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1.  The validation of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) in pre-operative patients with brain tumor in China 
Health related quality of life (HRQOL) has increasingly emphasized on cancer patients. The psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0) in brain tumor patients wasn't proven, and there was no baseline HRQOL in brain tumor patients prior to surgery.
The questionnaire EORTC QLQ-C30 (version 3.0) was administered at three time points: T1, the first or the second day that patients were hospitalized after the brain tumor suspected or diagnosed by MRI or CT; T2, 1 to 2 days after T1, (T1 and T2 were both before surgery); T3, the day before discharge. Clinical variables included disease histologic types, cognitive function, and Karnofsky Performance Status.
Cronbach's alpha coefficients for multi-item scales were greater than .70 and multitrait scaling analysis showed that most of the item-scale correlation coefficients met the standards of convergent and discriminant validity, except for the cognitive functioning scale. All scales and items exhibited construct validity. Score changes over peri-operation were observed in physical and role functioning scales. Compared with mixed cancer patients assessed after surgery but before adjuvant treatment, brain tumor patients assessed pre-surgery presented better function and fewer symptoms.
The standard Chinese version of the EORTC QLQ-C30 was overall a valid instrument to assess HRQOL in brain tumor patients in China. The baseline HRQOL in brain tumor patients pre-surgery was better than that in mixed cancer patients post-surgery. Future study should modify cognitive functioning scale and examine test-retest reliability and response validity.
PMCID: PMC3112193  PMID: 21513533
2.  GW182 controls Drosophila circadian behavior and PDF-Receptor signaling 
Neuron  2013;78(1):152-165.
The neuropeptide PDF is crucial for Drosophila circadian behavior: it keeps circadian neurons synchronized. Here, we identify GW182 as a key regulator of PDF signaling. Indeed, GW182 downregulation results in phenotypes similar to those of Pdf and Pdf-receptor (Pdfr) mutants. gw182 genetically interacts with Pdfr and cAMP signaling, which is essential for PDFR function. GW182 mediates miRNA-dependent gene silencing through its interaction with AGO1. Consistently, GW182's AGO1 interaction domain is required for GW182's circadian function. Moreover, our results indicate that GW182 modulates PDFR signaling by silencing the expression of the cAMP phosphodiesterase DUNCE. Importantly, this repression is under photic control, and GW182 activity level - which is limiting in circadian neurons - influences the responses of the circadian neural network to light. We propose that GW182's gene silencing activity functions as a rheostat for PDFR signaling, and thus profoundly impacts the circadian neural network and its response to environmental inputs.
PMCID: PMC3629553  PMID: 23583112
3.  Effects of withdrawal from chronic escalating-dose binge cocaine on conditioned place preference to cocaine and striatal preproenkephalin mRNA in C57BL/6J mice 
Neuropharmacology  2012;63(2):322-329.
Relapse is a serious problem for the effective treatment of cocaine addiction.
Examining cocaine re-exposure-induced behavioral and neurobiological alterations following chronic escalating-dose binge cocaine administration and withdrawal may provide insight into the neurobiological basis of cocaine relapse.
Our goal was to determine how exposure to chronic escalating-dose cocaine affects development of subsequent cocaine-induced conditioned place preference (CPP) and changes in endogenous opioid systems.
Mice were injected with either escalating-dose binge cocaine (15-30 mg/kg/injection × 3/day) or saline for 14 days and conditioned with 15 mg/kg of cocaine or saline (once per day for 10 days), starting either 1 or 14 days after the last day of binge injections.
Mice exposed to chronic escalating cocaine did not develop CPP to cocaine when conditioning commenced on the first day of withdrawal (CPP test on day 10 of withdrawal). By contrast, mice did develop CPP to cocaine when conditioning started on the 14th day of withdrawal (CPP test on day 24 of withdrawal). Furthermore, preproenkephalin (Penk) mRNA levels in caudate putamen were significantly higher in mice that received 14-day withdrawal from escalating-dose binge cocaine before the CPP procedure (tested 24 days post-binge) than those that received 1-day withdrawal (tested 10 days post-binge).
