Publications by authors named "Yunyun Chen"

102 Publications

Comparative Analysis of Morphology, Photosynthetic Physiology, and Transcriptome Between Diploid and Tetraploid Barley Derived From Microspore Culture.

Front Plant Sci 2021 26;12:626916. Epub 2021 Feb 26.

Biotechnology Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai, China.

Polyploids play an important role in the breeding of plant for superior characteristics, and many reports have focused on the effects upon photosynthesis from polyploidization in some plant species recently, yet surprisingly little of this is known for barley. In this study, homozygous diploid and tetraploid plants, derived from microspore culturing of the barley cultivar "H30," were used to assess differences between them in their cellular, photosynthetic, and transcriptomic characteristics. Our results showed that tetraploid barley has the distinct characteristics of polyploids, namely thicker and heavier leaves, enlarged stomata size or stomatal guard cell size, and more photosynthetic pigments and improved photosynthesis (especially under high light intensity). This enhanced photosynthesis of tetraploid barley was confirmed by several photosynthetic parameters, including net photosynthetic rate (P), stomatal conductance (G), intercellular CO concentration (C), transpiration rate (T), maximum net photosynthetic rate (P), light saturation point (LSP), maximum RuBP saturated rate carboxylation (V), and maximum rate of electron transport (J). Transcriptomic analyses revealed that just ~2.3% of all detected genes exhibited differential expression patterns [i.e., differentially expressed genes (DEGs)], and that most of these - 580 of 793 DEGs in total - were upregulated in the tetraploid barley. The follow-up KEGG analysis indicated that the most enriched pathway was related to photosynthesis-antenna proteins, while the downregulation of DEGs was related mainly to the light-harvesting cholorophyII /-binding protein (Lhcb1) component, both validated by quantitative PCR (qPCR). Taken together, our integrated analysis of morphology, photosynthetic physiology, and transcriptome provides evidences for understanding of how polyploidization enhances the photosynthetic capacity in tetraploids of barley.
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http://dx.doi.org/10.3389/fpls.2021.626916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970760PMC
February 2021

Development of a rational strategy for integration of lactate dehydrogenase A suppression into therapeutic algorithms for head and neck cancer.

Br J Cancer 2021 Mar 19. Epub 2021 Mar 19.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Lactate dehydrogenase (LDH) is a critical metabolic enzyme. LDH A (LDHA) overexpression is a hallmark of aggressive malignancies and has been linked to tumour initiation, reprogramming and progression in multiple tumour types. However, successful LDHA inhibition strategies have not materialised in the translational and clinical space. We sought to develop a rational strategy for LDHA suppression in the context of solid tumour treatment.

Methods: We utilised a doxycycline-inducible short hairpin RNA (shRNA) system to generate LDHA suppression. Lactate and LDH activity levels were measured biochemically and kinetically using hyperpolarised C-pyruvate nuclear magnetic resonance spectroscopy. We evaluated effects of LDHA suppression on cellular proliferation and clonogenic survival, as well as on tumour growth, in orthotopic models of anaplastic thyroid carcinoma (ATC) and head and neck squamous cell carcinoma (HNSCC), alone or in combination with radiation.

Results: shRNA suppression of LDHA generated a time-dependent decrease in LDH activity with transient shifts in intracellular lactate levels, a decrease in carbon flux from pyruvate into lactate and compensatory shifts in metabolic flux in glycolysis and the Krebs cycle. LDHA suppression decreased cellular proliferation and temporarily stunted tumour growth in ATC and HNSCC xenografts but did not by itself result in tumour cure, owing to the maintenance of residual viable cells. Only when chronic LDHA suppression was combined with radiation was a functional cure achieved.

Conclusions: Successful targeting of LDHA requires exquisite dose and temporal control without significant concomitant off-target toxicity. Combinatorial strategies with conventional radiation are feasible as long as the suppression is targeted, prolonged and non-toxic.
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http://dx.doi.org/10.1038/s41416-021-01297-xDOI Listing
March 2021

The Causal and Force Perception and Their Perceived Asymmetries in Flight Collisions.

Front Psychol 2020 7;11:1942. Epub 2020 Aug 7.

Shaanxi Key Laboratory of Behavior and Cognitive Neuroscience, School of Psychology, Shaanxi Normal University, Xi'an, China.

The present study was to investigate causal perception and force perception in ecological objects. Four experiments were designed to compare the perceived causality and force of one of the two objects on the other by changing the property of one or both of the objects involved in the launching effect. Our results support causal asymmetry and force asymmetry, in which the launcher has a greater causal effect and exerts more force on the target. Furthermore, we also found that, the ecological object, which is the airplane in this study, had a greater causal effect and exerted more force, resulting in strengthened asymmetries when the airplane acted as the launcher and weakened asymmetries when the airplane acted as the target. The properties of the object also impacted causal perception by attenuating the effect of the temporal gap on causality. Those results indicate that the airplane is perceived as the main cause for a collision compared with an abstract object. The influence of conceptual knowledge of the object and the sense of agency on changing the degree of perceived causality and force in a particular motion pattern was discussed.
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http://dx.doi.org/10.3389/fpsyg.2020.01942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427475PMC
August 2020

The Epidemiology of Respiratory Failure in the United States 2002-2017: A Serial Cross-Sectional Study.

Crit Care Explor 2020 Jun 10;2(6):e0128. Epub 2020 Jun 10.

Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA.

Objectives: Respiratory failure with mechanical ventilation is a limited labor-intensive resource that is associated with high mortality. Understanding the longitudinal national epidemiology is essential for the organization of healthcare resources.

