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1.  The correlation between CT and duplex evaluation of autogenous vein bypass grafts and their relationship to failure 
Journal of vascular surgery  2015;62(6):1546-1554.e1.
Objective
Duplex ultrasound(DUS) for vein bypass graft(VBG) surveillance is confounded by technical and physiologic factors that that reduce the sensitivity for detecting impending graft failure. In contrast, three-dimensional computed tomographic angiography(CTA) offers high fidelity anatomic characterization of VBGs but its utility in detecting at risk grafts is unknown. The current study sought to analyze the correlation between DUS and CTA for detection of vein graft stenosis and evaluate the relationship of the observed abnormalities to VBG failure.
Methods
Consecutive lower extremity VBG patients underwent surveillance with concurrent DUS and CTA at 1-week, 1-month, 6-month and 12-months postoperatively. A standardized algorithm was used for CT reconstruction and extraction of the lumen geometries at 1 mm intervals. At each time interval, CT derived cross-sectional areas were co-registered and correlated to DUS peak systolic velocities(PSV) within six pre-designated anatomic zones and then analyzed for outcome association. Vein graft failure was defined as pathological change within a given anatomic zone resulting in thrombosis, amputation or re-intervention within the six month period following the observed time point.
Results
Fifty-four patients were recruited and 10(18%) experienced failure within 18 months of implantation. The expected inverse relationship between CSA and PSV was only weakly correlated(Spearman rank coefficient= −0.19). Moderate elevations in PSV ratio(PSVr 2–3.5) were frequently transient, with 14 of 18 grafts(78%) demonstrating ratio reduction on subsequent imaging. A PSVr ≥ 3.5 was associated with a 67% failure rate. CT stenosis <50% was highly correlated with success(zero failures); however, high-grade(>80%) CT stenosis was more likely to succeed than fail(25%). Eighteen patients had significant discordance between CT and DUS. While 14 of these patients had CT stenosis > 70% with a PSVr < 3.5, only 2 subsequently failed. Conversely, 3 of 4 subjects with CT stenosis < 70% but PSVr > 3.5 experienced graft failure. Focused analysis of these cases using computational fluid dynamic modeling demonstrated that vein side branches, local tortuosity, regional diameter variations, and venovenostomies to be the drivers of these discrepancies.
Conclusion
This analysis demonstrated that a PSVr ≥ 3.5 is strongly correlated with VBG failure while the natural history of moderately elevated PSVr(2–3.5) is largely clinically benign. Although minimum stenosis on CT scan was highly predictive of success, high grade CT stenosis was infrequently associated with failure. The interaction of anatomic features with the local flow dynamics were identified as the primary confounder for a direct correlation between CT and DUS.
doi:10.1016/j.jvs.2015.06.220
PMCID: PMC4659752  PMID: 26365660
2.  Sex differences in intrinsic brain functional connectivity underlying human shyness 
Shyness is a fundamental trait associated with social-emotional maladaptive behaviors, including many forms of psychopathology. Neuroimaging studies have demonstrated that hyper-responsivity to social and emotional stimuli occurs in the frontal cortex and limbic system in shy individuals, but the relationship between shyness and brain-wide functional connectivity remains incompletely understood. Using resting-state functional magnetic resonance imaging, we addressed this issue by exploring the relationship between regional functional connectivity strength (rFCS) and scores of shyness in a cohort of 61 healthy young adults and controlling for the effects of social and trait anxiety scores. We observed that the rFCS of the insula positively correlated with shyness scores regardless of sex. Furthermore, we found that there were significant sex-by-shyness interactions in the dorsal anterior cingulate cortex and insula (two core nodes of the salience network) as well as the subgenual anterior cingulate cortex: the rFCS values of these regions positively correlated with shyness scores in females but negatively correlated in males. Taken together, we provide evidence for intrinsic functional connectivity differences in individuals with different degrees of shyness and that these differences are sex-dependent. These findings might have important implications on the understanding of biological mechanisms underlying emotional and cognitive processing associated with shyness.
doi:10.1093/scan/nsv052
PMCID: PMC4666102  PMID: 25994971
shyness; sex difference; resting-state fMRI; insula; salience network
3.  Insights into long noncoding RNAs of naked mole rat (Heterocephalus glaber) and their potential association with cancer resistance 
Background
Long noncoding RNAs (lncRNAs) are a class of ubiquitous noncoding RNAs and have been found to act as tumor suppressors or oncogenes, which dramatically altered our understanding of cancer. Naked mole rat (NMR, Heterocephalus glaber) is an exceptionally long-lived and cancer-resistant rodent; however, whether lncRNAs play roles in cancer resistance in this seductive species remains unknown.
