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1.  Satellite-Based Analysis of Evapotranspiration and Water Balance in the Grassland Ecosystems of Dryland East Asia 
PLoS ONE  2014;9(5):e97295.
The regression tree method is used to upscale evapotranspiration (ET) measurements at eddy-covariance (EC) towers to the grassland ecosystems over the Dryland East Asia (DEA). The regression tree model was driven by satellite and meteorology datasets, and explained 82% and 76% of the variations of ET observations in the calibration and validation datasets, respectively. The annual ET estimates ranged from 222.6 to 269.1 mm yr−1 over the DEA region with an average of 245.8 mm yr−1 from 1982 through 2009. Ecosystem ET showed decreased trends over 61% of the DEA region during this period, especially in most regions of Mongolia and eastern Inner Mongolia due to decreased precipitation. The increased ET occurred primarily in the western and southern DEA region. Over the entire study area, water balance (the difference between precipitation and ecosystem ET) decreased substantially during the summer and growing season. Precipitation reduction was an important cause for the severe water deficits. The drying trend occurring in the grassland ecosystems of the DEA region can exert profound impacts on a variety of terrestrial ecosystem processes and functions.
doi:10.1371/journal.pone.0097295
PMCID: PMC4028206  PMID: 24845063
2.  Visualization of inflammation and demyelination in 2D2 transgenic mice with rodent MRI 
Journal of neuroimmunology  2013;264(0):10.1016/j.jneuroim.2013.09.008.
Research tools are urgently needed to elucidate the specificities of NMO and MS due to their clinical similarity at the early stage of the diseases. Herein, using high-field-strength MRI we characterized the optic nerve and spinal cord lesions in 2D2tg mice (MOG 35-55 specific TCR). Specifically, early Blood-Brain Barrier breakdown was observed in 86% of the 2D2tg mice, while the majority of mice showed little to no brain lesions. Further, immunohistology showed inflammatory infiltrates and demyelination in the brain and spinal cord that mirrored sites of MRI lesions, along with a decrease in AQP4 protein at lesion sites. Collectively, 2D2tg mice develop optic and spinal cord lesions that can be visualized by high-field rodent MRI and verified by pathological assessment. The similarity of these lesions with those seen in NMO patients suggests that the 2D2tg mouse might serve as a model for NMO research.
doi:10.1016/j.jneuroim.2013.09.008
PMCID: PMC3839790  PMID: 24094460
Neuromeyelitis Optica; multiple sclerosis; TCR transgenic mice; MRI
3.  Tumor Suppressor DYRK1A Effects on Proliferation and Chemoresistance of AML Cells by Downregulating c-Myc 
PLoS ONE  2014;9(6):e98853.
Acute myeloid leukemia (AML), caused by abnormal proliferation and accumulation of hematopoietic progenitor cells, is one of the most common malignancies in adults. We reported here DYRK1A expression level was reduced in the bone marrow of adult AML patients, comparing to normal controls. Overexpression of DYRK1A inhibited the proliferation of AML cell lines by increasing the proportion of cells undergoing G0/G1 phase. We reasoned that the proliferative inhibition was due to downregulation of c-Myc by DYRK1A, through mediating its degradation. Moreover, overexpression of c-Myc markedly reversed AML cell growth inhibition induced by DYRK1A. DYRK1A also had significantly lower expression in relapsed/refractory AML patients, comparing to newly-diagnosed AML patients, which indicated the role of DYRK1A in chemoresistance of AML. Our study provided functional evidences for DYRK1A as a potential tumor suppressor in AML.
doi:10.1371/journal.pone.0098853
PMCID: PMC4047119  PMID: 24901999
4.  Evaluation of Paeonol Skin-Target Delivery from Its Microsponge Formulation: In Vitro Skin Permeation and In Vivo Microdialysis 
PLoS ONE  2013;8(11):e79881.
