Numerous studies have demonstrated that the high expression of CXC motif chemokine ligand 16(CXCL16)in cancer correlates with poor prognosis,as well as tumor cell proliferation,migration,and invasion.While CXCL16 can ...Numerous studies have demonstrated that the high expression of CXC motif chemokine ligand 16(CXCL16)in cancer correlates with poor prognosis,as well as tumor cell proliferation,migration,and invasion.While CXCL16 can serve as a tumor biomarker,the underlying mechanism in modulating head and neck squamous cell carcinoma(HNSCC)remains unclear.In this study,the aimed was to investigate the CXCL16 expression in HNSCC and to uncover the potential underlying mechanism.Hereby,we determined the high expression of CXCL16 in The Cancer Genome Atlas(TCGA)database,as well as in tissue samples from patients with HNSCC at our central hospital and from HNSCC cell lines.The results showed that CXCL16 knockdown inhibited the proliferation,migration,and invasion of HNSCC cells.Mechanistically,transcriptome sequencing revealed that CXCL16 may affect HNSCC cell growth by regulating the antioxidant pathway of glutathione peroxidase 1(GPX1).The reactive oxygen species(ROS)levels were elevated in small interfering CXCL16(si-CXCL16)cells,which may contribute to the inhibition of cell proliferation,migration,and invasion.Moreover,treatment of cells with the GPX1 inhibitor eldecalcitol(ED-71)revealed that HNSCC cell growth was significantly inhibited in the synergistic group of si-CXCL16 and GPX1 inhibitor compared to the si-CXCL16 group.In conclusion,CXCL16 contributed to the development of HNSCC cells by modulating the GPX1-mediated antioxidant pathway.Thus,targeting cellular CXCL16 expression seems to be a promising strategy for treating HNSCC.展开更多
Specific gravity segregation that occurs during the smelting process always leads to the low composition homogeneity and poor performance stability of the magnesium-rare earth(Mg-RE)alloys.In this study,the segregatio...Specific gravity segregation that occurs during the smelting process always leads to the low composition homogeneity and poor performance stability of the magnesium-rare earth(Mg-RE)alloys.In this study,the segregation behavior of Mg-Gd alloy was investigated by sampling from different locations in the ingot fabricated in a resistance furnace without a pouring process.The combined application of induction-heating and mechanical stirring with various speeds(0-130 r/min)was applied to promote the distribution homogeneity of Gd atoms.In the resistance-heating fabricated ingot,Gd content at the bottom section reaches 407%of that at the top.The coarse dendrites surrounded by the network-like eutectic structures are responsible for the brittle fracture with a poor elongation of 3.7%.By the combined employment of the induction heating and mechanical stirring with the speed of 87 r/min at 740℃for 40 s,the variation of the Gd content within the whole ingot can be reduced to be the minimum of 0.23 wt%.Corresponding formation and regulating models of segregation were also proposed.However,the cooling rate of the melt is reduced by the continuous increase of the stirring speed to 130 r/min,which results in the grain coarsening and lower homogeneity of the ingot.展开更多
Plants typically exhibit the purple phenomenon as a result of an increase in flavonoids and anthocyanins.A new tea germplasm'P113'was recently selected from Camellia tachangensis,which is purple in tender shoo...Plants typically exhibit the purple phenomenon as a result of an increase in flavonoids and anthocyanins.A new tea germplasm'P113'was recently selected from Camellia tachangensis,which is purple in tender shoots.In the present study,integrated transcriptome and metabolome were used to analyze the flavonoid metabolite components and the genes involved in flavonoid biosynthesis in'P113'.A total of 86 flavonoid metabolites were identified,including 70 significantly differential metabolites(p<0.05)and they were enriched to the three metabolic pathways of ko00941,ko00942 and ko00944 through KEGG pathway analysis.A total of 136 flavonoid involved genes were obtained from transcriptomic study,of which 53 were significantly differentially expressed in developmental shoots.The correlation between metabolite profiling and transcriptome,transcriptome and protein interactions suggested that transcription factor MYB12 and glycosyltransferase UGT78D2 had a good facilitation on purple tender shoots.The metabolic pathways and potential genes that underlie the coloration of the shoots in'P113'are clarified in this study.It also lays the groundwork for identifying potential genes involved in color variation and offers a theoretical framework for the creation and use of distinctive genetic resources and the breeding of new cultivars.展开更多
