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1.  “Plateau”-related summary statistics are uninformative for comparing working memory models 
Performance on visual working memory tasks decreases as more items need to be remembered. Over the past decade, a debate has unfolded between proponents of slot models and slotless models of this phenomenon. Zhang and Luck (2008) and Anderson, Vogel, and Awh (2011) noticed that as more items need to be remembered, “memory noise” seems to first increase and then reach a “stable plateau.” They argued that three summary statistics characterizing this plateau are consistent with slot models, but not with slotless models. Here, we assess the validity of their methods. We generated synthetic data both from a leading slot model and from a recent slotless model and quantified model evidence using log Bayes factors. We found that the summary statistics provided, at most, 0.15% of the expected model evidence in the raw data. In a model recovery analysis, a total of more than a million trials were required to achieve 99% correct recovery when models were compared on the basis of summary statistics, whereas fewer than 1,000 trials were sufficient when raw data were used. At realistic numbers of trials, plateau-related summary statistics are completely unreliable for model comparison. Applying the same analyses to subject data from Anderson et al. (2011), we found that the evidence in the summary statistics was, at most, 0.12% of the evidence in the raw data and far too weak to warrant any conclusions. These findings call into question claims about working memory that are based on summary statistics.
PMCID: PMC4194187  PMID: 24719235
2.  A Study of the Preparation and Properties of Antioxidative Copper Inks with High Electrical Conductivity 
Conductive ink using copper nanoparticles has attracted much attention in the printed electronics industry because of its low cost and high electrical conductivity. However, the problem of easy oxidation under heat and humidity conditions for copper material limits the wide applications. In this study, antioxidative copper inks were prepared by dispersing the nanoparticles in the solution, and then conductive copper films can be obtained after calcining the copper ink at 250 °C in nitrogen atmosphere for 30 min. A low sheet resistance of 47.6 mΩ/□ for the copper film was measured by using the four-point probe method. Importantly, we experimentally demonstrate that the electrical conductivity of copper films can be improved by increasing the calcination temperature. In addition, these highly conductive copper films can be placed in an atmospheric environment for more than 6 months without the oxidation phenomenon, which was verified by energy-dispersive X-ray spectroscopy (EDS). These observations strongly show that our conductive copper ink features high antioxidant properties and long-term stability and has a great potential for many printed electronics applications, such as flexible display systems, sensors, photovoltaic cells, and radio frequency identification.
PMCID: PMC4569602  PMID: 26370132
Conductive ink; Stability; Resistivity; Antioxidant
3.  miR-17 promotes expansion and adhesion of human cord blood CD34+ cells in vitro 
We have recently found that miR-17 is necessary in the cell-extrinsic control of cord blood (CB) CD34+ cell function. Here, we demonstrated that the proper level of miR-17 is also necessary in the cell-intrinsic control of the hematopoietic properties of CB CD34+ cells.
The miR-17 overexpression and knockdown models were created using primary CB CD34+ cells transfected by the indicated vectors. Long-term culture, colony forming, adhesion and trans-well migration assays were carried out to investigate the function of miR-17 on CB CD34+ cells in vitro. NOD prkdcscid Il2rgnull mice were used in a SCID repopulating cell assay to investigate the function of miR-17 on CB CD34+ cells in vivo. A two-tailed Student’s t-test was used for statistical comparisons.
In vitro assays revealed that ectopic expression of miR-17 promoted long-term expansion, especially in the colony-forming of CB CD34+ cells and CD34+CD38− cells. Conversely, downregulation of miR-17 inhibited the expansion of CB CD34+ cells. However, the overexpression of miR-17 in vivo reduced the hematopoietic reconstitution potential of CB CD34+ cells compared to that of control cells. The increased expression of major adhesion molecules in miR-17 overexpressed CB CD34+ cells suggests that the adhesion between miR-17 overexpressed CB CD34+ cells and their niche in vivo is regulated abnormally, which may further lead to the reduced hematopoietic reconstitution capability of 17/OE cells in engrafted mice.
We conclude that the proper expression of miR-17 is required, at least partly, for normal hematopoietic stem cell–niche interaction and for the regulation of adult hematopoiesis.
Electronic supplementary material
The online version of this article (doi:10.1186/s13287-015-0159-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4562375  PMID: 26345634
4.  Neural Population Coding of Multiple Stimuli 
The Journal of Neuroscience  2015;35(9):3825-3841.
