Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is ge...Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is generally preferred for use in practice.Herein,a versatile peptide,(HE)_(10)G_(5)R_(6)GDK(HE-RK),was engineered by integrating several motifs into a single sequence,including a masking segment(HE),a flexible linker(G_(5)),and a tumor-penetrating head(RK)which comprised a cell-penetrating peptide(R_(6))and a C-end Rule peptide(RGDK).The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells.Moreover,in our study,polymer micelles conjugated with the HE-RK peptide(PM-HE-RK)showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro,as well as extended blood circulation time and improved tumor targeting and penetration in vivo.Furthermore,the paclitaxel-loaded micelles(PTX/PM-HERK)demonstrated considerable antitumor efficacy,with an 81.48%tumor inhibition rate in the 4T1 mouse model.Overall,the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.展开更多
目的研究姜黄素和维生素C添加对三文鱼烤制过程中有害物杂环胺(heterocyclic amines,HAAs)和晚期糖基化终末产物(advanced glycation end products,AGEs)的抑制作用,以及外源添加物对烤三文鱼风味的影响。方法通过高效液相色谱-串联质...目的研究姜黄素和维生素C添加对三文鱼烤制过程中有害物杂环胺(heterocyclic amines,HAAs)和晚期糖基化终末产物(advanced glycation end products,AGEs)的抑制作用,以及外源添加物对烤三文鱼风味的影响。方法通过高效液相色谱-串联质谱法测定HAAs和AGEs浓度,进一步测定还原糖、肌酸、肌酐、乙二醛等前体物以及脂质氧化水平解析其抑制机制,运用气相色谱-离子迁移谱法分析三文鱼烤制中挥发性风味变化。结果与对照组相比,姜黄素和维生素C对HAAs和AGEs表现出显著抑制效果(P˂0.05),总HAAs抑制率分别为75.21%和59.52%;AGEs中Nε-羧甲基赖氨酸抑制率分别为90.56%和90.87%,N^(ε)-羧乙基赖氨酸抑制率为94.57%和94.80%。还原糖、肌酸、肌酐、乙二醛等前体物浓度与HAAs和AGEs含量呈现高度相关。此外,通过挥发性风味分析表明添加姜黄素和维生素C对烤三文鱼风味有一定影响,增加了香味物质3-羟基-2-丁酮、2,6-二甲基-7-辛烯-2-醇、薄荷醇等化合物浓度,为三文鱼总体气味贡献重要作用。结论姜黄素和维生素C影响了HAAs和AGEs形成的关键前体物、中间体,具有显著抑制效果。本研究的开展为鱼肉制品热加工有害物控制提供了理论指导,并为优化鱼肉制品加工工艺提供了参考。展开更多
目的:探讨血清高敏C反应蛋白(hsCRP)水平与致心律失常性心肌病(ACM)患者临床特征及预后的关系,评估其对终末期心力衰竭事件(ESHF)风险的预测价值。方法:回顾性纳入临界诊断及确诊ACM的患者328例,根据基线hsCRP实验室标准分为低水平组(≤...目的:探讨血清高敏C反应蛋白(hsCRP)水平与致心律失常性心肌病(ACM)患者临床特征及预后的关系,评估其对终末期心力衰竭事件(ESHF)风险的预测价值。方法:回顾性纳入临界诊断及确诊ACM的患者328例,根据基线hsCRP实验室标准分为低水平组(≤3 mg/L,251例)和高水平组(>3 mg/L,77例)。收集病史、检查及检验资料,并比较2组间差异。采用Spearman相关分析、受试者工作特征(ROC)曲线分析、Kaplan-Meier生存分析及Cox比例风险模型评估hsCRP与心功能关联及对ESHF的预测价值。结果:研究人群中,男性占68.9%,致病/可能致病基因突变检出率为44.8%。hsCRP高水平组患者心功能及左室射血分数(LVEF)较差,右心室扩张与氨基末端B型利钠肽前体(NT-proBNP)水平显著升高(P均<0.05),但既往恶性室性心律失常发生率比较,差异无统计学意义(P>0.05)。Spearman相关性分析显示,hsCRP与LVEF呈负相关(r=-0.257,P<0.001),与NT-proBNP(r=0.307,P<0.001)及右心室内径(r=0.115,P=0.039)呈正相关。基因阳性及阴性患者hsCRP水平相近,但在不同心室受累患者中分布不同,在双心室受累患者中水平更高(趋势P=0.005)。ROC曲线分析示,hsCRP预测1、3及5年ESHF事件的曲线下面积(AUC)分别为0.640、0.662、0.654。Kaplan-Meier分析示,hsCRP高水平组随访期间无ESHF生存率显著降低(平均生存97.2 vs 150.5个月,P<0.001)。多因素Cox回归示,hsCRP分别独立于传统心室结构及心力衰竭指标(LVEF、右心室扩张及NT-proBNP)与ESHF风险显著相关(hsCRP作连续及分类变量,P均<0.05)。矫正年龄、性别、NT-proBNP及右心室扩张后,hsCRP水平仍与ESHF风险独立相关(连续变量HR:1.071,95%CI:1.011~1.135,P=0.020;分类变量HR:1.833,95%CI:1.115~3.014,P=0.017)。结论:血清hsCRP升高与ACM患者的心力衰竭和不良结局密切相关,可作为潜在生物标志物用于辅助ACM患者未来ESHF事件的预测。展开更多
