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1.  The structure of an authentic spore photoproduct lesion in DNA suggests a basis for recognition. Corrigendum 
A correction is made to the article by Singh et al. [(2014). Acta Cryst. D70, 752–759].
The article by Singh et al. [ (2014). Acta Cryst. D70, 752–759] is corrected.
PMCID: PMC4030664
spore photoproduct; DNA; host–guest approach; corrigendum
2.  Measurement of serum procalcitonin levels for the early diagnosis of spontaneous bacterial peritonitis in patients with decompensated liver cirrhosis 
It is difficult to diagnose spontaneous bacterial peritonitis (SBP) early in decompensated liver cirrhotic ascites patients (DCPs). The aim of the study was to measure serum procalcitonin (PCT) levels and peripheral blood leukocyte/platelet (WBC/PLT) ratios to obtain an early diagnostic indication of SBP in DCPs.
Our cohort of 129 patients included 112 DCPs (94 of whom had infections) and 17 cases with compensated cirrhosis as controls. Bacterial cultures, ascitic fluid (AF) leukocyte and peripheral WBC/PLT counts, and serum PCT measurements at admission were carried out prior to the use of antibiotics. Receiver operating characteristic (ROC) curves were generated to test the accuracies and cut-off values for different inflammatory markers.
Among the 94 infected patients, 66 tested positive by bacterial culture, for which the positivity of blood, ascites and other secretions were 25.8%, 30.3% and 43.9%, respectively. Lung infection, SBP and unknown sites of infection accounted for 8.5%, 64.9% and 26.6% of the cases, respectively. Serum PCT levels (3.02 ± 3.30 ng/mL) in DCPs with infections were significantly higher than those in control patients (0.15 ± 0.08 ng/mL); p < 0.05. We used PCT ≥0.5 ng/mL as a cut-off value to diagnose infections, for which the sensitivity and specificity was 92.5% and 77.1%. The area under the curve (AUC) was 0.89 (95% confidence interval: 0.84–0.91). The sensitivity and specificity were 62.8% and 94.2% for the diagnosis of infections, and were 68.8% and 94.2% for the diagnosis of SBP in DCPs when PCT ≥2 ng/mL was used as a cut-off value. For the combined PCT and WBC/PLT measurements, the sensitivity was 76.8% and 83.6% for the diagnosis of infections or SBP in DCPs, respectively.
Serum PCT levels alone or in combination with WBC/PLT measurements seem to provide a satisfactory early diagnostic biomarker in DCPs with infections, especially for patients with SBP.
PMCID: PMC4332920
Cirrhosis; Infection; Spontaneous bacterial peritonitis; Procalcitonin; Early diagnosis
3.  A Therapeutic Strategy for Spinal Cord Defect: Human Dental Follicle Cells Combined with Aligned PCL/PLGA Electrospun Material 
BioMed Research International  2015;2015:197183.
Stem cell implantation has been utilized for the repair of spinal cord injury; however, it shows unsatisfactory performance in repairing large scale lesion of an organ. We hypothesized that dental follicle cells (DFCs), which possess multipotential capability, could reconstruct spinal cord defect (SCD) in combination with biomaterials. In the present study, mesenchymal and neurogenic lineage characteristics of human DFCs (hDFCs) were identified. Aligned electrospun PCL/PLGA material (AEM) was fabricated and it would not lead to cytotoxic reaction; furthermore, hDFCs could stretch along the oriented fibers and proliferate efficiently on AEM. Subsequently, hDFCs seeded AEM was transplanted to restore the defect in rat spinal cord. Functional observation was performed but results showed no statistical significance. The following histologic analyses proved that AEM allowed nerve fibers to pass through, and implanted hDFCs could express oligodendrogenic lineage maker Olig2 in vivo which was able to contribute to remyelination. Therefore, we concluded that hDFCs can be a candidate resource in neural regeneration. Aligned electrospun fibers can support spinal cord structure and induce cell/tissue polarity. This strategy can be considered as alternative proposals for the SCD regeneration studies.
PMCID: PMC4324737
4.  Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes 
Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 (CYP) enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e. styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. Dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes, relative to that in the wild-type mouse lung microsomes. However, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knock–out and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed similar susceptibility to lung toxicity of styrene as the wild-type animals. However, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene.
