Sequenced-defined oligomer has been emerged as one of the hot topics in polymer chemistry due to its capability of precisely controlling both chain length and monomer sequence.Recent efforts have focused on developmen...Sequenced-defined oligomer has been emerged as one of the hot topics in polymer chemistry due to its capability of precisely controlling both chain length and monomer sequence.Recent efforts have focused on development of synthetic methodologies using state-ofthe-art chemistry tools.However,investigating the impact of minor changes in monomer sequence on physical properties of these materials is still underdeveloped.Herein,four sequenced pentamers are synthesized by a reversible addition-fragmentation chain transfer(RAFT)single unit monomer insertion technique,in which a base pentamer possesses a relatively rigid backbone comprising of five cyclic monomer units.One of the cyclic units in this base pentamer is replaced by an acyclic monomer at different locations(the 1st,3rd and 5th unit)to produce three modified pentamers,which leads to a significant decrease of glass transition temperature(Tg)compared to the base pentamer.Meanwhile,the modified pentamers with identical primary structures but distinct monomer sequences also present different Tg values depending on the position of the acyclic monomer unit.The middle(3rd)position of the acyclic unit causes profound decrease of Tg due to its increased molecular flexibility.These synthetic pentamers have been demonstrated to be excellent oligomeric plasticizers to modulate thermal transitions of bulk polymer materials.展开更多
Electroactive hydrogels could guide the regeneration of nerves and promote their functional recovery.An aniline pentamer-crosslinked chitosan(CS-AP)hydrogel with better electroactivity and degradation was fabricated b...Electroactive hydrogels could guide the regeneration of nerves and promote their functional recovery.An aniline pentamer-crosslinked chitosan(CS-AP)hydrogel with better electroactivity and degradation was fabricated by the carbodiimide method,and then injected into the repair site of sciatic nerve damage,with its gelation time,tensile strength,and conductivity reaching 35 min,5.02-6.69 MPa,and from 2.97×10^(-4) to 3.25×10^(-4) S-cm^(-1),respectively,due to the cross-linkage and well-distribution of AP.There was better cytocompativility of CS-AP hydrogel on nerve cells.The results of the in vivo repair indicated that CS-AP10 hydrogel induced the capillaries formation and the repair of sciatic nerve defect,and re-innervated gastrocnemius muscle in the CS-AP10 group were obviously better than other experimental groups,due to the electroactivity of CS-AP and its degradation into fragments.These results indicated the potential application of CS-AP hydrogel in the regeneration and function recovery of peripheral nerve injury.展开更多
NBS-LRR (nucleotide binding sites and leucine rich repeat) protein plays a crucial role as sentries and as defense activators in plants. The structure and function of NBS-LRR proteins are closely related. Previous art...NBS-LRR (nucleotide binding sites and leucine rich repeat) protein plays a crucial role as sentries and as defense activators in plants. The structure and function of NBS-LRR proteins are closely related. Previous articles have announced that the activated ZAR1 (HopZ-Activated Resistance 1) forms a pentamer in the plasma membrane, which is a calcium permeable channel that can trigger plant immune signaling and cell death. However, the structure of galore NBS-LRRs in Arabidopsis is not yet clear. The functional sites of distinct