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1.  In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model 
Cell stem cell  2013;14(2):188-202.
Loss of neurons after brain injury and in neurodegenerative disease is often accompanied by reactive gliosis and scarring, which are difficult to reverse with existing treatment approaches. Here, we show that reactive glial cells in the cortex of stab-injured or Alzheimer’s disease (AD) model mice can be directly reprogrammed into functional neurons in vivo using retroviral expression of a single neural transcription factor, NeuroD1. Following expression of NeuroD1, astrocytes were reprogrammed into glutamatergic neurons, while NG2 cells were reprogrammed into glutamatergic and GABAergic neurons. Cortical slice recordings revealed both spontaneous and evoked synaptic responses in NeuroD1-converted neurons, suggesting that they integrated into local neural circuits. NeuroD1 expression was also able to reprogram cultured human cortical astrocytes into functional neurons. Our studies therefore suggest that direct reprogramming of reactive glial cells into functional neurons in vivo could provide an alternative approach for repair of injured or diseased brain.
PMCID: PMC3967760  PMID: 24360883
NeuroD1; reactive astrocytes; NG2 cells; reprogram; in vivo; Alzheimer’s disease; brain injury; cortex; neurons
2.  Attenuated Monocyte Apoptosis, a New Mechanism for Osteoporosis Suggested by a Transcriptome-Wide Expression Study of Monocytes 
PLoS ONE  2015;10(2):e0116792.
Osteoporosis is caused by excessive bone resorption (by osteoclasts) over bone formation (by osteoblasts). Monocytes are important to osteoporosis by serving as progenitors of osteoclasts and produce cytokines for osteoclastogenesis.
To identify osteoporosis-related genes, we performed microarray analyses of monocytes using Affymetrix 1.0 ST arrays in 42 (including 16 pre- and 26 postmenopausal) high hip BMD (bone mineral density) vs. 31 (including 15 pre- and 16 postmenopausal) low hip BMD Caucasian female subjects. Here, high vs. low BMD is defined as belonging to top vs. bottom 30% of BMD values in population.
Differential gene expression analysis in high vs. low BMD subjects was conducted in the total cohort as well as pre- and post-menopausal subjects. Focusing on the top differentially expressed genes identified in the total, the pre- and the postmenopausal subjects (with a p <5E-03), we performed replication of the findings in 3 independent datasets of microarray analyses of monocytes (total N = 125).
We identified (in the 73 subjects) and successfully replicated in all the 3 independent datasets 2 genes, DAXX and PLK3. Interestingly, both genes are apoptosis induction genes and both down-regulated in the low BMD subjects. Moreover, using the top 200 genes identified in the meta-analysis across all of the 4 microarray datasets, GO term enrichment analysis identified a number of terms related to induction of apoptosis, for which the majority of component genes are also down-regulated in the low BMD subjects. Overall, our result may suggest that there might be a decreased apoptosis activity of monocytes in the low BMD subjects.
Our study for the first time suggested a decreased apoptosis rate (hence an increased survival) of monocytes, an important osteoclastogenic cell, as a novel mechanism for osteoporosis.
PMCID: PMC4319757  PMID: 25659073
3.  Study on the Regulatory Mechanism of the Lipid Metabolism Pathways during Chicken Male Germ Cell Differentiation Based on RNA-Seq 
PLoS ONE  2015;10(2):e0109469.
Here, we explore the regulatory mechanism of lipid metabolic signaling pathways and related genes during differentiation of male germ cells in chickens, with the hope that better understanding of these pathways may improve in vitro induction. Fluorescence-activated cell sorting was used to obtain highly purified cultures of embryonic stem cells (ESCs), primitive germ cells (PGCs), and spermatogonial stem cells (SSCs). The total RNA was then extracted from each type of cell. High-throughput analysis methods (RNA-seq) were used to sequence the transcriptome of these cells. Gene Ontology (GO) analysis and the KEGG database were used to identify lipid metabolism pathways and related genes. Retinoic acid (RA), the end-product of the retinol metabolism pathway, induced in vitro differentiation of ESC into male germ cells. Quantitative real-time PCR (qRT-PCR) was used to detect changes in the expression of the genes involved in the retinol metabolic pathways. From the results of RNA-seq and the database analyses, we concluded that there are 328 genes in 27 lipid metabolic pathways continuously involved in lipid metabolism during the differentiation of ESC into SSC in vivo, including retinol metabolism. Alcohol dehydrogenase 5 (ADH5) and aldehyde dehydrogenase 1 family member A1 (ALDH1A1) are involved in RA synthesis in the cell. ADH5 was specifically expressed in PGC in our experiments and aldehyde dehydrogenase 1 family member A1 (ALDH1A1) persistently increased throughout development. CYP26b1, a member of the cytochrome P450 superfamily, is involved in the degradation of RA. Expression of CYP26b1, in contrast, decreased throughout development. Exogenous RA in the culture medium induced differentiation of ESC to SSC-like cells. The expression patterns of ADH5, ALDH1A1, and CYP26b1 were consistent with RNA-seq results. We conclude that the retinol metabolism pathway plays an important role in the process of chicken male germ cell differentiation.
