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1.  Quantifying the barrier lowering of ZnO Schottky nanodevices under UV light 
Scientific Reports  2015;5:15123.
In this study we measured the degrees to which the Schottky barrier heights (SBHs) are lowered in ZnO nanowire (NW) devices under illumination with UV light. We measured the I–V characteristics of ZnO nanowire devices to confirm that ZnO is an n-type semiconductor and that the on/off ratio is approximately 104. From temperature-dependent I–V measurements we obtained a SBH of 0.661 eV for a ZnO NW Schottky device in the dark. The photosensitivity of Schottky devices under UV illumination at a power density of 3 μW/cm2 was 9186%. Variations in the SBH account for the superior characteristics of n-type Schottky devices under illumination with UV light. The SBH variations were due to the coupled mechanism of adsorption and desorption of O2 and the increase in the carrier density. Furthermore, through temperature-dependent I–V measurements, we determined the SBHs in the dark and under illumination with UV light at power densities of 0.5, 1, 2, and 3 μW/cm2 to be 0.661, 0.216, 0.178, 0.125, and 0.068 eV, respectively. These findings should be applicable in the design of highly sensitive nanoscale optoelectronic devices.
PMCID: PMC4601028  PMID: 26456370
2.  The patterns and timing of recurrence after curative resection for gastric cancer in China 
The recurrence of gastric cancer after curative resection had adverse effects on patients’ survival. The treatment presence varied from different countries. The aims of this study were to understand the recurrence incidence, patterns, and timing and to explore the risk factors in China.
One thousand three hundred four patients who undergoing curative resection from more than 100 hospitals between January 1st 1986 and September 1st 2013, were surveyed in detail. Clinical pathological factors were examined as potential risk factors of each recurrence pattern using univariate and multivariate analyses. Recurrence timing was also analyzed based on disease-free survival.
Among 1304 gastric cancer patients, 793 patients (60.8%) experienced recurrence and 554 patients (42.5%) experienced recurrence within 2 years after operation. The median disease-free survival was 29.00 months (interquartile range [IQR] 12.07, 147.23). Receiving operation in general hospitals was one of independent risk factors of local-regional recurrence (OR = 1.724, 95% CI 1.312 to 2.265) and distant metastasis (OR = 1.496, 95% CI 1.164 to 1.940). Patients would suffer lower risk of distant metastasis if they received no more than 3 cycles adjuvant chemotherapy (OR = 0.640, 95% CI 0.433 to 0.943). Adjuvant radiotherapy could reduce the risk of recurrence (OR 0.259, 95% CI 0.100 to 0.670), especially distant metastasis (OR = 0.260, 95% CI 0.083 to 0.816).
More than 60% patients experienced recurrence after curative resection for gastric cancer, especially within 2 years after surgery. Risk factors were clarified between various recurrence patterns. Advanced gastric cancer and undergoing operation in general hospitals contributed to increased recurrence risk and worse survival. Enough number of lymph nodes harvest and standard D2 lymphadenectomy could reduce recurrence. Chinese patients would benefit from adjuvant chemotherapy and radiotherapy.
PMCID: PMC5146887  PMID: 27931221
Gastric cancer; Curative resection; Postoperative recurrence; Disease-free survival; Overall survival
3.  Clinical outcome in lung cancer with a second malignancy 
Medicine  2016;95(43):e5203.
The aim of the study was to determine the clinical outcome of lung cancer patients with a secondary malignancy according to the time sequence between the lung cancer and the secondary malignancy.
Retrospective review of all lung cancer patients with any secondary cancer treated from June 2004 to July 2012. The survival of patients with a secondary malignancy was compared to those patients without a secondary malignancy. According to the time sequence between the lung cancer and the secondary malignancy, patients were divided into 4 groups. Group I: lung cancer without any other malignancy, Group II: lung cancer with a secondary malignancy at follow-up, Group III: lung cancer with a pre-existing malignancy, Group IV: synchronous malignancies (diagnosis interval between lung cancer and a secondary malignancy of less than 3 months).
Patients with any secondary cancer in their history or at follow up included 157 patients (9.5%). Collectively; the median survival was significantly better for patients with a secondary malignancy, 19.09 months, compared to those without a secondary malignancy, 9.53 months, P < 0.001, HR 0.66 (95% CI 0.55 – 0.79). However, the survival differed significantly according to the time sequence between the lung cancer and the secondary malignancy. The median survival was 47.9 months for group II patients, 12.19 months for group III, 17.51 months for group IV, and 9.53 months for group I; P = 0.001. In Cox proportional hazard analysis, the risk of dying decreased by 68% in group II patients compared to group I patients, HR 0.32 (95% CI 0.21–0.5), P < 0.001. Although the risk of dying for group III and IV decreased by 19% and 16% respectively compared to group I patients, it did not reach statistical significance.
