Silicon photonics has attracted a great deal of interest for integrated photonics systems due to its large-scale electronics-photonics integration on a chip by leveraging the fabrication process of the complementary-m...Silicon photonics has attracted a great deal of interest for integrated photonics systems due to its large-scale electronics-photonics integration on a chip by leveraging the fabrication process of the complementary-metal-oxide semiconductor(CMOS)foundries[1−5].Germanium-on-silicon(Ge-on-Si)waveguide photodetector(PD)is an indispensable building block of silicon photonics technology which requires high sensitivity.展开更多
Objective:The aim of this study was to observe the inhibitory effect of application of COX-2 inhibitor,celecoxib,combined with cisplatin on the growth of human tongue squamous carcinoma Tca8113 cell xenograft by anima...Objective:The aim of this study was to observe the inhibitory effect of application of COX-2 inhibitor,celecoxib,combined with cisplatin on the growth of human tongue squamous carcinoma Tca8113 cell xenograft by animal experiment.Methods:The nude mice were transplanted subcutaneously with Tca 8113 cells,and then were administrated with celecoxib,cisplatin or celecoxib combined with cisplatin respectively,and were sacrificed after 35 days.The weight of xenograft was measured to calculate the tumor inhibition rate.The histological change was studied under light and electron microscope.The COX-2 protein expression was observed by immunohistological staining.And the COX-2 mRNA expression was determined by RT-PCR.Results:Celecoxib,the COX-2 inhibitor,could not only inhibit the growth of Tca8113 cell xenograft tumor and COX-2 protein expression,but also enhance the inhibitory effect cisplatin on xenograft tumor growth significantly.The tumor inhibition rates of celecoxib group,cisplatin group and celecoxib plus cisplatin group were 15.63%,37.50% and 82.81% respectively that was statistically significant compared to control group(P < 0.01).The combined application of celecoxib and cisplatin could inhibit tumor growth more significantly than that of separated application(P < 0.01).The inhibitory effect of celecoxib on COX-2 mRNA expression of Tca 8113 cell was weaker and not significant(P = 0.073).Conclusion:Celecoxib can not only inhibit xenograft tumor growth in nude mice,but also enhance the inhibitory effect of CDDP on Tca 8113 transplanted tumor growth in nude mice.The mechanism maybe related to inhibition of COX-2 protein expression,which offers beneficial reference to further explore the mechanism between inhibition of COX-2 enzyme activity and prevention of head and neck tumor.展开更多
The theoretical relationship between water injection multiple(i.e.injected pore volume)and water saturation is inferred from theoretical concepts of reservoir engineering.A mathematical model based on core displacemen...The theoretical relationship between water injection multiple(i.e.injected pore volume)and water saturation is inferred from theoretical concepts of reservoir engineering.A mathematical model based on core displacement tests is established for the entire injection process that satisfies both initial displacement and extreme displacement,simultaneously.The results show that prior to the flooding,the water injection multiple has a linear relationship with the water saturation,and the utilization rate of the injected water is the highest.As water breakthrough at the production end,the water-cut increases,and the injection multiple increases exponentially while the utilization efficiency of the injected water gradually decreases.When the injection multiple approaches infinity,the utilization efficiency of the injected water gradually decreases to 0,by which time the water-cut at the production end is always 1.At this time,the water saturation no longer changes,and the water flooding recovery rate reaches its limit.Based on the experimental test data,a mathematical model of the entire process of injection multiple and water saturation is established,which has high fitting accuracy that can predict the injection multiple in the different stages of development of a mature oil reservoir.The dynamically changing index of the injection water utilization efficiency in reservoir development by reactive water flooding can be obtained through reasonable transformation of the mathematical model.This is of great significance in guiding evaluations of the effects of reservoir development and formulating countermeasures.展开更多
Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication, mouse microglia and astrocytes were isolat...Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication, mouse microglia and astrocytes were isolated, infected with human H1N1 and avian H5N1 influenza viruses, and examined for their immune responses. We observed homogeneously distributed viral receptors, sialic acid (SA)-a2,3-Galactose (Gal) and SA-a2,6-Gal, on microglia and astrocytes. Both viruses were replicative and productive in microglia and astrocytes. Virus-induced apoptosis and cytopathy in infected cells were observed at 24 h post-infection (p.i.). Expression of IL-1β, IL-6 and TNF-a mRNA examined at 6 h and 24 h p.i. was up-regulated, and their expression levels were considerably higher in H5N1 infection. The amounts of secreted proinflammatory IL-1β, IL-6 and TNF-a at 6 h and 24 h p.i. were also induced, with greater induction by H5N1 infection. This study is the first demonstration that both human H1N1 and avian H5N1 influenza viruses can infect mouse microglia and astrocytes and induce apoptosis, cytopathy, and proinflammatory cytokine production in them in vitro. Our results suggest that the direct cellular damage and the consequences of immunopathological injury in the CNS contribute to the influenza viral pathogenesis. Cellular & Molecular Immunology.展开更多
Advances in biological and medical technologies have been providing us explosive vol- umes of biological and physiological data, such as medical images, electroencephalography, geno- mic and protein sequences. Learnin...Advances in biological and medical technologies have been providing us explosive vol- umes of biological and physiological data, such as medical images, electroencephalography, geno- mic and protein sequences. Learning from these data facilitates the understanding of human health and disease. Developed from artificial neural networks, deep learning-based algorithms show great promise in extracting features and learning patterns from complex data. The aim of this paper is to provide an overview of deep learning techniques and some of the state-of-the-art applications in the biomedical field. We first introduce the development of artificial neural network and deep learning. We then describe two main components of deep learning, i.e., deep learning architectures and model optimization. Subsequently, some examples are demonstrated for deep learning展开更多
Up to now, the light coupling schemes of germanium-on-silicon photodetectors(Ge-on-Si PDs) could be divided into three main categories:(1) vertical(or normal-incidence) illumination, which can be from the top or back ...Up to now, the light coupling schemes of germanium-on-silicon photodetectors(Ge-on-Si PDs) could be divided into three main categories:(1) vertical(or normal-incidence) illumination, which can be from the top or back of the wafer/chip, and waveguide-integrated coupling including(2) butt coupling and(3) evanescent coupling. In evanescent coupling the input waveguide can be positioned on top, at the bottom, or lateral to the absorber. Here,to the best of our knowledge, we propose the first concept of Ge-on-Si PD with double lateral silicon nitride(Si_(3)N_(4)) waveguides, which can serve as a novel waveguide-integrated coupling configuration: double lateral coupling. The Ge-on-Si PD with double lateral Si_(3)N_(4) waveguides features uniform optical field distribution in the Ge region, which is very beneficial to improving the operation speed for high input power. The proposed Ge-on-Si PD is comprehensively characterized by static and dynamic measurements. The typical internal responsivity is evaluated to be 0.52 A/W at an input power of 25 mW. The equivalent circuit model and theoretical 3 dB optoelectrical(OE) bandwidth investigation of Ge-on-Si PD with lateral coupling are implemented. Based on the small-signal(S21) radio-frequency measurements, under 4 mA photocurrent, a 60 GHz bandwidth operating at-3 V bias voltage is demonstrated. When the photocurrent is up to 12 mA, the 3 dB OE bandwidth still has 36 GHz. With 1 mA photocurrent, the 70, 80, 90, and 100 Gbit/s non-return-to-zero(NRZ) and 100,120, 140, and 150 Gbit/s four-level pulse amplitude modulation clear openings of eye diagrams are experimentally obtained without utilizing any offline digital signal processing at the receiver side. In order to verify the highpower handling performance in high-speed data transmission, we investigate the eye diagram variations with the increase of photocurrents. The clear open electrical eye diagrams of 60 Gbit/s NRZ under 20 mA photocurrent are also obtained. Overall, the proposed lateral Si_(3)N_(4) waveguide structure is flexibly extendable to a light coupling configuration of PDs, which makes it very attractive for developing high-performance silicon photonic integrated circuits in the future.展开更多
Redesigning the sequences of protein loops is a frequent practice in protein design. Based on the new results of protein loop database analysis, a rational computer simulation strategy is proposed to obtain functional...Redesigning the sequences of protein loops is a frequent practice in protein design. Based on the new results of protein loop database analysis, a rational computer simulation strategy is proposed to obtain functional proteins, which exploits a fast and accurate program to calculate the protein loop conformation, and at the same time, combines molecular docking method with combinatorial chemistry strategy to screen the combinatorial peptide library of pro-展开更多