PMCID: PMC4320113  PMID: 25658587
4.  Hematology research output from Chinese authors and other countries: a 10-year survey of the literature 
Hematologic disease affects people of all ages worldwide. In the past decade, researchers have made great progress in the field of hematology. In the present study we compared the hematology research output from China and other countries (USA, Germany, UK, Japan and South Korea) over the past 10 years and 5 years.
The related articles were extracted based on the PubMed database. We recorded the number of publications, clinical trials, randomized controlled trials, meta-analyses, case reports, reviews, citations, impact factors, articles in the top 10 journals and most published journals to assess the quantity and quality of research output in each region.
A total of 120,641 hematology-related articles were published from 2004 to 2013. The USA accounted for 27.13% (32,732/120,641) of the publications, followed by Germany (7,479/120,641; 6.20%), Japan (6,347/120,641; 5.26%), the UK (5,453/120,641; 4.52%), China (2,924/120,641; 2.42%) and South Korea (1,413/120,641; 1.17%). The ranking for cumulative impact factors was as follows: USA; Germany; UK; Japan; China and South Korea. The median impact factors in the UK, USA, and Germany were higher than Japan, South Korea, and China. Interestingly, the median impact factors in the three Asia countries were similar both in 2004–2013 and 2009–2013. The UK had the highest percentage of publications in the top 25% of journals, while China lagged behind and ranked last. When comparing the number of articles in the top 10 journals, the results were similar to the IF findings. Germany had the highest number of average citations, while China had the lowest number of average citation. The status of hematology research output from the 6 countries in 2009–2013 had little difference from 2004–2013.
Thus, the USA has had a dominant role in hematologic research in the past 10 years. Overall, the quality of publications in European countries was better than Asia countries. Although China has made considerable progress in hematology research, the quality of research needs improvement.
Electronic supplementary material
The online version of this article (doi:10.1186/s13045-014-0103-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4332745  PMID: 25653049
Hematology; Publications; Impact factor; Citations; Science Citation Index Expanded (SCIE)
5.  EWSR1-PBX3: A Novel Gene Fusion in Myoepithelial Tumors 
Genes, chromosomes & cancer  2014;54(2):63-71.
The genetics of myoepithelial tumors (ME) of soft tissue and bone have recently been investigated, with EWSR1 related gene fusions being seen in approximately half of the tumors. The fusion partners of EWSR1 so far described include POU5F1, PBX1, ZNF444 and, in a rare case, ATF1. We investigated by RNA sequencing an index case of EWSR1-rearranged ME of the tibia, lacking a known fusion partner, and identified a novel EWSR1-PBX3 fusion. The fusion was further validated by reverse transcriptase polymerase chain reaction (RT-PCR) and Fluorescence In Situ hybridization (FISH). To evaluate if this is a recurrent event, an additional cohort of 22 EWSR1-rearranged ME cases lacking a fusion partner were screened by FISH for abnormalities in PBX3 gene. Thus 2 additional cases were identified showing an EWSR1-PBX3 gene fusion. One of them was also intra-osseous involving the ankle, while the other occurred in the soft tissue of the index finger. The morphology of the EWSR1-PBX3 fusion positive cases showed similar findings, with nests or sheets of epithelioid to spindle cells in a partially myxoid to collagenous matrix. All the 3 cases showed expression of S100 and EMA by immunohistochemistry. In summary, we report a novel EWSR1-PBX3 gene fusion in a small subset of ME, thereby expanding the spectrum of EWSR1-related gene fusions seen in these tumors. This gene fusion seems to occur preferentially in skeletal ME, with 2 of the 3 study cases occurring in intraosseous locations.
PMCID: PMC4268355  PMID: 25231231
Myoepithelial tumor; EWSR1; PBX3
6.  Nanoscale simulation of shale transport properties using the lattice Boltzmann method: permeability and diffusivity 
Scientific Reports  2015;5:8089.
