Publications by authors named "Xiaobin Xie"

59 Publications

Single-step coating of mesoporous SiO onto nanoparticles: growth of yolk-shell structures from core-shell structures.

Nanoscale 2021 Jun 16;13(24):10925-10932. Epub 2021 Jun 16.

Soft Condensed Matter, Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 5, 3584 CC Utrecht, The Netherlands.

Yolk-shell nanoparticles based on mesoporous SiO (mSiO) coating of Au nanoparticles (Au NPs) hold great promise for many applications in e.g., catalysis, biomedicine, and sensing. Here, we present a single-step coating approach for synthesizing Au [email protected] yolk-shell particles with tunable size and tunable hollow space between yolk and shell. The Au NP-mSiO structure can be manipulated from core-shell to yolk-shell by varying the concentration of cetyltrimethylammonium chloride (CTAC), tetraethyl orthosilicate (TEOS), Au NPs, and NaOH. The growth mechanism of the yolk-shell particles was investigated in detail and consists of a concurrent process of growth, condensation, and internal etching through an outer shell. We also show by means of liquid-cell transmission electron microscopy (LC-TEM) that Au nanotriangle cores (Au NTs) in yolk-shell particles that are stuck on the mSiO shell, can be released by mild etching thereby making them mobile and tumbling in a liquid-filled volume. Due to the systematical investigation of the reaction parameters and understanding of the formation mechanism, the method can be scaled-up by at least an order of magnitude. This route can be generally used for the synthesis of yolk-shell structures with different Au nanoparticle shapes, e.g., nanoplatelets, nanorods, nanocubes, for yolk-shell structures with other metals at the core (Ag, Pd, and Pt), and additionally, using ligand exchange with other nanoparticles as cores and for synthesizing hollow mSiO spheres as well.
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http://dx.doi.org/10.1039/d1nr01242hDOI Listing
June 2021

Assessing accommodative presbyopic biometric changes of the entire anterior segment using single swept-source OCT image acquisitions.

Eye (Lond) 2021 Feb 25. Epub 2021 Feb 25.

Doheny Eye Institute and Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Background/objectives: To evaluate biometric changes throughout the anterior chamber during accommodation and presbyopia using single image acquisition swept-source anterior-segment optical coherence tomography (AS-OCT).

Subject/methods: Anterior-segment images were obtained using a new swept-source AS-OCT device (ANTERION, Heidelberg Engineering) from healthy volunteers (n = 71) across two centers in this prospective observational case series. In one image acquisition, cornea through posterior lens, including the ciliary muscle on both sides of the right eye, was imaged. Subjects undertook no accommodative effort and -1, -3, and -5 D of target vergence. Two-way repeated measures ANOVA modeling was performed for ciliary muscle measurements, lens parameters, aqueous depth (AD), and pupil diameter (PD). The first ANOVA factor was accommodative stimuli, and the second factor included age and refractive status.

Results: Maximum ciliary muscle thickness increased with accommodative stimuli (p < 0.001), while the distance from the scleral spur to the maximal point on the ciliary muscle and posterior ciliary muscle thickness (CMT2) decreased (p < 0.001-0.002). Older individuals showed no accommodative changes for ciliary muscle parameters, lens thickness, lens vault, PD, and AD (p = 0.07-0.32). Younger- and middle-aged eyes showed statistically significant accommodative structural alterations for these endpoints (p < 0.001-0.002), but with different patterns, including early loss of CMT2 contraction in middle-aged eyes. Within the middle-aged group, myopic eyes maintained better capacity for accommodative structural change.

Conclusions: Swept-source AS-OCT demonstrated multiple simultaneous anterior-segment biometric alterations in single acquisition images, including early loss of posterior ciliary muscle function and better maintained capacity for anterior-segment structural change in myopia.
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http://dx.doi.org/10.1038/s41433-020-01363-3DOI Listing
February 2021

Clinical characteristics, rates of blindness, and geographic features of PACD in China.

Can J Ophthalmol 2021 Jan 21. Epub 2021 Jan 21.

The Eye Hospital of Wenzhou Medical University, Wenzhou, China.

Objective: To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China.

Methods: A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed.

Results: A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes.

Conclusion: PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.
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http://dx.doi.org/10.1016/j.jcjo.2020.12.010DOI Listing
January 2021

Symmetric and asymmetric epitaxial growth of metals (Ag, Pd, and Pt) onto Au nanotriangles: effects of reductants and plasmonic properties.

Nanoscale 2021 Feb;13(5):2902-2913

Soft Condensed Matter, Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 5, 3584 CC Utrecht, The Netherlands.

The surface plasmon resonance of noble metals can be tuned by morphology and composition, offering interesting opportunities for applications in biomedicine, optoelectronics, photocatalysis, photovoltaics, and sensing. Here, we present the results of the symmetrical and asymmetrical overgrowth of metals (Ag, Pd, and Pt) onto triangular Au nanoplates using l-ascorbic acid (AA) and/or salicylic acid (SA) as reductants. By varying the reaction conditions, various types of Au nanotriangle-metal (Au NT-M) hetero-nanostructures were easily prepared. The plasmonic properties of as-synthesized nanoparticles were investigated by a combination of optical absorbance measurements and Finite-Difference Time-Domain (FDTD) simulations. We show that specific use of these reductants enables controlled growth of different metals on Au NTs, yielding different morphologies and allowing manipulation and tuning of the plasmonic properties of bimetallic Au NT-M (Ag, Pd, and Pt) structures.
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http://dx.doi.org/10.1039/d0nr06789jDOI Listing
February 2021

Natural food intake patterns have little synchronizing effect on peripheral circadian clocks.

BMC Biol 2020 11 6;18(1):160. Epub 2020 Nov 6.

Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, 3181 SW Sam Jackson Park Road - L606, Portland, OR, 97239, USA.

