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1.  De novo transcriptome sequencing and comprehensive analysis of the drought-responsive genes in the desert plant Cynanchum komarovii 
BMC Genomics  2015;16:753.
Cynanchum komarovii Al Iljinski is a xerophytic plant species widely distributing in the severely adverse environment of the deserts in northwest China. At present, the detailed transcriptomic and genomic data for C. komarovii are still insufficient in public databases.
To investigate changes of drought-responsive genes and explore the mechanisms of drought tolerance in C. komarovii, approximately 27.5 GB sequencing data were obtained using Illumina sequencing technology. After de novo assembly 148,715 unigenes were generated with an average length of 604 bp. Among these unigenes, 85,106 were annotated with gene descriptions, conserved domains, gene ontology terms, and metabolic pathways. The results showed that a great number of unigenes were significantly affected by drought stress. We identified 3134 unigenes as reliable differentially expressed genes (DEGs). During drought stress, the regulatory genes were involved in signaling transduction pathways and in controlling the expression of functional genes. Moreover, C. komarovii activated many functional genes that directly protected against stress and improved tolerance to adapt drought condition. Importantly, the DEGs were involved in biosynthesis, export, and regulation of plant cuticle, suggesting that plant cuticle may play a vital role in response to drought stress and the accumulation of cuticle may allow C. komarovii to improve the tolerance to drought stress.
This is the first large-scale reference sequence data of C. komarovii, which enlarge the genomic resources of this species. Our comprehensive transcriptome analysis will provide a valuable resource for further investigation into the molecular adaptation of desert plants under drought condition and facilitate the exploration of drought-tolerant candidate genes.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1873-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4594960  PMID: 26444539
Cynanchum komarovii; Drought-stress response; Illumina sequencing; Transcriptome
2.  A novel small-molecule compound diaporine A inhibits non-small cell lung cancer growth by regulating miR-99a/mTOR signaling 
Cancer Biology & Therapy  2014;15(10):1423-1430.
MicroRNAs (miRNAs) dysregulation is critically involved in lung cancer. Regulating miRNAs by natural agents may be a new strategy for cancer treatment. We previously found that a novel small-molecule compound diaporine A (D261), a natural product of endophytic fungus 3lp-10, had potential anti-cancer activites. In the present study, the inhibitory effect of D261 on non-small cell lung cancer (NSCLC) growth and its possible mechanisms involving miRNA regulation were investigated. By cell viability assay, cell proliferation analysis, and clonal growth assay, we proved that D261 effectively inhibited the proliferation of NSCLC cells (NCI-H460 and A549) in vitro. Administration of D261 (5 mg/kg) to NCI-H460 xenografts bearing mice also inhibited tumor growth and decreased the expression of cell proliferation regulator, midkine. Moreover, D261 induced cell cycle arrest with a reduced expression of various G1/S transition-related molecules including cyclin D1, cyclin E1, CDK4, and CDK2, but without influencing apoptosis in NSCLC cells. Intriguingly, D261 modified expressions of some miRNAs and especially upregulated miR-99a, whose direct target was mammalian target of rapamycin (mTOR). Furthermore, overexpression of miR-99a antagonized the anti-tumor actions of D261 including the suppression of mTOR pathway activation, cell cycle-related proteins and cell growth. In addition, blocking of miR-99a expression by transfection of miR-99a inhibitors before D261 treatment counteracted the anti-tumor effects of D261. These data suggest that miR-99a/mTOR pathway was involved in D261-induced tumor suppression in NSCLC cells. D261 might be a potent anti-cancer agent by upregulating miR-99a expression.
PMCID: PMC4130735  PMID: 25046358
diaporine A; natural agent; NSCLC; cell cycle; G1/S transition; miR-99a; mTOR
3.  Profiling small molecule inhibitors against helix–receptor interactions: the Bcl-2 family inhibitor BH3I-1 potently inhibits p53/hDM2†‡ 
We validate a practical methodology for the rapid profiling of small molecule inhibitors of protein–protein interactions. We find that a well known BH3 family inhibitor can potently inhibit the p53/hDM2 interaction.
PMCID: PMC4576826  PMID: 20856941
4.  Biomimetic chemical sensors using bioengineered olfactory and taste cells 
Bioengineered  2014;5(5):326-330.
