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Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer

Genes & Diseases 2024年第3期11卷 338-350页

作者： Xin Xu Yuan Fang Somaira Nowsheen Ye-Xiong Li Zhenkun lou Min Deng State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 200080China Department of General Surgery Zhongshan HospitalFudan UniversityShanghai 200032China Department of Dermatology University of California San DiegoSan DiegoCA 92093USA Department of Oncology Mayo ClinicRochesterMN 55905USA

The adenosine monophosphate(AMP)-activated protein kinase(AMPK)sits at a cen-tral node in the regulation of energy metabolism and tumor *** is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy *** studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic *** this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)*** found that AMPK is activated in cells when cultured under low ECM stiffness conditions and is functionally required for the metabolic switch induced by ECM *** regulation of AMPK requires the Hippo kinases but not LKB1/*** kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM ***,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival *** activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC ***,these findings establish a novel model for AMPK regulation by the mechanical properties of ECMs and provide a rationale for simultaneously targeting the ECM stiffness-Hippo kinases-AMPK signaling and low glucose-LKB1-AMPK signaling pathways as an effective therapeutic strategy against PDAC.

关键词： AMPKactivity Cellularmetabolic switch ECM stiffness Hippokinase signaling Pancreaticductal adenocarcinoma

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Pharmacotherapy of urethral stricture

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Asian Journal of Andrology 2024年第1期26卷 1-9页

作者： Hui Luo Ke-Cheng lou Ling-Yu Xie Fei Zeng Jun-Rong Zou The First Clinical College Gannan Medical UniversityGanzhou 341000China Department of Urology The First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000China Institute of Urology The First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000China Jiangxi Engineering Technology Research Center of Calculi Prevention Ganzhou 341000China

Urethral stricture is characterized by the chronic formation of fibrous tissue,leading to the narrowing of the urethral *** the availability of various endoscopic treatments,the recurrence of urethral strictures remains a common *** pharmacotherapy targeting tissue fibrosis is a promising option for reducing recurrence *** drugs cannot replace surgery,they can be used as adjuvant therapies to improve *** this regard,many drugs have been proposed based on the mechanisms underlying the pathophysiology of urethral *** studies have obtained substantial progress in treating urethral strictures,highlighting the potential for improved drug effectiveness through appropriate clinical delivery ***,this review summarizes the latest researches on the mechanisms related to the pathophysiology of urethral stricture and the drugs to provide a theoretical basis and new insights for the effective use and future advancements in drug therapy for urethral stricture.

关键词： adjuvant therapy pathophysiology pharmacotherapy urethra urethral stricture

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Multi-field Coupled Inverse Hall–Petch Relations for Ferroelectric Nanocrystals

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Acta Mechanica Solida Sinica 2024年第1期37卷 139-147页

作者： Xiaodong Zhang Wei Yan Xuhui lou Yujun Chen Zhihong Zhou Qingyuan Wang Lianhua Ma Xiaobao Tian Non-Destructive Testing Laboratory School of Quality and Technical SupervisionHebei UniversityBaoding 071002China AVIC Huiyang Aviation Propeller Co. LtdBaoding 071051China Department of Mechanics and Engineering Sichuan UniversityChengdu 610065China Yibin Institute of Industrial Technology Sichuan University Yibin ParkYibin 644000China Research Institute of Interdisciplinary Sciences(RISE) Dongguan University of TechnologyDongguan 523808China School of Materials Science and Engineering Dongguan University of TechnologyDongguan 523808China

Tailoring grain size can improve the strength of polycrystals by regulating the proportion of grains to grain boundaries and the interaction *** the grain size decreases to the nanoscale,the deformation mechanism in polycrystals shifts from being primarily mediated by dislocations to deformation occurring within the grains and grain ***,the mechanism responsible for fine-grain strengthening in ferroelectric materials remains unclear,primarily due to the complex multi-field coupling effect arising from spontaneous *** molecular dynamics simulations,we investigate the strengthening mechanism of barium titanate(BaTiO3),with extremely fine-grain *** material exhibits an inverse Hall–Petch relationship between grain size and strength,rooting in the inhomogeneous concentration of atomic strain and grain ***,we present a theoretical model to predict the transition from the inverse Hall–Petch stage to the Hall–Petch stage based on strength variations with size,which aligns well with the simulation *** has been found that the piezoelectric properties of the BaTiO3 are affected by polarization domain switching at various grain *** study enhances our understanding of the atomic-scale mechanisms that contribute to the performance evolution of fine-grain nano-ferroelectric *** also provides valuable insights into the design of extremely small-scale ferroelectric components.