PMCID: PMC4041473  PMID: 24320693
Styrene; reactive metabolites; P450 2E1; P450 2F2
5.  Rapamycin enhances long-term hematopoietic reconstitution of ex vivo expanded mouse hematopoietic stem cells by inhibiting senescence 
Transplantation  2014;97(1):10.1097/TP.0b013e3182a7fcf8.
The mTOR is an important regulator of HSCs self-renewal and its overactivation contributes to HSCs premature exhaustion in part via induction of HSCs senescence. Inhibition of mTOR with rapamycin has the potential to promote long term hematopoiesis of ex vivo expanded HSCs to facilitate the clinical application of HSCs transplantation for various hematological diseases.
A well-established ex vivo expansion system for mouse bone marrow HSCs was utilized to investigate whether inhibition of overactivated mTOR with rapamycin can promote long term hematopoiesis of ex vivo expanded HSCs and to elucidate the mechanisms of action of rapamycin.
HSCs-enriched mouse bone marrow LSK cells exhibited a time-dependent activation of mTOR after ex vivo expansion in a serum-free medium supplemented with SCF, TPO and FL. The overactivation of mTOR was associated with induction of senescence but not apoptosis in LSK cells and a significant reduction in the ability of HSCs to produce long-term hematopoietic reconstitution. Inhibition of overactivated mTOR with rapamycin promoted ex vivo expansion and long term hematopoietic reconstitution of HSCs. The increase in long term hematopoiesis of expanded HSCs is likely attributable in part to rapamycin-mediated upregulation of Bmi1 and downregulation of p16, which prevent HSCs from undergoing senescence during ex vivo expansion.
These findings suggest that mTOR plays an important role in the regulation of HSCs self-renewal in vitro and inhibition of mTOR hyperactivation with rapamycin may represent a novel approach to promote ex vivo expansion and their long term hematopoietic reconstitution of HSCs.
PMCID: PMC3877183  PMID: 24092377
hematopoietic stem cells; ex vivo expansion; long term hematopoietic reconstitution; mTOR; rapamycin; senescence
6.  Wnt signaling inhibits CTL memory programming 
Molecular immunology  2013;56(4):423-433.
Induction of functional CTLs is one of the major goals for vaccine development and cancer therapy. Inflammatory cytokines are critical for memory CTL generation. Wnt signaling is important for CTL priming and memory formation, but its role in cytokine-driven memory CTL programming is unclear. We found that wnt signaling inhibited IL-12-driven CTL activation and memory programming. This impaired memory CTL programming was attributed to up-regulation of eomes and down-regulation of T-bet. Wnt signaling suppressed the mTOR pathway during CTL activation, which was different to its effects on other cell types. Interestingly, the impaired memory CTL programming by wnt was partially rescued by mTOR inhibitor rapamycin. In conclusion, we found that crosstalk between wnt and the IL-12 signaling inhibits T-bet and mTOR pathways and impairs memory programming which can be recovered in part by rapamycin. In addition, direct inhibition of wnt signaling during CTL activation does not affect CTL memory programming. Therefore, wnt signaling may serve as a new tool for CTL manipulation in autoimmune diseases and immune therapy for certain cancers.
PMCID: PMC3783547  PMID: 23911398
T cells; cytotoxicity; wnt; GSK3; cytokines; memory; mTOR; rapamycin
7.  Multi-view optical resolution photoacoustic microscopy 
Optica  2014;1(4):217-222.
Optical resolution photoacoustic microscopy (OR-PAM), while providing high lateral resolution, has been limited by its relatively poor acoustically determined axial resolution. Although this limitation has been tackled in recent works by using either broadband acoustic detection or nonlinear photoacoustic effects, a flexible solution with three dimensional optical resolution in reflection mode remains desired. Herein we present a multi-view OR-PAM technique. By imaging the sample from multiple view angles and reconstructing the data using a multi-view deconvolution method, we have experimentally demonstrated an isotropic optical resolution in three dimensions.
PMCID: PMC4280660  PMID: 25558469
8.  Comparative genomic analysis of clinical and environmental strains provides insight into the pathogenicity and evolution of Vibrio parahaemolyticus 
BMC Genomics  2014;15(1):1135.
