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1.  Design of Advanced Photocatalysis System by Adatom Decoration in 2D Nanosheets of Group-IV and III–V Binary Compounds 
Scientific Reports  2016;6:23104.
Searching for novel photocatalysts is one of the most important topic in photocatalytic fields. In the present work, we propose a feasible approach to improve the photocatalytic activities of 2D bilayers through surface decoration, i.e. hydrogenation, halogenation, and hydroxylation. Our investigations demonstrate that after surface modification, the optical adsorption expands into the visible region, while a built-in electric field is induced due to the interlayer coupling, which can promote the charge separation for photogenerated electron-hole pairs. Our results show that the indirect-direct band gap transition of SiC, SnC, BN and GaN can be realised through adatom decoration. Furthermore, the surface-modified 2D bilayers have suitable VBM and CBM alignments with the oxidation and reduction potentials for water splitting, suggesting powerful potentials in energy and environmental applications.
PMCID: PMC4794804  PMID: 26983908
2.  One-Pot Solvothermal Synthesis of Bi4V2O11 as A New Solar Water Oxidation Photocatalyst 
Scientific Reports  2016;6:22727.
Bi4V2O11 was prepared via a one-pot solvothermal method and characterized via XRD, Raman, XPS, Electrochemical impedance spectroscopy. The as-prepared Bi4V2O11 sample displays excellent photocatalytic activity towards oxygen evolution under light irradiation. The hierarchical structure is in favour of the spatial separation of photogenerated electrons and holes. Furthermore, the internal polar field also plays a role in improving the charge separation. Both of the two results are responsible for excellent activity of O2 evolution. The resulting hierarchical Bi4V2O11 sample should be very promising photocatalyst for the application of photocatalytic O2 evolution in the future.
PMCID: PMC4779990  PMID: 26947126
3.  An outbreak caused by GII.17 norovirus with a wide spectrum of HBGA-associated susceptibility 
Scientific Reports  2015;5:17687.
During the past norovirus (NoV) epidemic season, a new GII.17 variant emerged as a predominant NoV strain, surpassed the GII.4 NoVs, causing outbreaks of acute gastroenteritis (AGE) in China. Here we report a study of an AGE outbreak in an elementary school in December 2014 caused by the new GII.17 NoV to explore the potential mechanism behind the sudden epidemics of the GII.17 NoV. A total of 276 individuals were sick with typical NoV infection symptoms of vomiting (93.4%), abdominal pain (90.4%), nausea (60.0%), and diarrhea (10.4%) at an attack rate of 5.7–16.9%. Genotyping of the symptomatic patients showed that individuals with a secretor positive status, including those with A, B, and O secretors and Lewis positive blood types, were sensitive to the virus, while the non-secretors and the Lewis negative individual were not. Accordingly, the recombinant capsid P protein of the GII.17 isolate showed a wide binding spectrum to saliva samples of all A, B, and O secretors. Thus, the broad binding spectrum of the new GII.17 variant could explain its widely spread nature in China and surrounding areas in the past two years.
PMCID: PMC4671059  PMID: 26639056
4.  Controlling the Electronic Structures and Properties of in-Plane Transition-Metal Dichalcogenides Quantum Wells 
Scientific Reports  2015;5:17578.
In-plane transition-metal dichalcogenides (TMDs) quantum wells have been studied on the basis of first-principles density functional calculations to reveal how to control the electronic structures and the properties. In collection of quantum confinement, strain and intrinsic electric field, TMD quantum wells offer a diverse of exciting new physics. The band gap can be continuously reduced ascribed to the potential drop over the embedded TMD and the strain substantially affects the band gap nature. The true type-II alignment forms due to the coherent lattice and strong interface coupling suggesting the effective separation and collection of excitons. Interestingly, two-dimensional quantum wells of in-plane TMD can enrich the photoluminescence properties of TMD materials. The intrinsic electric polarization enhances the spin-orbital coupling and demonstrates the possibility to achieve topological insulator state and valleytronics in TMD quantum wells. In-plane TMD quantum wells have opened up new possibilities of applications in next-generation devices at nanoscale.
