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1.  5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice 
PLoS ONE  2015;10(7):e0132074.
Objective
Sonodynamic therapy (SDT) is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5-Aminolevulinic Acid (5-ALA)-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro.
Methods
The dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (ΔψM), ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined.
Results
Treatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2) for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (P<0.01) and reduced the viability of UMR-106 cells (p<0.05). ALA-SDT further reduced the tumor volumes and viability of UMR-106 cells (p<0.01 for both). Pre-treatment with 5-ALA significantly enhanced the SDT-mediated apoptosis (p<0.01) and morphological changes. Furthermore, ALA-SDT significantly reduced the levels of ΔψM, but increased levels of ROS in UMR-106 cells (p<0.05 or p<0.01 vs. the Control or the Ultrasound). Moreover, ALA-SDT inhibited the proliferation of osteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (p<0.05 or p<0.01 vs. the Control or the Ultrasound).
Conclusions
The ALA-SDT significantly inhibited osteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway.
doi:10.1371/journal.pone.0132074
PMCID: PMC4498784  PMID: 26161801
2.  Targeted mutagenesis in soybean using the CRISPR-Cas9 system 
Scientific Reports  2015;5:10342.
Genome editing is a valuable technique for gene function analysis and crop improvement. Over the past two years, the CRISPR-Cas9 system has emerged as a powerful tool for precisely targeted gene editing. In this study, we predicted 11 U6 genes in soybean (Glycine max L.). We then constructed two vectors (pCas9-GmU6-sgRNA and pCas9-AtU6-sgRNA) using the soybean U6-10 and Arabidopsis U6-26 promoters, respectively, to produce synthetic guide RNAs (sgRNAs) for targeted gene mutagenesis. Three genes, Glyma06g14180, Glyma08g02290 and Glyma12g37050, were selected as targets. Mutations of these three genes were detected in soybean protoplasts. The vectors were then transformed into soybean hairy roots by Agrobacterium rhizogenes infection, resulting in efficient target gene editing. Mutation efficiencies ranged from 3.2–9.7% using the pCas9-AtU6-sgRNA vector and 14.7–20.2% with the pCas9-GmU6-sgRNA vector. Biallelic mutations in Glyma06g14180 and Glyma08g02290 were detected in transgenic hairy roots. Off-target activities associated with Glyma06g14180 and Glyma12g37050 were also detected. Off-target activity would improve mutation efficiency for the construction of a saturated gene mutation library in soybean. Targeted mutagenesis using the CRISPR-Cas9 system should advance soybean functional genomic research, especially that of genes involved in the roots and nodules.
doi:10.1038/srep10342
PMCID: PMC4448504  PMID: 26022141
3.  TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy 
Persistent HPV infection is recognized as the main etiologic factor for cervical cancer. HPV expresses the oncoproteins E6 and E7, both of which play key roles in maintaining viral infection and promoting carcinogenesis. While siRNA-mediated targeting of E6 and E7 transcripts temporarily induces apoptosis in HPV-positive cells, it does not eliminate viral DNA within the host genome, which can harbor escape mutants. Here, we demonstrated that specifically targeting E6 and E7 within host DNA with transcription activator–like effector nucleases (TALENs) induces apoptosis, inhibits growth, and reduces tumorigenicity in HPV-positive cell lines. TALEN treatment efficiently disrupted E6 and E7 oncogenes, leading to the restoration of host tumor suppressors p53 and retinoblastoma 1 (RB1), which are targeted by E6 and E7, respectively. In the K14-HPV16 transgenic mouse model of HPV-driven neoplasms, direct cervical application of HPV16-E7–targeted TALENs effectively mutated the E7 oncogene, reduced viral DNA load, and restored RB1 function and downstream targets transcription factor E2F1 and cycling-dependent kinase 2 (CDK2), thereby reversing the malignant phenotype. Together, the results from our study suggest that TALENs have potential as a therapeutic strategy for HPV infection and related cervical malignancy.
doi:10.1172/JCI78206
PMCID: PMC4382249  PMID: 25500889
4.  Cancerous inhibitor of PP2A is targeted by natural compound celastrol for degradation in non-small-cell lung cancer 
Carcinogenesis  2013;35(4):905-914.
