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Ganoderma microsporum immunomodulatory protein combined with KRASG12C inhibitor impedes intracellular AKT/ERK network to suppress lung cancer cells with KRAS mutation

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International Journal of Biological Macromolecules 2024年 259卷

作者： Hua, Wei-Jyun Hwang, Wei-Lun Yeh, Hsin Lin, Zhi-Hu Hsu, Wei-Hung Lin, Tung-Yi Program in Molecular Medicine National Yang Ming Chiao Tung University and Academia Sinica Taipei Taiwan Institute of Traditional Medicine National Yang Ming Chiao Tung University Taipei Taiwan Department of Biotechnology and Laboratory Science in Medicine National Yang Ming Chiao Tung University Taipei Taiwan LO-Sheng Hospital Ministry of Health and Welfare Taipei Taiwan School of Oral Hygiene College of Oral Medicine Taipei Medical University Taipei Taiwan Biomedical Industry Ph.D. Program National Yang Ming Chiao Tung University Taipei Taiwan Cancer and Immunology Research Center National Yang Ming Chiao Tung University Taipei Taiwan

KRAS mutations are tightly associated with lung cancer progression. despite the unprecedented clinical success of KRASG12C inhibitors, recurrent mechanisms of resistance and other KRAS mutations require further therapeutic approaches. GMI, a protein from the medicinal mushroom Ganoderma microsporum, possesses antitumor activity;whereas, the biological function of GMI on regulating KRAS mutant lung cancer cells remains unknown. Herein, RNA-sequencing and bioinformatics showed that GMI may regulate KRAS-modulated MAPK and PI3K-AKT pathways in A549 (KRASG12S) cells. Further experiments demonstrated that GMI inhibited KRAS activation and suppressed ERK1/2 and AKT signaling in A549 cells. Intriguingly, GMI inhibited AKT signaling but increased phosphorylation of ERK in H358 (KRASG12C) cells. GMI significantly suppressed tumor growth in LLC1 cells-allograft and H358 cells-xenograft mice. GMI showed a synergistic effect with KRASG12C inhibitors in inhibiting cell growth, KRAS activation and KRAS-mediated downstream signaling, leading to apoptosis in H358 cells. Combination of GMI and KRASG12C inhibitor, AMG 510, resulted in more durable inhibition of tumor growth and KRAS activity in H358 cells-xenograft mice. This study highlights the potential of GMI, a dietary fungal protein, as a viable therapeutic avenue for KRAS-mutant lung cancer in combination with KRASG12C inhibitors. © 2023

关键词： Proteins

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Exposure to phenols reduces melanogenesis in B16F10 cells and zebrafish

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Aquatic Toxicology 2024年 266卷 106806页

作者： Lin, Chung-Yu Wu, Chang-Yi Wang, Chia C. Lee, Che-Hsin Department of Biological Sciences National Sun Yat-sen University Kaohsiung 80424 Taiwan Department of Chemistry National Sun Yat-sen University Kaohsiung 80424 Taiwan Aerosol Science Research Center National Sun Yat-sen University Kaohsiung 80424 Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung 40433 Taiwan International Ph.D. Program for Science National Sun Yat-sen University Kaohsiung 80424 Taiwan

phenols, ubiquitous environmental contaminants found in water, soil, and air, pose risks to organisms even at minimal concentrations, and many are classified as hazardous pollutants. Skin pigmentation is a natural shield against ultraviolet-induced dNA damage and oxidative stress, pivotal in reducing skin cancer incidences. Studies on B16F10 melanoma cells and zebrafish offer valuable insights into potential therapeutic avenues for melanoma in the context of phenol exposure. Upon phenol treatment, there was a marked decrease in melanin content and melanogenesis-associated protein expression, such as tyrosinase and the microphthalmia-associated transcription factor (MITF) in these melanoma cells. Additionally, phenols led to diminished p38 phosphorylation, amplified extracellular signal-regulated kinase (ERK) phosphorylation, and curtailed melanin expression in zebrafish. These observations underscore the detrimental impact of phenols on melanogenesis and propose a mechanism of action centered on the ERK/p38 signaling pathway. Consequently, our data spotlight the adverse effects of phenols on melanogenesis." © 2023 Elsevier B.V.

