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1.  Clec11a/osteolectin is an osteogenic growth factor that promotes the maintenance of the adult skeleton 
eLife  null;5:e18782.
Bone marrow stromal cells maintain the adult skeleton by forming osteoblasts throughout life that regenerate bone and repair fractures. We discovered that subsets of these stromal cells, osteoblasts, osteocytes, and hypertrophic chondrocytes secrete a C-type lectin domain protein, Clec11a, which promotes osteogenesis. Clec11a-deficient mice appeared developmentally normal and had normal hematopoiesis but reduced limb and vertebral bone. Clec11a-deficient mice exhibited accelerated bone loss during aging, reduced bone strength, and delayed fracture healing. Bone marrow stromal cells from Clec11a-deficient mice showed impaired osteogenic differentiation, but normal adipogenic and chondrogenic differentiation. Recombinant Clec11a promoted osteogenesis by stromal cells in culture and increased bone mass in osteoporotic mice in vivo. Recombinant human Clec11a promoted osteogenesis by human bone marrow stromal cells in culture and in vivo. Clec11a thus maintains the adult skeleton by promoting the differentiation of mesenchymal progenitors into mature osteoblasts. In light of this, we propose to call this factor Osteolectin.
PMCID: PMC5158134  PMID: 27976999
osteogenesis; skeletal stem cells; osteoporosis; Mouse
2.  Hot electron induced non-saturation current behavior at high electric field in InAlN/GaN heterostructures with ultrathin barrier 
Scientific Reports  2016;6:37415.
The high-field transport characteristics of nearly lattice-matched InAlN/GaN heterostructures with different barrier thickness were investigated. It is found that the current in the InAlN/GaN heterostructures with ultrathin barrier shows unsaturated behaviors (or secondary rising) at high voltage, which is different from that of AlGaN/GaN heterostructures. This phenomenon is more obvious if the barrier thickness is thinner and the channel width is narrower. The experimental results demonstrate that it is the increasing carrier density excited from the more defect states by the hot electrons with larger electron saturation velocity that results in the unsaturated current behaviors in InAlN/GaN heterostructures. Our results pave a way for further optimizing InAlN barrier design and improving the reliability of InAlN/GaN HEMTs.
PMCID: PMC5120260  PMID: 27876766
3.  High-quality AlN epitaxy on nano-patterned sapphire substrates prepared by nano-imprint lithography 
Scientific Reports  2016;6:35934.
We report epitaxial growth of AlN films with atomically flat surface on nano-patterned sapphire substrates (NPSS) prepared by nano-imprint lithography. The crystalline quality can be greatly improved by using the optimized 1-μm-period NPSS. The X-ray diffraction ω-scan full width at half maximum values for (0002) and (102) reflections are 171 and 205 arcsec, respectively. The optimized NPSS contribute to eliminating almost entirely the threading dislocations (TDs) originating from the AlN/sapphire interface via bending the dislocations by image force from the void sidewalls before coalescence. In addition, reducing the misorientations of the adjacent regions during coalescence adopting the low lateral growth rate is also essential for decreasing TDs in the upper AlN epilayer.
PMCID: PMC5095705  PMID: 27812006
4.  miR-590-5p regulates gastric cancer cell growth and chemosensitivity through RECK and the AKT/ERK pathway 
OncoTargets and therapy  2016;9:6009-6019.
The aim of this study was to determine the role of miRNA-590-5p in gastric cancer (GC) progression.
Quantitative real-time polymerase chain reaction was performed to measure endogenous miR-590-5p levels in GC cells and tissues. Overexpression or knockdown of miR-590-5p in GC cells was performed by transfection with mimics or an inhibitor, respectively. MTT, matrigel transwell, and Western blot assays were used to assess the effects of miR-590-5p on cell proliferation, invasion, chemosensitivity of GC cells, and the AKT pathway, respectively. In silico prediction and luciferase reporter activity were used to identify potential targets of miR-590-5p. A xenograft model was also established to evaluate the function of miR-590-5p in vivo.
The expression of miR-590-5p was significantly increased in GC cells and tissues, and upregulated miR-590-5p was associated with increased tumor size, lymph node metastasis, and poor survival. Overexpression of miR-590-5p promoted cell proliferation and invasion and reduced the sensitivity of GC cells to cisplatin and paclitaxel. In contrast, inhibition of miR-590-5p had the opposite effects on GC cells. RECK was identified as a direct target of miR-590-5p. Knockdown of RECK accelerated cell proliferation and motility and decreased the drug sensitivity. Furthermore, reintroduction of RECK inhibited the oncogenic effects of miR-590-5p by suppressing cell proliferation and invasion and increasing drug sensitivity. We found that the AKT/ERK and STAT3 signaling pathways were activated by miR-590-5p overexpression. The chemoresistance of miR-590-5p was also verified by in vivo analysis.