Single cell sequencing can obtain genetic information of largescale cells at a single cell resolution.The technology has revolutionized life science research and accelerated discoveries in gene expression,cell develop...Single cell sequencing can obtain genetic information of largescale cells at a single cell resolution.The technology has revolutionized life science research and accelerated discoveries in gene expression,cell development,immunology,and others.For instance,single cell transcriptomics has promoted our capability in presenting cell types and status.The outcome sequencing data from single cell technologies allows us to build a comprehensive reference atlas for human cells,enabling us to target complex diseases such as cancers.展开更多
Non-structural protein 1(NS1)is an important virulence factor of the highly pathogenic H5N1 avian influenza virus.A five-amino-acid(5 aa)deletion at position 80–84 and an aspartic acid to glutamic acid substitution a...Non-structural protein 1(NS1)is an important virulence factor of the highly pathogenic H5N1 avian influenza virus.A five-amino-acid(5 aa)deletion at position 80–84 and an aspartic acid to glutamic acid substitution at position 92(D92E)are two major NS1 mutations that are highly correlated with enhanced virulence.To investigate the effect of these mutations in H5N1 virulence,three H5N1-NS1 variants were constructed:NS51(lacking 5 aa at position 80–84),NS51(I)(carrying a 5-aa insertion at position 80–84)and NS51(IM)(carrying both the 5-aa insertion and the D92E mutation).We examined the effects of these mutations on interferon(IFN)induction,tumor-necrosis factor(TNF)a response,p53 activity and apoptosis.We found that the D92E mutation eliminated NS1’s repressive effect on IFN induction,while the 5-aa deletion resulted in enhanced resistance to TNFa responses.We also observed that all three variants exhibited a similar suppressive effect on p53 transcriptional activity,although none of them significantly influenced apoptosis of host cells.Our findings shed new light on the role of NS1 in the pathogenicity of H5N1 virus.展开更多
The accelerating growth of the public microbial genomic data imposes substantial burden on the research community that uses such resources.Building databases for non-redundant reference sequences from massive microbia...The accelerating growth of the public microbial genomic data imposes substantial burden on the research community that uses such resources.Building databases for non-redundant reference sequences from massive microbial genomic data based on clustering analysis is essential.However,existing clustering algorithms perform poorly on long genomic sequences.In this article,we present Gclust,a parallel program for clustering complete or draft genomic sequences,where clustering is accelerated with a novel parallelization strategy and a fast sequence comparison algorithm using sparse suffix arrays(SSAs).Moreover,genome identity measures between two sequences are calculated based on their maximal exact matches(MEMs).In this paper,we demonstrate the high speed and clustering quality of Gclust by examining four genome sequence datasets.Gclust is freely available for non-commercial use at https://github.com/niu-lab/gclust.We also introduce a web server for clustering user-uploaded genomes at http://niulab.scgrid.cn/gclust.展开更多
Microbes play important roles in human health and disease.The interaction between microbes and hosts is a reciprocal relationship,which remains largely under-explored.Current computational resources lack manually and ...Microbes play important roles in human health and disease.The interaction between microbes and hosts is a reciprocal relationship,which remains largely under-explored.Current computational resources lack manually and consistently curated data to connect metagenomic data to pathogenic microbes,microbial core genes,and disease phenotypes.We developed the MicroPhenoDB database by manually curating and consistently integrating microbe-disease association data.MicroPhenoDB provides 5677 non-redundant associations between 1781 microbes and 542 human disease phenotypes across more than 22 human body sites.MicroPhenoDB also provides 696,934 relationships between 27,277 unique clade-specific core genes and 685 microbes.Disease phenotypes are classified and described using the Experimental Factor Ontology(EFO).A refined score model was developed to prioritize the associations based on evidential metrics.The sequence search option in MicroPhenoDB enables rapid identification of existing pathogenic microbes in samples without running the usual metagenomic data processing and assembly.MicroPhenoDB offers data browsing,searching,and visualization through user-friendly web interfaces and web service application programming interfaces.MicroPhenoDB is the first database platform to detail the relationships between pathogenic microbes,core genes,and disease phenotypes.It will accelerate metagenomic data analysis and assist studies in decoding microbes related to human diseases.MicroPhenoDB is available through http://www.liwzlab.cn/microphenodb and http://lilab2.sysu.edu.cn/microphenodb.展开更多