Results
In this study, we developed a pipeline and identified a total of 4422 lncRNAs across the NMR genome based on 12 published transcriptomes. Systematic analysis revealed that NMR lncRNAs share many common characteristics with other vertebrate species, such as tissue specificity and low expression. BLASTN against with 1057 human cancer-related lncRNAs showed that only 5 NMR lncRNAs displayed homology, demonstrating the low sequence conservation between NMR lncRNAs and human cancer-related lncRNAs. Further correlation analysis of lncRNAs and protein-coding genes indicated that a total of 1295 lncRNAs were intensively coexpressed (r ≥ 0.9 or r ≤ −0.9, cP value ≤ 0.01) with potential tumor-suppressor genes in NMR, and 194 lncRNAs exhibited strong correlation (r ≥ 0.8 or r ≤ −0.8, cP value ≤ 0.01) with four high-molecular-mass hyaluronan related genes that were previously identified to play key roles in cancer resistance of NMR.
Conclusion
In this study, we provide the first comprehensive genome-wide analysis of NMR lncRNAs and their possible associations with cancer resistance. Our results suggest that lncRNAs may have important effects on anticancer mechanism in NMR.
Electronic supplementary material
The online version of this article (doi:10.1186/s13072-016-0101-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s13072-016-0101-5
PMCID: PMC5103457  PMID: 27833660
Naked mole rat; Long noncoding RNA; Expression profiles; Coexpression; Cancer resistance
4.  White-Matter Structural Connectivity Underlying Human Laughter-Related Traits Processing 
Frontiers in Psychology  2016;7:1637.
Most research into the neural mechanisms of humor has not explicitly focused on the association between emotion and humor on the brain white matter networks mediating this connection. However, this connection is especially salient in gelotophobia (the fear of being laughed at), which is regarded as the presentation of humorlessness, and two related traits, gelotophilia (the enjoyment of being laughed at) and katagelasticism (the enjoyment of laughing at others). Here, we explored whether the topological properties of white matter networks can account for the individual differences in the laughter-related traits of 31 healthy adults. We observed a significant negative correlation between gelotophobia scores and the clustering coefficient, local efficiency and global efficiency, but a positive association between gelotophobia scores and path length in the brain's white matter network. Moreover, the current study revealed that with increasing individual fear of being laughed at, the linking efficiencies in superior frontal gyrus, anterior cingulate cortex, parahippocampal gyrus, and middle temporal gyrus decreased. However, there were no significant correlations between either gelotophilia or katagelasticism scores or the topological properties of the brain white matter network. These findings suggest that the fear of being laughed at is directly related to the level of local and global information processing of the brain network, which might provide new insights into the neural mechanisms of the humor information processing.
doi:10.3389/fpsyg.2016.01637
PMCID: PMC5082228  PMID: 27833572
gelotophobia; diffusion tensor imaging; graph theory; brain network; connectome
5.  Risk burdens of modifiable risk factors incorporating lipoprotein (a) and low serum albumin concentrations for first incident acute myocardial infarction 
Scientific Reports  2016;6:35463.
Risk burdens of modifiable risk factors incorporating lipoprotein (a) (Lp(a)) and low serum albumin (LSA) concentrations for first incident acute myocardial infarction (AMI) haven’t been studied previously. Cross-sectional study of 1552 cases and 6125 controls was performed for identifying the association of risk factors with first incident AMI and their corresponding population attributable risks (PARs). Modifiable risk factors incorporating LSA and Lp(a) accounted for up to 92% of PAR for first incident AMI. Effects of these risk factors were different in different sexes across different age categories. Overall, smoking and LSA were the 2 strongest risk factors, together accounting for 64% of PAR for first incident AMI. After multivariable adjustment, Lp(a) and LSA accounted for 19% and 41%, respectively, and together for more than a half (54%) of PAR for first incident AMI. Modifiable risk factors incorporating LSA and Lp(a) have accounted for an overwhelmingly large proportion of the risk of first incident AMI, indicating most first incident AMI is preventable. The knowledge of risk burdens for first incident AMI incorporating Lp (a) and LSA may be beneficial for further reducing first incident AMI from a new angle.
doi:10.1038/srep35463
PMCID: PMC5066202  PMID: 27748452
6.  Systematical Evaluation of Mechanically Strong 3D Printed Diluted magnesium Doping Wollastonite Scaffolds on Osteogenic Capacity in Rabbit Calvarial Defects 
Scientific Reports  2016;6:34029.
