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Human liver chimeric mouse model based on diphtheria toxin-induced liver injury

World Journal of Gastroenterology 2017年第27期23卷 4935-4941页

作者： Xiao-Nan ren rong-rong ren Hua Yang Bo-Yin Qin Xiu-Hua Peng Li-Xiang Chen Shun Li Meng-Jiao Yuan Chao Wang Xiao-Hui Zhou Shanghai Public Health Clinical Center Fudan University Key Laboratory of Medical Molecular Virology Ministry of Education and HealthFudan University

AIM To establish an inducible liver injury mouse model and transplant human hepatocytes to obtain liverhumanized *** We crossed three mouse strains,including albumin(Alb)-cre transgenic mice,inducible diphtheria toxin receptor(DTR) transgenic mice and severe combined immune deficient(SCID)-beige mice,to create Alb-cre/DTR/SCID-beige(ADSB) mice,which coincidentally harbor Alb-cre and DTR transgenes and are immunodeficient. As the Cre expression is driven by the liver-specific promoter Alb(encoding ALB),the DTR stop signal flanked by two lox P sites can be deleted in the ADSB mice,resulting in DTR expression in the liver. ADSB mice aged 8-10 wk were injected intraperitoneally(i.p.) with diphtheria toxin(DT) and liver damage was assessed by serum alanine aminotransferase(ALT) level. Two days later,mouse livers were sampled for histological analysis,and human hepatocytes were transplanted into the livers on the same day. A human ALB enzyme-linked immunosorbent assay was performed 7,14,21 and 28 d after transplantation. Human CD68 immunohistochemistry was performed 30 and 90 d after *** We crossed Alb-cre with DTR and SCID-beige mice to obtain ADSB mice. These mice were found to have liver damage 4 d after i.p. injection of 2.5 ng/g bodyweight DT. Bodyweight began to decrease on day 2,increased on day 7,and was lowest on day 4(range,10.5%-13.4%). Serum ALT activity began to increase on day 2 and reached a peak value of 289.7 ± 16.2 IU/m L on day 4,then returned to background values on day 7. After transplantation of human liver cells,peripheral blood human ALB level was 1580 ± 454.8 ng/m L(range,750.2-3064.9 ng/m L) after 28 d and Kupffer cells were present in the liver at 30 d in ADSB *** Human hepatocytes were successfully repopulated in the livers of ADSB mice. The inducible mouse model of humanized liver in ADSB mice may have functional applications,such as hepatocyte transplantation,hepatic regeneration and drug metabolism.

关键词： Liver disease Liver injury Diphtheria toxin Liver chimeric mouse model

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Effects of Proton Pump Inhibitors on the Gastrointestinal Microbiota in Gastroesophageal Reflux Disease

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Genomics, Proteomics & Bioinformatics 2019年第1期17卷 52-63页

作者： Yi-Chao Shi Shun-Tian Cai Ya-Ping Tian Hui-Jun Zhao Yan-Bing Zhang Jing Chen rong-rong ren Xi Luo Li-Hua Peng Gang Sun Yun-Sheng Yang Department of Gastroenterology and Hepatology Institute of Digestive Diseases Chinese PLA General Hospital School of Medicine Nankai University Core Laboratory of the Translational Medical Center Chinese PLA General Hospital Realbio Genomics Institute

Proton pump inhibitors(PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease(GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls(HCs) using 16 S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPIuser and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae,Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on shortterm PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.

关键词： Microbiota Gastroesophageal reflux disease Proton pump inhibitors Gastric mucosal Fecal

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Formation mechanism of fault accommodation zones under combined stress in graben basin:Implications from geomechanical modeling

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Petroleum Science 2024年第1期21卷 54-76页

作者： Qi-Qiang ren Jin-Liang Gao rong-Tao Jiang Jin Wang Meng-Ping Li Jian-Wei Feng Institute of Sedimentary Geology Chengdu University of TechnologyChengdu 610059SichuanChina PetroChina Research Institute of Petroleum Exploration and Development Beijing100083China Jianghan Oilfield Oil and Gas Production Capacity Construction Management Center Chongqing408000China Sinopec Chongqing Fuling Shale Gas Exploration and Development Company Chongqing408000China College of Energy Chengdu University of TechnologyChengdu 610059SichuanChina School of Geoscience China University of Petroleum(East China)Qingdao 266580ShandongChina

