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The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2

Cell 2025年

作者： Pekar, Jonathan E. Lytras, Spyros Ghafari, Mahan Magee, Andrew F. Parker, Edyth Wang, Yu Ji, Xiang Havens, Jennifer L. Katzourakis, Aris Vasylyeva, Tetyana I. Suchard, Marc A. Hughes, Alice C. Hughes, Joseph Rambaut, Andrew Robertson, David L. Dellicour, Simon Worobey, Michael Wertheim, Joel O. Lemey, Philippe Institute of Ecology and Evolution University of Edinburgh Edinburgh United Kingdom Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla 92093 CA United States Department of Biomedical Informatics University of California San Diego La Jolla 92093 CA United States Department of Medicine University of California San Diego La Jolla 92093 CA United States Division of Systems Virology Department of Microbiology and Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan Medical Research Council University of Glasgow Centre for Virus Research Glasgow United Kingdom Department of Biology University of Oxford Oxford United Kingdom Department of Human Genetics David Geffen School of Medicine University of California Los Angeles Los Angeles 90095 CA United States Department of Immunology and Microbiology The Scripps Research Institute La Jolla 92037 CA United States Institute of Genomics and Global Health Redeemer's University Osun State Ede Nigeria Department of Computer Science and Engineering University of California San Diego La Jolla 92093 CA United States Department of Mathematics School of Science and Engineering Tulane University New Orleans LA United States Department of Population Health and Disease Prevention University of California Irvine Irvine 92617 CA United States Department of Biostatistics Fielding School of Public Health University of California Los Angeles Los Angeles 90095 CA United States Department of Computational Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles 90095 CA United States School of Biological Sciences University of Hong Kong Hong Kong Hong Kong China Biodiversity Green Development Foundation Beijing China Spatial Epidemiology Lab (SpELL) Université Libre de Bruxelles CP160/12 50 av. FD Roosevelt Bruxelles 1050 Belgium Department of Microbiology Immunology and Transplantation Rega Institute

The emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 led to increased sampling of sarbecoviruses circulating in horseshoe bats. Employing phylogenetic inference while accounting for recombination of bat sarbecoviruses, we find that the closest-inferred bat virus ancestors of SARS-CoV and SARS-CoV-2 existed less than a decade prior to their emergence in humans. Phylogeographic analyses show bat sarbecoviruses traveled at rates approximating their horseshoe bat hosts and circulated in Asia for millennia. We find that the direct ancestors of SARS-CoV and SARS-CoV-2 are unlikely to have reached their respective sites of emergence via dispersal in the bat reservoir alone, supporting interactions with intermediate hosts through wildlife trade playing a role in zoonotic spillover. These results can guide future sampling efforts and demonstrate that viral genomic regions extremely closely related to SARS-CoV and SARS-CoV-2 were circulating in horseshoe bats, confirming their importance as the reservoir species for SARS viruses. © 2025 The Authors

关键词： molecular epidemiology phylogeography sarbecoviruses virus evolution

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In vitro activity of imipenem/relebactam, meropenem/vaborbactam and comparators against Enterobacterales from patients with intra-abdominal infections: Results of the study for Monitoring Antimicrobial Resistance Trends (SMART) in Taiwan, 2020

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Journal of Microbiology, Immunology and Infection 2023年第1期56卷 75-83页

作者： Lee, Yu-Lin Ko, Wen-Chien Hsueh, Po-Ren Department of Internal Medicine Changhua Christian Hospital Changhua Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University Taichung Taiwan Department of Internal Medicine Chung Shan Medical University Hospital Taichung Taiwan Department of Medicine College of Medicine National Cheng Kung University Tainan Taiwan Departments of Laboratory Medicine and Internal Medicine China Medical University Hospital Taichung Taiwan School of Medicine China Medical University Taichung Taiwan Ph.D Program for Aging School of Medicine China Medical University Taichung Taiwan Departments of Laboratory Medicine and Internal Medicine National Taiwan University Hospital National Taiwan University College of Medicine Taipei Taiwan

