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Aldo-keto reductase family member C3(AKR1C3)promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α

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Oncology Research 2024年第1期32卷 163-174页

作者： KUO-SHYANG JENG PO-yu CHENG yuEH-HSIEN LIN PO-CHUN LIU PING-HUI TSENG yu-CHAO WANG CHIUNG-FANG chang CHUEN-MIIN LEU Division of General Surgery Far Eastern Memorial HospitalNew Taipei City22060Taiwan Institute of Microbiology and Immunology National Yang Ming Chiao Tung UniversityTaipei City11221Taiwan Institute of Biochemistry and Molecular Biology National Yang Ming Chiao Tung UniversityTaipei City11221Taiwan Institute of Biomedical Informatics National Yang Ming Chiao Tung UniversityTaipei City11221Taiwan Department of Medical Research Far Eastern Memorial HospitalNew Taipei City22060Taiwan

Hepatocellular carcinoma(HCC)is a leading cause of death *** therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to ***,new therapeutic targets are *** analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly *** analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC *** vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell *** of AKR1C3 in Huh7 cells reduced tumor growth in *** explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target *** of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 *** of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC *** showed that indomethacin potentiated the sensitivity of Huh7 cells to *** summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC ***,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.

关键词： Hepatocellular carcinoma Aldo-keto reductase family member C3 Prostaglandin F2 alpha Prostaglandin F receptor

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Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 968-978页

作者： Ying-Qiao Zhang Qing-Hao Liu Lu Liu Peng-yu Guo Run-Ze Wang Zhi-chang Ba Department of Radiology Harbin Medical University Cancer HospitalHarbin 150010Heilongjiang ProvinceChina Department of Digestive Internal Medicine Harbin Medical University Cancer HospitalHarbin 150010Heilongjiang ProvinceChina

BACKGROUND Traditional treatments for pancreatic cancer(PC)are *** therapy(PDT)is non-invasive,and proven safe to kill cancer cells,including ***,the mitochondrial concentration of the photosensitizer,such as verteporfin,is *** To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs,*** Workable survival rates of PC cells(AsPC-1,BxPC-3)were determined with chemotherapy[doxorubicin(DOX)and gemcitabine(GEM)]and non-chemotherapy[sirolimus(SRL)and cetuximab(CTX)]drugs in vitro,with or without verteporfin,as measured via MTT,flow cytometry,and laser confocal *** cell proliferation was associated with GEM that was more enduring compared with *** laser microscopy allowed observation of GEM-and verteporfin-treated PC cells co-stained with 4’,6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin,*** Cell survival significantly dropped upon exposure to either chemotherapy drug,but not to SRL or *** cell lines responded similarly to *** intensity of fluorescence was associated with the concentration of *** experiments using GEM showed that survival rates of the PC cells treated with 10μmol/L verteporfin(but not less)were significantly lower relative to nil *** and dead stained cells treated with GEM were *** GEM treatment,verteporfin was observed primarily in the *** Verteporfin was observed in living *** GEM-treated human PC cells,verteporfin was particularly prevalent in the *** study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

关键词： Photodynamic therapy Pancreatic cancer Verteporfin Mitochondria Chemotherapy Gemcitabine

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Simultaneously enhancing erosion and compression resistance:designing AlCoCrFeNi high-entropy alloy strengthened Ag-based contacts

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Rare Metals 2024年第9期43卷 4476-4492页

作者： Xiao-Yang Xue Zhe Wang Hui-Ling Nie Zhao yuan Jun Wang chang-Hu Xu Kai Wen Cong-Hao yu School of Materials Science and Engineering Xi’an Polytechnic University School of Physics Xi’an Jiaotong University Key Laboratory of Pulsed Power Technology School of Electrical and Electronic EngineeringHuazhong University of Science and Technology State Key Laboratory of Advanced Electromagnetic Engineering and Technology School of Electrical and Electronic EngineeringHuazhong University of Science and Technology

