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1.  Biological Properties of Acidic Cosmetic Water from Seawater 
This current work was to investigate the biological effects of acidic cosmetic water (ACW) on various biological assays. ACW was isolated from seawater and demonstrated several bio-functions at various concentration ranges. ACW showed a satisfactory effect against Staphylococcus aureus, which reduced 90% of bacterial growth after a 5-second exposure. We used cultured human peripheral blood mononuclear cells (PBMCs) to test the properties of ACW in inflammatory cytokine release, and it did not induce inflammatory cytokine release from un-stimulated, normal PBMCs. However, ACW was able to inhibit bacterial lipopolysaccharide (LPS)-induced inflammatory cytokine TNF-α released from PBMCs, showing an anti-inflammation potential. Furthermore, ACW did not stimulate the rat basophilic leukemia cell (RBL-2H3) related allergy response on de-granulation. Our data presented ACW with a strong anti-oxidative ability in a superoxide anion radical scavenging assay. In mass spectrometry information, magnesium and zinc ions demonstrated bio-functional detections for anti-inflammation as well as other metal ions such as potassium and calcium were observed. ACW also had minor tyrosinase and melanin decreasing activities in human epidermal melanocytes (HEMn-MP) without apparent cytotoxicity. In addition, the cell proliferation assay illustrated anti-growth and anti-migration effects of ACW on human skin melanoma cells (A375.S2) indicating that it exerted the anti-cancer potential against skin cancer. The results obtained from biological assays showed that ACW possessed multiple bioactivities, including anti-microorganism, anti-inflammation, allergy-free, antioxidant, anti-melanin and anticancer properties. To our knowledge, this was the first report presenting these bioactivities on ACW.
doi:10.3390/ijms13055952
PMCID: PMC3382787  PMID: 22754342
acidic cosmetic water (ACW); antioxidant activity; anti-microorganism; anti-inflammation; allergy-free; skin-whitening; anti-melanoma
2.  Mechanotransduction Drives Post Ischemic Revascularization Through KATP Channel Closure and Production of Reactive Oxygen Species 
Antioxidants & Redox Signaling  2014;20(6):872-886.
Abstract
Aims: We reported earlier that ischemia results in the generation of reactive oxygen species (ROS) via the closure of a KATP channel which causes membrane depolarization and NADPH oxidase 2 (NOX2) activation. This study was undertaken to understand the role of ischemia-mediated ROS in signaling. Results: Angiogenic potential of pulmonary microvascular endothelial cells (PMVEC) was studied in vitro and in the hind limb in vivo. Flow adapted PMVEC injected into a Matrigel matrix showed significantly higher tube formation than cells grown under static conditions or cells from mice with knockout of KATP channels or the NOX2. Blocking of hypoxia inducible factor-1 alpha (HIF-1α) accumulation completely abrogated the tube formation in wild-type (WT) PMVEC. With ischemia in vivo (femoral artery ligation), revascularization was high in WT mice and was significantly decreased in mice with knockout of KATP channel and in mice orally fed with a KATP channel agonist. In transgenic mice with endothelial-specific NOX2 expression, the revascularization observed was intermediate between that of WT and knockout of KATP channel or NOX2. Increased HIF-1α activation and vascular endothelial growth factor (VEGF) expression was observed in ischemic tissue of WT mice but not in KATP channel and NOX2 null mice. Revascularization could be partially rescued in KATP channel null mice by delivering VEGF into the hind limb. Innovation: This is the first report of a mechanosensitive ion channel (KATP channel) initiating endothelial signaling that drives revascularization. Conclusion: The KATP channel responds to the stop of flow and activates signals for revascularization to restore the impeded blood flow. Antioxid. Redox Signal. 20, 872–886.
doi:10.1089/ars.2012.4971
PMCID: PMC3924794  PMID: 23758611
3.  Hiding scattering layers for noninvasive imaging of hidden objects 
Scientific Reports  2015;5:8375.
The ability to noninvasive image through turbid media has long been a major scientific and technological goal in many disciplines. A breakthrough has been made to observe objects that were completely hidden behind an opaque scattering layer. However, such approach needs not only to scan both illumination light and detector but further off-line procedures to numerically retrieve the image of the objects. Here, we report a distant invisibility-based noninvasive method that can hide scattering layers and allows to directly image objects behind. By recording holograms of the objects through a ground glass and then using the holograms produced time-reversal lights to re-illuminate the objects, we implemented to observe objects with feature size ranging from 39 μm to 80 μm that were hidden behind a 3 mm thick ground glass. Of importance, our approach opens a door towards real-time, high speed biomedical imaging and in-site inspection of integrated devices.
doi:10.1038/srep08375
PMCID: PMC4323654  PMID: 25669436
4.  Rebound Potentiation of Inhibition in Juvenile Visual Cortex Requires Vision-Induced BDNF Expression 
The Journal of Neuroscience  2014;34(32):10770-10779.
