Aortic dissection involving a right-sided aortic arch(RAA)is extremely rare with an incidence in adults of 0.04%to 0.1%^([1]).Thoracic aortic dissection associated with RAA is even a more uncommon and life-threate...Aortic dissection involving a right-sided aortic arch(RAA)is extremely rare with an incidence in adults of 0.04%to 0.1%^([1]).Thoracic aortic dissection associated with RAA is even a more uncommon and life-threatening condition.For complicated aortic dissection,conventional open surgical repair is considered a standard therapy^([2]).However,展开更多
As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen...As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-(IFN-),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate-adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.展开更多
Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seaso...Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seasonal H1N1 and highly pathogenic avian influenza(HPAI) A H5N1 infections, we identified an alternative antiviral role of tauroursodeoxycholic acid(TUDCA), a clinically available ER stress inhibitor, both in vitro and in vivo. Rather than modulating ER stress in host cells, TUDCA abolished the proton conductivity of viral M2 by disrupting its oligomeric states, which induces inefficient viral infection. We also showed that M2 penetrated cells, whose intracellular uptake depended on its proton channel activity,an effect observed in both TUDCA and M2 inhibitor amantadine. The identification and application of TUDCA as an inhibitor of M2 proton channel will expand our understanding of IAV biology and complement current anti-IAV arsenals.展开更多
Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, w...Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by whichtranscriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouselungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved inthe disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishmentincreased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 inducedTRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT byreducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.展开更多
Following the published article[1].the authors noticed an error duplication of image of DAPI in Fig.2c"AF"and"No pretreated and without TUDCA".The correct DAPI image was in the merged image of"...Following the published article[1].the authors noticed an error duplication of image of DAPI in Fig.2c"AF"and"No pretreated and without TUDCA".The correct DAPI image was in the merged image of"No pretreated and without TUDCA"of the published article.Therefore,the corrected Fig.2c should be as follows:The online version of the original artice can be found at https://doi.org/10.101/j.scib.2018.08.0131.展开更多
This paper discusses a queueing system with a retrial orbit and batch service, in which the quantity of customers’ rooms in the queue is finite and the space of retrial orbit is infinite. When the server starts servi...This paper discusses a queueing system with a retrial orbit and batch service, in which the quantity of customers’ rooms in the queue is finite and the space of retrial orbit is infinite. When the server starts serving, it serves all customers in the queue in a single batch, which is the so-called batch service. If a new customer or a retrial customer finds all the customers’ rooms are occupied, he will decide whether or not to join the retrial orbit. By using the censoring technique and the matrix analysis method, we first obtain the decay function of the stationary distribution for the quantity of customers in the retrial orbit and the quantity of customers in the queue. Then based on the form of decay rate function and the Karamata Tauberian theorem, we finally get the exact tail asymptotics of the stationary distribution.展开更多
The Getah virus(GETV),a mosquito-borne RNA virus,is widely distributed in Oceania and Asia.GETV is not the only pathogenic to horses,pigs,cattle,foxes and boars,but it can also cause fever in humans.Since its first re...The Getah virus(GETV),a mosquito-borne RNA virus,is widely distributed in Oceania and Asia.GETV is not the only pathogenic to horses,pigs,cattle,foxes and boars,but it can also cause fever in humans.Since its first reported case in Chinese mainland in 2017,the number of GETV-affected provinces has increased to seventeen till now.Therefore,we performed an epidemiologic investigation of GETV in the Xinjiang region,located in northwestern China,during the period of 2017-2020.ELISA was used to analyze 3299 serum samples collected from thoroughbred horse,local horse,sheep,goat,cattle,and pigs,with thoroughbred horse(74.8%),local horse(67.3%),goat(11.7%),sheep(10.0%),cattle(25.1%)and pigs(51.1%)being positive for anti-GETV antibodies.Interestingly,the neutralizing antibody titer in horses was much higher than in other species.Four samples from horses and pigs were positive for GETV according to RT-PCR.Furthermore,from the serum of a local horse,we isolated GETV which was designated as strain XJ-2019-07,and determined its complete genome sequence.From the phylogenetic relationships,it belongs to the Group III lineage.This is the first evidence of GETV associated to domestic animals in Xinjiang.Overall,GETV is prevalent in Xinjiang and probably has been for several years.Since no vaccine against GETV is available in China,detection and monitoring strategies should be improved in horses and pigs,especially imported and farmed,in order to prevent economic losses.展开更多