1.INTRODUCTION Epstein-Barr virus(EBV)is able to infect T and/or natural killer(NK)cells and trigger persistent EBV replication and intractable EBV-associated T/NK lymphoproliferative diseases(EBV-T/NK-LPDs)in rare ca...1.INTRODUCTION Epstein-Barr virus(EBV)is able to infect T and/or natural killer(NK)cells and trigger persistent EBV replication and intractable EBV-associated T/NK lymphoproliferative diseases(EBV-T/NK-LPDs)in rare cases,1,2 especially when the functionalities of tonsillar NK cells3 and CD8+T cells4,5 are impaired.Tumor necrosis factor–like receptors(TNFRs)are part of a superfamily heavily involved in the physiology of immune cells.Mutations in TNFRSF13B(encoding the transmembrane activator and cyclophilin interactor[TACI]protein)were previously reported to be associated with common variable immunodeficiency(CVID),6 indicating the complex imbalance of the immune system caused by TACI deficiency.Increasing evidence also suggests the potential role of TACI in responses of T cells.7,8 Here we report a series of novel heterozygous TNFRSF13B mutations in 6 patients diagnosed with EBV-T/NK-LPDs.In this work,we try to expand the routine panel of genes screened in the patients presenting with EBV-associated proliferative diseases and provide a new possible way to correlate the genetic predisposition,persistent EBV infection,and EBV-T/NK-LPDs etiopathology.展开更多
Adoptive therapeutic immune cells,such as chimeric antigen receptor(CAR)-T cells and natural killer cells,have established a new generation of precision medicine based on which dramatic breakthroughs have been achieve...Adoptive therapeutic immune cells,such as chimeric antigen receptor(CAR)-T cells and natural killer cells,have established a new generation of precision medicine based on which dramatic breakthroughs have been achieved in intractable lymphoma treatments.Currently,well-explored approaches focus on autologous cells due to their low immunogenicity,but they are highly restricted by the high costs,time consumption of processing,and the insufficiency of primary cells in some patients.Induced pluripotent stem cells(iPSCs)are cell sources that can theoretically produce indefinite well-differentiated immune cells.Based on the above facts,it may be reasonable to combine the iPSC technology and the CAR design to produce a series of highly controllable and economical"live"drugs.Manufacturing hypoimmunogenic iPSCs by inactivation or over-expression at the genetic level and then arming the derived cells with CAR have emerged as a form of"off-the-shelf"strategy to eliminate tumor cells efficiently and safely in a broader range of patients.This review describes the reasonability,feasibility,superiority,and drawbacks of such approaches,summarizes the current practices and relevant research progress,and provides insights into the possible new paths for personalized cell-based therapies.展开更多
基金supported by the Scientific Research Fund of the National Health Commission-Zhejiang Provincial Health Major Science and Technology Plan Project(No.WKJ-ZJ-2415)the Key Research and Development Program of Zhejiang Province(No.2024C03166)+1 种基金the Traditional Chinese Medicine Science and Technology Project of Zhejiang Province(No.2022ZB020)the Zhejiang Provincial Natural Science Foundation of China(No.LY21H160049).
文摘Numerous studies have demonstrated that the high expression of CXC motif chemokine ligand 16(CXCL16)in cancer correlates with poor prognosis,as well as tumor cell proliferation,migration,and invasion.While CXCL16 can serve as a tumor biomarker,the underlying mechanism in modulating head and neck squamous cell carcinoma(HNSCC)remains unclear.In this study,the aimed was to investigate the CXCL16 expression in HNSCC and to uncover the potential underlying mechanism.Hereby,we determined the high expression of CXCL16 in The Cancer Genome Atlas(TCGA)database,as well as in tissue samples from patients with HNSCC at our central hospital and from HNSCC cell lines.The results showed that CXCL16 knockdown inhibited the proliferation,migration,and invasion of HNSCC cells.Mechanistically,transcriptome sequencing revealed that CXCL16 may affect HNSCC cell growth by regulating the antioxidant pathway of glutathione peroxidase 1(GPX1).The reactive oxygen species(ROS)levels were elevated in small interfering CXCL16(si-CXCL16)cells,which may contribute to the inhibition of cell proliferation,migration,and invasion.Moreover,treatment of cells with the GPX1 inhibitor eldecalcitol(ED-71)revealed that HNSCC cell growth was significantly inhibited in the synergistic group of si-CXCL16 and GPX1 inhibitor compared to the si-CXCL16 group.In conclusion,CXCL16 contributed to the development of HNSCC cells by modulating the GPX1-mediated antioxidant pathway.Thus,targeting cellular CXCL16 expression seems to be a promising strategy for treating HNSCC.
