The number of dispersion curves increases significantly when the scale of a short-period dense array increases.Owing to a substantial increase in data volume,it is important to quickly evaluate dispersion curve qualit...The number of dispersion curves increases significantly when the scale of a short-period dense array increases.Owing to a substantial increase in data volume,it is important to quickly evaluate dispersion curve quality as well as select the available dispersion curve.Accordingly,this study quantitatively evaluated dispersion curve quality by training a convolutional neural network model for ambient noise tomography using a short-period dense array.The model can select high-quality dispersion curves that exhibit a≤10%difference between the results of manual screening and the proposed model.In addition,this study established a dispersion curve loss function by analyzing the quality of the dispersion curve and the corresponding influencing factors,thereby estimating the number of available dispersion curves for the existing observation systems.Furthermore,a Monte Carlo simulation experiment is used to illustrates the station-pair interval distance probability density function,which is independent of station number in the observational system with randomly deployed stations.The results suggested that the straight-line length should exceed 15 km to ensure that loss rate of dispersion curves remains<0.5,while maintaining the threshold ambient noise tomography accuracy within the study area.展开更多
Active-source surface wave exploration is advantageous because it has high imaging accuracy,is not affected by high-speed layers,and has a low cost;thus,it has unique advantages for investigating shallow surface struc...Active-source surface wave exploration is advantageous because it has high imaging accuracy,is not affected by high-speed layers,and has a low cost;thus,it has unique advantages for investigating shallow surface structures.For the development and utilization of urban underground space,two parameters in the shallow surface are important,namely,the shear wave velocity(V_(S))and the predominant period of the site,which determine the elevation and aseismic grade of the building design.The traditional method is mainly to obtain the two above-mentioned parameters through testing and measuring drilling samples.However,this method is extremely expensive and time consuming.Therefore,in this research,we used the multichannel surface wave acquisition method to extract the fundamental dispersion curve of single-shot data by using the phase shift method and obtain the V_(S) characteristics in the uppermost 40 m by inversion.We arrived at the following two conclusions based on the V_(S) profile.First,the study area can be roughly divided into five layers,among which the layers 0−8 m,14−20 m,and 20−30 m are low-velocity layers,corresponding to miscellaneous fill,a water-bearing sand layer,and a sand layer;therefore,the V_(S) is relatively low.In contrast,the layers at 8−14 m and 30−40 m are high-velocity layers that are mainly composed of clay,with a relatively better compactness and relatively high V_(S) values.In addition,a low-speed anomaly appears abruptly in the high-speed area at 20−40 m.This anomaly,when combined with geological data,suggests that it is an ancient river channel.Second,from the V_(S) value,the V_(Se)(equivalent shear wave velocity)was calculated.The construction site soil was categorized as class III,with good conditions for engineering geology.In addition,we calculated the predominant period of the site to be 0.56-0.77 s based on the V_(S).Therefore,in the overall structural design of the foundation engineering,the natural vibration period of the structure should be strictly controlled to avoid the predominant period of the site.展开更多
Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membran...Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.展开更多
The generation and application of replication-competent influenza A virus(IAV) expressing a reporter gene represent a valuable tool to elucidate the mechanism of viral pathogenesis and establish new countermeasures to...The generation and application of replication-competent influenza A virus(IAV) expressing a reporter gene represent a valuable tool to elucidate the mechanism of viral pathogenesis and establish new countermeasures to combat the threat of influenza. Here, replication-competent IAVs with a neuraminidase(NA) segment harboring a fluorescent reporter protein, Venus, were generated in the background of H5N1, H7N9, and H9N2 influenza viruses, the three subtypes of viruses with imminent pandemic potential. All three reporter viruses maintained virion morphology, replicated with similar or slightly reduced titers relative to their parental viruses, and stably expressed the fluorescent signal for at least two passages in embryonated chicken eggs. As a proof of concept, we demonstrated that these reporter viruses,used in combination with a high-content imaging system, can serve as a convenient and rapid tool for the screening of antivirals and host factors involved in the virus life cycle. Moreover, the reporter viruses demonstrated similar growth properties and tissue tropism as their parental viruses in mice, among which the H7N9 NA-Venus virus could potentially be used in ex vivo studies to better understand H7N9 pathogenesis or to develop novel therapeutics.展开更多
