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Therapeutic targeting of hepatocellular carcinoma cells with antrocinol, a novel, dual-specificity, small-molecule inhibitor of the KRAS and ERK oncogenic signaling pathways

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Chemico-Biological Interactions 2023年第1期370卷 110329页

作者： Hsu, Chia-Hung Weng, Pei-Wei Chen, Ming-Yao Yeh, Chi-Tai Setiawan, Syahru Agung Yadav, Vijesh Kumar Wu, Alexander T.H. Tzeng, David T.W. Gong, Jian-Xian Yang, Zhen Tzeng, Yew-Min Department of Emergency Medicine Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Graduate Institute of Injury Prevention and Control College of Public Health Taipei Medical University Taipei City 11031 Taiwan Department of Emergency Medicine School of Medicine Taipei Medical University Taipei 11031 Taiwan Department of Orthopaedics School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Department of Orthopaedics Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Shuang Ho Hospital New Taipei City 23561 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Continuing Education Program of Food Biotechnology Applications College of Science and Engineering National Taitung University Taitung 95092 Taiwan International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Ph.D. Program of Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan School of Life Sciences The Chinese University of Hong Kong 999077 Hong Kong Lifebit London EC2A 2AP United Kingdom Laboratory of Chemical Genomics School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School Shenzhen 518055 China State Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education and Beijing National Laboratory for Molecular Science College of Chemistry and Molecular Engineering Peking University Beijing 100871 China Shenzhen Bay Laboratory Shenzhen 518055 China Department of Applied Science National Taitung University Taitung

Until recently, sorafenib has been the only treatment approved by the U.S. Food and Drug Administration for patients with advanced hepatocellular carcinoma (HCC). Some patients, however, exhibit resistance to this treatment and subsequently experience cancer progression, recurrence, or death. Therefore, identifying a new alternative treatment for patients with little or no response to sorafenib treatment is vital. In this study, we explored the therapeutic potential and underlying molecular mechanism of antrocinol ((3aS,4R,6aS,10aR)-4-(hydroxymethyl)-7,7-dimethyldecahydro-1H-naphtho[1,8a-c]furan-1-one) in patients with HCC. The results indicated that antrocinol was more therapeutically effective than antrocin, Stivarga, and sorafenib against HCC cell lines. Antrocinol also substantially suppressed the expression of KRAS-GTP, p-MEK1/2, p-ERK1/2, and p-AKT in the Huh7 cell line. Additionally, antrocinol-induced apoptosis in the Huh7 cell line, inhibited the formation of tumorspheres, and suppressed the expression of cancer stem cell markers CD133, KLF4, CD44, OCT4, SOX2, and c-Myc. Animal studies revealed that antrocinol alone considerably suppressed tumor growth in nonobese diabetic/severe combined immunodeficient mice inoculated with Huh7 tumorspheres. It also synergistically enhanced the anticancer effect of sorafenib, resulting in enhanced suppression of tumor growth (p < 0.001) and tumorsphere formation (p < 0.001). In tumor samples resected from mice treated with antrocinol alone or in combination with sorafenib, immunohistochemical analysis revealed an increase in BAX expression and a decrease in ERK and AKT protein expression. To the best of our knowledge, this is the first report of the anti-HCC activity of antrocinol. With its higher therapeutic efficacy than that of sorafenib, antrocinol is a candidate drug for patients with HCC who demonstrate little or no response to sorafenib treatment. © 2022 Elsevier B.V.

