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1.  A hydrolase of trehalose dimycolate induces nutrient influx and stress sensitivity to balance intracellular growth of Mycobacterium tuberculosis 
Cell host & microbe  2014;15(2):153-163.
Summary
Chronic tuberculosis in an immunocompetent host is a consequence of the delicately balanced growth of Mycobacterium tuberculosis (Mtb) in the face of host defense mechanisms. We identify an Mtb enzyme (TdmhMtb) that hydrolyzes the mycobacterial glycolipid trehalose dimycolate and plays a critical role in balancing the intracellular growth of the pathogen. TdmhMtb is induced under nutrient limiting conditions and remodels the Mtb envelope to increase nutrient influx, but concomitantly sensitizes Mtb to stresses encountered in the host. Consistent with this, a ΔtdmhMtb mutant is more resilient to stress and grows to higher levels than wild-type in immunocompetent mice. By contrast, mutant growth is retarded in MyD88−/− mice indicating that TdmhMtb provides a growth advantage to intracellular Mtb in an immunocompromised host. Thus, the effects and counter-effects of TdmhMtb play an important role in balancing intracellular growth of Mtb in a manner that is directly responsive to host innate immunity.
doi:10.1016/j.chom.2014.01.008
PMCID: PMC3974621  PMID: 24528862
2.  A Multicenter, Randomized Clinical Trial Comparing the Three-Weekly Docetaxel Regimen plus Prednisone versus Mitoxantone plus Prednisone for Chinese Patients with Metastatic Castration Refractory Prostate Cancer 
PLoS ONE  2015;10(1):e0117002.
Purpose
To explore the feasibility and efficacy of docetaxel plus prednisone for Chinese population with metastatic castration refractory prostate cancer (mCRPC).
Patients and methods
A total of 228 patients recruited from 15 centers were randomized to receive 10 cycles of D3P arm (docetaxel: 75 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily) or M3P arm (mitoxantrone: 12 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily). Primary end point was overall survival, and secondary end points were events progression-free survival (PFS), response rate, response duration. Quality of life (QoL) was also assessed in both treatment groups.
Results
The median overall survival was 21.88 months in D3P arm and 13.67 months in M3P arm (P = 0.0011, hazard ratio = 0.63, 95% confidence interval, 0.46–0.86). Subgroup analysis was consistent with the results of overall analysis. Events progression-free survival (pain, PSA, tumor and disease) were significantly improved in D3P arm compared with M3P arm. PSA response rate was 35.11% for patients treated by D3P arm and 19.39% for M3P arm (P = 0.0155). Pain response rate was higher in D3P arm (61.11%, P = 0.0011) than in M3P (23.08%) arm. No statistical differences were found between D3P arm and M3P arm for QoL, tumor response rate and response duration of PSA and pain. The tolerability and overall safety of D3P arm were generally comparable to that of M3P arm.
Conclusions
Compared with M3P arm, D3P arm significantly prolonged overall survival for the Chinese patients with mCRPC and improved the response rate for PSA and pain.
Trial Registration
clinicaltrials.gov NCT00436839
doi:10.1371/journal.pone.0117002
PMCID: PMC4307981  PMID: 25625938
3.  Comparison of Primary Radial Head Replacement and ORIF (Open Reduction and Internal Fixation) in Mason Type III Fractures: A Retrospective Evaluation in 72 Elderly Patients 
Background
The aim of this study was to compare radial head prosthesis replacement with open reduction and internal fixation (ORIF) in the surgical treatment of Mason type III radial head fractures in 72 elderly patients.
Material/Methods
Seventy-two elderly patients (mean age, 67.1±1.25 years, range, 62–81 years) with Mason type III radial head fractures were treated from January 2001 to June 2012. Of these, 37 cases received radial prosthesis and 35 cases were treated with ORIF. All patients were followed up for 10 to 15.6 months.
Results
Based on the elbow functional evaluation criteria score by Broberg and Morrey, 29 cases achieved excellent results, 7 were good, and 1 was fair in the replacement group. In the ORIF group, excellent results were seen in 24 cases, good in 9, and fair in 2. The rates of good or excellent results were 78.4% and 68.6% for prosthesis replacement patients and ORIF patients, respectively (P<0.05). The Visual Analogue Scores (VAS) for replacement and ORIF groups were 2.25 and 1.67, respectively (P<0.05).
Conclusions
The radial head prosthesis replacement method is a relatively better surgical approach than ORIF in the treatment of elderly patients with Mason type III radial head fractures.
doi:10.12659/MSM.893048
PMCID: PMC4298279  PMID: 25567738
Arthroplasty, Replacement, Elbow; Fracture Fixation; Health Services for the Aged
4.  Preparation and Upconversion Emission Modification of Crystalline Colloidal Arrays and Rare Earth Fluoride Microcrystal Composites 
Scientific Reports  2015;5:7636.
