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中国化学快报:英文版 2023年第9期34卷 85-99页

作者： Meifang wang ping’an Ma jun Lin State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China

The cancer cells realize their proliferation and metastasis activities based on the special redox adaptation to increased reactive oxygen species(ROS)level,which inversely makes them sensitive to external interference with their redox state.In view of this,in recent decades,researchers have made great efforts to construct a series of novel nanoplatform-based ROS-mediated cancer therapies through increasing ROS generation and inhibiting the ROS elimination.Besides,the multidrug resistance and thermoresistance of tumor are closely related to tumor redox state.Recently,numerous works have shown that ROS regulation in cancer cells can intervene in the expression,function and stability of related proteins to achieve reversal of tumor resistance.In this review,the recent researches about ROS-regulating nanoagents on cancer therapy and tumor resistance alleviation have been well summarized.Finally,the challenges and research directions of ROS-regulating nanoagents for future clinical translation are also discussed.

关键词： Nanoagents ROS regulation ROS-mediated cancer therapy Multidrug resistance Thermoresistance

Role of intestinal microbiota and metabolites in inflammatory bowel disease

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Chinese Medical Journal 2019年第13期132卷 1610-1614页

作者： Li-Na Dong Mu wang Jian Guo Jun-Ping Wang Central Laboratory Shanxi Provincial People's HospitalAffiliate of Shanxi Medical UniversityTaiyuanShanxi 030012China Department of Neurology Shanxi Provincial People's HospitalAffiliate of Shanxi Medical UniversityTaiyuanShanxi 030012China Department of General Surgery Shanxi Provincial People's HospitalAffiliate of Shanxi Medical UniversityTaiyuanShanxi 030012China Department of Gastroenterology Shanxi Provincial People's HospitalAffiliate of Shanxi Medical UniversityTaiyuanShanxi 030012China

Objective:The metabolites produced by the gut microbiota are of interest to scientists.The objective of this review was to provide an updated summary of progress regarding the microbiota and their metabolites and influences on the pathogenesis of inflammatory bowel disease(IBD).Data sources:The author retrieved information from the PubMed database up to January 2018,using various combinations of search terms,including IBD,microbiota,and metabolite.Study selection:Both clinical studies and animal studies of intestinal microbiota and metabolites in IBD were selected.The information explaining the possible pathogenesis of microbiota in IBD was organized.Results:In IBD patients,the biodiversity of feces/mucosa-associated microbiota is decreased,and the probiotic microbiota is also decreased,whereas the pathogenic microbiota are increased.The gut microbiota may be a target for diagnosis and treatment of IBD.Substantial amounts of data support the view that the microbiota and their metabolites play pivotal roles in IBD by affecting intestinal permeability and the immune response.Conclusions:This review highlights the advances in recent gut microbiota research and clarifies the importance of the gut microbiota in IBD pathogenesis.Future research is needed to study the function of altered bacterial community compositions and the roles of metabolites.

关键词： Inflammatory bowel disease Metabolite Microbiota

Nonparametric Estimation for the Diffusion Coefficient of Multidimensional Time-Varying Diffusion Processes

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Journal of Systems Science & Complexity 2020年第5期33卷 1602-1631页

作者： wang jun CHEN ping Department of Science Nanjing University of Science andTechnologyNanjing 210000China

This paper proposes a kernel estimator for the coefficient of multidimensional time-varying diffusion processes as an extension of the estimation model for one dimensional diffusion coefficient to the multidimensional case.By using"time division",the authors overcome the problem of sample observation in time varying model.In addition,the authors prove the strong consistency and limit distribution of the estimator.Finally,the authors test the performance of the estimator through a simulation experiment and an empirical application.

关键词： Asymptotic properties kernel function multidimensional model nonparametric estimation time-inhomogeneous

Ubiquitin-conjugating enzyme E2T knockdown suppresses hepatocellular tumorigenesis via inducing cell cycle arrest and apoptosis

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World Journal of Gastroenterology 2019年第43期25卷 6386-6403页

