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Carbon Nanofibers in Predicted environmentally Relevant Concentrations Intensify Monocystis Sp. Infection and Affect the Lumbricus Terrestris Earthworms' Health

SSRN

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SSRN 2023年

作者： Montalvão, Mateus Flores Gomes, Alex Rodrigues Guimarães, Abraão Tiago Batista de Lima Rodrigues, Aline Sueli de Matos, Letícia Paiva dos Santos Mendonça, Juliana da Luz, Thiarlen Marinho da Silva Matos, Stênio Gonçalves Rahman, M. Safiur Ragavendran, Chinnasamy Senthil-Nathan, Sengottayan Guru, Ajay Rakib, Md. Refat Jahan Mubarak, Nabisab Mujawar Rahman, Md. Mostafizur Rocha, Thiago Lopes Towfiqul Islam, Abu Reza Md. Malafaia, Guilherme Post-Graduation Program in Ecology Conservation and Biodiversity Federal University of Uberlândia MG Uberlândia Brazil Laboratory of Toxicology Applied to the Environment Goiano Federal Institute Urutaí Campus. Rodovia Geraldo Silva Nascimento 25 Km Zona Rural GO Urutaí Brazil Post-Graduation Program in Conservation of Cerrado Natural Resources Goiano Federal Institute GO Urutaí Brazil Post-Graduation Program in Biotechnology and Biodiversity Federal University of Goiás GO Goiânia Brazil Bangladesh Atomic Energy Commission Bangladesh Periyar University India Division of Biopesticides and Environmental Toxicology Sri Paramakalyani Centre for Excellence in Environmental Sciences Manonmaniam Sundaranar University Alwarkurichi Tamil Nadu Tirunelveli627 412 India Department of Cariology Saveetha Dental College and Hospitals SIMATS Tamil Nadu Chennai600 077 India Noakhali Science and Technology University Noakhali Bangladesh Petroleum and Chemical Engineering Faculty of Engineering Universiti Teknologi Brunei Bandar Seri Begawan BE1410 Brunei Jahangirnagar University Dhaka1342 Bangladesh Laboratory of Environmental Biotechnology and Ecotoxicology Institute of Tropical Pathology and Public Health Federal University of Goiás Goiás Goiania Brazil Department of Disaster Management Begum Rokeya University Rangpur5400 Bangladesh

Although the ecotoxicity of carbon-based nanomaterials (CBNs) is known, the potential effect of carbon nanofibers (CNFs) on edaphic organisms has not been evaluated. Thus, we aimed at the ecotoxicity of CNFs (at 10 and 100 mg/kg) in Lumbricus terrestris earthworms naturally infected with Monocystis sp. After 28 days of exposure, treatments did not affect the survival rate. However, we observed a significant loss of body biomass, and Monocystis sp. infection in seminal vesicles was potentiated by exposure to CNFs. Earthworms exposed to CNFs showed a redox imbalance in the seminal vesicle, muscle, and intestine and an alteration in nitric oxide production in these organs. In muscles, we also noticed a significant reduction in AChE activity in earthworms exposed to CNFs. The histopathological analyses revealed the treatments' significant effect on the structures of the different evaluated tissues. Although we did not notice a concentration-response for several of the biomarkers, when taken together and after the application of IBRv2 and principal component analysis (PCA), we noticed that the response of earthworms to CNFs at 100 mg/kg showed a more significant deviation from the unexposed group. This was mainly determined by inhibiting antioxidant activity in the seminal vesicle, biochemical biomarkers assessed in muscle and intestine, and histomorphometric muscle biomarkers from earthworms exposed to CNFs at 100 mg/kg. Thus, we demonstrate that CNFs increase the parasite load of Monocystis sp. of adult L. terrestris earthworms and induce biochemical changes and histopathological changes, especially at 100 mg/kg. Our results point to the additional impact these nanomaterials can have on the health of earthworms, signaling the need for greater attention to their disposal and ecotoxicological effects on soil organisms. © 2023, The Authors. All rights reserved.

