BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untran...BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.展开更多
BACKGROUND Radiation induces rapid bone loss and enhances bone resorption and adipogenesis, leading to an increased risk of bone fracture. There is still a lack of effective preventive or therapeutic method for irradi...BACKGROUND Radiation induces rapid bone loss and enhances bone resorption and adipogenesis, leading to an increased risk of bone fracture. There is still a lack of effective preventive or therapeutic method for irradiation-induced bone injury.Receptor activator of nuclear factor κB ligand(RANKL) provides the crucial signal to induce osteoclast differentiation and plays an important role in bone resorption. However, the mechanisms of radiation-induced osteoporosis are not fully understood.AIM To investigate the role of CR6-interacting factor-1(Crif1) in osteoclastogenesis after radiation and its possible mechanism.METHODS C57 BL/6 mice were exposed to Co-60 gamma rays and received 5 Gy of wholebody sublethal irradiation at a rate of 0.69 Gy/min. For in vitro study, mouse bone marrow mesenchymal stem/stromal cells(BM-MSCs) were irradiated with Co-60 at a single dose of 9 Gy. For osteoclast induction, monocyte-macrophage RAW264.7 cells were cocultured with mouse BM-MSCs for 7 d. Clus Pro and Inter Pro Surf were used to investigate the interaction interface in Crif1 and protein kinase cyclic adenosine monophosphate(c AMP)-activited catalytic subunit alpha complex. Virtual screening using 462608 compounds from the Life Chemicals database around His120 of Crif1 was carried out using the program Autodock_vina. A tetrazolium salt(WST-8) assay was carried out to study the toxicity of compounds to different cells, including human BM-MSCs, mouse BMMSCs, and Vero cells.RESULTS Crif1 expression increased in bone marrow cells after radiation in mice.Overexpression of Crif1 in mouse BM-MSCs and radiation exposure could increase RANKL secretion and promote osteoclastogenesis in vitro. Deletion of Crif1 in BM-MSCs could reduce both adipogenesis and RANKL expression,resulting in the inhibition of osteoclastogenesis. Deletion of Crif1 in RAW264.7 cells did not affect the receptor activator of nuclear factor κB expression or osteoclast differentiation. Following treatment with protein kinase A(PKA)agonist(forskolin) and inhibitor(H-89) in mouse BM-MSCs, Crif1 induced RANKL secretion via the c AMP/PKA pathway. Moreover, we identified the Crif1-protein kinase cyclic adenosine monophosphate-activited catalytic subunit alpha interaction interface by in silico studies and shortlisted interface inhibitors through virtual screening on Crif1. Five compounds dramatically suppressed RANKL secretion and adipogenesis by inhibiting the c AMP/PKA pathway.CONCLUSION Crif1 promotes RANKL expression via the c AMP/PKA pathway, which induces osteoclastogenesis by binding to receptor activator of nuclear factor κB on monocytes-macrophages in the mouse model. These results suggest a role for Crif1 in modulating osteoclastogenesis and provide insights into potential therapeutic strategies targeting the balance between osteogenesis and adipogenesis for radiation-induced bone injury.展开更多
Metal-organic framework(MOF)derived hybrid materials have been developed as an efficient non-noblemetal electrocatalysts for clean energy conversion systems.In this work,a Co-based MOF containing nitrogen and oxygen h...Metal-organic framework(MOF)derived hybrid materials have been developed as an efficient non-noblemetal electrocatalysts for clean energy conversion systems.In this work,a Co-based MOF containing nitrogen and oxygen heteroatoms(Co-NOMOF)mixed with the thiomolybdate[Mo3S(13)]^2- nanoclusters was used to prepare the N,S,O-doped carbon encapsulating Co9S8 and MoS2(Co9S8/MoS2@NSOC)nanocomposite by one-step pyrolysis.The Co9S8/MoS2@NSOC nanocomposite exhibited remarkable catalytic performance for hydrogen evolution reaction(HER)with overpotential of 194 and 233 mV in 1 M KOH and 0.5 M H2SO4 solution under 10 mA cm^-2,respectively,which was ascribed to the multiheteroatom-doped hierarchical porous carbon matrix and the synergistic effect of intrinsic activity of Co9S8 and MoS2.This work provides new opportunity for developing highly efficient non-precious metal electrochemical catalysts.展开更多
