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Emerging contaminants:A One Health perspective

The Innovation 2024年第4期5卷 140-170,139页

作者： Fang Wang Leilei Xiang Kelvin Sze-Yin Leung Martin Elsner Ying Zhang Yuming Guo Bo Pan Hongwen Sun Taicheng An Guangguo Ying Bryan WBrooks Deyi Hou Damian EHelbling Jianqiang Sun Hao Qiu Timothy MVogel Wei Zhang Yanzheng Gao Myrna JSimpson Yi Luo Scott XChang Guanyong Su Bryan MWong Tzung-May Fu Dong Zhu Karl JJobst Chengjun Ge Frederic Coulon Jean Damascene Harindintwali Xiankui Zeng Haijun Wang Yuhao Fu Zhong Wei Rainer Lohmann Changer Chen Yang Song Concepcion Sanchez-Cid Yu Wang Ali El-Naggar Yiming Yao Yanran Huang Japhet Cheuk-Fung Law Chenggang Gu Huizhong Shen Yanpeng Gao Chao Qin Hao Li Tong Zhang Natàlia Corcoll Min Liu Daniel SAlessi Hui Li Kristian KBrandt Yolanda Pico Cheng Gu Jianhua Guo Jianqiang Su Philippe Corvini Mao Ye Teresa Rocha-Santos Huan He Yi Yang Meiping Tong Weina Zhang Fidèle Suanon Ferdi Brahushi Zhenyu Wang Syed AHashsham Marko Virta Qingbin Yuan Gaofei Jiang Louis A.Tremblay Qingwei Bu Jichun Wu Willie Peijnenburg Edward Topp Xinde Cao Xin Jiang Minghui Zheng Taolin Zhang Yongming Luo Lizhong Zhu Xiangdong Li DamiàBarceló Jianmin Chen Baoshan Xing Wulf Amelung Zongwei Cai Ravi Naidu Qirong Shen Janusz Pawliszyn Yong-guan Zhu Andreas Schaeffer Matthias C.Rillig Fengchang Wu Gang Yu James M.Tiedje State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of SciencesNanjing 210008China University of Chinese Academy of Sciences Beijing 100049China Department of Chemistry Hong Kong Baptist UniversityHong KongChina HKBU Institute of Research and Continuing Education Shenzhen Virtual University ParkShenzhenChina Technical University of Munich TUM School of Natural SciencesInstitute of Hydrochemistry85748 GarchingGermany School of Resources&Environment Northeast Agricultural UniversityHarbin 150030China Climate Air Quality Research UnitSchool of Public Health and Preventive MedicineMonash UniversityMelbourneVICAustralia Faculty of Environmental Science&Engineering Kunming University of Science&TechnologyKunming 650500China Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria College of Environmental Science and EngineeringNankai UniversityTianjin 300350China Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control School of Environmental Science and EngineeringInstitute of Environmental Health and Pollution ControlGuangdong University of TechnologyGuangzhou 510006China Ministry of Education Key Laboratory of Environmental Theoretical Chemistry South China Normal UniversityGuangzhouGuangdong 510006China Department of Environmental Science Baylor UniversityWacoTXUSA Center for Reservoir and Aquatic Systems Research(CRASR) Baylor UniversityWacoTXUSA School of Environment Tsinghua UniversityBeijing 100084China School of Civil and Environmental Engineering Cornell UniversityIthacaNY 14853USA Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province Zhejiang University of TechnologyHangzhou 310014China School of Environmental Science and Engineering Shanghai Jiao Tong UniversityShanghai 200240China Laboratoire d’Ecologie Microbienne Universite Claude Bernard Lyon 1UMR CNRS 5557UMR INRAE 1418VetAgro Sup69622 VilleurbanneFrance Department of Pla

Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary *** global efforts to mitigate legacy pollutants,the continuous introduction of new substances remains a major threat to both people and the *** response,global initiatives are focusing on risk assessment and regulation of emerging contaminants,as demonstrated by the ongoing efforts to establish the UN’s Intergovernmental Science-Policy Panel on Chemicals,Waste,and Pollution *** review identifies the sources and impacts of emerging contaminants on planetary health,emphasizing the importance of adopting a One Health *** for monitoring and addressing these pollutants are discussed,underscoring the need for robust and socially equitable environmental policies at both regional and international *** actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.