In this paper, highly ordered crystalline colloidal arrays containing rare earth fluoride microcrystals were fabricated. The upconversion emission property of rare earth fluoride microcrystals in crystalline colloidal arrays was studied and modified. A significant suppression and enhancement of the upconversion emission from the rare earth fluorides can be observed in the regions of the photonic band gap and its band edge, respectively. The suppression or enhancement factor was shown to be related to the ordered degree of the crystalline colloidal arrays and is critical in the preparation of upconversion displays and low-threshold lasers.
doi:10.1038/srep07636
PMCID: PMC4284515  PMID: 25560045
5.  An effective approach to prevent immune rejection of human ESC-derived allografts 
Cell stem cell  2014;14(1):121-130.
Summary
Human embryonic stem cells (hESCs) hold great promise for cell therapy as a source of diverse differentiated cell types. One key bottleneck to realizing such potential is allogenic immune rejection of hESC-derived cells by recipients. Here, we optimized humanized mice (Hu-mice) reconstituted with a functional human immune system that mounts a vigorous rejection of hESCs and their derivatives. We established knock-in hESCs that constitutively express CTLA4-Ig and PD-L1 before and after differentiation, denoted CP hESCs. We then demonstrated that allogenic CP hESC-derived teratomas, fibroblasts, and cardiomyocytes are immune protected in Hu-mice, while cells derived from parental hESCs are effectively rejected. Expression of both CTLA4-Ig, which disrupts T-cell co-stimulatory pathways, and PD-L1, which activates T-cell inhibitory pathway, is required to confer immune protection as neither was sufficient on their own. These findings are instrumental for developing a strategy to protect hESC-derived cells from allogenic immune responses without requiring systemic immune suppression.
doi:10.1016/j.stem.2013.11.014
PMCID: PMC4023958  PMID: 24388175
6.  Polycation-Functionalized Nanoporous Silicon Particles for Gene Silencing on Breast Cancer Cells 
Biomaterials  2013;35(1):10.1016/j.biomaterials.2013.09.033.
Nanoporous silicon particles (pSi), with a pore size in the range of 20~60 nm, were modified with polyethyleimine (PEI) to yield pSi-PEI particles, which were subsequently complexed with siRNA. Thus, pSi-PEI/siRNA particles were fabricated, with the PEI/siRNA nanocomplexes mainly anchored inside the nanopore of the pSi particles. These hybrid particles were used as carriers to deliver siRNA to human breast cancer cells. Due to the gradual degradation of the pSi matrix under physiological conditions, the PEI/siRNA nanocomplexes were released from the pore interior in a sustained manner. Physicochemical characterization revealed that the released PEI/siRNA nanocomplexes exhibited well-defined spherical shape and narrow particle size distribution between 15 and 30 nm. Gene knockdown against the ataxia telangiectasia mutated (ATM) cancer gene showed dramatic gene silencing efficacy. Moreover, comprehensive biocompatibility studies were performed for the pSi-PEI/siRNA particles both in vitro and in vivo and demonstrated that the pSi-PEI particles exhibited significantly enhanced biocompatibility. As a consequence, PEI-modified porous silicon particles may have substantial potential as safe and effective siRNA delivery systems.
doi:10.1016/j.biomaterials.2013.09.033
PMCID: PMC3842233  PMID: 24103653
non-viral gene delivery; polyplex; siRNA; porous silicon particles; breast cancer
7.  Sex-Specific Urinary Biomarkers for Diagnosing Bipolar Disorder 
PLoS ONE  2014;9(12):e115221.
Sex-based differences are prominent in affective disorders, but there are no biomarkers available to support sex-specific, laboratory-based diagnostics for male and female bipolar disorder (BD) patients. Here, a NMR-based metabonomic approach was used to preliminarily identify sex-specific urinary metabolite biomarkers for diagnosing male and female BD patients. A male-specific biomarker panel consisting of four metabolites (α-hydroxybutyrate, choline, formate, and N-methylnicotinamide) effectively discriminated between male BD and healthy controls (HC) subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.942. A female-specific biomarkers panel consisting of four metabolites (α-hydroxybutyrate, oxalacetate, acetone, and N-methylnicotinamide) effectively discriminated between female BD and HC subjects, achieving an AUC of 0.909. The male-specific biomarker panel displayed low discriminatory power in the female group, and the female-specific biomarker panel displayed low discriminatory power in the male group. Moreover, several other metabolites showed different trends between male and female BD subjects. These findings suggest that male and female BD patients have distinct biomarker fingerprints and that these two sex-specific biomarker panels may serve as effective diagnostic tools in distinguishing male and female BD patients from their healthy counterparts. Our work may provide a window into the mechanisms underlying the pathoetiology of BD in both men and women.
doi:10.1371/journal.pone.0115221
PMCID: PMC4274077  PMID: 25531985
8.  Nanotopography Alters Nuclear Protein Expression, Proliferation and Differentiation of Human Mesenchymal Stem/Stromal Cells 
PLoS ONE  2014;9(12):e114698.