Background: Circadian rhythms across mammalian tissues are coordinated by a master clock in the suprachiasmatic nucleus (SCN) that is principally entrained by light-dark cycles. Prior investigations have shown, however, that time-restricted feeding (TRF)-daily alternation of fasting and food availability-synchronizes peripheral clocks independent of the light-dark cycle and of the SCN. This has led to the idea that downstream peripheral clocks are entrained indirectly by food intake rhythms. However, TRF is not a normal eating pattern, and it imposes non-physiologic long fasts that rodents do not typically experience. Therefore, we tested whether normal feeding patterns can phase-shift or entrain peripheral tissues by measuring circadian rhythms of the liver, kidney, and submandibular gland in mPer2 mice under different food schedules.

Results: We employed home cage feeders to first measure ad libitum food intake and then to dispense 20-mg pellets on a schedule mimicking that pattern. In both conditions, PER2::LUC bioluminescence peaked during the night as expected. Surprisingly, shifting the scheduled feeding by 12 h advanced peripheral clocks by only 0-3 h, much less than predicted from TRF protocols. To isolate the effects of feeding from the light-dark cycle, clock phase was then measured in mice acclimated to scheduled feeding over the course of 3 months in constant darkness. In these conditions, peripheral clock phases were better predicted by the rest-activity cycle than by the food schedule, contrary to expectation based on TRF studies. At the end of both experiments, mice were exposed to a modified TRF with food provided in eight equally sized meals over 12 h. In the light-dark cycle, this advanced the phase of the liver and kidney, though less so than in TRF with ad libitum access; in darkness, this entrained the liver and kidney but had little effect on the submandibular gland or the rest-activity cycle.

Conclusions: These data suggest that natural feeding patterns can only weakly affect circadian clocks. Instead, in normally feeding mice, the central pacemaker in the brain may set the phase of peripheral organs via pathways that are independent of feeding behavior.
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http://dx.doi.org/10.1186/s12915-020-00872-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646075PMC
November 2020

Age- and refraction-related changes in anterior segment anatomical structures measured by swept-source anterior segment OCT.

PLoS One 2020 23;15(10):e0240110. Epub 2020 Oct 23.

Doheny Eye Institute and Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.

Purpose: To assess the effects of age and refractive status on anterior segment anatomical structures, including the ciliary body, using a new swept-source anterior segment optical coherence tomography (AS-OCT) device.

Methods: This prospective observational study included 63 healthy volunteers (mean age: 44.2 years). Images of the anterior segment were obtained using a new swept-source AS-OCT (ANTERION, Heidelberg Engineering GmbH, Heidelberg, Germany) with tracking and image averaging from the right eye of all participants. Repeatability as well as inter- and intra-observer reliability of biometric measurements were evaluated. The impact of image tracking and averaging on ciliary muscle measurements was tested. Univariate and multivariable statistical models were developed to evaluate the relationship of age and refractive status on anterior segment biometric measurements.

Results: For all test-retest repeatability and inter- and intra-observer reproducibility of swept-source AS-OCT measurements, high intraclass correlation (ICC) was noted (0.88-1.00). The nasal maximum ciliary muscle thickness (CMTMAX) and distance between scleral spur to the thickest point of the ciliary muscle (SSMAX) were larger than those on the temporal side (p<0.001 and p = 0.006, respectively). Nasal and temporal CMTMAX (p = 0.004 and p<0.001, respectively) and lens thickness (p<0.01) increased with age. Nasal and temporal SSMAX decreased with older age and increasing hyperopia (p = 0.01 and p<0.001, respectively). Image averaging resulted in improved ciliary muscle measurements (p = 0.008 to 0.02). Lens vault increased with older age and increased hyperopia (p<0.01). OCT measurements of the angle decreased with older age and increased hyperopia (p<0.001 to 0.03). Aqueous depth decreased with older age and increased hyperopia (p<0.01). Pupil diameter decreased with older age (p<0.01).

Conclusions: Repeatability and reproducibility of biometric measurements using the ANTERION AS-OCT were excellent. Image averaging improved the accuracy of ciliary muscle measurements. The device produced measurements of biometric parameters that described superficial and deep structures including the ciliary body and full lens thickness from a single image.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240110PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584205PMC
December 2020

CircCFL1/MiR-107 Axis Targeting HMGB1 Promotes the Malignant Progression of Diffuse Large B-Cell Lymphoma Tumors.

Cancer Manag Res 2020 30;12:9351-9362. Epub 2020 Sep 30.

Department of Hematology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou 510080, Guangdong, People's Republic of China.

Objective: The pathogenesis of diffuse large B-cell lymphoma (DLBCL) has not yet been fully elucidated. An increasing number of studies have shown that circular RNAs (circRNAs) play an important role in tumorigenesis and development. The aim of this study was to investigate the effect of CircCFL1 on the malignant progression of DLBCL.

Methods: RT-qPCR was used to detect the expression levels of CircCFL1 and miR-107. A dual-luciferase reporter gene experiment was conducted to verify that CircCFL1 targeted miR-107 and the miR-107 target gene HMGB1. BrdU, transwell, and MTT tests were performed to detect cell invasion and proliferation. Western blot analysis was used to detect the phosphorylation of proteins. Xenograft models were established to confirm the effect of CircCFL1 on DLBCL tumor growth in vivo.

Results: The expression of CircCFL1 in cells transfected with the CircCFL1 overexpression vector was higher than that in the control group. After overexpressing CircCFL1, the expression of miR-107 in cells decreased significantly, and the protein level of HMGB1 increased. The dual-luciferase reporter gene experiment showed that CircCFL1 directly bound to miR-107 and reduced the inhibition of the target gene HMGB1. After CircCFL1 was overexpressed, cell migration and proliferation were enhanced. The tumor volume and weight in the lentivirus CircCFL1 group were higher than those in the lentivirus NC group.

Conclusion: Results showed that the circRNA CircCFL1 could regulate the expression of HMGB1 through miR-107 to promote the proliferation and migration of DLBCL.
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http://dx.doi.org/10.2147/CMAR.S263222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533230PMC
September 2020

Aqueous humour outflow imaging: seeing is believing.

