Contaminated sites from electronic waste(e-waste)dismantling and coking plants feature high concentrations of heavy metals(HMs)and/or polycyclic aromatic hydrocarbons(PAHs)in soil.Mixed contamination(HMsþPAHs)hi...Contaminated sites from electronic waste(e-waste)dismantling and coking plants feature high concentrations of heavy metals(HMs)and/or polycyclic aromatic hydrocarbons(PAHs)in soil.Mixed contamination(HMsþPAHs)hinders land reclamation and affects the microbial diversity and function of soil microbiomes.In this study,we analyzed HM and PAH contamination from an e-waste dismantling plant and a coking plant and evaluated the influences of HM and PAH contamination on soil microbiomes.It was noticed that HMs and PAHs were found in all sites,although the major contaminants of the e-waste dismantling plant site were HMs(such as Cu at 5,947.58±433.44 mg kg^(-1),Zn at 4,961.38±436.51 mg kg^(-1),and Mn at 2,379.07±227.46 mg kg^(-1)),and the major contaminants of the coking plant site were PAHs(such as fluorene at 11,740.06±620.1 mg kg^(-1),acenaphthylene at 211.69±7.04 mg kg^(-1),and pyrene at 183.14±18.89 mg kg^(-1)).The microbiomes(diversity and abundance)of all sites were determined via high-throughput sequencing of 16S rRNA genes,and redundancy analysis was conducted to investigate the relations between soil microbiomes and contaminants.The results showed that the microbiomes of the contaminated sites divergently responded to HMs and PAHs.The abundances of the bacterial genera Sulfuritalea,Pseudomonas,and Sphingobium were positively related to PAHs,while the abundances of the bacterial genera Bryobacter,Nitrospira,and Steroidobacter were positively related to HMs.This study promotes an understanding of how soil microbiomes respond to single and mixed contamination with HMs and PAHs.展开更多
In tauopathies,memory impairment positively strongly correlates with the amount of abnormal tau aggregates;however,how tau accumulation induces synapse impairment is unclear.Recently,we found that human tau accumulati...In tauopathies,memory impairment positively strongly correlates with the amount of abnormal tau aggregates;however,how tau accumulation induces synapse impairment is unclear.Recently,we found that human tau accumulation activated Signal Transduction and Activator of Transcription-1(STAT1)to inhibit the transcription of synaptic N-methyl-D-aspartate receptors(NMDARs).Here,overexpressing human P301L mutant tau(P301L-hTau)increased the phosphorylated level of Signal Transduction and Activator of Transcription-3(STAT3)at Tyr705 by JAK2,which would promote STAT3 translocate into the nucleus and activate STAT3.However,STAT3 was found mainly located in the cytoplasm.Further study found that P301L-htau acetylated STAT1 to bind with STAT3 in the cytoplasm,and thus inhibited the nuclear translocation and inactivation of STAT3.Knockdown of STAT3 in STAT3flox/flox mice mimicked P301L-hTau-induced suppression of NMDARs expression,synaptic and memory impairments.Overexpressing STAT3 rescued P301L-hTau-induced synaptic and cognitive deficits by increasing NMDARs expression.Further study proved that STAT3 positively regulated NMDARs transcription through direct binding to the specific GAS element of NMDARs promoters.These findings indicate that accumulated P301L-hTau inactivating STAT3 to suppress NMDARs expression,revealed a novel mechanism for tau-associated synapse and cognition deficits,and STAT3 will hopefully serve as a potential pharmacological target for tauopathies treatment.展开更多
Dear Editor,Recently,lower hemoglobin/anemia in the elderly is found to be associated with cognitive impairment and Alzheimer’s disease(AD),1 implying that erythropoietin(EPO)may be of benefit for AD.As a clinically ...Dear Editor,Recently,lower hemoglobin/anemia in the elderly is found to be associated with cognitive impairment and Alzheimer’s disease(AD),1 implying that erythropoietin(EPO)may be of benefit for AD.As a clinically safe-to-use drug,besides its hematopoietic function,recombinant human EPO(rhEPO)is reported to present multifaceted neuroprotective effects.2 Unfortunately,few clinical studies investigated the effect of rhEPO in AD patients.展开更多
