One of the phenolic acids is 4-hydroxybenzoic acid(HBA)which takes the form of a white crystalline solid with a molecular formula of C 7H 6O 3,a melting point of 214.5℃and a molecular weight of 138.12 g·mol^(-1)...One of the phenolic acids is 4-hydroxybenzoic acid(HBA)which takes the form of a white crystalline solid with a molecular formula of C 7H 6O 3,a melting point of 214.5℃and a molecular weight of 138.12 g·mol^(-1).It soluble in polar organic solvents like acetone and alcohols,and slightly soluble in chloroform and water.The reactions between the metal ions and the HBA were carried out under specific conditions like(molar reaction was 2∶2(ligand to metal),reaction temperature was 60℃,media was neutral(pH 7),and solvent was H 2O∶MeOH(1∶1).Under these conditions,the HBA was deprotonated to form(HOC_(6)H_(4)CO^(2);L^(-)).The ligand L-was coordinated to the metal ions forming the metal complexation.The reaction of 4-hydroxybenzoic acid(HOC 6H 4CO 2H;HL)with the Ni(Ⅱ),Mn(Ⅱ)and Cu(Ⅱ)ions afford metal-complexes with gross formula of[Ni_(2)L_(2)(NO_(3))_(2)(H_(2)O)_(4)],[Mn_(2)L_(2)(NO_(3))_(2)(H_(2)O)_(4)]and[Cu_(2)L_(2)(NO_(3))_(2)(H_(2)O)_(4)],respectively.These complexes were characterized by elemental analysis(CHN),magnetic susceptibility,UV-Vis spectra,infrared(IR),and X-ray powder diffraction(XRD)techniques.The complexes of HBA are insoluble in common solvents and hence molar conductance could not be measured,but this very insolubility indicates that the complexes are neutral.Data has demonstrated that the ligand(L^(-))was coordinated to the metal ion by bidentate bridging carboxylate group(COO^(-)),with an octahedral geometry.Thus,HBA is expected to act as bidentate uninegative ions and the coordination number of the metal ions is six.XRD results showed that the complexes possess uniform and organized microstructures in the nanometer range with a main diameter in the range of 11~28 nm.展开更多
A new metal-organic framework based on bbi and PHBA（bbi = 1,1＇-（1, 4-butanediyl）bis（imidazole）, PHBA = p-hydroxybenzoic acid）, namely, [Cd（bbi）（PHBA）2]n（1） has been synthesized by the conventional method....A new metal-organic framework based on bbi and PHBA（bbi = 1,1＇-（1, 4-butanediyl）bis（imidazole）, PHBA = p-hydroxybenzoic acid）, namely, [Cd（bbi）（PHBA）2]n（1） has been synthesized by the conventional method. Compound 1 displays a two-dimensional（2D） layer structure possessing the left-and right-handed helical chains and stabilized by intermolecular hydrogen-bonding to form a three-dimensional（3D） supramolecular structure. Topologically, the 2D layer belongs to well-known（4,4） network topology. The structure has been determined by single-crystal X-ray diffraction analyses, and further characterized by infrared spectra（IR）, elemental analyses and powder X-ray diffraction. In addition, the thermal behavior and luminescent properties of [Cd（bbi）（PHBA）2]n have been investigated in detail.展开更多
A new complex [Cd（hba）2（bib）]n·nH2O（1,Hhba = 3-hydroxybenzoic acid,bib = 1,4-bis（imidazol-1-yl）-butane） has been hydrothermally synthesized and characterized by elemental analysis,IR spectrum,thermogravim...A new complex [Cd（hba）2（bib）]n·nH2O（1,Hhba = 3-hydroxybenzoic acid,bib = 1,4-bis（imidazol-1-yl）-butane） has been hydrothermally synthesized and characterized by elemental analysis,IR spectrum,thermogravimetric analysis,fluorescence spectrum,and singlecrystal X-ray diffraction.Yellow crystal crystallizes in the orthorhombic system,space group Pbca with a = 16.220（5）,b = 14.980（5）,c = 20.521（5） ？,V = 4986（3） ？~3,C（24）H（26）CdN4O7,Mr = 594.89,Dc = 1.585 g/cm^3,μ（Mo Kα） = 0.927 mm^（-1）,F（000） = 2416,Z = 8,the final R = 0.0242 and w R = 0.0589 for 4076 observed reflections（I 〉 2s（I））.In 1,the Cd（Ⅱ） ion takes a six-coordination mode,and bib ligand bridges adjacent Cd（Ⅱ） ions to generate 1D zigzag chains; these neighboring chains are connected by O–H···O hydrogen bonding interactions,producing a 2D folded layered structure.Furthermore,by O–H···O hydrogen bonding between layers and layers,a 3D supramolecular architecture is formed.In addition,we analyzed Natural Bond Orbital（NBO） in using the PBE0/LANL2 DZ method built in Gaussian 03 Program.The calculation results indicated obvious covalent interaction between the coordinated atoms and Cd（Ⅱ） ion.展开更多