The developmental increase in the strength of inhibitory synaptic circuits defines the time window of the critical period for plasticity in sensory cortices. Conceptually, plasticity of inhibitory synapses is an attractive mechanism to allow for homeostatic adaptation to the sensory environment. However, a brief duration of visual deprivation that causes maximal change in excitatory synapses produces minimal change in inhibitory synaptic transmission. Here we examined developmental and experience-dependent changes in inhibition by measuring miniature IPSCs (mIPSCs) in layer 2/3 pyramidal neurons of mouse visual cortex. During development from postnatal day 21 (P21) to P35, GABAA receptor function changed from fewer higher-conductance channels to more numerous lower-conductance channels without altering the average mIPSC amplitude. Although a week of visual deprivation did not alter the average mIPSC amplitude, a subsequent 2 h exposure to light produced a rapid rebound potentiation. This form of plasticity is restricted to a critical period before the developmental change in GABAergic synaptic properties is completed, and hence is absent by P35. Visual experience-dependent rebound potentiation of mIPSCs is accompanied by an increase in the open channel number and requires activity-dependent transcription of brain-derived neurotrophic factor (BDNF). Mice lacking BDNF transcription through promoter IV did not show developmental changes in inhibition and lacked rebound potentiation. Our results suggest that sensory experience may have distinct functional consequences in normal versus deprived sensory cortices, and that experience-dependent BDNF expression controls the plasticity of inhibitory synaptic transmission particularly when recovering vision during the critical period.
doi:10.1523/JNEUROSCI.5454-13.2014
PMCID: PMC4200113  PMID: 25100608
activity-dependent; BDNF; critical period; mIPSC; potentiation; visual cortex
5.  A Randomized Comparative Trial of Continued Abacavir/Lamivudine plus Efavirenz or Replacement with Efavirenz/Emtricitabine/Tenofovir DF in Hypercholesterolemic HIV-1 Infected Individuals 
PLoS ONE  2015;10(2):e0116297.
Background
Drug choice and metabolic changes with antiretroviral therapy contribute to cardiovascular risk in persons with HIV-1 infection.
Methods
A randomized, 12 week, open-label, comparative study of the impact on lipids of continuation of abacavir/lamivudine (ABC/3TC) plus efavirenz (EFV) or replacement with the single tablet regimen of EFV/emtricitabine/tenofovir DF (EFV/FTC/TDF) in hypercholesterolaemic subjects on successful antiretroviral therapy, with a 12-week extension with all subjects on EFV/FTC/TDF.
Results
157 subjects received study drug, 79 switched to EFV/FTC/TDF and 78 subjects continued ABC/3TC+EFV. At Week 12, 73 subjects on ABC/3TC+EFV switched to EFV/FTC/TDF. The switch was well tolerated and no subject experienced viral rebound. Median baseline fasting total cholesterol was 6.32mmol/L. 12 weeks following switch, the difference in the means (LSM) between treatment groups (EFV/FTC/TDF minus ABC/3TC+EFV) in total cholesterol change from baseline was -0.74mmol/l (95% CI −1.00, −0.47, p < 0.001). The median change from baseline in total cholesterol following switch in the EFV/FTC/TDF arm was -0.86mmol/l (p < 0.001) compared with +0.01mmol/l (p = 0.45) in the continuation arm at Week 12. Significant (p < 0.001) differences between treatment groups following switch were seen for all lipid fractions from baseline to Week 12: LDL cholesterol (−0.47 mmol/L [−0.70, −0.25]), HDL cholesterol (−0.15 mmol/L [−0.21, −0.08]), triglycerides (−0.43 mmol/L [-0.75, -0.11]), and non HDL cholesterol (−0.56 mmol/L [−0.80, −0.31]). In the extension phase, similar declines in total cholesterol were observed with a median change from Week 12 to Week 24 of −0.73mmol/L (p < 0.001).
Conclusions
Switching from ABC/3TC+EFV to EFV/FTC/TDF in persons with hypercholesterolemia maintains virological control and significantly improves key lipid parameters.
Trial Registration
ClinicalTrials.gov NCT00615810
doi:10.1371/journal.pone.0116297
PMCID: PMC4319732  PMID: 25658097
6.  EIF4EBP1 Overexpression Is Associated with Poor Survival and Disease Progression in Patients with Hepatocellular Carcinoma 
PLoS ONE  2015;10(2):e0117493.