Wollastonite (CaSiO3; CSi) ceramic is a promising bioactive material for bone defect repair due to slightly fast degradation of its porous constructs in vivo. In our previous strategy some key features of CSi ceramic have been significantly improved by dilute magnesium doping for regulating mechanical properties and biodegradation. Here we demonstrate that 6 ~ 14% of Ca substituted by Mg in CSi (CSi-Mgx, x = 6, 10, 14) can enhance the mechanical strength (>40 MPa) but not compromise biological performances of the 3D printed porous scaffolds with open porosity of 60‒63%. The in vitro cell culture tests in vitro indicated that the dilute Mg doping into CSi was beneficial for ALP activity and high expression of osteogenic marker genes of MC3T3-E1 cells in the scaffolds. A good bone tissue regeneration response and elastoplastic response in mechanical strength in vivo were determined after implantation in rabbit calvarial defects for 6‒12 weeks. Particularly, the CSi-Mg10 and CSi-Mg14 scaffolds could enhance new bone regeneration with a significant increase of newly formed bone tissue (18 ~ 22%) compared to the pure CSi (~14%) at 12 weeks post-implantation. It is reasonable to consider that, therefore, such CSi-Mgx scaffolds possessing excellent strength and reasonable degradability are promising for bone reconstruction in thin-wall bone defects.
doi:10.1038/srep34029
PMCID: PMC5034319  PMID: 27658481
7.  Protective Effect of Cyanidin-3-O-Glucoside against Ultraviolet B Radiation-Induced Cell Damage in Human HaCaT Keratinocytes 
Ultraviolet radiation is the major environmental harmful factor that has emotional impact on human skin. The aim of the present study was to determine the mechanism of protection of cyanidin-3-O-glucoside against ultraviolet B (UVB)-induced damage to human HaCaT keratinocytes. Our results show that cyanidin-3-O-glucoside decreased the levels of intracellular reactive oxygen species generated by UVB treatment. Cyanidin-3-O-glucoside also decreased the UVB-augmented levels of the DNA damage indicators phospho-p53 and phospho-ATM/ATR. In addition, cyanidin-3-O-glucoside protected keratinocytes from UVB-induced injury by overturning the disruption of mitochondrial membrane potential and reversing apoptosis. The expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) was attenuated in UVB-exposed cells but restored in UVB/cyanidin-3-O-glucoside-treated cells. Furthermore, expression of the proapoptotic proteins Bcl-2-associated X (Bax) and the key apoptosis executer cleaved caspase-3 were increased in UVB-irradiated cells and decreased in UVB/cyanidin-3-O-glucoside-treated cells. For these reasons, the results demonstrate that cyanidin-3-O-glucoside protects human keratinocytes against UVB-induced oxidative stress and apoptosis. Our study provides a theoretical basis for the use of cyanidin-3-O-glucoside in the fight against light damage.
doi:10.3389/fphar.2016.00301
PMCID: PMC5013811  PMID: 27656146
Cyanidin-3-O-glucoside; HaCaT keratinocytes; ultraviolet B radiation; reactive oxygen species; apoptosis
8.  Aberrant white matter networks mediate cognitive impairment in patients with silent lacunar infarcts in basal ganglia territory 
Silent lacunar infarcts, which are present in over 20% of healthy elderly individuals, are associated with subtle deficits in cognitive functions. However, it remains largely unclear how these silent brain infarcts lead to cognitive deficits and even dementia. Here, we used diffusion tensor imaging tractography and graph theory to examine the topological organization of white matter networks in 27 patients with silent lacunar infarcts in the basal ganglia territory and 30 healthy controls. A whole-brain white matter network was constructed for each subject, where the graph nodes represented brain regions and the edges represented interregional white matter tracts. Compared with the controls, the patients exhibited a significant reduction in local efficiency and global efficiency. In addition, a total of eighteen brain regions showed significantly reduced nodal efficiency in patients. Intriguingly, nodal efficiency–behavior associations were significantly different between the two groups. The present findings provide new aspects into our understanding of silent infarcts that even small lesions in subcortical brain regions may affect large-scale cortical white matter network, as such may be the link between subcortical silent infarcts and the associated cognitive impairments. Our findings highlight the need for network-level neuroimaging assessment and more medical care for individuals with silent subcortical infarcts.
doi:10.1038/jcbfm.2015.67
PMCID: PMC4640338  PMID: 25873426
connectome; diffusion tensor imaging; graph theory; silent lacunar infarcts; white matter network
9.  Cre-inducible human CD59 mediates rapid cell ablation after intermedilysin administration 
The Journal of Clinical Investigation  null;126(6):2321-2333.
Cell ablation is a powerful tool for studying cell lineage and/or function; however, current cell-ablation models have limitations. Intermedilysin (ILY), a cytolytic pore-forming toxin that is secreted by Streptococcus intermedius, lyses human cells exclusively by binding to the human complement regulator CD59 (hCD59), but does not react with CD59 from nonprimates. Here, we took advantage of this feature of ILY and developed a model of conditional and targeted cell ablation by generating floxed STOP-CD59 knockin mice (ihCD59), in which expression of human CD59 only occurs after Cre-mediated recombination. The administration of ILY to ihCD59+ mice crossed with various Cre-driver lines resulted in the rapid and specific ablation of immune, epithelial, or neural cells without off-target effects. ILY had a large pharmacological window, which allowed us to perform dose-dependent studies. Finally, the ILY/ihCD59-mediated cell-ablation method was tested in several disease models to study immune cell functionalities, hepatocyte and/or biliary epithelial damage and regeneration, and neural cell damage. Together, the results of this study demonstrate the utility of the ihCD59 mouse model for studying the effects of cell ablation in specific organ systems in a variety of developmental and disease states.
doi:10.1172/JCI84921
PMCID: PMC4887171  PMID: 27159394
10.  Endoplasmic reticulum stress-induced apoptosis in the penumbra aggravates secondary damage in rats with traumatic brain injury 
Neural Regeneration Research  2016;11(8):1260-1266.
Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated, mitochondrial, and endoplasmic reticulum stress pathways. Few studies have examined the endoplasmic reticulum-mediated apoptosis pathway in the penumbra after traumatic brain injury, and it remains unclear whether endoplasmic reticulum stress can activate the caspase-12-dependent apoptotic pathway in the traumatic penumbra. Here, we established rat models of fluid percussion-induced traumatic brain injury and found that protein expression of caspase-12, caspase-3 and the endoplasmic reticulum stress marker 78 kDa glucose-regulated protein increased in the traumatic penumbra 6 hours after injury and peaked at 24 hours. Furthermore, numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells in the traumatic penumbra also reached peak levels 24 hours after injury. These findings suggest that caspase-12-mediated endoplasmic reticulum-related apoptosis is activated in the traumatic penumbra, and may play an important role in the pathophysiology of secondary brain injury.
doi:10.4103/1673-5374.189190
PMCID: PMC5020824  PMID: 27651773
nerve regeneration; endoplasmic reticulum stress; apoptosis; caspase-12; caspase-3; traumatic penumbra; traumatic brain injury; neural regeneration
11.  Rapid detection of talcum powder in tea using FT-IR spectroscopy coupled with chemometrics 
Scientific Reports  2016;6:30313.
This paper investigated the feasibility of Fourier transform infrared transmission (FT-IR) spectroscopy to detect talcum powder illegally added in tea based on chemometric methods. Firstly, 210 samples of tea powder with 13 dose levels of talcum powder were prepared for FT-IR spectra acquirement. In order to highlight the slight variations in FT-IR spectra, smoothing, normalize and standard normal variate (SNV) were employed to preprocess the raw spectra. Among them, SNV preprocessing had the best performance with high correlation of prediction (RP = 0.948) and low root mean square error of prediction (RMSEP = 0.108) of partial least squares (PLS) model. Then 18 characteristic wavenumbers were selected based on a hybrid of backward interval partial least squares (biPLS) regression, competitive adaptive reweighted sampling (CARS) algorithm and successive projections algorithm (SPA). These characteristic wavenumbers only accounted for 0.64% of the full wavenumbers. Following that, 18 characteristic wavenumbers were used to build linear and nonlinear determination models by PLS regression and extreme learning machine (ELM), respectively. The optimal model with RP = 0.963 and RMSEP = 0.137 was achieved by ELM algorithm. These results demonstrated that FT-IR spectroscopy with chemometrics could be used successfully to detect talcum powder in tea.
doi:10.1038/srep30313
PMCID: PMC4965860  PMID: 27468701
12.  Glucose deprivation induces chemoresistance in colorectal cancer cells by increasing ATF4 expression 
World Journal of Gastroenterology  2016;22(27):6235-6245.
AIM: To investigate the role of activating transcription factor 4 (ATF4) in glucose deprivation (GD) induced colorectal cancer (CRC) drug resistance and the mechanism involved.
METHODS: Chemosensitivity and apoptosis were measured under the GD condition. Inhibition of ATF4 using short hairpin RNA in CRC cells under the GD condition and in ATF4-overexpressing CRC cells was performed to identify the role of ATF4 in the GD induced chemoresistance. Quantitative real-time RT-PCR and Western blot were used to detect the mRNA and protein expression of drug resistance gene 1 (MDR1), respectively.
RESULTS: GD protected CRC cells from drug-induced apoptosis (oxaliplatin and 5-fluorouracil) and induced the expression of ATF4, a key gene of the unfolded protein response. Depletion of ATF4 in CRC cells under the GD condition can induce apoptosis and drug re-sensitization. Similarly, inhibition of ATF4 in the ATF4-overexpressing CRC cells reintroduced therapeutic sensitivity and apoptosis. In addition, increased MDR1 expression was observed in GD-treated CRC cells.
CONCLUSION: These data indicate that GD promotes chemoresistance in CRC cells through up-regulating ATF4 expression.
doi:10.3748/wjg.v22.i27.6235
PMCID: PMC4945982  PMID: 27468213
Glucose deprivation; ATF4; Oxaliplatin; 5-Fluorouracil; Chemoresistance
13.  Research on the printability of hydrogels in 3D bioprinting 
Scientific Reports  2016;6:29977.
