Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidative stress-mediated mechanisms. Different pharmacological strategies have been explored to reduce the formation of these reactive oxygen sp...Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidative stress-mediated mechanisms. Different pharmacological strategies have been explored to reduce the formation of these reactive oxygen species and/or prevent their toxic effects in the treatment of paraquat poisoning. The present study was carried out to investigate whether the antioxidant (L-tocopherol, incorporated into liposomes and delivered directly to the lungs of rats, could protect the organ against the long-term toxic effects of paraquat.Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or α-tocopherol liposomes (8 mg α-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats wefe killed 0, 1, 4, 6, 8, 10, 12, 16, 19 or 24 days after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were extensively damaged,as evidenced by significant increases in lung weight and decreases in lung angiotensin converting enzyme (ACE) and alkaline phosphatase enzyme (AKP) activities. Moreover,paraquat treatme; resulted in a significant reduction in the number of neutrophils in the blood of rats with a concurrent increase in the pulmonary myeloperoxidase activity,suggestive of neutrophil infiltration in the lungs of treated animals. Pretreatment of rats with liposomes alone did not significantly alter the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with (t-tocopherol liposomes,24 h prior to paraquat challenge, attenuated paraquat-induced changes in ACE, AKP and myeloperoxidase activities but failed to prevent increases in lung weight. Thus, pretreatment of rats with liposome-associated α-tocopherol appears to protect the lung against some of the toxic effects of paraquat展开更多
Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4...Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4 ME) expressing prM-E protein of DENV serotype 4(DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4 ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 μg and 5 μg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4 ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 μg, but not 5 μg, of pV-D4 ME could provide stable protection(100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 μg pV-D4 ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.展开更多
SARS-CoV-2 infection is a global public health threat.Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic.As expected,deaths from SARS-CoV-2 infection have dropped dramatically ...SARS-CoV-2 infection is a global public health threat.Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic.As expected,deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination.However,there are concerns over the duration of vaccine-induced protection,as well as their effectiveness against emerging variants of concern.Here,we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2(Ad C68-S).Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of Ad C68-S.Notably,neutralizing antibodies were observed up to at least six months after vaccination,without substantial decline.Single or double doses Ad C68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term(21 days)and long-term(6 months).Histopathological examination of Ad C68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection.Taken together,this study demonstrates the efficacy and durability of the Ad C68-S vaccine and constitutes a promising candidate for clinical evaluation.展开更多
Human immunodeficiency virus(HIV)-infected individuals exhibit remarkable transcriptomic variation.Transcriptome analyses of antiretroviral therapy(ART)-free chronically infected HIV-1 patients with different clinical...Human immunodeficiency virus(HIV)-infected individuals exhibit remarkable transcriptomic variation.Transcriptome analyses of antiretroviral therapy(ART)-free chronically infected HIV-1 patients with different clinical outcomes are likely to aid the development of vaccine and immune therapies.Here,we performed microarray analyses on whole-blood derived RNA from 89 ART-free HIV-1-infected individuals from 2 cohorts.The differentially expressed genes were analyzed between long-term non-progressors,viremic non-progressors and typical progressors,and between elite controllers and non-elite controllers among the long-term nonprogressors.Several genes related to T-cell growth,proliferation and differentiation and antiapoptosis were upregulated,whereas interferon-stimulated genes and inflammatory genes were significantly downregulated in long-term non-progressors and viremic non-progressors.The observations above were further confirmed in the set of 261 genes that correlated with disease progression during a 5-year follow-up,which included 51 genes significantly associated with slower disease progression,and 210 genes associated with aggressive disease progression.Overall,our data suggest that it is vital to maintain the homeostasis of the immune system when mounting antiviral immune responses.Immune therapeutics able to reconstruct immune homeostasis are likely to be required for immune reconstitution in the context of ART,such as the administration of interleukin-7,healthy allogenic CD4^(+)T cells(providing CD4^(+)T-cell growth factors),or Tregs.展开更多
Habitat use and preferences may be subject to spatial and temporal changes. However, long-term studies of species-habitat relationships are the exception. In the prese nt research, I on g-term trends in habitat use by...Habitat use and preferences may be subject to spatial and temporal changes. However, long-term studies of species-habitat relationships are the exception. In the prese nt research, I on g-term trends in habitat use by an alpine ungulate, the Tatra chamois Rupicapra rupicapra tatrica, were analyzed. We exami ned how envir on mental changes attributable to climate cha nge, removal of sheep, and habituation to hikers, which took place over the last half-century have changed the spatial distribution of animals. Data on the localities of groups sighted between 1957 and 2013 during autumnal population surveys were used to evaluate habitat associations: these were correlated with year, group size, population size, and climatic conditions. The results indicate that the Tatra chamois is tending, over the long term, to lower its altitude of occurrenee, reduce its average distance to hiking trails, and stay less often on slopes with a southerly aspect. These trends are in dependent of group size, population size, and the weather conditions prevailing during observations, though not for altitude, where increases in air temperature are related to finding chamois at higher elevations. The proportion of alpine meadows and slope in the places used by chamois is correlated with population size, while the proportion of areas with trees and/or shrubs is correlated with group size and air temperature, though long-term changes were not evident for these variables. To the best of our knowledge, this work is the first to document Iong-term trends in habitat use by ungulates. It shows that a species' ecology is influe need by huma n-in duced cha nges: abandonment of pasturage, high-mountain tourism, and climate changes, which constitute the most probable reasons for this aspect of behavioral evolution in the Tatra chamois.展开更多
文摘Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidative stress-mediated mechanisms. Different pharmacological strategies have been explored to reduce the formation of these reactive oxygen species and/or prevent their toxic effects in the treatment of paraquat poisoning. The present study was carried out to investigate whether the antioxidant (L-tocopherol, incorporated into liposomes and delivered directly to the lungs of rats, could protect the organ against the long-term toxic effects of paraquat.Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or α-tocopherol liposomes (8 mg α-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats wefe killed 0, 1, 4, 6, 8, 10, 12, 16, 19 or 24 days after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were extensively damaged,as evidenced by significant increases in lung weight and decreases in lung angiotensin converting enzyme (ACE) and alkaline phosphatase enzyme (AKP) activities. Moreover,paraquat treatme; resulted in a significant reduction in the number of neutrophils in the blood of rats with a concurrent increase in the pulmonary myeloperoxidase activity,suggestive of neutrophil infiltration in the lungs of treated animals. Pretreatment of rats with liposomes alone did not significantly alter the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with (t-tocopherol liposomes,24 h prior to paraquat challenge, attenuated paraquat-induced changes in ACE, AKP and myeloperoxidase activities but failed to prevent increases in lung weight. Thus, pretreatment of rats with liposome-associated α-tocopherol appears to protect the lung against some of the toxic effects of paraquat
基金supported by the National Natural Science Foundation of China (81772172, 81471957, 81671971, U1602223)
文摘Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4 ME) expressing prM-E protein of DENV serotype 4(DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4 ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 μg and 5 μg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4 ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 μg, but not 5 μg, of pV-D4 ME could provide stable protection(100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 μg pV-D4 ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.
