BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid peroxidation.It is associated with the inactivation of glutathione peroxida...BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid peroxidation.It is associated with the inactivation of glutathione peroxidase(GPX)and the accumulation of lipid peroxides within cells.Ferroptosis is closely related to the occurrence and development of hepatocellular carcinoma(HCC).Chlorogenic acid(CGA),an important bioactive component found in 61 traditional Chinese medicines such as Eucommia ulmoides,has been extensively studied for its effects on various malignant tumors.However,the specific role and potential mechanism of CGA in HCC remain unclear.AIM To elucidate the anti-tumor characteristics and potential mechanisms of CGA in inducing ferroptosis in HCC cells.METHODS The effects of CGA on the proliferation,migration,and invasion of HCC cells were evaluated through in vitro experiments.Bioinformatics analysis combined with network pharmacology was used to study the potential targets and molecular mechanisms of CGA intervention in HCC ferroptosis.In vitro experiments were conducted to verify and explore the anti-HCC effects and mechanisms of CGA through the ferroptosis pathway.RESULTS In vitro experiments showed that CGA dose-dependently inhibited the proliferation,invasion,and migration of HCC cells.Bioinformatics analysis combined with network pharmacology revealed that the pathway of CGA intervention in HCC cell ferroptosis was mainly enriched in the prostaglandin endoperoxide synthase 2(PTGS2)/aldoketo reductase family 1 member C3(AKR1C3)/GPX4 signaling pathway,which was associated with arachidonic acid.In vitro experiments further confirmed that CGA-induced ferroptosis in HCC cells was related to mitochondrial damage through the reprogramming of arachidonic acid metabolism by regulating the PTGS2/AKR1C3/GPX4 signaling pathway.CONCLUSION This study demonstrates that CGA inhibits HCC cell proliferation,migration,and invasion by inducing ferroptosis through the PTGS2/AKR1C3/GPX4 axis,suggesting its potential as a novel ferroptosis inducer or anti-HCC drug.展开更多
The kagome metals AV_(3)Sb_(5)(A=K,Rb,Cs)feature intertwined Dirac fermions,topological flat bands,and van Hove singularities(vHS)near the Fermi level,which give rise to a range of exotic,strongly correlated phenomena...The kagome metals AV_(3)Sb_(5)(A=K,Rb,Cs)feature intertwined Dirac fermions,topological flat bands,and van Hove singularities(vHS)near the Fermi level,which give rise to a range of exotic,strongly correlated phenomena such as charge density waves(CDW)and superconductivity.Although the vHS from V 3d states have been implicated in CDW formation,their three-dimensional nature and temperature evolution remain poorly understood.In this study,we used high-resolution angle-resolved photoemission spectroscopy and density functional theory to reveal pronounced out-of-plane dispersion of vHS and their temperature dependence in KV_(3)Sb_(5).The identified c-axis band folding and scattering channels were directly linked to the CDW order.These results demonstrate that the CDW transition in this family involves cooperative coupling between electron correlations and structural modulation along the c axis.This offers new insights into the interplay of topology,correlations,and lattice instabilities in kagome metals.展开更多
Organocatalytic dynamic kinetic resolution of configurationally labile cyclic molecules represents one of the most efficient methods for the atroposelective construction of axially chiral molecules bearing a tetra-ort...Organocatalytic dynamic kinetic resolution of configurationally labile cyclic molecules represents one of the most efficient methods for the atroposelective construction of axially chiral molecules bearing a tetra-ortho-substituted chiral axis.Notably,this privileged strategy is limited to constructing a C–C chiral axis.Herein,organocatalytic dynamic kinetic resolution of configurationally labile N-arylindole lactams has been successfully achieved at the first time,allowing for access to a structurally diverse set of axially chiral N-arylindole amino esters with a tetra-ortho-substituted C–N chiral axis in excellent yields and atroposelectivities.In addition to the N-arylindole skeleton,N-aryl thieno[3,2-b]pyrrole,furo[3,2-b]pyrrole,and pyrrolo[2,3-b]pyridine skeletons are also compatible with this transformation.This transition-metal-free facile strategy features a broad substrate scope,mild reaction conditions,easy scale-up and excellent atom economy.Several potentially valuable molecules,such as axially chiral peptides,were efficiently generated from the resulting configurationally stable axially-chiral N-arylindole amino esters,demonstrating the power of this strategy.展开更多
基金the National Natural Science Foundation of China,No.82074425Natural Foundation of Hunan Province,No.2023JJ30364 and No.2023JJ30361+1 种基金Hunan Provincial Key R&D Program,No.2023SK2057Key Project of Hunan Provincial Administration of Traditional Chinese Medicine,No.A2023042.
