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(1) Background: Vitamin D (VD) plays a vital role in anti-viral innate immunity. However, the role of VD in anti-rotavirus and its mechanism is still unclear. The present study was performed to investigate whether VD alleviates rotavirus (RV) infection through a microRNA-155-5p (miR-155-5p)-mediated regulation of TANK-binding kinase 1 (TBK1)/interferon regulatory factors 3 (IRF3) signaling pathway in vivo and in vitro. (2) Methods: The efficacy of VD treatment was evaluated in DLY pig and IPEC-J2. Dual-luciferase reporter activity assay was performed to verify the role of miR-155-5p in 1α,25-dihydroxy-VD 3 (1,25D3) mediating the regulation of the TBK1/IRF3 signaling pathway. (3) Results: A 5000 IU·kg -1 dietary VD 3 supplementation attenuated RV-induced the decrease of the villus height and crypt depth ( p < 0.05), and up-regulated TBK1, IRF3, and IFN-β mRNA expressions in the jejunum ( p < 0.05). Incubation with 1,25D3 significantly decreased the RV mRNA expression and the RV antigen concentration, and increased the TBK1 mRNA and protein levels, and the phosphoprotein IRF3 (p-IRF3) level ( p < 0.05). The expression of miR-155-5p was up-regulated in response to an RV infection in vivo and in vitro ( p < 0.05). 1,25D3 significantly repressed the up-regulation of miR-155-5p in vivo and in vitro ( p < 0.05). Overexpression of miR-155-5p remarkably suppressed the mRNA and protein levels of TBK1 and p-IRF3 ( p < 0.01), while the inhibition of miR-155-5p had an opposite effect. Luciferase activity assays confirmed that miR-155-5p regulated RV replication by directly targeting TBK1, and miR-155-5p suppressed the TBK1 protein level ( p < 0.01). (4) Conclusions: These results indicate that miR-155-5p is involved in 1,25D3 mediating the regulation of the TBK1/IRF3 signaling pathway by directly targeting TBK1.

Immunological checkpoint inhibitors have been immensely successfully applied in the treatment of cancer, however, a portion of tumor patients can't benefit from checkpoint therapy. The low PD-1/CTLA-4 positive rate and involvement of multiple immunosuppressive pathways are thought to be one of the reasons for treatment failure in non-responding patients. A new immune checkpoint molecule, HHLA2, which was widely expressed in PD-1 negative human tumors, may be a promising target for the improvement of recent immune therapy. Yet, the prognostic value and transcriptional regulatory mechanisms of HHLA2 remains unclear. In this study, we aimed to evaluate the prognostic value and transcriptional regulation mechanism of HHLA2 according to clinical and experimental data from multiple databases, including cBioPortal, TCGA, Cistrome, TIMER, Oncomine, Kaplan-Meier, GeneXplain. It was found that the expression of HHLA2 was significantly elevated in renal tumors, and significantly decreased in colorectal tumors. Pan-cancer survival analysis indicates that HHLA2 was an independent prognostic factor in 9/20 of human cancers. Especially in renal clear cell carcinoma ( P = 3.0E-7). Through plotting survival curve in Kaplan-Meier Plotter, it was found that hypomethylation of HHLA2 DNA was a favorable prognostic factor for KIRC patients. Yet, the copy number variant of HHLA2 was not significantly correlated with the overall survival of KIRC patients. Finally, by analyzing the motif of HHLA2 co-expression genes, we identified 15 transcription factors that may be involved in the regulation of the HHLA2 co-expression network. Among these transcription factors, BATF in B lymphocyte and SMAD in monocyte were confirmed to be able to directly bind to HHLA2 DNA according to chip-seq experimental data from Cistrome database.

Purpose: Accurate segmentation of rectal tumors is a basic and crucial task for diagnosis and treatment of rectal cancer. To avoid tedious manual delineation, an automatic rectal tumor segmentation model is proposed., Methods: A pretrained Resnet50 model was introduced for feature extraction. To reduce the complexity of the model, all layers after the 13th residual block of ResNet50 were removed, and three side-output modules were added to the hidden layer of ResNet50 to guide multiscale feature learning. The final boundaries of tumors were determined by fusion of the predictions from side-output modules. The proposed model was compared with two other models, and the effects of different region of interest (ROI) sizes, loss functions, and side-output fusion strategy were also evaluated., Results: The models were trained and evaluated on data from four clinical centers; T2-weighted magnetic resonance images (T2W-MRIs) from 461 patients in the first clinical center were used for training, while T2W-MRIs from 51 patients in the same clinical center and 56 patients in three other clinical centers were used for performance evaluation. The proposed model was superior to the two other models and achieved an average Dice similarity coefficient of 82.39%, sensitivity of 86.32%, specificity of 92.25%, and Hausdorff distance of 12.10 px. In addition, when the ROI contained rectal tumors, the smaller the ROI size, the higher the segmentation accuracy. For a certain ROI size, there were no considerable differences in segmentation results among the loss functions. Compared to the models with single side-output module, the proposed model performed better., Conclusions: The results show that the proposed model has potential clinical applications in rectal cancer treatment, particularly with regard to therapeutic response evaluation and preoperative planning., (© 2019 American Association of Physicists in Medicine.)