Biological olfactory and taste systems are natural chemical sensing systems with unique performances for the detection of environmental chemical signals. With the advances in olfactory and taste transduction mechanisms, biomimetic chemical sensors have achieved significant progress due to their promising prospects and potential applications. Biomimetic chemical sensors exploit the unique capability of biological functional components for chemical sensing, which are often sourced from sensing units of biological olfactory or taste systems at the tissue level, cellular level, or molecular level. Specifically, at the cellular level, there are mainly two categories of cells have been employed for the development of biomimetic chemical sensors, which are natural cells and bioengineered cells, respectively. Natural cells are directly isolated from biological olfactory and taste systems, which are convenient to achieve. However, natural cells often suffer from the undefined sensing properties and limited amount of identical cells. On the other hand, bioengineered cells have shown decisive advantages to be applied in the development of biomimetic chemical sensors due to the powerful biotechnology for the reconstruction of the cell sensing properties. Here, we briefly summarized the most recent advances of biomimetic chemical sensors using bioengineered olfactory and taste cells. The development challenges and future trends are discussed as well.
PMCID: PMC4156494  PMID: 25482234
chemical sensor; bioengineered cell; olfactory; taste; biomimetic sensor
5.  Resistance of Trichoplusia ni Populations Selected by Bacillus thuringiensis Sprays to Cotton Plants Expressing Pyramided Bacillus thuringiensis Toxins Cry1Ac and Cry2Ab 
Two populations of Trichoplusia ni that had developed resistance to Bacillus thuringiensis sprays (Bt sprays) in commercial greenhouse vegetable production were tested for resistance to Bt cotton (BollGard II) plants expressing pyramided Cry1Ac and Cry2Ab. The T. ni colonies resistant to Bacillus thuringiensis serovar kurstaki formulations were not only resistant to the Bt toxin Cry1Ac, as previously reported, but also had a high frequency of Cry2Ab-resistant alleles, exhibiting ca. 20% survival on BollGard II foliage. BollGard II-resistant T. ni strains were established by selection with BollGard II foliage to further remove Cry2Ab-sensitive alleles in the T. ni populations. The BollGard II-resistant strains showed incomplete resistance to BollGard II, with adjusted survival values of 0.50 to 0.78 after 7 days. The resistance to the dual-toxin cotton plants was conferred by two genetically independent resistance mechanisms: one to Cry1Ac and one to Cry2Ab. The 50% lethal concentration of Cry2Ab for the resistant strain was at least 1,467-fold that for the susceptible T. ni strain. The resistance to Cry2Ab in resistant T. ni was an autosomally inherited, incompletely recessive monogenic trait. Results from this study indicate that insect populations under selection by Bt sprays in agriculture can be resistant to multiple Bt toxins and may potentially confer resistance to multitoxin Bt crops.
PMCID: PMC4325153  PMID: 25480752
6.  Reappraisal of the role of postoperative radiation therapy in patients with pIIIa-N2 non-small cell lung cancer: A propensity score matching analysis 
Thoracic Cancer  2015;6(5):570-578.
Reappraisal of the role of postoperative radiotherapy in pN2 non-small cell lung cancer (NSCLC) patients according to N1 lymph node involvement.
A total of 218 pIIIa-N2 NSCLC patients who underwent complete surgical resection with systematic nodal dissections were enrolled. Propensity scores were used for matching N1 involvement. Overall survival (OS) and disease-free survival (DFS) were analyzed retrospectively.
After matching, pN2b patients without N1 involvement (pN0N2b) exhibited better prognoses than those with N1 involvement (pN1N2b) (5-year OS: 37.5% vs. 7.1%, P = 0.008; 5-year DFS: 31.8% vs. 4.6%, P = 0.004). Similar results were not detected in pN2a disease (5-year OS: 37.8% vs. 31.0%, P = 0.517; 5-year DFS: 27.1% vs. 20.2%, P = 0.788). The five-year OS of patients who received no adjuvant therapy (22 pN2a cases, 7 pN0N2b, 5 pN1N2b), adjuvant chemotherapy alone (74 pN2a cases, 11 pN0N2b, 17 pN1N2b) or chemoradiotherapy (25 pN2a cases, 7 pN0N2b, 6 pN1N2b) were compared (pN2a: 31.3%, 37.0%, and 32.0%, P = 0.808; pN0N2b: 0.0%, 18.2%, and 71.4%, P = 0.108; pN1N2b: 0.0%, 0.0%, and 33.3%, P < 0.0001). The five-year DFS was also analyzed (pN2a: 31.6%, 24.0%, and 18.3%, P = 0.410; pN0N2b: 0.0%, 11.1%, and 57.1%, P = 0.192; pN1N2b: 0.0%, 0.0%, and 16.7%, P < 0.0001). Multivariate analysis revealed that the novel classification based on N1 involvement and pN2a/pN2b staging was an independent prognostic factor of OS and DFS.
