Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq dat...Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.展开更多
With the explosive increasing number of connecting devices such as smart phones, vehicles,drones, and satellites in the wireless networks, how to manage and control such a huge number of networking nodes has become a ...With the explosive increasing number of connecting devices such as smart phones, vehicles,drones, and satellites in the wireless networks, how to manage and control such a huge number of networking nodes has become a great challenge. In this paper, we combine the advantages of centralized networks and distributed networks approaches for vehicular networks with the aid of Unmanned Aerial Vehicle(UAV), and propose a Center-controlled Multihop Wireless(CMW) networking scheme consisting of data transmission plane performed by vehicles and the network control plane implemented by the UAV.Besides, we jointly explore the advantages of Medium Access Control(MAC) protocols in the link layer and routing schemes in the network layer to facilitate the multi-hop data transmission for the ground vehicles.Particularly, the network control plane in the UAV can manage the whole network effectively via fully exploiting the acquired network topology information and traffic requests from each vehicle, and implements various kinds of control based on different traffic demands, which can enhance the networking flexibility and scalability significantly in vehicular networks.Simulation results validate the advantages of the proposed scheme compared with existing methods.展开更多
Internet of Things (IoT) has emerged as one of the new use cases in the 5th Generation wireless networks. However, the transient nature of the data generated in IoT networks brings great challenges for content caching...Internet of Things (IoT) has emerged as one of the new use cases in the 5th Generation wireless networks. However, the transient nature of the data generated in IoT networks brings great challenges for content caching. In this paper, we study a joint content caching and updating strategy in IoT networks, taking both the energy consumption of the sensors and the freshness loss of the contents into account. In particular, we decide whether or not to cache the transient data and, if so, how often the servers should update their contents. We formulate this content caching and updating problem as a mixed 0–1 integer non-convex optimization programming, and devise a Harmony Search based content Caching and Updating (HSCU) algorithm, which is self-learning and derivativefree and hence stipulates no requirement on the relationship between the objective and variables. Finally, extensive simulation results verify the effectiveness of our proposed algorithm in terms of the achieved satisfaction ratio for content delivery, normalized energy consumption, and overall network utility, by comparing it with some baseline algorithms.展开更多
Particle χ_(c0)(3915) was first observed by the Belle experiment in the ωJ/ψ invariant mass spectrum in the process B→KωJ/ψ and subsequently confirmed by the BaBar experiment.Both experiments reported the resona...Particle χ_(c0)(3915) was first observed by the Belle experiment in the ωJ/ψ invariant mass spectrum in the process B→KωJ/ψ and subsequently confirmed by the BaBar experiment.Both experiments reported the resonant parameters of this particle in the processes γγ→ωJ/ψ and B→KωJ/ψ assuming χ_(c0)(3915) as an S-wave Breit-Wigner resonance.We performed a global fit to the distributions of invariant mass of ωJ/ψ measured by the Belle and BaBar experiments and additionally incorporated the measurements reported by the LHCb experiment to extract the mass and width of χ_(c0)(3915).We obtained M=3920.9±0.9 MeV/c^(2) and Γ=18.2±2.4 MeV,which are consistent with the values from PDG within one standard deviation but with higher precision.展开更多
African swine fever(ASF)is a devastating infectious disease in swine that is severely threatening the global pig industry.An efficacious vaccine is urgently required.Here,we used the Chinese ASFV HLJ/18 as a backbone ...African swine fever(ASF)is a devastating infectious disease in swine that is severely threatening the global pig industry.An efficacious vaccine is urgently required.Here,we used the Chinese ASFV HLJ/18 as a backbone and generated a series of genedeleted viruses.The virulence,immunogenicity,safety,and protective efficacy evaluation in specific-pathogen-free pigs,commercial pigs,and pregnant sows indicated that one virus,namely HLJ/18-7GD,which has seven genes deleted,is fully attenuated in pigs,cannot convert to the virulent strain,and provides complete protection of pigs against lethal ASFV challenge.Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV,and as such is expected to play an important role in controlling the spread of ASFV.展开更多
Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years.However,the quality control (QC) standards of SJZD are insufficient...Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years.However,the quality control (QC) standards of SJZD are insufficient.Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formularapidly.In this study,we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC.A total of 56 compounds in SJZD were characterized in vitro,and 23 compounds were discovered in vivo.A total of 58 biomarkers were related to SQDS,and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status.A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy.We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng;dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria;glycyrrhizic acid,isoglabrolide,and glycyrrhetnic acid as the q-markers of licorice;and 2-atractylenolide as the q-marker of macrocephala.According to the discovery of the SJZD q-markers,we can establish the quality standard that is related to efficacy.展开更多
High-throughput metabolomics can clarify the underlying molecular mechanism of diseases via the qualitative and quantitative analysis of metabolites.This study used the established Yang Huang syndrome(YHS)mouse model ...High-throughput metabolomics can clarify the underlying molecular mechanism of diseases via the qualitative and quantitative analysis of metabolites.This study used the established Yang Huang syndrome(YHS)mouse model to evaluate the efficacy of geniposide(GEN).Urine metabolic data were quantified by ultraperformance liquid chromatography-tandem mass spectrometry.The non-target screening of the massive biological information dataset was performed,and a total of 33 metabolites,including tyramine glucuronide,aurine,and L-cysteine,were identified relating to YHS.These differential metabolites directly participated in the disturbance of phase I reaction and hydrophilic transformation of bilirubin.Interestingly,they were completely reversed by GEN.While,as the auxiliary technical means,we also focused on the molecular prediction and docking results in network pharmacological and integrated analysis part.We used integrated analysis to communicate the multiple results of metabolomics and network pharmacology.This study is the first to report that GEN indirectly regulates the metabolite“tyramine glucuronide”through its direct effect on the target heme oxygenase 1 in vivo.Meanwhile,heme oxygenase-1,a prediction of network pharmacology,was the confirmed metabolic enzyme of phase I reaction in hepatocytes.Our study indicated that the combination of high-throughput metabolomics and network pharmacology is a robust combination for deciphering the pathogenesis of the traditional Chinese medicine(TCM)syndrome.展开更多
Existing works have addressed the interference mitigation by any two of the three approaches: link scheduling, power control, and successive interference cancellation(SIC). In this paper, we integrate the above approa...Existing works have addressed the interference mitigation by any two of the three approaches: link scheduling, power control, and successive interference cancellation(SIC). In this paper, we integrate the above approaches to further improve the spectral efficiency of the wireless networks and consider the max-min fairness to guarantee the transmission demand of the worst-case link. We formulate the link scheduling with joint power control and SIC(PCSIC) problem as a mixed-integer non-linear programming(MINLP), which has been proven to be NP-complete. Consequently, we propose an iterative algorithm to tackle the problem by decomposing it into a series of linear subproblems, and then the analysis shows that the algorithm has high complexity in the worst case. In order to reduce the computational complexity, we have further devised a two-stage algorithm with polynomial-time complexity. Numerical results show the performance improvements of our proposed algorithms in terms of the network throughput and power consumption compared with the link scheduling scheme only with SIC.展开更多
