Starch digestion rate and location in the gastrointestinal tract(GIT)are critical for human health.This review aims to present a comprehensive summary on our current understanding of physiological,biochemical,anatomic...Starch digestion rate and location in the gastrointestinal tract(GIT)are critical for human health.This review aims to present a comprehensive summary on our current understanding of physiological,biochemical,anatomical and geometrical factors of human digestive system that are related to in vivo starch digestibility.It is shown that all digestive compartments including mouth,stomach,small intestine,and large intestine play critical roles in regulating the overall starch digestion process.A proper investigation of starch digestion pattern should thus be based on the consideration of all these compartments.Main biological factors are summarized as oral mastication and salivation,gastric emptying and motility,small intestinal enzymes and motility,large intestinal resistant starch(RS)-microbiota interactions and gut-brain feedback control,as well as glucose adsorption and hormonal feedback control.However,connections among these biological factors in determining starch digestive behaviors remain elusive.This is due to the inherent complexity of human GIT anatomy,motility and biochemical conditions,as well as ethical,financial and technical issues in conducting clinical studies.Much technological and scientific efforts from both clinical studies and in vitro simulation models are required for a better understanding of in vivo starch digestion behaviors.展开更多
Creditors,such as banks,often use disclosed environmental information to assess a company’s environmental risk and ensure the safety of debt funds.Consequently,carbon disclosures have become an important consideratio...Creditors,such as banks,often use disclosed environmental information to assess a company’s environmental risk and ensure the safety of debt funds.Consequently,carbon disclosures have become an important consideration for creditors when making investments.This study explores the relationship between carbon disclosure and debt financing costs using data on listed companies from 2008 to 2019.The results show that carbon disclosure can reduce the debt financing costs of enterprises,and that this influence is more significant for private companies than for state-owned enterprises.Instrumental variables and Propensity Score Matching(PSM)were used to evaluate the robustness of negative relationships.Furthermore,carbon disclosure has a more significant impact on debt costs with less environmental supervision pressure,weak residents’environmental awareness,and weak product market competition.These findings provide guidance for companies’carbon information disclosure and support the establishment of official carbon disclosure standards.展开更多
The atomization characteristics play a key role in the highly efficient combustion of pyrolysis oil derived from waste tires.In this study,the fuel properties of tire pyrolysis oil(TPO)were initially studied,and then ...The atomization characteristics play a key role in the highly efficient combustion of pyrolysis oil derived from waste tires.In this study,the fuel properties of tire pyrolysis oil(TPO)were initially studied,and then a high-speed camera and a phase Doppler particle analyzer were employed to characterize the atomization feature of TPO.The influence of pressure and nozzle orifice diameter on atomization characteristics such as spray angle,droplet velocity,and droplet size distribution was investigated.The results showed that TPO had a high calorific value of about 43.6 MJ/kg and a low viscosity of 3.84×10^(–6)m^(2)/s at 40℃,which made it have the potential to be used as an alternative fuel.Higher pressure