N1 involvement significantly impacted the prognosis of pN2b NSCLC patients. The benefit of adjuvant therapy in pN2a and pN0N2b patients requires confirmation by further study.
PMCID: PMC4567001  PMID: 26445605
Chemoradiotherapy; non-small cell lung cancer; prognosis; propensity score
7.  Does the response to induction chemotherapy impact the timing of thoracic radiotherapy for limited-stage small-cell lung cancer? 
Thoracic Cancer  2015;6(5):605-612.
To investigate whether the response to induction chemotherapy (IC) would impact the timing of thoracic radiotherapy (TRT) in limited-stage small-cell lung cancer (LS-SCLC).
A total of 146 patients with LS-SCLC who had received two to six cycles of IC followed by TRT from January 2009 to December 2011 at our hospital were included in this study. Patients were divided into two groups based on the time TRT was administered: early TRT (administered after 2–3 cycles of chemotherapy) or late TRT (administered after 4–6 cycles). Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Multivariate Cox regression analysis was performed to evaluate the independent factors affecting survival.
The median OS for patients who received early TRT and late TRT was 29.0 and 19.9 months, respectively, (P = 0.018) and the median PFS was 18.5 and 13.8 months, respectively (P = 0.049). In patients who achieved complete remission (CR) or partial remission (PR) after two to three cycles of IC, the median OS was 36.1 and 22.5 months in the early and late TRT subgroups, respectively (P = 0.009); the corresponding median PFS was 20.2 and 13.8 months, respectively (P = 0.038). In the patients who did not achieve CR or PR, no statistic difference was found in OS or PFS between the two subgroups.
Patients who received early TRT had more favorable outcomes than those who received late TRT. Patients who achieved CR or PR after two to three cycles of IC obtained more benefit from early TRT.
PMCID: PMC4567006  PMID: 26445609
Induction chemotherapy; radiotherapy; small cell lung carcinoma
8.  Enhanced secretion of a methyl parathion hydrolase in Pichia pastoris using a combinational strategy 
Although Pichia pastoris has been successfully used to produce various recombinant heterologous proteins, the efficiency varies. In this study, we used methyl parathion hydrolase (MPH) from Ochrobactrum sp. M231 as an example to study the effect of protein amino acid sequence on secretion from P. pastoris.
The results indicated that the protein N-terminal sequence, the endoplasmic reticulum (ER) retention signal (KKXX) at the protein C-terminus, and the acidic stability of the protein could affect its secretion from P. pastoris. Mutations designed based on these sequence features markedly improved secretion from P. pastoris. In addition, we found that the secretion properties of a protein can be cumulative when all of the above strategies are combined. The final mutant (CHBD-DQR) designed by combining all of the strategies greatly improved secretion and the secreted MPH activity of CHBD-DQR was enhanced up to 195-fold compared with wild-type MPH without loss of catalytic efficiency.
These results demonstrate that the secretion of heterologous proteins from P. pastoris could be improved by combining changes in multiple protein sequence features.
Electronic supplementary material
The online version of this article (doi:10.1186/s12934-015-0315-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4551668  PMID: 26310666
Methyl parathion hydrolase; Cytochromes heme binding domain; KKXX retrieval signal; Acid stability; Secretory expression; Pichia pastoris
9.  The prognosis factor of adjuvant radiation therapy after surgery in uterine sarcomas 
OncoTargets and therapy  2015;8:2339-2344.
This retrospective study evaluated the role of adjuvant radiotherapy (AR) after surgery in patients with uterine sarcoma and analyzed the prognostic factors of local-regional failure-free survival (LRFFS) and overall survival (OS).
Patients and methods
A study of a total of 182 patients with uterine sarcoma was conducted between June 1994 and October 2014. Adjuvant radiotherapy was defined as postoperative external beam radiation to the pelvis (30–50 Gray/10–25 fractions at five fractions/week). The primary end point was LRFFS, and the secondary end point was OS. Kaplan–Meier curves were compared using the log-rank test. Cox regression analyses were used to determine prognosticators for LRFFS and OS.
The median follow-up time of all patients was 75 months, with a 5-year LRFFS of 62.1%. The 2-year and 5-year LRFFS rates were longer for those who received AR than for those who did not receive AR (83.4% vs 70.3%; 78% vs 55.3%; P=0.013). The 5-year OS of all patients was 56.2%, and no significant differences were observed in the 2-year and 5-year OS rates between these two groups (82.7% vs 71.4%; 64.1% vs 51.7%; P=0.067). Importantly, in patients with leiomyosarcoma, the 2-year and 5-year LRFFS and OS rates were longer for those who received AR than for those who did not receive AR (P=0.04 and P=0.02 for the 2-year and 5-year LRFFS, respectively).