As the biocompatible materials, hydrogels have been widely used in three- dimensional (3D) bioprinting/organ printing to load cell for tissue engineering. It is important to precisely control hydrogels deposition during printing the mimic organ structures. However, the printability of hydrogels about printing parameters is seldom addressed. In this paper, we systemically investigated the printability of hydrogels from printing lines (one dimensional, 1D structures) to printing lattices/films (two dimensional, 2D structures) and printing 3D structures with a special attention to the accurate printing. After a series of experiments, we discovered the relationships between the important factors such as air pressure, feedrate, or even printing distance and the printing quality of the expected structures. Dumbbell shape was observed in the lattice structures printing due to the hydrogel diffuses at the intersection. Collapses and fusion of adjacent layer would result in the error accumulation at Z direction which was an important fact that could cause printing failure. Finally, we successfully demonstrated a 3D printing hydrogel scaffold through harmonize with all the parameters. The cell viability after printing was compared with the casting and the results showed that our bioprinting method almost had no extra damage to the cells.
doi:10.1038/srep29977
PMCID: PMC4951698  PMID: 27436509
14.  Tacrolimus combined with low-dose corticosteroids is an effective and safe therapeutic option for refractory IgA nephropathy 
Tacrolimus (TAC) has been shown to improve remission from proteinuria in patients with refractory IgA nephropathy (IgAN); however, the efficacy and safety of TAC in such patients have not been fully explored. Therefore, the present study was conducted to evaluate the tolerance to and efficacy of TAC combined with low-dose corticosteroids in patients with refractory IgAN. This was a single-center retrospective study. A total of 28 patients with refractory IgAN were randomly included and received TAC plus corticosteroid; 26 patients received TAC and prednisone, and 2 patients received TAC and methylprednisolone. In addition, all patients were treated with an angiotensin inhibitor. Total urinary protein excretion, serum albumin, blood glucose, complete remission (CR), partial remission (PR), cholesterol, low-density lipoprotein (LDL), serum creatinine (Scr) and estimated GFR (eGFR) were tested at baseline and at 3, 6 and 12 months after the initiation of treatment in all patients. The primary endpoints were CR and PR. Secondary endpoints included changes of Scr, eGFR, clinical data and adverse events. After 12 months, CR was achieved in 40.1% of patients and PR in 43.4%, yielding a total response rate of 83.5%, and the total urinary protein excretion, serum albumin, cholesterol and LDL results were improved significantly compared with those at baseline. Proteinuria and serum albumin results were significantly improved by month 3 of treatment. Two patients relapsed during months 3–6 of follow-up. At the 12-month follow-up, renal function was improved compared with the baseline level as evidenced by eGFR and Scr, respectively. The blood glucose level was stable. One case of pneumococcal pneumonia developed in a patient treated with TAC plus low-dose methylprednisolone and one case of upper gastrointestinal hemorrhage was found in a patient treated with TAC plus low-dose prednisone; both cases completely recovered after treatment. In conclusion, TAC combined with low-dose corticosteroids may be an effective and safe therapeutic option for the treatment of refractory IgAN. However, given the small number of patients in this study, further prospective randomized controlled trials are required with a larger sample of participants and longer follow-up period.
doi:10.3892/etm.2016.3523
PMCID: PMC4998348  PMID: 27602099
IgA nephropathy; tacrolimus; prednisone; methylprednisolone; renal pathology; adverse events
15.  OVATE Family Protein 8 Positively Mediates Brassinosteroid Signaling through Interacting with the GSK3-like Kinase in Rice 
PLoS Genetics  2016;12(6):e1006118.
OVATE gene was first identified as a key regulator of fruit shape in tomato. OVATE family proteins (OFPs) are characterized as plant-specific transcription factors and conserved in Arabidopsis, tomato, and rice. Roles of OFPs involved in plant development and growth are largely unknown. Brassinosteroids (BRs) are a class of steroid hormones involved in diverse biological functions. OsGKS2 plays a critical role in BR signaling by phosphorylating downstream components such as OsBZR1 and DLT. Here we report in rice that OsOFP8 plays a positive role in BR signaling pathway. BL treatment induced the expression of OsOFP8 and led to enhanced accumulation of OsOFP8 protein. The gain-of-function mutant Osofp8 and OsOFP8 overexpression lines showed enhanced lamina joint inclination, whereas OsOFP8 RNAi transgenic lines showed more upright leaf phenotype, which suggest that OsOFP8 is involved in BR responses. Further analyses indicated that OsGSK2 interacts with and phosphorylates OsOFP8. BRZ treatment resulted in the cytoplasmic distribution of OsOFP8, and bikinin treatment reduced the cytoplasmic accumulation of OsOFP8. Phosphorylation of OsOFP8 by OsGSK2 is needed for its nuclear export. The phospphorylated OsOFP8 shuttles to the cytoplasm and is targeted for proteasomal degradation. These results indicate that OsOFP8 is a substrate of OsGSK2 and the function of OsOFP8 in plant growth and development is at least partly through the BR signaling pathway.