The rewarding effect of cocaine was blunted in early withdrawal from chronic escalating exposure, but recovered in more prolonged withdrawal. Time-dependent elevations in Penk mRNA levels may be part of the underlying mechanisms of this effect.
PMCID: PMC3979702  PMID: 22504589
Chronic escalating-dose binge cocaine; CPP; Withdrawal; Penk; MOP-r
4.  Mu opioid receptor knockdown in the substantia nigra/ventral tegmental area by synthetic small interfering RNA blocks the rewarding and locomotor effects of heroin 
Neuroscience  2008;158(2):474-483.
Mu opioid receptors (MOP-r) play an important role in the rewarding and locomotor stimulatory effects of heroin. The aim of the current study was to determine whether infusion of small interfering RNAs (siRNA) targeting MOP-r into the midbrain could knock down MOP-r mRNA and affect heroin-induced locomotor activity or heroin-induced conditioned place preference. Ten week old male C57BL/6J mice were surgically implanted bilaterally with guide cannulae directed between the substantia nigra and ventral tegmental area. After 4 days recovery, mice were infused bilaterally with siRNAs that target the MOP-r (2mM × 0.75 μl/side/day for 3 days) or control siRNA. Seven days after the last infusion, a procedure for conditioned place preference was begun with four heroin (3mg/kg i.p.) administration sessions alternating with four saline sessions. While heroin induced an increase in locomotor activity in all groups, siRNAs targeting specific regions of MOP-r significantly attenuated this effect. Of particular interest, mice infused with specific siRNAs targeting the MOP-r failed to develop and express conditioned place preference to heroin, or showed a significantly attenuated preference. These alterations in reward related behaviors are likely due to the reduction in MOP-r mRNA and protein, shown in separate studies by in situ hybridization and autoradiography using the same MOP-r- siRNA infusions. Taken together, these studies demonstrate the utility of siRNA in the neurobiological study of specific components of the reward system and should contribute to the study of other complex behaviors.
PMCID: PMC3977655  PMID: 18938225
siRNAs; locomotor activity; conditioned place preference; heroin; mouse; MOP-r
5.  Bayesian Analysis of Climate Change Effects on Observed and Projected Airborne Levels of Birch Pollen 
A Bayesian framework is presented for modeling Effects of climate change on pollen indices such as annual birch pollen count, maximum daily birch pollen count, start date of birch pollen season and the date of maximum daily birch pollen count. Annual mean CO2 concentration, mean spring temperature and the corresponding pollen index of prior year were found to be statistically significant accounting for Effects of climate change on four pollen indices. Results suggest that annual productions and peak values from 2020 to 2100 under different scenarios will be 1.3-8.0 and 1.1-7.3 times higher respectively than the mean values for 2000, and start and peak dates will occur around two to four weeks earlier. These results have been partly confirmed by the available historical data. As a demonstration, the emission profiles in future years were generated by incorporating the predicted pollen indices into an existing emission model.
PMCID: PMC3601922  PMID: 23526049
Climate change; Birch; Pollen; Bayesian analysis
6.  Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re-exposure: Effects on striatal dopamine and opioid systems in C57BL/6J mice 
Neuropharmacology  2012;67:259-266.
Cocaine addiction is a chronic relapsing disease with periods of chronic escalating self-exposure, separated by periods of abstinence/withdrawal of varying duration. Few studies compare such cycles in preclinical models. This study models an “addiction-like cycle” in mice to determine neurochemical/molecular alterations that underlie the chronic, relapsing nature of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14-day saline/14-day withdrawal /13-day saline + 1-day cocaine), chronic cocaine exposure (14 day cocaine) or chronic re-exposure (14-day cocaine/14-day withdrawal /14-day cocaine). Escalating-dose binge cocaine (15-30 mg/kg/injection x 3/day, i.p. at hourly intervals) or saline (14-day saline) was administered, modeling initial exposure. In “re-exposure” groups, after a 14-day injection-free period (modeling abstinence/withdrawal), mice that had received cocaine were re-injected with 14-day escalating-dose binge cocaine, whereas controls received saline. Microdialysis was conducted on the 14th day of exposure or re-exposure to determine striatal dopamine content. Messenger RNA levels of preprodynorphin (Pdyn), dopamine D1 (Drd1) and D2 (Drd2) in the caudate putamen were determined by real-time PCR. Basal striatal dopamine levels were lower in mice after 14-day escalating exposure or re-exposure than in those in the acute cocaine group and controls. Pdyn mRNA levels were higher in the cocaine groups than in controls. Long-term adaptation was observed across the stages of this addiction-like cycle, in that the effects of cocaine on dopamine levels were increased after re-exposure compared to exposure. Changes in striatal dopaminergic responses across chronic escalating cocaine exposure and re-exposure are a central feature of the neurobiology of relapsing addictive states.