Summary
Celastrol binds CIP2A and enhances CIP2A–CHIP interaction, leading to ubiquitination/degradation of CIP2A and inhibition of lung cancer cells in vitro and in vivo. Celastrol potentiates cisplatin’s efficacy by suppressing the CIP2A–Akt pathway, and therefore CIP2A inhibitors may represent novel therapeutics for cancer.
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein overexpressed and inversely associated with prognosis in lung and many other human cancers. It modulates phospho-Akt and stabilizes c-Myc, and is required for cell proliferation and malignant transformation, indicating that CIP2A may play an important role in carcinogenesis. We reported here that a small compound celastrol could induce a rapid degradation of CIP2A, through the ubiquitin–proteasome pathway with the carboxyl terminus of Hsp70-interacting protein (CHIP) as the E3 ligase. Celastrol directly bound CIP2A protein and promoted CIP2A–CHIP interaction, leading to subsequent degradation of CIP2A in non-small-cell lung cancer cells. Furthermore, celastrol effectively inhibited cell proliferation and induced apoptosis in non-small-cell lung cancer cells, whereas CIP2A silencing enhanced these effects. Celastrol also suppressed tumor growth in xenograft murine models. In addition, celastrol potentiated the inhibitory effect of cytotoxic agent cisplatin on lung cancer cells in vitro and in vivo via inhibition of CIP2A–Akt pathway. These data indicate that celastrol is a CIP2A-targeting agent that may have therapeutic potentials in lung cancer.
doi:10.1093/carcin/bgt395
PMCID: PMC4319067  PMID: 24293411
5.  A Non-Uniformly Under-Sampled Blade Tip-Timing Signal Reconstruction Method for Blade Vibration Monitoring 
Sensors (Basel, Switzerland)  2015;15(2):2419-2437.
High-speed blades are often prone to fatigue due to severe blade vibrations. In particular, synchronous vibrations can cause irreversible damages to the blade. Blade tip-timing methods (BTT) have become a promising way to monitor blade vibrations. However, synchronous vibrations are unsuitably monitored by uniform BTT sampling. Therefore, non-equally mounted probes have been used, which will result in the non-uniformity of the sampling signal. Since under-sampling is an intrinsic drawback of BTT methods, how to analyze non-uniformly under-sampled BTT signals is a big challenge. In this paper, a novel reconstruction method for non-uniformly under-sampled BTT data is presented. The method is based on the periodically non-uniform sampling theorem. Firstly, a mathematical model of a non-uniform BTT sampling process is built. It can be treated as the sum of certain uniform sample streams. For each stream, an interpolating function is required to prevent aliasing in the reconstructed signal. Secondly, simultaneous equations of all interpolating functions in each sub-band are built and corresponding solutions are ultimately derived to remove unwanted replicas of the original signal caused by the sampling, which may overlay the original signal. In the end, numerical simulations and experiments are carried out to validate the feasibility of the proposed method. The results demonstrate the accuracy of the reconstructed signal depends on the sampling frequency, the blade vibration frequency, the blade vibration bandwidth, the probe static offset and the number of samples. In practice, both types of blade vibration signals can be particularly reconstructed by non-uniform BTT data acquired from only two probes.
doi:10.3390/s150202419
PMCID: PMC4367313  PMID: 25621612
blade tip-timing; non-uniformly sampled signal; under-sampled signal reconstruction; on-line vibration; band-pass sampling
6.  Spin and field squeezing in a spin-orbit coupled Bose-Einstein condensate 
Scientific Reports  2015;5:8006.
