We report the structure and physical properties of two newly discovered compounds AV_(8)Sb_(12)and AV_(6)Sb_(6)(A=Cs,Rb),which have C_(2)(space group:Cmmm)and C_(3)(space group:R3 m)symmetry,respectively.The basic Vka...We report the structure and physical properties of two newly discovered compounds AV_(8)Sb_(12)and AV_(6)Sb_(6)(A=Cs,Rb),which have C_(2)(space group:Cmmm)and C_(3)(space group:R3 m)symmetry,respectively.The basic Vkagome unit appears in both compounds,but stacking differently.AV_(2)Sb_(2) layer is sandwiched between two V_(3)Sb_(5)layers in AV_(8)Sb_(12),altering the V-kagome lattice and lowering the symmetry of kagome layer from hexagonal to orthorhombic.In AV_(6)Sb_(6),the building block is a more complex slab made up of two half-V_(3)Sb_(5)layers that are intercalated by Cs cations along the c-axis.Transport property measurements demonstrate that both compounds are nonmagnetic metals,with carrier concentrations at around 10^(21)cm^(-3).No superconductivity has been observed in CsV_(8)Sb_(12)above 0.3 K under in situ pressure up to 46 GPa.Compared to CSV_(3)Sb_(5),theoretical calculations and angle-resolved photoemission spectroscopy reveal a quasi-two-dimensional electronic structure in CsV_(8)Sb_(12)with C_(2)symmetry and no van Hove singularities near the Fermi level.Our findings will stimulate more research into V-based kagome quantum materials.展开更多
In view of the fact that the current high efficiency video coding standard does not consider the characteristics of human vision, this paper proposes a perceptual video coding algorithm based on the just noticeable di...In view of the fact that the current high efficiency video coding standard does not consider the characteristics of human vision, this paper proposes a perceptual video coding algorithm based on the just noticeable distortion model (JND). The adjusted JND model is combined into the transformation quantization process in high efficiency video coding (HEVC) to remove more visual redundancy and maintain compatibility. First of all, we design the JND model based on pixel domain and transform domain respectively, and the pixel domain model can give the JND threshold more intuitively on the pixel. The transform domain model introduces the contrast sensitive function into the model, making the threshold estimation more precise. Secondly, the proposed JND model is embedded in the HEVC video coding framework. For the transformation skip mode (TSM) in HEVC, we adopt the existing pixel domain called nonlinear additively model (NAMM). For the non-transformation skip mode (non-TSM) in HEVC, we use transform domain JND model to further reduce visual redundancy. The simulation results show that in the case of the same visual subjective quality, the algorithm can save more bitrates.展开更多
The search for new materials with Dirac points has been a fascinating subject of condensed matter physics.Here we first report the growth and band structure of HfGe_(0.92)Te single crystals featuring three different t...The search for new materials with Dirac points has been a fascinating subject of condensed matter physics.Here we first report the growth and band structure of HfGe_(0.92)Te single crystals featuring three different types of Dirac points.HfGe_(0.92)Te crystallizes in a nonsymmorphic tetragonal space group P4/nmm(No.129),having a square Ge-atom plane with vacancies of about 8%.Using angle-resolved photoemission spectroscopy(ARPES),the Dirac nodal line composed of conventional Dirac points vulnerable to spin-orbit coupling(SOC)is observed,accompanied by robust Dirac points protected by the nonsymmorphic symmetry against SOC and vacancies.In particular,spin-orbit Dirac points(SDPs)originating from the surface formed under significant SOC could exist based on ARPES and calculations.Quasi-two-dimensional(quasi-2D)characteristics are confirmed by angular-resolved magnetoresistance.HfGe_(0.92)Te bulk crystals can be easily exfoliated to flakes with a thickness of approximately 5 nm for the quasi-2D nature.Thus,HfGe_(0.92)Te provides a good platform to explore exotic topological phases or topological properties with three different types of Dirac points,which is a potential candidate to achieve novel 2D SDPs.展开更多
Background:Inhibitor of apoptosis-stimulating protein of p53(iASPP)is an evolutionarily conserved p53 inhibitor.Mechanistically,iASPP can accelerate tumorigenesis by inhibiting the transactivation function of p53.Targ...Background:Inhibitor of apoptosis-stimulating protein of p53(iASPP)is an evolutionarily conserved p53 inhibitor.Mechanistically,iASPP can accelerate tumorigenesis by inhibiting the transactivation function of p53.Targeting the interaction between iASPP and p53 may be a potential therapy for restoring the activity of p53 in tumors.Methods:We constructed an iASPP-derived peptide,called A8,that was derived from the C-terminus of iASPP.Here,we transfected A8 into two wildtype(WT)p53 cell lines,U2OS and A549,and then determined the number of apoptotic cells.The mechanism by which A8 affected apoptosis was further examined by immunoprecipitation(IP),Dual-Luciferase reporter assays,and chromatin IP assays.Real-time polymerase chain reaction and western blots were also used to examine the expression levels of apoptosis-related factors.Results:Our data demonstrate that A8 can increase apoptosis rates in WT p53 cell lines.Functional analysis suggested that A8 restored the transcriptional function and DNA binding activities of p53 toward the Bax and PUMA gene promoters.Moreover,A8 reduced cell proliferation and inhibited tumor growth in xenograft nude mice.Conclusions:These data provide a new approach for restoring the tumor suppressor function of p53 in cancer cells that express WT p53 and therefore may serve as a novel cancer treatment strategy.展开更多
