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Utilization of hydralazine as a reactive matrix for enhanced detection and on-MALDI-target derivatization of saccharides

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Chinese Chemical Letters 2024年第5期35卷 386-391页

作者： Dan Ouyang Huan Huang Yanting He jiajing chen Jiali Lin Zhuling chen Zongwei Cai Zian Lin Ministry of Education Key Laboratory of Analytical Science for Food Safety and Biology Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food SafetyCollege of ChemistryFuzhou UniversityFuzhou 350108China School of Pharmacy Bengbu Medical UniversityBengbu 233000China Partner State Key Laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong KongChina

Saccharides are a sort of ubiquitous and vital molecules within the whole ***,the application of saccharides analysis with matrix-assisted laser desorption/ionization mass spectrometry(MALDI-MS)is restricted by their low ionization efficiency and the instability of the sialic acid *** strategy based on nonreductive amination provides a good solution,however,this is often time consuming and may result in sample loss due to removal of excessive derivatization ***,hydralazine(HZN)was utilized as a reactive matrix for labeling reducing saccharides directly on MALDI target which eliminated tedious sample preparation and avoided sample *** optimization,effective and reproducible on-MALDI-target derivatization of neutral and acidic saccharides was achieved in both positive and negative *** with 2,5-dihydroxybenzoic acid(DHB)and 9-aminoacridine(9-AA),HZN improved the detection sensitivity of reducing saccharides and provided more abundant fragment ions in MS/MS ***,26 kinds of neutral glycans and 5 kinds of sialic glycans were identified from ovalbumin(OVA)and bovine fetuin,*** with the statistical models,this strategy could be used to distinguish and predict samples of 6 brands of beer,and discriminate 2 kinds of beer fermentation *** addition,HZN was applied for quantitative analysis of glucose in urine samples,and the obtained urine glucose concentrations of diabetic patients were consistent with the clinical test results,showing the potential of qualitative and quantitative analysis of reducing saccharides in complex samples.

关键词： Hydralazine Reactive matrix On-MALDI-target derivatization Saccharides

ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3027-3048页

作者： Mengdie Dong Yunjia Zhang Minghong chen Yongkang Tan Jiao Min Xian He Fuhao Liu Jiaming Gu Hong Jiang Longbin Zheng jiajing chen Quanwen Yin Xuesong Li Xiang chen Yongfeng Shao Yong Ji Hongshan chen Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical Universityand Key Laboratory of Cardiovascular and Cerebrovascular MedicineSchool of PharmacyNational Vaccine Innovation PlatformNanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Department of Clinical Medicine Nanjing Medical University TIANYUAN Honors SchoolNanjing Medical UniversityNanjing 211166China Department of Anesthesiology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and Cerebrovascular Medicine Key Laboratory of Targeted Intervention of Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineState Key Laboratory of Reproductive MedicineSchool of Pharmacythe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversityNanjing 211166China National Key Laboratory of Frigid Zone Cardiovascular Diseases(NKLFZCD) Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China)College of PharmacyKey Laboratory of Cardiovascular Medicine Research and Key Laboratory of Myocardial IschemiaChinese Ministry of EducationNHC Key Laboratory of Cell Transplantationthe Central Laboratory of the First Affiliated HospitalHarbin Medical UniversityHarbin 150081China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiology Huai’an First People’s Hospital Affiliated with Nanjing Medical UniversityHuai’an 223399China

Endothelial-to-mesenchymal transition(EndMT)is a key driver of *** glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate *** lactylation,mediated by lactate,can regulate gene expression and participate in disease ***,whether histone lactylation is involved in atherosclerosis remains ***,we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactatedependent histone H3 lysine 18 lactylation(H3K18la)in vitro and in vivo,as well as in atherosclerotic patients’***,the histone chaperone ASF1A was first identified as a cofactor of P300,which precisely regulated the enrichment of H3K18la at the promoter of SNAI1,thereby activating SNAI1 transcription and promoting *** found that deletion of ASF1A inhibited EndMT and improved endothelial *** analysis based on Apoe^(KO)Asf1a^(ECKO) mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endotheliumspecific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis *** of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la,SNAI1 transcription,and EndMT-induced *** study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis,which provides emerging therapies for atherosclerosis.