基金Project supported by Key Research&Development Project of Guangdong Province(2020B010186002)National Natural Science Foundation of China(U2037601)Science and Technology Project of Sichuan Province(2020YFG0213)。
文摘Specific gravity segregation that occurs during the smelting process always leads to the low composition homogeneity and poor performance stability of the magnesium-rare earth(Mg-RE)alloys.In this study,the segregation behavior of Mg-Gd alloy was investigated by sampling from different locations in the ingot fabricated in a resistance furnace without a pouring process.The combined application of induction-heating and mechanical stirring with various speeds(0-130 r/min)was applied to promote the distribution homogeneity of Gd atoms.In the resistance-heating fabricated ingot,Gd content at the bottom section reaches 407%of that at the top.The coarse dendrites surrounded by the network-like eutectic structures are responsible for the brittle fracture with a poor elongation of 3.7%.By the combined employment of the induction heating and mechanical stirring with the speed of 87 r/min at 740℃for 40 s,the variation of the Gd content within the whole ingot can be reduced to be the minimum of 0.23 wt%.Corresponding formation and regulating models of segregation were also proposed.However,the cooling rate of the melt is reduced by the continuous increase of the stirring speed to 130 r/min,which results in the grain coarsening and lower homogeneity of the ingot.
基金supported by the Project of the National key R&D plan(2021YFD1200203-1)Science and Technology Plan Project of Guizhou province,in RP China([2019]1404)+2 种基金Project of the National Science Foundation,in RP China(32060700),Project of the key field project of Natural Science Foundation of Guizhou Provincial Department of education(KY[2021]042)Science and Technology Plan Project of Guizhou province,in RP China([2021]General Project 126)Project of the National key R&D plan(2021YFD1100307)。
文摘Plants typically exhibit the purple phenomenon as a result of an increase in flavonoids and anthocyanins.A new tea germplasm'P113'was recently selected from Camellia tachangensis,which is purple in tender shoots.In the present study,integrated transcriptome and metabolome were used to analyze the flavonoid metabolite components and the genes involved in flavonoid biosynthesis in'P113'.A total of 86 flavonoid metabolites were identified,including 70 significantly differential metabolites(p<0.05)and they were enriched to the three metabolic pathways of ko00941,ko00942 and ko00944 through KEGG pathway analysis.A total of 136 flavonoid involved genes were obtained from transcriptomic study,of which 53 were significantly differentially expressed in developmental shoots.The correlation between metabolite profiling and transcriptome,transcriptome and protein interactions suggested that transcription factor MYB12 and glycosyltransferase UGT78D2 had a good facilitation on purple tender shoots.The metabolic pathways and potential genes that underlie the coloration of the shoots in'P113'are clarified in this study.It also lays the groundwork for identifying potential genes involved in color variation and offers a theoretical framework for the creation and use of distinctive genetic resources and the breeding of new cultivars.
基金supported by the National Natural Science Foundation of China(No.81770211 and No.82270203 to M.X.).
文摘1.INTRODUCTION Epstein-Barr virus(EBV)is able to infect T and/or natural killer(NK)cells and trigger persistent EBV replication and intractable EBV-associated T/NK lymphoproliferative diseases(EBV-T/NK-LPDs)in rare cases,1,2 especially when the functionalities of tonsillar NK cells3 and CD8+T cells4,5 are impaired.Tumor necrosis factor–like receptors(TNFRs)are part of a superfamily heavily involved in the physiology of immune cells.Mutations in TNFRSF13B(encoding the transmembrane activator and cyclophilin interactor[TACI]protein)were previously reported to be associated with common variable immunodeficiency(CVID),6 indicating the complex imbalance of the immune system caused by TACI deficiency.Increasing evidence also suggests the potential role of TACI in responses of T cells.7,8 Here we report a series of novel heterozygous TNFRSF13B mutations in 6 patients diagnosed with EBV-T/NK-LPDs.In this work,we try to expand the routine panel of genes screened in the patients presenting with EBV-associated proliferative diseases and provide a new possible way to correlate the genetic predisposition,persistent EBV infection,and EBV-T/NK-LPDs etiopathology.
基金supported by the Key Program of the National Natural Science Foundation of China(Nos.81830008 and 81630006)the National Natural Science Foundation of China(No.81570197)and the Natural Science Foundation of Hubei Province(No.2018ACA140).
文摘Adoptive therapeutic immune cells,such as chimeric antigen receptor(CAR)-T cells and natural killer cells,have established a new generation of precision medicine based on which dramatic breakthroughs have been achieved in intractable lymphoma treatments.Currently,well-explored approaches focus on autologous cells due to their low immunogenicity,but they are highly restricted by the high costs,time consumption of processing,and the insufficiency of primary cells in some patients.Induced pluripotent stem cells(iPSCs)are cell sources that can theoretically produce indefinite well-differentiated immune cells.Based on the above facts,it may be reasonable to combine the iPSC technology and the CAR design to produce a series of highly controllable and economical"live"drugs.Manufacturing hypoimmunogenic iPSCs by inactivation or over-expression at the genetic level and then arming the derived cells with CAR have emerged as a form of"off-the-shelf"strategy to eliminate tumor cells efficiently and safely in a broader range of patients.This review describes the reasonability,feasibility,superiority,and drawbacks of such approaches,summarizes the current practices and relevant research progress,and provides insights into the possible new paths for personalized cell-based therapies.