expanded the spray angle and extended the spray in both the axial and radial directions.With increasing pressure,spray angle and droplet velocity raised,and the increase in crushing effect of air reduced the Sauter mean diameter(SMD)of the droplets.To obtain proper atomization quality for combustion,the pressure is expected to be higher than 1.25 MPa.With increasing nozzle orifice diameter,droplet velocity increased,and the SMD of the droplets increased as well due to weakened crushing effect of the orifice.Therefore,the pressure must be increased to maintain the atomization quality when using a nozzle with a larger orifice.Due to the lower viscosity,the velocity and particle size distribution of TPO droplets after atomization were smaller than those of diesel droplets.The extremely small carbon black contained in TPO also contributed to the breaking of droplets and played a certain role in the size reduction of the oil droplets,but it may cause the risk of nozzle blockage.In summary,TPO showed great atomization characteristics for alternative fuel applications.展开更多
新中国成立以来,我国已开展了大量陆生脊椎动物的本底调查和多样性研究项目,取得了一系列成果,并有学者针对兽类、鸟类和两栖爬行类的野外调查监测进行了总结和展望,但尚缺乏对所有陆生脊椎动物类群的调查历史和现状的分析及基于文献收...新中国成立以来,我国已开展了大量陆生脊椎动物的本底调查和多样性研究项目,取得了一系列成果,并有学者针对兽类、鸟类和两栖爬行类的野外调查监测进行了总结和展望,但尚缺乏对所有陆生脊椎动物类群的调查历史和现状的分析及基于文献收集的研究,特别是对调查方法和技术手段的对比与总结。因此,本文通过文献收集的方法,基于中国知网、Web of Science核心合集和以图书检索为主的读秀学术搜索,以“兽类”“鸟类”“爬行类”“两栖类”“动物资源”“调查”“监测”“新种”“新记录”和“物种多样性”作为检索词,检索并筛选了与兽类、鸟类、爬行类及两栖类陆生脊椎动物调查相关的文献资料共3,504篇,对陆生脊椎动物调查的研究文献在全国各省级行政区、生物多样性热点地区的分布,及其运用的调查方法和技术手段进行了系统的分析和比较。结果表明:相较兽类和两栖爬行类的调查,我国鸟类多样性的调查最多,发表文献占所有文献的70.26%。四川、云南的陆生脊椎动物调查最多,分别发表285篇、260篇文献。分布于我国的4个全球生物多样性热点地区的调查强度存在显著差异,印缅生物多样性热点地区和中国西南山地的研究文献较多,分别为348篇、324篇文献;中亚山地、喜马拉雅山地的研究文献较少,分别为71篇、66篇文献。陆生脊椎动物调查方法主要采用样线法、样点法、样方法和直接计数法,或将上述几种方法综合应用,样线法在所有场景(如:高山冻原、农田、城市等)中应用频率最高;技术手段以直接观察法、采集法、红外相机陷阱法为主,其中直接观察法在所有场景(如城市、湿地、草原等)中应用频率最高。当前,我国陆生脊椎动物调查已取得很多新进展,包括新兴物种采集和物种识别技术的发展(如无人机技术在大型兽类和集群水鸟上的应用、卫星追踪在迁徙鸟类上的应用等)、大数据时代下调查方法的改善和数据管理的提升等。未来我国的陆生脊椎动物调查,应拓宽新兴物种采集方法和识别技术的应用范围,进一步关注和发掘脊椎动物的新调查技术,以大数据为基础完善种群数据分析与调查管理体系,并朝着面向大众、服务社会的方向发展,以引起全社会对生物多样性保护的重视。本文以整体的视角概述了陆生脊椎动物各类群调查的情况,评估了不同地区调查强度的差异,并在调查方法和技术手段方面作了总结和展望,可为未来国内陆生脊椎动物野外调查工作的总体方向、调查侧重、方法运用等方面提供一定的参考。展开更多
印度野牛(Bos gaurus)在中国分布在云南省南部和西藏藏南地区。2016年2–3月和2016年11–12月,我们在西双版纳州、普洱市及高黎贡山区域开展印度野牛调查,并对藏南地区进行文献调研,共获得47处印度野牛有效出现位点数据。目前云南地区...印度野牛(Bos gaurus)在中国分布在云南省南部和西藏藏南地区。2016年2–3月和2016年11–12月,我们在西双版纳州、普洱市及高黎贡山区域开展印度野牛调查,并对藏南地区进行文献调研,共获得47处印度野牛有效出现位点数据。目前云南地区印度野牛种群数量约180–210头,面临着严重的生存危机;在高黎贡山未发现印度野牛。利用印度野牛分布位点数据,选取地形、土地覆被类型、人类足迹指数、距水源和道路距离以及气候共5类14种因子作为自变量建立MaxEnt生态位模型,通过模拟云南和西藏印度野牛的适宜分布区,分析各环境因子对该物种分布的影响。结果表明:模型预测精度较高,平均AUC (area under the curve)值为0.994。印度野牛潜在适宜栖息地可划分为高适宜、次适宜、低适宜和不适宜4个等级。高适宜栖息地主要分布在云南省西双版纳和藏南地区,其中西双版纳部分镶嵌有次适宜和低适宜栖息地斑块,面积为4,987 km2;藏南部分高适宜栖息地面积为13,995 km2。次适宜栖息地主要分布于云南省南部、高黎贡山区域以及藏南高适宜栖息地区的边缘,总面积为32,778 km2。低适宜和不适宜栖息地区连接成片,位于云南省中部、北部地区和藏南地区北部。Jackknife检验结果显示,季节温度变化和等温线对印度野牛潜在分布区的影响较大,而地形因子和降水变化的影响较弱。遥感地物分类结果表明:橡胶林等人工经济林的种植占据了西双版纳野牛的适宜栖息地,降低了景观连接度。建议管理部门加大对天然林的保护力度,控制橡胶林等人工林在野牛适宜栖息地的扩张,提高景观连接度,以促进该物种种群的恢复。展开更多
Interleukin(IL)17-producing T helper(Th17)cells play critical roles in the clearance of extracellular bacteria and fungi as well as the pathogenesis of various autoimmune diseases,such as multiple sclerosis,psoriasis,...Interleukin(IL)17-producing T helper(Th17)cells play critical roles in the clearance of extracellular bacteria and fungi as well as the pathogenesis of various autoimmune diseases,such as multiple sclerosis,psoriasis,and ulcerative colitis.Although a global transcriptional regulatory network of Th17 cell differentiation has been mapped recently,the participation of epigenetic modifications in the differentiation process has yet to be elucidated.We demonstrated here that histone H3 lysine-27(H3K27)demethylation,predominantly mediated by the H3K27 demethylase