PMCID: PMC4663467  PMID: 26616013
5.  Somatic mitochondrial DNA mutations do not increase neuronal vulnerability to MPTP in young POLG mutator mice 
Mitochondrial DNA (mtDNA) mutations are hypothesized to play a pathogenic role in aging and age-related neurodegenerative diseases such as Parkinson’s disease (PD). In support of this, high levels of somatic mtDNA mutations in “POLG mutator” mice carrying a proofreading-deficient form of mtDNA polymerase γ (PolgD257A) lead to a premature aging phenotype. However, the relevance of this finding to the normal aging process has been questioned as the number of mutations is greater even in young POLG mutator mice, which show no overt phenotype, than levels achieved during normal aging in mice. Vulnerability of dopaminergic neurons to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) increases with age, and we hypothesized that this may result in part from the accumulation with age of somatic mtDNA mutations. If correct, then levels of mutations in young (2~3 month old) POLG mutator mice should be sufficient to increase vulnerability to MPTP. In contrast, we find that susceptibility to MPTP in both heterozygous and homozygous POLG mutator mice at this young age is not different from that of wild type littermate controls as measured by levels of tyrosine hydroxylase positive (TH+) striatal terminals, striatal dopamine and its metabolites, a marker of oxidative damage, or stereological counts of TH+ and total substantia nigra neurons. These unexpected results do not support the hypothesis that somatic mtDNA mutations contribute to the age-related vulnerability of dopaminergic neurons to MPTP. It remains possible that somatic mtDNA mutations influence vulnerability to other stressors, or require additional time for the deleterious consequences to manifest. Furthermore, the impact of the higher levels of mutations present at older ages in these mice was not assessed in our study, although a prior study also failed to detect an increase in vulnerability to MPTP in older mice. With these caveats, the current data do not provide evidence for a role of somatic mtDNA mutations in determining the vulnerability to MPTP.
PMCID: PMC4293310  PMID: 25450660
aging; Parkinson’s disease; mtDNA mutations; oxidative stress; neurodegeneration; tyrosine hydroxylase
6.  Transarterial chemoembolization versus hepatic resection in hepatocellular carcinoma treatment: a meta-analysis 
A number of cohort studies have compared the outcomes of transarterial chemoembolization (TACE) and hepatic resection (HR) in the treatment of hepatocellular carcinoma (HCC). However, the effect of TACE versus HR remains controversial. Therefore, we conducted a meta-analysis to assess the effectiveness of TACE and HR in HCC treatment.
Materials and methods
PubMed, Embase, Web of Science, Scopus,, and Cochrane library were searched from their inception until February 27, 2015 for relevant studies. The literature search was updated on May 25, 2015. Eligible studies were cohort studies comparing the survival outcomes between HCC patients undergoing TACE and HR. The primary outcome was overall survival (OS). Secondary outcomes were the recurrence rate and prognostic factors for OS. The risk ratio (RR) was used for the meta-analysis and was expressed with 95% confidence intervals (CIs).
This meta-analysis included eleven cohort studies with 6,297 patients, all treated with TACE or HR. Pooled estimates showed that, compared with TACE, HR significantly improved the 3-year OS (RR =0.77; 95% CI, 0.63–0.93; P=0.009). TACE and HR had similar effects on OS after 1 year (RR =0.94; 95% CI, 0.86–1.01; P=0.103), 2 years (RR =0.50; 95% CI, 0.21–1.19; P=0.114), 4 years (RR =0.61; 95% CI, 0.58–1.10; P=0.174), and 5 years (RR =0.77; 95% CI, 0.59–1.01; P=0.06). There was no significant difference between the 3-year (RR =1.31; 95% CI, 0.65–2.64; P=0.457) and 5-year recurrence rates (RR =1.14; 95% CI, 0.69–1.89; P=0.597) in the TACE and HR groups. Age (>65 vs ≤65 years; hazard ratio =0.99; 95% CI, 0.98–1.00; P=0.000), sex (male vs female; hazard ratio =0.79; 95% CI, 0.65–0.96; P=0.02), treatment method (TACE vs HR; hazard ratio =1.90; 95% CI, 1.46–2.46; P=0.000), and Eastern Cooperative Oncology Group performance score (≥1 vs 0; hazard ratio =1.69; 95% CI, 1.22–2.33; P=0.002) were independent predictors for OS.
This meta-analysis suggests that the TACE and HR likely have similar effects in the treatment of HCC patients in terms of OS and recurrence rate. However, this conclusion should be interpreted cautiously due to the presence of further subgroup analyses with respect to outcomes in patients with different liver statuses (Barcelona Clinic Liver Cancer stage A or stage B).
PMCID: PMC4539084  PMID: 26309396
transarterial chemoembolization; hepatic resection; hepatocellular carcinoma; meta-analysis
7.  Ideal Spintronics in Molecule-Based Novel Organometallic Nanowires 
Scientific Reports  2015;5:12772.
