Publications by authors named "Yiying Liu"

31 Publications

Probiotics: their action against pathogens can be turned around.

Sci Rep 2021 Jun 24;11(1):13247. Epub 2021 Jun 24.

Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China.

Probiotics when applied in complex evolving (micro-)ecosystems, might be selectively beneficial or detrimental to pathogens when their prophylactic efficacies are prone to ambient interactions. Here, we document a counter-intuitive phenomenon that probiotic-treated zebrafish (Danio rerio) were respectively healthy at higher but succumbed at lower level of challenge with a pathogenic Vibrio isolate. This was confirmed by prominent dissimilarities in fish survival and histology. Based upon the profiling of the zebrafish microbiome, and the probiotic and the pathogen shared gene orthogroups (genetic niche overlaps in genomes), this consequently might have modified the probiotic metabolome as well as the virulence of the pathogen. Although it did not reshuffle the architecture of the commensal microbiome of the vertebrate host, it might have altered the probiotic-pathogen inter-genus and intra-species communications. Such in-depth analyses are needed to avoid counteractive phenomena of probiotics and to optimise their efficacies to magnify human and animal well-being. Moreover, such studies will be valuable to improve the relevant guidelines published by organisations such as FAO, OIE and WHO.
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http://dx.doi.org/10.1038/s41598-021-91542-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225825PMC
June 2021

Characterization of Cellular Heterogeneity and an Immune Subpopulation of Human Megakaryocytes.

Adv Sci (Weinh) 2021 May 26:e2100921. Epub 2021 May 26.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.

Megakaryocytes (MKs) and their progeny platelets function in a variety of biological processes including coagulation, hemostasis, inflammation, angiogenesis, and innate immunity. However, the divergent developmental and cellular landscape of adult MKs remains mysterious. Here, by deriving the single-cell transcriptomic profiling of MKs from human adult bone marrow (BM), cellular heterogeneity within MKs is unveiled and an MK subpopulation with high enrichment of immune-associated genes is identified. By performing the dynamic single-cell transcriptomic landscape of human megakaryopoiesis in vitro, it is found that the immune signatures of MKs can be traced back to the progenitor stage. Furthermore, two surface markers, CD148 and CD48, are identified for mature MKs with immune characteristics. At the functional level, these CD148 CD48 MKs can respond rapidly to immune stimuli both in vitro and in vivo, exhibit high-level expression of immune receptors and mediators, and may function as immune-surveillance cells. The findings uncover the cellular heterogeneity and a novel immune subset of human adult MKs and should greatly facilitate the understanding of the divergent functions of MKs under physiological and pathological conditions.
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http://dx.doi.org/10.1002/advs.202100921DOI Listing
May 2021

Association between Interleukin-1β Polymorphism at Rs16944 and Glucose Metabolism: A Cohort Study.

Immunol Invest 2021 Mar 19:1-11. Epub 2021 Mar 19.

Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

: This study explored the correlation between the interleukin-1β gene rs16944 polymorphism and diabetes through epidemiological and follow-up investigations.: The study was conducted on 600 subjects with normal glucose metabolism recruited from participants of the in Luzhou, China in 2011. All subjects received a unified standardized questionnaire, physical examination, laboratory examination, and follow-up in 2016. Subjects were divided into normal glucose metabolism (NC), pre-diabetes (PDM), and type 2 diabetes mellitus (T2DM) groups according to their glucose metabolism after follow-up. The gene rs16944 polymorphism was analyzed using the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique.: After follow-up, 386, 156, and 58 cases were observed in the NC, PDM, and T2DM groups, respectively. Serum IL-1β levels were compared to baselines at follow-up in the 3 groups; the difference in the T2DM group was statistically significant. The frequency distributions of the gene rs16944 genotypes, i.e., CC, CT, and TT, were significantly different in the 3 groups, and the distributions in the T2DM and NC groups were significantly different. The frequency distributions of the C and T alleles of rs16944 were not significantly different. Logistic regression analysis identified the CC+CT genotype as an independent risk factor for the development of diabetes in patients with normal glucose metabolism (OR = 2.457, 95% CI: 1.238-4.877).: The gene rs16944 C/T polymorphism may cause genetic susceptibility to T2DM in the Luzhou population. The CC+CT genotypes may increase T2DM risk.
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http://dx.doi.org/10.1080/08820139.2020.1860085DOI Listing
March 2021

PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK-STAT1/3-EMT signalling.

Int J Oral Sci 2021 03 10;13(1). Epub 2021 Mar 10.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Oral squamous cell carcinoma (OSCC) has a high incidence of metastasis. Tumour immunotherapy targeting PD-L1 or PD-1 has been revolutionary; however, only a few patients with OSCC respond to this treatment. Therefore, it is essential to gain insights into the molecular mechanisms underlying the growth and metastasis of OSCC. In this study, we analysed the expression levels of protein kinase D3 (PKD3) and PD-L1 and their correlation with the expression of mesenchymal and epithelial markers. We found that the expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased, which correlated positively with that of mesenchymal markers but negatively with that of epithelial markers. Silencing PKD3 significantly inhibited the growth, metastasis and invasion of OSCC cells, while its overexpression promoted these processes. Our further analyses revealed that there was positive feedback regulation between PKD3 and PD-L1, which could drive EMT of OSCC cells via the ERK/STAT1/3 pathway, thereby promoting tumour growth and metastasis. Furthermore, silencing PKD3 significantly inhibited the expression of PD-L1, and lymph node metastasis of OSCC was investigated with a mouse footpad xenograft model. Thus, our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis.
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http://dx.doi.org/10.1038/s41368-021-00112-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946959PMC
March 2021

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Predict Mortality in Patients with Diabetic Foot Ulcers Undergoing Amputations.

