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1.  Three-dimensional vortex wake structure of flapping wings in hovering flight 
Flapping wings continuously create and send vortices into their wake, while imparting downward momentum into the surrounding fluid. However, experimental studies concerning the details of the three-dimensional vorticity distribution and evolution in the far wake are limited. In this study, the three-dimensional vortex wake structure in both the near and far field of a dynamically scaled flapping wing was investigated experimentally, using volumetric three-component velocimetry. A single wing, with shape and kinematics similar to those of a fruitfly, was examined. The overall result of the wing action is to create an integrated vortex structure consisting of a tip vortex (TV), trailing-edge shear layer (TESL) and leading-edge vortex. The TESL rolls up into a root vortex (RV) as it is shed from the wing, and together with the TV, contracts radially and stretches tangentially in the downstream wake. The downwash is distributed in an arc-shaped region enclosed by the stretched tangential vorticity of the TVs and the RVs. A closed vortex ring structure is not observed in the current study owing to the lack of well-established starting and stopping vortex structures that smoothly connect the TV and RV. An evaluation of the vorticity transport equation shows that both the TV and the RV undergo vortex stretching while convecting downwards: a three-dimensional phenomenon in rotating flows. It also confirms that convection and secondary tilting and stretching effects dominate the evolution of vorticity.
PMCID: PMC3869174  PMID: 24335561
flapping wing; vortex wake; far wake; volumetric visualization; induced flow; hovering
2.  MiR-429 Inhibits Oral Squamous Cell Carcinoma Growth by Targeting ZEB1 
Oral squamous cell carcinoma (OSCC) is the sixth most common human malignancy worldwide. To develop new therapeutics requires elucidation of the underlying mechanism of OSCC pathogenesis. The role of miR-429 in OSCC remains unknown.
The level of miR-429 and ZEB1 in OSCC tissues and cell lines was measured by qRT-PCR. MiR-429 was down-regulated by miRNAs antisense oligonucleotides (ASO) transfection and up-regulated by miRNAs mimics. Cell proliferation was analyzed by MTT assay. Cell apoptosis was revealed by FACS analysis. Targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay.
MiR-429 was down-regulated in OSCC tissues, and miR-429 overexpression inhibited OSCC cell lines growth and vice versa. Further, we found that miR-429 could inhibit zinc finger E-boxbinding homeobox 1 (ZEB1) expression, and that miR-429 and ZEB1 expression in OSCC tissues were negatively correlated.
Our data demonstrate the tumor suppressor role of miR-429 in OSCC, and may provide a potential therapeutic target that warrants further investigation.
PMCID: PMC4324578  PMID: 25640197
Cell Growth Processes; MicroRNAs; Mouth Neoplasms
3.  Classification of Metagenomics Data at Lower Taxonomic Level Using a Robust Supervised Classifier 
As more and more completely sequenced genomes become available, the taxonomic classification of metagenomic data will benefit greatly from supervised classifiers that can be updated instantaneously in response to new genomes. Currently, some supervised classifiers have been developed to assess the organism of metagenomic sequences. We have found that the existing supervised classifiers usually cannot discriminate the training data from different classes accurately when the data contain some outliers. However, the training genomic data (bacterial and archaeal genomes) usually contain a portion of outliers, which come from sequencing errors, phage invasions, and some highly expressed genes, etc. The outliers, treated as noises, prohibit the development of classifiers with better prediction accuracy. To solve the problem, we present a robust supervised classifier, weighted support vector domain description (WSVDD), which can eliminate the interference from some outliers for training genomic data and then generate more accurate data domain descriptions for each taxonomic class. The experimental results demonstrate WSVDD is more robust than other classifiers for simulated Sanger and 454 reads with different outlier rates. In addition, in experiments performed on simulated metagenomes and real gut metagenomes, WSVDD also achieved better prediction accuracy than other classifiers.