Mesenchymal stem/stromal cells respond to physical cues present in their microenvironment such as substrate elasticity, geometry, or topography with respect to morphology, proliferation, and differentiation. Although studies have demonstrated the role of focal adhesions in topography-mediated changes of gene expression, information linking substrate topography to the nucleus remains scarce. Here we show by two-dimensional gel electrophoresis and western blotting that A-type lamins and retinoblastoma protein are downregulated in mesenchymal stem/stromal cells cultured on 350 nm gratings compared to planar substrates; these changes lead to a decrease in proliferation and changes in differentiation potential.
doi:10.1371/journal.pone.0114698
PMCID: PMC4270691  PMID: 25521962
9.  Effect of titanium dioxide nanoparticles on zebrafish embryos and developing retina 
AIM
To investigate the impact of titanium dioxide nanoparticles (TiO2 NPs) on embryonic development and retinal neurogenesis.
METHODS
The agglomeration and sedimentation of TiO2 NPs solutions at different dilutions were observed, and the ultraviolet-visible spectra of their supernatants were measured. Zebrafish embryos were experimentally exposed to TiO2 NPs until 72h postfertilization (hpf). The retinal neurogenesis and distribution of the microglia were analyzed by immunohistochemistry and whole mount in situ hybridization.
RESULTS
The 1 mg/L was determined to be an appropriate exposure dose. Embryos exposed to TiO2 NPs had a normal phenotype. The neurogenesis was initiated on time, and ganglion cells, cones and rods were well differentiated at 72 hpf. The expression of fms mRNA and the 4C4 antibody, which were specific to microglia in the central nervous system (CNS), closely resembled their endogenous profile.
CONCLUSION
These data demonstrate that short-term exposure to TiO2 NPs at a low dose does not lead to delayed embryonic development or retinal neurotoxicity.
doi:10.3980/j.issn.2222-3959.2014.06.01
PMCID: PMC4270981  PMID: 25540739
titanium dioxide nanoparticles; retina; microglia; zebrafish
10.  Live-cell single-molecule imaging reveals clathrin and caveolin-1 dependent docking of SMAD4 at the cell membrane 
FEBS letters  2013;587(24):3912-3920.
Transforming growth factor β (TGF-β) signaling is important for many biological processes. Although the sequential events of this cascade are known, the dynamics remain speculative. Here, live-cell single-molecule total internal reflection fluorescence microscopy was used to monitor the dynamics of SMAD4, a TGF-β downstream effector, in MDA-MB-231 breast cancer cells. Contrary to previous belief, SMAD4 was detectable at the cytoplasmic membrane, displaying two subpopulations with different membrane docking behaviors. These subpopulations were regulated by clathrin and caveolin-1, and had opposing roles in the nuclear shuttling of SMAD4 and the subsequent transcriptional regulation of genes associated with cell migration. The notion that membrane-docking behaviors of downstream molecules could predict the cellular response to growth factors may revolutionize the way we view cell signaling.
doi:10.1016/j.febslet.2013.10.041
PMCID: PMC3903459  PMID: 24211445
11.  Quantification of Bird-to-Bird and Bird-to-Human Infections during 2013 Novel H7N9 Avian Influenza Outbreak in China 
PLoS ONE  2014;9(12):e111834.
From February to May, 2013, 132 human avian influenza H7N9 cases were identified in China resulting in 37 deaths. We developed a novel, simple and effective compartmental modeling framework for transmissions among (wild and domestic) birds as well as from birds to human, to infer important epidemiological quantifiers, such as basic reproduction number for bird epidemic, bird-to-human infection rate and turning points of the epidemics, for the epidemic via human H7N9 case onset data and to acquire useful information regarding the bird-to-human transmission dynamics. Estimated basic reproduction number for infections among birds is 4.10 and the mean daily number of human infections per infected bird is 3.16*10−5 [3.08*10−5, 3.23*10−5]. The turning point of 2013 H7N9 epidemic is pinpointed at April 16 for bird infections and at April 9 for bird-to-human transmissions. Our result reveals very low level of bird-to-human infections, thus indicating minimal risk of widespread bird-to-human infections of H7N9 virus during the outbreak. Moreover, the turning point of the human epidemic, pinpointed at shortly after the implementation of full-scale control and intervention measures initiated in early April, further highlights the impact of timely actions on ending the outbreak. This is the first study where both the bird and human components of an avian influenza epidemic can be quantified using only the human case data.
doi:10.1371/journal.pone.0111834
PMCID: PMC4257544  PMID: 25479054
12.  Phenological Adaptations in Ficus tikoua Exhibit Convergence with Unrelated Extra-Tropical Fig Trees 
PLoS ONE  2014;9(12):e114344.
