BACKGROUND Ankylosing spondylitis(AS)is a chronic immune-mediated inflammatory disease.The prevailing theory links AS onset to infections in susceptible individuals.Furthermore,infections may impair the immune respons...BACKGROUND Ankylosing spondylitis(AS)is a chronic immune-mediated inflammatory disease.The prevailing theory links AS onset to infections in susceptible individuals.Furthermore,infections may impair the immune responses.Numerous studies have investigated links between AS and various infections-bacterial,viral,fungal,and other microorganism infections.However,limited attention has been given to the association between AS and Clonorchis sinensis(C.sinensis)infection.CASE SUMMARY A 27-year-old male with a 10-yr history of AS presented to our hospital with inflammatory lower back pain as the primary manifestation.Ten years ago,the patient had achieved a stable condition after treatment with biological agents.However,he experienced a recurrence of lumbosacral pain with an unexplained cause 10 d before hospital admission.A lumbosacral magnetic resonance imaging(MRI)scan revealed bone marrow edema in the left sacroiliac joint,and laboratory indicators were elevated.Moreover,the presence of C.sinensis eggs was detected in the stool.The patient was prescribed praziquantel,resulting in the disap-pearance of C.sinensis eggs in subsequent routine stool tests and relief from lumbosacral pain.A follow-up MRI scan performed after 4 months revealed a reduction in bone marrow edema around the left sacroiliac joint.CONCLUSION C.sinensis infections could potentially trigger the exacerbation of AS.Clinicians should pay attention to investigating the presence of infections.INTRODUCTION Ankylosing spondylitis(AS)is a chronic inflammatory and rheumatic disease resulting from an imbalance between innate and acquired immune responses[1].While it can affect any part of the spine,its primary symptoms are persistent back pain and stiffness in the lower back and pelvis.The prevalence of AS per 10000 individuals is 23.8 in Europe,31.9 in North America,16.7 in Asia,10.2 in Latin America,and 7.4 in Africa[2].Infections commonly occur in the first 3 months and may act as potential triggers for the first symptoms of AS,often manifesting as gastrointestinal,urinary tract,and respiratory infections of microbiological origin[3,4].Clonorchis sinensis(C.sinensis)infection is a severe parasitic disease affecting millions globally,especially prevalent in China,South Korea,the Far East of Russia,and Vietnam,with an estimated 15 million cases[5].Transmission occurs through the consumption of undercooked freshwater fish containing metacercariae.Adult C.sinensis parasites then establish themselves within the human hepatobiliary system[6].C.sinensis infection triggers the activation of sphingosine 1-phosphate receptor 2,leading to the injury and fibrosis of the hepatobiliary[7].Recent research in a rat model found that C.sinensis infection increases the risk of hepatocellular carcinoma by stimulating hepatic progenitor cell proliferation[8].Complications of C.sinensis infection include cholestasis,cholangitis,biliary system fibrosis,and in severe cases,the development of cholangiocarcinoma[9].Consequently,the primary preventive measure is to abstain from consuming raw or undercooked freshwater fish.Praziquantel is the recommended and effective treatment for this infection[10].While there is existing literature on the coexistence of AS and parasitic infections,there is limited research specifically addressing the simultaneous presence of AS and C.sinensis infection.This case report details a rare scenario of AS coexisting with C.sinensis infection,underscoring the potential impact of C.sinensis infection on AS disease activity.展开更多
目的:应用光学相干断层血管造影(OCTA)评估糖尿病视网膜病变(DR)患者中心凹无血管区(FAZ)和血管密度(VD)的变化。方法:对OCTA在DR诊断中的应用文献进行系统回顾。搜索Medline、Embase、Web of Science、PubMed、中国知网数据库、万方数...目的:应用光学相干断层血管造影(OCTA)评估糖尿病视网膜病变(DR)患者中心凹无血管区(FAZ)和血管密度(VD)的变化。方法:对OCTA在DR诊断中的应用文献进行系统回顾。搜索Medline、Embase、Web of Science、PubMed、中国知网数据库、万方数据库以查找相关研究,检索时间从建库截止到2020-09-20。仅检索中英文文献。两名研究者分别独立提取文献资料,包括浅层视网膜毛细血管层血管线性密度(VDSCP)、深层视网膜毛细血管层血管线性密度(VDDCP)、浅层FAZ面积和周长。绘制森林图、漏斗图,并采用Begg检验和敏感性分析,确保结果的准确性。结果:共检索得24篇文献,纳入2305眼。结果显示,糖尿病患者与健康对照组各指标均有差异(VDSCP:WMD=-5.78,95%CI:-7.67~-3.88,P<0.05;VDDCP:WMD=-5.08,95%CI:-6.49~-3.67,P<0.05;FAZ周长:WMD=0.57,95%CI:0.36~0.78,P<0.05;FAZ面积:WMD=0.08,95%CI:0.06~0.10,P<0.05)。结论:DR患者FAZ面积更大,周长更长,与DR患者对比,对照组FAZ的VD较高。虽然目前OCTA的实际适用性仍然存在问题,但随着技术的不断发展和改进,OCTA在DR中的诊断价值可能会变得明显。展开更多
