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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 progression.AMPK is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy stores.Previous studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic cancer.In this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)stiffness.We 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 stiffness.This regulation of AMPK requires the Hippo kinases but not LKB1/CaMKKp.Hippo kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM stiffness.Furthermore,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival outcome.The activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC growth.Together,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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An intelligent control method based on artificial neural network for numerical flight simulation of the basic finner projectile with pitching maneuver

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Defence Technology（防务技术） 2024年第2期32卷 663-674页

作者： Yiming liang Guangning li min xu Junmin Zhao Feng Hao Hongbo Shi Northwestern Polytechnical University School of Astronautics Xi’an 710072China China North Industries Group Corporation No 203 Research Institute Xi’an 710065China

In this paper,an intelligent control method applying on numerical virtual flight is proposed.The proposed algorithm is verified and evaluated by combining with the case of the basic finner projectile model and shows a good application prospect.Firstly,a numerical virtual flight simulation model based on overlapping dynamic mesh technology is constructed.In order to verify the accuracy of the dynamic grid technology and the calculation of unsteady flow,a numerical simulation of the basic finner projectile without control is carried out.The simulation results are in good agreement with the experiment data which shows that the algorithm used in this paper can also be used in the design and evaluation of the intelligent controller in the numerical virtual flight simulation.Secondly,combined with the real-time control requirements of aerodynamic,attitude and displacement parameters of the projectile during the flight process,the numerical simulations of the basic finner projectile’s pitch channel are carried out under the traditional PID(Proportional-Integral-Derivative)control strategy and the intelligent PID control strategy respectively.The intelligent PID controller based on BP(Back Propagation)neural network can realize online learning and self-optimization of control parameters according to the acquired real-time flight parameters.Compared with the traditional PID controller,the concerned control variable overshoot,rise time,transition time and steady state error and other performance indicators have been greatly improved,and the higher the learning efficiency or the inertia coefficient,the faster the system,the larger the overshoot,and the smaller the stability error.The intelligent control method applying on numerical virtual flight is capable of solving the complicated unsteady motion and flow with the intelligent PID control strategy and has a strong promotion to engineering application.

关键词： Numerical virtual flight Intelligent control BP neural network PID Moving chimera grid

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Large-disturbance Stability Analysis of Power Systems with Synchronous Generator and Converter-interfaced Generation

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Journal of Modern Power Systems and Clean Energy 2024年第3期12卷 997-1002页

作者： Lei Chen Yong min liangshuai Hao Guangzheng Xing Yalou li Shiyun xu IEEE Department of Electrical Engineering Tsinghua University China Electric Power Research Institute

This letter studies large-disturbance stability of the power system with a synchronous generator(SG) and a converter-interfaced generation(CIG) connected to infinite bus. The power system is multi-timescale and first simplified. It is shown that the boundary of region of attraction(ROA) of the simplified model is composed of stable manifolds of unstable equilibrium point(UEP) or semi-singular point(SSP), named anchor points, and singular surface pieces. The type of anchor point determines the dominant instability pattern of the power system. When the anchor point is UEP or SSP, the dominant instability pattern is the instability of rotor angle of SG or the instability of phase-locked loop and outer control loop(OCL) of CIG, respectively. Transition of dominant instability pattern can be analyzed with the relative position relationship between UEP and SSP. The effect of OCL is discussed. When the OCL is activated, the ROA becomes smaller and the system is more prone to instability of CIG. It is necessary to consider the OCL when studying the large-disturbance stability of the power system.

关键词： Power system stability Mathematical models Phase locked loops Stability criteria Transient analysis Power system dynamics Rotors

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Electronic structure and spin state regulation of vanadium nitride via a sulfur doping strategy toward flexible zinc-air batteries

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Journal of Energy Chemistry 2024年第2期89卷 239-249,I0007页

作者： Daijie Deng Honghui Zhang Jianchun Wu Xing Tang min ling Sihua Dong li xu Henan li Huaming li Institute for Energy Research Institute of Quantum and Sustainable TechnologySchool of Chemistry and Chemical EngineeringSchool of Materials Science and EngineeringJiangsu Province and Education Ministry Co-Sponsored Synergistic Innovation Center of Modern Agricultural EquipmentJiangsu UniversityZhenjiang 212013JiangsuChina Key Laboratory of Radio Frequency and Micro-Nano Electronics of Jiangsu Province Nanjing 210023JiangsuChina Zhenjiang Kangyuan Electrical Appliance Co. Ltd.Zhenjiang 212013JiangsuChina College of Chemical and Biological Engineering Zhejiang UniversityHangzhou 310027ZhejiangChina YTO Group Corporation Dongfanghong(Henan)Agricultural Service Technology Co. Ltd.Luoyang 471033HenanChina