关键词： Air pollutant Chemical leukoderma Melanin Melanogenesis phenol Zebrafish

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CsPbBr3 perovskite quantum-dot paper exhibiting a highest 3 dB bandwidth and realizing a flexible white-light system for visible-light communication

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photonics Research 2021年第12期9卷 2341-2350页

作者： KONTHOUJAM JAMES SINGH XIAOTONG FAN ANNAdA SANKAR SAdHU CHUN-HO LIN FANG-JYUN LIOU TINGZHU WU YU-JUNG LU JR-HAU HE ZHONG CHEN TOM WU HAO-CHUNG KUO Department of Photonics&Institute of Electro-Optical Engineering College of Electrical and Computer EngineeringNational Yang Ming Chiao Tung UniversityHsinchu 30010Taiwan International Ph.D.Program in Photonics(UST) College of Electrical and Computer EngineeringNational Yang Ming Chiao Tung UniversityHsinchu 30010Taiwan Department of Electronic Science Fujian Engineering Research Center for Solid-State LightingXiamen UniversityXiamen 361005China School of Materials Science and Engineering University of New South WalesSydneyNSW 2052Australia Research Center for Applied Sciences Academia SinicaTaipei 11529Taiwan Department of Materials Science and Engineering City University of Hong KongKowloon TongHong KongChina

We propose a flexible white-light system for high-speed visible-light communication(VLC)applications,which consists of a semipolar blue InGaN/GaN single-quantum-well micro-light-emitting diode(LEd)on a flexible substrate pumping green CsPbBr3 perovskite quantum-dot(PQd)paper in nanostructure form and red CdSe Qd *** highest bandwidth for CsPbBr3 PQd paper,229 MHz,is achieved with a blue micro-LEd pumping source and a high data transmission rate of 400 Mbps;this is very promising for VLC *** 817 MHz maximum bandwidth and a 1.5 Gbps transmission speed are attained by the proposed semipolar blue *** proposed flexible white light system and the high-bandwidth PQd paper could pave the way for VLC wearable devices.

关键词： pumping communication quantum

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Parameter estimation in OdE models with certified polynomial system solving

arXiv

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arXiv 2025年

作者： demin, Alexander Ovchinnikov, Alexey Rouillier, Fabrice HSE University Moscow Russia Department of Mathematics CUNY Queens College Ph.D. Programs is Mathematics and Computer Science CUNY Graduate Center New YorkNY United States Inria Paris Paris France

We consider dynamical models given by rational OdE systems. Parameter estimation is an important and challenging task of recovering parameter values from observed data. Recently, a method based on differential algebra and rational interpolation was proposed to express parameter estimation in terms of polynomial system solving. Typically, polynomial system solving is a bottleneck, hence the choice of the polynomial solver is crucial. In this contribution, we compare two polynomial system solvers applied to parameter estimation: homotopy continuation solver from *** and our new implementation of a certified solver based on rational univariate representation (RUR) and real root isolation. We show how the new RUR solver can tackle examples that are out of reach for the homotopy methods and vice *** Codes 68W30, 34-04, 93B30 Copyright © 2025, The Authors. All rights reserved.

关键词： Polynomials

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defect Engineering Centrosymmetric 2d Material Flexocatalysts

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Small 2024年第31期20卷 e2401116页

作者： Chen, Yu-Ching Chen, Po-Han Liao, Yin-Song Chou, Jyh-Pin Wu, Jyh Ming Department of Materials Science and Engineering National Tsing Hua University 101 Section 2 Kuang Fu Road Hsinchu300 Taiwan Ph.D. Program in Prospective Functional Materials Industry National Tsing Hua University 101 Section 2 Kuang Fu Road Hsinchu300 Taiwan Tsing Hua Interdisciplinary Program National Tsing Hua University 101 Section 2 Kuang Fu Road Hsinchu300 Taiwan Department of Physics National Changhua University of Education No. 1 Jin-De Road Changhua500 Taiwan High Entropy Materials Center National Tsing Hua University 101 Section 2 Kuang Fu Road Hsinchu300 Taiwan