作者： Jian Guo Mu wang Jun-Ping Wang Chang-Xin Wu Institute of Biotechnology Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of EducationInstitute of BiotechnologyShanxi UniversityTaiyuan 030006Shanxi ProvinceChina Department of General Surgery Shanxi Provincial People’s Hospitalthe Affiliated People’s Hospital of Shanxi Medical UniversityTaiyuan 030012Shanxi ProvinceChina Department of Neurology Shanxi Provincial People’s Hospitalthe Affiliated People’s Hospital of Shanxi Medical UniversityTaiyuan 030012Shanxi ProvinceChina Department of Gastroenterology Shanxi Provincial People’s Hospitalthe Affiliated People’s Hospital of Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina The Institutes of Biomedical Sciences Shanxi UniversityTaiyuan 03006Shanxi ProvinceChina Key Laboratory of Molecular Biology and Biochemistry of Ministry of Education Shanxi UniversityTaiyuan 030006Shanxi ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is now the most common primary liver malignancy worldwide,and multiple risk factors attribute to the occurrence and development of HCC.Recently,increasing studies suggest that ubiquitinconjugating enzyme E2T(UBE2T)serves as a promising prognostic factor in human cancers,although the molecular mechanism of UBE2T in HCC remains unclear.AIM To investigate the clinical relevance and role of UBE2T in HCC development.METHODS UBE2T expression in HCC tissues from the TCGA database and its association with patient survival were analyzed.A lentivirus-mediated strategy was used to knock down UBE2T in HCC cells.qRT-PCR and Western blot assays were performed to check the effect of UBE2T silencing in HCC cells.Cell growth in vitro and in vivo was analyzed by multiparametric high-content screening and the xenograft tumorigenicity assay,respectively.Cell cycle distribution and apoptosis were determined by flow cytometry.The genes regulated by UBE2T were profiled by microarray assay.RESULTS UBE2T was overexpressed in HCC tissues compared with paired and non-paired normal tissues.High expression of UBE2T predicted a poor overall survival in HCC patients.In vitro,lentivirus-mediated UBE2T knockdown significantly reduced the viability of both SMMC-7721 and BEL-7404 cells.In vivo,the xenograft tumorigenesis of SMMC-7721 cells was largely attenuated by UBE2T silencing.The cell cycle was arrested at G1/S phase in SMMC-7721 and BEL-7404 cells with UBE2T knockdown.Furthermore,apoptosis was increased by UBE2T knockdown.At the molecular level,numerous genes were dysregulated after UBE2T silencing,including IL-1B,FOSL1,PTGS2,and BMP6.CONCLUSION UBE2T plays an important role in cell cycle progression,apoptosis,and HCC development.

关键词： Hepatocellular carcinoma Ubiquitin-conjugating enzyme E2T Cell cycle Apoptosis Tumorigenesis

Recent advances in CRISPR-based genome editing technology and its applications in cardiovascular research

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Military Medical Research 2023年第6期10卷 862-880页

作者： Zhen-Hua Li jun wang Jing-ping Xu Jian wang Xiao Yang State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein SciencesBeijing Institute of LifeomicsBeijing 100071China Yaneng BIOScience(Shenzhen)Co. Ltd.Shenzhen 518102GuangdongChina

The rapid development of genome editing technology has brought major breakthroughs in the fields of life science and medicine. In recent years, the clustered regularly interspaced short palindromic repeats(CRISPR)-based genome editing toolbox has been greatly expanded, not only with emerging CRISPR-associated protein(Cas) nucleases, but also novel applications through combination with diverse effectors. Recently, transposon-associated programmable RNA-guided genome editing systems have been uncovered, adding myriads of potential new tools to the genome editing toolbox. CRISPR-based genome editing technology has also revolutionized cardiovascular research. Here we first summarize the advances involving newly identified Cas orthologs, engineered variants and novel genome editing systems, and then discuss the applications of the CRISPR-Cas systems in precise genome editing, such as base editing and prime editing. We also highlight recent progress in cardiovascular research using CRISPR-based genome editing technologies, including the generation of genetically modified in vitro and animal models of cardiovascular diseases(CVD) as well as the applications in treating different types of CVD. Finally, the current limitations and future prospects of genome editing technologies are discussed.

关键词： Genome editing CRISPR-Cas system Base editing Prime editing Transposon-associated genome editing Cardiovascular disease Heart Blood vessel Gene therapy

Novel synthesis of aluminum hydroxide gel-coated nano zero-valent iron and studies of its activity in flocculation-enhanced removal of tetracycline

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Journal of Environmental Sciences 2020年第3期32卷 194-205页

作者： Xiangyu wang Binbin Zhang jun Ma ping Ning Faculty of Environmental Science and Engineering Kunming University of Science and TechnologyKunming 650500China School of Environment Harbin Institute of TechnologyHarbin 150090China