Objective
EIF4EBP1 acts as a crucial effector in mTOR signaling pathway. Studies have suggested that EIF4EBP1 plays a critical role in carcinogenesis. However, the clinical significance and biological role of EIF4EBP1 in hepatocellular carcinoma (HCC) have not been elucidated. Therefore, we aimed to investigate the clinical significance of EIF4EBP1 in HCC.
Methods
Total 128 cases of HCCs were included in this study. EIF4EBP1 expression in HCC tissues was detected by qRT-PCR, Western blot and immunohistochemistry, respectively. Then the relationships between EIF4EBP1 expression and clinical features as well as survival were analyzed.
Results
The expression level of EIF4EBP1 mRNA is significantly higher in 60% (24/40) of fresh HCC tissues than that in the matched adjacent nontumor liver (NCL) tissues (P = 0.044). Similarly, EIF4EBP1 protein is notably upregulated in 8 HCC tissues (randomly selected from the 40 HCCs) measured by Western blot and is significantly increased in another 88 paraffin-embedded HCCs (53%, 47/88) by immunohistochemistry compared with the matched NCLs (P < 0.001). EIF4EBP1 protein expression in HCC tissues is significantly correlated with serum AFP (P = 0.003) and marginally significantly associated with pathological grade (P = 0.085), tumor number (P = 0.084), tumor embolus (P = 0.084) and capsulation (P = 0.073). Patients with higher EIF4EBP1 protein expression have a much worse 5-year overall survival (40.3% vs 73.6%) and 5-year disease-free survival (33.0% vs 49.0%) than those with low expression. Furthermore, Cox regression analysis shows that EIF4EBP1 protein is an independent prognostic factor for overall survival (HR, 2.285; 95% CI, 1.154–4.527; P = 0.018) and disease-free survival (HR, 1.901; 95% CI, 1.067–3.386; P = 0.029) in HCC patients.
Conclusions
Our results demonstrate for the first time that EIF4EBP1 mRNA and protein are markedly up-regulated in HCC tissues, and the protein overexpression is significantly associated with poor survival and progression, which provide a potential new prognostic marker and therapeutic target for HCC patients.
doi:10.1371/journal.pone.0117493
PMCID: PMC4319970  PMID: 25658620
7.  Cross-modal induction of thalamocortical potentiation leads to enhanced information processing in the auditory cortex 
Neuron  2014;81(3):664-673.
Summary
Sensory systems do not work in isolation; instead they show interactions that are specifically uncovered during sensory loss. To identify and characterize these interactions, we investigated whether visual deprivation leads to functional enhancement in primary auditory cortex (A1). We compared sound-evoked responses of A1 neurons in visually-deprived animals to those from normally-reared animals. Here we show that visual deprivation leads to improved frequency selectivity as well as increased frequency and intensity discrimination performance of A1 neurons. Furthermore, we demonstrate in vitro that in adults, visual deprivation strengthens thalamocortical (TC-) synapses in A1, but not in primary visual cortex (V1). Because deafening potentiated TC-synapses in V1 but not A1, cross-modal TC-potentiation seems to be a general property of adult cortex. Our results suggest that adults retain the capability for cross-modal changes while such capability is absent within a sensory modality. Thus multimodal training paradigms might be beneficial in sensory processing disorders.
doi:10.1016/j.neuron.2013.11.023
PMCID: PMC4023256  PMID: 24507197
10.  Coexistence of Hepatitis B Virus Quasispecies Enhances Viral Replication and the Ability To Induce Host Antibody and Cellular Immune Responses 
Journal of Virology  2014;88(15):8656-8666.
ABSTRACT
Hepatitis B virus (HBV) quasispecies contain a large number of variants that serve as a reservoir for viral selection under antiviral treatment and the immune response, leading to the acute exacerbation and subsequent development of liver failure. However, there is no clear experimental evidence for a significant role of HBV quasispecies in viral pathogenesis. In the present study, HBV sequences were amplified from a patient with severe liver disease and used for construction of HBV replication-competent plasmids. Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were performed to analyze the expression, secretion, and subcellular localization of viral proteins in vitro. Viral replication intermediates were detected by Southern blotting. HBV gene expression and replication and the induction of specific immune responses in an HBV hydrodynamic injection (HI) mouse model were investigated. The results demonstrated that two naturally occurring HBV variants, SH and SH-DPS, were identified. The variant SH-DPS expressed only a nonexportable hepatitis B virus surface antigen (HBsAg) with abnormal intracellular accumulation. The coexistence of the HBV variants at a ratio of 1 to 4 (SH to SH-DPS) increased HBV replication. Significantly stronger intrahepatic cytotoxic T lymphocyte (CTL) responses and antibody responses specific to HBsAg were induced in mice by the HBV variants when coapplied by HI. These findings uncovered an unexpected aspect of HBV quasispecies: the coexistence of different variants can significantly modulate specific host immune responses, representing a novel mechanism for the immunopathogenesis of HBV infection.