Eye (Lond) 2021 01 15;35(1):202-215. Epub 2020 Oct 15.

Doheny Eye Institute and Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.

Elevated intraocular pressure (IOP) is the primary risk factor for blindness in glaucoma. IOP is determined by many factors including aqueous humour production and aqueous humour outflow (AHO), where AHO disturbance represents the primary cause of increased IOP. With the recent development of new IOP lowering drugs and Minimally Invasive Glaucoma Surgeries (MIGS), renewed interest has arisen in shedding light on not only how but where AHO is occurring for the trabecular/conventional, uveoscleral/unconventional, and subconjunctival outflow pathways. Historical studies critical to understanding outflow anatomy will be presented, leading to the development of modern imaging methods. New biological behaviours uncovered by modern imaging methods will be discussed with relevance to glaucoma therapies emphasized.
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http://dx.doi.org/10.1038/s41433-020-01215-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852535PMC
January 2021

Diverse CBX family members as potential prognostic biomarkers in non-small-cell lung cancer.

FEBS Open Bio 2020 10 21;10(10):2206-2215. Epub 2020 Sep 21.

Department of Hematology, Guangzhou First People's Hospital, South China University of Technology School of Medicine, Guangzhou, China.

Chromobox (CBX) family members are vital epigenetic regulators that repress the transcription of target genes through chromatin modification. Several studies have investigated the role of CBX family members in cancer. However, the function and prognostic value of diverse CBX family members in non-small-cell lung cancer remain largely unknown. In this study, we reveal that CBX family members are overexpressed in non-small-cell lung cancer tissue compared with normal lung tissue, with the exception of CBX6. Kaplan-Meier analysis demonstrated that high expressions of CBX1 and CBX3 are correlated with overall survival, disease-specific survival, disease-free interval, and progression-free interval for patients with lung adenocarcinoma (LUAD). Furthermore, regression model analysis suggests that CBX3 may be suitable as an independent prediction factor for overall survival and progression-free interval in patients with LUAD. In addition, CBX3 mRNA expression was found to be associated with tumor diameter and lymph node metastasis. Gene enrichment analysis suggests that CBX3 is involved in the cell cycle and P53 signaling pathways. Aberrant expression of CBX3 in LUAD is correlated with DNA copy number alteration. In summary, our data imply that CBX3 plays an important role in the promotion of LUAD and may thus have potential as a prognostic biomarker and molecular therapeutic target for the disease.
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http://dx.doi.org/10.1002/2211-5463.12971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530393PMC
October 2020

Intradevice Repeatability and Interdevice Agreement of Ocular Biometric Measurements: A Comparison of Two Swept-Source Anterior Segment OCT Devices.

Transl Vis Sci Technol 2020 08 7;9(9):14. Epub 2020 Aug 7.

USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA.

Purpose: To assess the repeatability and agreement of ocular biometric parameters measured using the Tomey CASIA SS-1000 and Heidelberg ANTERION anterior segment optical coherence tomography (AS-OCT) devices.

Methods: Both eyes of subjects 18 years of age or older were scanned three times with the CASIA and ANTERION under standardized dark lighting. One AS-OCT image along the horizontal (temporal-nasal) meridian was analyzed per eye and per scan. Pupillary diameter (PD) was within 15% for all pairwise comparisons. Anterior chamber depth, lens vault, anterior chamber width, angle opening distance, trabecular iris space area, and scleral spur angle (SSA500) were measured using manufacturer-provided image analysis software. Intraclass correlation (ICC), Wilcoxon signed-rank, and Bland-Altman analyses were performed to assess intradevice repeatability and interdevice agreement of measurements.

Results: Thirty-two eyes of 21 subjects were analyzed. There was excellent agreement (ICC >0.98) and no significant difference ( > 0.05) in PD across all comparisons. Intradevice measurement repeatability was excellent for both the CASIA (ICC range 0.93-0.99) and ANTERION (ICC range 0.97-0.99). Interdevice measurement agreement was also excellent (ICC range 0.85-0.96). Measurements within and between devices were similar ( > 0.06) for all parameters except SSA500 ( = 0.03). Linear regression and Bland-Altman plots showed the relationship was consistent across the entire range of measurements.

Conclusions: Intradevice measurement repeatability is excellent for the CASIA and ANTERION. Interdevice measurement agreement between the two devices exceeds metrics reported by previous comparison studies.

Translational Relevance: Modern swept-source AS-OCT devices produce highly repeatable measurements of ocular biometric parameters that are nearly interchangeable across devices.
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http://dx.doi.org/10.1167/tvst.9.9.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442878PMC
August 2020

Assessment of stress markers in restrained individuals following physical stress with and without sham CED activation.

J Forensic Leg Med 2020 Aug 26;74:101982. Epub 2020 Jun 26.

Department of Emergency Medicine, University of California, San Diego, CA, USA.

Introduction: Law enforcement and pre-hospital care personnel often confront individuals who must be physically restrained. Many are under the influence of illicit substances, and law enforcement officers may need to use a controlled electrical device (CED) to gain control of the individual and they are often placed into the prone maximum restraint (PMR) position. These techniques have previously been evaluated for their physiologic effects. The purpose of this study was to investigate the psychological effects of anticipating and experiencing a sham CED activation in healthy human subjects who were exercised and restrained compared with no sham activation by assessing the differences in a panel of several known biomarkers of stress.

Methods: We performed a randomized, crossover controlled human subject trial to study the stress associated with exercise, physical exhaustion, and restraint with and without an added psychological stress simulating the field use of a CED. Twenty five total subjects; each subject performed two different trials each consisting of a brief period of intense exercise on a treadmill to exhaustion followed by placement in the PMR with and without induced psychological stress. Blood samples were collected for analysis pre and post exercise, as well as 10 min after completion of the exercise. A panel of hormones and stress markers were measured.

Results: We found no significant differences in any of the stress biomarkers measured between the two study groups. A trend towards higher levels of copeptin was measured in the sham CED activation arm.