Design: Serial cross-sectional study.

Setting: The 2002-2017 Healthcare Utilization Project's National Inpatient Sample datasets.

Interventions: None.

Measurements: We use six diagnosis codes and five procedural codes from , 9th Revision, Clinical Modification, and 19 diagnosis codes and 15 procedures codes from , 10th Revision, Clinical Modification to examine national epidemiology of different case definitions for respiratory failure.

Results: In the United States in 2017, there were an estimated 1,146,195 discharges with a diagnosis of respiratory failure and procedural code for mechanical ventilation, with an average length of stay of 10.5 days and hospital charge of $158,443. Over the study period, there was an 83% increase in incidence from 249 to 455 cases per 100,000 adults with a 48% decrease in hospital mortality from 34% to 23%. Exploring a case definition that captures only diagnosis codes for respiratory failure, there was a 197% increase in annual incidence, from 429 to 1,275 cases per 100,000 adults with a 57% decrease in hospital mortality from 28% to 12%. For invasive mechanical ventilation without a requisite diagnosis code, there was no change in incidence over the study period, with the 2017 incidence at 359 cases per 100,000 adults, but a 19% decrease in hospital mortality from 37% to 30%. For the noninvasive mechanical ventilation procedural codes, there was a 437% increase in incidence from 41 to 220 cases per 100,000 adults, with a 38% decrease in hospital mortality from 16% to 10%.

Conclusions: Examining different case definitions for respiratory failure, there was a large increase in the population incidence and decrease in the hospital mortality for respiratory failure diagnosis codes with more modest changes procedural codes for invasive mechanical ventilation. There was a large increase in incidence of noninvasive mechanical ventilation.
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http://dx.doi.org/10.1097/CCE.0000000000000128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314331PMC
June 2020

Accommodation is unrelated to myopia progression in Chinese myopic children.

Sci Rep 2020 07 21;10(1):12056. Epub 2020 Jul 21.

School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China.

This study shows accommodative accuracy and distance accommodation facility in myopic children do not play a role in myopia progression. In 144 subjects, the monocular distance accommodative facility (DAF) and continuous accommodative stimulus-response curves (ASRCs) were measured at the enrolment. Retrospective and prospective refraction with regard to the enrolment visit were obtained from the outpatient database system based on noncycloplegic subjective spherical equivalent refraction (SER). The rate of myopic progression at enrolment was the first derivative of the Gompertz function, which was fitted with each subject's longitudinal refractive error data, including at least four records of SER with an interval of more than 6 months between each visit. A mixed linear model for multilevel repeated-measures data was used to explore the associations between the rate of myopia progression and accommodative parameters. The mean rate of myopia progression at enrolment was -0.61 ± 0.31 D/y with a mean age of 12.27 ± 1.61 years. By adjusting for age and SER, it was shown that the myopic progression rate was not associated with the accommodative lag (F = 0.269, P = 0.604), accommodative lag area (F = 0.086, P = 0.354), slope of ASRC (F = 0.711, P = 0.399), and DAF (F = 0.619, P = 0.432).
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http://dx.doi.org/10.1038/s41598-020-68859-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374687PMC
July 2020

Highly Reactive Cyclic Monoaryl Iodoniums Tuned as Carbene Generators Couple with Nucleophiles under Metal-Free Conditions.

iScience 2020 Jul 23;23(7):101307. Epub 2020 Jun 23.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, China. Electronic address:

Cross-coupling reactions between aryl iodide and nucleophiles have been well developed. Iodoniums equipped with a reactive C-I(III) bond accelerate cross-coupling reactions of aryl iodide. Among them, cyclic diaryliodoniums are more atom economical; however; they are often in the trap of metal reliance and encounter regioselectivity issues. Now, we have developed a series of highly reactive cyclic monoaryl-vinyl iodoniums that can be tuned to construct C-N, C-O, and C-C bonds without metal catalysis. Under promotion of triethylamine, coupling reactions with aniline, phenol, aromatic acid, and indole proceed rapidly and regioselectively at room temperature. The carbene species is conceptualized as a key intermediate in our mechanism model. Furthermore, the coupling products enable diversity-oriented synthesis strategy to further build up a chemical library of diverse heterocyclic fragments that are in demand in the drug discovery field. Our current work provides a deep insight into the synthetic application of these highly reactive cyclic iodoniums.
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http://dx.doi.org/10.1016/j.isci.2020.101307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338778PMC
July 2020

Isolation, identification, and whole genome sequence analysis of the alginate-degrading bacterium Cobetia sp. cqz5-12.

Sci Rep 2020 07 2;10(1):10920. Epub 2020 Jul 2.

College of Life and Environmental Science, Wenzhou University, Wenzhou, 325035, People's Republic of China.

Alginate-degrading bacteria or alginate lyases can be used to oligomerize alginate. In this study, an alginate-degrading bacterium with high alginolytic activity was successfully screened by using Sargassum fusiforme sludge. When the strain was grown on a plate containing sodium alginate, the transparent ring diameter (D) was 2.2 cm and the ratio (D/d) of transparent ring diameter to colony diameter (d) was 8.8. After 36 h in culture at a temperature of 28 °C shaken at 150 r/min, the enzymatic activity of the fermentation supernatant reached 160 U/mL, and the enzymatic activity of the bacterial precipitate harvested was 2,645 U/mL. The strain was named Cobetia sp. cqz5-12. Its genome is circular in shape, 4,209,007 bp in size, with a 62.36% GC content. It contains 3,498 predicted coding genes, 72 tRNA genes, and 21 rRNA genes. The functional annotations for the coding genes demonstrated that there were 181 coding genes in the genome related to carbohydrate transport and metabolism and 699 coding genes with unknown functions. Three putative coding genes, alg2107, alg2108 and alg2112, related to alginate degradation were identified by analyzing the carbohydrate active enzyme (CAZy) database. Moreover, proteins Alg2107 and Alg2112 were successfully expressed and exhibited alginate lyase activity.
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http://dx.doi.org/10.1038/s41598-020-67921-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331586PMC
July 2020

The Impact of Social Value Orientation, Game Context and Trust on Cooperative Behavior After Cooperative Video Game Play.

