The preparation of polypeptide materials in continuous flow reactors shows great potential with improved reproducibility and scalability.However,conventional polypeptide synthesis from the polymerization of N-carboxya...The preparation of polypeptide materials in continuous flow reactors shows great potential with improved reproducibility and scalability.However,conventional polypeptide synthesis from the polymerization of N-carboxyanhydride(NCA)is conducted at relatively slow rates,requiring long tubing or ending up with low-molecular-weight polymers.Inspired by recent advances in accelerated NCA polymerization,we report the crown-ether-catalyzed,rapid synthesis of polypeptide materials in cosolvents in flow reactors.The incorporation of low-polarity dichloromethane and the use of catalysts enabled fast conversion of monomers in 30 min,yielding well-defined polypeptides(up to 30 k Da)through a 20-cm tubing reactor.Additionally,random or block copolypeptides were efficiently prepared by incorporating a second NCA monomer.We believe that this work highlights the accelerated polymerization design in flow polymerization processes,offering the continuous production of polypeptide materials.展开更多
BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CC...BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CCT6A)participates in various physiological and pathological processes.However,its effects on cell death and cancer therapy and the underlying mechanisms need further exploration in colorectal cancer(CRC)cells.AIM To explore the effects of CCT6A on cell death and cancer therapy and the underlying mechanisms in CRC.METHODS Cell proliferation was evaluated using the MTS assay,EdU staining,and colony growth assays.The expression of CCT6A was monitored by immunoblotting and quantitative PCR.CCT6A was knocked out by CRISPR-Cas9,and overexpressed by transfecting plasmids.Autophagy was examined by immunoblotting and the mCherry-GFP-LC3 assay.To monitor apoptosis and necroptosis,immunoblotting,co-immunoprecipitation,and flow cytometry were employed.RESULTS Cisplatin(DDP)exerted cytotoxic effects on CRC cells while simultaneously downregulating the expression of CCT6A.Depletion of CCT6A amplified the cytotoxic effects of DDP,whereas overexpression of CCT6A attenuated these adverse effects.CCT6A suppressed autophagy,apoptosis,and necroptosis under both basal and DDP-treated conditions.Autophagy inhibitors significantly enhanced the cytotoxic effects of DDP,whereas a necroptosis inhibitor partially reversed the cell viability loss induced by DDP.Furthermore,inhibiting autophagy enhanced both apoptosis and necroptosis induced by DDP.CONCLUSION CCT6A negatively modulates autophagy,apoptosis,and necroptosis,and CCT6A confers resistance to DDP therapy in CRC,suggesting its potential as a therapeutic target.展开更多
Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limite...Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limited therapeutic window of thrombolytic agents,most patients do not receive the drug at the right time.Moreover,these agents are associated with risks of hemorrhage and reperfusion damage.Herein,Angiopep-2(ANG)-black phosphorus(BP)-resveratrol(RES),a drug-loaded system,was used to deliver drugs across the blood–brain barrier(BBB).ANG-BP-RES has a uniform size,stable structure,good photothermal effect,and strong drug release ability under near-infrared(NIR)irradiation and acidic conditions.Furthermore,ANG-BP-RES can efficiently target the brain and improve BBB permeability,exerting a significant therapeutic effect against ischemic brain injury,especially after NIR irradiation.ANG-BP-RES is also biocompatible and shows minimal toxicity toward cells and tissues.This study offers novel insights into the therapeutic management of ischemic brain injury.展开更多