Diabetes Metab Syndr Obes 2021 24;14:821-829. Epub 2021 Feb 24.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.

Purpose: Elevated platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with poor outcomes in various diseases. The objectives of this study were to explore the utility of PLR and NLR in predicting all-cause mortality in patients with diabetic foot ulcers (DFU) undergoing amputations.

Patients And Methods: A retrospective observational study was performed that included a total of 348 DFU patients undergoing amputations. The primary end-point was all-cause death. According to the PLR and NLR cut-off values, patients were divided into two groups and Kaplan-Meier survival curves were constructed. Multivariable Cox regression was conducted to test the independent predictors of mortality in the study cohort.

Results: All-cause mortality was significantly higher in patients with a high PLR/NLR compared to those with a low PLR/NLR. In the low NLR group, the overall survival (OS) rates at 1, 3, and 5 years after amputation were 96.8%, 84% and 80.1%, respectively (=0.001). In the high NLR group the corresponding OS rates at 1, 3, and 5 years were 85.2%, 58.6% and 23.9% (<0.001). According to the multivariate analysis, age (HR 1.074, 95% CI 1.045-1.104, p<0.001), Wagner classification (HR 2.274, 95% CI 1.351-3.828, p=0.002), PLR (HR 1.794, 95% CI 1.014-3.174, p=0.045), NLR (HR 2.029, 95% CI 1.177-3.499, p=0.011), creatinine (HR 1.003, 95% CI 1.001-1.004, p<0.001) and direct bilirubin (HR 1.154, 95% CI 1.081-1.232, p<0.001) were independent predictors of mortality following amputation.

Conclusion: Postoperative PLR and NLR values may be reliable predictive biomarkers of mortality in patients following amputation for DFU. Considering the high mortality in those patients, the patients with elevated PLR/NLR should be given more intensive in clinical practice.
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http://dx.doi.org/10.2147/DMSO.S284583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917326PMC
February 2021

Characterization and Evaluation of the Pro-Coagulant and Immunomodulatory Activities of Polysaccharides from .

ACS Omega 2021 Jan 30;6(1):656-665. Epub 2020 Dec 30.

Jilin Engineering Research Center for Agricultural Resources and Comprehensive Utilization, Jilin Institute of Chemical Technology, Jilin 132022, PR China.

is widely used for stanching bleeding. In this study, polysaccharides from (BSP) were extracted by hot water. Four polysaccharides named BSP-1-BSP-4 were fractionated using DEAE-52 cellulose. BSP fractions contained sulfate, and the degrees of substitution of BSP-3 and BSP-4 were 1.59 and 1.70, respectively. Analysis of monosaccharide composition showed that four polysaccharides were mainly composed of mannan and glucose. The results showed that BSP-1-BSP-4 elicited pro-coagulant capacities by shortening the activating partial thromboplastin time, prothrombin time, and thrombin time and elevating the fibrinogen content. Immunomodulatory activity was evaluated by MTT assay, the pinocytic capacity and NO production. Although BSP fractions did not affect RAW 264.7 cell viability, they, especially BSP-2, enhanced the immunomodulatory activity by increasing the pinocytic capacity and NO production. Overall, BSP may be developed as a potential coagulant with immunomodulatory effects.
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http://dx.doi.org/10.1021/acsomega.0c05171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807737PMC
January 2021

The combined use of salivary biomarkers and clinical parameters to predict the outcome of scaling and root planing: A cohort study.

J Clin Periodontol 2020 11 13;47(11):1379-1390. Epub 2020 Oct 13.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Aim: To explore the application of the combined use of baseline salivary biomarkers and clinical parameters in predicting the outcome of scaling and root planing (SRP).

Materials And Methods: Forty patients with advanced periodontitis were included. Baseline saliva samples were analysed for interleukin-1β (IL-1β), matrix metalloproteinase-8 and the loads of Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans and Tannerella forsythia. After SRP, pocket closure and further attachment loss at 6 months post-treatment were chosen as outcome variables. Models to predict the outcomes were established by generalized estimating equations.

Results: The combined use of baseline clinical attachment level (CAL), site location and IL-1β (area under the curve [AUC] = 0.764) better predicted pocket closure than probing depth (AUC = 0.672), CAL (AUC = 0.679), site location (AUC = 0.654) or IL-1β (AUC = 0.579) alone. The combination of site location, tooth loss, percentage of deep pockets, detection of A. actinomycetemcomitans and T. forsythia load (AUC = 0.842) better predicted further clinical attachment loss than site location (AUC = 0.715), tooth loss (AUC = 0.530), percentage of deep pockets (AUC = 0.659) or T. forsythia load (AUC = 0.647) alone.

Conclusion: The combination of baseline salivary biomarkers and clinical parameters better predicted SRP outcomes than each alone. The current study indicates the possible usefulness of salivary biomarkers in addition to tooth-related parameters in predicting SRP outcomes.
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http://dx.doi.org/10.1111/jcpe.13367DOI Listing
November 2020

Identification of Clonal Neoantigens Derived From Driver Mutations in an -Mutated Lung Cancer Patient Benefitting From Anti-PD-1.

