Publications by authors named "Cheng-Yu Wu"

28 Publications

  • Page 1 of 1

Effect of clinical isolate or cleavage site mutations in the SARS-CoV-2 spike protein on protein stability, cleavage, and cell-cell fusion.

J Biol Chem 2021 Jul 20;297(1):100902. Epub 2021 Jun 20.

Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, USA. Electronic address:

The trimeric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) is the sole viral protein responsible for both viral binding to a host cell and the membrane fusion event needed for cell entry. In addition to facilitating fusion needed for viral entry, S can also drive cell-cell fusion, a pathogenic effect observed in the lungs of SARS-CoV-2-infected patients. While several studies have investigated S requirements involved in viral particle entry, examination of S stability and factors involved in S cell-cell fusion remain limited. A furin cleavage site at the border between the S1 and S2 subunits (S1/S2) has been identified, along with putative cathepsin L and transmembrane serine protease 2 cleavage sites within S2. We demonstrate that S must be processed at the S1/S2 border in order to mediate cell-cell fusion and that mutations at potential cleavage sites within the S2 subunit alter S processing at the S1/S2 border, thus preventing cell-cell fusion. We also identify residues within the internal fusion peptide and the cytoplasmic tail that modulate S-mediated cell-cell fusion. In addition, we examined S stability and protein cleavage kinetics in a variety of mammalian cell lines, including a bat cell line related to the likely reservoir species for SARS-CoV-2, and provide evidence that proteolytic processing alters the stability of the S trimer. This work therefore offers insight into S stability, proteolytic processing, and factors that mediate S cell-cell fusion, all of which help give a more comprehensive understanding of this high-profile therapeutic target.
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http://dx.doi.org/10.1016/j.jbc.2021.100902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214756PMC
July 2021

The effect of long-term doxycycline treatment in a mouse model of cigarette smoke-induced emphysema and pulmonary hypertension.

Am J Physiol Lung Cell Mol Physiol 2021 05 24;320(5):L903-L915. Epub 2021 Mar 24.

Cardiopulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.

Chronic obstructive pulmonary disease (COPD) is a major cause of death and a still incurable disease, comprising emphysema and chronic bronchitis. In addition to airflow limitation, patients with COPD can suffer from pulmonary hypertension (PH). Doxycycline, an antibiotic from the tetracycline family, in addition to its pronounced antimicrobial activity, acts as a matrix metalloproteinase (MMP) inhibitor and has anti-inflammatory properties. Furthermore, doxycycline treatment exhibited a beneficial effect in several preclinical cardiovascular disease models. In preclinical research, doxycycline is frequently employed for gene expression modulation in Tet-On/Tet-Off transgenic animal models. Therefore, it is crucial to know whether doxycycline treatment in Tet-On/Tet-Off systems has effects independent of gene expression modulation by such systems. Against this background, we assessed the possible curative effects of long-term doxycycline administration in a mouse model of chronic CS exposure. Animals were exposed to cigarette smoke (CS) for 8 mo and then subsequently treated with doxycycline for additional 3 mo in room air conditions. Doxycycline decreased the expression of MMPs and general pro-inflammatory markers in the lungs from CS-exposed mice. This downregulation was, however, insufficient to ameliorate CS-induced emphysema or PH. Tet-On/Tet-Off induction by doxycycline in such models is a feasible genetic approach to study curative effects at least in established CS-induced emphysema and PH. However, we report several parameters that are influenced by doxycycline and use of a Tet-On/Tet-Off system when evaluating those parameters should be interpreted with caution.
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http://dx.doi.org/10.1152/ajplung.00048.2021DOI Listing
May 2021

Effect of mutations in the SARS-CoV-2 spike protein on protein stability, cleavage, and cell-cell fusion function.

bioRxiv 2021 Jan 25. Epub 2021 Jan 25.

Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, USA.

The SARS-CoV-2 spike protein (S) is the sole viral protein responsible for both viral binding to a host cell and the membrane fusion event needed for cell entry. In addition to facilitating fusion needed for viral entry, S can also drive cell-cell fusion, a pathogenic effect observed in the lungs of SARS-CoV-2 infected patients. While several studies have investigated S requirements involved in viral particle entry, examination of S stability and factors involved in S cell-cell fusion remain limited. We demonstrate that S must be processed at the S1/S2 border in order to mediate cell-cell fusion, and that mutations at potential cleavage sites within the S2 subunit alter S processing at the S1/S2 border, thus preventing cell-cell fusion. We also identify residues within the internal fusion peptide and the cytoplasmic tail that modulate S cell-cell fusion. Additionally, we examine S stability and protein cleavage kinetics in a variety of mammalian cell lines, including a bat cell line related to the likely reservoir species for SARS-CoV-2, and provide evidence that proteolytic processing alters the stability of the S trimer. This work therefore offers insight into S stability, proteolytic processing, and factors that mediate S cell-cell fusion, all of which help give a more comprehensive understanding of this highly sought-after therapeutic target.
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http://dx.doi.org/10.1101/2021.01.24.428007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852270PMC
January 2021

[Molecular mechanism of Puerariae Lobatae Radix in treatment of hepatocellular carcinoma based on network pharmacology].