C\-\{60\}\|end\|bonded polystryrenes(PS\|C\-\{60\}\|Br) with narrow molecular weight polydispersity were prepared by atom transfer radical polymerization (ATRP) in good yield.GPC results show that the polydispersities...C\-\{60\}\|end\|bonded polystryrenes(PS\|C\-\{60\}\|Br) with narrow molecular weight polydispersity were prepared by atom transfer radical polymerization (ATRP) in good yield.GPC results show that the polydispersities of these fullerene polymeric derivatives were between 1.1 and 1.3.The brown color of the solution indicates that C\-\{60\} has been bonded into the polymer,which was confirm by UV\|vis.Furthermore,2\|amino\|acetonictrile was used as an IR label to react with PS\|C\-\{60\}\|Br,and the product show the characteristic absorption of CN group at 2369cm\+\{-1\}.These results reinforce the conclusion that C\-\{60\} has been covalently bonded into the polymer.A possible mechanism of the formation of C\-\{60\}\|end\|bonded PSt was deduced tentatively.展开更多
基金funded by the National Natural Science Foundation of China(22478438,32401048,and 82273882)the Science Fund for Distinguished Young Scholars of Jiangsu Province(BK20240098)the Special Research Fund from the State Key Laboratory of Natural Medicines at China Pharmaceutical University(SKLNMZZ2024JS19).
文摘Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is generally preferred for use in practice.Herein,a versatile peptide,(HE)_(10)G_(5)R_(6)GDK(HE-RK),was engineered by integrating several motifs into a single sequence,including a masking segment(HE),a flexible linker(G_(5)),and a tumor-penetrating head(RK)which comprised a cell-penetrating peptide(R_(6))and a C-end Rule peptide(RGDK).The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells.Moreover,in our study,polymer micelles conjugated with the HE-RK peptide(PM-HE-RK)showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro,as well as extended blood circulation time and improved tumor targeting and penetration in vivo.Furthermore,the paclitaxel-loaded micelles(PTX/PM-HERK)demonstrated considerable antitumor efficacy,with an 81.48%tumor inhibition rate in the 4T1 mouse model.Overall,the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.