In summary, we suggest that the miR-590-5p/RECK/AKT axis contributes to GC and may serve as a promising therapeutic target for treatment.
PMCID: PMC5055051  PMID: 27757042
miR-590; RECK; invasion; prognosis; AKT pathway; gastric cancer
5.  Non-surgical porto-mesenteric vein thrombosis is associated with worse long-term outcomes in inflammatory bowel diseases 
Gastroenterology Report  2015;4(3):210-215.
Objective: Our aim was to assess the risk factors for non-surgery-related portal and mesenteric vein thrombosis (PMVT) and its impact on the outcomes of inflammatory bowel diseases (IBD).
Methods: All patients with a concurrent diagnosis of IBD and PMVT between January 2004 and October 2013 were identified from the electronic medical record (study group; n = 20). Patients were matched for age, sex, and IBD phenotype with control IBD patients who had no PMVT, with a ratio of 1:3 (control group; n = 60). Risk factors for PMVT and IBD-related outcomes at one year after diagnosis of PMVT were compared between the two groups.
Results: Of the 20 patients in the Study group, 6 (30%) had UC, 14 (70%) had CD and 11 (55%) were male. On multivariable analysis, inpatient status (odds ratio [OR] 6.88; 95% confidence interval [CI] 1.88–25.12) and baseline corticosteroid use (OR 4.39; 95% CI 1.27–15.19) were found to be independent risk factors for the development of PMVT. At one-year follow-up, PMVT patients were more likely to have an adverse outcome of IBD, including subsequent emergency room visit (26.3% vs. 1.7%; P = 0.003), hospitalization for medical management (60.0% vs. 20.0%; P = 0.001) or IBD-related surgery (65.0% vs. 26.7%; P = 0.003) than the non-PMVT controls. In multivariable analysis, PMVT (OR 5.19; 95% CI 1.07–25.28) and inpatient status (OR 8.92; 95% CI 1.33–59.84) were found to be independent risk factors for poor outcome, whereas baseline immunomodulator use (OR 0.07; 95% CI 0.01–0.51) was found to be a protective factor.
Conclusions: IBD patients who were inpatients or receiving corticosteroid therapy had an increased risk of the development of PMVT. The presence of PMVT was associated with poor clinical outcomes in IBD.
PMCID: PMC4976678  PMID: 25922204
inflammatory bowel diseases; portal vein thrombosis; outcomes; risk factors
6.  Dynamic Predictive Scores for Cardiac Surgery–Associated Acute Kidney Injury 
Cardiac surgery–associated acute kidney injury (CSA‐AKI) is a common complication with a poor prognosis. In order to identify modifiable perioperative risk factors for AKI, which existing risk scores are insufficient to predict, a dynamic clinical risk score to allow clinicians to estimate the risk of CSA‐AKI from preoperative to early postoperative periods is needed.
Methods and Results
A total of 7233 cardiac surgery patients in our institution from January 2010 to April 2013 were enrolled prospectively and distributed into 2 cohorts. Among the derivation cohort, logistic regression was used to analyze CSA‐AKI risk factors preoperatively, on the day of ICU admittance and 24 hours after ICU admittance. Sex, age, valve surgery combined with coronary artery bypass grafting, preoperative NYHA score >2, previous cardiac surgery, preoperative kidney (without renal replacement therapy) disease, intraoperative cardiopulmonary bypass application, intraoperative erythrocyte transfusions, and postoperative low cardiac output syndrome were identified to be associated with CSA‐AKI. Among the other 1152 patients who served as a validation cohort, the point scoring of risk factor combinations led to area under receiver operator characteristics curves (AUROC) values for CSA‐AKI prediction of 0.74 (preoperative), 0.75 (on the day of ICU admission), and 0.82 (postoperative), and Hosmer–Lemeshow goodness‐of‐fit tests revealed a good agreement of expected and observed CSA‐AKI rates.
The first dynamic predictive score system, with Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition, was developed and predictive efficiency for CSA‐AKI was validated in cardiac surgery patients.