PMCID: PMC4309676
metagenomics; taxonomic classification; robustness; outliers; sequencing errors; support vector data description (SVDD)
4.  Prospective Study of Liver Transplant Recipients With HCV Infection: Evidence for a Causal Relationship Between HCV and Insulin Resistance 
An association between hepatitis C virus (HCV) infection and insulin resistance (IR) has been recently reported. However, causality has not been established. The cross-sectional nature of most reported studies and varying degrees of fibrosis have limited definitive conclusions about the independent role of HCV in development of IR. We sought to evaluate whether HCV induces IR by prospectively analyzing a cohort of adult liver transplant (LT) recipients. A total of 34 adults (14 HCV(+) and 20 HCV(−)) who underwent consecutive LT were followed during the first year posttransplantation. IR was estimated using the homeostasis model assessment (HOMA). Univariate and multivariate repeated measures analyses and Cox regression models were used. There were no significant differences between the groups with respect to age, body mass index (BMI), family history of diabetes, alcohol consumption, or laboratory indices. The cohort had no or minimal fibrosis. There was lower prednisone use in the HCV(+) group, and no difference in the use of tacrolimus between the two groups was found. IR was 77% higher in HCV(+) subjects during the first year post-LT when controlling for BMI (P = 0.035). Subjects with high HCV ribonucleic acid (RNA) levels reached high HOMA-IR significantly earlier than those with lower HCV RNA (P = 0.03). Following the first month post-LT, HCV(+) subjects were 4 times more likely to become diabetic than HCV(−) controls (P < 0.01). In conclusion, there is significantly higher IR in the HCV(+) group during the first year post-LT. This cannot be explained by differences in BMI, medications used, alcohol consumption, or degree of fibrosis. Higher HCV RNA levels were associated with earlier elevations in HOMA-IR. Collectively, these results provide strong evidence that HCV induces the development of IR.
PMCID: PMC4301430  PMID: 18236394
5.  Y-box binding protein 1 enhances DNA topoisomerase 1 activity and sensitivity to camptothecin via direct interaction 
The Y-box binding protein 1 (YB-1) possesses pleiotropic functions through its interactions with various cellular proteins, and its high expression levels make it a potential useful prognostic biomarker for cancer cells. Eukaryotic DNA topoisomerases, such as DNA topoisomerase 1 (TOPO1) and DNA topoisomerase 2 (TOPO2), are the essential DNA metabolism regulators that usually overexpressed in cancer cells, and multiple proteins have been reported to regulate the enzyme activity and the clinical efficacy of their inhibitors. The present study unraveled the interaction of YB-1 with TOPO1, and further investigated the related function and potential mechanisms during the interaction.
The direct association of TOPO1 with specific domain of YB-1 was explored by co-immunoprecipitation and GST pull-down assays. The interaction function was further clarified by DNA relaxation assays, co-immunoprecipitation and WST-8 assays with in vitro gain- and loss- of function models.
We found that YB-1 interacts directly with TOPO1 (but not with TOPO2) and promotes TOPO1 catalytic activity. Interactions between YB-1 and TOPO1 increased when cancer cells were treated with the TOPO1 inhibitor, camptothecin (CPT), but not with the TOPO2 inhibitor, adriamycin (ADM). Furthermore, we found that the interaction is prevented by pretreatment with the antioxidant agent, N-acetyl cysteine, and that YB-1 downregulation renders cells resistant to CPT.
Our findings suggest that nuclear YB-1 serves as an intracellular promoter of TOPO1 catalytic activity that enhances CPT sensitivity through its direct interaction with TOPO1.
PMCID: PMC4308875  PMID: 25539742
Drug resistance; Oxidative stress; Protein interaction domains and motifs; Topoisomerase 1; Y-box binding protein 1
6.  The draft genome of the large yellow croaker reveals well-developed innate immunity 
Nature Communications  2014;5:5227.
The large yellow croaker, Larimichthys crocea, is one of the most economically important marine fish species endemic to China. Its wild stocks have severely suffered from overfishing, and the aquacultured species are vulnerable to various marine pathogens. Here we report the creation of a draft genome of a wild large yellow croaker using a whole-genome sequencing strategy. We estimate the genome size to be 728 Mb with 19,362 protein-coding genes. Phylogenetic analysis shows that the stickleback is most closely related to the large yellow croaker. Rapidly evolving genes under positive selection are significantly enriched in pathways related to innate immunity. We also confirm the existence of several genes and identify the expansion of gene families that are important for innate immunity. Our results may reflect a well-developed innate immune system in the large yellow croaker, which could aid in the development of wild resource preservation and mariculture strategies.
The large yellow croaker, Larimichthys crocea, is an economically important marine fish in China. Here, the authors sequence the draft genome of a wild large yellow croaker and highlight genes that may have played a role in the development of innate immunity in this species.
PMCID: PMC4263168  PMID: 25407894
7.  MiR-210 Up-Regulation Inhibits Proliferation and Induces Apoptosis in Glioma Cells by Targeting SIN3A 
The aim of this study was to determine whether miR-210 can affect the apoptosis and proliferation of human U251 glioma cells from down-regulating SIN3A.