Zhongguo Zhong Yao Za Zhi 2020 Sep;45(17):4089-4098

Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University Nanjing 210009, China.

To investigate the potential mechanism of Puerariae Lobatae Radix in the treatment of hepatocellular carcinoma by network pharmacology and in vitro cell experiment. The main active components of Puerariae Lobatae Radix and their predicted targets were obtained from TCMSP, and the disease targets were obtained from GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets. The "compound-target-disease" network diagram was constructed in Cytoscape 3.7.1, and the common targets were input into the STRING database to build the PPI network of proteins interaction. GO function and KEGG pathway enrichment analysis on effective targets were performed by using R software. Autodock vina 1.1.2 was used for molecular docking. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The proliferation of human hepatocellular carcinoma cells was detected by CCK-8 and EDU enzyme staining, and the expressions of PTEN, PDK1, Akt and GSK3 were detected by Western blot. In this study, 10 components of Puerariae Lobatae Radix(9 components involved in hepatocellular carcinoma-related targets and signaling pathways), and 149 hepatocellular carcinoma-related targets and 156 signaling pathways were screened out. The results of network analysis indicated that Puerariae Lobatae Radix may play an anti-hepatocellular carcinoma effect on key targets, such as Akt, IL6, MAPK3, EGFR, and key pathways, such as PI3 K-Akt. The results of molecular docking indicated that puerarin, genistein and daidzein had a good binding ability with the key targets such as AKT1, MAPK3, MAPK1 and CASP3, and puerarin had the lowest Vina score with AKT1 and MAPK3 and also similar to them. In vitro cell experiments confirmed that puerarin has a significantly inhibitory effect on the proliferation of human hepatocellular carcinoma cells. Western blot results showed that puerarin could increase the phosphorylation of PTEN in human hepatocellular carcinoma cells through the PTEN/Akt/GSK3β signaling pathway, and the phosphorylation level of its downstream Akt decreased. This series of studies confirm that puerarin can treat hepatocellular carcinoma by blocking PTEN/Akt/GSK3β cellular signaling pathway, so as to provide ideas for subsequent studies for the molecular mechanism of puerarin in the treatment of liver cancer.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200427.402DOI Listing
September 2020

Role reversal of functional identity in host factors: Dissecting features affecting pro-viral versus antiviral functions of cellular DEAD-box helicases in tombusvirus replication.

PLoS Pathog 2020 10 9;16(10):e1008990. Epub 2020 Oct 9.

Department of Plant Pathology, University of Kentucky, Lexington, Lexington, United States of America.

Positive-stranded (+)RNA viruses greatly exploit host cells to support viral replication. However, unlike many other pathogens, (+)RNA viruses code for only a limited number of genes, making them highly dependent on numerous co-opted host factors for supporting viral replication and other viral processes during their infections. This excessive dependence on subverted host factors, however, renders (+)RNA viruses vulnerable to host restriction factors that could block virus replication. Interestingly, cellular ATP-dependent DEAD-box RNA helicases could promote or inhibit the replication of Tomato bushy stunt virus (TBSV) replication. However, it is currently unknown what features make a particular DEAD-box helicase either pro-viral or antiviral. In this work, we succeeded in reversing the viral function of the antiviral DDX17-like RH30 DEAD-box helicase by converting it to a pro-viral helicase. We also turned the pro-viral DDX3-like RH20 helicase into an antiviral helicase through deletion of a unique N-terminal domain. We demonstrate that in the absence of the N-terminal domain, the core helicase domain becomes unhinged, showing altered specificity in unwinding viral RNA duplexes containing cis-acting replication elements. The discovery of the sequence plasticity of DEAD-box helicases that can alter recognition of different cis-acting RNA elements in the viral genome illustrates the evolutionary potential of RNA helicases in the arms race between viruses and their hosts, including key roles of RNA helicases in plant innate immunity. Overall, these findings open up the possibility to turn the pro-viral host factors into antiviral factors, thus increasing the potential antiviral arsenal of the host for the benefit of agriculture and health science.
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http://dx.doi.org/10.1371/journal.ppat.1008990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577489PMC
October 2020

NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD.

Nat Metab 2020 06 8;2(6):532-546. Epub 2020 Jun 8.

Department of Surgery, Justus-Liebig University, Giessen, Germany.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and death worldwide. Peroxynitrite, formed from nitric oxide, which is derived from inducible nitric oxide synthase, and superoxide, has been implicated in the development of emphysema, but the source of the superoxide was hitherto not characterized. Here, we identify the non-phagocytic NADPH oxidase organizer 1 (NOXO1) as the superoxide source and an essential driver of smoke-induced emphysema and pulmonary hypertension development in mice. NOXO1 is consistently upregulated in two models of lung emphysema, Cybb (also known as NADPH oxidase 2, Nox2)-knockout mice and wild-type mice with tobacco-smoke-induced emphysema, and in human COPD. Noxo1-knockout mice are protected against tobacco-smoke-induced pulmonary hypertension and emphysema. Quantification of superoxide, nitrotyrosine and multiple NOXO1-dependent signalling pathways confirm that peroxynitrite formation from nitric oxide and superoxide is a driver of lung emphysema. Our results suggest that NOXO1 may have potential as a therapeutic target in emphysema.
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http://dx.doi.org/10.1038/s42255-020-0215-8DOI Listing
June 2020

Amelioration of elastase-induced lung emphysema and reversal of pulmonary hypertension by pharmacological iNOS inhibition in mice.