PMCID: PMC5015294  PMID: 27491837
acute kidney injury; cardiac surgery; risk factor; risk score; Clinical Studies; Risk Factors; Cardiovascular Surgery; Complications
7.  The effects of nanocavity and photonic crystal in InGaN/GaN nanorod LED arrays 
InGaN/GaN nanorod light-emitting diode (LED) arrays were fabricated using nanoimprint and reactive ion etching. The diameters of the nanorods range from 120 to 300 nm. The integral photoluminescence (PL) intensity for 120 nm nanorod LED array is enhanced as 13 times compared to that of the planar one. In angular-resolved PL (ARPL) measurements, there are some strong lobes as resonant regime appeared in the far-field radiation patterns of small size nanorod array, in which the PL spectra are sharp and intense. The PL lifetime for resonant regime is 0.088 ns, which is 40 % lower than that of non-resonant regime for 120 nm nanorod LED array. At last, three dimension finite difference time domain (FDTD) simulation is performed. The effects of guided modes coupling in nanocavity and extraction by photonic crystals are explored.
PMCID: PMC4954795  PMID: 27440081
GaN; Light emitting diode; Nanocavity; Photonic crystal; Guided modes
8.  Venom allergen 5 is Associated With Deltamethrin Resistance in Culex pipiens pallens (Diptera: Culicidae) 
Journal of Medical Entomology  2015;52(4):672-682.
The mosquito, Culex pipiens pallens (L.), is an important vector of encephalitis and filariasis in northern China. The control of these mosquitoes occurs primarily via the use of pyrethroid insecticides, such as deltamethrin. The widespread and improper application of pyrethroid has resulted in the evolution of pyrethroid resistance amongst many mosquito populations, including Cx. pipiens pallens. Previous studies using high-throughput transcriptome sequencing have identified that the venom allergen 5 gene is differentially expressed between deltamethrin-susceptible and deltamethrin-resistant Cx. pipiens pallens. In this study, quantitative real-time polymerase chain reaction analyses revealed that venom allergen 5 was significantly overexpressed in adult females of both deltamethrin-resistant laboratory populations and two field populations. The transcriptional level of venom allergen 5 in the laboratory populations was elevated as the levels of deltamethrin resistance increased. Full-length cDNAs of the venom allergen 5 gene were cloned from Cx. pipiens pallens, and contained an open reading frame of 765 bp, encoding a protein with 254 amino acids. The deduced amino acid sequence shared 100% identity with the ortholog in Culex quinquefasciatus Say. The overexpression of venom allergen 5 decreased the susceptibility of mosquito cells to deltamethrin, while knockdown of this gene by RNAi increased the susceptibility of mosquitoes to deltamethrin. This study provides the first evidence of the association between the venom allergen 5 gene and deltamethrin resistance in mosquitoes.
PMCID: PMC4592351  PMID: 26335474
Culex pipiens pallens; pyrethroid; quantitative real-time PCR; venom allergen 5; RNAi
9.  A Method of Data Aggregation for Wearable Sensor Systems 
Data aggregation has been considered as an effective way to decrease the data to be transferred in sensor networks. Particularly for wearable sensor systems, smaller battery has less energy, which makes energy conservation in data transmission more important. Nevertheless, wearable sensor systems usually have features like frequently dynamic changes of topologies and data over a large range, of which current aggregating methods can’t adapt to the demand. In this paper, we study the system composed of many wearable devices with sensors, such as the network of a tactical unit, and introduce an energy consumption-balanced method of data aggregation, named LDA-RT. In the proposed method, we develop a query algorithm based on the idea of ‘happened-before’ to construct a dynamic and energy-balancing routing tree. We also present a distributed data aggregating and sorting algorithm to execute top-k query and decrease the data that must be transferred among wearable devices. Combining these algorithms, LDA-RT tries to balance the energy consumptions for prolonging the lifetime of wearable sensor systems. Results of evaluation indicate that LDA-RT performs well in constructing routing trees and energy balances. It also outperforms the filter-based top-k monitoring approach in energy consumption, load balance, and the network’s lifetime, especially for highly dynamic data sources.
PMCID: PMC4970008  PMID: 27347953
wearable sensor systems; data query; routing tree; data aggregation
10.  Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy 
Cancer Medicine  2016;5(8):2061-2068.
Dual‐specificity phosphatase‐1 (DUSP1/MKP1), as a member of the threonine‐tyrosine dual‐specificity phosphatase family, was first found in cultured murine cells. The molecular mechanisms of DUSP1‐mediated extracellular signal‐regulated protein kinases (ERKs) dephosphorylation have been subsequently identified by studies using gene knockout mice and gene silencing technology. As a protein phosphatase, DUSP1 also downregulates p38 MAPKs and JNKs signaling through directly dephosphorylating threonine and tyrosine. It has been detected that DUSP1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. In various human cancers, abnormal expression of DUSP1 was observed which was associated with prognosis of tumor patients. Further studies have revealed its role in tumorigenesis and tumor progression. Besides, DUSP1 has been found to play a role in tumor chemotherapy, immunotherapy, and biotherapy. In this review, we will focus on the function and mechanism of DUSP1 in tumor cells and tumor treatment.