We utilized the glycosyl acceptor tagging method with ionic liquid support for synthesis of the core segment of Clostridium botulinum C2 toxin ligand through a divergent synthetic strategy without chromatographic puri...We utilized the glycosyl acceptor tagging method with ionic liquid support for synthesis of the core segment of Clostridium botulinum C2 toxin ligand through a divergent synthetic strategy without chromatographic purification.The total yield was 57.1% and the reaction was completed in 10 h.The efficient ionic liquid supported glycosylation and purification procedure was applied for the synthesis of branched glucosamine-containing oligosaccharides for the first time,which expanded the scope of ionic liquid supported synthesis of biologically important oligosaccharides.展开更多
An efficient route to prepare L-glucose and L-galactose is described. The L-sugars are achieved by using the strategy of switching the functional groups at C1 and C5 of D-glucose and D-mannose. The oxidation and reduc...An efficient route to prepare L-glucose and L-galactose is described. The L-sugars are achieved by using the strategy of switching the functional groups at C1 and C5 of D-glucose and D-mannose. The oxidation and reduction of the silyl enol ether at C1 and the lead（IV） tetraacetate mediated oxidative decarboxylation at C5 are the key steps. L-Glucose and L-galactose are prepared in a convenient and inexpensive way.展开更多
基金Supported by General Program of National Natural Science Foundation of China,No.81770197Scientific and Technological Research Major Program of Chongqing Municipal Education Commission,No.KJZD-M202312802+1 种基金Chongqing Natural Science Foundation of China,No.CSTB2022NSCQ-MSX0190,No.CSTB2022NSCQ-MSX0176,and No.cstc2020jcyj-msxmX0051Xinqiao Young Postdoc Talent Incubation Program,No.2022YQB098.
文摘BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.
基金National Natural Science Foundation of China,No.81502754 and No.31571352Interdisciplinary and International Cooperation Projects of The Second Affiliated Hospital,Third Military Medical University,No.2016YXKJC0。
文摘BACKGROUND Radiation induces rapid bone loss and enhances bone resorption and adipogenesis, leading to an increased risk of bone fracture. There is still a lack of effective preventive or therapeutic method for irradiation-induced bone injury.Receptor activator of nuclear factor κB ligand(RANKL) provides the crucial signal to induce osteoclast differentiation and plays an important role in bone resorption. However, the mechanisms of radiation-induced osteoporosis are not fully understood.AIM To investigate the role of CR6-interacting factor-1(Crif1) in osteoclastogenesis after radiation and its possible mechanism.METHODS C57 BL/6 mice were exposed to Co-60 gamma rays and received 5 Gy of wholebody sublethal irradiation at a rate of 0.69 Gy/min. For in vitro study, mouse bone marrow mesenchymal stem/stromal cells(BM-MSCs) were irradiated with Co-60 at a single dose of 9 Gy. For osteoclast induction, monocyte-macrophage RAW264.7 cells were cocultured with mouse BM-MSCs for 7 d. Clus Pro and Inter Pro Surf were used to investigate the interaction interface in Crif1 and protein kinase cyclic adenosine monophosphate(c AMP)-activited catalytic subunit alpha complex. Virtual screening using 462608 compounds from the Life Chemicals database around His120 of Crif1 was carried out using the program Autodock_vina. A tetrazolium salt(WST-8) assay was carried out to study the toxicity of compounds to different cells, including human BM-MSCs, mouse BMMSCs, and Vero cells.RESULTS Crif1 expression increased in bone marrow cells after radiation in mice.Overexpression of Crif1 in mouse BM-MSCs and radiation exposure could increase RANKL secretion and promote osteoclastogenesis in vitro. Deletion of Crif1 in BM-MSCs could reduce both adipogenesis and RANKL expression,resulting in the inhibition of osteoclastogenesis. Deletion of Crif1 in RAW264.7 cells did not affect the receptor activator of nuclear factor κB expression or osteoclast differentiation. Following treatment with protein kinase A(PKA)agonist(forskolin) and inhibitor(H-89) in mouse BM-MSCs, Crif1 induced RANKL secretion via the c AMP/PKA pathway. Moreover, we identified the Crif1-protein kinase cyclic adenosine monophosphate-activited catalytic subunit alpha interaction interface by in silico studies and shortlisted interface inhibitors through virtual screening on Crif1. Five compounds dramatically suppressed RANKL secretion and adipogenesis by inhibiting the c AMP/PKA pathway.CONCLUSION Crif1 promotes RANKL expression via the c AMP/PKA pathway, which induces osteoclastogenesis by binding to receptor activator of nuclear factor κB on monocytes-macrophages in the mouse model. These results suggest a role for Crif1 in modulating osteoclastogenesis and provide insights into potential therapeutic strategies targeting the balance between osteogenesis and adipogenesis for radiation-induced bone injury.
