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deep learning-based air pollution analysis on carbon monoxide in Taiwan

Ecological Informatics 2024年 80卷

作者： Cheng-Hong Yang Po-Hung Chen Chih-Hsien Wu Cheng-San Yang Li-Yeh Chuang Department of Information Management Tainan University of Technology Tainan Taiwan Department of Electronic Engineering National Kaohsiung University of Science and Technology Kaohsiung Taiwan Ph. D. Program in Biomedical Engineering Kaohsiung Medical University Kaohsiung Taiwan School of Dentistry Kaohsiung Medical University Kaohsiung Taiwan Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung Taiwan Division of Plastic and Reconstruction Surgery Department of Surgery Ditmanson Medical Foundation Chia-Yi Christian Hospital Chia-Yi Taiwan Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering I-Shou University Kaohsiung Taiwan

Global air pollution poses a threat to humanity. Specifically, CO directly affects cardiovascular and other organ tissues and leads to numerous chronic diseases and major public health problems. The effective implementation of a deep learning model for predicting variations in CO levels would enable the early formulation of policies for controlling air pollution. In this study, a seasonal gated recurrent unit (SGRU) model, which is a deep learning time-series prediction model, was developed to predict the levels of CO in Taiwan. Atmospheric CO measurements from 2005 to 2021 were collected from the Environmental Protection Administration of Taiwan and preprocessed using the Kalman filter to achieve accurate forecasting. The performance of the proposed SGRU model was compared with that of the autoregressive integrated moving average (ARIMA), seasonal ARIMA, exponential smoothing (ETS), Holt–Winters ETS, support vector regression, and seasonal long short-term memory models in terms of mean absolute percentage error (MAPE) and root mean square error. The SGRU model achieved the lowest MAPE value of 0.94, which demonstrated its superior performance. The construction of an accurate air pollution prediction model can assist government entities in formulating health and social care strategies and in planning future air pollution control measures.

关键词： Air pollution Carbon Monoxide (CO) deep learning Seasonal gated recurrent unit (SGRU)

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Genome-based characterization of conjugative IncHI1B plasmid carrying carbapenemase genes bla VIM-1 , bla IMP-23 , and truncated bla OXA-256 in Klebsiella pneumoniae NTU107224

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Infection, Genetics and Evolution 2023年 110卷

作者： Li-Li Wen Pei-Yun Kuo Tran Thi dieu Thuy Tran Thi Thuy duong Yu-Tsung Huang Po-Ren Hsueh Yu-Chen Chen Cheng-Yen Kao Graduate Institute of Medical Laboratory Science and Biotechnology Yuanpei University of Medical Technology Hsinchu City Taiwan Institute of Microbiology and Immunology College of Life Sciences National Yang Ming Chiao Tung University Taipei Taiwan Department of Laboratory Medicine and Internal Medicine National Taiwan University Hospital National Taiwan University College of Medicine Taipei Taiwan Ph.D. Program for Aging School of Medicine China Medical University Taichung Taiwan Department of Laboratory Medicine and Internal Medicine China Medical University Hospital School of Medicine China Medical University Taichung Taiwan Genomics Research Center Academia Sinica Taipei Taiwan

The wide dissemination of plasmids carrying antibiotic resistance determinants among bacteria is a severe threat to global public health. Here, we characterized an extensively drug-resistant (XdR) Klebsiella pneumoniae NTU107224 by whole genome sequencing (WGS) in combination with phenotypic tests. Broth dilution method was used to determine the minimal inhibitory concentrations (MICs) of NTU107224 to 24 antibiotics. The whole genome sequence of NTU107224 was determined by Nanopore/Illumina hybrid genome sequencing. Conjugation assay was performed to determine the transferability of plasmids in NTU107224 to recipient K. pneumoniae 1706. Larvae infection model was used to determine the effect(s) of conjugative plasmid pNTU107224–1 on bacterial virulence. Among the 24 antibiotics tested, XdR K. pneumoniae NTU107224 had low MICs only for amikacin (≤1 μg/mL), polymyxin B (0.25 μg/mL), colistin (0.25 μg/mL), eravacycline (0.25 μg/mL), cefepime/zidebactam (1 μg/mL), omadacycline (4 μg/mL), and tigecycline (0.5 μg/mL). Whole genome sequencing showed that the closed NTU107224 genome comprises a 5,076,795-bp chromosome, a 301,404-bp plasmid named pNTU107224–1, and a 78,479-bp plasmid named pNTU107224–2. IncHI1B plasmid pNTU107224–1 contained three class 1 integrons accumulated various antimicrobial resistance genes (including carbapenemase genes bla VIM-1 , bla IMP-23 , and truncated bla OXA-256 ) and the blast results suggested the dissemination of IncHI1B plasmids in China. By day 7 after infection, larvae infected with K. pneumoniae 1706 and transconjugant had 70% and 15% survival rates, respectively. We found that the conjugative plasmid pNTU107224–1 is closely related to IncHI1B plasmids disseminated in China and contributes to the virulence and antibiotic resistance of pathogens.