Two mutants sensitive to high light for growth and impaired in NDH-1 activity were isolated from a transposon-tagged library of Synechocystis sp. strain PCC 6803. Both mutants were tagged in the ssl3451 gene encoding a hypothetical protein, which shares a significant homology with the Arabidopsis (Arabidopsis thaliana) CHLORORESPIRATORY REDUCTION 42 (CRR42). In Arabidopsis, CRR42 associates only with an NDH-1 hydrophilic arm assembly intermediate (NAI) of about 400 kDa (NAI400), one of total three NAIs (NAI800, NAI500 and NAI400), and its deletion has little, if any, effect on accumulation of any NAIs in the stroma. In comparison, the ssl3451 product was localized mainly in the cytoplasm and associates with two NAIs of about 300 kDa (NAI300) and 130 kDa (NAI130). Deletion of Ssl3451 reduced the abundance of the NAI300 complex to levels no longer visible on gels and of the NAI130 complex to a low level, thereby impeding the assembly process of NDH-1 hydrophilic arm. Further, Ssl3451 interacts with another assembly factor Ssl3829 and they have a similar effect on accumulation of NAIs and NdhI maturation factor Slr1097 in the cytoplasm. We thus propose that Ssl3451 plays an important role in accumulation of the NAI300 and NAI130 complexes in the cytoplasm via its interacting protein Ssl3829., (� The Author(s) 2019. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This paper presents high-sensitivity, micromachined all-fiber Fabry-Pérot interferometric (FFPI) strain gauges and their integration in a force balance for hypersonic aerodynamic measurements. The FFPI strain gauge has a short Fabry-Pérot cavity fabricated using an excimer laser etching process, and the deformation of the cavity is detected by a white-light optical phase demodulator. A three-component force balance, using the proposed FFPI gauges as sensing elements, was fabricated, calibrated, and experimentally evaluated. To reduce thermal output of the balance, a simple and effective self-temperature compensation solution, without external temperature sensors, is proposed and examined through both oven heating and wind tunnel runs. As a result of this approach, researchers are able to use the balance continuously throughout a wide range of temperatures. During preliminary testing in a hypersonic wind tunnel with a free stream Mach number of 12, the measurement accuracies of the balance were clearly improved after applying the temperature self-compensation.

Background: Sinonovacula constricta is an economically important bivalve species in China, Korea and Japan that widely resides in estuarine and coastal areas where salinity fluctuates rapidly. However, little is known about its adaptation mechanisms to acute salt stresses., Objective: To reveal the underlying molecular mechanisms involved in acute salt stresses in juvenile S. constricta., Methods: Nine cDNA libraries (triplicate each trial) were established from juvenile S. constricta, which were subjected to low salinity (5 psu), optimal salinity (15 psu) and high salinity (25 psu) for 6 h, respectively., Results: Illumina sequencing generated 478,587,310 clean reads totally, which were assembled into 427,057 transcripts of 246,672 unigenes. Compared with the control, 1259 and 2163 differentially expressed genes (DEGs) were identified under acute low and high salt stresses, respectively. GO and KEGG enrichment analyses of DEGs revealed that several key metabolic modulations were mainly responsible for the acute salt stresses. According to the significantly highlighted KEGG pathways, some key DEGs were identified and discussed in details. Notably, based on which, some potential osmolytes were further speculated., Conclusion: Here, we carried out a unique report of comparative transcriptome analyses in juvenile S. constricta in response to acute salt stresses. The identified DEGs and their significantly enriched GO terms and KEGG pathways were critical for understanding and further investigating the underlying the physical and biochemical performances, and ultimately facilitated S. constricta breeding. Besides, the transcriptome data greatly enriched the genetic information of S. constricta, which were valuable for promoting its molecular biology researches.

A temperature-insensitive fiber-optic tip sensors array is proposed for multipoint refractive index measurement using optical carrier based on microwave reflection (OCMR). The tip sensors array is made of a series of cleaved fiber end-faces and is spatially multiplexed by physically connecting with a fiber-optic splitter with different lengths of short delay fiber. A sensors array with eight sensing tips is demonstrated for multipoint refractive index measurement. Experimental results show that it can offer a high refractive-index resolution of 3.60 × 10 -6 RIU and a low temperature-refractive index cross sensitivity of 3.74 × 10 -7 RIU/°C. Such a sensors array not only possesses excellent sensing performances, but also can be integrated into a chip for biochemical sensing applications.

Diabetic retinopathy (DR) is a retinal disease caused by metabolic disorders of glucose tolerance that can lead to irreversible blindness if not adequately treated. Retinal pigment epithelial cell (RPEC) dysfunction contributes to the pathogenesis of DR. In the present study the anti‑inflammatory effect of curcumin (CUR) was investigated in RPECs damaged by high glucose levels. RPEC treated with 30 mmol/l glucose was regarded as high glucose group, and cells treated with 24.4 mmol/l mannitol was set as equivalent osmolarity group. Cell Counting Kit‑8 assay was used to measure RPEC viability, the expression of phosphorylated (p)‑AKT and p‑mammalian target of rapamycin (mTOR) were assessed by western blot, and secretion of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑1β in the culture medium was measured by ELISA. Intracellular reactive oxygen species (ROS) levels were measured by laser scanning confocal microscope. The present data indicated that, compared with mannitol treatment, high glucose treatment reduced RPEC viability, increased TNF‑α, IL‑6 and IL‑1β secretion, increased ROS formation and promoted phosphorylation of AKT and mTOR. The antioxidant N‑acetylcysteine, the phosphoinositide 3‑kinase (PI3K)/AKT inhibitor LY294002 and the mTOR inhibitor rapamycin ameliorated the effects of high glucose. In addition, pretreatment with 10 µmol/l CUR reduced secretion levels of TNF‑α, IL‑6 and IL‑1β, ROS formation and phosphorylation of AKT and mTOR. In conclusion, CUR inhibited high glucose‑induced inflammatory injury in RPECs by interfering with the ROS/PI3K/AKT/mTOR signaling pathway. The present study may reveal the molecular mechanism of CUR inhibition effects to high glucose‑induced inflammatory injury in RPEC.