A newly designed aluminum hydroxide gel-coated nanoscale zero-valent iron(AHG@NZVI)with enhanced activity and dispersibility of NZVI was successfully synthesized.The AHG@NZVI composite was synthesized via control of the surface AHG content.AHG@NZVI-1,AHG@NZVI-2 and AHG@NZVI-3 were prepared under centrifugal mixing speeds of 1000,2000 and 4000 r/min,respectively.The activity of AHG@NZVI was evaluated by its tetracycline(TC) removal efficiency.The effects of AHG content,pH value,reaction temperature,and presence of competitive anions on TC removal were investigated.TC could be removed by both adsorption and chemical reduction on AHG@NZVI-2(centrifugal speed 2000 r/min) in a short time with high removal efficiency(≥98.1%) at the optimal conditions.Such excellent performance can be attributed to a synergistic interaction between aluminum hydroxide gel and NZVI:(1) AHG could enhance the stability and dispersity of NZVI;(2) aluminum hydroxide gel could absorb a certain amount of TC and Fe^2+/Fe^3+,which facilitated the mass transfer of TC onto the NZVI surface,resulting in acceleration of the reduction rate of TC by the AHG@NZVI composite;and(3) AHG-Fe^2+/Fe^3+could absorb a certain amount of TC by flocculation.The kinetics of TC removal by AHG@NZVI composite was found to follow a two-parameter pseudo-first-order model.The presence of competitive anions slightly inhibited the activity of AHG@NZVI systems for TC removal.Overall,this study provides a promising alternative material and environmental pollution management option for antibiotic wastewater treatment.

关键词： Nanoscale zerovalent iron Aluminum hydroxide gel Synergistic effect Tetracycline Flocculation

MiR-32-5p aggravates intestinal epithelial cell injury in pediatric enteritis induced by Helicobacter pylori

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World Journal of Gastroenterology 2019年第41期25卷 6222-6237页

作者： Jing Feng Jian Guo Jun-Ping Wang Bao-Feng Chai Institute of Loess Plateau Shanxi UniversityTaiyuan 030006Shanxi ProvinceChina Department of Gastroenterology Shanxi Provincial People's HospitalThe Affiliated People's Hospital of Shanxi Medical UniversityTaiyuan 030012Shanxi ProvinceChina Department of General Surgery Shanxi Provincial People's HospitalThe Affiliated People's Hospital of Shanxi Medical UniversityTaiyuan 030012Shanxi ProvinceChina

BACKGROUND Pediatric enteritis is one of the infectious diseases in the digestive system that causes a variety of digestive problems,including diarrhea,vomiting,and bellyache in children.Clinically,Helicobacter pylori(H.pylori)infection is one of the common factors to cause pediatric enteritis.It has been demonstrated that aberrant expression of microRNAs(miRNAs)is found in gastrointestinal diseases caused by H.pylori,and we discovered a significant increase of miR-32-5p in H.pylori-related pediatric enteritis.However,the exact role of miR-32-5p in it is still unknown.AIM To investigate the role of aberrant miR-32-5p in pediatric enteritis induced by H.pylori.METHODS MiR-32-5p expression was detected by quantitative real time-polymerase chain reaction.The biological role of miR-32-5p in H.pylori-treated intestinal epithelial cells was evaluated by Cell Counting Kit-8 assay and flow cytometry.The potential target of miR-32-5p was predicted with TargetScanHuman and verified by luciferase assay.The downstream mechanism of miR-32-5p was explored by using molecular biology methods.RESULTS We found that miR-32-5p was overexpressed in serum of H.pylori-induced pediatric enteritis.Further investigation revealed that H.pylori infection promoted the death of intestinal epithelial cells,and increased miR-32-5p expression.Moreover,miR-32-5p mimic further facilitated apoptosis and inflammatory cytokine secretion of intestinal epithelial cells.Further exploration revealed that SMAD family member 6(SMAD6)was the direct target of miR-32-5p,and SMAD6 overexpression partially rescued cell damage induced by H.pylori.The following experiments showed that miR-32-5p/SMAD6 participated in the apoptosis of intestinal epithelial cells induced by transforming growth factor-β-activated kinase 1(TAK1)-p38 activation under H.pylori infection.CONCLUSION Our work uncovered the crucial role of aberrant expression of miR-32-5p in H.pylori–related pediatric enteritis,and suggested that the TAK1-p38 pathway is involved in it.

关键词： MiR-32-5p SMAD family member 6 Transforming growth factor-β-activated kinase 1 Apoptosis Enteritis Helicobacter pylori

Heat distribution model under hydrogen-rich low-carbon conditions in blast furnace

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Journal of Iron and Steel Research(International) 2024年第3期31卷 584-594页

作者： Gang wang jun Xu Kun He Zhong-ping Zou Hao Bai School of Metallurgy and Ecological Engineering University of Science and Technology BeijingBeijing 100083China CISDI Low-Carbon Blast Furnace Research Office MCC Low-Carbon Technology Research InstituteChongqing 401122China