Background:Evidence has suggested that cytokine storms may be associated with T cell exhaustion(TEX)in COVID-19.However,the interaction mechanism between cytokine storms and TEX remains unclear.Methods:With the aim of...Background:Evidence has suggested that cytokine storms may be associated with T cell exhaustion(TEX)in COVID-19.However,the interaction mechanism between cytokine storms and TEX remains unclear.Methods:With the aim of dissecting the molecular relationship of cytokine storms and TEX through single-cell RNA sequencing data analysis,we identified 14 cell types from bronchoalveolar lavage fluid of COVID-19 patients and healthy people.We observed a novel subset of severely exhausted CD8 T cells(Exh T_CD8)that co-expressed multiple inhibitory receptors,and two macrophage subclasses that were the main source of cytokine storms in bronchoalveolar.Results:Correlation analysis between cytokine storm level and TEX level suggested that cytokine storms likely promoted TEX in severe COVID-19.Cell–cell communication analysis indicated that cytokines(e.g.CXCL10,CXCL11,CXCL2,CCL2,and CCL3)released by macrophages acted as ligands and significantly interacted with inhibitory receptors(e.g.CXCR3,DPP4,CCR1,CCR2,and CCR5)expressed by Exh T_CD8.These interactions formed the cytokine–receptor axes,which were also verified to be significantly correlated with cytokine storms and TEX in lung squamous cell carcinoma.Conclusions:Cytokine storms may promote TEX through cytokine-receptor axes and be associated with poor prognosis in COVID19.Blocking cytokine-receptor axes may reverse TEX.Our finding provides novel insights into TEX in COVID-19 and new clues for cytokine-targeted immunotherapy development.展开更多
基金This work was supported by National Key Research and Development Program of China(2019YFB2205201,2019YFB2205203)Hubei Technological Innovation Project(2019AAA054).
文摘Silicon photonics has attracted a great deal of interest for integrated photonics systems due to its large-scale electronics-photonics integration on a chip by leveraging the fabrication process of the complementary-metal-oxide semiconductor(CMOS)foundries[1−5].Germanium-on-silicon(Ge-on-Si)waveguide photodetector(PD)is an indispensable building block of silicon photonics technology which requires high sensitivity.
基金Supported by grants from the Natural Science Foundation of Guang-dong Province,China (06024396)Science & Technology Development Foundation of Guangdong,China (2009B060700053)
文摘Objective:The aim of this study was to observe the inhibitory effect of application of COX-2 inhibitor,celecoxib,combined with cisplatin on the growth of human tongue squamous carcinoma Tca8113 cell xenograft by animal experiment.Methods:The nude mice were transplanted subcutaneously with Tca 8113 cells,and then were administrated with celecoxib,cisplatin or celecoxib combined with cisplatin respectively,and were sacrificed after 35 days.The weight of xenograft was measured to calculate the tumor inhibition rate.The histological change was studied under light and electron microscope.The COX-2 protein expression was observed by immunohistological staining.And the COX-2 mRNA expression was determined by RT-PCR.Results:Celecoxib,the COX-2 inhibitor,could not only inhibit the growth of Tca8113 cell xenograft tumor and COX-2 protein expression,but also enhance the inhibitory effect cisplatin on xenograft tumor growth significantly.The tumor inhibition rates of celecoxib group,cisplatin group and celecoxib plus cisplatin group were 15.63%,37.50% and 82.81% respectively that was statistically significant compared to control group(P < 0.01).The combined application of celecoxib and cisplatin could inhibit tumor growth more significantly than that of separated application(P < 0.01).The inhibitory effect of celecoxib on COX-2 mRNA expression of Tca 8113 cell was weaker and not significant(P = 0.073).Conclusion:Celecoxib can not only inhibit xenograft tumor growth in nude mice,but also enhance the inhibitory effect of CDDP on Tca 8113 transplanted tumor growth in nude mice.The mechanism maybe related to inhibition of COX-2 protein expression,which offers beneficial reference to further explore the mechanism between inhibition of COX-2 enzyme activity and prevention of head and neck tumor.
