BACKGROUND N6-methyladenosine(m6A)methylation modification exists in Epstein-Barr virus(EBV)primary infection,latency,and lytic reactivation.It also modifies EBV latent genes and lytic genes.EBV-associated gastric can...BACKGROUND N6-methyladenosine(m6A)methylation modification exists in Epstein-Barr virus(EBV)primary infection,latency,and lytic reactivation.It also modifies EBV latent genes and lytic genes.EBV-associated gastric cancer(EBVaGC)is a distinctive molecular subtype of GC.We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC.AIM To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC.METHODS First,The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC(EBVnGC).Second,we identified Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment of m6A-related differentially expressed genes.We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment(TME).Finally,cell counting kit-8 cell proliferation test,transwell test,and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1(IGFBP1)in EBVaGC cell lines.RESULTS m6A methylation regulators were involved in the occurrence and development of EBVaGC.Compared with EBVnGC,the expression levels of m6A methylation regulators Wilms tumor 1-associated protein,RNA binding motif protein 15B,CBL proto-oncogene like 1,leucine rich pentatricopeptide repeat containing,heterogeneous nuclear ribonucleoprotein A2B1,IGFBP1,and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC(P<0.05).The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher(P=0.046).GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC.Compared with EBVnGC,the infiltration of activated CD4+T cells,activated CD8+T cells,monocytes,activated dendritic cells,and plasmacytoid dendritic cells were significantly upregulated in EBVaGC(P<0.001).In EBVaGC,the expression level of proinflammatory factors interleukin(IL)-17,IL-21,and interferon-γ and immunosuppressive factor IL-10 were significantly increased(P<0.05).In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line(SNU719)than in an EBVnGC cell line(AGS)(P<0.05).IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719.Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS.CONCLUSION m6A regulators could remodel the TME of EBVaGC,which is classified as an immune-inflamed phenotype and referred to as a“hot”tumor.Among these regulators,we demonstrated that IGFBP1 affected proliferation,migration,and apoptosis.展开更多
Nitrogen-14(^(14)N)overtone(OT)spectroscopy under fast magic angle spinning(MAS)conditions(>60 kHz)has emerged as a powerful technique for observing correlations and distances between ^(14)N and ^(1)H,owing to the ...Nitrogen-14(^(14)N)overtone(OT)spectroscopy under fast magic angle spinning(MAS)conditions(>60 kHz)has emerged as a powerful technique for observing correlations and distances between ^(14)N and ^(1)H,owing to the absence of the first-order quadrupolar broadenings.In addition,^(14)N^(OT) allows selective manipulation of ^(14)N nuclei for each site.Despite extensive theoretical and experimental studies,the spin dynamics of ^(14)N^(OT) remains under debate.In this study,we conducted experimental investigations to assess the spin dynamics of ^(14)N^(OT) using the rotational-echo saturation-pulse double-resonance(RESPDOR)sequence,which monitors population transfer induced by a^(14)N^(OT) pulse.The ^(14)N^(OT) spin dynamics is well represented by a model of a two-energy-level system.Unlike spin-1/2,the maximum excitation efficiency of ^(14)N^(OT) coherences of powdered solids,denoted by p,depends on the radiofrequency field(rf-field)strength due to orientation dependence of effective nutation fields even when pulse lengths are optimized.It is also found that the p factor,contributing to the ^(14)N^(OT) spin dynamics,is nearly independent of the B0 field.Consequently,the filtering efficiency of RESPDOR experiments exhibits negligible dependence on B0 when the ^(14)N^(OT) pulse length is optimized.The study also identifies the optimal experimental conditions for ^(14)N^(OT)/^(1)H RESPDOR correlation experiments.展开更多