In this study, the flexoelectric characteristics of 2d TiO2 nanosheets are examined. The theoretical calculations and experimental results reveal an excellent strain-induced flexoelectric potential (flexopotential) by an effective defect engineering strategy, which suppresses the recombination of electron–hole pairs, thus substantially improving the catalytic activity of the TiO2 nanosheets in the degradation of Rhodamine B dye and the hydrogen evolution reaction in a dark environment. The results indicate that strain-induced bandgap reduction enhances the catalytic activity of the TiO2 nanosheets. In addition, the TiO2 nanosheets degraded Rhodamine B, with kobs being ≈1.5 × 10−2 min−1 in dark, while TiO2 nanoparticles show only an adsorption effect. 2d TiO2 nanosheets achieve a hydrogen production rate of 137.9 µmol g−1 h−1 under a dark environment, 197% higher than those of TiO2 nanoparticles (70.1 µmol g−1 h−1). The flexopotential of the TiO2 nanosheets is enhanced by increasing the bending moment, with excellent flexopotential along the y-axis. density functional theory is used to identify the stress-induced bandgap reduction and oxygen vacancy formation, which results in the self-dissociation of H2O on the surface of the TiO in the dark. The present findings provide novel insights into the role of TiO2 flexocatalysis in electrochemical reactions. © 2024 Wiley-VCH GmbH.

关键词： Titanium dioxide

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A mathematical method for designing superresolution lenses using superoscillations

A mathematical method for designing superresolution lenses u...

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Frontiers in Optics, FIO 2019 - Part of Frontiers in Optics + Laser science APS/dLS

作者： Smith, Matt K. Gbur, Gregory J. Nanoscale Science Ph.D. Program University of North Carolina at Charlotte 9201 University City Blvd CharlotteNC28223 United States Department of Physics and Optical Science University of North Carolina at Charlotte 9201 University City Blvd CharlotteNC28223 United States

We demonstrate a mathematical method of designing a superresolution lens using a superoscillation technique. Our method is conceptually and mathematically simpler than other methods, allowing for ease of design. ©... 详细信息

ISBN: (纸本)9781943580675

关键词： design

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Exploration of anti-leukemic effect of soft coral-derived 13-acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II

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Kaohsiung Journal of Medical sciences 2023年第7期39卷 718-731页

作者： Chin, Hsien-Kuo Lu, Mei-Chin Hsu, Kai-Cheng El-Shazly, Mohamed Tsai, Tsen-Ni Lin, Tzu-Yung Shih, Shou-Ping Lin, Tony Eight Wen, Zhi-Hong Yang, Yu-Chen S. H. Liu, Yi-Chang Department of Marine Biotechnology and Resources National Sun Yat-Sen University Kaohsiung Taiwan Division of Cardiovascular Surgery Department of Surgery Kaohsiung Armed Forces General Hospital Kaohsiung Taiwan Graduate Institute of Marine Biology National Dong Hwa University Hualien Taiwan National Museum of Marine Biology and Aquarium Pingtung Taiwan Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan Master Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan TMU Research Center of Drug Discovery Taipei Medical University Taipei Taiwan Department of Pharmacognosy Faculty of Pharmacy Ain-Shams University Cairo Egypt Division of Hematology-Oncology Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan Department and Graduate Institute of Aquaculture National Kaohsiung University of Science and Technology Kaohsiung Taiwan Doctoral Degree Program in Marine Biotechnology National Sun Yat-Sen University Kaohsiung Taiwan Doctoral Degree Program in Marine Biotechnology Academia Sinica Taipei Taiwan Joint Biobank Office of Human Research Taipei Medical University Taipei Taiwan Department of Internal Medicine Faculty of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Cellular Therapy and Research Center Kaohsiung Medical University Hospital Kaohsiung Taiwan

13-Acetoxysarcocrassolide (13-AC) is a marine cembranoid derived from the aquaculture soft coral of Lobophytum crassum. The cytotoxic effect of 13-AC against leukemia cells was previously reported but its mechanism of action is still unexplored. In the current study, we showed that 13-AC induced apoptosis of human acute lymphoblastic leukemia Molt4 cells, as evidenced by the cleavage of PARP and caspases, phosphatidylserine externalization, as well as the disruption of mitochondrial membrane potential. The use of N-acetylcysteine (NAC), a reactive oxygen species (ROS) scavenger, attenuated the cytotoxic effect induced by 13-AC. Molecular docking and thermal shift assay indicated that the cytotoxic mechanism of action of 13-AC involved the inhibition of heat shock protein 90 (Hsp 90) activity by eliciting the level of Hsp 70 and topoisomerase IIα in Molt4 cells. 13-AC also exhibited potent antitumor activity by reducing the tumor volume (48.3%) and weight (72.5%) in the in vivo Molt4 xenograft mice model. Our findings suggested that the marine cembranoid, 13-AC, acted as a dual inhibitor of Hsp 90 and topoisomerase IIα, exerting more potent apoptotic activity via the enhancement of ROS generation. © 2023 The Authors. The Kaohsiung Journal of Medical sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.

