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Ser235 phosphorylation of hepatitis C virus NS5A is required for NS5A dimerization and drug resistance

Life sciences 2024年 337卷 122338页

作者： Lee, Wei-Ping Tsai, Keng-Chang Liao, Shi-Xian Huang, Yi-Hsiang Hou, Ming-Chih Lan, Keng-Hsin Department of Medical Research Taipei Veterans General Hospital Taipei Taiwan Institute of Biochemistry and Molecular Biology School of Life Sciences National Yang Ming Chiao Tung University Taipei Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei Taiwan The Ph.D. Program for Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan Division of Gastroenterology and Hepatology Department of Medicine Taipei Veterans General Hospital Taipei Taiwan School of Medicine College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Institute of Clinical Medicine School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Institute of Pharmacology College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan

Hepatitis C virus (HCV) infection is recognized as a major causative agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV non-structural protein 5A (NS5A) is a dimeric phosphoprotein with a hyperphosphorylated form to act as a switch that regulates HCV replication and assembly. NS5A inhibitors have been utilized as the scaffold for combination therapy of direct-acting antiviral agents (dAA). However, the mode of action of NS5A inhibitors is still unclear due to the lack of mechanistic detail regarding NS5A phosphorylation and dimerization in the HCV life cycle. It has been demonstrated that phosphorylation of NS5A at Ser235 is essential for RNA replication of the JFH1 strain. In this report, we found that NS5A phosphomimetic Ser235 substitution (Ser-to-Asp mutation) formed a dimer that was resistant to disruption by NS5A inhibitors as was the NS5A resistance-associated substitution Y93H. phosphorylation of NS5A at Ser235 residue was required for the interaction of two NS5A-WT molecules in JFH1-based cell culture system but not absolutely required for dimerization of the NS5A-Y93H mutant. Interestingly, HCV nonstructural proteins from the subgenomic replicon NS3-5A was required for NS5A-WT dimerization but not required for NS5A-Y93H dimerization. Our data suggest that spontaneous Ser235 phosphorylation of NS5A and ensuing dimerization account for resistance of the JFH1/NS5A-Y93H mutant to NS5A inhibitors. © 2023 Elsevier Inc.

关键词： drug resistance Hepatitis C virus NS5A dimerization Ser235 phosphorylation

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The need for precise and accurate imaging navigation in cervical spine surgery for rheumatoid arthritis

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International Journal of Rheumatic diseases 2024年第2期27卷 e15084-e15084页

作者： Huang, Chih-Wei Lin, Mao-Shih Tzeng, Chung-Yuh Chen, Tse-Yu Tsou, Hsi-Kai Department of Neurosurgery Neurological Institute Taichung Veterans General Hospital Taichung Taiwan Department of Rehabilitation Jen-Teh Junior College of Medicine Nursing and Management Houlong Miaoli County Taiwan Department of Orthopedics Taichung Veterans General Hospital Taichung Taiwan Department of Medicinal Botanicals and Foods on Health Applications Da-Yeh University Changhua County Taiwan Institute of Biomedical Sciences National Chung Hsing University Taichung Taiwan Ph.D. Program in Translational Medicine National Chung Hsing University Taichung Taiwan Functional Neurosurgery Division Neurological Institute Taichung Veterans General Hospital Taichung Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan College of Health National Taichung University of Science and Technology Taichung Taiwan

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Frailty in chronic myeloid leukemia: evidence from 2016–2018 Nationwide Inpatient Sample of the US

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BMC Geriatrics 2023年第1期23卷 334-334页

作者： Huan-Tze, Lin Yun-Ru, Liu Kuan-der, Lee Huey-En, Tzeng Department of Internal Medicine Division of Hematology and Oncology Taipei Medical University Hospital Taipei Taiwan Joint Biobank Office of Human Research Taipei Medical University Taipei Taiwan Department of Medical Research Taichung Veterans General Hospital 1650 Boulevard Sect. 4 Taichung City 40705 Taiwan Department of Medicine Division of Hematology/Medical Oncology Taichung Veterans General Hospital Taichung City Taiwan Ph.D. Program for Cancer Molecular Biology and Drug Discovery and Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan

Background: Frailty is a marker of poor prognosis in older adults with hematologic malignancies and contributes to the severe vulnerability of the aging population to adverse health outcomes. This study aimed to determine the association between frailty and outcomes in hospitalized patients with chronic myeloid leukemia (CML). Methods: The International Classification of diseases (ICd-10) identified data on hospitalized patients 20 years or older admitted with CML between 2016 and 2018 in the US National Inpatient Sample (NIS) database. The cohort was further divided into groups of patients with or without frailty. Logistic regression analysis was performed to determine associations between study variables and clinical outcomes. A stratified analysis of the association between frailty and in-hospital mortality by age group was also performed. Results: A total of 13,849 hospitalized patients with CML were included, 49.6% of whom had frailty. The mean age of the patients was 65.1 years, and 7,619 (56.2%) of them were male. Frailty was associated with nearly 4 times the risk of in-hospital mortality, 3 times the risk of unfavorable discharge, 3 times the risk of prolonged LOS, and significantly more in total hospital costs. In addition, frailty was associated with a significantly increased risk of in-hospital mortality in all age subgroups (< 40 years, 40–59 years, and > 60 years) compared with no frailty. Conclusions: Frailty strongly predicts poor clinical outcomes in US patients with CML. © 2023, The Author(s).

关键词： Chronic myeloid leukemia (CML) Frailty In-hospital outcome Nationwide Inpatient Sample (NIS)

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Predicting the sweetness level of avomango (Gadung Klonal 21) using multi-predictor local polynomial regression

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IOP Conference Series: Earth and Environmental science 2021年第1期733卷

作者： M Ulya N Chamidah T Saifudin Ph.D. Student of Mathematics and Natural Sciences Study Program Faculty of Science and Technology Airlangga University Indonesia Study Program of Agroindustrial Technology Faculty of Agriculture University of Trunojoyo Madura Indonesia Department of Mathematics Faculty of Science and Technology Airlangga University Indonesia

One of the mango's maturity aspects is the sweetness of the fruits. Mature Avomango has a high degree of sweetness, characterized by a high total soluble solids (TSS) content. Currently, many non-destructive tests are using Near Infra-Red (NIR) spectroscopy to find out the TSS content. NIR spectroscopy generates spectra data, which can be used as predictors to predict Avomangos sweetness level. This study aims to predict the level of Avomangos sweetness by using a multi-predictor local polynomial regression approach and compare it with multiple polynomial regression. In this study, we use 120 samples of Avomango divided into two parts, 100 as training data and 20 as testing data. The multi-predictor local polynomial regression has better performance with the value mean absolute percentage error (MAPE) is 8.554% that categorized as a highly accurate prediction for predicting Avomangos sweetness level.

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Review on fate, transport, toxicity and health risk of nanoparticles in natural ecosystems: Emerging challenges in the modern age and solutions toward a sustainable environment

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The science of the total environment 2024年 912卷 169331页

作者： Thien-Khanh Tran Minh-Ky Nguyen Chitsan Lin Tuan-dung Hoang Thanh-Cong Nguyen Aasif Mohmad Lone Akhil Pradiprao Khedulkar Mohamed S Gaballah Jagpreet Singh W Jin Chung d duc Nguyen Advanced Applied Sciences Research Group Dong Nai Technology University Bien Hoa City 76100 Viet Nam Faculty of Technology Dong Nai Technology University Bien Hoa City 76100 Viet Nam. Faculty of Environment and Natural Resources Nong Lam University 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. Electronic address: nmky@hcmuaf.edu.vn. 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. School of Chemistry and Life Science Hanoi University of Science and Technology No. 1 Dai Co Viet Hai Ba Trung Hanoi 100000 Viet Nam Vietnam National University Hanoi VNU Town Hoa Lac Thach That District Hanoi 155500 Viet Nam. Department of Civil Engineering Manipal Institute of Technology Manipal Academy of Higher Education Manipal 576104 Karnataka India. Department of Biomedical Engineering and Environmental Science National Tsing Hua University Hsinchu 30013 Taiwan. CAS Key Laboratory of Urban Pollutant Conversion Department of Environmental Science and Engineering University of Science and Technology of China Hefei 230026 China School of Engineering and Technology Central Michigan University Mt. Pleasant MI 48859 USA. Department of Chemistry University Centre for Research and Development Chandigarh University Gharuan Mohali 140413 India. Department of Civil & Energy System Engineering Kyonggi University Suwon 16227 South Korea. Department of Civil & Energy System Engineering Kyonggi University Suwon 16227 South Korea Institute of Applied Technology and Sustainable Development Nguyen Tat Thanh University Ho Chi Minh City 700000 Viet Nam. Electronic address: nguyensyduc@gmail.com.