关键词： Antrocinol Cancer stemness Hepatocellular carcinoma KRAS/AKT/ERK axis Sorafenib

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Memory seeds enable high structural phase purity in 2D perovskite films for high-efficiency devices

Research Square

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Research Square 2021年

作者： Sidhik, Siraj Li, Wenbin Samani, Mohammad H.K. Zhang, Hao Wang, Yafei Hoffman, Justin Fehr, Austin K. Wong, Michael Katan, Claudine Even, Jacky Marciel, Amanda B. Kanatzidis, Mercouri G. Blancon, Jean-Christophe Mohite, Aditya D. Department of Chemical and Biomolecular Engineering Rice University HoustonTX77005 United States Applied Physics Graduate Program Smalley‐Curl Institute Rice University HoustonTX77005 United States Department of Chemistry Department of Materials Science and Engineering Northwestern University EvanstonIL60208 United States UMR 6226 RennesF-35000 France Univ Rennes INSA Rennes CNRS Institut FOTON UMR 6082 RennesF-35000 France

Two-dimensional (2D) perovskites are a class of halide perovskites offering a pathway for realizing efficient and durable optoelectronic devices. However, the broad chemical phase space and lack of understanding of film formation have led to quasi-2D perovskite films with polydispersity in perovskite layer thicknesses, which have hindered devices performance and stability. Here, we demonstrate a scalable approach involving dissolution of single-phase crystalline powders with homogeneous perovskite layer thickness in desired solvents, to fabricate 2D perovskite thin-films with high phase purity. In-situ characterizations reveal the presence of sub-micron-sized seeds in solution that preserve the memory of the dissolved single-crystals and dictate the nucleation and growth of grains with identical thickness of the perovskite layers in thin-films. Photovoltaic devices fabricated with such films, yields an efficiency of 17.1% and 1.20V open-circuit voltage, while preserving 97.5% of their peak-performance after 800 hours under illumination without any external thermal management. © 2021, CC BY.

关键词： Nucleation

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Magnetic Control of Soft Chiral Phonons in PbTe

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Physical Review Letters 2022年第7期128卷 075901-075901页

作者： Andrey Baydin Felix G. G. Hernandez Martin Rodriguez-Vega Anderson K. Okazaki Fuyang Tay G. Timothy Noe, II Ikufumi Katayama Jun Takeda Hiroyuki Nojiri Paulo H. O. Rappl Eduardo Abramof Gregory A. Fiete Junichiro Kono Department of Electrical and Computer Engineering Rice University Houston Texas 77005 USA Smalley-Curl Institute Rice University Houston Texas 77005 USA Instituto de Física Universidade de São Paulo São Paulo São Paulo 05508-090 Brazil Theoretical Division Los Alamos National Laboratory Los Alamos New Mexico 87545 USA Laboratório Associado de Sensores e Materiais Instituto Nacional de Pesquisas Espaciais São José dos Campos São Paulo 12201-970 Brazil Applied Physics Graduate Program Smalley-Curl Institute Rice University Houston Texas 77005 USA Department of Physics Graduate School of Engineering Science Yokohama National University Yokohama 240-8501 Japan Institute for Materials Research Tohoku University Sendai 980-8577 Japan Department of Physics Northeastern University Boston Massachusetts 02115 USA Department of Physics Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Department of Physics and Astronomy Rice University Houston Texas 77005 USA Department of Material Science and NanoEngineering Rice University Houston Texas 77005 USA

PbTe crystals have a soft transverse optical phonon mode in the terahertz frequency range, which is known to efficiently decay into heat-carrying acoustic phonons, resulting in anomalously low thermal conductivity. Here, we studied this phonon via polarization-dependent terahertz spectroscopy. We observed softening of this mode with decreasing temperature, indicative of incipient ferroelectricity, which we explain through a model including strong anharmonicity with a quartic displacement term. In magnetic fields up to 25 T, the phonon mode splits into two modes with opposite handedness, exhibiting circular dichroism. Their frequencies display Zeeman splitting together with an overall diamagnetic shift with increasing magnetic field. Using a group-theoretical approach, we demonstrate that these observations are the result of magnetic field-induced morphic changes in the crystal symmetries through the Lorentz force exerted on the lattice ions. Thus, our Letter reveals a novel process of controlling phonon properties in a soft ionic lattice by a strong magnetic field.