Jmjd3,crucially regulated Th17 cell differentiation.Activation of naı¨ve CD41 T cells immediately induced high expression of Jmjd3.Genetic depletion of Jmjd3 in CD41 T cells specifically impaired Th17 cell differentiation both in vitro and in vivo.Ectopic expression of Jmjd3 largely rescued the impaired differentiation of Th17 cells in vitro in Jmjd3-deficientCD41 T cells.Importantly,Jmjd3-deficient mice were resistant to the induction of experimental autoimmune encephalomyelitis(EAE).Furthermore,inhibition of the H3K27 demethylase activity with the specific inhibitor GSK-J4 dramatically suppressed Th17 cell differentiation in vitro.At the molecular level,Jmjd3 directly bound to and reduced the level of H3K27 trimethylation(me3)at the genomic sites ofRorc,which encodes the masterTh17 transcription factorRorgt,and Th17 cytokine genes such as Il17,Il17f,and Il22.Therefore,our studies established acritical role of Jmjd3-mediatedH3K27demethylation inTh17 cell differentiation andsuggest that Jmjd3 can be a novel therapeutic target for suppressing autoimmune responses.展开更多
Histone methylation is a context-dependent modification that regulates gene expression,and the trimethylation of histone H3 lysine 27(H3K27me3)usually induces gene silencing.Overcoming colorectal cancer(CRC)chemoresis...Histone methylation is a context-dependent modification that regulates gene expression,and the trimethylation of histone H3 lysine 27(H3K27me3)usually induces gene silencing.Overcoming colorectal cancer(CRC)chemoresistance is currently a huge challenge,but the relationship between H3K27me3 modification and chemoresistance remains largely unclear.Here,we found that H3K27me3 levels positively correlated with the metastasis-free survival of CRC patients and a low H3K27me3 level predicted a poor outcome upon chemotherapeutic drug treatment.Oxaliplatin stimulation significantly induced the expression of H3K27 lysine demethylase 6A/6B(KDM6A/6B),thus decreasing the level of H3K27me3 in CRC cells.Elevation of H3K27me3 level through KDM6A/6B depletion or GSK-J4(a KDM6A/6B inhibitor)treatment significantly enhanced oxaliplatin-induced apoptosis.Conversely,when inhibiting the expression of H3K27me3 by EPZ-6438,an inhibitor of the histone methyltransferase EZH2,the proportion of apoptotic cells remarkably decreased.In addition,the combination of GSK-J4 and oxaliplatin significantly inhibited tumor growth in an oxaliplatin-resistant patient-derived xenograft model.Importantly,we revealed that oxaliplatin treatment dramatically induced NOTCH2 expression,which was caused by downregulation of H3K27me3 level on the NOTCH2 transcription initiation site.Thus,the activated NOTCH signaling promoted the expression of stemness-related genes,which resulted in oxaliplatin resistance.Furthermore,oxaliplatin-induced NOTCH signaling could be interrupted by GSK-J4 treatment.Collectively,our findings suggest that elevating H3K27me3 level can improve drug sensitivity in CRC patients.展开更多
Wnt/β-catenin signaling plays a critical role in colorectal cancer(CRC)tumorigenesis and the homeostasis of colorectal cancer stem cells(CSCs),but its molecular mechanism remains unclear.B-cell lymphoma 3(Bcl-3),a me...Wnt/β-catenin signaling plays a critical role in colorectal cancer(CRC)tumorigenesis and the homeostasis of colorectal cancer stem cells(CSCs),but its molecular mechanism remains unclear.B-cell lymphoma 3(Bcl-3),a member of the IκB family,is overexpressed in CRC and promotes tumorigenicity.Here,we report a novel function of Bcl-3 in maintaining colorectal CSC homeostasis by activating Wnt/β-catenin signaling.Silencing Bcl-3 suppresses the self-renewal capacity of colorectal CSCs and sensitizes CRC cells to chemotherapeutic drugs through a decrease in Wnt/β-catenin signaling.Moreover,our