Patients with uterine sarcoma who were treated with AR after surgery demonstrated an improved LRFFS compared with those who were treated with surgery alone, especially those patients with leiomyosarcoma. Therefore, the role of personalized adjuvant radiation for patients with uterine sarcoma still requires further discussion.
PMCID: PMC4559239  PMID: 26357482
uterine neoplasm; radiation; local-regional failure-free survival; overall survival
10.  Similar Outcomes of Standard Radiotherapy and Hypofractionated Radiotherapy Following Breast-Conserving Surgery 
Adjuvant radiation therapy is commonly administered to breast cancer patients who received breast-conserving surgery. However, lengthy treatment times of standard radiotherapy pose certain challenges. Here, we performed a prospective controlled study comparing standard radiation to hypofractionated radiotherapy in terms of efficacy and outcome.
Eighty breast cancer patients (tumor stage pT1-2N0-1M0) who had undergone breast-conservation surgery were randomly divided into 2 groups (40 patients/group). The experimental group received 43.2 Gy to the whole breast in 18 fractions for 24 days with a concomitant boost (50.4 Gy) to the tumor bed. The control group received 45 Gy to the whole breast in 25 fractions for 44 days with a boost to the tumor bed of 59 Gy. Survival, locoregional recurrence, adverse effects, and aesthetic results were all considered for analysis.
The following criteria were included as part of study follow-up: local control, survival, adverse skin reactions, cosmetic outcome, and hematological toxicity. At a median follow-up of 27 months (follow-up rate 100%), there were no statistical differences in any of the categories between the 2 groups. The 2-year survival rate of both groups was 100% without any locoregional recurrence. Although there was some skin toxicity, these instances were not severe and they cleared on their own within 6 weeks. The most common problems encountered by patients were breast fibrosis and altered pigmentation.
A shortened whole-breast hypofractionated irradiation schedule with a concomitant boost is as effective as standard radiation and may be a reasonable alternative following breast conservation surgery.
PMCID: PMC4529138  PMID: 26235604
Breast; Radiation; Radiotherapy, Computer-Assisted
11.  Restoration of MiR-17/20a in Solid Tumor Cells Enhances the Natural Killer Cell Antitumor Activity by Targeting Mekk2 
Cancer immunology research  2014;2(8):789-799.
Aberrant microRNA (miRNA) expression has been identified in various human solid cancers. However, whether the levels of miRNA expression in tumor cells have any effect on tumor progression has not been determined. In this proof-of-concept study, the restoration of high-level expression of the miR-17~92 cluster of miRNAs reveals its function as a tumor suppressor in murine solid cancer cells. Specifically, genetically engineered expression of higher levels of miR-17/20a in the miR-17~92 cluster in both murine breast cancer and colon cancer cells triggered natural killer (NK) cell recognition by inhibiting the expression of MHC class I (H-2D) through the Mekk2/Mek5/Erk5 pathway. Results from the mouse tumor studies were recapitulated using samples of human solid tumors. Together, these data indicate that miR-17/20amiRnas functions as a tumor suppressor by reprogramming tumor cells for NK cell-mediated cytotoxicity.
PMCID: PMC4396632  PMID: 24801835
miR-17/20a; miR-17~92 cluster; MHC class I; Mekk2/Erk5 pathway; colon cancer; breast cancer; NK cell tumor cytotoxicity
12.  Polo-like kinase 2 activates an antioxidant pathway to promote the survival of cells with mitochondrial dysfunction 
We previously reported that Polo-like kinase 2 (PLK2) is highly expressed in cells with defective mitochondrial respiration and is essential for their survival. Although PLK2 has been widely studied as a cell cycle regulator, we have uncovered an antioxidant function for this kinase that activates the GSK3-NRF2 signaling pathway. Here, we report that the expression of PLK2 is responsive to oxidative stress and that PLK2 mediates antioxidant signaling by phosphorylating GSK3, thereby promoting the nuclear translocation of NRF2. We further show that the antioxidant activity of PLK2 is essential for preventing p53-dependent necrotic cell death. Thus, the regulation of redox homeostasis by PLK2 promotes the survival of cells with dysfunctional mitochondria, which may have therapeutic implications for cancer and neurodegenerative diseases.
PMCID: PMC4115326  PMID: 24887096
Polo-like kinase 2; Antioxidant; Mitochondrial dysfunction; Oxidative stress; GSK3; NRF2; p53; Necrosis
13.  MiR-34a regulates blood–tumor barrier function by targeting protein kinase Cε 
Molecular Biology of the Cell  2015;26(10):1786-1796.