The aim of the present study was to design a novel topical skin-target drug-delivery system, the paeonol microsponge, and to investigate its drug-release patterns in dosage form, both in vitro and in vivo. Paeonol microsponges were prepared using the quasi-emulsion solvent-diffusion method. In vitro release studies were carried out using Franz diffusion cells, while in vivo studies were investigated by microdialysis after the paeonol microsponges were incorporated into a cream base. In vitro release studies showed that the drug delivered via microsponges increased the paeonol permeation rate. Ex vivo drug-deposition studies showed that the microsponge formulation improved drug residence in skin. In addition, in vivo microdialysis showed that the values for the area under the concentration versus time curve (AUC) for the paeonol microsponge cream was much higher than that of paeonol cream without microsponges. Maximum time (Tmax) was 220 min for paeonol microsponge cream and 480 min for paeonol cream, while the half-life (t1/2) of paeonol microsponge cream (935.1 min) was almost twice that of paeonol cream (548.6 min) in the skin (n = 3). Meanwhile, in the plasma, the AUC value for paeonol microsponge cream was half that of the paeonol cream. Based on these results, paeonol-loaded microsponge formulations could be a better alternative for treating skin disease, as the formulation increases drug bioavailability by lengthening the time of drug residence in the skin and should reduce side-effects because of the lower levels of paeonol moving into the circulation.
doi:10.1371/journal.pone.0079881
PMCID: PMC3835837  PMID: 24278204
5.  Optimization of fatty alcohol biosynthesis pathway for selectively enhanced production of C12/14 and C16/18 fatty alcohols in engineered Escherichia coli 
Background
With the increasing stress from oil price and environmental pollution, aroused attention has been paid to the microbial production of chemicals from renewable sources. The C12/14 and C16/18 alcohols are important feedstocks for the production of surfactants and detergents, which are widely used in the most respected consumer detergents, cleaning products and personal care products worldwide. Though bioproduction of fatty alcohols has been carried out in engineered E. coli, several key problems have not been solved in earlier studies, such as the quite low production of C16/18 alcohol, the lack of optimization of the fatty alcohol biosynthesis pathway, and the uncharacterized performance of the engineered strains in scaled-up system.
Results
We improved the fatty alcohol production by systematically optimizing the fatty alcohol biosynthesis pathway, mainly targeting three key steps from fatty acyl-acyl carrier proteins (ACPs) to fatty alcohols, which are sequentially catalyzed by thioesterase, acyl-coenzyme A (CoA) synthase and fatty acyl-CoA reductase. By coexpression of thioesterase gene BTE, acyl-CoA synthase gene fadD and fatty acyl-CoA reductase gene acr1, 210.1 mg/L C12/14 alcohol was obtained. A further optimization of expression level of BTE, fadD and acr1 increased the C12/14 alcohol production to 449.2 mg/L, accounting for 75.0% of the total fatty alcohol production (598.6 mg/L). In addition, by coexpression of thioesterase gene ‘tesA, acyl-CoA synthase gene fadD and fatty acyl-CoA reductase gene FAR, 101.5 mg/L C16/18 alcohol was obtained, with C16/18 alcohol accounting for 89.2% of the total fatty alcohol production.
Conclusions
To our knowledge, this is the first report on selective production of C12/14 and C16/18 alcohols by microbial fermentation. This work achieved high-specificity production of both C12/14 and C16/18 alcohols. The encouraging 598.6 mg/L of fatty alcohols represents the highest titer reported so far. In addition, the 101.5 mg/L 89.2% C16/18 alcohol suggests an important breakthrough in C16/18 alcohol production. A more detailed optimization of the expression level of fatty alcohol biosynthesis pathway may contribute to a further improvement of fatty alcohol production.
doi:10.1186/1475-2859-11-65
PMCID: PMC3439321  PMID: 22607313
Fatty alcohol; Escherichia coli; Pathway optimization; Selective production; Fermentation
6.  1,1′-(p-Phenyl­enedimethyl­idene)diimidazol-3-ium bis­{2-[(2-carb­oxy­phen­yl)disulfan­yl]benzoate} dihydrate 
The title salt, C14H16N4 2+·2C14H9O4S2 −·2H2O, was obtained by the co-crystalization of 2,2′-dithio­dibenzoic acid with 1,4-bis­(imidazol-1-ylmeth­yl)benzene. It consists of 2-[(2-carb­oxy­phen­yl)disulfan­yl]benzoate anions, centrosymmetric 1,1′-(p-phenyl­enedimethyl­idene)diimidazol-3-ium cations and water mol­ecules. O—H⋯O, O—H⋯S and N—H⋯O hydrogen-bonding inter­actions among the components lead to the formation of a three-dimensional network.