文摘The theoretical relationship between water injection multiple(i.e.injected pore volume)and water saturation is inferred from theoretical concepts of reservoir engineering.A mathematical model based on core displacement tests is established for the entire injection process that satisfies both initial displacement and extreme displacement,simultaneously.The results show that prior to the flooding,the water injection multiple has a linear relationship with the water saturation,and the utilization rate of the injected water is the highest.As water breakthrough at the production end,the water-cut increases,and the injection multiple increases exponentially while the utilization efficiency of the injected water gradually decreases.When the injection multiple approaches infinity,the utilization efficiency of the injected water gradually decreases to 0,by which time the water-cut at the production end is always 1.At this time,the water saturation no longer changes,and the water flooding recovery rate reaches its limit.Based on the experimental test data,a mathematical model of the entire process of injection multiple and water saturation is established,which has high fitting accuracy that can predict the injection multiple in the different stages of development of a mature oil reservoir.The dynamically changing index of the injection water utilization efficiency in reservoir development by reactive water flooding can be obtained through reasonable transformation of the mathematical model.This is of great significance in guiding evaluations of the effects of reservoir development and formulating countermeasures.
基金supported by grants from National Natural Science Foundation of China(No.30571674 and No.30771988)Guangdong Natural Science Foundation(No.05008347 and No.04020239).
文摘Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication, mouse microglia and astrocytes were isolated, infected with human H1N1 and avian H5N1 influenza viruses, and examined for their immune responses. We observed homogeneously distributed viral receptors, sialic acid (SA)-a2,3-Galactose (Gal) and SA-a2,6-Gal, on microglia and astrocytes. Both viruses were replicative and productive in microglia and astrocytes. Virus-induced apoptosis and cytopathy in infected cells were observed at 24 h post-infection (p.i.). Expression of IL-1β, IL-6 and TNF-a mRNA examined at 6 h and 24 h p.i. was up-regulated, and their expression levels were considerably higher in H5N1 infection. The amounts of secreted proinflammatory IL-1β, IL-6 and TNF-a at 6 h and 24 h p.i. were also induced, with greater induction by H5N1 infection. This study is the first demonstration that both human H1N1 and avian H5N1 influenza viruses can infect mouse microglia and astrocytes and induce apoptosis, cytopathy, and proinflammatory cytokine production in them in vitro. Our results suggest that the direct cellular damage and the consequences of immunopathological injury in the CNS contribute to the influenza viral pathogenesis. Cellular & Molecular Immunology.
基金supported by the Center for Precision Medicine, Sun Yat-sen University and the National High-tech R&D Program (863 Program Grant No. 2015AA020110) of China awarded to YZ
文摘Advances in biological and medical technologies have been providing us explosive vol- umes of biological and physiological data, such as medical images, electroencephalography, geno- mic and protein sequences. Learning from these data facilitates the understanding of human health and disease. Developed from artificial neural networks, deep learning-based algorithms show great promise in extracting features and learning patterns from complex data. The aim of this paper is to provide an overview of deep learning techniques and some of the state-of-the-art applications in the biomedical field. We first introduce the development of artificial neural network and deep learning. We then describe two main components of deep learning, i.e., deep learning architectures and model optimization. Subsequently, some examples are demonstrated for deep learning
基金National Key Research and Development Program of China(2019YFB2205201,2019YFB2205203)Hubei Technological Innovation Project(2019AAA054)Natural Science Foundation of Hubei Province(2019CFB216)。
文摘Up to now, the light coupling schemes of germanium-on-silicon photodetectors(Ge-on-Si PDs) could be divided into three main categories:(1) vertical(or normal-incidence) illumination, which can be from the top or back of the wafer/chip, and waveguide-integrated coupling including(2) butt coupling and(3) evanescent coupling. In evanescent coupling the input waveguide can be positioned on top, at the bottom, or lateral to the absorber. Here,to the best of our knowledge, we propose the first concept of Ge-on-Si PD with double lateral silicon nitride(Si_(3)N_(4)) waveguides, which can serve as a novel waveguide-integrated coupling configuration: double lateral coupling. The Ge-on-Si PD with double lateral Si_(3)N_(4) waveguides features uniform optical field distribution in the Ge region, which is very beneficial to improving the operation speed for high input power. The proposed Ge-on-Si PD is comprehensively characterized by static and dynamic measurements. The typical internal responsivity is evaluated to be 0.52 A/W at an input power of 25 mW. The equivalent circuit model and theoretical 3 dB optoelectrical(OE) bandwidth investigation of Ge-on-Si PD with lateral coupling are implemented. Based on the small-signal(S21) radio-frequency measurements, under 4 mA photocurrent, a 60 GHz bandwidth operating at-3 V bias voltage is demonstrated. When the photocurrent is up to 12 mA, the 3 dB OE bandwidth still has 36 GHz. With 1 mA photocurrent, the 70, 80, 90, and 100 Gbit/s non-return-to-zero(NRZ) and 100,120, 140, and 150 Gbit/s four-level pulse amplitude modulation clear openings of eye diagrams are experimentally obtained without utilizing any offline digital signal processing at the receiver side. In order to verify the highpower handling performance in high-speed data transmission, we investigate the eye diagram variations with the increase of photocurrents. The clear open electrical eye diagrams of 60 Gbit/s NRZ under 20 mA photocurrent are also obtained. Overall, the proposed lateral Si_(3)N_(4) waveguide structure is flexibly extendable to a light coupling configuration of PDs, which makes it very attractive for developing high-performance silicon photonic integrated circuits in the future.