It is shown for the first time that overexpression of miR-34a increases blood–tumor barrier permeability by targeting PKCε, which is activated by p-PKCε and directly regulates the expression of tight junction–related proteins.
MicroRNA-34a (miR-34a) functions to regulate protein expression at the posttranscriptional level by binding the 3′ UTR of target genes and regulates functions of vascular endothelial cells. However, the role of miR-34a in regulating blood–tumor barrier (BTB) permeability remains unknown. In this study, we show that miR-34a overexpression leads to significantly increased permeability of BTB, whereas miR-34a silencing reduces the permeability of the BTB. In addition, miR-34a overexpression significantly down-regulates the expression and distribution of tight junction–related proteins in glioma endothelial cells (GECs), paralleled by protein kinase Cε (PKCε) reduction. Moreover, luciferase reporter gene analysis shows that PKCε is the target gene of miR-34a. We also show that cotransfection of miR-34a and PKCε inversely coregulates BTB permeability and protein expression levels of tight junction–related proteins. Pretreatment of ψεRACK, a PKCε-specific activator, decreases BTB permeability in miR-34a–overexpressed GECs and up-regulates expression levels of tight junction proteins. In contrast, pretreatment of εV1-2, a specific PKCε inhibitor, gives opposite results. Collectively, our findings indicate that miR-34a regulates BTB function by targeting PKCε; after phosphorylation, PKCε is activated and contributes to regulation of the expression of tight junction–related proteins, ultimately altering BTB permeability.
PMCID: PMC4436826  PMID: 25788289
14.  Characterization of Chromosome Inheritance of the Intergeneric BC2 and BC3 Progeny between Saccharum spp. and Erianthus arundinaceus 
PLoS ONE  2015;10(7):e0133722.
Erianthus arundinaceus (E. arundinaceus) has many desirable agronomic traits for sugarcane improvement, such as high biomass, vigor, rationing ability, tolerance to drought, and water logging, as well as resistance to pests and disease. To investigate the introgression of the E. arundinaceus genome into sugarcane in the higher generations, intergeneric BC2 and BC3 progeny generated between Saccharum spp. and E. arundinaceus were studied using the genomic in situ hybridization (GISH) technique. The results showed that the BC2 and BC3 generations resulted from n + n chromosome transmission. Furthermore, chromosome translocation occurred at terminal fragments from the E. arundinaceus chromosome in some progeny of Saccharum spp. and E. arundinaceus. Notably, the translocated chromosomes could be stably transmitted to their progeny. This study illustrates the characterization of chromosome inheritance of the intergeneric BC2 and BC3 progeny between Saccharum spp. and E. arundinaceus. This work could provide more useful molecular cytogenetic information for the germplasm resources of E. arundinaceus, and may promote further understanding of the germplasm resources of E. arundinaceus for sugarcane breeders to accelerate its progress in sugarcane commercial breeding.
PMCID: PMC4510360  PMID: 26196281
15.  Host-Guest Carbon Dots for Enhanced Optical Properties and Beyond 
Scientific Reports  2015;5:12354.
Carbon dots, generally small carbon nanoparticles with various forms of surface passivation, have achieved the performance level of semiconductor quantum dots in the green spectral region, but their absorption and fluorescence in red/near-IR are relatively weaker. Conceptually similar to endofullerenes, host-guest carbon dots were designed and prepared with red/near-IR dyes encapsulated as guest in the carbon nanoparticle core. Beyond the desired enhancement in optical properties, the host-guest configuration may significantly broaden the field of carbon dots.
PMCID: PMC4508828  PMID: 26196598
16.  Microsecond Scale Vibrational Spectroscopic Imaging by Multiplex Stimulated Raman Scattering Microscopy 
Real-time vibrational spectroscopic imaging is desired for monitoring cellular states and cellular processes in a label-free manner. Raman spectroscopic imaging of highly dynamic systems is inhibited by relatively slow spectral acquisition on millisecond to second scale. Here, we report microsecond scale vibrational spectroscopic imaging by lock-in free parallel detection of spectrally dispersed stimulated Raman scattering signal. Using a homebuilt tuned amplifier array, our method enables Raman spectral acquisition, within the window defined by the broadband pulse, at the speed of 32 microseconds and with close to shot-noise limited detection sensitivity. Incorporated with multivariate curve resolution analysis, our platform allows compositional mapping of lipid droplets in single live cells, observation of intracellular retinoid metabolism, discrimination of fat droplets from protein-rich organelles in Caenorhabditis elegans, spectral detection of fast flowing tumor cells, and monitoring drug diffusion through skin tissue in vivo. The reported technique opens new opportunities for compositional analysis of cellular compartment in a microscope setting and high-throughput spectral profiling of single cells in a flow cytometer setting.
