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Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2

Nature Communications 2024年第1期15卷 7463页

作者： Wang, Rong-Hsuan Chen, Pin-Ru Chen, Yue-Ting Chen, Yi-Chang Chu, Yu-Hsin Chien, Chia-Chen Chien, Po-Chen Lo, Shao-Yun Wang, Zhong-Liang Tsou, Min-Chen Chen, Ssu-Yu Chiu, Guang-Shen Chen, Wen-Ling Wu, Yi-Hsuan Wang, Lily Hui-Ching Wang, Wen-Ching Lin, Shu-Yi Kung, Hsing-Jien Wang, Lu-Hai Cheng, Hui-Chun Lin, Kai-Ti Institute of Biotechnology National Tsing Hua University Hsinchu Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu Taiwan Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Taiwan Institute of Molecular and Cellular Biology National Tsing Hua University Hsinchu Taiwan Department of Medical Science National Tsing Hua University Hsinchu Taiwan School of Medicine National Tsing Hua University Hsinchu Taiwan Department of Life Science National Tsing Hua University Hsinchu Taiwan Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan Taiwan College of Medical Science and Technology PhD Program for Cancer Biology and Drug Discovery Taipei Medical University Taipei Taiwan Chiese Medicine Research Center and Institute of Integrated Medicine China Medical University Taichung City Taiwan

Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H₂S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H₂S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism. © The Author(s) 2024.

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Fate and state transitions during human blood vessel organoid development

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Cell 2025年第12期188卷 3329-3348.e31页

作者： Nikolova, Marina T. He, Zhisong Seimiya, Makiko Jonsson, Gustav Cao, Wuji Okuda, Ryo Wimmer, Reiner A. Okamoto, Ryoko Penninger, Josef M. Camp, J. Gray Treutlein, Barbara Department of Biosystems Science and Engineering ETH Zurich Basel Switzerland Institute of Molecular Biotechnology of the Austrian Academy of Sciences Vienna Austria Vienna BioCenter PhD Program Doctoral School of the University of Vienna and Medical University of Vienna Vienna 1030 Austria Roche Pharma Research and Early Development Roche Innovation Center Basel Switzerland Department of Medical Genetics Life Science Institute University of British Columbia Vancouver V6T 1Z3 BC Canada Department of Laboratory Medicine Medical University of Vienna Vienna Austria Helmholtz Centre for Infection Research Braunschweig Germany Institute of Human Biology Roche Pharma Research and Early Development Roche Innovation Center Basel Basel Switzerland Biozentrum University of Basel Basel Switzerland

Human blood vessel organoids (hBVOs) have emerged as a system to model human vascular development and disease. Here, we use single-cell multi-omics together with genetic and signaling pathway perturbations to reconstruct hBVO development. Mesodermal progenitors bifurcate into endothelial and mural fates in vitro, and xenografted BVOs acquire definitive arteriovenous endothelial cell specification. We infer a gene regulatory network and use single-cell genetic perturbations to identify transcription factors (TFs) and receptors involved in cell fate specification, including a role for MECOM in endothelial and mural specification. We assess the potential of BVOs to generate organotypic states, identify TFs lacking expression in hBVOs, and find that induced LEF1 overexpression increases brain vasculature specificity. Finally, we map vascular disease-associated genes to hBVO cell states and analyze an hBVO model of diabetes. Altogether, we provide a comprehensive cell state atlas of hBVO development and illuminate the power and limitation of hBVOs for translational research. © 2025 The Authors

关键词： arteriovenous specification human blood vessel organoid human development organoid cell atlas single-cell genomics single-cell perturbation screen

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Correction: The HDAC inhibitor, MPT0E028, enhances erlotinib induced cell death in EGFR-TKI-resistant NSCLC cells

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Cell death & disease 2024年第7期15卷 490页

作者： M -C Chen C -H Chen J -C Wang A -C Tsai J -P Liou S -L Pan C -M Teng Pharmacological Institute College of Medicine National Taiwan University Taipei Taiwan. The PhD Program for Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan. School of Pharmacy College of Pharmacy Taipei Medical University Taipei Taiwan. jpl@tmu.edu.tw. The PhD Program for Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan. slpan@tmu.edu.tw. Pharmacological Institute College of Medicine National Taiwan University Taipei Taiwan. cmteng@ntu.edu.tw.