Severe acute respiratory syndrome(SARS)is a highly contagious zoonotic disease caused by SARS coronavirus(SARS-Co V).Since its outbreak in Guangdong Province of China in 2002,SARS has caused 8096 infections and774 dea...Severe acute respiratory syndrome(SARS)is a highly contagious zoonotic disease caused by SARS coronavirus(SARS-Co V).Since its outbreak in Guangdong Province of China in 2002,SARS has caused 8096 infections and774 deaths by December 31st,2003.Although there have been no more SARS cases reported in human populations since 2004,the recent emergence of a novel coronavirus disease(COVID-19)indicates the potential of the recurrence of SARS and other coronavirus disease among humans.Thus,developing a rapid response SARS vaccine to provide protection for human populations is still needed.Spike(S)protein of SARS-Co V can induce neutralizing antibodies,which is a pivotal immunogenic antigen for vaccine development.Here we constructed a recombinant chimeric vesicular stomatitis virus(VSV)VSVΔG-SARS,in which the glycoprotein(G)gene is replaced with the SARS-Co V S gene.VSVΔG-SARS maintains the bullet-like shape of the native VSV,with the heterogeneous S protein incorporated into its surface instead of G protein.The results of safety trials revealed that VSVΔG-SARS is safe and effective in mice at a dose of 1×10^(6)TCID_(50).More importantly,only a single-dose immunization of 2×10^(7)TCID_(50)can provide high-level neutralizing antibodies and robust T cell responses to non-human primate animal models.Thus,our data indicate that VSVΔG-SARS can be used as a rapid response vaccine candidate.Our study on the recombinant VSV-vectored SARS-Co V vaccines can accumulate experience and provide a foundation for the new coronavirus disease in the future.展开更多
基金Liuzhou City's Top Ten Hundred Talents Project,Liuzhou Science and Technology Project(Grant Nos.2021CBC0126 and 2021CBC0123)Guangxi Zhuang Autonomous Region Health and Family Planning Commission Projects(Z20210561,Z20210903)+1 种基金liuzhou Scienceand Technology Plan Projects(2021CBC0121,2021CBC0128).
文摘Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.
基金supported in part by the National Natural Science Foundation of China under Grant 62071283,Grant 61771296,Grant 61872228 and Grant 62271513in part by the Natural Science Basic Research Plan in Shaanxi Province of China under Grant 2018JQ6048 and Grant 2018JZ6006+3 种基金in part by Shaanxi Key Industrial Innovation Chain Project in Industrial Domain under Grant 2020ZDLGY15-09in part by Guang Dong Basic and Applied Basic Research Foundation under Grant 2021A1515012631in part by China Postdoctoral Science Foundation under Grant 2016M600761in part by the Fundamental Research Funds for the Central Universities under Grant GK202003075 and Grant GK202103016。
文摘With the explosive increasing number of connecting devices such as smart phones, vehicles,drones, and satellites in the wireless networks, how to manage and control such a huge number of networking nodes has become a great challenge. In this paper, we combine the advantages of centralized networks and distributed networks approaches for vehicular networks with the aid of Unmanned Aerial Vehicle(UAV), and propose a Center-controlled Multihop Wireless(CMW) networking scheme consisting of data transmission plane performed by vehicles and the network control plane implemented by the UAV.Besides, we jointly explore the advantages of Medium Access Control(MAC) protocols in the link layer and routing schemes in the network layer to facilitate the multi-hop data transmission for the ground vehicles.Particularly, the network control plane in the UAV can manage the whole network effectively via fully exploiting the acquired network topology information and traffic requests from each vehicle, and implements various kinds of control based on different traffic demands, which can enhance the networking flexibility and scalability significantly in vehicular networks.Simulation results validate the advantages of the proposed scheme compared with existing methods.
基金National Natural Science Foundation of China(61701372)Talents Special Foundation of Northwest A&F University(Z111021801).
文摘Internet of Things (IoT) has emerged as one of the new use cases in the 5th Generation wireless networks. However, the transient nature of the data generated in IoT networks brings great challenges for content caching. In this paper, we study a joint content caching and updating strategy in IoT networks, taking both the energy consumption of the sensors and the freshness loss of the contents into account. In particular, we decide whether or not to cache the transient data and, if so, how often the servers should update their contents. We formulate this content caching and updating problem as a mixed 0–1 integer non-convex optimization programming, and devise a Harmony Search based content Caching and Updating (HSCU) algorithm, which is self-learning and derivativefree and hence stipulates no requirement on the relationship between the objective and variables. Finally, extensive simulation results verify the effectiveness of our proposed algorithm in terms of the achieved satisfaction ratio for content delivery, normalized energy consumption, and overall network utility, by comparing it with some baseline algorithms.