关键词： pollution planet contaminants

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Terahertz cavity magnon polaritons

arXiv

引用

arXiv 2023年

作者： Kritzell, T. Elijah Baydin, Andrey Tay, Fuyang Rodriguez, Rodolfo Nojiri, Hiroyuki Everitt, Henry O. Barsukov, Igor Kono, Junichiro Department of Electrical and Computer Engineering Rice University HoustonTX77005 United States Applied Physics Graduate Program Smalley-Curl Institute Rice University HoustonTX77005 United States Smalley-Curl Institute Rice University HoustonTX77005 United States Physics and Astronomy University of California RiversideCA92521 United States Institute for Materials Research Tohoku University Sendai980-8577 Japan DEVCOM Army Research Laboratory-South HoustonTX77005 United States Department of Physics and Astronomy Rice University HoustonTX77005 United States Department of Material Science and NanoEngineering Rice University HoustonTX77005 United States

Hybrid light-matter coupled states, or polaritons, in magnetic materials have attracted significant attention due to their potential for enabling novel applications in spintronics and quantum information processing. However, most studies to date have been carried out for ferromagnetic materials with magnon excitations at gigahertz frequencies. Here, we have investigated strong resonant photon-magnon coupling at frequencies above 1 terahertz for the first time in a prototypical room-temperature antiferromagnetic insulator, NiO, inside a Fabry-Pérot cavity. The cavity was formed by the crystal itself when it was thinned down to an optimized thickness. By using terahertz time-domain spectroscopy in high magnetic fields up to 25 T, we swept the magnon frequency through Fabry-Pérot cavity modes and observed photon-magnon anticrossing behavior, demonstrating clear vacuum Rabi splittings exceeding the polariton linewidths. These results show that NiO is a promising platform for exploring antiferromagnetic spintronics and cavity magnonics in the terahertz frequency range. Copyright © 2023, The Authors. All rights reserved.

关键词： Polariton

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Ten decadal advances in fungal biology leading towards human well‑being

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Fungal Diversity 2022年第5期116卷 547-614页

作者： Ausana Mapook·Kevin DHyde Kevin D.Hyde Khadija Hassan Blondelle Matio Kemkuignou Adela Cmokova Frank Surup Eric Kuhnert Pathompong Paomephan Tian Cheng Sybren de Hoog Yinggai Song Ruvishika S.Jayawardena Abdullah M.S.Al‑Hatmi Tokameh Mahmoudi Nadia Ponts Lena Studt‑Reinhold Florence Richard‑Forget K.W.Thilini Chethana Dulanjalee L.Harishchandra Peter E.Mortimer Huili Li Saisamorm Lumyong Worawoot Aiduang Jaturong Kumla Nakarin Suwannarach Chitrabhanu S.Bhunjun Feng‑Ming Yu Qi Zhao Doug Schaefer Marc Stadler Center of Excellence in Fungal Research Mae Fah Luang UniversityChiang Rai 57100Thailand School of Science Mae Fah Luang UniversityChiang Rai 57100Thailand Department Microbial Drugs Helmholtz Centre for Infection Research(HZI)and German Centre for Infection Research(DZIF)Partner Site Hannover‑BraunschweigInhoffenstrasse 738124 BrunswickGermany Institute of Microbiology Technische Universitat BraunschweigSpielmannstrase 738106 BrunswickGermany Laboratory of Fungal Genetics and Metabolism Institute of MicrobiologyCzech Academy of SciencesPragueCzech Republic Centre of Biomolecular Drug Research(BMWZ) Institute for Organic ChemistryLeibniz University HannoverSchneiderberg 3830167 HannoverGermany Department of Biotechnology Faculty of ScienceMahidol University272 Rama VI RoadRatchathewiBangkok 10400Thailand Center of Expertise in Mycology Radboud University Medical Center/Canisius Wilhelmina HospitalNijmegenThe Netherlands Key Laboratory of Environmental Pollution Monitoring and Disease Control Guizhou Medical UniversityGuiyangChina Microbiology Parasitology and Pathology Graduate ProgramFederal University of ParanaCuritibaBrazil Department of Dermatology Peking University First HospitalPeking UniversityBeijingChina Natural and Medical Sciences Research Center University of NizwaNizwaOman Department of Biochemistry Erasmus University Medical CenterRotterdamThe Netherlands INRAE UR1264 Mycology and Food Safety(MycSA)33882 Villenave d’OrnonFrance Department of Applied Genetics and Cell Biology Institute of Microbial GeneticsUniversity of Natural Resources and Life SciencesVienna(BOKU)Tulln an der DonauAustria Beijing Key Laboratory of Environment Friendly Management on Fruit Diseases and Pests in North China Institute of Plant ProtectionBeijing Academy of Agriculture and Forestry SciencesBeijing 100097China Key Laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of SciencesKunming 650201YunnanChina Centre for Mountai