High spatiotemporal resolution infrared radiances from FY-4A/AGRI(Advanced Geostationary Radiation Imager)can provide crucial information for rapidly developing severe convective weather.This study established a symme...High spatiotemporal resolution infrared radiances from FY-4A/AGRI(Advanced Geostationary Radiation Imager)can provide crucial information for rapidly developing severe convective weather.This study established a symmetric observation error model that differentiates between land and sea for FY-4A/AGRI all-sky assimilation,developed an all-sky assimilation scheme for FY-4A/AGRI based on hydrometeor control variables,and investigated the impacts of all-sky FY-4A/AGRI water vapor channels at different altitudes and rapid-update assimilation at different frequencies on the assimilation and forecasting of a severe convective weather event.Results show that simultaneous assimilation of two water vapor channels can enhance precipitation forecasts compared to single-channel assimilation,which is mainly attributable to a more accurate analysis of water vapor and hydrometeor information.Experiments with different assimilation frequencies demonstrate that the hourly assimilation frequency,compared to other frequencies,incorporates the high-frequency information from AGRI while reducing the impact of spurious oscillations caused by excessively high-frequency assimilation.This hourly assimilation frequency reduces the incoordination among thermal,dynamical,and water vapor conditions caused by excessively fast or slow assimilation frequencies,thus improving the forecast accuracy compared to other frequencies.展开更多
The rapid growth of distributed data-centric applications and AI workloads increases demand for low-latency,high-throughput communication,necessitating frequent and flexible updates to network routing configurations.H...The rapid growth of distributed data-centric applications and AI workloads increases demand for low-latency,high-throughput communication,necessitating frequent and flexible updates to network routing configurations.However,maintaining consistent forwarding states during these updates is challenging,particularly when rerouting multiple flows simultaneously.Existing approaches pay little attention to multi-flow update,where improper update sequences across data plane nodes may construct deadlock dependencies.Moreover,these methods typically involve excessive control-data plane interactions,incurring significant resource overhead and performance degradation.This paper presents P4LoF,an efficient loop-free update approach that enables the controller to reroute multiple flows through minimal interactions.P4LoF first utilizes a greedy-based algorithm to generate the shortest update dependency chain for the single-flow update.These chains are then dynamically merged into a dependency graph and resolved as a Shortest Common Super-sequence(SCS)problem to produce the update sequence of multi-flow update.To address deadlock dependencies in multi-flow updates,P4LoF builds a deadlock-fix forwarding model that leverages the flexible packet processing capabilities of the programmable data plane.Experimental results show that P4LoF reduces control-data plane interactions by at least 32.6%with modest overhead,while effectively guaranteeing loop-free consistency.展开更多
Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a ...Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.展开更多
Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kines...Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
基金the deanship of scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding program。
文摘One of the phenolic acids is 4-hydroxybenzoic acid(HBA)which takes the form of a white crystalline solid with a molecular formula of C 7H 6O 3,a melting point of 214.5℃and a molecular weight of 138.12 g·mol^(-1).It soluble in polar organic solvents like acetone and alcohols,and slightly soluble in chloroform and water.The reactions between the metal ions and the HBA were carried out under specific conditions like(molar reaction was 2∶2(ligand to metal),reaction temperature was 60℃,media was neutral(pH 7),and solvent was H 2O∶MeOH(1∶1).Under these conditions,the HBA was deprotonated to form(HOC_(6)H_(4)CO^(2);L^(-)).The ligand L-was coordinated to the metal ions forming the metal complexation.The reaction of 4-hydroxybenzoic acid(HOC 6H 4CO 2H;HL)with the Ni(Ⅱ),Mn(Ⅱ)and Cu(Ⅱ)ions afford metal-complexes with gross formula of[Ni_(2)L_(2)(NO_(3))_(2)(H_(2)O)_(4)],[Mn_(2)L_(2)(NO_(3))_(2)(H_(2)O)_(4)]and[Cu_(2)L_(2)(NO_(3))_(2)(H_(2)O)_(4)],respectively.These complexes were characterized by elemental analysis(CHN),magnetic susceptibility,UV-Vis spectra,infrared(IR),and X-ray powder diffraction(XRD)techniques.The complexes of HBA are insoluble in common solvents and hence molar conductance could not be measured,but this very insolubility indicates that the complexes are neutral.Data has demonstrated that the ligand(L^(-))was coordinated to the metal ion by bidentate bridging carboxylate group(COO^(-)),with an octahedral geometry.Thus,HBA is expected to act as bidentate uninegative ions and the coordination number of the metal ions is six.XRD results showed that the complexes possess uniform and organized microstructures in the nanometer range with a main diameter in the range of 11~28 nm.