Nowadays, secondary malignancy in lung cancer patients is a frequent finding. Better survival was observed for patient with secondary malignancy following lung cancer.
PMCID: PMC5089105  PMID: 27787376
lung cancer; secondary malignancy; survival
4.  MgZnO High Voltage Thin Film Transistors on Glass for Inverters in Building Integrated Photovoltaics 
Scientific Reports  2016;6:34169.
Building integrated photovoltaics (BIPV) have attracted considerable interests because of its aesthetically attractive appearance and overall low cost. In BIPV, system integration on a glass substrate like windows is essential to cover a large area of a building with low cost. However, the conventional high voltage devices in inverters have to be built on the specially selected single crystal substrates, limiting its application for large area electronic systems, such as the BIPV. We demonstrate a Magnesium Zinc Oxide (MZO) based high voltage thin film transistor (HVTFT) built on a transparent glass substrate. The devices are designed with unique ring-type structures and use modulated Mg doping in the channel - gate dielectric interface, resulting in a blocking voltage of over 600 V. In addition to BIPV, the MZO HVTFT based inverter technology also creates new opportunities for emerging self-powered smart glass.
PMCID: PMC5056374  PMID: 27721484
5.  High Fill Factors of Si Solar Cells Achieved by Using an Inverse Connection Between MOS and PN Junctions 
Fill factors (FFs) of ~0.87 have been obtained for crystalline Si (c-Si) solar cells based on Ag front contacts after rapid thermal annealing. The usual single PN junction model fails to explain the high FF result. A metal/oxide/semiconductor (MOS) junction at the emitter is found to be inversely connected to the PN one, and when its barrier height/e is close to the open-circuit voltage of the solar cell, very high FF is obtainable. In this work, although the open-circuit voltage (<580 mV) is not high here, the efficiency of c-Si solar cell still reaches the state-of-the-art value (>20 %) due to the high FF achieved.
PMCID: PMC5056919  PMID: 27726121
Si solar cell; Fill factor; Ag contact; MOS barrier
6.  Comparative Study between Robotic Total Thyroidectomy with Central Lymph Node Dissection via Bilateral Axillo-breast Approach and Conventional Open Procedure for Papillary Thyroid Microcarcinoma 
Chinese Medical Journal  2016;129(18):2160-2166.
A large proportion of the patients with papillary thyroid microcarcinoma are young women. Therefore, minimally invasive endoscopic thyroidectomy with central neck dissection (CND) emerged and showed well-accepted results with improved cosmetic outcome, accelerated healing, and comforting the patients. This study aimed to evaluate the safety and effectiveness of robotic total thyroidectomy with CND via bilateral axillo-breast approach (BABA), compared with conventional open procedure in papillary thyroid microcarcinoma.
One-hundred patients with papillary thyroid microcarcinoma from March 2014 to January 2015 in Jinan Military General Hospital of People's Liberation Army (PLA) were randomly assigned to robotic group or conventional open approach group (n = 50 in each group). The total operative time, estimated intraoperative blood loss, numbers of lymph node removed, visual analog scale (VAS), postoperative hospital stay time, complications, and numerical scoring system (NSS, used to assess cosmetic effect) were analyzed.
The robotic total thyroidectomy with CND via BABA was successfully performed in robotic group. There were no conversion from the robotic surgeries to open or endoscopic surgery. The subclinical central lymph node metastasis rate was 35%. The mean operative time of the robotic group was longer than that of the conventional open approach group (118.8 ± 16.5 min vs. 90.7 ± 10.3 min, P < 0.05). The study showed significant differences between the two groups in terms of the VASs (2.1 ± 1.0 vs. 3.8 ± 1.2, P < 0.05) and NSS (8.9 ± 0.8 vs. 4.8 ± 1.7, P < 0.05). The differences between the two groups in the estimated intraoperative blood loss, postoperative hospital stay time, numbers of lymph node removed, postoperative thyroglobulin levels, and complications were not statistically significant (all P > 0.05). Neither iatrogenic implantation nor metastasis occurred in punctured porous channel or chest wall in both groups. Postoperative cosmetic results were very satisfactory in the robotic group.
Robotic total thyroidectomy with CND via BABA is safe and effective for Chinese patients with papillary thyroid microcarcinoma who worry about the neck scars.
