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Fatty acid oxidation and autophagy promote endoxifen resistance and counter the effect of AKT inhibition in eR-positive breast cancer cells

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Journal of Molecular Cell Biology 2021年第6期13卷 433-444页

作者： Lei Duan Sarah Calhoun Daeun Shim Ricardo e.Perez Lothar A.Blatter Carl G.Maki Department of Cell and Molecular Medicine Rush University Medical CenterChicagoIL 60612USA Department of Molecular Biophysics and Physiology Rush University Medical CenterChicagoIL 60612USA

Tamoxifen(TAM)is the first-line endocrine therapy for estrogen receptor-positive(eR+)breast cancer(BC).However,acquired resistance occurs in∼50%***,although the PI3K/AKT/mTOR pathway is a viable target for treatment of endocrine therapy-refractory patients,complex signaling feedback loops exist,which can counter the effectiveness of inhibitors of this ***,we analyzed signaling pathways and metabolism in eR+MCF7 BC cell line and their TAM-resistant derivatives that are co-resistant to endoxifen using immunoblotting,quantitative polymerase chain reaction,and the Agilent Seahorse XF *** found that activation of AKT and the energy-sensing kinase AMPK was increased in TAM and endoxifen-resistant ***,eRRα/PGC-1βand their target genes MCAD and CPT-1 were increased and regulated by AMPK,which coincided with increased fatty acid oxidation(FAO)and autophagy in TAM-resistant *** of AKT feedback-activates AMPK and eRRα/PGC-1β-MCAD/CPT-1 with a consequent increase in FAO and autophagy that counters the therapeutic effect of endoxifen and AKT ***,our results indicate increased activation of AKT and AMPK with metabolic reprogramming and increased autophagy in TAM-resistant *** inhibition of AKT and FAO/autophagy is necessary to fully sensitize resistant cells to endoxifen.

关键词： endoxifen fatty acid oxidation autophagy AMPK AKT

Theoretical Analysis of Solidly Mounted Film Bulk Acoustic Resonator with Nanocrystalline Diamond as High Impedance Material of Bragg Reflector

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Journal of Harbin Institute of Technology(New Series) 2021年第2期28卷 1-7页

作者： Yujia e Sen Zhang Bing Dai Jiaqi Zhu Jiecai Han Center for Composite Materials and Structures Harbin Institute of TechnologyHarbin 150080China

In this paper,a solidly mounted resonator(SMR)was designed with nanocrystalline diamond(NCD)as the high acoustic impedance material of Bragg reflector to improve the *** used Mathcad to investigate the effect of the Bragg reflector on the performance of the SMR,as well as the influence of different materials and the number of layers of Bragg reflector on the quality factor *** show that the Bragg reflector could reduce energy loss effectively,and the higher the impedance of the high acoustic impedance layer,the better the *** parasitic factors of the SMR using two high acoustic impedance materials,tungsten(W)and NCD,were also simulated by an Advanced Design System(ADS)using the Mason *** was found that the parasitic effect caused by metal would significantly decrease the Q factor of the *** the frequency range below 6 GHz,within which the SMR works normally,NCD performed better than ***,NCD is a better choice of high acoustic impedance material in the design of the SMR,with improved quality at high frequency and low *** optimum number of layers of Bragg reflector is 6.

关键词： solidly mounted resonator(SMR) nanocrystalline diamond(NCD) Bragg reflector quality factor(Q) parasitic effect

AGe-0 SILVeR CARP AND GIZZARD SHAD DAILY GROWTH AND HATCH TIMING IN THe MIDDLe MISSISSIPPI RIVeR

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水生生物学报 2018年第6期42卷 1084-1088页

作者： WOLF Michael C. HAUPT Kevin PHeLPS Quinton e. Department of Natural Resources Fish and Wildlife Division204 Main Street East BaudetteMinnesota 56623USA U.S.Fish and Wildlife Service Carterville Fish and Wildlife Conservation Office 9053 Rt.148 Suite A MarionIllinois 62959USA West Virginia University Division of Forestry and Natural Resources307C Percival HallMorgantownWest Virginia 26505USA