基金Supported by the Science and Technology Development Plan of Jilin Province(20150520006JH)Science and Technology Research Project of Education Department of Jilin Province(2016219)Science and Technology Development Plan of Siping City(2013055)
文摘A new metal-organic framework based on bbi and PHBA（bbi = 1,1＇-（1, 4-butanediyl）bis（imidazole）, PHBA = p-hydroxybenzoic acid）, namely, [Cd（bbi）（PHBA）2]n（1） has been synthesized by the conventional method. Compound 1 displays a two-dimensional（2D） layer structure possessing the left-and right-handed helical chains and stabilized by intermolecular hydrogen-bonding to form a three-dimensional（3D） supramolecular structure. Topologically, the 2D layer belongs to well-known（4,4） network topology. The structure has been determined by single-crystal X-ray diffraction analyses, and further characterized by infrared spectra（IR）, elemental analyses and powder X-ray diffraction. In addition, the thermal behavior and luminescent properties of [Cd（bbi）（PHBA）2]n have been investigated in detail.
基金supported by the Science and Technology Development Project of Jilin Provincial Science&Technology Department(201205080)the Science and Technology Research Projects of the Education Office of Jilin Province(No.2013.384)
文摘A new complex [Cd（hba）2（bib）]n·nH2O（1,Hhba = 3-hydroxybenzoic acid,bib = 1,4-bis（imidazol-1-yl）-butane） has been hydrothermally synthesized and characterized by elemental analysis,IR spectrum,thermogravimetric analysis,fluorescence spectrum,and singlecrystal X-ray diffraction.Yellow crystal crystallizes in the orthorhombic system,space group Pbca with a = 16.220（5）,b = 14.980（5）,c = 20.521（5） ？,V = 4986（3） ？~3,C（24）H（26）CdN4O7,Mr = 594.89,Dc = 1.585 g/cm^3,μ（Mo Kα） = 0.927 mm^（-1）,F（000） = 2416,Z = 8,the final R = 0.0242 and w R = 0.0589 for 4076 observed reflections（I 〉 2s（I））.In 1,the Cd（Ⅱ） ion takes a six-coordination mode,and bib ligand bridges adjacent Cd（Ⅱ） ions to generate 1D zigzag chains; these neighboring chains are connected by O–H···O hydrogen bonding interactions,producing a 2D folded layered structure.Furthermore,by O–H···O hydrogen bonding between layers and layers,a 3D supramolecular architecture is formed.In addition,we analyzed Natural Bond Orbital（NBO） in using the PBE0/LANL2 DZ method built in Gaussian 03 Program.The calculation results indicated obvious covalent interaction between the coordinated atoms and Cd（Ⅱ） ion.
