65 colocalization with Aβplaques and NFTs.RESULTS In controls,NP65 was highly expressed in a wide-range of brain areas.AD cases showed significantly increased NP65 immunoreactivity across multiple brain regions,including the frontal and temporal cortex,hippocampus,and cerebellum,compared to controls.Western blot analysis consistently confirmed significantly elevated NP65 expression in the hippocampus of AD patients relative to controls.Double immunostaining demonstrated partial colocalization of NP65 with NFTs and Aβplaques in AD brain tissue.CONCLUSION Our findings demonstrate a significant increase of NP65 protein,which colocalizes with NFTs and Aβplaques in AD brains,providing direct evidence supporting a critical role of NP65 expression in the neuropathological mechanisms of this disease.
文摘Declining recognition of top university lists prompts China to look for new ways to evaluate its higher learning institutions Zhejiang University for the first time has overtaken Peking University and Tsinghua University to rank No.1 on the latest list of Chinese college rankings.The rankings are an important part of the book Picking Your University
文摘Syria’s ties to Russia and Iran make Western intervention unlikely After the fall of Muammar Gaddafi in Libya,Syria appeared to be the next target of Western powers.They have declared sanctions against Syria and publicly demanded Syrian President Bashar al-Assad step down.This Middle Eastern country now
文摘How does it feel,to be sitting at a Bob Dylan concert in Beijing?I had to keep asking myself that question when the living legend sauntered on to the stage at the Beijing Worker’s Gymnasium.The troubadour who blew in the wind like the pied piper all those years ago and has managed to roll
文摘The Mao-era public radio speakers are disappearing from China’s villages,but not everyone is happy中国农村的“大喇叭”广播曾给一代人留下了难忘的记忆,而现在它正离我们远去Wake up at 7 a.m.in rural China and you’ll likely hear the melodic strains of a love song,a popular talk show,or the local news wafting from an old speaker strung up on a telephone pole in the largest public space in the village.
基金supported by the Neural Regeneration Co-innovation Center of Jiangsu Province,Nantong University(to DC)the National Natural Science Foundation of China,Nos.81872853(to DC),81870941(to JHG)the Science and Technology Project of Nantong City,Nos.JC22022022(to FW)and JC2021059(to JM)。
文摘Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein.Recent studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease neurodegeneration.Tau physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like characteristics.In addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner.This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.
基金supported by the Natural Science Foundation under Grant No.61962009Major Scientific and Technological Special Project of Guizhou Province under Grant No.20183001Foundation of Guizhou Provincial Key Laboratory of Public Big Data under Grant No.2018BDKFJJ003,2018BDKFJJ005 and 2019BDKFJJ009.
文摘Wireless Sensor Network(WSN)is a distributed sensor network composed a large number of nodes with low cost,low performance and self-management.The special structure of WSN brings both convenience and vulnerability.For example,a malicious participant can launch attacks by capturing a physical device.Therefore,node authentication that can resist malicious attacks is very important to network security.Recently,blockchain technology has shown the potential to enhance the security of the Internet of Things(IoT).In this paper,we propose a Blockchain-empowered Authentication Scheme(BAS)for WSN.In our scheme,all nodes are managed by utilizing the identity information stored on the blockchain.Besides,the simulation experiment about worm detection is executed on BAS,and the security is evaluated from detection and infection rate.The experiment results indicate that the proposed scheme can effectively inhibit the spread and infection of worms in the network.
基金supported by an"Excellent Project"of the China Ministry of Human Resources for Return Overseas Chinese Scholarshippartly by the Research Foundation for"Key Laboratory of Neu-roscience and Neuroengineering"of South-Central University for Nationalities(No.XJS09001)the National Natural Science Foundation of China(No.31070961)
文摘Objective The production of neurotoxic β-amyloid and the formation of hyperphosphorylated tau are thought to be critical steps contributing to the neuropathological mechanisms in Alzheimer’s disease （AD）. However, there remains an argument as to their importance in the onset of AD.Recent studies have shown that axonopathy is considered as an early stage of AD. However, the exact relationship between axonopathy and the origin and development of classic neuropathological changes such as senile plaques （SPs） and neurofibrillary tangles （NFTs） is unclear. The present study aimed to investigate this relationship. Methods Postmortem tracing, combined with the immunohistochemical or immunofluo-rescence staining, was used to detect axonopathy and the formation of SPs and NFTs. Results ＂Axonal leakage＂–a novel type of axonopathy, was usually accompanied with the extensive swollen axons and varicosities, and was associated with the origin and development of Aβ plaques and hyperphosphorylated tau in the brains of AD patients. Conclusion Axonopathy, particularly axonal leakage, might be a key event in the initiation of the neuropathological processes in AD.
基金support of the Department of Science and Technology (DST),Govt.of India through the award of the INSPIRE fellowship
文摘We evaluate the monogamy inequality for symmetric, non-symmetric pure states of importance in terms of squared concurrence, squared entanglement of formation, squared negativity of partial transpose and compare the corresponding tangles. We show that though concurrence and concurrence tangle are zero for two special classes of mixed entangled states, both negativity tangle and entanglement of formation（EOF） tangle turn out to be non-zero. A comparison of different tangles is carried out in each case and it is shown that while the concurrence tangle captures the genuine multiqubit entanglement in N-qubit pure states with N distinct spinors（containing GHZ and superposition of W-, obverse W states）either negativity tangle or EOF tangle is to be used as a better measure of entanglement in the W-class of states with two distinct spinors and in the special classes of mixed multiqubit states.