PMCID: PMC5022334  PMID: 27625085
Bilateral Axillo-breast Approach; da Vinci Si Surgical System; Papillary Thyroid Microcarcinoma; Robotic Central Lymph Node Dissection; Robotic Total Thyroidectomy
7.  Asymmetric bulges and mismatches determine 20-nt microRNA formation in plants 
RNA Biology  2015;12(9):1054-1066.
Plant microRNAs (miRNAs) are predominantly 21 nucleotides (nt) long but non-canonical lengths of 22 and 20 nt are commonly observed in diverse plant species. While miRNAs longer than 21 nt can be attributed to the neglect of unpaired bases within asymmetric bulges by the ruler function of DICER-LIKE 1 (DCL1), how 20-nt miRNA is generated remains obscure. Analysis of small RNA data revealed that 20-nt miRNA can be divided into 3 main groups featured by atypical 3′ overhangs or shorter duplex regions. Asymmetric bulges or mismatches at specific positions are commonly observed within each group and were shown to be crucial for 20-nt miRNA formation. Analysis of DCL1 cleavage sites on 20-nt miRNA precursors suggests that these determinants might alter precursor structure or trigger 3′-end decay of mature miRNA. The results herein advance our understanding of miRNA biogenesis and demonstrate that the effect of asymmetric bulges on miRNA length could be position-dependent.
PMCID: PMC4615586  PMID: 26383777
asymmetric bulge; DICER-LIKE 1; microRNA duplex; microRNA length; mismatch
8.  Splenic CD11clowCD45RBhigh dendritic cells derived from endotoxin-tolerant mice attenuate experimental acute liver failure 
Scientific Reports  2016;6:33206.
Endotoxin tolerance (ET) is suggested to attenuate the severity of acute liver failure (ALF) in mice, possibly through both innate and adaptive immunity. However, the involvement of regulatory dendritic cells (DCregs) in ET has not been fully elucidated. In this study, their effect on ALF in mice was investigated. Splenic DCregs from ET-exposed mice (ET-DCregs) showed lower expression levels of CD40, CD80, and MHC-II markers and stronger inhibition of allogenic T cells and regulation of IL-10 and IL-12 secretion than splenic DCregs from normal mice (nDCregs). Moreover, the mRNA and protein levels of TNF-α and P65 in splenic ET-DCregs were significantly lower than those in the splenic nDCregs. The survival rate was significantly increased and liver injury was mitigated in mice with ALF treated with splenic ET-DCregs. In addition, A20 expression was decreased in the liver of ALF mice, but elevated after infusion of splenic nDCregs and ET-DCregs, and a much higher elevation was observed after infusing the latter cells. The functionality of splenic DCregs was altered after ET exposure, contributing to protection of the livers against D-GalN/LPS-induced ALF.
PMCID: PMC5021931  PMID: 27625297
9.  Resveratrol reverses P-glycoprotein-mediated multidrug resistance of U2OS/ADR cells by suppressing the activation of the NF-κB and p38 MAPK signaling pathways 
Oncology Letters  2016;12(5):4147-4154.
The present study aimed to investigate the reversal effect of resveratrol on the phenomenon of multidrug resistance in U2OS/adriamycin (ADR) cells and to clarify the molecular mechanisms. To examine the cell survival and half-inhibitory concentration (IC50) of ADR in U2OS and U2OS/ADR cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used. The accumulation of ADR in U2OS and U2OS/ADR cells was investigated by flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression of multidrug resistance protein 1 (MDR1), P-glycoprotein (P-gp), p65 and p38. Compared with U2OS cells, the IC50 value of ADR was significantly increased in U2OS/ADR cells, which exhibited high levels of MDR1/P-gp. However, resveratrol could drastically reduce the IC50 value of ADR and the expression of MDR1/P-gp, and increased the accumulation of ADR in U2OS/ADR cells. In addition, the expression levels of p38 (phosphorylated) and p65 (acetylated and total) in U2OS/ADR cells were also significantly suppressed by resveratrol. These results suggested that the nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) signaling pathways are correlated with ADR-induced drug resistance in U2OS/ADR cells. Furthermore, resveratrol could downregulate the expression of MDR1/P-gp and reverse the drug resistance phenomenon in U2OS/ADR cells partly at least by suppressing the activation of the NF-κB and p38 MAPK signaling pathways.
PMCID: PMC5104249  PMID: 27895784
resveratrol; transporter; P-glycoprotein; multidrug resistance; natural product
10.  Investigation of Motor Cortical Plasticity and Corticospinal Tract Diffusion Tensor Imaging in Patients with Parkinsons Disease and Essential Tremor 
PLoS ONE  2016;11(9):e0162265.