Psychol Rep 2020 Jul 1:33294120934705. Epub 2020 Jul 1.

School of Psychology, Shaanxi Normal University, Xi'an, China.

This study explores the effects of the cooperative video game context, social value orientation (SVO) and trust on cooperative behavior. The main finding is that collaborative game play significantly increases cooperative behavior, especially in prosocial individuals. In addition, a mediation model is established in which trust partially mediates the association between the game mode and cooperative behavior. The results indicate that playing collaborative games increases cooperation in prosocial people partially by facilitating the trust they have in their gaming partners. The theoretical and practical implications of these findings are discussed.
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http://dx.doi.org/10.1177/0033294120934705DOI Listing
July 2020

Acquisition of Cisplatin Resistance Shifts Head and Neck Squamous Cell Carcinoma Metabolism toward Neutralization of Oxidative Stress.

Cancers (Basel) 2020 Jun 24;12(6). Epub 2020 Jun 24.

Bobby R. Alford Department of Otolaryngology Head and Neck Surgery, Baylor College of Medicine, Houston, TX 77030, USA.

: Cisplatin (CDDP) is commonly utilized in the treatment of advanced solid tumors including head and neck squamous cell carcinoma (HNSCC). Cisplatin response remains highly variable among individual tumors and development of cisplatin resistance is common. We hypothesized that development of cisplatin resistance is partially driven by metabolic reprogramming. : Using a pre-clinical HNSCC model and an integrated approach to steady state metabolomics, metabolic flux and gene expression data we characterized the interaction between cisplatin resistance and metabolic reprogramming. : Cisplatin toxicity in HNSCC was driven by generation of intra-cellular oxidative stress. This was validated by demonstrating that acquisition of cisplatin resistance generates cross-resistance to ferroptosis agonists despite the fact that cisplatin itself does not trigger ferroptosis. Acquisition of cisplatin resistance dysregulated the expression of genes involved in amino acid, fatty acid metabolism and central carbon catabolic pathways, enhanced glucose catabolism and serine synthesis. Acute cisplatin exposure increased intra-tumoral levels of S-methyl-5-thiadenosine (MTA) precursors and metabotoxins indicative of generalized oxidative stress. Acquisition of cisplatin resistance is linked to metabolic recovery from oxidative stress. Although this portends poor effectiveness for directed metabolic targeting, it supports the potential for biomarker development of cisplatin effectiveness using an integrated approach.
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http://dx.doi.org/10.3390/cancers12061670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352569PMC
June 2020

Fabrication of biodegradable auto-fluorescent organosilica nanoparticles with dendritic mesoporous structures for pH/redox-responsive drug release.

Mater Sci Eng C Mater Biol Appl 2020 Jul 1;112:110914. Epub 2020 Apr 1.

Engineering Research Center for Nanomaterials, Henan University, Kaifeng 475004, China. Electronic address:

In this work, disulfide-bridged organic silica (OS) based nanocarriers were constructed for drug release. The broken of SS bonds in Si-O-Si skeleton would improve the degradation of Si-O-Si of OS carriers. The OS carriers have a central-radiated dendritic porous structure and a large specific surface area of 453.80 mg. The dextrin was selectively oxidized to dialdehyde dextrin (DAD) and then was modified on the surface of OS carriers by Schiff base bonds. Subsequently, cystamine (Cys) was linked with DAD to form DAD/Cys layer (OS-N=C-DAD/Cys) to seal the loaded drug. The DAD/Cys layer display the degradation performance of pH/GSH dual response The obtained OS-N=C-DAD/Cys carriers displayed low premature and the cumulative release was 6.5% under normal physiological conditions within 48 h. The Schiff base (-N=C-) structure in the DAD/Cys layer is also capable of monitoring acid-responsive drug release by fluorescence change. The prepared OS-N=C-DAD/Cys carriers and their degraded products have high biocompatibility.
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http://dx.doi.org/10.1016/j.msec.2020.110914DOI Listing
July 2020

Live-attenuated Salmonella enterica serotype Choleraesuis vaccine with regulated delayed fur mutation confer protection against Streptococcus suis in mice.

BMC Vet Res 2020 May 7;16(1):129. Epub 2020 May 7.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, People's Republic of China.

Background: Recombinant Salmonella enterica serotype Choleraesuis (S. Choleraesuis) vaccine vector could be used to deliver heterologous antigens to prevent and control pig diseases. We have previously shown that a live-attenuated S. Choleraesuis vaccine candidate strain rSC0011 (ΔP::TT araC Pcrp Δpmi-2426 ΔrelA199::araC PlacI TT ΔasdA33, Δ, deletion, TT, terminator) delivering SaoA, a conserved surface protein in most of S. suis serotypes, provided excellent protection against S. suis challenge, but occasionally lead to morbidity (enteritidis) in vaccinated mice (approximately 1 in every 10 mice). Thus, alternated attenuation method was sought to reduce the reactogenicity of strain rSC0011. Herein, we described another recombinant attenuated S. Choleraesuis vector, rSC0012 (ΔP:: TT araC Pfur Δpmi-2426 ΔrelA199:: araC PlacI TT ΔasdA33) with regulated delayed fur mutation to avoid inducing disease symptoms while exhibiting a high degree of immunogenicity.