Flowering phenology is central to the ecology and evolution of most flowering plants. In highly-specific nursery pollination systems, such as that involving fig trees (Ficus species) and fig wasps (Agaonidae), any mismatch in timing has serious consequences because the plants must balance seed production with maintenance of their pollinator populations. Most fig trees are found in tropical or subtropical habitats, but the dioecious Chinese Ficus tikoua has a more northerly distribution. We monitored how its fruiting phenology has adapted in response to a highly seasonal environment. Male trees (where fig wasps reproduce) had one to three crops annually, whereas many seed-producing female trees produced only one fig crop. The timing of release of Ceratosolen fig wasps from male figs in late May and June was synchronized with the presence of receptive figs on female trees, at a time when there were few receptive figs on male trees, thereby ensuring seed set while allowing remnant pollinator populations to persist. F. tikoua phenology has converged with those of other (unrelated) northern Ficus species, but there are differences. Unlike F. carica in Europe, all F. tikoua male figs contain male flowers, and unlike F. pumila in China, but like F. carica, it is the second annual generation of adult wasps that pollinate female figs. The phenologies of all three temperate fig trees generate annual bottlenecks in the size of pollinator populations and for female F. tikoua also a shortage of fig wasps that results in many figs failing to be pollinated.
doi:10.1371/journal.pone.0114344
PMCID: PMC4256256  PMID: 25474008
13.  Dual-Tree Complex Wavelet Transform and Image Block Residual-Based Multi-Focus Image Fusion in Visual Sensor Networks 
Sensors (Basel, Switzerland)  2014;14(12):22408-22430.
This paper presents a novel framework for the fusion of multi-focus images explicitly designed for visual sensor network (VSN) environments. Multi-scale based fusion methods can often obtain fused images with good visual effect. However, because of the defects of the fusion rules, it is almost impossible to completely avoid the loss of useful information in the thus obtained fused images. The proposed fusion scheme can be divided into two processes: initial fusion and final fusion. The initial fusion is based on a dual-tree complex wavelet transform (DTCWT). The Sum-Modified-Laplacian (SML)-based visual contrast and SML are employed to fuse the low- and high-frequency coefficients, respectively, and an initial composited image is obtained. In the final fusion process, the image block residuals technique and consistency verification are used to detect the focusing areas and then a decision map is obtained. The map is used to guide how to achieve the final fused image. The performance of the proposed method was extensively tested on a number of multi-focus images, including no-referenced images, referenced images, and images with different noise levels. The experimental results clearly indicate that the proposed method outperformed various state-of-the-art fusion methods, in terms of both subjective and objective evaluations, and is more suitable for VSNs.
doi:10.3390/s141222408
PMCID: PMC4299020  PMID: 25587878
multi-focus image fusion; dual-tree complex wavelet transform; image block residual; visual sensor networks
14.  Gene expression and genetic analysis reveal diverse causes of recessive self-compatibility in Brassica napus L. 
BMC Genomics  2014;15(1):1037.
Background
Brassica napus (AACC) is self-compatible, although its ancestor species Brassica rapa (AA) and Brassica oleracea (CC) are self-incompatible. Most B.napus accessions have dominant self-compatibility (SC) resulting from an insertion of 3.6 kb in the promoter region of BnSCR-1 on the A genome, while recessive SC in B.napus has rarely been observed. Expression and cloning of SRK and SCR genes and genetic analysis were carried out to dissect bases of recessive SC in B.napus.
Results
Eleven accessions were screened to identify stable recessive SC and had the S genotype BnS-7 on the A genome and BnS-6 on the C genome similarly to BrS-29 and BoS-15, respectively. In eight SC accessions, BnSCR-7 and BnSCR-6 were nearly undetectable and harbored no structural mutations in the promoters, while SRK genes were expressed at normal levels and contained intact CDS, with the exception of BnSRK-7 in line C32. SRK and SCR genes were expressed normally but their CDSs had no mutations in three SC accessions. In self-incompatible S-1300 and 11 F1 hybrids, SRK genes and BnSCR-1300 transcripts were present at high levels, while expression of the BnSCR-7 and BnSCR-6 were absent. Plants of S genotype S1300S1300 were completely SI, while SI phenotypes of SBnS-7SBnS-7 and S1300SBnS-7 plants were segregated in BC1 and F2 populations.