流行性感冒的所有已知的子类型 A 病毒在野水鸟被维持，这些病毒的自然水库。流行性感冒 A 病毒被孤立从许多有改变病态和死亡率的动物种类。更重要地，流行性感冒 A 病毒与潜在地致命的结果在人引起呼吸疾病。在人的本地或全球的爆发...流行性感冒的所有已知的子类型 A 病毒在野水鸟被维持，这些病毒的自然水库。流行性感冒 A 病毒被孤立从许多有改变病态和死亡率的动物种类。更重要地，流行性感冒 A 病毒与潜在地致命的结果在人引起呼吸疾病。在人的本地或全球的爆发被过量住院和死亡典型地描绘。在 1997， H5N1 子类型的高度病原的鸟的流行性感冒病毒在传给人的香港出现了，导致由鸟的流行性感冒病毒感染的人的死亡的首先记录的盒子。在越南，印度尼西亚，和泰国在家禽在 2003 年 7 月开始的新爆发，和高度病原的鸟的 H5N1 流行性感冒病毒后来在整个亚洲并且进欧洲和非洲传播了。这些病毒继续与高死亡率感染人并且引起隐约可见的世界范围的担心流行。而且， H5N1 病毒爆发在整个亚洲在家禽工业上有破坏效果。因为 H5N1 病毒爆发看起来从南部的中国发源，我们这里在中国检验 H5N1 流行性感冒病毒，与他们的生物性质上的一个重音。展开更多
In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A(serotype H1N1) and herpes simplex virus type 2(HSV-2), strain BH. All 10 investigated mu...In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A(serotype H1N1) and herpes simplex virus type 2(HSV-2), strain BH. All 10 investigated mushroom species inhibited the reproduction of influenza virus strain A/FM/1/47(H1N1) in MDCK cells reducing the infectious titer by 2.0–6.0 lg ID50. Four species, Pleurotus ostreatus, Fomes fomentarius, Auriporia aurea, and Trametes versicolor, were also determined to be effective against HSV-2 strain BH in RK-13 cells, with similar levels of inhibition as for influenza. For some of the investigated mushroom species—Pleurotus eryngii, Lyophyllum shimeji, and Flammulina velutipes—this is the first report of an anti-influenza effect. This study also reports the first data on the medicinal properties of A. aurea, including anti-influenza and antiherpetic activities. T. versicolor 353 mycelium was found to have a high therapeutic index(324.67), and may be a promising material for the pharmaceutical industry as an anti-influenza and antiherpetic agent with low toxicity. Mycelia with antiviral activity were obtained in our investigation by bioconversion of agricultural wastes(amaranth flour after CO2 extraction), which would reduce the cost of the final product and solve some ecological problems.展开更多
Objective:To investigate the effects of influenza A virus H1N1 infection on the proliferation and apoptosis of mouse astrocytes cells and its protein expression.Methods:After mouse astrocytes was infected with purifie...Objective:To investigate the effects of influenza A virus H1N1 infection on the proliferation and apoptosis of mouse astrocytes cells and its protein expression.Methods:After mouse astrocytes was infected with purified influenza A virus H1N1 in vitro,viral integration and replication status of the cells were detected by RT-PCR assay,cell proliferation and apoptosis was determined by MTT method and flow cytometry,respectively.Associated protein expression was delected by Western blotting.Results:Agarose gel electrophoresis showed H1N1 virus can infect astrocytes and can be copied.MTT staining showed H1N1 virus infection can inhibit the proliferation of mouse astrocytes,which makes cell viability decreased significantly.Flow cytometry showed that the proportion of Annein V staining positive vascular endothelial cells in the influenza A virus group was significantly higher than that in the control group.Western blot analysis showed after24 h and 32 h of infection,there were cells caspase-3 protein and the expression of its active form(lysed caspase-3 protein)increased.The proportion of Bax/Bcl-2 also increased.Conclusions:Influenza A virus can infect human vascular endothelial cells and proliferation and it can induce apoptosis of endothelial cells.展开更多
Since the first human case of H5N1 avian influenza virus infection was reported in 1997, this highly pathogenic virus has infected hundreds of people around the world and resulted in many deaths. The ability of H5N1 t...Since the first human case of H5N1 avian influenza virus infection was reported in 1997, this highly pathogenic virus has infected hundreds of people around the world and resulted in many deaths. The ability of H5N1 to cross species boundaries, and the presence of polymorphisms that enhance virulence, present challenges to developing clear strategies to prevent the pandemic spread of this highly pathogenic avian influenza (HPAI) virus. This review summarizes the current understanding of, and recent research on, the avian influenza H5N1 virus, including transmission, virulence, pathogenesis, clinical characteristics, treatment and prevention.展开更多
基金Supported by the Sub-Project of the National Key Research and Development Program,No.2021YFC2600263.