Br J Pharmacol 2021 01 28;178(1):152-171. Epub 2020 Apr 28.

Justus-Liebig University of Giessen (JLUG), Excellence Cluster Cardiopulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.

Background And Purpose: Chronic obstructive pulmonary disease, encompassing chronic airway obstruction and lung emphysema, is a major worldwide health problem and a severe socio-economic burden. Evidence previously provided by our group has shown that inhibition of inducible NOS (iNOS) prevents development of mild emphysema in a mouse model of chronic tobacco smoke exposure and can even trigger lung regeneration. Moreover, we could demonstrate that pulmonary hypertension is not only abolished in cigarette smoke-exposed iNOS mice but also precedes emphysema development. Possible regenerative effects of pharmacological iNOS inhibition in more severe models of emphysema not dependent on tobacco smoke, however, are hitherto unknown.

Experimental Approach: We have established a mouse model using a single dose of porcine pancreatic elastase or saline, intratracheally instilled in C57BL/6J mice. Emphysema, as well as pulmonary hypertension development was determined by both structural and functional measurements.

Key Results: Our data revealed that (i) emphysema is fully established after 21 days, with the same degree of emphysema after 21 and 28 days post instillation, (ii) emphysema is stable for at least 12 weeks and (iii) pulmonary hypertension is evident, in contrast to smoke models, only after emphysema development. Oral treatment with the iNOS inhibitor N(6)-(1-iminoethyl)-l-lysine (L-NIL) was started after emphysema establishment and continued for 12 weeks. This resulted in significant lung regeneration, evident in the improvement of emphysema and reversal of pulmonary hypertension.

Conclusion And Implications: Our data indicate that iNOS is a potential new therapeutic target to treat severe emphysema and associated pulmonary hypertension.

Linked Articles: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.
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http://dx.doi.org/10.1111/bph.15057DOI Listing
January 2021

Lung developmental arrest caused by PDGF-A deletion: consequences for the adult mouse lung.

Am J Physiol Lung Cell Mol Physiol 2020 04 18;318(4):L831-L843. Epub 2020 Mar 18.

Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

PDGF-A is a key contributor to lung development in mice. Its expression is needed for secondary septation of the alveoli and deletion of the gene leads to abnormally enlarged alveolar air spaces in mice. In humans, the same phenotype is the hallmark of bronchopulmonary dysplasia (BPD), a disease that affects premature babies and may have long lasting consequences in adulthood. So far, the knowledge regarding adult effects of developmental arrest in the lung is limited. This is attributable to few follow-up studies of BPD survivors and lack of good experimental models that could help predict the outcomes of this early age disease for the adult individual. In this study, we used the constitutive lung-specific deletion mouse model to analyze the consequences of developmental lung defects in adult mice. We assessed lung morphology, physiology, cellular content, ECM composition and proteomics data in mature mice, that perinatally exhibited lungs with a BPD-like morphology. Histological and physiological analyses both revealed that enlarged alveolar air spaces remained until adulthood, resulting in higher lung compliance and higher respiratory volume in knockout mice. Still, no or only small differences were seen in cellular, ECM and protein content when comparing knockout and control mice. Taken together, our results indicate that deletion-induced lung developmental arrest has consequences for the adult lung at the morphological and functional level. In addition, these mice can reach adulthood with a BPD-like phenotype, which makes them a robust model to further investigate the pathophysiological progression of the disease and test putative regenerative therapies.
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http://dx.doi.org/10.1152/ajplung.00295.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191480PMC
April 2020

Lung epithelium damage in COPD - An unstoppable pathological event?

Cell Signal 2020 04 15;68:109540. Epub 2020 Jan 15.

Department of Internal Medicine, Cardio-Pulmonary Institute (CPI), German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany; Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. Electronic address:

Chronic obstructive pulmonary disease (COPD) is a common term for alveolar septal wall destruction resulting in emphysema, and chronic bronchitis accompanied by conductive airway remodelling. In general, this disease is characterized by a disbalance of proteolytic/anti-proteolytic activity, augmented inflammatory response, increased oxidative/nitrosative stress, rise in number of apoptotic cells and decreased proliferation. As the first responder to the various environmental stimuli, epithelium occupies an important position in different lung pathologies, including COPD. Epithelium sequentially transitions from the upper airways in the direction of the gas exchange surface in the alveoli, and every cell type possesses a distinct role in the maintenance of the homeostasis. Basically, a thick ciliated structure of the airway epithelium has a major function in mucus secretion, whereas, alveolar epithelium which forms a thin barrier covered by surfactant has a function in gas exchange. Following this line, we will try to reveal whether or not the chronic bronchitis and emphysema, being two pathological phenotypes in COPD, could originate in two different types of epithelium. In addition, this review focuses on the role of lung epithelium in COPD pathology, and summarises underlying mechanisms and potential therapeutics.
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http://dx.doi.org/10.1016/j.cellsig.2020.109540DOI Listing
April 2020

Modulation of tumor microenvironment using a TLR-7/8 agonist-loaded nanoparticle system that exerts low-temperature hyperthermia and immunotherapy for in situ cancer vaccination.