Low carbon development of blast furnaces is one of the key technological directions in the current development of ironmaking.Owing to the differences in the physical and chemical properties of hydrogen and carbon,hydrogen-rich media entering a blast furnace will change the heat distribution,thus affecting the stability of production.Accordingly,a heat distribution model was proposed to study the temperature distribution in a blast furnace,simultaneously considering gas-solid heat exchange,slag and iron melting,and chemical reactions.The model was used to analyze the temperature distribution of a 2300 m^(3) blast furnace and was verified via comparison with actual production data.Subsequently,the effects of the injection rate of hydrogen-rich media,H2 concentration,and oxygen enrichment rate of the blast on the temperature distribution were investigated.Results indicated that the increase in the injection rate of the hydrogen-rich media decreased the amount of direct reduction and led to an increase in the furnace temperature.Furthermore,an increase in the oxygen enrichment rate led to a decrease in the furnace temperature,but could reduce the solid fuel ratio,while the change in H2 concentration had less effect on the temperature distribution.The combination of hydrogen-rich media injection and the increase in the oxygen enrichment rate would help to adjust the temperature distribution to the same level as the conventional blast furnace conditions.

关键词： Heat distribution Blast furnace Low-carbon condition Hydrogen enrichment Calculation model

Molecular mechanism of anionic stabilizer for telomere G-quadruplex

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Biophysics Reports 2022年第4期8卷 225-238页

作者： Zhiguo wang Jianfeng Li jun Liu Lihui wang Yanhua Lu jun-ping Liu Institute of Ageing Research School of Basic Medical Sciences Hangzhou Normal University Department of Immunology Central Eastern Clinical School Monash University Hudson Institute of Medical Research Department of Molecular and Translational Science Monash University

Telomere DNA assumes a high-order G-quadruplex(G4) structure, stabilization of which prevents telomere lengthening by telomerase in cancer. Through applying combined molecular simulation methods, an investigation on the selective binding mechanism of anionic phthalocyanine 3,4’,4’’,4’’’-tetrasulfonic acid(APC) and human hybrid(3 + 1) G4s was firstly performed at the atomic level. Compared to the groove binding mode of APC and the hybrid type I(hybrid-I) telomere G4, APC preferred to bind to the hybrid type II(hybrid-II) telomere G4 via end-stacking interactions, which showed much more favorable binding free energies. Analyses of the non-covalent interaction and binding free energy decomposition revealed a decisive role of van der Waals interaction in the binding of APC and telomere hybrid G4s. And the binding of APC and hybrid-II G4 that showed the highest binding affinity adopted the end-stacking binding mode to form the most extensive van der Waals interactions. These findings add new knowledge to the design of selective stabilizers targeting telomere G4 in cancer.

关键词： Telomere G-quadruplex Anionic stabilizer Selective mechanism Molecular dynamics MM/GBSA

Short-term efficacy and influencing factors of conventional chemotherapy combined with irinotecan in patients with advanced gastric cancer

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World Journal of Gastrointestinal Oncology 2023年第1期15卷 143-154页

作者： Jun-Ping Wang Jian-Lei Du Ya-Ying Li Pharmacy Department Zhumadian Central HospitalZhumadian 463000Henan ProvinceChina

BACKGROUND Gastric cancer is one of the most common cancers worldwide, with a 5-year survival rate of only 20%. The age of onset of gastric cancer is in line with the general rule of cancer. Most of them occur after middle age, mostly between 40and 60 years old, with an average age of about 50 years old, and only 5% of patients are under 30 years old. The incidence of male is higher than that of female.AIM To investigate the short-term efficacy and influencing factors of chemotherapy combined with irinotecan in patients with advanced gastric cancer.METHODS Eighty patients with advanced gastric cancer who were treated in our hospital from January 2019 to January 2022 were selected. The patients were divided into an observation group(n = 40) and control group(n = 40) by the envelope method.The control group was given preoperative routine chemotherapy. The observation group was treated with irinotecan in addition to the chemotherapy given to the control group. The short-term efficacy of treatment in the two groups, as well as tumor marker levels and quality of life before and after treatment were evaluated.RESULTS The short-term treatment effect in the observation group was better than that in the control group(P < 0.05), and the total effective rate was 57.50%. The age and proportion of tumor node metastasis(TNM) stage IV patients with ineffective chemotherapy in the observation group were(65.12 ± 5.71) years and 52.94%,respectively, which were notably higher than those of patients with effective chemotherapy(P < 0.05), while the Karnofsky Performance Scale score was(67.70± 3.83) points, which was apparently lower than that of patients with effective chemotherapy(P <0.05). After 3 mo of treatment, the SF-36 scale scores of physiological function, energy, emotional function, and mental health in the observation group were 65.12 ± 8.14, 54.76 ± 6.70, 47.58 ± 7.22,and 66.16 ± 8.11 points, respectively, which were considerably higher than those in the control group(P < 0.05). The incidence rates of grade Ⅲ-Ⅳ diarrhea a

关键词： Advanced gastric cancer Conventional chemotherapy Irinotecan Efficacy Quality of life