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Dual-Targeting EGCG/NO-Supplying protein assembled nanoparticles with Multi-Synergistic effects against atherosclerosis

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Chemical Engineering Journal 2024年 493卷

作者： Lin, Chi Cheng, Tsai-Mu Liu, Yun-Chun Hsu, Fang-Yu Shih, Chun-Ming Tsai, Min-Lang Shih, Chun-Che Mi, Fwu-Long Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan The PhD Program for Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei11031 Taiwan Taipei Heart Institute Taipei Medical University Taipei11031 Taiwan Department of Food Science National Taiwan Ocean University Keelung20224 Taiwan Department of Biochemistry and Molecular Cell Biology School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Division of Cardiology and Cardiovascular Research Center Taipei Medical University Hospital Taipei11031 Taiwan Division of Cardiovascular Surgery Department of Surgery Wan Fang Hospital Taipei Medical University Taipei11031 Taiwan Institute of Clinical Medicine School of Medicine National Yang-Ming Chiao Tung University Taipei Taiwan Department of Surgery School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan International Ph.D. Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei Taiwan

Limited therapeutic options are available to effectively preventing atherosclerosis. Inflammatory endothelial cells, foamy macrophages, and high protease levels contribute to atherosclerotic plaque formation. Studies have shown that catechins effectively scavenge reactive oxygen species (ROS), inhibit monocyte adhesion and reduce cholesterol levels, while nitric oxide (NO) enhances endothelial function. However, due to the poor stability and bioavailability of catechins and the toxicity from the burst release of current synthetic small molecules NO donor, effective delivery of these bioactive compounds to treat atherosclerosis is still a challenge. Herein, a catechin/protein-based NO donor co-delivery nanosystem was designed for combinatorial anti-atherosclerotic therapy. We engineered a (−)-epigallocatechin-3-gallate (EGCG)/NO-releasing protein co-assembled nanocomplex based on specific catechin-protein interactions. Furthermore, the nanocomplex was surface modified with fucoidan (Fu), a sulfated polysaccharide with anti-inflammatory activity. This nanocomplex exhibits sensitivity to ROS, pH, and enzymes. The Fu-functionalized nanoparticles specifically accumulates in atherosclerotic plaques mediated by P-selectin on inflamed endothelial cells and scavenger receptor A (SR-A) on foamy macrophages. Under environmental stimuli that simulate the condition of plaque, the nanoparticles are readily activated to release EGCG and NO in response to excess ROS and high protease levels, exerting the multi-synergistic anti-atherosclerosic effects on reducing monocyte adhesion, promoting NO production to proliferate endothelial cells, lowering ROS levels, and decreasing the foam cell formation in vitro, and reducing lipid accumulation, plaque size, and inflammatory cytokines release in high-fat diet-induced atherosclerosis model in ApoE−/− mice. The integration of plaques targeting ability and multiple therapeutic functions can provide an advanced therapeutic strategy for athero

关键词： Nitric oxide

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Synthesis of Gadolinium-Doped Molybdenum Diselenide Nanospheres for Ultrasensitive Electrochemical Determination of Essential Amino Acid in Human Serum and Milk Samples

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Journal of the Electrochemical Society 2023年第5期170卷 057501-057501页

作者： Jeromiyas, Nithiya Govindasamy, Mani Alothman, Asma A. Ouladsmane, Mohamed Huang, Chi-Hsien National Kaohsiung University of science and Technology Kaohsiung City81157 Taiwan Department of Chemistry Korea University Seongbuk-gu Seoul Korea Republic of Faculty International PhD Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Department of Research and Innovation Saveetha School of Engineering SIMATS Thandalam Chennai602105 India Chemistry Department College of Science King Saud University Riyadh11451 Saudi Arabia Department of Materials Engineering Ming Chi University of Technology New Taipei City243303 Taiwan Biochemical Technology R&D Center Ming Chi University of Technology New Taipei City243303 Taiwan

The electrocatalytic activity and electronic conductivity of 2D transition metal chalcogenides are usually enhanced by as follows the ideal strategy such as doping or substitution heterogeneous atoms. Here, a rare Earth metal ion of gadolinium (Gd3+) was doped with MoSe2 and synthesized through the hydrothermal method. The morphology and nanostructure of Gd3+ with MoSe2 spheres were analyzed under X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron, High-resolution transmission electron microscopy analysis, Field emission scanning electron microscopy, and energy-dispersive spectroscopy. Furthermore, the Gd3+ doped MoSe2 sphere modified glassy carbon electrode (Gd@MoSe2/GCE) was used for the sensing of tryptophan. The Gd@MoSe2 modified GCE shows remarkable sensing performance of tryptophan resulting in a linear range (20 nM-220 μM) with a low detection limit (6.7 nM). Under the optimal condition, the developed electrochemical sensor was successfully used to determine tryptophan (TRP) in blood serum and milk samples. The electrochemical biosensing results suggest that the doping of the Gd3+ doped MoSe2 sensor is a promising electrocatalyst in biological and food samples. © 2023 The Electrochemical Society ("ECS"). Published on behalf of ECS by IOP Publishing Limited.