The expression of miRNA-210 was detected by quantitative real-time PCR in normal brain tissue and glioma samples. The apoptosis and proliferation ability of U251 cells were analyzed by MTT and flow cytometry assay after anti-miR-210 transfection. For the regulation mechanism analysis of miR-210, TargetScan, PicTar, and microRNA were selected to predict some potential target genes of miR-210. The predicted gene was identified to be the direct and specific target gene of miR-210 by luciferase activities assay and Western blot. RNA interference technology was used to confirm that the apoptosis and proliferation effects of miR-210 were directly induced by SIN3A.
The expression of miR-210 increased significantly in glioma in comparison with normal brain tissue. The silence of miR-210 expression could inhibit the proliferation of U251 cells and induce the apoptosis. Mechanism analysis revealed that SIN3A was a specific and direct target gene of miR-210. The siRNA-SIN3A could down-regulate the expression of SIN3A protein, which was up-regulated in U251 cells by anti-miR-210 transfection, and our experiments found that silence of SIN3A could inhibit the apoptosis and sharply increase the proliferation of U251 cells. The regulation effects of anti-miR-210 on apoptosis and proliferation can be reversed respectively by the expression silence of SIN3A.
Aberrantly expressed miR-210 regulates human U251 glioma cells apoptosis and proliferation partly through directly down-regulating SIN3A protein expression. This might offer a new potential therapeutic stratagem for glioma.
PMCID: PMC4266365  PMID: 25481483
Glioma; MicroRNAs; Neoplastic Stem Cells
8.  Spatiotemporal Transmission Dynamics of Hemorrhagic Fever with Renal Syndrome in China, 2005–2012 
Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by many serotypes of hantaviruses. In China, HFRS has been recognized as a severe public health problem with 90% of the total reported cases in the world. This study describes the spatiotemporal dynamics of HFRS cases in China and identifies the regions, time, and populations at highest risk, which could help the planning and implementation of key preventative measures.
Data on all reported HFRS cases at the county level from January 2005 to December 2012 were collected from Chinese Center for Disease Control and Prevention. Geographic Information System-based spatiotemporal analyses including Local Indicators of Spatial Association and Kulldorff's space-time scan statistic were performed to detect local high-risk space-time clusters of HFRS in China. In addition, cases from high-risk and low-risk counties were compared to identify significant demographic differences.
A total of 100,868 cases were reported during 2005–2012 in mainland China. There were significant variations in the spatiotemporal dynamics of HFRS. HFRS cases occurred most frequently in June, November, and December. There was a significant positive spatial autocorrelation of HFRS incidence during the study periods, with Moran's I values ranging from 0.46 to 0.56 (P<0.05). Several distinct HFRS cluster areas were identified, mainly concentrated in northeastern, central, and eastern of China. Compared with cases from low-risk areas, a higher proportion of cases were younger, non-farmer, and floating residents in high-risk counties.
This study identified significant space-time clusters of HFRS in China during 2005–2012 indicating that preventative strategies for HFRS should be particularly focused on the northeastern, central, and eastern of China to achieve the most cost-effective outcomes.
Author Summary
Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne viral disease caused by many serotypes of hantaviruses. In China, HFRS has been recognized as a severe public health problem and accounts for 90% of the reported cases in the world. We examined the spatiotemporal dynamics of HFRS cases in China during 2005–2012 and compared characteristics between cases from high-risk and low-risk counties. Several distinct HFRS cluster areas were identified, concentrated in northeastern, central, and eastern of China. Compared with cases from low-risk areas, a higher proportion of cases were younger, non-farmer, and floating residents in high-risk counties. These findings suggest preventative strategies for HFRS should be focused on the identified clusters in order to achieve the most cost-effective outcomes.
PMCID: PMC4239011  PMID: 25412324
9.  Protective Effects of Astragaloside IV on db/db Mice with Diabetic Retinopathy 
PLoS ONE  2014;9(11):e112207.
Diabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the potential biological functions of astragaloside IV (AS IV) have long been described in traditional system of medicine, its protective effect on DR remains unclear. This study aims to investigate the function and mechanism of AS IV on type 2 diabetic db/db mice.
Db/db mice were treated with AS IV (4.5 mg/kg or 9 mg/kg) or physiological saline by oral gavage for 20 weeks along with db/m mice. In each group, retinal ganglion cell (RGC) function was measured by pattern electroretinogram (ERG) and apoptosis was determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Blood and retina aldose reductase (AR) activity were quantified by chemiluminescence analysis. The expressions of phosporylated-ERK1/2, NF-κB were determined by Western blot analysis. Furthermore, the expression of related downstream proteins were quantified by Label-based Mouse Antibody Array.