NBS-LRR in cells may vary. In addition, identifying pathogens and activating defense regions may occur in different subcellular compartments. Therefore, dissecting the specific structure and positioning of NBS-LRRs is an indispensable step in understanding their functions. In this article, we exploit AlphaFold to predict the structure of some designed NBS-LRRs, and utilize Agroinfiltration transient expression system, combined with biochemical fractionation, to dissect the localization of these NBS-LRR receptors from Arabidopsis. Structural data indicates that the identified NBS-LRRs share analogous conformation. Membrane fractionation assay demonstrates these NBS-LRRs are mainly associated with the membrane. These data show that the Ca2+-permeable channel activity may be evolutionarily conserved in NBS-LRR of Arabidopsis, and this study provides some reference clues for analyzing the structure and localization patterns of other plant immune receptors.展开更多
目的分析血清正五聚蛋白3(PTX3)、网膜素-1(Omentin-1)对妊娠期糖尿病(GDM)患者不良妊娠结局的预测效能。方法选取123例GDM患者,根据胰岛素抵抗程度不同分为轻度组53例,中重度组70例,分析血清PTX3、Omentin-1与GDM患者血糖、炎症反应、...目的分析血清正五聚蛋白3(PTX3)、网膜素-1(Omentin-1)对妊娠期糖尿病(GDM)患者不良妊娠结局的预测效能。方法选取123例GDM患者,根据胰岛素抵抗程度不同分为轻度组53例,中重度组70例,分析血清PTX3、Omentin-1与GDM患者血糖、炎症反应、胰岛素敏感性指标的相关性及对其不良妊娠结局的预测效能。结果中重度组的FBG、2 h PG、Hcy、Cycs、NGAL、GAL、PTX3均高于轻度组,Omentin-1低于中重度组,差异有统计学意义(P<0.05);血清PTX3与血糖水平、炎症指标、胰岛素敏感性指标正相关(P<0.05);Omentin-1与血糖水平、炎症指标、胰岛素敏感性指标负相关(P<0.05);123例GDM患者的不良妊娠结局发生率为26.83%(33/123);血清PTX3对GDM不良预后的预测灵敏度、特异度分别为82.62%、80.41%;血清Omentin-1对GDM不良预后的预测灵敏度、特异度分别为80.35%、79.33%(AUC>0.85)。结论血清PTX3、Omentin-1有望成为预测GDM患者不良妊娠结局的敏感指标。展开更多
AIM： TO define the potential role of programmed death-i/programmed death-ligand （PD-1/PD-L） pathway in different hepatitis B virus （HBV） infection disease status; we examined the expression of PD-1 on antigen spe...AIM： TO define the potential role of programmed death-i/programmed death-ligand （PD-1/PD-L） pathway in different hepatitis B virus （HBV） infection disease status; we examined the expression of PD-1 on antigen specific CD8＋T cells in peripheral blood of patients with chronic hepatitis B （CriB） and acute exacerbation of hepatitis B （AEHB） infection. METHODS： The PD-1 level on CD8＋ T lymphocytes and the number of HBV specific CD8＋ T lymphocytes in patients and healthy controls （HCs） were analyzed by staining with pentameric peptide-human leukocyte antigen2 （HLA2） complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction （PCR） was used to measure the serum HBV- DNA levels. RESULTS： The level of PD-1 expression on total CD8＋ T cells in CHB patients （13.86% ± 3.38%） was significantly higher than that in AEHB patients （6.80%± 2.19%, P 〈 0.01） and healthy individuals （4.63% ± 1.23%, P 〈 0.01）. Compared to AEHB patients （0.81% ± 0.73%）, lower frequency of HBV-specific CD8＋ T cells was detected in chronic hepatitis B patients （0.37% ± 0.43%, P 〈 0.05）. There was an inverse correlation between the strength of HBV-specific CD8＋ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8＋ T cells in CriB and AEHB subjects （R = 0.541, P 〈 0.01）. However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase （ALT） levels （R = 0.066, P 〉 0.05）. CONCLUSION： Our results confirm previous reports that HBV specific CD8＋T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B wlth persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8＋ T cell response.展开更多