PMCID: PMC4884638  PMID: 27227569
Carcinogenesis; DUSP1/MKP1; JNK; tumor therapy
11.  An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell suppressive function and therapeutic efficacy 
Mucosal immunology  2015;9(1):137-145.
Foxp3-expressing regulatory T cells (Tregs) are central regulators of immune homeostasis and tolerance. As it has been suggested that proper Treg function is compromised under inflammatory conditions, seeking for a pathway that enhances or stabilizes Treg function is a subject of considerable interest. We report that IL-27, an IL-12 family cytokine known to have both pro- and anti inflammatory roles in T cells, plays a pivotal role in enhancing Treg function to control T cell-induced colitis, a model for inflammatory bowel disease (IBD) in humans. Unlike wild type (WT) Tregs capable of inhibiting colitogenic T cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T cell responses. Tregs stimulated with IL-27 expressed substantially improved suppressive function in vitro and in vivo. IL-27 stimulation of Tregs induced expression of Lag3, a surface molecule implicated in negatively regulating immune responses. Lag3 expression in Tregs was critical to mediate Treg function in suppressing colitogenic responses. Human Tregs also displayed enhanced suppressive function and Lag3 expression following IL-27 stimulation. Collectively, these results highlight a novel function for the IL-27/Lag3 axis in modulating Treg regulation of inflammatory responses in the intestine.
PMCID: PMC4662649  PMID: 26013006
CD4; colitis; IBD; Interleukin-27; Lymphocyte activation gene 3; Treg
12.  Surface-modified Ba(Zr0.3Ti0.7)O3 nanofibers by polyvinylpyrrolidone filler for poly(vinylidene fluoride) composites with enhanced dielectric constant and energy storage density 
Scientific Reports  2016;6:26198.
Ferroelectric-relaxor behavior of Ba(Zr0.3Ti0.7)O3 nanofibers (BZT NF) with a large aspect ratio were prepared via electrospinning and surface modified by PVP as dielectric fillers. The nanocomposite flexible films based on surface modified BZT NF and polyvinylidene fluoride (PVDF) were fabricated via a solution casting. The results show that the surface-modified BZT NF fillers are highly dispersed and well integrated in the PVDF nanocomposites. The nanocomposites exhibit enhanced dielectric constant and reduced loss tangents at a low volume fraction of surface-modified BZT NF. The polymer nanocomposites maintain a relatively high breakdown strength, which is favorable for enhancing energy storage density in the nanocomposites. The nanocomposite containing of 2.5 vol. % of PVP modified BZT NF exhibits energy density as high as 6.3 J/cm3 at 3800 kV/cm, which is more than doubled that of the pure PVDF of 2.8 J/cm3 at 4000 kV/cm. Such significant enhancement could be attributed to the combined effects of the surface modification and large aspect ratio of the BZT NF. This work may provide a route for using the surface modified ferroelectric-relaxor behavior of ceramic nanofibers to enhance the dielectric energy density in ceramic-polymer nanocomposites.
PMCID: PMC4869030  PMID: 27184360
13.  Electrocardiographic Abnormalities and QTc Interval in Patients Undergoing Hemodialysis 
PLoS ONE  2016;11(5):e0155445.
Sudden cardiac death is one of the primary causes of mortality in chronic hemodialysis (HD) patients. Prolonged QTc interval is associated with increased rate of sudden cardiac death. The aim of this article is to assess the abnormalities found in electrocardiograms (ECGs), and to explore factors that can influence the QTc interval.
A total of 141 conventional HD patients were enrolled in this study. ECG tests were conducted on each patient before a single dialysis session and 15 minutes before the end of dialysis session (at peak stress). Echocardiography tests were conducted before dialysis session began. Blood samples were drawn by phlebotomy immediately before and after the dialysis session.
