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Interleukin-38-overexpressing adenovirus infection in dendritic cell-based treatment enhances immunotherapy for allergic asthma via inducing Foxp3⁺ regulatory T cells

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Biomedicine and pharmacotherapy 2024年 181卷 117738-117738页

作者： Chuang, Hsiao-Chi Chang, Jer-Hwa Fan, Yen-Yi Hsieh, Chia-Ling Lee, Yueh-Lun School of Respiratory Therapy College of Medicine Taipei Medical University Taipei Taiwan Division of Pulmonary Medicine Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Division of Pulmonary Medicine Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Pulmonary Research Center Wan Fang Hospital Taipei Medical University Taipei Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan The Ph.D. Program for Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan Department of Microbiology and Immunology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Cell Physiology and Molecular Image Research Center Wan Fang Hospital Taipei Medical University Taipei Taiwan

Allergic asthma is a chronic disease tied to unusual immune reactions involving type 2 T helper (Th2) cells specific to allergens. dendritic cells (dCs) play a crucial role in guiding T-cell responses. Regulatory T (Treg) cells have the ability to suppress effector T-cell responses, and interleukin (IL)-38 is involved in Treg cell differentiation. In this study, we explored impacts of IL-38 on the activation and function of dCs, and we then developed an IL-38-overexpressing adenovirus (Ad-IL38) to evaluate its effectiveness in treating allergic asthma in mice through the adaptive transfer of Ad-IL38-infected dCs (IL38-dCs). Treating lipopolysaccharide (LPS)-activated bone marrow-derived dCs with recombinant IL-38 reduced cluster of differentiation 80 (Cd80), Cd86, and major histocompatibility complex (MHC) II expressions and decreased IL-1β, IL-6, and tumor necrosis factor (TNF)-α while increasing IL-10 secretion. The simultaneous culture of these semi-mature dCs with allogeneic Cd4⁺ T cells facilitated the production of Forkhead box protein P3-positive (Foxp3⁺) Treg cells. A transcriptomic analysis revealed downregulation of the Chil3, Inhba, and Ctgf genes that are crucial for regulating inflammatory responses and cytokine-mediated signaling pathways in IL-38-treated dCs. In an animal model of asthma, IL38-dC treatment effectively decreased levels of an ovalbumin (OVA)-specific immunoglobulin E (IgE) antibody in serum, attenuated the severity of airway hyperresponsiveness, reduced the production of Th2-type cytokines (IL-4, IL-5, and IL-13) and proinflammatory cytokines (IL-6 and TNF-α) in bronchoalveolar lavage fluid, lowered expressions of the Th2-related cytokines IL-25 and thymic stromal-derived lymphopoietin (TSLP) by lung epithelial cells, and mitigated airway inflammation. Notably, enhanced expression of Foxp3⁺ Treg cells was linked to increased mRNA levels of transforming growth factor (TGF)-β production in vivo. In conclus

关键词： Adenovirus Allergic asthma dendritic cell Interleukin-38 T cell

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Structure-guided engineering of Cd112 receptor variants for optimized immunotherapy

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Molecular Therapy 2025年

作者： Singh, Srishti Julia, Estefania Kalita, Parismita Mason, Charlotte Ming, Qianqian Lee-Sam, Ansar Gordon, Sumai Buitrago, Maria Emilia Leung, daisy W. Hwu, Patrick Luca, Vincent C. Department of Immunology H. Lee Moffitt Cancer Center and Research Institute Tampa 33612 FL United States Cancer Biology Ph.D. Program University of South Florida Tampa 33612 FL United States Department of Clinical Science H. Lee Moffitt Cancer Center and Research Institute Tampa 33612 FL United States Division of Infectious Diseases Department of Medicine Washington University School of Medicine in St. Louis St. Louis MO United States

The immune checkpoint protein, Cd112 receptor (Cd112R, also known as PVRIG), suppresses T and natural killer (NK) cell activation upon binding to tumor-expressed Cd112 (Nectin-2) ligands. Here, we determine the structure of the Cd112-Cd112R complex and use it to guide the engineering of multiple Cd112-targeting immunotherapy candidates. The 2.2 Å-resolution crystal structure reveals an antiparallel, lock-and-key binding mode in which Cd112R disrupts Cd112 homodimerization. Structural analysis informed directed evolution campaigns focused on remodeling the Cd112-Cd112R interface, resulting in the isolation of Cd112R mutants with greatly increased expression and Cd112-binding affinity. The highest-affinity variant, Cd112R^IVE, potently inhibits Cd112-Cd112R interactions when utilized as a soluble Cd112 trap. Furthermore, incorporating Cd112R variants into chimeric antigen receptors (CARs) and T cell engagers (TCEs) leads to more robust T cell activation and killing of Cd112⁺ triple-negative breast cancer (TNBC) cells compared with wild-type Cd112R. This strategy demonstrates how structural insights can be leveraged to efficiently generate panels of “affinity-tuned” biologics for immunotherapy. © 2025 The American Society of Gene and Cell Therapy