With the purpose of searching for new intriguing nanomaterial for spintronics, a series of novel metalloporphyrin nanowires (M-PPNW, M = Cr, Mn, Fe, Co, Ni, Cu and Zn) and hybrid nanowires fabricated by metalloporphyrin and metal-phthalocyanine (M-PCNW) are systematically investigated by means of first-principles calculations. Our results indicate that the transition metal atoms (TMs) embedded in the frameworks distribute regularly and separately, without any trend to form clusters, thus leading to the ideally ordered spin distribution. Except for the cases embedded with Ni and Zn, the others are spin-polarized. Remarkably, the Mn-PPNW, Mn-PCNW, MnCu-PPNW, MnCr-PCNW, and MnCu-PCNW frameworks all favor the long-ranged ferromagnetic spin ordering and display half-metallic nature, which are of greatest interest and importance for electronics and spintronics. The predicted Curie temperature for the Mn-PCNW is about 150 K. In addition, it is found that the discrepancy in magnetic coupling for these materials is related to the competition mechanisms of through-bond and through-space exchange interactions. In the present work, we propose not only two novel sets of 1D frameworks with appealing magnetic properties, but also a new strategy in obtaining the half-metallic materials by the combination of different neighboring TMs.
PMCID: PMC4523865  PMID: 26239021
8.  Effects of Gray-Scale Ultrasonography Immediate Post-Contrast on Characterization of Focal Liver Lesions 
BioMed Research International  2015;2015:193178.
This study compared the imaging features of conventional gray scale ultrasound (US) before and after contrast-enhanced ultrasound (CEUS) for focal liver lesions and 22 evaluated the role of US post-CEUS in characterizing liver lesions. 126 patients with 158 focal liver lesions underwent CEUS and US post-CEUS examination and entered this study. There were 74 hepatocellular carcinomas (HCC), 43 hepatic metastases, and 41 hemangiomas. Imaging features of US pre-CEUS and US post-CEUS were analyzed offsite by two blinded experienced radiologists to evaluate size, boundary, echogenicity, internal texture, posterior acoustic enhancement, spatial resolution, and contrast resolution. In the end with pathological and clinical evidence, the diagnostic accuracy rate of US pre-CEUS was 53.8% (85/158 lesions), lower than that of CEUS (88.0%, 139/158 lesions); with the complementation of US post-CEUS the rate rose to 93.0% (147/158 lesions). US post-CEUS could improve the visibility of typical structures of focal liver lesions and might provide important complementary information for CEUS diagnosis. It also increases the visibility of small liver lesions compared with US pre-CEUS and helps to guide local interventional procedure.
PMCID: PMC4450236  PMID: 26090387
9.  Hospital Variation in Non-Invasive Positive Pressure Ventilation for Acute Decompensated Heart Failure 
Circulation. Heart failure  2014;7(3):427-433.
Although non-invasive positive pressure ventilation (NIPPV) for patients with acute decompensated heart failure (ADHF) was introduced almost 20 years ago, the variation in its use among hospitals remains unknown. We sought to define hospital practice patterns of NIPPV use for ADHF and their relationship with intubation and mortality.
Methods and Results
We conducted a cross-sectional study using a database maintained by Premier, Inc., that includes a date-stamped log of all billed items for hospitalizations at over 400 hospitals. We examined hospitalizations for ADHF in this database from 2005–2010 and included hospitals with annual average volume of greater than 25 such hospitalizations. We identified 384 hospitals that encompassed 524,430 hospitalizations (median annual average volume: 206). We used hierarchical logistic regression models to calculate hospital-level outcomes: risk-standardized NIPPV rate (RS-NIPPV), risk-standardized intubation rate (RSIR), and in-hospital risk-standardized mortality rate (RSMR). We grouped hospitals into quartiles by RS-NIPPV and compared RSMRs and RSIRs across quartiles. Median RS-NIPPV was 6.2% (interquartile range, 2.8–9.3%; 5th percentile, 0.2%; 95th percentile, 14.8%). There was no clear pattern of RSMRs across quartiles. The bottom quartile of hospitals had higher RSIR (11.4%) than each of the other quartiles (9.0%, 9.7%, and 9.1%; P<0.02 for all comparisons).
Substantial variation exists among hospitals in the use of NIPPV for ADHF without evidence for differences in mortality. There may be a threshold effect in relation to intubation rates, with the lowest utilizers of NIPPV having higher intubation rates.
PMCID: PMC4386575  PMID: 24633829
heart failure; mortality; ventilation
10.  Identifying differential transcription factor binding in ChIP-seq 
Frontiers in Genetics  2015;6:169.