Cholesterol is a major lipid in biological membranes.It not only plays a structural role but also modulates a wide range of functional properties of neurotransmitter and hormone receptors and ion channels.The membrane...Cholesterol is a major lipid in biological membranes.It not only plays a structural role but also modulates a wide range of functional properties of neurotransmitter and hormone receptors and ion channels.The membraneembedded segments of the paradigm neurotransmitter receptor for acetylcholine(nAChR)contain linear sequences of amino acids with the capacity to recognize cholesterol.These cholesterol consensus domains have been designated as“CARC”and its mirror sequence“CRAC”.CARC preferentially occurs in the exoplasmic-facing membrane leaflet,and CRAC,in the cytoplasmic-facing hemilayer.Both motifs are highly conserved among ion-channel and neurotransmitter receptor proteins in vertebrate nervous systems,where they recognize cholesterol,and in prokaryotic homologues in bacteria,where they recognize hopanoids.This phylogenetically conserved trait is an indication that the hopanoids in some bacteria and cholesterol in eukaryotes subserve analogous functions,probably contributing to the stability of membrane-embedded protein domains.Structural studies from our laboratory using superresolution optical microscopy(“nanoscopy”)have disclosed other interrelated functional and structural properties exerted by cholesterol on the nAChR.The neutral lipid content at the cell surface influences both the macromolecular organization of the receptor and its translational mobility(diffusion)in the plane of the membrane.展开更多
五聚体配基门控离子通道（Pentameric ligand-gated ion channels．pLGICs）在动物体内广泛表达，是神经电位传导的主要参与者之一。介导pLGICs神经传导的递质主要有乙酰胆碱（Ach）．γ－氨基丁酸（GABA）．甘氨酸，5-羟色胺。五聚体...五聚体配基门控离子通道（Pentameric ligand-gated ion channels．pLGICs）在动物体内广泛表达，是神经电位传导的主要参与者之一。介导pLGICs神经传导的递质主要有乙酰胆碱（Ach）．γ－氨基丁酸（GABA）．甘氨酸，5-羟色胺。五聚体配基门控离子通道家族不同成员在生理学及麻醉学中具有重要作用，它们受临床浓度的麻醉剂调节，在全麻机制的研究中发挥重要作用。但是．由于缺乏关于哺乳动物pLGIcs的完整的X线结构方面的信息。使得全麻药物与配体门控离子通道变构调节机制和作用位点的研究进展缓慢。现已明确pLGICs家族起源于原核生物，因为有20多种家族同系物在原核生物中克隆出来。特别是最近研究发现的原核无类囊体蓝藻（Gloebacter violaceus．GLlc），通过对其X线分子结构观察，使得人们首次高分辨率的了解了pLGICs家族．也为全麻药物与配体门控离子通道变构调节机制和作用位点的研究提供了新的信息。大量研究发现GLIC具有电生理特性，受质子和阳离子的激活而发挥门控效应，同时对临床浓度的麻醉药物敏感，甚至与一些麻醉药物显示出比pLGICs家族其他受体更强的亲和力。本文旨在对全麻药物敏感的GLIC配体门控离子通道的研究进展做一综述。展开更多
基金the Australian Research Council(ARC)and UNSW Sydney for the financial support under the schemes of Future Fellowship(No.FT160100095)and Startup Fund。
文摘Sequenced-defined oligomer has been emerged as one of the hot topics in polymer chemistry due to its capability of precisely controlling both chain length and monomer sequence.Recent efforts have focused on development of synthetic methodologies using state-ofthe-art chemistry tools.However,investigating the impact of minor changes in monomer sequence on physical properties of these materials is still underdeveloped.Herein,four sequenced pentamers are synthesized by a reversible addition-fragmentation chain transfer(RAFT)single unit monomer insertion technique,in which a base pentamer possesses a relatively rigid backbone comprising of five cyclic monomer units.One of the cyclic units in this base pentamer is replaced by an acyclic monomer at different locations(the 1st,3rd and 5th unit)to produce three modified pentamers,which leads to a significant decrease of glass transition temperature(Tg)compared to the base pentamer.Meanwhile,the modified pentamers with identical primary structures but distinct monomer sequences also present different Tg values depending on the position of the acyclic monomer unit.The middle(3rd)position of the acyclic unit causes profound decrease of Tg due to its increased molecular flexibility.These synthetic pentamers have been demonstrated to be excellent oligomeric plasticizers to modulate thermal transitions of bulk polymer materials.