In natural scenes, objects generally appear together with other objects. Yet, theoretical studies of neural population coding typically focus on the encoding of single objects in isolation. Experimental studies suggest that neural responses to multiple objects are well described by linear or nonlinear combinations of the responses to constituent objects, a phenomenon we call stimulus mixing. Here, we present a theoretical analysis of the consequences of common forms of stimulus mixing observed in cortical responses. We show that some of these mixing rules can severely compromise the brain's ability to decode the individual objects. This cost is usually greater than the cost incurred by even large reductions in the gain or large increases in neural variability, explaining why the benefits of attention can be understood primarily in terms of a stimulus selection, or demixing, mechanism rather than purely as a gain increase or noise reduction mechanism. The cost of stimulus mixing becomes even higher when the number of encoded objects increases, suggesting a novel mechanism that might contribute to set size effects observed in myriad psychophysical tasks. We further show that a specific form of neural correlation and heterogeneity in stimulus mixing among the neurons can partially alleviate the harmful effects of stimulus mixing. Finally, we derive simple conditions that must be satisfied for unharmful mixing of stimuli.
PMCID: PMC4461696  PMID: 25740513
computational neuroscience; Fisher information; neural decoding; neural encoding; population coding; theoretical neuroscience
5.  Kaempferol targets RSK2 and MSK1 to suppress ultraviolet radiation-induced skin cancer 
Solar ultraviolet (SUV) irradiation is a major factor in skin carcinogenesis, the most common form of cancer in the USA. The mitogen-activated protein (MAP) kinase cascades are activated by SUV irradiation. The 90 kDa ribosomal S6 kinase (RSK) and mitogen and stress activated protein kinase (MSK) proteins constitute a family of protein kinases that mediate signal transduction downstream of the MAP kinase cascades. In this study, phosphorylation of RSK and MSK1 was up-regulated in human squamous cell carcinoma (SCC) and solar UV-treated mouse skin. Kaempferol, a natural flavonol, found in tea, broccoli, grapes, apples and other plant sources, is known to have anticancer activity, but its mechanisms and direct target(s) in cancer chemoprevention are unclear. Kinase array results revealed that kaempferol inhibited RSK2 and MSK1. Pull-down assay results, ATP competition and in vitro kinase assay data revealed that kaempferol interacts with RSK2 and MSK1 at the ATP-binding pocket and inhibits their respective kinase activities. Mechanistic investigations showed that kaempferol suppresses RSK2 and MSK1 kinase activities to attenuate solar UV-induced phosphorylation of CREB and histone H3 in mouse skin cells. Kaempferol was a potent inhibitor of solar UV-induced mouse skin carcinogenesis. Further analysis showed that skin from the kaempferol-treated group exhibited a substantial reduction in solar UV-induced phosphorylation of cAMP response element-binding protein (CREB), c-Fos and histone H3. Overall, our results identify kaempferol as a safe and novel chemopreventive agent against solar UV-induced skin carcinogenesis that acts by targeting RSK2 and MSK1.
PMCID: PMC4154980  PMID: 24994661
kaempferol; SUV; skin cancer; RSK2; MSK1
6.  Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by sevoflurane anesthesia* #  
Objective: Though sevoflurane has been widely used as an anesthetic in surgery, recent studies have shown that exposure to sevoflurane alone could lead to postoperative cognitive dysfunction (POCD), of which the mechanisms still remain largely unknown. The medial prefrontal cortex (mPFC) is known to be implicated in various cognitive impairments, including working memory and attentional processes. In the present study, we tried to identify dysregulated gene expression in mPFC and investigate the underlying mechanisms involved in POCD. Methods: Behavioral tests, including elevated plus-maze, O-maze, and Y-maze tests, were performed on Wistar rats exposed to sevoflurane. Whole-genome mRNA profiling of mPFC from Wistar rats after exposure to sevoflurane was carried out. Real-time polymerase chain reaction (PCR) was done to verify the differentially expressed genes. Results: Significant impairment of working memory of rats after exposure to sevoflurane was observed. A total of 119 of 7319 detected mRNAs showed significantly different expression between rats with and without sevoflurane exposure (fold change (FC)>2.0, P<0.05, and false discovery rate (FDR)<0.05), among which 74 mRNAs were down-regulated and 45 mRNAs were up-regulated. Postsynaptic density-95 (PSD95, also named DLG4) showed the most significantly decreased expression in mPFC and further investigation indicated that PSD95 expression level was correlated with spatial working memory performance. Conclusions: Our study revealed that PSD95 might be involved in the mechanism of POCD, which could provide clues for preventing POCD in clinical operations.
