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Small molecule deoxynyboquinone triggers alkylation and ubiquitination of keap1 at Cys489 on kelch domain for Nrf2 activation and inflammatory therapy

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Journal of Pharmaceutical Analysis 2024年第3期14卷 401-415页

作者： ke-gang linghu Tian Zhang Guang-Tao Zhang Peng Lv Wen-Jun Zhang Guan-Ding Zhao Shi-Hang Xiong Qiu-Shuo Ma Ming-Ming Zhao Meiwan Chen Yuan-Jia Hu Chang-Sheng Zhang Hua Yu State key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Macao Centre for Research and Development in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina key Laboratory of Tropical Marine Bio-resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaRNAM Center for Marine MicrobiologySouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou510301China State key Laboratory of Functions and Applications of Medicinal Plants&School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang550025China

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by kelch-like ECH-associated protein 1(keap1)alkylation plays a central role in anti-inflammatory ***,activators of Nrf2 through alkylation of keap1-kelch domain have not been ***(DNQ)is a natural small molecule discovered from marine *** current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of *** exhibited significant anti-inflammatory properties both in vitro and in *** pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be theα,β-unsaturated amides moieties by a chemical reaction between DNQ and *** exerted anti-inflammatory effects through activation of Nrf2/ARE ***1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving *** specific alkylation site of DNQ on keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass *** triggered the ubiquitination and subsequent degradation of keap1 by alkylation of the cysteine residue 489(Cys489)on keap1-kelch domain,ultimately enabling the activation of *** findings revealed that DNQ exhibited potent anti-inflammatory capacity throughα,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of keap1-kelch domain,suggesting the potential values of targeting Cys489 on keap1-kelch domain by DNQ-like small molecules in inflammatory therapies.

关键词： Deoxynyboquinone Anti-inflammation Target keap1/Nrf2 Alkylation Ubiquitination

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Transcriptome analysis suggests broad jejunal alterations in linghu’s obesity-diarrhea syndrome:A pilot study

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World Journal of Gastroenterology 2024年第21期30卷 2777-2792页

作者： Xiao-Tong Niu Xiang-Yao Wang Yan Wang ke Han Nan Ru Jing-Yuan Xiang En-Qiang linghu Medical School of Chinese PLA Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology The First Medical Center of Chinese PLA General HospitalBeijing 100853China School of Medicine Nankai UniversityTianjin 300071China

BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely *** To reveal the transcriptomic changes in the jejunum involved in *** In a cohort of 6 ODS patients(JOD group),6 obese people without diarrhea(JO group),and 6 healthy controls(JC group),high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological *** another cohort of 16 ODS patients(SOD group),16 obese people without diarrhea(SO group),and 16 healthy controls(SC group),serum diamine oxidase(DAO)and D-lactate(DLA)concentrations were detected to assess changes in intestinal barrier *** The gene expression profiles of jejunal mucosa in the JO and JC groups were similar,with only 1 differentially expressed gene(DEG).The gene expression profile of the JOD group was significantly changed,with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group,129 of which *** enrichment analysis of these DEGs showed that the biological processes such as digestion,absorption,and transport of nutrients(especially lipids)tended to be up-regulated in the JOD group,while the biological processes such as rRNA processing,mitochondrial translation,antimicrobial humoral response,DNA replication,and DNA repair tended to be down-regulated in the JOD *** DEGs(CDT1,NHP2,EXOSC5,EPN3,NME1,REG3A,PLA2G2A,and PRSS2)may play a key regulatory role in the pathological process of ODS,and their expression levels were significantly decreased in ODS patients(Pkers(DAO and D-LA)were significantly increased in all obese individuals(P<0.01),but were higher in the SOD group than in the SO group(P<0.001).CONCLUSION Compared with health

关键词： Obesity Chronic diarrhea Jejunum Transcriptome Intestinal barrier

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Role of submucosal injection in radiofrequency ablation of gastric low-grade dysplasia: Effects on symptoms and outcomes

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中华医学杂志(英文版) 2024年第17期137卷 2099-2110页