The establishment of a highly efficient planktivore, Silver carp(Hypophthalmichthys molitrix), in the Mississippi River Basin has been documented as having negative impacts on native planktivore populations. Silver carp have the potential, to alter the trophic food web through negative interactions with native planktivores in large river systems. Due to increasing Silver carp ranges, interactions between Silver carp and other native planktivores is likely to increase. One abundant native planktivore that is often found in similar habitats as Silver carp is Gizzard shad(Dorosoma cepedianum). Potential competition for resources exists because of overlapping habitat use and forage. Given the similarities between these two planktivores, we sought to evaluate daily growth rates and determine hatch dates of age-0 Silver carp and Gizzard shad in the Middle Mississippi River. Silver carp and Gizzard shad were collected from the Middle Mississippi River using an electrified surface trawl from June through September with sizes ranging from 21—65 mm total length for Gizzard shad and 24—85 mm total length for Silver carp. A sample of age-0 fish(n=697) was collected at the end of the growing season including 292 Gizzard shad and 405 Silver carp. Size structure(total length in mm) of Silver carp(49.05±0.41; ± Se) was significantly greater(T= –16.43, df=695, Pes were similar between Silver carp(July 26 th to August 18 th) and Gizzard shad(July 28 th to August 19 th). Growth of Silver carp(2.24 mm per day) was significantly greater(Per day). Mortality was similar between Silver carp(28.1%)and Gizzard shad(25.1%) at this early life stage. The faster growth rates in Silver carp result in Silver carp entering the winter season larger in size with likely an increased capacity to consume plankton and decreased predation ultimately leading to higher recruitment. Knowing that there exists

关键词： Dorosoma cepedianum Silver carp

Measurement of hepatic functional mass by means of ^(13)C-methacetin and ^(13)C-phenylalanine breath tests in chronic liver disease: Comparison with Child-Pugh score and serum bile acid levels

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World Journal of Gastroenterology 2005年第1期11卷 142-148页

作者： D.Festi S.Capodicasa L.Sandri L.Colaiocco-Ferrante T.Staniscia e.Vitacolonna A.Vestito R.Simoni G.Mazzella P.Portincasa e.Roda A.Colecchia Department of Internal Medicine and Gastroenterology Department of Medicine and Aging Department of Internal Medicine and Public Medicine

AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid ***: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were ***: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile ***, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath ***: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.

关键词： Chronic hepatitis c Liver cirrhosis Breath Tests Hepatic functional mass

experimental platform for the investigation of magnetized-reverse-shock dynamics in the context of POLAR

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High Power Laser Science and engineering 2018年第3期6卷 36-49页

作者： B. Albertazzi e. Falize A. Pelka e Brack e Kroll R. Yurchak e. Brambrink e Mabey N. Ozaki S. Pikuz L. Van Box Som J. M. Bonnet-Bidaud J. e. Cross e. Filippov G. Gregori R. Kodama M. Mouchet T. Morita Y. Sakawa R. e Drake C. C. Kuranz M. J.-e. Manuel C. Li e Tzeferacos D. Lamb U. Schramm M. Koenig LULI- CNRS Ecole Polytechnique CEA: Universite Paris-Saclay UPMC Univ Paris 06: Sorbonne Universites- F-91128 Palaiseau cedex France CeA-DAM-DIF F-91297 Arpajon France CeA Saclay DSM/Irfu/Service d'Astrophysique F-91191 Gif-sur- Yvette France Helmholtz-Zentrum Dresden - Rossendorf HZDR Bautzner Landstrαβe 400 01328 Dresden Germany Department of Atmospheric Oceanic and Space Sciences University of Michigan Ann Arbor M148109 USA Graduate School of engineering Osaka University Suita Osaka 565-0871 Japan JIHT-RAS 13-2 lzhorskaya st. Moscow 125412 Russia National Research Nuclear University MePhl Moscow 115409 Russia Department of Physics University of Oxford Parks Road Oxford OX1 3PU UK Institute of Laser engineering Osaka University Suita Osaka 565-0871 Japan LUTH Observatoire de Paris UMR CNRS 8102 Universite Paris Diderot 92190 Meudon France Department of energy engineering Science Faculty of Engineering Sciences Kyushu University Japan General Atomics San Diego CA 92121 USA Plasma Science and Fusion Center Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge MA 02139 USA Flash Center for Computational Science University of Chicago IL 60637 USA