PMCID: PMC4498251  PMID: 26167336
Optical microscopy; Raman scattering; Vibrational spectroscopy
17.  A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging 
Science (New York, N.Y.)  2015;348(6239):1160-1163.
Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.
PMCID: PMC4494668  PMID: 25931448
18.  A Fast Cluster Motif Finding Algorithm for ChIP-Seq Data Sets 
BioMed Research International  2015;2015:218068.
New high-throughput technique ChIP-seq, coupling chromatin immunoprecipitation experiment with high-throughput sequencing technologies, has extended the identification of binding locations of a transcription factor to the genome-wide regions. However, the most existing motif discovery algorithms are time-consuming and limited to identify binding motifs in ChIP-seq data which normally has the significant characteristics of large scale data. In order to improve the efficiency, we propose a fast cluster motif finding algorithm, named as FCmotif, to identify the (l,  d) motifs in large scale ChIP-seq data set. It is inspired by the emerging substrings mining strategy to find the enriched substrings and then searching the neighborhood instances to construct PWM and cluster motifs in different length. FCmotif is not following the OOPS model constraint and can find long motifs. The effectiveness of proposed algorithm has been proved by experiments on the ChIP-seq data sets from mouse ES cells. The whole detection of the real binding motifs and processing of the full size data of several megabytes finished in a few minutes. The experimental results show that FCmotif has advantageous to deal with the (l,  d) motif finding in the ChIP-seq data; meanwhile it also demonstrates better performance than other current widely-used algorithms such as MEME, Weeder, ChIPMunk, and DREME.
PMCID: PMC4509496  PMID: 26236718
19.  Cold-inducible RNA-binding Protein Mediates Neuroinflammation in Cerebral Ischemia 
Biochimica et biophysica acta  2014;1840(7):2253-2261.
Neuroinflammation is a key cascade after cerebral ischemia. Excessive production of proinflammatory mediators in ischemia exacerbates brain injury. Cold-inducible RNA- binding protein (CIRP) is a newly discovered proinflammatory mediator that can be released into the circulation during hemorrhage or septic shock. Here, we examine the involvement of CIRP in brain injury during ischemic stroke.
Stroke was induced by middle cerebral artery occlusion (MCAO). In vitro hypoxia was conducted in a hypoxia chamber containing 1% oxygen. CIRP and tumor necrosis factor-α (TNF-α) levels were assessed by RT-PCR and Western blot analysis.
CIRP is elevated along with an upregulation of TNF-α expression in mouse brain after MCAO. In CIRP-deficient mice, the brain infarct volume, induction of TNF-α, and activation of microglia are markedly reduced after MCAO. Using microglial BV2 cells, we demonstrate that hypoxia induces the expression, translocation, and release of CIRP, which is associated with an increase of TNF-α levels. Addition of recombinant murine (rm) CIRP directly induces TNF-α release from BV2 cells and such induction is inhibited by neutralizing antisera to CIRP. Moreover, rmCIRP activates the NF-κB signaling pathway in BV2 cells. The conditioned medium from BV2 cells exposed to hypoxia triggers the apoptotic cascade by increasing caspase activity and decreasing Bcl-2 expression in neural SH-SY5Y cells, which is inhibited by antisera to CIRP.
Extracellular CIRP is a detrimental factor in stimulating inflammation to cause neuronal damage in cerebral ischemia.
General significance
Development of an anti-CIRP therapy may benefit patients with brain ischemia.
PMCID: PMC4061249  PMID: 24613680
Cerebral ischemia; Hypoxia; Cold shock protein; Inflammation; Microglia; Neural cells
20.  Bone regeneration via novel macroporous CPC scaffolds in critical-sized cranial defects in rats 
Calcium phosphate cement (CPC) is promising for dental and craniofacial applications due to its ability to be injected or filled into complex-shaped bone defects and molded for esthetics, and its resorbability and replacement by new bone. The objective of this study was to investigate bone regeneration via novel macroporous CPC containing absorbable fibers, hydrogel microbeads and growth factors in critical-sized cranial defects in rats.
Mannitol porogen and alginate hydrogel microbeads were incorporated into CPC. Absorbable fibers were used to provide mechanical reinforcement to CPC scaffolds. Six CPC groups were tested in rats: (1) Control CPC without macropores and microbeads; (2) Macroporous CPC + large fiber; (3) Macroporous CPC + large fiber + nanofiber; (4) Same as (3), but with rhBMP2 in CPC matrix; (5) Same as (3), but with rhBMP2 in CPC matrix + rhTGF-β1 in microbeads; (6) Same as (3), but with rhBMP2 in CPC matrix + VEGF in microbeads. Rats were sacrificed at 4 and 24 weeks for histological and micro-CT analyses.
