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1.  A modified bicanalicular intubation procedure to repair canalicular lacerations using silicone tubes 
Liang, X | Lin, Y | Wang, Z | Lin, L | Zeng, S | Liu, Z | Li, N | Wang, Z | Liu, Y
Eye  2012;26(12):1542-1547.
To explore a modified technique for silicone intubation for the repair of canalicular lacerations.
The surgery was performed on 35 eyes in 35 adult patients from October 2007 to September 2009. Using a modified soft probe, silicone tubes were inserted through the lacrimal punctum and left in the bicanaliculi for 3–10 months.
The surgery was performed successfully in all cases. The tubes were removed after 3–10 months (mean 5.3±1.8 months). The mean follow-up time after tube removal was 13.8 months (range, 6–22 months). Lower punctum splitting occurred in one case (2.86%) after the surgery. No other complications associated with the silicone tubes occurred. All the tubes were removed successfully without any difficulty. No iatrogenic injuries occurred during tube removal.
The modified bicanalicular intubation procedure described here is an effective and atraumatic procedure for the management of canalicular lacerations in adults, and it is associated with fewer complications than the traditional sutures of canalicular lacerations.
PMCID: PMC3522846  PMID: 23060024
modified; canalicular laceration; tube intubation
2.  10−7 m 17β-oestradiol enhances odonto/osteogenic potency of human dental pulp stem cells by activation of the NF-κB pathway 
Wang, Y | Zheng, Y | Wang, Z | Li, J | Wang, Z | Zhang, G | Yu, J
Cell Proliferation  2013;46(6):677-684.
Oestrogen has been proven to significantly enhance osteogenic potency, while oestrogen deficiency usually leads to impaired osteogenic differentiation of mesenchymal stem cells. However, little is known concerning direct effects of oestrogen on differentiation of human dental pulp stem cells (DPSCs).
Materials and methods
In this study, human DPSCs were isolated and treated with 10−7 m 17β-oestradiol (E2). Alkaline phosphatase (ALP) assay and alizarin red staining were performed.
Alkaline phosphatase and alizarin red showed that E2 treatment significantly enhanced ALP activity and mineralization ability of DPSCs, but had no effect on cell proliferation. Real-time RT-PCR and western blot assay demonstrated that odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN and DSPP/DSP) were significantly upregulated in the cells after E2 treatment. Moreover, phosphorylation of cytoplasmic IκBα/P65 and expression of nuclear P65 were enhanced in a time-dependent manner following E2 treatment, suggesting activation of NF-κB signaling. Conversely, inhibition of the NF-κB pathway suppressed E2-mediated upregulation of odonto/osteogenic markers, indicating that the NF-κB pathway was pivotal for E2-mediated differentiation.
These findings provide evidence that 10−7 m 17β-oestradiol promoted odonto/osteogenic differentiation of human DPSCs via activation of the NF-κB signaling pathway.
PMCID: PMC4065368  PMID: 24152244
3.  Jumonji domain-containing protein 2B silencing induces DNA damage response via STAT3 pathway in colorectal cancer 
Chen, L | Fu, L | Kong, X | Xu, J | Wang, Z | Ma, X | Akiyama, Y | Chen, Y | Fang, J
British Journal of Cancer  2014;110(4):1014-1026.
Jumonji domain-containing protein 2B (JMJD2B), directly targeted by hypoxia-inducible factor 1α, maintains the histone methylation balance important for the transcriptional activation of many oncogenes. Jumonji domain-containing protein 2B has been implicated in colorectal cancer (CRC) progression; however, the mechanism remains unclear.
Immunofluorescence and western blotting detected phosphorylated histone H2AX, characteristic of double-strand breaks, and comet assay was used to investigate DNA damage, in CRC cells after JMJD2B small interfering RNA (siRNA) transfection. We assessed the resulting in vitro responses, that is, cell cycle progression, apoptosis, and senescence coupled with JMJD2B silencing-induced DNA damage, studying the regulatory role of signal transducers and activators of transcription 3 (STAT3). The JMJD2B silencing anti-cancer effect was determined using an in vivo CRC xenograft model.
Jumonji domain-containing protein 2B knockdown induced DNA damage via ataxia telangiectasia-mutated (ATM) and ATM and Rad3-related pathway activation, resulting in cell cycle arrest, apoptosis, and senescence in both normoxia and hypoxia. Signal transducers and activators of transcription 3 suppression by JMJD2B silencing enhanced DNA damage. Intratumoural injection of JMJD2B siRNA suppressed tumour growth in vivo and activated the DNA damage response (DDR).