Fungi are an understudied resource possessing huge potential for developing products that can greatly improve human *** the current paper,we highlight some important discoveries and developments in applied mycology and interdisciplinary Life Science *** examples concern recently introduced drugs for the treatment of infections and neurological diseases;application of–OMICS techniques and genetic tools in medical mycology and the regulation of mycotoxin production;as well as some highlights of mushroom cultivaton in *** for new diagnostic tools in medical mycology and the exploitation of new candidates for therapeutic drugs,are also *** addition,two entries illustrating the latest developments in the use of fungi for biodegradation and fungal biomaterial production are *** other areas where there have been and/or will be significant developments are also *** is our hope that this paper will help realise the importance of fungi as a potential industrial resource and see the next two decades bring forward many new fungal and fungus-derived products.

关键词： Biomaterial CRISPR Drug development Morel cultivation Mushroom cultivation Mycotoxin biosynthesis Plastic degradation

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Manganese-doped oleic acid functionalized whitlockite/polycaprolactone nanocomposite scaffolds enhance bone regeneration through improved dispersibility and antioxidative capacity

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Chemical Engineering Journal 2025年 518卷

作者： Liu, Xiaofan Liu, Yang Wang, Peiyu Tian, Ye Zhao, Yuping Wang, Yuxuan Zheng, Wenqian Wang, Yi Shi, Yaru Xie, Yi Zhou, Na González, Fermín E. Sun, Hongchen Zhou, Ding Xu, Xiaowei Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of Stomatology Jilin University Changchun 130021 China Graduate Program in Applied Physics Northwestern University Evanston 60208 IL United States School of Pharmacy State Key Laboratory of Quality Research in Chinese Medicines and Laboratory of Drug Discovery from Natural Resources and Industrialization Macau University of Science and Technology Macau 999078 China Laboratory of Experimental Immunology & Cancer Faculty of Dentistry University of Chile Santiago 8380492 Chile

Bone defects present significant clinical challenges due to the complexities of healing. While polycaprolactone (PCL) scaffolds offer promising mechanical support for bone tissue engineering, their limited bioactivity and dispersibility issues with bioactive fillers restrict their effectiveness. Here, we develop manganese-doped oleic acid-functionalized whitlockite (Mn-OAWH) nanoparticles designed to enhance both the mechanical and biological properties of PCL scaffolds. The nanoparticles were synthesized via a hydrothermal approach using oleic acid as both solvent and surface ligand, enabling superior dispersibility in dichloromethane and uniform integration with PCL. Characterization of the resulting 3D printed Mn-OAWH/PCL composite scaffolds confirmed enhanced compressive strength, supported by both mechanical testing and finite element analysis. In vitro studies demonstrated that the release of Mn²⁺, Mg²⁺, and Ca²⁺ ions significantly promoted osteogenic proliferation, exhibited strong antioxidative properties, and accelerated osteogenic differentiation. Furthermore, in vivo implantation in a rat critical-sized cranial defect model revealed significantly improved bone formation compared to undoped and PCL-only controls. These findings establish Mn-OAWH/PCL composite scaffolds as a promising platform for bone tissue engineering, offering both enhanced mechanical support and biological functionality through improved nanoparticle dispersibility, strong antioxidative properties and osteogenic activity.