Front Immunol 2020 23;11:1366. Epub 2020 Jul 23.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Epidermal growth factor receptor () tyrosine kinase inhibitors (TKIs) have been recommended as the first-line therapy for non-small cell lung cancer (NSCLC) patients harboring mutations. However, acquired resistance to EGFR-TKIs is inevitable. Although immune checkpoint blockades (ICBs) targeting the programmed cell death 1 (PD-1)/PD-ligand (L)1 axis have achieved clinical success for many cancer types, the clinical efficacy of anti-PD-1/PD-L1 blockades in mutated NSCLC patients has been demonstrated to be lower than those without mutations. Here, we reported an advanced NSCLC patient with driver mutations benefitting from anti-PD-1 blockade therapy after acquiring resistance to EGFR-TKI. We characterized the mutational landscape of the patient with next-generation sequencing (NGS) and successfully identified specific T-cell responses to clonal neoantigens encoded by exon 19 deletion, and mutations. Our findings support the potential application of immune checkpoint blockades in NSCLC patients with acquired resistance to EGFR-TKIs in the context of specific clonal neoantigens with high immunogenicity. Personalized immunomodulatory therapy targeting these neoantigens should be explored for better clinical outcomes in mutated NSCLC patients.
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http://dx.doi.org/10.3389/fimmu.2020.01366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390822PMC
April 2021

Relationships among pancreatic beta cell function, the Nrf2 pathway, and IRS2: a cross-sectional study.

Postgrad Med 2020 Nov 6;132(8):720-726. Epub 2020 Aug 6.

Department of Endocrinology, The Affiliated Hospital of Southwest Medical University , Luzhou, Sichuan, China.

Objectives: This study aimed to investigate the relationships among islet function, the Nrf2 pathway, and insulin receptor substrate 2 (IRS2) in type 2 diabetes mellitus (T2DM), prediabetes mellitus (IGR), and normal glucose tolerance (NGT) populations.

Methods: Three hundred cases each were selected for the NGT, IGR, and T2DM groups; FBG, 2hPG, HbA1 c, FINS, TG, TC, HDL-C, and LDL-C levels and serum levels of nuclear factor in E2-related factor 2 (Nrf2), insulin receptor substrate 2 (IRS2), tumor necrosis factor alpha (TNF-α), and heme oxygenase 1 (HO-1) were evaluated.

Results: The T2DM group had lower islet β-cell function index and insulin sensitivity index than the NGT and IGR groups (P < 0.05). The Nrf2, IRS2, and HO-1 levels in the NGT, IGR, and T2DM groups followed a decreasing trend in the order mentioned, whereas the TNF-α levels followed an increasing trend.

Conclusions: Upon impairment of glucose regulation, the expression of TNF-α in the human body increased, which indicated the aggravation of oxidative stress (OS) and the inflammatory response. Islet function was maintained in the pre-diabetic population, and concurrently, the TNF-α, Nrf2, and HO-1 levels were moderately elevated, the expression of IRS2 was marginally inhibited, and the Nrf2 pathway was activated under mild OS stimulus to resist OS, inflammation, and injury, which may have been mediated through PI3 K/AKT. In patients with T2DM, islet function was significantly poorer, TNF-α amplification was enhanced significantly, and Nrf2, HO-1, and IRS2 expression reduced significantly; this suggested that, along with the aggravation of OS and the inflammatory response, Nrf2 pathway activation and HO-1 expression were both inhibited, the antioxidant capacity of the body was reduced, IRS2 degradation increased, and islet function was impaired.
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http://dx.doi.org/10.1080/00325481.2020.1797311DOI Listing
November 2020

The psychometric properties of a new oral health illness perception measure for adults aged 62 years and older.

PLoS One 2019 10;14(4):e0214082. Epub 2019 Apr 10.

Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.

Background: Based on the Common-Sense Model of Self-Regulation (CSM), a new integrated Illness Perception Questionnaire Revised for Dental Use in Older/Elder Adults (IPQ-RDE) was developed for single and multiple dental conditions. This study describes psychometric properties of the IPQ-RDE for adults 62 years and older.

Methods: Participants (n = 198) living in 16 subsidized housing facilities completed the IPQ-RDE and a questionnaire assessing their socio-demographics, frequency of dental visits, perceived condition of teeth/gums, depression, social support, and oral health quality of life (OHQOL). Participants received dental screening for presence/absence of teeth, coronal and root caries, and periodontitis. The 43-item IPQ-RDE was tested for internal (construct, discriminant) and external validity (concurrent, construct, discriminant, predictive) and reliability (internal consistency).

Results: Confirmatory factor analysis demonstrated that a ten-factor model in accordance with the CSM framework (identity, consequences, control, timeline, illness coherence, treatment burden, prioritization, causal relationship, activity restriction, emotional representations) had good construct validity based on significant factor loadings and acceptable model fit (RMSEA = 0.065, CFI = 0.902). Edentulous participants had significantly higher mean factor scores (inaccurate perception) for overall IPQ-RDE and four constructs indicating concurrent validity. Discriminant validity was suggested by non-relationship with external measures (education, dental visit frequency). Predictive validity was indicated by the negative correlation of most constructs with OHQOL suggesting that inaccurate perception was related to lower quality of life. Internal consistency of eight IPQ-RDE constructs was excellent (Cronbach's alpha > 0.73).

Conclusions: The IPQ-RDE is a valid and reliable new measure for assessing older adult's perception of dental conditions. It can be an important tool for oral health behavioral research to restructure older adult's perception of dental conditions, and subsequently prevent tooth loss and improve oral health quality of life.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214082PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457485PMC
December 2019

Decitabine improves platelet recovery by down-regulating IL-8 level in MDS/AML patients with thrombocytopenia.

Blood Cells Mol Dis 2019 05 20;76:66-71. Epub 2019 Feb 20.