关键词： Histone lactylation Atherosclerosis Endothelial-tomesenchymal transition ASF1A SNAI1 Endothelial dysfunction Lactate Epigenetic

Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4765-4784页

作者： Xuesong Li Xiang chen Longbin Zheng Minghong chen Yunjia Zhang Ruigong Zhu jiajing chen Jiaming Gu Quanwen Yin Hong Jiang Xuan Wu Xian Ji Xin Tang Mengdie Dong Qingguo Li Yuanqing Gao Hongshan chen Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Department of Anesthesiology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China Department of Pharmacy Huashan HospitalFudan UniversityShanghai 200040China Department of Cardiothoracic Surgery the Second Affliated Hospital of Nanjing Medical UniversityNanjing 211166China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiology Huai'an First People's Hospital Affliated with Nanjing Medical UniversityHuai'an 223399China

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis,while the underlying mechanism remains ***,we report that the non-canonical stimulator of interferon genes(STING)-PKR-like ER kinase(PERK)pathway was significantly activated in both human and mice atherosclerotic ***,STING activation leads to the activation of interferon regulatory factor 3(IRF3)and nuclear factor-kappa B(NF-κB)/p65,thereby facilitating IFN signals and *** contrast,our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4(BRD4)expression,which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines,thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation ***-specific STING and BRD4 deficiency significantly decreased the plaque area and ***,this pathway is triggered by leaked mitochondrial DNA(mtDNA)via mitochondrial permeability transition pore(mPTP),formed by voltage-dependent anion channel 1(VDAC1)oligomer interaction with oxidized mtDNA upon cholesterol oxidation ***,compared to macrophages,endothelial STING activation plays a more pronounced role in *** propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3,NF-κB and BRD4 in inflammatory responses,which provides emerging therapeutic modalities for vascular endothelial dysfunction.

关键词： Endothelial dysfunction Infiammation Mitochondrial DNA STING ROS PERK BRD4 Atherosclerosis

Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis via the TFEB-P300-BRD4 axis

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2280-2299页

作者： Xuesong Li Ruigong Zhu Hong Jiang Quanwen Yin Jiaming Gu jiajing chen Xian Ji Xuan Wu Haiping Fu Hui Wang Xin Tang Yuanqing Gao Bingjian Wang Yong Ji Hongshan chen Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiothoracic Surgery the Second Affiliated Hospital of Nanjing Medical UniversityNanjing 211166China Department of Cardiology Huai’an First People’s Hospital Affiliated with Nanjing Medical UniversityHuai’an 223399China

Disturbance of macrophage-associated lipid metabolism plays a key role in *** between autophagy deficiency and inflammation response in foam cells(FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized lowdensity lipoprotein(ox-LDL) leads to abnormal crosstalk between autophagy and inflammation,thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4(BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation(LLPS) on the regulatory regions of inflammatory genes. Curcumin(Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

关键词： Macrophage Autophagy TFEB P300 BRD4 Inflammation Atherosclerosis Curcumin

Melatonin antagonizes ovarian aging via YTHDF2-MAPK-NF-κB pathway

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Genes & Diseases 2022年第2期9卷 494-509页

作者： Ruigong Zhu Xian Ji Xuan Wu jiajing chen Xuesong Li Hong Jiang Haiping Fu Hui Wang Zhe Lin Xin Tang Shixiu Sun Qingguo Li Bingjian Wang Hongshan chen Key Laboratory of Cardiovascular&Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjingJiangsu 211166PR China Department of Cardiothoracic Surgery The Second Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210003PR China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjingJiangsu 211166PR China Department of Cardiology Huai'an First People's Hospital Affiliated with Nanjing Medical UniversityHuai'anJiangsu 223399PR China

Cellular senescence is closely associated with age-related *** aging,a special type of organ senescence,is the pathophysiological foundation of the diseases of the reproductive *** is characterized by the loss of integrity of the surface epithelium and a gradual decrease in the number of human ovarian surface epithelial cells(HOSEpiCs).To contribute to the research on delaying ovarian aging,we aimed to investigate the novel epigenetic mechanism of melatonin in protecting *** discovered that melatonin has antagonistic effects against the oncogene-induced senescence(OIS)of ***,the oncogene Ras decreased the expression of YTHDF2,which is the reader of RNA-m6A,by stimulating the generation of reactive oxygen species(ROS).Moreover,we found that the suppression of YTHDF2 increased the expression of MAP2K4 and MAP4K4 by enhancing the stability of the transcription of their mRNAs,thereby upregulating the expression of the senescence-associated secretory phenotype(SASP)through the activation of the MAP2K4 and MAP4K4-dependent nuclear factor-κB(NF-κB)signaling *** further determined that melatonin has antagonistic effects against the OIS of HOSEpiCs by inhibiting the ROS-YTHDF2-MAPK-NF-κB *** findings provide key insights into the potential avenues for preventing and treating ovarian aging.