作者： Niu Xiaotong Wang Nanjun Wang Yan Feng Jia Li Longsong Han ke Chai Ningli linghu Enqiang Medical School of Chinese PLA General Hospital Beijing China Department of Gastroenterology and Hepatology The First Medical Center Chinese PLA General Hospital Beijing China Nankai University School of Medicine Nankai University Tianjin China Department of Gastroenterology Bethune International Peace Hospital ShijiaZhuang Hebei China

Background: To date, there is still a lack of standardized management strategies for gastric low-grade dysplasia (LGD), which is a direct neoplastic precancerous lesion and requires specifically superficial destruction. Radiofrequency ablation (RFA) is expected to be an effective method for gastric LGD, but post-RFA pain may affect patients’ satisfaction and compliance. The current study aimed to evaluate the value of a submucosal injection prior to RFA (SI-RFA) for postoperative pain and treatment ***: Between October 2014 and July 2021, gastric LGDs without risk factors (size >2 cm, unclear boundary, and abnormal microsurface and microvascularity) undergoing regular RFA and SI-RFA were retrospectively analyzed. Postoperative pain scores, wound healing, and clinical efficacy were compared. Propensity score matching, stratified analysis, and multivariable logistic regression were performed to control the confounding ***: One hundred and ninety-seven gastric LGDs in 151 patients received regular RFA. Forty-nine gastric LGDs in 36 patients received SI-RFA. Thirty-six pairs of patients were selected for the assessment of postoperative pain by propensity score matching. Compared to regular RFA, SI-RFA significantly decreased the degree and duration of postoperative pain (OR, 0.32; 95% CI, 0.13-0.84;P = 0.020), improved wound healing rate (80.0% [36/45]vs. 58.9% [89/151],P = 0.012), increased the complete ablation rate (91.8% [45/49]vs. 86.3% [170/197],χ2 = 1.094,P = 0.295), but correlated with higher rates of local recurrence and progression (25.6% [10/39]vs. 13.2% [18/136],χ2 = 3.471,P = 0.062; 8.3% [3/36]vs. 0.9% [1/116],P = 0.042). The multivariable logistic regression model confirmed that submucosal injection was associated with local recurrence (OR, 2.93; 95% CI, 1.13-7.58;P = 0.027).Conclusions: Submucosal injections prior to RFA may reduce postoperative pain and scar formation while ensuring complete ablation of gastric LGD. However, lo

关键词： Gastric low-grade dysplasia Radiofrequency ablation Submucosal injection Postoperative pain Treatment outcome

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New direction for surgery:Super minimally invasive surgery

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World Journal of Gastroenterology 2024年第12期30卷 1676-1679页

作者： En-Qiang linghu Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China

The top goal of modern medicine is treating disease without destroying organ structures and making patients as healthy as they were before their *** invasive surgery(MIS)has dominated the surgical realm because of its lesser ***,changes in anatomical structures of the body and reconstruction of internal organs or different organs are common after traditional surgery or MIS,decreasing the quality of life of patients ***,I propose a new treatment mode,super MIS(SMIS),which is defined as“curing a disease or lesion which used to be treated by MIS while preserving the integrity of the organs”.In this study,I describe the origin,definition,operative channels,advantages,and future perspectives of SMIS.

关键词： Super minimally invasive surgery Minimally invasive surgery Treatment mode Traditional Surgery New direction for surgery

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Autophagy and its role in gastrointestinal diseases

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World Journal of Gastroenterology 2024年第36期30卷 4014-4020页

作者： Bo-Zong Shao Wen-gang Zhang Zhen-Yu Liu En-Qiang linghu Department of Gastroenterology First Medical Center of Chinese People’s Liberation Army General HospitalBeijing 100853China

Gastrointestinal disorders encompass a spectrum of conditions affecting various organs within the digestive system,such as the esophagus,stomach,colon,rectum,pancreas,liver,small intestine,and bile *** role of autophagy in the etiology and progression of gastrointestinal diseases has garnered significant *** paper seeks to evaluate the impact and mechanisms of autophagy in gastrointestinal disorders by synthesizing recent research ***,we delve into inflammation-related gastrointestinal conditions,including ulcerative colitis,Crohn’s disease,and pancreatitis,as well as gastrointestinal cancers such as esophageal,gastric,and colorectal ***,we provide commentary on a recent publication by Chang et al in the World Journal of *** objective is to offer fresh perspectives on the mechanisms and therapeutic approaches for these gastrointestinal *** review aims to offer new perspectives on the mechanisms and therapeutic strategies for gastrointestinal disorders by critically analyzing relevant *** discussed,the role of autophagy in gastrointestinal diseases is complex and,at times,*** harness the full therapeutic potential of autophagy in treating these conditions,more in-depth research is imperative.