Background and Aim: Data on the radiologic evaluation of perianal fistulizing Crohn's disease (PFCD) naïve to anti-tumor necrosis factor therapy are scarce, especially in Asian populations. We assessed the effectiveness of infliximab (IFX) on PFCD and explored predictors of 'deep remission' based on clinical and radiologic assessments., Methods: Patients with Crohn's disease and active anal fistulas attending our care center for IFX therapy were prospectively enrolled. Each patient underwent clinical examination according to the Fistula Drainage Assessment Index, endoscopy for assessment of Crohn's Disease Activity Index (CDAI) and Perianal Crohn's Disease Activity Index (PCDAI), magnetic resonance imaging (MRI) to determine Van Assche score and Ng score, and laboratory tests up to 2 weeks prior to the start of and up to 2 weeks after the sixth IFX therapy (Week 32)., Results: Among 38 patients treated with IFX, 52.6% achieved clinical remission based on the Fistula Drainage Assessment Index and 42.1% achieved deep remission based on Ng score. Van Assche score (from 14.5 ± 4.26 to 7.36 ± 7.53), CDAI (from 170 ± 92 to 71 ± 69) and PCDAI (from 7.45 ± 2.65 to 2.44 ± 3.20) decreased significantly after six IFX treatments. The only predictor of deep remission was simple fistula ( P  =   0.004, odds ratio = 3.802, 95% confidence interval: 1.541-9.383)., Conclusions: IFX has been shown to have appreciable effectiveness in Chinese patients with PFCD. MRI is the gold standard for evaluating PFCD, but Van Assche score has some limitations.

2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile (SYD007) is a small molecule compound that was synthesized according to the structure of diarylamine. In this study, we evaluated the anti-bladder activities of SYD007, and determined its cytotoxic mechanism. We found that SYD007 exerted cytotoxicity to bladder cancer cells. Furthermore, SYD007 induced bladder cancer cell early apoptosis and arrested cell cycle. Mechanistically, SYD007 suppressed phosphorylated signal transducer and activator of transcription 3 (p-STAT3) (Tyr705) level in parallel with increases of p-extracellular signal-regulated kinase (ERK) and p-AKT. SYD007 significantly inhibited insulin-like growth factor 1 (IGF-1)-induced STAT3 activation through down-regulation of total IGF-1R level. No dramatic changes in IGF-1R mRNA levels were observed in SYD007-treated cells, suggesting that SYD007 acted primarily at a posttranscriptional level. Using molecular docking analysis, SYD007 was identified as an IGF-1R inhibitor. In summary, we reported that SYD007 exerted anti-bladder activities, and these effects were partially due to inhibition of IGF-1R/STAT3 signaling.

Despite a close interaction between cadmium (Cd) and long-chain polyunsaturated fatty acid (LC-PUFA) metabolism, the influence of Cd exposure on the endogenous synthesis of LC-PUFA has received little attention. In the present study, we hypothesized that Cd exposure would affect the synthesis of LC-PUFA in the marine fish silver pomfret (Pampus argenteus). Therefore, the molecular basis of LC-PUFA biosynthesis and regulation was investigated as the first step to understanding the mechanisms underpinning the effects of Cd exposure. Thereafter, transcriptional regulation of the genes that participate in LC-PUFA biosynthesis and regulation by Cd exposure were also explored. Our results showed that fatty acyl desaturase 2 (Fads2) and elongases of very long-chain fatty acids 5 (Elovl5), two key enzymes involved in LC-PUFA biosynthesis, enabled silver pomfret to biosynthesize 20:3n-6 and 20:4n-3 from 18:2n-6 and 18:3n-3. The results also raise the possibility that silver pomfret may have the ability to produce docosahexaenoic acid (DHA, 22:6n-3) from endogenous eicosapentaenoic acid (EPA, 20:5n-3). The expression of silver pomfret fads2 and elovl5 was transcriptionally regulated by the peroxisome proliferator activated receptor α (Pparα). The expression of fads2, elovl5 and pparα in the brain was significantly increased in response to Cd exposure. In addition, Cd exposure significantly reduced the DHA concentration and significantly increased the malondialdehyde concentration in the brain of silver pomfret. Cd exposure likely increases brain-specific DHA synthesis from EPA by transcriptionally activating fads2 and elovl5 via Pparα in silver pomfret. This regulation may be a coping mechanism for the reduction of DHA caused by Cd-oxidative stress in the brains of silver pomfret., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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NaHSO 3 addition greatly increases the yield of H 2 photoproduction in a unicellular green alga Chlamydomonas reinhardtii through removing O 2 and activating hydrogenase but significantly impairs the activity of PSII, an electron source for H 2 photoproduction. Here, a stepwise addition mode of total 13 mM NaHSO 3 , an optimal concentration for H 2 photoproduction of C. reinhardtii identified in a previous one step addition method, significantly improved H 2 photoproduction. Such improvement was believed to be the result of increased residual PSII activity in an anaerobic background, but was at least independent of two alternative electron sinks for H 2 photoproduction, cyclic electron transport around PSI and CO 2 assimilation. Based on the above results, we propose that increased residual PSII activity in an anaerobic environment is an efficient strategy to enhance H 2 photoproduction in C. reinhardtii , and the stepwise NaHSO 3 addition mode is a case study in the strategy.