Dynamic Reactive Power Optimization(DRPO) is a large-scale, multi-period, and strongly coupled nonlinear mixed-integer programming problem that is difficult to solve directly. First, to handle discrete variables and s...Dynamic Reactive Power Optimization(DRPO) is a large-scale, multi-period, and strongly coupled nonlinear mixed-integer programming problem that is difficult to solve directly. First, to handle discrete variables and switching operation constraints, DRPO is formulated as a nonlinear constrained two-objective optimization problem in this paper. The first objective is to minimize the real power loss and the Total Voltage Deviations(TVDs), and the second objective is to minimize incremental system loss. Then a Filter Collaborative State Transition Algorithm(FCSTA) is presented for solving DRPO problems. Two populations corresponding to two different objectives are employed. Moreover, the filter technique is utilized to deal with constraints. Finally, the effectiveness of the proposed method is demonstrated through the results obtained for a 24-hour test on Ward & Hale 6 bus, IEEE 14 bus, and IEEE 30 bus test power systems. To substantiate the effectiveness of the proposed algorithms, the obtained results are compared with different approaches in the literature.展开更多
Cyclophilin A (CypA) is a peptidyl-prolyl cis/trans isomerase that interacts with the matrix protein (M1) of influenza A virus (IAV) and restricts virus replication by regulating the ubiquitin–proteasome-mediated deg...Cyclophilin A (CypA) is a peptidyl-prolyl cis/trans isomerase that interacts with the matrix protein (M1) of influenza A virus (IAV) and restricts virus replication by regulating the ubiquitin–proteasome-mediated degradation of M1. However,the mechanism by which CypA regulates M1 ubiquitination remains unknown. In this study, we reported that E3 ubiquitin ligase AIP4 promoted K48-linked ubiquitination of M1 at K102 and K104, and accelerated ubiquitin–proteasome-mediated degradation of M1. The recombinant IAV with mutant M1 (K102 R/K104 R) could not be rescued, suggesting that the ubiquitination of M1 at K102/K104 was essential for IAV replication. Furthermore, CypA inhibited AIP4-mediated M1 ubiquitination by impairing the interaction between AIP4 and M1. More importantly, both the mutations of M1 (K102 R/K104 R) and CypA inhibited the nuclear export of M1, indicating that CypA regulates the cellular localization of M1 via inhibition of AIP4-mediated M1 ubiquitination at K102 and K104, which results in the reduced replication of IAV.Collectively, our findings reveal a novel ubiquitination-based mechanism by which CypA regulates the replication of IAV.展开更多
Interferon,a natural protein that is produced by a variety of cells during viral infection,activates the transcription of multiple functional genes in cells,regulates synergy among various signaling pathways,and media...Interferon,a natural protein that is produced by a variety of cells during viral infection,activates the transcription of multiple functional genes in cells,regulates synergy among various signaling pathways,and mediates many biological functions such as antiviral activity,immune regulation,and cell growth.However,clinical research on interferon in livestock is lacking.In this study,recombinant porcine interferon(PoIFNα)was used as an adjuvant,in combination with inactivated influenza virus,to vaccinate 6-week-old pigs via nasal infusion.The transcription of target genes was then monitored and the functions of PoIFNαwere determined with respect to the activation of mucosal immunity.We found that a combination of low-dose PoIFNαand in activated influenza virus could significantly up-regulate the expression of immunoregulatory cytokines such as IL-2,IL-1β,IFN-γ,IL-6,and IL-10 by real-time PCR,suggesting the induction of a strong mucosal innate immune response after administration.In addition,low-dose PoIFNαcan significant enhancing the transcription of genes encoding homing factors including CCR9 and CCR10(P<0.001),thereby resulting in the induction of higher levels of HA-specific antibodies(P<0.05),which can be determined by ELISA and IFA.Post-immunization challenges with H1N1 virus demonstrated that PoIFNot,combined with inactivated influenza virus,could alleviate clinical signs in pigs during the early stages of viral infection.These studies reveal low-dose PoIFNαas a potential mucosal adjuvant for influenza virus in pigs.展开更多