Conclusions
The recessive SC in eight accessions is caused by the loss of function of BnSCR-7 and BnSCR-6 in pollen. Translational repression contributes to the recessive SC in three accessions, whose SRK and SCR genes were expressed normally and had identical CDSs to BrS-29 or BoS-15. SI in 11 F1 hybrids relies on the expression of BnSCR-1300 rather than SRK genes. Other factor(s) independent of the S locus are involved in recessive SC. Therefore, diverse causes underlie recessive SC in B. napus, yielding insight into these complex mechanisms.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-1037) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2164-15-1037
PMCID: PMC4301934  PMID: 25432521
Brassica napus; Self-incompatibility (SI); S locus genes; Gene expression; Genetic analysis
15.  High Capacity Nanoporous Silicon Carrier for Systemic Delivery of Gene Silencing Therapeutics 
ACS nano  2013;7(11):10.1021/nn4035316.
Gene silencing agents such as small interfering RNA (siRNA) and microRNA offer the promise to modulate expression of almost every gene for the treatment of human diseases including cancer. However, lack of vehicles for effective systemic delivery to the disease organs has greatly limited their in vivo applications. In this study, we developed a high capacity polycation-functionalized nanoporous silicon (PCPS) platform comprised of nanoporous silicon microparticles functionalized with arginine-polyethyleneimine inside the nanopores for effective delivery of gene silencing agents. Incubation of MDA-MB-231 human breast cancer cells with PCPS loaded with STAT3 siRNA (PCPS/STAT3) or GRP78 siRNA (PCPS/GRP78) resulted in 91% and 83% reduction of STAT3 and GRP78 gene expression in vitro. Treatment of cells with a microRNA-18a mimic in PCPS (PCPS/miR-18) knocked down 90% expression of the microRNA-18a target gene ATM. Systemic delivery of PCPS/STAT3 siRNA in murine model of MDA-MB-231 breast cancer enriched particles in tumor tissues and reduced STAT3 expression in cancer cells, causing significant reduction of cancer stem cells in the residual tumor tissue. At the therapeutic dosage, PCPS/STAT3 siRNA did not trigger acute immune response in FVB mice, including changes in serum cytokines, chemokines and colony-stimulating factors. In addition, weekly dosing of PCPS/STAT3 siRNA for four weeks did not cause signs of sub-acute toxicity based on changes in body weight, hematology, blood chemistry, and major organ histology. Collectively, the results suggest that we have developed a safe vehicle for effective delivery of gene silencing agents.
doi:10.1021/nn4035316
PMCID: PMC3868485  PMID: 24131405
porous silicon; siRNA; microRNA; delivery; cancer therapy
16.  A comprehensive study design reveals treatment- and transcript abundance–dependent concordance between RNA-seq and microarray data 
Nature biotechnology  2014;32(9):926-932.
RNA-seq facilitates unbiased genome-wide gene-expression profiling. However, its concordance with the well-established microarray platform must be rigorously assessed for confident uses in clinical and regulatory application. Here we use a comprehensive study design to generate Illumina RNA-seq and Affymetrix microarray data from the same set of liver samples of rats under varying degrees of perturbation by 27 chemicals representing multiple modes of action (MOA). The cross-platform concordance in terms of differentially expressed genes (DEGs) or enriched pathways is highly correlated with treatment effect size, gene-expression abundance and the biological complexity of the MOA. RNA-seq outperforms microarray (90% versus 76%) in DEG verification by quantitative PCR and the main gain is its improved accuracy for low expressed genes. Nonetheless, predictive classifiers derived from both platforms performed similarly. Therefore, the endpoint studied and its biological complexity, transcript abundance, and intended application are important factors in transcriptomic research and for decision-making.
doi:10.1038/nbt.3001
PMCID: PMC4243706  PMID: 25150839
17.  Hypomethylation of long interspersed nuclear element-1 promoter is associated with poor outcomes for curative resected hepatocellular carcinoma 
Liver International  2013;34(1):136-146.
Background
Epigenetic alterations are well documented in hepatocarcinogenesis. However, hypomethylation of long interspersed nuclear element 1(LINE-1) promoter and its relationship with clinicopathological features in hepatocellular carcinoma (HCC) remain unknown.
Methods
The bisulfite-specific PCR and DNA sequencing analysis was performed to assess the methylation status of LINE-1 promoter in a pilot cohort of 71 patients with HCC. Additionally, methylation levels of two hot CpG sites of LINE-1 promoter, site 7 and 18 were measured by real-time PCR and compared with clinicopathological parameters in a cohort of 172 HCC. All the patients included were in BCLC stage A or B.