Designing microstructures and unveiling dynamic erosion mechanisms remain important challenges for Ag-based contacts. To simultaneously enhance erosion and compression resistance, an Al Co Cr Fe Ni high-entropy alloy(HEA) is introduced into Ag-based materials to fabricate novel Ag-HEA contacts with island-and skeletonrestricted microstructures. The arc erosion experimental results reveal that the skeleton-restricted HEA microstructure is the key factor in reducing the hill and crater morphologies of the contact surface, effectively delaying material transfer between the movable and stationary contacts. The molten bridge evolution and compressive deformation behavior of Ag-HEA contacts with various microstructures are investigated using molecular dynamics(MD) simulations. MD results indicate that the constraint of Ag atom diffusion in the molten pool and the involvement of HEA atoms in the molten bridge are the primary mechanisms for improving erosion resistance. The skeleton-restricted HEA microstructure reduces the total energy and structural stability of the molten bridge system and promotes its fracture and disintegration. Moreover, the synergistic effect of the twin and Lomerz–Cottrell lock structures can hinder dislocation glide, generating dispersed and small-area stacking faults in the Ag matrix and mitigating the concentration of shear strains. Thus, the skeleton-restricted HEA microstructure contributes positively to compression resistance. This study presents a novel approach to designing Ag-based contacts.

关键词： Arc erosion Electrical contact materials High entropy alloys Microstructures Molecular dynamics

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Ultrasmall copper-based clusterzymes ameliorate Achilles tendinopathy by inhibiting acute oxidative stress

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Nano Research 2024年第6期17卷 5374-5389页

作者： Xuzhuo Chen Yi Du Yazi Huang Xianhao Zhou Xinru Xie chang Li Chen Zhao Fengrong Dai Xijiao yu Shanyong Zhang Department of Oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai 200011China Department of Endodontics Central LaboratoryJinan Stomatological HospitalJinan Key Laboratory of Oral Tissue RegenerationShandong Provincial Health Commission Key Laboratory of Oral Diseases and Tissue RegenerationJinan 250001China State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China Department of Chemistry College of Chemistry and EnvironmentGuangdong Ocean UniversityZhanjiang 524088China Department of Orthopedics Shanghai Key Laboratory of Orthopedic ImplantShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

Tendinopathy is a prevalent musculoskeletal disorder,accounting for over 30%of musculoskeletal ***,current therapeutic strategies for tendinopathy are limited and often yield unsatisfactory clinical ***,there is a critical need to explore novel therapeutic approaches with minimal side effects for tendinopathy and its early *** this study,we successfully designed and synthesized a copper(I)-based nanocluster,named Cu_(11),which possesses remarkable enzyme-like and ROS-scavenging *** unique combination of properties qualifies Cu_(11)as an attractive anti-inflammatory and anti-ROS *** Cu_(11)clusterzymes specifically target mitochondria,effectively scavenging excessive reactive oxygen species(ROS)and reducing oxidative ***,Cu_(11)clusterzymes inhibit the activation of key signaling pathways involved in inflammation,namely tumor necrosis factor(TNF),mitogen-activated protein kinase(MAPK),and nuclear factor(NF)-κB,leading to a decrease in the release of proinflammatory ***,our in vivo experiments using a collagenase-induced acute Achilles tendinopathy model demonstrated that Cu_(11)clusterzymes effectively alleviate inflammation and oxidative stress,without causing systemic *** study highlights the potential of copper-based clusterzymes as therapeutic agents for the treatment of Achilles tendinopathy and other inflammatory *** unique enzyme-like and ROS-scavenging activities of Cu_(11)make it a promising candidate for further development and clinical translation.

关键词： nanoclusters clusterzymes oxidative stress tendinopathy reactive oxygen species(ROS)

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Self-adaptive gas flow and phase change behaviors during hydrate exploitation by alternate injection of N2 and CO_(2)

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Petroleum Science 2024年第3期21卷 2120-2129页

作者： Bo-Jian Cao Yi-Fei Sun Hong-Nan Chen Jin-Rong Zhong Ming-Long Wang Ming Wang chang-yu Sun Guang-Jin Chen State Key Laboratory of Heavy Oil Processing China University of PetroleumBeijing102249China School of Chemistry and Chemical Engineering Changsha University of Science&TechnologyChangsha410114HunanChina