Author Summary
OVATE family proteins (OFPs) are characterized as plant-specific transcription factors and mainly function in affecting fruit shape, but the molecular mechanisms by which they function are largely unknown. Rice genome contains 31 OFPs, the roles of these OsOFPs involved in plant development and growth are not understood. Brassinosteroids (BRs) are a class of steroid hormones involved in diverse biological functions. Here we report in rice that OsOFP8 plays a positive role in BR signaling pathway by interacting with OsGKS2, a negative regulator in BR signaling pathway. Our results shed light on studying the functions of OFPs and provide a chance to explore the new components of BR signaling pathway.
doi:10.1371/journal.pgen.1006118
PMCID: PMC4917237  PMID: 27332964
16.  Hyperspectral Imaging for Determining Pigment Contents in Cucumber Leaves in Response to Angular Leaf Spot Disease 
Scientific Reports  2016;6:27790.
Hyperspectral imaging technique was employed to determine spatial distributions of chlorophyll (Chl), and carotenoid (Car) contents in cucumber leaves in response to angular leaf spot (ALS). Altogether, 196 hyperspectral images of cucumber leaves with five infection severities of ALS were captured by a hyperspectral imaging system in the range of 380–1,030 nm covering 512 wavebands. Mean spectrum were extracted from regions of interest (ROIs) in the hyperspectral images. Partial least square regression (PLSR) models were used to develop quantitative analysis between the spectra and the pigment contents measured by biochemical analyses. In addition, regression coefficients (RCs) in PLSR models were employed to select important wavelengths (IWs) for modelling. It was found that the PLSR models developed by the IWs provided the optimal measurement results with correlation coefficient (R) of prediction of 0.871 and 0.876 for Chl and Car contents, respectively. Finally, Chl and Car distributions in cucumber leaves with the ALS infection were mapped by applying the optimal models pixel-wise to the hyperspectral images. The results proved the feasibility of hyperspectral imaging for visualizing the pigment distributions in cucumber leaves in response to ALS.
doi:10.1038/srep27790
PMCID: PMC4901261  PMID: 27283050
17.  Laser-Induced Breakdown Spectroscopy Coupled with Multivariate Chemometrics for Variety Discrimination of Soil 
Scientific Reports  2016;6:27574.
The aim of this work was to analyze the variety of soil by laser-induced breakdown spectroscopy (LIBS) coupled with chemometrics methods. 6 certified reference materials (CRMs) of soil samples were selected and their LIBS spectra were captured. Characteristic emission lines of main elements were identified based on the LIBS curves and corresponding contents. From the identified emission lines, LIBS spectra in 7 lines with high signal-to-noise ratio (SNR) were chosen for further analysis. Principal component analysis (PCA) was carried out using the LIBS spectra at 7 selected lines and an obvious cluster of 6 soils was observed. Soft independent modeling of class analogy (SIMCA) and least-squares support vector machine (LS-SVM) were introduced to establish discriminant models for classifying the 6 types of soils, and they offered the correct discrimination rates of 90% and 100%, respectively. Receiver operating characteristic (ROC) curve was used to evaluate the performance of models and the results demonstrated that the LS-SVM model was promising. Lastly, 8 types of soils from different places were gathered to conduct the same experiments for verifying the selected 7 emission lines and LS-SVM model. The research revealed that LIBS technology coupled with chemometrics could conduct the variety discrimination of soil.
doi:10.1038/srep27574
PMCID: PMC4899786  PMID: 27279284
18.  Metformin restores crizotinib sensitivity in crizotinib-resistant human lung cancer cells through inhibition of IGF1-R signaling pathway 
Oncotarget  2016;7(23):34442-34452.
Aim
Despite the impressive efficacy of crizotinib for the treatment of ALK-positive non-small cell lung cancer, patients invariably develop therapeutic resistance. Suppression of the IGF-1R signaling pathway may abrogate this acquired mechanism of drug resistance to crizotinib. Metformin, a widely used antidiabetic agent, may reverse crizotinib resistance through inhibition of IGF-1R signaling.
Results
The present study revealed that metformin effectively increased the sensitivity of both crizotinib-sensitive and -resistant non-small cell lung cancer cells to crizotinib, as evidenced by decreased proliferation and invasion and enhanced apoptosis. Metformin reduced IGF-1R signaling activation in crizotinib-resistant cells. Furthermore, the addition of IGF-1 to crizotinib-sensitive H2228 cells induced crizotinib resistance, which was overcome by metformin.
Experimental design
The effects of metformin to reverse crizotinib resistance were examined in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT), invasion assay, ki67 incorporation assay, flow cytometry analysis, Western blot analysis, and colony-forming assay.