The macroporous CPC scaffolds containing porogen, absorbable fibers and hydrogel microbeads had mechanical properties similar to cancellous bone. At 4 weeks, the new bone area fraction (mean ± sd; n = 5) in CPC control group was the lowest at (14.8 ± 3.3)%, and that of group 6 (rhBMP2 + VEGF) was (31.0 ± 13.8)% (p < 0.05). At 24 weeks, group 4 (rhBMP2) had the most new bone of (38.8 ± 15.6)%, higher than (12.7 ± 5.3)% of CPC control (p < 0.05). Micro-CT revealed nearly complete bridging of the critical-sized defects with new bone for several macroporous CPC groups, compared to much less new bone formation for CPC control.
Macroporous CPC scaffolds containing porogen, fibers and microbeads with growth factors were investigated in rat cranial defects for the first time. Macroporous CPCs had new bone up to 2-fold that of traditional CPC control at 4 weeks, and 3-fold that of traditional CPC at 24 weeks, and hence may be useful for dental, craniofacial and orthopedic applications.
PMCID: PMC4312701  PMID: 24768062
Calcium phosphate cement; macroporous scaffold; strength and toughness; bone regeneration; growth factors; critical-sized cranial defects
21.  Changes in short-chain acyl-coA dehydrogenase during rat cardiac development and stress 
This study was designed to investigate the expression of short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme of fatty acid β-oxidation, during rat heart development and the difference of SCAD between pathological and physiological cardiac hypertrophy. The expression of SCAD was lowest in the foetal and neonatal heart, which had time-dependent increase during normal heart development. In contrast, a significant decrease in SCAD expression was observed in different ages of spontaneously hypertensive rats (SHR). On the other hand, swim-trained rats developed physiological cardiac hypertrophy, whereas SHR developed pathological cardiac hypertrophy. The two kinds of cardiac hypertrophy exhibited divergent SCAD changes in myocardial fatty acids utilization. In addition, the expression of SCAD was significantly decreased in pathological cardiomyocyte hypertrophy, however, increased in physiological cardiomyocyte hypertrophy. SCAD siRNA treatment triggered the pathological cardiomyocyte hypertrophy, which showed that the down-regulation of SCAD expression may play an important role in pathological cardiac hypertrophy. The changes in peroxisome proliferator-activated receptor α (PPARα) was accordant with that of SCAD. Moreover, the specific PPARα ligand fenofibrate treatment increased the expression of SCAD and inhibited pathological cardiac hypertrophy. Therefore, we speculate that the down-regulated expression of SCAD in pathological cardiac hypertrophy may be responsible for ‘the recapitulation of foetal energy metabolism’. The deactivation of PPARα may result in the decrease in SCAD expression in pathological cardiac hypertrophy. Changes in SCAD are different in pathological and physiological cardiac hypertrophy, which may be used as the molecular markers of pathological and physiological cardiac hypertrophy.
PMCID: PMC4511364  PMID: 25753319
short-chain acyl-CoA dehydrogenase; peroxisome proliferator-activated receptor α; heart development; pathological cardiac hypertrophy; physiological cardiac hypertrophy
22.  Simultaneous quantification of crocetin esters and picrocrocin changes in Chinese saffron by high-performance liquid chromatography-diode array detector during 15 years of storage 
Pharmacognosy Magazine  2015;11(43):540-545.
Saffron, which is made up of the dried stigmas of Crocus sativus L., has been successfully cultivated in China since 1970s and Zhejiang province is now the largest producing area in China, but the contents of crocetin esters and picrocrocin in saffron from Zhejiang province has not been determined simultaneously by high-performance liquid chromatography (HPLC) and changes of these constituents in Chinese saffron during storage for years has not been studied.
To establish a simple method quantification of the five main compounds including picrocrocin and four crocetin esters in saffron from main producing areas of China and study the influence of storage time on the changes of saffron constituents.
Materials and Methods:
A simple, sensitive, and accurate HPLC method was developed for simultaneous determination of five major active components in saffron and eight samples which collected from the same farm of Zhejiang province in different years were analyzed.