基金Supported by National Natural Science Foundation of China(NSFC)(11805090)。
文摘Particle χ_(c0)(3915) was first observed by the Belle experiment in the ωJ/ψ invariant mass spectrum in the process B→KωJ/ψ and subsequently confirmed by the BaBar experiment.Both experiments reported the resonant parameters of this particle in the processes γγ→ωJ/ψ and B→KωJ/ψ assuming χ_(c0)(3915) as an S-wave Breit-Wigner resonance.We performed a global fit to the distributions of invariant mass of ωJ/ψ measured by the Belle and BaBar experiments and additionally incorporated the measurements reported by the LHCb experiment to extract the mass and width of χ_(c0)(3915).We obtained M=3920.9±0.9 MeV/c^(2) and Γ=18.2±2.4 MeV,which are consistent with the values from PDG within one standard deviation but with higher precision.
基金supported by the National Key R&D Program of China(2018YFC1200601)Applied Technology Research and Development Project of Heilongjiang Province(GA19B301)+1 种基金Key-Area Research and Development Program of Guangdong Province(2019B020211004)the grant from the State Key Laboratory of Veterinary Biotechnology Program(SKLVBP201801)。
文摘African swine fever(ASF)is a devastating infectious disease in swine that is severely threatening the global pig industry.An efficacious vaccine is urgently required.Here,we used the Chinese ASFV HLJ/18 as a backbone and generated a series of genedeleted viruses.The virulence,immunogenicity,safety,and protective efficacy evaluation in specific-pathogen-free pigs,commercial pigs,and pregnant sows indicated that one virus,namely HLJ/18-7GD,which has seven genes deleted,is fully attenuated in pigs,cannot convert to the virulent strain,and provides complete protection of pigs against lethal ASFV challenge.Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV,and as such is expected to play an important role in controlling the spread of ASFV.
基金This work was supported by grants from the National Key Research and Development Program of China(No.2018YFC1706103)Key Program of National Natural Science Foundation of China(Nos.81830110,8181101160,81430093,81673586,81703685,81302-905,81503386,and 81373930)+4 种基金National Key Subject of Drug Innovation(Nos.2015ZX09101043-005 and 2015ZX09101043-011)TCM State Administration Subject of Public Welfare of(No.2015468004)Major Projects of Application Technology Research and Development Plan in Heilongjiang Province(No.GX16C003)TCM State Administration Subject of Public Welfare(No.2015468004),Young Talent Lift Engineering Project of China Association of Traditional Chinese Medicine(No.QNRC2-B06)Outstanding Talents Foundation of Heilongjiang University of Chinese Medicine(No.2018jc01).
文摘Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years.However,the quality control (QC) standards of SJZD are insufficient.Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formularapidly.In this study,we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC.A total of 56 compounds in SJZD were characterized in vitro,and 23 compounds were discovered in vivo.A total of 58 biomarkers were related to SQDS,and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status.A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy.We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng;dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria;glycyrrhizic acid,isoglabrolide,and glycyrrhetnic acid as the q-markers of licorice;and 2-atractylenolide as the q-marker of macrocephala.According to the discovery of the SJZD q-markers,we can establish the quality standard that is related to efficacy.
基金This work was supported by grants from the National Key Research and Development Program of China(No.2018YFC1706103)Key Program of National Natural Science Foundation of China(Nos.81830110,8181101160,81430093,81673586,81703685,81302905,81503386,and 81373930)+5 种基金National Key Subject of Drug Innovation(Nos.2015ZX09101043-005 and 2015ZX-09101043-011)TCM State Administration Subject of Public Welfare(No.2015468004)Major Projects of Application Technology Research and Development Plan in Heilongjiang Province(No.GX16C003)Young Talent Lift Engineering Project of China Association of Traditional Chinese Medicine(No.QNRC2-B06)Natural Science Foundation of Heilongjiang Province(Nos.YQ2019H030 and H2016056)Foundation of Heilongjiang University of Chinese Medicine(Nos.2018jc01,2018bs02,and 201809).
