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Interferon-gamma inhibits aldehyde dehydrogenase^(bright)cancer stem cells in the 4T1 mouse model of breast cancer

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Chinese Medical Journal 2022年第2期135卷 194-204页

作者： Xiufen Zhuang Guilan Shi Xiao Hu Huiru Wang Wen Sun Yanhong Wu Department of Oncology Affiliated Hospital of Jiangsu UniversityZhenjiangJiangsu 212000China Department of Immunology Zibo Vocational Institute Health SchoolZiboShandong 255000China Department of Medical Engineering Morsani College of MedicineTampaFL 33612USA Department of Oncology Suqian First HospitalSuqianJiangsu 223800China Department of Blood Transfusion The First Affiliated Hospital of USTCHefeiAnhui 230001China Department of Medical Microbiology and Immunology School of Basic Medical SciencesWannan Medical CollegeWuhuAnhui 241002China.

Background:Despite improvements in disease diagnosis,treatment,and prognosis,breast cancer is still a leading cause of cancer death for women.Compelling evidence suggests that targeting cancer stem cells(CSCs)have a crucial impact on overcoming the current shortcomings of chemotherapy and radiotherapy.In the present study,we aimed to study the effects of T cells and a critical anti-tumor cytokine,interferon-gamma(IFN-γ),on breast cancer stem cells.Methods:BALB/c mice and BALB/c nude mice were subcutaneously injected with 4T1 tumor cells.Tumor growth and pulmonary metastasis were assessed.ALDEFLOUR™assays were performed to identify aldehyde dehydrogenase^(bright)(ALDH^(br))tumor cells.ALDH^(br)cells as well as T cells from tumor-bearing BALB/c mice were analyzed using flow cytometry.The effects of CD8^(+)T cells on ALDH^(br)tumor cells were assessed in vitro and in vivo.The expression profiles of ALDH^(br)and ALDH^(dim)4T1 tumor cells were determined.The levels of plasma IFN-γwere measured by enzyme-linked immunosorbent assay,and their associations with the percentages of ALDH^(br)tumor cells were evaluated.The effects of IFN-γon ALDH expression and the malignancy of 4T1 tumor cells were analyzed in vitro.Results:There were fewer metastatic nodules in tumor-bearing BALB/c mice than those in tumor-bearing BALB/c nude mice(25.40 vs.54.67,P<0.050).CD8^(+)T cells decreased the percentages of ALDH^(br)4T1 tumor cells in vitro(control vs.effector to target ratio of 1:1,10.15%vs.5.76%,P<0.050)and in vivo(control vs.CD8^(+)T cell depletion,10.15%vs.21.75%,P<0.001).The functions of upregulated genes in ALDH^(br)4T1 tumor cells were enriched in the pathway of response to IFN-γ.The levels of plasma IFN-γdecreased gradually in tumor-bearing BALB/c mice,while the percentages of ALDH^(br)tumor cells in primary tumors increased.IFN-γat a concentration of 26.68 ng/mL decreased the percentages of ALDH^(br)4T1 tumor cells(22.88%vs.9.88%,P<0.050)and the protein levels of aldehyde dehydrogenase 1 family member A1 in 4T1 tumor cells(0

关键词： Cancer stem cells Aldehyde dehydrogenase Interferon-gamma CD8+T cells

Mori fructus aqueous extracts attenuates liver injury by inhibiting ferroptosis via the Nrf2 pathway

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Journal of Animal Science and Biotechnology 2023年第4期14卷 1418-1437页

作者： Yuanyuan Wei Chen Gao Huiru Wang Yannan Zhang Jinhua Gu Xiuying Zhang Xuhao Gong Zhihui Hao Innovation Centre of Chinese veterinary medicine College of Veterinary MedicineChina Agricultural UniversityNo.2 Yuanmingyuan West RoadBeijing 100193China Key Biology Laboratory of Chinese Veterinary Medicine Ministry of Agriculture and Rural AffairsBeijing 100193P.R.China National Center of Technology Innovation for Medicinal function of Food National Food and Strategic Reserves AdministrationBeijingChina China Institute of Veterinary Drug Control Beijing 100081China