doi:10.1107/S1600536810047021
PMCID: PMC3011651  PMID: 21589520
7.  Transcriptome Analysis of a cDNA Library from Adult Human Epididymis 
Mammalian Gene Collection (MGC) verified over 9000 human full-ORF genes and FLJ Program reported 21 243 cDNAs of which 14 409 were unique ones and 5416 seemed to be protein-coding. The pity is that epididymis cDNA library was missing in their sequencing target list. Epididymis is a very important male accessory sex organ for sperm maturation and storage. Fully differentiated spermatozoa left from testis acquire their motility and capacity for fertilization via interactions with the epididymal epithelium duct lumen during passage through this convoluted duct. Here, we report that 20 000 clones from a healthy male epididymis cDNA library have been sequenced. The sequencing data provided 8234 known sequences and 650 unknown cDNA fragments. Hundred and six of 650 unknown cDNA clone inserts were randomly selected for fully sequencing. There were 25 unknown unique sequences and 19 released but unreported sequences came out. By northern blot analysis, four sequences randomly selected from the 19 released sequences with no known function showed positive mRNA signals in epididymis and testis. The signals for three of six from those unknown group showed as epididymis abundant in a region-specific manner but not in the testis and other tissues tested. All the sequencing data will be available on the website www.sdscli.com.
doi:10.1093/dnares/dsn005
PMCID: PMC2650638  PMID: 18390568
human epididymis cDNA library; transcriptomes for human epididymis; sperm maturation
8.  Novel Agent Nitidine Chloride Induces Erythroid Differentiation and Apoptosis in CML Cells through c-Myc-miRNAs Axis 
PLoS ONE  2015;10(2):e0116880.
The proto-oncogene c-Myc plays critical roles in human malignancies including chronic myeloid leukemia (CML), suggesting that the discovery of specific agents targeting c-Myc would be extremely valuable for CML treatment. Nitidine Chloride (NC), a natural bioactive alkaloid, is suggested to possess anti-tumor effects. However, the function of NC in leukemia and the underlying molecular mechanisms have not been established. In this study, we found that NC induced erythroid differentiation, accompanied by increased expression of erythroid differentiation markers, e. g. α-, ε-, γ-globin, CD235a, CD71 and α-hemoglobin stabilizing protein (AHSP) in CML cells. We also observed that NC induced apoptosis and upregulated cleaved caspase-3 and Parp-1 in K562 cells. These effects were associated with concomitant attenuation of c-Myc. Our study showed that NC treatment in CML cells enhanced phosphorylation of Thr58 residue and subsequently accelerated degradation of c-Myc. A specific group of miRNAs, which had been reported to be activated by c-Myc, mediated biological functions of c-Myc. We found that most of these miRNAs, especially miR-17 and miR-20a showed strong decrement after NC treatment or c-Myc interference. Furthermore, overexpression of c-Myc or miR-17/20a alleviated NC induced differentiation and apoptosis in K562 cells. More importantly, NC enhanced the effects of imatinib in K562 and primary CML cells. We further found that even imatinib resistant CML cell line (K562/G01) and CML primary cells exhibited high sensitivity to NC, which showed potential possibility to overcome imatinib resistance. Taken together, our results clearly suggested that NC promoted erythroid differentiation and apoptosis through c-Myc-miRNAs regulatory axis, providing potential possibility to overcome imatinib resistance.
doi:10.1371/journal.pone.0116880
PMCID: PMC4315404  PMID: 25647305
9.  Ganglioside promotes the bridging of sciatic nerve defects in cryopreserved peripheral nerve allografts 
Neural Regeneration Research  2014;9(20):1820-1823.
Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation. In this study, 10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation and were used for the repair of left sciatic nerve defects through allograft bridging. Three days later, 1 mL ganglioside solution (1 g/L) was subcutaneously injected into the right hind leg of rabbits. Compared with non-injected rats, muscle wet weight ratio was increased at 2–12 weeks after modeling. The quantity of myelinated fibers in regenerated sciatic nerve, myelin thickness and fiber diameter were elevated at 4–12 weeks after modeling. Sciatic nerve potential amplitude and conduction velocity were raised at 8 and 12 weeks, while conduction latencies were decreased at 12 weeks. Experimental findings indicate that ganglioside can promote the regeneration of sciatic nerve defects after repair with cryopreserved peripheral nerve allografts.
doi:10.4103/1673-5374.143429
PMCID: PMC4239772  PMID: 25422644
nerve regeneration; ganglioside; peripheral nerve; bridge; repair; nerve graft; cryopreservation; nerve allograft; sciatic nerve; neural regeneration
10.  HER-2 positive breast cancer is associated with an increased risk of positive cavity margins after initial lumpectomy 
Background
The effect of breast cancer subtype on margin status after lumpectomy remains unclear. This study aims to determine whether approximated breast cancer subtype is associated with positive margins after lumpectomy, which could be used to determine if there is an increased risk of developing local recurrence (LR) following breast-conserving surgery.
