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Human Placental Mesenchymal Stem Cells Relieve Primary Sclerosing Cholangitis via Upregulation of TGR5 in Mdr2^(-/-)Mice and Human Intrahepatic Cholangiocyte Organoid Models

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research 2024年第2期2023卷 355-372页

作者： Qigu Yao Wenyi Chen Yingduo Yu Feiqiong Gao Jiahang Zhou Jian Wu Qiaoling Pan Jinfeng Yang Lingling Zhou Jiong Yu Hongcui Cao Lanjuan Li State Key Laboratory for the Diagnosis and treatment of Infectious Diseases Cllaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affliated HospitalZhejang University School of Medicine79 Qingchun Rd.Hangzhou 310003China National Clinical research center for Infectious Diseases HangzhouChina Key Laboratory of Diagnosis and treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province 79 Qingchun Rd.Hangzhou 310003China Jjinan Microecological Biomedicine Shandong Laboratory Jinan 250117China

Primary sclerosing cholangitis(PSC)is a biliary disease accompanied by chronic inflammation of the liver and biliary *** stem cells(msCs)are used to treat liver diseases because of their immune regulation and regeneration-promoting *** study was performed to explore the therapeutic potential of human placental msCs(hP-msCs)in PSC through the Takeda G protein-coupled receptor 5(TGR5)receptor *** tissues were collected from patients with PSC and healthy donors(n=4)for RNA sequencing and intrahepatic cholangiocyte organoid ***-msCs were injected via the tail vein into Mdr2^(-/-),bile duct ligation(BDL),and 3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC)mouse models or co-cultured with organoids to confirm their therapeutic effect on biliary *** in bile acid metabolic profile were analyzed by liquid chromatography/tandem mass spectrometry(LC-ms/ms).Compared with healthy controls,liver tissues and intrahepatic cholangiocyte organoids from PSC patients were characterized by inflammation and cholestasis,and marked downregulation of bile acid receptor TGR5 ***-msC treatment apparently reduced the inflammation,cholestasis,and fibrosis in Mdr2^(-/-),BDL,and DDC model *** activating the phosphatidylinositol 3 kinase/extracellular signal-regulated protein kinase pathway,hP-msC treatment promoted the proliferation of cholangiocytes,and affected the transcription of downstream nuclear factorκB through regulation of the binding of TGR5 and Pellino3,thereby affecting the cholangiocyte inflammatory phenotype.

关键词： inflammation TGR5 Human

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SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation

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Cancer Communications 2024年第3期44卷 384-407页

作者： Shiyu Zhang Xing Jia Haojiang Dai Xingxin Zhu Wenfeng Song Suchen Bian Hao Wu Shinuo Chen Yangbo Tang Junran Chen Cheng Jin Mengqiao Zhou Haiyang Xie Shusen Zheng Penghong Song Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China National Health Commission Key Laboratory of Combined Multi-organ Transplantation HangzhouZhejiangP.R.China Key Laboratory of the Diagnosis and treatment of Organ Transplantation Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic CancerChinese Academy of Medical SciencesHangzhouZhejiangP.R.China Key Laboratory of Organ Transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesHangzhouZhejiangP.R.China State Key Laboratory for Diagnosis and treatment of Infectious Diseases First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China

Background:Liver cancer is a malignancy with high morbidity and mortality *** family E member 2(SERPINE2)has been reported to play a key role in the metastasis of many *** this study,we aimed to investigate the potential mechanism of SERPINE2 in liver cancer ***:The Cancer Genome Atlas database(TCGA),including DNA methy-lation and transcriptome sequencing data,was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver *** from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clin-ical parameters of *** methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and *** sequencing,cytokine assays,immunoprecipitation(IP)and mass spectrometry(ms)assays,protein stability assays,and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer ***-derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using ***:Based on the public database screening,SERPINE2 was identified as a tumor promoter regulated by DNA ***2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver ***2 promoted liver cancer metas-tasis by enhancing cell pseudopodia formation,cell adhesion,cancer-associated fibroblast activation,extracellular matrix remodeling,and ***/ms assays confirmed that SERPINE2 activated epidermal growth factor receptor(EGFR)and its downstream signaling pathways by interacting with ***,SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase,***,EGFR was activated in liver cancer cells after sorafenib treatment,and SER

关键词： liver cancer metastasis DNA methylation SERPINE2 EGFR c-Cbl ubiquitination

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Phosphotungstic acid ionic liquid for efficient photocatalytic desulfurization:Synthesis,application and mechanism

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Chinese Journal of Chemical Engineering 2024年第5期69卷 101-111页