关键词： Biomarkers

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Fluctuating interaction network and time-varying stability of a natural fish community (vol 554, pg 360, 2018)

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NATURE 2022年第7911期605卷 E9-E9页

作者： Ushio, Masayuki Hsieh, Chih-hao Masuda, Reiji Deyle, Ethan R. Ye, Hao Chang, Chun-Wei Sugihara, George Kondoh, Michio Department of Environmental Solution Technology Faculty of Science and Technology Ryukoku University Otsu Japan Joint Research Center for Science and Technology Ryukoku University Otsu Japan Center for Ecological Research Kyoto University Otsu Japan PRESTO Japan Science and Technology Agency Kawaguchi Japan Institute of Oceanography Institute of Ecology and Evolutionary Biology and Department of Life Science National Taiwan University Taipei Taiwan Taiwan International Graduate Program (TIGP)–Earth System Science Program Academia Sinica and National Central University Taipei Taiwan National Center for Theoretical Science Taipei Taiwan Maizuru Fisheries Research Station Field Science Education and Research Center Kyoto University Maizuru Kyoto Japan Scripps Institution of Oceanography University of California at San Diego La Jolla California USA Department of Wildlife Ecology and Conservation University of Florida Gainesville Florida USA

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Improving the Performance of Asphalt Mixtures with Highly Acidic Aggregates in Central Vietnam Using Modifier Based on Styrene-Butadiene-Styrene and Rosin Resin

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Journal of Materials in Civil Engineering 2025年第7期37卷

作者： Nguyen, Lan Ngoc Lee, Hosin David Bui, Lam Tung Kim, Young-Ik Truong, Van Quyet Nguyen, May Huu Nguyen, Du Van Dept. of Construction Materials Faculty of Construction Engineering Univ. of Transport and Communications No. 03 Cau Giay Hanoi100000 Viet Nam Dept. of Civil and Environmental Engineering Iowa Technology Institute The Univ. of Iowa Iowa CityIA52242 United States Research Dept. Hansoo Natech Co. Ltd. 6-20 Yuseong-daero 1205beon-gil Yuseong-gu Daejeon34104 Korea Republic of Civil and Environmental Engineering Program Graduate School of Advanced Science and Engineering Hiroshima Univ. 1-4-1 Kagamiyama Higashi-Hiroshima Hiroshima739-8527 Japan Faculty of Civil Engineering Univ. of Transport and Communications Campus in Ho Chi Minh City Ho Chi Minh City700000 Viet Nam

In Central Vietnam, the aggregate typically originates from highly acidic rocks containing a significant amount of silicon dioxide (SiO2), leading to poor adhesion quality with virgin asphalt binder. Hence, the asphalt mixture production usually needs to utilize adhesion promoters. Based on the chemical compositions of the sample aggregate (up to 72.3% SiO2), research has been conducted to introduce an adhesive agent called rubber modified compound (RMC-160), which is composed of styrene-butadiene-styrene (SBS) with petroleum hydrocarbon resin, treated clay and mineral oil. This article presents the research findings regarding the adhesion effectiveness of RMC-160-modified asphalt binder to high acid-based aggregate through laboratory and field tests, along with the mixture performance under both short-term oven aging (STOA) and long-term oven aging (LTOA). The test results exhibited remarkable effects, whereby the asphalt binder modified with RMC-160 additive significantly increased the adhesion level from Grade 2 to Grade 4, and the asphalt mixtures containing RMC-160 had lower rutting and higher cracking tolerance (CTIndex) under both the STOA and LTOA conditions. © 2025 American Society of Civil Engineers.

关键词： Silicon oxides

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Maternal Progesterone and Adipose mPRΕ in Pregnancy Regulate the Embryonic Nutritional State

SSRN

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SSRN 2024年

作者： Watanabe, Keita Yamano, Mayu Miyamoto, Junki Ohue-Kitano, Ryuji Masujima, Yuki Sasahara, Daiki Mouri, Yuki Kono, Nozomu Inuki, Shunsuke Osakada, Fumitaka Nagaoka, Kentaro Aoki, Junken Sugiura, Yuki Ohno, Hiroaki Kondoh, Eiji Kimura, Ikuo Laboratory of Molecular Neurobiology Graduate School of Biostudies Kyoto University Sakyo-ku Kyoto606-8501 Japan Department of Molecular Endocrinology Graduate School of Pharmaceutical Sciences Kyoto University Sakyo-ku Kyoto606-8501 Japan Department of Applied Biological Science Graduate School of Agriculture Tokyo University of Agriculture and Technology Fuchu Tokyo183-8509 Japan Department of Biological & Environmental Chemistry Kindai University 11-6 Kayanomori Iizuka Fukuoka820-8555 Japan Noster Inc. Kamiueno Muko-shi Kyoto617-0006 Japan Graduate School of Pharmaceutical Sciences The University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo113-0033 Japan Department of Bioorganic Medicinal Chemistry Graduate School of Pharmaceutical Sciences Kyoto University Sakyo-ku Kyoto606-8501 Japan Laboratory of Cellular Pharmacology Graduate School of Pharmaceutical Sciences Nagoya University Japan Laboratory of Neural Information Processing Institute for Advanced Research Nagoya University Japan AMED-CREST Japan Agency for Medical Research and Development Chiyoda-ku Tokyo100-0004 Japan Laboratory of Veterinary Physiology Graduate School of Agriculture Tokyo University of Agriculture and Technology Fuchu Tokyo183-8509 Japan Department of Moonshot Research and Development Program Japan Science and Technology Agency Chiyoda-ku Tokyo102-0076 Japan Center for Cancer Immunotherapy and Immunobiology Kyoto University Graduate School of Medicine Kyoto Japan Department of Obstetrics and Gynecology Faculty of Life Sciences Kumamoto University 1-1-1 Honjo Chuo-Ku Kumamoto Kumamoto860-8556 Japan