Parkinson’s disease (PD) and essential tremor (ET) are characterized with motor dysfunctions. Motor circuit dysfunctions can be complementarily investigated by paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like plasticity and diffusion tensor imaging (DTI) of the corticospinal tract (CST). Three groups of twelve subjects with moderate severity PD, ET with intention tremor and healthy controls (HC) were studied. The primary motor cortex (M1) excitability, measured by motor evoked potential (MEP) amplitude and by short-interval and long-interval intracortical inhibition (SICI and LICI) was compared between the three groups before and after PAS. The DTI measures of fractional anisotropy (FA) and mean diffusivity (MD) were acquired. PAS effects and DTI data were simultaneously examined between groups. PAS increased MEP amplitude in HC but not in PD and ET. SICI and LICI were significantly reduced after PAS irrespective of groups. No significant differences of the mean FA and MD were found between groups. There was no significant correlation between the PAS effects and the DTI measures. Findings suggest that both PD and ET with intention tremor have impairment of the associative LTP-like corticospinal excitability change in M1. The microstructure of the CST is not relevant to the deficiency of M1 associative plasticity in PD and ET.
PMCID: PMC5014415  PMID: 27603204
11.  Increased Serum Levels of Anti-Carbamylated 78-kDa Glucose-Regulated Protein Antibody in Patients with Rheumatoid Arthritis 
The objective of this study was to investigate the presence and titer of anti-carbamylated 78-kDa glucose-regulated protein (anti-CarGRP78) antibody in serum from controls, and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). Thirty-three RA patients, 20 SLE patients, 20 pSS patients, and 20 controls were enrolled from our outpatient clinic. GRP78 was cloned and carbamylated. Serum titers of anti- cyclic citrullinated peptides (anti-CCP), anti-GRP78, and anti-CarGRP78 were measured with an enzyme-linked immunosorbent assay. No differences in serum titers of anti-GRP78 antibody in patients with RA, SLE, or pSS compared with the controls were observed. Serum levels of anti-carGRP78 antibody in patients with RA, but not SLE or pSS, were significantly higher compared with the controls (OD405 0.15 ± 0.08 versus 0.11 ± 0.03, p = 0.033). There was a positive correlation between the serum levels of anti-GRP78 antibody, but not anti-CarGRP78 antibody, with the levels of anti-CCP antibody in patients with RA. Both anti-GRP78 and anti-carGRP78 antibodies failed to correlate with C-reactive protein levels in patients with RA. In conclusion, we demonstrated the presence of anti-CarGRP78 antibody in patients with RA. In addition, the serum titer of anti-CarGRP78 antibody was significantly elevated in patients with RA compared with the controls. Anti-CarGRP78 antibody could also be detected in patients with SLE or pSS.
PMCID: PMC5037787  PMID: 27618024
GRP78; autoantibodies; rheumatoid arthritis; systemic autoimmune diseases
12.  Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury 
Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow-derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-α and IL-1β by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p < 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05). Meanwhile, mRNA levels of TNF-α, IL-1β, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI.
PMCID: PMC5037660  PMID: 27563878
neural stem cells; spinal cord injury; macrophage; inflammatory cytokine
13.  A high-throughput-compatible assay to measure the degradation of endogenous Huntingtin proteins 
Acta Pharmacologica Sinica  2016;37(10):1307-1314.
The accumulation of disease-causing proteins is a common hallmark of many neurodegenerative disorders. Measuring the degradation of such proteins using high-throughput-compatible assays is highly desired for the identification of genetic and chemical modulators of degradation. For example, Huntington's disease (HD) is an incurable hereditary neurodegenerative disorder caused by the cytotoxicity of mutant huntingtin protein (mHTT). The high-throughput measurement of mHTT degradation is important in HD drug discovery and research. Existing methods for such purposes have limitations due to their dependence on protein tags or pan protein synthesis inhibitors. Here, we report a high-throughput-compatible pulse-chase method (CH-chase) for the measurement of endogenous tag-free huntingtin protein (HTT) degradation based on Click chemistry and Homogeneous Time Resolved Fluorescence (HTRF) technologies.
The pulsed-labeled proteins were conjugated with biotin using the click reaction strain-promoted alkyne-azide cycloaddition (SPAAC), and the chase signals were calculated by measuring the reduction percentage of the HTT HTRF signals after pull-down with streptavidin beads.