The influence of a strong external magnetic field on the collimation of a high Mach number plasma flow and its collision with a solid obstacle is investigated experimentally and numerically. The laser irradiation （I - 2 × 10^14 W. cm-2） of a multilayer target generates a shock wave that produces a rear side plasma expanding flow. Immersed in a homogeneous 10 T external magnetic field, this plasma flow propagates in vacuum and impacts an obstacle located a few mm from the main target. A reverse shock is then formed with typical velocities of the order of 15-20 4- 5 km/s. The experimental results are compared with 2D radiative magnetohydrodynamic simulations using the FLASH code. This platform allows investigating the dynamics of reverse shock, mimicking the processes occurring in a cataclysmic variable of polar type.

关键词： accretion processes high-power laser hydrodynamics laboratory astrophysics polar radiative shocks

Nanovolcano microelectrode arrays: toward long- term on-demand registration of transmembrane action potentials by controlled electroporation

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Microsystems & Nanoengineering 2020年第1期6卷 578-589页

作者： Benoit X.e.Desbiolles etienne de Coulon Nicolas Maino Arnaud Bertsch Stephan Rohr Philippe Renaud Laboratory of Microsystems LMIS4 Ecole Polytechnique Federale de LausanneLausanneSwitzerland Department of Physiology Laboratory of Cellular Optics IIUniversity of BernBernSwitzerland

Volcano-shaped microelectrodes(nanovolcanoes)functionalized with nanopatterned self-assembled monolayers have recently been demonstrated to report cardiomyocyte action potentials after gaining spontaneous intracellular *** nanovolcanoes exhibit recording characteristics similar to those of state-of-the-art micro-nanoelectrode arrays that use electroporation as an insertion *** this study,we investigated whether the use of electroporation improves the performance of nanovolcano arrays in terms of action potential amplitudes,recording durations,and *** with neonatal rat cardiomyocyte monolayers grown on nanovolcano arrays demonstrated that electroporation pulses with characteristics derived from analytical models increased the efficiency of nanovolcano recordings,as they enabled multiple on-demand registration of intracellular action potentials with amplitudes as high as 62 mV and parallel recordings in up to~76%of the available *** performance of nanovolcanoes showed no dependence on the presence of functionalized nanopatterns,indicating that the tip geometry itself is instrumental for establishing a tight seal at the cell–electrode interface,which ultimately determines the quality of ***,the use of electroporation permitted the recording of attenuated cardiomyocyte action potentials during consecutive days at identical sites,indicating that nanovolcano recordings are nondestructive and permit long-term on-demand recordings from excitable cardiac *** from demonstrating that less complex manufacturing processes can be used for next-generation nanovolcano arrays,the finding that the devices are suitable for performing on-demand recordings of electrical activity from multiple sites of excitable cardiac tissues over extended periods of time opens the possibility of using the devices not only in basic research but also in the context of comprehensive drug testing.

关键词： arrays recording action

Dietary fatty acids in gut health: Absorption, metabolism and function

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Animal Nutrition 2021年第4期7卷 1337-1344页

作者： e.Xu Chao Chen Jie Fu Luoyi Zhu Junlan Shu Mingliang Jin Yizhen Wang Xin Zong Key laboratory of animal genetics breeding and reproduction in the plateau mountainous regionministry of educationcollege of aniaml scienceguizhou university550025 guiyangchina Key laboratory of molecular animal nutrition ministry of educationcollege of animal scienceszhejiang university310058 hangzhouchina Key laboratory of animal nutrition and feed science in eastern china ministry of agriculturecollege of animal scienceszhejiang university310058 hangzhouchina

In biological responses,fatty acids(FA)are absorbed and metabolized in the form of substrates for energy *** molecular structures(number of double bonds and chain length)and composition of dietary FA impact digestion,absorption and metabolism,and the biological roles of ***,increasing evidence indicates that FA are essentially utilized as an energy source and are signaling molecules that exert physiological activity of gut microbiota and immune *** addition,FA could serve as natural ligands for orphan G protein-coupled receptors(GPCR),also called free fatty acid receptors(FFAR),which intertwine metabolic and immune systems via multiple *** present review explores the recent findings on FA absorption and its impact on gut health,particularly addressing the mechanism by which dietary FA potentially influences intestinal microbiota and epithelial ***,this work attempts to uncover research ideas for devising future strategies for manipulating the composition of dietary FA to regulate gut health and support a normal immune system for metabolic and immune disorders.