文摘BACKGROUND N6-methyladenosine(m6A)methylation modification exists in Epstein-Barr virus(EBV)primary infection,latency,and lytic reactivation.It also modifies EBV latent genes and lytic genes.EBV-associated gastric cancer(EBVaGC)is a distinctive molecular subtype of GC.We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC.AIM To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC.METHODS First,The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC(EBVnGC).Second,we identified Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment of m6A-related differentially expressed genes.We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment(TME).Finally,cell counting kit-8 cell proliferation test,transwell test,and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1(IGFBP1)in EBVaGC cell lines.RESULTS m6A methylation regulators were involved in the occurrence and development of EBVaGC.Compared with EBVnGC,the expression levels of m6A methylation regulators Wilms tumor 1-associated protein,RNA binding motif protein 15B,CBL proto-oncogene like 1,leucine rich pentatricopeptide repeat containing,heterogeneous nuclear ribonucleoprotein A2B1,IGFBP1,and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC(P<0.05).The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher(P=0.046).GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC.Compared with EBVnGC,the infiltration of activated CD4+T cells,activated CD8+T cells,monocytes,activated dendritic cells,and plasmacytoid dendritic cells were significantly upregulated in EBVaGC(P<0.001).In EBVaGC,the expression level of proinflammatory factors interleukin(IL)-17,IL-21,and interferon-γ and immunosuppressive factor IL-10 were significantly increased(P<0.05).In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line(SNU719)than in an EBVnGC cell line(AGS)(P<0.05).IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719.Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS.CONCLUSION m6A regulators could remodel the TME of EBVaGC,which is classified as an immune-inflamed phenotype and referred to as a“hot”tumor.Among these regulators,we demonstrated that IGFBP1 affected proliferation,migration,and apoptosis.
文摘Nitrogen-14(^(14)N)overtone(OT)spectroscopy under fast magic angle spinning(MAS)conditions(>60 kHz)has emerged as a powerful technique for observing correlations and distances between ^(14)N and ^(1)H,owing to the absence of the first-order quadrupolar broadenings.In addition,^(14)N^(OT) allows selective manipulation of ^(14)N nuclei for each site.Despite extensive theoretical and experimental studies,the spin dynamics of ^(14)N^(OT) remains under debate.In this study,we conducted experimental investigations to assess the spin dynamics of ^(14)N^(OT) using the rotational-echo saturation-pulse double-resonance(RESPDOR)sequence,which monitors population transfer induced by a^(14)N^(OT) pulse.The ^(14)N^(OT) spin dynamics is well represented by a model of a two-energy-level system.Unlike spin-1/2,the maximum excitation efficiency of ^(14)N^(OT) coherences of powdered solids,denoted by p,depends on the radiofrequency field(rf-field)strength due to orientation dependence of effective nutation fields even when pulse lengths are optimized.It is also found that the p factor,contributing to the ^(14)N^(OT) spin dynamics,is nearly independent of the B0 field.Consequently,the filtering efficiency of RESPDOR experiments exhibits negligible dependence on B0 when the ^(14)N^(OT) pulse length is optimized.The study also identifies the optimal experimental conditions for ^(14)N^(OT)/^(1)H RESPDOR correlation experiments.
