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HvMPK4 phosphorylates HvWRKY1 to enhance its suppression of barley immunity to powdery mildew fungus

Journal of Genetics and Genomics 2024年第3期51卷 313-325页

作者： Pengya Xue Ling Zhang Renchun Fan Yanan Li Xinyun Han Ting Qi lifang zhao Deshui Yu Qian-Hua Shen State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China CAS Center for Excellence in Biotic Interactions College of Advanced Agricultural SciencesUniversity of Chinese Academy of SciencesBeijing 100049China Department of Nutritional Sciences&Toxicology University of CaliforniaBerkeleyCA 94720USA Lushan Botanical Garden Chinese Academy of ScienceJiujiangJiangxi 332900China

Mitogen-activated protein kinase(MAPK)cascades play important roles in disease resistance in model plant species.However,the functions of MAPK signaling pathways in crop disease resistance are largely unknown.Here we report the function of HvMKK1-HvMPK4-HvWRKY1 module in barley immune system.HvMPK4 is identified to play a negative role in barley immune response against Bgh,as virus-induced gene silencing of HvMPK4 results in enhanced disease resistance whilst stably overexpressing HvMPK4 leads to super-susceptibility to Bgh infection.Furthermore,the barley MAPK kinase HvMKK1 is found to specifically interact with HvMPK4,and the activated HvMKK1^(DD) variant specifically phosphorylates HvMPK4 in vitro.Moreover,the transcription factor HvWRKY1 is identified to be a downstream target of HvMPK4 and phosphorylated by HvMPK4 in vitro in the presence of HvMKK1^(DD).Phosphorylation assay coupled with mutagenesis analyses identifies S122,T284,and S347 in HvWRKY1 as the major residues phosphorylated by HvMPK4.HvWRKY1 is phosphorylated in barley at the early stages of Bgh infection,which enhances its suppression on barley immunity likely due to enhanced DNA-binding and transcriptional repression activity.Our data suggest that the HvMKK1-HvMPK4 kinase pair acts upstream of HvWRKY1 to negatively regulate barley immunity against powdery mildew.

关键词： Barley MPK4 WRKY1 Phosphorylation Disease resistance Powdery mildew

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TGR5 deficiency activates antitumor immunity in non-small cell lung cancer via restraining M2 macrophage polarization

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Acta Pharmaceutica Sinica B 2022年第2期12卷 787-800页

作者： lifang zhao Hongyan Zhang Xueqing Liu Shan Xue Dongfang Chen Jing Zou Handong Jiang Department of Respiratory and Critical Care Medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages,and plays a critical role in regulating inflammatory response.Our previous work has shown its role in promoting the progression of non-small cell lung cancer(NSCLC),yet the mechanism remains unclear.Here,using Tgr5-knockout mice,we show that TGR5 is required for M2 polarization of tumorassociated macrophages(TAMs)and suppresses antitumor immunity in NSCLC via involving TAMsmediated CD8+T cell suppression.Mechanistically,we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating c AMP-STAT3/STAT6 signaling.Induction of c AMP production restores M2-like phenotypes in TGR5-deficient macrophages.In NSCLC tissues from human patients,the expression of TGR5 is associated with the infiltration of TAMs.The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients.Together,this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC,highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.

关键词： TGR5 Bile acids Tumor-associated macrophages(TAMs) Tumor microenvironment(TME) Non-small cell lung cancer(NSCLC) Antitumor immunity Immunotherapy c AMP-STAT3/STAT6

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Point-of-care detection of Microcystin-LR with a personal glucose meter in drinking water source

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Chinese Chemical Letters 2019年第5期30卷 1035-1037页

作者： lifang zhao Long Teng Juan Zhang He Li School of Chemistry and Chemical Engineering University of JinanJi'nan 250022China Shandong Product Quality Inspection Research Institute Ji'nan 250102China Environmental Engineering Co. Ltd.of Shandong Academy of Environmental SciencesJi'nan 250103China

In this study,a point-of-care sensing protocol has been reported for rapid and sensitive detection of Microcystin-LR(MC-LR)in water by personal glucose meter.The proposed immunosensor has been fabricated by using a primary antibody coated ZnFe2O4 nanoparticles to capture the target MC-LR.Consequently,the invertase@secondary antibody-conjugated graphene oxide-Au NPs can be immobilized for formating the sandwich immuno-complexes,which allowed for enzymatic conversion of sucrose to glucose.Thus,the concentration of MC-LR can be refelected by the converted glucose,which can be easily measured by the personal glucose meter(PGM).The PGM readout immunosensing method possessed good reproducibility and stability,which may have significant potential for other applications.