Alzheimer’s disease(AD)is a chronic neurodegenerative disease that mainly causes dementia.It is a serious threat to the health of the global elderly population.Considerable money and effort has been invested in the d...Alzheimer’s disease(AD)is a chronic neurodegenerative disease that mainly causes dementia.It is a serious threat to the health of the global elderly population.Considerable money and effort has been invested in the development of drug therapy for AD worldwide.Many drug therapies are currently under development or in clinical trials,based on two known mechanisms of AD,namely,Aβtoxicity and the abnormal Tau hyperphosphorylation.Numerous drugs are also being developed for other AD associated mechanisms such as neuroinflammation,neurotransmitter imbalance,oxidative damage and mitochondrial dysfunction,neuron loss and degeneration.Even so,the number of drugs that can successfully improve symptoms or delay the progression of the disease remains very limited.However,multi-drug combinations may provide a new avenue for drug therapy for AD.In addition,early diagnosis of AD and timely initiation of treatment may allow drugs that act on the early pathological processes of AD to help improve the symptoms and prevent the progression of the condition.展开更多
Protein phosphatase 2A(PP2A)is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes.As a confirmed tumor suppressor,PP2A activity is downregulated in tumors and its ...Protein phosphatase 2A(PP2A)is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes.As a confirmed tumor suppressor,PP2A activity is downregulated in tumors and its re-activation can induce apoptosis of cancer cells.In the brains of Alzheimer's disease(AD)patients,decreased PP2A activity also plays a key role in promoting tau hyperphosphorylation and A0 generation.In this review,we discussed compounds aiming at modulating PP2A activity in the treatment of cancer or AD.The upstream factors that inactivate PP2A in diseases have not been fully elucidated and further studies are needed.It will help for the refinement and development of novel and clinically tractable PP2A-targeted compounds or therapies for the treatment of tumor and AD.展开更多
Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of m...Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of millions of people. Although the exact pathogenesis of AD has not been fully elucidated, amyloid plaques, neurofibrillary tangles (NFTs), and sustaining neuroinflammation dominate its characteristics. As one of the major tau kinases leading to hyperphosphorylation and aggregation of tau, glycogen synthase kinase-3β (GSK-3β) has been drawing great attention in various AD studies. Another research focus of AD in recent years is the inflammasome, a multiprotein complex acting as a regulator in immunological reactions to exogenous and endogenous danger signals, of which the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome has been studied mostly in AD and proven to play a significant role in AD development by its activation and downstream effects such as caspase-1 maturation and interleukin (IL)-1β release. Studies have shown that the NLRP3 inflammasome is activated in a GSK-3β-dependent way and that inhibition of the NLRP3 inflammasome downregulates GSK-3β, suggesting that these two important proteins are closely related. This article reviews the respective roles of GSK-3β and the NLRP3 inflammasome in AD as well as their relationship and interaction.展开更多
Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by ...Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by the investigators revealed that the upregulation of CREB improves the MK801-related SZ cognitive deficit.The present study further investigates the mechanism on how CREB deficiency is associated with SZ-related cognitive impairment.Methods MK-801 was used to induce SZ in rats.Western blotting and immunofluorescence were performed to investigate CREB and the CREB-related pathway implicated in MK801 rats.The long-term potentiation and behavioral tests were performed to assess the synaptic plasticity and cognitive impairment,respectively.Results The phosphorylation of CREB at Ser133 decreased in the hippocampus of SZ rats.Interestingly,among the upstream kinases of CREB,merely ERK1/2 was downregulated,while CaMKII and PKA remained unchanged in the brain of MK801-related SZ rats.The inhibition of ERK1/2 by PD98059 reduced the phosphorylation of CREB-Ser133,and induced synaptic dysfunction in primary hippocampal neurons.Conversely,the activation of CREB attenuated the ERK1/2 inhibitor-induced synaptic and cognitive impairment.Conclusion These present findings partially suggest that the deficiency of the ERK1/2-CREB pathway is involved in MK801-related SZ cognitive impairment.The activation of the ERK1/2-CREB pathway may be therapeutically useful for treating SZ cognitive deficits.展开更多
