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1.  Beraprost sodium protects against chronic brain injury in aluminum-overload rats 
Aluminum overload can cause severe brain injury and neurodegeneration. Previous studies suggest that prostacyclin synthase (PGIS) expression and prostacyclin receptor (IP) activation are beneficial for treatment of acute traumatic and ischemic brain injury. However, the potential value of PGIS/IP signaling pathway to chronic brain injury is still unclear. In this study, we investigated the change of PGIS/IP signaling pathway and the effect of beraprost sodium (BPS) on chronic brain injury in chronic aluminum-overload rats.
Rat model of chronic cerebral injury was established by chronic intragastric administration of aluminum gluconate(Al3+ 200 mg/kg per day,5d a week for 20 weeks). The methods of ELISA, qRT-PCR and Western blotting were used to detect the PGI2 level and the PGIS and IP mRNA and protein levels in hippocampi of chronic aluminum-overload rats, respectively. Rat hippocampal superoxide dismutase (SOD) activity and malondialdehyde (MDA) content also were measured. The effects of BPS (6, 12 and 24 μg⋅kg-1) on brain injury in chronic aluminum-overload rats were evaluated.
Compared with the control group, PGIS mRNA expression, PGI2 level, and the IP mRNA and protein expressions significantly increased in hippocampi of chronic aluminum-overload rats. Administration of BPS significantly improved spatial learning and memory function impairment and hippocampal neuron injury induced by chronic aluminum overload in rats. Meanwhile, administration of BPS resulted in a decrease of PGI2 level and downregulation of PGIS and IP expressions in a dose-dependent manner. Aluminum overload also caused a decrease of SOD activity and an increase of MDA content. Administration of BPS significantly blunted the decrease of SOD activity and the increase of MDA content induced by aluminum overload in rats.
BPS has a significant neuroprotective effect on chronic brain injury induced by aluminum overload in rats. Remodeling the balance of PGIS/IP signaling pathway and inhibition of oxidative stress involve in the neuroprotective mechanism of BPS in aluminum-overload rats. The PGIS/IP signaling pathway is a potential therapeutic strategy for chronic brain injury patients.
PMCID: PMC4326490
Chronic brain injury; Beraprost sodium; PGI2 level; PGIS; IP receptor
2.  Mertk Deficiency Affects Macrophage Directional Migration via Disruption of Cytoskeletal Organization 
PLoS ONE  2015;10(1):e0117787.
Mertk belongs to the Tyro3, Axl and Mertk (TAM) family of receptor tyrosine kinases, and plays a pivotal role in regulation of cytoskeletal rearrangement during phagocytosis. Phagocytosis by either professional or non-professional phagocytes is impaired in the Mertk deficient individual. In the present study, we further investigated the effects of Mertk mutation on peritoneal macrophage morphology, attachment, spreading and movement. Mertk-mutated macrophages exhibited decreased attachment, weak spreading, loss of spindle-like body shape and lack of clear leading and trailing edges within the first few hours of culture, as observed by environmental scanning electron microscopy. Time-lapse video photography recording showed that macrophage without Mertk conducted mainly random movement with oscillating swing around the cell body, and lost the directional migration action seen on the WT cells. Western blotting showed a decreased phosphorylation of focal adhesion kinase (FAK). Immunocytochemistry revealed that actin filaments and dynamic protein myosin II failed to concentrate in the leading edge of migrating cells. Microtubules were localized mainly in one side of mutant cell body, with no clear MTOC and associated radially-distributed microtubule bundles, which were clearly evident in the WT cells. Our results suggest that Mertk deficiency affects not only phagocytosis but also cell shape and migration, likely through a common regulatory mechanism on cytoskeletons.
PMCID: PMC4305281  PMID: 25617898
3.  Role of microRNAs in diagnosis and treatment of the pathogenesis of gastric cancer 
We aim to detect the miRNAs that are correlated with the gastric cancer cell line SGC-7901 to provide theoretical basis for clinical application. We first analyzed miRNA expression profiles of gastric cancer patients compared with normal controls by microarray analysis and validated the results by real-time qPCR. We also determined the absolute copy numbers of these three miRNAs in normal adults. The results showed that three miRNAs (miR-150, miR-23a, and miR-130a) were identified to significantly decrease in expanded 38 gastric cancer patients compared with 90 normal controls. Molecular and statistical analysis showed that the decreased miRNAs were significant in clinical analysis. Generally speaking, this finding suggest vital roles of these miRNAs in human gastric cancer genesis and as potential biomarkers in gastric cancer diagnosis.