关键词： Chirality Diamagnetism Magneto-dielectric effect Optical phonons Thermal conductivity Zeeman effect Terahertz time-domain spectroscopy

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Unveiling the dopant segregation effect at hematite interfaces

arXiv

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arXiv 2021年

作者： de Lima, Felipe Crasto Schleder, Gabriel R. Souza Junior, João B. Souza, Flavio L. Destro, Fabrício B. Miwa, Roberto H. Leite, Edson R. Fazzio, Adalberto Brazilian Nanotechnology National Laboratory C.P. 6192 SP Campinas13083-970 Brazil Federal University of ABC Santo André SP09210-580 Brazil Graduate Program in Materials Science and Engineering Department of Materials Engineering SP São Carlos13565-905 Brazil Instituto de Física Universidade Federal de Uberlândia C.P. 593 MG Uberlândia38400-902 Brazil Departamento de Química Universidade Federal de São Carlos 13565-905 Brazil

Understanding the effects of atomic structure modification in hematite photoanodes is essential for the rational design of high-efficiency functionalizations. Recently it was found that interface modification with Sn/Sb segregates considerably increases hematite photocatalytic efficiency. However, the understanding of the different electronic effects of these modifications at the atomic level is still lacking. This letter describes the segregation effects of two different dopants-Sn and Sb-on both the solid-solid (grain-boundaries) and solid-liquid interfaces (surfaces) of hematite. Within an ab initio approach, we quantitatively extract the potential barrier reduction on polycrystalline interfaces due to the dopant, which causes an increase in the inter-grain electron transport. Concomitantly, the dopants' segregation on hematite surfaces results in a decrease of the oxygen vacancy formation energy. Such vacancies lead to the experimentally observed rise of the flat-band potential. The comprehension of the electronic effects of dopants on both types of interfaces explains the experimental peak efficiency of interface-modified hematite with dopant segregates, also enabling the control and design of interfaces for different higher-efficiency applications. Copyright © 2021, The Authors. All rights reserved.

关键词： Hematite

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Enhanced light-matter interaction in two-dimensional transition metal dichalcogenides

arXiv

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arXiv 2021年

作者： Huang, Lujun Krasnok, Alex Alú, Andrea Yu, Yiling Neshev, Dragomir Miroshnichenko, Andrey E. School of Engineering and Information Technologies University of New South Wales CanberraACT2600 Australia Photonics Initiative Advanced Science Research Center City University of New York New YorkNY10031 United States Physics Program Graduate Center City University of New York New YorkNY10016 United States Center for Nanophase Materials Sciences Oak Ridge National Laboratory Oak RidgeTN37831 United States Department of Electronic Materials Engineering Research School of Physics The Australian National University CanberraACT2601 Australia

Two dimensional (2D) transition metal dichalcogenide (TMDC) materials, such as MoS2, WS2, MoSe2, and WSe2, have received extensive attention in the past decade due to their extraordinary electronic, optical and thermal properties. 2D TMDC materials evolve from indirect bandgap semiconductors to direct bandgap semiconductors while their layer number is reduced from few layers to a monolayer limit. Consequently, there is strong photoluminescence in a monolayer (1L) TMDC due to the large quantum yield. Moreover, such monolayer semiconductors have two other exciting properties: large binding energy of excitons and valley polarization. These properties make them become ideal materials for various electronic, photonic and optoelectronic devices. However, their performance is limited by the relatively weak light-matter interactions due to their atomically thin form factor. Resonant nanophotonic structures provide a viable way to address this issue and enhance light-matter interactions in 2D TMDCs. Here, we provide an overview of this research area, showcasing relevant applications, including exotic light emission, absorption and scattering features. We start by overviewing the concept of excitons in 1L-TMDC and the fundamental theory of cavity-enhanced emission, followed by a discussion on the recent progress of enhanced light emission, strong coupling and valleytronics. The atomically thin nature of 1L-TMDC enables a broad range of ways to tune its electric and optical properties. Thus, we continue by reviewing advances in TMDC-based tunable photonic devices. Next, we survey the recent progress in enhanced light absorption over narrow and broad bandwidths using 1L or few-layer TMDCs, and their applications for photovoltaics and photodetectors. We also review recent efforts of engineering light scattering, e.g., inducing Fano resonances, wavefront engineering in 1L or few-layer TMDCs by either integrating resonant structures, such as plasmonic/Mie resonant metasurfaces, or