文摘Redesigning the sequences of protein loops is a frequent practice in protein design. Based on the new results of protein loop database analysis, a rational computer simulation strategy is proposed to obtain functional proteins, which exploits a fast and accurate program to calculate the protein loop conformation, and at the same time, combines molecular docking method with combinatorial chemistry strategy to screen the combinatorial peptide library of pro-
基金supported by the National Key R&D Program of China(Grants No.2021YFF1200900 and 2021YFF1200903)the Natural Science Foundation of Guangdong Province(Grant No.2022B1515120077).
文摘Single cell sequencing can obtain genetic information of largescale cells at a single cell resolution.The technology has revolutionized life science research and accelerated discoveries in gene expression,cell development,immunology,and others.For instance,single cell transcriptomics has promoted our capability in presenting cell types and status.The outcome sequencing data from single cell technologies allows us to build a comprehensive reference atlas for human cells,enabling us to target complex diseases such as cancers.
基金We are grateful to Dr William Ba-Thein for helpful discussion and editing of the manuscript.We thank Dr Xu Liyan for the use of a TD20/20 luminometer.This work was supported by the National Natural Science Foundation of China(No.30771988and No.30972766)Specialized Research Fund for the Doctoral Program of Higher Education(No.20094402110004)+3 种基金Guangdong Natural Science Foundation(No.8151503102000022 and 9451503102003499)Outstanding Young Scientists Foundation of Guangdong Province Education Department(No.LYM08056)State Key Lab of Agriculture Microbiology Open Foundation(No.AML200910)Shantou University Medical College Research Foundation.
文摘Non-structural protein 1(NS1)is an important virulence factor of the highly pathogenic H5N1 avian influenza virus.A five-amino-acid(5 aa)deletion at position 80–84 and an aspartic acid to glutamic acid substitution at position 92(D92E)are two major NS1 mutations that are highly correlated with enhanced virulence.To investigate the effect of these mutations in H5N1 virulence,three H5N1-NS1 variants were constructed:NS51(lacking 5 aa at position 80–84),NS51(I)(carrying a 5-aa insertion at position 80–84)and NS51(IM)(carrying both the 5-aa insertion and the D92E mutation).We examined the effects of these mutations on interferon(IFN)induction,tumor-necrosis factor(TNF)a response,p53 activity and apoptosis.We found that the D92E mutation eliminated NS1’s repressive effect on IFN induction,while the 5-aa deletion resulted in enhanced resistance to TNFa responses.We also observed that all three variants exhibited a similar suppressive effect on p53 transcriptional activity,although none of them significantly influenced apoptosis of host cells.Our findings shed new light on the role of NS1 in the pathogenicity of H5N1 virus.
基金the National Key R&D Program of China(Grant Nos.2018YFB0203903,2016YFC0503607,and 2016YFB0200300)the National Natural Science Foundation of China(Grant Nos.31771466 and 61702476)+3 种基金the Transformation Project in Scientific and Technological Achievements of Qinghai Province,China(Grant No.2016-SF-127)the Special Project of Informatization(Grant No.XXH13504-08)the Strategic Pilot Science and Technology Project(Grant No.XDA12010000)the 100-Talents Program(awarded to BN)of the Chinese Academy of Sciences,China.