Jumonji domain-containing protein 2B has an essential role in cancer cell survival and tumour growth via DDR mediation, which STAT3 partially regulates, suggesting that JMJD2B is a potential anti-cancer target.
PMCID: PMC3929886  PMID: 24473398
JMJD2B; DNA damage response; hypoxia; STAT3; colorectal cancer
4.  Local structure order in Pd78Cu6Si16 liquid 
Scientific Reports  2015;5:8277.
The short-range order (SRO) in Pd78Cu6Si16 liquid was studied by high energy x-ray diffraction and ab initio molecular dynamics (MD) simulations. The calculated pair correlation functions at different temperatures agree well with the experimental results. The partial pair correlation functions from ab intio MD simulations indicate that Si atoms prefer to be uniformly distributed while Cu atoms tend to aggregate. By performing structure analysis using Honeycutt-Andersen index, Voronoi tessellation, and atomic cluster alignment method, we show that the icosahedron and face-centered cubic SRO increase upon cooling. The dominant SRO is the Pd-centered Pd9Si2 motif, namely the structure of which motif is similar to the structure of Pd-centered clusters in the Pd9Si2 crystal. The study further confirms the existence of trigonal prism capped with three half-octahedra that is reported as a structural unit in Pd-based amorphous alloys. The majority of Cu-centered clusters are icosahedra, suggesting that the presence of Cu is benefit to promote the glass forming ability.
PMCID: PMC4317692  PMID: 25652079
5.  Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-κB and MAPK/HO-1 signalling 
British Journal of Cancer  2013;110(2):341-352.
Gambogic acid (GA) has been reported to have potent anticancer activity and is authorised to be tested in phase II clinical trials for treatment of non-small-cell lung cancer (NSCLC). The present study aims to investigate whether GA would be synergistic with cisplatin (CDDP) against the NSCLC.
1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), combination index (CI) isobologram, western blot, quantitative PCR, flow cytometry, electrophoretic mobility shift assay, xenograft tumour models and terminal deoxynucleotide transferase-mediated dUTP nick-end labelling analysis were used in this study.
The cell viability results showed that sequential CDDP-GA treatment resulted in a strong synergistic action in A549, NCI-H460, and NCI-H1299 cell lines, whereas the reverse sequence and simultaneous treatments led to a slight synergistic or additive action. Increased sub-G1 phase cells and enhanced PARP cleavage demonstrated that the sequence of CDDP-GA treatment markedly increased apoptosis in comparison with other treatments. Furthermore, the sequential combination could enhance the activation of caspase-3, -8, and 9, increase the expression of Fas and Bax, and decrease the expression of Bcl-2, survivin and X-inhibitor of apoptosis protein (X-IAP) in A549 and NCI-H460 cell lines. In addition, increased apoptosis was correlated with enhanced reactive oxygen species generation. Importantly, it was found that, followed by CDDP treatment, GA could inhibit NF-κB and mitogen-activated protein kinase (MAPK)/heme oxygenase-1 (HO-1) signalling pathways, which have been validated to reduce ROS release and confer CDDP resistance. The roles of NF-κB and MAPK pathways were further confirmed by using specific inhibitors, which significantly increased ROS release and apoptosis induced by the sequential combination of CDDP and GA. Moreover, our results indicated that the combination of CDDP and GA exerted increased antitumour effects on A549 xenograft models through inhibiting NF-κB, HO-1, and subsequently inducing apoptosis.
Gambogic acid sensitises lung cancer cells to CDDP in vitro and in vivo in NSCLC through inactivation of NF-κB and MAPK/HO-1 signalling pathways, providing a rationale for the combined use of CDDP and GA in lung cancer chemotherapy.
PMCID: PMC3899775  PMID: 24300974
gambogic acid; cisplatin; lung cancer; NF-κB; apoptosis; heme oxygenase-1
6.  HIV Tat protein affects circadian rhythmicity by interfering with the circadian system 
Wang, T | Jiang, Z | Hou, W | Li, Z | Cheng, S | Green, LA | Wang, Y | Wen, X | Cai, L | Clauss, M | Wang, Z
HIV Medicine  2014;15(9):565-570.