Conclusions
Metformin may be used in combination with crizotinib in ALK+ NSCLC patients to overcome crizotinib resistance and prolong survival.
doi:10.18632/oncotarget.9120
PMCID: PMC5085167  PMID: 27144340
metformin; crizotinib; IGF-1R; lung cancer; resistance
19.  Intensive plaque modification with rotational atherectomy and cutting balloon before drug-eluting stent implantation for patients with severely calcified coronary lesions: a pilot clinical study 
Background
This study investigated whether, for patients with severely calcified coronary lesions, use of a cutting balloon (CB) during rotational atherectomy (RA) before placing a drug-eluting stent will improve periprocedural outcomes, compared to RA with a conventional plain balloon.
Methods
In a randomized controlled trial, patients with severely calcified lesions of calcium arc ≥180° were apportioned to receive intensive plaque modification with RA and CB (RA + CB; n = 35) or RA with conventional plain balloon (RA; n = 36). Intravascular ultrasound was applied for quantitative or qualitative analyses of percutaneous coronary intervention outcomes. The primary outcome was acute lumen gain after drug-eluting stent.
Results
The RA + CB and RA groups were similar in baseline mean arcs of superficial calcium, and minimum lumen cross-sectional areas (CSAs). The mean minimum stent CSA after percutaneous coronary intervention (PCI) of the RA + CB group (5.9 ± 1.7 mm2) was significantly larger than that of the RA group (5.0 ± 1.4 mm2; P = 0.021). Patients in the RA + CB group achieved significantly larger acute CSA gain after PCI (4.5 ± 1.5 mm2) relative to the RA group (3.8 ± 1.5 mm2; P = 0.035). The groups were similar in rates of periprocedural complications, but at the 1-year follow-up the RA + CB had a lower rate of revascularization for restenosis of the target vessel and MACE (5.7 %) than did the RA group (22.2 %, P = 0.046).
Conclusion
Aggressive plaque preparation with RA and CB seems to be safe and effective for patients with severely calcified coronary lesions.
Trial registration
Current Controlled Trials ChiCTR-INR-16008274. Retrospectively registered 12 April 2016.
doi:10.1186/s12872-016-0273-8
PMCID: PMC4882826  PMID: 27230875
Coronary calcification; Rotational atherectomy; Cutting balloon; Randomized controlled trial
20.  Development of Human Brain Structural Networks Through Infancy and Childhood 
Cerebral Cortex (New York, NY)  2013;25(5):1389-1404.
During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers.
doi:10.1093/cercor/bht335
PMCID: PMC4397575  PMID: 24335033
brain development; connectome; fractional anisotropy; module; pruning
21.  Development of a Near Ground Remote Sensing System 
Unmanned Aerial Vehicles (UAVs) have shown great potential in agriculture and are increasingly being developed for agricultural use. There are still a lot of experiments that need to be done to improve their performance and explore new uses, but experiments using UAVs are limited by many conditions like weather and location and the time it takes to prepare for a flight. To promote UAV remote sensing, a near ground remote sensing platform was developed. This platform consists of three major parts: (1) mechanical structures like a horizontal rail, vertical cylinder, and three axes gimbal; (2) power supply and control parts; (3) onboard application components. This platform covers five degrees of freedom (DOFs): horizontal, vertical, pitch, roll, yaw. A stm32 ARM single chip was used as the controller of the whole platform and another stm32 MCU was used to stabilize the gimbal. The gimbal stabilizer communicates with the main controller via a CAN bus. A multispectral camera was mounted on the gimbal. Software written in C++ language was developed as the graphical user interface. Operating parameters were set via this software and the working status was displayed in this software. To test how well the system works, a laser distance meter was used to measure the slide rail’s repeat accuracy. A 3-axis vibration analyzer was used to test the system stability. Test results show that the horizontal repeat accuracy was less than 2 mm; vertical repeat accuracy was less than 1 mm; vibration was less than 2 g and remained at an acceptable level. This system has high accuracy and stability and can therefore be used for various near ground remote sensing studies.
doi:10.3390/s16050648
PMCID: PMC4883339  PMID: 27164111
UAV; aerial imaging; simulation platform; slideways
22.  Spectrum and Image Texture Features Analysis for Early Blight Disease Detection on Eggplant Leaves 
This study investigated both spectrum and texture features for detecting early blight disease on eggplant leaves. Hyperspectral images for healthy and diseased samples were acquired covering the wavelengths from 380 to 1023 nm. Four gray images were identified according to the effective wavelengths (408, 535, 624 and 703 nm). Hyperspectral images were then converted into RGB, HSV and HLS images. Finally, eight texture features (mean, variance, homogeneity, contrast, dissimilarity, entropy, second moment and correlation) based on gray level co-occurrence matrix (GLCM) were extracted from gray images, RGB, HSV and HLS images, respectively. The dependent variables for healthy and diseased samples were set as 0 and 1. K-Nearest Neighbor (KNN) and AdaBoost classification models were established for detecting healthy and infected samples. All models obtained good results with the classification rates (CRs) over 88.46% in the testing sets. The results demonstrated that spectrum and texture features were effective for early blight disease detection on eggplant leaves.
doi:10.3390/s16050676
PMCID: PMC4883367  PMID: 27187387
texture feature; hyperspectral imaging; RGB/HSV/HLS image; classification; early blight disease; eggplant
23.  The Role of miR-34a in Tritiated Water Toxicity in Human Umbilical Vein Endothelial Cells 
Dose-Response  2016;14(2):1559325816638585.