data show that Bcl-3 is a crucial component of Wnt/β-catenin signaling and is essential forβ-catenin transcriptional activity in CRC cells.Interestingly,Wnt3a increases the level and nuclear translocation of Bcl-3,which binds directly toβ-catenin and enhances the acetylation ofβ-catenin at lysine 49(Ac-K49-β-catenin)and transcriptional activity.Bcl-3 depletion decreases the Ac-K49-β-catenin level by increasing the level of histone deacetylase 1 to remove acetyl groups fromβ-catenin,thus interrupting Wnt/β-catenin activity.In CRC clinical specimens,Bcl-3 expression negatively correlates with the overall survival of CRC patients.A significantly positive correlation was found between the expression of Bcl-3 and Ac-K49-β-catenin.Collectively,our data reveal that Bcl-3 plays a crucial role in CRC chemoresistance and colorectal CSC maintenance via its modulation of the Ac-K49-β-catenin,which serves as a promising therapeutic target for CRC.展开更多
Single-ion conducting polymer electrolytes have attracted great attention as safe alternatives to liquid electrolytes in high energy density lithium-ion batteries.Herein,we report the first example of a crystalline an...Single-ion conducting polymer electrolytes have attracted great attention as safe alternatives to liquid electrolytes in high energy density lithium-ion batteries.Herein,we report the first example of a crystalline anionic helical polymer as a single lithium-ion conducting solid polymer electrolyte(SPE).Single-crystal X-ray analysis shows that the polymer folds into densely packed double helices,with bundles of unidirectional negatively charged channels formed that can facilitate lithium-ion transportation.展开更多
Covalent organic frameworks(COFs)have garnered increasing attention as promising electrode materials for sodium-ion batteries(SIBs)due to their ordered backbones,uniform pore sizes,and high surface areas.However,they ...Covalent organic frameworks(COFs)have garnered increasing attention as promising electrode materials for sodium-ion batteries(SIBs)due to their ordered backbones,uniform pore sizes,and high surface areas.However,they also face challenges,including low capacity,unsatisfactory rate performance,and limited cycling stability,which pose the primary obstacles to their practical use.Herein,a pyrenoimidazole-based COF,denoted as PyIm-COF,has been synthesized as a novel electrode material for highperformance SIBs using an efficient synthetic strategy.With extended fully conjugated backbones and readily accessible redox-active sites,PyIm-COF demonstrates remarkable high-rate performance,delivering around 250 m Ah g^(−1)and excellent cycling stability,retaining 97.2%of its capacity even after 2500 cycles at 5 A g^(−1),which is higher than that of most previously reported COF-based SIBs.This work provides valuable insights into the development of nitrogen-rich conjugated COF electrode materials for rechargeable SIBs.展开更多
基金financial support from National Natural Science Foundation of China(32001646)Natural Science Foundation of Jiangsu Province(BK20190906)+2 种基金Jiangsu Yangzhou Key Research and Development Program(SSF2018000008)Jiangsu Provincial Entrepreneurial and Innovation Phd ProgramYangzhou Lvyangjinfeng Talent Program。