PMCID: PMC3616618  PMID: 23164614
8.  Pattern of cerebral hyperperfusion in Alzheimer’s disease and amnestic mild cognitive impairment using voxel-based analysis of 3D arterial spin-labeling imaging: initial experience 
A three-dimensional (3D) continuous pulse arterial spin labeling (ASL) technique was used to investigate cerebral blood flow (CBF) changes in patients with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), and age- and sex-matched healthy controls.
Materials and methods
Three groups were recruited for comparison, 24 AD patients, 17 MCI patients, and 21 age- and sex-matched control subjects. Three-dimensional ASL scans covering the entire brain were acquired with a 3.0 T magnetic resonance scanner. Spatial processing was performed with statistical parametric mapping 8. A second-level one-way analysis of variance analysis (threshold at P<0.05) was performed on the preprocessed ASL data. An average whole-brain CBF for each subject was also included as group-level covariates for the perfusion data, to control for individual CBF variations.
Significantly increased CBF was detected in bilateral frontal lobes and right temporal subgyral regions in aMCI compared with controls. When comparing AD with aMCI, the major hyperperfusion regions were the right limbic lobe and basal ganglia regions, including the putamen, caudate, lentiform nucleus, and thalamus, and hypoperfusion was found in the left medial frontal lobe, parietal cortex, the right middle temporo-occipital lobe, and particularly, the left anterior cingulate gyrus. We also found decreased CBF in the bilateral temporo-parieto-occipital cortices and left limbic lobe in AD patients, relative to the control group. aMCI subjects showed decreased blood flow in the left occipital lobe, bilateral inferior temporal cortex, and right middle temporal cortex.
Our results indicated that ASL provided useful perfusion information in AD disease and may be used as an appealing alternative for further pathologic and neuropsychological studies, especially of compensatory mechanisms for cerebral hypoperfusion.
PMCID: PMC3971940
Alzheimer’s disease; amnestic mild cognitive impairment; perfusion image; arterial spin labeling
9.  Microyielding of Core-Shell Crystal Dendrites in a Bulk-metallic-glass Matrix Composite 
Scientific Reports  2014;4:4394.
In-situ synchrotron x-ray experiments have been used to follow the evolution of the diffraction peaks for crystalline dendrites embedded in a bulk metallic glass matrix subjected to a compressive loading-unloading cycle. We observe irreversible diffraction-peak splitting even though the load does not go beyond half of the bulk yield strength. The chemical analysis coupled with the transmission electron microscopy mapping suggests that the observed peak splitting originates from the chemical heterogeneity between the core (major peak) and the stiffer shell (minor peak) of the dendrites. A molecular dynamics model has been developed to compare the hkl-dependent microyielding of the bulk metallic-glass matrix composite. The complementary diffraction measurements and the simulation results suggest that the interface, as Maxwell damper, between the amorphous matrix and the (211) crystalline planes relax under prolonged load that causes a delay in the reload curve which ultimately catches up with the original path.
PMCID: PMC3957129  PMID: 24637714
10.  Tuned Critical Avalanche Scaling in Bulk Metallic Glasses 
Scientific Reports  2014;4:4382.