PMCID: PMC4307587  PMID: 25664140
microRNAs; gastric cancer; SGC-7901; diagnosis biomarker
4.  Clinical characteristics and prognosis of primary pancreatic carcinoid tumors: A report of 13 cases from a single institution 
Oncology Letters  2014;9(2):780-784.
The present study aimed to analyze the diagnosis and treatment of 13 cases of pancreatic carcinoid tumors during a 56-year period at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China). The data from 13 cases, consisting of 5 males and 8 females (mean age, 50 years), were collected and analyzed. Hematoxylin-eosin and immunohistochemistry staining were performed to investigate the expression of neuron-specific enolase (NSE), cytokeratin (CK), chromogranin A (CgA) and synaptophysin (Syn) in the tumors. The affected patients suffered abdominal and/or back pain without typical carcinoid syndrome. Radical resection was performed in 10 cases and regional resection in one case. The remaining two patients exhbited remote metastasis, and so were treated with single and double bypass surgery (choledochojejunostomy and gastrojejunostomy/choledochojejunostomy, respectively). The expression of CK, Syn, CgA and NSE was positive in nine (69.23%), 10 (76.92%), five (38.46%) and eight (61.54%) cases, respectively. The median survival time was 26.6 months. In conclusion, in patients with pancreatic carcinoid tumors that exhibit no typical carcinoid syndrome, such as those in the present study, the diagnosis can be confirmed by pathological examination and surgery is the most effective treatment.
PMCID: PMC4301509  PMID: 25621051
pancreatic carcinoid tumor; diagnosis; treatment; prognosis; pathology
5.  Whole Genome Expression Profiling and Signal Pathway Screening of MSCs in Ankylosing Spondylitis 
Stem Cells International  2014;2014:913050.
The pathogenesis of dysfunctional immunoregulation of mesenchymal stem cells (MSCs) in ankylosing spondylitis (AS) is thought to be a complex process that involves multiple genetic alterations. In this study, MSCs derived from both healthy donors and AS patients were cultured in normal media or media mimicking an inflammatory environment. Whole genome expression profiling analysis of 33,351 genes was performed and differentially expressed genes related to AS were analyzed by GO term analysis and KEGG pathway analysis. Our results showed that in normal media 676 genes were differentially expressed in AS, 354 upregulated and 322 downregulated, while in an inflammatory environment 1767 genes were differentially expressed in AS, 1230 upregulated and 537 downregulated. GO analysis showed that these genes were mainly related to cellular processes, physiological processes, biological regulation, regulation of biological processes, and binding. In addition, by KEGG pathway analysis, 14 key genes from the MAPK signaling and 8 key genes from the TLR signaling pathway were identified as differentially regulated. The results of qRT-PCR verified the expression variation of the 9 genes mentioned above. Our study found that in an inflammatory environment ankylosing spondylitis pathogenesis may be related to activation of the MAPK and TLR signaling pathways.
PMCID: PMC4269092  PMID: 25544849
6.  Processing Deficits of Motion of Contrast-Modulated Gratings in Anisometropic Amblyopia 
PLoS ONE  2014;9(11):e113400.
Several studies have indicated substantial processing deficits for static second-order stimuli in amblyopia. However, less is known about the perception of second-order moving gratings. To investigate this issue, we measured the contrast sensitivity for second-order (contrast-modulated) moving gratings in seven anisometropic amblyopes and ten normal controls. The measurements were performed with non-equated carriers and a series of equated carriers. For comparison, the sensitivity for first-order motion and static second-order stimuli was also measured. Most of the amblyopic eyes (AEs) showed reduced sensitivity for second-order moving gratings relative to their non-amblyopic eyes (NAEs) and the dominant eyes (CEs) of normal control subjects, even when the detectability of the noise carriers was carefully controlled, suggesting substantial processing deficits of motion of contrast-modulated gratings in anisometropic amblyopia. In contrast, the non-amblyopic eyes of the anisometropic amblyopes were relatively spared. As a group, NAEs showed statistically comparable performance to CEs. We also found that contrast sensitivity for static second-order stimuli was strongly impaired in AEs and part of the NAEs of anisometropic amblyopes, consistent with previous studies. In addition, some amblyopes showed impaired performance in perception of static second-order stimuli but not in that of second-order moving gratings. These results may suggest a dissociation between the processing of static and moving second-order gratings in anisometropic amblyopia.
PMCID: PMC4237427  PMID: 25409477
7.  Optimization of lentiviral vector production using polyethylenimine-mediated transfection 
Oncology Letters  2014;9(1):55-62.