Before dialysis, 93.62% of the patients were in sinus rhythm, and approximately 65% of the patients showed a prolonged QTc interval (i.e., a QTc interval above 440 ms in males and above 460ms in females). A comparison of ECG parameters before dialysis and at peak stress showed increases in heart rate (77.45±11.92 vs. 80.38±14.65 bpm, p = 0.001) and QTc interval (460.05±24.53 ms vs. 470.93±24.92 ms, p<0.001). After dividing patients into two groups according to the QTc interval, lower pre-dialysis serum concentrations of potassium (K+), calcium (Ca2+), phosphorus, calcium* phosphorus (Ca*P), and higher concentrations of plasma brain natriuretic peptide (BNP) were found in the group with prolonged QTc intervals. Patients in this group also had a larger left atrial diameter (LAD) and a thicker interventricular septum, and they tended to be older than patients in the other group. Then patients were divided into two groups according to ΔQTc (ΔQTc = QTc peak-stress- QTc pre-HD). When analyzing the patients whose QTc intervals were longer at peak stress than before HD, we found that they had higher concentrations of Ca2+ and P5+ and lower concentrations of K+, ferritin, UA, and BNP. They were also more likely to be female. In addition, more cardiac construction abnormalities were found in this group. In multiple regression analyses, serum Ca2+ concentration before HD and LAD were independent variables of QTc interval prolongation. UA, ferritin, and interventricular septum were independent variables of ΔQTc.
Prolonged QT interval is very common in HD patients and is associated with several risk factors. An appropriate concentration of dialysate electrolytes should be chosen depending on patients’ clinical conditions.
PMCID: PMC4865146  PMID: 27171393
14.  Identification of differentially expressed microRNAs in Culex pipiens and their potential roles in pyrethroid resistance 
Pyrethroids are the major class of insecticides used for mosquito control. Excessive and improper use of insecticides, however, has resulted in pyrethroid resistance, which has become a major obstacle for mosquito control. The development of pyrethroid resistance is a complex process involving many genes, and information on post-transcription regulation of pyrethroid resistance is lacking. In this study, we extracted RNA from mosquitoes in various life stages (fourth-instar larvae, pupae, male and female adult mosquitoes) from deltamethrin-sensitive (DS) and resistant (DR) strains. Using Illumina sequencing, we obtained 13760296 and 12355472 reads for DS-strains and DR-strains, respectively. We identified 100 conserved miRNAs and 42 novel miRNAs derived from 21 miRNA precursors in Culex pipiens. After normalization, we identified 28 differentially expressed miRNAs between the two strains. Additionally, we found that cpp-miR-71 was significant down regulated in female adults from the DR-strain. Based on microinjection and CDC Bottle Bioassay data, we found that cpp-miR-71 may play a contributing role in deltamethrin resistance. The present study provides the firstly large-scale characterization of miRNAs in Culex pipiens and provides evidence of post-transcription regulation. The differentially expressed miRNAs between the two strains are expected to contribute to the development of pyrethroid resistance.
PMCID: PMC4420719  PMID: 25446390
Culex pipiens; pyrethroid resistance; expression profile; differentially expressed microRNA; microinjection; American CDC Bottle Bioassay
15.  Practice pattern of ileal pouch surveillance in academic medical centers in the United States 
Gastroenterology Report  2015;4(2):119-124.
Objective: There is no consensus on whether, when and how to surveil an ileal pouch. The aims of this study were to evaluate experts’ opinions and practice patterns on pouch surveillance and to determine if they were associated with detection of neoplasia.
Methods: Eligible physicians were identified by searching the literature in MEDLINE and the physician list of the Crohn’s and Colitis Foundation of America and surveying by questionnaire.
Results: Fifty-two eligible participants from 32 tertiary institutions were identified. Forty-one physicians (79%) felt that surveillance pouchoscopy was necessary, and 36 (69%) believed that pouchoscopy with biopsy was effective for the detection of neoplasia. Great variation exists with regard to the frequency of surveillance pouchoscopy. Eighteen physicians (35%) reported the detection of a total of 4 pouch dysplasias and 15 pouch cancers within the previous 5 years. The follow-up number of ileal pouches per year was significantly higher in the neoplasia detection group (50 vs 25, P = 0.041). Those who reported detecting neoplasia took even fewer biopsies from the ileal pouch body during the pouchoscopy examination (>3 biopsies per location, 44% vs 82%, P = 0.005). Multivariable analysis showed that the number of patients with ileal pouches followed up per year was the only independent factor associated with the detection of pouch neoplasia (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.1–2.1; P = 0.005).
Conclusion: Most experts agree with performing pouchoscopy and biopsy for surveillance of ileal pouch neoplasia, although the optimal interval varies greatly. The detection of pouch neoplasia appears to be related to patient volume and physician experience.
PMCID: PMC4863190  PMID: 26668095
ileal pouch-anal anastomosis; neoplasia; restorative proctocolectomy; ulcerative colitis
16.  Moderate exercise prevents neurodegeneration in D-galactose-induced aging mice 
Neural Regeneration Research  2016;11(5):807-815.