Ingots of the bulk metallic glass (BMG), Zr64.13Cu15.75Ni10.12Al10 in atomic percent (at. %), are compressed at slow strain rates. The deformation behavior is characterized by discrete, jerky stress-drop bursts (serrations). Here we present a quantitative theory for the serration behavior of BMGs, which is a critical issue for the understanding of the deformation characteristics of BMGs. The mean-field interaction model predicts the scaling behavior of the distribution, D(S), of avalanche sizes, S, in the experiments. D(S) follows a power law multiplied by an exponentially-decaying scaling function. The size of the largest observed avalanche depends on experimental tuning-parameters, such as either imposed strain rate or stress. Similar to crystalline materials, the plasticity of BMGs reflects tuned criticality showing remarkable quantitative agreement with the slip statistics of slowly-compressed nanocrystals. The results imply that material-evaluation methods based on slip statistics apply to both crystalline and BMG materials.
PMCID: PMC3955902  PMID: 24632786
11.  OVA66, a Tumor Associated Protein, Induces Oncogenic Transformation of NIH3T3 Cells 
PLoS ONE  2014;9(3):e85705.
The tumor associated antigen OVA66 has been demonstrated to be highly expressed in malignant tumors and implicated in various cellular processes. To further elucidate its oncogenic character, we established an OVA66 stably overexpressed NIH3T3 cell line and a vector transfected control, named NIH3T3-flagOVA66 and NIH3T3-mock, respectively. NIH3T3-flagOVA66 cells showed faster cell cycling, proliferation, cell migration and more resistance to 5-fluorouracil-induced apoptosis. When NIH3T3-flagOVA66 and NIH3T3-mock cells were injected into nude mice for xenograft tumorigenicity assays, the NIH3T3-flagOVA66 cells formed tumors whereas no tumors were observed in mice inoculated with NIH3T3-mock cells. Analysis of PI3K/AKT and ERK1/2 MAPK signaling pathways by serum stimulation indicated hyperactivation of AKT and ERK1/2 in NIH3T3-flagOVA66 cells compared with NIH3T3-mock cells, while a decreased level of p-AKT and p-ERK1/2 were observed in OVA66 knocked down HeLa cells. To further validate if the p-AKT or p-ERK1/2 is essential for OVA66 induced oncogenic transformation, we treated the cells with the PI3K/AKT specific inhibitor LY294002 and the ERK1/2 MAPK specific inhibitor PD98059 and found either inhibitor can attenuate the cell colony forming ability in soft agar and the cell viability of NIH3T3-flagOVA66 cells, suggesting aberrantly activated AKT and ERK1/2 signaling be indispensible of the tumorigenic role of OVA66. Our results indicate that OVA66 is important in oncogenic transformation, promoting proliferation, cell migration and reducing apoptosis via hyperactivating PI3K/AKT and ERK1/2 MAPK signaling pathway. Thus, OVA66 might be a novel target for early detection, prevention and treatment of tumors in the future.
PMCID: PMC3954546  PMID: 24633332
12.  Germline Transmission of an Embryonic Stem Cell Line Derived from BALB/c Cataract Mice 
PLoS ONE  2014;9(3):e90707.
Mice embryonic stem (ES) cells have enabled the generation of mouse strains with defined mutation(s) in their genome for putative disease loci analysis. In the study of cataract, the complex genetic background of this disease and lack of long-term self-renewal ES cells have hampered the functional researches of cataract-related genes. In this study, we aimed to establish ES cells from inherited cataract mice (BALB/CCat/Cat). Embryos of cataract mice were cultured in chemical-defined N2B27 medium with the presence of two small molecules PD0325901 and CHIR99021 (2i) and an ES cell line (named EH-BES) was successfully established. EH-BES showed long-term self-renewal in 2i medium and maintained capacity of germline transmission. Most importantly, the produced chimera and offspring developed congenital cataract as well. Flow cytometry assay revealed that EH-BES are homogeneous in expression of Oct4 and Rex1in 2i medium, which may account for their self-renewal ability. With long-term self-renewal ability and germline-competent, EH-BES cell line can facilitate genetic and functional researches of cataract-related genes and better address mechanisms of cataract.
PMCID: PMC3942454  PMID: 24595217
13.  Complete Genome Characterization of a Novel Enterovirus Type EV-B106 Isolated in China, 2012 
Scientific Reports  2014;4:4255.
