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Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition

Acta Pharmaceutica Sinica B 2024年第4期14卷 1711-1725页

作者： yingting Wu Jiaqi Xin Xinyu Li Ting Yang yi Liu Yongsheng Zhao Wen Xie Mengxi jiang Department of Pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Department of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijing 100069China

Drug repurposing offers an efficient approach to therapeutic *** this study,our bioinformatic analysis first predicted an association between obesity and lansoprazole(LPZ),a commonly prescribed drug for gastrointestinal *** went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity,insulin resistance,and hepatic stea-tosis in *** with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes,and induced cold tolerance in cold-exposed mice,suggesting the activity of LPZ in promoting adipose thermogenesis and energy ***,LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1(PHOSPHOI)and produces metabolic benefits in a PHOS-PHO1-dependent *** results suggested that LPZ may stimulate adipose thermogenesis by inhi-biting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid(2-AG-LPA)to 2-arachidonoylglycerol(2-AG)and reduce the activity of the thermogenic-suppressive cannabinoid recep-tor *** summary,we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome,and identified a potential metabolic basis by which LPZ improves energy metabolism.

关键词： Lansoprazole Proton pump inhibitors Adipose thermogenesis Energy expenditure Metabolic syndrome PHOSPHO1 inhibitor Cannabinoid receptor signaling Drug repurposing

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Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

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Journal of Animal Science and Biotechnology 2024年第1期15卷 201-217页

作者： Hao Zhang Xia Zha yi Zheng Xiaoyun Liu Mabrouk Elsabagh Hongrong Wang Honghua jiang Mengzhi Wang Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition College of Animal Science and TechnologyYangzhou UniversityYangzhou 225009P.R.China Joint International Research Laboratory of Agriculture and Agri‑Product Safety Ministry of Education of ChinaYangzhou UniversityYangzhou 225009P.R.China Department of Animal Production and Technology Faculty of Agricultural Sciences and TechnologiesNiğde Omer Halisdemir UniversityNigde 51240Turkey Department of Nutrition and Clinical Nutrition Faculty of Veterinary MedicineKafrelsheikh UniversityKafrelSheikhEgypt Department of Pediatrics Northern Jiangsu People’s HospitalClinical Medical CollegeYangzhou UniversityYangzhou 225001China State Key Laboratory of Sheep Genetic Improvement and Healthy Production Xinjiang Academy of Agricultural Reclamation ScienceShihezi 832000China

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of *** hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be *** In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates *** OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 *** In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A *** vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier ***,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflamm

关键词： Autophagy Bisphenol A Endoplasmic reticulum stress Fetal growth restriction Inflammatory responses Sheep

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Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

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Zoological Research 2024年第3期45卷 617-632页

作者： Jing-Hang jiang yi-Fu Wang Jie Zheng yi-Ming Lei Zhong-Yuan Chen yi Guo Ya-Jie Guo Bing-Qian Guo Yu-Fang Lv Hong-Hong Wang Juan-Juan Xie yi-Xuan Liu Ting-Wei Jin Bi-Qi Li Xiao-Shu Zhu Yong-Hua jiang Zeng-Nan Mo Center for Genomic and Personalized Medicine Guangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Medical UniversityNanningGuangxi 530021China Department of Urology First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Reproductive Medicine Center Jingmen People’s HospitalJingChu University of Technology Affiliated Central HospitalJingmenHubei 448000China School of Computer Science and Engineering Yulin Normal UniversityYulinGuangxi 537000China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Department of Pathology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China Department of Obstetrics and Gynecology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in ***,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and *** compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and *** showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and *** analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal ***,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association ***,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal *** comprehensive results(publicly available at http://***:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

关键词： Tree shrew Adrenal gland Dehydroepiandrosterone Genome-wide association studies Disease model

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High Speed Sintering:Assessing the Influence of Energy Input on Microstructure and Mechanical Properties of Polyether Block Amide(PEBA)Parts

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Chinese Journal of Polymer Science 2024年第5期42卷 675-682,I0004,I0010页

作者： jiang-Tao Sun Zhi-Yong Fan yi-Wei Mao Wei Li Wei Zhu Dao-Sheng Cai Qing-Song Wei State Key Laboratory of Materials Processing and Die&Mould Technology Huazhong University of Science and TechnologyWuhan430074China State Key Laboratory of Refractories and Metallurgy Wuhan University of Science and TechnologyWuhan430074China National Engineering Research Centre for High Efficiency Grinding Hunan UniversityChangsha410082China Wuhan EasyMFG Technology CO. LTDWuhan430074China

