Synthesis and characteristics of poly(3,4-azopyridylene)(PAP),conductivity and oxygen-binding affinity of its complex with meso-α,α,α,α-tetrakis(o-pivalamidophenyl)porphyrinatocobalt(II)(COP)were studied.PAP was p...Synthesis and characteristics of poly(3,4-azopyridylene)(PAP),conductivity and oxygen-binding affinity of its complex with meso-α,α,α,α-tetrakis(o-pivalamidophenyl)porphyrinatocobalt(II)(COP)were studied.PAP was prepared by oxidative polymerization of 3,4-diaminopyridine(DAP)in DMF solution using CuCl/pyridine as the catalyst.IR and NMR results showed that the peak of amido group in DAP was converted to the azo group in PAP and a π conjugated polymer was synthesized.The average molecular weight of PAP was determined to be 5.0×10~3.The PAP-CoP complex was prepared by complexing the pyridyl group of PAP with the fifth coordination site of CoP in DMF solution.In comparison with the CoP complex with a non-π conjugated polymer,the PAP-CoP complex shows good electroconductivity of 5.8×10^(-6) S cm^(-1).The PAP-CoP complex displays a reversible change in the UV-Visible absorption spectrum from the deoxy form to the oxy or oxygen-binding one with an isosbestic point,in response to the partial oxygen pressure of the atmosphere.The oxygen- response behavior was monitored at the absorbance ascribed to the oxy form at 548 nm to give the oxygen-binding affinity. The oxygen-binding equilibrium curves of PAP-CoP complex obey a Langmuir isotherm.DMF has great effects on the oxygen-binding properties of the PAP-CoP complex.The oxygen-binding affinity of PAP-CoP complex in the solid state is higher than that in DMF solution.With decreasing temperature,the oxygen-binding affinity of the PAP-CoP complex increases.展开更多
The extent to which counterions bind to polyelectrolytes influences a variety of polymer-based applications, including polyelectrolyte enhanced ultrafiltration and forward osmosis using polyelectrolytes as draw agents...The extent to which counterions bind to polyelectrolytes influences a variety of polymer-based applications, including polyelectrolyte enhanced ultrafiltration and forward osmosis using polyelectrolytes as draw agents. Potentiometric titrations of poly (2-vinylpyridine) (P2VP), poly (3-vinylpyridine) (P3VP), and poly (4-vinylpydine) (P4VP) were performed using HBr, HCl, HNO<sub>3</sub>, and HClO<sub>4</sub> in both the presence and absence of added NaCl. Because of the systematic differences among the three polyelectrolytes, titration results provide insight into the role of polymer structure in the relative extents to which various counterions bind. Titration data reveal that ionization properties vary as functions of polymer investigated, titrant used, degree of protonation, and added salt concentration. Acid dissociation constants of the pyridinium moieties were found to generally increase with increasing degree of protonation, though appreciable differences were exhibited among the three polymers investigated. For all three polymers, Cl<sup>-</sup> demonstrated the lowest affinity for the charged pyridinium residues, while the affinities associated with Br<sup>-</sup> and NO<sup>-</sup>3</sub> were nearly identical to each other. The relative extent of binding for CIO<sup>-</sup>4</sub> varied across the polymers investigated, and was greatest for P4VP.展开更多
Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capa...Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capacity compared to olaparib.It is not affected by adenosine triphosphate(ATP)-binding cassette transporters.展开更多
目的:探究多聚胞嘧啶结合蛋白2[poly(C)-binding protein 2,PCBP2]如何通过调节铁死亡参与大别班达病毒(Dabie Banda virus,DBV)感染后的致病过程及其作用机制。方法:以人单核细胞系THP-1为模型,采用qRT-PCR和Western blot技术检测DBV...目的:探究多聚胞嘧啶结合蛋白2[poly(C)-binding protein 2,PCBP2]如何通过调节铁死亡参与大别班达病毒(Dabie Banda virus,DBV)感染后的致病过程及其作用机制。方法:以人单核细胞系THP-1为模型,采用qRT-PCR和Western blot技术检测DBV感染的THP-1细胞中PCBP2的mRNA及蛋白表达水平。通过透射电镜观察病毒感染下的线粒体结构变化,在THP-1细胞中构建了慢病毒介导的PCBP2过表达和敲低稳转细胞系。FerroOrange荧光探针检测Fe^(2+)水平,2,7-二氯荧光素二乙酸酯(2,7-dichlorofluorescein diacetate,DCFH-DA)探针测定活性氧(reactive oxygen species,ROS)水平,Western blot检测铁死亡相关溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)和谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)蛋白表达,以评估PCBP2调控对铁死亡的影响。使用铁死亡诱导剂(RSL3、erastin)和抑制剂(Fer-1、Lip-1)处理细胞,qRT-PCR和免疫荧光检测病毒复制水平变化,探索PCBP2是否可以通过调控铁死亡影响DBV复制。结果:在DBV感染的细胞模型中,PCBP2的mRNA和蛋白表达水平显著下调,DBV感染诱导典型铁死亡特征(线粒体嵴减少、肿胀)。通过qRT-PCR和Western blot验证,PCBP2敲低和过表达的THP-1细胞系构建成功,PCBP2敲低下调了铁死亡相关基因SLC7A11和GPX4的表达,导致ROS和Fe^(2+)水平升高;相反,PCBP2过表达使得SLC7A11和GPX4的表达水平升高,ROS和Fe^(2+)的水平降低。半数组织培养感染剂量与蛋白水平的检测进一步证实:铁死亡诱导剂可部分抵消PCBP2过表达促病毒复制的效应,铁死亡抑制剂可部分逆转PCBP2敲低抑制病毒复制的效应。结论:研究发现PCBP2可以通过维持SLC7A11/GPX4系统功能抑制铁死亡,从而限制DBV复制。这不仅阐明了PCBP2在DBV感染中的调控作用,为发热伴血小板减少综合征(severe fever with thrombocytope-nia syndrome,SFTS)的发病机制提供了新见解,同时靶向PCBP2-铁死亡通路可能成为SFTS治疗的潜在策略,为抗病毒药物的研发提供新思路。展开更多
The effect of temperature on the electrical conductivity(σ)and Seebeck coefficient(S)of n-type vapor grown carbon nanofibers(CNFs)and poly(vinylidene fluoride)(PVDF)melt-mixed with 15 wt%of those CNFs is analyzed.At ...The effect of temperature on the electrical conductivity(σ)and Seebeck coefficient(S)of n-type vapor grown carbon nanofibers(CNFs)and poly(vinylidene fluoride)(PVDF)melt-mixed with 15 wt%of those CNFs is analyzed.At 40°C,the CNFs show stable n-type character(S=-4.8μV·K^(-1))with anσof ca.165 S·m^(-1),while the PVDF/CNF composite film shows anσof ca.9 S·m^(-1)and near-zero S(S=-0.5μV·K^(-1)).This experimental reduction in S is studied by the density functional tight binding(DFTB)method revealing a contact electron transfer from the CNFs to the PVDF in the interface.Moreover,in the temperature range from 40°C to 100°C,theσ(T)of the CNFs and PVDF/CNF film,successfully described by the 3D variable range hopping(VRH)model,is explained as consequence of a thermally activated backscattering mechanism.On the contrary,the S(T)from 40°C to 100°C of the PVDF/CNF film,which satisfactorily matches the model proposed for some multi-walled carbon nanotube(MWCNT)doped mats;however,it does not follow the increase in S(T)found for CNFs.All these findings are presented with the aim of discerning the role of these n-type vapor grown carbon nanofibers on theσand S of their melt-mixed polymer composites.展开更多
Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits...Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PLGA-COOH and PLGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DLS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PLGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PLGA-PEG-NH2 indicating conformational changes in the protein structure.展开更多