Recently, strong spin-orbit coupling with equal Rashba and Dresselhaus strength has been realized in neutral atomic Bose-Einstein condensates via a pair of Raman lasers. In this report, we investigate spin and field squeezing of the ground state in spin-orbit coupled Bose-Einstein condensate. By mapping the spin-orbit coupled BEC to the well-known quantum Dicke model, the Dicke type quantum phase transition is presented with the order parameters quantified by the spin polarization and occupation number of harmonic trap mode. This Dicke type quantum phase transition may be captured by the spin and field squeezing arising from the spin-orbit coupling. We further consider the effect of a finite detuning on the ground state and show the spin polarization and the quasi-momentum exhibit a step jump at zero detuning. Meanwhile, we also find that the presence of the detuning enhances the occupation number of harmonic trap mode, while it suppresses the spin and the field squeezing.
doi:10.1038/srep08006
PMCID: PMC4306133  PMID: 25620051
8.  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
9.  Disruption of human papillomavirus 16 E6 gene by clustered regularly interspaced short palindromic repeat/Cas system in human cervical cancer cells 
OncoTargets and therapy  2014;8:37-44.
High-risk human papillomavirus (HPV), especially HPV16, is considered a main causative agent of cervical cancer. Upon HPV infection, the viral oncoprotein E6 disrupts the host tumor-suppressor protein p53, thus promoting malignant transformation of normal cervical cells. Here, we used the newly developed programmable ribonucleic acid-guided clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system to disrupt the HPV16 E6 gene. We showed that HPV16 E6 deoxyribonucleic acid was cleaved at specific sites, leading to apoptosis and growth inhibition of HPV16-positive SiHa and CaSki cells, but not HPV-negative C33A or human embryonic kidney 293 cells. We also observed downregulation of the E6 protein and restoration of the p53 protein. These data proved that the HPV16 E6 ribonucleic acid-guided CRISPR/Cas system might be an effective therapeutic agent in treating HPV infection-related cervical malignancy.
doi:10.2147/OTT.S64092
PMCID: PMC4278796  PMID: 25565864
CRISPR/Cas system; E6; p53; SiHa; CaSki; cervical cancer
10.  Boost Up Carrier Mobility for Ferroelectric Organic Transistor Memory via Buffering Interfacial Polarization Fluctuation 
Scientific Reports  2014;4:7227.
Ferroelectric organic field-effect transistors (Fe-OFETs) have been attractive for a variety of non-volatile memory device applications. One of the critical issues of Fe-OFETs is the improvement of carrier mobility in semiconducting channels. In this article, we propose a novel interfacial buffering method that inserts an ultrathin poly(methyl methacrylate) (PMMA) between ferroelectric polymer and organic semiconductor layers. A high field-effect mobility (μFET) up to 4.6 cm2 V−1 s−1 is obtained. Subsequently, the programming process in our Fe-OFETs is mainly dominated by the switching between two ferroelectric polarizations rather than by the mobility-determined charge accumulation at the channel. Thus, the “reading” and “programming” speeds are significantly improved. Investigations show that the polarization fluctuation at semiconductor/insulator interfaces, which affect the charge transport in conducting channels, can be suppressed effectively using our method.
doi:10.1038/srep07227
PMCID: PMC4245676  PMID: 25428665
11.  Five New Secondary Metabolites Produced by a Marine-Associated Fungus, Daldinia eschscholzii 
Marine Drugs  2014;12(11):5563-5575.