Porous structures of shales are reconstructed using the markov chain monte carlo (MCMC) method based on scanning electron microscopy (SEM) images of shale samples from Sichuan Basin, China. Characterization analysis of the reconstructed shales is performed, including porosity, pore size distribution, specific surface area and pore connectivity. The lattice Boltzmann method (LBM) is adopted to simulate fluid flow and Knudsen diffusion within the reconstructed shales. Simulation results reveal that the tortuosity of the shales is much higher than that commonly employed in the Bruggeman equation, and such high tortuosity leads to extremely low intrinsic permeability. Correction of the intrinsic permeability is performed based on the dusty gas model (DGM) by considering the contribution of Knudsen diffusion to the total flow flux, resulting in apparent permeability. The correction factor over a range of Knudsen number and pressure is estimated and compared with empirical correlations in the literature. For the wide pressure range investigated, the correction factor is always greater than 1, indicating Knudsen diffusion always plays a role on shale gas transport mechanisms in the reconstructed shales. Specifically, we found that most of the values of correction factor fall in the slip and transition regime, with no Darcy flow regime observed.
PMCID: PMC4308705  PMID: 25627247
7.  Functional characterization of a vanillin dehydrogenase in Corynebacterium glutamicum 
Scientific Reports  2015;5:8044.
Vanillin dehydrogenase (VDH) is a crucial enzyme involved in the degradation of lignin-derived aromatic compounds. Herein, the VDH from Corynebacterium glutamicum was characterized. The relative molecular mass (Mr) determined by SDS-PAGE was ~51kDa, whereas the apparent native Mr values revealed by gel filtration chromatography were 49.5, 92.3, 159.0 and 199.2kDa, indicating the presence of dimeric, trimeric and tetrameric forms. Moreover, the enzyme showed its highest level of activity toward vanillin at pH 7.0 and 30C, and interestingly, it could utilize NAD+ and NADP+ as coenzymes with similar efficiency and showed no obvious difference toward NAD+ and NADP+. In addition to vanillin, this enzyme exhibited catalytic activity toward a broad range of substrates, including p-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, o-phthaldialdehyde, cinnamaldehyde, syringaldehyde and benzaldehyde. Conserved catalytic residues or putative cofactor interactive sites were identified based on sequence alignment and comparison with previous studies, and the function of selected residues were verified by site-directed mutagenesis analysis. Finally, the vdh deletion mutant partially lost its ability to grow on vanillin, indicating the presence of alternative VDH(s) in Corynebacterium glutamicum. Taken together, this study contributes to understanding the VDH diversity from bacteria and the aromatic metabolism pathways in C. glutamicum.
PMCID: PMC4306973  PMID: 25622822
8.  The Role of IL-23/Th17 Pathway in Patients with Primary Immune Thrombocytopenia 
PLoS ONE  2015;10(1):e0117704.
Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with an unclear etiology. This study aims to investigate the role of IL-23/Th17 pathway in patients with ITP.
The gene expressions of IL-17, IL-23 and their receptors in ITP patients and healthy controls were analyzed by quantitative real-time PCR. ELISA was used to test the IL-17 and IL-23 levels in plasma. Flow cytometry was used to detect the frequency of Th17 cells. The correlation between plasma IL-23 and IL-17 levels, Th17 cells, platelets were analyzed. The level of Th17-related cytokines was measured by ELISA following stimulation with IL-23. Subsequently, the IL-23 and IL-17 levels were measured in patients post-treatment.
The PBMCs of ITP patients showed increased mRNA expression levels in each of the following: IL-23p19, IL-12p40, IL-23R, IL-12Rβ1, IL-17A, IL-17F, and RORC. In addition, elevated Th17 cells and plasma IL-17, IL-23 levels were also observed in these ITP patients. Furthermore, it was found that IL-23 levels in plasma are positively correlated with IL-17 levels and Th17 cells, yet negatively correlated with platelet count. Following IL-23 stimulation in vitro, IL-17 levels showed significant elevation. Furthermore, both IL-23 and IL-17 levels decreased after effective treatment.
The IL-23/Th17 pathway may be involved in the pathogenesis of ITP through enhancement of the Th17 response. Moreover, our results suggest that the IL-23/Th17 pathway is a potential therapeutic target in future attempts of ITP treatment.
PMCID: PMC4306550  PMID: 25621490
9.  Cellulosic ethanol production by natural bacterial consortia is enhanced by Pseudoxanthomonas taiwanensis 
Natural bacterial consortia are considered a promising solution for one-step production of ethanol from lignocellulose because of their adaptation to a wide range of natural lignocellulosic substrates and their capacity for efficient cellulose degradation. However, their low ethanol conversion efficiency has greatly limited the development and application of natural bacterial consortia.