Objective Post-stroke cognitive impairment(PSCI)develops in approximately one-third of stroke survivors and is associated with ingravescence.Nonetheless,the biochemical mechanisms underlying PSCI remain unclear.The st...Objective Post-stroke cognitive impairment(PSCI)develops in approximately one-third of stroke survivors and is associated with ingravescence.Nonetheless,the biochemical mechanisms underlying PSCI remain unclear.The study aimed to establish an ischemic mouse model by means of transient unilateral middle cerebral artery occlusions(MCAOs)and to explore the biochemical mechanisms of p25/cyclin-dependent kinase 5(CDK5)-mediated tau hyperphosphorylation on the PSCI behavior.Methods Cognitive behavior was investigated,followed by the detection of tau hyperphosphorylation,mobilization,activation of kinases and/or inhibition of phosphatases in the lateral and contralateral cerebrum of mice following ischemia in MACO mice.Finally,we treated HEK293/tau cells with oxygen-glucose deprivation(OGD)and a CDK5 inhibitor(Roscovitine)or a GSK3βinhibitor(LiCl)to the roles of CDK5 and GSK3βin mediating ischemia-reperfusion-induced tau phosphorylation.Results Ischemia induced cognitive impairments within 2 months,as well as causing tau hyperphosphorylation and its localization to neuronal somata in both ipsilateral and contralateral cerebra.Furthermore,p25 that promotes CDK5 hyperactivation had significantly higher expression in the mice with MCAO than in the shamoperation(control)group,while the expression levels of protein phosphatase 2(PP2A)and the phosphorylation level at Tyr307 were comparable between the two groups.In addition,the CDK5 inhibitor rescued tau from hyperphosphorylation induced by OGD.Conclusion These findings demonstrate that upregulation of CDK5 mediates tau hyperphosphorylation and localization in both ipsilateral and contralateral cerebra,contributing to the pathogenesis of PSCI.展开更多
The article“Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease”,written by Hui WEI,Hui-liang ZHANG,Jia-zhao XIE,Dong-li MENG,Xiao-chuan WANG,Dan KE,Ji ZENG,Rong LIU,was or...The article“Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease”,written by Hui WEI,Hui-liang ZHANG,Jia-zhao XIE,Dong-li MENG,Xiao-chuan WANG,Dan KE,Ji ZENG,Rong LIU,was originally published electronically on the publisher's internet portal on 13 March 2020 without open access.With the author(s)'decision to opt for Open Choice the copyright of the article changed to O The Author(s)2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License(https://creativecommons.org/licenses/by/4.0/),which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.展开更多
It has been more than 3 years since the novel coronavirus(SARS-CoV-2)pandemic raged globally.The coronavirus disease 2019(COVID-19)has greatly influenced human society.According to data from the World Health Organizat...It has been more than 3 years since the novel coronavirus(SARS-CoV-2)pandemic raged globally.The coronavirus disease 2019(COVID-19)has greatly influenced human society.According to data from the World Health Organization(WHO),there were over 656 million confirmed cases of COVID-19 in the world as of January 1,2023,including over 6.6 million deaths[1].展开更多
Here we report the discovery of superconductivity in the ternary LaRu2As2 compound. The polycrystalline LaRu2As2 samples were synthesized by the conventional solid state reaction method. Powder X-ray diffraction analy...Here we report the discovery of superconductivity in the ternary LaRu2As2 compound. The polycrystalline LaRu2As2 samples were synthesized by the conventional solid state reaction method. Powder X-ray diffraction analysis indicates that LaRu2As2 crystallizes in the ThCr2Si2-type crystal structure with the space group 14/ mmm (No. 139), and the refined lattice parameters are a = 4.182(6)A and c = 10.590(3)A. The temperature dependent resistivity measurement shows a clear superconducting transition with the onset Tc (critical tempera- ture) at 7.8 K, and zero resistivity happens at 6.8 K. The upper critical field at zero temperature μ0Hc2(0) was estimated to be 1.6 T from the resistivity measurement. DC magnetic susceptibility measurement shows a bulk superconducting Meissner transition at 7.0 K, and the isothermal magnetization measurement indicates that LaRu2As2 is a type-II superconductor.展开更多