关键词： Ferroelectrics Multi-field coupling Molecular dynamics Fine-grain reinforcement Inverse Hall-Petch effect

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Decomposition solutions and B?cklund transformations of the B-type and C-type Kadomtsev–Petviashvili equations

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Communications in Theoretical Physics 2024年第6期 36-46页

作者： Xiazhi Hao S Y lou College of Science Zhejiang University of Technology School of Physical Science and Technology Ningbo University

This paper introduces a modified formal variable separation approach, showcasing a systematic and notably straightforward methodology for analyzing the B-type Kadomtsev–Petviashvili(BKP) equation. Through the application of this approach, we successfully ascertain decomposition solutions, B?cklund transformations, the Lax pair, and the linear superposition solution associated with the aforementioned equation. Furthermore, we expand the utilization of this technique to the C-type Kadomtsev–Petviashvili(CKP) equation, leading to the derivation of decomposition solutions, B?cklund transformations, and the Lax pair specific to this *** results obtained not only underscore the efficacy of the proposed approach, but also highlight its potential in offering a profound comprehension of integrable behaviors in nonlinear systems. Moreover, this approach demonstrates an efficient framework for establishing interrelations between diverse systems.

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Influence of Mixture Gas Conditions on the Laminar Combustion Characteristics of Natural Gas

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Journal of Thermal Science 2024年第3期33卷 1231-1241页

作者： lou Diming ZHU Kan ZHANG Yunhua REN Yedi TAN Piqiang FANG Liang FAN Lanlan School of Automotive Studies Tongji UniversityShanghai201804China Ji’nan Power Co.Ltd Sinotruk GroupJi’nan250200China

Natural gas is a promising alternative fuel for the internal combustion engine,and natural gas engine has become an efficient and feasible measure to deal with the energy shortage and climate *** the laminar flame characteristics are the foundation of the turbulent flame,the laminar flame characteristics of natural gas have a significant impact on the combustion status and efficiency of the engine.A visual constant volume bomb was used to study the influence of the gas components,different excess air coefficient(λ),and initial conditions on the laminar combustion characteristics of natural *** experimental results showed that when the initial pressure and temperature were 0.1 MPa and 300 K respectively,compared to propane,ethane had a remarkable influence on the equivalent-combustion laminar-combustion-speed,with an average increase of approximately 5.1%for every 2.5%increase in the ethane *** laminar combustion velocity of the natural gas under different excess air coefficients had a maximum value at aboutλ=1.0,and the Markstein length of the flame decreased with the increase of theλ.The increase in the initial pressure of the mixture resulted in a decrease in the equivalent-combustion laminar-combustion-speed of the flame,a significant decrease in the Markstein *** increase of the initial temperature of the mixture led to a rapid increase of the equivalent-combustion laminar-combustion-speed,but the effect on the flame Markstein length was not dominant.

关键词： constant volume bomb natural gas engine combustion characteristics laminar combustion velocity Markstein length

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A study of the soil water potential threshold values to trigger irrigation of ‘Shimizu Hakuto’ peach at pivotal fruit developmental stages

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Horticultural Plant Journal 2024年第2期10卷 376-386页

作者： Yusui lou yuepeng Han Yubin Miao Hongquan Shang Zhongwei Lv Lei Wang Shiping Wang Horticulture Reseach Institute Henan Academy of Agricultural SciencesZhengzhouHenan 450002China School of Agriculture and Biology Shanghai Jiao Tong UniversityShanghai 200240China Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture Wuhan Botanical Garden of the Chinese Academy of SciencesWuhanHubei 430074China School of Mechanical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Water management is an important practice that affects fruit size and *** implementation of irrigation scheduling requires knowledge of the appropriate indicators and thresholds,which are established manly based on the effects of water deficits on final fruit *** studies have focused on the real-time effects of water status on fruit and shoot *** establish soil water potential (ψ_(soil)) thresholds to trigger irrigation of peach at pivotal fruit developmental stages,photogrammetry,^(13)C labelling,and other techniques were used in this study to investigate real-time changes in stem diameter,fruit projected area,net leaf photosynthetic rate (P_(n)),and allocation of photoassimilates to fruit under soil water potential conditions ranging from saturation to stress in 6-year-old Shimizu hakuto’*** growth,fruit growth,and P_n exhibited gradually decreasing sensitivity to water deficits during fruit developmental stages I,II,and *** diameter growth was significantly inhibited whenψ_(soil)dropped to-8.5,-7.6,and-5.4 k Pa,*** growth rate was low,reaching zero when theψ_(soil)was-9.0 to-23.1,-14.9 to-21.4,and-16.5 to-23.3 k Pa,respectively,and P_ndecreased significantly when theψ_(soil)reached-24.2,-22.7,and-20.4 kPa,*** addition,more photoassimilates were allocated to fruit under moderateψ_(soil)conditions (-10.1 to-17.0 k Pa) than under otherψ_(soil)*** results revealed threeψ_(soil)thresholds,-10.0,-15.0,and-15.0 kPa,suitable for triggering irrigation during stages I,II,and III,*** thresholds can be helpful for controlling excessive tree vigor,maintaining rapid fruit growth and leaf photosynthesis,and promoting the allocation of more photoassimilates to fruit.