Human enterovirus B106 (EV-B106) is a recently identified member of enterovirus species B. In this study, we report the complete genomic characterization of an EV-B106 strain (148/YN/CHN/12) isolated from an acute flaccid paralysis patient in Yunnan Province, China. The new strain had 79.2–81.3% nucleotide and 89.1–94.8% amino acid similarity in the VP1 region with the other two EV-B106 strains from Bolivia and Pakistan. When compared with other EV serotypes, it had the highest (73.3%) VP1 nucleotide similarity with the EV-B77 prototype strain CF496-99. However, when aligned with all EV-B106 and EV-B77 sequences available from the GenBank database, two major frame shifts were observed in the VP1 coding region, which resulted in substantial (20.5%) VP1 amino acid divergence between the two serotypes. Phylogenetic analysis and similarity plot analysis revealed multiple recombination events in the genome of this strain. This is the first report of the complete genome of EV-B106.
PMCID: PMC3939458  PMID: 24584702
14.  New Coxsackievirus B4 Genotype Circulating in Inner Mongolia Autonomous Region, China 
PLoS ONE  2014;9(3):e90379.
Hand, foot, and mouth disease (HFMD) surveillance was initiated in the Inner Mongolia Autonomous Region of China in 2007, a crucial scrutiny for monitoring the prevalence of enterovirus serotypes associated with HFMD patients. However, this surveillance mostly focused on enterovirus 71 (EV-A71) and coxsackievirus A16; therefore, information on other enterovirus serotypes is limited. To identify the other circulating enterovirus serotypes in the HFMD outbreaks in Inner Mongolia in 2010, clinical samples from HFMD patients were investigated. Six coxsackievirus B4 (CVB4) strains were isolated and phylogenetic analyses of VP1 sequences were performed. Full-length genome sequences of two representative CVB4 isolates were acquired and similarity plot and bootscanning analyses were performed. The phylogenetic dendrogram indicated that all CVB4 strains could be divided into 5 genotypes (Genotypes I–V) with high bootstrap support (90–100%). The CVB4 prototype strain (JVB) was the sole member of genotype I. CVB4 strains belonging to genotype II, which were once common in Europe and the Americas, seemingly disappeared and gave way to genotype III and IV strains, which appear to be the dominant circulating strains in the world. All Chinese CVB4 strains belonged to Genotype V, a newly identified genotype supported by a high bootstrap value (100%), and are circulating only in mainland of China. Intertypic recombination occurred in the Chinese CVB4 strains with novel unknown serotype EV-B donor sequences. Two Chinese CVB4 strains had a virulent residue at position 129 of VP1, and one strain also had a virulent residue at position 16 of VP4. Increased surveillance is needed to monitor the emergence of new genetic lineages of enteroviruses in areas that are often associated with large-scale outbreaks. In addition, continued monitoring of enteroviruses by clinical surveillance and genetic characterization should be enhanced.
PMCID: PMC3940859  PMID: 24595311
15.  Transplanted Neural Stem Cells Modulate Regulatory T, γδ T Cells and Corresponding Cytokines after Intracerebral Hemorrhage in Rats 
The immune system, particularly T lymphocytes and cytokines, has been implicated in the progression of brain injury after intracerebral hemorrhage (ICH). Although studies have shown that transplanted neural stem cells (NSCs) protect the central nervous system (CNS) from inflammatory damage, their effects on subpopulations of T lymphocytes and their corresponding cytokines are largely unexplored. Here, rats were subjected to ICH and NSCs were intracerebrally injected at 3 h after ICH. The profiles of subpopulations of T cells in the brain and peripheral blood were analyzed by flow cytometry. We found that regulatory T (Treg) cells in the brain and peripheral blood were increased, but γδT cells (gamma delta T cells) were decreased, along with increased anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) and decreased pro-inflammatory cytokines (IL-6, and IFN-γ), compared to the vehicle-treated control. Our data suggest that transplanted NSCs protect brain injury after ICH via modulation of Treg and γδT cell infiltration and anti- and pro-inflammatory cytokine release.