The aim of the present study was to optimize the polyethylenimine (PEI)-mediated transfection method in order to simplify the efficient production of lentiviral vectors (LvVs), and to compare the CaPO4- and PEI-mediated transfection methods for producing LvVs. Different titration methods of LvV stocks, as well as different culture media, culture durations, cell densities and DNA quantities were compared to obtain an optimized procedure for the production of LvVs. Optimization of the production method for LvVs was achieved using PEI-mediated transient transfections. Serum-free Opti-MEM® was used to directly produce LvVs that could be harvested 48 h after transfection. Furthermore, a cell density of 15×106 cells/10-cm plate and a DNA concentration of 1X were selected for the optimum production of LvVs. The optimized LvV titration method was simple and direct; it involved LvVs carrying fluorescent reporters, which proved to be faster than the standard methods but equally as sensitive. In conclusion, a scalable process for production of LvVs by PEI-mediated transfection was established and optimized. The optimized PEI-mediated transfection method was easy to use, as well as providing greater reliability with a higher degree of reproducibility and consistency. Despite using less DNA, the PEI-mediated transfection method resulted in viral titers that were the same as those achieved using the CaPO4-mediated method.
PMCID: PMC4246624  PMID: 25435933
lentivirus; vector production; polyethylenimine; calcium phosphate
8.  Evaluation of “top-down” treatment of early Crohn’s disease by double balloon enteroscopy 
World Journal of Gastroenterology : WJG  2014;20(39):14479-14487.
AIM: To assess “top-down” treatment for deep remission of early moderate to severe Crohn’s disease (CD) by double balloon enteroscopy.
METHODS: Patients with early active moderate to severe ileocolonic CD received either infusion of infliximab 5 mg/kg at weeks 0, 2, 6, 14, 22 and 30 with azathioprine from week 6 onwards (Group I), or prednisone from week 0 as induction therapy with azathioprine from week 6 onwards (Group II). Endoscopic evaluation was performed at weeks 0, 30, 54 and 102 by double balloon enteroscopy. The primary endpoints were deep remission rates at weeks 30, 54 and 102. Secondary endpoints included the time to achieve clinical remission, clinical remission rates at weeks 2, 6, 14, 22, 30, 54 and 102, and improvement of Crohn’s Disease Endoscopic Index of Severity scores at weeks 30 and 54 relative to baseline. Intention-to-treat analyses of the endpoints were performed.
RESULTS: Seventy-seven patients were enrolled, with 38 in Group I and 39 in Group II. By week 30, deep remission rates were 44.7% and 17.9% in Groups I and II, respectively (P = 0.011). The median time to clinical remission was longer for patients in Group II (14.2 wk) than for patients in Group I (6.8 wk, P = 0.009). More patients in Group I were in clinical remission than in Group II at weeks 2, 6, 22 and 30 (2 wk: 26.3% vs 2.6%; 6 wk: 65.8% vs 28.2%; 22 wk: 71.1% vs 46.2%; 30 wk: 68.4% vs 43.6%, P < 0.05). The rates of clinical remission and deep remission were greater at weeks 54 and 102 in Group I, but the differences were insignificant.
CONCLUSION: Top-down treatment with infliximab and azathioprine, as compared with corticosteroid and azathioprine, results in higher rates of earlier deep remission in early CD.
PMCID: PMC4202377  PMID: 25339835
Crohn’s disease; Top-down treatment; Deep remission; Double balloon enteroscopy; Mucosal healing
9.  The 2011 IASLC/ATS/ERS pulmonary adenocarcinoma classification: a landmark in personalized medicine for lung cancer management 
Journal of Thoracic Disease  2014;6(Suppl 5):S589-S596.
In 2011, three authoritative academic communities, International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society (IASLC/ATS/ERS), published a novel lung adenocarcinoma histologic classification. The major modifications of this classification include the abolishment of the term “bronchioloalveolar carcinoma (BAC)”, the establishment of new classification systems for resection and small biopsy or cytology specimens, the emphasis of molecular test and comprehensive histologic evaluation for tumor specimens, etc. This new lung adenocarcinoma classification signifies the era of personalized medicine comes to real-world practice in lung cancer field. Here, we introduce the background why the lung adenocarcinoma classification needs to be revised, and what we should consider in clinical practice according to this new classification.
PMCID: PMC4209390  PMID: 25349710
Adenocarcinoma; lung neoplasms; classification
10.  Improved Derivation Efficiency and Pluripotency of Stem Cells from the Refractory Inbred C57BL/6 Mouse Strain by Small Molecules 
PLoS ONE  2014;9(9):e106916.
