Constructing a framework carrier to stabilize protein conformation,induce high embedding efficiency,and acquire low mass-transfer resistance is an urgent issue in the development of immobilized enzymes.Hydrogen-bonded...Constructing a framework carrier to stabilize protein conformation,induce high embedding efficiency,and acquire low mass-transfer resistance is an urgent issue in the development of immobilized enzymes.Hydrogen-bonded organic frameworks(HOFs)have promising application potential for embedding enzymes.In fact,no metal involvement is required,and HOFs exhibit superior biocompatibility,and free access to substrates in mesoporous channels.Herein,a facile in situ growth approach was proposed for the self-assembly of alcohol dehydrogenase encapsulated in HOF.The micron-scale bio-catalytic composite was rapidly synthesized under mild conditions(aqueous phase and ambient temperature)with a controllable embedding rate.The high crystallinity and periodic arrangement channels of HOF were preserved at a high enzyme encapsulation efficiency of 59%.This bio-composite improved the tolerance of the enzyme to the acid-base environment and retained 81%of its initial activity after five cycles of batch hydrogenation involving NADH coenzyme.Based on this controllably synthesized bio-catalytic material and a common lipase,we further developed a two-stage cascade microchemical system and achieved the continuous production of chiral hydroxybutyric acid(R-3-HBA).展开更多
Background:Ferroptosis is a type of regulated cell death characterized by iron-dependent lipid peroxidation,which has been linked to tumor progression and therapeutic resistance.However,the contribution of lactate met...Background:Ferroptosis is a type of regulated cell death characterized by iron-dependent lipid peroxidation,which has been linked to tumor progression and therapeutic resistance.However,the contribution of lactate metabolism and its receptor,hydroxycarboxylic acid receptor 1(HCAR1),in ferroptosis regulation in gastric cancer(GC)remains poorly understood.Focusing specifically on its effects on cell proliferation,ferroptosis regulation,and the disruption of lactate-mediatedmetabolic pathways,the study aimed to clarify the role ofHCAR1 in GC progression.Methods:Bioinformatics analysis identified prognostic genes associated with ferroptosis in GC.Receiver operating characteristic(ROC)curves were generated to assess the diagnostic potential of the predictive genes.The biological role of HCAR1 was investigated through gain and loss-of-function experiments in GC cell lines,followed by assessments of cell viability,oxidative stress indicators,gene/protein expression,and ferroptosis sensitivity under lactate stimulation or HCAR1modulation.Results:HCAR1 was significantly upregulated in GC tissues and linked to poor patient outcomes.Silencing HCAR1 inhibited GC cell growth and induced ferroptosis,as shown by increased levels of reactive oxygen species(ROS)and malondialdehyde(MDA),along with decreased expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).Conversely,HCAR1 overexpression or exposure to extracellular lactate inhibited ferroptosis and activated antioxidant defenses.Mechanistically,lactate activation of HCAR1 increases ATP levels,which in turn inactivates AMP-activated protein kinase(AMPK).It also upregulates stearoyl-CoA desaturase 1(SCD1)through the sterol regulatory element binding protein 1(SREBP1)signaling pathway.Blocking HCAR1 reversed these effects and restored ferroptosis sensitivity.Conclusion:HCAR1 mediates lactate-driven ferroptosis resistance in GC through the AMPK-SCD1 signaling pathway.Targeting the HCAR1-lactate axis may offer a promising strategy for overcoming metabolic adaptation and improving GC treatment outcomes.展开更多
imeric ammonium(glycollate)dioxovanadium (NH4)2[V2O4(OCH2COO )2]has been prepared. The complex crystallizes in triclinic space group Pl with unitcell parameters: a = 0. 6124(1)nm, b= 0. 6952 (1)nm, c= 0. 8449 (1)nm, ...imeric ammonium(glycollate)dioxovanadium (NH4)2[V2O4(OCH2COO )2]has been prepared. The complex crystallizes in triclinic space group Pl with unitcell parameters: a = 0. 6124(1)nm, b= 0. 6952 (1)nm, c= 0. 8449 (1)nm, α=66. 08 (1),β=64. 21(1),γ= 78. 01(1)°V=0. 2958 nms, Z=1, R=0. 041. Thedimer contains a quasicentrosymmetric planar four-membered V2O2 ring with twoexocyclic glycollate entities coordinated by the oxygen atoms of hydroxy- and car-boxy late ligands .展开更多
基金supported by the National Key Research and Development Program of China(2019YFA0905100)the National Natural Science Foundation of China(21991102,22378227).