In tauopathies,memory impairment positively strongly correlates with the amount of abnormal tau aggregates;however,how tau accumulation induces synapse impairment is unclear.Recently,we found that human tau accumulati...In tauopathies,memory impairment positively strongly correlates with the amount of abnormal tau aggregates;however,how tau accumulation induces synapse impairment is unclear.Recently,we found that human tau accumulation activated Signal Transduction and Activator of Transcription-1(STAT1)to inhibit the transcription of synaptic N-methyl-D-aspartate receptors(NMDARs).Here,overexpressing human P301L mutant tau(P301L-hTau)increased the phosphorylated level of Signal Transduction and Activator of Transcription-3(STAT3)at Tyr705 by JAK2,which would promote STAT3 translocate into the nucleus and activate STAT3.However,STAT3 was found mainly located in the cytoplasm.Further study found that P301L-htau acetylated STAT1 to bind with STAT3 in the cytoplasm,and thus inhibited the nuclear translocation and inactivation of STAT3.Knockdown of STAT3 in STAT3^(flox/flox) mice mimicked P301L-hTau-induced suppression of NMDARs expression,synaptic and memory impairments.Overexpressing STAT3 rescued P301L-hTau-induced synaptic and cognitive deficits by increasing NMDARs expression.Further study proved that STAT3 positively regulated NMDARs transcription through direct binding to the specific GAS element of NMDARs promoters.These findings indicate that accumulated P301L-hTau inactivating STAT3 to suppress NMDARs expression,revealed a novel mechanism for tau-associated synapse and cognition deficits,and STAT3 will hopefully serve as a potential pharmacological target for tauopathies treatment.展开更多
基金the National Natural Science Foundation of China(Grants No.41991333 and 31861133002)the European Unions Horizon 2020 Research and Innovation Program Under Grant Agreement(No.826244)+1 种基金the CAS Engineering Laboratory for Advanced Microbial Technology of Agriculture,Chinese Academy of Sciences(KFJ-PTXM-016)the Science and Technology Basic Resources Survey Special Project(2019FY100700).
文摘Contaminated sites from electronic waste(e-waste)dismantling and coking plants feature high concentrations of heavy metals(HMs)and/or polycyclic aromatic hydrocarbons(PAHs)in soil.Mixed contamination(HMsþPAHs)hinders land reclamation and affects the microbial diversity and function of soil microbiomes.In this study,we analyzed HM and PAH contamination from an e-waste dismantling plant and a coking plant and evaluated the influences of HM and PAH contamination on soil microbiomes.It was noticed that HMs and PAHs were found in all sites,although the major contaminants of the e-waste dismantling plant site were HMs(such as Cu at 5,947.58±433.44 mg kg^(-1),Zn at 4,961.38±436.51 mg kg^(-1),and Mn at 2,379.07±227.46 mg kg^(-1)),and the major contaminants of the coking plant site were PAHs(such as fluorene at 11,740.06±620.1 mg kg^(-1),acenaphthylene at 211.69±7.04 mg kg^(-1),and pyrene at 183.14±18.89 mg kg^(-1)).The microbiomes(diversity and abundance)of all sites were determined via high-throughput sequencing of 16S rRNA genes,and redundancy analysis was conducted to investigate the relations between soil microbiomes and contaminants.The results showed that the microbiomes of the contaminated sites divergently responded to HMs and PAHs.The abundances of the bacterial genera Sulfuritalea,Pseudomonas,and Sphingobium were positively related to PAHs,while the abundances of the bacterial genera Bryobacter,Nitrospira,and Steroidobacter were positively related to HMs.This study promotes an understanding of how soil microbiomes respond to single and mixed contamination with HMs and PAHs.