Vibrio parahaemolyticus is a Gram-negative halophilic bacterium. Infections with the bacterium could become systemic and can be life-threatening to immunocompromised individuals. Genome sequences of a few clinical isolates of V. parahaemolyticus are currently available, but the genome dynamics across the species and virulence potential of environmental strains on a genome-scale have not been described before.
Here we present genome sequences of four V. parahaemolyticus clinical strains from stool samples of patients and five environmental strains in Hong Kong. Phylogenomics analysis based on single nucleotide polymorphisms revealed a clear distinction between the clinical and environmental isolates. A new gene cluster belonging to the biofilm associated proteins of V. parahaemolyticus was found in clincial strains. In addition, a novel small genomic island frequently found among clinical isolates was reported. A few environmental strains were found harboring virulence genes and prophage elements, indicating their virulence potential. A unique biphenyl degradation pathway was also reported. A database for V. parahaemolyticus ( was constructed here as a platform to access and analyze genome sequences and annotations of the bacterium.
We have performed a comparative genomics analysis of clinical and environmental strains of V. parahaemolyticus. Our analyses could facilitate understanding of the phylogenetic diversity and niche adaptation of this bacterium.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-1135) contains supplementary material, which is available to authorized users.
PMCID: PMC4320434  PMID: 25518728
Vibrio parahaemolyticus; Comparative genomics; Clinical; Environment
9.  The BRCA1-interacting protein, Abraxas, is required for genomic stability and tumor suppression 
Cell reports  2014;8(3):807-817.
Germline mutations of BRCA1 confer hereditary susceptibility to breast and ovarian cancer. However, somatic mutation of BRCA1 is infrequent in sporadic breast cancers. The BRCA1 protein C-terminus BRCT domains interact with multiple proteins and are required for BRCA1's tumor suppressor function. In this study, we demonstrated that Abraxas, a BRCA1 BRCT domain-interacting protein, plays a role in tumor suppression. Abraxas exerts its function through binding to BRCA1 to regulate DNA repair and maintain genome stability. Both homozygous and heterozygous Abraxas knockout mice exhibited decreased survival and increased tumor incidence. The gene encoding Abraxas suffers from gene copy loss and somatic mutations in multiple human cancers including breast, ovarian, and endometrial cancers, suggesting that mutation and loss of function of Abraxas may contribute to tumor development in human patients.
PMCID: PMC4149256  PMID: 25066119
10.  TNF-α induced epithelial mesenchymal transition increases stemness properties in renal cell carcinoma cells 
Objective: Emerging evidence suggest that the acquisition of epithelial mesenchymal transition (EMT) and induction of cancer stem cell (CSC) or cancer stem-like cell phenotype are interrelated and contribute to tumor recurrence and drug resistance. The aim of this study is to shed light on the relationship between EMT and CSCs by using renal cell carcinoma (RCC) cell line, ACHN and 786-0. Methods: RCC cells were treated with 50 ng/ml of TNF-α for 14 days. To evaluate EMT, morphological changes were assessed by light microscopy. RT-PCR and Western blot for EMT-related markers. On TNF-α treated and untreated RCC cells, we performed stemness tests and stemness markers expression. Results: TNF-α treated ACHN cell lost its epithelial morphology assuming a fibroblast-like appearance. The same results were obtained for the 786-0 cells. RT-PCR and Western blot showed up-regulation of Vimentin and down-regulation of E-cadherin in TNF-α treated ACHN and 786-0 cells. Slug and ZEB1 mRNA transcripts were up-regulated in TNF-α treated RCC cells confirming EMT. This two cell line also showed overexpression of Oct4, Nanog, and Bmi-1, all genes of stemness. In addition, in TNF-α treated RCC cell, an increased tumorsphere-forming capacity was detectable. Conclusions: The induction of EMT by TNF-α exposure, in RCC cell results in the acquisition of mesenchymal profile and in the expression of stemness markers.