Administration of AS IV significantly improved the amplitude in pattern ERG and reduced the apoptosis of db/db mice. Furthermore, downregulation of AR activity, ERK1/2 phosphorylation, NF-κB and related cytokine were observed in AS IV treatment group.
Our study indicated that AS IV, as an inhibitor of AR, could prevent the activation of ERK1/2 phosporylation and NF-kB and further relieve the RGCs disfunction in db/db mice with DR. It has provided a basis for investigating the clinical efficacy of AR inhibitors in preventing DR.
PMCID: PMC4239035  PMID: 25411784
10.  Molecular Interactions between (−)-Epigallocatechin Gallate Analogs and Pancreatic Lipase 
PLoS ONE  2014;9(11):e111143.
The molecular interactions between pancreatic lipase (PL) and four tea polyphenols (EGCG analogs), like (−)-epigallocatechin gallate (EGCG), (−)-gallocatechin gallate (GCG), (−)-epicatechin gallate (ECG), and (−)-epigallocatechin (EC), were studied from PL activity, conformation, kinetics and thermodynamics. It was observed that EGCG analogs inhibited PL activity, and their inhibitory rates decreased by the order of EGCG>GCG>ECG>EC. PL activity at first decreased rapidly and then slowly with the increase of EGCG analogs concentrations. α-Helix content of PL secondary structure decreased dependent on EGCG analogs concentration by the order of EGCG>GCG>ECG>EC. EGCG, ECG, and EC could quench PL fluorescence both dynamically and statically, while GCG only quenched statically. EGCG analogs would induce PL self-assembly into complexes and the hydrodynamic radii of the complexes possessed a close relationship with the inhibitory rates. Kinetics analysis showed that EGCG analogs non-competitively inhibited PL activity and did not bind to PL catalytic site. DSC measurement revealed that EGCG analogs decreased the transition midpoint temperature of PL enzyme, suggesting that these compounds reduced PL enzyme thermostability. In vitro renaturation through urea solution indicated that interactions between PL and EGCG analogs were weak and non-covalent.
PMCID: PMC4218840  PMID: 25365042
11.  Inhaled sevoflurane for lower gastrointestinal endoscopy with possible propofol anaphylaxis 
Sedation with propofol is widely used for the outpatient examination. Although anaphylaxis to propofol is rare, there were some reports of anaphylaxis following propofol administration. We present a case of female patient under sedation for lower gastrointestinal endoscopy with possible propofol anaphylaxis. Then sevoflurane was successfully used for the examination and the following surgery. We discussed the possible feasibility of sevoflurane for the examination of lower gastrointestinal endoscopy. Propofol is widely used for the sedation of outpatient with lower gastrointestinal endoscopy. But it may cause some allergic reaction. Inhaled sevoflurane may provide a satisfactory and safe alternative for adult outpatients’ endoscopy.
PMCID: PMC4238506  PMID: 25419408
Inhaled anesthetics; propofol; gastrointestinal endoscopy; anaphylaxis
12.  Atomic-scale control of TiO6 octahedra through solution chemistry towards giant dielectric response 
Scientific Reports  2014;4:6582.
The structures of many important functional oxides contain networks of metal-oxygen polyhedral units i.e. MOn. The correlation between the configurations and connectivities of these MOn to properties is essentially important to be well established to conduct the design, synthesis and application of new MOn-based functional materials. In this paper, we report on an atomic-scale solution-chemistry approach that for the first time enables TiO6 octahedral network control starting from metastable brookite TiO2 through simultaneously tuning pH values and interfering ions (Fe3+, Sc3+, and Sm3+). The relationship between solution chemistry and the resultant configuration/connectivity of TiO6 octahedra in TiO2 and lepidocrocite titanate is mapped out. Apart from differing crystalline phases and morphologies, atomic-scale TiO6 octahedral control also endows numerous defect dipoles for giant dielectric responses. The structural and property evolutions are well interpreted by the associated H+/OH− species in solution and/or defect states associated with Fe3+ occupation within TiO6 octahedra. This work therefore provides fundamental new insights into controlling TiO6 octahedral arrangement essential for atomic-scale structure-property design.
PMCID: PMC4192633  PMID: 25301286
13.  Up-regulation of S100A16 expression promotes epithelial-mesenchymal transition via Notch1 pathway in breast cancer 
Our previous studies demonstrated that S100A16 promotes adipogenesis and is involved in weight gain attenuation induced by dietary calcium. Till now, the function of S100A16 in the breast cancer remains to be elucidated.