State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China; Hematopoietic Stem Cell Transplant Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China. Electronic address:

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http://dx.doi.org/10.1016/j.bcmd.2019.02.003DOI Listing
May 2019

Does quorum sensing interference affect the fitness of bacterial pathogens in the real world?

Environ Microbiol 2018 11 30;20(11):3918-3926. Epub 2018 Oct 30.

Center for Microbial Ecology and Technology (CMET), Ghent University, Ghent, Belgium.

Many bacterial pathogens rely on quorum sensing to control virulence gene expression. Based on numerous experiments conducted under well-defined conditions, quorum sensing interference is considered as a promising strategy to tackle infections and thus might have the potential to (partially) replace antibiotics. Despite the promising results in well-defined (artificial) laboratory experiments, there still is a lack of knowledge with respect to the impact of quorum sensing interference on the fitness of pathogens in more realistic scenarios, including interactions with a host, the external environment and complex microbial communities. In this article, we critically evaluate the current knowledge with respect to these three facets of the real world that can affect the fitness of quorum sensing bacterial pathogens. We argue that further research is needed in order to determine how these factors interplay with quorum sensing and to what extent they can influence the selective pressure that might be exerted by quorum sensing interference (and thus determine the risk of resistance development against quorum sensing interference). This kind of information is indispensable in order to optimize quorum sensing interference-based therapeutic strategies.
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http://dx.doi.org/10.1111/1462-2920.14446DOI Listing
November 2018

Generalized causal mediation and path analysis: Extensions and practical considerations.

Stat Methods Med Res 2019 06 5;28(6):1793-1807. Epub 2018 Jun 5.

2 Department of Community Dentistry, Case School of Dental Medicine, Cleveland, OH, USA.

Causal mediation analysis seeks to decompose the effect of a treatment or exposure among multiple possible paths and provide casually interpretable path-specific effect estimates. Recent advances have extended causal mediation analysis to situations with a sequence of mediators or multiple contemporaneous mediators. However, available methods still have limitations, and computational and other challenges remain. The present paper provides an extended causal mediation and path analysis methodology. The new method, implemented in the new R package, gmediation (described in a companion paper), accommodates both a sequence (two stages) of mediators and multiple mediators at each stage, and allows for multiple types of outcomes following generalized linear models. The methodology can also handle unsaturated models and clustered data. Addressing other practical issues, we provide new guidelines for the choice of a decomposition, and for the choice of a reference group multiplier for the reduction of Monte Carlo error in mediation formula computations. The new method is applied to data from a cohort study to illuminate the contribution of alternative biological and behavioral paths in the effect of socioeconomic status on dental caries in adolescence.
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http://dx.doi.org/10.1177/0962280218776483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428612PMC
June 2019

Exploring fish microbial communities to mitigate emerging diseases in aquaculture.

FEMS Microbiol Ecol 2018 01;94(1)

Department of Microbial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Droevendaalsesteeg 10, Wageningen 6708PB, The Netherlands.

Aquaculture is the fastest growing animal food sector worldwide and expected to further increase to feed the growing human population. However, existing and (re-)emerging diseases are hampering fish and shellfish cultivation and yield. For many diseases, vaccination protocols are not in place and the excessive use of antibiotics and other chemicals is of substantial concern. A more sustainable disease control strategy to protect fish and shellfish from (re-)emerging diseases could be achieved by introduction or augmentation of beneficial microbes. To establish and maintain a 'healthy' fish microbiome, a fundamental understanding of the diversity and temporal-spatial dynamics of fish-associated microbial communities and their impact on growth and health of their aquatic hosts is required. This review describes insights in the diversity and functions of the fish bacterial communities elucidated with next-generation sequencing and discusses the potential of the microbes to mitigate (re-)emerging diseases in aquaculture.
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http://dx.doi.org/10.1093/femsec/fix161DOI Listing
January 2018

Magnetic capture of polydopamine-encapsulated Hela cells for the analysis of cell surface proteins.

J Proteomics 2018 02 16;172:76-81. Epub 2017 Oct 16.

Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China. Electronic address:

A novel method to characterize cell surface proteins and complexes has been developed. Polydopamine (PDA)-encapsulated Hela cells were prepared for plasma membrane proteome research. Since the PDA protection, the encapsulated cells could be maintained for more than two weeks. Amino groups functionalized magnetic nanoparticles were also used for cell capture by the reaction with the PDA coatings. Plasma membrane fragments were isolated and enriched with assistance of an external magnetic field after disruption of the coated cells by ultrasonic treatment. Plasma membrane proteins (PMPs) and complexes were well preserved on the fragments and identified by shot-gun proteomic analytical strategy. 385 PMPs and 1411 non-PMPs were identified using the method. 85.2% of these PMPs were lipid-raft associated proteins. Ingenuity Pathway Analysis was employed for bio-information extraction from the identified proteins. It was found that 653 non-PMPs had interactions with 140 PMPs. Among them, epidermal growth factor receptor and its complexes, and a series of important pathways including STAT3 pathway were observed. All these results demonstrated that the new approach is of great importance in applying to the research of physiological function and mechanism of the plasma membrane proteins.

Significance: This work developed a novel strategy for the proteomic analysis of cell surface proteins. According to the results, 73.3% of total identified proteins were lipid-raft associated proteins, which imply that the proposed method is of great potential in the identification of lipid-raft associated proteins. In addition, a series of protein-protein interactions and pathways related to Hela cells were pointed out. All these results demonstrated that our proposed approach is of great importance and could well be applied to the physiological function and mechanism research of plasma membrane proteins.
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http://dx.doi.org/10.1016/j.jprot.2017.10.009DOI Listing
February 2018

Effect of Pericardial Fat Volume and Density on Markers of Insulin Resistance and Inflammation in Patients With Human Immunodeficiency Virus Infection.