关键词： Bacteremia Carbapenemase Conjugative Extensively drug-resistant Whole genome sequencing ARG Antimicrobial resistance gene CFU Colony-forming unit CRKP Carbapenem-resistant Klebsiella pneumoniae ESBL Extended-spectrum β-lactamase MIC Minimal inhibitory concentration MLST Multi-locus sequence typing WGS Whole genome sequencing

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Tannic Acid Impedes the Proliferation of Bladder Cancer Cells by Elevating Mitochondrial Pathways of Apoptosis

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Cell biochemistry and biophysics 2024年第2期82卷 1325-1333页

作者： Chi-Cheng Li Bruce Chi-Kang Tsai Selvaraj Annseles Rajula Chiung-Hung Hsu Ming-Cheng Chen Chia-Hua Kuo Chung-Min Yeh dennis Jine-Yuan Hsieh Wei-Wen Kuo Chih-Yang Huang Center of Stem Cell and Precision Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan. School of Medicine Tzu Chi University Hualien Taiwan. Department of Hematology and Oncology Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan. Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan. Division of Colorectal Surgery Department of Surgery Taichung Veterans General Hospital Taichung Taiwan. Faculty of Medicine National Yang Ming Chiao Tung University Taipei Taiwan. Department of Sports Sciences University of Taipei Taipei Taiwan. Laboratory of Exercise Biochemistry University of Taipei Tianmu Campus Taipei Taiwan. Department of Kinesiology and Health Science College of William and Mary Williamsburg VA USA. School of Physical Education and Sports Science Soochow University Suzhou China. Department of Pathology Changhua Christian Hospital Changhua Taiwan. Department of Medical Technology Jen-Teh Junior College of Medicine Nursing and Management Miaoli Taiwan. Department of Surgical Pathology Changhua Christian Hospital Changhua Taiwan. Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan. Clinical Laboratory Chung Shan Medical University Hospital Taichung Taiwan. Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan. wwkuo@mail.cmu.edu.tw. Ph.D. Program for Biotechnology Industry China Medical University Taichung Taiwan. wwkuo@mail.cmu.edu.tw. School of Pharmacy China Medical University Taichung Taiwan. wwkuo@mail.cmu.edu.tw. Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan. cyhuang@mail.cmu.edu.tw. Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan. cyhuang@mail.cmu.edu.tw. Departmen

Bladder cancer stands as a prevailing neoplasm among men globally, distinguished for its pronounced malignancy attributed to invasiveness and metastatic proclivity. Tannic acid (TA), an organic compound in many plants, has garnered recent attention for its discernible anti-mutagenic attributes. This investigation endeavored to scrutinize the repercussions of TA on grade II bladder cancer, with a concerted focus on unraveling its anti-cancer mechanisms. The cytotoxic effects of TA on grade II bladder cancer cells were investigated using multiple techniques, including MTT assay, flow cytometry, TUNEL assay, and western blot. Our findings revealed that elevated concentrations of TA induced cytotoxic effects in grade II bladder cancer cells. Both flow cytometry and the TUNEL assay substantiated the dose-dependent capacity of TA to prompt apoptosis. Western blot analysis corroborated that TA treatment in bladder cancer cells resulted in the upregulation of cleaved caspase-3 expression and PARP. Furthermore, heightened TA dosage elicited an augmentation in the expression of pro-apoptotic proteins, namely Bax and Bak, alongside a reduction in the expression of the anti-apoptotic protein Bcl-2 within bladder cancer cells. This study confirms TA as a potential anticancer agent, demonstrably diminishing the viability of bladder cancer cells. TA exerts cytotoxicity through the activation of mitochondrial apoptotic pathways. Specifically, TA initiates the cleavage of PARP and caspase-3, concurrently augmenting the expression of pro-apoptotic proteins to facilitate apoptosis. Collectively, the present study indicates that TA effectively impedes the proliferation of bladder cancer cells by instigating apoptosis through the intrinsic mitochondrial pathway.