Biomaterials 2020 02 15;230:119629. Epub 2019 Nov 15.

Department of Chemical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, Taiwan, ROC. Electronic address:

Most cancer vaccines under development are associated with defined tumor antigens rather than with all antigens of whole tumor cells, limiting the anti-tumor immune responses that they elicit. This work proposes an immunomodulator (R848)-loaded nanoparticle system ([email protected]) that can absorb near-infrared light (+NIR) to cause low-temperature hyperthermia that interacts synergistically with its loaded R848 to relieve the tumor-mediated immunosuppressive microenvironment, generating robust anti-tumor memory immunity. In vitro results reveal that the [email protected] could be effectively internalized by dendritic cells, causing their maturation and the subsequent regulation of their anti-tumor immune responses. Post-treatment observations in mice in which tumors were heat-treated at high temperatures reveal that tumor growth was significantly inhibited initially but not in the longer term, while low-temperature hyperthermia or immunotherapy alone simply delayed tumor growth. In contrast, a combined therapy that involved low-temperature hyperthermia and immunotherapy using [email protected]/+NIR induced a long-lasting immunologic memory and consequently inhibited tumor growth and prevented cancer recurrence and metastasis. These results suggest that the method that is proposed herein is promising for generating cancer vaccines in situ, by using the tumor itself as the antigen source and the introduced [email protected]/+NIR to generate a long-term anti-tumor immunity, for personalized immunotherapy.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119629DOI Listing
February 2020

Multi-walled carbon-nanotube-decorated tungsten ditelluride nanostars as anode material for lithium-ion batteries.

Nanotechnology 2020 Jan 27;31(3):035406. Epub 2019 Sep 27.

Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, 30013 Taiwan.

Multi-walled carbon-nanotube (MWCNT)-decorated WTe nanostars ([email protected] nanocomposites) are to be employed for the first time as anode candidates in the development of lithium-ion (Li-ion) batteries. [email protected] nanocomposites deliver a high discharge capacity of 1097, 475, 439, 408, 395 and 381 mA h g with an increasing current density of 100, 200, 400, 600, 800 and 1000 mA g, respectively, while WTe nanostars exhibit a reversible capacity of 655, 402, 400, 362, 290 and 197 mA h g with the aforementioned current densities. Furthermore, [email protected] nanocomposites exhibit a superior reversible capacity of 592 mA h g at 500 mA g with a capacity retention of 100% achieved over 500 cycles, while bare WTe nanostars deliver ∼85 mA h g over 350 cycles. This remarkable Li cycling performance is attributed to MWCNTs interconnected with WTe nanostars. In addition, the exposed active interlayers of the WTe nanostars, which are responsible for maintaining the structural integrity of the electrodes, buffer the large volume expansion within the WTe nanostars, avoiding the agglomeration of the particles. The layered WTe nanostars were synthesized via the solution-phase method, and present extremely good possibilities for the scaling-up of Li-ion battery storage systems.
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http://dx.doi.org/10.1088/1361-6528/ab48b2DOI Listing
January 2020

Blocking tombusvirus replication through the antiviral functions of DDX17-like RH30 DEAD-box helicase.

PLoS Pathog 2019 05 28;15(5):e1007771. Epub 2019 May 28.

Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, United States of America.

Positive-stranded RNA viruses replicate inside cells and depend on many co-opted cellular factors to complete their infection cycles. To combat viruses, the hosts use conserved restriction factors, such as DEAD-box RNA helicases, which can function as viral RNA sensors or as effectors by blocking RNA virus replication. In this paper, we have established that the plant DDX17-like RH30 DEAD-box helicase conducts strong inhibitory function on tombusvirus replication when expressed in plants and yeast surrogate host. The helicase function of RH30 was required for restriction of tomato bushy stunt virus (TBSV) replication. Knock-down of RH30 levels in Nicotiana benthamiana led to increased TBSV accumulation and RH30 knockout lines of Arabidopsis supported higher level accumulation of turnip crinkle virus. We show that RH30 DEAD-box helicase interacts with p33 and p92pol replication proteins of TBSV, which facilitates targeting of RH30 from the nucleus to the large TBSV replication compartment consisting of aggregated peroxisomes. Enrichment of RH30 in the nucleus via fusion with a nuclear retention signal at the expense of the cytosolic pool of RH30 prevented the re-localization of RH30 into the replication compartment and canceled out the antiviral effect of RH30. In vitro replicase reconstitution assay was used to demonstrate that RH30 helicase blocks the assembly of viral replicase complex, the activation of the RNA-dependent RNA polymerase function of p92pol and binding of p33 replication protein to critical cis-acting element in the TBSV RNA. Altogether, these results firmly establish that the plant DDX17-like RH30 DEAD-box helicase is a potent, effector-type, restriction factor of tombusviruses and related viruses. The discovery of the antiviral role of RH30 DEAD-box helicase illustrates the likely ancient roles of RNA helicases in plant innate immunity.
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http://dx.doi.org/10.1371/journal.ppat.1007771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555533PMC
May 2019

Persistent development of adomavirus and aquareovirus in a novel cell line from marbled eel with petechial skin haemorrhage.