In today's era, nanoparticles (NPs) have become an integral part of human life, finding extensive applications in various fields of science, pharmacy, medicine, industry, electronics, and communication. The increasing popularity of NP usage worldwide is a testament to their tremendous potential. However, the widespread deployment of NPs unavoidably leads to their release into the environmental matrices, resulting in persistence in ecosystems and bioaccumulation in organisms. Understanding the environmental behavior of NPs poses a significant challenge due to their nanoscale size. Given the current environmental releases of NPs, known negative consequences, and the limited knowledge available for risk management, comprehending the toxicity of NPs in ecosystems is both awaiting and crucial. The present review aims to unravel the potential environmental influences of nano-scaled materials, and provides in-depth inferences of the current knowledge and understanding in this field. The review comprehensively summarizes the sources, fate, transport, toxicity, health risks, and remediation solutions associated with NP pollution in aquatic and soil ecosystems. Furthermore, it addresses the knowledge gaps and outlines further investigation priorities for the sustainable control of NP pollution in these environments. By gaining a holistic understanding of these aspects, we can work toward ensuring the responsible and sustainable use of NPs in today's fast-growing world.

关键词： Bioavailability Fate and transport Nanosized particles Nanotoxicology Silver nanoparticles Toxicity

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Corrigendum to "SnO2-xNx based tpod nanostructure for SARS-CoV2 spike protein detection" [234 (2023) Oct 1, 116505]

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Environmental research 2024年 242卷 117677页

作者： Nallin Sharma Chia-Hung Chi deepak dabur Andrew Chi-Chang Tsai Hui-Fen Wu Department of Chemistry National Sun Yat-Sen University Kaohsiung 70 Lien-Hai Road Kaohsiung 80424 Taiwan. International Ph.D. Program for Science National Sun Yat-Sen University Kaohsiung 80424 Taiwan. Jeenn Chwanq Enterprise Co. Ltd No. 14 Dazhu Road Kaohsiung 833 Taiwan. Department of Chemistry National Sun Yat-Sen University Kaohsiung 70 Lien-Hai Road Kaohsiung 80424 Taiwan School of Pharmacy College of Pharmacy Kaohsiung Medical University Kaohsiung 807 Taiwan Institute of Precision Medicine College of Medicine National Sun Yat-Sen University Kaohsiung 80424 Taiwan International Ph.D. Program for Science National Sun Yat-Sen University Kaohsiung 80424 Taiwan Institute of Medical Science and Technology National Sun Yat-Sen University Kaohsiung 80424 Taiwan. Electronic address: hwu@faculty.nsysu.edu.tw.

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design of an ultrasensitive electrochemical sensor using a carbon black/zinc-organic framework nanocomposite for quantifying quercetin in fruits

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Food Chemistry 2025年 491卷

作者： Arunkumar Selvam Gopika Meenakumari Gopakumar Chih-Yu Kuo Kareem Yusuf Beena Saraswathyamma Mani Govindasamy Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei 10608 Taiwan International Graduate Program in Energy and Optoelectronic Materials (EOMP) National Taipei University of Technology Taipei 10608 Taiwan Department of Chemistry Amrita Vishwa Vidyapeetham Amritapuri Campus Clappana P O Kollam Kerala 690525 India High-Value Biomaterials Research and Commercialization Center National Taipei University of Technology Taipei 106 Taiwan Department of Chemistry College of Science King Saud University Riyadh 11451 Saudi Arabia International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan Research Center for Intelligent Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan Department of Chemistry Korea University Seongbuk-gu Seoul Republic of Korea

Quercetin, a potent flavonoid recognized for its antioxidant and anti-inflammatory attributes, is abundantly found in fruits and vegetables, considerably enhancing their health benefits. Monitoring quercetin concentrations in food matrices is crucial for quality assurance, nutritional assessment, and substantiating health claims. We report a unique zinc-based metal–organic framework (Zn-MOF) incorporated with carbon black (CB) to create a highly sensitive electrochemical sensor specifically designed for quercetin detection. The distinctive porous architecture of the Zn-MOF, together with the superior conductivity of carbon black, have a synergistic effect that improves electron transfer. The sensor reports a wide linear range of 0.05–350.9 μM and a lowest detection limit of 3.7 nM. Furthermore, Zn-MOF@CB/GCE demonstrates excellent current retention (95.64 %) over a period of one month, together with commendable repeatability and reproducibility. The real-sample study of the proposed sensor demonstrates an effective recovery range for fruits: apple (95.0–99.0 %), grapes (96.0–98.0 %), and guava (97.0–101.0 %).