ChIP seq is a widely used assay to measure genome-wide protein binding. The decrease in costs associated with sequencing has led to a rise in the number of studies that investigate protein binding across treatment conditions or cell lines. In addition to the identification of binding sites, new studies evaluate the variation in protein binding between conditions. A number of approaches to study differential transcription factor binding have recently been developed. Several of these methods build upon established methods from RNA-seq to quantify differences in read counts. We compare how these new approaches perform on different data sets from the ENCODE project to illustrate the impact of data processing pipelines under different study designs. The performance of normalization methods for differential ChIP-seq depends strongly on the variation in total amount of protein bound between conditions, with total read count outperforming effective library size, or variants thereof, when a large variation in binding was studied. Use of input subtraction to correct for non-specific binding showed a relatively modest impact on the number of differential peaks found and the fold change accuracy to biological validation, however a larger impact might be expected for samples with more extreme copy number variations between them. Still, it did identify a small subset of novel differential regions while excluding some differential peaks in regions with high background signal. These results highlight proper scaling for between-sample data normalization as critical for differential transcription factor binding analysis and suggest bioinformaticians need to know about the variation in level of total protein binding between conditions to select the best analysis method. At the same time, validation using fold-change estimates from qRT-PCR suggests there is still room for further method improvement.
PMCID: PMC4413818  PMID: 25972895
ChIP-seq; differential binding; methods comparison; normalization; validation
11.  Antigenic Relatedness of Norovirus GII.4 Variants Determined by Human Challenge Sera 
PLoS ONE  2015;10(4):e0124945.
The GII.4 noroviruses (NoVs) are a single genotype that is responsible for over 50% of NoV gastroenteritis epidemics worldwide. However, GII.4 NoVs have been found to undergo antigenic drifts, likely selected by host herd immunity, which raises an issue for vaccine strategies against NoVs. We previously characterized GII.4 NoV antigenic variations and found significant levels of antigenic relatedness among different GII.4 variants. Further characterization of the genetic and antigenic relatedness of recent GII.4 variants (2008b and 2010 cluster) was performed in this study. The amino acid sequences of the receptor binding interfaces were highly conserved among all GII.4 variants from the past two decades. Using serum samples from patients enrolled in a GII.4 virus challenge study, significant cross-reactivity between major GII.4 variants from 1998 to 2012 was observed using enzyme-linked immunosorbent assays and HBGA receptor blocking assays. The overall abilities of GII.4 NoVs to bind to the A/B/H HBGAs were maintained while their binding affinities to individual ABH antigens varied. These results highlight the importance of human HBGAs in NoV evolution and how conserved antigenic types impact vaccine development against GII.4 variants.
PMCID: PMC4411064  PMID: 25915764
12.  Mitochondrial proteomics with siRNA knockdown to reveal ACAT1 and MDH2 in the development of doxorubicin-resistant uterine cancer 
Mitochondria are key organelles in mammary cells in responsible for a number of cellular functions including cell survival and energy metabolism. Moreover, mitochondria are one of the major targets under doxorubicin treatment. In this study, low-abundant mitochondrial proteins were enriched for proteomic analysis with the state-of-the-art two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assistant laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy to compare and identify the mitochondrial protein profiling changes in response to the development of doxorubicin resistance in human uterine cancer cells. The mitochondrial proteomic results demonstrate more than fifteen hundred protein features were resolved from the equal amount pooled of three purified mitochondrial proteins and 101 differentially expressed spots were identified. In which, 39 out of these 101 identified proteins belong to mitochondrial proteins. Mitochondrial proteins such as acetyl-CoA acetyltransferase (ACAT1) and malate dehydrogenase (MDH2) have not been reported with the roles on the formation of doxorubicin resistance in our knowledge. Further studies have used RNA interference and cell viability analysis to evidence the essential roles of ACAT1 and MDH2 on their potency in the formation of doxorubicin resistance through increased cell viability and decreased cell apoptosis during doxorubicin treatment. To sum up, our current mitochondrial proteomic approaches allowed us to identify numerous proteins, including ACAT1 and MDH2, involved in various drug-resistance-forming mechanisms. Our results provide potential diagnostic markers and therapeutic candidates for the treatment of doxorubicin-resistant uterine cancer.
PMCID: PMC4395189  PMID: 25639359
mitochondrial; DIGE; doxorubicin; resistance; uterine cancer
13.  Synthesis and characterization of ZnS with controlled amount of S vacancies for photocatalytic H2 production under visible light 
Scientific Reports  2015;5:8544.