Background: Multi-drug resistant Enterobacterales is a growing health threat. Imipenem/relebactam and meropenem/vaborbactam, are not clinically used in Taiwan and the susceptibility is lack from routine laboratory tests. Methods: Broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints criteria. Isolates that were not susceptible to imipenem (MIC ≥ 2 mg/L), imipenem/relebactam (MIC ≥ 2 mg/L), or ceftolozane-tazobactam (MIC ≥ 4 mg/L) were selected for further molecular testing for genes encoding extended-spectrum beta-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases by multiplex PCR assays. Results: A total of 290 Enterobacterales isolates from 9 participating hospitals were collected in 2020. Escherichia coli (n = 135, 46.6%) and Klebsiella pneumoniae (n = 88, 30.3%) were two leading pathogens of all Enterobacterales isolates. The antimicrobial agents with susceptibility rates more than 90% included amikacin (99.3%, 288/290), ertapenem (90.0%, 261/290), meropenem (97.2%, 282/290), imipenem/relebactam (94.8%, 275/290) and meropenem/vaborbactam (99.3%, 288/290). K. pneumoniae isolates were less susceptible to ertapenem, imipenem, meropenem, piperacillin-tazobactam and ceftozolane/tazobactam than E. coli (all p < 0.05). ESBL, AmpC, and carbapenemase were detected in 40.5% (17/42), 45.2% (19/42) and 11.9% (5/42) among tested isolates, respectively. The 5 carbapenemase genes included 4 bla_KPC and 1 bla_IMP. The imipenem-non-susceptible isolates (n = 30) had higher susceptibility rates to meropenem/vaborbactam (93.3%, 28/30) than imipenem/relebactam (50%, 12/30) (p < 0.05). Conclusions: Imipenem/relebactam and meropenem/vaborbactam had excellent efficacy against Enterobacterales isolates. Meropenem/vaborbactam allowed better salvage therapy for carbapenem-resistant Enterobacterales infections. © 2022

关键词： Carbapenem resistance Cross resistance Enterobacterales Multidrug resistance (MDR) Novel β-lactam combination agents

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Phosphoproteomics of Klebsiella pneumoniae NTUH-K2044 reveals a tight link between tyrosine phosphorylation and virulence

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Molecular and Cellular proteomics 2009年第12期8卷 2613-2623页

作者： Lin, Miao-Hsia Hsu, Tung-Li Lin, Shu-Yu Pan, Yi-Jiun Jan, Jia-Tsrong Wang, Jin-Town Khoo, Kay-Hooi Wu, Shih-Hsiung Institute of Biochemical Sciences College of Life Sciences National Taiwan University Taipei 106 Taiwan Institute of Biological Chemistry Academia Sinica Taipei 115 Taiwan National Research Program for Genomic Medicine Core Facilities for Proteomics Research Academia Sinica Taipei 115 Taiwan Genomics Research Center Academia Sinica Taipei 115 Taiwan Department of Microbiology National Taiwan University College of Medicine Taipei 100 Taiwan

Encapsulated Klebsiella pneumoniae is the predominant causative agent of pyogenic liver abscess, an emerging infectious disease that often complicates metastatic meningitis or endophthalmitis. The capsular polysaccharide on K. pneumoniae surface was determined as the key to virulence. Although the regulation of capsular polysaccharide biosynthesis is largely unclear, it was found that protein-tyrosine kinases and phosphatases are involved. Therefore, the identification and characterization of such kinases, phosphatases, and their substrates would advance our knowledge of the underlying mechanism in capsule formation and could contribute to the development of new therapeutic strategies. Here, we analyzed the phosphoproteome of K. pneumoniae NTUH-K2044 with a shotgun approach and identified 117 unique phosphopeptides along with 93 in vivo phosphorylated sites corresponding to 81 proteins. Interestingly, three of the identified tyrosine phosphorylated proteins, namely protein-tyrosine kinase (Wzc), phosphomannomutase (ManB), and undecaprenyl-phosphate glycosyltransferase (WcaJ), were found to be distributed in the cps locus and thus were speculated to be involved in the converging signal transduction of capsule biosynthesis. Consequently, we decided to focus on the lesser studied ManB and WcaJ for mutation analysis. The capsular polysaccharides of WcaJ mutant (WcaJY5F) were dramatically reduced quantitatively, and the LD₅₀ increased by 200-fold in a mouse peritonitis model compared with the wild-type strain. However, the capsular polysaccharides of ManB mutant (ManBY26F) showed no difference in quantity, and the LD₅₀ increased by merely 6-fold in mice test. Our study provided a clear trend that WcaJ tyrosine phosphorylation can regulate the biosynthesis of capsular polysaccharides and result in the pathogenicity of K. pneumoniae NTUH-K2044. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