Results: The strain rSC0012 strain with the ΔP::TT araC Pfur mutation induced less production of inflammatory cytokines than strain rSC0011 with the ΔP::TT araC Pcrp mutation in mice. When delivering the same pS-SaoA plasmid, the intraperitoneal LD of rSC0012 was 18.2 times higher than that of rSC0011 in 3-week-old BALB/C mice. rSC0012 with either pS-SaoA or pYA3493 was cleared from spleen and liver tissues 7 days earlier than rSC0011 with same vectors after oral inoculation. The strain rSC0012 synthesizing SaoA induced high titers of anti-SaoA antibodies in both systemic (IgG in serum) and mucosal (IgA in vaginal washes) sites, as well as increased level of IL-4, the facilitator of Th2-type T cell immune response in mice. The recombinant vaccine rSC0012(pS-SaoA) conferred high percentage of protection against S. suis or S. Choleraesuis challenge in BALB/C mice.

Conclusions: The live-attenuated Salmonella enterica serotype Choleraesuis vaccine rSC0012(pS-SaoA) with regulated delayed fur mutation provides a foundation for the development of a safe and effective vaccine against S. Choleraesuis and S. suis.
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http://dx.doi.org/10.1186/s12917-020-02340-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203871PMC
May 2020

High-sensitivity microliter blood pressure sensors based on patterned micro-nanostructure arrays.

Lab Chip 2020 05 25;20(9):1554-1561. Epub 2020 Apr 25.

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 130012, P. R. China.

Herein we present a micro-nanostructure integrated liquid pressure sensor, which features an ultra-high sensitivity of 16.71 mbar, a low-pressure regime of 2 mbar, a trace sample volume of less than 1.3 μL and a visible display element. The measurable pressure ranges of the sensors include not only from micro-scale fluids to bulk liquids but also from hydraulic pressures to blood pressures, opening a window for liquid pressure sensing in lab-on-chip platforms, point-of-care diagnostics, and even robotics.
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http://dx.doi.org/10.1039/d0lc00063aDOI Listing
May 2020

Targeting SOX2 Protein with Peptide Aptamers for Therapeutic Gains against Esophageal Squamous Cell Carcinoma.

Mol Ther 2020 03 15;28(3):901-913. Epub 2020 Jan 15.

School of Medicine, Xiamen University or Institute for Laboratory Medicine, 900 Hospital of the Joint Logistics Team, Fuzhou, Fujian 350025, China.

Esophageal squamous cell carcinoma (ESCC) is a predominant cancer type in developing countries such as China, where ESCC accounts for approximately 90% of esophageal malignancies. Lacking effective and targeted therapy contributes to the poor 5-year survival rate. Recent studies showed that about 30% of ESCC cases have high levels of SOX2. Herein, we aim to target this transcription factor with aptamer. We established a peptide aptamer library and then performed an unbiased screening to identify several peptide aptamers including P42 that can bind and inhibit SOX2 downstream target genes. We further found that P42 overexpression or incubation with a synthetic peptide 42 inhibited the proliferation, migration, and invasion of ESCC cells. Moreover, peptide 42 treatment inhibited the growth and metastasis of ESCC xenografts in mouse and zebrafish. Further analysis revealed that P42 overexpression led to alternations in the levels of proteins that are important for the proliferation and migration of ESCC cells. Taken together, our study identified the peptide 42 as a key inhibitor of SOX2 function, reducing the proliferation and migration of ESCC cells in vitro and in vivo, and thereby offering a potential therapy against ESCC.
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http://dx.doi.org/10.1016/j.ymthe.2020.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054732PMC
March 2020

Transcriptome Analysis Identifies Candidate Genes and Functional Pathways Controlling the Response of Two Contrasting Barley Varieties to Powdery Mildew Infection.

Int J Mol Sci 2019 Dec 24;21(1). Epub 2019 Dec 24.

Biotech Research Institute, Shanghai Academy of Agricultural Sciences/Key Laboratory of Agricultural Genetics and Breeding, Shanghai 201106, China.

Powdery mildew caused by f. sp. () is one of the most serious diseases in barley. The numerous barley varieties across China provide valuable genetic resources to screen the resistant germplasm and to discover the primary genes of resistance to powdery mildew. In this study, Chinese barley variety Feng 7 was identified as a highly resistant genotype which limited colonization by cell apoptosis using leaf staining assay, while another variety Hua 30 showed high susceptibility. The performance of high resistance to in F plants from the two varieties suggested dominant gene(s) controlled the resistance to powdery mildew in Feng 7. To understand the host transcriptional response to infection, these two barley varieties Feng 7 and Hua 30 were inoculated with , and their transcriptional profiling using RNA sequencing (RNA-seq) at four time points (12 h post-inoculation (hpi), 24 hpi, 48 hpi, and 72 hpi) were compared. 4318 differentially expressed genes (DEGs), including 2244 upregulated and 2074 downregulated genes, were detected in Feng 7, compared with Hua 30 at 12 hpi. 4907 DEGs (2488 upregulated and 2419 downregulated) were detected at 24 hpi. 4758 DEGs (2295 upregulated and 2463 downregulated) were detected at 48 hpi. 3817 DEGs (2036 upregulated and 1781 downregulated) were detected at 72 hpi. The results showed the number of DEGs between two varieties peaked at 24 hpi (for the upregulated) or 48 hpi (for the downregulated), which is matched with the processing of infection. In addition, the number of upregulated DEGs involved in the functional pathways of plant defense (mitogen-activated protein kinase (MAPK) pathway and plant hormone signal transduction) is elevated remarkably at 24 hpi. Six candidate genes (, , and ) were identified in Feng 7. All of them present continuous expression at higher levels upon infection, compared with the performance in Hua 30, which revealed the potential contribution to Feng 7 mediate resistance to . In conclusion, the candidate genes and relevant pathways provided key information towards understanding the defense of barley to attack and the molecular mechanisms of different genetic resistance to powdery mildew.
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http://dx.doi.org/10.3390/ijms21010151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982059PMC
December 2019

The space contraction asymmetry in Michotte's launching effect.