Controlling amount of intrinsic S vacancies was achieved in ZnS spheres which were synthesized by a hydrothermal method using Zn and S powders in concentrated NaOH solution with NaBH4 added as reducing agent. These S vacancies efficiently extend absorption spectra of ZnS to visible region. Their photocatalytic activities for H2 production under visible light were evaluated by gas chromatograph, and the midgap states of ZnS introduced by S vacancies were examined by density functional calculations. Our study reveals that the concentration of S vacancies in the ZnS samples can be controlled by varying the amount of the reducing agent NaBH4 in the synthesis, and the prepared ZnS samples exhibit photocatalytic activity for H2 production under visible-light irradiation without loading noble metal. This photocatalytic activity of ZnS increases steadily with increasing the concentration of S vacancies until the latter reaches an optimum value. Our density functional calculations show that S vacancies generate midgap defect states in ZnS, which lead to visible-light absorption and responded.
PMCID: PMC4339798  PMID: 25712901
14.  Global analysis of the rat and human platelet proteome – the molecular blueprint for illustrating multi-functional platelets and cross-species function evolution 
Proteomics  2010;10(13):2444-2457.
Emerging evidences indicate that blood platelets function in multiple biological processes including immune response, bone metastasis and liver regeneration in addition to their known roles in hemostasis and thrombosis. Global elucidation of platelet proteome will provide the molecular base of these platelet functions. Here, we set up a high throughput platform for maximum exploration of the rat/human platelet proteome using integrated proteomics technologies, and then applied to identify the largest number of the proteins expressed in both rat and human platelets. After stringent statistical filtration, a total of 837 unique proteins matched with at least two unique peptides were precisely identified, making it the first comprehensive protein database so far for rat platelets. Meanwhile, quantitative analyses of the thrombin-stimulated platelets offered great insights into the biological functions of platelet proteins and therefore confirmed our global profiling data. A comparative proteomic analysis between rat and human platelets was also conducted, which revealed not only a significant similarity, but also an across-species evolutionary link that the orthologous proteins representing ‘core proteome’, and the ‘evolutionary proteome’ is actually a relatively static proteome.
PMCID: PMC4302335  PMID: 20443191
Blood platelets; multidimensional separation; mass spectrometry; global profiling; cross-species comparison
15.  Identification of inflammatory mediators in patients with rhegmatogenous retinal detachment associated with choroidal detachment 
Molecular Vision  2015;21:417-427.
To investigate the expression profile of intravitreous cytokines, chemokines, and growth factors in patients with rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) in comparison with patients with only rhegmatogenous retinal detachment (RRD).
Twenty RRDCD patients and 30 RRD patients were included in this case-control study. A multiplex bead-based immunoassay was performed to determine the expression of a wide range of 29 inflammatory mediators in undiluted vitreous from the patients. Data were analyzed using the Mann–Whitney U-test for nonparametric values and multivariate logistic regression analysis.
Compared with the patients with RRD, intravitreous inflammatory mediators, including migration inhibitor factor (MIF), interleukin-6 (IL-6), CCL4, CCL11, CCL17, CCL19, CCL22, CXCL9, CXCL8, soluble inter-cellular adhesion molecule 1 (sICAM-1), transforming growth factor β3 (TGF-β3), and platelet-derived growth factor AA (PDGF-AA), were upregulated in patients with RRDCD. After calibrating the factors duration of detachment, preoperative proliferative vitreoretinopathy grade, and presence or absence of macular hole, the PDGF-AA concentrations were not significantly different according to the multivariate logistic regression analysis. MIF and sICAM-1 markers were significantly different between the two groups and represented a forward stepwise logistic regression trend.
This is the first report to use multiplex bead analysis to investigate inflammatory mediators related to RRDCD. We proposed that the upregulated expression of these mediators may be involved in the inflammation process of RRDCD and that regulation of their expression may be potentially therapeutic by altering local inflammation.
PMCID: PMC4443581  PMID: 26015767
16.  Evaluation of hormone receptor, human epidermal growth factor receptor-2 and Ki-67 with core needle biopsy and neoadjuvant chemotherapy effects in breast cancer patients 
Thoracic Cancer  2015;6(1):64-69.
We investigated the reliability of core needle biopsy (CNB) in evaluating the status of hormone receptor (HR), human epidermal growth factor receptor (HER)-2, and Ki-67 status, and the effect of neoadjuvant chemotherapy (NAC) on the expression of these immunohistochemical markers.
Among 177 patients with breast adenocarcinoma, 95 patients underwent NAC and the remaining 82 patients made up the control group. Immunohistochemistry (IHC) was used to evaluate the expression status of estrogen receptor (ER), progesterone receptor (PR), HER-2, and Ki-67 in the specimens obtained by surgical excision or CNB.