In this study, we observed that S100A16 was expressed in higher levels in human breast cancer tissues compared with paired adjacent non-cancerous tissues. Further examination showed that overexpression of S100A16 in MCF-7 cells could increase cell proliferation and colony formation. One major mechanistic change was that S100A16 was able to up-regulate the transcription factors Notch1, ZEB1, and ZEB2, which had the capacities to directly repress the expression of epithelial markers E-cadherin and β-catenin but increase mesenchymal markers N-cadherin and vimentin, a characterized phenotype of epithelial-mensenchymal transition (EMT). In addition to display with morphologic change, migration and invasion were increased in S100A16 over-expressed MCF-7 cells. Importantly, knockdown of Notch1 by specific siRNA could reverse the EMT induced by S100A16 overexpression, which confirmed that Notch1 played a critical role in the process of EMT induced by S100A16.
All together, our data indicated that S100A16 had a potential function to regulate some embryonic transcription factors to promote EMT in breast cancer cells which may be an important target site for the therapy of breast cancer.
Electronic supplementary material
The online version of this article (doi:10.1186/s12929-014-0097-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4197258  PMID: 25287362
Breast cancer; S100A16; EMT; Notch1; MCF-7
14.  An Integrated Model for Robust Multisensor Data Fusion 
Sensors (Basel, Switzerland)  2014;14(10):19669-19686.
This paper presents an integrated model aimed at obtaining robust and reliable results in decision level multisensor data fusion applications. The proposed model is based on the connection of Dempster-Shafer evidence theory and an extreme learning machine. It includes three main improvement aspects: a mass constructing algorithm to build reasonable basic belief assignments (BBAs); an evidence synthesis method to get a comprehensive BBA for an information source from several mass functions or experts; and a new way to make high-precision decisions based on an extreme learning machine (ELM). Compared to some universal classification methods, the proposed one can be directly applied in multisensor data fusion applications, but not only for conventional classifications. Experimental results demonstrate that the proposed model is able to yield robust and reliable results in multisensor data fusion problems. In addition, this paper also draws some meaningful conclusions, which have significant implications for future studies.
PMCID: PMC4239917  PMID: 25340445
multisensors; data fusion; Dempster-Shafer theory; extreme learning machine
15.  Automatic Crack Detection and Classification Method for Subway Tunnel Safety Monitoring 
Sensors (Basel, Switzerland)  2014;14(10):19307-19328.
Cracks are an important indicator reflecting the safety status of infrastructures. This paper presents an automatic crack detection and classification methodology for subway tunnel safety monitoring. With the application of high-speed complementary metal-oxide-semiconductor (CMOS) industrial cameras, the tunnel surface can be captured and stored in digital images. In a next step, the local dark regions with potential crack defects are segmented from the original gray-scale images by utilizing morphological image processing techniques and thresholding operations. In the feature extraction process, we present a distance histogram based shape descriptor that effectively describes the spatial shape difference between cracks and other irrelevant objects. Along with other features, the classification results successfully remove over 90% misidentified objects. Also, compared with the original gray-scale images, over 90% of the crack length is preserved in the last output binary images. The proposed approach was tested on the safety monitoring for Beijing Subway Line 1. The experimental results revealed the rules of parameter settings and also proved that the proposed approach is effective and efficient for automatic crack detection and classification.
PMCID: PMC4239952  PMID: 25325337
crack detection; crack classification; subway tunnel; line scan cameras
16.  Abnormal chromosome behavior during meiosis in the allotetraploid of Carassius auratus red var. (♀) × Megalobrama amblycephala (♂) 
BMC Genetics  2014;15:95.
Allopolyploids generally undergo bivalent pairing at meiosis because only homologous chromosomes pair up. On the other hand, several studies have documented abnormal chromosome behavior during mitosis and meiosis in allopolyploids plants leading to the production of gametes with complete paternal or maternal chromosomes. Polyploidy is relatively rare in animals compared with plants; thus, chromosome behavior at meiosis in the allopolyploid animals is poorly understood.
Tetraploid hybrids (abbreviated as 4nRB) (4n = 148, RRBB) of Carassius auratus red var. (abbreviated as RCC) (2n = 100, RR) (♀) × Megalobrama amblycephala (abbreviated as BSB) (2n = 48, BB) (♂) generated gametes of different size. To test the genetic composition of these gametes, the gynogenetic offspring and backcross progenies of 4nRB were produced, and their genetic composition were examined by chromosome analysis and FISH. Our results suggest that 4nRB can produce several types of gametes with different genetic compositions, including allotetraploid (RRBB), autotriploid (RRR), autodiploid (RR), and haploid (R) gametes.