Atten Percept Psychophys 2020 Jun;82(3):1431-1442

Shaanxi Key Laboratory of Behavior and Cognitive Neuroscience, School of Psychology, Shaanxi Normal University, No.199, South Chang'an Road, Xi'an, Shaanxi Province, 710062, People's Republic of China.

Previous studies have found that, compared with noncausal events, spatial contraction exists between the causal object and the effect object due to the perceived causality. The present research aims to examine whether the causal object and the effect object have the same effect on spatial contraction. A modified launching effect, in which a bar bridges the spatial gap between the final position of the launcher and the initial position of the target, was adopted. Experiment 1 validates the absolute underestimation of the bar's length between the launcher and the target. Experiment 2a finds that in the direct launching effect, the perceived position of the bar's trailing edge that was contacted by the final launcher was displaced along the objects' direction of movement. Meanwhile, the perceived position of the bar's leading edge that was contacted by the initial target was displaced in opposite direction to the moving direction. The magnitude of the former's displacement was significantly larger than that of the latter, displaying a significant contraction asymmetry. Experiment 2b demonstrates that the contraction asymmetry did not result from the launcher remaining in contact with the edge of the bar. Experiment 3 indicates that contraction asymmetry showed a type of postdictive effect; that is, to some extent, this asymmetry depends on what happens after contact. In conclusion, the space between the causal object and effect object contracts asymmetrically in the launching effect, which implies that the causal object and effect object are perceived as shifting toward each other nonequidistantly in visual space.
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http://dx.doi.org/10.3758/s13414-019-01912-3DOI Listing
June 2020

The Homeobox gene, HOXB13, Regulates a Mitotic Protein-Kinase Interaction Network in Metastatic Prostate Cancers.

Sci Rep 2019 07 4;9(1):9715. Epub 2019 Jul 4.

Department of Surgery, Washington University in St. Louis, MO, USA.

HOXB13, a homeodomain transcription factor, is linked to recurrence following radical prostatectomy. While HOXB13 regulates Androgen Receptor (AR) functions in a context dependent manner, its critical effectors in prostate cancer (PC) metastasis remain largely unknown. To identify HOXB13 transcriptional targets in metastatic PCs, we performed integrative bioinformatics analysis of differentially expressed genes (DEGs) in the proximity of the human prostate tumor-specific AR binding sites. Unsupervised Principal Component Analysis (PCA) led to a focused core HOXB13 target gene-set referred to as HOTPAM9 (HOXB13 Targets separating Primary And Metastatic PCs). HOTPAM9 comprised 7 mitotic kinase genes overexpressed in metastatic PCs, TRPM8, and the heat shock protein HSPB8, whose levels were significantly lower in metastatic PCs compared to the primary disease. The expression of a two-gene set, CIT and HSPB8 with an overall balanced accuracy of 98.8% and a threshold value of 0.2347, was sufficient to classify metastasis. HSPB8 mRNA expression was significantly increased following HOXB13 depletion in multiple metastatic CRPC models. Increased expression of HSPB8 by the microtubule inhibitor Colchicine or by exogenous means suppressed migration of mCRPC cells. Collectively, our results indicate that HOXB13 promotes metastasis of PCs by coordinated regulation of mitotic kinases and blockade of a putative tumor suppressor gene.
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http://dx.doi.org/10.1038/s41598-019-46064-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609629PMC
July 2019

Development of a novel ssDNA aptamer targeting neutrophil gelatinase-associated lipocalin and its application in clinical trials.

J Transl Med 2019 06 18;17(1):204. Epub 2019 Jun 18.

Institute for Laboratory Medicine, 900 Hospital of the Joint Logistics Team, Navy Medical University (Second Military Medical University) or Dongfang Hospital, Fuzhou, 350025, Fujian, China.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of early diagnosis and prediction for acute kidney injury (AKI). However, the current program for NGAL detection is not extensively applied in clinics due to the high expense of antibodies. Nucleic acid aptamers are single-strand DNAs or RNAs which could bind to targets with high specificity and affinity, and they have been widely used in the diagnosis and therapy for multiple diseases. It is valuable for us to develop a new method for NGAL detection using aptamers instead of antibodies to achieve increased efficiency and decreased cost.

Methods: Nucleic acid aptamers against NGAL were obtained after SELEX process using magnetic beads, and an enzyme-linked aptamer analysis (ELAA), which can be widely used in clinical diagnosis at low cost, were successfully established. The feasibility of ELAA was further validated with urine samples harvested from 43 AKI patients and 30 healthy people.