基金supported by National Key Research and Development Program of China(Grant No.2018YFC1106800)Sichuan Science and Technology Project(Grant No.2018JY0535).
文摘Electroactive hydrogels could guide the regeneration of nerves and promote their functional recovery.An aniline pentamer-crosslinked chitosan(CS-AP)hydrogel with better electroactivity and degradation was fabricated by the carbodiimide method,and then injected into the repair site of sciatic nerve damage,with its gelation time,tensile strength,and conductivity reaching 35 min,5.02-6.69 MPa,and from 2.97×10^(-4) to 3.25×10^(-4) S-cm^(-1),respectively,due to the cross-linkage and well-distribution of AP.There was better cytocompativility of CS-AP hydrogel on nerve cells.The results of the in vivo repair indicated that CS-AP10 hydrogel induced the capillaries formation and the repair of sciatic nerve defect,and re-innervated gastrocnemius muscle in the CS-AP10 group were obviously better than other experimental groups,due to the electroactivity of CS-AP and its degradation into fragments.These results indicated the potential application of CS-AP hydrogel in the regeneration and function recovery of peripheral nerve injury.
文摘NBS-LRR (nucleotide binding sites and leucine rich repeat) protein plays a crucial role as sentries and as defense activators in plants. The structure and function of NBS-LRR proteins are closely related. Previous articles have announced that the activated ZAR1 (HopZ-Activated Resistance 1) forms a pentamer in the plasma membrane, which is a calcium permeable channel that can trigger plant immune signaling and cell death. However, the structure of galore NBS-LRRs in Arabidopsis is not yet clear. The functional sites of distinct NBS-LRR in cells may vary. In addition, identifying pathogens and activating defense regions may occur in different subcellular compartments. Therefore, dissecting the specific structure and positioning of NBS-LRRs is an indispensable step in understanding their functions. In this article, we exploit AlphaFold to predict the structure of some designed NBS-LRRs, and utilize Agroinfiltration transient expression system, combined with biochemical fractionation, to dissect the localization of these NBS-LRR receptors from Arabidopsis. Structural data indicates that the identified NBS-LRRs share analogous conformation. Membrane fractionation assay demonstrates these NBS-LRRs are mainly associated with the membrane. These data show that the Ca2+-permeable channel activity may be evolutionarily conserved in NBS-LRR of Arabidopsis, and this study provides some reference clues for analyzing the structure and localization patterns of other plant immune receptors.
文摘目的分析血清正五聚蛋白3(PTX3)、网膜素-1(Omentin-1)对妊娠期糖尿病(GDM)患者不良妊娠结局的预测效能。方法选取123例GDM患者,根据胰岛素抵抗程度不同分为轻度组53例,中重度组70例,分析血清PTX3、Omentin-1与GDM患者血糖、炎症反应、胰岛素敏感性指标的相关性及对其不良妊娠结局的预测效能。结果中重度组的FBG、2 h PG、Hcy、Cycs、NGAL、GAL、PTX3均高于轻度组,Omentin-1低于中重度组,差异有统计学意义(P<0.05);血清PTX3与血糖水平、炎症指标、胰岛素敏感性指标正相关(P<0.05);Omentin-1与血糖水平、炎症指标、胰岛素敏感性指标负相关(P<0.05);123例GDM患者的不良妊娠结局发生率为26.83%(33/123);血清PTX3对GDM不良预后的预测灵敏度、特异度分别为82.62%、80.41%;血清Omentin-1对GDM不良预后的预测灵敏度、特异度分别为80.35%、79.33%(AUC>0.85)。结论血清PTX3、Omentin-1有望成为预测GDM患者不良妊娠结局的敏感指标。