关键词： Microcystin-LR Personal glucose meter Point-of-care detection Graphene oxide Immunoassay

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A gelable pure organic luminogen with fluorescence-phosphorescence dual emission

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Science China Chemistry 2017年第6期60卷 806-812页

作者： Kaixuan Li lifang zhao Yongyang Gong Wang-Zhang Yuan Yongming Zhang School of Chemistry and Chemical Engineering Shanghai Key Lab of Electrical Insulation and Thermal AgingShanghai Electrochemical Energy Devices Research Center Shanghai Jiao Tong University Shanghai 200240 China

Pure organic luminogens with room temperature phosphorescence(RTP) have drawn much attention due to their fundamental importance and promising applications in optoelectronic devices, bioimaging, sensing, etc. Fluorescence-phosphorescence dual emission at room temperature, however, is rarely observed in pure organic materials. Herein, we reported a metal-and heavy-atom free pure organic luminogen with tert-butyl groups, DtBuCZBP, which is ready to form organogels in dimethylsulfoxide(DMSO).It emits prompt and delayed fluorescence, as well as RTP, namely dual emission in as-prepared solid, gels and polymeric films.To the best of our knowledge, it is the first example of metal-and heavy-atom free pure organic gelator with RTP emission. Such unique RTP and moreover dual emission properties in different states make DtBuCZBP a potential material for diverse applications.

关键词： pure organic luminogens dual emission room temperature phosphorescence organogel

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Application of a real-ambient fine particulate matter exposure system on different animal models

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Journal of Environmental Sciences 2021年第7期33卷 64-70页

作者： Yuanyuan Song lifang zhao Zenghua Qi Yanhao Zhang Guodong Cao Ruijin Li Lin Zhu Zhu Yang Chuan Dong Zongwei Cai State Key Laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong Kong SARChina Institute of Environmental Science Shanxi UniversityTaiyuan 030006China School of Environmental Science and Engineering Guangdong University of TechnologyGuangzhou 510006China

Simulation of fine particulate matter(PM_(2.5))exposure is essential for evaluating adverse health effects.In this work,an ambient exposure system that mimicked real atmospheric conditions was installed in Taiyuan,China to study impacts of chronic PM_(2.5) exposure on adult and aged mice as well as Sirtuin3 knockout(Sirt3 KO)mice and wild-type(WT)mice.The real-ambient exposure system eliminated the possible artificial effects caused from exposure experiments and maintained the physiochemical characteristics of PM_(2.5).The case studies indicated that aged mice exhibited apparent heart dysfunction involving in-creased heart rate and decreased blood pressure after 17-week of real-ambient PM_(2.5) exposure.Meanwhile,15-week of real-ambient PM_(2.5) exposure decreased the heart rate and amounts of associated catecholamines to induce heart failure in Sirt3 KO mice.Additionally,the increased pro-inflammatory cytokines and decreased platelet related indices suggested that inflammation occurred.The changes of biomarkers detected by targeted metabolomics confirmed metabolic disorder in WT and Sirt3 KO mice after exposed to real-ambient PM_(2.5).These results indicated that the real-ambient PM_(2.5) exposure system could evaluate the risks of certain diseases associated with air pollution and have great potential for support-ing the investigations of PM_(2.5) effects on other types of rodent models.

关键词： Real-ambient PM_(2.5)exposure system Adverse effects Sirt3 KO Aged mice

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不同给药方式用于分娩镇痛的效果研究

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中国基层医药 2024年第2期31卷 239-242页

作者：李会会赵利芳范解放新乡市中心医院麻醉与围术期医学科新乡453000

目的探讨不同给药方式用于分娩镇痛的临床效果。方法选取新乡市中心医院2023年2—6月经阴道分娩的产妇152例进行随机对照研究,按照随机数字表法分为对照组、观察组各76例。对照组常规硬膜外置管后给予0.1%盐酸罗哌卡因3 mL,并于3 min后... 详细信息