Methods
We studied 1,032 consecutive patients with invasive cancer who received lumpectomies and cavity margin (CM) assessments from January 2003 to November 2012. The following data were collected: patient age, cT stage, pT stage, grade, status of CM, lymph node status, menopausal status, ER, PR, HER-2, and Ki67, as well as the presence of extensive intraductal component (EIC) and lymphovascular invasion (LVI). A χ2 test was used to compare categorical baseline characteristics. Univariate and multivariate logistic regression analyses were performed to evaluate associations between pathologic features of CM status. Kaplan-Meier actuarial cumulative rates of LR (ipsilateral in-breast) were calculated.
Results
A total of 7,884 pieces of marginal tissue were collected from 1,032 patients, and 209 patients had positive CMs. Of the patients tested, 52.3% had luminal A subtype, 14.9% were luminal B, 12.8% were luminal-HER-2, 8.1% were HER-2 enriched, and 11.8% were triple negative. Univariate analysis showed that EIC (P <0.001), LVI (P = 0.026), pN stage (N1 vs. N0: P = 0.018; N3 vs. N0: P <0.001), and luminal B (P = 0.001) and HER-2 (P <0.001) subtypes were associated with positive CMs. Multivariable analysis indicated that only EIC (P <0.001), pN stage (P = 0.003), and HER-2 subtype (P <0.001) were significantly correlated with positive CMs. On multivariable analysis, HER-2 subtype was an independent prognostic factor in LR (P = 0.031).
Conclusions
The HER-2 subtype was the predictive factor most associated with positive CMs and an independent prognostic factor for LR. This result suggests that the increased risk of LR in HER-2 breast cancer is due to an increased microscopic invasive tumor burden, which is indicated by margin status after lumpectomy.
Electronic supplementary material
The online version of this article (doi:10.1186/1477-7819-12-289) contains supplementary material, which is available to authorized users.
doi:10.1186/1477-7819-12-289
PMCID: PMC4190445  PMID: 25241216
Breast cancer subtype; Breast-conserving surgery; Cavity margin; HER-2
11.  Infection of equine monocyte-derived macrophages with an attenuated equine infectious anemia virus (EIAV) strain induces a strong resistance to the infection by a virulent EIAV strain 
Veterinary Research  2014;45(1):82.
The Chinese attenuated equine infectious anemia virus (EIAV) vaccine has successfully protected millions of equine animals from EIA disease in China. Given that the induction of immune protection results from the interactions between viruses and hosts, a better understanding of the characteristics of vaccine strain infection and host responses would be useful for elucidating the mechanism of the induction of immune protection by the Chinese attenuated EIAV strain. In this study, we demonstrate in equine monocyte-derived macrophages (eMDM) that EIAVFDDV13, a Chinese attenuated EIAV strain, induced a strong resistance to subsequent infection by a pathogenic strain, EIAVUK3. Further experiments indicate that the expression of the soluble EIAV receptor sELR1, Toll-like receptor 3 (TLR3) and interferon β (IFNβ) was up-regulated in eMDM infected with EIAVFDDV13 compared with eMDM infected with EIAVUK3. Stimulating eMDM with poly I:C resulted in similar resistance to EIAV infection as induced by EIAVFDDV13 and was correlated with enhanced TLR3, sELR1 and IFNβ expression. The knock down of TLR3 mRNA significantly impaired poly I:C-stimulated resistance to EIAV, greatly reducing the expression of sELR1 and IFNβ and lowered the level of infection resistance induced by EIAVFDDV13. These results indicate that the induction of restraining infection by EIAVFDDV13 in macrophages is partially mediated through the up-regulated expression of the soluble viral receptor and IFNβ, and that the TLR3 pathway activation plays an important role in the development of an EIAV-resistant intracellular environment.
Electronic supplementary material
The online version of this article (doi:10.1186/s13567-014-0082-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s13567-014-0082-y
PMCID: PMC4283155  PMID: 25106750
12.  Impact of Neoadjuvant Chemotherapy on Immediate Breast Reconstruction: A Meta-Analysis 
PLoS ONE  2014;9(5):e98225.