关键词： Bone regeneration Homogeneous nanocomposite scaffold Manganese doping Oleic acid-functionalized whitlockite nanoparticles Oxidative stress alleviation

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Non-linear optics at twist interfaces in h-BN/SiC heterostructures

arXiv

引用

arXiv 2023年

作者： Biswas, Abhijit Xu, Rui Alvarez, Gustavo A. Zhang, Jin Christiansen-Salameh, Joyce Puthirath, Anand B. Burns, Kory Hachtel, Jordan A. Li, Tao Iyengar, Sathvik Ajay Gray, Tia Li, Chenxi Zhang, Xiang Kannan, Harikishan Elkins, Jacob Pieshkov, Tymofii S. Vajtai, Robert Birdwell, A. Glen Neupane, Mahesh R. Garratt, Elias J. Ivanov, Tony Pate, Bradford B. Zhao, Yuji Zhu, Hanyu Tian, Zhiting Rubio, Angel Ajayan, Pulickel M. Department of Materials Science and Nanoengineering Rice University HoustonTX77005 United States Sibley School of Mechanical and Aerospace Engineering Cornell University IthacaNY14853 United States Max Planck Institute for the Structure and Dynamics of Matter Center for Free-Electron Laser Science Luruper Chaussee 149 22761 Germany Department of Materials Science & Engineering University of Virginia CharlottesvilleVA22904 United States Center for Nanophase Materials Sciences Oak Ridge National Laboratory Oak RidgeTN37831 United States Department of Electrical and Computer Engineering Rice University HoustonTX77005 United States DEVCOM Army Research Laboratory RF Devices and Circuits AdelphiMD20783 United States Chemistry Division Naval Research Laboratory WashingtonDC20375 United States Applied Physics Graduate Program Smalley-Curl Institute Rice University HoustonTX77005 United States Flatiron Institute New YorkNY10010 United States

Understanding the emergent electronic structure in twisted atomically thin layers has led to the exciting field of twistronics. However, practical applications of such systems are challenging since the specific angular correlations between the layers must be precisely controlled and the layers have to be single crystalline with uniform atomic ordering. Here, we suggest an alternative, simple and scalable approach where nanocrystalline two-dimensional (2D) film on three-dimensional (3D) substrates yield twisted-interface-dependent properties. Ultrawidebandgap hexagonal boron nitride (h-BN) thin films are directly grown on high in-plane lattice mismatched wide-bandgap silicon carbide (4H-SiC) substrates to explore the twist-dependent structure-property correlations. Concurrently, nanocrystalline h-BN thin film shows strong nonlinear second-harmonic generation and ultra-low cross-plane thermal conductivity at room temperature, which are attributed to the twisted domain edges between van der Waals stacked nanocrystals with random in-plane orientations. First-principles calculations based on time-dependent density functional theory manifest strong even-order optical nonlinearity in twisted h-BN layers. Our work unveils that directly deposited 2D nanocrystalline thin film on 3D substrates could provide easily accessible twist-interfaces, therefore enabling a simple and scalable approach to utilize the 2D-twistronics integrated in 3D material devices for next-generation nanotechnology. © 2023, CC BY.

关键词： Harmonic generation

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Açaí (Euterpe oleracea Mart.) byproduct reduces tumor size and modulates inflammation in Ehrlich mice model

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Journal of Functional Foods 2023年 103卷

作者： Custódio Neto da Silva, Marcos Antonio Araújo Souza Wolff, Laís Assunção Borges, Kátia Regina Alvares Marques Vale, André Silva de Azevedo-Santos, Ana Paula Pascoal Xavier, Marcelo Antonio Lacerda Barbosa, Maria do Carmo Soares Brandão Nascimento, Maria do Desterro Ernesto de Carvalho, João Faculty of Medical Science Post-graduate Program in Internal Medicine Universidade Estadual de Campinas Rua Tessália Vieira de Camargo 126. Cidade Universitária Zeferino Vaz SP Campinas CEP 13083-887 Brazil Medicine Course Federal University of Maranhão Imperatriz CEP 65915-060 Brazil Federal University of Maranhão (UFMA) Post-graduate Program in Adult Heath Department of Patology MA São Luís 65080-805 Brazil Laboratory of Applied Cancer Immunology Biological and Health Sciences Center Federal University of Maranhão Avenida dos Portugueses 1966 Bacanga Maranhão São Luis 65080-085 Brazil Federal University of Minas Gerais (UFMG) Department of Pathological Anatomy and Forensic Medicine and René Rachou Research Center Oswaldo Cruz Foundation (FIOCRUZ) Minas Gerais Belo Horizonte Brazil Federal University of Maranhão (UFMA) Post-graduate Program in Family Health Department of Medicine I MA São Luís 65080-805 Brazil Faculty of Pharmaceutical Sciences State University of Campinas SP Campinas 13083-859 Brazil Post-graduate Program in Health Sciences MA São Luís 65080-805 Brazil