文摘Starch digestion rate and location in the gastrointestinal tract(GIT)are critical for human health.This review aims to present a comprehensive summary on our current understanding of physiological,biochemical,anatomical and geometrical factors of human digestive system that are related to in vivo starch digestibility.It is shown that all digestive compartments including mouth,stomach,small intestine,and large intestine play critical roles in regulating the overall starch digestion process.A proper investigation of starch digestion pattern should thus be based on the consideration of all these compartments.Main biological factors are summarized as oral mastication and salivation,gastric emptying and motility,small intestinal enzymes and motility,large intestinal resistant starch(RS)-microbiota interactions and gut-brain feedback control,as well as glucose adsorption and hormonal feedback control.However,connections among these biological factors in determining starch digestive behaviors remain elusive.This is due to the inherent complexity of human GIT anatomy,motility and biochemical conditions,as well as ethical,financial and technical issues in conducting clinical studies.Much technological and scientific efforts from both clinical studies and in vitro simulation models are required for a better understanding of in vivo starch digestion behaviors.
文摘Creditors,such as banks,often use disclosed environmental information to assess a company’s environmental risk and ensure the safety of debt funds.Consequently,carbon disclosures have become an important consideration for creditors when making investments.This study explores the relationship between carbon disclosure and debt financing costs using data on listed companies from 2008 to 2019.The results show that carbon disclosure can reduce the debt financing costs of enterprises,and that this influence is more significant for private companies than for state-owned enterprises.Instrumental variables and Propensity Score Matching(PSM)were used to evaluate the robustness of negative relationships.Furthermore,carbon disclosure has a more significant impact on debt costs with less environmental supervision pressure,weak residents’environmental awareness,and weak product market competition.These findings provide guidance for companies’carbon information disclosure and support the establishment of official carbon disclosure standards.
基金the National Natural Science Foundation of China(No.52076190)Zhejiang Provincial Key Research and Development Program(No.2023C03129).
文摘The atomization characteristics play a key role in the highly efficient combustion of pyrolysis oil derived from waste tires.In this study,the fuel properties of tire pyrolysis oil(TPO)were initially studied,and then a high-speed camera and a phase Doppler particle analyzer were employed to characterize the atomization feature of TPO.The influence of pressure and nozzle orifice diameter on atomization characteristics such as spray angle,droplet velocity,and droplet size distribution was investigated.The results showed that TPO had a high calorific value of about 43.6 MJ/kg and a low viscosity of 3.84×10^(–6)m^(2)/s at 40℃,which made it have the potential to be used as an alternative fuel.Higher pressure expanded the spray angle and extended the spray in both the axial and radial directions.With increasing pressure,spray angle and droplet velocity raised,and the increase in crushing effect of air reduced the Sauter mean diameter(SMD)of the droplets.To obtain proper atomization quality for combustion,the pressure is expected to be higher than 1.25 MPa.With increasing nozzle orifice diameter,droplet velocity increased,and the SMD of the droplets increased as well due to weakened crushing effect of the orifice.Therefore,the pressure must be increased to maintain the atomization quality when using a nozzle with a larger orifice.Due to the lower viscosity,the velocity and particle size distribution of TPO droplets after atomization were smaller than those of diesel droplets.The extremely small carbon black contained in TPO also contributed to the breaking of droplets and played a certain role in the size reduction of the oil droplets,but it may cause the risk of nozzle blockage.In summary,TPO showed great atomization characteristics for alternative fuel applications.