Sex steroid hormones such as progesterone play a pivotal role in reproductive functions and maintaining pregnancy;however, the impact of progesterone on the interaction between mother and embryo is unclear. Here, we demonstrate that the relationship between maternal progesterone and membrane progesterone receptor epsilon (mPRΕ) in adipose tissue regulates embryonic nutritional environment and growth after birth in mice. The activation of adipose mPRΕ by increased progesterone during pregnancy enhanced maternal insulin resistance through the production of prostaglandins, thereby efficiently providing glucose to embryos. The offspring of mPRΕ-deficient mothers exhibited metabolic dysfunction, whereas mPRΕ-deficient mothers with high-fat-diet-induced obesity exhibited improved insulin sensitivity. These findings establish the importance of progesterone as a nutritional regulator between mother and embryo, and suggest that mPRΕ modulators could be developed to treat pregnant glycemic control disorders such as gestational diabetes mellitus, as well as metabolic syndrome in offspring. © 2024, The Authors. All rights reserved.

关键词： Obstetrics

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Theoretical insights into the chemical bonding, electronic structure, and spectroscopic properties of the lanarkite Pb2SO5 structure

arXiv

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arXiv 2023年

作者： Fabris, Guilherme S.L. Ferrer, Mateus M. Sambrano, Julio R. Almeida, Cláudio R.R. Paskocimas, Carlos A. La Porta, Felipe A. Graduate Program in Materials Science and Engineering Technological Development Center Universidade Federal de Pelotas RS Pelotas96010-610 Brazil Modeling and Molecular Simulation Group São Paulo State University Bauru São Paulo17033-360 Brazil Department of Materials Engineering Federal University of Rio Grande do Norte RN Natal59078-970 Brazil Postgraduate Program in Science and Engineering of Materials Federal University of Rio Grande do Norte RN Natal59078-970 Brazil Federal University of Technology - Paraná Nanotechnology and Computational Chemistry Laboratory Avenida dos Pioneiros 3131 CEP PR Londrina86036-370 Brazil State University of Londrina Post-Graduation Program in Chemistry Rodovia Celso Garcia Cid 445 km 380 CEP PR Londrina86057-970 Brazil

Lanarkite is a mineral formed by a combination of lead, sulphur, and oxygen atoms arranged in the general chemical formula Pb2SO5 (PSO) that crystallises with monoclinic symmetry (belonging to the C2/m space group, No. 12). This mineral was first discovered in Lanarkshire, Scotland and was named after its location. PSO has a unique structure comprising alternating penta-coordinated lead [PbO5] and tetra-coordinated sulphur [SO4] clusters. This lanarkite-type structure has recently attracted significant scientific interest and has been the focus of the superconducting material research community. However, its chemistry needs to be explored further. This article presents a comprehensive investigation on the chemical bonding, electronic structure, and spectroscopic properties of the lanarkite-type PSO structure from a computational perspective. Thus, different functionals in the DFT (e.g., PBE, PBE0, PBESOL, PBESOL0, BLYP, WC1LYP37, and B3LYP) were assessed to accurately predict their fundamental properties. All the DFT calculations were performed using a triple-zeta valence plus polarisation basis set. Among all the DFT functionals tested in this study, PBE showed the best agreement with the experimental data available in the literature. Our results also reveal that the [PbO5] clusters are formed with three Pb–O bond lengths, with values of about 2.32, 2.59, and 2.84 Å, respectively, while the [SO4] clusters have the same S–O bond length of 1.57 Å. We performed a complete topological analysis of this system to comprehend these structural differences. Additionally, the PSO structure has an indirect band gap energy of 2.9 eV and an effective mass ratio (mℎ∗ /me∗) of about 0.415 (using PBE calculations) which may, in principle, indicate a low recombination of electron-hole pairs in the lanarkite structure. Therefore, we believe that a detailed understanding of their electronic structures, spectroscopic properties as well as their chemical bonding is critically important