关键词： CAR T cells Cd112 Cd112R checkpoint blockade immunotherapy protein engineering structural biology T cell engagers

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Gene set correlation enrichment analysis for interpreting and annotating gene expression profiles

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Nucleic Acids Research 2024年第3期52卷 E17页

作者： Chang, Lan-Yun Lee, Meng-Zhan Wu, Yujia Lee, Wen-Kai Ma, Chia-Liang Chang, Jun-Mao Chen, Ciao-Wen Huang, Tzu-Chun Lee, Chia-Hwa Lee, Jih-Chin Tseng, Yu-Yao Lin, Chun-Yu Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu 300 Taiwan School of Medical Laboratory Science and Biotechnology College of Medical Science and Technology Taipei Medical University New Taipei City 235 Taiwan Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) National Yang Ming Chiao Tung University Hsinchu 300 Taiwan TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei 110 Taiwan Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University New Taipei City 235 Taiwan Department of Otolaryngology-Head and Neck Surgery Tri-Service General Hospital National Defense Medical Center Taipei 110 Taiwan Department of Food Science Nutrition and Nutraceutical Biotechnology Shih Chien University Taipei 104 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu 300 Taiwan Cancer and Immunology Research Center National Yang Ming Chiao Tung University Taipei 112 Taiwan Institute of Data Science and Engineering National Yang Ming Chiao Tung University Hsinchu 300 Taiwan School of Dentistry Kaohsiung Medical University Kaohsiung 807 Taiwan

Pathway analysis, including nontopology-based (non-TB) and topology-based (TB) methods, is widely used to interpret the biological phenomena underlying differences in expression data between two phenotypes. By considering dependencies and interactions between genes, TB methods usually perform better than non-TB methods in identifying pathways that include closely relevant or directly causative genes for a given phenotype. However, most TB methods may be limited by incomplete pathway data used as the reference network or by difficulties in selecting appropriate reference networks for different research topics. Here, we propose a gene set correlation enrichment analysis method, Gscore, based on an expression dataset-derived coexpression network to examine whether a differentially expressed gene (dEG) list (or each of its dEGs) is associated with a known gene set. Gscore is better able to identify target pathways in 89 human disease expression datasets than eight other state-of-the-art methods and offers insight into how disease-wide and pathway-wide associations reflect clinical outcomes. When applied to RNA-seq data from COVId-19-related cells and patient samples, Gscore provided a means for studying how dEGs are implicated in COVId-19-related pathways. In summary, Gscore offers a powerful analytical approach for annotating individual dEGs, dEG lists, and genome-wide expression profiles based on existing biological knowledge. © 2024 Oxford University Press. All rights reserved.

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Towards efficient density functional theory calculations without self-interaction: The Fermi-Löwdin orbital self-interaction correction

arXiv

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arXiv 2019年

作者： Jackson, K.A. Peralta, J.E. Joshi, R.P. Withanage, K.P. Trepte, K. Sharkas, K. Johnson, A.I. Physics Department and Science of Advanced Materials Ph.D. Program Central Michigan University Mt. PleasantMI United States

The Fermi-Löwdin orbital (FLO) approach to the Perdew-Zunger self-interaction correction (PZ-SIC) to density functional theory (dFT) is described and an improved approach to the problem of optimizing the Fermi-orbitals in order to minimize the dFT-SIC total energy is introduced. To illustrate the use of the FLO-SIC method, results are given for several applications involving problems where self-interaction errors are pronounced. Copyright © 2019, The Authors. All rights reserved.