IMPORTANCE Hepatitis B virus (HBV) is an important human pathogen. HBV quasispecies with genetically heterogenous variants are thought to play a role in the progression of HBV-associated liver diseases. So far, direct evidence is available in only a few cases to confirm the proposed role of HBV variants in the pathogenesis. We report here that the coexistence of two naturally occurring HBV variants at a ratio of 1 to 4 increased HBV replication and induced significantly stronger intrahepatic cytotoxic T lymphocyte responses and antibody responses specific to HBV surface antigen (HBsAg) in mice. Our discovery uncovered an unexpected aspect of HBV quasispecies: the coexistence of different variants can significantly modulate specific host immune responses and may enhance immune-mediated liver damage under some circumstances, representing a novel mechanism for the immunopathogenesis of HBV infection.
doi:10.1128/JVI.01123-14
PMCID: PMC4135971  PMID: 24850745
11.  An outbreak following importation of wild poliovirus in Xinjiang Uyghur Autonomous Region, China, 2011 
Background
After more than 10 years without a case of wild poliovirus (WPV) in China, an outbreak occurred in 2011 in Xinjiang Uyghur Autonomous Region.
Methods
Acute flaccid paralysis (AFP) case surveillance was strengthened with epidemiological investigations and specimen collection and serological surveys were conducted among hospitalized patients.
Results
There were 21 WPV cases and 23 clinical compatible polio cases reported. WPV was isolated from 14 contacts of AFP cases and 13 in the healthy population. Incidence of WPV and clinical compatible polio cases were both highest among children <1 years, however, 24/44 (54.5%) polio cases were reported among adults aged 15–39 years.
Conclusions
High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Expansion of AFP case surveillance and use of serologic surveys to estimate population immunity should be conducted rapidly to guide preparedness and response planning for future WPV outbreaks.
doi:10.1186/s12879-015-0761-y
PMCID: PMC4336520  PMID: 25636581
Wild poliovirus; Importation; Acute flaccid paralysis; Supplementary immunization activities; Serological survey
12.  The Role of IL-23/Th17 Pathway in Patients with Primary Immune Thrombocytopenia 
PLoS ONE  2015;10(1):e0117704.
Background
Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with an unclear etiology. This study aims to investigate the role of IL-23/Th17 pathway in patients with ITP.
Method
The gene expressions of IL-17, IL-23 and their receptors in ITP patients and healthy controls were analyzed by quantitative real-time PCR. ELISA was used to test the IL-17 and IL-23 levels in plasma. Flow cytometry was used to detect the frequency of Th17 cells. The correlation between plasma IL-23 and IL-17 levels, Th17 cells, platelets were analyzed. The level of Th17-related cytokines was measured by ELISA following stimulation with IL-23. Subsequently, the IL-23 and IL-17 levels were measured in patients post-treatment.
Results
The PBMCs of ITP patients showed increased mRNA expression levels in each of the following: IL-23p19, IL-12p40, IL-23R, IL-12Rβ1, IL-17A, IL-17F, and RORC. In addition, elevated Th17 cells and plasma IL-17, IL-23 levels were also observed in these ITP patients. Furthermore, it was found that IL-23 levels in plasma are positively correlated with IL-17 levels and Th17 cells, yet negatively correlated with platelet count. Following IL-23 stimulation in vitro, IL-17 levels showed significant elevation. Furthermore, both IL-23 and IL-17 levels decreased after effective treatment.
Conclusion
The IL-23/Th17 pathway may be involved in the pathogenesis of ITP through enhancement of the Th17 response. Moreover, our results suggest that the IL-23/Th17 pathway is a potential therapeutic target in future attempts of ITP treatment.
doi:10.1371/journal.pone.0117704
PMCID: PMC4306550  PMID: 25621490
13.  A medical costs study of older patients with acute myocardial infarction and metabolic syndrome in hospital 
Background
Older patients with acute myocardial infarction (AMI) usually have a poor prognosis, but whether this poor prognosis leads to high hospital costs remains unclear. This study investigated the clinical outcomes of and costs incurred by older patients with AMI and metabolic syndrome (MS) in hospital.