We validated that the signals were within the linear detection range and were HTT-specific. We successfully measured the degradation of endogenous HTT in a high-throughput-compatible format using 96-well plates. The predicted changes of HTT degradation by known modifiers were observed, which confirmed that the assay is suitable for the identification of HTT degradation modifiers.
We have established the first high-throughput-compatible assay capable of measuring endogenous, tag-free HTT degradation, providing a valuable tool for HD research and drug discovery. The method could be applied to other proteins and can facilitate research on other neurodegenerative disorders and proteinopathies.
PMCID: PMC5057231  PMID: 27264314
click chemistry; SPAAC; high-throughput; pulse-chase; protein degradation; Huntington's disease; PolyQ
14.  Preservation of Cognitive Function by Lepidium meyenii (Maca) Is Associated with Improvement of Mitochondrial Activity and Upregulation of Autophagy-Related Proteins in Middle-Aged Mouse Cortex 
Maca has been used as a foodstuff and a traditional medicine in the Andean region for over 2,000 years. Recently the neuroprotective effects of maca also arouse interest of researchers. Decrease in mitochondrial function and decline in autophagy signaling may participate in the process of age-related cognitive decline. This study aimed to investigate if maca could improve cognitive function of middle-aged mice and if this effect was associated with improvement of mitochondrial activity and modulation of autophagy signaling in mouse cortex. Fourteen-month-old male ICR mice received maca powder administered by gavage for five weeks. Maca improved cognitive function, motor coordination, and endurance capacity in middle-aged mice, accompanied by increased mitochondrial respiratory function and upregulation of autophagy-related proteins in cortex. Our findings suggest that maca is a newly defined nutritional plant which can improve mitochondrial function and upregulate autophagy-related proteins and may be an effective functional food for slowing down age-related cognitive decline.
PMCID: PMC5018343  PMID: 27648102
15.  Uncoupling protein 2 modulation of the NLRP3 inflammasome in astrocytes and its implications in depression 
Redox Biology  2016;9:178-187.
Mitochondrial uncoupling protein 2 (UCP2) has been well characterized to control the production of reactive oxygen species (ROS) and astrocytes are the major cells responsible for the ROS production and the inflammatory responses in the brain. However, the function of UCP2 in astrocytes and the contribution of astrocytic UCP2 to depression remain undefined. Herein, we demonstrated that UCP2 knockout (KO) mice displayed aggravated depressive-like behaviors, impaired neurogenesis, and enhanced loss of astrocytes in the chronic mild stress (CMS)-induced anhedonia model of depression. We further found that UCP2 ablation significantly enhanced the activation of the nod-like receptor protein 3 (NLRP3) inflammasome in the hippocampus and in astrocytes. Furthermore, UCP2 deficiency promoted the injury of mitochondria, the generation of ROS and the physical association between thioredoxin-interacting protein (TXNIP) and NLRP3 in astrocytes. Moreover, transiently expressing exogenous UCP2 partially rescued the deleterious effects of UCP2 ablation on the astrocytes. These data indicate that UCP2 negatively regulates the activation of NLRP3 inflammasome and inhibited the ROS-TXNIP-NLRP3 pathway in astrocytes. Collectively, our findings reveal that UCP2 regulates inflammation responses in astrocytes and plays an important role in the pathogenesis of depression and that UCP2 may be a promising therapeutic target for depression.
Graphical abstract
•UCP2 knockout exacerbates depressive behaviors in mice.•UCP2 knockout aggravates CMS-induced the inhibition of neurogenesis.•UCP2 deletion enhances NLRP3 inflammasome activation in hippocampus and in astrocyte.•UCP2 inhibits the ROS-TXNIP-NLRP3 signaling.
PMCID: PMC5007434  PMID: 27566281
Uncoupling protein 2; NLRP3 inflammasome; Astrocyte; Depression; Reactive oxygen species
16.  Work Related Psychosocial and Organizational Factors for Neck Pain in Workers in the United States 
Neck pain is a prevalent musculoskeletal condition among workers in the United States. This study explores a set of workplace psychosocial and organization-related factors for neck pain.
Data used for this study comes from the 2010 National Health interview Survey which provides a representative sample of the US population. To account for the complex sampling design, the Taylor linearized variance estimation method was used. Logistic regression models were constructed to measure the associations.
This study demonstrated significant associations between neck pain and a set of workplace risk factors including work-family imbalance, exposure to a hostile work environment and job insecurity, non-standard work arrangements, multiple jobs and long work hours.
Workers with neck pain may benefit from intervention programs that address issues related to these workplace risk factors. Future studies exploring both psychosocial risk factors and physical risk factors with a longitudinal design will be important.