The ability of small molecules to maintain self-renewal and to inhibit differentiation of pluripotent stem cells has been well-demonstrated. Two widely used molecules are PD 98059 (PD), an inhibitor of extracellular-signal-regulated kinase 1 (ERK), and SC1 (Pluripotin), which inhibits the RasGAP and ERK pathways. However, no studies have been conducted to compare their effects on the pluripotency and derivation of embryonic stem (ES) cells from inbred mice C57BL/6, an important mouse strain frequently used to model behavior, cognitive functions, immune system, and metabolic disorders in humans and also the first mouse strain chosen to be sequenced for its entire genome. We found significantly increased derivation efficiency of ES cells from in vivo fertilized embryos (fES) of C57BL/6 with the use of PD (71.4% over the control of 35.3%). Because fES and ES from cloned embryos (ntES) are not distinguishable in transcription or translation profiles, we used ntES cells to compare the effect of small molecules on their in vitro characteristics, in vitro differentiation ability, and the ability to generate full-term ntES-4N pups by tetraploid complementation. NtES cells exhibited typical ES characteristics and up-regulated Sox2 expression in media with either small-molecule. Higher rates of full term ntES-4N pup were generated by the supplementation of PD or SC1. We obtained the highest efficiency of ntES-4N pup generation ever reported from this strain by supplementing ES medium with SC1. Lastly, we compared the pluripotency of fES, ntES and induced pluripotent stem (iPS) cells of C57BL/6 background using the tetraploid complementation assay. A significant increase in implantation sites and the number of full-term pups were obtained when fES, ntES, and iPS cells were cultured with SC1 compared to the control ES medium. In conclusion, supplementing ES cell culture medium with PD and SC1 increases the derivation efficiency and pluripotency, respectively, of stem cells derived from the refractory inbred C57BL/6 strain.
PMCID: PMC4161378  PMID: 25211343
11.  Transcriptional profiles of bovine in vivo pre-implantation development 
BMC Genomics  2014;15(1):756.
During mammalian pre-implantation embryonic development dramatic and orchestrated changes occur in gene transcription. The identification of the complete changes has not been possible until the development of the Next Generation Sequencing Technology.
Here we report comprehensive transcriptome dynamics of single matured bovine oocytes and pre-implantation embryos developed in vivo. Surprisingly, more than half of the estimated 22,000 bovine genes, 11,488 to 12,729 involved in more than 100 pathways, is expressed in oocytes and early embryos. Despite the similarity in the total numbers of genes expressed across stages, the nature of the expressed genes is dramatically different. A total of 2,845 genes were differentially expressed among different stages, of which the largest change was observed between the 4- and 8-cell stages, demonstrating that the bovine embryonic genome is activated at this transition. Additionally, 774 genes were identified as only expressed/highly enriched in particular stages of development, suggesting their stage-specific roles in embryogenesis. Using weighted gene co-expression network analysis, we found 12 stage-specific modules of co-expressed genes that can be used to represent the corresponding stage of development. Furthermore, we identified conserved key members (or hub genes) of the bovine expressed gene networks. Their vast association with other embryonic genes suggests that they may have important regulatory roles in embryo development; yet, the majority of the hub genes are relatively unknown/under-studied in embryos. We also conducted the first comparison of embryonic expression profiles across three mammalian species, human, mouse and bovine, for which RNA-seq data are available. We found that the three species share more maternally deposited genes than embryonic genome activated genes. More importantly, there are more similarities in embryonic transcriptomes between bovine and humans than between humans and mice, demonstrating that bovine embryos are better models for human embryonic development.
This study provides a comprehensive examination of gene activities in bovine embryos and identified little-known potential master regulators of pre-implantation development.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-756) contains supplementary material, which is available to authorized users.
PMCID: PMC4162962  PMID: 25185836
Pre-implantation development; Embryonic genome activation; RNA-seq; Stage specific module; Hub genes; Bovine; Human; Mouse
12.  Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway 
Neuron  2013;79(3):447-460.
The convergence of APP (substrate) and BACE-1 (enzyme) is a rate-limiting, obligatory event triggering the amyloidogenic pathway – a key step in Alzheimer’s disease (AD) pathology. However, as both APP/BACE-1 are highly expressed in brain, mechanisms precluding their unabated convergence are unclear. Exploring dynamic localization of APP/BACE-1 in cultured hippocampal neurons, we found that after synthesis via the secretory-pathway, dendritic APP/BACE-1-containing vesicles are largely segregated in physiologic states. While BACE-1 is largely sorted into acidic recycling endosomes, APP is conveyed in Golgi-derived vesicles. However upon activity-induction – a known trigger of the amyloidogenic pathway – APP is routed into BACE-1-positive recycling endosomes via a clathrin-dependent mechanism. A partitioning/convergence of APP/BACE-1 vesicles is also apparent in control/AD brains respectively. Considering BACE-1 is optimally active in an acidic environment, our experiments suggest that neurons have evolved trafficking strategies that normally limit APP/BACE-1 proximity; and also uncover a pathway routing APP into BACE-1-containing organelles – triggering amyloidogenesis.