Methods and results
Patients with AMI seen at Qilu Hospital of Shandong University between January 2011 and May 2013 were separated into four groups: young non-MS patients (n=282), older non-MS patients (n=324), young MS patients (n=217), and older MS patients (n=174). We found that advanced age was significantly associated with worse clinical outcomes, and that the clinical outcomes in patients with AMI and MS are also worsened. At the same cost (RMB¥10,000), older patients with and without MS had a markedly increased number of cardiovascular incidences compared with younger patients without MS. In a comparison of the incremental cost-effectiveness ratio (ICER) of percutaneous coronary intervention, older patients without MS had a lower ICER for cardiovascular incidences and a higher ICER for cardiac event-free survival rate when compared with young patients without MS, but a lower ICER for cardiovascular incidences and a higher ICER for cardiac event-free survival rate when compared with older MS patients.
Conclusion
Older AMI patients have poor clinical outcomes and their treatment is not cost-effective; however, the results are worse in patients with AMI and MS. Percutaneous coronary intervention is a cost-effective therapy in older patients with AMI, but its cost-effectiveness decreases in patients with AMI and MS.
doi:10.2147/CIA.S70372
PMCID: PMC4315548
metabolic syndrome; aging; vascular; acute myocardial infarction; cost-effectiveness
14.  Biocompatibility and osteogenic properties of porous tantalum 
Porous tantalum has been reported to be a promising material for use in bone tissue engineering. In the present study, the biocompatibility and osteogenic properties of porous tantalum were studied in vitro and in vivo. The morphology of porous tantalum was observed using scanning electron microscopy (SEM). Osteoblasts were cultured with porous tantalum, and cell morphology, adhesion and proliferation were investigated using optical microscopy and SEM. In addition, porous tantalum rods were implanted in rabbits, and osteogenesis was observed using laser scanning confocal microscopy and hard tissue slice examination. The osteoblasts were observed to proliferate over time and adhere to the tantalum surface and pore walls, exhibiting a variety of shapes and intercellular connections. The porous tantalum rod connected tightly with the host bone. At weeks 2 and 4 following implantation, new bone and small blood vessels were observed at the tantalum-host bone interface and pores. At week 10 after the porous tantalum implantation, new bone tissue was observed at the tantalum-host bone interface and pores. By week 12, the tantalum-host bone interface and pores were covered with new bone tissue and the bone trabeculae had matured and connected directly with the materials. Therefore, the results of the present study indicate that porous tantalum is non-toxic, biocompatible and a promising material for use in bone tissue engineering applications.
doi:10.3892/etm.2015.2208
PMCID: PMC4316955  PMID: 25667628
porous tantalum; osteogenesis; biocompatibility; cell toxicity; bone tissue engineering
15.  Dual Stimuli – Dual Response Nanoassemblies Prepared from a Simple Homopolymer 
ACS macro letters  2013;3(1):1-5.
A dual stimuli responsive nanogel-polyelectrolyte complex based on electrostatic coating has been developed. The nanoassembly is designed to elicit two disparate responses (viz. surface property change and guest encapsulation stability) from two different stimuli (viz. pH and redox variations). The components of the nanogel and the polyelectrolyte have been conveniently achieved from a simple homopolymer, poly(pentafluorophenylacrylate).
doi:10.1021/mz400515s
PMCID: PMC3917511  PMID: 24516780
16.  Successful endoscopic hemoclipping of massive lower gastrointestinal bleeding from paratyphoid A fever 
Paratyphoid fever can be complicated by massive lower gastrointestinal bleeding with ileocolonic ulcerations, which are commonly localized using colonoscopy. The most common manifestations include multiple, variable-sized, round or oval-shaped, punched-out ulcers. Occasionally, massive lower gastrointestinal bleeding can occur from erosion of blood vessels. We present a rare case of severe lower gastrointestinal bleeding due to paratyphoid A fever that was successfully controlled with hemoclippings. A 30-year-old man experienced high fever and hematochezia whose blood culture showed Salmonella paratyphi A. A complete colonoscopy was successfully performed up to the level of the terminal ileum, which showed multiple, shallow, ulcerated lesions over the entire terminal ileum. A bleeding vessel was seen in one of the ulcers, with overlaying blood clots. Endoscopic hemostasis was successfully performed with four pieces of endoclip and without immediate complication. This report highlights the use of colonoscopy and endoscopic therapy with endoclips for lower gastrointestinal bleeding, which should be considered before surgery.
doi:10.3748/wjg.v21.i3.1040
PMCID: PMC4299324  PMID: 25624745
Endoscopic hemoclipping hemostasis; Lower gastrointestinal bleeding; Paratyphoid A fever
17.  Tick-borne pathogens and the vector potential of ticks in China 
Parasites & Vectors  2015;8:24.