Sleep disorders are common in patients with HIV/AIDS, and can lead to poor quality of life. Although many studies have investigated the aetiology of these disorders, it is still unclear whether impaired sleep quality is associated with HIV itself, social problems, or side effects of antiretroviral therapy (ART). Moreover, despite its known neurological associations, little is known about the role of the trans-activator of transcription (Tat) protein in sleep disorders in patients with HIV/AIDS. The purpose of this study was to test the hypothesis that the sleep quality of patients with HIV/AIDS affected by an altered circadian rhythm correlates with cerebrospinal HIV Tat protein concentration.
Ninety-six patients with HIV/AIDS between 20 and 69 years old completed the Pittsburgh Sleep Quality Index. Their circadian rhythm parameters of blood pressure, Tat concentration in cerebrospinal fluid, melatonin concentration, CD4 cell count and HIV RNA viral load in serum were measured.
The circadian amplitude of systolic blood pressure and the score for sleep quality (Pittsburgh Sleep Quality Index) were negatively correlated with HIV Tat protein concentration, while the melatonin value was positively correlated with Tat protein concentration.
The HIV Tat protein affects circadian rhythmicity by interfering with the circadian system in patients with HIV/AIDS and further increases the melatonin excretion value. A Tat protein-related high melatonin value may counteract HIV-related poor sleep quality during the progression of HIV infection. This study provides the first clinical evidence offering an explanation for why sleep quality did not show an association with progression of HIV infection in previous studies.
PMCID: PMC4285855  PMID: 24750691
circadian rhythm; HIV/AIDS; sleep; Tat protein
7.  Integrated analysis of the Wnt responsive proteome in human cells reveals diverse and cell-type specific networks 
Molecular bioSystems  2014;10(1):45-53.
Wnt signalling is a fundamentally important signalling pathway that regulates many aspects of metazoan development and is frequently dysregulated in cancer. Although many of the core components of the Wnt signalling pathway, such as β-catenin, have been extensively studied, the broad systems level responses of the mammalian cell to Wnt signalling are less well understood. In addition, the cell- or tissue-specific protein networks that modulate Wnt signalling in the diverse tissues or developmental stages in which it functions remain to be defined. To address these questions, we undertook a broad survey of the Wnt response in different human cell lines using both interaction and expression proteomics approaches. Our data reveal both similar and divergent responses of pathways and processes in the three cell-lines analyzed as well as a marked attenuation of the response to exogenous Wnt treatment in cells harbouring a stabilizing (activating) mutation of β-catenin. We also identify cell-type specific components of the Wnt signalling network and find that by integrating expression and interaction proteomics data a more complete description of the Wnt interaction network can be achieved. Finally, our results attest to the power of LCMS/MS to reveal novel cellular responses in even relatively well studied biological pathways such as Wnt signalling.
PMCID: PMC3909504  PMID: 24201312
8.  Autophagy collaborates with ubiquitination to downregulate oncoprotein E2A/Pbx1 in B-cell acute lymphoblastic leukemia 
Yuan, N | Song, L | Lin, W | Cao, Y | Xu, F | Liu, S | Zhang, A | Wang, Z | Li, X | Fang, Y | Zhang, H | Zhao, W | Hu, S | Wang, J | Zhang, S
Blood Cancer Journal  2015;5(1):e274-.
B-cell acute lymphoblastic leukemia (B-ALL) accounts for the most cancer incidences in children. We present here that autophagy is downregulated in pediatric B-ALL, suggesting a possible link between autophagy failure and pediatric B-ALL leukemogenesis. With a pediatric t(1;19) B-ALL xenograft mouse model, we show here that activation of autophagy by preventive administration of rapamycin improved the survival of leukemia animals by partial restoration of hematopoietic stem/progenitor cells, whereas treatment of the animals with rapamycin caused leukemia bone marrow cell-cycle arrest. Activation of autophagy in vitro or in vivo by rapamycin or starvation downregulated oncogenic fusion protein E2A/Pbx1. Furthermore, E2A/Pbx1 was found to be colocalized with autophagy marker LC3 in autolysosomes and with ubiquitin in response to autophagy stimuli, whereas autophagy or ubiquitination inhibitor blocked these colocalizations. Together, our data suggest a collaborative action between autophagy and ubiquitination in the degradation of E2A/Pbx1, thereby revealing a novel strategy for targeted preventive or treatment therapy on the pediatric ALL.
