A novel avian-origin H7N9 influenza virus was discovered in March in China and has caused a total of131 people infected including 39 deaths in China as of June 9, 2013. Adaptation of avian viruses to efficiently infec...A novel avian-origin H7N9 influenza virus was discovered in March in China and has caused a total of131 people infected including 39 deaths in China as of June 9, 2013. Adaptation of avian viruses to efficiently infect humans requires the viral hemagglutinin(HA) binding switches from avian to human type receptors with help of some mutations in HA. As such it is critical for pandemic assessment to discover these mutations as hallmarks of adaptation. To continue our previous study of this novel H7N9 virus, we identified two sets of mutations in HA. The first set of mutations are present in the current circulating strains of 2013 H7N9 in China, and the second set are potential mutations that were found when compared to the HAs of previous human H7 subtype. These two sets of mutations exhibited unique features. The first group of mutations, on average, enhanced the HA binding to human type receptors whereas reduced that to avian types. Further the reduction of avian binding was almost three times of the increase of the human binding. The second group increased the binding to both human and avian types.But the increase in human types was almost three times of that in the avian types. Though different in their way of changing the binding preference, these two sets of mutations both contained more mutations to decrease the avian binding and increase the human binding than those that did the opposite. Our research highlighted the pandemic potential of this novel virus by showing the important mutations that could potentially help it to adapt to human hosts. Our findings offered new insights into the current state of evolution of this virus, which might be helpful for the continued surveillance of the emergence of H7N9 strains having the ability of human-to-human transmission.展开更多
A molecularly imprinted polymer was synthesized using 2-(diethylamino)ethylmethacry -late(DEM) and bismethacryloyl-β-cyclodextrin(BMA-β-CD) as bi-functional monomers and norfloxacin(NOF) as a template. The r...A molecularly imprinted polymer was synthesized using 2-(diethylamino)ethylmethacry -late(DEM) and bismethacryloyl-β-cyclodextrin(BMA-β-CD) as bi-functional monomers and norfloxacin(NOF) as a template. The results of equilibrium binding experiments indicated that the polymer has affinity and specificity for NOF in aqueous media, and that its selective recognition ability for the template was higher than that of the imprinted polymers synthesized with a single functional monomer (BMA-β-CD or DEM).展开更多
Anti-HER2 monoclonal antibody (Sc7301)-paclitaxel (TAX) immunoconjugate was pre- pared and its specific binding to tumor cells was investigated in this study. Sc7301 was conjugated to TAX by the active ester metho...Anti-HER2 monoclonal antibody (Sc7301)-paclitaxel (TAX) immunoconjugate was pre- pared and its specific binding to tumor cells was investigated in this study. Sc7301 was conjugated to TAX by the active ester method and then the TAX-Sc7301 immunoconjugate was obtained. After purification and labeling by Cyano-fluorescein isothiocyanate (FITC), the specific binding of TAX-Sc7301 to HER2-positive tumor cells (SKOV3) and HER2-negative tumor cells (HepG2) was evaluated respectively. TAX-Sc7301 (20 nmol/L) showed distinct specific binding to SKOV3 cells rather than HepG2 cells. And the uptake of the immunoconjugate by SKOV3 cells was increased with the TAX-So7301 concentration (3-48 nmol/L) and the incubation time (P〈0.05). It was concluded that the TAX-Sc7301 immunoconjugate is ootentially applicable as a targeted agent against HER2-10ositive tumor cells.展开更多
P[3]rotavirus(RV)has been identified in many species,including human,simian,dog,and bat.Several glycans,including sialic acid,histo-blood group antigens(HBGAs)are reported as RV attachment factors.The glycan binding s...P[3]rotavirus(RV)has been identified in many species,including human,simian,dog,and bat.Several glycans,including sialic acid,histo-blood group antigens(HBGAs)are reported as RV attachment factors.The glycan binding specificity of different P[3]RV VP8*s were investigated in this study.Human HCR3 A and dog P[3]RV VP8*s recognized glycans with terminal sialic acid and hemagglutinated the red blood cells,while bat P[3]VP8*showed neither binding to glycans nor hemagglutination.However,the bat P[3]VP8*mutant of C189 Y obtained the