J Fish Dis 2019 Mar 11;42(3):345-355. Epub 2019 Jan 11.

Department of Life Sciences, National University of Kaohsiung, Kaohsiung, Taiwan.

In Taiwan, a petechial haemorrhage disease associated with mortality has affected marbled eels (Anguilla marmorata). The eels were revealed to be infected with adomavirus (MEAdoV, previously recognized as a polyoma-like virus). In this study, cell line DMEPF-5 was established from the pectoral fin of a diseased eel. DMEPF-5 was passaged >70 times and thoroughly proliferated in L-15 medium containing 2%-15% foetal bovine serum at 20-30°C. Transcripts of neural cell adhesion molecule 1 and nestin genes, and nucleic acids of MEAdoV and a novel reovirus (MERV) in the cells were demonstrated by reverse transcription-polymerase chain reaction analysis. Phylogenetic analysis revealed that the AdoV LO8 proteins mostly relate to adenovirus adenain, whereas MERV is close to American grass carp reovirus in Aquareovirus G, based on a partial VP2 nucleotide sequence. DMEPF-5 cells are susceptible to additional viral infection. Taken together, the marbled eels with the haemorrhagic disease have coinfection with MEAdoV and MERV, and the pathogenic role of MEAdoV and MERV warrants research. DMEPF-5 has gene expression associated with mesenchymal stem and progenitor cells and is the first cell line persistently infected with adomavirus and aquareovirus. DMEPF-5 can facilitate studies of such viruses and haemorrhagic disease.
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http://dx.doi.org/10.1111/jfd.12939DOI Listing
March 2019

Elastoplastic behavior of highly cross-linked and vitamin E-stabilized polyethylene - A biomechanical study.

Clin Biomech (Bristol, Avon) 2018 11 20;59:152-158. Epub 2018 Sep 20.

Biomechanics Research Laboratory, Department of Medical Research, MacKay Memorial Hospital (MMH), Taipei County, Taiwan; Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan; School of Dentistry, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Background: Vitamin E-stabilized cross-linked polyethylene has been touted to alleviate the negative effects of oxidation. Although it has demonstrated significant improvements in wear resistance, bio-tribology, and oxidative resistance, little is known about the effect of antioxidants and dosage of cross-linking on the mechanical strength. This study aimed to evaluate the mechanical properties of these novel materials, which are commonly used in orthopedic implants.

Methods: Samples of different polymers were prepared with various levels of cross-linking and with or without vitamin E-stabilization and then tested according to ASTM D695 and D638. The elastoplastic characteristics under compression and tension were compared between the groups.

Findings: Vitamin E-stabilized cross-linked polyethylene showed a significant increase in elastic modulus over other groups, with a maximum increase of 26% in compression and 40% in tension when compared to the highly cross-linked group without vitamin E stabilization. The elastoplastic behavior under compression differed to that in tension for all polymers, demonstrating the anisotropic characteristics of these polymers.

Interpretation: The lower mechanical strength of highly cross-linked polyethylene has been a complication with the use of this polymer in orthopedic liners. This current study suggests that vitamin E-stabilized cross-linked polyethylene could be a suitable alternative material for knee implants because of its improved strength in resisting external forces.
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http://dx.doi.org/10.1016/j.clinbiomech.2018.09.021DOI Listing
November 2018

Toward Long-Term Stable and Efficient Large-Area Organic Solar Cells.

ChemSusChem 2017 07 12;10(13):2778-2787. Epub 2017 Jun 12.

Department of Physics, Chung Yuan Christian University, 200 Chung Pei Road, Chung Li, 32023, Taiwan.

Here, we report that long-term stable and efficient organic solar cells (OSCs) can be obtained through the following strategies: i) combination of rapid-drying blade-coating deposition with an appropriate thermal annealing treatment to obtain an optimized morphology of the active layer; ii) insertion of interfacial layers to optimize the interfacial properties. The resulting devices based on poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b;4,5-b']dithiophene-2,6-diyl-alt-(4-(2-ethylhexyl)-3-fluorothieno[3,4-b]thiophene-2-carboxylate-2,6-diyl)] (PBDTTT-EFT):[6,6]-phenyl C butyric acid methyl ester (PC BM) blend as the active layer exhibits a power conversion efficiency (PCE) up to 9.57 %, which represents the highest efficiency ever reported for blade-coated OSCs. Importantly, the conventional structure devices based on poly(3-hexylthiophene) (P3HT):phenyl-C -butyric acid methyl ester (PCBM) blend can retain approximately 65 % of their initial PCE for almost 2 years under operating conditions, which is the best result ever reported for long-term stable OSCs under operational conditions. More encouragingly, long-term stable large-area OSCs (active area=216 cm ) based on P3HT:PCBM blend are also demonstrated. Our findings represent an important step toward the development of large-area OSCs with high performance and long-term stability.
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http://dx.doi.org/10.1002/cssc.201700601DOI Listing
July 2017

Chitosan-assisted differentiation of porcine adipose tissue-derived stem cells into glucose-responsive insulin-secreting clusters.

PLoS One 2017 2;12(3):e0172922. Epub 2017 Mar 2.

Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan, R.O.C.

The unique advantage of easy access and abundance make the adipose-derived stem cells (ADSCs) a promising system of multipotent cells for transplantation and regenerative medicine. Among the available sources, porcine ADSCs (pADSCs) deserve especial attention due to the close resemblance of human and porcine physiology, as well as for the upcoming availability of humanized porcine models. Here, we report on the isolation and conversion of pADSCs into glucose-responsive insulin-secreting cells. We used the stromal-vascular fraction of the dorsal subcutaneous adipose from 9-day-old male piglets to isolate pADSCs, and subjected the cells to an induction scheme for differentiation on chitosan-coated plates. This one-step procedure promoted differentiation of pADSCs into pancreatic islet-like clusters (PILC) that are characterized by the expression of a repertoire of pancreatic proteins, including pancreatic and duodenal homeobox (Pdx-1), insulin gene enhancer protein (ISL-1) and insulin. Upon glucose challenge, these PILC secreted high amounts of insulin in a dose-dependent manner. Our data also suggest that chitosan plays roles not only to enhance the differentiation potential of pADSCs, but also to increase the glucose responsiveness of PILCs. Our novel approach is, therefore, of great potential for transplantation-based amelioration of type 1 diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172922PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333835PMC
September 2017

Tombusviruses upregulate phospholipid biosynthesis via interaction between p33 replication protein and yeast lipid sensor proteins during virus replication in yeast.

Virology 2014 Dec 28;471-473:72-80. Epub 2014 Oct 28.

Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, United States. Electronic address:

Positive-stranded RNA viruses induce new membranous structures and promote membrane proliferation in infected cells to facilitate viral replication. In this paper, the authors show that a plant-infecting tombusvirus upregulates transcription of phospholipid biosynthesis genes, such as INO1, OPI3 and CHO1, and increases phospholipid levels in yeast model host. This is accomplished by the viral p33 replication protein, which interacts with Opi1p FFAT domain protein and Scs2p VAP protein. Opi1p and Scs2p are phospholipid sensor proteins and they repress the expression of phospholipid genes. Accordingly, deletion of OPI1 transcription repressor in yeast has a stimulatory effect on TBSV RNA accumulation and enhanced tombusvirus replicase activity in an in vitro assay. Altogether, the presented data convincingly demonstrate that de novo lipid biosynthesis is required for optimal TBSV replication. Overall, this work reveals that a (+)RNA virus reprograms the phospholipid biosynthesis pathway in a unique way to facilitate its replication in yeast cells.
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http://dx.doi.org/10.1016/j.virol.2014.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775091PMC
December 2014

The implantable and biodegradable PHBHHx 3D scaffolds loaded with protein-phospholipid complex for sustained delivery of proteins.

Pharm Res 2013 Apr 7;30(4):1077-85. Epub 2012 Dec 7.

Key Laboratory of Drug Targeting and Drug Delivery System Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Section 3, South Renmin Road, Chengdu, 610041, People's Republic of China.

Purpose: PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) is an excellent biomaterial for tissue repair. Here, we aim to develop a PHBHHx-based three-dimensional (3D) scaffold system for sustained delivery of proteins (insulin serves as a model protein).

Methods: The insulin-phospholipid complex (INS-PLC) was prepared to enhance the insulin lipophilicity. INS-PLC loaded PHBHHx 3D scaffolds (INS-PLC-SCAs) containing PEG-2000 were fabricated by lyophilization. In vitro release was performed in the medium with or without lipase. The bioactivity of INS-PLC-SCAs was measured in diabetic rats.

Results: In vitro release shows that the release rate of INS-PLC-SCAs was very slow (~6% of total insulin was released within 120 days), and PEG-2000 or lipase had no effect on its release pattern. The bioactivity test shows that the hypoglycaemic effect of insulin was maintained after formulated into scaffolds. After subcutaneous (s.c.) implantation, its therapeutic effect lasted for over 130 h, and its bioavailability was enhanced by 4-fold.

Conclusions: PHBHHx based 3D scaffold has a great potential for sustained delivery of proteins, especially growth factors. When growth factors are incorporated, it can serve as a bifunctional system that provides a porous skeleton for cells attachment and proliferation, as well as a matrix for long term release of the loaded growth factors.
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http://dx.doi.org/10.1007/s11095-012-0944-9DOI Listing
April 2013

Synthesis and two-photon absorption property characterizations of small dendritic chromophores containing functionalized quinoxaliniod heterocycles.

Chemistry 2013 Jan 21;19(2):749-60. Epub 2012 Nov 21.

Photonic Materials Research Laboratory, Department of Chemistry, National Central University, Jhong-Li 32001, Taiwan.