关键词： Fatty acids Gut Absorption Metabolism G protein coupled receptor

Can crop science really help us to produce more betterquality food while reducing the world-wide environmental footprint of agriculture?

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Frontiers of Agricultural Science and engineering 2020年第1期7卷 28-44页

作者： William J.DAVIeS Susan e.WARD Alan WILSON Lancaster environment Centre Lancaster UniversityLancasterLAI 4YQUK Waitrose and Partners Food RetailersWaite HouseBracknellRG128YAUK

This paper reviews recent developments in crop science that can be the basis of a revolution in the global food system but it is also emphasized that such a revolution requires more than changes in food production and *** must more effectively feed a growing global population with a healthy diet while also defining and delivering the kinds of sustainable food systems that will minimise damage to our *** are exciting new developments in crop production biology but much existing crop science can be exploited to increase yields with the aid of a knowledge exchange(Ke)framework requiring the use of new technology now available to most people across the *** discuss novel approaches at both the plant and the crop level that will enhance nutrient and water productivity and we also outline ways in which energy use and greenhouse gas(GHG)emissions can be reduced and labor shortages *** of new biology and new engineering opportunities will require development of public-private partnerships and collaborations across the disciplines to allow us to move effectively from discovery science to practical *** is also important that consumers contribute to the debate over proposed changes to food and farming and so effective Ke mechanisms are required between all relevant communities.

关键词： food security environmental sustainability crop water use efficiency crop science diet and health

Pancreaticβ-cell dysfunction in type 2 diabetes:Implications of inflammation and oxidative stress

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World Journal of Diabetes 2023年第3期14卷 130-146页

作者： Phiwayinkosi V Dludla Sihle e Mabhida Khanyisani Ziqubu Bongani B Nkambule Sithandiwe e Mazibuko-Mbeje Sidney Hanser Albert Kotze Basson Carmen Pheiffer Andre Pascal Kengne Biomedical Research and Innovation Platform South African Medical Research CouncilCape Town 7505South Africa Department of Biochemistry and Microbiology University of ZululandKwaDlangezwa 3880South Africa Department of Biochemistry North-West UniversityMmabatho 2745South Africa School of Laboratory Medicine and Medical Sciences University of KwaZulu-NatalDurban 4000South Africa Department of Physiology and environmental Health University of LimpopoSovenga 0727South Africa Department of Medicine University of Cape TownCape Town 7500South Africa Non-Communicable Diseases Research Unit South African Medical Research CouncilTygerberg 7505South Africa

Insulin resistance and pancreaticβ-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes(T2D).Beyond the detrimental effects of insulin resistance,inflammation and oxidative stress have emerged as critical features of T2D that defineβ-cell *** markers of inflammation such as C-reactive protein,tumor necrosis factor alpha,and interleukin-1βare consistently associated withβ-cell failure in preclinical models and in people with ***,important markers of oxidative stress,such as increased reactive oxygen species and depleted intracellular antioxidants,are consistent with pancreaticβ-cell damage in conditions of *** effects illustrate a pathological relationship between an abnormal inflammatory response and generation of oxidative stress during the progression of *** current review explores preclinical and clinical research on the pathological implications of inflammation and oxidative stress during the development ofβ-cell dysfunction in ***,important molecular mechanisms and relevant biomarkers involved in this process are discussed to divulge a pathological link between inflammation and oxidative stress duringβ-cell failure in *** the clinical relevance of the review,a systematic analysis of evidence from randomized controlled trials is covered,on the potential therapeutic effects of some commonly used antidiabetic agents in modulating inflammatory makers to improveβ-cell function.

关键词： Type 2 diabetes Insulin resistance β-cell dysfunction Inflammation Oxidative stress