基金supported in part by an award from the Soy Health Research Program(SHRP,United Soybean Board,Chesterfield,MO,USA)(to SKR)a grant(SCIRF-2015-I-01) from South Carolina Spinal Cord Injury Research Fund(Columbia,SC,USA)(to SKR)earlier R01 grants(CA-091460,and NS-057811)(to SKR) from the National Institutes of Health(Bethesda,MD,USA)
文摘All retinoids, which can be natural and synthetic, are chemically related to vitamin A. Both natural and synthetic retinoids use specific nuclear receptors such as retinoic acid receptors and retinoid X receptors to activate specific signaling pathways in the cells. Retinoic acid signaling is extremely important in the central nervous system. Impairment of retinoic acid signaling pathways causes severe pathological processes in the central nervous system, especially in the adult brain. Retinoids have major roles in neural patterning, differentiation, axon outgrowth in normal development, and function of the brain. Impaired retinoic acid signaling results in neuroinflammation, oxidative stress, mitochondrial malfunction, and neurodegeneration leading to progressive Alzheimer’s disease, which is pathologically characterized by extra-neuronal accumulation of amyloid plaques(aggregated amyloid-beta) and intra-neurofibrillary tangles(hyperphosphorylated tau protein) in the temporal lobe of the brain. Alzheimer’s disease is the most common cause of dementia and loss of memory in old adults. Inactive cholinergic neurotransmission is responsible for cognitive deficits in Alzheimer’s disease patients. Deficiency or deprivation of retinoic acid in mice is associated with loss of spatial learning and memory. Retinoids inhibit expression of chemokines and neuroinflammatory cytokines in microglia and astrocytes, which are activated in Alzheimer’s disease. Stimulation of retinoic acid receptors and retinoid X receptors slows down accumulation of amyloids, reduces neurodegeneration, and thereby prevents pathogenesis of Alzheimer’s disease in mice. In this review, we described chemistry and biochemistry of some natural and synthetic retinoids and potentials of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer’s disease.
基金the support by the Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
文摘Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles.Most of the Alzheimer’s drugs targeting amyloidβhave been failed in clinical trials.Particularly,tau pathology connects greatly in the pathogenesis of Alzheimer’s disease.Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron.Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved.The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its conformation and structural state.Therefore,aberrant phosphorylation,as well as truncation of tau protein,has come into focus as significant mechanisms that make tau protein in a pathological entity.Furthermore,the shape-shifting nature of tau advocates to comprehend the progression of Alzheimer’s disease precisely.In this review,we emphasize the recent studies about the toxic and shape-shifting nature of tau in the pathogenesis of Alzheimer’s disease.
基金supported by the National Natural Science Foundation of China,No.21771126(to XBD)the Shenzhen Bureau of Science,Technology and Information of China,No.JCYJ20180305124000597(to XBD)。
文摘Hydrogen exhibits the potential to treat Alzheimer's disease. Stereotactic injection has been previously used as an invasive method of administering active hydrogen, but this method has limitations in clinical practice. In this study, triple transgenic(3×Tg) Alzheimer's disease mice were treated with hydrogen-rich water for 7 months. The results showed that hydrogen-rich water prevented synaptic loss and neuronal death, inhibited senile plaques, and reduced hyperphosphorylated tau and neurofibrillary tangles in 3×Tg Alzheimer's disease mice. In addition, hydrogen-rich water improved brain energy metabolism disorders and intestinal flora imbalances and reduced inflammatory reactions. These findings suggest that hydrogen-rich water is an effective hydrogen donor that can treat Alzheimer's disease. This study was approved by the Animal Ethics and Welfare Committee of Shenzhen University, China(approval No. AEWC-20140615-002) on June 15, 2014.
基金supported by FIS/IMSS project No.FIS/IMSS/PROT/G13/1216COFAA+1 种基金SIP-IPNby DGAPA-UNAM IN203616
文摘Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles （NFTs）; these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone （TIB） have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB （0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks） on the content of total and hyperphosphorylated Tau （PHF-1） proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB： it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.
基金partially funded by ‘‘Sanjin Scholars’’ of Shanxi Province and the National Natural Science Foundation of China(31471080,31600865,and31700918)sponsored by the Fund for Shanxi Key Subjects Construction+1 种基金Shanxi ‘‘1331 Project’’ Key Subjects ConstructionKey Laboratory of Cellular Physiology(Shanxi Medical University) in Shanxi Province
文摘Alzheimer＇s disease （AD） is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflam- mation in the brain, as well as impaired cognitive behaviors. A sex difference in the prevalence of AD has been noted, while sex differences in the cerebral pathology and relevant molecular mechanisms are not well clarified. In the present study, we systematically investigated the sex differences in pathological characteristics and cognitive behavior in 12-month-old male and female APP/PSI/tau triple-trans- genic AD mice （3xTg-AD mice） and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofib- rillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expres- sion levels of hippocampal protein kinase A-cAMP response element-binding protein （PKA-CREB） and p38- mitogen-activated protein kinases （MAPK） also showed sex difference in the AD mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in the p-p38 in female, but not male, 3×Tg-AD mice. We suggest that an estrogen deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3×Tg-AD mice might be involved in the serious pathological and cognitive damage in these mice. Therefore, sex differences should be taken into account in investigating AD biomarkers and related target molecules, and estrogen supplementation or PKA-CREB- MAPK stabilization could be beneficial in relieving the pathological damage in AD and improving the cognitive behavior of reproductively-senescent females.