With the rapid development of artificial intelligence(AI)technology and its successful application in various fields,modeling and simulation technology,especially multi-agent modeling and simulation(MAMS),of complex s...With the rapid development of artificial intelligence(AI)technology and its successful application in various fields,modeling and simulation technology,especially multi-agent modeling and simulation(MAMS),of complex systems has rapidly advanced.In this study,we first describe the concept,technical advantages,research steps,and research status of MAMS.Then we review the development status of the hybrid modeling and simulation combining multi-agent and system dynamics,the modeling and simulation of multi-agent reinforcement learning,and the modeling and simulation of large-scale multi-agent.Lastly,we introduce existing MAMS platforms and their comparative studies.This work summarizes the current research situation of MAMS,thus helping scholars understand the systematic technology development of MAMS in the AI era.It also paves the way for further research on MAMS technology.展开更多
As COVID-19 continues to spread rapidly worldwide and variants continue to emerge,the development and deployment of safe and effective vaccines are urgently needed.Here,we developed an mRNA vaccine based on the trimer...As COVID-19 continues to spread rapidly worldwide and variants continue to emerge,the development and deployment of safe and effective vaccines are urgently needed.Here,we developed an mRNA vaccine based on the trimeric receptor-binding domain(RBD)of the SARS-CoV-2 spike(S)protein fused to ferritin-formed nanoparticles(TF-RBD).Compared to the trimeric form of the RBD mRNA vaccine(T-RBD),TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th 1-biased cellular response.After further challenge with live SARS-CoV-2,immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice.In addition,the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations.The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha(B.1.1.7)and Beta(B.1.351)variants.This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a referenee for the design of mRNA vaccines targeting SARS-CoV-2.展开更多
Mode distortion induced by stimulated Raman scattering(SRS)has become a new obstacle for the further development of high-power fiber lasers with high beam quality.Here,an approach for effective suppression of the SRS-...Mode distortion induced by stimulated Raman scattering(SRS)has become a new obstacle for the further development of high-power fiber lasers with high beam quality.Here,an approach for effective suppression of the SRS-induced mode distortion in high-power fiber amplifiers has been demonstrated experimentally by adjusting the seed power(output power of seed source)and forward feedback coefficient of the rear port in the seed source.It is shown that the threshold power of the SRS-induced mode distortion can be increased significantly by reducing the seed power or the forward feedback coefficient.Moreover,it has also been found that the threshold power is extremely sensitive to the forward feedback power value from the rear port.The influence of the seed power on the threshold power can be attributed to the fact that the seed power plays an important role in the effective length of the gain fiber in the amplifier.The influence of the forward feedback coefficient on the threshold power can be attributed to the enhanced SRS configuration because the end surface of the rear port together with the fiber in the amplifier constitutes a half-opening cavity.This suppression approach will be very helpful to further develop the high-power fiber amplifiers with high beam quality.展开更多
A Projection Pursuit Dynamic Cluster(PPDC) model optimized by Memetic Algorithm(MA) was proposed to solve the practical problems of nonlinearity and high dimensions of sample data, which appear in the context of evalu...A Projection Pursuit Dynamic Cluster(PPDC) model optimized by Memetic Algorithm(MA) was proposed to solve the practical problems of nonlinearity and high dimensions of sample data, which appear in the context of evaluation or prediction in complex systems. Projection pursuit theory was used to determine the optimal projection direction; then dynamic clusters and minimal total distance within clusters(min TDc) were used to build a PPDC model. 17 agronomic traits of 19 tomato varieties were evaluated by a PPDC model. The projection direction was optimized by Simulated Annealing(SA) algorithm, Particle Swarm Optimization(PSO), and MA. A PPDC model,based on an MA, avoids the problem of parameter calibration in Projection Pursuit Cluster(PPC) models. Its final results can be output directly, making the cluster results objective and definite. The calculation results show that a PPDC model based on an MA can solve the practical difficulties of nonlinearity and high dimensionality of sample data.展开更多