A fault accommodation zone is a type of structure that is defined as regulating displacement and strain between faults *** numbers of fault accommodation zones are being identified in graben basins,indicating the potential exploration target and petroleum accumulation *** study aims to analyze the formation mechanism and development of fault accommodation zones under combined stress by a numerical simulation method considering geomechanical *** three-dimensional(3-D)seismic interpretation and fractal dimension method,exampled with the Dongxin fault zone,the fault activity and fault combination pattern were conducted to quantitatively characterize the activity difference in fault accommodation *** with mechanical experiment test,a geomehcanical model was established for fault accommodation zones in a graben *** the paleostress numerical simulations and structural physical simulation experiment,the developmental characteristics and genetic mechanism of fault accommodation zones were *** by multi movements and combined stresses,three significant tectonic evolution stages of the Dongxing Fault Zone(DXFZ)were distinguished:During the E_(s)^(3)sedimentary period,the large difference in the stress,strain,and rupture distribution in various faults were significant,and this stage was the key generation period for the prototype of the DXFZ,including the FAZ between large-scale *** the E_(s)^(2)sedimentary period,the EW-trending symmetric with opposite dipping normal faults and the NE-SW trending faults with large scale were furtherly *** junction area of two secondary normal faults were prone to be ruptured,performing significant period for inheriting and developing characteristics of fault accommodation *** the Es1 sedimentary period,the high-order faults in the DXFZ exhibited the obvious fault depressions and strike-slip activity,and the fault accommodation zones were

关键词： Fault accommodation zone Graben basin Fault activity Tectonic physical simulation experiment Finite element numerical simulation Dongxin fault zone

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Self-assembled aggregations in Coptidis Rhizoma decoction dynamically regulate intestinal tissue permeability through Peyer's patch-associated immunity

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Chinese Herbal Medicines 2021年第3期13卷 370-380页

作者： Qing-qing Zhang Ye Yang rong-rong ren Qing-qing Chen Jing-jing Wu Yu-yu Zheng Xiao-hui Hou Yu-feng Zhang Ming-song Xue Deng-ke Yin School of Pharmacy Anhui University of Chinese MedicineHefei 230012China Institute of Pharmaceutics Anhui Academy of Chinese MedicineHefei 230012China Engineering Technology Research Center of Modernized Pharmaceutics Education Office of Anhui ProvinceHefei 230012China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

Objective:To investigate the dynamic regulation of self-assembled aggregations(SAA)in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism ***:The effects of SAA on berberine(Ber)absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer’s patches(PPs).The expression levels of ZO-1,Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction(TJ)between intestinal epithelium *** expression levels of T-box-containing protein expressed in T cells,signal transducers and activators of tranion-6,retinoic acid receptor-related orphan receptor ct and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-c(IFN-c),interleukin-4(IL-4),interleukin-17(IL-17)and transforming growth factor-b(TGF-b)in PPs were evaluated by immunohistochemistry,to reflect the differentiation of T lymphocyte in PPs to helper T(Th)cell 1,Th2,Th17 and regulatory T(Treg)*** confirm the correlation between SAA in Coptidis Rhizoma decoction,PPs-associated immunity and intestinal epithelium permeability,SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins ***:SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment,with the participation of *** dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in *** administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation,inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins ***:

关键词： Coptidis Rhizoma decoction intestinal absorption intestinal mucosal immunity Peyer’s patches self-assembled aggregations

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A self-powered solar-blind UV-enhanced Bi_(2)Se_(3)/a-Ga_(2)O_(3)/p-Si heterojunction photodetector for full spectral photoresponse and imaging

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Nano Research 2024年第4期17卷 2960-2970页

作者： Yajie Han Shujie Jiao Jiangcheng Jing Lei Chen Ping rong Shuai ren Dongbo Wang Shiyong Gao Jinzhong Wang School of Materials Science and Engineering Harbin Institute of TechnologyHarbin 150001China