D-galactose has been widely used in aging research because of its efficacy in inducing senescence and accelerating aging in animal models. The present study investigated the benefits of exercise for preventing neurodegeneration, such as synaptic plasticity, spatial learning and memory abilities, in mouse models of aging. D-galactose-induced aging mice were administered daily subcutaneous injections of D-galactose at the base of the neck for 10 consecutive weeks. Then, the mice were subjected to exercise training by running on a treadmill for 6 days a week. Shortened escape latency in a Morris water maze test indicated that exercise improved learning and memory in aging mice. The ameliorative changes were likely induced by an upregulation of Bcl-2 and brain-derived neurotrophic factor, the repression of apoptosis factors such as Fas and Bax, and an increase in the activity of glucose transporters-1 and 4. The data suggest moderate exercise may retard or inhibit neurodegeneration in D-galactose-induced aging mice.
PMCID: PMC4904473  PMID: 27335566
nerve regeneration; D-galactose; brain aging; behavioral performance; brain-derived neurotrophic factor; neuronal apoptosis; glucose transporters; synaptic plasticity; neurodegeneration; neural regeneration
17.  Caspase-1 inhibition attenuates activation of BV2 microglia induced by LPS-treated RAW264.7 macrophages 
Journal of Biomedical Research  2016;30(3):225-233.
Neuroinflammation has been recognized as a factor in the pathogenesis of neurodegenerative diseases. Emerging evidence suggests that peripheral inflammation, besides neuroinflammation, functions as a modulator of disease progression and neuropathology in several neurodegenerative diseases. However, detailed correlations among peripheral inflammation, neuroinflammation and neurodegeneration remain unknown. In the present study, we prepared a peripheral inflammation model with lipopolysaccharides (LPS)-stimulated RAW264.7 macrophages to explore its activation on BV2 microglia. We found that LPS induced the production of IL-1β, IL-6 and TNF-α in the culture medium of RAW264.7 macrophages. We further showed that LPS plus ATP activated inflammasome, evidenced by the upregulation of caspase-1 and IL-1β, which was suppressed by ZYVAD, a caspase-1 inhibitor. Furthermore, the conditioned medium obtained from LPS-treated RAW264.7 macrophages activated BV2 microglia, stimulating the release of IL-1β, IL-6 and TNF-α from BV2 cells. ZYVAD pretreatment markedly suppressed BV2 microglia activation induced by RAW264.7 cells conditioned medium. Taken together, our study indicates that macrophage-mediated peripheral inflammation subsequently evokes neuroinflammation and may aggravate neural damage. Inflammasome and caspase-1 may be potential targets for modulating systemic inflammatory responses in neurodegenerative diseases.
PMCID: PMC4885171  PMID: 27533933
peripheral inflammation; neuroinflammation; neurodegenerative diseases; NLRP3 inflammasome; caspase-1
18.  Mechanism of stress-driven composition evolution during hetero-epitaxy in a ternary AlGaN system 
Scientific Reports  2016;6:25124.
Two AlGaN samples with different strain were designed to investigate mechanism of stress-driven composition evolution. It is discovered that AlGaN grown on AlN or (AlN/GaN superlattices (SLs))/GaN both consist of two distinct regions with different compositions: transition region and uniform region, which is attributed to the compositional pulling effect. The formation of the transition region is due to the partial stress release caused by the generation of misfit dislocations near the hetero-interface. And the Al composition in the uniform region depends on the magnitude of residual strain. The difference in relaxation degree is 80.5% for the AlGaN epilayers grown on different underlayers, leading to a large Al composition difference of 22%. The evolutionary process of Al composition along [0001] direction was investigated in detail.
PMCID: PMC4844960  PMID: 27112969
19.  Acute Effects of Hemodiafiltration Versus Conventional Hemodialysis on Endothelial Function and Inflammation 
Medicine  2016;95(16):e3440.
Endothelial dysfunction and chronic inflammatory process are prevalent in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). The aim of this study was to evaluate the acute and short-term effects of online hemodiafiltration (OL-HDF) versus conventional HD on endothelial function and inflammation.
A prospective, randomized, crossover trial.
Twenty stable ESRD patients undergoing chronic HD treatments were randomly assigned with a 1:1 ratio to conventional HD and to OL-HDF both for 2 weeks (either HD followed by OL-HDF or OL-HDF followed by HD). Markers of endothelial dysfunction such as flow-mediated dilatation (FMD) of the brachial artery, soluble endothelial protein C receptor (sEPCR), and soluble thrombomodulin (sTM) were measured at baseline, after the first dialysis session and after 2 weeks. Meanwhile, serum interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) levels were measured as well.