Conclusion: During a brief period of intense exercise followed by the psychological stress of anticipated CED application, there did not appear to be statistically significant changes in the stress panel of biomarkers measured, only a trend towards significance for higher copeptin levels in the patients exposed to the psychological stress.
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http://dx.doi.org/10.1016/j.jflm.2020.101982DOI Listing
August 2020

Quantitative 3D Characterization of Elemental Diffusion Dynamics in Individual [email protected] Nanoparticles with Different Shapes.

ACS Nano 2019 Nov 25;13(11):13421-13429. Epub 2019 Oct 25.

EMAT , University of Antwerp , Groenenborgerlaan 171 , 2020 Antwerp , Belgium.

Anisotropic bimetallic nanoparticles are promising candidates for plasmonic and catalytic applications. Their catalytic performance and plasmonic properties are closely linked to the distribution of the two metals, which can change during applications in which the particles are exposed to heat. Due to this fact, correlating the thermal stability of complex heterogeneous nanoparticles to their microstructural properties is of high interest for the practical applications of such materials. Here, we employ quantitative electron tomography in high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) mode to measure the 3D elemental diffusion dynamics in individual anisotropic Au-Ag nanoparticles upon heating . This approach allows us to study the elemental redistribution in complex, asymmetric nanoparticles on a single particle level, which has been inaccessible to other techniques so far. In this work, we apply the proposed method to compare the alloying dynamics of Au-Ag nanoparticles with different shapes and compositions and find that the shape of the nanoparticle does not exhibit a significant effect on the alloying speed whereas the composition does. Finally, comparing the experimental results to diffusion simulations allows us to estimate the diffusion coefficients of the metals for individual nanoparticles.
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http://dx.doi.org/10.1021/acsnano.9b06848DOI Listing
November 2019

CPSF3 is a promising prognostic biomarker and predicts recurrence of non-small cell lung cancer.

Oncol Lett 2019 Sep 24;18(3):2835-2844. Epub 2019 Jul 24.

Department of Pathology, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China.

Cleavage polyadenylation specificity factor (CPSF) is the core component of the 3'-end processing complex, which determines the site of 3'-end cleavage interactions of specific sequence elements within pre-mRNAs. The present study revealed that all members of the CPSF complex were overexpressed in lung cancer tissue from The Cancer Genome Atlas (TCGA) Lung Cancer Cohort compared with normal lung tissue. Analysis of overall survival and recurrence-free survival verified that only CPSF3 was associated with prognosis and recurrence of lung adenocarcinoma (LUAD), and thus could be a promising biomarker. Additionally, receiver operating characteristic curve analysis revealed that CPSF3 may function as a diagnostic biomarker to distinguish between two histological subtypes of non-small cell lung cancer. Furthermore, analysis of the association of CPSF3 expression with clinicopathological parameters indicated that CPSF3 was associated with smoking history, tumor diameter, lymph node metastasis, clinical stage and radiation therapy in LUAD. Additionally, analysis of the DNA methylation data of the TCGA-LUAD Cohort revealed that CPSF3 DNA CpG sites (cg12057242 and cg25739938) were generally hypomethylated in LUAD compared with normal lung tissue. Correlation analysis identified the CPSF3 DNA CpG site cg25739938 to be negatively correlated with CPSF3 expression, while no correlation was identified with cg12057242. In addition, correlation analysis demonstrated that the overexpression of CPSF3 was correlated with CPSF3 DNA copy number variants (CNAs). The findings indicate that abnormal expression of CPSF3 may be caused by DNA CNAs; and DNA hypermethylation and function may be a promising diagnostic and prognostic indicator for LUAD.
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http://dx.doi.org/10.3892/ol.2019.10659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704296PMC
September 2019

Cellular and cytoskeletal alterations of scleral fibroblasts in response to glucocorticoid steroids.

Exp Eye Res 2019 10 23;187:107774. Epub 2019 Aug 23.

Doheny Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address:

Steroid-induced ocular hypertension can be seen even after trabecular meshwork (TM) bypass/ablation. Thus, the purpose was to investigate steroid-response in cells distal to the TM by using primary scleral fibroblasts. Primary scleral cell cultures were generated using mid-depth scleral wedges from human donor corneo-scleral rims (n = 5) after corneal transplantation. Cells were treated with dexamethasone (DEX; 100 nM) and compared to media (MED)/vehicle (DMSO) controls. Cell size, shape, and migration were studied using the IncuCyte Live-Cell Analysis System. Cytoskeleton was compared using Alexa Fluor-568 Phalloidin and senescence tested by evaluating beta-galactosidase. Western blot comparison was performed for α-SMA, FKBP-51, fibronectin, phospho-myosin light chain, and myocilin. Scleral fibroblasts upregulated FKBP-51 in response to DEX indicating the existence of steroid-responsive pathways. Compared to controls, DEX-treated cells proliferated slower (~50%; p < 0.01-0.02), grew larger (~1.3-fold; p < 0.001), and migrated less (p = 0.01-0.006). Alexa Fluor 568 Phalloidin actin stress fiber labeling was more diffuse in DEX-treated cells (p = 0.001-0.004). DEX-treated cells showed more senescence compared to controls (~1.7-fold; p = 0.01-0.02). However, DEX-treated cells did not show increased cross-linked actin network formation or elevated myocilin/fibronectin/α-SMA/phospho-myosin light chain protein expression. For all parameters, MED- and DMSO-treated control cells were not significantly different. Primary scleral fibroblasts, grown from tissue collected immediately distal to the TM, demonstrated scleral-response behaviors that were similar to, but not identical with, classic TM steroid-response. Further study is needed to understand how these scleral cellular alterations may contribute to steroid-response IOP elevation after TM bypass/ablation surgery.
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http://dx.doi.org/10.1016/j.exer.2019.107774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759408PMC
October 2019

EXCITATION study: Unexplained in-custody deaths: Evaluating biomarkers of stress and agitation.