Five new compounds, including a benzopyran ribonic glycoside, daldiniside A (1), two isocoumarin ribonic glycosides, daldinisides B (2) and C (3), and two alkaloids, 1-(3-indolyl)-2R,3-dihydroxypropan-1-one (4) and 3-ethyl-2,5-pyrazinedipropanoic acid (5), along with five known compounds (6–10), were isolated from the EtOAc extract of the marine-associated fungus, Daldinia eschscholzii. Their structures were elucidated by extensive physicochemical and spectroscopic properties, besides comparison with literature data. The absolute configurations of compounds 1–3 were corroborated by chemical transformation, GC analysis and X-ray crystallographic analysis. Meanwhile, the absolute configuration of compound 4 and the planar structure of compound 6 were also determined based on the X-ray diffraction analysis. The cytotoxicity of compounds 1–10, antifungal and anti-HIV activities of compounds 1–5 and the in vitro assay for glucose consumption of compounds 1–3 were done in the anti-diabetic model, whereas none showed obvious activity.
doi:10.3390/md12115563
PMCID: PMC4245545  PMID: 25419997
marine-associated fungus; Daldinia eschscholzii; secondary metabolites; hydrolysis; GC analysis; X-ray diffraction analysis
12.  Meta-analysis of nonsteroidal anti-inflammatory drug intake and prostate cancer risk 
Background
Epidemiological studies of the association between nonsteroidal anti-inflammatory drug (NSAID) intake and the risk of prostate cancer still remain controversial. Therefore, we conducted a meta-analysis to evaluate the potential association between NSAID intake and prostate cancer risk.
Methods
Eligible studies were retrieved by both computerized searches and reviews of references. Subgroup analyses on country and design of study were also performed. Random or fixed-effect models were used to pool estimates of odds ratios (ORs) with 95% confidence intervals (CIs).
Results
We observed that the intake of aspirin was associated with a marginally decreased risk of prostate cancer (OR =0.95, 95% CI =0.93 to 0.98). A similar result was found between nonaspirin NSAIDs and prostate cancer risk (OR =0.94, 95% CI =0.90 to 0.98). However, a positive relation between all-NSAID intake and prostate cancer risk was observed (OR =1.18, 95% CI =1.15 to 1.22).
Conclusions
We observed a marginally inverse correlation between the intake of aspirin and prostate cancer risk. On the contrary, a positive relationship between all-NSAID intake and prostate cancer was detected. Further research needs to be conducted to better clarify potential biological mechanisms.
doi:10.1186/1477-7819-12-304
PMCID: PMC4194408  PMID: 25282624
Etiology; Meta-analysis; NSAIDs; Prostate cancer
13.  Genetic Diagnosis of Two Dopa-Responsive Dystonia Families by Exome Sequencing 
PLoS ONE  2014;9(9):e106388.
Dopa-responsive dystonia, a rare disorder typically presenting in early childhood with lower limb dystonia and gait abnormality, responds well to levodopa. However, it is often misdiagnosed with the wide spectrum of phenotypes. By exome sequencing, we make a rapid genetic diagnosis for two atypical dopa-responsive dystonia pedigrees. One pedigree, presented with prominent parkinsonism, was misdiagnosed as Parkinson's disease until a known mutation in GCH1 (GTP cyclohydrolase 1) gene (NM_000161.2: c.631_632delAT, p.Met211ValfsX38) was found. The other pedigree was detected with a new compound heterozygous mutation in TH (tyrosine hydroxylase) gene [(NM_000360.3: c.911C>T, p.Ala304Val) and (NM_000360.3: c.1358G>A, p.Arg453His)], whose proband, a pregnant woman, required a rapid and less-biased genetic diagnosis. In conclusion, we demonstrated that exome sequencing could provide a precise and rapid genetic testing in the diagnosis of Mendelian diseases, especially for diseases with wide phenotypes.
doi:10.1371/journal.pone.0106388
PMCID: PMC4152247  PMID: 25181484
14.  Exploring MicroRNA-Like Small RNAs in the Filamentous Fungus Fusarium oxysporum 
PLoS ONE  2014;9(8):e104956.