Accurate measurement of strain is one of the most important issues for high temperature environments. We present a highly integrated all-fiber sensor to achieve precise measurements of strain/high-pressure, which consists of a fiber Bragg grating (FBG) inscribed by an 800 nm femtosecond laser cascaded with a micro extrinsic Fabry⁻Perot (FP) cavity fabricated by the 157 nm laser micromachining technique. FBG is sensitive to temperature, but insensitive to strain/pressure, whereas the FP is sensitive to strain/pressure, but has a small dependence on temperature. Therefore, such a cascaded sensor could be used for dual-parameter measurement and can work well at high temperatures. Experimental results indicate that this device exhibits a good strain characteristic at high temperatures and excellent high-pressure performance at room temperature. Due to its highly sensitive wavelength response, the proposed sensor will have remarkable potential applications in dual parameter sensing in harsh environments.

Women with aggressive triple-negative breast cancer (TNBC) are at high risk of brain metastasis, which has no effective therapeutic option partially due to the poor penetration of drugs across the blood-brain barrier. Trifluoperazine (TFP) is an approved antipsychotic drug with good bioavailability in brain and had shown anticancer effect in several types of cancer. It drives us to investigate its activities to suppress TNBC, especially the brain metastasis. In this study, we chose three TNBC cell lines MDA-MB-468, MDA-MB-231, and 4T1 to assess its anticancer activities along with the possible mechanisms. In vitro, it induced G0/G1 cell cycle arrest via decreasing the expression of both cyclinD1/CDK4 and cyclinE/CDK2, and stimulated mitochondria-mediated apoptosis. In vivo, TFP suppressed the growth of subcutaneous xenograft tumor and brain metastasis without causing detectable side effects. Importantly, it prolonged the survival of mice bearing brain metastasis. Immunohistochemical analysis of Ki67 and cleaved caspase-3 indicated TFP could suppress the growth and induce apoptosis of cancer cells in vivo. Taken together, TFP might be a potential available drug for treating TNBC with brain metastasis, which urgently needs novel treatment options.

Objective: We wished to ascertain the relationship between expression of vascular endothelial growth factor (VEGF), cyclo-oxygenase (COX)-2, and matrix metallopeptidase (MMP)-9 and various features of ultrasound images in breast cancer (BC) patients., Methods: Eighty-nine breast lesions were confirmed to have BC by ultrasound, surgery and pathology. According to the Breast Imaging Reporting and Data System classification method published by the American College of Radiology, six groups were created: spiculation and non-Burr sign; calcification and non-calcification; vascular anomaly syndrome and non-vascular anomaly syndrome; lymph node metastasis (LNM) and non-LNM. In each case, the expression of VEGF, COX-2 and MMP-9 was detected by immunohistochemistry., Results: Expression of VEGF, COX-2 and MMP-9 was higher in BC patients with the Burr sign than in those without it (P<0.05). There was no significant difference in expression of VEGF, COX-2, and MMP-9 between the calcification group and non-calcification group of BC patients (P>0.05). Expression of VEGF, COX-2, and MMP-9 was higher in those with vascular abnormalities than in those without them (P<0.05), as well as in the LNM group compared with the non-LNM group (P<0.05)., Conclusions: The high expression of VEGF, COX-2, and MMP-9 could have an influence on the Burr sign, abnormal blood vessels, and LNM in BC patients using ultrasound., Competing Interests: None., (IJCEP Copyright © 2018.)

Bantam is a conserved miRNA highly expressed in insects. We previously showed that the antisense inhibitor (antagomiR) of bantam improved the infection by baculovirus Autographa californica nucleopolyhedrovirus (AcMNPV) in Spodoptera exigua and S. litura larvae. Here, we constructed a recombinant AcMNPV (vPH-banS) expressing bantam sponge, an mRNA containing eight antisense binding sites for bantam . Infection with wild type AcMNPV (WT) or the control recombinant virus vPH resulted in a significant increase of bantam level, whereas infection with vPH-banS led to an approximately 40% reduction of bantam in both Sf9 cells and S. exigua larvae. Although, comparable production of budded virus and polyhedra were detected in vPH-banS-, vPH-, and WT-infected Sf9 cells, vPH-banS showed remarkably increased insecticidal activity in S. exigua larvae. The 50% lethal concentration and the median lethal time of vPH-banS was only 1/40 and 1/2, respectively, of both vPH and WT. Further analysis showed that the level of molting hormone 20-hydroxyecdysone (20E) was significantly higher in larvae infected with vPH-banS than those infected with vPH or WT. This was confirmed by the result that the larvae treated with bantam inhibitor also had a markedly increased 20E level. Moreover, feeding larvae with 20E increased the virus-mediated mortality, whereas feeding with juvenile hormone partially reverted the high insecticidal effect of vPH-banS. Together, our results revealed that vPH-banS infection suppresses the level of bantam , and in turn elevates level of 20E in infected insects, resulting in increased susceptibility to baculovirus infection. Our study provided a novel approach to improve a baculovirus bio-insecticide by interfering with a key homeostasis-regulating miRNA of the host.