目的:探讨GLP-1受体激动剂(GLP-1RA)Exendin4作用下胰岛β细胞的胰岛素及胰淀粉样多肽(IAPP)的分泌模式。方法:观察小鼠胰岛瘤细胞系MIN6细胞在不同浓度Exendin4作用不同时间后的细胞形态的变化;利用MTT实验检测MIN6细胞在不同干预后的...目的:探讨GLP-1受体激动剂(GLP-1RA)Exendin4作用下胰岛β细胞的胰岛素及胰淀粉样多肽(IAPP)的分泌模式。方法:观察小鼠胰岛瘤细胞系MIN6细胞在不同浓度Exendin4作用不同时间后的细胞形态的变化;利用MTT实验检测MIN6细胞在不同干预后的细胞活性的变化;采用葡萄糖刺激胰岛素分泌实验,检测MIN6细胞在不同干预后培养液上清中的胰岛素和IAPP分泌量的变化;采用荧光定量PCR(RT-PCR)检测各组MIN6细胞的胰岛素和IAPP m RNA表达水平的变化。结果:与正常对照组比较,Exendin4组的细胞数量增加,贴壁牢固,形态正常;细胞活性随Exendin4作用浓度以及作用时间的增加而显著增加,具有一定的浓度及时间依赖性;胰岛素和IAPP的分泌水平随Exendin4作用浓度以及作用时间的增加而显著增加,具有一定的浓度及时间依赖性,而IAPP/胰岛素的比值随作用浓度以及作用时间的增加而减小;胰岛素和IAPP m RNA水平均随Exendin4作用浓度以及作用时间的增加而上调,具有一定的浓度及时间依赖性,IAPP/胰岛素m RNA比值随作用浓度以及作用时间的增加而减小。结论:Exendin4作用于MIN6细胞可增加细胞数量和细胞活性,改善细胞状态,保护胰岛细胞功能;并且可引起胰岛素以及IAPP分泌水平增加,胰岛素和IAPP m RNA表达水平增加,而IAPP/胰岛素比值下降。展开更多
基金financially supported by the National Natural Science Foundation of China(No.22101194)Natural Science Foundation of Jiangsu Province(No.BK20210733)+3 种基金Suzhou Municipal Science and Technology Bureau(No.ZXL2021447)Collaborative Innovation Center of Suzhou Nano Science&Technologythe 111 ProjectJoint International Research Laboratory of Carbon-Based Functional Materials and Devices。
文摘The preparation of polypeptide materials in continuous flow reactors shows great potential with improved reproducibility and scalability.However,conventional polypeptide synthesis from the polymerization of N-carboxyanhydride(NCA)is conducted at relatively slow rates,requiring long tubing or ending up with low-molecular-weight polymers.Inspired by recent advances in accelerated NCA polymerization,we report the crown-ether-catalyzed,rapid synthesis of polypeptide materials in cosolvents in flow reactors.The incorporation of low-polarity dichloromethane and the use of catalysts enabled fast conversion of monomers in 30 min,yielding well-defined polypeptides(up to 30 k Da)through a 20-cm tubing reactor.Additionally,random or block copolypeptides were efficiently prepared by incorporating a second NCA monomer.We believe that this work highlights the accelerated polymerization design in flow polymerization processes,offering the continuous production of polypeptide materials.
基金Supported by Shandong Provincial Natural Science Foundation,No.ZR2023MH329Project of Shandong Province Higher Educational Youth Innovation Science and Technology Program,No.2023KJ263and Natural Science Foundation of Gansu Province,China,No.22JR5RA953.
文摘BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CCT6A)participates in various physiological and pathological processes.However,its effects on cell death and cancer therapy and the underlying mechanisms need further exploration in colorectal cancer(CRC)cells.AIM To explore the effects of CCT6A on cell death and cancer therapy and the underlying mechanisms in CRC.METHODS Cell proliferation was evaluated using the MTS assay,EdU staining,and colony growth assays.The expression of CCT6A was monitored by immunoblotting and quantitative PCR.CCT6A was knocked out by CRISPR-Cas9,and overexpressed by transfecting plasmids.Autophagy was examined by immunoblotting and the mCherry-GFP-LC3 assay.To monitor apoptosis and necroptosis,immunoblotting,co-immunoprecipitation,and flow cytometry were employed.RESULTS Cisplatin(DDP)exerted cytotoxic effects on CRC cells while simultaneously downregulating the expression of CCT6A.Depletion of CCT6A amplified the cytotoxic effects of DDP,whereas overexpression of CCT6A attenuated these adverse effects.CCT6A suppressed autophagy,apoptosis,and necroptosis under both basal and DDP-treated conditions.Autophagy inhibitors significantly enhanced the cytotoxic effects of DDP,whereas a necroptosis inhibitor partially reversed the cell viability loss induced by DDP.Furthermore,inhibiting autophagy enhanced both apoptosis and necroptosis induced by DDP.CONCLUSION CCT6A negatively modulates autophagy,apoptosis,and necroptosis,and CCT6A confers resistance to DDP therapy in CRC,suggesting its potential as a therapeutic target.