This study provides direct evidence of abnormal chromosome behavior during meiosis in an allotetraploid fish.
PMCID: PMC4236601  PMID: 25178799
Allotetraploid; Chromosome behavior; FISH; Gamete
17.  Easily manageable prognostic factors in 152 Chinese elderly acute myeloid leukemia patients: a single-center retrospective study 
Journal of Biomedical Research  2014;28(5):396-405.
We retrospectively investigated the prognostic factors of acute myeloid leukemia (AML) in 152 Chinese patients with de novo AML who were older than 60 years of age and who received treatment at our hospital. Log-rank test showed that 6 parameters including older age, higher white blood cell (WBC) counts, lactate dehydrogenase (LDH) and bone marrow (BM) blasts at diagnosis, unfavorable risk cytogenetics, and non-mutated CEBPα were significant adverse prognostic factors of overall survival (OS) for elderly AML patients (P  =  0.0013, 0.0358, 0.0132, 0.0242, 0.0236 and 0.0130, respectively). Moreover, older age and higher LDH were significant adverse predictors for relapse-free survival (RFS) (P  =  0.0447 and 0.0470, respectively). Univariate analysis revealed similar results for OS to those of the log-rank test and only higher LDH at diagnosis was a significant adverse predictor for RFS (P  =  0.028, HR: 1.979, 95%CI: 1.075–3.644). In multivariate analysis, we identified 2 trends towards independent prognostic factors for OS, including BM blasts at diagnosis (P  =  0.057, HR: 1.676, 95%CI: 0.984–2.854) and mutation status of CEBPα (P  =  0.064, HR: 4.173, 95%CI: 0.918–18.966). Our data indicated that older age, gender and a previous history of hematologic diseases resulted in lower complete remission rate (P  =  0.012, 0.051 and 0.086, respectively). We further developed an easy scoring system for predicting prognosis and response to induction therapy in older AML patients. Patients who had lower scores showed significantly longer OS and RFS (P  =  0.0006 and 0.1001, respectively) and higher CR rate (P  =  0.014). Our research is limited by its retrospective nature and the results from our study need to be further validated by prospective randomized clinical trials.
PMCID: PMC4197391  PMID: 25332712
acute myeloid leukemia; elderly patients; prognosis factors
18.  Detecting Both the Mass and Position of an Accreted Particle by a Micro/Nano-Mechanical Resonator Sensor 
Sensors (Basel, Switzerland)  2014;14(9):16296-16310.
In the application of a micro-/nano-mechanical resonator, the position of an accreted particle and the resonant frequencies are measured by two different physical systems. Detecting the particle position sometimes can be extremely difficult or even impossible, especially when the particle is as small as an atom or a molecule. Using the resonant frequencies to determine the mass and position of an accreted particle formulates an inverse problem. The Dirac delta function and Galerkin method are used to model and formulate an eigenvalue problem of a beam with an accreted particle. An approximate method is proposed by ignoring the off-diagonal elements of the eigenvalue matrix. Based on the approximate method, the mass and position of an accreted particle can be decoupled and uniquely determined by measuring at most three resonant frequencies. The approximate method is demonstrated to be very accurate when the particle mass is small, which is the application scenario for much of the mass sensing of micro-/nano-mechanical resonators. By solving the inverse problem, the position measurement becomes unnecessary, which is of some help to the mass sensing application of a micro-/nano-mechanical resonator by reducing two measurement systems to one. How to apply the method to the general scenario of multiple accreted particles is also discussed.
PMCID: PMC4208176  PMID: 25184493
inverse problem; mass sensing; resonator sensor; resonant frequency; Galerkin method
19.  A role for c-Abl in cell senescence and spontaneous immortalization 
Age  2012;35(4):1251-1262.
c-Abl is a proto-oncogene that is essential for mouse development and tissue homeostasis. Misregulation of c-Abl, as seen in the constitutively active BCR-ABL, is the leading cause of human chronic myeloid leukemia. However, how the Abl proteins execute their functions still remains largely unknown. Here, we report an important role for c-Abl in replicative senescence and immortalization by regulating the expression of two tumor suppressors that induce cellular senescence, p53 and p16INK4a. Using primary mouse embryonic fibroblasts (MEFs), we show that c-Abl−/− cells were more resistant to immortalization than wildtype cells using a standard 3T3 or 3T9 protocol. We could only immortalize three out of nine c-Abl−/− MEF cultures even when we increased the number of starting cells. This resistance was attributed to premature senescence and reduced survival in senescent c-Abl−/− cells due to an increase in p16INK4a and p53 expression. Deleting p53 allows c-Abl−/−p53−/− MEFs to bypass senescence to be spontaneously immortalized. Cell immortalization, but not senescence, was generally accompanied by mutations in p53 in both wildtype and c-Abl−/− MEFs, although the spectrum is different from that of human tumors. The role for c-Abl in regulating cell senescence and immortalization might explain some of the developmental defects in c-Abl−/− mice and how BCR-ABL transforms cells.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-012-9452-4) contains supplementary material, which is available to authorized users.