基金the National Natural Science Foundation of China(No.32070933 to J.M.Lan and Y.F.Yao)the Natural Science Foundation of Shanghai(No.20ZR1463900 to J.M.Lan)+3 种基金financially the STS regional key project(KFJ-STS-QYZD-2021-12-001 to Z.M.Yuan and C.Shan)from Chinese Academy of SciencesNational Key R&D Program of China 2021YFE0201900 to C.Shan and 2021YFC0863300 to Z.M.Yuan and C.Shanthe National Key R&D Program of China(No.2021YFC0863400)funding from Institut Pasteur,Fondation Merieux and the Chinese Academy of Sciences to G.W。
文摘SARS-CoV-2 infection is a global public health threat.Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic.As expected,deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination.However,there are concerns over the duration of vaccine-induced protection,as well as their effectiveness against emerging variants of concern.Here,we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2(Ad C68-S).Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of Ad C68-S.Notably,neutralizing antibodies were observed up to at least six months after vaccination,without substantial decline.Single or double doses Ad C68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term(21 days)and long-term(6 months).Histopathological examination of Ad C68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection.Taken together,this study demonstrates the efficacy and durability of the Ad C68-S vaccine and constitutes a promising candidate for clinical evaluation.
基金This work was supported by the National Grand Program on Key Infectious Disease Control(No.2017ZX10202102)the National Nature Science Foundation of China(No.81561128008).
文摘Human immunodeficiency virus(HIV)-infected individuals exhibit remarkable transcriptomic variation.Transcriptome analyses of antiretroviral therapy(ART)-free chronically infected HIV-1 patients with different clinical outcomes are likely to aid the development of vaccine and immune therapies.Here,we performed microarray analyses on whole-blood derived RNA from 89 ART-free HIV-1-infected individuals from 2 cohorts.The differentially expressed genes were analyzed between long-term non-progressors,viremic non-progressors and typical progressors,and between elite controllers and non-elite controllers among the long-term nonprogressors.Several genes related to T-cell growth,proliferation and differentiation and antiapoptosis were upregulated,whereas interferon-stimulated genes and inflammatory genes were significantly downregulated in long-term non-progressors and viremic non-progressors.The observations above were further confirmed in the set of 261 genes that correlated with disease progression during a 5-year follow-up,which included 51 genes significantly associated with slower disease progression,and 210 genes associated with aggressive disease progression.Overall,our data suggest that it is vital to maintain the homeostasis of the immune system when mounting antiviral immune responses.Immune therapeutics able to reconstruct immune homeostasis are likely to be required for immune reconstitution in the context of ART,such as the administration of interleukin-7,healthy allogenic CD4^(+)T cells(providing CD4^(+)T-cell growth factors),or Tregs.
文摘Habitat use and preferences may be subject to spatial and temporal changes. However, long-term studies of species-habitat relationships are the exception. In the prese nt research, I on g-term trends in habitat use by an alpine ungulate, the Tatra chamois Rupicapra rupicapra tatrica, were analyzed. We exami ned how envir on mental changes attributable to climate cha nge, removal of sheep, and habituation to hikers, which took place over the last half-century have changed the spatial distribution of animals. Data on the localities of groups sighted between 1957 and 2013 during autumnal population surveys were used to evaluate habitat associations: these were correlated with year, group size, population size, and climatic conditions. The results indicate that the Tatra chamois is tending, over the long term, to lower its altitude of occurrenee, reduce its average distance to hiking trails, and stay less often on slopes with a southerly aspect. These trends are in dependent of group size, population size, and the weather conditions prevailing during observations, though not for altitude, where increases in air temperature are related to finding chamois at higher elevations. The proportion of alpine meadows and slope in the places used by chamois is correlated with population size, while the proportion of areas with trees and/or shrubs is correlated with group size and air temperature, though long-term changes were not evident for these variables. To the best of our knowledge, this work is the first to document Iong-term trends in habitat use by ungulates. It shows that a species' ecology is influe need by huma n-in duced cha nges: abandonment of pasturage, high-mountain tourism, and climate changes, which constitute the most probable reasons for this aspect of behavioral evolution in the Tatra chamois.