The supercritical carbon dioxide(SC-CO2)jet has a wide application prospect for rock breaking and jet fracturing in the development of the unconventional shale energy,due to its special physicochemical properties.To i...The supercritical carbon dioxide(SC-CO2)jet has a wide application prospect for rock breaking and jet fracturing in the development of the unconventional shale energy,due to its special physicochemical properties.To investigate its jet flow characteristics,the high-speed photography is used in experiments and the simulations through a compressible numerical model are carried out.It is shown that the jet flow field can be divided into three typical regions,the mixing layer possesses the same characteristics as a gas/gas turbulent mixing layer,with the divergent angles evidently smaller than those of the incompressible jets.The predicted results by the numerical model are in a good agreement with those of the experimentations.Through the dimensionless analysis,the potential core shows a length of about 9d and an increasing trend with the increase of the inlet pressure while the decay rate shows a decreasing trend,and the radial profiles consistent well with the 41 Ue-η''normalized method.In addition,a significant temperature drop of the SC-CO2 is observed between the nozzle inlet and the exit.A simple and convenient semi-empirical equation for calculating this temperature variation is deduced.Finally,the flow characteristics suggest that the SC-CO2 jet should be treated as a compressible jet.展开更多
We report the discovery and characterization of a novel 112-type iron pnictide EuFeAs2, with La-doping induced superconductivity in a series of Eu1- xLaxFeAs2. The polycrystalline samples were synthesized through soli...We report the discovery and characterization of a novel 112-type iron pnictide EuFeAs2, with La-doping induced superconductivity in a series of Eu1- xLaxFeAs2. The polycrystalline samples were synthesized through solid state reaction method only within a very narrow temperature window around 1073 K. Small single crystals were also grown from a flux method with the size about 100μm. The crystal structure was identified by single crystal X-ray diffraction analysis as a monoclinic structure with space group of P2 1/m. From resistivity and magnetic susceptibility measurements, we found that the parent compound EuFeAs2 shows distinct anomalies probably due to the Fe2+ related antiferromagnetic/structural phase transition near 110K and the Eu2+ related antiferromagnetic phase transition near 40K. La-doping suppressed both phase transitions to lower temperatures and induced superconducting transitions with a Tc - 11 K for Eu0.85La0.15FeAs2.展开更多
Coronavirus disease 2019(COVID-19)is a public health disaster that has not been encountered for a hundred years.On January 12,2020,the World Health Organization(WHO)confirmed and named the coronavirus which caused une...Coronavirus disease 2019(COVID-19)is a public health disaster that has not been encountered for a hundred years.On January 12,2020,the World Health Organization(WHO)confirmed and named the coronavirus which caused unexplained pneumonia as 2019 novel coronavirus(2019-nCoV).Since then,the disease caused by this virus had been named as coronavirus disease 2019(COVID-19).On February 11,2020,the International Committee on Taxonomy of Viruses announced that the English name of the novel coronavirus was severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[1].At present,SARS-CoV-2 infection is still rampant worldwide.As of September 10,2021,there were about 222 million confirmed cases of COVID-19 and more than 4.5 million deaths worldwide[2].According to the American Centers for Disease Control and Prevention,by July 29,2021,4.19 million pediatric COVID-19 cases had been reported in the United States。展开更多
Coronavirus disease 2019(COVID-19)remains a global epidemic.As of August 18,2021,the number of reported cases has exceeded 207 million globally,with more than 4.3 million deaths.COVID-19 has brought devastating losses...Coronavirus disease 2019(COVID-19)remains a global epidemic.As of August 18,2021,the number of reported cases has exceeded 207 million globally,with more than 4.3 million deaths.COVID-19 has brought devastating losses to human society.The overall crude mortality rate is 1-3%.Although pediatric deaths from COVID-19 are rare,they do occur,as over 9,000 children have died from COVID-19 globally to date[1].With the gradual and broad application of COVID-19 vaccines around the world,the rising proportion of cases among children and unvaccinated young adults demands attention.According to World Health Organization surveillance data.展开更多
基金Supported by Chongqing Municipal Health Commission's Key Discipline Construction Project of Traditional Chinese Medicine Bi Disease,Yu Traditional Chinese Medicine(2021),No.16.