文摘新中国成立以来,我国已开展了大量陆生脊椎动物的本底调查和多样性研究项目,取得了一系列成果,并有学者针对兽类、鸟类和两栖爬行类的野外调查监测进行了总结和展望,但尚缺乏对所有陆生脊椎动物类群的调查历史和现状的分析及基于文献收集的研究,特别是对调查方法和技术手段的对比与总结。因此,本文通过文献收集的方法,基于中国知网、Web of Science核心合集和以图书检索为主的读秀学术搜索,以“兽类”“鸟类”“爬行类”“两栖类”“动物资源”“调查”“监测”“新种”“新记录”和“物种多样性”作为检索词,检索并筛选了与兽类、鸟类、爬行类及两栖类陆生脊椎动物调查相关的文献资料共3,504篇,对陆生脊椎动物调查的研究文献在全国各省级行政区、生物多样性热点地区的分布,及其运用的调查方法和技术手段进行了系统的分析和比较。结果表明:相较兽类和两栖爬行类的调查,我国鸟类多样性的调查最多,发表文献占所有文献的70.26%。四川、云南的陆生脊椎动物调查最多,分别发表285篇、260篇文献。分布于我国的4个全球生物多样性热点地区的调查强度存在显著差异,印缅生物多样性热点地区和中国西南山地的研究文献较多,分别为348篇、324篇文献;中亚山地、喜马拉雅山地的研究文献较少,分别为71篇、66篇文献。陆生脊椎动物调查方法主要采用样线法、样点法、样方法和直接计数法,或将上述几种方法综合应用,样线法在所有场景(如:高山冻原、农田、城市等)中应用频率最高;技术手段以直接观察法、采集法、红外相机陷阱法为主,其中直接观察法在所有场景(如城市、湿地、草原等)中应用频率最高。当前,我国陆生脊椎动物调查已取得很多新进展,包括新兴物种采集和物种识别技术的发展(如无人机技术在大型兽类和集群水鸟上的应用、卫星追踪在迁徙鸟类上的应用等)、大数据时代下调查方法的改善和数据管理的提升等。未来我国的陆生脊椎动物调查,应拓宽新兴物种采集方法和识别技术的应用范围,进一步关注和发掘脊椎动物的新调查技术,以大数据为基础完善种群数据分析与调查管理体系,并朝着面向大众、服务社会的方向发展,以引起全社会对生物多样性保护的重视。本文以整体的视角概述了陆生脊椎动物各类群调查的情况,评估了不同地区调查强度的差异,并在调查方法和技术手段方面作了总结和展望,可为未来国内陆生脊椎动物野外调查工作的总体方向、调查侧重、方法运用等方面提供一定的参考。
文摘印度野牛(Bos gaurus)在中国分布在云南省南部和西藏藏南地区。2016年2–3月和2016年11–12月,我们在西双版纳州、普洱市及高黎贡山区域开展印度野牛调查,并对藏南地区进行文献调研,共获得47处印度野牛有效出现位点数据。目前云南地区印度野牛种群数量约180–210头,面临着严重的生存危机;在高黎贡山未发现印度野牛。利用印度野牛分布位点数据,选取地形、土地覆被类型、人类足迹指数、距水源和道路距离以及气候共5类14种因子作为自变量建立MaxEnt生态位模型,通过模拟云南和西藏印度野牛的适宜分布区,分析各环境因子对该物种分布的影响。结果表明:模型预测精度较高,平均AUC (area under the curve)值为0.994。印度野牛潜在适宜栖息地可划分为高适宜、次适宜、低适宜和不适宜4个等级。高适宜栖息地主要分布在云南省西双版纳和藏南地区,其中西双版纳部分镶嵌有次适宜和低适宜栖息地斑块,面积为4,987 km2;藏南部分高适宜栖息地面积为13,995 km2。次适宜栖息地主要分布于云南省南部、高黎贡山区域以及藏南高适宜栖息地区的边缘,总面积为32,778 km2。低适宜和不适宜栖息地区连接成片,位于云南省中部、北部地区和藏南地区北部。Jackknife检验结果显示,季节温度变化和等温线对印度野牛潜在分布区的影响较大,而地形因子和降水变化的影响较弱。遥感地物分类结果表明:橡胶林等人工经济林的种植占据了西双版纳野牛的适宜栖息地,降低了景观连接度。建议管理部门加大对天然林的保护力度,控制橡胶林等人工林在野牛适宜栖息地的扩张,提高景观连接度,以促进该物种种群的恢复。
基金supported by grants from the National Basic Research Program(2014CB541904,2011CB946102,and 2014CB943600)the National Natural Science Foundation of China(31370881,90919017,and 30972695)+1 种基金the Knowledge Innovation Project of Chinese Academy of Sciences(KSCX1-YW-22)the CAS-CSIRO Cooperative Research Program(GJHZ1409).