目的探讨聚(rC)结合蛋白1[Poly(rC)-binding protein 1,PCBP1]在镉(Cadmium,Cd)诱导小鼠神经细胞Neuro-2a(N2A)铁死亡中的作用。方法以N2A细胞构建浓度梯度(0、1、2、4μmol/L)CdCl_(2)体外暴露模型(72 h)。通过台盼蓝染色检测细胞存活...目的探讨聚(rC)结合蛋白1[Poly(rC)-binding protein 1,PCBP1]在镉(Cadmium,Cd)诱导小鼠神经细胞Neuro-2a(N2A)铁死亡中的作用。方法以N2A细胞构建浓度梯度(0、1、2、4μmol/L)CdCl_(2)体外暴露模型(72 h)。通过台盼蓝染色检测细胞存活率,Western blot分析铁死亡相关蛋白(GPX4、HMOX1、ACSL4)及PCBP1表达。以FerroOrange和BODIPY^(581/591)C11探针检测胞内Fe^(2+)和脂质过氧化水平。应用铁死亡抑制剂Fer-1明确铁死亡在镉暴露抑制N2A细胞存活率中的重要作用。以分子对接技术解析PCBP1与铁蛋白的互作模式及与Cd^(2+)的结合位点。进一步构建PCBP1过表达质粒验证其重要作用及功能。结果镉暴露以剂量依赖性方式抑制细胞存活率(P<0.01),显著下调GPX4表达水平(P<0.05),上调HMOX1表达水平(P<0.01),诱导Fe^(2+)过量蓄积及脂质过氧化水平显著增加(P<0.01)。分子对接揭示,Cd^(2+)可直接结合PCBP1的KH2结构域,并且可共同结合于铁蛋白重链外侧。过表达PCBP1可明显逆转镉暴露诱导的Fe^(2+)蓄积、GPX4表达下调、过氧化脂质增加及细胞存活率下降。结论镉暴露通过抑制PCBP1表达及以金属离子竞争扰乱PCBP1介导的铁稳态网络,协同驱动Fe^(2+)超载触发铁死亡级联反应,最终导致神经毒性。靶向PCBP1介导的铁稳态可有效抑制铁死亡,为干预镉神经毒性提供新策略。展开更多
目的探究受体酪氨酸激酶样孤儿受体2(receptor tyrosine kinase like orphan receptor 2,ROR2)是否通过调控聚(rc)结合蛋白1[poly(rc)-inding protein 1,PCBP1)]激活PI3K/AKT信号通路,从而调控胃癌细胞增殖、侵袭和细胞周期进程。方法...目的探究受体酪氨酸激酶样孤儿受体2(receptor tyrosine kinase like orphan receptor 2,ROR2)是否通过调控聚(rc)结合蛋白1[poly(rc)-inding protein 1,PCBP1)]激活PI3K/AKT信号通路,从而调控胃癌细胞增殖、侵袭和细胞周期进程。方法将胃癌细胞HGC-27通过免疫共沉淀/高效液相色谱联合质谱(co-immunoprecipitation/liquid chromatography-tandem mass spectrometry,Co-IP/LC-MS/MS)分析鉴定出ROR2潜在相互结合蛋白。通过Co-IP实验及蛋白-蛋白对接实验检测PCBP1与ROR2的相互结合。通过Western blot实验检测人胃癌细胞AGS、MKN-45、HGC-27及MGC-803中ROR2降表达及过表达后PCBP1的蛋白表达情况。通过Western blot、生长指数(growth index,GI)和Transwell实验检测ROR2通过PCBP1对PI3K/AKT信号通路及胃癌细胞增殖、侵袭和细胞周期进程的调控情况。通过免疫组织化学染色技术(immunohistochemistry,IHC)检测人胃癌临床样本、裸鼠胃癌皮下成瘤组织中ROR2与PCBP1的表达。通过R2在线数据库分析ROR2与PCBP1在胃癌中表达的相关性。结果Co-IP/LC-MS/MS、Co-IP及蛋白-蛋白对接实验表明,ROR2与PCBP1相互结合。Western blot实验表明,在人胃癌细胞中,过表达ROR2上调PCBP1蛋白水平,降表达ROR2下调PCBP1蛋白水平,差异均有统计学意义(P均<0.05)。Western blot、GI及Transwell实验表明,ROR2通过上调PCBP1表达激活PI3K/AKT信号通路,从而促进胃癌细胞增殖、侵袭和细胞周期进程,差异有统计学意义(P均<0.05)。IHC表明,在人胃癌组织及ROR2过表达的裸鼠皮下成瘤组织中,ROR2与PCBP1表达呈正相关,差异均有统计学意义(P均<0.05)。数据库分析表明,ROR2与PCBP1的表达呈正相关,差异均有统计学意义(P均<0.05)。结论ROR2与PCBP1在胃癌中相互作用,ROR2和PCBP1在胃癌中高表达且ROR2在细胞水平、动物水平及临床样本水平都正向调控PCBP1。ROR2通过上调PCBP1蛋白表达激活PI3K/AKT信号通路,从而促进胃癌细胞增殖、侵袭和细胞周期进程。展开更多
基金This work was supported by the National Natural Science Foundation of China(No.50373035)Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry
文摘Synthesis and characteristics of poly(3,4-azopyridylene)(PAP),conductivity and oxygen-binding affinity of its complex with meso-α,α,α,α-tetrakis(o-pivalamidophenyl)porphyrinatocobalt(II)(COP)were studied.PAP was prepared by oxidative polymerization of 3,4-diaminopyridine(DAP)in DMF solution using CuCl/pyridine as the catalyst.IR and NMR results showed that the peak of amido group in DAP was converted to the azo group in PAP and a π conjugated polymer was synthesized.The average molecular weight of PAP was determined to be 5.0×10~3.The PAP-CoP complex was prepared by complexing the pyridyl group of PAP with the fifth coordination site of CoP in DMF solution.In comparison with the CoP complex with a non-π conjugated polymer,the PAP-CoP complex shows good electroconductivity of 5.8×10^(-6) S cm^(-1).The PAP-CoP complex displays a reversible change in the UV-Visible absorption spectrum from the deoxy form to the oxy or oxygen-binding one with an isosbestic point,in response to the partial oxygen pressure of the atmosphere.The oxygen- response behavior was monitored at the absorbance ascribed to the oxy form at 548 nm to give the oxygen-binding affinity. The oxygen-binding equilibrium curves of PAP-CoP complex obey a Langmuir isotherm.DMF has great effects on the oxygen-binding properties of the PAP-CoP complex.The oxygen-binding affinity of PAP-CoP complex in the solid state is higher than that in DMF solution.With decreasing temperature,the oxygen-binding affinity of the PAP-CoP complex increases.