Am J Cardiol 2017 Oct 24;120(8):1427-1433. Epub 2017 Jul 24.

Case Western Reserve University School of Medicine, Cleveland, Ohio; University Hospitals Cleveland Medical Center, Cleveland, Ohio.

Treated human immunodeficiency virus (HIV) infection is characterized by ectopic fat deposition, a persistent inflammatory state, and increased cardiometabolic risk. In this secondary analysis of a placebo controlled trial of rosuvastatin among 147 HIV+ subjects (median age 46; 78% men) on stable antiretroviral therapy, we aimed to evaluate longitudinal associations between computed tomography (CT) measures of pericardial fat (PCF) volume and density, insulin resistance, and inflammation. We measured PCF volume and density (mean attenuation in Hounsfield units) by noncontrast gated CT at baseline and week 96. Homeostatic model of insulin resistance was calculated from fasting insulin and glucose at entry, 24, 48, and 96 weeks. At baseline, insulin resistance correlated positively with PCF volume and negatively with density. Similarly divergent correlations of volume and density were observed with waist:hip ratio, nadir CD4+ count, and duration of antiretroviral therapy. In a linear mixed model, PCF density was associated with insulin resistance independent of PCF volume, body mass index, metabolic syndrome, and biomarkers of immune activation and systemic inflammation; however, baseline PCF measures were not associated with longitudinal changes in insulin resistance. Soluble CD163, a marker of monocyte activation, positively correlated with PCF volume and was associated with insulin resistance in linear models. Statin treatment assignment did not affect PCF volume or density change (both p > 0.8). In conclusion, the quantity and quality (i.e., radiodensity) of PCF are differentially related to insulin resistance and inflammation in patients with treated HIV infection.
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http://dx.doi.org/10.1016/j.amjcard.2017.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614847PMC
October 2017

Enhanced activity of macrophage M1/M2 phenotypes in periodontitis.

Arch Oral Biol 2018 Dec 11;96:234-242. Epub 2017 Mar 11.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Periodontology, West China College of Stomatology, Sichuan University, Chengdu, China. Electronic address:

Objective: Monocytes/macrophages play a key role in mobilizing host defense against microbial infection. The selectivity of gene expression can turn macrophages into M1- or M2-type and the plasticity and differentiation of both M1 and M2 macrophages may play important roles in the development of periodontal disease. Our research aimed to study the association between the ratio of M1/M2 macrophage and inflammatory cytokines IL-1β, MMP-9, and investigate the expressions of M1-and M2-type macrophages in gingivitis and chronic periodontitis.

Methods: Forty specimens were collected from gingivitis individuals (n=20) and chronic periodontitis (n=20). Probing depth (PD), clinical attachment level (CAL), plaque index (PI) and bleeding on probing (BOP) were recorded. The expressions of M1- and M2-type macrophages are detected with immunohistochemical method and the relative expressions of M1-, M2-type macrophage, IL-1β and MMP-9 were assayed using real-time polymerase chain reactions.

Results: The M1 and M2 peptide were mainly observed in the cytoplasm of gingival connective tissue. The ratio of M1/M2 was significant higher in chronic periodontitis group compared with that in gingivitis one. In addition, the relative expressions of IL-1β and MMP-9 also increased in periodontitis group and was correlated with the ratios of M1/M2. Meanwhile, PD was positively correlated with ratios of M1/M2.

Conclusions: Periodontal inflammation associates with an enhancement of ratio of M1/M2 phenotypes of macrophages. M1/M2 ratio could provide useful information on the periodontal tissue health status.
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http://dx.doi.org/10.1016/j.archoralbio.2017.03.006DOI Listing
December 2018

A review of the literature: antibiotic usage and its relevance to the infection in periodontal flaps.

Acta Odontol Scand 2017 May 10;75(4):288-293. Epub 2017 Mar 10.

a State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu , China.

Objective: This study aimed to investigate the systemic antibiotic usage in the perioperative period of periodontal flaps and its relevance to the infection after surgeries through reviewing the papers of the last decade.

Materials And Methods: A search was conducted for the studies of randomized clinical trials between 2005 and 2014 that reported periodontal flaps in chronic periodontitis patients. Data were extracted and the rate of the systemic antibiotic use, the infection rate after surgeries and the number needed to treat (NNT) to prevent one infected case were calculated. The impact of antibiotic use and materials used in surgeries on the infection was evaluated.

Results: Eighty-three trials were included. Antibiotics were used in 73.7% of the patients and 75.4% of the flaps. Infection occurred in only five flaps where enamel matrix proteins (EMD) or EMD + bone grafts were used in intrabony defects. Only 0.170% of the surgeries got infected in total. When all kinds of surgeries were included for analysis, the infection rate was 0.073% for the surgeries using antibiotics, which was lower than the infection rate 0.693% for the surgeries not using antibiotics (p < .05). The infection rate was very low in general. NNT was 203 when all the surgeries were included for analysis. Therefore, the difference of the infection rates between using antibiotics and not might lack clinical significance.

Conclusions: Considering the very low incidence of the infection and the disadvantages of the systemic antibiotic use, we suggest not using systemic antibiotics in the perioperative period of periodontal flaps to prevent infection.
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http://dx.doi.org/10.1080/00016357.2017.1295165DOI Listing
May 2017

[Developments of neutrophil function and the relationship between neutrophils dysfunction and periodontitis].