Results: Three candidate aptamers, including NA36, NA42 and NA53, were obtained after 8 rounds of SELEX process with magnetic beads and verified by quantitative polymerase chain reaction (qPCR), and the Kd value of each aptamer was 43.59, 66.55 and 32.52 nM, respectively. Moreover, the linear relationship was consistent at the range of 125-4000 ng/mL, and the detection limit of ELAA assay was 30.45 ng/mL. We also found that NGAL could be exclusively detected with NA53, and no cross-reaction between NA53 and human albumin or globulin occurred, the coefficient of variation (CV) between inner-plate and inter-plate was less than 15%, and the recovery rate was between 80 and 110%. Moreover, the sensitivity and specificity of ELAA assay in this study are 100% and 90%, respectively. Consistently, these results could also diagnose whether the occurrence of AKI in lots of patients, which has been demonstrated with the ELAA method we established after using NA53.

Conclusions: Taken together, NA53, the best candidate aptamer targeting NGAL protein, can be applied in clinical testing.
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http://dx.doi.org/10.1186/s12967-019-1955-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582607PMC
June 2019

Etiology, cancer stem cells and potential diagnostic biomarkers for esophageal cancer.

Cancer Lett 2019 08 21;458:21-28. Epub 2019 May 21.

Division of Digestive and Liver Diseases and Center for Human Development, Department of Medicine, Columbia University, NY, 10032, USA. Electronic address:

Esophageal cancer (EC) has been a leading cause of cancer death worldwide in part due to late detection and lack of precision treatment. EC includes two major malignancies, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Recent studies reveal that ESCC and EAC have distinct cell of origin and contain cancer stem cells (also known as tumor initiating cells) expressing different cell surface markers. These biomarkers have potentially important values for both early detection and finding effective therapy. In this review we summarize the updated findings for cell of origin and provide an overview of cancer cell biomarkers that have been tested for ESCC and EAC. In addition, we also discuss recent progress in the study of molecular mechanisms leading to these malignancies.
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http://dx.doi.org/10.1016/j.canlet.2019.05.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597177PMC
August 2019

CK2 Accumulates in Nuclei, Nucleoli, at Septal Pores and Forms a Large Ring Structure in Appressoria, and Is Involved in Rice Blast Pathogenesis.

Front Cell Infect Microbiol 2019 17;9:113. Epub 2019 Apr 17.

State Key Laboratory for Ecological Pest Control of Fujian and Taiwan Crops, College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, China.

(Mo) is a model pathogen causing rice blast resulting in yield and economic losses world-wide. CK2 is a constitutively active, serine/threonine kinase in eukaryotes, having a wide array of known substrates, and involved in many cellular processes. We investigated the localization and role of MoCK2 during growth and infection. BLAST search for MoCK2 components and targeted deletion of subunits was combined with protein-GFP fusions to investigate localization. We found one CKa and two CKb subunits of the CK2 holoenzyme. Deletion of the catalytic subunit CKa was not possible and might indicate that such deletions are lethal. The CKb subunits could be deleted but they were both necessary for normal growth and pathogenicity. Localization studies showed that the CK2 holoenzyme needed to be intact for normal localization at septal pores and at appressorium penetration pores. Nuclear localization of CKa was however not dependent on the intact CK2 holoenzyme. In appressoria, CK2 formed a large ring perpendicular to the penetration pore and the ring formation was dependent on the presence of all CK2 subunits. The effects on growth and pathogenicity of deletion of the b subunits combined with the localization indicate that CK2 can have important regulatory functions not only in the nucleus/nucleolus but also at fungal specific structures such as septa and appressorial pores.
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http://dx.doi.org/10.3389/fcimb.2019.00113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478894PMC
December 2019

Correction: Small-molecule inhibition of STAT3 in radioresistant head and neck squamous cell carcinoma.

Oncotarget 2019 02 22;10(16):1603. Epub 2019 Feb 22.

Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

[This corrects the article DOI: 10.18632/oncotarget.8368.].
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http://dx.doi.org/10.18632/oncotarget.26743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422187PMC
February 2019

Repeatability of two subjective accommodative amplitude measurements and agreement with an objective method.

Clin Exp Optom 2019 07 13;102(4):412-417. Epub 2019 Mar 13.

School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China.

Background: The aim was to compare the repeatability of subjective accommodative amplitude (AA) measurements obtained using the modified push-up and minus-lens methods and determine the agreement with objective AA by an autorefractor.

Methods: The right eyes of 47 adults aged 22-30 years (mean 25.1 ± 1.9) were measured by subjective AA using the modified push-up and minus-lens methods. Subjective AAs with first sustained blur and unreadable criteria were obtained with an average of three consecutive measurements. Measurements of the objective AA were simulated by the minus lens using an open-field autorefractor. The repeatability of two subjective AA methods and the agreement among the different methods was assessed.

Results: The AA value was dependent on the measuring method (F = 139.68, p < 0.001). The AA of the minus-lens method with first sustained blur criterion (10.10 ± 1.71 D) was closest to the objective AA (9.01 ± 1.49 D). The minus-lens method with unreadable criterion had the best repeatability. The agreement between the minus-lens method and the objective methods was better than that between the modified push-up and the objective methods based on the difference and 95 per cent limits of agreement. The agreement was highest between the minus-lens method with the first sustained blur criterion and the objective method, which had the lowest average difference and a narrow 95 per cent limits of agreement.

Conclusions: The subjective minus-lens method was more accurate for assessing the subjective AA in adults than the modified push-up method. The minus-lens method with the first sustained blur criterion was the optimal method for subjective AA. The minus-lens method with unreadable criterion can also be applied to clinical measurements, although it was approximately 0.95 D larger than the minus-lens method with the first sustained blur criterion.
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http://dx.doi.org/10.1111/cxo.12884DOI Listing
July 2019

Targeting the BRD4-HOXB13 Coregulated Transcriptional Networks with Bromodomain-Kinase Inhibitors to Suppress Metastatic Castration-Resistant Prostate Cancer.