In the control group, the expression of ER, PR, HER-2, and Ki-67 was highly consistent between samples from surgical excision or CNB (all r > 0.8, P < 0.05). In the NAC group, the proportions of samples with changes in ER, PR, HER-2, and Ki-67 expression were 12.7%, 24.1%, 5.1%, and 38.0%, respectively; the figures in the control group were 2.4%, 4.9%, 2.4%, and 7.3%, respectively, which significantly differed in ER, PR, and Ki-67 (P < 0.05), but not HER-2 (P > 0.05). In the NAC group, pre- and post-treatment ER+ rates did not significantly differ (P > 0.05), although PR+ and high Ki-67 expression rates did significantly differ (P < 0.05).
Neither CNB nor surgical excision samples gave highly consistent results in HR, HER-2, and Ki-67 status. NAC can alter HR and Ki-67 status in breast adenocarcinoma patients. NAC decreased PR+ rate and Ki-67 expression. The mean ER+ rate exhibited a decreasing, but insignificant trend after NAC treatment. NAC had no significant effect on HER-2 expression.
PMCID: PMC4448469  PMID: 26273337
Biological markers; breast adenocarcinoma; core needle biopsy; neoadjuvant chemotherapy
17.  Strain-induced quantum spin Hall effect in methyl-substituted germanane GeCH3 
Scientific Reports  2014;4:7297.
Quantum spin Hall (QSH) insulators exhibit a bulk insulting gap and metallic edge states characterized by nontrivial topology. We investigated the electronic structure of an isolated layer of methyl substituted germanane GeCH3 by density functional calculations (DFT), and its dynamic stability by phonon dispersion calculations. Our results show that an isolated GeCH3 layer has no dynamic instability, and is a QSH insulator under reasonable strain. This QSH insulator has a large enough band gap (up to 108 meV) at 12% strain. The advantageous features of this QSH insulator for practical room-temperature applications are discussed.
PMCID: PMC4252893  PMID: 25465887
18.  Distinct, genome-wide, gene-specific selectivity patterns of four glucocorticoid receptor coregulators 
Glucocorticoids are a class of steroid hormones that bind to and activate the glucocorticoid receptor (GR), which then positively or negatively regulates transcription of many genes that govern multiple important physiological pathways such as inflammation and metabolism of glucose, fat and bone. The remodeling of chromatin and regulated assembly or disassembly of active transcription complexes by GR and other DNA-binding transcription factors is mediated and modulated by several hundred transcriptional coregulator proteins. Previous studies focusing on single coregulators demonstrated that each coregulator is required for regulation of only a subset of all the genes regulated by a steroid hormone. We hypothesized that the gene-specific patterns of coregulators may correspond to specific physiological pathways such that different coregulators modulate the pathway-specificity of hormone action, thereby providing a mechanism for fine tuning of the hormone response. We tested this by direct comparison of multiple coregulators, using siRNA to deplete the products of four steroid hormone receptor coregulator genes (CCAR1, CCAR2, CALCOCO1 and ZNF282). Global analysis of glucocorticoid-regulated gene expression after siRNA mediated depletion of coregulators confirmed that each coregulator acted in a selective and gene-specific manner and demonstrated both positive and negative effects on glucocorticoid-regulated expression of different genes. We identified several classes of hormone-regulated genes based on the effects of coregulator depletion. Each coregulator supported hormonal regulation of some genes and opposed hormonal regulation of other genes (coregulator-modulated genes), blocked hormonal regulation of a second class of genes (coregulator-blocked genes), and had no effect on hormonal regulation of a third gene class (coregulator-independent genes). In spite of previously demonstrated physical and functional interactions among these four coregulators, the majority of the several hundred modulated and blocked genes for each of the four coregulators tested were unique to that coregulator. Finally, pathway analysis on coregulator-modulated genes supported the hypothesis that individual coregulators may regulate only a subset of the many physiological pathways controlled by glucocorticoids. We conclude that gene-specific actions of coregulators correspond to specific physiological pathways, suggesting that coregulators provide a potential mechanism for physiological fine tuning in vivo and may thus represent attractive targets for therapeutic intervention.
PMCID: PMC4242289  PMID: 25422592
coregulators; gene expression; microarray; glucocorticoid receptor; gene regulation
19.  Sentinel lymph node biopsy does not apply to all axillary lymph node-positive breast cancer patients after neoadjuvant chemotherapy 
Thoracic Cancer  2014;5(6):550-555.