PMCID: PMC4569684  PMID: 26365118
Sevoflurane; Cognitive dysfunction; PSD95
7.  Probabilistic brains: knowns and unknowns 
Nature neuroscience  2013;16(9):1170-1178.
There is strong behavioral and physiological evidence that the brain both represents probability distributions and performs probabilistic inference. Computational neuroscientists have started to shed light on how these probabilistic representations and computations might be implemented in neural circuits. One particularly appealing aspect of these theories is their generality: they can be used to model a wide range of tasks, from sensory processing to high-level cognition. To date, however, these theories have only been applied to very simple tasks. Here we discuss the challenges that will emerge as researchers start focusing their efforts on real-life computations, with a focus on probabilistic learning, structural learning and approximate inference.
PMCID: PMC4487650  PMID: 23955561
8.  Not Noisy, Just Wrong: The Role of Suboptimal Inference in Behavioral Variability 
Neuron  2012;74(1):30-39.
Behavior varies from trial to trial even when the stimulus is maintained as constant as possible. In many models, this variability is attributed to noise in the brain. Here, we propose that there is another major source of variability: suboptimal inference. Importantly, we argue that in most tasks of interest, and particularly complex ones, suboptimal inference is likely to be the dominant component of behavioral variability. This perspective explains a variety of intriguing observations, including why variability appears to be larger on the sensory than on the motor side, and why our sensors are sometimes surprisingly unreliable.
PMCID: PMC4486264  PMID: 22500627
9.  Impacts of Different Grades of Tropical Cyclones on Infectious Diarrhea in Guangdong, 2005-2011 
PLoS ONE  2015;10(6):e0131423.
Guangdong province is one of the most vulnerable provinces to tropical cyclones in China. Most prior studies concentrated on the relationship between tropical cyclones and injuries and mortality. This study aimed to explore the impacts of different grades of tropical cyclones on infectious diarrhea incidence in Guangdong province, from 2005 to 2011.
Mann-Whitney U test was firstly used to examine if infectious diarrhea were sensitive to tropical cyclone. Then unidirectional 1:1 case-crossover design was performed to quantitatively evaluate the relationship between daily number of infectious diarrhea and tropical cyclone from 2005 to 2011 in Guangdong, China. Principal component analysis (PCA) was applied to eliminate multicollinearity. Multivariate logistic regression model was used to estimate the hazard ratios (HRs) and the 95% confidence intervals (CI).
There were no significant relationships between tropical cyclone and bacillary dysentery, amebic dysentery, typhoid, and paratyphoid cases. Infectious diarrhea other than cholera, dysentery, typhoid and paratyphoid significantly increased after tropical cyclones. The strongest effect were shown on lag 1 day (HRs = 1.95, 95%CI = 1.22, 3.12) and no lagged effect was detected for tropical depression, tropical storm, severe tropical storm and typhoon, with the largest HRs (95%CI) of 2.16 (95%CI = 1.69, 2.76), 2.43 (95%CI = 1.65, 3.58) and 2.21 (95%CI = 1.65, 2.69), respectively. Among children below 5 years old, the impacts of all grades of tropical cyclones were strongest at lag 0 day. And HRs were 2.67 (95%CI = 1.10, 6.48), 2.49 (95%CI = 1.80, 3.44), 4.89 (95%CI = 2.37, 7.37) and 3.18 (95%CI = 2.10, 4.81), respectively.
All grades of tropical cyclones could increase risk of other infectious diarrhea. Severe tropical storm has the strongest influence on other infectious diarrhea. The impacts of tropical cyclones on children under 5 years old were higher than total population.
PMCID: PMC4479563  PMID: 26106882
10.  Soil Tillage Management Affects Maize Grain Yield by Regulating Spatial Distribution Coordination of Roots, Soil Moisture and Nitrogen Status 
PLoS ONE  2015;10(6):e0129231.