作者： Chenchao Hu Suhang Xun Desheng Liu Junjie Zhang Minqiang He Wei Jiang Huaming Li Wenshuai Zhu Institute of Environmental Health and Ecological Security School of Environment and Safety EngineeringJiangsu UniversityZhenjiang 212013China School of Chemistry and Chemical Engineering Institute for Energy ResearchJiangsu UniversityZhenjiang 212013China Jiangsu Collaborative Innovation center of Technology and Material of Water treatment Suzhou University of Science and TechnologySuzhou 215009China

An efficient mass transfer process is a critical factor for regulating catalytic activity in a photocatalytic desulfurization ***,a phosphotungstic acid(HPW)active center is successfully composited with a quaternary ammonium phosphotungstate-based hexadecyltrimethylammonium chloride ionic liquid(CTAC-HPW)by the ion exchange method for the photocatalytic oxidative desulfurization of dibenzothiophene *** keggin structure of HPW and highly mass transfer performance of organic cations synergistically enhanced the photocatalytic activity towards the effective convertion of dibenzothiophene(DBT)with the excitation of visible *** deep desulfurization(ms),proving that the final product is the corresponding *** trapping experiment and electron spin resonance(ESR)analysis confirmed that h^(+)and,COOH played critical roles in the oxidation *** work offers a practicable strategy for efficiently converting DBT to DBTO_(2) with added value.

关键词： Photocatalytic desulfurization Extraction Ionic liquid CTAC-HPW

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Highly active and durable core-shell electrocatalysts for proton exchange membrane fuel cells

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Nano research 2024年第10期17卷 8772-8784页

作者： Hsiwen Wu Fei Xiao Jing Wang Meng Gu Minhua Shao Department of Chemical and Biological Engineering The Hong Kong University of Science and TechnologyClear Water BayHong KongChina Department of Materials Science and Engineering Southern University of Science and TechnologyShenzhen 518055China Fok Ying Tung research Institute The Hong Kong University of Science and TechnologyGuangzhou 511458China Energy Institute and Chinese National Engineering research center for Control&treatment of Heavy Metal Pollution The Hong Kong University of Science and TechnologyClear Water BayHong KongChina

This work presents simple post-treatment methods to selectively and partially remove the Pd core of Pd-Pt core–shell(Pt@Pd/C)*** proton exchange membrane fuel cell with the post-treated Pt@Pd/C cathode(Pt loading:0.10 mg·cm^(-2))delivers an impressive peak power density of 1.2 W·cm^(-2).The partial removal of Pd core endows an ultrahigh oxygen reduction reaction(ORR)mass activity of 0.32 A·g_(PGM)-1 when normalized to the platinum group metal(PGM)mass,or equivalently 0.55 A·mg_(Pt)^(-1) at 0.9 V measured in a fuel *** post-treatment thickens the Pt shells and mitigates the Pd dissolution during potential *** a result,the post-treated core-shell catalyst demonstrates superior durability in ORR mass activity and polarization power density retention than untreated core-shell catalyst and benchmark Pt/***-situ inductively coupled plasmamass spectrometry(ICP-ms)results highlight that the amount of dissolved Pd in post-treated core–shell catalyst is 17-times lower than that of the untreated *** findings highlight the importance of structural tuning of catalysts in enhancing their mass activity and durability.

关键词： core-shell catalyst platinum monolayer proton exchange membrane fuel cell oxygen reduction reaction durability

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Hydrogen bond-bridged phosphorene flexible film for photodynamic inhibiting Staphylococcus aureus

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Nano research 2024年第6期17卷 5461-5468页

作者： Ziyu Wei Wenting Li Zhifang Liu Yongfa Zhu Huaqiang Cao Department of Chemistry Engineering Research Center of Advanced Rare Earth MaterialsTsinghua UniversityBeijing 100084China

Antibiotics are a widely used and effective treatment for bacterial ***,bacteria can gradually evolve during infection,leading to developing resistance to antibiotics,which renders previously effective treatments *** a useful and convenient manner to treat bacterial infections is a great ***,we report a flexible hydrogen-bond-bridged phosphorene film with photodynamic antibacterial properties and excellent mechanical properties,fabricated from electrochemical exfoliation of black phosphorus(BP).When illuminated under 700 nm light,the hydrogen bond-bridged phosphorene flexible film is capable of converting ground-state triplet oxygen(O_(2))into excited-state singlet oxygen(^(1)O_(2)),destroying the structure of the membrane of Staphylococcus aureus,and eventually leading to bacterial death,via breaking the C=C of unsaturated fatty acids within the bacterial cell membrane after the reaction between^(1)O_(2)and unsaturated fatty acids,thus realizing a highly efficient antibacterial approach,which is supported by gas chromatography-mass spectrometry(GC-ms)*** work establishes an effective phototherapy platform for treating bacterial traumatic infections.