文摘High-throughput metabolomics can clarify the underlying molecular mechanism of diseases via the qualitative and quantitative analysis of metabolites.This study used the established Yang Huang syndrome(YHS)mouse model to evaluate the efficacy of geniposide(GEN).Urine metabolic data were quantified by ultraperformance liquid chromatography-tandem mass spectrometry.The non-target screening of the massive biological information dataset was performed,and a total of 33 metabolites,including tyramine glucuronide,aurine,and L-cysteine,were identified relating to YHS.These differential metabolites directly participated in the disturbance of phase I reaction and hydrophilic transformation of bilirubin.Interestingly,they were completely reversed by GEN.While,as the auxiliary technical means,we also focused on the molecular prediction and docking results in network pharmacological and integrated analysis part.We used integrated analysis to communicate the multiple results of metabolomics and network pharmacology.This study is the first to report that GEN indirectly regulates the metabolite“tyramine glucuronide”through its direct effect on the target heme oxygenase 1 in vivo.Meanwhile,heme oxygenase-1,a prediction of network pharmacology,was the confirmed metabolic enzyme of phase I reaction in hepatocytes.Our study indicated that the combination of high-throughput metabolomics and network pharmacology is a robust combination for deciphering the pathogenesis of the traditional Chinese medicine(TCM)syndrome.
基金supported by National Natural Science Foundation of China(Grant Nos.61231008,61172079,61201141,61301176,91338114)Science and Technology on Information Transmission and Dissemination in Communication Networks Laboratory Fund Project+1 种基金Programme of Introducing Talents of Discipline to Universities(Grant No.B08038)National High Technology Research and Development Program of China(Grant No.2014AA01A701)
文摘Existing works have addressed the interference mitigation by any two of the three approaches: link scheduling, power control, and successive interference cancellation(SIC). In this paper, we integrate the above approaches to further improve the spectral efficiency of the wireless networks and consider the max-min fairness to guarantee the transmission demand of the worst-case link. We formulate the link scheduling with joint power control and SIC(PCSIC) problem as a mixed-integer non-linear programming(MINLP), which has been proven to be NP-complete. Consequently, we propose an iterative algorithm to tackle the problem by decomposing it into a series of linear subproblems, and then the analysis shows that the algorithm has high complexity in the worst case. In order to reduce the computational complexity, we have further devised a two-stage algorithm with polynomial-time complexity. Numerical results show the performance improvements of our proposed algorithms in terms of the network throughput and power consumption compared with the link scheduling scheme only with SIC.
基金supported by grants from the National Key Research and Development Program of China(2017YFD0501804)。
文摘Severe acute respiratory syndrome(SARS)is a highly contagious zoonotic disease caused by SARS coronavirus(SARS-Co V).Since its outbreak in Guangdong Province of China in 2002,SARS has caused 8096 infections and774 deaths by December 31st,2003.Although there have been no more SARS cases reported in human populations since 2004,the recent emergence of a novel coronavirus disease(COVID-19)indicates the potential of the recurrence of SARS and other coronavirus disease among humans.Thus,developing a rapid response SARS vaccine to provide protection for human populations is still needed.Spike(S)protein of SARS-Co V can induce neutralizing antibodies,which is a pivotal immunogenic antigen for vaccine development.Here we constructed a recombinant chimeric vesicular stomatitis virus(VSV)VSVΔG-SARS,in which the glycoprotein(G)gene is replaced with the SARS-Co V S gene.VSVΔG-SARS maintains the bullet-like shape of the native VSV,with the heterogeneous S protein incorporated into its surface instead of G protein.The results of safety trials revealed that VSVΔG-SARS is safe and effective in mice at a dose of 1×10^(6)TCID_(50).More importantly,only a single-dose immunization of 2×10^(7)TCID_(50)can provide high-level neutralizing antibodies and robust T cell responses to non-human primate animal models.Thus,our data indicate that VSVΔG-SARS can be used as a rapid response vaccine candidate.Our study on the recombinant VSV-vectored SARS-Co V vaccines can accumulate experience and provide a foundation for the new coronavirus disease in the future.