Mutations in viral proteins can lead to the cold adaption of influenza A virus and the cold-adapted virus is an important vaccination instrument.Here,we identify a novel strain of influenza A virus with cold sensitivi...Mutations in viral proteins can lead to the cold adaption of influenza A virus and the cold-adapted virus is an important vaccination instrument.Here,we identify a novel strain of influenza A virus with cold sensitivity conferred by a mutation at a phosphorylation site within the nucleoprotein(NP).The highly conserved tyrosine 385 residue(Y385)of NP was identified as a phosphorylation site by mass spectrometry.The constructive NP phosphorylation mimicked by Y385 E mutation was fatal for virus replication,while the continuous Y385 dephosphorylation mimicked by Y385 F mutation had little impact on virus replication in vitro.Notably,the Y385 F virus showed much lower replicative capacity in turbinates of mice compared with the wild type virus.Moreover,the replication of Y385 F virus was significantly reduced in both A549 and MDCK cells grown at 33℃,when compared to that at 37℃.These results indicated that the Y385 F mutation led to cold sensitivity of virus.We further found that the cold sensitivity of Y385 F virus could be attributed to diminished NP oligomerization rather than any changes in intracellular localization.Taken together,these findings suggest that the phosphorylation of NP may be a critical factor that regulates the temperature sensitivity of influenza A virus.展开更多
A safe and effective vaccine is critical to combat the COVID-19 pandemic.Here,we developed a trimeric SARS-CoV-2 receptor-binding domain(RBD)subunit vaccine candidate that simulates the natural structure of the spike(...A safe and effective vaccine is critical to combat the COVID-19 pandemic.Here,we developed a trimeric SARS-CoV-2 receptor-binding domain(RBD)subunit vaccine candidate that simulates the natural structure of the spike(S)trimer glycoprotein.Immunization with the RBD trimer-induced robust humoral and cellular immune responses,and a high level of neutralizing antibodies was maintained for at least 4.5 months.Moreover,the antibodies that were produced in response to the vaccine effectively cross-neutralized the SARS-CoV-2501Y.V2 variant(B.1.351).Of note,when the vaccine-induced antibodies dropped to a sufficiently low level,only one boost quickly activated the anamnestic immune response,conferring full protection against a SARSCoV-2 challenge in rhesus macaques without typical histopathological changes in the lung tissues.These results demonstrated that the SARS-CoV-2 RBD trimer vaccine candidate is highly immunogenic and safe,providing long-lasting,broad,and significant immunity protection in nonhuman primates,thereby offering an optimal vaccination strategy against COVID-19.展开更多
To reduce intermediate levels of splitting process and enhance sampling accuracy, a multilevel splitting algorithm for quick sampling is proposed in this paper. Firstly, the selected area of the elite set is expanded ...To reduce intermediate levels of splitting process and enhance sampling accuracy, a multilevel splitting algorithm for quick sampling is proposed in this paper. Firstly, the selected area of the elite set is expanded to maintain the diversity of the samples. Secondly, the combined use of an adaptive difference evolution algorithm and a local searching algorithm is proposed for the splitting procedure. Finally, a suite of benchmark functions are used for performance testing. The results indicate that the convergence rate and stability of this algorithm are superior to those of the classical importance splitting algorithm and an adaptive multilevel splitting algorithm.展开更多
基金Supported by the National Key Research and Development Program of China(Grant Nos.2017YFA0304700 and 2018YFE0202601)the National Natural Science Foundation of China(Grant Nos.51922105,51772322,52025025,and 52072400)the Beijing Natural Science Foundation(Grant No.Z200005)。
文摘We report the structure and physical properties of two newly discovered compounds AV_(8)Sb_(12)and AV_(6)Sb_(6)(A=Cs,Rb),which have C_(2)(space group:Cmmm)and C_(3)(space group:R3 m)symmetry,respectively.The basic Vkagome unit appears in both compounds,but stacking differently.AV_(2)Sb_(2) layer is sandwiched between two V_(3)Sb_(5)layers in AV_(8)Sb_(12),altering the V-kagome lattice and lowering the symmetry of kagome layer from hexagonal to orthorhombic.In AV_(6)Sb_(6),the building block is a more complex slab made up of two half-V_(3)Sb_(5)layers that are intercalated by Cs cations along the c-axis.Transport property measurements demonstrate that both compounds are nonmagnetic metals,with carrier concentrations at around 10^(21)cm^(-3).No superconductivity has been observed in CsV_(8)Sb_(12)above 0.3 K under in situ pressure up to 46 GPa.Compared to CSV_(3)Sb_(5),theoretical calculations and angle-resolved photoemission spectroscopy reveal a quasi-two-dimensional electronic structure in CsV_(8)Sb_(12)with C_(2)symmetry and no van Hove singularities near the Fermi level.Our findings will stimulate more research into V-based kagome quantum materials.
