Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration.However,the role of B cells in ischemic stroke remains unclear.In this study,we identified a novel phenotype...Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration.However,the role of B cells in ischemic stroke remains unclear.In this study,we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45.Macrophage-like B cells chara cterized by co-expression of B-cell and macrophage markers,showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes.Gene Ontology analysis found that the expression of genes associated with phagocytosis,including phagosome-and lysosome-related genes,was upregulated in macrophage-like B cells.The phagocytic activity of macrophage-like B cells was ve rified by immunostaining and three-dimensional reconstruction,in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia.Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways.Single-cell RNA sequencing showed that the transdiffe rentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP fa mily to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage.Furthermore,this distinct B cell phenotype was detected in brain tissues from mice or patients with traumatic brain injury,Alzheimer’s disease,and glioblastoma.Overall,these results provide a new perspective on the phagocytic capability and chemotactic function of B cells in the ischemic brain.These cells may serve as an immunotherapeutic target for regulating the immune response of ischemic stroke.展开更多
Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging,exerting complex influences on the pathophysiological processes of diseases that manifest upon it.Using ...Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging,exerting complex influences on the pathophysiological processes of diseases that manifest upon it.Using a combination of single-cell RNA sequencing,cytometry by time of flight,and various immunological assays,we investigated the characteristics of immunosenescence in the peripheral blood of aged mice and its impact on the cerebral immune environment after ischemic stroke.Our results revealed some features of immunosenescence.We observed an increase in neutrophil counts,concurrent with accelerated neutrophil aging,characterized by altered expression of aging-associated markers like CD62L and consequential changes in neutrophil-mediated immune functions.Monocytes/macrophages in aged mice exhibited enhanced antigen-presentation capabilities.T cell profiles shifted from naive to effector or memory states,with a specific rise in T helper 1 cells and T helper 17 cells subpopulations and increased regulatory T cell activation in CD4 T cells.Furthermore,regulatory CD8 T cells marked by Klra decreased with aging,while a subpopulation of exhausted-like CD8 T cells expanded,retaining potent immunostimulatory and proinflammatory functions.Critically,these inherent disparities not only persisted but were further amplified within the ischemic hemispheres following stroke.In summary,our comprehensive insights into the key attributes of peripheral immunosenescence provide a vital theoretical foundation for understanding not only ischemic strokes but also other age-associated diseases.展开更多
The importance of dissolved organic phosphorus(DOP) as a potential nutrient source for primary producers in marine systems has been recognized for up to eight decades, but currently, the understanding of the biogeoche...The importance of dissolved organic phosphorus(DOP) as a potential nutrient source for primary producers in marine systems has been recognized for up to eight decades, but currently, the understanding of the biogeochemistry of DOP is in its infancy. In the present study, monthly data between 2000 and 2014 were used to analyze the temporal and spatial distributions of DOP in the Mir Bay, the northern South China Sea. The DOP residence time(TDOP) was also investigated using a simple regression analysis in combination with chlorophyll a(Chl a) measurements while excess DOP(ΔDOP), produced by the biogeochemical processes of autotrophic production and heterotrophic removal, was determined using a two-component mixing mass-balance model in combination with salinity measurements. The results showed that the DOP concentration was(0.017±0.010) mg/L higher in the surface-water compared with the bottom-water and higher in the inner Tolo Harbour and waters adjacent to Shatoujiao compared with the main zone of the bay. Although seasonal changes and annual variability in the DOP were small, the surface DOP concentration was higher in the wet season(April–September)than in the dry season(October–March) due to the impacts of seaward discharges and atmospheric deposition into the bay. Measurement and regression results showed that the DOP release rate from phytoplankton production was about 1.83(gP)/(gChl a) and the TDOP was about 7 d, which implied that the DOP cycle in the bay was rapid. The ΔDOP was calculated from the model to be about 0.000 mg/L in the main zone of the bay and about 0.002 mg/L in the inner Tolo Harbour and waters adjacent to Shaotoujiao, suggesting that the autotrophic production of DOP was almost balanced by the heterotrophic removal in the main zone of the bay and dominated in the inner Tolo Harbour and waters adjacent to Shaotoujiao. In conclusion, the Mirs Bay is very productive and fairly heterotrophic.展开更多