关键词： Monolayers

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Controlled synthetic chirality in macroscopic assemblies of carbon nanotubes

arXiv

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arXiv 2023年

作者： Doumani, Jacques Lou, Minhan Dewey, Oliver Hong, Nina Fan, Jichao Baydin, Andrey Yomogida, Yohei Yanagi, Kazuhiro Pasquali, Matteo Saito, Riichiro Kono, Junichiro Gao, Weilu Department of Electrical and Computer Engineering Rice University HoustonTX United States Applied Physics Graduate Program Smalley–Curl Institute Rice University HoustonTX United States Department of Electrical and Computer Engineering The University of Utah Salt Lake CityUT United States Carbon Hub Rice University HoustonTX United States Department of Chemical and Biomolecular Engineering Rice University HoustonTX United States J.A. Woollam Co. Inc. LincolnNE United States Smalley–Curl Institute Rice University HoustonTX United States Department of Physics Tokyo Metropolitan University Tokyo Japan Department of Chemistry Rice University HoustonTX United States Department of Materials Science and NanoEngineering Rice University HoustonTX United States Department of Physics Tohoku University Sendai Japan Department Physics and Astronomy Rice University HoustonTX United States

There is an emerging recognition that successful utilization of chiral degrees of freedom can bring new scientific and technological opportunities to diverse research areas. Hence, methods are being sought for creating artificial matter with controllable chirality in an uncomplicated and reproducible manner. Here, we report the development of two straightforward methods for fabricating wafer-scale chiral architectures of ordered carbon nanotubes (CNTs) with tunable and giant circular dichroism (CD). Both methods employ simple approaches, (i) mechanical rotation and (ii) twist-stacking, based on controlled vacuum filtration and do not involve any sophisticated nanofabrication processes. We used a racemic mixture of CNTs as the starting material, so the intrinsic chirality of chiral CNTs is not responsible for the observed chirality. In particular, by controlling the stacking angle and handedness in (ii), we were able to maximize the CD response and achieve a record-high deep-ultraviolet ellipticity of 40 ± 1 mdeg/nm. Our theoretical simulations using the transfer matrix method reproduce the salient features of the experimentally observed CD spectra and further predict that a film of twist-stacked CNTs with an optimized thickness will exhibit an ellipticity as high as 150 mdeg/nm. The created wafer-scale objects represent a new class of synthetic chiral matter consisting of ordered quantum wires whose macroscopic properties are governed by nanoscopic electronic signatures such as van Hove singularities. These artificial structures with engineered chirality will not only provide playgrounds for uncovering new chiral phenomena but also open up new opportunities for developing high-performance chiral photonic and optoelectronic devices. © 2023, CC BY.

关键词： Carbon nanotubes

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THz Emission from Exchange-Coupled Fe/Ru/Ni Spintronic Emitters

THz Emission from Exchange-Coupled Fe/Ru/Ni Spintronic Emitt...

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International Conference on Infrared and Millimeter Waves

作者： R. Adam C. Greb D. E. Bürgler D. Cao S. Heidtfeld F. Wang J. Cheng D. Chakraborty I. Komissarov H. Hardtdegen M. Mikulics M. Büscher C. M. Schneider Roman Sobolewski Research Centre Jülich Peter Grünberg Institute (PGI-6) Jülich Germany Institut für Laser- und Plasmaphysik Heinrich Heine Universität Düsseldorf Düsseldorf Germany College of Physics Center for Marine Observation and Communications Qingdao University Qingdao China Materials Science Graduate Program University of Rochester Rochester New York USA Laboratory for Laser Energetics University of Rochester Rochester New York USA Department of Electrical and Computer Engineering University of Rochester Rochester New York USA Research Centre Jülich Ernst Ruska Centre for Microscopy and Spectroscopy with Electrons Jülich Germany Faculty of Physics University Duisburg-Essen Duisburg Germany Department of Physics University of California Davis Davis California USA