文摘In view of the fact that the current high efficiency video coding standard does not consider the characteristics of human vision, this paper proposes a perceptual video coding algorithm based on the just noticeable distortion model (JND). The adjusted JND model is combined into the transformation quantization process in high efficiency video coding (HEVC) to remove more visual redundancy and maintain compatibility. First of all, we design the JND model based on pixel domain and transform domain respectively, and the pixel domain model can give the JND threshold more intuitively on the pixel. The transform domain model introduces the contrast sensitive function into the model, making the threshold estimation more precise. Secondly, the proposed JND model is embedded in the HEVC video coding framework. For the transformation skip mode (TSM) in HEVC, we adopt the existing pixel domain called nonlinear additively model (NAMM). For the non-transformation skip mode (non-TSM) in HEVC, we use transform domain JND model to further reduce visual redundancy. The simulation results show that in the case of the same visual subjective quality, the algorithm can save more bitrates.
基金supported by the National Natural Science Foundation of China(U1832202,11888101,11920101005,12141402,and 12274459)the Chinese Academy of Sciences(QYZDB-SSW-SLH043,XDB33020100,and XDB28000000)+4 种基金the Beijing Municipal Science and Technology Commission(Z171100002017018,and Z200005)the National Key R&D Program of China(2018YFE0202600,2022YFA1403100,and 2022YFA1403800)the Fundamental Research Funds for the Central Universities and Research Funds of Renmin University of China(RUC)(18XNLG14,19XNLG13,19XNLG17,and 20XNH062)the Synergic Extreme Condition User Facility,Beijing,ChinaBeijing National Laboratory for Condensed Matter Physics。
基金partially supported by the National Natural Science Foundation of China(Grant Nos.51832010,51902055,11925408,12005251,and 11921004)National Key Research and Development Program of China(Grant Nos.2018YFE0202602,2018YFA0305700,and 2017YFA0302902)。
文摘The search for new materials with Dirac points has been a fascinating subject of condensed matter physics.Here we first report the growth and band structure of HfGe_(0.92)Te single crystals featuring three different types of Dirac points.HfGe_(0.92)Te crystallizes in a nonsymmorphic tetragonal space group P4/nmm(No.129),having a square Ge-atom plane with vacancies of about 8%.Using angle-resolved photoemission spectroscopy(ARPES),the Dirac nodal line composed of conventional Dirac points vulnerable to spin-orbit coupling(SOC)is observed,accompanied by robust Dirac points protected by the nonsymmorphic symmetry against SOC and vacancies.In particular,spin-orbit Dirac points(SDPs)originating from the surface formed under significant SOC could exist based on ARPES and calculations.Quasi-two-dimensional(quasi-2D)characteristics are confirmed by angular-resolved magnetoresistance.HfGe_(0.92)Te bulk crystals can be easily exfoliated to flakes with a thickness of approximately 5 nm for the quasi-2D nature.Thus,HfGe_(0.92)Te provides a good platform to explore exotic topological phases or topological properties with three different types of Dirac points,which is a potential candidate to achieve novel 2D SDPs.