Tripartite motif(TRIM)family proteins are important effectors of innate immunity against viral infections.Here we identified TRIM35 as a regulator of TRAF3 activation.Deficiency in or inhibition of TRIM35 suppressed t...Tripartite motif(TRIM)family proteins are important effectors of innate immunity against viral infections.Here we identified TRIM35 as a regulator of TRAF3 activation.Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon(IFN)in response to viral infection.777m35-deficient mice were more susceptible to influenza A virus(IAV)infection than were wild-type mice.TRIM35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1.IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3.TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2,thereby antagonizing its suppression of TRAF3 activation.Our in vitro and in vivo findings thus reveal novel roles of TRIM35,through catalyzing Lys63-or Lys48-linked polyubiquitination,in RIG-I antiviral immunity and mechanism of defense against IAV infection.展开更多
As a major component of the viral ribonucleoprotein(vRNP)complex in influenza A virus(IAV),nucleoprotein(NP)interacts with isoforms of importinαfamily members,leading to the import of itself and vRNP complex into the...As a major component of the viral ribonucleoprotein(vRNP)complex in influenza A virus(IAV),nucleoprotein(NP)interacts with isoforms of importinαfamily members,leading to the import of itself and vRNP complex into the nucleus,a process pivotal in the replication cycle of IAV.In this study,we found that BinCARD1,an isoform of Bcl10-interacting protein with CARD(BinCARD),was leveraged by IAV for efficient viral replication.BinCARD1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex activity.Moreover,we found that BinCARD1 interacted with NP to promote NP binding to importinα7,an adaptor in the host nuclear import pathway.However,we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3,and that TBK1 appeared to degrade BinCARD1.We showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage,which was recognized by the TBK1-p62 axis for autophagic degradation.Overall,our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication,and two mechanisms in the host defense system are triggered—innate immune signaling and autophagic degradation—to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.展开更多
The North Himalayan gneiss domes(NHGD),as one of the extensional structures widely distributed across the southern Tibetan Plateau,are an important window for studying post-collisional diastrophism and magmation as we...The North Himalayan gneiss domes(NHGD),as one of the extensional structures widely distributed across the southern Tibetan Plateau,are an important window for studying post-collisional diastrophism and magmation as well as polymetallic mineralization.However,the deep mechanism for the formation of NHGD remains controversial.The magnetotelluric(MT)method was adopted to study the deep structure of the Cuonadong dome in the Northern Himalayas.The characteristics of the dome were explored by using the MT sounding curves and phase tensors.Three-dimensional(3D)MT inversion was performed to determine the electrical resistivity structure beneath the Cuonadong dome.The preferred 3D electrical resistivity model shows that an obvious low-resistivity anomaly develops beneath the Cuonadong dome which is overlaid by a high-resistivity body and surrounded by an apparent subcircular zone of low-resistivity anomalies.The integrated conductivity(longitudinal conductance)from depths of 1-20 km indicates that the average longitudinal conductance at the core of the Cuonadong dome is about 10,000 S.The high-conductivity anomaly at the core is found to be analogous to that of lava,mainly resulting from the crustal partial melting,and the estimated melt content is 11.0-17.3%.The high conductance surrounding the dome reaches 20,000 S on average,which is mainly attributed to saline fluids.MT results in this study support that the Cuonadong dome experienced magmatic diapirism.Taken together with previous geological and geochemical studies,we suggest that under the east-west(E-W)extensional tectonic setting in southern Tibet,deep crustal partial melting constantly accumulated beneath the dome,and therefore the magmatic diapirism resulted in the formation of the Cuonadong dome.In addition,the MT results also indicate that the development of the Cuonadong dome provides abundant mineralizing fluids and the space for migration of metallogenic fluids for(rare-metal)polymetallic mineralization.展开更多
基金supported by the Second Tibetan Plateau Scientific Expedition and Research Program(STEP)(No.2019QZKK0701)the Fund from the Key Laboratory of Deep-Earth Dynamics of the Ministry of Natural Resources(No.J1901-38)+1 种基金the National Natural Science Foundation of China(Nos.42174121 and 91962109)the China Geological Survey Project(No.DD20190001).