PMCID: PMC3741682  PMID: 23931995
amyloid precursor protein (APP); β-site APP cleaving enzyme (BACE-1); vesicle trafficking; neuronal activity; recycling endosomes
13.  Cystitis glandularis: A controversial premalignant lesion 
Oncology Letters  2014;8(4):1662-1664.
Cystitis glandularis (CG) has been hypothesized as a potential precursor of adenocarcinoma, although this remains controversial. The present study reports data accumulated from 166 cases of cystitis glandularis with follow-up periods ranging between 0.5 and 17 years. The association between intestinal and typical CG and bladder carcinoma was retrospectively evaluated. The patients included in the present study had presented with typical (n=155) or intestinal (n=11) CG between 1994 and 2010. Of those patients, concurrent carcinoma of the bladder was identified in 15 (9.0%) patients, including two cases of squamous cell carcinoma and 1 case of sarcoma. The cases of carcinoma were identified either prior to or concurrently with the diagnosis of CG. Follow-up was available for 9/11 (81.8%) patients with intestinal CG. Nine months following transurethral fulguration, 8/11 (72.7%) patients were in complete remission and 1/11 (9.1%) complained of urgency and dysuria; two patients were lost to follow-up. The follow-up of the patients ranged from 0.7 to 4.5 years (median, 2.67 years; mean, 2.82 years). No evidence of subsequent carcinoma was identified in any of the patients during the follow-up of the intestinal and typical CG groups. In addition, there was no evidence of carcinoma subsequent to CG in either of the typical or intestinal CG groups. The results did not support that CG increases the future risk of malignancy in the short term and repeated cystoscopies over a short period of time are not recommended.
PMCID: PMC4156188  PMID: 25202387
bladder; cystitis; carcinoma
14.  Detoxification of Corncob Acid Hydrolysate with SAA Pretreatment and Xylitol Production by Immobilized Candida tropicalis 
The Scientific World Journal  2014;2014:214632.
Xylitol fermentation production from corncob acid hydrolysate has become an attractive and promising process. However, corncob acid hydrolysate cannot be directly used as fermentation substrate owing to various inhibitors. In this work, soaking in aqueous ammonia (SAA) pretreatment was employed to reduce the inhibitors in acid hydrolysate. After detoxification, the corncob acid hydrolysate was fermented by immobilized Candida tropicalis cell to produce xylitol. Results revealed that SAA pretreatment showed high delignification and efficient removal of acetyl group compounds without effect on cellulose and xylan content. Acetic acid was completely removed, and the content of phenolic compounds was reduced by 80%. Furthermore, kinetic behaviors of xylitol production by immobilized C. tropicalis cell were elucidated from corncob acid hydrolysate detoxified with SAA pretreatment and two-step adsorption method, respectively. The immobilized C. tropicalis cell showed higher productivity efficiency using the corncob acid hydrolysate as fermentation substrate after detoxification with SAA pretreatment than by two-step adsorption method in the five successive batch fermentation rounds. After the fifth round fermentation, about 60 g xylitol/L fermentation substrate was obtained for SAA pretreatment detoxification, while about 30 g xylitol/L fermentation substrate was obtained for two-step adsorption detoxification.
PMCID: PMC4123689  PMID: 25133211
15.  Prognostic significance of preoperative fibrinogen in patients with colon cancer 
AIM: To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients.
METHODS: A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1st 2005 to June 1st 2008 were enrolled in the study. All patients received radical surgery as their primary treatment method. Preoperative fibrinogen was detected by the Clauss method, and all patients were followed up after surgery. Preoperative fibrinogen measurements were correlated with a number of clinicopathological parameters using the Student t test and analysis of variance. Survival analyses were performed by the Kaplan-Meier method and Cox regression modeling to measure 5-year disease-free survival (DFS) and overall survival (OS).