In the present study, we analyzed 16 different natural bacterial consortia from a variety of habitats in China and found that the HP consortium exhibited relatively high ethanol production (2.06 g/L ethanol titer from 7 g/L α-cellulose at 55°C in 6 days). Further studies showed that Pseudoxanthomonas taiwanensis played an important role in the high ethanol productivity of HP and that this strain effectively boosted the ethanol production of various other natural bacterial consortia. Finally, we developed a new consortium, termed HPP, by optimizing the proportion of P. taiwanensis in the HP consortium to achieve the highest ethanol production reported for natural consortia. The ethanol conversion ratio reached 78%, with ethanol titers up to 2.5 g/L.
In the present study, we found a natural bacterial consortium with outstanding ethanol production performance, and revealed an efficient method with potentially broad applicability for further improving the ethanol production of natural bacterial consortia.
Electronic supplementary material
The online version of this article (doi:10.1186/s13068-014-0186-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4308921  PMID: 25648981
Natural consortium; Biomass; Pseudoxanthomonas taiwanensis; Ethanol; Cellulose
10.  Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation 
Aberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center cohort of patients.
In a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo (range: 3–144 mo). Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index (MI), a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence.
Thirty (4.5%) patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 (range: 2–139) months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI (P = 0.001) were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI (P = 0.007) was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A (P = 0.039), lack of bladder recurrence prior to contralateral UTUC (P = 0.009), history of renal transplantation (P < 0.001), and preoperative renal insufficiency (P = 0.002) are independent risk factors for contralateral UTUC recurrence after RNU.
Our data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.
PMCID: PMC4307673  PMID: 25613404
Methylation; Upper tract urothelial carcinoma; Contralateral recurrence; Radical nephroureterectomy; Predictors
11.  Unusual ferromagnetic critical behavior owing to short-range antiferromagnetic correlations in antiperovskite Cu1-xNMn3+x (0.1 ≤ x ≤ 0.4) 
Scientific Reports  2015;5:7933.
For ferromagnets, varying from simple metals to strongly correlated oxides,the critical behaviors near the Curie temperature (TC) can be grouped into several universal classes. In this paper, we report an unusual critical behavior in manganese nitrides Cu1-xNMn3+x (0.1 ≤ x ≤ 0.4). Although the critical behavior below TC can be well described by mean field (MF) theory, robust critical fluctuations beyond the expectations of any universal classes are observed above TC in x = 0.1. The critical fluctuations become weaker when x increases, and the MF-like critical behavior is finally restored at x = 0.4. In addition, the paramagnetic susceptibility of all the samples deviates from the Curie-Weiss (CW) law just above TC. This deviation is gradually smeared as x increases. The short-range antiferromagnetic ordering above TC revealed by our electron spin resonance measurement explains both the unusual critical behavior and the breakdown of the CW law.
PMCID: PMC4300457  PMID: 25604754
12.  hMOB3 modulates MST1 apoptotic signaling and supports tumor growth in glioblastoma multiforme 
Cancer research  2014;74(14):3779-3789.
New therapeutic targets are needed that circumvent inherent therapeutic resistance of glioblastoma multiforme (GBM). Here we report such a candidate target in the uncharacterized adaptor protein hMOB3, which we show is upregulated in GBM. In a search for its biochemical function, we found that hMOB3 specifically interacts with MST1 kinase in response to apoptotic stimuli and cell-cell contact. Moreover, hMOB3 negatively regulated apoptotic signaling by MST1 in GBM cells by inhibiting the MST1 cleavage-based activation process. Physical interaction between hMOB3 and MST1 was essential for this process. In vivo investigations established that hMOB3 sustains GBM cell growth at high cell density and promotes tumorigenesis. Our results suggest hMOB3 as a candidate therapeutic target for the treatment of malignant gliomas.
PMCID: PMC4102567  PMID: 24872389
apoptosis; etoposide; proliferation; STK4; caspase cleavage
13.  Investigating the interaction between peptides of the amphipathic helix of Hcf106 and the phospholipid bilayer by solid-state NMR spectroscopy 
Biochimica et biophysica acta  2013;1838(1):10.1016/j.bbamem.2013.10.007.