基金supported in parts by Natural Science Foundation of China(81870846)the Ministry of Science and Technology of China(2016YFC13058001)Sanming Project of Medicine in Shenzhen(SZSM201611090).
文摘In tauopathies,memory impairment positively strongly correlates with the amount of abnormal tau aggregates;however,how tau accumulation induces synapse impairment is unclear.Recently,we found that human tau accumulation activated Signal Transduction and Activator of Transcription-1(STAT1)to inhibit the transcription of synaptic N-methyl-D-aspartate receptors(NMDARs).Here,overexpressing human P301L mutant tau(P301L-hTau)increased the phosphorylated level of Signal Transduction and Activator of Transcription-3(STAT3)at Tyr705 by JAK2,which would promote STAT3 translocate into the nucleus and activate STAT3.However,STAT3 was found mainly located in the cytoplasm.Further study found that P301L-htau acetylated STAT1 to bind with STAT3 in the cytoplasm,and thus inhibited the nuclear translocation and inactivation of STAT3.Knockdown of STAT3 in STAT3flox/flox mice mimicked P301L-hTau-induced suppression of NMDARs expression,synaptic and memory impairments.Overexpressing STAT3 rescued P301L-hTau-induced synaptic and cognitive deficits by increasing NMDARs expression.Further study proved that STAT3 positively regulated NMDARs transcription through direct binding to the specific GAS element of NMDARs promoters.These findings indicate that accumulated P301L-hTau inactivating STAT3 to suppress NMDARs expression,revealed a novel mechanism for tau-associated synapse and cognition deficits,and STAT3 will hopefully serve as a potential pharmacological target for tauopathies treatment.
基金supported in parts by the Natural Science Foundation of China(82071221 and 81870846).
文摘Dear Editor,Recently,lower hemoglobin/anemia in the elderly is found to be associated with cognitive impairment and Alzheimer’s disease(AD),1 implying that erythropoietin(EPO)may be of benefit for AD.As a clinically safe-to-use drug,besides its hematopoietic function,recombinant human EPO(rhEPO)is reported to present multifaceted neuroprotective effects.2 Unfortunately,few clinical studies investigated the effect of rhEPO in AD patients.
基金This work was supported in parts by Natural Science Foundation of China(81870846)the Ministry of Science and Technology of China(2016YFC13058001)Sanming Project of Medicine in Shenzhen(SZSM201611090).
文摘In tauopathies,memory impairment positively strongly correlates with the amount of abnormal tau aggregates;however,how tau accumulation induces synapse impairment is unclear.Recently,we found that human tau accumulation activated Signal Transduction and Activator of Transcription-1(STAT1)to inhibit the transcription of synaptic N-methyl-D-aspartate receptors(NMDARs).Here,overexpressing human P301L mutant tau(P301L-hTau)increased the phosphorylated level of Signal Transduction and Activator of Transcription-3(STAT3)at Tyr705 by JAK2,which would promote STAT3 translocate into the nucleus and activate STAT3.However,STAT3 was found mainly located in the cytoplasm.Further study found that P301L-htau acetylated STAT1 to bind with STAT3 in the cytoplasm,and thus inhibited the nuclear translocation and inactivation of STAT3.Knockdown of STAT3 in STAT3^(flox/flox) mice mimicked P301L-hTau-induced suppression of NMDARs expression,synaptic and memory impairments.Overexpressing STAT3 rescued P301L-hTau-induced synaptic and cognitive deficits by increasing NMDARs expression.Further study proved that STAT3 positively regulated NMDARs transcription through direct binding to the specific GAS element of NMDARs promoters.These findings indicate that accumulated P301L-hTau inactivating STAT3 to suppress NMDARs expression,revealed a novel mechanism for tau-associated synapse and cognition deficits,and STAT3 will hopefully serve as a potential pharmacological target for tauopathies treatment.