A series of star-shaped multi-polar chromophores (compounds 1-3) containing functionalized quinoxaline and quinoxalinoid (indenoquinoxaline and pyridopyrazine) units has been synthesized and characterized for their two-photon absorption (2PA) properties both in the femtosecond and the nanosecond time domain. Under our experimental conditions, these model fluorophores are found to manifest strong and wide-dispersed two-photon absorption in the near-infrared region. It is demonstrated that molecular structures with multi-branched π frameworks incorporating properly functionalized quinoxalinoid units would possess large molecular nonlinear absorptivities within the studied spectral range. Effective optical-power attenuation and stabilization behaviors in the nanosecond time domain of a selected representative dye molecule (i.e., compound 2) from this model compound set were also investigated and the results indicate that such structural motif could be a useful approach for the molecular design toward strong two-photon-absorbing material systems for quick-responsive and broadband optical-suppressing-related applications, particularly to confront long laser pulses.
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http://dx.doi.org/10.1002/chem.201202178DOI Listing
January 2013

[Evaluation on effectiveness of comprehensive control model for soil-transmitted nematodiasis].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2011 Oct;23(5):518-23

Sichuan Provincial Center for Disease Control and Prevention, Chengdu 610041, China.

Objective: To evaluate the effect of a comprehensive control model for soil-transmitted nematodiasis.

Methods: Danling County was selected as a demonstration county carrying out the comprehensive prevention model centering on health education, nematode deworming, and drinking water and lavatories changing. On the other side, Hejiang was selected as a control. The effects were evaluated by comparing some indicators such as the infection rates of soil-transmitted nematodiasis and so on.

Results: The infection rates of soil-transmitted nematodiasis declined obviously from 2006 to 2009 in the demonstration county. The infection rates of Ascaris lumbricoides, hookworms, Trichiuris trichiura decreased by 91.14%, 81.65% and 65.77%. In the control county, those rates did not have downward tendency. In 2006, those rates in the demonstration county were higher than those in the control, but in 2009 those rates in the demonstration county were lower than those in the control.

Conclusions: Through the three-year comprehensive prevention, the infection rates of soil-transmitted nematodiasis declined obviously in the demonstration county. The epidemic situation of soil-transmitted nematodiasis could be controlled effectively by the comprehensive prevention model.
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October 2011

[Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity].

Zhong Xi Yi Jie He Xue Bao 2010 Nov;8(11):1023-8

School of Administration, Beijing University of Chinese Medicine, Beijing 100029, China.

Objective: To explore the relationships between traditional Chinese medicine (TCM) constitutional types and overweight or obesity so as to provide evidence for adjusting constitutional bias and preventing and treating obesity.

Methods: The data comes from a cross-sectional survey on TCM constitution of 18 805 samples aged above 18 in Beijing and 8 provinces (Jiangsu, Anhui, Gansu, Qinghai, Fujian, Jilin, Jiangxi and Henan) in China. The survey of TCM constitution was performed by standardized constitution in Chinese medicine questionnaire (CCMQ). Discriminatory analysis method was used to judge the individual's constitutional type (gentleness type, qi-deficiency type, yang-deficiency type, yin-deficiency type, phlegm-dampness type, dampness-heat type, blood-stasis type, qi-depression type and special diathesis type). The relationships between TCM constitution types and overweight or obesity was investigated by logistic regression analysis.

Results: Compared with gentleness type, the risk of overweight (OR, 2.05; 95% CI, 1.79-2.35) and obesity (OR, 4.34; 95% CI, 3.52-5.36) in phlegm-dampness type is significantly increased; the risk of obesity (OR, 1.60; 95% CI, 1.30-1.98) in qi-deficiency type is significantly higher; the risk of overweight and obesity in yang-deficiency type, blood-stasis type, and qi-depression type is significantly lower.

Conclusion: Phlegm-dampness type and qi-deficiency type are the main constitutional risk factors of overweight or obesity.
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http://dx.doi.org/10.3736/jcim20101104DOI Listing
November 2010

Facile synthesis of CeO2 nanoplates and nanorods by [100] oriented growth.

J Colloid Interface Sci 2010 Jan 23;341(1):12-7. Epub 2009 Apr 23.

Department of Materials Science and Engineering, Far East University, Hsin-Shih, Tainan County 74448, Taiwan, ROC.

This study demonstrated a facile method for the synthesis of CeO(2) nanoplates and nanorods via the thermal decomposition of a mixture of cerium acetate, oleic acid, oleyamine and 1-octadecene under controlled atmospheres. Morphologies of the produced cerium oxides were controlled by the adding procedures of activators. Activators added at room temperature and heated with the reaction mixture result in the formation of nanoplates. Injection of activators at high temperature leads to the formation of nanorods. Both the nanoplates and nanorods are achieved via the [100] oriented assembly of smaller particles. A blue-shifting of the UV absorption threshold edge are observed for the cerium oxide nanoplates and nanorods, contrasting with the bulk commercial powders.
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http://dx.doi.org/10.1016/j.jcis.2009.04.047DOI Listing
January 2010

[Changes of endocrine and immune function in subjects of yang deficiency constitution].

Zhong Xi Yi Jie He Xue Bao 2008 Dec;6(12):1226-32

Research Center for Reproduction Medicine and Body Constitution in Traditional Chinese Medicine, School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

Objective: To investigate the changes of endocrine, cyclic nucleotide and immune systems in subjects of yang deficiency constitution, and to explore the relationship among characteristics and causes of yang deficiency constitution, the physiological and biochemical parameters.