Owing to the distinctive structural characteristics,vanadium nitride(VN)is highly regarded as a catalyst for oxygen reduction reaction(ORR)in zinc-air batteries(ZABs).However,VN exhibits limited intrinsic ORR activity due to the weak adsorption ability to O-containing species.Here,the S-doped VN anchored on N,S-doped multi-dimensional carbon(S-VN/Co/NS-MC)was constructed using the solvothermal and in-situ doping methods.Incorporating sulfur atoms into VN species alters the electron spin state of vanadium in the S-VN/Co/NS-MC for regulating the adsorption energy of vanadium sites to oxygen molecules.The introduced sulfur atoms polarize the V 3d_(z)^(2) electrons,shifting spin-down electrons closer to the Fermi level in the S-VN/Co/NS-MC.Consequently,the introduction of sulfur atoms into VN species enhances the adsorption energy of vanadium sites for oxygen molecules.The*OOH dissociation transitions from being unspontaneous on the VN surface to a spontaneous state on the S-doped VN surface.Then,the ORR barrier on the S-VN/Co/NS-MC surface is reduced.The S-VN/Co/NS-MC demonstrates a higher half-wave potential and limiting current density compared to the VN/Co/N-MC.The S-VN/Co/NS-MC-based liquid ZABs display a power density of 195.7 m W cm^(-2),a specific capacity of 815.7 m A h g^(-1),and a cycling stability exceeding 250 h.The S-VN/Co/NS-MC-based flexible ZABs are successfully employed to charge both a smart watch and a mobile phone.This approach holds promise for advancing the commercial utilization of VN-based catalysts in ZABs.

关键词： S-doped VN Electronic structures Spin state regulation Oxygen reduction reaction Zinc-air batteries

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Subclinical paraganglioma of the retroperitoneum:A case report

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World Journal of Clinical Cases 2024年第15期12卷 2672-2677页

作者： li-min Kang Fa-Kun Yu Fu-Wei Zhang Lei xu Department of Hepatobiliary and Pancreatic Surgery Puer People's HospitalPuer 665000Yunnan ProvinceChina

BACKGROUND Paraganglioma(PGL)located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location,lack of specific symptoms in the early stages,and absence of distinctive manifestations on imaging.CASE SUMMARY A 56-year-old woman presented with a left upper abdominal mass discovered 1 wk ago during a physical examination.She did not have a history of smoking,alcohol consumption,or other harmful habits,no surgical procedures or infectious diseases,and had a 4-year history of hypertension.Upon admission,she did not exhibit fever,vomiting,or abdominal distension.Physical examination indicated mild percussion pain in the left upper abdomen,with no palpable enlargement of the liver or spleen.Laboratory tests and tumor markers showed no significant abnormalities.Enhanced computed tomography and magnetic resonance imaging of the upper abdomen revealed a cystic solid mass in the left epigastrium measuring approximately 6.5 cm×4.5 cm,with inhomogeneous enhancement in the arterial phase,closely associated with the lesser curvature of the stomach and the pancreas.The patient underwent laparoscopic resection of the retroperitoneal mass,which was successfully removed without tumor rupture.A 12-month postoperative follow-up period showed good recovery.CONCLUSION This case report details the successful laparoscopic resection of a retroperitoneal subclinical PGL,resulting in a good recovery observed at the 12-month follow-up.Interestingly,the patient also experienced unexpected cure of hypertensive disease.

关键词： Paraganglioma Retroperitoneal anatomy Subclinical Pheochromocytoma Laparoscopy Case report

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Decreased AKAP4/PKA signaling pathway in high DFI sperm affects sperm capacitation

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Asian Journal of Andrology 2024年第1期26卷 25-33页

作者： Kun Zhang Xiu-Hua xu Jian Wu Ning Wang Gang li Gui-min Hao Jin-Feng Cao Hebei Key Laboratory of Infertility and Genetics Department of Reproductive MedicineSecond Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of Reproductive Medicine Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000China Department of Neurology The 980th Hospital of the People's Liberation Army Joint Logistics Support Force(Bethune International Peace Hospital)Shijiazhuang 050000China.