目的探讨不同给药方式用于分娩镇痛的临床效果。方法选取新乡市中心医院2023年2—6月经阴道分娩的产妇152例进行随机对照研究,按照随机数字表法分为对照组、观察组各76例。对照组常规硬膜外置管后给予0.1%盐酸罗哌卡因3 mL,并于3 min后予镇痛药物3 mL,无特殊反应者3 min后给予镇痛泵内药物9 mL并连接镇痛泵,开启至分娩后拔出导管。观察组导管置入硬膜外腔前给予试验量0.1%盐酸罗哌卡因3 mL,常规置入硬膜外导管,3 min后产妇躺平再次给予镇痛泵内药物3 mL,3 min后给予镇痛泵内药物9 mL,连接镇痛泵并开启至分娩后拔出导管。观察两组硬膜外置管不畅发生率,产妇硬膜外穿刺前(T1)、镇痛开始30 min(T2)、宫口开全(T3)3个时间点的视觉模拟评分法(VAS)评分,产妇自主追加镇痛泵次数,产妇满意度,转剖宫产例数,恶心呕吐、发热等不良反应发生率以及新生儿Apgar评分。结果观察组置管不畅发生率为1.3%(1/76),显著低于对照组的10.5%(8/76)(χ^(2)=5.79,P<0.05)。观察组T2、T3时间点的VAS评分分别为(0.89±0.08)分、(2.1±0.07)分,均低于对照组的(2.55±0.07)分、(3.35±0.07)分(t=238.54、133.17,均P<0.001)。观察组自主追加镇痛泵次数[(1.00±0.84)次]少于对照组[(4.00±0.65)次](t=29.47,P<0.001)。观察组产妇满意度[100.0%(76/76)]高于对照组[92.1%(70/76)](χ^(2)=6.25,P<0.05),转剖宫产率为0(0/76),低于对照组的52.6%(4/76)(χ^(2)=4.10,P<0.05)。结论行硬膜外置管分娩镇痛时于置入硬膜外导管前给予试验量0.1%盐酸罗哌卡因3 mL有利于置管且可显著提高分娩镇痛效果,有一定的应用价值。

关键词：麻醉和镇痛镇痛,硬膜外镇痛,产科镇痛,病人控制疼痛测定阿普加评分随机对照试验

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沙库巴曲缬沙坦钠与美托洛尔联合用药对冠心病并发慢性心力衰竭患者心功能的影响研究

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心电与循环 2024年第1期43卷 63-66页

作者：赵利芳李文绍兴市中心医院医共体总院药剂科 312030

目的探讨沙库巴曲缬沙坦钠与美托洛尔联合用药对冠心病并发慢性心力衰竭(CHF)患者心功能的影响。方法选择2020年3月至2021年10月绍兴市中心医院医共体总院收治的冠心病并发CHF患者216例,分为观察组和对照组,各108例。两组患者均给予包... 详细信息

目的探讨沙库巴曲缬沙坦钠与美托洛尔联合用药对冠心病并发慢性心力衰竭(CHF)患者心功能的影响。方法选择2020年3月至2021年10月绍兴市中心医院医共体总院收治的冠心病并发CHF患者216例,分为观察组和对照组,各108例。两组患者均给予包括美托洛尔的常规治疗,观察组加用沙库巴曲缬沙坦钠。比较两组患者临床疗效、心功能及血清指标水平。结果观察组患者有效率高于对照组,差异有统计学意义(P=0.001)。治疗后观察组舒张早期最大充盈速度(E)、左心室射血分数(LVEF)高于对照组,且高于治疗前,舒张晚期最大充盈速度(A)低于对照组及治疗前,差异均有统计学意义(均P<0.05)。治疗后观察组生长分化因子15、人亲环蛋白、N末端脑钠肽前体水平低于对照组,且低于治疗前,差异均有统计学意义(均P<0.05)。结论沙库巴曲缬沙坦钠联合美托洛尔能明显改善冠心病并发CHF患者的心功能。

关键词：冠心病慢性心力衰竭沙库巴曲缬沙坦钠美托洛尔

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Powdery mildew disease resistance and markerassisted screening at the Pm60 locus in wild diploid wheat Triticum urartu

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The Crop Journal 2020年第2期8卷 252-259页

作者： Fukai zhao Yinghui Li Baoju Yang Hongbo Yuan Cong Jin Lixun Zhou Hongcui Pei lifang zhao Yiwen Li Yilin Zhou Jiankun Xie Qian-Hua Shen College of Life Sciences Jiangxi Normal UniversityNanchang 330022JiangxiChina State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China

Triticum urartu,a diploid wild wheat and progenitor of the A genome of bread wheat,is an important resource for resistance to powdery mildew fungus caused by Blumeria graminis f.***.tritici(Bgt).In the present study we systematically characterized the interaction between the Bgt fungus and T.urartu at the microscopic level.We also tested 227 T.urartu accessions for reaction to Bgt isolate E09 and discovered previously uncategorized powdery mildew resistance in this collection.Pm60 is a CC-NB-LRR type powdery mildew resistance gene that has at least three functional alleles,Pm60,Pm60a,and Pm60b.A marker-assisted screen targeting the Pm60 locus identified a non-functional allele of Pm60a,designated as Pm60a′.A sequence comparison of Pm60a′and Pm60a revealed that they differed by 58 SNPs and one 3-nucleotide deletion.Based on the sequence variations two molecular markers were developed to differentiate the functional Pm60a allele from the non-functional Pm60a′.Our screen revealed the presence of a previously uncharacterized powdery mildew resistance in T.urartu and provides new insights into the Pm60 locus.We believe that the two molecular markers developed here and new T.urartu resistant accessions will facilitate further identification of novel powdery mildew resistance genes and benefit breeding for powdery mildew resistance.