The aim of this study was to investigate the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuant chemotherapy (NAC) in breast cancer patients with confirmed axillary nodal metastases.
We enrolled 51 patients with breast cancer who received NAC. All patients were proven to have axillary nodal metastases by histopathology biopsy prior to NAC. They all underwent SLNB before breast surgery, and complete axillary lymph node dissection immediately followed.
The identification rate for SLNB was 87.5% (84/96); the false negative rate was 24.5% (12/49). The clinicopathological factors were not significantly correlated with the identification and false negative rate of the SLNB. Lymphatic mapping, blue dye or radionuclide methods tended to decrease the identification rate of SLNB (P = 0.073). Clinical nodal status before NAC has a trend to increase the false-negative rates of the SLNB (P = 0.059). For patients with N1 clinical axillary lymph nodal status, the identification rate was 93.9%, and the false negative rate was 5.9%, compared with N2-3 patients with 73.9% and 38.9%, respectively.
SLNB is feasible for the patients whose axillary lymph nodal status before NAC is N1. However, for N2-3 patients, SLNB cannot be used as an infallible indicator of non-SLN status.
PMCID: PMC4704328  PMID: 26767051
Axillary lymph node status; biopsy; breast cancer; neoadjuant chemotherapy; sentinel lymph node
20.  Identification of Chemokines and Growth Factors in Proliferative Diabetic Retinopathy Vitreous 
BioMed Research International  2014;2014:486386.
Associations were investigated between levels of chemokines and growth factors in the vitreous and proliferative diabetic retinopathy (PDR). Enrolled were 58 patients (58 eyes) requiring pars plana vitrectomy (PPV), with PDR (n = 32, none with traction retinal detachment) or not (non-PDR). In the latter, 16 had macular hole (MH) and 10 had epiretinal membrane (ERM). With a multiplex bead immunoassay, levels of 11 chemokines and growth factors were measured from the undiluted vitreous sample from each patient. In the non-PDR eyes, the levels of the 11 chemokines and growth factors tested were similar between patients with MH and those with ERM. However, the levels of all 11 were significantly higher in the PDR eyes relative to the non-PDR; CCL17, CCL19, and TGFβ3 were markedly upregulated and have not been investigated in PDR previously. The significantly higher levels of CCL4 and CCL11 in PDR contradict the results of previous reports. Based on Spearman's nonparametric test, moderate-to-strong correlations were found between VEGF and other mediators. Our results indicate that these chemokines and growth factors could be candidates for research into targeted therapies applied either singly or in combination with anti-VEGF drugs for the treatment of PDR.
PMCID: PMC4226181  PMID: 25401103
21.  Non-Genetic Direct Reprogramming and Biomimetic Platforms in a Preliminary Study for Adipose-Derived Stem Cells into Corneal Endothelia-Like Cells 
PLoS ONE  2014;9(10):e109856.
Cell fate and function can be regulated and reprogrammed by intrinsic genetic program, extrinsic factors and niche microenvironment. Direct reprogramming has shown many advantages in the field of cellular reprogramming. Here we tried the possibility to generate corneal endothelia (CE) -like cells from human adipose-derived stem cells (ADSCs) by the non-genetic direct reprogramming of recombinant cell-penetrating proteins Oct4/Klf4/Sox2 (PTD-OKS) and small molecules (purmorphamine, RG108 and other reprogramming chemical reagents), as well as biomimetic platforms of simulate microgravity (SMG) bioreactor. Co-cultured with corneal cells and decellularized corneal ECM, Reprogrammed ADSCs revealed spherical growth and positively expressing Nanog for RT-PCR analysis and CD34 for immunofluorescence staining after 7 days-treatment of both purmorphamine and PTD-OKS (P-OKS) and in SMG culture. ADSCs changed to CEC polygonal morphology from spindle shape after the sequential non-genetic direct reprogramming and biomimetic platforms. At the same time, induced cells converted to weakly express CD31, AQP-1 and ZO-1. These findings demonstrated that the treatments were able to promote the stem-cell reprogramming for human ADSCs. Our study also indicates for the first time that SMG rotary cell culture system can be used as a non-genetic means to promote direct reprogramming. Our methods of reprogramming provide an alternative strategy for engineering patient-specific multipotent cells for cellular plasticity research and future autologous CEC replacement therapy that avoids complications associated with the use of human pluripotent stem cells.
PMCID: PMC4198143  PMID: 25333522
22.  Behavioral and metabolic characterization of heterozygous and homozygous POLG mutator mice 
Mitochondrion  2013;13(4):282-291.