Açaí, Euterpe oleracea Mart. is rich in several phytochemical substances with antioxidant, anti-inflammatory and antitumor activities. The açaí seed is a waste product, being little used in the economy, being relevant to study the antitumor properties of this by-product. This study aims to analyze the effects of hydroalcoholic açaí seed extract in Ehrlich mice model in preventive and treatment schemes. The animals were treated with different concentrations of the extract (100, 300 and 1000 mg/kg) by gavage in preventive (30 days before tumor induction) and intervention (15 days after tumor induction) regimens. In in vivo experiments, the use of the extract at a dose of 1000 mg/kg in preventive regimens reduced tumor volume, decreased tumor weight, maintained the weight of treated animals and induced an immunomodulatory response, with an increase in TNF-α. The treatment also increased the area of tumor necrosis when compared to the control. Our results suggest the antitumor potential of açaí seed extract in in vivo models of breast cancer, contributing to obtain an active drug from a known natural product. In addition, the use of açaí seed residue will contribute to the local economy and sustainability. © 2023

关键词： Breast cancer Ehrlich mice model Euterpe oleracea Mart Inflammation

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A rapid and sensitive analytical methodology for the simultaneous biomonitoring of two direct oral anticoagulant drugs and their major metabolites in thromboembolic disordered patients samples for clinical evaluations

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Journal of Chromatography A 2024年 1717卷 464689页

作者： Prakasham, Karthikeyan Pan, Tzu-Yu Tan, Chun-Hsiang Wu, Chia-Fang Chandra, Pranjal Cheng, Ching-Mei Chen, Wei Tsai, Wei-Chung Ponnusamy, Vinoth Kumar Wu, Ming-Tsang Research Center for Precision Environmental Medicine Kaohsiung Medical University Kaohsiung City Taiwan Ph.D. Program in Environmental and Occupational Medicine College of Medicine Kaohsiung Medical University Kaohsiung City Taiwan Department of Neurology Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung City Taiwan Graduate Institute of Clinical Medicine College of Medicine Kaohsiung Medical University Kaohsiung City Taiwan Department of Family Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung City Taiwan International Master Program of Translational Medicine National United University Taiwan Varanasi Varanasi221005 India Department of Laboratory Medicine Kaohsiung Municipal Hsiao-Kang Hospital Kaohsiung City Taiwan Department of Public Health Kaohsiung Medical University Kaohsiung City Taiwan Division of Cardiology Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung City Taiwan Faculty of Medicine College of Medicine Kaohsiung Medical University Taiwan Department of Medicinal and Applied Chemistry Kaohsiung Medical University Kaohsiung City-807 Taiwan Department of Medical Research Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung City Taiwan