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A Bayesian mixture model for clustering on the stiefel manifold

arXiv

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arXiv 2017年

作者： Sengupta, Subhajit Pal, Subhadip Mitra, Riten Guo, Ying Banerjee, Arunava Ji, Yuan Program for Computational Genomics and Medicine NorthShore University HealthSystem Department of Bioinformatics and Biostatistics University of Louisville Department of Biostatistics and Bioinformatics Emory University Department of Computer and Information Science and Engineering University of Florida Department of Public Health Sciences University of Chicago

Analysis of a Bayesian mixture model for the Matrix Langevin distribution on the Stiefel manifold is presented. The model exploits a particular parametrization of the Matrix Langevin distribution, various aspects of which are elaborated on. A general, and novel, family of conjugate priors, and an efficient Markov chain Monte Carlo (MCMC) sampling scheme for the corresponding posteriors is then developed for the mixture model. Theoretical properties of the prior and posterior distributions, including posterior consistency, are explored in detail. Extensive simulation experiments are presented to validate the efficacy of the framework. Real-world examples, including a large scale neuroimaging dataset, are analyzed to demonstrate the computational tractability of the approach. Copyright © 2017, The Authors. All rights reserved.

关键词： Mixtures

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Worm Perturb-Seq: massively parallel whole-animal RNAi and RNA-seq

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Nature communications 2025年第1期16卷 4785页

作者： Hefei Zhang Xuhang Li Dongyuan Song Onur Yukselen Shivani Nanda Alper Kucukural Jingyi Jessica Li Manuel Garber Albertha J M Walhout Department of Systems Biology University of Massachusetts Chan Medical School Worcester MA USA. Bioinformatics Interdepartmental Ph.D. Program University of California Los Angeles CA USA. Department of Genetics and Genome Sciences University of Connecticut Health Center Farmington CT USA. Via Scientific Inc. Cambridge MA USA. Pathology Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USA. Department of Genomics and Computational Biology University of Massachusetts Chan Medical School Worcester MA USA. Department of Statistics and Data Science Department of Biostatistics Department of Computational Medicine and Department of Human Genetics University of California Los Angeles CA USA. Department of Genomics and Computational Biology University of Massachusetts Chan Medical School Worcester MA USA. manuel.garber@umassmed.edu. Department of Systems Biology University of Massachusetts Chan Medical School Worcester MA USA. marian.walhout@umassmed.edu.

Transcriptomes provide highly informative molecular phenotypes that, combined with gene perturbation, can connect genotype to phenotype. An ultimate goal is to perturb every gene and measure transcriptome changes, however, this is challenging, especially in whole animals. Here, we present 'Worm Perturb-Seq (WPS)', a method that provides high-resolution RNA-sequencing profiles for hundreds of replicate perturbations at a time in living animals. WPS introduces multiple experimental advances combining strengths of Caenhorhabditis elegans genetics and multiplexed RNA-sequencing with a novel analytical framework, EmpirDE. EmpirDE leverages the unique power of large transcriptomic datasets and improves statistical rigor by using gene-specific empirical null distributions to identify DEGs. We apply WPS to 103 nuclear hormone receptors (NHRs) and find a striking 'pairwise modularity' in which pairs of NHRs regulate shared target genes. We envision the advances of WPS to be useful not only for C. elegans, but broadly for other models, including human cells.