PMCID: PMC4314458  PMID: 25615280
9.  CeO2 nanocubes-graphene oxide as durable and highly active catalyst support for proton exchange membrane fuel cell 
Scientific Reports  2014;4:7415.
Rapid degradation of cell performance still remains a significant challenge for proton exchange membrane fuel cell (PEMFC). In this work, we develop novel CeO2 nanocubes-graphene oxide nanocomposites as durable and highly active catalyst support for proton exchange membrane fuel cell. We show that the use of CeO2 as the radical scavenger in the catalysts remarkably improves the durability of the catalyst. The catalytic activity retention of Pt-graphene oxide-8 wt.% CeO2 nanocomposites reaches as high as 69% after 5000 CV-cycles at a high voltage range of 0.8–1.23 V, in contrast to 19% for that of the Pt-graphene oxide composites. The excellent durability of the Pt-CeO2 nanocubes-graphene oxide catalyst is attributed to the free radical scavenging activity of CeO2, which significantly slows down the chemical degradation of Nafion binder in catalytic layers, and then alleviates the decay of Pt catalysts, resulting in the excellent cycle life of Pt-CeO2-graphene oxide nanocomposite catalysts. Additionally, the performance of single cell assembled with Nafion 211 membrane and Pt-CeO2-graphene oxide catalysts with different CeO2 contents in the cathode as well as the Pt-C catalysts in the anode are also recorded and discussed in this study.
PMCID: PMC4261163  PMID: 25491655
10.  Adherence to oral bisphosphonates and the risk of subtrochanteric and femoral shaft fractures among female medicare beneficiaries 
Previous studies have shown an association between duration of bisphosphonate use and atypical femur fractures. This cohort study showed an increasingly higher risk of subtrochanteric and femoral shaft fractures among those who were more adherent to oral bisphosphonates.
Long-term use of oral bisphosphonates has been implicated in an increased risk of atypical femur fractures located in subtrochanteric and femoral shaft regions. Another measure of drug exposure, medication adherence, however, has not been investigated.
Among all Medicare fee-for-service female beneficiaries from 2006–2010, we followed 522,287 new bisphosphonate users from their index prescription until being censored or having a primary diagnosis of closed subtrochanteric/ femoral shaft or intertrochanteric/femoral neck fractures. Data about radiographs of fracture site and features were not available. Adherence was classified according to the medication possession ratio (MPR) as the following: MPR<1/3 as less compliant, MPR≥1/3–<2/3 as compliant, and MPR≥2/3 as highly compliant. Alternative cutoff points at 50 and 80 % were also used. Survival analysis was used to determine the cumulative incidence and hazard of subtrochanteric/femoral shaft or intertrochanteric/femoral neck fractures.
There was a graded increase in incidence of subtrochanteric/femoral shaft fractures as the level of adherence increased (Gray’s test, P<0.001). The adjusted hazard ratio (HR) for the highly compliant vs. the less compliant was 1.23 (95 % Confidence Interval [CI] 1.06–1.43) overall, became significant after 2 years of follow-up (HR=1.51, 95 % CI 1.06–2.15) and reached the highest risk in the fifth year (HR=4.06, 95 % CI 1.47–11.19). However, age-adjusted incidence rates of intertrochanteric/femoral neck fractures were significantly lower among highly compliant beneficiaries, compared to less compliant users (HR=0.69, 95 % CI 0.66–0.73). Similar results were obtained when the cutoff points for being compliant and highly compliant were set at 50 and 80 %, respectively.
Subtrochanteric/femoral shaft fractures, unlike intertrochanteric/femoral neck fractures, are positively associated with higher adherence to long-term (≥3 years) oral bisphosphonates in the elderly female Medicare population.
PMCID: PMC4254800  PMID: 24846316
Bisphosphonates; Fracture; Osteoporosis; Atypical femur fracture
11.  Neuroimaging Characteristics of MRI-negative Orbitofrontal Epilepsy with Focus on Voxel-based Morphometric MRI Post-processing 
Epilepsia  2013;54(12):2195-2203.
The orbitofrontal (OF) region is one of the least explored regions of the cerebral cortex. There are few studies on patients with electrophysiologically and surgically confirmed OF epilepsy and a negative MRI. We aimed to examine the neuroimaging characteristics of MRI-negative OF epilepsy with the focus on a voxel-based morphometric MRI post-processing technique.