文摘AIM： TO define the potential role of programmed death-i/programmed death-ligand （PD-1/PD-L） pathway in different hepatitis B virus （HBV） infection disease status; we examined the expression of PD-1 on antigen specific CD8＋T cells in peripheral blood of patients with chronic hepatitis B （CriB） and acute exacerbation of hepatitis B （AEHB） infection. METHODS： The PD-1 level on CD8＋ T lymphocytes and the number of HBV specific CD8＋ T lymphocytes in patients and healthy controls （HCs） were analyzed by staining with pentameric peptide-human leukocyte antigen2 （HLA2） complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction （PCR） was used to measure the serum HBV- DNA levels. RESULTS： The level of PD-1 expression on total CD8＋ T cells in CHB patients （13.86% ± 3.38%） was significantly higher than that in AEHB patients （6.80%± 2.19%, P 〈 0.01） and healthy individuals （4.63% ± 1.23%, P 〈 0.01）. Compared to AEHB patients （0.81% ± 0.73%）, lower frequency of HBV-specific CD8＋ T cells was detected in chronic hepatitis B patients （0.37% ± 0.43%, P 〈 0.05）. There was an inverse correlation between the strength of HBV-specific CD8＋ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8＋ T cells in CriB and AEHB subjects （R = 0.541, P 〈 0.01）. However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase （ALT） levels （R = 0.066, P 〉 0.05）. CONCLUSION： Our results confirm previous reports that HBV specific CD8＋T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B wlth persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8＋ T cell response.
文摘Cholesterol is a major lipid in biological membranes.It not only plays a structural role but also modulates a wide range of functional properties of neurotransmitter and hormone receptors and ion channels.The membraneembedded segments of the paradigm neurotransmitter receptor for acetylcholine(nAChR)contain linear sequences of amino acids with the capacity to recognize cholesterol.These cholesterol consensus domains have been designated as“CARC”and its mirror sequence“CRAC”.CARC preferentially occurs in the exoplasmic-facing membrane leaflet,and CRAC,in the cytoplasmic-facing hemilayer.Both motifs are highly conserved among ion-channel and neurotransmitter receptor proteins in vertebrate nervous systems,where they recognize cholesterol,and in prokaryotic homologues in bacteria,where they recognize hopanoids.This phylogenetically conserved trait is an indication that the hopanoids in some bacteria and cholesterol in eukaryotes subserve analogous functions,probably contributing to the stability of membrane-embedded protein domains.Structural studies from our laboratory using superresolution optical microscopy(“nanoscopy”)have disclosed other interrelated functional and structural properties exerted by cholesterol on the nAChR.The neutral lipid content at the cell surface influences both the macromolecular organization of the receptor and its translational mobility(diffusion)in the plane of the membrane.
文摘五聚体配基门控离子通道（Pentameric ligand-gated ion channels．pLGICs）在动物体内广泛表达，是神经电位传导的主要参与者之一。介导pLGICs神经传导的递质主要有乙酰胆碱（Ach）．γ－氨基丁酸（GABA）．甘氨酸，5-羟色胺。五聚体配基门控离子通道家族不同成员在生理学及麻醉学中具有重要作用，它们受临床浓度的麻醉剂调节，在全麻机制的研究中发挥重要作用。但是．由于缺乏关于哺乳动物pLGIcs的完整的X线结构方面的信息。使得全麻药物与配体门控离子通道变构调节机制和作用位点的研究进展缓慢。现已明确pLGICs家族起源于原核生物，因为有20多种家族同系物在原核生物中克隆出来。特别是最近研究发现的原核无类囊体蓝藻（Gloebacter violaceus．GLlc），通过对其X线分子结构观察，使得人们首次高分辨率的了解了pLGICs家族．也为全麻药物与配体门控离子通道变构调节机制和作用位点的研究提供了新的信息。大量研究发现GLIC具有电生理特性，受质子和阳离子的激活而发挥门控效应，同时对临床浓度的麻醉药物敏感，甚至与一些麻醉药物显示出比pLGICs家族其他受体更强的亲和力。本文旨在对全麻药物敏感的GLIC配体门控离子通道的研究进展做一综述。