Ticks, as obligate blood-sucking ectoparasites, attack a broad range of vertebrates and transmit a great diversity of pathogenic microorganisms. They are considered second only to mosquitoes as vectors of human disease, and the most important vector of pathogens of domestic and wild animals. Of the 117 described species in the Chinese tick fauna, 60 are known to transmit one or more diseases: 36 species isolated within China and 24 species isolated outside China. Moreover, 38 of these species carry multiple pathogens, indicating the potentially vast role of these vectors in transmitting pathogens. Spotted fever is the most common tick-borne disease, and is carried by at least 27 tick species, with Lyme disease and human granulocytic anaplasmosis ranked as the second and third most widespread tick-borne diseases, carried by 13 and 10 species, respectively. Such knowledge provides us with clues for the identification of tick-associated pathogens and suggests ideas for the control of tick-borne diseases in China. However, the numbers of tick-associated pathogens and tick-borne diseases in China are probably underestimated because of the complex distribution and great diversity of tick species in this country.
doi:10.1186/s13071-014-0628-x
PMCID: PMC4300027  PMID: 25586007
Ticks; Tick-borne pathogens; Vector potential; China
18.  Increasing expression of substance P and calcitonin gene-related peptide in synovial tissue and fluid contribute to the progress of arthritis in developmental dysplasia of the hip 
Introduction
Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder that has pain and loss of joint function as major pathological features. In the present study, we explored the mechanisms of possible involvement and regulation of substance P (SP) and calcitonin gene-related peptide (CGRP) in the pathological and inflammatory processes of arthritis in DDH.
Methods
Blood, synovial tissue and fluid samples were collected from patients diagnosed with different severities of DDH and from patients with femoral neck fracture. Levels of SP, CGRP and inflammatory cytokines in synovium and synovial fluid (SF) in the different groups were evaluated by immunohistochemistry, real-time PCR and enzyme-linked immunosorbent assay (ELISA). Correlations between neuropeptides and inflammatory cytokines in SF were evaluated by partial correlation analysis. The proinflammatory effects of SP and CGRP on synoviocytes obtained from patients with moderate DDH were investigated in vitro by real-time PCR and ELISA. The mechanisms of those effects were evaluated by Western blot analysis and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) DNA binding assay.
Results
Significantly increased levels of neuropeptides and inflammatory cytokines were observed in synovium and SF from patients in the severe DDH group compared with the moderate DDH and control groups. In moderate DDH samples, SP in SF correlated with tumor necrosis factor (TNF)-α, and CGRP in SF correlated with TNF-α and interleukin (IL)-10. In the severe DDH group, SP in SF correlated with interleukin (IL)-1β, TNF-α and IL-10. CGRP in SF correlated with TNF-α. Additionally, SP might have had obvious proinflammatory effects on synoviocytes through the activation of NF-κB.
Conclusions
The upregulation of SP and CGRP in synovium and SF might participate in the inflammatory process of arthritis in DDH. The activation of the NF-κB pathway seems indispensable in the proinflammatory effect of SP on synoviocytes. This original discovery may indicate a potential clinical drug target and the development of innovative therapies for DDH.
doi:10.1186/s13075-014-0513-1
PMCID: PMC4320827  PMID: 25578529
19.  X-Ray Photoelectron Spectroscopy Investigation of the Nitrogen Species in Photoactive Perfluorophenylazide-Modified Surfaces 
X-ray Photoelectron Spectroscopy (XPS) was used to characterize the nitrogen species in perfluorophenylazide (PFPA) self-assembled monolayers. PFPA chemistry is a novel immobilization method for tailoring the surface properties of materials. It is a simple route for the efficient immobilization of graphene, proteins, carbohydrates and synthetic polymers onto a variety of surfaces. Upon light irradiation, the azido group in PFPA is converted to a highly reactive singlet nitrene species that readily undergoes CH insertion and C=C addition reactions. Here, the challenge of characterizing the PFPA modified surfaces was addressed by detailed XPS experimental analyses. The three nitrogen peaks detected in the XPS N1s spectra were assigned to amine/amide (400.5 eV) and azide (402.1 and 405.6 eV) species. The observed 2:1 ratio of the areas from the 402.1 eV to 405.6 eV peaks suggests the assignment of the peak at 402.1 eV to the two outer nitrogen atoms in the azido group and assignment of the peak at 405.6 eV to the central nitrogen atom in the azido group. The azide decomposition as the function of x-ray exposure was also determined. Finally, XPS analyses were conducted on patterned graphene to investigate the covalent bond formation between the PFPA and graphene. This study provides strong evidence for the formation of covalent bonds during the PFPA photocoupling process.
doi:10.1021/jp409338y
PMCID: PMC3923990  PMID: 24535931
PFPA; XPS; Surface Characterization; Graphene
20.  Functionalizable Amine-based Polymer Nanoparticles 
ACS macro letters  2013;2(10):948-951.