We included 6 patients with OF epilepsy, who met the following criteria: surgical resection of the OF lobe with/without adjacent cortex, seizure-free for ≥ 12 months, invasive video-EEG monitoring showing ictal onset from the OF area, and pre-operative MRI regarded negative. Patients were investigated in terms of their image postprocessing and functional neuroimaging characteristics, electroclinical characteristics obtained from noninvasive and invasive evaluations, and surgical pathology. MRI postprocessing on T1-weighted high-resolution scans was implemented with a Morphometric Analysis Program (MAP) in MATLAB SPM5.
Key findings
Single MAP+ abnormalities were found in 4 patients; three were in the OF region and one in the ipsilateral mesial frontal area. These abnormalities were included in the resection. One patient had bilateral MAP+ abnormalities in the OF region, with the ipsilateral one completely removed. The MAP+ foci were concordant with invasive electrophysiological data in the majority of MAP+ patients (4 of 5). The localization value of FDG-PET and ictal SPECT is low in this cohort. Surgical pathology included focal cortical dysplasia, remote infarct, rosenthal fiber formation and gliosis.
Our study highlights the importance of MRI post-processing in the process of presurgical evaluation of patients with suspected orbitofrontal epilepsy and “normal” MRI. Using MAP, we were able to positively identify subtle focal abnormalities in the majority of the patients. MAP results need to be interpreted in the context of their electroclinical findings and can provide valuable targets in the process of planning invasive evaluation.
PMCID: PMC3982614  PMID: 24116733
epilepsy; MRI; presurgical evaluation; MRI post-processing; MRI-negative epilepsy; voxel-based morphometry; orbitofrontal epilepsy; focal cortical dysplasia
12.  Mechanism of spin crossover in LaCoO3 resolved by shape magnetostriction in pulsed magnetic fields 
Scientific Reports  2014;4:7003.
In the scientific description of unconventional transport properties of oxides (spin-dependent transport, superconductivity etc.), the spin-state degree of freedom plays a fundamental role. Because of this, temperature- or magnetic field-induced spin-state transitions are in the focus of solid-state physics. Cobaltites, e.g. LaCoO3, are prominent examples showing these spin transitions. However, the microscopic nature of the spontaneous spin crossover in LaCoO3 is still controversial. Here we report magnetostriction measurements on LaCoO3 in magnetic fields up to 70 T to study the sharp, field-induced transition at Hc ≈ 60 T. Measurements of both longitudinal and transversal magnetostriction allow us to separate magnetovolume and magnetodistortive changes. We find a large increase in volume, but only a very small increase in tetragonal distortion at Hc. The results, supported by electronic energy calculations by the configuration interaction cluster method, provide compelling evidence that above Hc LaCoO3 adopts a correlated low spin/high spin state.
PMCID: PMC4227009  PMID: 25384532
13.  Two-step retrograde closed stenting: a novel method for treating canalicular lacerations in Chinese patients 
Eye  2013;27(11):1275-1280.
To evaluate the efficacy of two-step retrograde closed stenting for treating canalicular laceration.
Forty-eight consecutive canalicular laceration cases (48 eyes) were randomised and divided into two groups: a one-step group and a two-step group. In the two-step group (23 cases), the first step was performed in the outpatient department and included identifying the medial cut end of the canaliculus and probing under a slit-lamp microscope, followed by a retrograde canalicular stenting assisted by a memory titanium stylet. The second step was canalicular anastomosis, which was performed in the operating room. In the one-step group (25 cases), all of the surgical procedures were performed when preoperative preparations were simultaneously available.
The time elapsed from the doctor visit to the treatment was 4.3±2.4 h in the two-step group and 18.8±6.3 h in the one-step group (P<0.01). The canalicular medial cut ends were found in all cases, but 8.6±3.5 min was needed in the two-step group, and 51.4±24.2 min was needed in the one-step group (P<0.01). The numerical rating scale for pain during surgery was 1.8±1.2 in the two-step group and 5.4±2.2 in the one-step group (P<0.01). One case (2.63%) in the two-step group and nine cases (36%) in the one-step group required other assisted methods to locate the medial cut end (P=0.007). Twenty-one cases (91.3%) in the two-step group and 20 cases (80%) in the one-step group achieved patent lacrimal drainage systems during a 12-month follow-up (P=0.528).