RESULTS: The mean preoperative fibrinogen concentration of all colon cancer patients was 3.17 ± 0.88 g/L. Statistically significant differences were found between preoperative fibrinogen levels and the clinicopathological parameters of age, smoking status, tumor size, tumor location, tumor-node-metastasis (TNM) stage, modified Glasgow prognostic scores (mGPS), white blood cell (WBC) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) levels. Univariate survival analysis showed that TNM stage, tumor cell differentiation grade, vascular invasion, mGPS score, preoperative fibrinogen, WBC, NLR, PLR and CEA all correlated with both OS and DFS. Alpha-fetoprotein (AFP) and body mass index correlated only with OS. Kaplan-Meier analysis revealed that both OS and DFS of the total cohort, as well as of the stage II and III patients, were higher in the hypofibrinogen group compared to the hyperfibrinogen group (all P < 0.05). In contrast, there was no significant difference between OS and DFS in stage I patients with low or high fibrinogen levels. Cox regression analysis indicated preoperative fibrinogen levels, TNM stage, mGPS score, CEA, and AFP levels correlated with both OS and DFS.
CONCLUSION: Preoperative fibrinogen levels can serve as an independent prognostic marker to evaluate patient response to colon cancer treatment.
PMCID: PMC4093707  PMID: 25024612
Fibrinogen; Colon cancer; Clinicopathological parameters; Relationship; Prognosis
16.  A Review of CO2 Sequestration Projects and Application in China 
The Scientific World Journal  2014;2014:381854.
In 2008, the top CO2 emitters were China, United States, and European Union. The rapid growing economy and the heavy reliance on coal in China give rise to the continued growth of CO2 emission, deterioration of anthropogenic climate change, and urgent need of new technologies. Carbon Capture and sequestration is one of the effective ways to provide reduction of CO2 emission and mitigation of pollution. Coal-fired power plants are the focus of CO2 source supply due to their excessive emission and the energy structure in China. And over 80% of the large CO2 sources are located nearby storage reservoirs. In China, the CO2 storage potential capacity is of about 3.6 × 109 t for all onshore oilfields; 30.483 × 109 t for major gas fields between 900 m and 3500 m of depth; 143.505 × 109 t for saline aquifers; and 142.67 × 109 t for coal beds. On the other hand, planation, soil carbon sequestration, and CH4–CO2 reforming also contribute a lot to carbon sequestration. This paper illustrates some main situations about CO2 sequestration applications in China with the demonstration of several projects regarding different ways of storage. It is concluded that China possesses immense potential and promising future of CO2 sequestration.
PMCID: PMC4181513  PMID: 25302323
17.  A system of nonlinear set valued variational inclusions 
SpringerPlus  2014;3:318.
In this paper, we studied the existence theorems and techniques for finding the solutions of a system of nonlinear set valued variational inclusions in Hilbert spaces. To overcome the difficulties, due to the presence of a proper convex lower semicontinuous function ϕ and a mapping g which appeared in the considered problems, we have used the resolvent operator technique to suggest an iterative algorithm to compute approximate solutions of the system of nonlinear set valued variational inclusions. The convergence of the iterative sequences generated by algorithm is also proved.
AMS Mathematics subject classification
49J40; 47H06
PMCID: PMC4112201  PMID: 25077055
System of nonlinear set valued variational inclusions; Lipschitz continuity; Resolvent operators; Iterative sequences; Hilbert spaces
18.  Chaperone-mediated acetylation of histones by Rtt109 identified by quantitative proteomics 
Journal of proteomics  2012;81:80-90.
Rtt109 is a fungal-specific histone acetyltransferase (HAT) that associates with either Vps75 or Asf1 to acetylate histone H3. Recent biochemical and structural studies suggest that site-specific acetylation of H3 by Rtt109 is dictated by the binding chaperone where Rtt109-Asf1 acetylates K56, while Rtt109-Vps75 acetylates K9 and K27. To gain further insights into the roles of Vps75 and Asf1 in directing site-specific acetylation of H3, we used quantitative proteomics to profile the global and site-specific changes in H3 and H4 during in vitro acetylation assays with Rtt109 and its chaperones. Our analyses showed that Rtt109-Vps75 preferentially acetylates H3 K9 and K23, the former residue being the major acetylation site. At high enzyme to substrate ratio, Rtt109 also acetylated K14, K18, K27 and to a lower extent K56 of histone H3. Importantly, this study revealed that in contrast to Rtt109-Vps75, Rtt109-Asf1 displayed a far greater site-specificity, with K56 being the primary site of acetylation. For the first time, we also report the acetylation of histone H4 K12 by Rtt109-Vps75, whereas Rtt109-Asf1 showed no detectable activity toward H4.