Azathioprine (AZA) 2 to 2.5 mg/kg/d is recommended for European patients with Crohn disease (CD), but several Asian studies reported that low dose of AZA was also effective to treat CD. To confirm those observations, we perform this prospective observational study to compare the efficacy and safety of low and standard doses of AZA in the treatment of active CD.This was a prospective, open-labeled observational study. Two hundred twenty-six active CD patients were divided into 2 groups and treated with AZA 1.5 or 2.0 mg/kg/d respectively, combined with steroid therapy. Patients were followed up for 96 weeks. The complete remission (CR) rate, response rate, relapse rate, and adverse effect rate were assessed at weeks 24, 48, and 96 by intention-to-treat (ITT) analysis.Azathioprine 1.5 mg/kg/d showed no significant difference compared with AZA 2 mg/kg/d in CR rate, response rate and relapse rate by ITT analysis at week 24, 48, or 96 (all P > .05). Their adverse effect rates had no significant difference either (P > .05). Up to 21.7% (49/226) of the patients reported adverse events and 69.4% (34/49) of them were myelosuppresion.Azathioprine 1.5 mg/kg/d combined with steroids is as effective as AZA 2.0 mg/kg/d to induce remission of active CD in the first 6 months, and to maintain remission of inactive CD in the first 2 years, without increasing the recurrence of active CD after clinical remission. The most common adverse effect is myelosuppression.

Influenza viruses infect the epithelial cells of the swine respiratory tract. Cell lines derived from the respiratory tract of pigs could serve as an excellent in vitro model for studying the pathogenesis of influenza viruses. In this study, we examined the replication of influenza viruses in the MK1-OSU cell line, which was clonally derived from pig airway epithelium. MK1-OSU cells expressed both cytokeratin and vimentin proteins and displayed several sugar moieties on the cell membrane. These cells also expressed both Sial2-3Gal and Sial2-6Gal receptors and were susceptible to swine influenza A, but not to human B and C viruses. Interestingly, these cells were also permissive to infection by influenza D virus that utilized 9- O -acetylated glycans. To study the differences in the expression of pattern recognition receptors (PRRs) upon influenza virus infection in the respiratory and digestive tract, we compared the protein expression of various PRRs in MK1-OSU cells with that in the SD-PJEC cell line, a clonally derived cell line from the porcine jejunal epithelium. Toll-like receptor 7 (TLR-7) and melanoma differentiation-associated protein 5 (MDA5) receptors showed decreased expression in influenza A infected MK1-OSU cells, while only TLR-7 expression decreased in SD-PJEC cells. Further research is warranted to study the mechanism behind the virus-mediated suppression of these proteins. Overall, this study shows that the porcine respiratory epithelial cell line, MK1-OSU, could serve as an in-vitro model for studying the pathogenesis and innate immune responses to porcine influenza viruses.

Transjugular Intrahepatic Portal Systemic Shunt is a comprehensive interventional therapy for portal hypertension. During this intervention, puncturing from hepatic vein into portal vein is a difficult step. Selecting puncture needle with a proper bending angle is vital to accurate puncture. Thus, this prospective study provides a method to calculate the angle of the puncture needle using preinterventional contrast-enhanced CT imaging. According to the geometrical characteristics of puncture needle, Bezier curve equation was adopted to describe its bending part. By testing whether each point in a specific region satisfied the equation set of Bezier curves, the possible position of needle tip was obtained. Then, the bending angle of puncture needle was obtained by calculating curvature. The method was evaluated in 13 patients from 2 centers showing now a success rate of 100% and a duration of the procedure of 141 and 161 minutes. The method based on Bezier curve equation for calculating a proper bending angle of puncture needle was proven to be effective. And the clinical study is preliminary and additional work for clinical evaluation is necessary.

To investigate the endogenous long-chain polyunsaturated fatty acid (LC-PUFA) biosynthetic ability in Sinonovacula constricta, fatty acid desaturases (Fads) of this bivalve, namely, Scfad5a, Scfad5b, and Scfad6, were cloned and characterized in the current study. Meanwhile, the tissue distributions of S. constricta Fads and fatty acids (FAs) were examined. Heterologous expression in yeasts confirmed that Scfad5a and Scfad5b were both Δ5 Fads, while Scfad6 was a Δ6 Fad. However, compared with Fads in other organisms, the desaturation activities of S. constricta Fads were relatively low (especially for Scfad6), indicating an adaptation to living conditions. S. constricta Fads were expressed in all tissues examined, and particularly high expressions were found in intestine and gonad. Moreover, FAs were differently distributed among tissues, which might be correlated with their corresponding physiological roles. Taken together, the results provided an insight into LC-PUFA biosynthesis in S. constricta. Notably, Scfad6 was the first functionally characterized Δ6 Fad in marine molluscs to date.

Influenza B virus (FLUBV) is an important pathogen that infects humans and causes seasonal influenza epidemics. To date, little is known about defective genomes of FLUBV and their roles in viral replication. In this study, by using a next-generation sequencing approach, we analyzed total mRNAs extracted from A549 cells infected with B/Brisbane/60/2008 virus (Victoria lineage), and identified four defective FLUBV genomes with two (PB1∆A and PB1∆B) from the polymerase basic subunit 1 (PB1) segment and the other two (M∆A and M∆B) from the matrix (M) protein-encoding segment. These defective genomes contained significant deletions in the central regions with each having the potential for encoding a novel polypeptide. Significantly, each of the discovered defective RNAs can potently inhibit the replication of B/Yamanashi/166/98 (Yamagata lineage). Furthermore, PB1∆A was able to interfere modestly with influenza A virus (FLUAV) replication. In summary, our study provides important initial insights into FLUBV defective-interfering genomes, which can be further explored to achieve better understanding of the replication, pathogenesis and evolution of FLUBV.