Background Liver fibrosis and hepatocellular carcinogenesis secondary to liver fibrosis are serious liver diseases with no effective treatments.Mori fructus aqueous extracts(MFAEs)have served as successful treatments for many types of liver injury including fibrosis although the molecular mechanisms are unknown at present.Purpose To investigate the effect of MFAEs in alleviating acute and chronic liver injury and tried to decipher the underlying mechanism.Methods and results Mice were divided into 5 groups(n ps:contro=8)for acute(groups:control,0.3%CCl_(4),bifendate(BD),100 and 200 mg/kg MFAEs,7 d)and chronic(groul,10%CCl_(4),BD,100 and 200 mg/kg MFAEs,4 weeks)liver injury study.Each mouse was injected intraperitoneally with 10μL/g corn oil containing CCl_(4)expect the control group.HepG2 cells were used in vitro study.Eighteen communal components were identified by UPLC-LTQOrbitrap-MS.We utilized a mouse model for acute and chronic liver injury using CCl_(4)and MFAEs administration effectively blocked fibrosis and significantly inhibited inflammation in the liver.MFAEs activated the nuclear factor erythroid derived 2 like 2/heme oxygenase 1(Nrf2/HO-1)pathway and promoted the synthesis of the antioxidants glutathione(GSH),superoxidedismutase(SOD)and glutathione peroxidase(GSH-Px)that resulted in reduced levels of CCl_(4)-induced oxidative stress molecules including reactive oxygen species.These extracts administered to mice also inhibited ferroptosis in the liver by regulating the expression of Acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),thus reducing the occurrence of liver fibrosis.Both in vivo and in vitro tests indicated that the mechanism of MFAEs protection against liver fibrosis was linked to activation of Nrf2 signaling.These effects were blocked in vitro by the addition of a specific Nrf2 inhibitor.Conclusion MFAEs inhibited oxidative stress,ferroptosis and inflammation of the liver by activating Nrf2 signal pathway an

关键词： Acute and chronic liver injury Ferroptosis Mori fructus aqueous extracts Nrf2 Oxidative stress

Challenges in Analysis of Hydrophilic Metabolites Using Chromatography Coupled with Mass Spectrometry

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Journal of Analysis and Testing 2020年第3期4卷 140-162页

作者： Qingyu Hu huiru Tang Yulan wang CAS Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Centre for Magnetic Resonance in WuhanWuhan Institute of Physics and MathematicsInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of Sciences(CAS)Wuhan 430071People’s Republic of China University of Chinese Academy of Sciences Beijing 10049People’s Republic of China State Key Laboratory of Genetic Engineering Zhongshan Hospital and School of Life SciencesLaboratory of Metabonomics and Systems BiologyHuman Phenome InstituteFudan UniversityShanghai 200433People’s Republic of China Singapore Phenome Center Lee Kong Chian School of MedicineNanyang Technological UniversitySingapore 639798Singapore

Hydrophilic metabolites play important roles in cellular energy metabolism,signal transduction,immunity.However,there are challenges in both identification and quantification of the hydrophilic metabolites due to their weak interactions with C18-reversed-phase liquid chromatography(RPLC),leading to poor retention of hydrophilic metabolites on the columns.Many strategies have been put forward to increase the retention behavior of hydrophilic metabolites in the RPLC system.Non-derivatization methods are mainly focused on the development of new chromatographic techniques with different separation mechanisms,such as capillary electrophoresis,ion-pairing RPLC etc.Derivatization methods improve the hydrophobicity of metabolites and can enhance the MS response.This review mainly focused on the illustration of challenges of LCMS in the analysis of hydrophilic metabolomics field,and summarized the non-derivatization and derivatization strategies,with the intention of providing multiple choices for analysis of hydrophilic metabolites.

关键词： Hydrophilic metabolites Hydrophilic interaction chromatography Ion-pairing reversed-phase liquid chromatography Ion chromatography Capillary electrophoresis Derivatization

Research on the Chinese Path to Modernization in History,Key Topics,and Outlook:A Cite Space-based Bibliometric Analysis

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Contemporary Social Sciences 2023年第6期8卷 75-96页

作者： wang Linmei Yang huiru Sichuan University

In the speech delivered at the centenary celebration of the Communist Party of China(CPC),Xi Jinping,general secretary of the Communist Party of China(CPC)Central Committee,made important remarks on the“Chinese path to modernization.”This term represents the latest achievement China has scored in adapting Marxism to the Chinese context and the needs of the times.It has set the course as China embarks on a new journey of building a strong socialist country with Chinese characteristics and achieving national rejuvenation.Drawing on CiteSpace,we conducted a visualized bibliometric analysis of literature on the Chinese path to modernization by searching the CNKI database using subject terms such as“Chinese modernization,Chinese path to modernization,and Chinese-style modernization.”The findings reveal that:(a)Research on the Chinese path to modernization has gone through three stages:initial establishment,pioneering exploration,and comprehensive in-depth development.(b)Existing literature has covered the four key topics associated with the Chinese path to modernization,namely its essence,goal,methodology,and pioneering achievements.(c)Future research may focus on building up China’s strength in agriculture,developing the digital economy,modernizing China’s system and capacity for governance,and establishing a unique socialist discourse system for Chinese modernization.