The chloroplast twin arginine translocation (cpTat) system transports highly folded precursor proteins into the thylakoid lumen using the protonmotive force as its only energy source. Hcf106, as one of the core components of the cpTat system, is part of the precursor receptor complex and functions in the initial precursor-binding step. Hcf106 is predicted to contain a single amino terminal transmembrane domain followed by a Pro-Gly hinge, a predicted amphipathic α-helix (APH), and a loosely structured carboxy terminus. Hcf106 has been shown biochemically to insert spontaneously into thylakoid membranes. To better understand the membrane active capabilities of Hcf106, we used solid-state NMR spectroscopy to investigate those properties of the APH. In this study, synthesized peptides of the predicted Hcf106 APH (amino acids 28–65) were incorporated at increasing mol% into 1-palmitoyl-2-oleoyl-sn-glycero-phosphocholine (POPC) and POPC/MGDG (monogalactosyldiacylglycerol; mole ratio 85:15) multilamellar vesicles (MLVs) to probe the peptide-lipid interaction. Solid-state 31P NMR and 2H NMR spectroscopic experiments revealed that the peptide perturbs the headgroup and the acyl chain regions of phospholipids as indicated by changes in spectral lineshape, chemical shift anisotropy (CSA) line width, and 2H order SCD parameters. In addition, the comparison between POPC MLVs and POPC/MGDG MLVs indicated that the lipid bilayer composition affected peptide perturbation of the lipids, and such perturbation appeared to be more intense in a system more closely mimicking a thylakoid membrane.
PMCID: PMC3864105  PMID: 24144541
amphipathic helix; membrane active peptide; twin arginine transport; chloroplast TatB
14.  HbA1c, fasting and 2-hour plasma glucose in current-, ex-, and non-smokers: a meta-analysis 
Diabetologia  2013;57(1):30-39.
The relations between smoking and glycaemic parameters are not well explored. We compare HbA1c, fasting plasma glucose (FPG) and 2-hour plasma glucose (2H-PG) in current-, ex- and never-smokers.
This meta-analysis used individual data from 16 886 men and 18 539 women without known diabetes, in 12 DETECT-2 consortium studies and in the French D.E.S.I.R. and TELECOM studies. Means of the three glycaemic parameters in current-, ex- and never-smokers were modelled by linear regression, with study as a random factor. The I2 statistic evaluated heterogeneity among studies.
HbA1c was 0.10 (95%CI:0.08,0.12) % [1.1 (0.9,1.3) mmol/mol] higher in current-smokers and 0.03 (0.01,0.05) % [0.3 (0.1,0.5) mmol/l] higher in ex-smokers, compared with never-smokers. For FPG, there was no significant difference between current- and never-smokers: −0.004 (−0.03,0.02) mmol/l but FPG was higher in ex-smokers: 0.12 (0.09,0.14) mmol/l. In comparison to never-smokers, 2H-PG was lower: −0.44 (−0.52,−0.37) mmol/l in current-smokers, with no difference for ex-smokers: 0.02 (−0.06,0.09) mmol/l. There was a large and unexplained heterogeneity among studies, with I2 always higher than 50%: after stratification by sex and adjustment for age and BMI, I2 changed little. In this study population, current-smokers had a prevalence of diabetes as screened by HbA1c, 1.30% higher and that screened by 2H-PG, 0.52% lower than in comparison to never-smokers.
Current-smokers had a higher HbA1c and a lower 2H-PG than never-smokers, across this heterogeneous group of studies; this will effect the chances of smokers being diagnosed with diabetes.
PMCID: PMC4240946  PMID: 24065153
HbA1c; FPG; 2H-PG; smoking
15.  A Genetic Dichotomy between Pure Sclerosing Epithelioid Fibrosarcoma (SEF) and Hybrid SEF/Low Grade Fibromyxoid Sarcoma: A Pathologic and Molecular Study of 18 cases 
Genes, chromosomes & cancer  2014;54(1):28-38.
Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue tumor exhibiting considerable morphologic overlap with low grade fibromyxoid sarcoma (LGFMS). Moreover, both SEF and LGFMS show MUC4 expression by immunohistochemistry. While the majority of LGFMS cases are characterized by a FUS-CREB3L1 fusion, both FUS-CREB3L2 and EWSR1-CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors. In contrast, recent studies pointed out that SEF harbor frequent EWSR1 rearrangements, with only a minority of cases showing FUS-CREB3L2 fusions. In an effort to further characterize the molecular characteristics of pure SEF and hybrid SEF/LGFMS lesions, we undertook a clinicopathologic, immunohistochemical and genetic analysis of a series of 10 SEF and 8 hybrid SEF/LGFMS tumors. The mortality rate was similar between the two groups, 44% within the pure SEF group and 37% in the hybrid SEF/LGFMS with a mean overall follow-up of 66 months. All but one pure SEF and all hybrid SEF/LGFMS tested cases showed MUC4 immunoreactivity. The majority (90%) of pure SEF cases showed EWSR1 gene rearrangements by FISH with only one case exhibiting FUS rearrangement. Of the 9 EWSR1 positive cases, 6 cases harbored CREB3L1 break-apart, two had CREB3L2 rearrangement (a previously unreported finding) and one lacked evidence of CREB3L1/2 abnormalities. In contrast, all hybrid SEF/LGFMS tumors exhibited FUS and CREB3L2 rearrangements. These results further demarcate a relative cytogenetic dichotomy between pure SEF, often characterized by EWSR1 rearrangements, and hybrid SEF/LGFMS, harboring FUS-CREB3L2 fusion; the latter group recapitulating the genotype of LGFMS.