文摘Constructing a framework carrier to stabilize protein conformation,induce high embedding efficiency,and acquire low mass-transfer resistance is an urgent issue in the development of immobilized enzymes.Hydrogen-bonded organic frameworks(HOFs)have promising application potential for embedding enzymes.In fact,no metal involvement is required,and HOFs exhibit superior biocompatibility,and free access to substrates in mesoporous channels.Herein,a facile in situ growth approach was proposed for the self-assembly of alcohol dehydrogenase encapsulated in HOF.The micron-scale bio-catalytic composite was rapidly synthesized under mild conditions(aqueous phase and ambient temperature)with a controllable embedding rate.The high crystallinity and periodic arrangement channels of HOF were preserved at a high enzyme encapsulation efficiency of 59%.This bio-composite improved the tolerance of the enzyme to the acid-base environment and retained 81%of its initial activity after five cycles of batch hydrogenation involving NADH coenzyme.Based on this controllably synthesized bio-catalytic material and a common lipase,we further developed a two-stage cascade microchemical system and achieved the continuous production of chiral hydroxybutyric acid(R-3-HBA).
文摘Background:Ferroptosis is a type of regulated cell death characterized by iron-dependent lipid peroxidation,which has been linked to tumor progression and therapeutic resistance.However,the contribution of lactate metabolism and its receptor,hydroxycarboxylic acid receptor 1(HCAR1),in ferroptosis regulation in gastric cancer(GC)remains poorly understood.Focusing specifically on its effects on cell proliferation,ferroptosis regulation,and the disruption of lactate-mediatedmetabolic pathways,the study aimed to clarify the role ofHCAR1 in GC progression.Methods:Bioinformatics analysis identified prognostic genes associated with ferroptosis in GC.Receiver operating characteristic(ROC)curves were generated to assess the diagnostic potential of the predictive genes.The biological role of HCAR1 was investigated through gain and loss-of-function experiments in GC cell lines,followed by assessments of cell viability,oxidative stress indicators,gene/protein expression,and ferroptosis sensitivity under lactate stimulation or HCAR1modulation.Results:HCAR1 was significantly upregulated in GC tissues and linked to poor patient outcomes.Silencing HCAR1 inhibited GC cell growth and induced ferroptosis,as shown by increased levels of reactive oxygen species(ROS)and malondialdehyde(MDA),along with decreased expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).Conversely,HCAR1 overexpression or exposure to extracellular lactate inhibited ferroptosis and activated antioxidant defenses.Mechanistically,lactate activation of HCAR1 increases ATP levels,which in turn inactivates AMP-activated protein kinase(AMPK).It also upregulates stearoyl-CoA desaturase 1(SCD1)through the sterol regulatory element binding protein 1(SREBP1)signaling pathway.Blocking HCAR1 reversed these effects and restored ferroptosis sensitivity.Conclusion:HCAR1 mediates lactate-driven ferroptosis resistance in GC through the AMPK-SCD1 signaling pathway.Targeting the HCAR1-lactate axis may offer a promising strategy for overcoming metabolic adaptation and improving GC treatment outcomes.
文摘imeric ammonium(glycollate)dioxovanadium (NH4)2[V2O4(OCH2COO )2]has been prepared. The complex crystallizes in triclinic space group Pl with unitcell parameters: a = 0. 6124(1)nm, b= 0. 6952 (1)nm, c= 0. 8449 (1)nm, α=66. 08 (1),β=64. 21(1),γ= 78. 01(1)°V=0. 2958 nms, Z=1, R=0. 041. Thedimer contains a quasicentrosymmetric planar four-membered V2O2 ring with twoexocyclic glycollate entities coordinated by the oxygen atoms of hydroxy- and car-boxy late ligands .