Apixaban and dabigatran are the two major direct oral anticoagulant drugs to treat thromboembolic disordered patients. Increasing the clinical application for the thromboembolic disorder and monitoring the concentrations of apixaban, dabigatran, and their metabolites are essential in most clinical circumstances. In this work, we developed a rapid analytical methodology comprising of vortex-assisted salt-enhanced liquid-liquid microextraction technique coupled with UHPLC-MS/MS for the extraction and simultaneous determination of two major direct oral anticoagulant drugs (apixaban, dabigatran), and their two major metabolites from plasma, serum, and urine samples of patients. The developed method was optimized with various procedural steps and validated to study the analytical merits. The developed method yielded a good detection limit of 0.01 ∼ 0.37 ng/mL, 0.01 ∼ 0.32 ng/ml, and 0.01 ∼ 0.27 ng/mL for four target analytes in the plasma, serum, and urine matrices. Moreover, extraction recoveries ranged from 85.11 – 113.57% (for plasma), 89.63 – 110.47% (for serum), and 87.44 –106.79% (for urine samples) with 8.78% RSD. In addition, the method exhibited good R2 values of 0.999 for all four target analytes, and the specificity and carryover study revealed no carryover effect from the UHPLC-MS/MS system for determining the apixaban, dabigatran, and their metabolites. Due to the above advantages, the developed analytical technique was applied to examine 11 real-time clinical patients’ samples, and the observed results were satisfactory for all three different sample matrices. Therefore, this analytical method can be applied for biomonitoring apixaban, dabigatran, and their two major metabolites with high sensitivity in a short time for various clinical applications. © 2024 Elsevier B.V.

关键词： Metabolites

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Vacuum Ultraviolet Light-Generating Metalens

Vacuum Ultraviolet Light-Generating Metalens

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Pacific Rim Conference on Lasers and Electro-Optics (CLEO/Pacific Rim)

作者： Ming Lun Tseng Michael Semmlinger Ming Zhang Catherine Arndt Tzu-Ting Huang Jian Yang Hsin Yu Kuo Vin-Cent Su Mu Ku Chen Cheng Hung Chu Benjamin Cerjan Din Ping Tsai Peter Nordlander Naomi J. Halas Institute of Electronics National Yang Ming Chiao Tung University Hsinchu Taiwan Research Center for Applied Sciences Academia Sinica Taipei Taiwan Department of Electrical and Computer Engineering Rice University Houston Texas USA Laboratory for Nanophotonics Rice University Houston Texas USA Applied Physics Graduate Program Rice University Houston Texas USA Department of Physics and Astronomy Rice University Houston Texas USA Department of Physics National Taiwan University Taipei Taiwan Department of Electrical Engineering National United University Miaoli Taiwan Department of Electrical Engineering City University of Hong Kong Kowloon Hong Kong Department of Chemistry Rice University Houston Texas USA

Vacuum ultraviolet (VUV) light is of great importance to many applications such as photochemistry and nanolithography. In this talk, a nonlinear metalens composed of ZnO nanoantennas for VUV generation and focusing wi...

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Diarylheptanoid 35d overcomes EGFR TKI resistance by inducing hsp70-mediated lysosomal degradation of EGFR in EGFR-mutant lung adenocarcinoma

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Journal of Biological Chemistry 2023年第6期299卷 104814页

作者： Hong, Xuan Hsieh, Min-Tsang Tseng, Tzu-Yu Lin, Hui-Yi Chang, Hung-Chih Yau, Sir-Theng Cheng, Wei-Chung Ke, Baozhen Liao, Hsiao-Hui Wu, Chih-Ying Liu, An-An Wu, Meei-Maan Huang, Kuo-Yen Yang, Pan-Chyr Kuo, Sheng-Chu Hung, Mien-Chie Lee, Pei-Chih Department of Medical Oncology Harbin Medical University Cancer Hospital Harbin China School of Pharmacy China Medical University Taichung Taiwan Research Center for Chinese Herbal Medicine China Medical University Taichung Taiwan Chinese Medicinal Research and Development Center China Medical University Hospital Taichung Taiwan Research Center for Cancer Biology China Medical University Taichung Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Ph.D. Program for Cancer Molecular Biology and Drug Discovery China Medical University Taichung Taiwan Department of Molecular and Cellular Oncology The University of Texas MD Anderson Cancer Center HoustonTX United States Department of Pathology and Laboratory Medicine Taichung Veterans General Hospital Taichung Taiwan Department of Public Health School of Medicine College of Medicine Taipei Medical University Taipei Taiwan School of Public Health College of Public Health Taipei Medical University Taipei Taiwan Master Program in Applied Epidemiology College of Public Health Taipei Medical University Taipei Taiwan Institute of Biomedical Sciences Academia Sinica Taipei Taiwan Department of Internal Medicine National Taiwan University Hospital and National Taiwan University College of Medicine Taipei Taiwan Genomics Research Center Academia Sinica Taipei Taiwan

Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LUAD) patients often respond to EGFR tyrosine kinase inhibitors (TKIs) initially but eventually develop resistance to TKIs. The switch of EGFR downstream signaling from TKI-sensitive to TKI-insensitive is a critical mechanism-driving resistance to TKIs. Identification of potential therapies to target EGFR effectively is a potential strategy to treat TKI-resistant LUADs. In this study, we developed a small molecule diarylheptanoid 35d, a curcumin derivative, that effectively suppressed EGFR protein expression, killed multiple TKI-resistant LUAD cells in vitro, and suppressed tumor growth of EGFR-mutant LUAD xenografts with variant TKI-resistant mechanisms including EGFR C797S mutations in vivo. Mechanically, 35d triggers heat shock protein 70–mediated lysosomal pathway through transcriptional activation of several components in the pathway, such as HSPA1B, to induce EGFR protein degradation. Interestingly, higher HSPA1B expression in LUAD tumors associated with longer survival of EGFR-mutant, TKI-treated patients, suggesting the role of HSPA1B on retarding TKI resistance and providing a rationale for combining 35d with EGFR TKIs. Our data showed that combination of 35d significantly inhibits tumor reprogression on osimertinib and prolongs mice survival. Overall, our results suggest 35d as a promising lead compound to suppress EGFR expression and provide important insights into the development of combination therapies for TKI-resistant LUADs, which could have translational potential for the treatment of this deadly disease. © 2023 The Authors

关键词： Tumors

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TAF2, within the TFIID complex, regulates the expression of a subset of protein-coding genes

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Cell Death Discovery 2024年第1期10卷 244页

作者： Cheng, I-Hsin Pi, Wen-Chieh Hsu, Chung-Hao Guo, Yiran Lai, Jun-Lin Wang, Gang G. Chung, Bon-Chu Roeder, Robert G. Chen, Wei-Yi Institute of Biochemistry and Molecular Biology National Yang Ming Chiao Tung University Taipei Taiwan School of Medicine College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Department of Pharmacology and Cancer Biology Duke University School of Medicine Durham 27710 NC United States Duke Cancer Institute Durham 27710 NC United States Program in Molecular Medicine National Yang Ming Chiao Tung University and Academia Sinica Taipei Taiwan Insitute of Molecular Biology Academia Sinica Taipei Taiwan Graduate Institute of Biomedical Sciences Neuroscience and Brain Disease Center China Medical University Taichung Taiwan National Laboratory Animal Center National Applied Research Laboratories Taipei Taiwan Laboratory of Biochemistry and Molecular Biology The Rockefeller University New York 10065 NY United States Cancer and Immunology Research Center National Yang Ming Chiao Tung University Taipei Taiwan

TFIID, one of the general transcription factor (GTF), regulates transcriptional initiation of protein-coding genes through direct binding to promoter elements and subsequent recruitment of other GTFs and RNA polymerase II. Although generally required for most protein-coding genes, accumulated studies have also demonstrated promoter-specific functions for several TFIID subunits in gene activation. Here, we report that TBP-associated factor 2 (TAF2) specifically regulates TFIID binding to a small subset of protein-coding genes and is essential for cell growth of multiple cancer lines. Co-immunoprecipitation assays revealed that TAF2 may be sub-stoichiometrically associated with the TFIID complex, thus indicating a minor fraction of TAF2-containing TFIID in cells. Consistently, integrated genome-wide profiles show that TAF2 binds to and regulates only a small subset of protein-coding genes. Furthermore, through the use of an inducible TAF2 degradation system, our results reveal a reduction of TBP/TFIID binding to several ribosomal genes upon selective ablation of TAF2. In addition, depletion of TAF2, as well as the TAF2-regulated ribosomal protein genes RPL30 and RPL39, decreases ribosome assembly and global protein translation. Collectively, this study suggests that TAF2 within the TFIID complex is of functional importance for TBP/TFIID binding to and expression of a small subset of protein-coding genes, thus establishing a previously unappreciated promoter-selective function for TAF2. © The Author(s) 2024.

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