A new 18-norschiartane bisnortriterpenoid,12-angeloyl wuweizidilactone I(1)and nine known compounds,wuweizidilactone I(2),wuweizidilactone G(3),deoxychizandrin(4),sasanquin(5),orcinol-O-β-D-glucopyranoside(6),okanin-...A new 18-norschiartane bisnortriterpenoid,12-angeloyl wuweizidilactone I(1)and nine known compounds,wuweizidilactone I(2),wuweizidilactone G(3),deoxychizandrin(4),sasanquin(5),orcinol-O-β-D-glucopyranoside(6),okanin-4-methyl ether-3’-O-β-Dglucopyranoside(7),evemic acid(8),juglansol A(9)and 2-acetoxybenzyl benzoate(10),were isolated from the fruits of Schisandra Chinensis.Their structures were established by a combination of spectroscopic data analysis in addition to comparison with literature data.Compound 1 was new,and compounds 6–10 were isolated from Schisandrae Chinensis for the first time.展开更多
Background:Glioma is the most common malignant tumor in the central nervous system,with unclear pathogenesis and poor treatment outcomes.Recent research reveals that the brain–gut axis—involving gut microbiota and i...Background:Glioma is the most common malignant tumor in the central nervous system,with unclear pathogenesis and poor treatment outcomes.Recent research reveals that the brain–gut axis—involving gut microbiota and immune activity—influences central nervous system tumors.Given the pivotal role of the brain-gut axis in glioma,our study aimed to elucidate the causal association between gut microbiota and glioma,and to identify potential immune-mediated effects and therapeutic targets.Methods:Based on publicly available genome-wide association study data,our research employed multi-subgroup,replicated,Bayesian weighted,and summary statistics-based two-sample Mendelian randomization(MR)studies,combined with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)systematic review strategy,to systematically evaluate the potential causal effects of gut microbiota on glioma and their immune-mediated traits.Results:The initial screening identified 53 gut microbiota and 58 plasma immune traits with potential causal associations with glioma.Through external data and systematic review from six studies,we ultimately confirmed five gut microbiota-plasma immune trait-glioma pathways.CD28^(+)CD45RA^(-)CD8dim Treg(OR=0.019,p=0.007)mediated the risk of Bacteroides A plebeius A(OR=0.149,p=0.036)on glioma,accounting for 2.99% of the effect;the proportion of CD4^(+)memory T cells in whole blood(OR=0.066,p=0.029)mediated the risk of Bacteroides sp002160055(OR=0.158,p=0.024)on non-glioblastoma(GBM),accounting for 8.51% of the effect,while the risk of Faecalicoccus(OR=0.345,p=0.005)on non-GBM was jointly mediated by the absolute number of Naive CD8br and the expression of CD19 in IgD^(+)CD38br B cells.The protective effect of Faecalibacterium sp002160895 on GBM was mediated by 7.59% of the expression level of CD4 in Treg cells.Conclusion:Our study,through MR analysis,revealed the causal relationship between gut microbiota and the susceptibility to glioma,and for the first time proposed the important role of circulating immune cells in this process,providing new potential biomarkers for the early diagnosis and treatment of glioma.展开更多
Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention(EPR) effect without introduction of inactive substances,and some nanodrugs can al...Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention(EPR) effect without introduction of inactive substances,and some nanodrugs can alter the immune environment. We synthesized a peptidyl arginine deiminase 4(PAD4) molecular inhibitor, ZD-E-1 M. It could self-assembled into nanodrug ZD-E-1. Using confocal laser scanning microscopy, we observed its cellular colocalization, PAD4 activity and neutrophil extracellular traps(NETs) formation. The populations of immune cells and expression of immune-related proteins were determined by single-cell mass cytometry. ZD-E-1 formed nanoflowers in an acidic environment, whereas it formed nanospheres at pH 7.4. Accumulation of ZD-E-1 at tumor was pHresponsive because of its pH-dependent differences in the size and shape. It could enter the nucleus and bind to PAD4 to prolong the intracellular retention time. In mice, ZD-E-1 inhibited tumor growth and metastasis by inhibiting PAD4 activity and NETs formation. Besides, ZD-E-1 could regulate the ratio of immune cells in LLC tumor-bearing mice. Immunosuppressive proteins like LAG3 were suppressed,while IFN-γ and TNF-a as stimulators of tumor immune response were upregulated. Overall, ZD-E-1 is a self-assembling carrier-free nanodrug that responds to pH, inhibits PAD4 activity, blocks neutrophil extracellular traps formation, and improves the tumor immune microenvironment.展开更多
Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiolog...Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance.Methods: Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics.Results: The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2-6%, 0.8-2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics.Conclusions: The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically.展开更多
To the Editor:During the coronavirus disease 2019(COVID-19)pandemic,patients with severe respiratory failure required ventilators or even higher levels of life support,bringing extracorporeal membrane oxygenation(ECMO...To the Editor:During the coronavirus disease 2019(COVID-19)pandemic,patients with severe respiratory failure required ventilators or even higher levels of life support,bringing extracorporeal membrane oxygenation(ECMO)into the spotlight.[1]ECMO is commonly used for the rescue and treatment of patients with severe cardiopulmonary failure;its core components are the membrane lung(oxygenator)and blood pump with two fundamental support modes:venovenous(V-V)and venoarterial(V-A)ECMO.COVID-19 patients may require V-V ECMO for acute respiratory distress syndrome and when combined cardio-circulatory support is needed;the support mode could be V-A ECMO.展开更多
文摘A new 18-norschiartane bisnortriterpenoid,12-angeloyl wuweizidilactone I(1)and nine known compounds,wuweizidilactone I(2),wuweizidilactone G(3),deoxychizandrin(4),sasanquin(5),orcinol-O-β-D-glucopyranoside(6),okanin-4-methyl ether-3’-O-β-Dglucopyranoside(7),evemic acid(8),juglansol A(9)and 2-acetoxybenzyl benzoate(10),were isolated from the fruits of Schisandra Chinensis.Their structures were established by a combination of spectroscopic data analysis in addition to comparison with literature data.Compound 1 was new,and compounds 6–10 were isolated from Schisandrae Chinensis for the first time.
基金supported by the Talent Introduction Fund of Beijing Tiantan Hospital(RCYJ-2020-2025-LWB)the Beijing Clinical Key Specialty Project(2-1-2-038)+2 种基金the National Natural Science Foundation of China General Program(32471036)the National Natural Science Foundation of China(82303822)the Exploratory Study on the Mechanism of Action of Oncolytic Virus(OH2)in the Treatment of Glioma(HX-A-048(2021)).
文摘Background:Glioma is the most common malignant tumor in the central nervous system,with unclear pathogenesis and poor treatment outcomes.Recent research reveals that the brain–gut axis—involving gut microbiota and immune activity—influences central nervous system tumors.Given the pivotal role of the brain-gut axis in glioma,our study aimed to elucidate the causal association between gut microbiota and glioma,and to identify potential immune-mediated effects and therapeutic targets.Methods:Based on publicly available genome-wide association study data,our research employed multi-subgroup,replicated,Bayesian weighted,and summary statistics-based two-sample Mendelian randomization(MR)studies,combined with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)systematic review strategy,to systematically evaluate the potential causal effects of gut microbiota on glioma and their immune-mediated traits.Results:The initial screening identified 53 gut microbiota and 58 plasma immune traits with potential causal associations with glioma.Through external data and systematic review from six studies,we ultimately confirmed five gut microbiota-plasma immune trait-glioma pathways.CD28^(+)CD45RA^(-)CD8dim Treg(OR=0.019,p=0.007)mediated the risk of Bacteroides A plebeius A(OR=0.149,p=0.036)on glioma,accounting for 2.99% of the effect;the proportion of CD4^(+)memory T cells in whole blood(OR=0.066,p=0.029)mediated the risk of Bacteroides sp002160055(OR=0.158,p=0.024)on non-glioblastoma(GBM),accounting for 8.51% of the effect,while the risk of Faecalicoccus(OR=0.345,p=0.005)on non-GBM was jointly mediated by the absolute number of Naive CD8br and the expression of CD19 in IgD^(+)CD38br B cells.The protective effect of Faecalibacterium sp002160895 on GBM was mediated by 7.59% of the expression level of CD4 in Treg cells.Conclusion:Our study,through MR analysis,revealed the causal relationship between gut microbiota and the susceptibility to glioma,and for the first time proposed the important role of circulating immune cells in this process,providing new potential biomarkers for the early diagnosis and treatment of glioma.