Objective
The objective of this study was to perform a meta-analysis of published studies for evaluating the impact of neoadjuvant chemotherapy (NAC) on immediate breast reconstruction.
Methods
We searched medical databases to identify appropriate studies that assessed the impact of NAC on immediate breast reconstruction from the inception of this technique through April 2013. We then performed a meta-analysis of these studies.
Results
Our searches identified 11 studies among 1,840 citations. In the meta-analysis, NAC did not increase the overall rate of complications after immediate breast reconstruction (odds ratio [OR] = 0.59; 95% confidence interval[CI] = 0.38–0.91). The complication rate was also unaffected by NAC when we considered infections (OR = 0.82; 95% CI = 0.46–1.45), hematomas (OR = 1.35; 95% CI = 0.57–3.21), and seromas (OR = 0.77; 95% CI = 0.23–2.55). Additionally, expander or implant loss did not significantly increase in patients after NAC (OR = 1.59; 95% CI = 0.91–2.79). Only 2 studies (202 procedures) had reported total autologous flap loss, and they were included in our analysis; both studies found no association between NAC and total flap loss.
Conclusion
Our analysis suggests that NAC does not increase the complication rate after immediate breast reconstruction. For appropriately selected patients, immediate breast reconstruction following NAC is a safe procedure. The best way to study this issue in the future is to conduct a multicenter prospective study with a longer follow-up period and more clearly defined parameters.
doi:10.1371/journal.pone.0098225
PMCID: PMC4039499  PMID: 24878776
13.  Perineal lipoblastoma: a case report and review of literature 
Lipoblastoma is a rare benign mesenchymal tumor that composes of embryonal white fat tissue and typically occurs in infants or young children under 3 years of age. It usually affects the extremities, trunk, head, and neck. The perineum is a rare location with only 7 cases reported in the literature. We describe a case of 3-year-old girl with a lipoblastoma arising from perineum. An approximately 4.5 cm × 3.5 cm × 2.5 cm nodule was resected in left perineum with satisfied results. Pathological examination showed that it was composed of small lobules of mature and immature fat cells, separated by fibrous septa containing small dilated blood vessels. The left perineal lipoblastoma, although rare, should be differentiated from some other mesenchymal tumors with similar histologic and cytological features.
PMCID: PMC4097269  PMID: 25031762
Perineum; lipoblastoma; myxoid liposarcoma; childhood; pathology
14.  Visual Working Memory Capacity for Color Is Independent of Representation Resolution 
PLoS ONE  2014;9(3):e91681.
Background
The relationship between visual working memory (VWM) capacity and resolution of representation have been extensively investigated. Several recent ERP studies using orientation (or arrow) stimuli suggest that there is an inverse relationship between VWM capacity and representation resolution. However, different results have been obtained in studies using color stimuli. This could be due to important differences in the experimental paradigms used in previous studies.
Methodology/Principal Findings
We examined whether the same relationship between capacity and resolution holds for color information. Participants performed a color change detection task while their electroencephalography was recorded. We manipulated representation resolution by asking participants to detect either a salient change (low-resolution) or a subtle change (high-resolution) in color. We used an ERP component known as contralateral delay activity (CDA) to index the amount of information maintained in VWM. The result demonstrated the same pattern for both low- and high-resolution conditions, with no difference between conditions.
Conclusions/Significance
This result suggests that VWM always represents a fixed number of approximately 3–4 colors regardless of the resolution of representation.
doi:10.1371/journal.pone.0091681
PMCID: PMC3950244  PMID: 24618685
15.  Responses of soil microbial activity to cadmium pollution and elevated CO2 
Scientific Reports  2014;4:4287.
To address the combined effects of cadmium (Cd) and elevated CO2 on soil microbial communities, DGGE (denaturing gradient gel electrophoresis) profiles, respiration, carbon (C) and nitrogen (N) concentrations, loessial soils were exposed to four levels of Cd, i.e., 0 (Cd0), 1.5 (Cd1.5), 3.0 (Cd3.0) and 6.0 (Cd6.0) mg Cd kg−1 soil, and two levels of CO2, i.e., 360 (aCO2) and 480 (eCO2) ppm. Compared to Cd0, Cd1.5 increased fungal abundance but decreased bacterial abundance under both CO2 levels, whilst Cd3.0 and Cd6.0 decreased both fungal and bacterial abundance. Profiles of DGGE revealed alteration of soil microbial communities under eCO2. Soil respiration decreased with Cd concentrations and was greater under eCO2 than under aCO2. Soil total C and N were greater under higher Cd. These results suggest eCO2 could stimulate, while Cd pollution could restrain microbial reproduction and C decomposition with the restraint effect alleviated by eCO2.
doi:10.1038/srep04287
PMCID: PMC3944317  PMID: 24598728
16.  Microbial production of sabinene—a new terpene-based precursor of advanced biofuel 
Background
Sabinene, one kind of monoterpene, accumulated limitedly in natural organisms, is being explored as a potential component for the next generation of aircraft fuels. And demand for advanced fuels impels us to develop biosynthetic routes for the production of sabinene from renewable sugar.