Both a single OL-HDF session and 2-week OL-HDF significantly improved brachial FMD% (18.7 ± 6.9% at baseline; 21.5 ± 5.4% after the first dialysis; 21.5 ± 5.7% after 2 weeks; P < 0.05 vs baseline), decreased the levels of sEPCR (from 394.4 [297.9–457.0] ng/ml at baseline to 234.7 [174.1–345.5] ng/ml after the first dialysis, and to 191.5 [138.2–255.0] ng/ml after 2 weeks; P < 0.01 vs baseline) and sTM. In contrast, HD did not change FMD%, even increased the levels of sEPCR and sTM. A reduction in IL-6 level was observed in OL-HDF patients after 2-week dialysis, while IL-6 did not change in HD patients. There was no significant difference in change of hs-CRP level between the OL-HDF and HD treatments.
OL-HDF has both acute and short-term beneficial effects on endothelial dysfunction compared to conventional HD.
PMCID: PMC4845844  PMID: 27100440
20.  A novel ammonia-oxidizing archaeon from wastewater treatment plant: Its enrichment, physiological and genomic characteristics 
Scientific Reports  2016;6:23747.
Ammonia-oxidizing archaea (AOA) are recently found to participate in the ammonia removal processes in wastewater treatment plants (WWTPs), similar to their bacterial counterparts. However, due to lack of cultivated AOA strains from WWTPs, their functions and contributions in these systems remain unclear. Here we report a novel AOA strain SAT1 enriched from activated sludge, with its physiological and genomic characteristics investigated. The maximal 16S rRNA gene similarity between SAT1 and other reported AOA strain is 96% (with “Ca. Nitrosotenuis chungbukensis”), and it is affiliated with Wastewater Cluster B (WWC-B) based on amoA gene phylogeny, a cluster within group I.1a and specific for activated sludge. Our strain is autotrophic, mesophilic (25 °C–33 °C) and neutrophilic (pH 5.0–7.0). Its genome size is 1.62 Mb, with a large fragment inversion (accounted for 68% genomic size) inside. The strain could not utilize urea due to truncation of the urea transporter gene. The lack of the pathways to synthesize usual compatible solutes makes it intolerant to high salinity (>0.03%), but could adapt to low salinity (0.005%) environments. This adaptation, together with possibly enhanced cell-biofilm attachment ability, makes it suitable for WWTPs environment. We propose the name “Candidatus Nitrosotenuis cloacae” for the strain SAT1.
PMCID: PMC4814877  PMID: 27030530
21.  Antitumor effects of cecropin B-LHRH’ on drug-resistant ovarian and endometrial cancer cells 
BMC Cancer  2016;16:251.
Luteinizing hormone-releasing hormone receptor (LHRHr) represents a promising therapeutic target for treating sex hormone-dependent tumors. We coupled cecropin B, an antimicrobial peptide, to LHRH’, a form of LHRH modified at carboxyl-terminal residues 4–10, which binds to LHRHr without interfering with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. This study aimed to assess the antitumor effects of cecropin B-LHRH’ (CB-LHRH’) in drug-resistant ovarian and endometrial cancers.
To evaluate the antitumor effects of CB-LHRH’, three drug resistant ovarian cancer cell lines (SKOV-3, ES-2, NIH:OVCAR-3) and an endometrial cancer cell line (HEC-1A) were treated with CB-LHRH’. Cell morphology changes were assessed using inverted and electron microscopes. In addition, cell growth and cell cytotoxicity were measured by MTT assay and LDH release, respectively. In addition, hemolysis was measured. Furthermore, radioligand receptor binding, hypersensitization and minimal inhibitory concentrations (against Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, and Acinetobacter baumannii) were determined. Finally, the impact on tumor growth in BALB/c-nu mice was assessed in an ES-2 xenograft model.
CB-LHRH’ bound LHRHr with high-affinity (dissociation constant, Kd = 0.252 ± 0.061nM). Interestingly, CB-LHRH’ significantly inhibited the cell viability of SKOV-3, ES-2, NIH:OVCAR-3 and HEC-1A, but not that of normal eukaryotic cells. CB-LHRH’ was active against bacteria at micromolar concentrations, and caused no hypersensitivity in guinea pigs. Furthermore, CB-LHRH’ inhibited tumor growth with a 23.8 and 20.4 % reduction in tumor weight at 50 and 25 mg/kg.d, respectively.