PMCID: PMC4016993  PMID: 23036725
Histone; histone acetyltransferase; chaperone; acetylation; proteomics; mass spectrometry
19.  Association of serine racemase gene variants with type 2 diabetes in the Chinese Han population 
A genome‐wide association study in the Chinese Han population has identified several novel genetic variants of the serine racemase (SRR) gene in type 2 diabetes. Our purpose was to systematically evaluate the contribution of SRR variants in the Chinese Han population. rs391300 and rs4523957 in SRR were genotyped respectively in the two independent populations. A meta‐analysis was used to estimate the effects of SRR in 21,305 Chinese Han individuals. Associations between single‐nucleotide polymorphisms and diabetes‐related phenotypes were analyzed among 2,615 newly diagnosed type 2 diabetes patients and 5,029 controls. Neither rs391300 nor rs4523957 were associated with type 2 diabetes in populations. Furthermore, meta‐analysis did not confirm an association between type 2 diabetes and SRR. In the controls, rs391300‐A and rs4523957‐G were associated with higher 30‐min plasma glucose in an oral glucose tolerance test. The present study did not confirm that SRR was associated with type 2 diabetes.
PMCID: PMC4020332  PMID: 24843776
Serine racemase gene; Single‐nucleotide polymorphisms; Type 2 diabetes mellitus
20.  Immature visual neural system in children reflected by contrast sensitivity with adaptive optics correction 
Scientific Reports  2014;4:4687.
This study aimed to explore the neural development status of the visual system of children (around 8 years old) using contrast sensitivity. We achieved this by eliminating the influence of higher order aberrations (HOAs) with adaptive optics correction. We measured HOAs, modulation transfer functions (MTFs) and contrast sensitivity functions (CSFs) of six children and five adults with both corrected and uncorrected HOAs. We found that when HOAs were corrected, children and adults both showed improvements in MTF and CSF. However, the CSF of children was still lower than the adult level, indicating the difference in contrast sensitivity between groups cannot be explained by differences in optical factors. Further study showed that the difference between the groups also could not be explained by differences in non-visual factors. With these results we concluded that the neural systems underlying vision in children of around 8 years old are still immature in contrast sensitivity.
PMCID: PMC3986699  PMID: 24732728
21.  Ataxin-3 expression correlates with the clinicopathologic features of gastric cancer 
To investigate the expression of Ataxin-3 in human gastric cancer tissues and cell lines, and explore its clinical pathologic significance. Methods: The expression of Ataxin-3 in gastric cancer (n=536) and noncancerous gastric mucosa (n=312) was determined by immunohistochemistry and correlated to clinicopathologic features such as histologic differentiation and tumor size. The expression of Ataxin-3 protein in the human gastric cancer cell lines MKN45, SGC7901 and in normal human gastric epithelial cells (GES-1) was also evaluated by Western blot analysis. Quantitative real-time PCR was used to determine Ataxin-3 mRNA expression in human gastric cancer cell lines and tissues. Results: The expression of Ataxin-3 protein was decreased in the gastric cancer compared to noncancerous gastric tissue, and correlated with tumor size, Lauren classification, histologic differentiation, and mutant p53 protein (P < 0.05). Similarly, Ataxin-3 mRNA expression was decreased in the gastric cancers compared to the noncancerous gastric tissue. Ataxin-3 protein and mRNA expression was lower in MKN45, SGC7901 cells than in the normal GES-1 cells. Conclusion: Decreased expression of Ataxin-3 may play an important role in gastric carcinogenesis and development of gastric cancer.
PMCID: PMC4057849  PMID: 24955170
Ataxin-3; gastric cancer; clinicopathologic features
22.  Fast Vesicle Transport Is Required for the Slow Axonal Transport of Synapsin 
The Journal of Neuroscience  2013;33(39):15362-15375.
Although it is known that cytosolic/soluble proteins synthesized in cell bodies are transported at much lower overall velocities than vesicles in fast axonal transport, the fundamental basis for this slow movement is unknown. Recently, we found that cytosolic proteins in axons of mouse cultured neurons are conveyed in a manner that superficially resembles diffusion, but with a slow anterograde bias that is energy- and motor-dependent (Scott et al., 2011). Here we show that slow axonal transport of synapsin, a prototypical member of this rate class, is dependent upon fast vesicle transport. Despite the distinct overall dynamics of slow and fast transport, experimentally induced and intrinsic variations in vesicle transport have analogous effects on slow transport of synapsin as well. Dynamic cotransport of vesicles and synapsin particles is also seen in axons, consistent with a model where higher-order assemblies of synapsin are conveyed by transient and probabilistic associations with vesicles moving in fast axonal transport. We posit that such dynamic associations generate the slow overall anterogradely biased flow of the population (“dynamic-recruitment model”). Our studies uncover the underlying kinetic basis for a classic cytosolic/soluble protein moving in slow axonal transport and reveal previously unknown links between slow and fast transport, offering a clearer conceptual picture of this curious phenomenon.