文摘BACKGROUND Ankylosing spondylitis(AS)is a chronic immune-mediated inflammatory disease.The prevailing theory links AS onset to infections in susceptible individuals.Furthermore,infections may impair the immune responses.Numerous studies have investigated links between AS and various infections-bacterial,viral,fungal,and other microorganism infections.However,limited attention has been given to the association between AS and Clonorchis sinensis(C.sinensis)infection.CASE SUMMARY A 27-year-old male with a 10-yr history of AS presented to our hospital with inflammatory lower back pain as the primary manifestation.Ten years ago,the patient had achieved a stable condition after treatment with biological agents.However,he experienced a recurrence of lumbosacral pain with an unexplained cause 10 d before hospital admission.A lumbosacral magnetic resonance imaging(MRI)scan revealed bone marrow edema in the left sacroiliac joint,and laboratory indicators were elevated.Moreover,the presence of C.sinensis eggs was detected in the stool.The patient was prescribed praziquantel,resulting in the disap-pearance of C.sinensis eggs in subsequent routine stool tests and relief from lumbosacral pain.A follow-up MRI scan performed after 4 months revealed a reduction in bone marrow edema around the left sacroiliac joint.CONCLUSION C.sinensis infections could potentially trigger the exacerbation of AS.Clinicians should pay attention to investigating the presence of infections.INTRODUCTION Ankylosing spondylitis(AS)is a chronic inflammatory and rheumatic disease resulting from an imbalance between innate and acquired immune responses[1].While it can affect any part of the spine,its primary symptoms are persistent back pain and stiffness in the lower back and pelvis.The prevalence of AS per 10000 individuals is 23.8 in Europe,31.9 in North America,16.7 in Asia,10.2 in Latin America,and 7.4 in Africa[2].Infections commonly occur in the first 3 months and may act as potential triggers for the first symptoms of AS,often manifesting as gastrointestinal,urinary tract,and respiratory infections of microbiological origin[3,4].Clonorchis sinensis(C.sinensis)infection is a severe parasitic disease affecting millions globally,especially prevalent in China,South Korea,the Far East of Russia,and Vietnam,with an estimated 15 million cases[5].Transmission occurs through the consumption of undercooked freshwater fish containing metacercariae.Adult C.sinensis parasites then establish themselves within the human hepatobiliary system[6].C.sinensis infection triggers the activation of sphingosine 1-phosphate receptor 2,leading to the injury and fibrosis of the hepatobiliary[7].Recent research in a rat model found that C.sinensis infection increases the risk of hepatocellular carcinoma by stimulating hepatic progenitor cell proliferation[8].Complications of C.sinensis infection include cholestasis,cholangitis,biliary system fibrosis,and in severe cases,the development of cholangiocarcinoma[9].Consequently,the primary preventive measure is to abstain from consuming raw or undercooked freshwater fish.Praziquantel is the recommended and effective treatment for this infection[10].While there is existing literature on the coexistence of AS and parasitic infections,there is limited research specifically addressing the simultaneous presence of AS and C.sinensis infection.This case report details a rare scenario of AS coexisting with C.sinensis infection,underscoring the potential impact of C.sinensis infection on AS disease activity.