PMCID: PMC4307439  PMID: 25663992
Renal cell carcinoma; epithelial mesenchymal transition; cancer stem cell; TNF-α; stemness
11.  Disruption of Gene pqqA or pqqB Reduces Plant Growth Promotion Activity and Biocontrol of Crown Gall Disease by Rahnella aquatilis HX2 
PLoS ONE  2014;9(12):e115010.
Rahnella aquatilis strain HX2 has the ability to promote maize growth and suppress sunflower crown gall disease caused by Agrobacterium vitis, A. tumefaciens, and A. rhizogenes. Pyrroloquinoline quinone (PQQ), a cofactor of aldose and alcohol dehydrogenases, is required for the synthesis of an antibacterial substance, gluconic acid, by HX2. Mutants of HX2 unable to produce PQQ were obtained by in-frame deletion of either the pqqA or pqqB gene. In this study, we report the independent functions of pqqA and pqqB genes in relation to PQQ synthesis. Interestingly, both the pqqA and pqqB mutants of R. aquatilis eliminated the ability of strain HX2 to produce antibacterial substance, which in turn, reduced the effectiveness of the strain for biological control of sunflower crown gall disease. The mutation also resulted in decreased mineral phosphate solubilization by HX2, which reduced the efficacy of this strain as a biological fertilizer. These functions were restored by complementation with the wild-type pqq gene cluster. Additionally, the phenotypes of HX2 derivatives, including colony morphology, growth dynamic, and pH change of culture medium were impacted to different extents. Our findings suggested that pqqA and pqqB genes individually play important functions in PQQ biosynthesis and are required for antibacterial activity and phosphorous solubilization. These traits are essential for R. aquatilis efficacy as a biological control and plant growth promoting strain. This study enhances our fundamental understanding of the biosynthesis of an environmentally significant cofactor produced by a promising biocontrol and biological fertilizer strain.
PMCID: PMC4263746  PMID: 25502691
12.  Anterior vs conventional approach hepatectomy for large liver cancer: A meta-analysis 
World Journal of Gastroenterology : WJG  2014;20(45):17235-17243.
AIM: To evaluate the clinical outcomes and safety of anterior- and conventional-approach hepatectomy for patients with large liver tumors.
METHODS: PubMed, EMBASE, Google Scholar and the Cochrane Library databases were searched for randomized controlled trials (RCTs) and controlled clinical trials comparing anterior-approach hepatectomy (AAH) and conventional-approach hepatectomy (CAH). Two observers independently extracted the data using a spreadsheet and assessed the studies for inclusion. Studies that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were further assessed using either fixed effects or random effects models.
RESULTS: Two RCTs and six controlled clinical trials involving 807 patients met the predefined inclusion criteria. A total of 363 patients underwent AAH and 444 underwent CAH. Meta-analysis indicated that the AAH group had fewer requirements for transfusion (OR = 0.37, 95%CI: 0.21-0.63), less recurrence (OR = 0.57, 95%CI: 0.37-0.87), and lower mortality (OR = 0.29, 95%CI: 0.13-0.63). There were no significant differences between AAH and CAH with regard to perioperative complications (OR = 0.94, 95%CI: 0.58-1.51), intraoperative tumor rupture (OR = 0.98, 95%CI: 0.40-2.40), or length of hospital stay (weighted mean difference = -0.17, 95%CI: -2.36-2.02).
CONCLUSION: AAH has advantages of decreased transfusion, mortality and recurrence compared to CAH. It is a safe and effective method for large cancers requiring right hepatectomy.
PMCID: PMC4258596  PMID: 25493040
Anterior approach; Conventional approach; Hepatectomy; Liver tumor; Meta-analysis
13.  Circulating MicroRNA Profiles Differ between Qi-Stagnation and Qi-Deficiency in Coronary Heart Disease Patients with Blood Stasis Syndrome 
We compared the circulating microRNA profiles of Qi-stagnation (QSB) and Qi-deficiency (QDB) in coronary heart disease (CHD) patients with blood stasis syndrome. Twenty-nine CHD patients were divided into QSB group and QDB group. The analysis was carried out through comparing their circulating microRNA profiles and the following bioinformatics analysis. The number of differential miRNAs in QDB group was much more than that in QSB group. Functional annotations of the differentially expressed miRNAs target genes in the QSB group and QDB group were, respectively, related to regulation of cellular component organization, regulation of glucose metabolic process, and so forth and protein kinase cascade, phosphate metabolic process, and so forth. KEGG pathway analysis showed that the process Qi-deficiency was associated with phagocytosis including endocytosis and mTOR signaling pathway. Specifically, pathway of cell adhesion molecules played the crucial role in the pathological process of Qi-stagnation, with a unique upregulation except for pathways associated with cancer signal. MicroRNA-gene-net analysis indicated that let-7c, miR-4487, miR-619, miR-8075, miR-6735, and miR-32-5p and miR-17-5p, miR-130a, and miR 320 family had the most important and extensive regulatory function for Qi-stagnation syndromes and Qi-deficiency syndromes, respectively. Differentially expressed miRNAs and concerned pathways suggest different molecular mechanisms that may mediate the pathological process of QSB and QDB syndromes.