PMCID: PMC4979741  PMID: 27184340
neck pain; occupational health; psychosocial risk factors; work organization; epidemiology
17.  Osteopontin Deficiency Alters Biliary Homeostasis and Protects against Gallstone Formation 
Scientific Reports  2016;6:30215.
The precipitation of excess biliary cholesterol as solid crystals is a prerequisite for cholesterol gallstone formation, which occurs due to disturbed biliary homeostasis. Biliary homeostasis is regulated by an elaborate network of genes in hepatocytes. If unmanaged, the cholesterol crystals will aggregate, fuse and form gallstones. We have previously observed that the levels of osteopontin (OPN) in bile and gallbladder were reduced in gallstone patients. However, the role and mechanism for hepatic OPN in cholesterol gallstone formation is undetermined. In this study, we found that the expression of hepatic OPN was increased in gallstone patients compared with gallstone-free counterparts. Then, we observed that OPN-deficient mice were less vulnerable to cholesterol gallstone formation than wild type mice. Further mechanistic studies revealed that this protective effect was associated with alterations of bile composition and was caused by the increased hepatic CYP7A1 expression and the reduced expression of hepatic SHP, ATP8B1, SR-B1 and SREBP-2. Finally, the correlations between the expression of hepatic OPN and the expression of these hepatic genes were validated in gallstone patients. Taken together, our findings reveal that hepatic OPN contributes to cholesterol gallstone formation by regulating biliary metabolism and might be developed as a therapeutic target for gallstone treatments.
PMCID: PMC4971489  PMID: 27484115
18.  Crystallization and X-ray diffraction of virus-like particles from a piscine betanodavirus 
This is the first report of the crystallization conditions for VLPs from a grouper fish nervous necrosis virus, and the VLP structure diffracted X-rays to 7.5 Å with high completeness.
Dragon grouper nervous necrosis virus (DGNNV), a member of the genus Betanodavirus, causes high mortality of larvae and juveniles of the grouper fish Epinephelus lanceolatus. Currently, there is no reported crystal structure of a fish nodavirus. The DGNNV virion capsid is derived from a single open reading frame that encodes a 338-amino-acid protein of approximately 37 kDa. The capsid protein of DGNNV was expressed to form virus-like particles (VLPs) in Escherichia coli. The VLP shape is T = 3 quasi-symmetric with a diameter of ∼38 nm in cryo-electron microscopy images and is highly similar to the native virion. In this report, crystals of DGNNV VLPs were grown to a size of 0.27 mm within two weeks by the hanging-drop vapour-diffusion method at 283 K and diffracted X-rays to ∼7.5 Å resolution. In-house X-ray diffraction data of the DGNNV VLP crystals showed that the crystals belonged to space group R32, with unit-cell parameters a = b = 353.00, c = 800.40 Å, α = β = 90, γ = 120°. 23 268 unique reflections were acquired with an overall R merge of 18.2% and a completeness of 93.2%. Self-rotation function maps confirmed the fivefold, threefold and twofold symmetries of the icosahedron of DGNNV VLPs.
PMCID: PMC4118809  PMID: 25084387
Dragon grouper nervous necrosis virus (DGNNV); Betanodavirus; Epinephelus lanceolatus
19.  Pancreatic Acinar Cells Employ miRNAs as Mediators of Intercellular Communication to Participate in the Regulation of Pancreatitis-Associated Macrophage Activation 
Mediators of Inflammation  2016;2016:6340457.
Macrophage activation plays an important role in the inflammatory response in acute pancreatitis. In the present study, the activation of AR42J pancreatic acinar cells was induced by taurolithocholate treatment. The results showed that the culture medium from the activated AR42J cells significantly enhanced NFκB activation in the macrophages compared to that without taurolithocholate treatment. Additionally, the precipitates obtained from ultracentrifugation of the culture media that were rich in exosomes were markedly more potent in activating macrophages compared with the supernatant fraction lacking exosomes. The results indicated that the mediators carried by the exosomes played important roles in macrophage activation. Exosomal miRNAs were extracted and examined using microarrays. A total of 115 differentially expressed miRNAs were identified, and 30 showed upregulated expression, while 85 displayed downregulated expression. Target genes of the differentially expressed miRNAs were predicted using TargetScan, MiRanda, and PicTar software programs. The putative target genes were subjected to KEGG functional analysis. The functions of the target genes were primarily enriched in MAPK pathways. Specifically, the target genes regulated macrophage activation through the TRAF6-TAB2-TAK1-NIK/IKK-NFκB pathway. As the mediators of signal transduction, miRNAs and their predicted target mRNAs regulate every step in the MAPK pathway.