PMCID: PMC3705115  PMID: 22791394
Senescence; Abl; p16; p53
20.  Automatic Foreground Extraction Based on Difference of Gaussian 
The Scientific World Journal  2014;2014:296074.
A novel algorithm for automatic foreground extraction based on difference of Gaussian (DoG) is presented. In our algorithm, DoG is employed to find the candidate keypoints of an input image in different color layers. Then, a keypoints filter algorithm is proposed to get the keypoints by removing the pseudo-keypoints and rebuilding the important keypoints. Finally, Normalized cut (Ncut) is used to segment an image into several regions and locate the foreground with the number of keypoints in each region. Experiments on the given image data set demonstrate the effectiveness of our algorithm.
PMCID: PMC4127285  PMID: 25136655
21.  Meta-analysis of postoperative efficacy in patients receiving chemoradiotherapy followed by surgery for resectable esophageal carcinoma 
Diagnostic Pathology  2014;9:151.
Many studies have demonstrated that chemoradiotherapy followed by surgery (CRTS) prolongs the 5-year survival rate of resectable esophageal carcinoma patients. However, the effect of CRTS on postoperative complications, local recurrence and distant metastasis remains controversial. We performed a systematic review of the literature and conducted a meta-analysis to assess the postoperative efficacy of CRTS compared with surgery alone (SA).
Pubmed, Web of Science and the Cochrane library Databases were used to identify published studies between 2000 and 2013 that directly compared CRTS with SA. The pooled relative risk (RR) and its corresponding 95% confidence interval (95% CI) constituted the principal measure of treatment effects. Heterogeneity was assessed by the χ2 and I2 statistic.
The final analysis included 1930 resectable esophageal carcinoma cases from 13 randomized controlled trials (RCTs). Compared with SA, CRTS was associated with significantly decreased postoperative mortality, local recurrence and distant metastasis rates, with RR (95% CI) = 0.64 (0.49–0.84), 0.53 (0.39–0.73), 0.82 (0.68–0.98); p = 0.001, <0.00001, =0.03, respectively. However, there was no significant difference in postoperative complication incidence between the two groups (RR, 1.09; 95% CI, 0.96–1.24; p = 0.18).
CRTS significantly decreased postoperative mortality, local recurrence and distant metastasis rates compared to SA. Additionally, there were no increased postoperative complications for patients with resectable esophageal carcinoma.
Virtual Slides
The virtual slide(s) for this article can be found here:
PMCID: PMC4223621  PMID: 25030066
Esophageal carcinoma; Chemoradiotherapy followed by surgery; Surgery alone; Randomized controlled trial; Meta-analysis
22.  Concordant podoplanin expression in cancer-associated fibroblasts and tumor cells is an adverse prognostic factor in esophageal squamous cell carcinoma 
There is growing evidence that cancer-associated fibroblasts (CAFs) interact with tumor cells and play important roles in tumor progression and invasion. Podoplanin is a type-1 transmembrane glycoprotein expressed in a variety of normal human tissues, including lymphatic endothelium. Tumor cell expression of podoplanin correlates with nodal metastasis and poor prognosis in squamous cell carcinoma (SCC) of oral cavity and esophagus. Recently, podoplanin-positive CAFs have been shown to exert adverse or beneficial prognostic effect on different cancer types. However, the significance of podoplanin-positive CAFs in esophageal SCC has not been investigated. This is the first study to investigate podoplanin expression in CAFs and tumor cells by immunohistochemistry in 59 cases of surgically resected esophageal SCC. We found significant association of podoplanin expression between CAFs and tumor cells (P = 0.031). Although the abundance of podoplanin-positive CAFs per se had no prognostic effect, concordant podoplanin expression in CAFs and tumor cells (both high or both low) was strongly associated with short survival (P = 0.00088). Multivariate analysis showed that concordant podoplanin expression was the strongest independent adverse prognostic factor (hazard ratio: 3.62; 95% confidence interval: 1.69-7.77; P = 0.00094). Our data suggest that interaction between podoplanin-positive CAFs and tumor cells is important in tumor biology of esophageal SCC.