基金funded by the National Natural Science Foundation of China (No. 81960334)the Guiding Plan of Xinjiang Production Construction Corps (No. 2022ZD007)+4 种基金the Science and Technology Innovation Leading Talents Program of Guangdong Province (No. 2019TX05C343)the Basic and Applied Basic Research Foundation of Guangdong Province-Regional Joint Fund-Key Projects (No. 2019B1515120043)the Project supported by the State Key Laboratory of Luminescence and Applications (No. SKLA-2020-03)the support from Instrumental Analysis Center of Shenzhen University (Xili Campus)Instrumental Analysis Center of Shihezi University.
文摘Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limited therapeutic window of thrombolytic agents,most patients do not receive the drug at the right time.Moreover,these agents are associated with risks of hemorrhage and reperfusion damage.Herein,Angiopep-2(ANG)-black phosphorus(BP)-resveratrol(RES),a drug-loaded system,was used to deliver drugs across the blood–brain barrier(BBB).ANG-BP-RES has a uniform size,stable structure,good photothermal effect,and strong drug release ability under near-infrared(NIR)irradiation and acidic conditions.Furthermore,ANG-BP-RES can efficiently target the brain and improve BBB permeability,exerting a significant therapeutic effect against ischemic brain injury,especially after NIR irradiation.ANG-BP-RES is also biocompatible and shows minimal toxicity toward cells and tissues.This study offers novel insights into the therapeutic management of ischemic brain injury.
文摘无线局域网络中的核心设备——无线接入点(Access Point),其性能的好坏将直接影响网络的系统容量与业务处理能力,无线接入点的研究对于无线局域网的应用与发展具有重要意义.为此,IEEE 802.11无线局域网标准工作组制订了IAPP(Inter-Access Point Protocol)协议,支持无线用户在AP间的移动.通过分析IAPP协议和在AP上实现IAPP功能,从理论和实践两个方面对无线局域网移动性进行了深入研究.
文摘目的:探讨GLP-1受体激动剂(GLP-1RA)Exendin4作用下胰岛β细胞的胰岛素及胰淀粉样多肽(IAPP)的分泌模式。方法:观察小鼠胰岛瘤细胞系MIN6细胞在不同浓度Exendin4作用不同时间后的细胞形态的变化;利用MTT实验检测MIN6细胞在不同干预后的细胞活性的变化;采用葡萄糖刺激胰岛素分泌实验,检测MIN6细胞在不同干预后培养液上清中的胰岛素和IAPP分泌量的变化;采用荧光定量PCR(RT-PCR)检测各组MIN6细胞的胰岛素和IAPP m RNA表达水平的变化。结果:与正常对照组比较,Exendin4组的细胞数量增加,贴壁牢固,形态正常;细胞活性随Exendin4作用浓度以及作用时间的增加而显著增加,具有一定的浓度及时间依赖性;胰岛素和IAPP的分泌水平随Exendin4作用浓度以及作用时间的增加而显著增加,具有一定的浓度及时间依赖性,而IAPP/胰岛素的比值随作用浓度以及作用时间的增加而减小;胰岛素和IAPP m RNA水平均随Exendin4作用浓度以及作用时间的增加而上调,具有一定的浓度及时间依赖性,IAPP/胰岛素m RNA比值随作用浓度以及作用时间的增加而减小。结论:Exendin4作用于MIN6细胞可增加细胞数量和细胞活性,改善细胞状态,保护胰岛细胞功能;并且可引起胰岛素以及IAPP分泌水平增加,胰岛素和IAPP m RNA表达水平增加,而IAPP/胰岛素比值下降。