PMCID: PMC4980583  PMID: 27546996
20.  Genetic Structure of Water Chestnut Beetle: Providing Evidence for Origin of Water Chestnut 
PLoS ONE  2016;11(7):e0159557.
Water chestnut beetle (Galerucella birmanica Jacoby) is a pest of the water chestnut (Trapa natans L.). To analyze the phylogeny and biogeography of the beetle and provide evidence for the origin of T. natans in China, we conducted this by using three mitochondrial genes (COI, COII and Cytb) and nuclear ITS2 ribosomal DNA of G. birmanica. As for mtDNA genes, the beetle could be subdivided into three groups: northeastern China (NEC), central-northern-southern China (CC-NC-SC) and southwestern China (SWC) based on SAMOVA, phylogenetic analyses and haplotype networks. But for ITS2, no obvious lineages were obtained but individuals which were from NEC region clustered into one clade, which might be due to sequence conservation of ITS2. Significant genetic variation was observed among the three groups with infrequent gene flow between groups, which may have been restricted due to natural barriers and events in the Late Pleistocene. Based on our analyses of genetic variation in the CC-NC-SC geographical region, the star-like haplotype networks, approximate Bayesian computation, niche modelling and phylogeographic variation of the beetle, we concluded that the beetle population has been lasting in the lower, central reaches of the Yangtze River Basin with its host plant, water chestnut, which is consistent with archaeological records. Moreover, we speculate that the CC-NC-SC population of G. birmanica may have undergone a period of expansion coincident with domestication of the water chestnut approximately 113,900–126,500 years ago.
PMCID: PMC4961436  PMID: 27459279
21.  Proteomics Suggests a Role for APC-Survivin in Response to Somatostatin Analog Treatment of Neuroendocrine Tumors 
Somatostatin analogs are established in the treatment of neuroendocrine tumors (NETs) including small intestinal NET; however, the molecular mechanisms are not well known. Here, we examined the direct effects of lanreotide in NET cell line models.
Setting and Design:
The cell lines HC45 and H727 were treated with 10nM lanreotide for different time periods and alterations of the proteome were analyzed by in-depth high-resolution isoelectric focusing tandem liquid chromatography-mass spectrometry. We next investigated whether the observed suppression of survivin was mediated by adenomatous polyposis coli (APC) and possible effects on tumor proliferation in vitro. Expression of survivin was assessed by immunohistochemistry in 112 NET cases and compared with patient outcome.
We quantified 6451 and 7801 proteins in HC45 and H727, respectively. After short time lanreotide treatment APC was increased and survivin reduced. Overexpression of APC in H727 cells decreased, and APC knock-down elevated the survivin level. The lanreotide regulation of APC-survivin could be suppressed by small interfering RNA against somatostatin receptor 2. Although lanreotide only gave slight inhibition of proliferation, targeting of survivin with the small molecule YM155 dramatically reduced proliferation. Moderate or high as compared with low or absent total survivin expression was associated with shorter progression-free survival, independent of tumor stage, grade, and localization.
We report a proteome-wide analysis of changes in response to lanreotide in NET cell lines. This analysis suggests a connection between somatostatin analog, APC, and survivin levels. Survivin is a possible prognostic factor and a new potential therapeutic target in NETs.
A link between lanreotide treatment, APC and survivin was identified in proteome-wide and functional studies of NET cells, and shorter survival of NET patients was associated with survivin expression.
PMCID: PMC5052342  PMID: 27459532
22.  Defluviitalea phaphyphila sp. nov., a Novel Thermophilic Bacterium That Degrades Brown Algae 
Brown algae are one of the largest groups of oceanic primary producers for CO2 removal and carbon sinks for coastal regions. However, the mechanism for brown alga assimilation remains largely unknown in thermophilic microorganisms. In this work, a thermophilic alginolytic community was enriched from coastal sediment, from which an obligate anaerobic and thermophilic bacterial strain, designated Alg1, was isolated. Alg1 shared a 16S rRNA gene identity of 94.6% with Defluviitalea saccharophila LIND6LT2T. Phenotypic, chemotaxonomic, and phylogenetic studies suggested strain Alg1 represented a novel species of the genus Defluviitalea, for which the name Defluviitalea phaphyphila sp. nov. is proposed. Alg1 exhibited an intriguing ability to convert carbohydrates of brown algae, including alginate, laminarin, and mannitol, to ethanol and acetic acid. Three gene clusters participating in this process were predicted to be in the genome, and candidate enzymes were successfully expressed, purified, and characterized. Six alginate lyases were demonstrated to synergistically deconstruct alginate into unsaturated monosaccharide, followed by one uronic acid reductase and two 2-keto-3-deoxy-d-gluconate (KDG) kinases to produce pyruvate. A nonclassical mannitol 1-phosphate dehydrogenase, catalyzing d-mannitol 1-phosphate to fructose 1-phosphate in the presence of NAD+, and one laminarase also were disclosed. This work revealed that a thermophilic brown alga-decomposing system containing numerous novel thermophilic alginate lyases and a unique mannitol 1-phosphate dehydrogenase was adopted by the natural ethanologenic strain Alg1 during the process of evolution in hostile habitats.