关键词： density functional theory

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Ultrasensitive detection of ornidazole–antibiotic drug residues in water using NiMOFs functionalized MWCNT modified electrode

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Microchemical Journal 2024年 197卷

作者： Vignesh, Kondusamy Senthil Kumar, Annamalai Arumugam Napoleon, Ayyakannu Kuo, Chih-Yu Yusuf, Kareem Govindasamy, Mani Nano and Bioelectrochemistry Research Laboratory Carbon dioxide Research and Green Technology Centre and Department of Chemistry School of Advanced Sciences Vellore Institute of Technology Vellore 632 014 India Department of Chemistry School of Advanced Sciences Vellore Institute of Technology Vellore 632 014 India International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei 10608 Taiwan Department of Chemistry College of Science King Saud University Riyadh 11451 Saudi Arabia Centre for Applied Research Saveetha School of Engineering Saveetha Institute of Medical and Technical Sciences (SIMATS) Tamil Nadu Chennai 602105 India Research Center for Intelligence Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan

Nitroimidazole-based drugs are widely used as an antibiotic for the treatment of anaerobic bacterial and parasite illnesses. The widespread use of these drugs in animal feed and the consequent environmental pollution have become significant concerns in recent years. Simple, sensitive, and rapid detection of the antibody in various real samples is demanding research interest. Herein, we report a Nickel-metal organic framework functionalized Multiwalled Carbon nanotubes modified glassy carbon electrode (MWCNT@NiMOFs) as an ultrasensitive and rapid voltammetric sensor for the detection of ornidazole (ORdZ) in a neutral ph solution. The MWCNT@NiMOFs were prepared using a microwave-assisted solvothermal technique accompanied by an ultrasonication method. The designed MWCNT@NiMOFs offered a low charge transfer resistance (R_ct) of 141 Ω along with excellent electrocatalytic activity, and high current density at the lowered cathodic peak potential (-0.62 V vs Ag/AgCl) for ORdZ detection. The surface adsorption capacity (Γ_s) in terms of surface excess and heterogeneous charge transfer rate constant (k⁰) of the MWCNT@NiMOFs were calculated to be 3.29 × 10^-9 mol cm⁻² and 5.33 × 10^-3 cm s⁻¹, respectively. Under an optimal working condition, differential pulse voltammetry measurements of ORdZ have shown concentration linearity in a window, 100 nm to 10 µM range with excellent sensitivity, 5.69 × 10^-5A µM⁻¹ cm⁻², and detection limit, 26 nM (3.3/s). The designed MWCNT@NiMOFs offered appreciable reproducibility, and repeatability up to 30 days of storage time. The real-time quantitative evaluation of ORdZ in human urine and tap water specimens was done along with ∼ 100 % recovery values. Since the new approach is simple, selective, and separation-free, it can be extendable to a variety of real-time practical applications. © 2024 Elsevier B.V.

关键词： Electrocatalytic reduction Multi-walled carbon nanotubes Nickel Metal-organic frameworks Ornidazole drug Ultrasensitive detection

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Retraction notice to "Organic composts as A vehicle for the entry of microplastics into the environment: A comprehensive review" [Sci. Total Environ. 892 (2023) 164758]

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The science of the total environment 2024年 957卷 177731页

作者： Van-Re Le Minh-Ky Nguyen Hoang-Lam Nguyen Chitsan Lin Md Refat Jahan Rakib Van-Anh Thai Van-Giang Le Guilherme Malafaia Abubakr M Idris Ho Chi Minh City University of Food Industry (HUFI) 140 Le Trong Tan Street Tan Phu District Ho Chi Minh City 700000 Viet Nam. Faculty of Environment and Natural Resources Nong Lam University of Ho Chi Minh City Hamlet 6 Linh Trung Ward Thu Duc City Ho Chi Minh City 700000 Viet Nam Ph.D. Program in Maritime Science and Technology National Kaohsiung University of Science and Technology Kaohsiung 81157 Taiwan. Department of Civil Engineering McGill University Montreal Canada. Ph.D. Program in Maritime Science and Technology National Kaohsiung University of Science and Technology Kaohsiung 81157 Taiwan Department of Marine Environmental Engineering National Kaohsiung University of Science and Technology Kaohsiung 81157 Taiwan. Department of Fisheries and Marine Science Faculty of Science Noakhali Science and Technology University Noakhali 3814 Bangladesh. Institute of Aquatic Science and Technology National Kaohsiung University of Science and Technology Kaohsiung City 81157 Taiwan. Central Institute for Natural Resources and Environmental Studies Vietnam National University Hanoi 111000 Viet Nam. Post-Graduation Program in Ecology Conservation and Biodiversity Federal University of Uberlândia Uberlândia MG Brazil Post-Graduation Program in Biotechnology and Biodiversity Federal University of Goiás Goiânia GO Brazil Post-Graduation Program in Conservation of Cerrado Natural Resources Goiano Federal Institute Urutaí GO Brazil. Department of Chemistry College of Science King Khalid University 61431 Abha Saudi Arabia Research Center for Advanced Materials Science (RCAMS) King Khalid University Abha 61421 Saudi Arabia.