文摘The extent to which counterions bind to polyelectrolytes influences a variety of polymer-based applications, including polyelectrolyte enhanced ultrafiltration and forward osmosis using polyelectrolytes as draw agents. Potentiometric titrations of poly (2-vinylpyridine) (P2VP), poly (3-vinylpyridine) (P3VP), and poly (4-vinylpydine) (P4VP) were performed using HBr, HCl, HNO<sub>3</sub>, and HClO<sub>4</sub> in both the presence and absence of added NaCl. Because of the systematic differences among the three polyelectrolytes, titration results provide insight into the role of polymer structure in the relative extents to which various counterions bind. Titration data reveal that ionization properties vary as functions of polymer investigated, titrant used, degree of protonation, and added salt concentration. Acid dissociation constants of the pyridinium moieties were found to generally increase with increasing degree of protonation, though appreciable differences were exhibited among the three polymers investigated. For all three polymers, Cl<sup>-</sup> demonstrated the lowest affinity for the charged pyridinium residues, while the affinities associated with Br<sup>-</sup> and NO<sup>-</sup>3</sub> were nearly identical to each other. The relative extent of binding for CIO<sup>-</sup>4</sub> varied across the polymers investigated, and was greatest for P4VP.
基金supported in part by funding from BeiGene,Ltd.,USA(Grant No.:KPR081)with additional support from the Alessandra Bono Foundation,Italy.
文摘Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capacity compared to olaparib.It is not affected by adenosine triphosphate(ATP)-binding cassette transporters.
文摘目的:探究多聚胞嘧啶结合蛋白2[poly(C)-binding protein 2,PCBP2]如何通过调节铁死亡参与大别班达病毒(Dabie Banda virus,DBV)感染后的致病过程及其作用机制。方法:以人单核细胞系THP-1为模型,采用qRT-PCR和Western blot技术检测DBV感染的THP-1细胞中PCBP2的mRNA及蛋白表达水平。通过透射电镜观察病毒感染下的线粒体结构变化,在THP-1细胞中构建了慢病毒介导的PCBP2过表达和敲低稳转细胞系。FerroOrange荧光探针检测Fe^(2+)水平,2,7-二氯荧光素二乙酸酯(2,7-dichlorofluorescein diacetate,DCFH-DA)探针测定活性氧(reactive oxygen species,ROS)水平,Western blot检测铁死亡相关溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)和谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)蛋白表达,以评估PCBP2调控对铁死亡的影响。使用铁死亡诱导剂(RSL3、erastin)和抑制剂(Fer-1、Lip-1)处理细胞,qRT-PCR和免疫荧光检测病毒复制水平变化,探索PCBP2是否可以通过调控铁死亡影响DBV复制。结果:在DBV感染的细胞模型中,PCBP2的mRNA和蛋白表达水平显著下调,DBV感染诱导典型铁死亡特征(线粒体嵴减少、肿胀)。通过qRT-PCR和Western blot验证,PCBP2敲低和过表达的THP-1细胞系构建成功,PCBP2敲低下调了铁死亡相关基因SLC7A11和GPX4的表达,导致ROS和Fe^(2+)水平升高;相反,PCBP2过表达使得SLC7A11和GPX4的表达水平升高,ROS和Fe^(2+)的水平降低。半数组织培养感染剂量与蛋白水平的检测进一步证实:铁死亡诱导剂可部分抵消PCBP2过表达促病毒复制的效应,铁死亡抑制剂可部分逆转PCBP2敲低抑制病毒复制的效应。结论:研究发现PCBP2可以通过维持SLC7A11/GPX4系统功能抑制铁死亡,从而限制DBV复制。这不仅阐明了PCBP2在DBV感染中的调控作用,为发热伴血小板减少综合征(severe fever with thrombocytope-nia syndrome,SFTS)的发病机制提供了新见解,同时靶向PCBP2-铁死亡通路可能成为SFTS治疗的潜在策略,为抗病毒药物的研发提供新思路。