Self-powered full-spectrum photodetectors(PDs)offer numerous advantages,such as broad application fields,high precision,efficiency,and multi-functionality,which represent a highly promising and potentially valuable class of detectors for future ***,insensitive response to solar-blind ultraviolet(UV)and complex and expensive preparation processes greatly limit their performance and practical *** this study,a self-powered full-spectrum Bi_(2)Se_(3)/a-Ga_(2)O_(3)/p-Si heterojunction PD with high sensitivity for solar-blind UV band prepared by a simple and low-cost two-step synthesis method is *** results reveal that the developed PD has an excellent performance,such as high sensitivity from 200 to 850 nm,and a responsivity of 1.38 mA/W as well as a detectivity of 3.22×10^(10) Jones under 254 nm light at zero ***,the unencapsulated device displays exceptional stability and imaging *** is expected that Bi_(2)Se_(3)/a-Ga_(2)O_(3)/p-Si heterojunction PD with a simple and low-cost synthesis method has great potential for self-powered full-spectrum photodetectors.

关键词： Bi_(2)Se_(3)/a-Ga_(2)O_(3)/p-Si self-powered photodetector full spectral photoresponse imaging

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Enantioselective Synthesis of Benzimidazole Atropisomers Featuring a N-N Axis

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Chinese Journal of Chemistry 2024年第7期42卷 711-718页

作者： Fang-Bei Ge Qi-Kun Yin Chuan-Jun Lu Xuan Xuan Jia Feng ren-rong Liu College of Chemistry and Chemical Engineering Qingdao UniversityQingdaoShandong 266071China School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationYantai UniversityYantaiShandong 264005China

Atroposelective synthesis of N-N atropisomers is an emerging area but remains underexplored;in particular,the synthesis of N-N benzimidazole atropisomers is still ***,the first enantioselective synthesis of N-N benzimidazole atropisomers via the palladium-catalyzed de novo construction of benzimidazole skeleton is *** readily available palladium catalyst and biphosphine ligand,a broad range of nonbiaryl benzimidazole and indole-benzimidazole atropisomers were conveniently ac-cessed in high yields and with excellent ***,these N-N benzimidazole atropisomers showed great anti-tumor activity and selectivity to breast cancer MCF-7 *** simple catalytic system,broad substrate scope,high enantioselectivi-ty,and good bioactivity make this approach highly attractive.

关键词： Asymmetric synthesis Atropisomerism Palladium Benzimidazole Antitumor

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Efficacy and safety of Y- 2 sublingual tablet for patients with acute ischaemic stroke: protocol of a phase III randomised double- blind placebo- controlled multicentre trial

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Stroke & Vascular Neurology 2024年第1期9卷 90-95页

作者： Yu Fu renhong Tang rong Chen Anxin Wang Jinsheng ren Shunwei Zhu Xiaofei Feng Dongsheng Fan Deparment of Neurology Peking University Third HospitalBeijingChina State Key Laboratory of Neurology and Oncology Drug Development NanjingJiangsuChina Simcere Pharmaceutical Group Limited NanjingJiangsuChina Neurodawn Pharmaceutical Co. LtdNanjingJiangsuChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina

Background and purpose Clinical studies have demonstrated that edaravone dexborneol can improve the functional outcomes in patients with acute ischaemic stroke(AIS).The present clinical trial aimed at testing the efficacy and safety of Y-2 sublingual tablet on 90-day functional outcome in patients with *** and design This is a randomised,double-blind,placebo-controlled,multicentre,parallel-group trial of Y-2 sublingual tablet on patients with *** estimated 914 patients at age of 18–80 years with AIS within 48 hours after symptom onset from 40 hospitals will be randomly assigned to receive Y-2 sublingual tablet or placebo for 14 *** are at score 6–20 points on National Institutes of Health Stroke Scale(NIHSS)and had a modified Rankin Scale(mRS)≤1 before this stroke,except mechanical thrombectomy and neuroprotective agents *** outcomes The primary outcome is the proportion of patients with mRS≤1 on day 90 after *** efficacy outcomes include mRS score on day 90,the proportion of patients with mRS≤2 on day 90;the change of NIHSS score from baseline to day 14 and the proportion of patients with NIHSS score≤1 at the days 14,30 and *** This trial will provide valuable evidence for the efficacy and safety of Y-2 sublingual table for improving 90 days the functional outcomes in patients with *** registration number NCT04950920.