Hua Xi Kou Qiang Yi Xue Za Zhi 2016 Apr;34(2):210-4

Polymorphonuclear neutrophil leukocyte (PMN) is an important member of the human immune cells. Recentyears, the recognition of the PMN function and the relationship between PMN and periodontitis have been updated. Besidesthe pathogens killing and phagocytosis, PMN also play an important role in immunoregulation and proresolving. The maintaining of PMN homeostasis is an intricate process and the precondition of defense function, which involves activation, adhesion, recruitment, apoptosis and efferocytosis. The regulatory mechanism of PMN homeostasis called neutrophil rheostat, it works through several cytokines and cells. Any factors that break the homeostasis will result in the damage of host immunity,and may relate to the occurrence of periodontitis. Moreover, PMN dysfunction, because of host factors or microorganism factors, is closely related to periodontitis, especially those associated with systemic diseases and gene defect.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029976PMC
April 2016

Integrated system for extraction, purification, and digestion of membrane proteins.

Anal Bioanal Chem 2016 May 27;408(13):3495-502. Epub 2016 Feb 27.

Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China.

An integrated system was developed for directly processing living cells into peptides of membrane proteins. Living cells were directly injected into the system and cracked in a capillary column by ultrasonic treatment. Owing to hydrophilicity for broken pieces of the cell membrane, the obtained membranes were retained in a well-designed bi-filter. While cytoplasm proteins were eluted from the bi-filter, the membranes were dissolved and protein released by flushing 4% SDS buffer through the bi-filter. The membrane proteins were subsequently transferred into a micro-reactor and covalently bound in the reactor for purification and digestion. As the system greatly simplified the whole pretreatment processes and minimized both sample loss and contamination, it could be used to analyze the membrane proteome samples of thousand-cell-scales with acceptable reliability and stability. We totally identified 1348 proteins from 5000 HepG2 cells, 615 of which were annotated as membrane proteins. In contrast, with conventional method, only 233 membrane proteins were identified. It is adequately demonstrated that the integrated system shows promising practicability for the membrane proteome analysis of small amount of cells.
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http://dx.doi.org/10.1007/s00216-016-9427-xDOI Listing
May 2016

Simultaneous T and T Brain Relaxometry in Asymptomatic Volunteers using Magnetic Resonance Fingerprinting.

Tomography 2015 Dec;1(2):136-144

Department of Radiology, Case Western Reserve University and University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.

Magnetic resonance fingerprinting (MRF) is a method of image acquisition that produces multiple MR parametric maps from a single scan. Here, we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. 56 normal volunteers (ages 11-71 years, M:F 24:32) were scanned. Regions of interest were drawn on T and T maps in 38 areas, including lobar and deep white matter, deep gray nuclei, thalami and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model including either gender, age, or both, where variables were included if they contributed significantly (p<0.05). Additionally, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t-tests. Using this protocol, MRF-derived T and T in frontal WM regions were found to increase in with age, while occipital and temporal regions remained relatively stable. Deep gray nuclei, including substantia nigra, were found to have age-related decreases in relaxometry. Gender differences were observed in T and T of temporal regions, cerebellum and pons. Males were also found to have more rapid age-related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between genu and splenium of corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification can measure relaxometry trends in healthy individuals that are in agreement with current understanding of neuroanatomy and neurobiology, and has the ability to uncover additional patterns that have not yet been explored.
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http://dx.doi.org/10.18383/j.tom.2015.00166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727840PMC
December 2015

Elucidating the Diversity of Aquatic Microdochium and Trichoderma Species and Their Activity against the Fish Pathogen Saprolegnia diclina.

Int J Mol Sci 2016 Jan 21;17(1). Epub 2016 Jan 21.

Department of Microbial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Wageningen 6708 PB, The Netherlands.

Animals and plants are increasingly threatened by emerging fungal and oomycete diseases. Amongst oomycetes, Saprolegnia species cause population declines in aquatic animals, especially fish and amphibians, resulting in significant perturbation in biodiversity, ecological balance and food security. Due to the prohibition of several chemical control agents, novel sustainable measures are required to control Saprolegnia infections in aquaculture. Previously, fungal community analysis by terminal restriction fragment length polymorphism (T-RFLP) revealed that the Ascomycota, specifically the genus Microdochium, was an abundant fungal phylum associated with salmon eggs from a commercial fish farm. Here, phylogenetic analyses showed that most fungal isolates obtained from salmon eggs were closely related to Microdochium lycopodinum/Microdochium phragmitis and Trichoderma viride species. Phylogenetic and quantitative PCR analyses showed both a quantitative and qualitative difference in Trichoderma population between diseased and healthy salmon eggs, which was not the case for the Microdochium population. In vitro antagonistic activity of the fungi against Saprolegnia diclina was isolate-dependent; for most Trichoderma isolates, the typical mycoparasitic coiling around and/or formation of papilla-like structures on S. diclina hyphae were observed. These results suggest that among the fungal community associated with salmon eggs, Trichoderma species may play a role in Saprolegnia suppression in aquaculture.
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http://dx.doi.org/10.3390/ijms17010140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730379PMC
January 2016

Psychometric properties of a caregiver illness perception measure for caries in children under 6 years old.

J Psychosom Res 2016 Feb 7;81:46-53. Epub 2016 Jan 7.

Objective: Based on the Common-Sense Model of Self-Regulation (CSM), the Revised Illness Perception Questionnaire (IPQ-R) was developed to measure patients' perceptions of their chronic medical illness. Such a measure does not exist for dental conditions. This study describes psychometric properties of the IPQ-R for Dental (IPQ-RD) for parent/caregivers of children under 6 years of age.