基金financially supported by the European Regional Development Fund through the Operational Competitiveness Program and the National Foundation for Science and Technology of Portugal(FCT)(No.UID/CTM/00264/2020 of Centre for Textile Science and Technology(2C2T)on its components Base and programmatic)support from project GreenAuto-Green Innovation for the Automotive Industry-PPS 3-Technical Textiles for the vehicle(Refa C6448637037-00000013)financed by EU funds,through the Plano de Recuperacao e Resiliência(PRR),managed by IAPMEI,I.P.-Agência para a Competitividade e Inovacao+2 种基金support within the scope of the project CICECO-Aveiro Institute of Materials,UIDB/50011/2020,UIDP/50011/2020&LA/P/0006/2020,financed by national funds through the FCT/MCTES(PIDDAC)support from the Spanish Ministry of Universities with European Union funds-Next Generation EU through a Margarita Salas fellowshipsupport received from National Science Foundation under PREM award DMR 2122178。
文摘The effect of temperature on the electrical conductivity(σ)and Seebeck coefficient(S)of n-type vapor grown carbon nanofibers(CNFs)and poly(vinylidene fluoride)(PVDF)melt-mixed with 15 wt%of those CNFs is analyzed.At 40°C,the CNFs show stable n-type character(S=-4.8μV·K^(-1))with anσof ca.165 S·m^(-1),while the PVDF/CNF composite film shows anσof ca.9 S·m^(-1)and near-zero S(S=-0.5μV·K^(-1)).This experimental reduction in S is studied by the density functional tight binding(DFTB)method revealing a contact electron transfer from the CNFs to the PVDF in the interface.Moreover,in the temperature range from 40°C to 100°C,theσ(T)of the CNFs and PVDF/CNF film,successfully described by the 3D variable range hopping(VRH)model,is explained as consequence of a thermally activated backscattering mechanism.On the contrary,the S(T)from 40°C to 100°C of the PVDF/CNF film,which satisfactorily matches the model proposed for some multi-walled carbon nanotube(MWCNT)doped mats;however,it does not follow the increase in S(T)found for CNFs.All these findings are presented with the aim of discerning the role of these n-type vapor grown carbon nanofibers on theσand S of their melt-mixed polymer composites.
文摘Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PLGA-COOH and PLGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DLS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PLGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PLGA-PEG-NH2 indicating conformational changes in the protein structure.
文摘目的探讨聚(rC)结合蛋白1[Poly(rC)-binding protein 1,PCBP1]在镉(Cadmium,Cd)诱导小鼠神经细胞Neuro-2a(N2A)铁死亡中的作用。方法以N2A细胞构建浓度梯度(0、1、2、4μmol/L)CdCl_(2)体外暴露模型(72 h)。通过台盼蓝染色检测细胞存活率,Western blot分析铁死亡相关蛋白(GPX4、HMOX1、ACSL4)及PCBP1表达。以FerroOrange和BODIPY^(581/591)C11探针检测胞内Fe^(2+)和脂质过氧化水平。应用铁死亡抑制剂Fer-1明确铁死亡在镉暴露抑制N2A细胞存活率中的重要作用。以分子对接技术解析PCBP1与铁蛋白的互作模式及与Cd^(2+)的结合位点。进一步构建PCBP1过表达质粒验证其重要作用及功能。结果镉暴露以剂量依赖性方式抑制细胞存活率(P<0.01),显著下调GPX4表达水平(P<0.05),上调HMOX1表达水平(P<0.01),诱导Fe^(2+)过量蓄积及脂质过氧化水平显著增加(P<0.01)。分子对接揭示,Cd^(2+)可直接结合PCBP1的KH2结构域,并且可共同结合于铁蛋白重链外侧。过表达PCBP1可明显逆转镉暴露诱导的Fe^(2+)蓄积、GPX4表达下调、过氧化脂质增加及细胞存活率下降。结论镉暴露通过抑制PCBP1表达及以金属离子竞争扰乱PCBP1介导的铁稳态网络,协同驱动Fe^(2+)超载触发铁死亡级联反应,最终导致神经毒性。靶向PCBP1介导的铁稳态可有效抑制铁死亡,为干预镉神经毒性提供新策略。