The spatial distribution of the root system through the soil profile has an impact on moisture and nutrient uptake by plants, affecting growth and productivity. The spatial distribution of the roots, soil moisture, and fertility are affected by tillage practices. The combination of high soil density and the presence of a soil plow pan typically impede the growth of maize (Zea mays L.).We investigated the spatial distribution coordination of the root system, soil moisture, and N status in response to different soil tillage treatments (NT: no-tillage, RT: rotary-tillage, SS: subsoiling) and the subsequent impact on maize yield, and identify yield-increasing mechanisms and optimal soil tillage management practices. Field experiments were conducted on the Huang-Huai-Hai plain in China during 2011 and 2012. The SS and RT treatments significantly reduced soil bulk density in the top 0–20 cm layer of the soil profile, while SS significantly decreased soil bulk density in the 20–30 cm layer. Soil moisture in the 20–50 cm profile layer was significantly higher for the SS treatment compared to the RT and NT treatment. In the 0-20 cm topsoil layer, the NT treatment had higher soil moisture than the SS and RT treatments. Root length density of the SS treatment was significantly greater than density of the RT and NT treatments, as soil depth increased. Soil moisture was reduced in the soil profile where root concentration was high. SS had greater soil moisture depletion and a more concentration root system than RT and NT in deep soil. Our results suggest that the SS treatment improved the spatial distribution of root density, soil moisture and N states, thereby promoting the absorption of soil moisture and reducing N leaching via the root system in the 20–50 cm layer of the profile. Within the context of the SS treatment, a root architecture densely distributed deep into the soil profile, played a pivotal role in plants’ ability to access nutrients and water. An optimal combination of deeper deployment of roots and resource (water and N) availability was realized where the soil was prone to leaching. The correlation between the depletion of resources and distribution of patchy roots endorsed the SS tillage practice. It resulted in significantly greater post-silking biomass and grain yield compared to the RT and NT treatments, for summer maize on the Huang-Huai-Hai plain.
PMCID: PMC4476672  PMID: 26098548
11.  Comprehensive analysis of gene-expression profile in chronic obstructive pulmonary disease 
To investigate the gene-expression profile of chronic obstructive pulmonary disease (COPD) patients and explore the possible therapeutic targets.
The microarray raw dataset GSE29133, including three COPD samples and three normal samples, was obtained from Gene Expression Omnibus. After data preprocessing with the Affy package, Student’s t-test was employed to identify the differentially expressed genes (DEGs). The up- and downregulated DEGs were then pooled for gene-ontology and pathway-enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The upstream regulatory elements of these DEGs were also explored by using Whole-Genome rVISTA. Furthermore, we constructed a protein–protein interaction (PPI) network for DEGs. The surfactant protein D (SP-D) serum level and HLA-A gene frequency in COPD patients and healthy controls were also measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction, respectively.
A total of 39 up- and 15 downregulated DEGs were screened. Most of the upregulated genes were involved in the immune response process, while the downregulated genes were involved in the steroid metabolic process. Moreover, we also found that HLA-A has the highest degree in the PPI network. The SP-D serum level and HLA-A gene frequency in COPD patients were significantly higher than those in healthy controls (13.62±2.09 ng/mL vs 10.28±2.86 ng/mL; 62.5% vs 12.5%; P<0.05).
Our results may help further the understanding of the mechanisms of COPD. The identified DEGs, especially HLA-A, may serve as diagnosis markers for COPD.
PMCID: PMC4468932  PMID: 26089660
chronic obstructive pulmonary disease; differentially expressed genes; gene-ontology analysis; protein–protein interaction
12.  Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive 
The duration and quality of human performance depend on both intrinsic motivation and external incentives. However, little is known about the neuroscientific basis of this interplay between internal and external motivators. Here, we used functional magnetic resonance imaging to examine the neural substrates of intrinsic motivation, operationalized as free-choice time spent on a task when not required, and tested the neural and behavioral effects of external reward on intrinsic motivation. We found that increased duration of free-choice time was predicted by generally diminished neural response in regions associated with cognitive and affective regulation. By comparison, the possibility of additional reward improved task accuracy and specifically increased neural and behavioral responses following errors. Those individuals with the smallest neural responses associated with intrinsic motivation exhibited the greatest error-related neural enhancement under the external contingency of possible reward. Together, these data suggest a ‘tonic’ and ‘phasic’ relationship between the neural substrates of intrinsic motivation (tonic) and the impact of external incentives (phasic) that guides human performance.