Methods: Parent/caregivers (n=160) of children aged <6 years attending a pediatric dental clinic completed the IPQ-RD and a questionnaire assessing their socio-demographics, dental anxiety, oral health self-efficacy, and child's preventive dental visits. Dental charts were abstracted for child's decayed, missing, filled teeth (dmft) information. The 33-item IPQ-RD was tested for internal (construct, discriminant) and external validity (concurrent, convergent, discriminant) and reliability (internal consistency).

Results: Confirmatory factor analysis demonstrated that the eight-factor model in accordance with the CSM framework (identity, consequences-child, consequences-caregiver, control-child, control-caregiver, timeline, illness coherence, emotional representations) had good construct validity based on significant factor loadings and acceptable to excellent model fit (RMSEA=0.078, CFI=0.951). Concurrent validity was demonstrated by significant negative correlations and higher mean factor scores for five constructs for children without dental visits indicating inaccurate caregiver perception of cavities. Discriminant validity was suggested by non-relationship with external measures (dental anxiety, self-efficacy). Internal consistency of six IPQ-RD constructs was excellent (Cronbach's alpha >0.74).

Conclusion: The IPQ-RD is a valid and reliable measure to assess parent/caregivers' representation of young children's cavities with potential to be a valuable risk assessment tool for oral health behavioral research.
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http://dx.doi.org/10.1016/j.jpsychores.2016.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724635PMC
February 2016

Membrane protein isolation and identification by covalent binding for proteome research.

Proteomics 2015 Nov 23;15(22):3892-900. Epub 2015 Oct 23.

Department of Chemistry, Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.

A novel method to achieve highly efficient identification of membrane proteins (MPs) has been developed based on a covalent binding (CB) strategy. For this purpose, magnetic nanoparticles coated with a PEG layer were synthesized. The PEG chain end was functionalized to form the PEG-tresyl group, which is an octopus-like long arm to capture the free amino groups of MPs. The long arm could be used to bind proteins in a high concentration of the SDS medium. Then, the SDS and interfering substances were completely depleted by washing. The CB proteins could form a molecular monolayer on the surface of the nanoparticles in the denatured state, which was significantly favorable for the proteolysis of MPs. Therefore, isolation with CB and highly efficient digestion resulted in a larger scale of MPs. The method has been verified by a proteome identification of mouse liver samples. A total of 2946 MPs were identified in an MP fraction. A total of 1505 proteins were characterized as integral MPs, and 735 MPs were identified beyond the largest database summarized by PeptideAtlas. This approach has great potential for membrane proteome research.
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http://dx.doi.org/10.1002/pmic.201400572DOI Listing
November 2015

Investigation on the response of fused taper couplers to ultrasonic wave.

Appl Opt 2015 Aug;54(23):6986-93

The responses of fused taper couplers with different structure parameters to ultrasonic waves have been investigated theoretically and experimentally. A comprehensive analysis of the acousto-optic interaction was presented, taking into account the elasto-optic geometric effect. It is found that direct deformation of the coupler induced by ultrasonic waves is the critical factor in the sensing mechanism and is closely related to the sensor sensitivity. Moreover, the strain response of the coupler with different structure parameters was analyzed using a 3D coupled acoustic-solid numerical model, which was based on the developed mathematical model. According to the theoretical analyses, related experiments were carried out, and experimental results show that this ultrasonic sensor with a longer stretching length has higher sensitivity and the sensitivity of the sensor takes a nonmonotonic relation with an aspect ratio, which are consistent with the theoretical analyses results. We argue that our work may provide a useful guide in designing and optimizing more sensitive ultrasonic sensors used in practical ultrasonic detection.
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http://dx.doi.org/10.1364/AO.54.006986DOI Listing
August 2015

Phase I dose-escalation study of stereotactic body radiotherapy (SBRT) for poor surgical candidates with localized renal cell carcinoma.

Radiother Oncol 2015 Oct 8;117(1):183-7. Epub 2015 Sep 8.

Department of Urology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, USA; Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, USA.

Purpose: To evaluate the tolerability of escalating doses of stereotactic body radiotherapy (SBRT) for primary treatment of localized renal cell carcinoma (RCC) in poor surgical candidates.

Patients And Methods: Eligible patients included those with clinically staged radiographic and or pathologically confirmed RCC who had not undergone previous abdominal or pelvic radiotherapy. All patients had comorbid medical conditions which precluded surgery. Median (range) patient age was 77.6years (range 59-89) years and all patients had Karnofsky Performance Status of ⩾60. Median tumor volume was 57.9cm(3) (range 13.8-174.7cm(3)). Dose-limiting toxicity (DLT) was defined as grade 3 or worse gastrointestinal/genitourinary toxicity by Common Terminology Criteria of Adverse Events (version 4). Tumor response was assessed by imaging results using Response Evaluation Criteria In Solid Tumors (RECIST) measurement and percutaneous biopsy.

Results: A total of 19 patients (13 men and 6 women) were treated on protocol from June 2006 through August 2011. Groups of 3-6 patients received 24, 32, 40, and 48Gy in 4 fractions. Median (range) follow-up was 13. 7months (5.9-34.7months). For possibly treatment-related acute toxicities, one patient developed grade 2 fatigue and one developed grade 4 duodenal ulcer. For possibly treatment-related late toxicities, 2 patients experienced grade 3 renal toxicity (worsening chronic kidney disease), one reported grade 2 urinary incontinence and one developed grade 4 duodenal ulcer. Among the 15 patients with evaluable response, 3 and 12 had partial response and stable disease, respectively, utilizing RECIST criteria. Among the 11 patients who had post-SBRT biopsy, only one (9%) was negative on first biopsy and an additional one (9%) turned negative without further therapy on second biopsy.