关键词： Amino acids

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Eclipse timing variations in the WD+dM eclipsing binary RR Cae

arXiv

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arXiv 2021年

作者： Rattanamala, R. Awiphan, S. Komonjinda, S. Phriksee, A. Sappankum, P. A-Thano, N. Chitchak, S. Rittipruk, P. Sawangwit, U. Poshyachinda, S. Reichart, D.E. Haislip, J.B. PhD Program in Astronomy Department of Physics and Materials Science Faculty of Science Chiang Mai University Chiang Mai50200 Thailand Physics and General Science Program Faculty of Science and Technology Nakhon Ratchasima Rajabhat University Nakhon Ratchasima30000 Thailand 260 Moo 4 Donkaew Mae Rim Chiang Mai50180 Thailand Department of Physics and Materials Science Faculty of Science Chiang Mai University Chiang Mai50200 Thailand Institute of Astronomy National Tsing Hua University Hsinchu30013 Taiwan Department of Physics Faculty of Science Udon Thani Rajabhat University Udon Thani41000 Thailand Department of Physics and Astronomy University of North Carolina at Chapel Hill Chapel HillNC27599 United States

We present the binary model and the eclipse timing variations of the eclipsing binary RR Cae, which consists of a white dwarf eclipsed by an M-type dwarf companion. The multi-wavelength optical photometry from the Transiting Exoplanet Survey Satellite (TESS), the 0.6-m PROMPT-8 telescope, and the 0.7-m Thai Robotic Telescope at Spring Brook Observatory, combined with archive H-alpha radial velocities from the Very Large Telescope (VLT) are analysed. From the data, the physical parameters of the system are obtained along with 430 new times of minima. The TESS light curves in 2018 and 2020 show out-of-eclipse variations, which might be caused by a large spot on the secondary component. The light travel time effect models due to the gravitational interaction of one or two circumbinary objects are adopted to fit the cyclic variations in the RR Cae’s O-C curve. The fitting solution of the O-C curve with one circumbinary object model shows a periodic variation with a period of 16.6 ± 0.2 yr and an amplitude of 14 ± 1 s, which can be caused by a planet with a minimum mass of 3.4 ± 0.2 MJup. When we consider the model with two circumbinary objects, the O-C curve shows cyclic variations with periods of 15.0 ± 0.5 yr and 39 ± 5 yr and amplitudes of 12 ± 1 s and 20 ± 5 s, respectively, corresponding to minimum masses of 3.0 ± 0.3 MJup and 2.7 ± 0.7 MJup Copyright © 2021, The Authors. All rights reserved.

关键词： Travel time

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Comparative analysis of various oxygen production techniques using multi-criteria decision-making methods

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International Journal of Thermofluids 2023年 17卷

作者： Aljaghoub, Haya Alasad, Shamma Alashkar, Adnan AlMallahi, Maryam Hasan, Ranem Obaideen, Khaled Alami, Abdul Hai Department of Industrial Engineering and Engineering Management University of Sharjah Sharjah United Arab Emirates Mechanical Engineering Department American University of Sharjah Sharjah United Arab Emirates Materials Science and Engineering PhD Program American University of Sharjah Sharjah United Arab Emirates Department of Mechanical and Aerospace Engineering United Arab Emirates University Al Ain City United Arab Emirates Department of Sustainable and Renewable Energy Engineering University of Sharjah Sharjah United Arab Emirates Sustainable Energy and Power Systems Research Center RISE University of Sharjah Sharjah United Arab Emirates Center for Advanced Materials Research University of Sharjah Sharjah United Arab Emirates

The current pandemic has adversely affected oxygen production and supply chain, where oxygen treatment is essential for the emergency treatment protocol of patients infected by the virus. This work reports on various techniques of oxygen generation methods, as well as the challenges facing its production, storage, and transportation. Moreover, this study offers a comparative analysis of various oxygen production techniques using Multi-Criteria Decision-Making Methods (MCDM). Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), in addition to the weighting methodologies, Multiplicative Exponential Weighting (MEW) and Simple Additive Weighting (SAW) are chosen as tools to carry out the statistical analysis and rank the oxygen production methods. The ranking criteria includes cost, performance, environmental impact and safety. Moreover, this paper utilizes the Entropy Weight Method (EWM), Criteria Importance Through Inter-criteria Correlation (CRITIC) method, and the Stochastic Dominance (SD) method to distribute the criteria weights. The results show thar oxygen production using membrane technologies is the optimal technique based on all the provided tools and criteria. as it attained the maximum Entropy and Sd values of 0.548 through the TOPSIS method, and the highest CRITIC value through SAW and MEW methods which were 0.260 and 0.236, respectively. © 2022 The Author(s)