Results
In this study, sabinene was significantly produced by assembling a biosynthetic pathway using the methylerythritol 4-phosphate (MEP) or heterologous mevalonate (MVA) pathway combining the GPP and sabinene synthase genes in an engineered Escherichia coli strain. Subsequently, the culture medium and process conditions were optimized to enhance sabinene production with a maximum titer of 82.18 mg/L. Finally, the fed-batch fermentation of sabinene was evaluated using the optimized culture medium and process conditions, which reached a maximum concentration of 2.65 g/L with an average productivity of 0.018 g h-1 g-1 dry cells, and the conversion efficiency of glycerol to sabinene (gram to gram) reached 3.49%.
Conclusions
This is the first report of microbial synthesis of sabinene using an engineered E. coli strain with the renewable carbon source as feedstock. Therefore, a green and sustainable production strategy has been established for sabinene.
doi:10.1186/1475-2859-13-20
PMCID: PMC3923588  PMID: 24512040
Sabinene; Geranyl diphosphate synthase; Sabinene synthase; Escherichia coli
17.  CX3CR1 deficiency suppresses activation and neurotoxicity of microglia/macrophage in experimental ischemic stroke 
Background
Chemokine (C-X3-C motif) ligand 1 (CX3CL1)/ CX3C chemokine receptor 1 (CX3CR1) signaling is important in modulating the communication between neurons and resident microglia/migrated macrophages in the central nervous system (CNS). Although CX3CR1 deficiency is associated with an improved outcome following ischemic brain injury, the mechanism of this observation is largely unknown. The aim of this study was to investigate how CX3CR1 deficiency influences microglia/macrophage functions in the context of its protection following brain ischemia.
Methods
Wild-type (WT) and CX3CR1-deficient (CX3CR1-/-) mice were subjected to transient middle cerebral artery occlusion (MCAO) and reperfusion. The ischemic brain damage was monitored by rodent high-field magnetic resonance imaging. Neurological deficit was assessed daily. Neuronal apoptotic death and reactive oxygen species (ROS) production were analyzed by immunostaining and live imaging. Activation/inflammatory response of microglia/macrophage were assessed using immunohistochemistry, flow cytometry, 5-bromo-2-deoxyuridine labeling, cytokine ELISA, and real-time PCR.
Results
CX3CR1-/- mice displayed significantly smaller infarcts and less severe neurological deficits compared to WT controls, following MCAO. In addition, CX3CR1-/- MCAO mice displayed fewer apoptotic neurons and reduced ROS levels. Impaired CX3CR1 signaling abrogated the recruitment of monocyte-derived macrophages from the periphery, suppressed the proliferation of CNS microglia and infiltrated macrophage, facilitated the alternative activation (M2 state) of microglia/macrophages, and attenuated their ability to synthesize and release inflammatory cytokines.
Conclusion
Our results suggest that inhibition of CX3CR1 signaling could function as a therapeutic modality in ischemic brain injury, by reducing recruitment of peripheral macrophages and expansion/activation of CNS microglia and macrophages, resulting in protection of neurological function.
doi:10.1186/1742-2094-11-26
PMCID: PMC3942808  PMID: 24490760
CX3CR1-/-; Microglia; Macrophage; Ischemic stroke; Middle cerebral artery occlusion
18.  Testing the Potential of Proposed DNA Barcoding Markers in Nezara virudula and Nezara antennata When Geographic Variation and Closely Related Species Were Considered 
The COI gene as the core of the DNA barcoding system for animals has received significant attention. The observed wide overlap between intra- and interspecific sequence variability has led researchers to envisage the primary COI-based method. The sequences of 16S rDNA, COI, and Cyt b genes of Nezara virudula (L.) (Hemiptera: Pentatomidae) from 13 countries and the same sequences of N. antennata Scott were chosen as molecular markers to analyze the intra- and interspecific relationships between the closely related species in this study. The results support that Cyt b gene may be a good candidate alongside COI, when the combined factors of geographic variation and closely related species are taken into account.
doi:10.1673/031.014.79
PMCID: PMC4212858  PMID: 25373226
16S rDNA; COI; Cyt b; molecular markers
19.  Lin28 Induces Epithelial-to-Mesenchymal Transition and Stemness via Downregulation of Let-7a in Breast Cancer Cells 
PLoS ONE  2013;8(12):e83083.