PMCID: PMC4273468  PMID: 25548593
14.  The mINO80 chromatin remodeling complex is required for efficient telomere replication and maintenance of genome stability 
Cell Research  2013;23(12):1396-1413.
The INO80 (inositol requiring mutant 80) chromatin remodeling complex plays important roles in transcriptional regulation and DNA replication and repair, and consists of several functional protein subunits, including the critical Ino80 ATPase catalytic subunit. While the function of INO80 has been studied in yeast and mammalian cell lines, we do not know how mIno80 contributes to the maintenance of genome stability to prevent cancer development in mice. Here, we use a conditional knockout approach to explore the cellular and organismal functions of mIno80. Deletion of mIno80 results in profound cellular proliferative defects and activation of p21-dependent cellular senescence. While mIno80 is required for efficient repair of DNA double strand breaks, its depletion did not impact upon the formation of γ-H2AX and 53BP1 DNA damage foci, or the activation of the ATM-CHK2-dependent DNA damage response. mIno80 deletion inhibited the generation of single-strand DNA, resulting in defects in homology-directed DNA repair (HDR) at telomeres. Fragile telomeres were prominent in mIno80Δ/Δ MEFs, suggesting that chromatin remodeling is required for efficient telomere replication. mIno80−/− mouse embryos die early during embryogenesis, while conditional deletion of mIno80 in adult mice results in weight loss and premature death. In a p53−/− tumor-prone background, mIno80 haploinsufficiency favored the development of sarcomas. Our studies suggest that the mIno80 chromatin remodeling complex plays important roles in telomere replication, HDR-mediated repair of dysfunctional telomeres, and maintenance of genome stability.
PMCID: PMC3847565  PMID: 23979016
DNA damage; telomere; cancer; genome instability; chromatin; replication
15.  Immunogenicity of Haemophilus influenzae Type b Protein Conjugate Vaccines in Very Low Birth Weight Infants 
PMCID: PMC3960569  PMID: 24569312
Infant; premature; infant; very low birth weight; Haemophilus influenzae vacines; immunization; vaccines
16.  Epithelioid angiosarcoma of the ilium: a case report 
Bone epithelioid angiosarcoma (EA) is rare and characterized by large, mildly to moderately pleomorphic epithelioid cells, with abundant eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. The tumors may arise in various locations in bone and the patients may present with unifocal or multifocal osseous disease. We present a unifocal lesion case of EA of the ilium in a 62-year-old woman. A needle biopsy of the ilium was performed and first diagnosed poorly differentiated adenocarcinoma based on CKpan and CK18 immunopositivity. The tumor was treated initially with curettage followed by chemotherapy. The final diagnosis on the surgical specimen was epithelioid angiosarcoma.