关键词： 13-Acetoxysarcocrassolide heat shock protein 90 leukemia oxidative stress topoisomerase II

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A nigroincertal projection mediates aversion and enhances coping responses to potential threat

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FASEB Journal 2023年第12期37卷 e23322页

作者： Ho, Ping-Chen Hsiao, Fu-Yun Chiu, Shi-Hong Lee, Syun-Ruei Yau, Hau-Jie The Laboratory for Neural Circuits and Behaviors Graduate Institute of Brain and Mind Sciences National Taiwan University Taipei Taiwan School of Medicine National Taiwan University Taipei Taiwan Neurobiology and Cognitive Science Center National Taiwan University Taipei Taiwan Taiwan International Graduate Program in Interdisciplinary Neuroscience National Taiwan University and Academia Sinica Taipei Taiwan Ph.D. Program in Translational Medicine National Taiwan University and Academia Sinica Taipei Taiwan

Recent studies have shown that the non-dA neurons in the ventral tegmental area (VTA) and substantia nigra (SN) not only modulate motivational behaviors but also regulate defensive behaviors. While zona incerta (ZI) is a threat-responsive substrate and receives innervations from the ventral midbrain, the function of the ventral midbrain-to-ZI connection remains poorly defined. Here, we demonstrate that the ZI receives heterogenous innervations from the ventral midbrain. By utilizing a retrograde AAV preferentially labeling non-dA neurons in the ventral midbrain, we found that ZI-projecting non-dA cells in the ventral midbrain are activated by restraint stress. We focused on the SN and found that SN-to-ZI GABAergic input is engaged by a predatory odor. Sustained pan-neuronal SN-to-ZI activation results in aversion and enhances defensive behaviors, likely through a disinhibition mechanism to recruit downstream brain regions that regulate defensive behaviors. Collectively, our results reveal a novel role of nigroincertal projection in mediating negative valence and regulating defensive behaviors. © 2023 Federation of American Societies for Experimental Biology.

关键词： defensive behavior stress substantia nigra ventral tegmental area zona increta

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Evaluating the Robustness of Complementary Channel Ferroelectric FETs Against Total Ionizing dose Towards Radiation-Tolerant Embedded Nonvolatile Memory

TechRxiv

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TechRxiv 2023年

作者： Jiang, Zhouhang Guo, Zixiang Luo, Xuyi Sayed, Munazza Faris, Zubair Mulaosmanovic, Halid duenkel, Stefan Soss, Steven Beyer, Sven Gong, Xiao Kurinec, Santosh Narayanan, Vijaykrishnan Amrouch, Hussam Zhang, Enxia Fleetwood, daniel M. Schrimpf, Ronald d. Ni, Kai The Microsystems Engineering Ph.D. Program The Mechanical Engineering Rochester Institute of Technology RochesterNY14623 United States The Department of Electrical and Computer Engineering Vanderbilt University NashvilleTN37235 United States University of Stuttgart Stuttgart70174 Germany Germany The Munich Institute of Robotics and Machine Intelligence Arcisstrasse 21 Munich80333 Germany The GlobalFoundries Fab1 LLC Dresden Germany The Department of Electrical Computer Engineering National University of Singapore 119077 Singapore The Department of Computer Science and Engineering Penn State University University ParkPA16802 United States The Department of Electrical and Microelectric Engineering Rochester Institute of Technology RochesterNY14623 United States

In this work, a thorough assessment of the robustness of complementary channel HfO2 ferroelectric FET (FeFET) against total ionizing dose (TId) radiation is conducted, with the goal of determining its suitability for use as high-performance and energy-efficient embedded nonvolatile memory (eNVM) for space applications. We demonstrate that: i) ferroelectric HfO2 thin film is robust against X-ray and proton irradiation;ii) FeFET exhibits a polarization state dependent radiation sensitivity where the high-VTH (HVT) state sees noticeable negative VTH shift and low-VTH (LVT) is immune to irradiation, irrespective of the channel type;iii) the state dependence is ascribed to the depolarization field in the HVT, which points toward the channel and facilitates the transport and trapping of radiation-generated holes close to the channel. In the future, radiation hardening techniques need to be considered. © 2023, CC BY.