Since hydrate resources play a part of the stratigraphic framework structure in sediments,establishing a safe and economic method for hydrates exploitation remains the primary challenge to this *** the proposed methods,the spontaneous displacement of CH_(4) from hydrate cages by CO_(2) seems to be a perfect mechanism to address gas production and CO_(2) storage,especially in today's strong demand for carbon reduction and replacing clean *** extensive lab researches,in the past decade,injecting a mixture of CO_(2) and small molecule gas has become a key means to enhance displacement efficiency and has great potential for ***,there is a lack of in-depth research on gas flow in the reservoir,while the injected gas always passes through low-saturated hydrate areas with high permeability and then occurs gas channel in a short term,finally resulting in the decreases in gas production efficiency and produced gas ***,we explored a new injection-production mode of alternate injection of N2 and CO_(2) in order to fully coordinate the advantages of N2 in enhanced hydrate decomposition and CO_(2) in solid storage and heat *** alternate"taking"and"storing"processes perfectly repair the problem of the gas channel,achieving self-regulation effect of CH_(4) recovery and CO_(2) *** 3-D experimental results show that compared to the mixed gas injection,CH_(4) recovery is increased by>50%and CO_(2) storage is increased by>70%.Additionally,this alternate injection mode presented a better performance in CH_(4) concentration of produced gas and showed outstanding N2 utilization ***,we analyzed its self-adaptive gas flow mechanism and proposed an application model of"one injection and multiple production".We look forward to this study accelerating the application of CO_(2)-CH_(4) replacement technology.

关键词： Hydrate Replacement CH_(4) recovery CO_(2)storage Reservoir remediation

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A novel complex-high-order graph convolutional network paradigm:ChyGCN

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Chinese Physics B 2024年第5期33卷 665-672页

作者：郑和翔苗书宇顾长贵 Business School University of Shanghai for Science and TechnologyShanghai 200093China Ant Group Shanghai 200000China

In recent years,there has been a growing interest in graph convolutional networks(GCN).However,existing GCN and variants are predominantly based on simple graph or hypergraph structures,which restricts their ability to handle complex data correlations in practical *** limitations stem from the difficulty in establishing multiple hierarchies and acquiring adaptive weights for each of *** address this issue,this paper introduces the latest concept of complex hypergraphs and constructs a versatile high-order multi-level data correlation *** model is realized by establishing a three-tier structure of ***,we start by establishing hyperedge clusters on a foundational network,utilizing a second-order hypergraph structure to depict potential *** this second-order structure,truncation methods are used to assess and generate a three-layer composite *** the construction of the composite structure,an adaptive learning strategy is implemented to merge correlations across different *** evaluate this model on several popular datasets and compare it with recent state-of-the-art *** comprehensive assessment results demonstrate that the proposed model surpasses the existing methods,particularly in modeling implicit data correlations(the classification accuracy of nodes on five public datasets Cora,Citeseer,Pubmed,Github Web ML,and Facebook are 86.1±0.33,79.2±0.35,83.1±0.46,83.8±0.23,and 80.1±0.37,respectively).This indicates that our approach possesses advantages in handling datasets with implicit multi-level structures.

关键词： raph convolutional network complex modeling complex hypergraph

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Mechanisms of fracture propagation from multi-cluster using a phase field based HMD coupling model in fractured reservoir

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Petroleum Science 2024年第3期21卷 1829-1851页

作者： yun-Jin Wang Bo Wang Hang Su Tu chang Ren-Cheng Dong Li-Zhe Li Wei-yu Tang Ting-Xue Jiang Fu-Jian Zhou State Key Laboratory of Petroleum Resources and Engineering China University of Petroleum-BeijingBejing2249China China University of Petroleum-Beijing at Karamay Karamay834000XinjiangChina China National Oil and Gas Exploration and Development Corporation Ltd. Beijing100034China University of Texas at Austin United States SINOPEC Research Institute of Petroleum Engineering Beijing100101China

Natural fractures(NFs)are common in shale and tight reservoirs,where staged multi-cluster fracturing of horizontal wells is a prevalent technique for reservoir *** NFs and stress interference are recognized as significant factors affecting hydraulic fracture(HF)propagation,the combined influence of these factors remains poorly *** address this knowledge gap,a novel coupled hydromechanical-damage(HMD)model based on the phase field method is developed to investigate the propagation of multi-cluster HFs in fractured *** comprehensive energy functional and control functions are established,while incorporating dynamic fluid distribution between multiple perforation clusters and refined changes in rock mechanical parameters during hydraulic *** HMD coupled multi-cluster HF propagation model investigates various scenarios,including single HF and single NF,reservoir heterogeneity,single HF and NF clusters,and multi-cluster HFs with NF *** results show that the HMD coupling model can accurately capture the impact of approach angle(θ),stress difference and cementation strength on the interaction of HF and *** criterion of the open and cross zones is not *** NF angle(a)is not a decisive parameter to discriminate the *** to the relationship between approach angle(θ)and NF angle(a),the contact relationship of HF can be divided into three categories(θ=a,θa).The connected NF can increase the complexity of HF by inducing it to form branch fracture,resulting in a fractal dimension of HF as high as2.1280 at angles of±45°.Inter-fracture interference from the heel to the toe of HF shows the phenomenon of no,strong and weak ***,under the influence of NFs,distant HFs from the injection can become dominant ***,as a gradually increases,inter-fracture stress interference becomes the primary factor influencing HF propagation,gradually superseding the dominance of NF