ability to hemagglutinate the red blood cells,while human P[3]HCR3 A/M2-102 mutants of Y189 C lost the ability.Sequence alignment and structural analysis indicated that residue 189 played an important role in the ligand recognition and may contribute to the cross-species transmission.Structural superimposition exhibited that bat P[3]VP8*model was quite different from the simian P[3]Rhesus rotavirus(RRV)P[3]VP8*,indicating that bat P[3]RV was relatively distinct and partially contributed to the no binding to tested glycans.These results promote our understanding of P[3]VP8*/glycans interactions and the potential transmission of bat/human P[3]RVs,offering more insight into the RV infection and prevalence.展开更多
Rotavirus(RV)causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens(HBGAs)function as cell attachment factors affecting RV host susceptibil...Rotavirus(RV)causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens(HBGAs)function as cell attachment factors affecting RV host susceptibility and prevalence.P[8]is the predominant RV genotype in humans,but the structural basis of how P[8]RVs interact with glycan ligands remains elusive.In this study,we characterized the interactions between P[8]VP8~*s and glycans which showed that VP8~*,the RV glycan binding domain,recognized both mucin core 2 and H type 1 antigens according to the ELISA-based oligosaccharide binding assays.Importantly,we determined the structural basis of P[8]RV-glycans interaction from the crystal structures of a Rotateq P[8]VP8~*in complex with core 2 and H type 1 glycans at 1.82.3?,respectively,revealing a common binding pocket and similar binding mode.Structural and sequence analysis demonstrated that the glycan binding site is conserved among RVs in the P[Ⅱ]genogroup,while genotype-specific amino acid variations determined different glycan binding preference.Our data elucidated the detailed structural basis of the interactions between human P[8]RVs and different host glycan factors,shedding light on RV infection,epidemiology,and development of anti-viral agents.展开更多
文摘A novel avian-origin H7N9 influenza virus was discovered in March in China and has caused a total of131 people infected including 39 deaths in China as of June 9, 2013. Adaptation of avian viruses to efficiently infect humans requires the viral hemagglutinin(HA) binding switches from avian to human type receptors with help of some mutations in HA. As such it is critical for pandemic assessment to discover these mutations as hallmarks of adaptation. To continue our previous study of this novel H7N9 virus, we identified two sets of mutations in HA. The first set of mutations are present in the current circulating strains of 2013 H7N9 in China, and the second set are potential mutations that were found when compared to the HAs of previous human H7 subtype. These two sets of mutations exhibited unique features. The first group of mutations, on average, enhanced the HA binding to human type receptors whereas reduced that to avian types. Further the reduction of avian binding was almost three times of the increase of the human binding. The second group increased the binding to both human and avian types.But the increase in human types was almost three times of that in the avian types. Though different in their way of changing the binding preference, these two sets of mutations both contained more mutations to decrease the avian binding and increase the human binding than those that did the opposite. Our research highlighted the pandemic potential of this novel virus by showing the important mutations that could potentially help it to adapt to human hosts. Our findings offered new insights into the current state of evolution of this virus, which might be helpful for the continued surveillance of the emergence of H7N9 strains having the ability of human-to-human transmission.
基金the National Natural Science Foundation of China(No.20202015)the Doctoral Program Foundation of Institution of High Education of China(No.20020558026)for the financial support to the research.
文摘A molecularly imprinted polymer was synthesized using 2-(diethylamino)ethylmethacry -late(DEM) and bismethacryloyl-β-cyclodextrin(BMA-β-CD) as bi-functional monomers and norfloxacin(NOF) as a template. The results of equilibrium binding experiments indicated that the polymer has affinity and specificity for NOF in aqueous media, and that its selective recognition ability for the template was higher than that of the imprinted polymers synthesized with a single functional monomer (BMA-β-CD or DEM).