CB-LHRH’ is a candidate for targeted chemotherapy against ovarian and endometrial cancers.
PMCID: PMC4809036  PMID: 27021903
Luteinizing hormone releasing-hormone receptor; Cecropin B peptide; Ovarian cancer; Endometrial cancer
22.  Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients 
World Journal of Gastroenterology  2016;22(11):3227-3233.
AIM: To investigate Fusobacterium nucleatum (F. nucleatum) abundance in colorectal cancer (CRC) tissues and its association with CRC invasiveness in Chinese patients.
METHODS: The resected cancer and adjacent normal tissues (10 cm beyond cancer margins) from 101 consecutive patients with CRC were collected. Fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to detect F. nucleatum in CRC and normal tissues. The difference of F. nucleatum abundance between cancer and normal tissues and the relationship of F. nucleatum abundance with clinical variables were evaluated. Fluorescence in situ hybridization (FISH) analysis was performed on 22 CRC tissues with the highest F. nucleatum abundance by FQ-PCR testing to confirm FQ-PCR results.
RESULTS: The median abundance of F. nucleatum in CRC tissues [0.242 (0.178-0.276)] was significantly higher than that in normal controls [0.050 (0.023-0.067)] (P < 0.001). F. nucleatum was over-represented in 88/101 (87.1%) CRC samples. The abundance of F. nucleatum determined by 2-ΔCT was significantly greater in tumor samples [0.242 (0.178, 0.276)] than in normal controls [0.050 (0.023, 0.067)] (P < 0.001). The frequency of patients with lymph node metastases was higher in the over-abundance group [52/88 (59.1%)] than in the under-abundance group [0/13 (0%)] (P < 0.005). No significant association of F. nucleatum with other clinico-pathological variables was observed (P > 0.05). FISH analysis also found more F. nucleatum in CRC than in normal tissues (median number 6, 25th 3, 75th 10 vs 2, 25th 1, 75th 5) (P < 0.01).
CONCLUSION: F. nucleatum was enriched in CRC tissues and associated with CRC development and metastasis.
PMCID: PMC4789998  PMID: 27004000
Colorectal cancer; Fusobacterium nucleatum; Metastases; Fluorescent quantitative polymerase chain reaction; Fluorescence in situ hybridization
23.  Correction: Empirical Study of User Preferences Based on Rating Data of Movies 
PLoS ONE  2016;11(3):e0152350.
PMCID: PMC4801168  PMID: 26999253
24.  Growth of high quality and uniformity AlGaN/GaN heterostructures on Si substrates using a single AlGaN layer with low Al composition 
Scientific Reports  2016;6:23020.
By employing a single AlGaN layer with low Al composition, high quality and uniformity AlGaN/GaN heterostructures have been successfully grown on Si substrates by metal-organic chemical vapor deposition (MOCVD). The heterostructures exhibit a high electron mobility of 2150 cm2/Vs with an electron density of 9.3 × 1012 cm−2. The sheet resistance is 313 ± 4 Ω/◻ with ±1.3% variation. The high uniformity is attributed to the reduced wafer bow resulting from the balance of the compressive stress induced and consumed during the growth, and the thermal tensile stress induced during the cooling down process. By a combination of theoretical calculations and in situ wafer curvature measurements, we find that the compressive stress consumed by the dislocation relaxation (~1.2 GPa) is comparable to the value of the thermal tensile stress (~1.4 GPa) and we should pay more attention to it during growth of GaN on Si substrates. Our results demonstrate a promising approach to simplifying the growth processes of GaN-on-Si to reduce the wafer bow and lower the cost while maintaining high material quality.
PMCID: PMC4785338  PMID: 26960730
25.  Study on Light Extraction from GaN-based Green Light-Emitting Diodes Using Anodic Aluminum Oxide Pattern and Nanoimprint Lithography 
Scientific Reports  2016;6:21573.
An anodic aluminum oxide (AAO) patterned sapphire substrate, with the lattice constant of 520 ± 40 nm, pore dimension of 375 ± 50 nm, and height of 450 ± 25 nm was firstly used as a nanoimprint lithography (NIL) stamp and imprinted onto the surface of the green light-emitting diode (LED). A significant light extraction efficiency (LEE) was improved by 116% in comparison to that of the planar LED. A uniform broad protrusion in the central area and some sharp lobes were also obtained in the angular resolution photoluminescence (ARPL) for the AAO patterned LED. The mechanism of the enhancement was correlated to the fluctuations of the lattice constant and domain orientation of the AAO-pattern, which enabled the extraction of more guided modes from the LED device.
PMCID: PMC4763243  PMID: 26902178

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