文摘目的:应用光学相干断层血管造影(OCTA)评估糖尿病视网膜病变(DR)患者中心凹无血管区(FAZ)和血管密度(VD)的变化。方法:对OCTA在DR诊断中的应用文献进行系统回顾。搜索Medline、Embase、Web of Science、PubMed、中国知网数据库、万方数据库以查找相关研究,检索时间从建库截止到2020-09-20。仅检索中英文文献。两名研究者分别独立提取文献资料,包括浅层视网膜毛细血管层血管线性密度(VDSCP)、深层视网膜毛细血管层血管线性密度(VDDCP)、浅层FAZ面积和周长。绘制森林图、漏斗图,并采用Begg检验和敏感性分析,确保结果的准确性。结果:共检索得24篇文献,纳入2305眼。结果显示,糖尿病患者与健康对照组各指标均有差异(VDSCP:WMD=-5.78,95%CI:-7.67~-3.88,P<0.05;VDDCP:WMD=-5.08,95%CI:-6.49~-3.67,P<0.05;FAZ周长:WMD=0.57,95%CI:0.36~0.78,P<0.05;FAZ面积:WMD=0.08,95%CI:0.06~0.10,P<0.05)。结论:DR患者FAZ面积更大,周长更长,与DR患者对比,对照组FAZ的VD较高。虽然目前OCTA的实际适用性仍然存在问题,但随着技术的不断发展和改进,OCTA在DR中的诊断价值可能会变得明显。
基金This study was supported by the Ministry of Science and Technology of China(No.2016YFC1305800)the National Natural Science Foundation of China(No.31771114 and No.31929002)+1 种基金the Innovative Research Groups of the National Natural Science Foundation of China(No.81721005)the Academic Frontier Youth Team Project to Xiao-chuan WANG from Huazhong University of Science and Technology。
文摘Alzheimer’s disease(AD)is a chronic neurodegenerative disease that mainly causes dementia.It is a serious threat to the health of the global elderly population.Considerable money and effort has been invested in the development of drug therapy for AD worldwide.Many drug therapies are currently under development or in clinical trials,based on two known mechanisms of AD,namely,Aβtoxicity and the abnormal Tau hyperphosphorylation.Numerous drugs are also being developed for other AD associated mechanisms such as neuroinflammation,neurotransmitter imbalance,oxidative damage and mitochondrial dysfunction,neuron loss and degeneration.Even so,the number of drugs that can successfully improve symptoms or delay the progression of the disease remains very limited.However,multi-drug combinations may provide a new avenue for drug therapy for AD.In addition,early diagnosis of AD and timely initiation of treatment may allow drugs that act on the early pathological processes of AD to help improve the symptoms and prevent the progression of the condition.
基金grants from National Natural Science Foundation of China(No.31970964 and No.31771189)Natural Science Foundation of Hubei Province,China(No.2017CFA065)Wuhan Health and Family Planning Commission(No.WX18C17).
文摘Protein phosphatase 2A(PP2A)is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes.As a confirmed tumor suppressor,PP2A activity is downregulated in tumors and its re-activation can induce apoptosis of cancer cells.In the brains of Alzheimer's disease(AD)patients,decreased PP2A activity also plays a key role in promoting tau hyperphosphorylation and A0 generation.In this review,we discussed compounds aiming at modulating PP2A activity in the treatment of cancer or AD.The upstream factors that inactivate PP2A in diseases have not been fully elucidated and further studies are needed.It will help for the refinement and development of novel and clinically tractable PP2A-targeted compounds or therapies for the treatment of tumor and AD.
基金supported by grants from the National Natural Science Foundation of China(No.92049107 and No.31929002)the Innovative Research Groups of the National Natural Science Foundation of China(No.81721005)the Academic Frontier Youth Team Project to Xiaochuan Wang from Huazhong University of Science and Technology.
文摘Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of millions of people. Although the exact pathogenesis of AD has not been fully elucidated, amyloid plaques, neurofibrillary tangles (NFTs), and sustaining neuroinflammation dominate its characteristics. As one of the major tau kinases leading to hyperphosphorylation and aggregation of tau, glycogen synthase kinase-3β (GSK-3β) has been drawing great attention in various AD studies. Another research focus of AD in recent years is the inflammasome, a multiprotein complex acting as a regulator in immunological reactions to exogenous and endogenous danger signals, of which the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome has been studied mostly in AD and proven to play a significant role in AD development by its activation and downstream effects such as caspase-1 maturation and interleukin (IL)-1β release. Studies have shown that the NLRP3 inflammasome is activated in a GSK-3β-dependent way and that inhibition of the NLRP3 inflammasome downregulates GSK-3β, suggesting that these two important proteins are closely related. This article reviews the respective roles of GSK-3β and the NLRP3 inflammasome in AD as well as their relationship and interaction.
基金supported in part by grants from National Natural Science Foundation of China(No.31929002,No.82201326 No.82071440 and No.92049107)Science,Technology and Innovation Commission of Shenzhen Municipality(No.JCYJ20210324141405014)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2020B1515120017)the Academic Frontier Youth Team Project to Xiao-chuan WANG from Huazhong University of Science and Technology.