RNA silencing such as quelling and meiotic silencing by unpaired DNA (MSUD) and several other classes of special small RNAs have been discovered in filamentous fungi recently. More than four different mechanisms of microRNA-like RNAs (milRNAs) production have been illustrated in the model fungus Neurospora crassa including a dicer-independent pathway. To date, very little work focusing on small RNAs in fungi has been reported and no universal or particular characteristic of milRNAs were defined clearly. In this study, small RNA and degradome libraries were constructed and subsequently deep sequenced for investigating milRNAs and their potential cleavage targets on the genome level in the filamentous fungus F. oxysporum f. sp. lycopersici. As a result, there is no intersection of conserved miRNAs found by BLASTing against the miRBase. Further analysis showed that the small RNA population of F. oxysporum shared many common features with the small RNAs from N. crassa and other fungi. According to the known standards of miRNA prediction in plants and animals, milRNA candidates from 8 families (comprising 19 members) were screened out and identified. However, none of them could trigger target cleavage based on the degradome data. Moreover, most major signals of cleavage in transcripts could not match appropriate complementary small RNAs, suggesting that other predominant modes for milRNA-mediated gene regulation could exist in F. oxysporum. In addition, the PAREsnip program was utilized for comprehensive analysis and 3 families of small RNAs leading to transcript cleavage were experimentally validated. Altogether, our findings provided valuable information and important hints for better understanding the functions of the small RNAs and milRNAs in the fungal kingdom.
doi:10.1371/journal.pone.0104956
PMCID: PMC4139310  PMID: 25141304
15.  Analytical and Numerical Investigations into Hemisphere-Shaped Electrostatic Sensors 
Sensors (Basel, Switzerland)  2014;14(8):14021-14037.
Electrostatic sensors have been widely used in many applications due to their advantages of low cost and robustness. Their spatial sensitivity and time-frequency characteristics are two important performance parameters. In this paper, an analytical model of the induced charge on a novel hemisphere-shaped electrostatic sensor was presented to investigate its accurate sensing characteristics. Firstly a Poisson model was built for electric fields produced by charged particles. Then the spatial sensitivity and time-frequency response functions were directly derived by the Green function. Finally, numerical calculations were done to validate the theoretical results. The results demonstrate that the hemisphere-shaped sensors have highly 3D-symmetrical spatial sensitivity expressed in terms of elementary function, and the spatial sensitivity is higher and less homogeneous near the hemispherical surface and vice versa. Additionally, the whole monitoring system, consisting of an electrostatic probe and a signal conditioner circuit, acts as a band-pass filter. The time-frequency characteristics depend strongly on the spatial position and velocity of the charged particle, the radius of the probe as well as the equivalent resistance and capacitance of the circuit.
doi:10.3390/s140814021
PMCID: PMC4179042  PMID: 25090419
electrostatic monitoring; hemisphere-shaped sensors; Green function; spatial sensitivity; induced charge
16.  Disruption of HPV16-E7 by CRISPR/Cas System Induces Apoptosis and Growth Inhibition in HPV16 Positive Human Cervical Cancer Cells 
BioMed Research International  2014;2014:612823.
High-risk human papillomavirus (HR-HPV) has been recognized as a major causative agent for cervical cancer. Upon HPV infection, early genes E6 and E7 play important roles in maintaining malignant phenotype of cervical cancer cells. By using clustered regularly interspaced short palindromic repeats- (CRISPR-) associated protein system (CRISPR/Cas system), a widely used genome editing tool in many organisms, to target HPV16-E7 DNA in HPV positive cell lines, we showed for the first time that the HPV16-E7 single-guide RNA (sgRNA) guided CRISPR/Cas system could disrupt HPV16-E7 DNA at specific sites, inducing apoptosis and growth inhibition in HPV positive SiHa and Caski cells, but not in HPV negative C33A and HEK293 cells. Moreover, disruption of E7 DNA directly leads to downregulation of E7 protein and upregulation of tumor suppressor protein pRb. Therefore, our results suggest that HPV16-E7 gRNA guided CRISPR/Cas system might be used as a therapeutic strategy for the treatment of cervical cancer.
doi:10.1155/2014/612823
PMCID: PMC4127252  PMID: 25136604
17.  Highly efficient generation of airway and lung epithelial cells from human pluripotent stem cells 
Nature biotechnology  2013;32(1):84-91.