基金National Natural Science Foundation of China,Grant/Award Number:81602710。
文摘Background:Inhibitor of apoptosis-stimulating protein of p53(iASPP)is an evolutionarily conserved p53 inhibitor.Mechanistically,iASPP can accelerate tumorigenesis by inhibiting the transactivation function of p53.Targeting the interaction between iASPP and p53 may be a potential therapy for restoring the activity of p53 in tumors.Methods:We constructed an iASPP-derived peptide,called A8,that was derived from the C-terminus of iASPP.Here,we transfected A8 into two wildtype(WT)p53 cell lines,U2OS and A549,and then determined the number of apoptotic cells.The mechanism by which A8 affected apoptosis was further examined by immunoprecipitation(IP),Dual-Luciferase reporter assays,and chromatin IP assays.Real-time polymerase chain reaction and western blots were also used to examine the expression levels of apoptosis-related factors.Results:Our data demonstrate that A8 can increase apoptosis rates in WT p53 cell lines.Functional analysis suggested that A8 restored the transcriptional function and DNA binding activities of p53 toward the Bax and PUMA gene promoters.Moreover,A8 reduced cell proliferation and inhibited tumor growth in xenograft nude mice.Conclusions:These data provide a new approach for restoring the tumor suppressor function of p53 in cancer cells that express WT p53 and therefore may serve as a novel cancer treatment strategy.
基金supported by the National Natural Science Foundation of China(Nos.51767022 and 51575469)
文摘Dynamic Reactive Power Optimization(DRPO) is a large-scale, multi-period, and strongly coupled nonlinear mixed-integer programming problem that is difficult to solve directly. First, to handle discrete variables and switching operation constraints, DRPO is formulated as a nonlinear constrained two-objective optimization problem in this paper. The first objective is to minimize the real power loss and the Total Voltage Deviations(TVDs), and the second objective is to minimize incremental system loss. Then a Filter Collaborative State Transition Algorithm(FCSTA) is presented for solving DRPO problems. Two populations corresponding to two different objectives are employed. Moreover, the filter technique is utilized to deal with constraints. Finally, the effectiveness of the proposed method is demonstrated through the results obtained for a 24-hour test on Ward & Hale 6 bus, IEEE 14 bus, and IEEE 30 bus test power systems. To substantiate the effectiveness of the proposed algorithms, the obtained results are compared with different approaches in the literature.
基金supported by grants from the National Natural Science Foundation of China (31630079,31672531,31572526,and 31802164)the National Key R&D Program of China (2016YFD0500206,2015BAD11B02)+3 种基金the Strategic Priority Research Program of Chinese Academy of Sciences (XDB29010000)the National Science and Technology Major Project (2018ZX10101004)the Emergency Technology Research Issue on Prevention and Control for Human Infection with A (H7N9) Avian Influenza Virus (10600100000015001206)Wenjun Liu is the principal investigator of the Innovative Research Group of National Natural Science Foundation of China (Grant No.81621091)
文摘Cyclophilin A (CypA) is a peptidyl-prolyl cis/trans isomerase that interacts with the matrix protein (M1) of influenza A virus (IAV) and restricts virus replication by regulating the ubiquitin–proteasome-mediated degradation of M1. However,the mechanism by which CypA regulates M1 ubiquitination remains unknown. In this study, we reported that E3 ubiquitin ligase AIP4 promoted K48-linked ubiquitination of M1 at K102 and K104, and accelerated ubiquitin–proteasome-mediated degradation of M1. The recombinant IAV with mutant M1 (K102 R/K104 R) could not be rescued, suggesting that the ubiquitination of M1 at K102/K104 was essential for IAV replication. Furthermore, CypA inhibited AIP4-mediated M1 ubiquitination by impairing the interaction between AIP4 and M1. More importantly, both the mutations of M1 (K102 R/K104 R) and CypA inhibited the nuclear export of M1, indicating that CypA regulates the cellular localization of M1 via inhibition of AIP4-mediated M1 ubiquitination at K102 and K104, which results in the reduced replication of IAV.Collectively, our findings reveal a novel ubiquitination-based mechanism by which CypA regulates the replication of IAV.