The sperm DNA fragmentation index(DFI)is a metric used to assess DNA fragmentation within sperm.During in vitro fertilizationembryo transfer(IVF-ET),high sperm DFI can lead to a low fertilization rate,poor embryo development,early miscarriage,etc.A kinase anchoring protein(AKAP)is a scaffold protein that can bind protein kinase A(PKA)to subcellular sites of specific substrates and protects the biophosphorylation reaction.Sperm protein antigen 17(SPA17)can also bind to AKAP.This study intends to explore the reason for the decreased fertilization rate observed in high sperm DFI(H-DFI)patients during IVF-ET.In addition,the study investigates the expression of AKAP,protein kinase A regulatory subunit(PKARIl),and SPA17 between H-DFI and low sperm DFI(L-DFI)patients.SPA17 at the transcriptional level is abnormal,the translational level increases in H-DFI patients,and the expression of AKAP4/PKARIl protein decreases.H,O,has been used to simulate oxidative stress damage to spermatozoa during the formation of sperm DFI.It indicates that H,O,increases the expression of sperm SPA17 protein and suppresses AKAP4/PKARIl protein expression.These processes inhibit sperm capacitation and reduce acrosomal reactions.Embryo culture data and IVF outcomes have been documented.The H-DFI group has a lower fertilization rate.Therefore,the results indicate that the possible causes for the decreased fertilization rate in the H-DFI patients have included loss of sperm AKAP4/PKARIl proteins,blocked sperm capacitation,and reduced occurrence of acrosome reaction.

关键词： AKAP PKA SPA17 sperm capacitation sperm DNA fragmentation index

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OsPDR20 is an ABCG metal transporter regulating cadmium accumulation in rice

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Journal of Environmental Sciences 2024年第2期136卷 21-34页

作者： He li Chao li Di Sun Zhi min Yang Department of Biochemistry and Molecular Biology College of Life SciencesNanjing Agricultural UniversityNanjing 210095China

Cadmium(Cd)is a non-essential toxic heavy metal,seriously posing high environmental risks to human health.Digging genetic resources relevant to functional genes is important for understanding the metal absorption and accumulation in crops and bioremediation of Cd-polluted environments.This study investigated a functionally uncharacterized ATP binding cassette transporter G family(ABCG)gene encoding a Pleiotropic Drug Resistance 20(PDR20)type metal transporter which is localized to the plasma membrane of rice.OsPDR20 was transcriptionally expressed in almost all tissues and organs in lifespan and was strongly induced in roots and shoots of young rice under Cd stress.Ectopic expression of OsPDR20 in a yeast mutant ycf1 sensitive to Cd conferred cellular tolerance with less Cd accumulation.Knockdown of OsPDR20 by RNA interference(RNAi)moderately attenuated root/shoot elongation and biomass,with reduced chlorophylls in rice grown under hydroponic medium with 2 and 10μmol/L Cd,but led to more Cd accumulation.A field trial of rice grown in a realistic Cd-contaminated soil(0.40 mg/kg)showed that RNAi plants growth and development were also compromised compared to wild-type(WT),with smaller panicles and lower spikelet fertility but little effect on yield of grains.However,OsPDR20 suppression resulted in unexpectedly higher levels of Cd accumulation in rice straw including lower leaves and culm and grain.These results suggest that OsPDR20 is actively involved in Cd accumulation and homeostasis in rice crops.The increased Cd accumulation in the RNAi plants has the potential application in phytoremediation of Cd-polluted wetland soils.

关键词： Rice ABCG transporter Cadmium accumulation Phytoremediation

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Ultrathin curved PdNiRu nanosheets as bifunctional catalysts for oxygen reduction and ethylene glycol oxidation

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Nano Research 2024年第5期17卷 3777-3784页

作者： Xianzeng li Tingyu Lu Huan Pang mingyi Zhang Dongdong xu lin xu min Han Jun Yang Jiangsu Key Laboratory of New Power Batteries Jiangsu Collaborative Innovation Center of Biomedical Functional MaterialsSchool of Chemistry and Materials ScienceNanjing Normal UniversityNanjing 210023China Fujian Cross Strait Institute of Flexible Electronics(Future Technology) Fujian Normal UniversityFuzhou 350117China State Key Laboratory of Multiphase Complex Systems Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China State Key Laboratory of Coordination Chemistry Nanjing UniversityNanjing 210023China School of Chemistry and Chemical Engineering Yangzhou UniversityYangzhou 225009China Key Laboratory for Photonic and Electronic Bandgap Materials Ministry of EducationSchool of Physics and Electronic EngineeringHarbin Normal UniversityHarbin 150025China