关键词： Lead compounds

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Front Cover: Potassium Carbonate as a Low-Cost and Highly Active Solid Base Catalyst for Low-Temperature Methanolysis of Polycarbonate (ChemSusChem 2/2025)

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ChemSusChem 2025年第2期18卷

作者： Tzu-Ming Lin Philip Anggo Krisbiantoro Miyu Sato Yu-Chia Chang Eduardo C. Atayde Dr. Weisheng Liao Prof. Yuichi Kamiya Dr. Ryoichi Otomo Prof. Kevin C.-W. Wu Department of Chemical Engineering National Taiwan University Taipei 10617 Taiwan Molecular Science and Technology Program Taiwan International Graduate Program Academia Sinica Taipei 11529 Taiwan International Graduate Program of Molecular Science and Technology National Taiwan University Taipei 10617 Taiwan Graduate School of Environmental Science Hokkaido University Nishi 5 Kita 10 Kita-ku Sapporo 060-0810 Japan Department of Chemistry National Tsing Hua University Hsinchu 30013 Taiwan Faculty of Environmental Earth Science Hokkaido University Nishi 5 Kita 10 Kita-ku Sapporo Japan Department of Chemical Engineering and Materials Science Yuan Ze University Chung-Li Taoyuan Taiwan Department of Chemical Engineering Chung Yuan Christian University Taoyuan City 320 Taiwan

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Effect of pyrolysis temperature on characteristics of tunable magnetic biochar synthesized from watermelon rind and its tetracycline adsorption performance

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Journal of the Taiwan Institute of Chemical Engineers 2024年 160卷

作者： Thairattananon, Phisit Le, Giang T.T. Matsumura, Yukihiko Wu, Kevin C.W. Charinpanitkul, Tawatchai Department of Chemical Engineering Faculty of Engineering Center of Excellence in Particle and Material Processing Technology Chulalongkorn University Bangkok10330 Thailand Institute of Fundamental and Applied Sciences Duy Tan University Ho Chi Minh700000 Viet Nam Faculty of Environmental and Chemical Engineering Duy Tan University Da Nang550000 Viet Nam Mechanical Engineering Program Graduate School of Advanced Science and Engineering Kagamiyama Hiroshima Higashi-Hiroshima739-8527 Japan Department of Chemical Engineering National Taiwan University Taipei10617 Taiwan Department of Chemical Engineering and Materials Science Yuan Ze University Chung-Li Taoyuan Taiwan Research Network of NANOTEC-KU on Nanocatalyst and Nanomaterials for Sustainable Energy and Environment Bangkok10900 Thailand

Background: Tetracycline is an emerging contaminant in water reservoirs, causing undesirable influences on human society. The promising usage of magnetic biochar (MBC) derived from watermelon rind has been explored in the adsorption of various contaminants owing to its high specific surface area and separability;however, the temperature-dependent changes of MBC and its sorption ability toward antibiotics have not been widely examined. Method: Tunable MBCs could be synthesized via simple pyrolysis of watermelon rind impregnated with FeCl3 at different temperatures (700–900 °C). The as-synthesized MBCs were characterized using scanning electron microscopy (SEM), an elemental analyzer, N2 adsorption/desorption, Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffractometry (XRD), and vibrating sample magnetometry (VSM). Then Tetracycline, an emerging contaminant in water reservoirs, was employed as the target contaminant, while adsorption kinetics, isotherm, the effect of pH, and reusability were investigated. Significant findings: The tunability of as-synthesized MBCs could be observed by their distinct changes in structural characteristics when varying pyrolysis temperature. MBC synthesized at 900 °C (MBC900) possessed a high-specific surface area (401 m2.g−1) and saturation magnetization (55.29 emu.g−1), resulting in a greater amount of sorption sites. Tetracycline adsorption by MBCs followed a pseudo-second-order kinetic model and fitted well with the Freundlich model. MBC900 is an excellent adsorbent with a maximum adsorption capacity of 77.6 mg.g−1 and could be used for at least five cycles with an insignificant decrease in the adsorption capacity. © 2024 Taiwan Institute of Chemical Engineers