基金supported by Grants from the National Key R&D Programme of China (2017YFD051105)the National Natural Science Foundation of China (31630079)+2 种基金the National Science and Technology Major Project (2018ZX10101004)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29010000)supported by Youth Innovation Promotion Association of CAS (2019)
文摘Interferon,a natural protein that is produced by a variety of cells during viral infection,activates the transcription of multiple functional genes in cells,regulates synergy among various signaling pathways,and mediates many biological functions such as antiviral activity,immune regulation,and cell growth.However,clinical research on interferon in livestock is lacking.In this study,recombinant porcine interferon(PoIFNα)was used as an adjuvant,in combination with inactivated influenza virus,to vaccinate 6-week-old pigs via nasal infusion.The transcription of target genes was then monitored and the functions of PoIFNαwere determined with respect to the activation of mucosal immunity.We found that a combination of low-dose PoIFNαand in activated influenza virus could significantly up-regulate the expression of immunoregulatory cytokines such as IL-2,IL-1β,IFN-γ,IL-6,and IL-10 by real-time PCR,suggesting the induction of a strong mucosal innate immune response after administration.In addition,low-dose PoIFNαcan significant enhancing the transcription of genes encoding homing factors including CCR9 and CCR10(P<0.001),thereby resulting in the induction of higher levels of HA-specific antibodies(P<0.05),which can be determined by ELISA and IFA.Post-immunization challenges with H1N1 virus demonstrated that PoIFNot,combined with inactivated influenza virus,could alleviate clinical signs in pigs during the early stages of viral infection.These studies reveal low-dose PoIFNαas a potential mucosal adjuvant for influenza virus in pigs.
文摘With the rapid development of artificial intelligence(AI)technology and its successful application in various fields,modeling and simulation technology,especially multi-agent modeling and simulation(MAMS),of complex systems has rapidly advanced.In this study,we first describe the concept,technical advantages,research steps,and research status of MAMS.Then we review the development status of the hybrid modeling and simulation combining multi-agent and system dynamics,the modeling and simulation of multi-agent reinforcement learning,and the modeling and simulation of large-scale multi-agent.Lastly,we introduce existing MAMS platforms and their comparative studies.This work summarizes the current research situation of MAMS,thus helping scholars understand the systematic technology development of MAMS in the AI era.It also paves the way for further research on MAMS technology.
基金supported by Strategic Priority Research Program of CAS(XDB29010000)the National Natural Science Foundation of China(31970153)+1 种基金the National Key R&D Program of China(2016YFD0500206)partially financial supported by Institute of infection disease of Shenzhen Bay laboratory.J.L.is supported by the Youth Innovation Promotion Association of CAS(2019091).
文摘As COVID-19 continues to spread rapidly worldwide and variants continue to emerge,the development and deployment of safe and effective vaccines are urgently needed.Here,we developed an mRNA vaccine based on the trimeric receptor-binding domain(RBD)of the SARS-CoV-2 spike(S)protein fused to ferritin-formed nanoparticles(TF-RBD).Compared to the trimeric form of the RBD mRNA vaccine(T-RBD),TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th 1-biased cellular response.After further challenge with live SARS-CoV-2,immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice.In addition,the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations.The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha(B.1.1.7)and Beta(B.1.351)variants.This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a referenee for the design of mRNA vaccines targeting SARS-CoV-2.
基金National Natural Science Foundation of China(Nos.62005310 and 61675230)Equipment Pre-research Foundation of China(No.61406190302)+1 种基金Key R&D Program of Shaanxi Province(No.2018ZDXMGY-060)National Key R&D Program of China(No.2017YFB1104400).
文摘Mode distortion induced by stimulated Raman scattering(SRS)has become a new obstacle for the further development of high-power fiber lasers with high beam quality.Here,an approach for effective suppression of the SRS-induced mode distortion in high-power fiber amplifiers has been demonstrated experimentally by adjusting the seed power(output power of seed source)and forward feedback coefficient of the rear port in the seed source.It is shown that the threshold power of the SRS-induced mode distortion can be increased significantly by reducing the seed power or the forward feedback coefficient.Moreover,it has also been found that the threshold power is extremely sensitive to the forward feedback power value from the rear port.The influence of the seed power on the threshold power can be attributed to the fact that the seed power plays an important role in the effective length of the gain fiber in the amplifier.The influence of the forward feedback coefficient on the threshold power can be attributed to the enhanced SRS configuration because the end surface of the rear port together with the fiber in the amplifier constitutes a half-opening cavity.This suppression approach will be very helpful to further develop the high-power fiber amplifiers with high beam quality.