Plant hormones can improve the phytoremediation capabilities of heavy metal hyperaccumulator plants. In this study, different doses of indole-3-butytric acid (IBA) were sprayed on the leaves of the lead (Pb) and zinc (Zn) accumulator plant Pseudostellaria maximowicziana, which was planted in Pb-Zn contaminated soil, and the effects of IBA on Pb and Zn accumulation levels in P. maximowicziana were studied. Spraying 25- and 50-mg/L IBA doses increased the stem, leaf and shoot biomasses of P. maximowicziana compared with the control, while 75- and 100-mg/L IBA doses decreased them. The 50-mg/L IBA dose increased the P. maximowicziana contents of chlorophyll a, total chlorophyll and carotenoid of compared with the control, and other doses had no significant effects or decreased these values. Spraying IBA reduced the superoxide dismutase activity of P. maximowicziana compared with the control, but improved the peroxidase and catalase activities. The 50-, 75-, and 100-mg/L IBA doses increased the Pb and Zn contents in P. maximowicziana compared with the control and also increased the amounts of Pb and Zn extracted by P. maximowicziana. Thus, 50 mg/L of IBA could promote the growth and the Pb and Zn phytoremediation capabilities of P. maximowicziana.

Crohn's disease (CD) is often accompanied by the complications of intestinal strictures and fistulas. These complications remain obstacles in CD treatment. In recent years, the importance of epithelial-mesenchymal transition in the pathogenesis of CD-associated fistulas and intestinal fibrosis has become apparent. Epithelial-mesenchymal transition refers to a dynamic change, wherein epithelial cells lose their polarity and adherence and acquire migratory function and fibroblast features. During formation of CD-associated fistulas, intestinal epithelial cells dislocate from the basement membrane and migrate to the lining of the fistula tracts, where they convert into transitional cells as a compensatory response under the insufficient wound healing condition. In CD-associated intestinal fibrosis, epithelial-mesenchymal transition may serve as a source of new fibroblasts and consequently lead to overproduction of extracellular matrix. In this review, we present current knowledge of epithelial-mesenchymal transition and its role in the pathogenesis of CD in order to highlight new therapy targets for the associated complications.

Background: Steryl glycosides (SGs) are sterol conjugates found in various plants, especially in those making up human diets. It has been demonstrated that SGs have potential health benefits, and they could be used as food supplements in a variety of food matrixes. Marine microalgae are a potential resource for human food and ingredients. In this study, gas chromatography-triple quadrupole mass spectrometry (GC-QQQ-MS) was used to characterize unknown SGs in eight microalgae belonging to different classes (Isochrysis galbana 3011, Pavlova viridis, Platymonas helgolandica, Conticribra weissflogii, Thalassiosira pseudonana, Nitzschia closterium, Gymnodinium sp., and Karlodinum veneficum)., Results: The SGs were first extracted from lyophilized algae with chloroform-methanol, purified by solid-phase extraction and analyzed as trimethylsilyl derivatives. Nine SGs have been identified. In particular, new SGs like occelasteryl glycoside and stellasteryl glycoside were found in Gymnodinium sp., 24-methylene cholesteryl glycoside was detected in P. helgolandica, and 4,24-dimethylcholestan-3-yl glycoside was identified as the main constituent of microalga K. veneficum. The results also showed that the compositions of SGs in different microalgae varied, with a range of 5.234 to 0.036 g kg -1 , and microalga P. viridis contained the most abundant SGs., Conclusion: GC-QQQ-MS is a powerful tool to detect SGs with different structures from a variety of microalgae. The compositions of SGs in different microalgae varied greatly. Microalgae are a good source of highly valued SGs. © 2017 Society of Chemical Industry., (© 2017 Society of Chemical Industry.)

Microalgae can effectively absorb nitrogen (N) and phosphorus (P) in wastewater, while growth characteristics can be affected by such nutrients. The influences of the N and P concentration on growth, biomass yield, protein yield, and cell ultrastructure of Chlamydomonas reinhardtii (C. reinhardtii) were investigated in this study. The results showed that, in the optimum conditions (24-72 mg/L for N and 4.5-13.5 mg/L for P), the final biomass and protein content of C. reinhardtii could reach maximum value, and the cell organelles (chloroplast, mitochondria,etc.) showed good structures with larger chloroplasts, and more and neater thylakoids. However, if the concentration of nutrients was much higher or lower than the optimal value, it would cause adverse effects on the growth of C. reinhardtii, especially in high nitrogen (1000 mg/L) and low phosphorus (0.5 mg/L) conditions. Under these extreme conditions, the ultrastructure of the cells was also damaged significantly as follows: the majority of the organelles were deformed, the chloroplast membrane became shrunken, and the mitochondria became swollen, even partial disintegrated (differing slightly under high-N and low-P conditions); furthermore, it is found that C. reinhardtii was more sensitive to low-P stress. On the basis of these results, our findings have general implications in the application of wastewater treatment.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Sinonovacula constricta is an economically and nutritionally important bivalve native to the estuaries and mudflats of China, Japan and Korea. In the present study, S. constricta, cultured either under experimental conditions or collected directly from natural coastal areas with different seawater salinities, was investigated for changes in proximates, amino acids and lipids., Results: When culture salinity was increased, levels of moisture, carbohydrate, crude protein and crude lipid were significantly decreased, whereas the level of ash was significantly increased. The level of Ala was increased by 1.5- to 2-fold, whereas the contents of most lipids were significantly decreased, and the proportion of phosphatidylethanolamine was significantly increased. Notably, a high proportion of ceramide aminoethylphosphonates was detected in S. constricta reared at all salinities. The energy content appears to be higher in S. constricta reared at higher salinity. In experimental S. constricta, when the salinity was enhanced, the changes of compositions were very close to those reared at constant high salinity., Conclusion: Sinonovacula constricta reared at higher salinities possesses a superior quality. A short period of exposure to a higher salinity for farmed S. constricta reared at a lower salinity before harvest would be useful with respect to improving its nutritive value. © 2017 Society of Chemical Industry., (© 2017 Society of Chemical Industry.)