关键词： Peach Soil water potential Irrigation threshold Fruit expansion Photosynthesis

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Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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Chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU Tong QIAO Yan-fang GU Shu-xiao CHAI Xin-lou School of Traditional Chinese Medicine Beijing University of Traditional Chinese MedicineBeijing102401China

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol (LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor (LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9 (PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

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Extraction and evolution of grader’s bionic morphological feature line using shape structure behavior function model

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International Journal of Agricultural and Biological Engineering 2024年第2期17卷 74-84页

作者： Bin Qi Yubin Lan Xiaoming Sun He Zhu Yanhao Li Ke lou College of Agricultural Engineering and Food Science Shandong University of TechnologyZibo 255049ShandongChina Shandong Provincial Engineering Technology Research Center for Agricultural Aviation Intelligent Equipment Zibo 255049China

To improve the innovation of agricultural machinery product styling,this paper proposes a shape structure behavior function(SSBF)model suitable for the industrial design *** feature line evolution method combining shape grammar and genetic algorithm was used for modelling the of the grader,which not only maintains the product style characteristics but also reflects the typical identification characteristics of the bionic prototype and produces a new product modelling *** conducting cognitive and recognition experiments on product styling features,the ranking of product styling features and the contribution of each component to product styling were *** method of combining shape grammar and quadratic Bézier curve was used to express and encode feature lines,and genetic algorithm was used to evolve biomimetic forms to form product feature lines with typical biological morphological features;The extracted form bionic elements were integrated into the grader modelling design,and the interaction evaluation was carried out through the genetic algorithm evolution *** basic form elements were extracted and analyzed,and the deduction rules were formulated and *** derived feature line geometric data considered the product’s image features and the bio-inspired prototype,which can be used for the follow-up guidance of industrial design schemes.

关键词： bionic design shape-structure-behavior-function SSBF biologically inspired design BID shape grammars Quadratic Bézier curves

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毒死蜱激活小胶质细胞对多巴胺能神经元的影响

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生物医学工程学杂志 2016年第3期33卷 506-511页

作者：楼跃李雅国浙江医院神经内科杭州310000

小胶质细胞的激活可导致神经元损伤,从而导致神经退行性疾病如帕金森病的发病。为了探讨毒死蜱(CPF)对小胶质细胞激活、炎症因子表达分泌,以及对多巴胺能神经元存活率的影响,本研究采用逆转录-聚合酶链反应(RT-PCR)、Western blot检测CP... 详细信息

小胶质细胞的激活可导致神经元损伤,从而导致神经退行性疾病如帕金森病的发病。为了探讨毒死蜱(CPF)对小胶质细胞激活、炎症因子表达分泌,以及对多巴胺能神经元存活率的影响,本研究采用逆转录-聚合酶链反应(RT-PCR)、Western blot检测CPF刺激BV-2细胞(0、1、3、6、12、24h)后BV-2细胞形态的改变及诱导型一氧化氮合成酶(iNOS)、环氧化酶2(COX-2)mRNA和蛋白表达的变化;然后将BV-2细胞分为CPF组、DMSO对照组、NS对照组,分别刺激BV-2细胞12h后,将各BV-2细胞培养液加入SH-SY5Y细胞共培养24h。采用MTT方法检测经不同处理的BV-2细胞的条件培养液对SH-SY5Y存活率的影响。发现CPF作用下,BV-2小胶质细胞激活,炎症因子iNOS mRNA、COX-2mRNA及其蛋白表达水平均升高。激活的BV-2细胞通过分泌炎症因子造成神经元损伤。总之,CPF作用下小胶质细胞激活产生炎症因子,介导对神经元的损伤,进而可能参与了帕金森病的发病过程。

关键词：毒死蜱小胶质细胞多巴胺能神经元帕金森病

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Recombination and repeat-induced point mutation landscapes reveal trade-offs between the sexual and asexual cycles of Magnaporthe oryzae

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Journal of Genetics and Genomics 2024年第7期51卷 723-734页

作者： Xifang Zong Yaxin lou Mengshuang Xia Kunyang Zhao Jingxuan Chen Ju Huang Sihai Yang Long Wang State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjingJiangsu 210000China State Key Laboratory for Crop Genetics and Germplasm Enhancement Bioinformatics CenterAcademy for Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjingJiangsu 210000China Co-Innovation Center for Sustainable Forestry in Southern China Nanjing Forestry UniversityNanjingJiangsu 210000China

The fungal disease caused by Magnaporthe oryzae is one of the most devastating diseases that endanger many crops *** shows that sexual reproduction can be advantageous for fungal diseases as hybridization facilitates ***,the pervasive clonal lineages of *** observed in natural fields contradict this expectation.A better understanding of the roles of recombination and the fungi-specific repeat-induced point mutation(RIP)in shaping its evolutionary trajectory is essential to bridge this knowledge *** we systematically investigate the RIP and recombination landscapes in *** using a whole genome sequencing data from 252 population samples and 92 cross *** data reveal that the RIP can robustly capture the population history of ***,and we provide accurate estimations of the recombination and RIP rates across different *** ***,our results highlight a parent-of-origin bias in both recombination and RIP rates,tightly associating with their sexual potential and variations of effector *** bias suggests a critical trade-off between generating novel allelic combinations in the sexual cycle to facilitate host-jumping and stimulating transposon-associated diversification of effectors in the asexual cycle to facilitate host *** findings provide unique insights into understanding the evolution of blast fungus.

关键词： Magnaporthe oryzae Crossover Repeat-induced point mutation(RiP) Effectors Sexual reproduction

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