关键词： Radiation effects

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Understanding AdC variation by fat content effect using a dual-function MRI phantom

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European Radiology Experimental 2024年第1期8卷 1-11页

作者： Liu, Yi-Jui Tsai, Tung-Sheng Li, Ya-Hui Peng, Jo-Hua Chang, Hing-Chiu Peng, Hsu-Hsia Lee, Ying-Chieh Lee, Tung-Yang Liou, Chang-Hsien Lin, Tz-Feng Chew, Fatt-Yang Chou, Ruey-Hwang Juan, Chun-Jung Department of Automatic Control Engineering Feng Chia University Taichung Taiwan Ph.D. Program in Electrical and Communication Engineering Feng Chia University Taichung Taiwan Department of Medical Imaging China Medical University Hsinchu Hospital 199 Sec. 1 Xinglong Rd. Hsinchu County Zhubei City 302 Taiwan Department of Biomedical Engineering and Environmental Sciences National Tsing Hua University Hsinchu Taiwan Department of Biomedical Engineering Chinese University of Hong Kong Hong Kong Master’s Program of Biomedical Informatics and Biomedical Engineering Feng Chia University Taichung Taiwan Cheng Ching Hospital Taichung Taiwan Institute of Nuclear Engineering and Science National Tsing Hua University Hsinchu Taiwan Department of Fiber and Composite Materials Feng Chia University Taichung Taiwan Department of Medical Imaging China Medical University Hospital Taichung Taiwan Department of Radiology School of Medicine China Medical University Taichung Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung 406 Taiwan Center for Molecular Medicine China Medical University Hospital Taichung Taiwan Department of Medical Laboratory and Biotechnology Asia University Taichung Taiwan

Background: A dual-function phantom designed to quantify the apparent diffusion coefficient (AdC) in different fat contents (FCs) and glass bead densities (GBds) to simulate the human tissues has not been documented yet. We propose a dual-function phantom to quantify the FC and to measure the AdC at different FCs and different GBds. Methods: A fat-containing diffusion phantom comprised by 30 glass-bead-containing fat-water emulsions consisting of six different FCs (0, 10, 20, 30, 40, and 50%) multiplied by five different GBds (0, 0.1, 0.25, 0.5, and 1.0 g/50 mL). The FC and AdC were measured by the “iterative decomposition of water and fat with echo asymmetry and least squares estimation-IQ,” IdEAL-IQ, and single-shot echo-planar diffusion-weighted imaging, SS-EP-dWI, sequences, respectively. Linear regression analysis was used to evaluate the relationship among the fat fraction (FF) measured by IdEAL-IQ, GBd, and AdC. Results: The AdC was significantly, negatively, and linearly associated with the FF (the linear slope ranged from -0.005 to -0.017, R² = 0.925 to 0.986, all p < 0.001). The slope of the linear relationship between the AdC and the FF, however, varied among different GBds (the higher the GBd, the lower the slope). AdCs among emulsions across different GBds and FFs were overlapped. Emulsions with low GBds plus high FFs shared a same lower AdC range with those with median or high GBds plus median or lower FFs. Conclusions: A novel dual-function phantom simulating the human tissues allowed to quantify the influence of FC and GBd on AdC. Relevance statement: The study developed an innovative dual-function MRI phantom to explore the impact of FC on AdC variation that can affect clinical results. The results revealed the superimposed effect on FF and GBd density on AdC measurements. Key points: • A dual-function phantom made of glass bead density (GBd) and fat fraction (FF) emulsion has been developed. • Apparent diffusion coefficient (AdC) values

关键词： Adipose tissue diffusion magnetic resonance imaging phantoms (imaging) Quality assurance (healthcare) Quality control

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