文摘The number of dispersion curves increases significantly when the scale of a short-period dense array increases.Owing to a substantial increase in data volume,it is important to quickly evaluate dispersion curve quality as well as select the available dispersion curve.Accordingly,this study quantitatively evaluated dispersion curve quality by training a convolutional neural network model for ambient noise tomography using a short-period dense array.The model can select high-quality dispersion curves that exhibit a≤10%difference between the results of manual screening and the proposed model.In addition,this study established a dispersion curve loss function by analyzing the quality of the dispersion curve and the corresponding influencing factors,thereby estimating the number of available dispersion curves for the existing observation systems.Furthermore,a Monte Carlo simulation experiment is used to illustrates the station-pair interval distance probability density function,which is independent of station number in the observational system with randomly deployed stations.The results suggested that the straight-line length should exceed 15 km to ensure that loss rate of dispersion curves remains<0.5,while maintaining the threshold ambient noise tomography accuracy within the study area.
基金This study was supported by the National Natural Science Foundation of China(grant nos.42074115,41574094)the National Key R&D Program of China(grant no.2017YFC0601301)+1 种基金the Geological Survey Project of the China Geological Survey(grant no.DD20189132)the Key Laboratory of Deep-Earth Dynamics,Ministry of Natural Resources(grant no.J1901-3).
文摘Active-source surface wave exploration is advantageous because it has high imaging accuracy,is not affected by high-speed layers,and has a low cost;thus,it has unique advantages for investigating shallow surface structures.For the development and utilization of urban underground space,two parameters in the shallow surface are important,namely,the shear wave velocity(V_(S))and the predominant period of the site,which determine the elevation and aseismic grade of the building design.The traditional method is mainly to obtain the two above-mentioned parameters through testing and measuring drilling samples.However,this method is extremely expensive and time consuming.Therefore,in this research,we used the multichannel surface wave acquisition method to extract the fundamental dispersion curve of single-shot data by using the phase shift method and obtain the V_(S) characteristics in the uppermost 40 m by inversion.We arrived at the following two conclusions based on the V_(S) profile.First,the study area can be roughly divided into five layers,among which the layers 0−8 m,14−20 m,and 20−30 m are low-velocity layers,corresponding to miscellaneous fill,a water-bearing sand layer,and a sand layer;therefore,the V_(S) is relatively low.In contrast,the layers at 8−14 m and 30−40 m are high-velocity layers that are mainly composed of clay,with a relatively better compactness and relatively high V_(S) values.In addition,a low-speed anomaly appears abruptly in the high-speed area at 20−40 m.This anomaly,when combined with geological data,suggests that it is an ancient river channel.Second,from the V_(S) value,the V_(Se)(equivalent shear wave velocity)was calculated.The construction site soil was categorized as class III,with good conditions for engineering geology.In addition,we calculated the predominant period of the site to be 0.56-0.77 s based on the V_(S).Therefore,in the overall structural design of the foundation engineering,the natural vibration period of the structure should be strictly controlled to avoid the predominant period of the site.
基金supported by the National Natural Science Foundation of China(32192453,32172847)the National Key Research and Development Program of China(2021YFD1800204)+1 种基金the Laboratory of Lingnan Modern Agriculture Project(NT2021007)the earmarked fund for CARS-41。
文摘Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.
基金supported by the National Natural Science Foundation of China(31472215,31521005,31422054,31402206)the National Key R&D Program of China(2016YFD0500205)
文摘The generation and application of replication-competent influenza A virus(IAV) expressing a reporter gene represent a valuable tool to elucidate the mechanism of viral pathogenesis and establish new countermeasures to combat the threat of influenza. Here, replication-competent IAVs with a neuraminidase(NA) segment harboring a fluorescent reporter protein, Venus, were generated in the background of H5N1, H7N9, and H9N2 influenza viruses, the three subtypes of viruses with imminent pandemic potential. All three reporter viruses maintained virion morphology, replicated with similar or slightly reduced titers relative to their parental viruses, and stably expressed the fluorescent signal for at least two passages in embryonated chicken eggs. As a proof of concept, we demonstrated that these reporter viruses,used in combination with a high-content imaging system, can serve as a convenient and rapid tool for the screening of antivirals and host factors involved in the virus life cycle. Moreover, the reporter viruses demonstrated similar growth properties and tissue tropism as their parental viruses in mice, among which the H7N9 NA-Venus virus could potentially be used in ex vivo studies to better understand H7N9 pathogenesis or to develop novel therapeutics.