High speed sintering,a new powder-bed fusion additive manufacturing technology,utilizes infrared lights(IR)to intensely heat and melt polymer *** presence of defects such as porosity,which is associated with particle coalescence,is highly dependdent on the level of energy *** study investigate the influcence of energy input on porosity and its subsequent effects on the mechanical properties and microstructures of PEBA *** parts were manufactured with a variety of lamp powers,resulting in a range of energy input levels spanning from low to ***,they underwent testing using Archimedes’method,followed by tensile *** porosity,mechanical characteristics,and energy input exhibit a strong correlation;inadequate energy input was the primary cause of pore *** the reduced IR light power resulted in the following outcomes:porosity,ultimate tensile strength,and elongation of 1.37%,7.6 MPa,and 194.2%,*** the energy input was further increased,the porosity was reduced to as low as 0.05%and the ultimate tensile strength and elongation were increased to their peak values of 233.8%and 9.1 MPa,respectively.

关键词： High speed sintering Additive manufacturing Energy input Powder bed fusion PEBA

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{1012}twin–twin intersection-induced lattice rotation and dynamic recrystallization in Mg–6Al–3Sn–2Zn alloy

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Journal of Magnesium and Alloys 2024年第4期12卷 1529-1539页

作者： Bin-jiang Lv Sen Wang Fu-Hao Gao Ning Cui yi-Nan Li Tie-Wei Xu Feng Guo School of Mechanical and Automotive Engineering Qingdao University of Technology266520China Key Lab of industrial Fluid Energy Conservation and Pollution Control Qingdao University of Technology266520China

This study investigated the formation mechanism of new grains due to twin–twin intersections in a coarse-grained Mg–6Al–3Sn–2Zn alloy during different strain rates of an isothermal *** results of electron backscattered diffraction investigations showed that the activated twins were primarily{1012}tension twins,and 60°boundaries formed due to twin–twin intersections under different strain *** twin variants with 60°boundaries transformed into new grains through lattice rotations at a low strain rate(0.01 s^(−1)).At a high strain rate(10 s^(−1)),the regions surrounded by subgrain boundaries through high-density dislocation arrangement and the 60°boundaries transformed into new grains via dynamic recrystallization.

关键词： Mg alloy Twin-twin intersection Lattice rotation Dynamic recrystallization

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Geant4 simulation of fast-electron bremsstrahlung imaging at the HL-3 tokamak

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Nuclear Science and Techniques 2024年第9期35卷 213-229页

作者： Shi-Kui Cheng yi-Po Zhang Yue-jiang Shi Jie Zhang Shuai Guan Hong-Bing Xu Qiu-Lei Yang College of Science Chongqing University of TechnologyChongqing 400054China Chongqing Key Laboratory of New Energy Storage Materials and Devices Chongqing 400054China Southwestern Institute of Physics Chengdu 610041China Hebei Key Laboratory of Compact Fusion Langfang 065001China ENN Science and Technology Development Co. Ltd.Langfang 065001China

To further research on high-parameter plasma,we plan to develop a two-dimensional hard X-ray(HXR)imaging system at the HL-3 tokamak to measure HXRs with energies ranging from 20 to 300 *** application of an array-structured detector ensures that this system can measure HXR-radiation spectra from the entire plasma cross ***,it is suitable for the study of fast-electron physics,such as radio-frequency wave current drives,fast electrons driving instabilities,and plasma disruptions in fusion *** this study,we develop a simulation for calculating fast-electron bremsstrahlung in the HL-3 tokamak based on the Monte Carlo simulation code Geant4,in which the plasma geometry and forward scattering of fast-electron bremsstrahlung are *** preliminary calculation results indicate that the HXR energy deposi-tion on the detector is symmetrically distributed,even though the plasma distribution is asymmetric owing to the toroidal *** simulation results are helpful in constructing the relationship between the energy deposition on the detector and parameter distribution on the plasma cross section during HL-3 *** is beneficial for the reconstruction of the fast-electron-distribution function and for optimizing the design of the HXR-imaging system.