Surface functionalization of nanoparticles and host-guest properties of nanoassemblies are two critical features in the utilization of nanostructures in a variety of applications in materials, chemical, and biological nanotechnology. However, simultaneously incorporating these two features in one nanoparticle design is a rather challenging task. We have developed a simple and versatile nanoparticle platform that addresses this challenge. We have designed and characterized a polymer nanoparticle that provides the ability to encapsulate hydrophobic guest molecules and surface functionalization with a wide range of functional groups. In addition, we have also demonstrated a new and simple approach to tune the size of the nanoparticles.
PMCID: PMC4286340  PMID: 25580372
21.  Bruker Biotyper Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry System for Identification of Nocardia, Rhodococcus, Kocuria, Gordonia, Tsukamurella, and Listeria Species 
Journal of Clinical Microbiology  2014;52(7):2371-2379.
We evaluated whether the Bruker Biotyper matrix-associated laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) system provides accurate species-level identifications of 147 isolates of aerobically growing Gram-positive rods (GPRs). The bacterial isolates included Nocardia (n = 74), Listeria (n = 39), Kocuria (n = 15), Rhodococcus (n = 10), Gordonia (n = 7), and Tsukamurella (n = 2) species, which had all been identified by conventional methods, molecular methods, or both. In total, 89.7% of Listeria monocytogenes, 80% of Rhodococcus species, 26.7% of Kocuria species, and 14.9% of Nocardia species (n = 11, all N. nova and N. otitidiscaviarum) were correctly identified to the species level (score values, ≥2.0). A clustering analysis of spectra generated by the Bruker Biotyper identified six clusters of Nocardia species, i.e., cluster 1 (N. cyriacigeorgica), cluster 2 (N. brasiliensis), cluster 3 (N. farcinica), cluster 4 (N. puris), cluster 5 (N. asiatica), and cluster 6 (N. beijingensis), based on the six peaks generated by ClinProTools with the genetic algorithm, i.e., m/z 2,774.477 (cluster 1), m/z 5,389.792 (cluster 2), m/z 6,505.720 (cluster 3), m/z 5,428.795 (cluster 4), m/z 6,525.326 (cluster 5), and m/z 16,085.216 (cluster 6). Two clusters of L. monocytogenes spectra were also found according to the five peaks, i.e., m/z 5,594.85, m/z 6,184.39, and m/z 11,187.31, for cluster 1 (serotype 1/2a) and m/z 5,601.21 and m/z 11,199.33 for cluster 2 (serotypes 1/2b and 4b). The Bruker Biotyper system was unable to accurately identify Nocardia (except for N. nova and N. otitidiscaviarum), Tsukamurella, or Gordonia species. Continuous expansion of the MALDI-TOF MS databases to include more GPRs is necessary.
doi:10.1128/JCM.00456-14
PMCID: PMC4097692  PMID: 24759706
22.  Serial optical coherence scanner for large-scale brain imaging at microscopic resolution 
NeuroImage  2013;84:1007-1017.
We describe a serial optical coherence scanner (SOCS) for high resolution imaging of ex-vivo brain. SOCS integrates a multi-contrast optical coherence tomography and a vibratome slicer to establish comprehensive brain anatomy and fiber pathways in three-dimensional space. Rat brain images are demonstrated by utilizing intrinsic optical contrasts including back-scattering, birefringence and optic axis orientation, which are simultaneously generated from the same dataset. Volumetric images from serial scans are combined to realize large scale brain maps. Nerve fiber tracts are globally described in 3D by retardance, and delicately delineated by cross-polarization at the resolution of 15 × 15 × 5.5 μm3. In-plane orientations of the tracts are quantified by optic axis orientation. SOCS offers a new solution for complete reconstructions of macroscopic tissues such as primate and human brains at microscopic resolution. The technique also opens up varieties of opportunities for connectome studies and systematic investigations on neurological diseases and brain disorders.
doi:10.1016/j.neuroimage.2013.09.063
PMCID: PMC3928112  PMID: 24099843
fiber pathways; nerve fiber orientation; connectivity; brain anatomy; optical coherence tomography; polarization
23.  Bystander-initiated CPR in an Asian metropolitan: Does the socioeconomic status matter?☆ 
Resuscitation  2013;85(1):53-58.
Objectives
To determine the association of neighborhood socioeconomic status (SES) with bystander-initiated cardiopulmonary resuscitation (CPR) and patient outcomes of out of hospital cardiac arrests (OHCAs) in an Asian metropolitan area.