文摘Interleukin(IL)17-producing T helper(Th17)cells play critical roles in the clearance of extracellular bacteria and fungi as well as the pathogenesis of various autoimmune diseases,such as multiple sclerosis,psoriasis,and ulcerative colitis.Although a global transcriptional regulatory network of Th17 cell differentiation has been mapped recently,the participation of epigenetic modifications in the differentiation process has yet to be elucidated.We demonstrated here that histone H3 lysine-27(H3K27)demethylation,predominantly mediated by the H3K27 demethylase Jmjd3,crucially regulated Th17 cell differentiation.Activation of naı¨ve CD41 T cells immediately induced high expression of Jmjd3.Genetic depletion of Jmjd3 in CD41 T cells specifically impaired Th17 cell differentiation both in vitro and in vivo.Ectopic expression of Jmjd3 largely rescued the impaired differentiation of Th17 cells in vitro in Jmjd3-deficientCD41 T cells.Importantly,Jmjd3-deficient mice were resistant to the induction of experimental autoimmune encephalomyelitis(EAE).Furthermore,inhibition of the H3K27 demethylase activity with the specific inhibitor GSK-J4 dramatically suppressed Th17 cell differentiation in vitro.At the molecular level,Jmjd3 directly bound to and reduced the level of H3K27 trimethylation(me3)at the genomic sites ofRorc,which encodes the masterTh17 transcription factorRorgt,and Th17 cytokine genes such as Il17,Il17f,and Il22.Therefore,our studies established acritical role of Jmjd3-mediatedH3K27demethylation inTh17 cell differentiation andsuggest that Jmjd3 can be a novel therapeutic target for suppressing autoimmune responses.
基金This work was supported by the National Program on Key Research(2018YFA0107500 and 2016YFC1302400)the National Natural Science Foundation of China(91742113 and 31570902)Natural Science Foundation of Shanghai(14ZR14-26300,18ZR1424400,18ZR1446400,and 18431902700).
文摘Histone methylation is a context-dependent modification that regulates gene expression,and the trimethylation of histone H3 lysine 27(H3K27me3)usually induces gene silencing.Overcoming colorectal cancer(CRC)chemoresistance is currently a huge challenge,but the relationship between H3K27me3 modification and chemoresistance remains largely unclear.Here,we found that H3K27me3 levels positively correlated with the metastasis-free survival of CRC patients and a low H3K27me3 level predicted a poor outcome upon chemotherapeutic drug treatment.Oxaliplatin stimulation significantly induced the expression of H3K27 lysine demethylase 6A/6B(KDM6A/6B),thus decreasing the level of H3K27me3 in CRC cells.Elevation of H3K27me3 level through KDM6A/6B depletion or GSK-J4(a KDM6A/6B inhibitor)treatment significantly enhanced oxaliplatin-induced apoptosis.Conversely,when inhibiting the expression of H3K27me3 by EPZ-6438,an inhibitor of the histone methyltransferase EZH2,the proportion of apoptotic cells remarkably decreased.In addition,the combination of GSK-J4 and oxaliplatin significantly inhibited tumor growth in an oxaliplatin-resistant patient-derived xenograft model.Importantly,we revealed that oxaliplatin treatment dramatically induced NOTCH2 expression,which was caused by downregulation of H3K27me3 level on the NOTCH2 transcription initiation site.Thus,the activated NOTCH signaling promoted the expression of stemness-related genes,which resulted in oxaliplatin resistance.Furthermore,oxaliplatin-induced NOTCH signaling could be interrupted by GSK-J4 treatment.Collectively,our findings suggest that elevating H3K27me3 level can improve drug sensitivity in CRC patients.