Understanding the damage behavior and cracking mechanism of brittle shale is crucial for hydraulic fracturing design.In this research,uniaxial compression tests are conducted on shale samples with different bedding pl...Understanding the damage behavior and cracking mechanism of brittle shale is crucial for hydraulic fracturing design.In this research,uniaxial compression tests are conducted on shale samples with different bedding plane orientations,and acoustic emission monitoring is implemented synchronously.The results indicate that the apparent elastic modulus increases with increasing bedding orientation.For the bedding orienta-tions of 45°and 90°,the lateral deformation is anisotropic due to the bedding structure,revealing the anisotropic Poisson effect.A shear failure surface and tensile failure surfaces form parallel to the bedding plane for bedding orientations of 45°and 90°,respectively.For the bedding orientation of 0°,shear failure mainly occurs through the bedding planes.Additionally,the damage mechanism of shale is investigated by crack classification based on AE parameters.It is found that crack initiation is induced by the generation of shear cracks for the bedding orientation of 45°,whereas by the generation of tensile cracks for other bedding orientations.According to damage attributable to different type cracks,shear cracks dominate the damage behavior for bedding orientations of 0°and 45°,whereas tensile cracks dominate the damage behavior for bedding orientation of 90°.Finally,the information entropy is calculated by AE energy.A low value of information entropy,approximately 0.36,predicts failure with a low degree of instability for the bedding orientation of 0°,whereas a high value of information entropy,more than 1.5,predicts failure with a high degree of instability for other bedding orientations.This finding indicates that the failure behavior is gradual progressive damage for bedding orientation of 0°,whereas sudden damage dominates failure behavior for other bedding orientations.展开更多
文摘Aortic dissection involving a right-sided aortic arch(RAA)is extremely rare with an incidence in adults of 0.04%to 0.1%^([1]).Thoracic aortic dissection associated with RAA is even a more uncommon and life-threatening condition.For complicated aortic dissection,conventional open surgical repair is considered a standard therapy^([2]).However,
文摘As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-(IFN-),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate-adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.
基金supported by the National Natural Science Foundation of China (81788101, 81573587 and 81490531)the Ministry of Science and Technology of China (2015CB5534/6)+3 种基金111 project (B08007)the Peking Union Medical College Youth FundFundamental Research Funds for Central Universities (3332013132)the CAMS Innovation Fund for Medical Sciences (2017-I2M-1-009)
文摘Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seasonal H1N1 and highly pathogenic avian influenza(HPAI) A H5N1 infections, we identified an alternative antiviral role of tauroursodeoxycholic acid(TUDCA), a clinically available ER stress inhibitor, both in vitro and in vivo. Rather than modulating ER stress in host cells, TUDCA abolished the proton conductivity of viral M2 by disrupting its oligomeric states, which induces inefficient viral infection. We also showed that M2 penetrated cells, whose intracellular uptake depended on its proton channel activity,an effect observed in both TUDCA and M2 inhibitor amantadine. The identification and application of TUDCA as an inhibitor of M2 proton channel will expand our understanding of IAV biology and complement current anti-IAV arsenals.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(81788101,31870163,and 32100104)the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-022)+6 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDB29010102)CAS Southest Asia Biodiversity Research Institute(151C53KYSB20210023)Beijing Natural Science Foundation(L192007)National Pathogen Resource Center,and State Key Laboratory Special Fund(2060204)Y.B.is supported by the NSFC Outstanding Young Scholars(31822055)Youth Innovation Promotion Association of the CAS(2017122 and Y2021034)Overseas Expertise Introduction Center for Discipline Innovation(“111 Center”)(BP0820029).
文摘Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by whichtranscriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouselungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved inthe disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishmentincreased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 inducedTRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT byreducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.