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PCC-hippocampal functional connectivity associated with stress biomarker changes after meditation training for healthy adults

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Neuroscience letters 2025年 138272页

作者： Diane Joss Gunes Sevinc John W Denninger Sat Bir Singh Khalsa Elizabeth A Hoge Manoj Bhasin Jeffery A Dusek Eric Macklin Towia A Libermann Gregory L Fricchione Herbert Benson Sara W Lazar Department of Psychiatry Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA. Electronic address: djoss@cha.harvard.edu. Department of Psychiatry Massachusetts General Hospital Boston MA USA. Harvard Medical School Boston MA USA Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital Boston MA USA. Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital Boston MA USA Department of Medicine Brigham and Women's Hospital Harvard Medical School USA. Department of Psychiatry Georgetown University Medical Center Washington DC USA. Department of Biomedical Informatics Emory University School of Medicine Atlanta GA USA. Susan Samueli Integrative Health Institute University of California-Irvine Irvine CA USA School of Medicine University of California-Irvine Irvine CA USA. Harvard Medical School Boston MA USA. Genomics Proteomics Bioinformatics and Systems Biology Center Beth Israel Deaconess Medical Center Boston MA USA.

Meditation training has been shown to improve physical and mental health and promote neural plasticity, but more research is needed on the relationships between these effects. This study analyzed the Resting State Functional Connectivity (RSFC) of posterior cingulate cortex (PCC) among 94 chronically stressed but otherwise healthy adults randomized 1:1:1 to receive eight weeks of in-person one-on-one interventions focused either on meditation (n = 32), yoga (n = 31), or stress education (n = 31). We found only in the meditation arm, there was a significant reduction of PCC RSFC with the left hippocampus (p < 0.05, FWE corrected). Post-intervention changes of PCC-hippocampal RSFC were significantly (all p ≤ 0.01) correlated with changes of perceived stress (r = 0.54), allostatic load index (r = 0.58), and NF-κB anti-inflammatory gene expression (r = -0.55), suggesting the neural effects of meditation are closely associated with biomarkers of physical wellness. No significant changes with PCC RSFC were observed within the yoga or stress education arm, suggesting this neurobiological mechanism might be unique to meditation training.

关键词： Biomarker Inflammation MRI Meditation Wellbeing Wellness Yoga

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Evaluation of using WGS/WES to characterize ACMG actionable genes in genetic testing reports

Evaluation of using WGS/WES to characterize ACMG actionable ...

引用

2021 IEEE International Conference on bioinformatics and Biomedicine, BIBM 2021

作者： Yang, Wen-Tse Wu, Dong-Chi Liu, Jen-Feng Hong, Jin-Bon Wu, June-Tai Chen, Pei-Lung Chen, Chien-Yu National Taiwan University Department of Biomechatronics Engineering Taipei Taiwan National Taiwan University and Academia Sinica Genome and Systems Biology Degree Program Taipei Taiwan Institute of Molecular Medicine National Taiwan University College of Medicine Taipei Taiwan National Taiwan University Hospital Department of Dermatology Taipei Taiwan Graduate Institute of Medical Genomics and Proteomics National Taiwan University College of Medicine Taipei Taiwan

ISBN: (纸本)9781665401265

Since the American College of Medical Genetics and genomics (ACMG) published recommendations for reporting incidental findings in clinical exome and genome sequencing in 2013, the list of suggested actionable genes appear more and more frequently in the reports of genetic testing. However, the existence of low-coverage regions, no matter happening systematically or randomly, in whole genome sequencing (WGS) or whole exome sequencing (WES) raise the chances of false negatives when reporting pathogenicity in variant discovery. To evaluate the effectivity of different sequencing methods, this study developed a workflow to examine low-coverage regions in ACMG actionable genes (version 2 contains 59 genes) on three groups of sequencing data, including 5 samples of 30X WGS, 41 samples of 40X WGS, and 11 samples of WES. By extracting the ACMG regions of the alignment files, we first found that per-base mean coverage in WES is significantly higher in some chromosomes (2, 5, 6, 9, 13, 14, 17, 18) than the others, and the overall average (44.5) is higher than 30X WGS (32.4) and 40X WGS (36.2). However, the total length of the low-coverage regions in ACMG actionable genes is higher in WES samples: 23 times higher than 40X WGS, and 8 times higher than 30X WGS. When looking into ClinVar significance of pathogenic/likely pathogenic (P/LP) variants (the 2020/03/16 release contains 21,388 P/LP variants falling in the 59 actionable genes), 100% (11/11) WES samples and 80% (4/5) 30X WGS samples have more than 20 P/LP variants in the low-coverage regions, while only 2.4% (1/41) 40X WGS samples have such a risk of missing >20 P/LP variants. We conclude that in order to reduce the possibility of missing clinically significant variants, 40X WGS are more recommended than 30X WGS and WES to achieve satisfied quality of characterizing ACMG actionable genes in genetic testing. © 2021 IEEE.