PMCID: PMC4412758  PMID: 25348668
intrinsic motivation; functional magnetic resonance imaging (fMRI); internal and external incentives; neural substrates; behavioral performance
13.  Vertical Distribution of Bacterial Community Diversity and Water Quality during the Reservoir Thermal Stratification 
Reservoir thermal stratification drives the water temperature and dissolved oxygen gradient, however, the characteristic of vertical water microbial community during thermal stratification is so far poorly understood. In this work, water bacterial community diversity was determined using the Illumina Miseq sequencing technique. The results showed that epilimnion, metalimnion and hypolimnion were formed steadily in the JINPEN drinking water reservoir. Water temperature decreased steadily from the surface (23.11 °C) to the bottom (9.17 °C). Total nitrogen ranged from 1.07 to 2.06 mg/L and nitrate nitrogen ranged from 0.8 to 1.84 mg/L. The dissolved oxygen concentration decreased sharply below 50 m, and reached zero at 65 m. The Miseq sequencing revealed a total of 4127 operational taxonomic units (OTUs) with 97% similarity, which were affiliated with 15 phyla including Acidobacteria, Actinobacteria, Armatimonadetes, Bacteroidetes, Caldiserica, Chlamydiae, Chlorobi, Chloroflexi, Cyanobacteria, Firmicutes, Gemmatimonadetes, Nitrospirae, Planctomycetes, Proteobacteria, and Verrucomicrobia. The highest Shannon diversity was 4.41 in 45 m, and the highest Chao 1 diversity was 506 in 5 m. Rhodobacter dominated in 55 m (23.24%) and 65 m (12.58%). Prosthecobacter dominated from 0.5 to 50 m. The heat map profile and redundancy analysis (RDA) indicated significant difference in vertical water bacterial community composition in the reservoir. Meanwhile, water quality properties including dissolved oxygen, conductivity, nitrate nitrogen and total nitrogen have a dramatic influence on vertical distribution of bacterial communities.
PMCID: PMC4483740  PMID: 26090607
reservoir; thermal stratification; water bacterial community; high-throughput sequencing
14.  MicroRNA-34a suppresses the breast cancer stem cell-like characteristics by downregulating Notch1 pathway 
Cancer Science  2015;106(6):700-708.
MicroRNAs play pivotal roles in cancer stem cell regulation. Previous studies have shown that microRNA-34a (miR-34a) is downregulated in human breast cancer. However, it is unknown whether and how miR-34a regulates breast cancer stem cells. Notch signaling is one of the most important pathways in stem cell maintenance and function. In this study, we verified that miR-34a directly and functionally targeted Notch1 in MCF-7 cells. We reported that miR-34a negatively regulated cell proliferation, migration, and invasion and breast cancer stem cell propagation by downregulating Notch1. The expression of miR-34a was negatively correlated with tumor stages, metastasis, and Notch1 expression in breast cancer tissues. Furthermore, overexpression of miR-34a increased chemosensitivity of breast cancer cells to paclitaxel (PTX) by downregulating the Notch1 pathway. Mammosphere formation and expression of the stemness factor ALDH1 were also reduced in the cells treated with miR-34a and PTX compared to those treated with PTX alone. Taken together, our results indicate that miR-34a inhibited breast cancer stemness and increased the chemosensitivity to PTX partially by downregulating the Notch1 pathway, suggesting that miR-34a/Notch1 play an important role in regulating breast cancer stem cells. Thus miR-34a is a potential target for prevention and therapy of breast cancer.
PMCID: PMC4471794  PMID: 25783790
Breast cancer stem cell; drug resistance; miR-34a; Notch1; paclitaxel
15.  Bridge- and Solvent-Mediated Intramolecular Electronic Communications in Ubiquinone-Based Biomolecular Wires 
Scientific Reports  2015;5:10352.
Intramolecular electronic communications of molecular wires play a crucial role for developing molecular devices. In the present work, we describe different degrees of intramolecular electronic communications in the redox processes of three ubiquinone-based biomolecular wires (Bis-CoQ0s) evaluated by electrochemistry and Density Functional Theory (DFT) methods in different solvents. We found that the bridges linkers have a significant effect on the electronic communications between the two peripheral ubiquinone moieties and solvents effects are limited and mostly depend on the nature of solvents. The DFT calculations for the first time indicate the intensity of the electronic communications during the redox processes rely on the molecular orbital elements VL for electron transfer (half of the energy splitting of the LUMO and LUMO+1), which is could be affected by the bridges linkers. The DFT calculations also demonstrates the effect of solvents on the latter two-electron transfer of Bis-CoQ0s is more significant than the former two electrons transfer as the observed electrochemical behaviors of three Bis-CoQ0s. In addition, the electrochemistry and theoretical calculations reveal the intramolecular electronic communications vary in the four-electron redox processes of three Bis-CoQ0s.