Conclusions: Dose escalation to 48Gy in 4 fractions has been achieved successfully without dose-limiting toxicities. A planned extension of this phase I trial is currently underway treating patients to 60Gy in 3 fractions to further evaluate this experimental therapy.
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http://dx.doi.org/10.1016/j.radonc.2015.08.030DOI Listing
October 2015

Diversity of Aquatic Pseudomonas Species and Their Activity against the Fish Pathogenic Oomycete Saprolegnia.

PLoS One 2015 28;10(8):e0136241. Epub 2015 Aug 28.

Department of Microbial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, The Netherlands.

Emerging fungal and oomycete pathogens are increasingly threatening animals and plants globally. Amongst oomycetes, Saprolegnia species adversely affect wild and cultivated populations of amphibians and fish, leading to substantial reductions in biodiversity and food productivity. With the ban of several chemical control measures, new sustainable methods are needed to mitigate Saprolegnia infections in aquaculture. Here, PhyloChip-based community analyses showed that the Pseudomonadales, particularly Pseudomonas species, represent one of the largest bacterial orders associated with salmon eggs from a commercial hatchery. Among the Pseudomonas species isolated from salmon eggs, significantly more biosurfactant producers were retrieved from healthy salmon eggs than from Saprolegnia-infected eggs. Subsequent in vivo activity bioassays showed that Pseudomonas isolate H6 significantly reduced salmon egg mortality caused by Saprolegnia diclina. Live colony mass spectrometry showed that strain H6 produces a viscosin-like lipopeptide surfactant. This biosurfactant inhibited growth of Saprolegnia in vitro, but no significant protection of salmon eggs against Saprolegniosis was observed. These results indicate that live inocula of aquatic Pseudomonas strains, instead of their bioactive compound, can provide new (micro)biological and sustainable means to mitigate oomycete diseases in aquaculture.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136241PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552890PMC
May 2016

Towards the feasibility of using ultrasound to determine mechanical properties of tissues in a bioreactor.

Ann Biomed Eng 2014 Oct 5;42(10):2190-202. Epub 2014 Aug 5.

Department of Mechanical & Aerospace Engineering, Case Western Reserve University, 2123 Martin Luther King Jr. Drive, Glennan Building Room 616A, Cleveland, OH, 44106, USA,

Our ultimate goal is to non-destructively evaluate mechanical properties of tissue-engineered (TE) cartilage using ultrasound (US). We used agarose gels as surrogates for TE cartilage. Previously, we showed that mechanical properties measured using conventional methods were related to those measured using US, which suggested a way to non-destructively predict mechanical properties of samples with known volume fractions. In this study, we sought to determine whether the mechanical properties of samples, with unknown volume fractions could be predicted by US. Aggregate moduli were calculated for hydrogels as a function of SOS, based on concentration and density using a poroelastic model. The data were used to train a statistical model, which we then used to predict volume fractions and mechanical properties of unknown samples. Young's and storage moduli were measured mechanically. The statistical model generally predicted the Young's moduli in compression to within <10% of their mechanically measured value. We defined positive linear correlations between the aggregate modulus predicted from US and both the storage and Young's moduli determined from mechanical tests. Mechanical properties of hydrogels with unknown volume fractions can be predicted successfully from US measurements. This method has the potential to predict mechanical properties of TE cartilage non-destructively in a bioreactor.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088715PMC
http://dx.doi.org/10.1007/s10439-014-1079-4DOI Listing
October 2014

Deciphering microbial landscapes of fish eggs to mitigate emerging diseases.

ISME J 2014 Oct 27;8(10):2002-14. Epub 2014 Mar 27.

1] Department of Microbial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, The Netherlands [2] Laboratory of Phytopathology, Wageningen University, Wageningen, The Netherlands.

Animals and plants are increasingly suffering from diseases caused by fungi and oomycetes. These emerging pathogens are now recognized as a global threat to biodiversity and food security. Among oomycetes, Saprolegnia species cause significant declines in fish and amphibian populations. Fish eggs have an immature adaptive immune system and depend on nonspecific innate defences to ward off pathogens. Here, meta-taxonomic analyses revealed that Atlantic salmon eggs are home to diverse fungal, oomycete and bacterial communities. Although virulent Saprolegnia isolates were found in all salmon egg samples, a low incidence of Saprolegniosis was strongly correlated with a high richness and abundance of specific commensal Actinobacteria, with the genus Frondihabitans (Microbacteriaceae) effectively inhibiting attachment of Saprolegniato salmon eggs. These results highlight that fundamental insights into microbial landscapes of fish eggs may provide new sustainable means to mitigate emerging diseases.
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http://dx.doi.org/10.1038/ismej.2014.44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184010PMC
October 2014

Investigation of evanescent coupling between tapered fiber and a multimode slab waveguide.

Appl Opt 2012 Apr;51(10):C152-7

State Key Laboratory of Electrical Insulation and Power Equipment, Xian Jiaotong University, Xi'an, China.

A tapered fiber-slab waveguide coupler (TFSC) is proposed in this paper. Both the numerical analysis based on the beam propagation method and experiments are used for investigating the dependencies of TFSC transmission features on their geometric parameters. From the simulations and experimental results, the rules for fabricating a TFSC with low transmission loss and sharp resonant spectra by optimizing the configuration parameters are presented. The conclusions derived from our work may provide helpful references for optimally designing and fabricating TFSC-based devices, such as sensors, wavelength filters, and intensity modulators.
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http://dx.doi.org/10.1364/AO.51.00C152DOI Listing
April 2012
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