PMCID: PMC4313960
Epithelioid angiosarcoma; bone
17.  Meta-Analysis of Oncological Outcome After Abdominoperineal Resection or Low Anterior Resection for Lower Rectal Cancer 
In lower rectal cancer, postoperative outcome is still subject of controversy between the advocates of abdominoperineal resection (APR) and low anterior resection (LAR). Reports suggest that low anterior resection may be oncologically superior to abdominoperineal excision, although no good evidence exists to support this. Publications were identified which assessed the differences comparing 5-year survival, local recurrence, circumferential resection margin rate, complications and so on. A meta-analysis was performed to clarify the safety and feasibility of the two procedures with several types of outcome measures. A total of 13 studies met the inclusion criteria, and comprised 6,850 cases. Analysis of these data showed that LAR group was highly correlated with 5-year survival (pooled OR = 1.73, 95%CI: 1.30–2.29, P = 0.0002 random-effect). And local recurrence rate of APR group was significantly higher than that in LAR group (pooled OR = 0.63, 95%CI: 0.53–0.75, P < 0.00001 fixed-effect). Also, the circumferential resection margin (CRM) were high involved in APR group than in LAR group. (5 trials reported the data, pooled OR = 0.43, 95%CI: 0.36–0.52, P < 0.00001 fixed-effect). Besides, the incidents of overall complications of APR group was higher compared with LAR group (pooled OR = 0.52, 95%CI: 0.29–0.92, P = 0.03 random-effect). Patients treated by APR have a higher rate of CRM involvement, a higher local recurrence, and poorer prognosis than LAR. And there is evidence that in selected low rectal cancer patients, LAR can be used safely with a better oncological outcome than APR. due to the inherent limitations of the present study, for example, the trails available for this systematic review are limited and the finite retrospective data, future prospective randomized controlled trials will be useful to fully investigate these outcome measures and to confirm this conclusion.
PMCID: PMC4287681  PMID: 25430561
Low anterior resection; Abdominoperineal resection; Lower rectal cancer; Prognosis
18.  detectIR: A Novel Program for Detecting Perfect and Imperfect Inverted Repeats Using Complex Numbers and Vector Calculation 
PLoS ONE  2014;9(11):e113349.
Inverted repeats are present in abundance in both prokaryotic and eukaryotic genomes and can form DNA secondary structures – hairpins and cruciforms that are involved in many important biological processes. Bioinformatics tools for efficient and accurate detection of inverted repeats are desirable, because existing tools are often less accurate and time consuming, sometimes incapable of dealing with genome-scale input data. Here, we present a MATLAB-based program called detectIR for the perfect and imperfect inverted repeat detection that utilizes complex numbers and vector calculation and allows genome-scale data inputs. A novel algorithm is adopted in detectIR to convert the conventional sequence string comparison in inverted repeat detection into vector calculation of complex numbers, allowing non-complementary pairs (mismatches) in the pairing stem and a non-palindromic spacer (loop or gaps) in the middle of inverted repeats. Compared with existing popular tools, our program performs with significantly higher accuracy and efficiency. Using genome sequence data from HIV-1, Arabidopsis thaliana, Homo sapiens and Zea mays for comparison, detectIR can find lots of inverted repeats missed by existing tools whose outputs often contain many invalid cases. detectIR is open source and its source code is freely available at:
PMCID: PMC4237412  PMID: 25409465
19.  Examining the base stacking interaction in a dinucleotide context via reversible cyclobutane dimer analogue formation under UV irradiation 
RSC advances  2013;3(42):10.1039/C3RA41702F.
Substituted tolyl groups are considered as close isosteres of the thymine (T) residue. They can be recognized by DNA polymerases as if they were thymine. Although these toluene derivatives are relatively inert toward radical additions, our recent finding suggests that the dinucleotide analogue TpTo (To = 2'-deoxy-1-(3-tolyl)-β-D-ribofuranose) supports an ortho photocycloaddition reaction upon UV irradiation, producing two cyclobutane pyrimidine dimer (CPD) analogues 2 and 3. Our report here further shows that formation of these CPD species is reversible under UVC irradiation, resembling the photochemical property of the CPD species formed between two Ts. Analyzing the stability of these CPD analogues suggests that one (2) is more stable than the other (3). The TpTo conformer responsible for 2 formation is also more stable than that responsible for 3 formation, as indicated by the Gibbs free energy change calculated from the constructed Bordwell thermodynamic cycle. These different stabilities are not due to the varying photochemical properties, as proved by quantum yields determined from the corresponding photoreactions. Instead, they are ascribed to the different stacking interaction between the T and the To rings both in the TpTo dinucleotide as well as in the formed CPD analogues. Factors contributing to the ring stacking interactions are also discussed. Our proof-of-concept approach suggests that a carefully designed Bordwell cycle coupled with reversible CPD formations under UV irradiation can be very useful in studying DNA base interactions.