Results
Most patients with HCC (87.3%) showed hypomethylation of LINE-1 promoter compared with HBV-related cirrhosis and normal controls (P < 0.001). The HCC patients with LINE-1 promoter hypomethylation had a median tumour-free survival (TFS) and overall survival (OS) post-resection of 22.0 (95% CI: 13.3–30.7) months and 35.0 (95% CI: 24.0–46.1) months, respectively, compared with 40 months and ∼60 months for those with LINE-1 promoter hypermethylation (P < 0.05). Multivariate analyses showed that the hypomethylation level at CpG site 7 and 18 of LINE-1 promoter, along with tumour size and tumour differentiation, was independently associated with both TFS and OS for patients with HCC after resection.
Conclusion
Promoter hypomethylation of LINE-1, especially at the CpG site 7 and 18, was associated with a poor prognosis in HCC.
doi:10.1111/liv.12264
PMCID: PMC4238827  PMID: 23875825
Hepatocellular carcinoma; long interspersed nuclear element-1; methylation
18.  Synthesis and discovery of 18α-GAMG as anticancer agent in vitro and in vivo via down expression of protein p65 
Scientific Reports  2014;4:7106.
Glycyrrhizic acid (GA) is a natural product with favorable antitumor activity. But, glycyrrhetinic acid monoglucuronide (GAMG) showed stronger antitumor activity than GA. It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. So, in this study, 18α-GAMG was synthesized via biotransformation. In vitro studies showed that it displayed potent anticancer activity and high selectivity on tumor liver cell SMMC-7721 versus human normal liver cell L-02. The further results in vivo confirmed that it could significantly improve pathological changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. Western blot and immunofluorescence results indicated that the expression of p65-telomerase reverse transcriptase (TERT) was clearly down-regulated treated with it. Taken together, this study for the first time identified an active compound with high selectivity on tumor liver cell in mice. Furthermore, the title compound could inhibit the expression of protein p65 and TERT. These data support further studies to assess the rational design of more efficient p65 modulators in the future.
doi:10.1038/srep07106
PMCID: PMC4236752  PMID: 25407586
19.  Causes and managements of postoperative complications after degenerative scoliosis treatments with internal fixation 
Objective: To investigate the causes and managements of early postoperative complications of degenerative scoliosis (DS) treated with internal pedicle screw fixation. Methods: From Jan 2000 to Apr 2013, 325 DS patients treated with internal pedicle screw fixation in our hospital were retrospectively involved. The categories, causes, managements and outcomes of early postoperative complications were statistically analyzed. Results: Early postoperative complications occurred in 10.76% of the patients including 16 cases of lower limb numb or pain, 6 cases of decreased lower limb sensitivity and motor functions, which accounted for 62.86% of all complications, followed by incision infections (4/35, 11.43%) and rare cases of cerebrospinal fluid leakage, cardiac and renal inadequacy, urinary system and pulmonary infections. The incidence of overall complications (19.79%, p = 0.001) and nerve injuries (11.46%, p = 0.000) were significantly higher in long-segment than in short-segment fixations. Improper screw implanting, over correction of scoliosis and insufficient blood supply of the spinal cord during operation were risk factors for early postoperative complications and most of them were cured by anti-infection medication, incision dressing change, nerve nourishment, adjusting the screws and anti-osteoporosis treatments within 6 months after surgery. Only three cases with severe nerve injury did not improve until the 6 months postoperative follow-up. Conclusions: Most of the postoperative complications in our DS patients disappeared within 6 months after surgery and more than half of complications were nerve injuries.
PMCID: PMC4276203  PMID: 25550945
Degenerative scoliosis; internal fixation; postoperative complications
20.  Two-staged stent-assisted angioplasty treatment strategy for severe left main coronary distal bifurcation stenosis associated with the right coronary chronic total occlusion 
A 63-year-old female patient, with history of 8-year hypertension and 10-year hyperlipidemia, presented with severe left main coronary bifurcation stenosis (LMCS) associated with the right coronary artery chronic total occlusion (CTO-RCA). On the day of admission, she received drug treatment with aspirin, clopidogrel, heparin, statins, angiotensin converting enzyme inhibitors and β-blocker. On the next day, she underwent CTO recanalization with 6F guiding-catheter and two rapamycin-eluting stents, and showed no postoperative discomfort after interventional treatment. Considering having hypertensive nephropathy and chronic renal insufficiency, the patient then received intravenous saline full hydration therapy. Two weeks after successful completion of the RCA revascularization, the original collateral circulation in the blood flow from the LMC to RCA became two-way flow. Under the safe and reliable protective condition, staged percutaneous coronary intervention (PCI) with 6F XB3.0 guiding catheter and rapamycin-eluting stents was applied to treat the LMCL. 9-month postoperative follow-up with coronary computed tomographic imaging showed no restenosis inside the original stent, without any myocardial ischemic event. Our successful approach to turn the original unprotected LMCS combined with CTO-RCA into a protective one reduces the interventional risk and provides additional option besides coronary artery bypass graft surgery to treat such complex coronary artery disease (CAD).