PMCID: PMC4152045  PMID: 25197355
Podoplanin; cancer-associated fibroblast; esophagus; squamous cell carcinoma; prognosis
23.  Detoxification of Corncob Acid Hydrolysate with SAA Pretreatment and Xylitol Production by Immobilized Candida tropicalis 
The Scientific World Journal  2014;2014:214632.
Xylitol fermentation production from corncob acid hydrolysate has become an attractive and promising process. However, corncob acid hydrolysate cannot be directly used as fermentation substrate owing to various inhibitors. In this work, soaking in aqueous ammonia (SAA) pretreatment was employed to reduce the inhibitors in acid hydrolysate. After detoxification, the corncob acid hydrolysate was fermented by immobilized Candida tropicalis cell to produce xylitol. Results revealed that SAA pretreatment showed high delignification and efficient removal of acetyl group compounds without effect on cellulose and xylan content. Acetic acid was completely removed, and the content of phenolic compounds was reduced by 80%. Furthermore, kinetic behaviors of xylitol production by immobilized C. tropicalis cell were elucidated from corncob acid hydrolysate detoxified with SAA pretreatment and two-step adsorption method, respectively. The immobilized C. tropicalis cell showed higher productivity efficiency using the corncob acid hydrolysate as fermentation substrate after detoxification with SAA pretreatment than by two-step adsorption method in the five successive batch fermentation rounds. After the fifth round fermentation, about 60 g xylitol/L fermentation substrate was obtained for SAA pretreatment detoxification, while about 30 g xylitol/L fermentation substrate was obtained for two-step adsorption detoxification.
PMCID: PMC4123689  PMID: 25133211
24.  Highly Effective Ex Vivo Gene Manipulation to Study Kidney Development Using Self-Complementary Adenoassociated Viruses 
The Scientific World Journal  2014;2014:682189.
Background. Ex vivo culture of intact embryonic kidney has become a powerful system for studying renal development. However, few methods have been available for gene manipulation and have impeded the identification and investigation of genes in this developmental process. Results. Here we systemically compared eight different serotypes of pseudotyped self-complementary adenoassociated viruses (scAAVs) transduction in cultured embryonic kidney with a modified culture procedure. We demonstrated that scAAV was highly effective in delivering genes into and expressing in compacted tissues. scAAV serotypes 2 and 8 exhibited higher efficiency of transduction compared to others. Expression kinetics assay revealed that scAAV can be used for gene manipulation at the study of UB branching and nephrogenesis. Repressing WT1 in cultured kidney using shRNA impairs tubule formation. We for the first time employed and validated scAAV as a gene delivery tool in cultured kidney. Conclusions. These findings are expected to expedite the use of the ex vivo embryonic kidney cultures for kidney development research. For other ex vivo cultured organ models, scAAV could also be a promising tool for organogenesis study.
PMCID: PMC4123690  PMID: 25133251
25.  NF-κB signaling and vesicle transport are correlated with the reactivation of the memory trace of morphine dependence 
Diagnostic Pathology  2014;9:142.
Morphine has been widely used as a clinical anesthetic and analgesic. However, abuse of morphine might result in psychological and physiological dependence. Previous studies have indicated that memory mechanisms play critical roles in morphine dependence.
Morphine dependence was established in mice utilizing place preference conditioning (CPP). We observed changes in the methylome and transcriptome of the nucleus accumbens during the reactivation of the memory trace. We also monitored for changes in the methylome and transcriptome of mice that were acutely exposed to morphine.
We detected 165 and 18 differentially expressed genes (DEGs) and 6 and 24 significant methyl-sensitive cut counting (MSCC) windows in the acute morphine treatment and the CPP model, respectively. The changes in the methylome and transcriptome during the acute treatment were mainly caused by a response to the morphine stimulus; most of the DEGs were correlated with hormone or transcription factor activity regulation. The expression levels of Lcn2 and Hspb1, which participate in the activation of NF-κB, were significantly decreased in the CPP morphine treatment model. Besides, the alternative splicing of the curtailed isoform of Caps1 was significantly increased in the CPP morphine-treated group, and the methylation levels of Arf4, Vapa, and Gga3 were decreased. These genes play critical roles in the regulation of the Golgi network.
The current study indicates that NF-κB signaling and vesicular transport are correlated with the reactivation of the memory trace in morphine-dependent mice. The results obtained in our study agree with previous observations and identify additional candidate genes for further research.
Virtual Slides
The virtual slide(s) for this article can be found here:
PMCID: PMC4227096  PMID: 25012590
CPP; Morphine; Transcriptome; Methylome; NF-κB

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