关键词： Geant4 simulation HL-3 tokamak Fast-electron bremsstrahlung Hard X-ray imaging

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Circadian disturbance induces erectile dysfunction by impairing endothelial function

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Asian Journal of Andrology 2024年第2期26卷 205-211页

作者： Tao Li yi-Ting jiang Xin-Zhu Qi Peng Chen Jun-Hao Zhang Fu Luo Jun Qiao jiang Gu Guang-Shi Du Qiang Wang Department of Urology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China Department of Urology Guizhou Provincial People's HospitalGuiyang 550002China Department of Otorhinolaryngology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China Guizhou Institute for Food and Drug Control Guiyang 550004China Department of Reproductive Center Guizhou Provincial People's HospitalGuiyang 550002China Translational Medicine Research Center of Guizhou Medical University Guiyang 550025China

In order to explore the impact of circadian disturbance on erectile function,we randomly divided 24 adult male rats into groups of control(light on at 8:00 *** off at 8:00 p.m.),dark/dark(DD;constant dark),light/light(LL;constant light),and shift dark/light(DL;light off at 8:00 *** on at 8:0o p.m.).Four weeks later,erectile function was measured and corpora cavernosa were harvested for *** maximum intracavernous pressure(mlcP)and mCP/mean arterial pressure(MAP)ratio in the DD,LL,and DL groups were significantly lower than that in the control *** LL and DL groups showed significantly attenuated endothelial nitric oxide synthase(eNOS),while DD,LL,and DL showed reduced neuronal nitric oxide synthase(nNOS)at both mRNA and protein *** production of nitric oxide(NO)and cyclic guanosinemonophosphate(cGMP)was inhibited by altered light/dark cycles to varying *** disturbance impaired endothelial function and contributed to erectile *** the core circadian elements,mRNA expression of circadian locomotor output cycles kaput(Clock)and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1(Bmal1)was elevated in the DL group,but their protein expression was not significantly ***,LL,and DL increased period 1(Per1)and Per3 levels,while LL and DL increased PER1 *** significant difference was found for Per2levels,and PER2 and PER3 concentrations were not significantly ***,LL and DL significantly increased cryptochrome-1(CRY1)and CRY2 at both mRNA and protein *** altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial ***,the core circadian elements were detected in the corpora cavernosa,but these were ***,which circadian element regulates erectile function and how it works need further analysis.

关键词： circadian disturbance endothelial function erectile function light/dark cycle NO/cGMP

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Clinical characteristics of peripapillary hyperreflective ovoid mass-like structures in myopic children

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1292-1299页

作者： Lu Zhang Zuo-Hui-Zi yi Xuan jiang Gong-Peng Sun Fang Zhao Li Zhang yi Xiang Chang-Zheng Chen Department of Ophthalmology the Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014Hubei ProvinceChina Eye Center Renmin Hospital of Wuhan UniversityWuhan 430060Hubei ProvinceChina

AIM:To describe the characteristics of peripapillary hyperreflective ovoid mass-like structure(PHOMS)in myopic children and to investigate factors associated with ***:This retrospective observational study included 101 eyes of 101 children(age≤17y)with *** included patients underwent comprehensive clinical *** nerve canal parameters,including disc diameter,optic nerve head(ONH)tilt angle,and border tissue angle were measured using serial enhanced-depth imaging spectral-domain optical coherence tomography(EDI-OCT).Based on the optic disc drusen consortium’s definition of PHOMS,eyes were classified as PHOMS group and non-PHOMS *** was categorized according to ***:Sixty-seven(66.3%)eyes were found with *** PHOMS could only be detected by optical coherence tomography(OCT).Medium PHOMS could be seen with blurred optic disc borders corresponding to *** most frequent location of PHOMS was at the nasosuperior(91%,61 of 67 eyes)to ONH *** axial length and spherical equivalent were more myopic in the PHOMS group than in the non-PHOMS group(both P<0.001).ONH tilt angle was also significantly greater in PHOMS group than in non-PHOMS group[8.90(7.16-10.54)vs 3.93(3.09-5.25),P<0.001].Border tissue angle was significantly smaller in PHOMS group than in non-PHOMS group[29.70(20.90-43.81)vs 45.62(35.18-60.45),P<0.001].In the multivariable analysis,spherical equivalent(OR=3.246,95%CI=1.209-8.718,P=0.019)and ONH tilt angle(OR=3.275,95%CI=1.422-7.542,P=0.005)were significantly correlated with *** was no disc diameter associated with *** the linear regression analysis,border tissue angle was negatively associated with PHOMS height(β=-2.227,P<0.001).CONCLUSION:PHOMS is associated with optic disc tilt and optic disc nasal shift in *** diameter is not a risk factor for *** changes in ONH caused by axial elongation facilitated an understanding of the mechanism of PHOMS.