关键词： Genome

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Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation (vol 21, pg 432, 2018)

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NATURE NEUROSCIENCE 2018年第7期21卷 1015-1015页

作者： Preissl, Sebastian Fang, Rongxin Huang, Hui Zhao, Yuan Raviram, Ramya Gorkin, David U. Zhang, Yanxiao Sos, Brandon C. Afzal, Veena Dickel, Diane E. Kuan, Samantha Visel, Axel Pennacchio, Len A. Zhang, Kun Ren, Bing Ludwig Institute for Cancer Research La Jolla CA USA Center for Epigenomics Department of Cellular and Molecular Medicine University of California San Diego School of Medicine La Jolla CA USA Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA USA Biomedical Sciences Graduate Program University of California San Diego La Jolla CA USA Department of Bioengineering University of California San Diego La Jolla CA USA Environmental Genomics and Systems Biology Division Lawrence Berkeley National Laboratory Berkeley CA USA US Department of Energy Joint Genome Institute Walnut Creek CA USA School of Natural Sciences University of California Merced Merced CA USA Comparative Biochemistry Program University of California Berkeley Berkeley CA USA Institute of Genomic Medicine Moores Cancer Center University of California San Diego School of Medicine La Jolla CA USA

Analysis of chromatin accessibility can reveal transcriptional regulatory sequences, but heterogeneity of primary tissues poses a significant challenge in mapping the precise chromatin landscape in specific cell types. Here we report single-nucleus ATAC-seq, a combinatorial barcoding-assisted single-cell assay for transposase-accessible chromatin that is optimized for use on flash-frozen primary tissue samples. We apply this technique to the mouse forebrain through eight developmental stages. Through analysis of more than 15,000 nuclei, we identify 20 distinct cell populations corresponding to major neuronal and non-neuronal cell types. We further define cell-type-specific transcriptional regulatory sequences, infer potential master transcriptional regulators and delineate developmental changes in forebrain cellular composition. Our results provide insight into the molecular and cellular dynamics that underlie forebrain development in the mouse and establish technical and analytical frameworks that are broadly applicable to other heterogeneous tissues.

关键词： Cell type diversity Chromatin Chromatin analysis Epigenomics

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Distinct adipose progenitor cells emerging with age drive active adipogenesis

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Science (New York, N.Y.) 2025年第6745期388卷 eadj0430页

作者： Wang, Guan Li, Gaoyan Song, Anying Zhao, Yutian Yu, Jiayu Wang, Yifan Dai, Wenting Salas, Martha Qin, Hanjun Medrano, Leonard Dow, Joan Li, Aimin Armstrong, Brian Fueger, Patrick T. Yu, Hua Zhu, Yi Shao, Mengle Wu, Xiwei Jiang, Lei Campisi, Judith Yang, Xia Wang, Qiong A. Department of Molecular and Cellular Endocrinology Arthur Riggs Diabetes and Metabolism Research Institute City of Hope Medical Center Duarte CA USA Department of Integrative Biology and Physiology University of California Los Angeles CA United States Light Microscopy Core City of Hope Medical Center Duarte CA USA The Integrative Genomics Core City of Hope Medical Center Duarte CA USA Division of Developmental and Translational Diabetes and Endocrinology Research City of Hope Medical Center Duarte CA USA Comprehensive Metabolic Phenotyping Core City of Hope Medical Center Duarte CA USA Pathology Core of Shared Resources City of Hope Medical Center Duarte CA USA Comprehensive Cancer Center Beckman Research Institute City of Hope Medical Center Duarte CA USA Children's Nutrition Research Center Department of Pediatrics Baylor College of Medicine Houston TX United States Key Laboratory of Immune Response and Immunotherapy Shanghai Institute of Immunity and Infection Chinese Academy of Sciences Shanghai China Buck Institute for Research on Aging Novato CA United States Bioinformatics Interdepartmental Program University of California Los Angeles CA United States Institute for Quantitative and Computational Biosciences University of California Los Angeles CA United States Molecular and Medical Pharmacology University of California Los Angeles CA United States