PMCID: PMC4440530  PMID: 25996306
16.  Anti-Restenotic Roles of Dihydroaustrasulfone Alcohol Involved in Inhibiting PDGF-BB-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells 
Marine Drugs  2015;13(5):3046-3060.
Dihydroaustrasulfone alcohol (DA), an active compound firstly isolated from marine corals, has been reported to reveal anti-cancer and anti-inflammation activities. These reported activities of DA raised a possible application in anti-restenosis. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) and the stimulation of platelet-derived growth factor (PDGF)-BB play major pathological processes involved in the development of restenosis. Experimental results showed that DA markedly reduced balloon injury-induced neointima formation in the rat carotid artery model and significantly inhibited PDGF-BB-stimulated proliferation and migration of VSMCs. Our data further demonstrated that translational and active levels of several critical signaling cascades involved in VSMC proliferation, such as extracellular signal-regulated kinase/mitogen-activated protein kinases (ERK/MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT, and signal transducer and activator of transcription (STAT), were obviously inhibited. In addition, DA also decreased the activation and expression levels of gelatinases (matrix metalloproteinase (MMP)-2 and MMP-9) involved in cell migration. In conclusion, our findings indicate that DA can reduce balloon injury-neointimal hyperplasia, the effect of which may be modulated through suppression of VSMC proliferation and migration. These results suggest that DA has potential application as an anti-restenotic agent for the prevention of restenosis.
PMCID: PMC4446617  PMID: 25988521
dihydroaustrasulfone alcohol; anti-restenosis; neointimal hyperplasia; marine origin
17.  Dysregulation of the miR-34a-SIRT1 axis inhibits breast cancer stemness 
Oncotarget  2015;6(12):10432-10444.
Enforced expression of miR-34a eliminates cancer stem cells in some malignant tumors. Sirtuin-1 (SIRT1) is a direct target of miR-34a. Here we found low levels of miR-34a and high levels of SIRT1 in CD44+/CD24− breast cancer stem cells (BCSCs). MiR-34a overexpression and knockdown of SIRT1 decreased proportion of BSCSs and mammosphere formation. Expression of CSC markers, ALDH1, BMI1 and Nanog was decreased. In nude mice xenografts, stable expression of miR-34a and silencing of SIRT1 reduced tumor burden. Taken together, our results demonstrated that miR-34a inhibits proliferative potential of BCSCs in vitro and in vivo, at least partially by downregulating SIRT1. The miR-34a-SIRT1 axis may play role in self-renewal of BCSCs.
PMCID: PMC4496365  PMID: 25826085
miR-34α; SIRT1; CD44+/CD24−BCSCs; stemness
18.  A Novel 96well-formatted Micro-gap Plate Enabling Drug Response Profiling on Primary Tumour Samples 
Scientific Reports  2015;5:9656.
Drug-based treatments are the most widely used interventions for cancer management. Personalized drug response profiling remains inherently challenging with low cell count harvested from tumour sample. We present a 96well-formatted microfluidic plate with built-in micro-gap that preserves up to 99.2% of cells during multiple assay/wash operation and only 9,000 cells needed for a single reagent test (i.e. 1,000 cells per test spot x 3 selected concentration x triplication), enabling drug screening and compatibility with conventional automated workstations. Results with MCF7 and MDA-MB-231 cell lines showed that no statistical significance was found in dose-response between the device and conventional 96-well plate control. Primary tumour samples from breast cancer patients tested in the device also showed good IC50 prediction. With drug screening of primary cancer cells must consider a wide range of scenarios, e.g. suspended/attached cell types and rare/abundant cell availability, the device enables high throughput screening even for suspended cells with low cell count since the signature microfluidic cell-trapping feature ensures cell preservation in a multiple solution exchange protocol.
PMCID: PMC4394194  PMID: 25866290
19.  Fasciculations masquerading as minipolymyoclonus in bulbospinal muscular atrophy 
Minipolymyoclonus has been described in both anterior horn cell disorders and central nervous system degenerative conditions. While its etiology remains unclear and speculative, a central generator has been previously proposed. We describe a case of bulbospinal muscular atrophy (Kennedy's disease), where minipolymyoclonus-like movements corresponded to fasciculations in neurophysiological studies. Our novel finding suggests that the etiologies of minipolymyoclonus in central and peripheral nervous system disorders are distinct, despite outward clinical similarity. The term “minipolyfasciculations” may be more reflective of the underlying process causing minipolymyoclonus-like movements in lower motor neuron disorders.