PMCID: PMC3975405  PMID: 24633197
ICH; transplantation; NSCs; T lymphocyte subpopulations; immunomodulation
16.  Proteomic Analysis of the Follicular Fluid of Tianzhu White Yak during Diestrus 
The aim of this study was to identify differentially expressed proteins in the follicular fluid of Tianzhu white yak during diestrus. Follicles obtained from female yak were divided into four groups according to their diameter: 0–2, 2–4, 4–6 mm, and greater than 6 mm. The follicular fluid was directly aspirated from the follicles and mixed according to follicular size, and two-dimensional gel electrophoresis was carried out on the crude follicular fluid samples. Thirty-four differentially expressed spots were generated from these four sizes of follicles. Fourteen of these spots were analyzed by MALDI-TOF/TOF-MS and identified as: AS3MT, VDP, ANKRD6, C10orf107 protein, MRP4, MAPKAP1, AGO3, profilin-β-actin, SPT2 homolog, AGP, AR, RNF20, obscurin-like-1, and one unnamed protein. These proteins were first reported in follicular fluid, in addition to VDP and AGP. Based on existing knowledge of their function and patterns of expression, we hypothesize that most of these differentially expressed proteins play a role in ovarian follicular growth and development, dominant follicle selection, or follicular atresia and development of oocytes; however, the function of the other differentially expressed proteins in reproduction remains ambiguous.
PMCID: PMC3975409  PMID: 24633201
Tianzhu white yak; follicular fluid; proteomic analysis; two-dimensional gel electrophoresis; diestrus
17.  Improved site-specific recombinase-based method to produce selectable marker- and vector-backbone-free transgenic cells 
Scientific Reports  2014;4:4240.
PhiC31 integrase-mediated gene delivery has been extensively used in gene therapy and animal transgenesis. However, random integration events are observed in phiC31-mediated integration in different types of mammalian cells; as a result, the efficiencies of pseudo attP site integration and evaluation of site-specific integration are compromised. To improve this system, we used an attB-TK fusion gene as a negative selection marker, thereby eliminating random integration during phiC31-mediated transfection. We also excised the selection system and plasmid bacterial backbone by using two other site-specific recombinases, Cre and Dre. Thus, we generated clean transgenic bovine fetal fibroblast cells free of selectable marker and plasmid bacterial backbone. These clean cells were used as donor nuclei for somatic cell nuclear transfer (SCNT), indicating a similar developmental competence of SCNT embryos to that of non-transgenic cells. Therefore, the present gene delivery system facilitated the development of gene therapy and agricultural biotechnology.
PMCID: PMC3937794  PMID: 24577484
18.  Baicalein Reduces the Invasion of Glioma Cells via Reducing the Activity of p38 Signaling Pathway 
PLoS ONE  2014;9(2):e90318.
Baicalein, one of the major flavonids in Scutellaria baicalensis, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and related mechanism(s) in glioma are still unclear. In this study, we thus utilized glioma cell lines U87MG and U251MG to explore the effect of baicalein. We found that administration of baicalein significantly inhibited migration and invasion of glioma cells. In addition, after treating with baicalein for 24 h, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression as well as proteinase activity in glioma cells. Conversely, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 was increased in a dose-dependent manner. Moreover, baicalein treatment significantly decreased the phosphorylated level of p38, but not ERK1/2, JNK1/2 and PI3K/Akt. Combined treatment with a p38 inhibitor (SB203580) and baicalein resulted in the synergistic reduction of MMP-2 and MMP-9 expression and then increase of TIMP-1 and TIMP-2 expression; and the invasive capabilities of U87MG cells were also inhibited. However, p38 chemical activator (anisomycin) could block these effects produced by baicalein, suggesting baicalein directly downregulate the p38 signaling pathway. In conclusion, baicalein inhibits glioma cells invasion and metastasis by reducing cell motility and migration via suppression of p38 signaling pathway, suggesting that baicalein is a potential therapeutic agent for glioma.
PMCID: PMC3938668  PMID: 24587321
19.  Co-Circulation of Multiple Hemorrhagic Fever Diseases with Distinct Clinical Characteristics in Dandong, China 
PLoS ONE  2014;9(2):e89896.
Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011–2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.