J Forensic Leg Med 2019 Aug 21;66:100-106. Epub 2019 Jun 21.

University of California, San Diego Medical Center, Department of Emergency Medicine, San Diego, CA, USA.

Background: Law enforcement personnel often confront violent and dangerous individuals suffering from Excited Delirium Syndrome (ExDS) who need emergent medical evaluation and treatment to optimize the best outcomes for this potentially lethal medical emergency. These subjects typically require physical restraint and use of force measures to control them. We sought to determine if stress-related biomarkers can differentiate ExDS subjects when compared with agitation and stress under other circumstances, including agitation and extreme physical exhaustion and restraint coupled with emotional stressors.

Methods: This was a prospective multi-center study enrolling a convenience sample of patients who presented with agitation or ExDS. Patients were enrolled from three academic emergency departments (ED), two in the United States and one in Canada. Three study groups (SG) included: SG1) patients brought to the ED with ExDS based on the use of standardized clinical criteria; SG2) ED patients with acute agitation who were not in a clinical state of ExDS but required sedation; SG3) a laboratory control group of subjects exercised to physical exhaustion, restrained, and psychologically stressed with threat of Conducted Energy Device (CED) activation. We examined a panel of stress-related biomarkers, including norepinephrine (NE), cortisol, copeptin, orexin A, and dynorphin (Dyn) from the blood of enrolled subjects.

Results: A total of 82 subjects were enrolled: 31 in the agitation group, 21 in the ExDS group, and 30 in the laboratory control group. Data were analyzed, comparing the findings between ExDS and the two other groups to determine if specific stress-related biomarkers are associated with ExDS. Biomarker comparisons between subjects identified with ExDS, agitation, and control groups demonstrated that cortisol levels were more elevated in the ExDS group compared with the other groups. Orexin was only significant in ExDs (with Agitated tendency but lot of variability in the group). NE and Dyn increased as response to stress in Agitated and ExDS.

Conclusions: Cortisol levels were more elevated in subjects in the ExDS group compared with the other comparison groups and orexin was elevated in ExDS compared to controls, a trend that did not reach statistical significance in the agitated group. The clinical or diagnostic significance of these difference have yet to be defined and warrants further study.
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http://dx.doi.org/10.1016/j.jflm.2019.06.009DOI Listing
August 2019

Thermal enhancement and quenching of upconversion emission in nanocrystals.

Nanoscale 2019 Jul 14;11(25):12188-12197. Epub 2019 Jun 14.

Condensed Matter and Interfaces, Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 1, 3584 CC Utrecht, The Netherlands.

Photoluminescence is a powerful tool in temperature sensing. Recently, the application of upconversion (UC) nanocrystals (NCs) has shown great potential for nanothermometry due to high spatial resolution, superior accuracy, and its non-invasive nature. In addition to spectral changes upon heating, anomalous thermal enhancement of UC emission has been reported for UC NCs, but the underlying mechanism remains unclear. Here, we report on NaY(WO) doped with the Er-Yb UC couple in NCs and the bulk material, and investigate the temperature-dependent luminescence in both air and dry nitrogen. For UC NCs in air, strong thermal enhancement of UC emission is observed with good reversibility and accompanied by a lengthening of the decay time for the Er UC emission and Yb IR emission. In contrast, the measurements carried out on NCs in dry nitrogen demonstrate a transition from thermal enhancement in the first cycle to thermal quenching in the subsequent cycles. The thermal quenching is similar to that in bulk materials. Thermogravimetric analysis (TGA) and Fourier transform infrared (FT-IR) measurements reveal the presence of water coupled on the NC surface that evaporates upon heating up to ∼470 K but is readsorbed upon cooling. Based on these observations, we explain the anomalous thermal enhancement of UC NCs in air by quenching of the Yb and Er emissions via surface adsorbed water molecules. The present study highlights the importance of careful characterization of surface adsorbed molecules which is crucial for understanding the luminescence properties of NCs, and enables the exploration of UC NCs with higher quantum efficiencies.
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http://dx.doi.org/10.1039/c9nr02271fDOI Listing
July 2019

Visual Assessment of Aqueous Humor Outflow.

Asia Pac J Ophthalmol (Phila) 2019 Mar 27. Epub 2019 Mar 27.

UCLA Department of Ophthalmology, Doheny Eye Institute, Los Angeles, CA, United States.

In the past decade, many new pharmacological and surgical treatments have become available to lower intraocular pressure (IOP) for glaucoma. The majority of these options have targeted improving aqueous humor outflow (AHO). At the same time, in addition to new treatments, research advances in AHO assessment have led to the development of new tools to structurally assess AHO pathways and to visualize where aqueous is flowing in the eye. These new imaging modalities have uncovered novel AHO observations that challenge traditional AHO concepts. New behaviors including segmental, pulsatile, and dynamic AHO may have relevance to the disease and the level of therapeutic response for IOP-lowering treatments. By better understanding the regulation of segmental, pulsatile, and dynamic AHO, it may be possible to find new and innovative treatments for glaucoma aiming at these new AHO behaviors.
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http://dx.doi.org/10.22608/APO.201911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028348PMC
March 2019

Size-Dependent Band-Gap and Molar Absorption Coefficients of Colloidal CuInS Quantum Dots.

ACS Nano 2018 Aug 13;12(8):8350-8361. Epub 2018 Aug 13.

Condensed Matter and Interfaces , Debye Institute for Nanomaterials Science, Utrecht University , 3508 TA Utrecht , The Netherlands.