Mol Cancer Ther 2018 12 21;17(12):2796-2810. Epub 2018 Sep 21.

Tumor Biology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Resistance to androgen receptor (AR) antagonists is a significant problem in the treatment of castration-resistant prostate cancers (CRPC). Identification of the mechanisms by which CRPCs evade androgen deprivation therapies (ADT) is critical to develop novel therapeutics. We uncovered that CRPCs rely on BRD4-HOXB13 epigenetic reprogramming for androgen-independent cell proliferation. Mechanistically, BRD4, a member of the BET bromodomain family, epigenetically promotes HOXB13 expression. Consistently, genetic disruption of or pharmacological suppression of its mRNA and protein expression by the novel dual-activity BET bromodomain-kinase inhibitors directly correlates with rapid induction of apoptosis, potent inhibition of tumor cell proliferation and cell migration, and suppression of CRPC growth. Integrative analysis revealed that the BRD4-HOXB13 transcriptome comprises a proliferative gene network implicated in cell-cycle progression, nucleotide metabolism, and chromatin assembly. Notably, although the core HOXB13 target genes responsive to BET inhibitors (HOTBIN10) are overexpressed in metastatic cases, in ADT-treated CRPC cell lines and patient-derived circulating tumor cells (CTC) they are insensitive to AR depletion or blockade. Among the HOTBIN10 genes, AURKB and MELK expression correlates with HOXB13 expression in CTCs of mCRPC patients who did not respond to abiraterone (ABR), suggesting that AURKB inhibitors could be used additionally against high-risk HOXB13-positive metastatic prostate cancers. Combined, our study demonstrates that BRD4-HOXB13-HOTBIN10 regulatory circuit maintains the malignant state of CRPCs and identifies a core proproliferative network driving ADT resistance that is targetable with potent dual-activity bromodomain-kinase inhibitors.
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http://dx.doi.org/10.1158/1535-7163.MCT-18-0602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528782PMC
December 2018

Cp*Co(iii)-Catalyzed oxidative [5+2] annulation: regioselective synthesis of 2-aminobenzoxepines via C-H/O-H functionalization of 2-vinylphenols with ynamides.

Chem Commun (Camb) 2018 Oct;54(82):11562-11565

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.

A Cp*Co(iii)-catalyzed [5+2] C-H annulation reaction of 2-vinylphenols with ynamides was developed. The reaction led to the efficient synthesis of valuable 2-aminobenzoxepines in high regioselectivity. Mild reaction conditions, good functional group tolerance, and moderate to good yields were observed. The synthetic utility was demonstrated by a gram-scale synthesis and further transformations of the products. Preliminary mechanistic studies were conducted, and a possible catalytic cycle was proposed.
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http://dx.doi.org/10.1039/c8cc06807kDOI Listing
October 2018

Heterocyclic Iodoniums for the Assembly of Oxygen-Bridged Polycyclic Heteroarenes with Water as the Oxygen Source.

Org Lett 2018 08 27;20(16):4815-4818. Epub 2018 Jul 27.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Sun Yat-sen University Cancer Center , 651 Dongfeng East Road , Guangzhou 510060 , China.

A diverse set of novel heterocyclic iodoniums was synthesized for the first time. The reactions of these unique iodoniums with environmentally benign water as the oxygen source provided structurally complex oxygen-incorporated heteropolycycles that are essential motifs in natural products and biologically active compounds. The transformation only required low-cost copper acetate. Further derivatization of the obtained polycycles expanded the structural diversity, which is important in the building of chemical libraries for drug discovery.
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http://dx.doi.org/10.1021/acs.orglett.8b01969DOI Listing
August 2018

Intrahepatic Cholangiocarcinoma Treated with Transarterial Yttrium-90 Glass Microsphere Radioembolization: Results of a Single Institution Retrospective Study.

J Vasc Interv Radiol 2018 08 2;29(8):1101-1108. Epub 2018 Jul 2.

Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612. Electronic address:

Purpose: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC).

Materials And Methods: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test.

Results: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS.

Conclusions: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile.
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http://dx.doi.org/10.1016/j.jvir.2018.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771272PMC
August 2018

Neurofibromin level directs RAS pathway signaling and mediates sensitivity to targeted agents in malignant peripheral nerve sheath tumors.

Oncotarget 2018 Apr 27;9(32):22571-22585. Epub 2018 Apr 27.

Sunshine Project Translational Research Lab, Tampa, FL 33612, Florida, USA.

Malignant peripheral nerve sheath tumor (MPNST) is a type of soft-tissue sarcoma strongly associated with dysfunction in neurofibromin; an inhibitor of the RAS pathway. We performed high-throughput screening of an array of FDA approved and promising agents in clinical development both alone and in combination at physiologically achievable concentrations against a panel of established MPNST cell line models. We found that drugs targeting a variety of factors in the RAS pathway can effectively lead to cell death with considerable drug combination synergy in regimens that target MEK or mTOR. We observed that the degree of relative sensitivity to chemotherapeutic agents was associated with the status of neurofibromin in these cell line models. Using a combination of agents that target MEK and mTORC1/2, we effectively silenced RAS/PI3K/MEK/mTOR signaling . Moreover, we employed RNAi against to establish that MPNST drug sensitivity is directly proportional to relative level of intracellular neurofibromin. Thus, two-drug combinations that target MEK and mTORC1/2 are most effective in halting the RAS signaling cascade, and the relative success of this and related small molecule interventions in MPNSTs may be predicated upon the molecular status of neurofibromin.
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http://dx.doi.org/10.18632/oncotarget.25181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978249PMC
April 2018

Cisplatin generates oxidative stress which is accompanied by rapid shifts in central carbon metabolism.