The mitochondrial DNA (mtDNA) polymerase γ (POLG) mutator mice provide the first experimental evidence that high levels of somatic mtDNA mutations can be functionally significant. Here we report that older homozygous, but not heterozygous, POLG mice show significant reductions in striatal dopaminergic terminals as well as deficits in motor function. However, resting oxygen consumption, heat production, mtDNA content and mitochondrial electron transport chain activities are significantly decreased at older ages in both homozygous and heterozygous mice. These results indicate that high levels of somatic mtDNA mutations can contribute to dopaminergic dysfunction and to behavioral and metabolic deficits.
PMCID: PMC3682692  PMID: 23542163
mtDNA polymerase γ; mtDNA mutation; Parkinson’s disease; dopamine; behavioral deficits; metabolic deficits
23.  A Dual Chicken IgY Against Rotavirus and Norovirus 
Antiviral research  2012;97(3):293-300.
Rotavirus (RV) and norovirus (NoV) are the two most important causes of viral gastroenteritis. While vaccine remains an effective prophylactic strategy, development of other approaches, such as passive immunization to control and treat clinical infection and illness of the two pathogens, is necessary. Previously we demonstrated that high titers of NoV-specific IgY were readily developed by immunization of chickens with the NoV P particles. In this study, we developed a dual IgY against both RV and NoV through immunization of chickens with a divalent vaccine comprising neutralizing antigens of both RV and NoV. This divalent vaccine, named P-VP8* particle, is made of the NoV P particle as a carrier with the RV spike protein VP8* as a surface insertion. Approximately 45 mg of IgY were readily obtained from each yolk with high titers of anti-P particle and anti-VP8* antibodies detected by ELISA, Western blot, HBGA blocking (NoV and RV) and neutralization (RV) assays. Reductions of RV replication were observed with viruses treated with the IgY before and after inoculation into cells, suggesting an application of the IgY as both prophylactic and a therapeutic treatment. Collectively, our data suggested that the P-VP8* based IgY could serve as a practical approach against both NoV and RV.
PMCID: PMC3995418  PMID: 23267830
rotavirus; norovirus; diarrhea; immunoglobulin Y (IgY); passive immunization
24.  Noble-metal-free plasmonic photocatalyst: hydrogen doped semiconductors 
Scientific Reports  2014;4:3986.
The unique capacity of localized surface plasmon resonance (LSPR) offers a new opportunity to overcome the limited efficiency of semiconductor photocatalyst. Here we unravel that LSPR, which usually occurs in noble metal nanoparticles, can be realized by hydrogen doping in noble-metal-free semiconductor using TiO2 as a model photocatalyst. Moreover, its LSPR is located in infrared region, which supplements that of noble metal whose LSPR is generally in the visible region, making it possible to extend the light response of photocatalyst to infrared region. The near field enhancement is shown to be comparable with that of noble-metal nanoparticles, indicating that highly enhanced light absorption rate can be expected. The present work can provide a key guideline for the creation of highly efficient noble-metal-free plasmonic photocatalysts and have a much wider impact in infrared bioimaging and spectroscopy where infrared LSPR is essential.
PMCID: PMC3913932  PMID: 24496400
25.  Evaluation of anti-norovirus IgY from egg yolk of chickens immunized with norovirus P particles 
Journal of virological methods  2012;186(1-2):126-131.
Noroviruses (NoVs) are a leading cause of epidemic acute gastroenteritis affecting millions of people worldwide. Understanding of NoV remains limited due to the lack of a cell culture system and small animal models. Currently, there are no available vaccines or antivirals against NoVs. In this study, an approach for large-scale production of anti-NoV antibodies for use as a potential treatment for NoV disease using passive immunization was evaluated. NoV-specific immunoglobulins (IgY) were produced by immunizing chickens with NoV P particles. The birds continuously produced high titers of antibodies in their eggs for at least 3 months, in which NoV-specific antibody levels reached 4.7-9.2 mg/egg yolk. The egg yolk antibodies strongly reacted with NoV P particles by both ELISA and Western blot and blocked NoV virus-like particle (VLP) and P particle binding to the histo-blood group antigen (HBGA) receptors with a BT50 of about 1:800. The blocking activity of the chicken IgY remained after an incubation at 70°C for 30 min or treatment at pH 4 to 9 for 3 h. These data suggested that chicken IgY could be a practical strategy for large-scale production of anti-NoV antibodies for potential use as passive immunization against NoV infection, as well as for diagnostic purposes.
PMCID: PMC3496071  PMID: 22867844
Norovirus; Immunoglobulin; IgY; Chicken; Norovirus P particle; Diarrhea

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