关键词： hydrogen bond-bridged phosphorene flexible film photodynamic Staphylococcus aureus

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Altered spontaneous brain activity patterns in hypertensive retinopathy using fractional amplitude of low-frequency fluctuations:a functional magnetic resonance imaging study

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International Journal of Ophthalmology(English edition) 2024年第9期17卷 1665-1674页

作者： Xue-Lin Wang Xu-Jun Zheng Li-Juan Zhang Jin-Yu Hu Hong Wei Qian Ling Liang-Qi He Cheng Chen Yi-Xin Wang Xu Chen Yi Shao Department of Ophthalmology the First Affiliated Hospital of Jiangxi Medical CollegeEye Hospital of Shangrao CityShangrao 334000Jiangxi ProvinceChina Jiangxi Medical College Shangrao 334000Jiangxi ProvinceChina Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong University School of MedicineNational Clinical Research Center for Eye DiseasesShanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghai 200080China Department of Ophthalmology The First Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina School of Optometry and Vision Science Cardiff UniversityCardiff CF244HQWalesUK Ophthalmology Centre of Maastricht University Maastricht 6200MSLimburg ProvincieNetherlands

AIM:To study functional brain abnormalities in patients with hypertensive retinopathy(HR)and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations(fALFFs)***:Twenty HR patients and 20 healthy controls(HCs)were respectively *** age,gender,and educational background characteristics of the two groups were *** functional magnetic resonance imaging(fMRI)scanning,the subjects’spontaneous brain activity was evaluated with the fALFF *** operating characteristic(ROC)curve analysis was used to classify the ***,we used Pearson’s correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with ***:The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus(RO-MFG)and right lingual *** contrast,the values of fALFFs in the left middle temporal gyrus(MTG),left superior temporal pole(STP),left middle frontal gyrus(MFG),left superior marginal gyrus(SMG),left superior parietal lobule(SPL),and right supplementary motor area(SMA)were higher in the HR *** results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group(Pms of HR.

关键词： hypertensive retinopathy fractional amplitude of low-frequency fluctuation brain region magnetic resonance imaging

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A retrospective analysis of mature T-and NK-cell lymphomas

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Cancer Biology & Medicine 2024年第3期21卷 223-229页

作者： Junlei Jia Xiaohui Wang Zheng Song Shen Meng Yue Fei Jingwei Yu Xia Liu Xue Han Lanfang Li Lihua Qiu Zhengzi Qian Shiyong Zhou Wenchen Gong Bin Meng Xiubao Ren Xianhuo Wang Huilai Zhang National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine and Department of LymphomaTianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinThe Sino-US Center for Lymphoma and Leukemia ResearchTianjin 300060China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China Department of Pathology Department of Immunology/Biotherapy Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin 300060China

Mature T-and natural killer(NK)-cell lymphomas are heterogeneous groups of malignant lymphoid neoplasms arising from T and NK cells. The incidence of mature T-and NK-cell lymphomas is 2.1 per 100,000 people, according... 详细信息

关键词： lymphoma neoplasms killer

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Anti-biofilm and anti-virulence potential of cell free supernatant of Akkermansia muciniphila against Salmonella

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Food Science and Human Wellness 2024年第5期13卷 2677-2689页

作者： Jiaxiu Liu Wenxiu Zhu Huanhuan Liu Xiaomeng Ren Ningbo Qin Xiaodong Xia National Engineering research center of Seafood School of Food Science and TechnologyDalian Polytechnic UniversityDalian 116034China

Akkermansia muciniphila is one of the commensals residing within the mammalian gut and co-evolving with the *** studies have demonstrated the benefits of *** in ameliorating metabolic disorders,while little is known about the antimicrobial potential of *** against ***,we examined the antimicrobial and anti-virulence properties of cell free supernatant(CFS)of *** against Salmonella *** retarded bacterial growth and inhibited the motility of *** SL1344 and *** *** dose-dependently reduced cell hydrophobicity and auto-aggregation of both ***,CFS from *** significantly attenuated biofilm *** with untreated bacteria,CFS-treated bacteria significantly decreased adhesion and invasion to Caco-2 cells,and reduced intracellular survival in *** maintained antimicrobial properties after treatment with high temperatures and various proteases,while it lost its antimicrobial activity after pH *** chromatography-mass spectrometry(GC-ms)confirmed that *** produced a certain amount of acetate and propionate,and ultra-high-performance liquid chromatography-mass spectrometry(UHPLCms)identified other organic acids and metabolites in *** summary,CFS from *** exhibited anti-biofilm and anti-virulence properties against Salmonella and could be potentially utilized in the food industry for controlling Salmonella contamination and reducing infection.