基金supported by a grant from the National Natural Science Foundation of China(No.30300429)
文摘Anti-HER2 monoclonal antibody (Sc7301)-paclitaxel (TAX) immunoconjugate was pre- pared and its specific binding to tumor cells was investigated in this study. Sc7301 was conjugated to TAX by the active ester method and then the TAX-Sc7301 immunoconjugate was obtained. After purification and labeling by Cyano-fluorescein isothiocyanate (FITC), the specific binding of TAX-Sc7301 to HER2-positive tumor cells (SKOV3) and HER2-negative tumor cells (HepG2) was evaluated respectively. TAX-Sc7301 (20 nmol/L) showed distinct specific binding to SKOV3 cells rather than HepG2 cells. And the uptake of the immunoconjugate by SKOV3 cells was increased with the TAX-So7301 concentration (3-48 nmol/L) and the incubation time (P〈0.05). It was concluded that the TAX-Sc7301 immunoconjugate is ootentially applicable as a targeted agent against HER2-10ositive tumor cells.
基金the participation of the ProteinGlycan Interaction Resource of the CFG(supporting grant R24 GM098791)the National Center for Functional Glycomics(NCFG)at Beth Israel Deaconess Medical Center,Harvard Medical School(supporting grant P41 GM103694)+1 种基金supported by grants from the National Natural Science Foundation of China(NSFC)(No.21934005)National Key Research and Development Program of China(2018YFC1200602)。
文摘P[3]rotavirus(RV)has been identified in many species,including human,simian,dog,and bat.Several glycans,including sialic acid,histo-blood group antigens(HBGAs)are reported as RV attachment factors.The glycan binding specificity of different P[3]RV VP8*s were investigated in this study.Human HCR3 A and dog P[3]RV VP8*s recognized glycans with terminal sialic acid and hemagglutinated the red blood cells,while bat P[3]VP8*showed neither binding to glycans nor hemagglutination.However,the bat P[3]VP8*mutant of C189 Y obtained the ability to hemagglutinate the red blood cells,while human P[3]HCR3 A/M2-102 mutants of Y189 C lost the ability.Sequence alignment and structural analysis indicated that residue 189 played an important role in the ligand recognition and may contribute to the cross-species transmission.Structural superimposition exhibited that bat P[3]VP8*model was quite different from the simian P[3]Rhesus rotavirus(RRV)P[3]VP8*,indicating that bat P[3]RV was relatively distinct and partially contributed to the no binding to tested glycans.These results promote our understanding of P[3]VP8*/glycans interactions and the potential transmission of bat/human P[3]RVs,offering more insight into the RV infection and prevalence.
基金This research was supported by grants from the National Science and Technology Major Project(2018ZX10711-001)the National Natural Science Foundation of China(NSFC)(No.81601813).
文摘Rotavirus(RV)causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens(HBGAs)function as cell attachment factors affecting RV host susceptibility and prevalence.P[8]is the predominant RV genotype in humans,but the structural basis of how P[8]RVs interact with glycan ligands remains elusive.In this study,we characterized the interactions between P[8]VP8~*s and glycans which showed that VP8~*,the RV glycan binding domain,recognized both mucin core 2 and H type 1 antigens according to the ELISA-based oligosaccharide binding assays.Importantly,we determined the structural basis of P[8]RV-glycans interaction from the crystal structures of a Rotateq P[8]VP8~*in complex with core 2 and H type 1 glycans at 1.82.3?,respectively,revealing a common binding pocket and similar binding mode.Structural and sequence analysis demonstrated that the glycan binding site is conserved among RVs in the P[Ⅱ]genogroup,while genotype-specific amino acid variations determined different glycan binding preference.Our data elucidated the detailed structural basis of the interactions between human P[8]RVs and different host glycan factors,shedding light on RV infection,epidemiology,and development of anti-viral agents.