PMCID: PMC3821078  PMID: 24223299
20.  Study on the Anti-Cerebral Ischemia Effect of Borneol and Its Mechanism 
Borneol is the processed item from resin of Dryobalanops aromatica Gaertn. f. It can enhance the activity of antioxidant enzymes in brain tissue and reduce inflammatory response by improving the energy metabolism of ischemic brain regions, and thereby reduces brain tissue damage. The objective of this paper was to study the anti-cerebral ischemia effect of borneol and its mechanism.
Materials and Methods
The anti-cerebral ischemia effect of borneol was studied by ligation of bilateral common carotid arteries (CCA), and vagus nerves in mice and the acute cerebral ischemia-reperfusion experiment in rats.
Compared with the blank and solvent control groups, the borneol low-; medium-; and high-dose groups can significantly prolong the gasping time of mice after decapitation, and extend the survival time of mice after ligation of bilateral CCA, and vagus nerves.
Compared with the Xueshuantong injection group, the prolongation of survival time of mice after ligation of bilateral CCA, and vagus nerves was more apparent in the high-dose borneol experimental group; each experimental group can significantly reduce the number of leukocyte infiltration, the number of ICAM-1-positive vessels, as well as the number of TNF-α-positive cells.
Borneol has an anti-cerebral ischemia effect.
PMCID: PMC3957259  PMID: 24653571
borneol; cerebral ischemia-reperfusion; IL-1β, TNF-α; ICAM-1
21.  HIV-1 tat and rev upregulates osteoclast bone resorption 
Journal of the International AIDS Society  2014;17(4Suppl 3):19724.
Disruption in bone homeostasis with increased osteoclastic resorption may lead to osteoporosis. HIV tat has been found to increase differentiation of precursor cells into osteoclast (OC) [1]. Presence of soluble HIV proteins in virally suppressed HIV patients on ART may drive a bone resorption phenotype. We investigated the role of soluble HIV proteins (tat, gp120 Mn and Bal, rev and p55-gag) on osteoclastogenesis and OC resorptive capacity.
Mouse monocyte RAW 264.7 cells were cultured in vitro and induced to differentiate into OCs with 50 ng/mL RANKL and 25 ng/mL mCSF. Medium was supplemented with 100 ng/mL of recombinant HIV tat, gp120 (Mn and Bal), rev, nef and p55-gag, respectively, with zolendronate as negative control. Differentiated OCs were stained for TRAP and counted. OC resorption function was examined by culturing differentiated OCs (in the presence of respective HIV proteins) on dentin-coated plates and examining the following (i) sealing zone formation, (ii) volume of resorption pits and (iii) area of resorption pits per field using confocal microscopy. Expression of OC specific genes including NFATc1 and cathepsin K was investigated by qPCR. Reactive oxygen species (ROS) production is essential in RANKL-induced OC differentiation [2,3]; effect of these proteins on ROS production was assessed using the fluorescent H2DCFH-DA. Mean fluorescence intensity was then measured by flow cytometry. TNFα production by OC precursors when incubated with tat and rev was measured by ELISA.
Tat and rev treatment was associated with increased OC formation by 70 and 26%, respectively (p<0.01), relative to control, while zolendronate significantly inhibited OC formation by 75%. Gp120 Mn and Bal, nef and p55-gag treatment had no effect on OC differentiation. Interestingly, neither tat nor rev treatment caused significant increases in sealing zone formation but increased dentin resorption pit area by 28 and 19%, respectively, and resorption pit volume by 11 and 6%, respectively. Tat protein treatment was associated with upregulation of NFATc1 and cathepsin K mRNA expression by 20 and 15%, respectively. Incubation with tat and rev led to a dose-dependent increase in intracellular ROS production in the monocytes and OC precursors and significant upregulation in TNFα cytokine production by the OC precursors.
In addition to their effect of OC differentiation, we demonstrated the effects of tat and rev on OC resorption. HIV tat and rev are both biologically active in driving a pro-osteoclastic phenotype.
PMCID: PMC4225338  PMID: 25397470
22.  Efficient Enzymatic Synthesis of Guanosine 5′-Diphosphate-Sugars and Derivatives 
Organic letters  2013;15(21):5528-5530.