PMCID: PMC4445210  PMID: 26019432
Bulbospinal muscular atrophy; EMG-EEG back averaging; Kennedy's disease; minipolymyoclonus; polyminimyoclonus
20.  Indole diketopiperazines from endophytic Chaetomium sp 88194 induce breast cancer cell apoptotic death 
Scientific Reports  2015;5:9294.
Diketopiperazines are important secondary metabolites of the fungi with variety bioactivities. Several species belonging to genus Chaetomium produce compounds of this class, such as chetomin. To identify new antitumor agents, secondary metabolites of fungus Chaetomium sp 88194 were investigated and three new indole diketopiperazines, Chaetocochins G (1), Oidioperazines E (2) and Chetoseminudin E (3), along with two known compounds Chetoseminudins C (4) and N-acetyl-β-oxotryptamine (5), were obtained. Chaetocochins G and Chetoseminudin E were recrystallized in CHCl3 containing a small amount of MeOH, and their structures with absolute configuration were established by spectroscopic data interpretation and single-crystal X-ray diffraction analysis. The absolute configuration of Oidioperazines E was defined by comparing of experimental and calculated electronic circular dichroism spectra. These isolates were also evaluated the anticancer activity, and Chaetocochins G displayed more potent cytotoxicity in MCF-7 cells than the common chemotherapeutic agent (5-fluorouracil) associated with G2/M cell cycle arrest. More importantly, Chaetocochins G induced cell apoptotic death via caspase-3 induction and proteolytic cleavage of poly (ADP-ribose) polymerase, concomitantly with increased Bax and decreased Bcl-2 expression. Our findings suggested that indole diketopiperazines from endophytic Chaetomium sp 88194 may be potential resource for developing anti-cancer reagents.
PMCID: PMC4365412  PMID: 25787158
21.  Establishment of Hairy Root Cultures by Agrobacterium Rhizogenes Mediated Transformation of Isatis Tinctoria L. for the Efficient Production of Flavonoids and Evaluation of Antioxidant Activities 
PLoS ONE  2015;10(3):e0119022.
In this work, Isatis tinctoria hairy root cultures (ITHRCs) were established as an alternative source for flavonoids (FL) production. I. tinctoria hairy root line V was found to be the most efficient line and was further confirmed by the PCR amplification of rolB, rolC and aux1 genes. Culture parameters of ITHRCs were optimized by Box-Behnken design (BBD), and eight bioactive FL constituents (rutin, neohesperidin, buddleoside, liquiritigenin, quercetin, isorhamnetin, kaempferol and isoliquiritigenin) were quali-quantitatively determined by LC-MS/MS. Under optimal conditions, the total FL accumulation of ITHRCs (24 day-old) achieved was 438.10 μg/g dry weight (DW), which exhibited significant superiority as against that of 2 year-old field grown roots (341.73 μg/g DW). Additionally, in vitro antioxidant assays demonstrated that ITHRCs extracts exhibited better antioxidant activities with lower IC50 values (0.41 and 0.39, mg/mL) as compared to those of field grown roots (0.56 and 0.48, mg/mL). To the best of our knowledge, this is the first report describing FL production and antioxidant activities from ITHRCs.
PMCID: PMC4364778  PMID: 25785699
22.  Rsite: a computational method to identify the functional sites of noncoding RNAs 
Scientific Reports  2015;5:9179.
There is an increasing demand for identifying the functional sites of noncoding RNAs (ncRNAs). Here we introduce a tertiary-structure based computational approach, Rsite, which first calculates the Euclidean distances between each nucleotide and all the other nucleotides in a RNA molecule and then determines the nucleotides that are the extreme points in the distance curve as the functional sites. By analyzing two ncRNAs, tRNA (Lys) and Diels-Alder ribozyme, we demonstrated the efficiency of Rsite. As a result, Rsite recognized all of the known functional sites of the two ncRNAs, suggesting that Rsite could be a potentially useful tool for discovering the functional sites of ncRNAs. The source codes and data sets of Rsite are available at
PMCID: PMC4361870  PMID: 25776805
23.  Overexpression of N-myc downstream-regulated gene 1 inhibits human glioma proliferation and invasion via phosphoinositide 3-kinase/AKT pathways 
Molecular Medicine Reports  2015;12(1):1050-1058.