文摘BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid peroxidation.It is associated with the inactivation of glutathione peroxidase(GPX)and the accumulation of lipid peroxides within cells.Ferroptosis is closely related to the occurrence and development of hepatocellular carcinoma(HCC).Chlorogenic acid(CGA),an important bioactive component found in 61 traditional Chinese medicines such as Eucommia ulmoides,has been extensively studied for its effects on various malignant tumors.However,the specific role and potential mechanism of CGA in HCC remain unclear.AIM To elucidate the anti-tumor characteristics and potential mechanisms of CGA in inducing ferroptosis in HCC cells.METHODS The effects of CGA on the proliferation,migration,and invasion of HCC cells were evaluated through in vitro experiments.Bioinformatics analysis combined with network pharmacology was used to study the potential targets and molecular mechanisms of CGA intervention in HCC ferroptosis.In vitro experiments were conducted to verify and explore the anti-HCC effects and mechanisms of CGA through the ferroptosis pathway.RESULTS In vitro experiments showed that CGA dose-dependently inhibited the proliferation,invasion,and migration of HCC cells.Bioinformatics analysis combined with network pharmacology revealed that the pathway of CGA intervention in HCC cell ferroptosis was mainly enriched in the prostaglandin endoperoxide synthase 2(PTGS2)/aldoketo reductase family 1 member C3(AKR1C3)/GPX4 signaling pathway,which was associated with arachidonic acid.In vitro experiments further confirmed that CGA-induced ferroptosis in HCC cells was related to mitochondrial damage through the reprogramming of arachidonic acid metabolism by regulating the PTGS2/AKR1C3/GPX4 signaling pathway.CONCLUSION This study demonstrates that CGA inhibits HCC cell proliferation,migration,and invasion by inducing ferroptosis through the PTGS2/AKR1C3/GPX4 axis,suggesting its potential as a novel ferroptosis inducer or anti-HCC drug.
基金supported by the National Key R&D Program of China(Grant Nos.2023YFA1406304 and 2024YFA1408103)the National Science Foundation of China(Grant Nos.12494593 and 12004405)+5 种基金the Anhui Provincial Natural Science Foundation(Grant No.2408085J003)the National Key R&D Program of China(Grant No.2023YFA1406100)the open projects of the State Key Laboratory of Functional Materials for Informatics(Grant No.SKL2022)the China National Postdoctoral Program for Innovative Talents(BX20240348)support from the National Natural Science Foundation of China(Grant No.12404186)the Shanghai Sailing Program(Grant No.23YF1426900)。
文摘The kagome metals AV_(3)Sb_(5)(A=K,Rb,Cs)feature intertwined Dirac fermions,topological flat bands,and van Hove singularities(vHS)near the Fermi level,which give rise to a range of exotic,strongly correlated phenomena such as charge density waves(CDW)and superconductivity.Although the vHS from V 3d states have been implicated in CDW formation,their three-dimensional nature and temperature evolution remain poorly understood.In this study,we used high-resolution angle-resolved photoemission spectroscopy and density functional theory to reveal pronounced out-of-plane dispersion of vHS and their temperature dependence in KV_(3)Sb_(5).The identified c-axis band folding and scattering channels were directly linked to the CDW order.These results demonstrate that the CDW transition in this family involves cooperative coupling between electron correlations and structural modulation along the c axis.This offers new insights into the interplay of topology,correlations,and lattice instabilities in kagome metals.
基金supported by the National Key Research and Development Program of China (2017YFA0204704)the General Program of Chongqing Natural Science Foundation Project (cstc2020jcyjmsxmX0712)+2 种基金Ningbo Natural Science Foundation (202003N4063)the National Natural Science Foundation of China (21602105, 22174065)the Natural Science Foundation of Jiangsu Province (BK20171460)。
文摘Organocatalytic dynamic kinetic resolution of configurationally labile cyclic molecules represents one of the most efficient methods for the atroposelective construction of axially chiral molecules bearing a tetra-ortho-substituted chiral axis.Notably,this privileged strategy is limited to constructing a C–C chiral axis.Herein,organocatalytic dynamic kinetic resolution of configurationally labile N-arylindole lactams has been successfully achieved at the first time,allowing for access to a structurally diverse set of axially chiral N-arylindole amino esters with a tetra-ortho-substituted C–N chiral axis in excellent yields and atroposelectivities.In addition to the N-arylindole skeleton,N-aryl thieno[3,2-b]pyrrole,furo[3,2-b]pyrrole,and pyrrolo[2,3-b]pyridine skeletons are also compatible with this transformation.This transition-metal-free facile strategy features a broad substrate scope,mild reaction conditions,easy scale-up and excellent atom economy.Several potentially valuable molecules,such as axially chiral peptides,were efficiently generated from the resulting configurationally stable axially-chiral N-arylindole amino esters,demonstrating the power of this strategy.