关键词： Bax Bladder cancer Caspase Mitochondria Tannic acid

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Corrigendum to "WNK1 kinase signaling in metastasis and angiogenesis"

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Cellular signalling 2022年 96卷 110377页

作者： Chia-Ying Hou Chung-Yung Ma Chiou-Hwa Yuh Institute of Molecular and Genomic Medicine National Health Research Institutes Miaoli Taiwan Institute of Biotechnology National Tsing Hua University Hsinchu Taiwan. Institute of Molecular and Genomic Medicine National Health Research Institutes Miaoli Taiwan. Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu Taiwan Department of Biological Science and Technology National Chiao Tung University Hsinchu Taiwan Ph.D. Program in Environmental and Occupational Medicine Kaohsiung Medical University Kaohsiung Taiwan. Electronic address: chyuh@nhri.edu.tw.

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Therapeutic effects of kefir peptides on adjuvant-induced arthritis in rats through anti-inflammation and downregulation of matrix metalloproteinases

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Life sciences 2023年 317卷 121411页

作者： Kai-Cheng Chuang Yun-Wen Lai Chi-Hua Ko Chih-Ching Yen Hsiao-Ling Chen Ying-Wei Lan Chien-Fu Chen Wei Chen Chuan-Mu Chen Department of Life Sciences Ph.D. Program in Translational Medicine National Chung Hsing University Taichung 402 Taiwan. Department of Life Sciences Ph.D. Program in Translational Medicine National Chung Hsing University Taichung 402 Taiwan Division of Rheumatology Allergy and Immunology Chang Gung Memorial Hospital Yunlin 638 Taiwan. Department of Internal Medicine China Medical University Hospital College of Health Care China Medical University Taichung 404 Taiwan. Department of Biomedical Sciences Department of Bioresources Da-Yeh University Changhwa 515 Taiwan. Division of Pulmonary Biology Cincinnati Children's Hospital Medical Center University of Cincinnati OH USA. Department of Orthopedic Surgery Taichung Armed Forces General Hospital Taichung 411 Taiwan. Division of Pulmonary and Critical Care Medicine Chia-Yi Christian Hospital Chiayi Taiwan. The iEGG and Animal Biotechnology Center The Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung 402 Taiwan. Electronic address: chchen1@dragon.nchu.edu.tw.

AIMS:Rheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features are synovial inflammation, bone erosion, and joint structural damages. Our previous studies have shown that kefir peptides (KPs) can reduce cardiovascular disease, osteoporosis and renal inflammation. In this study, we further evaluate the efficacy of KPs on adjuvant-induced arthritis (AIA) in a rat model. MAIN METHOdS:After the 14th day of adjuvant induction, rats were subsequently orally administered KPs (83 or 166 mg/day/kg) or tofacitinib (6.2 mg/day/kg) for 14 days. On the 28th day, the rats were anesthetized with isoflurane for ultrasonic, in vivo imaging system (IVIS), and radiographic imaging and then sacrificed for ankle tissues collection and analysis. In vitro, IL-1β-treated human synovial cells (SW982) were subjected to anti-arthritis mechanism study in the presence of KPs. KEY FINdINGS:The results of ultrasonography, radiograph, histology, the expression of matrix metalloproteinases (MMPs), inflammatory cytokines and RANKL/OPG ratio demonstrated decreasing severity of synovitis and bone erosion in the ankle joints after KPs treatment. Activation of the NF-κB and MAPK pathways was significantly reduced in KPs treated AIA group. Furthermore, KPs attenuated IL-1β-induced inflammatory cytokine production and the expression of MMPs in a human synovial cell line SW982. These results demonstrated that KPs alleviated adjuvant-induced arthritis in rats by inhibiting IL-1β-related inflammation and MMPs production. SIGNIFICANCE:We concluded that KPs can exhibit anti-inflammatory effects by reducing the levels of macrophage-related inflammatory cytokines and MMPs, thus alleviating bone erosion in the ankle joint and constituting a potential therapeutic strategy for rheumatoid arthritis.