关键词： Adsorption

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Sustainability assessment of groundwater in south-eastern parts of the western region of Ghana for water supply

Cleaner Water

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Cleaner Water 2024年 1卷

作者： Ernest Biney Bernard Akwasi Mintah Ernest Ankomah Albert Elikplim Agbenorhevi Daniel Buston Yankey Ernestina Annan Department of Geomatic Engineering Kwame Nkrumah University of Science and Technology University Post Office Box PMB Kumasi Ghana WASCAL Graduate Research Programme on Climate Change and Land Use Department of Civil Engineering Kwame Nkrumah University of Science and Technology Kumasi Ghana Department of Geological Engineering University of Mines and Technology Tarkwa Ghana Graduate Research Program on Climate Change and Water Resources West African Science Service Center on Climate Change and Adapted Land Use (WASCAL) University of Abomey-Calavi Benin

The study assessed the physicochemical and biological properties of selected groundwater sources in the Southeastern part of the Western Region, to assess the impact on water quality and health risk. The Piper Trilinear plot was used to categorize the water samples into water types based on the dominant anion and cation concentrations. Statistical analysis (One way ANOVA and two sample t-test) was used to determine the sources of variation in the data at 95% confidence interval. The Water Quality Index (WQI) and Hazard Quotient (HQ) were used to estimate the water quality and health risk respectively. TDS and turbidity were above the acceptable WHO guidelines in 16.7% of the samples with a mildly acidic pH in 83.3% of the water samples. Also, 91.7% of the water samples were contaminated with total coliform (TC) and 25% with e-coli. Generally, the groundwater samples were dominated by Ca 2+ and HCO 3- ion water types. The variations between parameters were found not significant for all the parameters (p>0.05). Water samples in the North are of good quality with a mean WQI of 96, but of poor quality in the South with a mean WQI of 144.6. HQ values for all the samples were less than 0.1, suggesting less harmful impacts of the heavy metal concentrations on human health. Overall, the results showed the presence of heavy metals in the groundwater sources sampled, however in quantities with low health risks either through oral or dermal channels. Groundwater within the communities is good for domestic purposes but needs treatment for drinking. To improve upon the study, it is recommended that further studies consider a higher number of samples and include other accessible groundwater stations where possible.

关键词： Health Risk Assessment Groundwater GIS Trace elements Water Quality Index

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Bioactivity, Efficacy, and Safety of a Wound Healing Ointment With Medicinal Plant Bioactives: In Vitro and In Vivo Preclinical Evaluations

Scientific World Journal

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Scientific World Journal 2025年第1期2025卷 9466270页

作者： Floriano, Juliana Ferreira Rodrigues, Daniel Ohara, Rie Almeida, Nara Lígia Martins Lara, Vanessa Soares Sartorelli, Patricia Graeff, Carlos Frederico de Oliveira Grecco, Simone dos Santos González, Alejandra Hortencia Miranda D’Alpino, Paulo Henrique Perlatti Imperial College London National Heart and Lung Institute imperial.ac.uk GBR London United Kingdom Botucatu Medical School São Paulo State University (UNESP) São Paulo unesp.br BRA Botucatu Brazil Bioengineering and Biomaterials Group School of Pharmaceutical Sciences São Paulo State University (UNESP) unesp.br BRA Araraquara São Paulo Brazil Biotechnology and Innovation in Health Program Universidade Anhanguera de São Paulo (UNIAN) São Paulo BRA Brazil Brazil Department of Health Management Fundação Nacional de Gestão de Saúde São Paulo Brazil Undergraduate Program Medical School Universidade Nove de Julho Bauru São Paulo Brazil Department of Surgery Stomatology Pathology and Radiology Bauru School of Dentistry University of São Paulo (USP) São Paulo usp.br BRA Bauru Brazil Department of Chemistry Institute of Environmental Chemical and Pharmaceutical Sciences Federal University of São Paulo São Paulo unifesp.br BRA Diadema Brazil Department of Physics School of Sciences POSMAT-Post-Graduate Program in Materials Science and Technology São Paulo State University (UNESP) São Paulo Bauru Brazil Department of Research and Development (RD) and Innovation Center Triplet Biotechnology Solutions Inc Bauru São Paulo Brazil Post-Graduate Program in Dentistry Uniderp Anhanguera University Mato Grosso do Sul Campo Grande Brazil Post-Graduate Program in Integrated Dental Sciences University of Cuiabá (UNIC) Mato Grosso do Sul Cuiabá Brazil Department of Physics School of Sciences São Paulo State University (UNESP) São Paulo unesp.br BRA Bauru Brazil