基金supported by the Beijing Municipal Colleges and Universities High Level Talents Introduction and Cultivate Project-Beijing Great Wall Scholar Program (CIT&TCD 20180332,China)。
文摘Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention(EPR) effect without introduction of inactive substances,and some nanodrugs can alter the immune environment. We synthesized a peptidyl arginine deiminase 4(PAD4) molecular inhibitor, ZD-E-1 M. It could self-assembled into nanodrug ZD-E-1. Using confocal laser scanning microscopy, we observed its cellular colocalization, PAD4 activity and neutrophil extracellular traps(NETs) formation. The populations of immune cells and expression of immune-related proteins were determined by single-cell mass cytometry. ZD-E-1 formed nanoflowers in an acidic environment, whereas it formed nanospheres at pH 7.4. Accumulation of ZD-E-1 at tumor was pHresponsive because of its pH-dependent differences in the size and shape. It could enter the nucleus and bind to PAD4 to prolong the intracellular retention time. In mice, ZD-E-1 inhibited tumor growth and metastasis by inhibiting PAD4 activity and NETs formation. Besides, ZD-E-1 could regulate the ratio of immune cells in LLC tumor-bearing mice. Immunosuppressive proteins like LAG3 were suppressed,while IFN-γ and TNF-a as stimulators of tumor immune response were upregulated. Overall, ZD-E-1 is a self-assembling carrier-free nanodrug that responds to pH, inhibits PAD4 activity, blocks neutrophil extracellular traps formation, and improves the tumor immune microenvironment.
基金This study was supported by the National Key R&D Program of China(2020YFC120104)the National Institutes of Health+3 种基金the USA(AI136850)the National Natural Science Foundation of China(82072311)the Guang‑zhou Synergy Innovation Key Program for Health(201803040006 and 201508020263)the Guangzhou International Science and Technology Cooperation Program(2012J5100026).
文摘Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance.Methods: Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics.Results: The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2-6%, 0.8-2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics.Conclusions: The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically.
基金supported by the Beijing Municipal Government grant(Beijing Laboratory of Oral Health,PXM2021-014226000041)the Beijing Municipal Science and Technology Commission(Z181100001718208)+7 种基金the Beijing Municipal Education Commission(119207020201)the Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)the Chinese Research Unit of Tooth Development and Regeneration,Academy of Medical Sciences(2019-12M-5031)the National Natural Science Foundation of China(92049201,82030031,81991504,and 92149301)the Beijing Advanced Innovation Center for Big Data-based Precision Medicine(PXM2021_014226_000026)the Beijing Municipal Government(Beijing Scholar Program,PXM2020_014226_000005 and PXM2021_014226_000020)the Beijing Municipal Colleges and Universities High Level Talents Introduction and Cultivate Project-Beijing Great Wall Scholar Program(CIT&TCD 20180332)the National Key Research and development Program(2022YFA1104401)。
基金supported by grants from Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023YFC2507100)National Medical Products Administration Key Laboratory for Extracorporeal Circulation Devices:Open Project(No.2024YB01).
文摘To the Editor:During the coronavirus disease 2019(COVID-19)pandemic,patients with severe respiratory failure required ventilators or even higher levels of life support,bringing extracorporeal membrane oxygenation(ECMO)into the spotlight.[1]ECMO is commonly used for the rescue and treatment of patients with severe cardiopulmonary failure;its core components are the membrane lung(oxygenator)and blood pump with two fundamental support modes:venovenous(V-V)and venoarterial(V-A)ECMO.COVID-19 patients may require V-V ECMO for acute respiratory distress syndrome and when combined cardio-circulatory support is needed;the support mode could be V-A ECMO.