文摘Following the published article[1].the authors noticed an error duplication of image of DAPI in Fig.2c"AF"and"No pretreated and without TUDCA".The correct DAPI image was in the merged image of"No pretreated and without TUDCA"of the published article.Therefore,the corrected Fig.2c should be as follows:The online version of the original artice can be found at https://doi.org/10.101/j.scib.2018.08.0131.
文摘This paper discusses a queueing system with a retrial orbit and batch service, in which the quantity of customers’ rooms in the queue is finite and the space of retrial orbit is infinite. When the server starts serving, it serves all customers in the queue in a single batch, which is the so-called batch service. If a new customer or a retrial customer finds all the customers’ rooms are occupied, he will decide whether or not to join the retrial orbit. By using the censoring technique and the matrix analysis method, we first obtain the decay function of the stationary distribution for the quantity of customers in the retrial orbit and the quantity of customers in the queue. Then based on the form of decay rate function and the Karamata Tauberian theorem, we finally get the exact tail asymptotics of the stationary distribution.
基金supported by the National Program on Key Research Project of China(2018YFD0500104 and 2018YFD0500803)Technologies for Prevention and Control of Virus Zoonoses,Chinese Academy of Medical Sciences(2020-12M-5-001)。
文摘The Getah virus(GETV),a mosquito-borne RNA virus,is widely distributed in Oceania and Asia.GETV is not the only pathogenic to horses,pigs,cattle,foxes and boars,but it can also cause fever in humans.Since its first reported case in Chinese mainland in 2017,the number of GETV-affected provinces has increased to seventeen till now.Therefore,we performed an epidemiologic investigation of GETV in the Xinjiang region,located in northwestern China,during the period of 2017-2020.ELISA was used to analyze 3299 serum samples collected from thoroughbred horse,local horse,sheep,goat,cattle,and pigs,with thoroughbred horse(74.8%),local horse(67.3%),goat(11.7%),sheep(10.0%),cattle(25.1%)and pigs(51.1%)being positive for anti-GETV antibodies.Interestingly,the neutralizing antibody titer in horses was much higher than in other species.Four samples from horses and pigs were positive for GETV according to RT-PCR.Furthermore,from the serum of a local horse,we isolated GETV which was designated as strain XJ-2019-07,and determined its complete genome sequence.From the phylogenetic relationships,it belongs to the Group III lineage.This is the first evidence of GETV associated to domestic animals in Xinjiang.Overall,GETV is prevalent in Xinjiang and probably has been for several years.Since no vaccine against GETV is available in China,detection and monitoring strategies should be improved in horses and pigs,especially imported and farmed,in order to prevent economic losses.
基金supported by the National Natural Science Foundation of China(Grant No.51704198)the Department of Science and Technology of Sichuan Province(No.2021YFH0030).
文摘Understanding the damage behavior and cracking mechanism of brittle shale is crucial for hydraulic fracturing design.In this research,uniaxial compression tests are conducted on shale samples with different bedding plane orientations,and acoustic emission monitoring is implemented synchronously.The results indicate that the apparent elastic modulus increases with increasing bedding orientation.For the bedding orienta-tions of 45°and 90°,the lateral deformation is anisotropic due to the bedding structure,revealing the anisotropic Poisson effect.A shear failure surface and tensile failure surfaces form parallel to the bedding plane for bedding orientations of 45°and 90°,respectively.For the bedding orientation of 0°,shear failure mainly occurs through the bedding planes.Additionally,the damage mechanism of shale is investigated by crack classification based on AE parameters.It is found that crack initiation is induced by the generation of shear cracks for the bedding orientation of 45°,whereas by the generation of tensile cracks for other bedding orientations.According to damage attributable to different type cracks,shear cracks dominate the damage behavior for bedding orientations of 0°and 45°,whereas tensile cracks dominate the damage behavior for bedding orientation of 90°.Finally,the information entropy is calculated by AE energy.A low value of information entropy,approximately 0.36,predicts failure with a low degree of instability for the bedding orientation of 0°,whereas a high value of information entropy,more than 1.5,predicts failure with a high degree of instability for other bedding orientations.This finding indicates that the failure behavior is gradual progressive damage for bedding orientation of 0°,whereas sudden damage dominates failure behavior for other bedding orientations.