The knowledge of the quantum dot (QD) concentration in a colloidal suspension and the quantitative understanding of the size-dependence of the band gap of QDs are of crucial importance from both applied and fundamental viewpoints. In this work, we investigate the size-dependence of the optical properties of nearly spherical wurtzite (wz) CuInS (CIS) QDs in the 2.7 to 6.1 nm diameter range (polydispersity ≤10%). The QDs are synthesized by partial Cu for In cation exchange in template CuS nanocrystals, which yields CIS QDs with very small composition variations (In/Cu = 0.91 ± 0.11), regardless of their sizes. These well-defined QDs are used to investigate the size-dependence of the band gap of wz CIS QDs. A sizing curve is also constructed for chalcopyrite CIS QDs by collecting and reanalyzing literature data. We observe that both sizing curves follow primarily a 1/ d dependence. Moreover, the molar absorption coefficients and the absorption cross-section per CIS formula unit, both at 3.1 eV and at the band gap, are analyzed. The results demonstrate that the molar absorption coefficients of CIS QDs follow a power law at the first exciton transition energy (ε = 5208 d) and scale with the QD volume at 3.1 eV. This latter observation implies that the absorption cross-section per unit cell at 3.1 eV is size-independent and therefore can be estimated from bulk optical constants. These results also demonstrate that the molar absorption coefficients at 3.1 eV are more reliable for analytical purposes, since they are less sensitive to size and shape dispersion.
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http://dx.doi.org/10.1021/acsnano.8b03641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117745PMC
August 2018

Circadian disruption of food availability significantly reduces reproductive success in mice.

Horm Behav 2018 09 5;105:177-184. Epub 2018 Sep 5.

Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR, United States of America; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States of America. Electronic address:

Circadian disruptions impair reproductive health in human populations and in animal models. We tested the hypothesis that mistimed food, a common disruptive feature of shift work, impairs reproductive success in mice. Male and female mPer2 mice on a C57BL/6 background were fed during the light or dark phase in two experiments. Food-induced internal misalignment of the liver clock was verified by in vivo bioluminescence in anesthetized mice in both experiments. In Experiment 1, food-restricted pairs were monitored for litters for 18 weeks. In the light-fed group, birth of the first litter was significantly delayed, and total reproductive output was significantly reduced by 38%. In Experiment 2, estrous cycling was monitored for 3 weeks, and then after pairing, copulatory plugs, pregnancy, litter sizes, and uterine implantation sites were measured. Fewer light-fed females birthed litters (25% versus 73%). This was attributable to a difference in behavior as mating success was significantly reduced in light-fed mice: 42% were observed with a copulatory plug compared to 82% for dark-fed mice. The proportion of mice displaying uterine implantation sites was the same as the proportion observed with copulatory plugs, suggesting no deficit in initiating pregnancy after mating. Estrous cycling and pregnancy maintenance did not differ between the groups. We conclude that mistimed feeding inhibits reproduction in mice by reducing successful mating behavior.
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http://dx.doi.org/10.1016/j.yhbeh.2018.07.006DOI Listing
September 2018

Noninvasive evaluation of cerebrospinal fluid pressure in ocular hypertension: a preliminary study.

Acta Ophthalmol 2018 Aug 24;96(5):e570-e576. Epub 2018 Mar 24.

Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Purpose: To compare the orbital cerebral spinal fluid pressure (CSFP) and trans-lamina cribrosa pressure difference (TLCPD) determined noninvasively in ocular hypertensive (OH) subjects and controls.

Methods: Cross-sectional observational study. Magnetic resonance imaging was used to measure orbital subarachnoid space width (OSASW). The CSFP (mm Hg) was estimated from a published formula as 17.54 × MRI derived OSASW at 15 mm behind the globe + 0.47 × body mass index + 0.13 × mean arterial blood pressure -21.52. Estimated TLCPD was calculated as IOP- CSFP.

Results: The orbital subarachnoid space width was significantly wider (p = 0.01) in the OH group than in the control group at all three measurement locations. The MRI derived CSFP value in OH (14.9 ± 2.9 mm Hg) was significantly higher than in the normal group (12.0 ± 2.8 mm Hg; p < 0.01). The estimated TLCPD value in OH (9.0 ± 4.2 mm Hg) was significantly higher than in controls (3.6 ± 3.0 mm Hg; p < 0.01).

Conclusion: The wider OSASW and higher estimated CSFP in OH subjects suggest a higher orbital CSFP. Despite a higher orbital CSFP that could be protective, the higher TLCPD in OH may play a significant role in the risk of developing glaucoma.
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http://dx.doi.org/10.1111/aos.13724DOI Listing
August 2018

MicroRNA-26a regulates ANXA1, rather than DAL-1, in the development of lung cancer.

Oncol Lett 2018 Apr 14;15(4):5893-5902. Epub 2018 Feb 14.

Department of Pathology, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China.

The aim of the present study was to investigate the expression and role of microRNA-26a (miR-26a) in lung cancer, and to verify whether differentially expressed in adenocarcinoma of the lung (DAL-1) is the target protein of miR-26a. mRNA expression levels of miR-26a and DAL-1 were detected using reverse transcription-quantitative polymerase chain reaction. Protein expression levels of DAL-1 and annexin A1 (ANXA1) were evaluated by western blot analysis. Cell Counting Kit-8, Transwell and wound scratch healing assays were used to characterize the function of miR-26a in lung cancer cells. The association of DAL-1 with miR-26a or ANXA1 was determined by dual-luciferase reporter or two-dimensional gel electrophoresis assays. miR-26a revealed decreased expression levels in lung cancer tissues compared with normal lung tissues, and decreased expression levels in lung cancer cells compared with 16HBE cells. Inhibition of miR-26a promoted lung cancer cell growth, migration and invasion. The DAL-1 protein exhibited downregulated expression levels in lung cancer tissues. DAL-1 was not the direct target gene of miR-26a. The two-dimensional gel electrophoresis assay confirmed that DAL-1 and ANXA1 were associated proteins. Expression levels of the ANXA1 protein were increased following DAL-1 gene silencing. The altered expression level of miR-26a affected the expression of ANXA1, and not of DAL-1. miR-26a demonstrated decreased expression levels in lung cancer cells, and it has an important effect on the biological function of lung cancer cells. However, DAL-1 was not a target gene of miR-26a. As a DAL-1 associated protein, ANXA1 was regulated by miR-26a.
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http://dx.doi.org/10.3892/ol.2018.8048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840747PMC
April 2018

Bio-Inspired Growth of Silver Nanoparticles on 2D Material's Scaffolds as Heterostructures with Their Enhanced Antibacterial Property.