PMCID: PMC3937409  PMID: 24587107
20.  Control of hematopoietic stem cell emergence by antagonistic functions of ribosomal protein paralogs 
Developmental cell  2013;24(4):411-425.
It remains controversial whether the highly-homologous ribosomal protein (RP) paralogs found in lower eukaryotes have distinct functions and this has not been explored in vertebrates. Here we demonstrate that despite ubiquitous expression, the RP paralogs, Rpl22 and Rpl22-like1 (Rpl22l1) play essential, distinct, and antagonistic roles in hematopoietic development. Knockdown of rpl22 in zebrafish embryos selectively blocks the development of T lineage progenitors after they have seeded the thymus. In contrast, knockdown of the rpl22 paralog, rpl22l1, impairs the emergence of hematopoietic stem cells (HSC) in the aorta-gonad-mesonephros by abrogating Smad1 expression and the consequent induction of essential transcriptional regulator, Runx1. Indeed, despite the ability of both paralogs to bind Smad1 RNA, Rpl22 and Rpl22l1 have opposing effects on Smad1 expression. Accordingly, circumstances that tip the balance of these paralogs in favor of Rpl22 (e.g., Rpl22l1 knockdown or Rpl22 overexpression) result in repression of Smad1 and blockade of HSC emergence.
PMCID: PMC3586312  PMID: 23449473
ribosomal protein; paralog; T cell development; hematopoietic stem cell; Rpl22; Rpl22l1
21.  Immunoglobulin E and mast cell proteases are potential risk factors of impaired fasting glucose and impaired glucose tolerance in humans 
Annals of medicine  2012;45(3):220-229.
Mast cells are important in experimental diabetes. Plasma levels of immunoglobulin E (IgE), tryptases, and chymases are inflammatory markers of human diabetes. Whether they also correlate with the risk of pre-diabetes, however, remains unknown.
Methods and results
A total of 260 subjects 55–75 years of age were grouped as normal glucose tolerance (NGT), isolated impaired fasting glucose (I-IFG), isolated impaired glucose tolerance (I-IGT), and mixed IFG/IGT. There were significant differences in plasma levels of high-sensitivity C-reactive protein (hsCRP) (P < 0.001) and IgE (P=0.003) among all subgroups of pre-diabetes, and chymase in I-IGT (P=0.043) and mixed IFG/IGT (P=0.037) subgroups compared with NGT group. High-sensitivity CRP was a risk factor in all subgroups of pre-diabetes; IgE was a risk factor of mixed IFG/IGT; and chymase was a risk factor of I-IGT and mixed IFG/IGT. Interactions between hsCRP and high waist circumference (WC), waist-to-hip ratio (WHR), or HOMA-β index, and interactions between IgE and high WC or tryptase levels all increased further the risk of developing I-IFG, I-IGT, or mixed IFG/IGT.
Plasma hsCRP, IgE, and chymase levels associate with pre-diabetes status. While hsCRP, IgE, and chymase are individual risk factors of pre-diabetes, interactions with metabolic parameters increased further the risk of pre-diabetes.
PMCID: PMC3934348  PMID: 23110545
Chymase; C-reactive protein; immunoglobulin E; pre-diabetes; tryptase
22.  Spinal Changes of a Newly Isolated Neuropeptide Endomorphin-2 Concomitant with Vincristine-Induced Allodynia 
PLoS ONE  2014;9(2):e89583.
Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain unclear. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, we used a vincristine-evoked rat CNP model displaying mechanical allodynia and central sensitization, and observed a significant decrease in the expression of spinal EM2 in CNP. Also, while intrathecal administration of exogenous EM2 attenuated allodynia and central sensitization, the mu-opioid receptor antagonist β-funaltrexamine facilitated these events. We found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of chemotherapy-induced oxidative stress. Taken together, our findings suggest that a decrease in spinal EM2 expression causes the loss of endogenous analgesia and leads to enhanced pain sensation in CNP.
PMCID: PMC3933549  PMID: 24586889
23.  Accelerated regeneration of the skeletal muscle in RNF13-knockout mice is mediated by macrophage-secreted IL-4/IL-6 
Protein & Cell  2014;5(3):235-247.