文摘Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by the investigators revealed that the upregulation of CREB improves the MK801-related SZ cognitive deficit.The present study further investigates the mechanism on how CREB deficiency is associated with SZ-related cognitive impairment.Methods MK-801 was used to induce SZ in rats.Western blotting and immunofluorescence were performed to investigate CREB and the CREB-related pathway implicated in MK801 rats.The long-term potentiation and behavioral tests were performed to assess the synaptic plasticity and cognitive impairment,respectively.Results The phosphorylation of CREB at Ser133 decreased in the hippocampus of SZ rats.Interestingly,among the upstream kinases of CREB,merely ERK1/2 was downregulated,while CaMKII and PKA remained unchanged in the brain of MK801-related SZ rats.The inhibition of ERK1/2 by PD98059 reduced the phosphorylation of CREB-Ser133,and induced synaptic dysfunction in primary hippocampal neurons.Conversely,the activation of CREB attenuated the ERK1/2 inhibitor-induced synaptic and cognitive impairment.Conclusion These present findings partially suggest that the deficiency of the ERK1/2-CREB pathway is involved in MK801-related SZ cognitive impairment.The activation of the ERK1/2-CREB pathway may be therapeutically useful for treating SZ cognitive deficits.
基金the National Natural Science Foundation of China(No.31800851)Natural Science Foundation of Hubei Province(No.2022CFB456)The Research Fund of Jianghan University(No.08210011).
文摘Objective Post-stroke cognitive impairment(PSCI)develops in approximately one-third of stroke survivors and is associated with ingravescence.Nonetheless,the biochemical mechanisms underlying PSCI remain unclear.The study aimed to establish an ischemic mouse model by means of transient unilateral middle cerebral artery occlusions(MCAOs)and to explore the biochemical mechanisms of p25/cyclin-dependent kinase 5(CDK5)-mediated tau hyperphosphorylation on the PSCI behavior.Methods Cognitive behavior was investigated,followed by the detection of tau hyperphosphorylation,mobilization,activation of kinases and/or inhibition of phosphatases in the lateral and contralateral cerebrum of mice following ischemia in MACO mice.Finally,we treated HEK293/tau cells with oxygen-glucose deprivation(OGD)and a CDK5 inhibitor(Roscovitine)or a GSK3βinhibitor(LiCl)to the roles of CDK5 and GSK3βin mediating ischemia-reperfusion-induced tau phosphorylation.Results Ischemia induced cognitive impairments within 2 months,as well as causing tau hyperphosphorylation and its localization to neuronal somata in both ipsilateral and contralateral cerebra.Furthermore,p25 that promotes CDK5 hyperactivation had significantly higher expression in the mice with MCAO than in the shamoperation(control)group,while the expression levels of protein phosphatase 2(PP2A)and the phosphorylation level at Tyr307 were comparable between the two groups.In addition,the CDK5 inhibitor rescued tau from hyperphosphorylation induced by OGD.Conclusion These findings demonstrate that upregulation of CDK5 mediates tau hyperphosphorylation and localization in both ipsilateral and contralateral cerebra,contributing to the pathogenesis of PSCI.
文摘The article“Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease”,written by Hui WEI,Hui-liang ZHANG,Jia-zhao XIE,Dong-li MENG,Xiao-chuan WANG,Dan KE,Ji ZENG,Rong LIU,was originally published electronically on the publisher's internet portal on 13 March 2020 without open access.With the author(s)'decision to opt for Open Choice the copyright of the article changed to O The Author(s)2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License(https://creativecommons.org/licenses/by/4.0/),which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.
基金National Natural Science Foundation of China(72174138)High-level Public health Talents Training Program of Beijing Municipal Health Commission(2022-2-002).
文摘It has been more than 3 years since the novel coronavirus(SARS-CoV-2)pandemic raged globally.The coronavirus disease 2019(COVID-19)has greatly influenced human society.According to data from the World Health Organization(WHO),there were over 656 million confirmed cases of COVID-19 in the world as of January 1,2023,including over 6.6 million deaths[1].