Sphingolipid compositions are crucial for the structural and physiological properties of microalgae membranes. In the present study, we developed a quadrupole time-of-flight (Q-TOF) mass spectrometric method based on MS E data collection for the identification of sphingolipids with high efficiency, selectivity, sensitivity and mass accuracy and applied this method for precise structural identification and quantitative profiling of ceramides and glycosphingolipids in total lipid extracts from 17 strains of microalgae, including 11 strains of diatom, 3 strains of dinoflagellate and 3 strains of haptophyta. Using this method, four species of sphingolipids including 27 ceramides, 13 monosaccharide ceramides, 18 disaccharide ceramides and 18 trisaccharide ceramides were identified. The compositions of sphingolipid-included glycosyl moieties, long chain bases and N-acyl chains showed a significant difference among different microalgae categories. Some long chain bases including d19:2, d19:3 and d19:4, glycosyl moieties including disaccharide and trisaccharide, and N-acyl chains such as 14:0, 14:1, 24:0, 24:1, h18:1, h19:1 and h22:0-2 can be chosen as the molecular signature for microalgae from three major phyla. This methodology will be useful for a wide range of physiological and pathological studies of sphingolipids. Furthermore, the diversity of sphingolipid structure could provide a new criterion for microalgae chemotaxonomy., (Copyright © 2017. Published by Elsevier B.V.)

In this study, the effect of three Mg/Ca molar ratios (5.0, 3.8 and 1.7) on denitrifying phosphate removal performance, biomass morphology, and Extracellular Polymeric Substances (EPS) were examined. Results showed that when the influent Mg/Ca molar ratio was 3.8, the anaerobic-anoxic EBPR performed complete phosphate removal. The microbial bacterial population was a mixed culture comprised of 81±3% DPAO and 13±2% denitrifying glycogen accumulating organisms (DGAO). A higher influent Mg/Ca molar ratio (5.0) had a distinct impact on phosphate removal, biomass morphology, and EPS. This probably induced the deterioration of the anaerobic-anoxic Enhanced Biological Phosphorus Removal (EBPR). The results of this study may inform the proper operation of an anaerobic-anoxic EBPR, and contribute to its application in the real world., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to observe the inhibitory effects of mitogen activated protein kinase (MAPK/ERK) specific inhibitor PD98059 on Mtb-Ag activated γδΤ cells and to investigate the role of MAPK in MAPK/ERK pathway of γδΤ cells activated by Mtb-Ag., Methods: Healthy human peripheral blood mononuclear cell (PBMC) was isolated from the peripheral blood, and then stimulated by phorbol esters (PMA), ionomycin (IM) and Mtb-Ag. PBMC of the experimental group was pretreated by PD98059 of 0, 1, 10 or 100 μmol/L while the control group was given no pretreatment. Flow cytometry was applied to detect the expression of CD69 in γδΤ cells at 0 h, 6 h, 12 h, 24 h, 48 h and 72 h after treatment respectively. The influence of PD98059 on the amplification of γδΤ cells was also detected., Results: After stimulated by PMA and IM for 6 hours, the expression of CD69 in γδΤ reached the peak of (99.3±1.09)%, while in the Mtb-Ag stimulation group, it reached the highest level of 75.2% at 24 hours. The level of CD69 in two group was significant difference between the two groups at each time respectively (p<0.05). Pretreated with PD98059 of 0, 1, 10, 100 μmol/L, the level of CD 69 expression in Mtb-Ag stimulated γδΤ was 79±0.8%, 75±0.7%, 54±0.5% and 17±0.2% respectively; In PMA+IM stimulated group, CD69 expression were all more than 98% in different concentration of PD98059. After treated with PD98059 of 0, 1, 10, 100 μmol/L, total cell number increased from 1.5×10 6 to (10.3±2.5)×10 6 , (9.5±2.1)×10 6 , (5.8±1.8)×10 6 and (2.1±0.5)×10 6 respectively. Number of γδΤ cells reached to (6.2±0.9)×10 6 , (5.02±0.8)×10 6 , (2.05±0.5)×10 6 and (0.41±0.1)×10 6 respectively., Conclusion: γδΤ cells were specifically activated by Mtb-Ag, and the activation was depended on MAPK/ERK pathway. The activation effects of Mtb-Ag on γδΤ cells can be obviously inhibited by PD98059., Competing Interests: None., (IJCEP Copyright © 2017.)