Pd-based metallic nanosheets with advanced physicochemical properties have been widely prepared and employed in various electrocatalytic reactions.However,few concerns were focused on their multiple performances in different electrocatalysis.Here,highly curved and ultrathin PdNiRu nanosheets(NSs)are developed by facile wet-chemistry strategy and exhibit excellent electrocatalytic performance toward both oxygen reduction reaction(ORR)and ethylene glycol oxidation reaction(EGOR).Owing to the synergistically structural(e.g.,ultrathin,curved,defects/steps-rich)and compositional(ternary alloy)advantages,PdNiRu NSs exhibited enhanced ORR and EGOR specific/mass activities and better stability/durability than control electrocatalysts.The specific activity(5.52 mA·cm^(−2))and mass activity(1.13 A·mg_(Pd)^(−1))of the PdNiRu NSs in ORR are 4.8 and 3.4 times as the ones of commercial Pt/C,respectively.The mass activity of PdNiRu NSs(3.86 A·mg_(Pd)^(−1))in EGOR is 2.6 times as commercial Pd/C(1.51 A·mg_(Pd)^(−1)).This study is helpful for the development of desired electrocatalysts with multi-functional application in practical fuel cells.

关键词： ultrathin nanosheets noble metal electrocatalysts bifunctional

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Apically guiding electron/mass transfer reaction induced by Ag/FeNx Mott-Schottky effect within a hollow star reactor toward high performance zinc-air batteries

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Journal of Energy Chemistry 2024年第8期95卷 106-116页

作者： Kaixiang Shi Kaixin Wang Tong li Junhao li Jie Ren xu li Yonggang min Zhouguang Lu Wei Tan Quanbing liu Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center(Rongjiang Laboratory) Guangdong University of Technology Guangzhou Key Laboratory of Clean Transportation Energy Chemistry Guangdong Provincial Key Laboratory of Plant Resources Biorefinery School of Chemical Engineering and Light Industry Guangdong University of Technology Key Laboratory of Electrochemical Energy Storage and Energy Conversion of Hainan Province School of Chemistry and Chemical Engineering Hainan Normal University School of Materials and Energy Guangdong University of Technology Department of Materials Science and Engineering Southern University of Science and Technology

The disparity in the transfer of carriers（electrons/mass） during the reaction in zinc-air batteries（ZABs）results in sluggish kinetics of the oxygen reduction reaction（ORR） and oxygen evolution reaction（OER）,along with elevated overpotentials,thereby imposing additional constraints on its utilization.Therefore,the pre-design and target-development of inexpensive,high-performance,and long-term stable bifunctional catalysts are urgently needed.In this work,an apically guiding dual-functional electrocatalyst（Ag-FeNx-N-C） was prepared,in which a hierarchical porous nitrogen-doped carbon with three-dimensional（3D） hollow star-shaped structure is used as a substrate and high-conductivity Ag nanoparticles are coupled with iron nitride（FeNx） nanoparticles.Theoretical calculations indicate that the Mott-Schottky heterojunction as an inherent electric field comes from the two-phase bound of Ag and FeNx,of which electron accumulation in the FeNxphase region and electron depletion in the Ag phase region promote orientated-guiding charge migration.The effective modulation of local electronic structures felicitously reforms the d-band electron-group distribution,and intellectually tunes the masstransfer reaction energy barriers for both ORR/OER.Additionally,the hollow star-s haped hierarchical porous structure provides an apical region for fast mass transfer.Experimental results show that the halfwave potential for ORR is 0.914 V,and the overpotential for OER is only 327 mV at 10 mA cm-2.A rechargeable ZAB with Ag-FeNx-N-C as the air cathode demonstrates long-term cycling performance exceeding 1500 cycles（500 h）,with a power density of 180 mW cm-2.Moreover,when employing AgFeNx-N-C as the air cathode,flexible ZABs demonstrate a notable open-circuit voltage of 1.42 V and achieve a maximum power density of 65.6 mW cm-2.Ag-FeNx-N-C shows guiding electron/mass transfer route and apical reaction microenvironment for the electrocatalyst architecture in the exploration prospects of ZABs.

关键词： Apically guiding effect Bifunctional catalysis Hollow star structure Mott-Schottky effect Zinc-air batteries

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Pseudomonotonicity of Nonlinear Transformations on Euclidean Jordan Algebras

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Acta Mathematicae Applicatae Sinica 2024年第1期40卷 192-204页

作者： Yuan-min li School of Mathematics and Statistics Xidian UniversityXi’an710071China

In this paper, we have introduced the concepts of pseudomonotonicity properties for nonlinear transformations defined on Euclidean Jordan algebras. The implications between this property and other P-properties have been studied. More importantly, we have solved the solvability problem of the nonlinear pseudomonotone complementarity problems over symmetric cones.

关键词： Euclidean Jordan algebra nonlinear transformation complementarity problem pseudomonotone

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