关键词： Triticum breeding resistance

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SnRK1 Phosphorylates and Destabilizes WRKY3 to Enhance Barley Immunity to Powdery Mildew

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Plant Communications 2020年第4期1卷 115-128页

作者： Xinyun Han Ling Zhang lifang zhao Pengya Xue Ting Qi Chunlei Zhang Hongbo Yuan Lixun Zhou Daowen Wang Jinlong Qiuand Qian-Hua Shen State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesInnovation Academy for Seed DesignBeijing 100101China CAS Center for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Plant Genomics Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China

Plants recognize pathogens and activate immune responses,which usually involve massive transcriptional reprogramming.The evolutionarily conserved kinase,Sucrose non-fermenting-related kinase 1(SnRK1),functions as a metabolic regulator that is essential for plant growth and stress responses.Here,we identify barley SnRK1 and a WRKY3 transcription factor by screening a cDNA library.SnRK1 interacts with WRKY3 in yeast,as confirmed by pull-down and luciferase complementation assays.Förster resonance energy transfer combined with noninvasive fluorescence lifetime imaging analysis indicates that the interaction occurs in the barley nucleus.Transient expression and virus-induced gene silencing analyses indicate that WRKY3 acts as a repressor of disease resistance to the Bgh fungus.Barley plants overexpressing WRKY3 have enhanced fungal microcolony formation and sporulation.Phosphorylation assays show that SnRK1 phosphorylates WRKY3 mainly at Ser83 and Ser112 to destabilize the repressor,and WRKY3 non-phosphorylation-null mutants at these two sites are more stable than the wild-type protein.SnRK1-overexpressing barley plants display enhanced disease resistance to Bgh.Transient expression of SnRK1 reduces fungal haustorium formation in barley cells,which probably requires SnRK1 nuclear localization and kinase activity.Together,these findings suggest that SnRK1 is directly involved in plant immunity through phosphorylation and destabilization of the WRKY3 repressor,revealing a new regulatory mechanism of immune derepression in plants.

关键词： SnRK1 phosphorylation WRKY transcription factor immunity powdery mildew fungus

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三腔二囊管3种固定方法在食管胃底静脉曲张破裂出血患者压迫止血中的效果观察

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河北医学 2024年第4期30卷 629-634页

作者：郭蕾赵丽芳路伟空军军医大学第一附属医院消化急诊陕西西安710032

目的:探讨采用三腔二囊管3种固定方法在食管胃底静脉曲张破裂出血患者压迫止血中的应用疗效。方法:选取2021年1月至2022年10月我院收治的食管胃底静脉曲张破裂出血患者210例为研究对象,采用抽签法将患者完全随机分为传统固定组、鼻塞固... 详细信息

目的:探讨采用三腔二囊管3种固定方法在食管胃底静脉曲张破裂出血患者压迫止血中的应用疗效。方法:选取2021年1月至2022年10月我院收治的食管胃底静脉曲张破裂出血患者210例为研究对象,采用抽签法将患者完全随机分为传统固定组、鼻塞固定组、乒乓球固定组各70例,其中传统组采用传统法固定三腔二囊管,鼻塞固定组采用鼻塞法固定,乒乓球固定组采用乒乓球法固定。比较三组患者临床疗效(止血有效率、出血控制时间、输血量、再出血率)、并发症发生率(鼻黏膜破损、室息、胸闷、胸骨后疼痛、咽喉部损伤)及气囊破损率、置管成功率差异,记录治疗前及治疗后6个月时出血相关生化指标(血红蛋白、尿素氮、血小板数量)、凝血功能指标(纤维蛋白原含量、凝血酶原时间、凝血活酶时间)差异。结果:止血有效率、置管成功率组间比较结果均为乒乓球固定组(97.44%、100%)>鼻塞固定组(94.87%、97.14%)>传统固定组(87.50%、78.57%),且差异均具有统计学意义(P鼻塞固定组>传统固定组;尿素氮浓度明显降低(P鼻塞固定组>传统固定组;三组患者再出血率、气囊破损率、凝血功能指标均无显著差异(P>0.05)。结论:与鼻塞固定法及传统固定法相比,乒乓球固定三腔二囊管有效提高临床止血疗效,能够最大程度减少并发症的发生概率,且具有较高成功率。

关键词：三腔二囊管食管胃底静脉曲张破裂止血效果

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