We explored THz emission from $\mathrm{Si}^{2} / \mathrm{SiO}_{2} / / \mathrm{Ta} / \mathrm{Fe} / \mathrm{Ru} /$ $\mathrm{Ni} / \mathrm{Al}_{2} \mathrm{O}_{3}$ spintronic emitters. We tuned magnetization alignment of Fe and Ni layers by varying the interlayer exchange coupling (IEC) strength using a range of Ru layer thickness t. Depending on IEC strength, magnetization hysteresis shows either ferromagnetic $(t=1.1 \mathrm{~nm}, 1.5 \mathrm{~nm})$, antiferromagnetic $(t=1.3 \mathrm{~nm})$ or canted $(t=1.7 \mathrm{~nm}, 1.9 \mathrm{~nm})$ relative alignment. Competition between IEC and an external magnetic field results in a dramatic difference in THz emission from the ferromagnetically (FM) and anti-ferromagnetically (AFM) coupled structures. The resulting THz emission from IEC structures is a result of an interference of THz transiens generated by the individual $\mathrm{Fe} / \mathrm{Ru}$ and $\mathrm{Ru} / \mathrm{Ni}$ emitters.

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Development of a Selective Wet-Chemical Etchant for 3D Structuring of Silicon via Nonlinear Laser Lithography

arXiv

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arXiv 2023年

作者： Borra, Mona Zolfaghari Radfar, Behrad Nasser, Hisham Çolakoğlu, Tahir Tokel, Onur Turnalı, Ahmet Demirtaş, Merve Ustunel, Hande Toffoli, Daniele Ömer İlday, F. Turan, Raşit Pavlov, Ihor Bek, Alpan ODTÜ-GÜNAM Middle East Technical University Ankara06800 Turkey Ankara06800 Turkey Department of Electronics and Nanoengineering Aalto University Tietotie 3 EspooFI-02150 Finland Department of Physics Engineering Ankara University Ankara06100 Turkey Department of Physics Bilkent University Ankara06800 Turkey UNAM National Nanotechnology Research Center Institute of Materials Science and Nanotechnology Bilkent University Ankara06800 Turkey Department of Electrical and Electronics Engineering Bilkent University Ankara06800 Turkey Department of Electrical and Computer Engineering Boston University 8 Saint Mary’s Street BostonMA02215 United States Ankara06800 Turkey Network Technologies Department TUBITAK ULAKBIM Ankara06800 Turkey Department of Chemical and Pharmaceutical Sciences Trieste University Trieste Italy IOM-CNR Istituto Officina dei Materiali Trieste34149 Italy Micro and Nanotechnology Graduate Program of Natural and Applied Sciences Middle East Technical Turkey

Recently-demonstrated high-quality three-dimensional (3D) subsurface laser processing inside crystalline silicon (c-Si) wafers opens a door to a wide range of novel applications in multidisciplinary research areas. Using this technique, a novel maskless micro-pillars with precise control on the surface reflection and coverage are successfully fabricated by etching the laser processed region of c-Si wafer. To achieve this, a particular selective wet chemical etching is developed to follow subsurface laser processing of c-Si to reveal the desired 3D structures with smooth surfaces. Here, we report the development of a novel chromium-free chemical etching recipe based on copper nitrate, which yields substantially smooth surfaces at high etch rate and selectivity on the both laser-processed Si surface and subsurface, i.e., without significant etching of the unmodified Si. Our results show that the etch rate and surface morphology are interrelated and strongly influenced by the composition of the adopted etching solution. After an extensive compositional study performed at room temperature, we identify an etchant with a selectivity of over 1600 times for laser-modified Si with respect to unmodified Si. We also support our findings using density functional theory calculations of HF and Cu adsorption energies, indicating significant diversity on the c-Si and laser-modified surfaces. Copyright © 2023, The Authors. All rights reserved.