RING finger protein 13 (RNF13) is a newly identified E3 ligase reported to be functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. In this study, the function of RNF13 in cardiotoxin-induced skeletal muscle regeneration was investigated using RNF13-knockout mice. RNF13-/- mice exhibited enhanced muscle regeneration—characterized by accelerated satellite cell proliferation—compared with wild-type mice. The expression of RNF13 was remarkably induced in macrophages rather than in the satellite cells of wild-type mice at the very early stage of muscle damage. This result indicated that inflammatory cells are important in RNF13-mediated satellite cell functions. The cytokine levels in skeletal muscles were further analyzed and showed that RNF13-/- mice produced greater amounts of various cytokines than wild-type mice. Among these, IL-4 and IL-6 levels significantly increased in RNF13-/- mice. The accelerated muscle regeneration phenotype was abrogated by inhibiting IL-4/IL-6 action in RNF13-/- mice with blocking antibodies. These results indicate that RNF13 deficiency promotes skeletal muscle regeneration via the effects on satellite cell niche mediated by IL-4 and IL-6.
Electronic supplementary material
The online version of this article (doi:10.1007/s13238-014-0025-4) contains supplementary material, which is available to authorized users.
PMCID: PMC3967074  PMID: 24563216
RNF13; muscle regeneration; satellite cell niche; IL-4/IL-6
24.  Accelerated regeneration of the skeletal muscle in RNF13-knockout mice is mediated by macrophage-secreted IL-4/IL-6 
Protein & Cell  2014;5(3):235-247.
RING finger protein 13 (RNF13) is a newly identified E3 ligase reported to be functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. In this study, the function of RNF13 in cardiotoxin-induced skeletal muscle regeneration was investigated using RNF13-knockout mice. RNF13-/- mice exhibited enhanced muscle regeneration—characterized by accelerated satellite cell proliferation—compared with wild-type mice. The expression of RNF13 was remarkably induced in macrophages rather than in the satellite cells of wild-type mice at the very early stage of muscle damage. This result indicated that inflammatory cells are important in RNF13-mediated satellite cell functions. The cytokine levels in skeletal muscles were further analyzed and showed that RNF13-/- mice produced greater amounts of various cytokines than wild-type mice. Among these, IL-4 and IL-6 levels significantly increased in RNF13-/- mice. The accelerated muscle regeneration phenotype was abrogated by inhibiting IL-4/IL-6 action in RNF13-/- mice with blocking antibodies. These results indicate that RNF13 deficiency promotes skeletal muscle regeneration via the effects on satellite cell niche mediated by IL-4 and IL-6.
Electronic supplementary material
The online version of this article (doi:10.1007/s13238-014-0025-4) contains supplementary material, which is available to authorized users.
PMCID: PMC3967074  PMID: 24563216
RNF13; muscle regeneration; satellite cell niche; IL-4/IL-6
25.  Biologically enhanced cathode design for improved capacity and cycle life for lithium-oxygen batteries 
Nature communications  2013;4:2756.
Lithium-oxygen batteries have a great potential to enhance the gravimetric energy density of fully packaged batteries by 2–3 times that of lithium-ion cells. Recent studies have focused on finding stable electrolytes to address poor cycling capability and improve practical limitations of current lithium-oxygen batteries. In this study, the catalyst electrode, where discharge products are deposited and decomposed, was investigated since it plays a critical role in the operation of rechargeable lithium-oxygen batteries. Here we report the electrode design principle to improve specific capacity and cycling performance of lithium-oxygen batteries by utilizing high efficiency nanocatalysts assembled by M13 virus with earth abundant elements, such as manganese oxides. By incorporating only 3–5 wt % of palladium nanoparticles in the electrode, this hybrid nanocatalyst achieves 13,350 mAh g−1c (7,340 mAh g−1c+catalyst) of specific capacity at 0.4 A g−1c and a stable cycle life up to 50 cycles (4,000 mAh g−1c, 400 mAh g−1c+catalyst) at 1 A g−1c.
PMCID: PMC3930201  PMID: 24220635

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