关键词： Adjuvant-induced arthritis (AIA) Inflammatory cytokines Kefir peptides (KPs) Matrix metalloproteinases (MMPs) Rheumatoid arthritis (RA) Ultrasound imaging

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Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy

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Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2023年 160卷 114397页

作者： Thi Thuy Nguyen Er-Yuan Chuang Ya-Ping Chen Po-Chun Tseng Ming-Kai Jhan Chun-Yi Lai Yung-Ting Wang Yu-Ping Hung Chun Austin Changou Chi-Ming Lee Chia-Ling Chen Chiou-Feng Lin International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan Department of Oncology Hue University of Medicine and Pharmacy Hue University Hue Viet Nam. Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan Cell Physiology and Molecular Image Research Center Taipei Medical University-Wan Fang Hospital Taipei 11696 Taiwan. Division of Hematology Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan. Department of Microbiology and Immunology School of Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan Core Laboratory of Immune Monitoring Office of Research & Development Taipei Medical University Taipei 110 Taiwan. Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei 110 Taiwan. Core Laboratory of Immune Monitoring Office of Research & Development Taipei Medical University Taipei 110 Taiwan Core Facility Center Office of Research and Development Taipei Medical University Taipei 11031 Taiwan. School of Respiratory Therapy College of Medicine Taipei Medical University Taipei 110 Taiwan. Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei 110 Taiwan. Electronic address: cflin2014@tmu.edu.tw.

As an alternative strategy for cancer treatment, the combination of cancer nanomedicine and immunotherapy is promising with regard to efficacy and safety; however, precise modulation of the activation of antitumor immunity remains challenging. Therefore, the aim of the present study was to describe an intelligent nanocomposite polymer immunomodulator, drug-free polypyrrole-polyethyleneimine nanozyme (PPY-PEI NZ), which responds to the B-cell lymphoma tumor microenvironment, for precision cancer immunotherapy. Earlier engulfment of PPY-PEI NZs in an endocytosis-dependent manner resulted in rapid binding in four different types of B-cell lymphoma cells. The PPY-PEI NZ effectively suppressed B cell colony-like growth in vitro accompanied by cytotoxicity via apoptosis induction. during PPY-PEI NZ-induced cell death, mitochondrial swelling, loss of mitochondrial transmembrane potential (MTP), downregulation of antiapoptotic proteins, and caspase-dependent apoptosis were observed. deregulated AKT and ERK signaling contributed to glycogen synthase kinase-3-regulated cell apoptosis following deregulation of Mcl-1 and MTP loss. Additionally, PPY-PEI NZs induced lysosomal membrane permeabilization while inhibiting endosomal acidification, partly protecting cells from lysosomal apoptosis. PPY-PEI NZs selectively bound and eliminated exogenous malignant B cells in a mixed culture system with healthy leukocytes ex vivo. While PPY-PEI NZs showed no cytotoxicity in wild-type mice, they provided long-term and efficient inhibition of the growth of B-cell lymphoma-driven nodules in a subcutaneous xenograft model. This study explores a potential PPY-PEI NZ-based anticancer agent against B-cell lymphoma.