In this work, we investigated the toxic effects of tritiated water (HTO) on the cardiovascular system. We examined the role of microRNA-34a (miR-34a) in DNA damage and repair in human umbilical vein endothelial cells (HUVECs) exposed to HTO. Cell proliferation capacity was evaluated by cell counting, and miR-34a expression was detected using quantitative PCR (QT-PCR). The Comet assay and γ-H2AX immunostaining were used to measure DNA double-strand breaks (DSBs). Reverse transcription polymerase chain reaction was used to measure the expression level of c-myc messenger RNA (mRNA). The cells exposed to HTO showed significantly lower proliferation than the control cells over 3 days. The DNA damage in the HTO group was more severe than that in the control group, at each time point examined. The expression of miR-34a mimics caused increased DNA DSBs whereas that of the miR-34a inhibitor caused decreased DNA DSBs. The proliferation viability was the opposite for the miR-34a mimics and inhibitor groups. The expression levels of c-myc mRNA in cells transfected with miR-34a mimics were lower than that in cells transfected with the miR-34a-5p inhibitor, at 0.5 hours and 2 hours after transfection. In summary, miR-34a mediates HTO toxicity in HUVECs by downregulating the expression of c-myc.
doi:10.1177/1559325816638585
PMCID: PMC4822198  PMID: 27099602
MiR-34a; tritiated water; DNA damage; c-myc
24.  Intrinsic Functional Connectivity Patterns Predict Consciousness Level and Recovery Outcome in Acquired Brain Injury 
The Journal of Neuroscience  2015;35(37):12932-12946.
For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI.
SIGNIFICANCE STATEMENT Varying degrees of consciousness loss and recovery are commonly observed in acquired brain injury patients, yet the underlying neurobiological mechanisms remain elusive. Using a large sample of patients with varying degrees of consciousness loss, we demonstrate that intrinsic functional connectivity strength in many brain regions, especially in the posterior cingulate cortex and precuneus, significantly correlated with consciousness level and recovery outcome. We further demonstrate that the functional connectivity pattern of these regions can predict patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%. Our study thus provides potentially important biomarkers of acquired brain injury in clinical diagnosis, prediction of recovery outcome, and decision making for treatment strategies for patients with severe loss of consciousness.
doi:10.1523/JNEUROSCI.0415-15.2015
PMCID: PMC4571611  PMID: 26377477
acquired brain injury; hub; posterior cingulate cortex/precuneus; prediction; recovery outcome; resting state fMRI
25.  Pontine infarction: Diffusion-Tensor Imaging of Motor Pathways—A Longitudinal Study1 
Radiology  2014;274(3):841-850.
Purpose
To investigate the dynamic evolution of diffusion indexes in the corticospinal tract (CST) distal to a pontine infarct by using diffusion-tensor imaging, to determine the relationship of these indexes with clinical prognosis, and to explore the structural changes in the motor pathway during recovery.
Materials and Methods
This study was approved by the institutional ethics committee, and written informed consent was obtained from each participant. Seventeen patients with pontine infarct underwent five diffusion-tensor imaging examinations during a period of 6 months (within 7 days of onset, 14, 30, 90, and 180 after onset). Fractional anisotropic values were measured in the medulla, cerebral peduncle, internal capsule, and centrum semiovale. Fractional anisotropic values of the CST in the ipsilateral side of the infarct were compared with those in the contralateral sides and those in control subjects by using the Student t test and one-way analysis of variance, and their relationships with clinical scores were analyzed by using Pearson correlation analysis. Reconstructions of the CST were performed. Structural changes of the damaged CST were followed up.
Results
Fractional anisotropic ratios in the CST above the pons decreased significantly compared with those in the contralateral side and those in control subjects within 7 days, on day 14, and on day 30 after onset (P < .001). Fractional anisotropic ratios above the pons on day 14 correlated positively with Fugl-Meyer scores on day 90 (r = 0.771, P < .001) and day 180 (r = 0.730, P = .001). Follow-up diffusion-tensor tractographic images showed regeneration and reorganization of the motor pathways.
Conclusion
Secondary degeneration of the CST can be detected at diffusion-tensor imaging in the early stages after pontine infarction, which could help predict the motor outcomes. Diffusion-tensor tractography can allow detection of regeneration and reorganization of the motor pathways during recovery.
doi:10.1148/radiol.14140373
PMCID: PMC4556232  PMID: 25356962

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