PMCID: PMC4232448  PMID: 25231134
sclerosing epithelioid fibrosarcoma; fibromyxoid sarcoma; EWSR1; FUS; CREB3L1; CREB3L2; fusion
16.  Thoracic Epithelioid Malignant Vascular Tumors: A Clinicopathologic Study of 52 Cases with Emphasis on Pathologic Grading and Molecular Studies of WWTR1-CAMTA1 Fusions 
Malignant thoracic epithelioid vascular tumors are an uncommon and heterogenous group of tumors that include low to intermediate grade epithelioid hemangioendothelioma (EHE) and high grade epithelioid angiosarcoma (EAS). We examine the morphologic and immunohistochemical features of 52 malignant epithelioid vascular tumors (10 low-grade EHE, 29 intermediate grade EHE and 13 EAS) involving the thorax (lung, pleura, mediastinum, heart, great vessels) including cases with exclusively thoracic disease (35) and with multiorgan disease including the thorax (17). Intermediate grade EHE differs from low-grade EHE by the presence of necrosis, increased mitotic activity and increased atypia. Morphologic features such as intranuclear inclusions, intracytoplasmic vacuoles, stromal changes (chondroid, myxoid or hyalinized stroma) are seen more frequently in EHE, whereas blood lakes, proliferation of slit-like vessels and prominent nucleoli favor EAS. FISH analysis showed CAMTA1-WWTR1 fusions in 4/7 low grade and 23/23 intermediate grade EHE (p<0.001). In EAS, CAMTA1 rearrangement was negative in all cases, while a WWTR1 complex abnormality was found in 1/5 case (p<0.001). This offers an objective means of differentiating intermediate grade EHE from EAS, especially on limited biopsies. All cases show expression of at least one vascular marker, which allows differentiation from primary thoracic epithelial malignancies, although keratin expression is a potential pitfall with 29% of EHE and 25% of EAS showing keratin expression. Survival analysis shows that higher tumor grade for all tumors (p=0.026) as well as lung and pleural tumors only (p=0.010) and the presence of pleural involvement in lung and/or pleural tumors (p=0.042) correlate with poor prognosis.
PMCID: PMC4268225  PMID: 25353289
epithelioid hemangioendothelioma; angiosarcoma; WWTR1; CAMTA1; thoracic; prognosis
18.  Exploring HIV Prevention Strategies among Street-Based Female Sex Workers in Chongqing, China 
Background: Commercial sex plays an increasingly important role in China’s growing HIV and sexually transmitted infection (STI) epidemics. In China, street-based sex workers (SSWs) are a subgroup of female sex workers with a particularly high risk of HIV/STI infections but are neglected in responses to HIV. This study assesses changes in HIV voluntary counseling and testing (VCT) utilization and high-risk sexual behaviors following a three-month HIV preventive intervention among SSWs in Chongqing, China. Methods: A three-month intervention was conducted by a team of peer educators, outreach workers from community-based organizations and health professionals. It mainly included distribution of free pamphlets and condoms and delivery of onsite and clinic-based VCT. Cross-sectional surveys were conducted prior to (n = 100) and immediately following (n = 112) the intervention to assess its impact. In-depth interviews were conducted among 12 SSWs after the intervention to further explore potential barriers to HIV prevention. Results: The intervention significantly increased SSWs’ participation in VCT (from 2.0%–15.2%, P < 0.001). Despite participants’ improved HIV-related knowledge level (from 24.0%–73.2%, P < 0.001), there were minimal changes in the levels of condom use with clients. Qualitative research revealed that fear of police arrest and stigma were the main barriers to VCT utilization. Low condom use was associated with family financial constraints, inadequate power in condom negotiation, low awareness and misconceptions of HIV infection risks. Conclusion: HIV intervention improved VCT utilization and knowledge but we did not observe an increase in condom use after this short intervention. SSWs faced substantial economic, social and environmental barriers to VCT utilization and condom use.