Methods: Based on the diagnostic criteria for the clinical epidemiological investigation, sixty subjects of yang deficiency constitution and fifty of normal constitution were selected. Eight milliliters venous blood were taken from overnight fasted subjects at 8:00-9:00. The sera were obtained by centrifugation of the blood at the speed of 3000 r/min for 5 minutes, and they were stored at -70 degrees C until use. The serum levels of corticosterone, cortisol, adrenocorticotrophic hormone (ACTH), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropic-stimulating hormone (TSH), interleukin-1beta and interleukin-2 were measured by enzyme-linked immunosorbent assay; the cAMP/cGMP ratio was also computed; and the differences of the above indexes were compared between the two types of subjects.

Results: The serum levels of corticosterone, interleukin-1beta, TSH and cAMP/cGMP ratio of yang deficiency constitution significantly increased as compared with those of normal constitution, and the serum levels of cortisol, ACTH, cGMP and FT4 of yang deficiency constitution significantly decreased in comparison with those of normal constitution.

Conclusion: Subjects of yang deficiency constitution may be not only related to hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-thyroid axis, but also related to the functional disorders of cyclic nucleotide and immune systems.
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http://dx.doi.org/10.3736/jcim20081204DOI Listing
December 2008

Spontaneous hemoperitoneum in pregnancy from a ruptured superficial uterine vessel.

Taiwan J Obstet Gynecol 2007 Mar;46(1):77-80

Department of Obstetrics and Gynecology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.

A 31-year-old multipara woman pregnant at gestational age 32+ weeks with twins encountered hemoperitoneum resulting from superficial uterine vessel rupture during tocolytic course. The initial presentations were unspecific and sonographic examination was negative. Later the aggravated symptoms led to an impression of abruption placentae and emergent cesarean section was performed. A superficial venous bleeder was located on the posterior uterine wall and the internal bleeding was up to 3 L. Maternal and fetal outcome were good. Hemoperitoneum during pregnancy is rare but life-threatening to both mother and fetus, and it mimics placenta abruption in many ways. However, by careful investigations with cardiotocogram and bedside echo, they are quite distinguishable. Aggressive fluid replacement and immediate surgical intervention after rapid diagnosis provides the best prognosis.
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http://dx.doi.org/10.1016/S1028-4559(08)60114-XDOI Listing
March 2007

[Neuroendocrine differentiation in prostate cancer].

Zhonghua Bing Li Xue Za Zhi 2006 Sep;35(9):565-7

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September 2006

Specific IgE to 5 different major house dust mites among asthmatic children.

Acta Paediatr Taiwan 2002 Sep-Oct;43(5):265-70

Department of Pediatrics, Mackay Memorial Hospital, No. 92, Sec. 2, Chung-Shan North Road, Taipei 104, Taiwan.

Asthma is one of the most commonly occurring manifestation of allergy in Taiwan. Sensitivity to house dust mites is closely related to childhood asthma. This study was designed to investigate sensitized rates and average concentrations of specific IgE antibodies to 5 major house dust mites (HDMs) among asthmatic children. A total of 93 asthmatic children aged from 3 to 15 years were enrolled to measure their specific IgE concentrations in response to 5 different species of mites: Dermatophagoides pteronyssinus (Dp), Dermatophagoides farinae (Df), Dermatophagoides microceras (Dm), Euroglyphus maynei (Em), and Blomia tropicalis (Bt). The severity of hypersensitivity was classified based on the concentration of specific IgE as mild (0.35-3.5 kuA/L), moderate (3.5-50 kuA/L), and severe (> 50 kuA/L). Sixty-three asthmatic children were found to have specific IgE to at least one mite. The percentage of these 63 children who had specific IgE to Dp, Df, Dm, Em and Bt were 87%, 85%, 84%, 77%, and 65%, respectively. Patients with specific IgE to Dp, Df, Dm, and Bt, had a high percentage of moderate and severe hypersensitivity (83.6%, 83.4%, 81.4%, 70.6%, respectively). However, patients sensitized to Em have relatively lower concentration of specific IgE Ab, with 75% of them in the mild range. Some patients had positive IgE antibody to Em (3.2%), and Bt (3.2%) even though they had none to Dp and Df. We conclude that Dm and Bt are also important mite allergens in atopic children. Conventional testing that assays only for sensitivity to Dp and Df would fail to demonstrate 6.4% of mite sensitized asthmatic children.
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March 2003

Juvenile idiopathic arthritis with pulmonary hemosiderosis: a case report.

J Microbiol Immunol Infect 2002 Jun;35(2):133-5

Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan, ROC.

Pleuropulmonary disease is occasionally seen in association with juvenile idiopathic arthritis. There have been few case reports of pulmonary hemosiderosis associated with juvenile idiopathic arthritis. We describe a case of a 3-year-old girl with iron deficiency anemia, juvenile idiopathic arthritis, and pulmonary hemosiderosis. Arthralgia of the left knee was noted 2 weeks after the diagnosis of iron deficiency anemia, and juvenile idiopathic arthritis was diagnosed 9 months later. She was treated with naproxen and prednisolone. Her joint symptoms were well controlled after the treatment. Six months later, hemoptysis developed and pulmonary hemosiderosis was diagnosed. She was again treated with naproxen and prednisolone and no more pulmonary or joint symptoms developed during more than 1-year follow-up.
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June 2002
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