基金Acknowledgments We thank Susan Watson for editing the manuscript and those in our laboratories who contributed to the data cited in this review. We also thank Ryo Takano for the preparation of figures. Research in HC＇s group is supported by the Ministry of Science and Technology, China （2004BA519A-57, 2006BAD06A05）. Research in GFG＇s group is supported by the Ministry of Science and Technology, China （MOST, 2005CB523001 and 2006BAD06A01）, the National Natural Science Foundation of China （NSFC, Grant #3059934, #30525010） and the US National Institutes of Health （U19 AI051915-05S1）. Research in YS＇s group is supported by the Ministry of Science and Technology, China （MOST, 2005CB523006 and 2006BAD06A15）, and the National Natural Science Foundation of China （NSFC, Grant #30599433）. Research in YK＇s group is supported by National Institute of Allergy and Infectious Diseases Public Health Service research grants by CREST and ERATO （Japan Science and Technology Agency）, and by grants-in-aid and a contract research fund for the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
文摘流行性感冒的所有已知的子类型 A 病毒在野水鸟被维持，这些病毒的自然水库。流行性感冒 A 病毒被孤立从许多有改变病态和死亡率的动物种类。更重要地，流行性感冒 A 病毒与潜在地致命的结果在人引起呼吸疾病。在人的本地或全球的爆发被过量住院和死亡典型地描绘。在 1997， H5N1 子类型的高度病原的鸟的流行性感冒病毒在传给人的香港出现了，导致由鸟的流行性感冒病毒感染的人的死亡的首先记录的盒子。在越南，印度尼西亚，和泰国在家禽在 2003 年 7 月开始的新爆发，和高度病原的鸟的 H5N1 流行性感冒病毒后来在整个亚洲并且进欧洲和非洲传播了。这些病毒继续与高死亡率感染人并且引起隐约可见的世界范围的担心流行。而且， H5N1 病毒爆发在整个亚洲在家禽工业上有破坏效果。因为 H5N1 病毒爆发看起来从南部的中国发源，我们这里在中国检验 H5N1 流行性感冒病毒，与他们的生物性质上的一个重音。
文摘In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A(serotype H1N1) and herpes simplex virus type 2(HSV-2), strain BH. All 10 investigated mushroom species inhibited the reproduction of influenza virus strain A/FM/1/47(H1N1) in MDCK cells reducing the infectious titer by 2.0–6.0 lg ID50. Four species, Pleurotus ostreatus, Fomes fomentarius, Auriporia aurea, and Trametes versicolor, were also determined to be effective against HSV-2 strain BH in RK-13 cells, with similar levels of inhibition as for influenza. For some of the investigated mushroom species—Pleurotus eryngii, Lyophyllum shimeji, and Flammulina velutipes—this is the first report of an anti-influenza effect. This study also reports the first data on the medicinal properties of A. aurea, including anti-influenza and antiherpetic activities. T. versicolor 353 mycelium was found to have a high therapeutic index(324.67), and may be a promising material for the pharmaceutical industry as an anti-influenza and antiherpetic agent with low toxicity. Mycelia with antiviral activity were obtained in our investigation by bioconversion of agricultural wastes(amaranth flour after CO2 extraction), which would reduce the cost of the final product and solve some ecological problems.
文摘Objective:To investigate the effects of influenza A virus H1N1 infection on the proliferation and apoptosis of mouse astrocytes cells and its protein expression.Methods:After mouse astrocytes was infected with purified influenza A virus H1N1 in vitro,viral integration and replication status of the cells were detected by RT-PCR assay,cell proliferation and apoptosis was determined by MTT method and flow cytometry,respectively.Associated protein expression was delected by Western blotting.Results:Agarose gel electrophoresis showed H1N1 virus can infect astrocytes and can be copied.MTT staining showed H1N1 virus infection can inhibit the proliferation of mouse astrocytes,which makes cell viability decreased significantly.Flow cytometry showed that the proportion of Annein V staining positive vascular endothelial cells in the influenza A virus group was significantly higher than that in the control group.Western blot analysis showed after24 h and 32 h of infection,there were cells caspase-3 protein and the expression of its active form(lysed caspase-3 protein)increased.The proportion of Bax/Bcl-2 also increased.Conclusions:Influenza A virus can infect human vascular endothelial cells and proliferation and it can induce apoptosis of endothelial cells.
基金National Natural Science Foundation of China (30979144 and 81271821)
文摘Since the first human case of H5N1 avian influenza virus infection was reported in 1997, this highly pathogenic virus has infected hundreds of people around the world and resulted in many deaths. The ability of H5N1 to cross species boundaries, and the presence of polymorphisms that enhance virulence, present challenges to developing clear strategies to prevent the pandemic spread of this highly pathogenic avian influenza (HPAI) virus. This review summarizes the current understanding of, and recent research on, the avian influenza H5N1 virus, including transmission, virulence, pathogenesis, clinical characteristics, treatment and prevention.