关键词： peripapillary hyperreflective ovoid masslike structure myopia optic disc edema enhanced-depth imaging spectral-domain optical coherence tomography

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Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury

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World Journal of Gastroenterology 2024年第9期30卷 1189-1212页

作者： Jin-Lian jiang yi-Yang Zhou Wei-Wei Zhong Lin-Yan Luo Si-ying Liu Xiao-Yu Xie Mao-Yuan Mu Zhi-Gang jiang Yuan Xue Jian Zhang yi-Huai He Department of Infectious Diseases Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Department of Infectious Diseases Jingmen Central HospitalJingmen 448000Hubei ProvinceChina Department of Respiratory Medicine Anshun People’s HospitalAnshun 561099Guizhou ProvinceChina Department of General Practice Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Department of Intervention Radiology Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina School of Public Health Zunyi Medical UniversityZunyi 563099Guizhou ProvinceChina Department of Liver Diseases Third People’s Hospital of ChangzhouChangzhou 213000Jiangsu ProvinceChina Department of Digestion Dafang County People’s HospitalBijie 551600Guizhou ProvinceChina

BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous ***,its contribution to the progression of liver damage remains *** To determine the role and mechanism of UGT1A1 in liver damage *** We investigated the relationship between UGT1A1 expression and liver injury through clinical ***,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model *** Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic *** suggests that low UGT1A1 levels may be associated with the progression of liver *** mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be *** mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ***1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid *** UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver ***1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

关键词： Uridine diphosphate glucuronosyltransferase 1A1 Liver injury progression Endoplasmic reticulum stress Oxidative stress Lipid metabolism disorders

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High-pressure capacity expansion and water injection mechanism and indicator curve model for fractured-vuggy carbonate reservoirs

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PETROLEUM 2024年第3期10卷 511-519页

作者： Chen, Lixin Jia, Chengzao Zhang, Rujie Yue, Ping jiang, Xujian Wang, Junfang Su, Zhou Xiao, yun Lv, Yuan China Univ Petr Inst Unconvent Oil & Gas Sci & Technol Beijing 102249 Peoples R China Southwest Petr Univ State Key Lab Reservoir Geol & Dev Chengdu 610500 Peoples R China Tarim Oil field Co PetroChina Korla 841000 Peoples R China

Water injection for oil displacement is one of the most effective ways to develop fractured-vuggy carbonate reservoirs. With the increase in the number of rounds of water injection, the development effect gradually fails. The emergence of high-pressure capacity expansion and water injection technology allows increased production from old wells. Although high-pressure capacity expansion and water injection technology has been implemented in practice for nearly 10 years in fractured-vuggy reservoirs, its mechanism remains unclear, and the water injection curve is not apparent. In the past, evaluating its effect could only be done by measuring the injection-production volume. In this study, we analyze the mechanism of high-pressure capacity expansion and water injection. We propose a fluid exchange index for high-pressure capacity expansion and water injection and establish a discrete model suitable for high-pressure capacity expansion and water injection curves in fractured-vuggy reservoirs. We propose the following mechanisms: replenishing energy, increasing energy, replacing energy, and releasing energy. The above mechanisms can be identified by the high-pressure capacity expansion and water injection curve of the well HA6X in the Halahatang Oilfield in the Tarim Basin. By solving the basic model, the relative errors of Reservoirs I and II are found to be 1.9% and 1.5%, respectively, and the application of field examples demonstrates that our proposed high-pressure capacity expansion and water injection indicator curve is reasonable and reliable. This research can provide theoretical support for high-pressure capacity expansion and water injection technology in fracture-vuggy carbonate reservoirs.

关键词： Fractured-vuggy carbonate reservoirs High-pressure capacity expansion and water injection Mechanism Water injection indicator curve ENHANCED OIL-RECOVERY STRESS SENSITIVITY TARIM BASIN FIELD

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