文摘The accelerating growth of the public microbial genomic data imposes substantial burden on the research community that uses such resources.Building databases for non-redundant reference sequences from massive microbial genomic data based on clustering analysis is essential.However,existing clustering algorithms perform poorly on long genomic sequences.In this article,we present Gclust,a parallel program for clustering complete or draft genomic sequences,where clustering is accelerated with a novel parallelization strategy and a fast sequence comparison algorithm using sparse suffix arrays(SSAs).Moreover,genome identity measures between two sequences are calculated based on their maximal exact matches(MEMs).In this paper,we demonstrate the high speed and clustering quality of Gclust by examining four genome sequence datasets.Gclust is freely available for non-commercial use at https://github.com/niu-lab/gclust.We also introduce a web server for clustering user-uploaded genomes at http://niulab.scgrid.cn/gclust.
基金This work was supported by the National Key R&D Programof China(Grant Nos.2016YFC0901604 and2018YFC0910401)the National Natural Science Founda-tion of China(Grant No.31771478)to WL.
文摘Microbes play important roles in human health and disease.The interaction between microbes and hosts is a reciprocal relationship,which remains largely under-explored.Current computational resources lack manually and consistently curated data to connect metagenomic data to pathogenic microbes,microbial core genes,and disease phenotypes.We developed the MicroPhenoDB database by manually curating and consistently integrating microbe-disease association data.MicroPhenoDB provides 5677 non-redundant associations between 1781 microbes and 542 human disease phenotypes across more than 22 human body sites.MicroPhenoDB also provides 696,934 relationships between 27,277 unique clade-specific core genes and 685 microbes.Disease phenotypes are classified and described using the Experimental Factor Ontology(EFO).A refined score model was developed to prioritize the associations based on evidential metrics.The sequence search option in MicroPhenoDB enables rapid identification of existing pathogenic microbes in samples without running the usual metagenomic data processing and assembly.MicroPhenoDB offers data browsing,searching,and visualization through user-friendly web interfaces and web service application programming interfaces.MicroPhenoDB is the first database platform to detail the relationships between pathogenic microbes,core genes,and disease phenotypes.It will accelerate metagenomic data analysis and assist studies in decoding microbes related to human diseases.MicroPhenoDB is available through http://www.liwzlab.cn/microphenodb and http://lilab2.sysu.edu.cn/microphenodb.
基金supported by the National Key R&D Program of China(Grants No.2021YFF1200900,2021YFF1200903,2016YFC0901604&2018YFC091040)the Natural Science Foundation of Guangdong Province(Grant No.2021A1515012108)+1 种基金the Guangdong Project(Grant No.2017GC010608)the Support Scheme of Guangzhou for Leading Talents in Innovation and Entrepreneurship(Grant No.2020007).
文摘Background:Evidence has suggested that cytokine storms may be associated with T cell exhaustion(TEX)in COVID-19.However,the interaction mechanism between cytokine storms and TEX remains unclear.Methods:With the aim of dissecting the molecular relationship of cytokine storms and TEX through single-cell RNA sequencing data analysis,we identified 14 cell types from bronchoalveolar lavage fluid of COVID-19 patients and healthy people.We observed a novel subset of severely exhausted CD8 T cells(Exh T_CD8)that co-expressed multiple inhibitory receptors,and two macrophage subclasses that were the main source of cytokine storms in bronchoalveolar.Results:Correlation analysis between cytokine storm level and TEX level suggested that cytokine storms likely promoted TEX in severe COVID-19.Cell–cell communication analysis indicated that cytokines(e.g.CXCL10,CXCL11,CXCL2,CCL2,and CCL3)released by macrophages acted as ligands and significantly interacted with inhibitory receptors(e.g.CXCR3,DPP4,CCR1,CCR2,and CCR5)expressed by Exh T_CD8.These interactions formed the cytokine–receptor axes,which were also verified to be significantly correlated with cytokine storms and TEX in lung squamous cell carcinoma.Conclusions:Cytokine storms may promote TEX through cytokine-receptor axes and be associated with poor prognosis in COVID19.Blocking cytokine-receptor axes may reverse TEX.Our finding provides novel insights into TEX in COVID-19 and new clues for cytokine-targeted immunotherapy development.