The ability to generate lung and airway epithelial cells from human pluripotent stem cells (hPSCs) would have applications in regenerative medicine, drug screening and modeling of lung disease, and studies of human lung development. We established, based on developmental paradigms, a highly efficient method for directed differentiation of hPSCs into lung and airway epithelial cells. Long-term differentiation in vivo and in vitro yielded basal, goblet, Clara, ciliated, type I and type II alveolar epithelial cells. Type II alveolar epithelial cells generated were capable of surfactant protein-B uptake and stimulated surfactant release, providing evidence of specific function. Inhibiting or removing agonists to signaling pathways critical for early lung development in the mouse—retinoic acid, Wnt and BMP—recapitulated defects in corresponding genetic mouse knockouts. The capability of this protocol to generate most cell types of the respiratory system suggests its utility for deriving patient-specific therapeutic cells.
doi:10.1038/nbt.2754
PMCID: PMC4101921  PMID: 24291815
18.  Enhanced Cold Field Emission of Large-area Arrays of Vertically Aligned ZnO-nanotapers via Sharpening: Experiment and Theory 
Scientific Reports  2014;4:4676.
Large-area arrays of vertically aligned ZnO-nanotapers with tailored taper angle and height are electrodeposited on planar Zn-plate via continuously tuning the Zn(NH3)4(NO3)2 concentration in the electrolyte. Experimental measurements reveal that the field-emission performance of the ZnO-nanotaper arrays is enhanced with the sharpness and height of the ZnO-nanotapers. Theoretically, the ZnO-nanotaper is simplified to a “charge disc” model, based on which the characteristic macroscopic field enhancement factor (γC) is quantified. The theoretically calculated γC values are in good agreement with the experimental ones measured from arrays of ZnO-nanotapers with a series of geometrical parameters. The ZnO-nanotaper arrays have promising potentials in field-emission. The electrochemical synthetic strategy we developed may be extended to nanotaper arrays of other materials that are amenable to electrodeposition, and the “charge disc” model can be used for quasi-one-dimensional field emitters of other materials with nano-sized diameters.
doi:10.1038/srep04676
PMCID: PMC3985081  PMID: 24728408
19.  Alpha-enolase as a potential cancer prognostic marker promotes cell growth, migration, and invasion in glioma 
Molecular Cancer  2014;13:65.
Background
The success of using glycolytic inhibitors for cancer treatment relies on better understanding the roles of each frequently deregulated glycolytic genes in cancer. This report analyzed the involvement of a key glycolytic enzyme, alpha-enolase (ENO1), in tumor progression and prognosis of human glioma.
Methods
ENO1 expression levels were examined in glioma tissues and normal brain (NB) tissues. The molecular mechanisms of ENO1 expression and its effects on cell growth, migration and invasion were also explored by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, Transwell chamber assay, Boyden chamber assay, Western blot and in vivo tumorigenesis in nude mice.
Results
ENO1 mRNA and protein levels were upregulated in glioma tissues compared to NB. In addition, increased ENO1 was associated disease progression in glioma samples. Knocking down ENO1 expression not only significantly decreased cell proliferation, but also markedly inhibited cell migration and invasion as well as in vivo tumorigenesis. Mechanistic analyses revealed that Cyclin D1, Cyclin E1, pRb, and NF-κB were downregulated after stable ENO1 knockdown in glioma U251 and U87 cells. Conversely, knockdown of ENO1 resulted in restoration of E-cadherin expression and suppression of mesenchymal cell markers, such as Vimentin, Snail, N-Cadherin, β-Catenin and Slug. Furthermore, ENO1 suppression inactivated PI3K/Akt pathway regulating the cell growth and epithelial-mesenchymal transition (EMT) progression.