The RNA-binding protein Lin28 is known to promote malignancy by inhibiting the biogenesis of let-7, which functions as a tumor suppressor. However, the role of the Lin28/let-7 axis in the epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer has not been clearly expatiated. In our previous study, we demonstrated that let-7 regulates self-renewal and tumorigenicity of breast cancer stem cells. In the present study, we demonstrated that Lin28 was highly expressed in mesenchymal (M) type cells (MDA-MB-231 and SK-3rd), but it was barely detectable in epithelial (E) type cells (MCF-7 and BT-474). Lin28 remarkably induced the EMT, increased a higher mammosphere formation rate and ALDH activity and subsequently promoted colony formation, as well as adhesion and migration in breast cancer cells. Furthermore, we demonstrated that Lin28 induced EMT in breast cancer cells via downregulation of let-7a. Strikingly, Lin28 overexpression was found in breast cancers that had undergone metastasis and was strongly predictive of poor prognoses in breast cancers. Given that Lin28 induced the EMT via let-7a and promoted breast cancer metastasis, Lin28 may be a therapeutic target for the eradication of breast cancer metastasis.
doi:10.1371/journal.pone.0083083
PMCID: PMC3859647  PMID: 24349438
20.  Primary solitary fibrous tumors of liver: a case report and literature review 
Diagnostic Pathology  2013;8:195.
A 42-year-old male presented right upper abdomen pain for more than 6 days, which misdiagnose calculus of intrahepatic duct and acute cholecystitis. An approximately 1.5 cm x 1.0 cm x 1.0 cm nodule was found and resected in left lateral lobe of hepatic. Pathological examination showed spindle cell and fibroblast -like cells within the collagenous stroma. Immunohistochemically, these spindle tumor cells showed diffuse Vim and Bcl-2 positive reactivity, but S-100 protein and HMB45 were negative. The post-operative course was uneventful. Solitary fibrous tumors of the liver, although rare, should be differentiated from mesenchymal lesions of the liver.
Virtual slide
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4214341041091088.
doi:10.1186/1746-1596-8-195
PMCID: PMC3942811  PMID: 24294990
Solitary fibrous tumors; Liver; Pathology
21.  Evaluation of the Comet Assay for Assessing the Dose-Response Relationship of DNA Damage Induced by Ionizing Radiation 
Dose- and time-response curves were combined to assess the potential of the comet assay in radiation biodosimetry. The neutral comet assay was used to detect DNA double-strand breaks in lymphocytes caused by γ-ray irradiation. A clear dose-response relationship with DNA double-strand breaks using the comet assay was found at different times after irradiation (p < 0.001). A time-response relationship was also found within 72 h after irradiation (p < 0.001). The curves for DNA double-strand breaks and DNA repair in vitro of human lymphocytes presented a nice model, and a smooth, three-dimensional plane model was obtained when the two curves were combined.
doi:10.3390/ijms141122449
PMCID: PMC3856073  PMID: 24240807
radiation; dose-response relationship; DNA damage; comet assay
22.  Characteristics of human infection with avian influenza viruses and development of new antiviral agents 
Acta Pharmacologica Sinica  2013;34(10):1257-1269.
Since 1997, several epizootic avian influenza viruses (AIVs) have been transmitted to humans, causing diseases and even deaths. The recent emergence of severe human infections with AIV (H7N9) in China has raised concerns about efficient interpersonal viral transmission, polygenic traits in viral pathogenicity and the management of newly emerging strains. The symptoms associated with viral infection are different in various AI strains: H5N1 and newly emerged H7N9 induce severe pneumonia and related complications in patients, while some H7 and H9 subtypes cause only conjunctivitis or mild respiratory symptoms. The virulence and tissue tropism of viruses as well as the host responses contribute to the pathogenesis of human AIV infection. Several preventive and therapeutic approaches have been proposed to combat AIV infection, including antiviral drugs such as M2 inhibitors, neuraminidase inhibitors, RNA polymerase inhibitors, attachment inhibitors and signal-transduction inhibitors etc. In this article, we summarize the recent progress in researches on the epidemiology, clinical features, pathogenicity determinants, and available or potential antivirals of AIV.