关键词： Anticancer Apoptosis B-cell lymphoma Nanozyme Polyethyleneimine Polypyrrole

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Briavioid d, a rare 7β,8β-epoxybriarane from Briareum violaceum

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Tetrahedron Letters 2023年 118卷

作者： Thanh Hao Huynh Chou-Yuan Ko Hsin-Tzu Liu Yen-Po Chen Mingzi M. Zhang Lun Kelvin Tsou Zhi-Hong Wen Su-Ying Chien Ping-Jyun Sung Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung 804201 Taiwan National Museum of Marine Biology and Aquarium Pingtung 944401 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Kaohsiung Armed Forces General Hospital Kaohsiung 802301 Taiwan Institute of Medical Science and Technology National Sun Yat-sen University Kaohsiung 804201 Taiwan Department of Medical Research Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien 970473 Taiwan Department of Obstetrics and Gynecology Kaohsiung Armed Forces General Hospital Kaohsiung 802301 Taiwan Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Miaoli 350401 Taiwan Institute of Biotechnology and Pharmaceutical Research National Health Research Institutes Zhunan Miaoli 350401 Taiwan Institute of BioPharmaceutical Sciences National Sun Yat-sen University Kaohsiung 804201 Taiwan Instrumentation Center National Taiwan University Taipei 106319 Taiwan Chinese Medicine Research and Development Center China Medical University Hospital Taichung 404394 Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung 807378 Taiwan Ph.D. Program in Pharmaceutical Biotechnology Fu Jen Catholic University New Taipei City 242062 Taiwan

A rare 7β,8β-epoxybriarane, briavioid d ( 1 ), has been isolated from a cultured octocoral Briareum violaceum . The structure of 1 was deduced by extensive 2d NMR studies. Single-crystal X-ray diffraction analysis was performed to identify the structure of 1 and this compound was found to reduce the release of iNOS to 85.77 %, at a concentration of 10 μM.

关键词： Briareum violaceum Briavioid Briarane X-ray iNOS

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Crystal structure revision of the natural 3β,11-dihydroxy-9,11-secosteroids bearing a 5,6-epoxy group by single-crystal X-ray diffraction and NMR data

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Journal of Molecular Structure 2025年 1342卷

作者： Sheu, Jyh-Horng Ahmed, Atallah F. Chen, You-Ying Zheng, Li-Guo Chien, Su-Ying Tseng, Yen-Ju Su, Jui-Hsin Sung, Ping-Jyun Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung804201 Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung807378 Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung404394 Taiwan Department of Pharmacognosy College of Pharmacy King Saud University Riyadh11451 Saudi Arabia Department of Pharmacognosy Faculty of Pharmacy Mansoura University Mansoura35516 Egypt National Museum of Marine Biology and Aquarium Pingtung944401 Taiwan Instrumentation Center National Taiwan University Taipei106319 Taiwan Chinese Medicine Research and Development Center China Medical University Hospital China Medical University Taichung404394 Taiwan Ph. D. Program in Pharmaceutical Biotechnology Fu Jen Catholic University New Taipei City242062 Taiwan Department of Biochemistry and Molecular Medicine National Dong Hwa University Hualien974301 Taiwan

A comprehensive structural analysis of a reported natural product, previously identified as 3β,11-dihydroxy-5β,6β-epoxy-24-methylene-9,11-secocholestan-9-one (1) and reisolated from the Taiwanese octocoral Sinularia lochmodes, was conducted. Reanalysis of the NMR spectra together with X-ray crystallographic data, led to the revision of this compound from structue 1 to its stereoisomer, 3β,11-dihydroxy-5α,6α-epoxy-24-methylene-9,11-secocholestan-9-one (2). Based on the NMR data of 2, several reported 3β,11-dihydroxy-9-oxo-9,11-secosteroids structures possessing 5,6-epoxy group should be revised. This study also provides the relationship between the 1H/13C NMR spectroscopic data and the absolute configurations of the 9,11-secosteroids possessing either 5α,6α- or 5β,6β-epoxy group. © 2025 Elsevier B.V.