关键词： the Chinese path to modernization history key topics outlook

Effects of varying dietary folic acid during weaning stress of piglets

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Animal Nutrition 2021年第1期7卷 101-110页

作者： Lei wang Xian Tan Huiru Wang Qiye wang Pengfei Huang Yali Li Jianzhong Li Jing Huang Huansheng Yang Yulong Yin Laboratory of Animal Nutrition and Human Health Hunan International Joint Laboratory of Animal Intestinal Ecology and HealthCollege of Life ScienceHunan Normal UniversityChangsha410081China Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionKey Laboratory of Agro-ecological Processes in Subtropical RegionScientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-CentralMinistry of AgricultureInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha410125China Department of Neuroscience Hengyang School of MedicineUniversity of South ChinaHengyang421000China

The present study was conducted to evaluate the effect of dietary folic acid on the growth performance,intestinal morphology,and intestinal epithelial cells renewal in post-weaning piglets.Twenty-eight piglets(weaned at day 21,initial body weight of 6.73±0.62 kg)were randomly allotted to 4 treat-ments with 7 pens per diet and 1 piglet per pen.The piglets were fed the same antibiotic-free and zinc oxide-free basal diets supplemented with folic acid at 0,3,9,and 18 mg/kg for 14 days.The results showed that dietary supplementation with folic acid increased villus height(VH)(P=0.003;linear,P=0.001),VH-to-crypt depth(VH:CD)ratio(P=0.002;linear,P=0.001),villus surface area(VSA)(P=0.026;linear,P=0.010).The analyzed parameters ADG,serum urea nitrogen(BUN)content,VH,VSA,and serum folate(SF)concentration responded linearly to the dietary folic acid concentration when the dietary folic acid concentration was below 4.42,5.26,4.79,3.47,and 3.53 mg/kg respectively(R2=0.995,0.995,0.999,0.999,0.872,P=0.09,0.07,0.09,0.09,0.36,respectively),as assessed by a two-linear broken-line regression.Above these breakpoints,the response of ADG,VH,VSA,and SF plateaued in response to changes in dietary folic acid concentration.Moreover,dietary supplementation with folic acid significantly increased the lactase(P=0.001;linear,P=0.001)and sucrase activities(P=0.021;linear,P=0.010)in the jejunal mucosa of weaned piglets.The mRNA expression of solute carrier family 6 member 19(SLC6a19),solute carrier family 1 member 1(SLC7a1),tumor necrosis factor-α(TNF-α),the number of Ki67 positive cells,and cell shedding rate had a significant linear contrast(P=0.023,0.021,0.038,0.049,and 0.008,respectively)in dietary folic acid groups.In conclusion,our results indicate that folic acid supplementation can improve the growth performance and intestinal morphology of weaned piglets by maintaining the balance of epithelial cell renewal.

关键词： Folic acid Growth performance Antibiotic-free Intestinal morphology Post-weaning piglet

A betaxanthin-based visible and fluorescent reporter for monitoring plant transformation

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The Crop Journal 2023年第2期11卷 666-671页

作者： Yuanjie Deng Aoqi Duan Tong Li Huiru Wang Aisheng Xiong State Key Laboratory of Crop Genetics and Germplasm Enhancement Ministry of Agriculture and Rural Affairs Key Laboratory of Biology and Germplasm Enhancement of Horticultural Crops in East ChinaCollege of HorticultureNanjing Agricultural UniversityNanjing 210095JiangsuChina

Commonly used reporters rely on a single property,such as the fluorescence of GFP and visible color of anthocyanins,therefore these reporters hardly handle the complicated condition in practice.Betaxanthins are a group of plant natural products derived from the amino acid tyrosine.Its visible yellow-orange color and green fluorescence under blue light make it a promising new reporter.Only two enzymatic reactions are required to convert tyrosine into betaxanthins.Here,we synthesized an open reading frame named Bx that contained all the betaxanthins biosynthetic genes and demonstrated its use as a powerful and efficient reporter in tobacco,carrot,and tomato.