基金The authors would like to acknowledge Prof.Yifu Ding of the University of Colorado Boulder for the instrumentation support with DMA.This work was supported by the University of Colorado Boulder,Wong KC Education Foundation,and the National Natural Science Foundation of China(51673072).Su Z would like to thank China Scholarship Council(CSC)for financial support.
基金funded by the National Program on Key Research(2018YFA0107500,2016YFC1302400)National Basic Research Program(2014CB541904 and 2014CB943600)+3 种基金National Natural Science Foundation of China(91742113,31570902,81702950,81772798,91949102 and 81771752)Natural Science Foundation of Shanghai(14ZR1426300,18ZR1424400,18ZR1446400,18431902700)China Postdoctoral Science Foundation(2017M611633)Guangzhou Key Medical Discipline Construction Project Fund.
文摘Wnt/β-catenin signaling plays a critical role in colorectal cancer(CRC)tumorigenesis and the homeostasis of colorectal cancer stem cells(CSCs),but its molecular mechanism remains unclear.B-cell lymphoma 3(Bcl-3),a member of the IκB family,is overexpressed in CRC and promotes tumorigenicity.Here,we report a novel function of Bcl-3 in maintaining colorectal CSC homeostasis by activating Wnt/β-catenin signaling.Silencing Bcl-3 suppresses the self-renewal capacity of colorectal CSCs and sensitizes CRC cells to chemotherapeutic drugs through a decrease in Wnt/β-catenin signaling.Moreover,our data show that Bcl-3 is a crucial component of Wnt/β-catenin signaling and is essential forβ-catenin transcriptional activity in CRC cells.Interestingly,Wnt3a increases the level and nuclear translocation of Bcl-3,which binds directly toβ-catenin and enhances the acetylation ofβ-catenin at lysine 49(Ac-K49-β-catenin)and transcriptional activity.Bcl-3 depletion decreases the Ac-K49-β-catenin level by increasing the level of histone deacetylase 1 to remove acetyl groups fromβ-catenin,thus interrupting Wnt/β-catenin activity.In CRC clinical specimens,Bcl-3 expression negatively correlates with the overall survival of CRC patients.A significantly positive correlation was found between the expression of Bcl-3 and Ac-K49-β-catenin.Collectively,our data reveal that Bcl-3 plays a crucial role in CRC chemoresistance and colorectal CSC maintenance via its modulation of the Ac-K49-β-catenin,which serves as a promising therapeutic target for CRC.
基金supported by the University of Colorado Boulder。
文摘Single-ion conducting polymer electrolytes have attracted great attention as safe alternatives to liquid electrolytes in high energy density lithium-ion batteries.Herein,we report the first example of a crystalline anionic helical polymer as a single lithium-ion conducting solid polymer electrolyte(SPE).Single-crystal X-ray analysis shows that the polymer folds into densely packed double helices,with bundles of unidirectional negatively charged channels formed that can facilitate lithium-ion transportation.
基金the Natural Science Foundation of Liaoning province(grant no.2019-MS-046)W.Zhang thanks the University of Colorado Boulder for financial support of this work+1 种基金W.Huang acknowledges the support from the National Natural Science Foundation of China(grant no.21875206)The authors acknowledge the assistance of the Dalian University of Technology Instrumental Analysis Center.
文摘Covalent organic frameworks(COFs)have garnered increasing attention as promising electrode materials for sodium-ion batteries(SIBs)due to their ordered backbones,uniform pore sizes,and high surface areas.However,they also face challenges,including low capacity,unsatisfactory rate performance,and limited cycling stability,which pose the primary obstacles to their practical use.Herein,a pyrenoimidazole-based COF,denoted as PyIm-COF,has been synthesized as a novel electrode material for highperformance SIBs using an efficient synthetic strategy.With extended fully conjugated backbones and readily accessible redox-active sites,PyIm-COF demonstrates remarkable high-rate performance,delivering around 250 m Ah g^(−1)and excellent cycling stability,retaining 97.2%of its capacity even after 2500 cycles at 5 A g^(−1),which is higher than that of most previously reported COF-based SIBs.This work provides valuable insights into the development of nitrogen-rich conjugated COF electrode materials for rechargeable SIBs.