关键词： Gene expression Inflammation Melatonin Senescence YTHDF2

The IAA-and ABA-responsive transcription factor CgMYB58 upregulates lignin biosynthesis and triggers juice sac granulation in pummelo

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Horticulture Research 2020年第1期7卷 846-859页

作者： Meiyan Shi Xiao Liu Haipeng Zhang Zhenyu He Hongbin Yang jiajing chen Jia Feng Wenhui Yang Youwu Jiang Jia-Long Yao Cecilia Hong Deng Juan Xu Key Laboratory of Horticultural Plant Biology Ministry of EducationWuhanHubei 430070China The New Zealand Institute for Plant and Food Research Limited Private Bag 92169Auckland 1142New Zealand

In citrus,lignin overaccumulation in the juice sac results in granulation and an unpleasant fruit texture and *** integrating metabolic phenotyping and transcriptomic analyses,we found 702 differentially expressed genes(DEGs),including 24 transcription factors(TFs),to be significantly correlated with lignin ***58 was further identified as a critical R2R3 MYB TF involved in lignin overaccumulation owing to its high transcript levels in Huanong Red-fleshed pummelo(HR,Citrus grandis)*** expression of CgMYB58 led to an increase in the lignin content in the pummelo fruit mesocarp,whereas its stable overexpression significantly promoted lignin accumulation and upregulated 19 lignin biosynthetic *** these genes,CgPAL1,CgPAL2,Cg4CL1,and CgC3H were directly modulated by CgMYB58 through interaction with their promoter ***,we showed that juice sac granulation in pummelo fruits could be affected by indole-3-acetic acid(IAA)and abscisic acid(ABA)*** HR pummelo,ABA significantly accelerated this granulation,whereas IAA effectively inhibited this *** together,these results provide novel insight into the lignin accumulation mechanism in citrus *** also revealed the theoretical basis via exogenous IAA application,which repressed the expression of CgMYB58 and its target genes,thus alleviating juice sac granulation in orchards.

关键词： integrating treatment citrus

Nonlinear Dynamic Analysis of Flexible Marine-Risers

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China Ocean Engineering 1991年第4期6卷 373-384页

作者： chen jiajing and Wang Dongjiao Professor, South China University of Technology, Guangzhou PhD Student, Hong Kong Polytechnic Formerly, South China University of Technology, Guangzhou

A nonlinear dynamic analysis model is estabilished on the basis of 'lumped mass' approach, which takes the influence of the fluid flow within the pipe into consideration. Numerical results are compared with the published works, and the effects of internal fluid flow, internal pressure, dyanmics as well as the nonlinear characteristics on the behavior of flexible risers are discussed. From this work, some useful conclusions are drawn.

关键词： flexible riser nonlinear dynamic analysis model irregular wave oilfield exploitation

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基于SPH方法的船体海洋飞沫生成形态模拟

船舶工程 2024年第4期46卷 66-72,89页

作者：陈家静白旭江苏科技大学船舶与海洋工程学院江苏镇江212003

为了研究海洋飞沫的生成形态,采用光滑粒子法(SPH)的粒子捕捉技术,分析4种常见的船首特征对海洋飞沫轨迹的影响。研究发现,船首的设计在飞沫的生成和运动特性上起着决定性作用。球鼻艏和破冰艏通过镇压波浪减少飞沫的覆盖范围,而飞剪艏... 详细信息

为了研究海洋飞沫的生成形态,采用光滑粒子法(SPH)的粒子捕捉技术,分析4种常见的船首特征对海洋飞沫轨迹的影响。研究发现,船首的设计在飞沫的生成和运动特性上起着决定性作用。球鼻艏和破冰艏通过镇压波浪减少飞沫的覆盖范围,而飞剪艏和前倾艏则利用其独特的流线型设计有效地对飞沫进行引流,但却导致飞沫的生成高度较高,覆盖范围较广。此外,研究还揭示了不同类型的飞沫(如崩波破碎、卷波和激散波破碎)在船首附近的工况和轨迹模式。研究结果可为船舶设计优化及防除冰技术提供重要理论支持。

关键词：船舶积冰海洋飞沫船首形状光滑粒子法

NMR backbone assignment of large proteins using 13Cα-only triple resonance experiments

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NMR backbone assignment of large proteins using 13Cα-only t...