基金the financial supports from the National Natural Science Foundation of China (11474339)the National Basic Research Program of China (2010CB923000 and 2011CBA00100)the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB07020100)
文摘Here we report the discovery of superconductivity in the ternary LaRu2As2 compound. The polycrystalline LaRu2As2 samples were synthesized by the conventional solid state reaction method. Powder X-ray diffraction analysis indicates that LaRu2As2 crystallizes in the ThCr2Si2-type crystal structure with the space group 14/ mmm (No. 139), and the refined lattice parameters are a = 4.182(6)A and c = 10.590(3)A. The temperature dependent resistivity measurement shows a clear superconducting transition with the onset Tc (critical tempera- ture) at 7.8 K, and zero resistivity happens at 6.8 K. The upper critical field at zero temperature μ0Hc2(0) was estimated to be 1.6 T from the resistivity measurement. DC magnetic susceptibility measurement shows a bulk superconducting Meissner transition at 7.0 K, and the isothermal magnetization measurement indicates that LaRu2As2 is a type-II superconductor.
基金the National Key Basic Research Development Program of China(973 Program,Grant No.2014CB239203)the National Natural Science Foundation of China(Grant No.51474158)the Program for New Century Excellent Talents in University of Ministry of Education(Grant No.NCET-12-0424).
文摘The supercritical carbon dioxide(SC-CO2)jet has a wide application prospect for rock breaking and jet fracturing in the development of the unconventional shale energy,due to its special physicochemical properties.To investigate its jet flow characteristics,the high-speed photography is used in experiments and the simulations through a compressible numerical model are carried out.It is shown that the jet flow field can be divided into three typical regions,the mixing layer possesses the same characteristics as a gas/gas turbulent mixing layer,with the divergent angles evidently smaller than those of the incompressible jets.The predicted results by the numerical model are in a good agreement with those of the experimentations.Through the dimensionless analysis,the potential core shows a length of about 9d and an increasing trend with the increase of the inlet pressure while the decay rate shows a decreasing trend,and the radial profiles consistent well with the 41 Ue-η''normalized method.In addition,a significant temperature drop of the SC-CO2 is observed between the nozzle inlet and the exit.A simple and convenient semi-empirical equation for calculating this temperature variation is deduced.Finally,the flow characteristics suggest that the SC-CO2 jet should be treated as a compressible jet.
基金the financial supports from the National Natural Science Foundation of China (11474339)the National Basic Research Program of China (973 Program, 2016YFA0300301, 2010CB923000 and 2011CBA00100)the Youth Innovation Promotion Association of the Chinese Academy of Sciences
文摘We report the discovery and characterization of a novel 112-type iron pnictide EuFeAs2, with La-doping induced superconductivity in a series of Eu1- xLaxFeAs2. The polycrystalline samples were synthesized through solid state reaction method only within a very narrow temperature window around 1073 K. Small single crystals were also grown from a flux method with the size about 100μm. The crystal structure was identified by single crystal X-ray diffraction analysis as a monoclinic structure with space group of P2 1/m. From resistivity and magnetic susceptibility measurements, we found that the parent compound EuFeAs2 shows distinct anomalies probably due to the Fe2+ related antiferromagnetic/structural phase transition near 110K and the Eu2+ related antiferromagnetic phase transition near 40K. La-doping suppressed both phase transitions to lower temperatures and induced superconducting transitions with a Tc - 11 K for Eu0.85La0.15FeAs2.
文摘Coronavirus disease 2019(COVID-19)is a public health disaster that has not been encountered for a hundred years.On January 12,2020,the World Health Organization(WHO)confirmed and named the coronavirus which caused unexplained pneumonia as 2019 novel coronavirus(2019-nCoV).Since then,the disease caused by this virus had been named as coronavirus disease 2019(COVID-19).On February 11,2020,the International Committee on Taxonomy of Viruses announced that the English name of the novel coronavirus was severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[1].At present,SARS-CoV-2 infection is still rampant worldwide.As of September 10,2021,there were about 222 million confirmed cases of COVID-19 and more than 4.5 million deaths worldwide[2].According to the American Centers for Disease Control and Prevention,by July 29,2021,4.19 million pediatric COVID-19 cases had been reported in the United States。
文摘Coronavirus disease 2019(COVID-19)remains a global epidemic.As of August 18,2021,the number of reported cases has exceeded 207 million globally,with more than 4.3 million deaths.COVID-19 has brought devastating losses to human society.The overall crude mortality rate is 1-3%.Although pediatric deaths from COVID-19 are rare,they do occur,as over 9,000 children have died from COVID-19 globally to date[1].With the gradual and broad application of COVID-19 vaccines around the world,the rising proportion of cases among children and unvaccinated young adults demands attention.According to World Health Organization surveillance data.