PMCID: PMC4725288  PMID: 26590273
23.  Manipulating one-way space wave and its refraction by time-reversal and parity symmetry breaking 
Scientific Reports  2016;6:29380.
One-way transmission and negative refraction are the exotic wave properties founded in photonic crystals which attract a great attention due to their promising applications in photonic devices. How to integrate such two phenomena in one material or device is interesting and valuable. In this work, we theoretically and experimentally demonstrate that one-way electromagnetic space wave can be realized by means of two-dimensional magnetic photonic crystals. Simultaneously breaking the time-reversal and parity symmetries of the magnetic photonic crystals designed, we observe oblique incident space wave propagating one-way in the magnetic photonic crystals with positive or negative refraction occurring at interfaces, which can be manipulated upon the incident angle and operating frequency. Our work may offer a potential platform to realize some exotic photoelectronic and microwave devices such as one-way imaging and one-way cloaking.
PMCID: PMC4937394  PMID: 27387438
24.  The characteristics and prognostic value of signet ring cell histology in gastric cancer: A retrospective cohort study of 2199 consecutive patients 
Medicine  2016;95(27):e4052.
Supplemental Digital Content is available in the text
Although signet ring cell cancer (SRCC) has long been regarded as an adverse prognostic factor of gastric cancer, the findings of existing studies on this issue are inconsistent. We conducted a retrospective cohort study of 2199 consecutive patients with gastric cancer treated in a tertiary cancer hospital in Beijing, China, 1994 to 2013. The characteristics of SRCC and non-SRCC were compared. The prognostic effects of SRCC and other important clinicopathological factors on overall survival were evaluated by both univariate and multivariate Cox regression analyses and expressed as hazard ratio (HR) with 95% confidence interval (CI). SRCC accounted for 16.1% of gastric cancer, increasing from 6% to 20% over the last 2 decades, and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. SRCC (HR: 1.387, 95% CI: 1.177–1.634), stage (HR: 1.752, 95% CI: 1.458–2.106), surgery (palliative resection: HR: 0.712, 95% CI: 0.590–0.859; curative resection: HR: 0.490, 95% CI: 0.380–0.633), performance status (HR: 1.849, 95% CI: 1.553–2.201), and age (HR: 1.070, 95% CI: 1.001–1.143) were independent prognostic factors for gastric cancer, whereas time period of diagnosis, sex, and tumor location were not statistically significantly associated with overall survival. Subgroup analyses showed that the prognostic value of SRCC did not vary much with age, sex, performance status, stage, and surgery and chemotherapy status. As compared with non-SRCC, SRCC accounted for increasingly more of gastric cancer and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. It was an independent prognostic factor associated with worse survival in gastric cancer.
PMCID: PMC5058817  PMID: 27399088
cohort study; gastric cancer; prognosis; review; signet ring cell; survival
25.  Acupuncture as a primary and independent treatment in the acute phases of sudden sensorineural hearing loss 
Medicine  2016;95(26):e4062.
Sudden sensorineural hearing loss (SSHL) is an otological emergency defined as a rapid hearing loss, seriously affects patient's social life. To data, no study has reported the treatment by acupuncture alone in the acute phase. In this report, Acupuncture and Moxibustion therapy of excitation-focus transfer is outlined.
The patient was a 26-year-old young woman who had an SSHL coupled with ear fullness. The patient had no past medical history, but she had undergone variable emotions and had a history of excessive noise exposure. The patient refused to receive any medicine especially steroids and hyperbaric oxygen therapy. She just only received acupuncture treatment.
Her symptoms and outcome measurements were improved every week and completely recovered after the last week.
Even though the article presents a single case and is based on self-reports, there are very clear trends on how patients with SSHL responded to acupuncture treatments.
PMCID: PMC4937959  PMID: 27368045
acupuncture; acute phases; independent treatment; sudden sensorineural hearing loss

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