PMCID: PMC3782618  PMID: 24068803
23.  Enhancement of fermentable sugar yield by competitive adsorption of non-enzymatic substances from yeast and cellulase on lignin 
BMC Biotechnology  2014;14:21.
Enhancement of enzymatic digestibility by some supplementations could reduce enzyme loading and cost, which is still too high to realize economical production of lignocellulosic biofuels. A recent study indicates that yeast hydrolysates (YH) have improved the efficiency of cellulases on digestibility of furfural residues (FR). In the current work, the components of YH were separated by centrifugation and size exclusion chromatography and finally characterized in order to better understand this positive effect.
A 60.8% of nitrogen of yeast cells was remained in the slurry (YHS) after hydrothermal treatment. In the supernatant of YH (YHL), substances of high molecular weight were identified as proteins and other UV-absorbing compounds, which showed close molecular weight to components of cellulases. Those substances attributed to a synergetic positive effect on enzymatic hydrolysis of FR. The fraction of YHL ranged from 1.19 to 2.19 mL (elution volume) contained over 50% of proteins in YHL and had the best performance in stimulating the release of glucose. Experiment results proved the adsorption of proteins in YHL on lignin.
Supplementation of cellulases with YH enhances enzymatic digestibility of FR mainly by a competitive adsorption of non-enzymatic substances on lignin. The molecular weight of these substances has a significant impact on their performance. Different strategies can be used for a good utilization of yeast cells in terms of biorefinery concept.
PMCID: PMC3984015  PMID: 24650152
Cellulases; Enzymatic hydrolysis; Yeast hydrolysate; Competitive adsorption
24.  Modified total en bloc spondylectomy for thoracolumbar spinal tumors via a single posterior approach 
European Spine Journal  2012;22(3):556-564.
The objectives of this study were to describe our surgical management with a modified total en bloc spondylectomy (TES) and to evaluate the clinical effects in patients with thoracolumbar tumors.
Sixteen consecutive patients with thoracolumbar neoplasms underwent a modified TES via single posterior approach followed by dorsoventral reconstruction from December 2008 to July 2011. Details of the modified technique were described and the patients’ clinical information was retrospectively reviewed and analyzed.
Significant improvements in neurological function were achieved in most of the patients. Local pain or radicular leg pain was relieved postoperatively. The mean operation time was 7.2 h, with an average blood loss of 2,300 ml. No major complications, instrumentation failure or local recurrence was found at the final follow-up. Five patients died of the disease during mean 14-month (3.0–23) follow-up.
The modified TES with a single posterior approach is feasible, safe and effective for thoracolumbar spine tumors.
PMCID: PMC3585635  PMID: 22864795
Total en bloc spondylectomy; Modified surgical techniques; Spinal tumors; Single posterior approach; Thoracolumbar spine
25.  Epidemiology of Spinal Cord Injuries and Risk Factors for Complete Injuries in Guangdong, China: A Retrospective Study 
PLoS ONE  2014;9(1):e84733.
Spinal cord injuries are highly disabling and deadly injuries. Currently, few studies focus on non-traumatic spinal cord injuries, and there is little information regarding the risk factors for complete injuries. This study aims to describe the demographics and the injury characteristics for both traumatic and non-traumatic spinal cord injuries and to explore the risk factors for complete spinal cord injuries.
A retrospective study was performed by reviewing the medical records of 3,832 patients with spinal cord injuries who were first admitted to the sampled hospitals in Guangdong, China. The demographics and injury characteristics of the patients were described and compared between the different groups using the chi-square test. Logistic regression was conducted to analyze the risk factors for complete spinal cord injuries.
The proportion of patients increased from 7.0% to 14.0% from 2003 to 2011. The male-to-female ratio was 3.0∶1. The major cause of spinal cord injuries was traffic accidents (21.7%). Many of the injured were workers (36.2%), peasants (22.8%), and unemployed people (13.9%); these occupations accounted for 72.9% of the total sample. A multivariate logistic regression model revealed that the OR (95% CI) for male gender compared to female gender was 1.25 (1.07–1.89), the OR (95%CI) for having a spinal fracture was 1.56 (1.35–2.60), the OR (95%CI) for having a thoracic injury was 1.23 (1.10–2.00), and the OR (95%CI) for having complications was 2.47 (1.96–3.13).
The proportion of males was higher than the proportion of females. Workers, peasants and the unemployed comprised the high-risk occupational categories. Male gender, having a spinal fracture, having a thoracic injury, and having complications were the major risk factors for a complete injury. We recommend that preventive measures should focus on high-risk populations, such as young males.
PMCID: PMC3904832  PMID: 24489652

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