J Nanosci Nanotechnol 2018 Jun;18(6):3893-3900

Guangdong Key Laboratory of Nanomedicine, CAS Key Lab for Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, P. R. China.

We developed a facile and green bio-inspired strategy to fabricate silver nano-particles growth in-situ on different scaffolds materials, building novel heterostructures for promoting their antibacterial activities and durability. Firstly, fluorinated graphene oxide (FGO) nanosheets, layered molybdenum disulfide (MoS2), and layered tungsten disulfide (WS2) were exfoliated by chemical liquid with intense sonication. And silicon dioxide (SiO2) nano-spheres were prepared via wet chemical method. Then, silver nanoparticles were grown onto those surfaces of layered nanosheets and nano-spheres, hybridizing three dimensional hetero-architectures. The obtained silver-hybridized nanoarchitechtures were further analyzed by TEM and EDS. Additionally, three bacteria were applied to evaluate their antibacterial property, illustrating distinctive antibacterial effects, expecting to explore more applications in water disinfection and food packing fields.
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http://dx.doi.org/10.1166/jnn.2018.15027DOI Listing
June 2018

Altered Dopamine Synaptic Markers in Postmortem Brain of Obese Subjects.

Front Hum Neurosci 2017 3;11:386. Epub 2017 Aug 3.

Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of MiamiMiami, FL, United States.

Dopaminergic signaling in the reward pathway in the brain has been shown to play an important role in food intake and the development of obesity. Obese rats release less dopamine (DA) in the nucleus accumbens (NAc) after food intake, and amphetamine stimulated striatal DA release is reduced in obese subjects. These studies suggest that DA hypofunction associated with hedonic dysregulation is involved in the pathophysiology of obesity. To identify brain changes in obesity, quantitative measures of DA synaptic markers were compared in postmortem brain tissues of normal weight and obese subjects over a range of increasing body mass indices (BMI). DA transporter (DAT) numbers in the striatum were compared to the relative expression of DAT, tyrosine hydroxylase (TH) and D2 dopamine receptors (DRD2) in midbrain DA neurons. Radioligand binding assays of [H]WIN35,428 demonstrated that the number of striatal DAT binding sites was inversely correlated with increasing BMI ( = -0.47; < 0.01). DAT and TH gene expression were significantly decreased in the somatodendritic compartment of obese subjects ( < 0.001), with no significant change in DRD2 compared to normal weight subjects. The reduced density of striatal DAT with corresponding reductions in DAT and TH gene expression in substantia nigra (SN) suggests, that obesity is associated with hypodopaminergic function. A DA reward deficiency syndrome has been suggested to underlie abnormal eating behavior that leads to obesity. Neurobiological changes in presynaptic DA markers demonstrated postmortem in human brain support a link between hedonic DA dysregulation and obesity.
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http://dx.doi.org/10.3389/fnhum.2017.00386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541030PMC
August 2017

Taxifolin protects RPE cells against oxidative stress-induced apoptosis.

Mol Vis 2017 27;23:520-528. Epub 2017 Jul 27.

Eye Hospital of China Academy of Chinese Medical Sciences, Beijing, China.

Purpose: Oxidative stress-induced damage to RPE cells has been suggested to be an important factor in the pathogenesis of age-related macular degeneration. Taxifolin, a flavonol, has been shown to exhibit significant antioxidant properties. The purpose of this study was to investigate the potential protective effects of taxifolin on RPE cells cultured under oxidative stress conditions and to elucidate the underlying mechanisms.

Methods: Human RPE (ARPE-19) cells were treated with different concentrations of taxifolin and 0.4 mM of HO for 24 h. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was quantitatively measured by annexin V/propidium iodide double staining, and the expression levels of poly (ADP-ribose) polymerase (PARP) were evaluated by western blotting. Reactive oxygen species (ROS) were measured using a commercially available ROS detection system. The expressions of phase II enzymes, including NAD(P)H quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase modifier (GCLM) and catalytic (GCLC) subunits, were examined using real-time PCR and western blotting. The nuclear localization of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) protein was detected by western blotting. Results: Taxifolin clearly inhibited the decrease in HO-induced cell viability, cell apoptosis, and intracellular ROS generation. In addition, taxifolin inhibited the H2O2-induced PARP cleavage. Moreover, treatment with taxifolin activated mRNA and the protein expression of NRF2 by inducing the translocation of NRF2 to the nucleus. Consequently, the mRNA and protein levels of the phase II enzymes NQO1, HO-1, GCLM, and GCLC increased. Conclusions: Taxifolin was shown to protect RPE cells against oxidative stress-induced apoptosis. The potential mechanism appears to involve the activation of NRF2 and the phase II antioxidant enzyme system.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534490PMC
April 2018

Efficient and Stable Luminescence from Mn in Core and Core-Isocrystalline Shell CsPbCl Perovskite Nanocrystals.

Chem Mater 2017 May 23;29(10):4265-4272. Epub 2017 Apr 23.

Condensed Matter and Interfaces, Debye Institute for Nanomaterials Science, Utrecht University, 3508 TA Utrecht, The Netherlands.

There has been a growing interest in applying CsPbX (X = Cl, Br, I) nanocrystals (NCs) for optoelectronic application. However, research on doping of this new class of promising NCs with optically active and/or magnetic transition metal ions is still limited. Here we report a facile room temperature method for Mn doping into CsPbCl NCs. By addition of a small amount of concentrated HCl acid to a clear solution containing Mn, Cs, and Pb precursors, Mn-doped CsPbCl NCs with strong orange luminescence of Mn at ∼600 nm are obtained. Mn-doped CsPbCl NCs show the characteristic cubic phase structure very similar to the undoped counterpart, indicating that the nucleation and growth mechanism are not significantly modified for the doping concentrations realized (0.1 at. % - 2.1 at. %). To enhance the Mn emission intensity and to improve the stability of the doped NCs, isocrystalline shell growth was applied. Growth of an undoped CsPbCl shell greatly enhanced the emission intensity of Mn and resulted in lengthening the radiative lifetime of the Mn emission to 1.4 ms. The core-shell NCs also show superior thermal stability and no thermal degradation up to at least 110 °C, which is important in applications.
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http://dx.doi.org/10.1021/acs.chemmater.7b00345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445715PMC
May 2017

Toward hybrid Au nanorods @ M (Au, Ag, Pd and Pt) core-shell heterostructures for ultrasensitive SERS probes.