关键词： Reporter Betaxanthins Visible Fluorescent Plant transformation

Highly Efficient Labeling of Human Lung Cancer Cells Using Cationic Poly-L-lysine-Assisted Magnetic Iron Oxide Nanoparticles

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Nano-Micro Letters 2015年第4期7卷 374-384页

作者： Xueqin wang huiru Zhang Hongjuan Jing Liuqing Cui College of Bioengineering Henan University of Technology

Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological properties of human lung carcinoma cells remain scarcely reported.Therefore,in the present study the magnetic c-Fe2O3nanoparticles(MNPs)were firstly synthesized and surface-modified with cationic poly-L-lysine(PLL)to construct the PLL-MNPs,which were then used to magnetically label human A549 lung cancer cells.Cell viability and proliferation were evaluated with propidium iodide/fluorescein diacetate double staining and standard 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium)bromide assay,and the cytoskeleton was immunocytochemically stained.The cell cycle of the PLL-MNPlabeled A549 lung cancer cells was analyzed using flow cytometry.Apoptotic cells were fluorescently analyzed with nuclear-specific staining after the PLL-MNP labeling.The results showed that the constructed PLL-MNPs efficiently magnetically labeled A549 lung cancer cells and that,at low concentrations,labeling did not affect cellular viability,proliferation capability,cell cycle,and apoptosis.Furthermore,the cytoskeleton in the treated cells was detected intact in comparison with the untreated counterparts.However,the results also showed that at high concentration(400 lg m L-1),the PLL-MNPs would slightly impair cell viability,proliferation,cell cycle,and apoptosis and disrupt the cytoskeleton in the treated A549 lung cancer cells.Therefore,the present results indicated that the PLL-MNPs at adequate concentrations can be efficiently used for labeling A549 lung cancer cells and could be considered as a feasible approach for magnetic targeted anti-cancer drug/gene delivery,targeted diagnosis,and therapy in lung cancer treatment.

关键词： Magnetic labeling Iron oxide nanoparticles Poly-L-lysine Human A549 lung cancer cells Cancer treatment

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供应链人权尽责边界的比较分析与法理反思

人权 2024年第2期 124-147页

作者：王惠茹中国社会科学院国际法研究所

随着全球供应链日益冗长和复杂,供应链人权尽责正成为跨国公司问责领域备受争议的焦点话题。近年来,人权尽责领域的立法实践呈现出从自愿性软法向强制性硬法转化,从公司对自身业务的尽责向整个供应链尽责拓展的趋势。然而,对于人权尽责... 详细信息

随着全球供应链日益冗长和复杂,供应链人权尽责正成为跨国公司问责领域备受争议的焦点话题。近年来,人权尽责领域的立法实践呈现出从自愿性软法向强制性硬法转化,从公司对自身业务的尽责向整个供应链尽责拓展的趋势。然而,对于人权尽责应在多大程度上拓展至供应链以及应以何种模式纳入国内法律政策,各国实践立场迥异。国际软法围绕供应链人权尽责边界的多中心化解释,不仅使其面临解释多元化、界限模糊化和实施程序化的风险,而且面临被误读和滥用的风险。与此同时,一些国家和地区极力推动强制性供应链人权尽责立法,对全球供应链稳定与国际经贸秩序产生深远影响。在此背景下,探讨供应链人权尽责的合理边界具有重要意义。供应链人权尽责不应一概而论,而应兼顾法律因素的合理性与现实因素的复杂性,根据公司与供应链中负面人权影响之间的不同联系程度分情境适用。中国应尤为警惕强制性供应链人权尽责立法的“寒蝉效应”,高度重视国家供应链安全与国际供应链竞争,积极推进联合国框架下自愿性人权尽责的实施,加快提升中国参与工商业与人权领域国际规则制定的话语权。

关键词：工商业与人权人权尽责供应链国际软法强制性尽责

Development and validation of an improved probabilistic quotient normalization method for LC/MS-and NMR-based metabonomic analysis

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Chinese Chemical Letters 2020年第7期31卷 1827-1830页

作者： Yanpeng An Si Liu Fuhua Hao Yulan wang huiru Tang State Key Laboratory of Genetic Engineering Zhongshan Hospital and School of Life SciencesHuman Phenome InstituteMetabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular PhenomicsFudan UniversityShanghai 200438China C4S Key Laboratory of Magnetic Resonance in Biological Systems Stare Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsWuhan Institute of Physics and MathematicsUniversity of Chinese Academy of SciencesWuhan 430071China Singapore Phenome Center Lee Kong Chian School of MedicineSchool of Biological SciencesNanyang Technological UniversitySingapore 636921Singapore

Robust normalization is a prerequisite for reliable metabonomic analysis especially when intervention treatments cause drastic metabolomic changes or when spot urinary samples are employed without knowing the drinking water quantity.With the simulated and real datasets,here,we report a probabilistic quotient normalization method based on the mode-of-quotients(mPQN)which is suitable for metabonomic analysis of both NMR and LC-MS data with little and/or drastic metabolite changes.When applied to metabonomic analysis of both animal plasma samples and human urinary samples,this newly proposed method has clearly shown better robustness than all classical normalization methods especially when drastic changes of some metabolites occur.

关键词： Metabonomics Normalization Probabilistic quotient normalization NMR LC-MS