The correlation coefficient values (R2 > 0.9997) indicated good correlations between the investigated compounds’ concentrations and their peak areas within the test ranges. The limits of quantification and detection of the five compounds were 0.53–2.76 μg/mL and 0.11–0.77 μg/mL, respectively. The recoveries ranged from 94.67% to 101.31%, and the overall relative standard deviations for intra-day and inter-day were lower than 3.49%. The method was applied to study the changes of crocetin esters and picrocrocin contents in saffron samples during 15 years of storage. The losses of crocetin esters and picrocrocin in saffron with 1 -year storage were 52.2% and 54.3%, respectively. The trend then declined during subsequent storage.
The developed method can be applied to the intrinsic quality control of saffron.
PMCID: PMC4522840  PMID: 26246729
Crocetin esters; high-performance liquid chromatography-diode array detector; picrocrocin; saffron; storage
23.  EPO protects Müller cell under high glucose state through BDNF/TrkB pathway 
Neurotrophic factor decreased in the early stage of diabetic retinal nerve cells. Neurons damage brain derived neurotrophic factor (BDNF) and receptor TrkB expression reduced. Erythropoietin (EPO) plays an important role in protecting early diabetic retinopathy. The rats were euthanized at 24 h after EPO vitreous injection and the retina was separated. HE staining was applied to observe the pathological tissue morphology. Immunohistochemistry, immunofluorescence, and Western blot were used to detect BDNF, TrkB, extracellular signal-regulated kinase (ERK), and glial fibrillary acidic portein (GFAP) expression. Retinal structure was clear in group C, while the retinal thickness and RGCs number decreased in group B at 24 w. Retinal thickness in group E was greater than in group B but lower than in group C. GFAP and ERK expression increased in both group B and E, whereas the latter was significantly lower than the former. TrkB protein level was in group E > B > C at 4 w, while it was in group C > group E > group B at 24 w. BDNF expression in group B was higher than in group C at 4 w, whereas it was opposite at 24 w. BDNF expression increased in group E at 4 w, and it was similar in group E compared with group C at 24 w. EPO vitreous injection can increase BDNF and TrkB expression, while reduce GFAP and ERK expression in diabetes rat retina. It could protect Müller cells through BDNF/TrkB pathway to play a role of nerve nutrition.
PMCID: PMC4555703  PMID: 26339375
24.  Analysis of clinical efficacy of CyberKnife® treatment for locally advanced pancreatic cancer 
OncoTargets and therapy  2015;8:1427-1431.
To evaluate the efficacy and safety of CyberKnife® treatment for locally-advanced pancreatic cancer (LAPC).
The efficacy of CyberKnife® treatment was analyzed in 59 LAPC patients treated between October 2006 and September 2014. The median tumor volume was 27.1 mL (13.0–125.145 mL). The median prescribed dose was 45 Gy (35–50 Gy), delivered in 5 fractions (3–8 fractions). The overall survival (OS) rates and freedom from local progression (FFLP) rates were estimated using the Kaplan–Meier survival curve.
The median follow-up for all patients was 10.9 months (3.2–48.7 months) and 15.6 months (3.9–37.6 months) among surviving patients. The median OS was 12.5 months, and the 1-year and 2-year survival rates were 53.9% and 35.1%, respectively. The 1-year FFLP rate was 90.8% based on the computed tomography (CT) evaluation. Grade 1–2 acute and late-stage gastrointestinal (GI) reactions were observed in 61% of the patients. One patient experienced grade 3 toxicity.
Excellent clinical efficacy was obtained after treatment of LAPC using CyberKnife®, with minimal toxicity.
PMCID: PMC4472027  PMID: 26109866
pancreatic cancer; stereotactic body radiotherapy; CyberKnife®; local control; toxicity
25.  Phylogenetic relationships of subfamilies in the family Hesperiidae (Lepidoptera: Hesperioidea) from China 
Scientific Reports  2015;5:11140.
Hesperiidae is one of the largest families of butterflies. Our knowledge of the higher systematics on hesperiids from China is still very limited. We infer the phylogenetic relationships of the subfamilies of Chinese skippers based on three mitochondrial genes (cytochrome b (Cytb), the NADH dehydrogenase subunit 1 (ND1) and cytochrome oxidase I (COI)). In this study, 30 species in 23 genera were included in the Bayesian and maximum likelihood analyses. The subfamily Coeliadinae, Eudaminae, Pyrginae and Heteropterinae were recovered as a monophyletic clade with strong support. The subfamily Hesperiinae formed a clade, but support for monophyly was weak. Our results imply that the five subfamilies of Chinese Hesperiidae should be divided into: Coeliadinae, Eudaminae, Pyrginae, Heteropterinae and Hesperiinae. The relationships of the five subfamilies should be as follows: Coeliadinae + (Eudaminae + (Pyrginae + (Heteropterinae + Hesperiinae))).
PMCID: PMC4461911  PMID: 26059470

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