基金supported by the National Key R&D Program of China(Grant No.2022YFC3080500)the National Natural Science Foundation of China(Grant Nos.U2142208,42475158,and 42105149)the High-Performance Computing Center of Nanjing University of Information Science&Technology for supporting this work。
文摘High spatiotemporal resolution infrared radiances from FY-4A/AGRI(Advanced Geostationary Radiation Imager)can provide crucial information for rapidly developing severe convective weather.This study established a symmetric observation error model that differentiates between land and sea for FY-4A/AGRI all-sky assimilation,developed an all-sky assimilation scheme for FY-4A/AGRI based on hydrometeor control variables,and investigated the impacts of all-sky FY-4A/AGRI water vapor channels at different altitudes and rapid-update assimilation at different frequencies on the assimilation and forecasting of a severe convective weather event.Results show that simultaneous assimilation of two water vapor channels can enhance precipitation forecasts compared to single-channel assimilation,which is mainly attributable to a more accurate analysis of water vapor and hydrometeor information.Experiments with different assimilation frequencies demonstrate that the hourly assimilation frequency,compared to other frequencies,incorporates the high-frequency information from AGRI while reducing the impact of spurious oscillations caused by excessively high-frequency assimilation.This hourly assimilation frequency reduces the incoordination among thermal,dynamical,and water vapor conditions caused by excessively fast or slow assimilation frequencies,thus improving the forecast accuracy compared to other frequencies.
基金supported by the National Key Research and Development Program of China under Grant 2022YFB2901501in part by the Science and Technology Innovation leading Talents Subsidy Project of Central Plains under Grant 244200510038.
文摘The rapid growth of distributed data-centric applications and AI workloads increases demand for low-latency,high-throughput communication,necessitating frequent and flexible updates to network routing configurations.However,maintaining consistent forwarding states during these updates is challenging,particularly when rerouting multiple flows simultaneously.Existing approaches pay little attention to multi-flow update,where improper update sequences across data plane nodes may construct deadlock dependencies.Moreover,these methods typically involve excessive control-data plane interactions,incurring significant resource overhead and performance degradation.This paper presents P4LoF,an efficient loop-free update approach that enables the controller to reroute multiple flows through minimal interactions.P4LoF first utilizes a greedy-based algorithm to generate the shortest update dependency chain for the single-flow update.These chains are then dynamically merged into a dependency graph and resolved as a Shortest Common Super-sequence(SCS)problem to produce the update sequence of multi-flow update.To address deadlock dependencies in multi-flow updates,P4LoF builds a deadlock-fix forwarding model that leverages the flexible packet processing capabilities of the programmable data plane.Experimental results show that P4LoF reduces control-data plane interactions by at least 32.6%with modest overhead,while effectively guaranteeing loop-free consistency.
基金supported by the Chinese Medicine"Dual Chain Integration"Young and Middle-aged Scientific Research and Innovation Teams(No.2022-SLRH-YQ-006)the Key R&D Programme Projects of Xianyang Municipality(No.L2023-ZDYF-SF-014)+1 种基金the Shaanxi University of Traditional Chinese Medicine Science,Education and Research Collaborative Educational Achievement Transformation Project(No.2024KC03)the open research topic from the Key Laboratory of Neurological Diseases in Traditional Chinese Medicine,Shaanxi Province(No.KF202315).
文摘Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.
基金supported by the Portuguese Foundation for Science and Technology(FCT),Centro 2020 and Portugol2020 and the EU FEDER program,via the project GoBack to SIV(PTDC/CVT-CVT/32261/2017,CENTRO-01-0145-FEDER-032261)the doctoral grants of PDC(SFRH/BD/139974/2018)and BMS(2020.06525.BD and DOI 10.54499/2020.06525.BD)+5 种基金the post-doctoral grant to JPF(SFRH/BPD/113359/2015-program-contract described in paragraphs 4,5,6 of art.23 of Law no.100157/2016,of August 29,as amended by Law no.57/2017 of July 2019),the project PTDC/MED-NEU/1677/2021 to JBRthe Institute of Biomedicine iBiMED(UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020,UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020)its LiM Bioimaging Facility-a PPBI node(POCI-01-0145-FEDER-022122)supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University(HHU)Düsseldorf,of the Biologisch-Medizinisches Forschungszentrum(BMFZ)of HHUfinanced by the Spanish"Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica,Ministerio de Economia y Competitividad(Instituto de Salud CarlosⅢ)",co-financed by the European Union(FEDER program),(grant FIS P/20/00318 and FIS P23/00337 to VC)grant CPP2021-009070 to VC by the"Proyectos de colaboracion publico-privada,Plan de Investigacion Cientifica,Tecnica y de inovacion 2021-2023,Ministerio de Ciencia e Innovacion,Union Europea,Agencia Estatal de Investigacion,Espana"。
文摘Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