N-myc downstream-regulated gene 1 (NDRG1) was previously shown to exhibit low expression in glioma tissue as compared with that in normal brain tissue; however, the role of NDRG1 in human glioma cells has remained to be elucidated. The present study used the U87 MG and SHG-44 human glioma cell lines as well as the normal human astrocyte cell line 1800, which are known to have differential NDRG1 expression. Small interfering (si)RNA targeting NDRG1, and NDRG1 overexpression vectors were transfected into the SHG-44 and U87 MG glioma cells, respectively. Cell proliferation, invasion, apoptosis and cell cycle arrest were subsequently examined by MTT assay, transwell chamber assay, flow cytometry and western blot analysis, respectively. Furthermore, a subcutaneous tumor mouse model was used to investigate the effects of NDRG1 on the growth of glioma cells in vivo. Overexpression of NDRG1 was shown to inhibit cell proliferation and invasion, and induce apoptosis in the U87 MG glioma cells, whereas NDRG1 downregulation increased proliferation, suppressed apoptosis and promoted invasion of the SHG-44 glioma cells. In addition, in the subcutaneous tumor mouse model, overexpression of NDRG1 in U-87 MG cells suppressed tumorigenicity in vivo. The findings of the present study indicated that NDRG1 is required for the inhibition of gliomagenesis; therefore, targeting NDRG1 and its downstream targets may represent novel therapies for the treatment of glioma.
PMCID: PMC4438970  PMID: 25777142
glioma; N-myc downstream-regulated gene 1; apoptosis; metastasis; AKT
24.  Median effective effect-site concentration of sufentanil for wake-up test in adolescents undergoing surgery: a randomized trial 
BMC Anesthesiology  2015;15:27.
To determine the median effective concentration of sufentanil as an analgesic during wake-up tests after sevoflurane anesthesia during surgery for adolescent idiopathic scoliosis (AIS).
This is a randomised controlled trial. Sixty patients aged 13–18 years scheduled for AIS surgery were randomized into six groups of 10 patients each to receive target effect-site concentrations of sufentanil of 0.19, 0.1809, 0.1723, 0.1641, 0.1563, and 0.1489 ng/ml (target concentration ratio, 1.05). Wake-up time was recorded. Median EC50 and 95% confidence interval (CI) for sufentanil target-controlled infusion (TCI) were determined using Kärber’s method. The primary outcome was median EC50 for sufentanil TCI as an analgesic during the wake-up test after sevoflurane anesthesia during surgery for AIS.
The EC50 and 95% CI of sufentanil TCI were 0.1682 ng/ml and 0.1641 ~ 0.1724 ng/ml, respectively.
The EC50 of sufentanil TCI was 0.1682 ng/ml (95% CI: 0.1641 ~ 0.1724 ng/ml) during sevoflurane anesthesia in adolescents undergoing surgery for idiopathic scoliosis with intraoperative wake-up tests.
Trial registration identifier: ChiCTR-TTRCC-12002696.
PMCID: PMC4359582  PMID: 25774090
Sufentanil; Idiopathic scoliosis; Intraoperative wake-up test
25.  The Association of Chinese Hospital Work Environment with Nurse Burnout, Job Satisfaction, and Intention to Leave 
Nursing outlook  2013;62(2):128-137.
The purpose of this study was to describe nurse burnout, job satisfaction, and intention to leave, and to explore the relationship of work environment to nurse outcomes in a sample of 9,698 nurses from 181 hospitals in China. Nurses reported moderate levels of emotional exhaustion and depersonalization, and high levels of reduced personal accomplishment. Nearly one fifth of the nurses reported high levels of burnout on all three dimensions. Forty-five percent of the nurses were dissatisfied with their current job; these nurses were most dissatisfied with their salary. Five percent of nurses reported intention to leave. Nurses reporting mixed and good work environments were less likely to report high burnout, job dissatisfaction, and intention to leave compared with those in poor work environments. The results suggest that high burnout and low job satisfaction are prominent problems for Chinese nurses, and improving work environment might be an effective strategy for better nurse outcomes in Chinese hospitals.
PMCID: PMC3959248  PMID: 24345617
burnout; job satisfaction; retention; turnover; nurse; work environment; nursing in China

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