PMCID: PMC4306897  PMID: 25602971
street-based sex worker; Human Immunodeficiency Virus; condom use; commercial sex; peer-based intervention
19.  Treatment Strategies for Aneurysms Associated with Moyamoya Disease 
The treatment of aneurysms associated with moyamoya disease (MMD) is difficult for neurosurgeons, and little is known of strategy options. This report constitutes a comprehensive review of the literature. We summarize the known treatments and their clinical outcomes according to the site of the aneurysm: in major arteries, peripheral arteries, moyamoya vessels, meningeal arteries, or at the site of anastomosis. The literature review indicates that the treatment of MMD-associated aneurysms varies according to the site of the aneurysm and its hemodynamic characteristics. In particular, the treatment for basilar tip aneurysms remains challenging, since both endovascular embolization and direct clipping are difficult. The potential risk for ischemia should be considered in selecting endovascular or surgical approaches. Revascularization surgery, which is important for the treatment of MMD, also determines the clinical treatment outcome of aneurysms associated with MMD.
PMCID: PMC4323361
Moyamoya disease; aneurysms; treatment
20.  Thermophysical Properties of Lignocellulose: A Cell-Scale Study Down to 41K 
PLoS ONE  2014;9(12):e114821.
Thermal energy transport is of great importance in lignocellulose pyrolysis for biofuels. The thermophysical properties of lignocellulose significantly affect the overall properties of bio-composites and the related thermal transport. In this work, cell-scale lignocellulose (mono-layer plant cells) is prepared to characterize their thermal properties from room temperature down to ∼40 K. The thermal conductivities of cell-scale lignocellulose along different directions show a little anisotropy due to the cell structure anisotropy. It is found that with temperature going down, the volumetric specific heat of the lignocellulose shows a slower decreasing trend against temperature than microcrystalline cellulose, and its value is always higher than that of microcrystalline cellulose. The thermal conductivity of lignocellulose decreases with temperature from 243 K to 317 K due to increasing phonon-phonon scatterings. From 41 K to 243 K, the thermal conductivity rises with temperature and its change mainly depends on the heat capacity's change.
PMCID: PMC4273982  PMID: 25532131
21.  Comparison of clinical characteristics between neuromyelitis optica spectrum disorders with and without spinal cord atrophy 
BMC Neurology  2014;14(1):246.
Spinal cord lesions is one of the predominant characteristics in patients with neuromyelitis optica spectrum disorders (NMOSD). Interestingly, mounting evidence indicates that spinal cord atrophy (SCA) is one of common clinical features in multiple sclerosis (MS) patients, and correlates closely with the neurological disability. However, Clinical studies related to the SCA aspects of NMOSD are still scarce.
We retrospectively analyzed 185 patients with NMOSD, including 23 patients with SCA and 162 patients without SCA. Data were collected regarding clinical characteristics, laboratory tests, and magnetic resonance imaging findings.
12.4% of patients had SCA in NMOSD. Patients with SCA had a longer disease duration and higher EDSS at clinical onset and last visit. More importantly, SCA patients were more prone to reach disability milestones (EDSS ≥ 6.0). Bowel or bladder dysfunction, movement disorders, and sensory disturbances symptoms were more common in patients with SCA. ESR and CRP were significantly higher in patients with SCA than those without SCA. Patients with SCA were more frequently complicated with cervical cord lesions. However, the ARR, progression index, seropositive rate of NMO-IgG and OCB were similar in the two groups. Futhermore, LETM did not differ significantly between patients with SCA and without SCA in NMOSD patients.
Patients with SCA might have longer disease duration, more severe clinical disability, and more frequently complicated with cervical spinal cord lesions. SCA might be predictive of the more severe neurologic dysfunction and worse prognosis in NMOSD. Inflammation contributes to the development of SCA in NMOSD.
PMCID: PMC4302083  PMID: 25526927
Neuromyelitis optica spectrum disorders; Spinal cord atrophy; Longitudinally extensive transverse myelitis; Magnetic resonance imaging
22.  Regulation of UCP1 in the Browning of Epididymal Adipose Tissue by β3-Adrenergic Agonist: A Role for MicroRNAs 
Background. White adipose tissue browning may be a promising strategy to combat obesity. UCP1 is strongly induced in White adipose tissue with β3-adrenergic agonist treatment, but the causes of this increase have not been fully elucidated. This study aims to explore more miRNAs involved in the process of browning of visceral adipose tissue. Methods. Total of fourteen mice were randomly divided into control and study group. Study group mice were injected intraperitoneally with CL316243 once daily for seven days; meanwhile the control group were treated with 0.9% NaCl. After a 7-day period, the expression of genes involved in WAT browning and potential UCP1-targeting miRNAs in adipose tissues was analyzed by qPCR. Results. qPCR analysis revealed that UCP1, DIO2, CIDEA, and CPT1B in epididymal adipose tissue were overexpressed in CL316243 group. Furthermore, potential UCP1-targeting miR-9 and miR-338-3p in epididymal adipose tissue were significantly decreased in CL316243 group. Conclusion. This suggests that potential UCP1-targeting miR-9 and miR-338-3p may be involved in the browning of epididymal adipose tissue by regulating UCP1 gene expression. In this study, we demonstrated that this increase of UCP1 is due, at least in part, to the decreased expression of certain UCP1-targeting miRNAs in epididymal adipose tissue compared to control.