The two-step canalicular anastomosis method allows an early search for the medial cut end of the canaliculus and improves the chances of finding it; it is also a quicker, less invasive method for treating canalicular lacerations.
PMCID: PMC3831126  PMID: 23970028
canalicular laceration; canalicular stenting; canalicular anastomosis; lacrimal surgery
14.  Mechanistic model of mass-specific basal metabolic rate: evaluation in healthy young adults 
Mass-specific basal metabolic rate (mass-specific BMR), defined as the resting energy expenditure per unit body mass per day, is an important parameter in energy metabolism research. However, a mechanistic explanation for magnitude of mass-specific BMR remains lacking. The objective of the present study was to validate the applicability of a proposed mass-specific BMR model in healthy adults. A mechanistic model was developed at the organ-tissue level, mass-specific BMR = Σ(Ki × Fi), where Fi is the fraction of body mass as individual organs and tissues, and Ki is the specific resting metabolic rate of major organs and tissues. The Fi values were measured by multiple MRI scans and the Ki values were suggested by Elia in 1992. A database of healthy non-elderly non-obese adults (age 20 – 49 yrs, BMI <30 kg/m2) included 49 men and 57 women. Measured and predicted mass-specific BMR of all subjects was 21.6 ± 1.9 (mean ± SD) and 21.7 ± 1.6 kcal/kg per day, respectively. The measured mass-specific BMR was correlated with the predicted mass-specific BMR (r = 0.82, P <0.001). A Bland-Altman plot showed no significant trend (r = 0.022, P = 0.50) between the measured and predicted mass-specific BMR, versus the average of measured and predicted mass-specific BMR. In conclusion, the proposed mechanistic model was validated in non-elderly non-obese adults and can help to understand the inherent relationship between mass-specific BMR and body composition.
PMCID: PMC4192648  PMID: 25309131
magnetic resonance imaging; organ; specific resting metabolic rate; tissue
15.  Household chaos moderates the link between maternal attribution bias and parenting 
Parenting, science and practice  2013;13(4):10.1080/15295192.2013.832569.
Parents who attribute child misbehavior to children's intentions and dismiss situational factors tend to show more hostility and less warmth in their parenting behavior, and are at greater risk for maltreatment. We extended this literature by investigating the role of household chaos as a moderator of the link between maternal attribution biases and parenting behaviors.
The current sample included 160 mothers of 3- to7-year-old children. Mothers provided reports on their attribution biases and household chaos levels. Maternal negativity and positivity were measured using self-reports and observers’ ratings.
The links between attribution bias and parenting behavior were stronger in more chaotic environments, with the moderating effect of chaos being particularly strong for internal attribution bias.
The findings point to the importance of social cognitive biases in the etiology of maternal behavior in family contexts that lack order and predictability.
PMCID: PMC3864824  PMID: 24358017
attribution bias; household chaos; parenting
16.  Ribosomal s6 protein kinase 4: a prognostic factor for renal cell carcinoma 
Fan, L | Li, P | Yin, Z | Fu, G | Liao, D J | Liu, Y | Zhu, J | Zhang, Y | Wang, L | Yan, Q | Guo, Y | Shao, C | Huang, G | Wang, Z
British Journal of Cancer  2013;109(5):1137-1146.
The expression and function of ribosomal s6 protein kinase 4 (RSK4) in renal cell carcinoma (RCC) are unknown.
Immunohistochemistry was used to detect the expression of RSK4 in RCC, and the relationship between RSK4 expression and clinicopathological features as well as prognosis of RCC patients was statistically analysed. Ectopic RSK4 expression in RCC cell lines was performed to determine its effect on cell cycle regulation, tumour invasiveness, and metastatic capability.
RSK4 was overexpressed in RCCs (P=0.003), compared with normal tissues, and the expression varied in different RCC subtypes (P=0.021), especially in two subtypes of papillary RCCs (P=0.001). RSK4 expression was positively correlated with high pT stage (P<0.001), high Fuhrman grade (P<0.001), lymph node involvement (P<0.001), and presence of distant metastasis (P=0.039), and could predict poor outcome in RCC patients. Molecular studies showed that overexpression of RSK4 could promote cell cycle progression and enhance the invasive and metastatic capability of RCC cell lines and vice versa.