Natural two-dimensional （2D） kaolinite nanoclay has been incorporated into an emerging drug delivery system. The basal spacing of the kaolinite nanoclay was expanded from 0.72 to 4.16 nm through the intercalation of...Natural two-dimensional （2D） kaolinite nanoclay has been incorporated into an emerging drug delivery system. The basal spacing of the kaolinite nanoclay was expanded from 0.72 to 4.16 nm through the intercalation of various organic guest species of different chain lengths, which can increase the efficiency in drug delivery and reduce the toxicity of doxorubicin （DOX）. Original kaolinite （Kaolin） and the Kaolin intercalation compounds exhibited a high level of biocompatibility and very low toxicity towards cells of pancreatic cancer, gastric cancer, prostate cancer, breast cancer, colorectal cancer, esophageal cancer, and differentiated thyroid cancer. However, lung cancer and hepatocellular cancer cells need more strict compositional, structural, and morphological modulations for drug delivery carriers. DOX-Kaolin and the DOX-Kaolin intercalation compounds showed dramatically faster drug release in moderately acidic solution than in neutral condition, and exhibited enhanced therapeutic effects against ten model cancer cell cultures in a dose-dependent manner. The use of 2D nanoclay materials for a novel drug delivery system could feasibly pave a way towards high-performance nanotherapeutics, with superior antitumor efficacy and significantly reduced side effects.展开更多
An innovative cancer therapy strategy regarding the interface engineering of kaolinite has been designed. The exposed silanol group facilitates more guest species with high dispersion on the supports. Mn_3O_4 magnetic...An innovative cancer therapy strategy regarding the interface engineering of kaolinite has been designed. The exposed silanol group facilitates more guest species with high dispersion on the supports. Mn_3O_4 magnetic nanoparticles are uniformly distributed on external surfaces of the Kaolin_(C12N)with the Al–O–Mn bond for the detection of the tumor microenvironment by T1-MRI; Doxorubicin(DOX) are loaded in the interlayer space with the electrostatic interaction for chemo-treating; and KI is coated on the outer layer of the nanocomposites based on the electrostatic interaction for thyroid cancer targeting. The synergetic effects and the treatment mechanism enhanced by the interface engineering, KI@DOX-Mn_3O_4-Kaolin_(C12N)can cause remarkably low cell viability(57%, 200 μg/mL), tumor shrinking(75%, 20 μg/kg), and accumulation into the tumor tissues. The novel kaolinite based drug delivery system is expected to incorporate imaging diagnosis, targeted therapy and drug delivery into one single system for postoperative residual thyroid cancer treatment and observation for metastasis of focal area.展开更多
基金National Natural Science Foundation of China,No.82001460the Natural Science Foundation of Zhejiang Province,No.LQ21H250001 (both to LS)。
文摘Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration.However,the role of B cells in ischemic stroke remains unclear.In this study,we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45.Macrophage-like B cells chara cterized by co-expression of B-cell and macrophage markers,showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes.Gene Ontology analysis found that the expression of genes associated with phagocytosis,including phagosome-and lysosome-related genes,was upregulated in macrophage-like B cells.The phagocytic activity of macrophage-like B cells was ve rified by immunostaining and three-dimensional reconstruction,in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia.Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways.Single-cell RNA sequencing showed that the transdiffe rentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP fa mily to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage.Furthermore,this distinct B cell phenotype was detected in brain tissues from mice or patients with traumatic brain injury,Alzheimer’s disease,and glioblastoma.Overall,these results provide a new perspective on the phagocytic capability and chemotactic function of B cells in the ischemic brain.These cells may serve as an immunotherapeutic target for regulating the immune response of ischemic stroke.
基金grants from the Natural Science Foundation of Zhejiang Province(LQ21H250001)the National Natural Science Foundation of China(82322022 and 82001460).
文摘Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging,exerting complex influences on the pathophysiological processes of diseases that manifest upon it.Using a combination of single-cell RNA sequencing,cytometry by time of flight,and various immunological assays,we investigated the characteristics of immunosenescence in the peripheral blood of aged mice and its impact on the cerebral immune environment after ischemic stroke.Our results revealed some features of immunosenescence.We observed an increase in neutrophil counts,concurrent with accelerated neutrophil aging,characterized by altered expression of aging-associated markers like CD62L and consequential changes in neutrophil-mediated immune functions.Monocytes/macrophages in aged mice exhibited enhanced antigen-presentation capabilities.T cell profiles shifted from naive to effector or memory states,with a specific rise in T helper 1 cells and T helper 17 cells subpopulations and increased regulatory T cell activation in CD4 T cells.Furthermore,regulatory CD8 T cells marked by Klra decreased with aging,while a subpopulation of exhausted-like CD8 T cells expanded,retaining potent immunostimulatory and proinflammatory functions.Critically,these inherent disparities not only persisted but were further amplified within the ischemic hemispheres following stroke.In summary,our comprehensive insights into the key attributes of peripheral immunosenescence provide a vital theoretical foundation for understanding not only ischemic strokes but also other age-associated diseases.