基金The work was supported by the National Key Research and Development Program of China(2016YFD0500205)the National Natural Science Foundation of China(NSFC)(Grant Nos.31521005,31672582,31422054,and 31472215)+1 种基金the Natural Science Foundation of Heilongjiang Province(JQ2019C005)by the Central Public-Interest Scientific Institution Basal Research Fund(No.Y2017JC35).
文摘Tripartite motif(TRIM)family proteins are important effectors of innate immunity against viral infections.Here we identified TRIM35 as a regulator of TRAF3 activation.Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon(IFN)in response to viral infection.777m35-deficient mice were more susceptible to influenza A virus(IAV)infection than were wild-type mice.TRIM35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1.IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3.TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2,thereby antagonizing its suppression of TRAF3 activation.Our in vitro and in vivo findings thus reveal novel roles of TRIM35,through catalyzing Lys63-or Lys48-linked polyubiquitination,in RIG-I antiviral immunity and mechanism of defense against IAV infection.
基金This investigation was funded by a grant from the Laboratory of Lingnan Modern Agriculture Project(NT2021007 to HC and CL)the National Natural Science Foundation of China(NSFC)(32192453 to CL,32172847 to LJ)+2 种基金the National Key Research and Development Program of China(2021YFD1800203 to HC,2021YFD1800204 to CL)the Natural Science Foundation of Heilongjiang Province(JQ2019C005 to CL)the Central Public-Interest Scientific Institution Basal Research Fund(Y2017JC35 to GT).
文摘As a major component of the viral ribonucleoprotein(vRNP)complex in influenza A virus(IAV),nucleoprotein(NP)interacts with isoforms of importinαfamily members,leading to the import of itself and vRNP complex into the nucleus,a process pivotal in the replication cycle of IAV.In this study,we found that BinCARD1,an isoform of Bcl10-interacting protein with CARD(BinCARD),was leveraged by IAV for efficient viral replication.BinCARD1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex activity.Moreover,we found that BinCARD1 interacted with NP to promote NP binding to importinα7,an adaptor in the host nuclear import pathway.However,we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3,and that TBK1 appeared to degrade BinCARD1.We showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage,which was recognized by the TBK1-p62 axis for autophagic degradation.Overall,our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication,and two mechanisms in the host defense system are triggered—innate immune signaling and autophagic degradation—to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.
基金supported by the National Natural Science Foundation of China(Grant Nos.91962109,42174094)the Second Tibetan Plateau Scientific Expedition and Research Program(STEP)(Grant No.2019QZKK0701)+1 种基金the Fund of Chinese Geological Survey(Grant No.DD20190016)the Basic Scientific Research Fund of the Institute of Geology,Chinese Academy of Geological Sciences(Grant No.J2015)。
文摘The North Himalayan gneiss domes(NHGD),as one of the extensional structures widely distributed across the southern Tibetan Plateau,are an important window for studying post-collisional diastrophism and magmation as well as polymetallic mineralization.However,the deep mechanism for the formation of NHGD remains controversial.The magnetotelluric(MT)method was adopted to study the deep structure of the Cuonadong dome in the Northern Himalayas.The characteristics of the dome were explored by using the MT sounding curves and phase tensors.Three-dimensional(3D)MT inversion was performed to determine the electrical resistivity structure beneath the Cuonadong dome.The preferred 3D electrical resistivity model shows that an obvious low-resistivity anomaly develops beneath the Cuonadong dome which is overlaid by a high-resistivity body and surrounded by an apparent subcircular zone of low-resistivity anomalies.The integrated conductivity(longitudinal conductance)from depths of 1-20 km indicates that the average longitudinal conductance at the core of the Cuonadong dome is about 10,000 S.The high-conductivity anomaly at the core is found to be analogous to that of lava,mainly resulting from the crustal partial melting,and the estimated melt content is 11.0-17.3%.The high conductance surrounding the dome reaches 20,000 S on average,which is mainly attributed to saline fluids.MT results in this study support that the Cuonadong dome experienced magmatic diapirism.Taken together with previous geological and geochemical studies,we suggest that under the east-west(E-W)extensional tectonic setting in southern Tibet,deep crustal partial melting constantly accumulated beneath the dome,and therefore the magmatic diapirism resulted in the formation of the Cuonadong dome.In addition,the MT results also indicate that the development of the Cuonadong dome provides abundant mineralizing fluids and the space for migration of metallogenic fluids for(rare-metal)polymetallic mineralization.