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OpenMM 8: Molecular dynamics Simulation with Machine Learning Potentials

arXiv

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arXiv 2023年

作者： Eastman, Peter Galvelis, Raimondas Peláez, Raúl P. Abreu, Charlles R.A. Farr, Stephen E. Gallicchio, Emilio Gorenko, Anton Henry, Michael M. Hu, Frank Huang, Jing Krämer, Andreas Michel, Julien Mitchell, Joshua A. Pande, Vijay S. Rodrigues, João P.G.L.M. Rodriguez-Guerra, Jaime Simmonett, Andrew C. Singh, Sukrit Swails, Jason Turner, philip Wang, Yuanqing Zhang, Ivy Chodera, John d. de Fabritiis, Gianni Markland, Thomas E. Department of Chemistry Stanford University StanfordCA94305 United States Acellera Labs C Dr Trueta 183 Barcelona08005 Spain C Dr. Aiguader 88 Barcelona08003 Spain Chemical Engineering Department School of Chemistry Federal University of Rio de Janeiro Rio de Janeiro68542 Brazil Redesign Science Inc. 180 Varick St. New YorkNY10014 United States EaStCHEM School of Chemistry University of Edinburgh EH9 3FJ United Kingdom Department of Chemistry and Biochemistry Brooklyn College The City University of New York NY United States Ph.D. Program in Chemistry Ph.D. Program in Biochemistry The Graduate Center of the City University of New York New YorkNY United States Stream HPC Koningin Wilhelminaplein 1 - 40601 Amsterdam1062 HG Netherlands Computational and Systems Biology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New YorkNY10065 United States Key Laboratory of Structural Biology of Zhejiang Province School of Life Sciences Westlake University 18 Shilongshan Road Zhejiang Hangzhou310024 China Department of Mathematics and Computer Science Freie Universität Berlin Arnimallee 12 Berlin14195 Germany The Open Force Field Initiative Open Molecular Software Foundation DavisCA95616 United States Andreessen Horowitz 2865 Sand Hill Rd Menlo ParkCA94025 United States Department of Structural Biology Stanford University StanfordCA94305 United States Charité Universitätsmedizin Berlin In silico Toxicology and Structural Bioinformatics Virchowweg 6 Berlin10117 Germany Laboratory of Computational Biology National Heart Lung and Blood Institute National Institutes of Health BethesdaMD20892 United States Entos Inc. 9310 Athena Circle La Jolla CA92037 United States College of Engineering Virginia Polytechnic Institute State University BlacksburgVA24061 United States Simons Center for Computational Physical Chemistry Center for Data Science New York University 24 Waverly Place New YorkNY10004 United States T

Machine learning plays an important and growing role in molecular simulation. The newest version of the OpenMM molecular dynamics toolkit introduces new features to support the use of machine learning potentials. Arbitrary PyTorch models can be added to a simulation and used to compute forces and energy. A higher-level interface allows users to easily model their molecules of interest with general purpose, pretrained potential functions. A collection of optimized CUdA kernels and custom PyTorch operations greatly improves the speed of simulations. We demonstrate these features on simulations of cyclin-dependent kinase 8 (CdK8) and the green fluorescent protein (GFP) chromophore in water. Taken together, these features make it practical to use machine learning to improve the accuracy of simulations at only a modest increase in cost. Copyright © 2023, The Authors. All rights reserved.

关键词： Machine learning

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Ultrasensitive and selective electrochemical detection of hydroquinone using electropolymerized 7-amino cephalosporanic acid modified GCE

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Surface and Coatings Technology 2025年 512卷

作者： Sathya, H. Varatharajan, Pandiaraja Ashkar, M.A. Chandhru, M. Govindasamy, Mani Rani, S. Kutti Vasimalai, N. Department of Chemistry B.S. Abdur Rahman Crescent Institute of Science and Technology Chennai Vandalur600 048 India International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Department of Physics B.S. Abdur Rahman Crescent Institute of Science and Technology Chennai Vandalur600 048 India Tamil Nadu Chennai602105 India Research Center for Intelligent Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan

Industrial wastewater pollution harms ecosystems and hinders sustainable development growth. Particularly, hydroquinone (HQ) has transitioned from a commercial chemical to an environmental hazard because of its extensive use in beauty products, pharmaceuticals, chemicals, and food industries. Therefore, developing electrochemical sensors for the detection of HQ is very important for environmental safety. Herein, the 7-ACA monomer was electropolymerized on the glassy carbon electrode (GCE) surface to examine the electrochemical oxidation of HQ utilizing CV (cyclic voltammetry) and dPV (differential pulse voltammetry) techniques. Scanning electron microscopy (SEM) characterization verified the deposition of the p-7-ACA on the glassy carbon electrode (GCE) surface. The designed p-7-ACA@GCE sensor exhibited better electrocatalytic properties. The acquired dPV observations for the p-7-ACA@GCE demonstrated excellent limit of detection (LOd) 8.86 nmol L−1 and broad linear range (0.33 μM to 955 μM) for the detection of HQ. The developed sensor exhibits excellent repeatability, reproducibility, selectivity and better cyclic stability. In addition, the fabricated p-7-ACA@GCE was used to determine the HQ in a different environmental water sample. © 2025

关键词： Cyclic voltammetry

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Tn antigen suppresses lipopolysaccharide-induced dermatitis via Clec10a

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Biochemical and Biophysical Research Communications 2025年 772卷 152024页

作者： Shigematsu, Katsunobu Matsuda, Kenshiro Nabekura, Tsukasa Kanemaru, Kazumasa Shibuya, Kazuko Tateno, Hiroaki Shibuya, Akira Department of Immunology Institute of Medicine University of Tsukuba Ibaraki Tsukuba 305-8577 Japan Ph.D. Program in Humanics University of Tsukuba Ibaraki Tsukuba 305-8577 Japan Life Science Center for Survival Dynamics Tsukuba Advanced Research Alliance University of Tsukuba Ibaraki Tsukuba 305-8577 Japan R&D Center for Innovative Drug Discovery University of Tsukuba Ibaraki Tsukuba 305-8577 Japan Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology (AIST) Tsukuba Central 6 1-1-1 Higashi Ibaraki Tsukuba 305-8566 Japan

C-type lectin domain family 10 member A (Clec10a), also called macrophage galactose-type lectin 1 (MGL1) or Cd301a, is expressed on myeloid cells, including macrophages in the skin. Several pieces of evidence suggest that Clec10a physically binds to O-linked mucin-like molecules, but the functional ligand that mediates signaling in macrophages remains undetermined. We previously reported that house dust mite (HdM) treatment on the skin produced a greater amount of Toll-like receptor 4 (TLR4)-mediated inflammatory cytokines from macrophage in Clec10a-deficient mice than in wild-type (WT) mice, suggesting that a functional ligand for Clec10a contained in HdM inhibited TLR4-mediated skin macrophage activation. In this study, we investigated the glycan structure of a functional Clec10a ligand (Clec10a-L) contained in HdM. We showed that Clec10a bound to O-linked mucin-like molecules such as polyacrylamide (PAA)-conjugated Tn antigen (Tn antigen-PAA), Core1-PAA, LacNAc-PAA, Lewis A-PAA, and Lewis X-PAA. Among them, plate-coated Tn antigen-PAA, Lewis A-PAA, and Lewis X-PAA activated Clec10a expressed on the reporter cells. However, intradermal injection of only Tn antigen-PAA, but not Lewis A-PAA and Lewis X-PAA, ameliorated LPS-induced dermatitis in WT but not Clec10a-deficient mice. Moreover, Tn antigen-PAA suppressed LPS-induced production of inflammatory cytokines IL-6 and TNF-α by bone marrow-derived cultured macrophage in vitro. These results indicate that Tn antigen is a functional Clec10a-L in HdM that suppresses TLR4-induced macrophage activation in the skin. © 2025 The Authors

关键词： Atopic dermatitis House dust mite NC/Nga mouse Toll-like receptors

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P-239 Effectiveness and safety of palliative surgical interventions for bowel obstruction in advanced staged colorectal cancer: A systematic review and network meta-analysis

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Annals of Oncology 2023年 34卷 S100-S100页

作者： N. Vo K. Tran N. Nguyen M. doan K. Tam Department of Hepatobiliary and Pancreatic Surgery Cho Ray Hospital Ho Chi Minh City Viet Nam Ho Chi Minh City Viet Nam International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei City Taiwan Programs of Nutrition Science Schol of Life Science National Taiwan Normal University Taipei City Taiwan Division of General Surgery Department of Surgery College of Medicine Taipei Medical University Taipei City Taiwan

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