关键词： Akkermansia muciniphila Salmonella Biofilm Motility Short-chain fatty acid Adhesion Invasion

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Intraperitoneal injection but not oral administration of ellagic acid: A novel immunomodulator via targeting casein kinase 2 signaling pathway

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Food Science and Human Wellness 2024年

作者： Wen-Hui Qi Bing Han Ting-Ting Cui Pei-Xin Shen Zhuo-Hua Zhao Ya-Ping Yan Li-Bin Wang Xin-Yu Lu Yuan Zhang Xing Li Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University)， The Ministry of Education College of Life Sciences， Shaanxi Normal University Department of Pharmacology， School of Pharmacy， Fourth Military Medical University The Nervous System Disease Diagnosis and treatment Engineering Technology research center of Ningxia School of Medical Technology， Xi'an Medical University

Immunosuppressants currently approved for the treatment of autoimmune diseases and organ transplant rejection present diverse adverse effects that impair the life quality of patients. Therefore， the development of novel immunomodulators with high efficiency and low toxicity is essential. Ellagic acid (EA)， a natural polyphenol compound widely distributed in berries， is metabolically transformed by gut microbiome to exert systemic health benefits. Here， we identified that intraperitoneal administration of EA with no cytotoxicity， beyond its well-known oral metabolic fate， effectively decreased clinical severity and CNS inflammation/demyelination in experimental autoimmune encephalomyelitis (EAE)， a mouse model of an autoimmune disease multiple sclerosis (ms). Interestingly， intraperitoneal EA administration at incredibly low doses (0.1 mg/kg/d) is dose-sparing with fingolimod (FTY720)， the first FDA-approved oral drug for ms. In addition， intraperitoneal EA also ameliorated the brain damage in a neuromyelitis optica (NMO) model， and significantly prevented the immune rejection of allograft skin graft. Evidence from pharmacological studies combined with RNA-seq indicate that prototype EA functions by a mechanism that involves direct inhibition of casein kinase II (CKII) to suppress the expression of IL-17 and promote the expression of Cpt1a to regulate Th17 differentiation. In conclusion， our study demonstrates that the prototype EA entering the blood circulation acts as a novel therapeutic immunomodulator for the treatment of autoimmune diseases and transplant rejection through the CKⅡ-mediated JAK/STAT/Cpt1a signaling pathway.

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Peroxidase-like nanozyme based microenvironment-responsive injectable hydrogel for bacteria-infected wound healing

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Science China Technological Sciences 2024年第10期67卷 3247-3260页

作者： ZHOU Wei LI XiaNan TANG MengCheng PAN LingFeng WANG BeiBei ZHANG Hao ZHANG Han WANG ShiBo KONG XiangDong Institute of Smart Biomaterial Materials School of Materials Science and EngineeringZhejiang University of Science & Technology Zhejiang-Mauritius Joint research center for Biomaterials and Tissue Engineering Zhejiang University of Science & Technology

Hydrogel stands out as one of the most attractive wound dressings due to its excellent moisturizing properties and capacity to absorb wound exudates. However, conventional hydrogel dressings often lack responsiveness to the microenvironment, merely acting as protective barriers for the wound. Consequently, they exhibit limited effectiveness in preventing infection and facilitating wound repair. To address these problems, we have developed a multifunctional injectable hydrogel, CF/ms@HG, based on peroxidase-like nanozymes, aiming at rapidly healing bacterial-infected wounds. The hydrogel is mainly composed of oxidized sodium alginate, aminated gelatin, and polylysine, encapsulating MIL-101(CuFe) NPs(CF) and manganese selenide nanoparticles(MnSe2NPs, or ms NPs). After injection, the complex rapidly gelatinizes at the infected wound site through a Schiff base reaction. In vitro experiments have demonstrated the hydrogel's strong adhesion and self-healing ***, CF exhibiting peroxidase(POD)-like activity, catalyzes in situ hydrogen peroxide(H2O2) to generate highly toxic hydroxyl radicals(·OH) within the wound microenvironment, inducing oxidative damage to bacteria. Meanwhile, ms decomposes into H2Se in the slightly acidic wound microenvironment, disrupting bacterial metabolism and inhibiting *** addition of polylysine further enhances the hydrogel's antibacterial properties. In vivo experiments have shown that the hydrogel exhibits excellent biological safety and significantly promotes wound healing. This multifunctional smart hydrogel holds great promise for the treatment of bacterial-infected wounds.

关键词： peroxidase-like nanozyme manganese selenide injectable hydrogel bacterial infection wound healing

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