关键词： Morphology

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Topology of three-dimensional Dirac semimetals and generalized quantum spin Hall systems without gapless edge modes

arXiv

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arXiv 2020年

作者： Tyner, Alexander C. Sur, Shouvik Puggioni, Danilo Rondinelli, James M. Goswami, Pallab Graduate Program in Applied Physics Northwestern University EvanstonIL60208 United States Department of Physics and Astronomy Northwestern University EvanstonIL60208 United States Department of Materials Science and Engineering Northwestern University IL60208 United States Northwestern Argonne Institute for Science and Engineering EvanstonIL60208 United States

Usually the quantum spin Hall states are expected to possess gapless, helical edge modes. Are there clean, non-interacting, quantum spin Hall states without gapless, edge modes? We show the generic, n-fold-symmetric, momentum planes of three-dimensional, stable Dirac semi-metals, which are orthogonal to the direction of nodal separation are examples of such generalized quantum spin Hall systems. We demonstrate that the planes lying between two Dirac points and the celebrated Bernevig-Zhang-Hughes model support identical quantized, non-Abelian Berry flux of magnitude 2π. Consequently, both systems exhibit spin-charge separation in response to electromagnetic, π-flux vortex. The Dirac points are identified as the unit-strength, monopoles of SO(5) Berry connections, describing topological quantum phase transitions between generalized, quantum spin Hall and trivial insulators. Our work identifies precise bulk invariant and quantized response of Dirac semimetals and shows that many two-dimensional higher-order topological insulators can be understood as generalized quantum spin Hall systems, possessing gapped edge states. Copyright © 2020, The Authors. All rights reserved.

关键词： Fruits

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A genuine correlation in piezoelectric properties of two-dimensional materials: A high-throughput computational study

arXiv

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arXiv 2020年

作者： Arlı, Cihan Kocabaş, Tugbey Çakır, Deniz Sevik, Cem Department of Materials Science and Engineering Institute of Graduate Program Eskisehir Technical University Eskiehir TR26555 Turkey Department of Physics and Astrophysics University of North Dakota Grand ForksND58202 United States Department of Mechanical Engineering Faculty of Engineering Eskisehir Technical University Eskiehir TR26555 Turkey

The rational design of two-dimensional piezoelectric materials has recently garnered increasing interest because of harnessing these materials in technological applications, including sensor technology, actuating devices, energy harvesting, and medical applications. Several materials possessing high piezoelectric response have been reported so far, but a high-throughput first-principles approach to estimate the piezoelectric potential of layered materials has not been performed yet. In this respect, we systematically investigated the piezoelectric (e11, d11) and elastic (C11 and C12) properties of 108 thermodynamically stable two-dimensional (2D) semiconductor materials by employing first-principle methods. Our calculations found a notable difference between the relaxed ion coefficients calculated with GGA and LDA functionals, indicating a strong exchange-correlation functional dependence. Nevertheless, both functionals yield the same trends for the elastic constants and piezoelectric coefficients. Our high-throughput approach demonstrates that the materials containing Group-V elements produce notably high piezoelectric strain constants, d11 > 40 pmV−1, and 42 of considered materials have the e11 coefficient higher than MoS2 insomuch as BrSSb has one of the largest d11 with a value of 503.6 pmV−1. Besides, we established simple empirical models to estimate the d11 coefficients by utilizing the relative ionic motion in the unit cell and the polarizability of the individual elements in the compounds. The proposed models, tested for both exchange-correlation functionals, are successful in estimating the piezoelectric constants of the studied materials with sufficient accuracy. Copyright © 2020, The Authors. All rights reserved.

关键词： Piezoelectricity

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