Conclusion
Overexpression of ENO1 is associated with glioma progression. Knockdown of ENO1 expression led to suppressed cell growth, migration and invasion progression by inactivating the PI3K/Akt pathway in glioma cells.
doi:10.1186/1476-4598-13-65
PMCID: PMC3994408  PMID: 24650096
ENO1; Glioma; Cell growth; EMT; PI3K/Akt
20.  Genome sequence of the anaerobic bacterium Bacillus sp. strain ZYK, a selenite and nitrate reducer from paddy soil 
Standards in Genomic Sciences  2014;9(3):646-654.
Bacillus sp. strain ZYK, a member of the phylum Firmicutes, is of interest for its ability to reduce nitrate and selenite and for its resistance to arsenic under anaerobic conditions. Here we describe some key features of this organism, together with the complete genome sequence and annotation. The 3,575,797 bp long chromosome with its 3,454 protein-coding and 70 RNA genes, and the information gained from its sequence will be relevant to the elucidation of microbially-mediated transformations of nitrogen, selenium and arsenic in paddy soil.
doi:10.4056/sigs.3817480
PMCID: PMC4148952  PMID: 25197451
anaerobic; spore-forming; Gram-positive; nitrate-reduction; selenite-reduction; arsenic resistance; paddy soil; Bacillaceae
21.  Tea consumption and prostate cancer: an updated meta-analysis 
Objectives
Tea is supposed to have chemopreventive effect against various cancers. However, the protective role of tea in prostate cancer is still controversial. The aim of this study is to elucidate the association between tea consumption and prostate cancer risk by meta-analysis.
Methods
A total of 21 published articles were retrieved via both computerized searches and review of references. Estimates of OR/RR for highest versus non/lowest tea consumption levels were pooled on the basis of random effect model or fixed effect model as appropriate. Stratified analyses on tea type, population and study design were also conducted.
Results
No statistical significance was detected between tea consumption and prostate cancer risk in meta-analysis of all included studies (odds ratio (OR) = 0.86, 95% CI (0.69-1.04)). Furthermore, stratified analyses on population (Asian, OR = 0.81, 95% CI (0.55-1.08); non-Asian, OR = 0.89, 95% CI (0.72-1.07)) and tea type (green tea, OR = 0.79, 95% CI (0.43-1.14); black tea, OR = 0.88, 95% CI (0.73-1.02)) also yielded non-significant association. Only the case–control study subgroup demonstrated a borderline protective effect for tea consumption against prostate cancer (OR = 0.77, 95% CI (0.55-0.98)).
Conclusion
Our analyses did not support the conclusion that tea consumption could reduce prostate cancer risk. Further epidemiology studies are needed.
doi:10.1186/1477-7819-12-38
PMCID: PMC3925323  PMID: 24528523
Prostate cancer; Tea; Meta-analysis
22.  Analysis of promoters of microRNAs from a Glycine max degradome library* #  
Objective: MicroRNAs (miRNAs) are genome-encoded, small non-coding RNAs that play important functions in development, biotic and abiotic stress responses, and other processes. Our aim was to explore the regulation of miRNA expression. Methods: We used bioinformatics methods to predict the core promoters of 440 miRNAs identified from a soybean (Glycine max) degradome library and to analyze cis-acting elements for 369 miRNAs. Results: The prediction results showed that 83.86% of the 440 miRNAs contained promoters in their upstream sequences, and 8.64% (38 loci) in their downstream sequences. The distributions of two core promoter elements, TATA-boxes and transcription start sites (TSSs), were similar. The cis-acting elements were examined to provide clues to the function and regulation of spatiotemporal expression of the miRNAs. Analyses of miRNA cis-elements and targets indicated a potential auxin response factor (ARF)- and gibberellin response factor (GARF)-mediated negative feedback loop for miRNA expression. Conclusions: The features of miRNAs from a Glycine max degradome library obtained here provide insights into the transcription regulation and functions of miRNAs in soybean.
doi:10.1631/jzus.B1300179
PMCID: PMC3924388  PMID: 24510705
Glycine max; MicroRNA (miRNA); Promoter; Cis-acting element; Prediction
23.  Age-Dependent Transition from Cell-Level to Population-Level Control in Murine Intestinal Homeostasis Revealed by Coalescence Analysis 
PLoS Genetics  2013;9(2):e1003326.