关键词： Biomedical and health care Carbon materials Food sample analysis Health analysis Quercetin Sonochemical synthesis

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Exploration of dark chemical genomics space via portal learning: Applied to targeting the undruggable genome and COVId-19 anti-infective polypharmacology

arXiv

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arXiv 2021年

作者： Cai, Tian Xie, Li Chen, Muge Liu, Yang He, di Zhang, Shuo Mura, Cameron Bourne, philip E. Xie, Lei Ph.D. Program in Computer Science The Graduate Center The City University of New York New York10016 United States Department of Computer Science Hunter College The City University of New York New York10065 United States Master Program in Computer Science Courant Institute of Mathematical Sciences New York University United States School of Data Science Department of Biomedical Engineering University of Virginia VA22903 United States Helen and Robert Appel Alzheimer’s Disease Research Institute Feil Family Brain & Mind Research Institute Weill Cornell Medicine Cornell University New York10021 United States

Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones—a common dilemma in scientific inquiry. We have developed a new deep learning framework, called Portal Learning, to explore dark chemical and biological space. Three key, novel components of our approach include: (i) end-to-end, step-wise transfer learning, in recognition of biology’s sequence-structure-function paradigm, (ii) out-of-cluster meta-learning, and (iii) stress model selection. Portal Learning provides a practical solution to the out-of-distribution (OOd) problem in statistical machine learning. Here, we have implemented Portal Learning to predict chemical-protein interactions on a genome-wide scale. Systematic studies demonstrate that Portal Learning can effectively assign ligands to unexplored gene families (unknown functions), versus existing state-of-the-art methods, thereby allowing us to target previously "undruggable" proteins and design novel polypharmacological agents for disrupting interactions between SARS-CoV-2 and human proteins. Portal Learning is general-purpose and can be further applied to other areas of scientific *** Codes 68T07 © 2021, CC BY.

关键词： Genes

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Exploration of dark Chemical Genomics Space via Portal Learning: Applied to Targeting the Undruggable Genome and COVId-19 Anti-Infective Polypharmacology

Research Square

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Research Square 2021年

Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones—a common dilemma in scientific inquiry. We have developed a new deep learning framework, called Portal Learning, to explore dark chemical and biological space. Three key, novel components of our approach include: (i) end-to-end, step-wise transfer learning, in recognition of biology’s sequence-structure-function paradigm, (ii) out-of-cluster meta-learning, and (iii) stress model selection. Portal Learning provides a practical solution to the out-of-distribution (OOd) problem in statistical machine learning. Here, we have implemented Portal Learning to predict chemical-protein interactions on a genome-wide scale. Systematic studies demonstrate that Portal Learning can effectively assign ligands to unexplored gene families (unknown functions), versus existing state-of-the-art methods. Compared with AlphaFold2-based protein-ligand docking, Portal Learning significantly improved the performance by 79% in PR-AUC and 27% in ROC-AUC, respectively. The superior performance of Portal Learning allowed us to target previously "undruggable" proteins and design novel polypharmacological agents for disrupting interactions between SARS-CoV-2 and human proteins. Portal Learning is general-purpose and can be further applied to other areas of scientific inquiry. © 2021, CC BY.

关键词： Coronavirus

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Analysis of discharge and area of the debris flow based on geological structural and rainfall levels in the slopes of Mount Abang, Kintamani

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IOP Conference Series: Materials science and engineering 2021年第2期1098卷

作者： I N Sinarta P I Wahyuni P Aryastana Department of Civil Engineering Universitas Warmadewa Jl. Terompong No.24 Denpasar Bali Indonesia International Ph.D. Program in Environmental Science and Technology (University System of Taiwan) National Central University Taiwan

Geological structural and rainfall intensity causes the parameters of soil shear strength to decline, especially in the surface layer of soil in volcanic rocks that have not experienced weathering. Study of geological structures and rainfall intensity against the hazard of a landslide was destroyed on the slopes of Mount Abang in the Abang Batudinding Village. Soil investigations using the Geoelectric method and sampling at 6 boreholes. Geological analysis on interpretation of slope outcrops, average rainfall analysis of the Thiessen Polygon method and analysis of design flood discharge using the NHSU method. Analysis results show the morphology of the slopes of Mount Abang with a slope of more than 40% and lithology of weathered volcanic rocks consisting of volcanic breccias, and tuffs breccias in conditions rather mild to moderate weathering, if have average effective rainfall for 10-50 years at 238 mm/day. The results also show that the peak discharge of debris flow was 98.639 m3/sec with the volume of debris flow 50072.85 m3 and the width of the range was 49.5 m. This debris flow volume indicated that residents around the river with a range of 49.5 m are at risk of debris flow sediment with a thickness of 1-1.5 m.

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