基金supported by the National Natural Science Foundation of China (No. 51575469)
文摘A Projection Pursuit Dynamic Cluster(PPDC) model optimized by Memetic Algorithm(MA) was proposed to solve the practical problems of nonlinearity and high dimensions of sample data, which appear in the context of evaluation or prediction in complex systems. Projection pursuit theory was used to determine the optimal projection direction; then dynamic clusters and minimal total distance within clusters(min TDc) were used to build a PPDC model. 17 agronomic traits of 19 tomato varieties were evaluated by a PPDC model. The projection direction was optimized by Simulated Annealing(SA) algorithm, Particle Swarm Optimization(PSO), and MA. A PPDC model,based on an MA, avoids the problem of parameter calibration in Projection Pursuit Cluster(PPC) models. Its final results can be output directly, making the cluster results objective and definite. The calculation results show that a PPDC model based on an MA can solve the practical difficulties of nonlinearity and high dimensionality of sample data.
基金supported by grants from the Strategic Priority Research Program of Chinese Academy of Sciences(XDB29010000)the National Natural Science Foundation of China(31630079,31972657,31672531)+2 种基金the National Key Research and Development Program of China(2016YFD0500206)the Mega-Project of Guangxi Natural Science Foundation(2015GXNSFEA139002)supported by Youth Innovation Promotion Association of CAS(2019091)。
文摘Mutations in viral proteins can lead to the cold adaption of influenza A virus and the cold-adapted virus is an important vaccination instrument.Here,we identify a novel strain of influenza A virus with cold sensitivity conferred by a mutation at a phosphorylation site within the nucleoprotein(NP).The highly conserved tyrosine 385 residue(Y385)of NP was identified as a phosphorylation site by mass spectrometry.The constructive NP phosphorylation mimicked by Y385 E mutation was fatal for virus replication,while the continuous Y385 dephosphorylation mimicked by Y385 F mutation had little impact on virus replication in vitro.Notably,the Y385 F virus showed much lower replicative capacity in turbinates of mice compared with the wild type virus.Moreover,the replication of Y385 F virus was significantly reduced in both A549 and MDCK cells grown at 33℃,when compared to that at 37℃.These results indicated that the Y385 F mutation led to cold sensitivity of virus.We further found that the cold sensitivity of Y385 F virus could be attributed to diminished NP oligomerization rather than any changes in intracellular localization.Taken together,these findings suggest that the phosphorylation of NP may be a critical factor that regulates the temperature sensitivity of influenza A virus.
基金This study was funded by National Key Technologies Research and Development Program grants 2018YFC1200600 and 2018YFC1200500 to L.M.Y.a grant from Strategic Priority Research Program of the Chinese Academy of Sciences XDB29010000 to W.J.L.and XDB29010102 to Y.H.B.+1 种基金the National Natural Science Foundation of China(NSFC)grants 32041010 and 31900155 to Y.H.B.Youth Innovation Promotion Association of CAS grant 2017122 to Y.H.B.
文摘A safe and effective vaccine is critical to combat the COVID-19 pandemic.Here,we developed a trimeric SARS-CoV-2 receptor-binding domain(RBD)subunit vaccine candidate that simulates the natural structure of the spike(S)trimer glycoprotein.Immunization with the RBD trimer-induced robust humoral and cellular immune responses,and a high level of neutralizing antibodies was maintained for at least 4.5 months.Moreover,the antibodies that were produced in response to the vaccine effectively cross-neutralized the SARS-CoV-2501Y.V2 variant(B.1.351).Of note,when the vaccine-induced antibodies dropped to a sufficiently low level,only one boost quickly activated the anamnestic immune response,conferring full protection against a SARSCoV-2 challenge in rhesus macaques without typical histopathological changes in the lung tissues.These results demonstrated that the SARS-CoV-2 RBD trimer vaccine candidate is highly immunogenic and safe,providing long-lasting,broad,and significant immunity protection in nonhuman primates,thereby offering an optimal vaccination strategy against COVID-19.
文摘To reduce intermediate levels of splitting process and enhance sampling accuracy, a multilevel splitting algorithm for quick sampling is proposed in this paper. Firstly, the selected area of the elite set is expanded to maintain the diversity of the samples. Secondly, the combined use of an adaptive difference evolution algorithm and a local searching algorithm is proposed for the splitting procedure. Finally, a suite of benchmark functions are used for performance testing. The results indicate that the convergence rate and stability of this algorithm are superior to those of the classical importance splitting algorithm and an adaptive multilevel splitting algorithm.