Chronic wounds have a significant impact on patients’ quality of life, necessitating the management of pain, infection, bleeding, and emotional challenges. Debridement, which involves the removal of nonviable tissue, is crucial for promoting wound healing. In addition to surgical methods, cost-effective alternatives such as local solutions and ointments with biological properties have been explored. The use of natural compounds with anti-inflammatory, antibacterial, and collagen-synthesizing abilities holds promise for wound healing. This in vitro and in vivo preclinical study aimed to assess the safety and effectiveness of a wound healing ointment containing bioactive ingredients derived from medicinal plants (extracts, essential oils, and vegetable oils). The chemical composition of the ointment was characterized using Fourier transform infrared (FTIR) spectroscopy to gain insights into its synergistic action. Preclinical tests were conducted following standardized protocols. FTIR analysis revealed similarities between the product’s spectrum and that of bioactive compounds. The in vitro tests demonstrated that all formulations of the ointment induced no cell death, DNA damage, or acute toxicity in cell cultures (p < 0.05). No lethal dose was observed, indicating the safety of the ointment at all concentrations. The ointment also stimulated a notably more organized, significantly higher collagen production compared to control groups (p < 0.05). In vivo preclinical analyses also demonstrated no adverse responses being effective in the healing process compared to the control group (silver sulfadiazine) in terms of wound contraction and ulcer re-epithelization (p < 0.05). Significantly higher means of wound contraction were observed in the groups treated with the bioactive-containing ointment when compared to both the positive control group (sulfadiazine) and the control untreated groups (p < 0.05). The regenerative ointment exhibited excellent biocompatibility and bi

关键词： biocompatibility chronic wounds natural compounds preclinical tests wound care

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Structural optimization and biological evaluation of indolin-2-one derivatives as novel CDK8 inhibitors for idiopathic pulmonary fibrosis

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Biomedicine and Pharmacotherapy 2025年 184卷 117891-117891页

作者： Hsu, Jui-Yi Hsu, Kai-Cheng Chou, Ching-Hsuan He, Tzu-Ying Lin, Tony Eight Sung, Tzu-Ying Yen, Shih-Chung Hsieh, Jui-Hua Yang, Chia-Ron Huang, Wei-Jan Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei Taiwan Graduate Institute of Cancer 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 Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taipei Taiwan TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei Taiwan Cancer Center Wan Fang Hospital Taipei Medical University Taipei Taiwan School of Pharmacy College of Medicine National Taiwan University Taipei Taiwan Warshel Institute for Computational Biology School of Medicine The Chinese University of Hong Kong (Shenzhen) Shenzhen China Division of Translational Toxicology National Institute of Environmental Health Sciences National Institutes of Health Durham NC United States School of Pharmacy Taipei Medical University Taipei Taiwan

Cyclin-dependent kinase 8 (CDK8) plays a crucial role in the transforming growth factor beta (TGF-β) signaling pathway, which is critical to the pathology of idiopathic pulmonary fibrosis (IPF). CDK8 promotes the epithelial-mesenchymal transition (EMT) and excessive extracellular matrix (ECM) deposition, making it a promising target for IPF treatment. This study focused on optimizing F059–1017, a previously identified CDK8 inhibitor, to enhance its potency. Through integrated structure-based modifications, a series of compounds was synthesized, and their inhibitory effects on CDK8 were tested. Results indicated that substituting with cyclopentanone significantly improved the inhibitory activity, and compound 4j demonstrated the best potency (IC₅₀ = 16 nM). Notably, compared to F059–1017, its potency increased 35-fold, and kinase profiling revealed that the compound was selective for CDK8. Compound 4j inhibited the TGF-β1-induced EMT, cell migration, and morphological changes in A549 cells at a concentration of 0.1 μM and inhibited ECM and EMT protein expressions. In addition, the compound blocked TGF-β1-induced transcriptional changes and inhibited Smad3 and RNA polymerase II phosphorylation. These results highlight the potential of the optimized CDK8 inhibitor as a prospective drug for IPF treatment. © 2025 The Authors

关键词： Cyclin-dependent protein kinase 8 Epithelial-mesenchymal transition Indolin-2-one, Idiopathic pulmonary fibrosis Structural optimization Transforming growth factor beta

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