PMCID: PMC4276235  PMID: 25550977
Left main coronary artery stenosis; the right coronary artery chronic total occlusion; angiography; percutaneous coronary intervention
21.  A Meta-Analysis of Unilateral versus Bilateral Pedicle Screw Fixation in Minimally Invasive Lumbar Interbody Fusion 
PLoS ONE  2014;9(11):e111979.
Study Design
Meta-analysis.
Background
Bilateral pedicle screw fixation (PS) after lumbar interbody fusion is a widely accepted method of managing various spinal diseases. Recently, unilateral PS fixation has been reported as effective as bilateral PS fixation. This meta-analysis aimed to comparatively assess the efficacy and safety of unilateral PS fixation and bilateral PS fixation in the minimally invasive (MIS) lumbar interbody fusion for one-level degenerative lumbar spine disease.
Methods
MEDLINE/PubMed, EMBASE, BIOSIS Previews, and Cochrane Library were searched through March 30, 2014. Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on unilateral versus bilateral PS fixation in MIS lumbar interbody fusion that met the inclusion criteria and the methodological quality standard were retrieved and reviewed. Data on participant characteristics, interventions, follow-up period, and outcomes were extracted from the included studies and analyzed by Review Manager 5.2.
Results
Six studies (5 RCTs and 1 CCT) involving 298 patients were selected. There were no significant differences between unilateral and bilateral PS fixation procedures in fusion rate, complications, visual analogue score (VAS) for leg pain, VAS for back pain, Oswestry disability index (ODI). Both fixation procedures had similar length of hospital stay (MD = 0.38, 95% CI = −0.83 to 1.58; P = 0.54). In contrast, bilateral PS fixation was associated with significantly more intra-operative blood loss (P = 0.002) and significantly longer operation time (P = 0.02) as compared with unilateral PS fixation.
Conclusions
Unilateral PS fixation appears as effective and safe as bilateral PS fixation in MIS lumbar interbody fusion but requires less operative time and causes less blood loss, thus offering a simple alternative approach for one-level lumbar degenerative disease.
doi:10.1371/journal.pone.0111979
PMCID: PMC4223107  PMID: 25375315
22.  A study on the mechanical characteristics of the EBM-printed Ti-6Al-4V LCP plates in vitro 
Purpose
The electron beam melting (EBM) Ti-6Al-4V material technology has been developed over a short time period. It was introduced through a research to develop Ti-6Al-4V implants for patients, but EBM printed locking compression plates have not been used for clinical implants. The main purpose of this study is to find whether the EBM Ti-6Al-4V plate suit for clinical implants.
Methods
First, we scanned an AO-locking compression plate (LCP) and printed LCP samples using EBM. Next, we evaluated the EBM plate surface roughness through optical microscopy as well as the LCP and EBM plates’ mechanical characteristics using the ASTM standard, which is commonly used to test the mechanical properties of bone plates subject to bending. Each sample was examined using a single-cycle four-point bending test and hardness testing to acquire data on bending stiffness, bending strength, bending structural stiffness, and hardness.
Results
The results show significant differences in bending stiffness, bending strength, bending structural stiffness, and hardness between the samples using EBM and the original LCP plates. The EBM-printed samples’ surface roughness was 0.49 ± 0.02 μm. The mean hardness of the LCP sample was 266.67 HV10 ± 5.8, and the EBM-printed sample mean hardness was 341.1 HV10 ± 1.93. The EBM samples’ bending stiffness was 87.67%, which is greater than using the LCP plates’; and the bending strength was 190.7% greater, the bending structural stiffness was 73.2% greater, and the hardness was 27.9% greater.
Conclusions
The results show that the EBM plates’ general mechanical strength was significantly greater than the LCP plates. An EBM plate is advantageous for clinical implants because it can be customized with great potential for improvement.
doi:10.1186/s13018-014-0106-3
PMCID: PMC4221727  PMID: 25370215
Ti-6Al-4V; EBM; Mechanical properties; Bone plate
23.  A Novel Algorithm to Enhance P300 in Single Trials: Application to Lie Detection Using F-Score and SVM 
PLoS ONE  2014;9(11):e109700.