doi:10.1038/aps.2013.121
PMCID: PMC3791557  PMID: 24096642
avian influenza; human infection; pathogenicity; antiviral agent; M2 inhibitor; neuraminidase inhibitor; polymerase inhibitor; ribavirin; arbidol
23.  Cloning and primary characterizations of rLcn9, a new member of epididymal lipocalins in rat 
Lipocalins are a structurally conserved and diversely functional family of proteins that are of potential importance in epididymis functions. The rat Lcn9 gene was cloned by in silico methods and genome walking based on homology to the rhesus monkey epididymal ESC513 and its polyclonal antisera were prepared. The rat Lcn9 gene is located on chromosome 3p13 spanning 7 exons, contains 2.3 kb and encodes 179 amino acids with a 17-amino acid signal peptide. Northern blot, western blot, and immunohistochemical staining analysis revealed that rat Lcn9 was a novel epididymis-specific gene, expressed selectively in the proximal caput region, influenced by luminal fluid testicular factors. Moreover, Lcn9 protein was modified by N-glycosylation and bound on the postacrosomal domain of caput sperm. In conclusion, the rat Lcn9 exhibited tissue-, region-, and temporal-specific expression patterns and its expression was regulated by luminal testicular factors. Its potential roles in sperm maturation are discussed.
doi:10.1093/abbs/gms072
PMCID: PMC3459353  PMID: 23017836
epididymis; lipocalin; Lcn9 gene
24.  Cytogenetic Abnormalities in Lymphocytes from Victims Exposed to Cobalt-60 Radiation 
The present study investigates cytogenetic damage in lymphocytes, derived from three victims who were unfortunately exposed to cobalt-60 (60Co) radiation (the 1999 accident occurred in a village in China’s Henan province). Case A of the three victims was exposed to a higher dose of 60Co radiation than Cases B and C. The chromosomal aberrations, cytokinesis-block micronucleus (CBMN, the CBMN assay), and DNA double-strand breaks (DSBs, the comet assay) examined in this study are biomarkers for cytogenetic abnormalities. After the lymphocytes collected from the victims were cultured, the frequencies of dicentric chromosomes and rings (dic + r) and CBMN in the first mitotic division detected in the lymphocytes of Case A were found to be substantially higher than in Cases B and C. Similarly, the DNA-DSB level found in the peripheral blood collected from Case A was much higher than those of Cases B and C. These results suggest that an acutely enhanced induction of the 60Co-induced cytogenetic abnormality frequency in humans depends on the dose of 60Co radiation. This finding is supported by the data obtained using practical techniques to evaluate early lymphoid-tissue abnormalities induced after exposure to acute radiation.
doi:10.3390/ijms140917525
PMCID: PMC3794739  PMID: 23985825
radiation accident; chromosome aberration; micronucleus assay; comet assay; DNA-DSB
25.  TGFA and IRF6 Contribute to the Risk of Nonsyndromic Cleft Lip with or without Cleft Palate in Northeast China 
PLoS ONE  2013;8(8):e70754.
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) are common birth defects with a complex etiology. Multiple interacting loci and possible environmental factors influence the risk of NSCL/P. 12 single nucleotide polymorphisms (SNPs) in 7 candidate genes were tested using an allele-specific primer extension for case-control and case-parent analyses in northeast China in 236 unrelated patients, 185 mothers and 154 fathers, including 128 complete trios, and 400 control individuals. TGFA and IRF6 genes showed a significant association with NSCL/P. In IRF6, statistical evidence of an association between rs2235371 (p = 0.003), rs2013162 (p<0.0001) and NSCL/P was observed in case-control analyses. Family based association tests (FBATs) showed over-transmission of the C allele at the rs2235371 polymorphism (p = 0.007). In TGFA, associations between rs3771494, rs3771523 (G3822A), rs11466285 (T3851C) and NSCL/P were observed in case-control and FBAT analyses. Associations between other genes (BCL3, TGFB3, MTHFR, PVRL1 and SUMO1) and NSCL/P were not detected.
doi:10.1371/journal.pone.0070754
PMCID: PMC3735505  PMID: 23940636

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