关键词： Stochastic systems

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Overexpression of tyrosine phosphorylated proteins in reproductive tissues of polycystic ovary syndrome rats induced by letrozole

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Asian pacific Journal of Reproduction 2020年第6期9卷 275-282页

作者： Sudtida Bunsueb Supatcharee Arun Arada Chaiyamoon Alexander Tsang-Hsien Wu Sitthichai Iamsaard Department of Anatomy Faculty of MedicineKhon Kaen UniversityKhon Kaen40002Thailand Research Institute for Human High Performance and Health Promotion Khon Kaen University40002Khon KaenThailand The PhD Program for Translational Medicine College of Medical Science and TechnologyTaipei Medical University and Academia SinicaTaipei Graduate Institute of Medical Sciences National Defense Medical CenterTaipei

Objective:To identify the alteration of tyrosine phosphorylated protein expression in rats with polycystic ovary syndrome(PCOS).Methods:Sixteen female Sprague-Dawley rats were divided into the control and letrozole-induced PCOS *** oestrus cycle of rats was performed by vaginal *** hormones and morphology of the ovary,oviduct,and uterus were *** and intensity of androgen receptor and tyrosine phosphorylated proteins of reproductive organs were investigated by Western ***:Various polycysts and increased androgen receptor expression were present in the ovary of the PCOS *** levels of follicle-stimulating hormone and testosteone were significantly higher in the PCOS group while progesterone and estradiol levels were significantly decreased as compared with the control group(P<0.05).Only the size of uterus in the PCOS group was significantly smaller than the control ***,the density of collagen fibers observed in PCOS uterus was greater than the control ***,tyrosine phosphorylated proteins were significantly overexpressed in ovary(52,42,and 28 kDa),oviduct(72,56,42,and 28 kDa),and uterus(53 and 42 kDa)of the PCOS group compared to the control ***:Presence of tyrosine phosphorylated proteins in the ovary,oviduct and uterus suggests that overexpression of tyrosine phosphorylated proteins may be involved in potential mechanism of female infertility especially in PCOS.

关键词： Polycystic ovary syndrome Overexpression Tyrosine phosphorylated proteins Ovary Oviduct Uterus

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A plug-and-play molecular approach for room temperature polariton condensation

arXiv

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arXiv 2023年

作者： Deshmukh, Prathmesh Satapathy, Sitakanta Michail, Evripidis Olsson, Andrew H. Bushati, Rezlind Yadav, Ravindra Kumar Khatoniar, Mandeep Chen, Junsheng John, George Laursen, Bo W. Flood, Amar H. Sfeir, Matthew Y. Menon, Vinod M. Department of Physics Center for Discovery and Innovation The City College of New York 85 St. Nicholas Terrace New YorkNY10031 United States The PhD Program in Physics The Graduate Center of the City University of New York 365 5th Ave New YorkNY10016 United States Photonics Initiative Advanced Science Research Center City University of New York New YorkNY10031 United States Department of Chemistry Indiana University BloomingtonIN47405 United States Nano-Science Center Department of Chemistry University of Copenhagen Denmark Department of Chemistry Center for Discovery and Innovation The City College of New York 85 St. Nicholas Terrace New YorkNY10031 United States

Exciton-polaritons (EP), half-light half-matter quasiparticles that form in optical cavities, are attractive platforms for creating macroscopic coherent states like BECs. EPs based on organic molecules are of particular interest for realizing such states at room temperature while offering the promise of synthetic tunability. However, the demonstrations of such condensates have been limited to a few specific molecular systems1. Here we report a universal platform for realizing molecular polariton condensates using commercial dyes that solves long standing material challenges. This solution is made possible using a new and programable molecular material called small-molecule, ionic isolation lattices (SMILES) with the potential to incorporate a wide array of molecular fluorophores2. We show EP condensation in rhodamine by incorporating it into SMILES lattice placed in a planar microcavity. The SMILES approach overcomes the major drawbacks of organic molecular photophysical systems such as self-quenching, which sets the foundation for realizing practical polaritonic devices operating at ambient temperatures covering wide spectral range. © 2023, CC BY-NC-ND.

关键词： Condensation

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Success and the next generation of physician-scientists

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Journal of clinical and translational science 2020年第6期4卷 477-479页

作者： Chu J Hsiao Adriana M Fresquez Briana Christophers Department of Anthropology University of Florida MD-PhD Program College of Medicine and College of Liberal Arts and Sciences University of Florida Gainesville FL USA. Chicago Medical School and School of Graduate and Postdoctoral Studies Rosalind Franklin University of Medicine & Science North Chicago IL USA. Weill Cornell/Rockefeller/Memorial Sloan Kettering Tri-Institutional MD-PhD Program New York NY USA.

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