An N-acetylhexosamine 1-kinase from Bifidobacterium infantis (NahK_15697), a guanosine 5′-diphosphate (GDP)-mannose pyrophosphorylase from Pyrococcus furiosus (PFManC), and an Escherichia coli inorganic pyrophosphatase (EcPpA) were used efficiently for a one-pot three-enzyme synthesis of GDP-mannose, GDPglucose, their derivatives, and GDP-talose. This study represents the first facile and efficient enzymatic synthesis of GDP-sugars and derivatives starting from monosaccharides and derivatives.
PMCID: PMC3915774  PMID: 24117142
23.  SEME: A Fast Mapper of Illumina Sequencing Reads with Statistical Evaluation 
Journal of Computational Biology  2013;20(11):847-860.
Mapping reads to a reference genome is a routine yet computationally intensive task in research based on high-throughput sequencing. In recent years, the sequencing reads of the Illumina platform have become longer and their quality scores higher. According to our calculation, this allows perfect k-mer seed match for almost all reads when a close reference genome is available subject to reasonable specificity. Our other observation is that the majority reads contain at most one short INDEL polymorphism. Based on these observations, we propose a fast-mapping approach, referred to as “SEME,” which has two core steps: First it scans a read sequentially in a specific order for a k-mer exact match seed; next it extends the alignment on both sides allowing, at most, one short INDEL each using a novel method called “auto-match function.” We decompose the evaluation of the sensitivity and specificity into two parts corresponding to the seed and extension step, and the composite result provides an approximate overall reliability estimate of each mapping. We compare SEME with some existing mapping methods on several datasets, and SEME shows better performance in terms of both running time and mapping rates.
PMCID: PMC3822393  PMID: 24195707
auto-match function high-throughput sequencing; INDEL; mapping; perfect match
24.  Validation of Bmi1 as a Therapeutic Target of Hepatocellular Carcinoma in Mice 
Bmi1 is a member of the polycomb group family of proteins, and it drives the carcinogenesis of various cancers and governs the self-renewal of multiple types of stem cells. Our previous studies have revealed that Bmi1 acts as an oncogene in hepatic carcinogenesis in an INK4a/ARF locus independent manner. However, whether Bmi1 can be used as a potential target for hepatocellular carcinoma treatment has not been fully confirmed yet. Here, we show that perturbation of Bmi1 expression by using short hairpin RNA can inhibit the tumorigenicity and tumor growth of hepatocellular carcinoma cells both in vitro and in vivo. Importantly, Bmi1 knockdown can block the tumor growth, both in the initiating stages and the fast growing stages. Cellular biology analysis revealed that Bmi1 knockdown induces cell cycle arrest and apoptosis. Our findings verify Bmi1 as a qualified treatment target for hepatocellular carcinoma (HCC) and support Bmi1 targeting treatment with chemotherapeutic agents.
PMCID: PMC4264152  PMID: 25372945
Bmi1; HCC; knockdown; proliferation; treatment
25.  A Review of Imaging Techniques for Plant Phenotyping 
Sensors (Basel, Switzerland)  2014;14(11):20078-20111.
Given the rapid development of plant genomic technologies, a lack of access to plant phenotyping capabilities limits our ability to dissect the genetics of quantitative traits. Effective, high-throughput phenotyping platforms have recently been developed to solve this problem. In high-throughput phenotyping platforms, a variety of imaging methodologies are being used to collect data for quantitative studies of complex traits related to the growth, yield and adaptation to biotic or abiotic stress (disease, insects, drought and salinity). These imaging techniques include visible imaging (machine vision), imaging spectroscopy (multispectral and hyperspectral remote sensing), thermal infrared imaging, fluorescence imaging, 3D imaging and tomographic imaging (MRT, PET and CT). This paper presents a brief review on these imaging techniques and their applications in plant phenotyping. The features used to apply these imaging techniques to plant phenotyping are described and discussed in this review.
PMCID: PMC4279472  PMID: 25347588
phenotyping phenotype; fluorescence imaging; thermal infrared imaging; visible light imaging; imaging spectroscopy; three dimensional imaging

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