PMCID: PMC4281391  PMID: 25587272
23.  Phosphine-Catalyzed [3+2] and [4+3]Annulation Reactions of C,N-Cyclic Azomethine Imines with Allenoates 
Advanced synthesis & catalysis  2012;354(6):1023-1034.
Phosphine-catalyzed [3+2] and [4+3]annulation reactions of C,N-cyclic azomethine imines with allenoates have been developed to give a variety of pharmaceutically attractive tetrahydroisoquinoline derivatives in moderate to excellent yields. The two distinct reaction pathways, [3+2] and [4+3]cyclization, depend on the nature of the nucleophilic phosphine and the allenoate. Generally, for α-alkylallenoates, the reactions always proceed with [3 +2]cyclization as the major pathway no matter what phosphine was used; for α-ArCH2-substituted allenoates, the reaction pathway was controlled by the phosphine catalyst used.
PMCID: PMC4266944  PMID: 25525424
allenoates; annulation; azomethine imines; catalysis; phosphines
24.  Functional Characterization of Corynebacterium glutamicum Mycothiol S-Conjugate Amidase 
PLoS ONE  2014;9(12):e115075.
The present study focuses on the genetic and biochemical characterization of mycothiol S-conjugate amidase (Mca) of Corynebacterium glutamicum. Recombinant C. glutamicum Mca was heterologously expressed in Escherichia coli and purified to apparent homogeneity. The molecular weight of native Mca protein determined by gel filtration chromatography was 35 kDa, indicating that Mca exists as monomers in the purification condition. Mca showed amidase activity with mycothiol S-conjugate of monobromobimane (MSmB) in vivo while mca mutant lost the ability to cleave MSmB. In addition, Mca showed limited deacetylase activity with N-acetyl-D-glucosamine (GlcNAc) as substrate. Optimum pH for amidase activity was between 7.5 and 8.5, while the highest activity in the presence of Zn2+ confirmed Mca as a zinc metalloprotein. Amino acid residues conserved among Mca family members were located in C. glutamicum Mca and site-directed mutagenesis of these residues indicated that Asp14, Tyr137, His139 and Asp141 were important for activity. The mca deletion mutant showed decreased resistance to antibiotics, alkylating agents, oxidants and heavy metals, and these sensitive phenotypes were recovered in the complementary strain to a great extent. The physiological roles of Mca in resistance to various toxins were further supported by the induced expression of Mca in C. glutamicum under various stress conditions, directly under the control of the stress-responsive extracytoplasmic function-sigma (ECF-σ) factor SigH.
PMCID: PMC4267739  PMID: 25514023
25.  The diagnosis of diabetic acute complications using the glucose-ketone meter in outpatients at endocrinology department 
Objective: To determine urine ketone and blood β-hydroxybutyrate acid (β-HBA) in outpatients of endocrinology department and to investigate the association between urine ketone or blood β-HBA and diabetic ketosis (DK) or diabetic ketoacidosis (DKA). Methods: Urine ketone, blood β-HBA, body mass index (BMI) and glycosylated hemoglobin (HbA1c) were determined in 134 patients with blood glucose ≥ 13.9 mmol/L. Results: In 134 patients with severe hyperglycemia, there were 30 patients (22.4%) with acute complications of diabetes, including 24 patients (17.9%) diagnosed with DK and 6 patients (4.5%) diagnosed with DKA. Among them, 6 patients (20%) were withdrawal, 2 (6.7%) were infected, and 19 (63.3%) were not treated. When there was a negative urine ketone, 10% patients would have had blood β-HBA ≥ 0.3 mmol/L. When there was a positive urine ketone (+ to +++), 22.62% patients would have had blood β-HBA < 0.3 mmol/L. Conclusions: Blood β-HBA had a positive correlation with blood glucose (r = 0.34, P < 0.001). Complications of severe hyperglycemia could be diagnosed quickly and accurately by analyzing blood β-HBA using the glucose-ketone meter.
PMCID: PMC4307541  PMID: 25664094
Diabetic ketoacidosis; urine ketone; β-hydroxybutyrate acid; glucose-ketone meter

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