The investigation of lie detection methods based on P300 potentials has drawn much interest in recent years. We presented a novel algorithm to enhance signal-to-noise ratio (SNR) of P300 and applied it in lie detection to increase the classification accuracy. Thirty-four subjects were divided randomly into guilty and innocent groups, and the EEG signals on 14 electrodes were recorded. A novel spatial denoising algorithm (SDA) was proposed to reconstruct the P300 with a high SNR based on independent component analysis. The differences between the proposed method and our/other early published methods mainly lie in the extraction and feature selection method of P300. Three groups of features were extracted from the denoised waves; then, the optimal features were selected by the F-score method. Selected feature samples were finally fed into three classical classifiers to make a performance comparison. The optimal parameter values in the SDA and the classifiers were tuned using a grid-searching training procedure with cross-validation. The support vector machine (SVM) approach was adopted to combine with an F-score because this approach had the best performance. The presented model F-score_SVM reaches a significantly higher classification accuracy for P300 (specificity of 96.05%) and non-P300 (sensitivity of 96.11%) compared with the results obtained without using SDA and compared with the results obtained by other classification models. Moreover, a higher individual diagnosis rate can be obtained compared with previous methods, and the presented method requires only a small number of stimuli in the real testing application.
doi:10.1371/journal.pone.0109700
PMCID: PMC4218862  PMID: 25365325
24.  Non-specific physiological background effects of acupuncture revealed by proteomic analysis in normal rats 
Background
The total effects of adequate real acupuncture treatment consist of pathologic-specific and non-specific physiological effects. The latter may be the fundamental component of the therapeutic effects of acupuncture. This study investigated the physiological background effects of acupuncture in normal rats treated with acupuncture.
Methods
Manual acupuncture was performed on normal rats at experienced acupoints, GV14 (Dazhui), BL12 (Fengmen) and BL13 (Feishu), once every other day for two weeks. The proteomic profile of rat lung tissue was examined using 2-DE/MS-based proteomic techniques. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were analyzed for differentially expressed proteins using the WebGestalt toolkit.
Results
In total, 25 differentially expressed protein spots were detected in the 2-DE gels. Among these spots, 24 corresponded to 20 unique proteins that were successfully identified using mass spectrometry. Subsequent GO and KEGG pathway analyses demonstrated that these altered proteins were mainly involved in biological processes, such as ‘protein stabilization’, ‘glycolysis/gluconeogenesis’ and ‘response to stimulus’.
Conclusions
Our study indicated the non-specific background effects of acupuncture at acupoints GV14, BL12 and BL13 likely maintained internal homeostasis via regulation of the local stimulus response, energy metabolism, and biomolecule function balance, which may be important contributors to the therapeutic effects of acupuncture.
doi:10.1186/1472-6882-14-375
PMCID: PMC4192787  PMID: 25282142
Acupuncture; Non-specific effect; Proteomics
25.  Development and Validation of a Multiplex Reverse Transcription PCR Assay for Simultaneous Detection of Three Papaya Viruses 
Viruses  2014;6(10):3893-3906.
Papaya ringspot virus (PRSV), Papaya leaf distortion mosaic virus (PLDMV), and Papaya mosaic virus (PapMV) produce similar symptoms in papaya. Each threatens commercial production of papaya on Hainan Island, China. In this study, a multiplex reverse transcription PCR assay was developed to detect simultaneously these three viruses by screening combinations of mixed primer pairs and optimizing the multiplex RT-PCR reaction conditions. A mixture of three specific primer pairs was used to amplify three distinct fragments of 613 bp from the P3 gene of PRSV, 355 bp from the CP gene of PLDMV, and 205 bp from the CP gene of PapMV, demonstrating the assay’s specificity. The sensitivity of the multiplex RT-PCR was evaluated by showing plasmids containing each of the viral target genes with 1.44 × 103, 1.79 × 103, and 1.91 × 102 copies for the three viruses could be detected successfully. The multiplex RT-PCR was applied successfully for detection of three viruses from 341 field samples collected from 18 counties of Hainan Island, China. Rates of single infections were 186/341 (54.5%), 93/341 (27.3%), and 3/341 (0.9%), for PRSV, PLDMV, and PapMV, respectively; 59/341 (17.3%) of the samples were co-infected with PRSV and PLDMV, which is the first time being reported in Hainan Island. This multiplex RT-PCR assay is a simple, rapid, sensitive, and cost-effective method for detecting multiple viruses in papaya and can be used for routine molecular diagnosis and epidemiological studies in papaya.
doi:10.3390/v6103893
PMCID: PMC4213569  PMID: 25337891
PRSV; PLDMV; PapMV; multiplex RT-PCR; detection; papaya

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