关键词： Nuclear magnetic resonance spectroscopy

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Application of impulse oscillometry to detect interstitial lung disease and airway disease in adults with rheumatoid arthritis

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BMC pulmonary medicine 2023年第1期23卷 331页

作者： Wen-Chien Cheng Shih-Hsin Chang Wei-Chun Chen Bing-Ru Wu Chia-Hung Chen Chi-Chien Lin Wu-Huei Hsu Joung-Liang Lan der-Yuan Chen Division of Pulmonary and Critical Care Department of Internal Medicine China Medical University Hospital Taichung Taiwan. Department of Life Science National Chung Hsing University Taichung Taiwan. Ph.D. Program in Translational Medicine National Chung Hsing University Taichung Taiwan. Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung Taiwan. Department of Life Science National Chung Hsing University Taichung Taiwan. sherry61976@***. Ph.D. Program in Translational Medicine National Chung Hsing University Taichung Taiwan. sherry61976@***. Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung Taiwan. sherry61976@***. Rheumatology and Immunology Center China Medical University Hospital Taichung Taiwan. sherry61976@***. and Animal Biotechnology Center Institute of Biomedical Science the iEGG National Chung-Hsing University Taichung Taiwan. Department of Life Science National Chung Hsing University Taichung Taiwan. dychen1957@***. College of Medicine China Medical University Taichung Taiwan. dychen1957@***. College of Medicine National Chung Hsing University Taichung Taiwan. dychen1957@***.

BACKGROUNd:We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILd) and airway involvement are common in this population. METHOdS:We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images. RESULTS:In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILd and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease. CONCLUSION:Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients.

关键词： Impulse Oscillometry Interstitial lung disease Rheumatoid arthritis Small airway disease

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disulfiram inhibits coronaviral main protease by conjugating to its substrate entry site

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International journal of biological macromolecules 2024年第PT 2期276卷 133955页

作者： Ying Kuan Hsu-Feng Chu Pang-Hung Hsu Kai-Cheng Hsu Ta-Hsien Lin Chun-Hsiang Huang Wei-Yi Chen Program in Molecular Medicine National Yang Ming Chiao Tung University and Academia Sinica Taipei Taiwan. Biomedical Industry Ph.D. Program National Yang Ming Chiao Tung University Taipei Taiwan. Department of Bioscience and Biotechnology National Taiwan Ocean University Keelung 20224 Taiwan. Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Division of Basic Research Department of Medical Research Taipei Veterans General Hospital Taipei 112 Taiwan Institute of Biochemistry and Molecular Biology National Yang Ming Chiao Tung University Taipei 112 Taiwan. National Synchrotron Radiation Research Center Hsinchu City 30076 Taiwan. Electronic address: huang.conann@nsrrc.org.tw. Program in Molecular Medicine National Yang Ming Chiao Tung University and Academia Sinica Taipei Taiwan Institute of Biochemistry and Molecular Biology National Yang Ming Chiao Tung University Taipei 112 Taiwan Cancer and Immunology Research Center National Yang Ming Chiao Tung University Taipei Taiwan. Electronic address: chenwy@nycu.edu.tw.

Coronaviruses (CoV) are highly pathogenic single-strand RNA viruses. CoV infections cause fatal respiratory symptoms and lung injuries in humans and significant economic losses in livestock. Since the SARS-2 outbreak in 2019, the highly conserved main protease (M), also termed 3-chymotrypsin-like protease (3CL), has been considered an attractive drug target for treating CoV infections. M mediates the proteolytic cleavage of eleven sites in viral polypeptides necessary for virus replication. Here, we report that disulfiram, an FdA-approved drug for alcoholic treatment, exhibits a broad-spectrum inhibitory effect on CoV Ms. Analytical ultracentrifugation and circular dichroism analyses indicated that disulfiram treatment blocks the dimeric formation of SARS and PEdV Ms and decreases the thermostability of SARS, SARS-2, and PEdV Ms, whereas it facilitates the dimerization and stability of MERS M. Furthermore, mass spectrometry and structural alignment revealed that disulfiram targets the Cys44 residue of Ms, which is located at the substrate entrance and close to the catalytic His41. In addition, molecular docking analysis suggests that disulfiram conjugation interferes with substrate entry to the catalytic center. In agreement, mutation of Cys44 modulates the disulfiram sensitivity of CoV Ms. Our study suggests a broad-spectrum inhibitory function of disulfiram against CoV Ms.

关键词： 3C-like protease (3CL(pro)) disulfiram (dSF) Main protease (M(pro))

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