Starting at middle age, adults often suffer from visceral adiposity and associated adverse metabolic disorders. Lineage tracing in mice revealed that adipose progenitor cells (APCs) in visceral fat undergo extensive adipogenesis during middle age. Thus, despite the low turnover rate of adipocytes in young adults, adipogenesis is unlocked during middle age. Transplantations quantitatively showed that APCs in middle-aged mice exhibited high adipogenic capacity cell-autonomously. Single-cell RNA sequencing identified a distinct APC population, the committed preadipocyte, age-enriched (CP-A), emerging at this age. CP-As demonstrated elevated proliferation and adipogenesis activity. Pharmacological and genetic manipulations indicated that leukemia inhibitory factor receptor signaling was indispensable for CP-A adipogenesis and visceral fat expansion. These findings uncover a fundamental mechanism of age-dependent adipose remodeling, offering critical insights into age-related metabolic diseases.

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Importance of surface charge of soot nanoparticles in determining inhalation toxicity in mice

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Environmental Science and Pollution Research 2023年第7期30卷 18985-18997页

作者： Hsiao, Ta-Chih Han, Chia-Li Yang, Tzu-Ting Lee, Yueh-Lun Shen, Yu-Fang Jheng, Yu-Teng Lee, Chii-Hong Chang, Jer-Hwa Chung, Kian Fan Kuo, Han-Pin Chuang, Hsiao-Chi Graduate Institute of Environmental Engineering National Taiwan University Taipei Taiwan Master Program in Clinical Genomics and Proteomics College of Pharmacy Taipei Medical University Taipei Taiwan Department of Environmental Engineering and Health Yuanpei University of Medical Technology Hsin Chu City Taiwan Department of Microbiology and Immunology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Environmental Engineering National Center University Tauyoun Taiwan Genome and Systems Biology Degree Program Academia Sinica and National Taiwan University Taipei Taiwan Department of Pathology Taipei City Hospital Heping Fuyou Branch Taipei Taiwan School of Respiratory Therapy College of Medicine Taipei Medical University Taipei Taiwan Division of Pulmonary Medicine Department of Internal Medicine Wan Fang Hospital Taipei Medical University Taipei Taiwan National Heart and Lung Institute Imperial College London London United Kingdom Division of Pulmonary Medicine Department of Internal Medicine School of Medicine 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 Cell Physiology and Molecular Image Research Center Wan Fang Hospital Taipei Medical University Taipei Taiwan

Physicochemical properties of nanoparticles are important in regulating nanoparticle toxicity;however, the contribution of nanoparticle charge remains unclear. The objective of this study was to investigate the pulmonary effects of inhalation of charged soot nanoparticles. We established a stably charged nanoparticle generation system for whole-body exposure in BALB/c mice, which produced positively charged, negatively charged, and neutral soot nanoparticles in a wide range of concentrations. After a 7-day exposure, pulmonary toxicity was assessed, together with proteomics analysis. The charged soot nanoparticles on average carried 1.17–1.35 electric charges, and the sizes for nanoparticles under different charging conditions were all fixed at 69 ~ 72 nm. We observed that charged soot nanoparticles induced cytotoxic LDH and increased lung permeability, with the release of 8-isoprostane and caspase-3 and systemic IL-6 in mice, especially for positively charged soot nanoparticles. Next, we observed that positive-charged soot nanoparticles upregulated Eif2, Eif4, sirtuin, mammalian target of rapamycin (mTOR), peroxisome proliferator-activated receptors (PPAR), and HIPPO-related signaling pathways in the lungs compared with negatively charged soot nanoparticles. HIF1α, sirt1, E-cadherin, and Yap were increased in mice’s lungs by positively charged soot nanoparticle exposure. In conclusion, carbonaceous nanoparticles carrying electric ions, especially positive-charged, are particularly toxic when inhaled and should be of concern in terms of pulmonary health protection. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

关键词： Nanoparticles

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