关键词： Autophagy Inflammation Cancer Inflammatory bowel disease Pancreatitis

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A porous Eu-PTA/Tb-SSA/ZrO_(2)/ZnZrO_(3) light color adjustable phosphor:Luminescent property and application of warm white LED

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Journal of Rare Earths 2024年第8期42卷 1421-1428,I0001页

作者： Yunxiao Ma Chao linghu Ming Yang Hui Yu Xiangting Dong Long Xia School of Chemistry and Environmental Engineering Changchun University of Science and TechnologyChangchun130022China School of Materials Science and Engineering Harbin Institute of Technology(Weihai)Weihai264209China

Light emitting diode(LED) is the fourth generation lighting source,but it has some shortcomings such as complex chip packaging process and the unbalanced light color of phosphor in long-time *** this study,a kind of Eu-terephthalic acid/Tb-sulfosalicylate/ZrO_(2)/ZnZrO_(3)(Eu-PTA/Tb-SSA/ZrO_(2)/ZnZrO_(3))phosphor with warm white light emission properties was prepared,and the warm white light LED(wWLEDs) was successfully prepared by encapsulating Eu-PTA/Tb-SSA/ZrO_(2)/ZnZrO_(3) phosphors together with 270 nm *** ZrO_(2)/ZnZrO_(3),Tb-SSA/ZrO_(2)/ZnZrO_(3) and Eu-PTA/ZrO_(2)/ZnZrO_(3) samples show blue emission,green emission and red emission under deep ultraviolet(UV,270 nm) excitation,*** Tb-SSA and Eu-PTA are co-doped into ZrO_(2)/ZnZrO_(3) matrix with blue emission to achieve the warm white light emission,and the light color can be adjusted by controlling the doping amount of Eu^(3+)-and Tb^(3+).Through the excitation method of single-component phosphor by the single chip,the complex chip packaging process of w-LED can be *** doping rare earth organic complexes into porous ZrO_(2)/ZnZrO_(3) matrix,the problems of the light color unbalanced of phosphor and the low luminescence intensity of rare earth doped metal oxides composites can be solved.

关键词： Eu-PTA/Tb-SSA/ZrO_(2)/ZnZrO_(3) Luminescence material Light color adjustable phosphor Warm white emission W-WLEDs Rare earths

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The new criteria for differential diagnosis of indeterminate biliary stricture under super minimally invasive peroral cholangioscopy

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Chinese Medical Journal 2024年第3期137卷 255-256页

作者： Wengang Zhang Ningli Chai Qingzhen Wu Enqiang linghu Department of Gastroenterology Chinese PLA General HospitalBeijing 100853China

Indeterminate biliary stricture(IBS)refers to biliary stricture with an uncertain histological diagnosis^([1])and can be classified as non-neoplastic stricture or neoplastic *** former is mainly caused by various inflammatory biliopancreatic diseases,congenital malformations,or postoperative bile duct injury,while the latter exists in neoplastic lesions such as cholangiocarcinoma,invasion from pancreatic cancer,and adenomas in the bile *** non-neoplastic strictures can be relieved by endoscopic or conservative medical treatment,and only a few require surgical ***,radical surgery or palliative biliary drainage should be applied for neoplastic strictures according to the progression of the ***,it is essential to obtain an accurate diagnosis for IBS in clinical work.