In multi-cellular organisms, tissue homeostasis is maintained by an exquisite balance between stem cell proliferation and differentiation. This equilibrium can be achieved either at the single cell level (a.k.a. cell asymmetry), where stem cells follow strict asymmetric divisions, or the population level (a.k.a. population asymmetry), where gains and losses in individual stem cell lineages are randomly distributed, but the net effect is homeostasis. In the mature mouse intestinal crypt, previous evidence has revealed a pattern of population asymmetry through predominantly symmetric divisions of stem cells. In this work, using population genetic theory together with previously published crypt single-cell data obtained at different mouse life stages, we reveal a strikingly dynamic pattern of stem cell homeostatic control. We find that single-cell asymmetric divisions are gradually replaced by stochastic population-level asymmetry as the mouse matures to adulthood. This lifelong process has important developmental and evolutionary implications in understanding how adult tissues maintain their homeostasis integrating the trade-off between intrinsic and extrinsic regulations.
Author Summary
In multi-cellular organisms, there is a static equilibrium maintaining cells of various forms. This homeostasis is achieved by an exquisite balance between stem cell proliferation and differentiation. Understanding how different species and organ types maintain this dynamic equilibrium has been an interesting question for both evolutionary and developmental biologists. Using population genetic theory together with previously published single-cell sequencing data collected from mouse intestinal crypts at two points in development, we have revealed a dynamic picture of stem cell renewal in intestinal crypts. We found that intestinal equilibrium is maintained at the single-cell level through predominantly asymmetric stem cell divisions at early life stages, but progressively switches to a population level homeostasis with only symmetric divisions as the mouse matures to adulthood. This dynamic process, likely to be conserved across species, has important developmental and evolutionary implications in understanding how adult tissues maintain their homeostasis integrating lifelong trade-offs between intrinsic and extrinsic factors.
doi:10.1371/journal.pgen.1003326
PMCID: PMC3585040  PMID: 23468655
24.  Human lymphohematopoietic reconstitution and immune function in immunodeficient mice receiving cotransplantation of human thymic tissue and CD34+ cells 
Cellular & molecular immunology  2012;9(3):232-236.
Small animal models with functional human lymphohematopoietic systems are highly valuable for the study of human immune function under physiological and pathological conditions. Over the last two decades, numerous efforts have been devoted towards the development of such humanized mouse models. This review is focused on human lymphohematopoietic reconstitution and immune function in humanized mice by cotransplantation of human fetal thymic tissue and CD34+ cells. The potential use of these humanized mice in translational biomedical research is also discussed.
doi:10.1038/cmi.2011.63
PMCID: PMC3346882  PMID: 22307039
25.  Human lymphohematopoietic reconstitution and immune function in immunodeficient mice receiving cotransplantation of human thymic tissue and CD34+ cells 
Small animal models with functional human lymphohematopoietic systems are highly valuable for the study of human immune function under physiological and pathological conditions. Over the last two decades, numerous efforts have been devoted towards the development of such humanized mouse models. This review is focused on human lymphohematopoietic reconstitution and immune function in humanized mice by cotransplantation of human fetal thymic tissue and CD34+ cells. The potential use of these humanized mice in translational biomedical research is also discussed.
doi:10.1038/cmi.2011.63
PMCID: PMC3346882  PMID: 22307039
humanized mouse; hematopoiesis; immune system; immunodeficient mouse; thymopoiesis

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