The expression pattern and molecular mechanisms of RSK4 in RCCs indicate that it could be a potential independent prognostic factor and serve as a new potential therapeutic target for RCC patients.
PMCID: PMC3778307  PMID: 23942078
ribosomal s6 protein kinase 4; renal cell carcinoma; prognosis; invasion; metastasis
17.  Gingivae Contain Neural-crest- and Mesoderm-derived Mesenchymal Stem Cells 
Journal of Dental Research  2013;92(9):825-832.
Gingivae represent a unique soft tissue that serves as a biological barrier to cover the oral cavity side of the maxilla and mandible. Recently, the gingivae were identified as containing mesenchymal stem cells (GMSCs). However, it is unknown whether the GMSCs are derived from cranial neural crest cells (CNCC) or the mesoderm. In this study, we show that around 90% of GMSCs are derived from CNCC and 10% from the mesoderm. In comparison with mesoderm MSCs (M-GMSCs), CNCC-derived GMSCs (N-GMSCs) show an elevated capacity to differentiate into neural cells and chondrocytes and induce activated T-cell apoptosis in vitro. When transplanted into mice with dextran sulfate sodium (DSS)-induced colitis, N-GMSCs showed superior effects in ameliorating inflammatory-related disease phenotype in comparison with the M-GMSC treatment group. Mechanistically, the increased immunomodulatory effect of N-GMSCs is associated with up-regulated expression of FAS ligand (FASL), a transmembrane protein that plays an important role in MSC-based immunomodulation. In summary, our study indicates that the gingivae contain both neural-crest- and mesoderm-derived MSCs with distinctive stem cell properties.
PMCID: PMC3744273  PMID: 23867762
gingiva; mesenchymal stem cells; neural crest cells; differentiation; immunomodulation; apoptosis
18.  Role of leptin receptor gene polymorphisms in susceptibility to the development of essential hypertension: a case–control association study in a Northern Han Chinese population 
Journal of human hypertension  2014;28(9):551-556.
In order to explore the potential association between the leptin receptor (LEPR) gene polymorphisms and essential hypertension (EH) risk in the Northern Han Chinese population, we recruited 823 hypertensive subjects and 491 healthy control subjects from the Northern Han Chinese. Genotyping was performed to identify the Lys109Arg, Gln223Arg and Lys656Asn polymorphisms of the LEPR gene. Significant associations were found in a dominant genetic model ([GG+AG] vs AA), P=0.007, odds ratio (OR)=3.697, 95% confidence interval (CI) 1.442–9.482), and in homozygote comparison (GG vs AA, P=0.005, OR=3.890, 95% CI 1.501–10.077) for the Gln223Arg polymorphism. No significant association could be found between Lys109Arg or Lys656Asn polymorphism and EH risk. Linkage disequilibrium was detected between the Lys109Arg and Gln223Arg polymorphisms, and haplotype analyses identified that the G-A haplotype was a protective haplotype for EH. Our studies demonstrated that the LEPR Gln223Arg polymorphism had an important role in a patient's susceptibility to EH in the Northern Han Chinese population.
PMCID: PMC4133281  PMID: 24522342
leptin receptor; polymorphism; essential hypertension; Chinese; linkage disequilibrium; haplotypes
19.  High fidelity quantum state transfer in electromechanical systems with intermediate coupling 
Scientific Reports  2014;4:6237.
Hybrid quantum systems usually consist of two or more subsystems, which may take the advantages of the different systems. Recently, the hybrid system consisting of circuit electromechanical subsystems have attracted great attention due to its advanced fabrication and scalable integrated photonic circuit techniques. Here, we propose a scheme for high fidelity quantum state transfer between a superconducting qubit and a nitrogen-vacancy center in diamond, which are coupled to a superconducting transmission-line resonator with coupling strength g1 and a nanomechanical resonator with coupling strength g2, respectively. Meanwhile, the two resonators are parametrically coupled with coupling strength J. The system dynamics, including the decoherence effects, is numerical investigated. It is found that both the small () and large () coupling regimes of this hybrid system can not support high fidelity quantum state transfer before significant technique advances. However, in the intermediate coupling regime (J ~ g1 ~ g2), in contrast to a conventional wisdom, high fidelity quantum information transfer can be implemented, providing a promising route towards high fidelity quantum state transfer in similar coupled resonators systems.