关键词： diagnosis stricture biliary

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Reveal more mechanisms of precondition mesenchymal stem cells inhibiting inflammation

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World Journal of Stem Cells 2024年第4期16卷 459-461页

作者： Yi Li Qian-Qian Chen En-Qiang linghu Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology and Hepatology First Medical Center of Chinese PLA General HospitalBeijing 100853China

Hypoxia can get more ability to inhibit *** how it impact on survival time of mesenchymal stem cells(MSCs)is confusing and how preconditioned MSCs inhibiting inflammation are partially *** issues decided the value of ... 详细信息

关键词： Mesenchymal stem cell Hypoxia-inducible factor 1α Hypoxia Inflammation Macrophage

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A novel thermally-stable single-phase phosphor Ca2InTaO6:Dy3+ for NUV-excited white LEDs

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Journal of Rare Earths 2024年第10期42卷 1855-1864页

作者： Jian Hu Ruirui Cui Jun Zhang Peng linghu Youzhen Shi Xiang Guo key Laboratory of Micro-Nano-Electronics and Software Technology of Guizhou Province College of Big Data and Information EngineeringGuizhou University College of Computer and Information Engineering Guizhou University of Commerce

The work focuses on the utilization of the conventional solid-state sintering procedure to synthesize white phosphors Ca2InTaO6:xDy3+（0.02≤x≤0.12）.Utilizing X-ray diffraction,the phase structure of samples was examined,and the crystal structure was refined using the Rietveld method.A scanning electron microscope was used to analyze the microstructure of ***-principles calculations confirm that the indirect bandgap of Ca2InTaO6is 3.786 eV,The luminous properties and energy transfer mechanism of Ca2InTaO6:xDy3+were studied using photoluminescence ***4F9/2→6H13/2transition of Dy3+ions is responsible for the greatest emission peak,which was measured at 575 *** to research,the lifespan falls as the concentration of Dy3+doping amount rises because of frequent interaction and ene rgy transfer between Dy3+*** correlated color temperature of the WLEDs packaged with Ca2InTaO6:0.08Dy3+is 4677 K and CIE 1931 chromaticity coordinates are（0.3578,0.3831）.Meantime,the phosphor also shows outstanding te mperature stability property,which maintains 83.8% of its initial emission intensity at 450 K（activation energy of 0.1467 eV）.The W-LEDs retain their performance for 100 min when powered at 3.4 V voltage and 600 mA current,demonstrating the packed W-LEDs' sustaine d operation at high temperatures.

关键词： Ca2InTaO6:Dy3+ phosphors Photoluminescence Rare earths Thermal imaging Thermal stability W-LEDs

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Adverse effects of exposure to fine particles and ultrafine particles in the environment on different organs of organisms

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Journal of Environmental Sciences 2024年第1期135卷 449-473页

作者： Jianwei Zhang Zhao Chen Dan Shan Yang Wu Yue Zhao Chen Li Yue Shu Xiaoyu linghu Baiqi Wang Department of Occupational and Environmental Health School of Public HealthTianjin Medical UniversityTianjin 300070China Department of Medical Tianjin Stomatological HospitalSchool of MedicineNankai UniversityTianjin 300041China Tianjin key Laboratory of Environment Nutrition and Public HealthTianjin 300070China National Demonstration Center for Experimental Preventive Medicine Education(Tianjin Medical University) Tianjin 300070China

Particulate pollution is a global risk factor that seriously threatens human *** particles(FPs)and ultrafine particles(UFPs)have small particle diameters and large specific surface areas,which can easily adsorb metals,microorganisms and other *** and UFPs can enter the human body in multiple ways and can be easily and quickly absorbed by the cells,tissues and *** the body,the particles can induce oxidative stress,inflammatory response and apoptosis,furthermore causing great adverse *** studies mainly take the population as the research object to study the distribution of diseases and health conditions in a specific population and to focus on the identification of influencing ***,the mechanism by which a substance harms the health of organisms is mainly demonstrated through toxicological *** epidemiological studies with toxicological studies will provide a more systematic and comprehensive understanding of the impact of PM on the health of *** this review,the sources,compositions,and morphologies of FPs and UFPs are briefly introduced in the first *** effects and action mechanisms of exposure to FPs and UFPs on the heart,lungs,brain,liver,spleen,kidneys,pancreas,gastrointestinal tract,joints and reproductive system are systematically *** addition,challenges are further pointed out at the end of the *** work provides useful theoretical guidance and a strong experimental foundation for investigating and preventing the adverse effects of FPs and UFPs on human health.

关键词： Fine particles Ultrafine particles Organs Adverse effect

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