文摘目的研究姜黄素和维生素C添加对三文鱼烤制过程中有害物杂环胺(heterocyclic amines,HAAs)和晚期糖基化终末产物(advanced glycation end products,AGEs)的抑制作用,以及外源添加物对烤三文鱼风味的影响。方法通过高效液相色谱-串联质谱法测定HAAs和AGEs浓度,进一步测定还原糖、肌酸、肌酐、乙二醛等前体物以及脂质氧化水平解析其抑制机制,运用气相色谱-离子迁移谱法分析三文鱼烤制中挥发性风味变化。结果与对照组相比,姜黄素和维生素C对HAAs和AGEs表现出显著抑制效果(P˂0.05),总HAAs抑制率分别为75.21%和59.52%;AGEs中Nε-羧甲基赖氨酸抑制率分别为90.56%和90.87%,N^(ε)-羧乙基赖氨酸抑制率为94.57%和94.80%。还原糖、肌酸、肌酐、乙二醛等前体物浓度与HAAs和AGEs含量呈现高度相关。此外,通过挥发性风味分析表明添加姜黄素和维生素C对烤三文鱼风味有一定影响,增加了香味物质3-羟基-2-丁酮、2,6-二甲基-7-辛烯-2-醇、薄荷醇等化合物浓度,为三文鱼总体气味贡献重要作用。结论姜黄素和维生素C影响了HAAs和AGEs形成的关键前体物、中间体,具有显著抑制效果。本研究的开展为鱼肉制品热加工有害物控制提供了理论指导,并为优化鱼肉制品加工工艺提供了参考。
文摘目的:探讨血清高敏C反应蛋白(hsCRP)水平与致心律失常性心肌病(ACM)患者临床特征及预后的关系,评估其对终末期心力衰竭事件(ESHF)风险的预测价值。方法:回顾性纳入临界诊断及确诊ACM的患者328例,根据基线hsCRP实验室标准分为低水平组(≤3 mg/L,251例)和高水平组(>3 mg/L,77例)。收集病史、检查及检验资料,并比较2组间差异。采用Spearman相关分析、受试者工作特征(ROC)曲线分析、Kaplan-Meier生存分析及Cox比例风险模型评估hsCRP与心功能关联及对ESHF的预测价值。结果:研究人群中,男性占68.9%,致病/可能致病基因突变检出率为44.8%。hsCRP高水平组患者心功能及左室射血分数(LVEF)较差,右心室扩张与氨基末端B型利钠肽前体(NT-proBNP)水平显著升高(P均<0.05),但既往恶性室性心律失常发生率比较,差异无统计学意义(P>0.05)。Spearman相关性分析显示,hsCRP与LVEF呈负相关(r=-0.257,P<0.001),与NT-proBNP(r=0.307,P<0.001)及右心室内径(r=0.115,P=0.039)呈正相关。基因阳性及阴性患者hsCRP水平相近,但在不同心室受累患者中分布不同,在双心室受累患者中水平更高(趋势P=0.005)。ROC曲线分析示,hsCRP预测1、3及5年ESHF事件的曲线下面积(AUC)分别为0.640、0.662、0.654。Kaplan-Meier分析示,hsCRP高水平组随访期间无ESHF生存率显著降低(平均生存97.2 vs 150.5个月,P<0.001)。多因素Cox回归示,hsCRP分别独立于传统心室结构及心力衰竭指标(LVEF、右心室扩张及NT-proBNP)与ESHF风险显著相关(hsCRP作连续及分类变量,P均<0.05)。矫正年龄、性别、NT-proBNP及右心室扩张后,hsCRP水平仍与ESHF风险独立相关(连续变量HR:1.071,95%CI:1.011~1.135,P=0.020;分类变量HR:1.833,95%CI:1.115~3.014,P=0.017)。结论:血清hsCRP升高与ACM患者的心力衰竭和不良结局密切相关,可作为潜在生物标志物用于辅助ACM患者未来ESHF事件的预测。
文摘C\-\{60\}\|end\|bonded polystryrenes(PS\|C\-\{60\}\|Br) with narrow molecular weight polydispersity were prepared by atom transfer radical polymerization (ATRP) in good yield.GPC results show that the polydispersities of these fullerene polymeric derivatives were between 1.1 and 1.3.The brown color of the solution indicates that C\-\{60\} has been bonded into the polymer,which was confirm by UV\|vis.Furthermore,2\|amino\|acetonictrile was used as an IR label to react with PS\|C\-\{60\}\|Br,and the product show the characteristic absorption of CN group at 2369cm\+\{-1\}.These results reinforce the conclusion that C\-\{60\} has been covalently bonded into the polymer.A possible mechanism of the formation of C\-\{60\}\|end\|bonded PSt was deduced tentatively.