基金supported by the National Science Fund for Distinguished Young Scholars (No. 21825106)National Natural Science Foundation of China (No. 21671175)+2 种基金Program for Science & Technology Innovation Talents in Universities of Henan Province (No. 164100510005)Key Scientific Research Project Plan in Colleges and Universities of Henan Province (No. 16A150045)Program for Innovative Research Team (in Science and Technology) in Universities of Henan Province (No. 19IRTSTHN022).
文摘Metal-organic framework(MOF)derived hybrid materials have been developed as an efficient non-noblemetal electrocatalysts for clean energy conversion systems.In this work,a Co-based MOF containing nitrogen and oxygen heteroatoms(Co-NOMOF)mixed with the thiomolybdate[Mo3S(13)]^2- nanoclusters was used to prepare the N,S,O-doped carbon encapsulating Co9S8 and MoS2(Co9S8/MoS2@NSOC)nanocomposite by one-step pyrolysis.The Co9S8/MoS2@NSOC nanocomposite exhibited remarkable catalytic performance for hydrogen evolution reaction(HER)with overpotential of 194 and 233 mV in 1 M KOH and 0.5 M H2SO4 solution under 10 mA cm^-2,respectively,which was ascribed to the multiheteroatom-doped hierarchical porous carbon matrix and the synergistic effect of intrinsic activity of Co9S8 and MoS2.This work provides new opportunity for developing highly efficient non-precious metal electrochemical catalysts.
基金supported by the National Basic Research Program of China(973 Program,No.2012CB822100)the National Key Technology R&D Program "New Drug Innovation" of China (No.2012ZX09502001-001)the National Natural Science Foundation of China(Nos.91213301,21232002)
文摘We utilized the glycosyl acceptor tagging method with ionic liquid support for synthesis of the core segment of Clostridium botulinum C2 toxin ligand through a divergent synthetic strategy without chromatographic purification.The total yield was 57.1% and the reaction was completed in 10 h.The efficient ionic liquid supported glycosylation and purification procedure was applied for the synthesis of branched glucosamine-containing oligosaccharides for the first time,which expanded the scope of ionic liquid supported synthesis of biologically important oligosaccharides.
基金supported by the National Basic Research Program of China(973 Program,No.2012CB822100)the National Key Technology R&D Program‘‘New Drug Innovation’’ of China(No.2012ZX09502001-001)the National Natural Science Foundation of China(Nos.20972012 and 21232002)
文摘An efficient route to prepare L-glucose and L-galactose is described. The L-sugars are achieved by using the strategy of switching the functional groups at C1 and C5 of D-glucose and D-mannose. The oxidation and reduction of the silyl enol ether at C1 and the lead（IV） tetraacetate mediated oxidative decarboxylation at C5 are the key steps. L-Glucose and L-galactose are prepared in a convenient and inexpensive way.