Methods
We performed a retrospective study in a prospectively collected cohort from the Utstein registry of adult non-traumatic OHCAs in Taipei, Taiwan. Average real estate value was assessed as the first proxy of SES. Twelve administrative districts in Taipei City were categorized into low versus high SES areas to test the association. The primary outcome was bystander-initiated CPR, and the secondary outcome was patient survival status. Factors associated with bystander-initiated CPR were adjusted for in multivariate analysis. The mean household income was assessed as the second proxy of SES to validate the association.
Results
From January 1, 2008 to December 30, 2009, 3573 OHCAs received prehospital resuscitation in the community. Among these, 617 (17.3%) cases received bystander CPR. The proportion of bystander CPR in low-SES vs. high-SES areas was 14.5% vs. 19.6% (p < 0.01). Odds ratio of receiving bystander-initiated CPR in low-SES areas was 0.72 (95% confidence interval: [0.60–0.88]) after adjusting for age, gender, witnessed status, public collapse, and OHCA unrecognized by the online dispatcher. Survival to discharge rate was significantly lower in low-SES areas vs. high-SES areas (4.3% vs. 6.8%; p < 0.01). All results above remained consistent in the analyses by mean household income.
Conclusions
Patients who experienced an OHCA in low-SES areas were less likely to receive bystander-initiated CPR, and demonstrated worse survival outcomes.
doi:10.1016/j.resuscitation.2013.07.033
PMCID: PMC4023511  PMID: 24056397
Cardiopulmonary resuscitation (CPR); Emergency medical system (EMS); Education; Socioeconomic status (SES); Neighborhood; First responder
24.  miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways 
The Journal of Clinical Investigation  2014;124(10):4489-4502.
Glioblastoma (GBM) is the most common and lethal brain tumor in adults. Glioma-initiating cells (GICs) are stem-like cells that have been implicated in glioblastoma progression and recurrence; however, the distinct properties of GICs and non-GICs within GBM tumors are largely uncharacterized. Here, we evaluated stem cell–associated microRNA (miR) expression in GICs from GBM patients and GICs derived from xenografted human glioma cell lines and determined that miR-33a promotes GIC growth and self-renewal. Moreover, evaluation of a GBM tissue array revealed that higher miR-33a expression was associated with poor prognosis of GBM patients. Antagonizing miR-33a function in GICs reduced self-renewal and tumor progression in immune-compromised mice, whereas overexpression of miR-33a in non-GICs promoted the display of features associated with GICs. We identified the mRNAs encoding phosphodiesterase 8A (PDE8A) and UV radiation resistance–associated gene (UVRAG) as direct miR-33a targets. PDE8A and UVRAG negatively regulated the cAMP/PKA and NOTCH pathways, respectively; therefore, miR-33a–dependent reduction of these proteins promoted growth and self-renewal of GICs by enhancing PKA and NOTCH activity. Furthermore, in GBM specimens, there was an inverse correlation between the expression levels of miR-33a and PDE8A and UVRAG expression. These findings reveal a miR-33a–centered signaling network that promotes GIC maintenance and has potential as a therapeutic target for GBM treatment.
doi:10.1172/JCI75284
PMCID: PMC4191031  PMID: 25202981
25.  Meshless Method with Operator Splitting Technique for Transient Nonlinear Bioheat Transfer in Two-Dimensional Skin Tissues 
A meshless numerical scheme combining the operator splitting method (OSM), the radial basis function (RBF) interpolation, and the method of fundamental solutions (MFS) is developed for solving transient nonlinear bioheat problems in two-dimensional (2D) skin tissues. In the numerical scheme, the nonlinearity caused by linear and exponential relationships of temperature-dependent blood perfusion rate (TDBPR) is taken into consideration. In the analysis, the OSM is used first to separate the Laplacian operator and the nonlinear source term, and then the second-order time-stepping schemes are employed for approximating two splitting operators to convert the original governing equation into a linear nonhomogeneous Helmholtz-type governing equation (NHGE) at each time step. Subsequently, the RBF interpolation and the MFS involving the fundamental solution of the Laplace equation are respectively employed to obtain approximated particular and homogeneous solutions of the nonhomogeneous Helmholtz-type governing equation. Finally, the full fields consisting of the particular and homogeneous solutions are enforced to fit the NHGE at interpolation points and the boundary conditions at boundary collocations for determining unknowns at each time step. The proposed method is verified by comparison of other methods. Furthermore, the sensitivity of the coefficients in the cases of a linear and an exponential relationship of TDBPR is investigated to reveal their bioheat effect on the skin tissue.
doi:10.3390/ijms16012001
PMCID: PMC4307345  PMID: 25603180
transient nonlinear bioheat transfer; meshless method; operator splitting; radial basis function; method of fundamental solutions

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