Sci Rep 2018 03 9;8(1):4306. Epub 2018 Mar 9.

Bobby R. Alford Department of Otolaryngology Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.

Cisplatin is commonly utilized in the treatment of solid tumors. Its mechanism of action is complex and multiple mechanisms of resistance have been described. We sought to determine the impact of cisplatin-generated oxidative stress on head and neck squamous cell carcinoma (HNSCC) proliferation, survival and metabolic activity in order to identify a potential metabolic signature associated with cisplatin response. DNA-bound cisplatin represents a small fraction of total intra-cellular cisplatin but generates a robust oxidative stress response. Neutralization of oxidative stress reverses cisplatin toxicity independent of the mechanism of cell death and TP53 mutational status. Cisplatin-induced oxidative stress triggers rapid shifts in carbon flux in 3 commonly utilized catabolic pathways: glycolysis, pentose phosphate pathway and citric acid cycle. Among these metabolic shifts, decreased flux from pyruvate into lactate is the only metabolic effect consistently observed across multiple HNSCC cell lines of varying genomic backgrounds and may reflect differential cisplatin sensitivity. Oxidative stress is a critical component of cisplatin cytotoxicity in HNSCC and is reflected in acute changes in carbon flux from pyruvate into lactate. This suggests that lactate may contribute to a metabolic signature of acute cisplatin toxicity, and could prove useful in optimizing cisplatin-based treatment regimens in HNSCC.
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http://dx.doi.org/10.1038/s41598-018-22640-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844883PMC
March 2018

Design of a New Near-Infrared Ratiometric Fluorescent Nanoprobe for Real-Time Imaging of Superoxide Anions and Hydroxyl Radicals in Live Cells and in Situ Tracing of the Inflammation Process in Vivo.

Anal Chem 2018 04 16;90(7):4452-4460. Epub 2018 Mar 16.

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, College of Chemistry and Pharmacy , Guangxi Normal University , Guilin 541004 , China.

The superoxide anion (O) and hydroxyl radical (OH) are important reactive oxygen species (ROS) used as biomarkers in physiological and pathological processes. ROS generation is closely related to the development of a variety of inflammatory diseases. However, the changes of ROS are difficult to ascertain with in situ tracing of the inflammation process by real-time monitoring, owing to the short half-lives of ROS and high tissue autofluorescence in vivo. Here we developed a new near-infrared (NIR) ratiometric fluorescence imaging approach by using a Förster resonance energy transfer (FRET)-based ratiometric fluorescent nanoprobe for real-time monitoring of O and OH generation and also by using in situ tracing of the inflammation process in vivo. The proposed nanoprobe was composed of PEG functionalized GQDs as the energy donor connecting to hydroIR783, serving as both the O/OH recognizing ligand and the energy acceptor. The nanoprobe not only exhibited a fast response to O and OH but also presented good biocomapatibility as well as a high photostability and signal-to-noise ratio. We have demonstrated that the proposed NIR ratiometric fluorescent nanoprobe can monitor the changes of O and OH in living RAW 264.7 cells via a drug mediating inflammation model and further realized visual monitoring of the change of O and OH in mice for in situ tracing of the inflammation process. Our design may provide a new paradigm for long-term and real-time imaging applications for in vivo tracing of the pathological process related to the inflammatory diseases.
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http://dx.doi.org/10.1021/acs.analchem.7b04488DOI Listing
April 2018

Propagation of on-axis and off-axis Bessel beams in a gradient-index medium.

J Opt Soc Am A Opt Image Sci Vis 2018 Feb;35(2):230-235

Bessel beams have been increasingly used for their advantages of non-diffraction and long focal depth. In this paper, we studied the propagation of on-axis and off-axis Bessel beams in a gradient-index medium. By expressing a Bessel beam in integral form, the analytical expression of an on-axis, decentered, and tilted Bessel beam through a paraxial optical system is derived with the ABCD matrix method and Collins diffraction integral formula. Main lobe size and trajectory of the zeroth- and second-order Bessel beam are obtained, demonstrating that the Bessel beam is focused by the gradient-index medium and its main lobe trajectory is exactly the same as the corresponding geometrical ray for both the decentered and tilted Bessel beam. Effects of beam apodization are finally studied by the Fourier beam propagation method, showing that the side lobes of the Bessel beam vanish when the beam is focused inside the medium as only part of the beam enters the lens.
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http://dx.doi.org/10.1364/JOSAA.35.000230DOI Listing
February 2018

Polarization-insensitive and wide-incident-angle optical absorber with periodically patterned graphene-dielectric arrays.

Opt Lett 2018 Jan;43(1):46-49

A polarization-insensitive and angle-independent graphene absorber (GA) with periodically patterned grating is demonstrated. A periodic nanocavity composed of multilayer subwavelength grating and metal substrate supports a strongly localized mode inside the cavity, where the mode helps to absorb more electromagnetic waves. The proposed GA exhibits polarization-insensitive behavior and maintains the high absorption above 90% within a wide range of incident angle (more than 80°). We attribute the high absorption to the excitation of the cavity mode resonance and magnetic resonance for the transverse electric and transverse magnetic polarizations, respectively. The proposed GA has potential applications in the design of various devices, such as optical modulators or tunable absorption filters because of its remarkable angle-insensitive absorption performance.
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http://dx.doi.org/10.1364/OL.43.000046DOI Listing
January 2018