PMCID: PMC4148701  PMID: 25168206
20.  Enantioselective Intramolecular C-H Amination Catalyzed by Engineered Cytochrome P450 Enzymes in vivo and in vitro 
PMCID: PMC3988694  PMID: 23893546
cytochromes; C-H activation; enzyme catalysis; protein engineering; synthetic biology
22.  ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells 
The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.
PMCID: PMC4143205  PMID: 25075574
Glycyrrhizic acid; Neuroprotection; Glutamate; ERKs; Mitochondria
23.  Energy deposition by heavy ions: Additivity of kinetic and potential energy contributions in hillock formation on CaF2 
Scientific Reports  2014;4:5742.
Modification of surface and bulk properties of solids by irradiation with ion beams is a widely used technique with many applications in material science. In this study, we show that nano-hillocks on CaF2 crystal surfaces can be formed by individual impact of medium energy (3 and 5 MeV) highly charged ions (Xe22+ to Xe30+) as well as swift (kinetic energies between 12 and 58 MeV) heavy xenon ions. For very slow highly charged ions the appearance of hillocks is known to be linked to a threshold in potential energy (Ep) while for swift heavy ions a minimum electronic energy loss per unit length (Se) is necessary. With our results we bridge the gap between these two extreme cases and demonstrate, that with increasing energy deposition via Se the Ep-threshold for hillock production can be lowered substantially. Surprisingly, both mechanisms of energy deposition in the target surface seem to contribute in an additive way, which can be visualized in a phase diagram. We show that the inelastic thermal spike model, originally developed to describe such material modifications for swift heavy ions, can be extended to the case where both kinetic and potential energies are deposited into the surface.
PMCID: PMC4102904  PMID: 25034006
24.  The effects of sleeve gastrectomy on hormonal regulation of glucose metabolism in Goto–Kakizaki rats 
European Surgery  2014;46(5):189-196.
The antidiabetic effect of sleeve gastrectomy (SG) has been interpreted as a conceivable result of surgically induced weight loss in the obese type 2 diabetes mellitus (T2DM) subjects. However, the blood glucose control often occurs within days, before significant weight loss has been reached. This work aims to investigate the major mechanism and persistence regarding how SG improves glucose metabolism in nonobese T2DM rats.
These Goto Kakizaki rats (n = 21) were randomly assigned into three groups: SG, sham SG, and pair-fed (PF) group, whose weight, food intake, oral glucose tolerance test, insulin tolerance test, plasma insulin, homeostasis model assessment for insulin resistance (HOMA-IR), ghrelin, and glucagon-like peptide-1 (GLP-1) were measured.
According to the experiment, from the 2nd week until the 24th week, the fasting blood glucose of the rats in the SG group had significantly decreased with the improved glucose tolerance. At the 2nd week postoperation, the area under the blood glucose concentration curve (AUC) received a distinct reduction of 28.1 % (P < 0.0001). The ghrelin secretion of the SG group was significantly decreased (P < 0.005). The GLP-1 had increased (P < 0.0001), while the HOMA-IR values decreased (P < 0.05) throughout the experimental period. These effects were not seen in the sham-SG and PF groups despite similar changes of weight loss or food intake.
The above results suggest that SG can conduct a direct control on T2DM instead of secondarily to weight loss or food intake around the whole experimental period. The changes of the gastrointestinal hormones may be the major mechanism of the antidiabetic effect.
PMCID: PMC4223536  PMID: 25400659
Sleeve gastrectomy; Glucose metabolism; Type 2 diabetes mellitus; Insulin resistance; Gastrointestinal hormones
25.  Encoding a qubit with Majorana modes in superconducting circuits 
Scientific Reports  2014;4:5535.
Majorana fermions are long-sought exotic particles that are their own antiparticles. Here we propose to utilize superconducting circuits to construct two superconducting-qubit arrays where Majorana modes can occur. A so-called Majorana qubit is encoded by using the unpaired Majorana modes, which emerge at the left and right ends of the chain in the Majorana-fermion representation. We also show this Majorana qubit in the spin representation and its advantage, over a single superconducting qubit, regarding quantum coherence. Moreover, we propose to use four superconducting qubits as the smallest system to demonstrate the braiding of Majorana modes and show how the states before and after braiding Majoranas can be discriminated.
PMCID: PMC4078313  PMID: 24985708

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