关键词： HMD coupling Phase field Natural fracture Flow distribution Hydraulic fracturing Inter-fracture interference

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Palmitic acid reduces the methylation of the FOXO1 promoter to suppress the development of diffuse large B-cell lymphoma via modulating the miR-429/DNMT3A axis

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Chinese Journal of Natural Medicines 2024年第6期22卷 554-567页

作者： LI Weiming GAO Ming XUE Weili LI Xiaoli chang yu ZHANG Kaixin WEN Chenyu ZHANG Mingzhi Department of Oncology Henan University of Traditional Chinese MedicineZhengzhou 450000China Department of Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China

Diffuse large B-cell lymphoma(DLBCL)is characterized by significant treatment *** acid(PA)has shown promising antitumor *** study aims to elucidate the molecular mechanisms by which PA influences DLBCL *** quantified the expression levels of microRNAs(miRNAs),Forkhead box protein O1(FOXO1),and DNA methyltransferase 3A(DNMT3A)in both untreated and PA-treated DLBCL tumors and cell *** were made of cell viability,apoptosis,and autophagy-related protein expression following PA *** analyses among miR-429,DNMT3A,and FOXO1 were conducted using luciferase reporter assays and methylation-specific(MSP)Polymerase chain reaction(PCR).After transfecting the miR-429 inhibitor,negative control(NC)inhibitor,shRNA against DNMT3A(sh-DNMT3A),shRNA negative control(sh-NC),over-expression vector for DNMT3A(oe-DNMT3A),or overexpression negative control(oe-NC),we evaluated the effects of miR-429 and DNMT3A on cell viability,mortality,and autophagy-related protein expression in PA-treated DLBCL cell *** efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse ***-429 and FOXO1 expression levels were downregulated,whereas DNMT3A was upregulated in DLBCL compared to the control *** treatment was associated with enhanced autophagy,mediated by the upregulation of miR-429 and downregulation of *** luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A,thereby reducing FOXO1 *** experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 *** vivo PA signific-antly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 *** acid may modulate autophagy and inhibit DLBCL progression by targeting the miR-429/DNMT3A/FOXO1 signaling pathway,suggesting a novel therapeutic target for DLBCL management.

关键词： Palmitic acid Diffuse large B-cell lymphoma MiR-429 DNMT3A FOXO1 Autophagy

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Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

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World Journal of Diabetes 2024年第1期15卷 105-125页

作者： Wei-Long Xu Pei-Pei Zhou Xu yu Ting Tian Jin-Jing Bao chang-Rong Ni Min Zha Xiao Wu Jiang-Yi yu Department of Endocrinology Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina Department of Pharmacy Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina Department of Pneumology Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal ***-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains *** To investigate the effects of myricetin on DN and explore its potential therapeutic *** Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 ***,blood and urine indexes were assessed,along with examination of renal tissue *** morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and ***,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 *** both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and *** In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and ***,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related ***,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 ***,myricetin modulated the M1-type polarization of the RAW 264.7 *** docking and bioinformatic analyses revealed Akt as the target of *** protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inh

关键词： Myricetin Diabetic nephropathy PI3K/Akt pathway Renal tubulointerstitial fibrosis Macrophage Polarization

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Immunoglobulin superfamily containing leucine-rich repeat(ISLR)negatively regulates osteogenic differentiation through the BMP-Smad signaling pathway

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Genes & Diseases 2024年第4期11卷 138-140页

作者： Lei Xiong Miaomiao Lan chang Liu Lei Li YingYing yu Tongtong Wang Fan Liu Kun Wang Jin Liu Qingyong Meng State Key Laboratory of Agrobiotechnology College of Biological SciencesChina Agricultural UniversityBeijing 100094China

Osteoporosis(OP)is an aging-associated condition that significantly affects the quality of life in aging humans and has few treatment *** an important marker,recombinant immunoglobulin superfamily containing leucinerich repeat(ISLR)could be used as a gene therapy for *** herein used alkaline phosphatase(ALP)and alizarin red S(ARS)staining to evaluate osteogenic differentiation potential.

关键词： Immunoglobulin alkaline herein

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