基金The National Key Basic Research Special Foundation of China under contract No.2013CB965101the Marine Science and Technology Foundation of the South China Sea Sub-administration,SOA,China under contract No.1624
文摘The importance of dissolved organic phosphorus(DOP) as a potential nutrient source for primary producers in marine systems has been recognized for up to eight decades, but currently, the understanding of the biogeochemistry of DOP is in its infancy. In the present study, monthly data between 2000 and 2014 were used to analyze the temporal and spatial distributions of DOP in the Mir Bay, the northern South China Sea. The DOP residence time(TDOP) was also investigated using a simple regression analysis in combination with chlorophyll a(Chl a) measurements while excess DOP(ΔDOP), produced by the biogeochemical processes of autotrophic production and heterotrophic removal, was determined using a two-component mixing mass-balance model in combination with salinity measurements. The results showed that the DOP concentration was(0.017±0.010) mg/L higher in the surface-water compared with the bottom-water and higher in the inner Tolo Harbour and waters adjacent to Shatoujiao compared with the main zone of the bay. Although seasonal changes and annual variability in the DOP were small, the surface DOP concentration was higher in the wet season(April–September)than in the dry season(October–March) due to the impacts of seaward discharges and atmospheric deposition into the bay. Measurement and regression results showed that the DOP release rate from phytoplankton production was about 1.83(gP)/(gChl a) and the TDOP was about 7 d, which implied that the DOP cycle in the bay was rapid. The ΔDOP was calculated from the model to be about 0.000 mg/L in the main zone of the bay and about 0.002 mg/L in the inner Tolo Harbour and waters adjacent to Shaotoujiao, suggesting that the autotrophic production of DOP was almost balanced by the heterotrophic removal in the main zone of the bay and dominated in the inner Tolo Harbour and waters adjacent to Shaotoujiao. In conclusion, the Mirs Bay is very productive and fairly heterotrophic.
基金This work was supported by the National Natural Science Foundation of China （Nos. 51225403 and 41572036）, the Hunan Provincial Science and Technology Project （Nos. 2016RS2004 and 2015TP1006）, the Postdoctoral Science Foundation of Central South University （No. 155219） and the China Postdoctoral Science Foundation （No. 2015M582346）.
文摘Natural two-dimensional （2D） kaolinite nanoclay has been incorporated into an emerging drug delivery system. The basal spacing of the kaolinite nanoclay was expanded from 0.72 to 4.16 nm through the intercalation of various organic guest species of different chain lengths, which can increase the efficiency in drug delivery and reduce the toxicity of doxorubicin （DOX）. Original kaolinite （Kaolin） and the Kaolin intercalation compounds exhibited a high level of biocompatibility and very low toxicity towards cells of pancreatic cancer, gastric cancer, prostate cancer, breast cancer, colorectal cancer, esophageal cancer, and differentiated thyroid cancer. However, lung cancer and hepatocellular cancer cells need more strict compositional, structural, and morphological modulations for drug delivery carriers. DOX-Kaolin and the DOX-Kaolin intercalation compounds showed dramatically faster drug release in moderately acidic solution than in neutral condition, and exhibited enhanced therapeutic effects against ten model cancer cell cultures in a dose-dependent manner. The use of 2D nanoclay materials for a novel drug delivery system could feasibly pave a way towards high-performance nanotherapeutics, with superior antitumor efficacy and significantly reduced side effects.
基金supported by the National Natural Science Foundation of China(21878341,51804343,41572036,51225403)the Strategic Priority Research Program of Central South University(ZLXD2017005)+2 种基金the Natural Science Foundation of Hunan Province(2018JJ3670)the Key R&D Program of Hunan Province(2017GK2251)Hunan Provincial Science and Technology Project(2016RS2004,2015TP1006)
文摘An innovative cancer therapy strategy regarding the interface engineering of kaolinite has been designed. The exposed silanol group facilitates more guest species with high dispersion on the supports. Mn_3O_4 magnetic nanoparticles are uniformly distributed on external surfaces of the Kaolin_(C12N)with the Al–O–Mn bond for the detection of the tumor microenvironment by T1-MRI; Doxorubicin(DOX) are loaded in the interlayer space with the electrostatic interaction for chemo-treating; and KI is coated on the outer layer of the nanocomposites based on the electrostatic interaction for thyroid cancer targeting. The synergetic effects and the treatment mechanism enhanced by the interface engineering, KI@DOX-Mn_3O_4-Kaolin_(C12N)can cause remarkably low cell viability(57%, 200 μg/mL), tumor shrinking(75%, 20 μg/kg), and accumulation into the tumor tissues. The novel kaolinite based drug delivery system is expected to incorporate imaging diagnosis, targeted therapy and drug delivery into one single system for postoperative residual thyroid cancer treatment and observation for metastasis of focal area.