Nanotechnology 2017 Jun;28(24):245602

Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, People's Republic of China. Soft Condensed Mater, Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 5, 3584 CC Utrecht, Netherlands.

Being able to precisely control the morphologies of noble metallic nanostructures is of essential significance for promoting the surface-enhanced Raman scattering (SERS) effect. Herein, we demonstrate an overgrowth strategy for synthesizing Au @ M (M = Au, Ag, Pd, Pt) core-shell heterogeneous nanocrystals with an orientated structural evolution and highly improved properties by using Au nanorods as seeds. With the same reaction condition system applied, we obtain four well-designed heterostructures with diverse shapes, including Au concave nanocuboids (Au CNs), Au @ Ag crystalizing face central cube nanopeanuts, Au @ Pd porous nanocuboids and Au @ Pt nanotrepangs. Subsequently, the exact overgrowth mechanism of the above heterostructural building blocks is further analysed via the systematic optimiziation of a series of fabrications. Remarkably, the well-defined Au CNs and Au @ Ag nanopeanuts both exhibit highly promoted SERS activity. We expect to be able to supply a facile strategy for the fabrication of multimetallic heterogeneous nanostructures, exploring the high SERS effect and catalytic activities.
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http://dx.doi.org/10.1088/1361-6528/aa70f3DOI Listing
June 2017

Knockdown of ANXA1 suppresses the biological behavior of human NSCLC cells in vitro.

Mol Med Rep 2016 May 21;13(5):3858-66. Epub 2016 Mar 21.

Department of Pathology, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.

Annexin A1 (ANXA1) is a member of the annexin superfamily. Previous studies have reported that ANXA1 is highly expressed in various types of malignant tumor; however, its role in the progression of non‑small cell lung cancer (NSCLC) remains to be fully clarified. The present study aimed to investigate the oncogenic role of ANXA1 in NSCLC cells in vitro. RNA interference was used to downregulate ANXA1 expression in A549 and H1299 cells using a small interfering RNA lentiviral vector. Subsequently, cell proliferation and migration were detected using Cell Counting kit‑8, clone formation, wound healing and Transwell chamber assays. Successful transfection was confirmed using fluorescence microscopy, which demonstrated that ANXA1 had been efficiently inhibited. ANXA1 knockdown suppressed the proliferation, migration and invasion of NSCLC cells. In conclusion, the present study provided evidence suggesting that ANXA1 may contribute to the growth and invasion of NSCLC cell lines, and ANXA1 may be exploited as an in vitro therapeutic target for the treatment of NSCLC.
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http://dx.doi.org/10.3892/mmr.2016.5022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838122PMC
May 2016

Pressure balance and imbalance in the optic nerve chamber: The Beijing Intracranial and Intraocular Pressure (iCOP) Study.

Sci China Life Sci 2016 May 26;59(5):495-503. Epub 2016 Feb 26.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, 100730, China.

To determine the interdependence of intracranial pressure (ICP) and intraocular pressure (IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure (LCP), optic nerve subarachnoid space pressure (ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP (via shunting cerebrospinal fluid (CSF) from the ventricle) were recorded. At baseline, all examined pressures were different (ICP0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient (TLPG) remained stable (ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined (ICP-IOP independent zone). The optic nerve pressure gradient (ONPG) and trans-optic nerve pressure gradient (TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.
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http://dx.doi.org/10.1007/s11427-016-5022-9DOI Listing
May 2016

Intracranial pressure (ICP) and optic nerve subarachnoid space pressure (ONSP) correlation in the optic nerve chamber: the Beijing Intracranial and Intraocular Pressure (iCOP) study.

Brain Res 2016 Mar 12;1635:201-8. Epub 2016 Jan 12.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China; Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. Electronic address:

Purpose: Because a lowered intracranial pressure (ICP) is a possible mechanism of optic neuropathy, we wished to study the CSF dynamics in the optic nerve chamber by recording possible changes in the optic nerve subarachnoid space pressure (ONSP) and the impact on it when acutely lowering ICP.

Methods: In eight normal dogs pressure probes were implanted in the left brain ventricle, lumbar cistern, optic nerve subarachnoid space and in the anterior eye chamber. Following CSF shunting from the brain ventricle we monitored changes of ICP, lumbar cistern pressure (LCP), ONSP and intraocular pressure (IOP).

Results: At baseline, the pressures were different with ICP>LCP>ONSP but correlated with each other (P<0.001). The "trans-lamina cribrosa pressure gradient" (TLPG) was highest for IOP-ONSP, lower for IOP-LCP, and lowest for IOP-ICP (P<0.001). During CSF shunting the ICP gradually decreased in a linear fashion together with the ONSP ("ICP-depended zone"). But when the ICP fell below a critical breakpoint, ICP and ONSP became uncoupled and ONSP remained constant despite further ICP decline ("ICP-independent zone").

Conclusions: Because the parallel decline of ICP and ONSP breaks down when ICP decreases below a critical breakpoint, we interpret this as a sign of CSF communication arrest between the intracranial and optic nerve SAS. This may be caused by obstructions of either CSF inflow through the optic canal or outflow into the intra-orbital cavity. This CSF exchange arrest may be a contributing factor to optic nerve damage and the optic nerve chamber syndrome which may influence the loss of vision or its restoration.
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http://dx.doi.org/10.1016/j.brainres.2016.01.011DOI Listing
March 2016
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