关键词： patients protective centre

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Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

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World Journal of Hepatology 2024年第4期16卷 601-611页

作者： Shuai-Jun ren Jia-Ting Feng Ting Xiang Cai-Lian Liao Yu-Ping Zhou rong-rong Xuan Department of Obstetrics and Gynecology The First Affiliated Hospital of Ningbo UniversityNingbo 315100Zhejiang ProvinceChina Health Science Center Ningbo UniversityNingbo 315211Zhejiang ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Ningbo UniversityNingbo 315211Zhejiang ProvinceChina Institute of Digestive Disease Ningbo UniversityNingbo 315020Zhejiang ProvinceChina

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of ***-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such ***,the metabolic profile of SCFAs in patients with ICP remains *** To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these *** Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these *** Significant differences in maternal SCFAs were observed between the ICP and NP *** SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal *** analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of ***,the SCFA levels in maternal serum and cord blood were significantly positively ***,certain maternal serum SCFAs,specifically caproic and acetic acids,demonst

关键词： Intrahepatic cholestasis of pregnancy Short-chain fatty acids Maternal serum Cord blood Caproic acid

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Nanomaterial‑Based Repurposing of Macrophage Metabolism and Its Applications

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Nano-Micro Letters 2024年第11期16卷 494-528页

作者： Tingting Meng Danfeng He Zhuolei Han rong Shi Yuhan Wang Bibo ren Cheng Zhang Zhengwei Mao Gaoxing Luo Jun Den Institute of Burn Research Southwest HospitalState Key Laboratory of Trauma and Chemical PoisoningArmy Medical UniversityChongqing 400038People’s Republic of China Department of Breast Surgery Gansu Provincial HospitalLanzhouGansu 730030People’s Republic of China MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027People’s Republic of China

Macrophage immunotherapy represents an emerging therapeutic approach aimed at modulating the immune response to alleviate disease ***(NMs)have been engineered to monitor macrophage metabolism,enabling the evaluation of disease progression and the replication of intricate physiological signal *** achieve this either directly or by delivering regulatory signals,thereby mapping phenotype to effector functions through metabolic repurposing to customize macrophage fate for ***,a comprehensive summary regarding NM-mediated macrophage visualization and coordinated metabolic rewiring to maintain phenotypic equilibrium is currently *** review aims to address this gap by outlining recent advancements in NM-based metabolic *** initially explore the relationship between metabolism,polarization,and disease,before delving into recent NM innovations that visualize macrophage activity to elucidate disease onset and fine-tune its fate through metabolic remodeling for macrophage-centered ***,we discuss the prospects and challenges of NM-mediated metabolic immunotherapy,aiming to accelerate clinical *** anticipate that this review will serve as a valuable reference for researchers seeking to leverage novel metabolic intervention-matched immunomodulators in macrophages or other fields of immune engineering.

关键词： Immunomodulatory nanomaterial Macrophage polarization Macrophage metabolic reprogramming Immune engineering

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Recent progress on electro-sorption technology for lithium recovery from aqueous sources

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Nano Research 2024年第4期17卷 2563-2573页

作者： Qichen Lu Peng Liu Tianyi Zhou Ruling Huang Kexin Zhang Lin Hu rong Liu Zhibo ren Jinyi Wang Xiaolong Wang Huaneng Clean Energy Research Institute Beijing 102209China

Lithium is known as the“white petroleum”of the electrification era,and the global demand for lithium grows rapidly with the quick development of new energy *** aqueous solutions,such as salt lake brine,underground brine,and seawater,have large lithium reserves,thus this kind of lithium resource has become a research hotspot *** with other lithium extraction technologies,electro-sorption method shows good prospects for practical applications with advantages in the aspects of efficiency,recovery ratio,cost,and ***,this review covers recent progress on electro-sorption technology for lithium recovery from aqueous solutions,including the concept illustration,research progress of the applied working electrodes and counter electrodes,and the evaluation indicators of electro-sorption ***,some prospects for the development of this technology are also *** hope this review is beneficial for the construction of high-efficient electrochemical lithium recovery system to achieve an adequate lithium supply in the future.

关键词： lithium extraction electro-sorption technology lithium selective electrode counter electrode system evaluation method

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