This study examined the feasibility of α-amylase activation and immobilization, using lignin from bamboo shoot shells (BSS). Our results demonstrated that BSS lignin is an excellent α-amylase activator and it elevated α-amylase activity more than two-fold at a concentration of 5mg/ml. For immobilization of α-amylase via adsorption, BSS lignin was incubated in an α-amylase solution (5mg/ml) for 20min, and the maximum specific activity, amount of loaded protein and activity recovery were 92.4U/mg, 19.0mg/g and 111%, respectively. In contrast to its free counterpart, immobilized α-amylase improved the catalytic efficiency and storage stability, under comparable working conditions (temperature and pH). Regarding its convenient usage, immobilized enzyme can be suspended in advance, but a suspension incubated at 60°C should be used within 30min. The residual activity after 14 re-uses remained at a reasonable level (53.2%). In conclusion, this study reveals a novel support for enzyme immobilization., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

An integrated sensor via overlapping a micro Fabry-Perot (MFP) cavity with a micro-channel on a regenerated fiber Bragg grating (RFBG) is constructed for dual-parameter sensing of temperature, strain, and gas pressure under a high temperature (600°C). The MFP is fabricated by using a 157 nm micro-machining on H 2 -loaded bendinsensitive fiber. A fiber Bragg grating (FBG) is inscribed at the same position of the MFP using 248 nm laser exposure, and then successfully regenerated after a required annealing process which enhances the strain sensitivity of MFP more than three times. The micro-channel created on the MFP is used to improve gas pressure sensitivity of the MFP nearly 100 times. Since the MFP and RFBG have different sensitivities to gas pressure, strain, and temperature, the sensor head could be used to perform dual-parameter measurement by simultaneous measurement of high temperature and strain, and high temperature and gas pressure.

Antibiotic exposure in early life can lead to a significant change of the gut microbiota and may contribute to later onset of inflammatory bowel disease (IBD). However, the relationship between early-life antibiotic treatment and IBD is ambiguous, according to contradicting results of epidemiologic studies. In the present study, we demonstrated that low-dose penicillin pre-treatment had a unique protective effect against mouse colitis induced by dextran sodium sulfate (DSS). Low-dose penicillin also suppressed the expression of pro-inflammatory cytokine IL-17 in various intestinal tissues, and decreased the amount of Th17 cells in small-intestine lamina propria. Neither metronidazole nor enrofloxacin had a similar effect. We further confirmed that low-dose penicillin could cause specific changes of the gut microbiota, especially the eradication of segmented filamentous bacteria (SFB). Mice without SFB inoculation showed no disparity when treated with penicillin or water. Taken together, the results showed that low-dose penicillin can achieve a highly specific manipulation of sensitive bacteria and interfere with development of intestinal immune system in early life. The study may further indicate the possibility of achieving a favorable immune state among a certain group of patients with IBD, or other autoimmune diseases, by fine-tuning the gut microbiota.

Inflammatory bowel disease (IBD) is an autoimmune disorder characterized by chronic, relapsing intestinal inflammation. Autoimmune liver disease (AILD) may be involved in IBD as an extra-intestinal manifestation (EIM). Epidemiologic and anatomic evidence have demonstrated an intimate crosstalk between the gut and the liver. In this review, we briefly introduced nine groups of susceptibility loci shared by inflammatory bowel and autoimmune liver disease for the first time. The genome-wide association studies (GWAS) evidence of pathways involving crosstalk between the gut and the liver is clarified and explained. It has been found that HNF4-α, GPR35, MST1R, CARD9, IL2/IL21/IL2R, BACH2, TNFRSF14, MAdCAM-1, and FUT2 are the genes involved in tight junction formation, macrophage function, T helper cell or T reg cell cycle and function, TNF secretion, lymphocyte homing or intestinal dysbiosis, respectively. The intimate crosstalk between the gut and liver in immunity is also highlighted and discussed in this review., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Aims: The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage. This study aimed to investigate whether antibiotics could interfere with ILCs-dependent tissue repair., Methods: Dextran sodium sulfate (DSS)-induced colitis was established in mice pre-treated with reagent of different antibiotic spectrum. Both morphological and molecular markers of tissue repair after DSS cessation were detected. ILCs population and function status were also recorded. Further attention was paid to the response of dendritic cells after antibiotics treatment, which were claimed to regulate colonic ILC3s in an IL-23 dependent way., Results: Using of vancomycin resulted in delayed tissue repairing after experimental colitis. Both colonic IL-22/pSTAT3 axis and ILC3 population were found decreased in this situation. Vancomycin treatment diminished the upstream IL-23 and producer dendritic cell population. The reduced dendritic cell number may due to inadequate chemokines and colony-stimulating factors supply., Conclusion: Presence of vancomycin-sensitive microbiota is required for the maturation of ILC3-activating dendritic cells hence maintain the sufficient IL-22/pSTAT3 level in the colon during tissue healing. Manipulation of colonic microbiota may help achieve colonic mucosal healing post inflammation and injury., (Copyright © 2016. Published by Elsevier Inc.)

Background/aims: Inflammatory bowel disease (IBD) primarily involves the intestinal tract and can affect vitamin absorption. This study was designed to assess the prevalence of vitamin B 12 and folate deficiencies in patients with IBD, and to identify the risk factors associated with abnormal serum vitamin B 12 and folate levels., Methods: We evaluated the medical records of 195 patients with Crohn's disease (CD) and 62 patients with ulcerative colitis (UC), and selected 118 healthy subjects for the control group., Results: There were more CD patients with vitamin B 12 deficiency than UC patients (14.9% vs. 3.2%, P =0.014) and controls (14.9% vs. 4.2%, P =0.003). The prevalence of folate deficiency was higher in CD patients than in controls (13.3% vs. 3.4%, P =0.004). There were no significant differences in the serum vitamin B 12 and folate statuses of the UC and control groups. Patients with prior ileal or ileocolic resection showed a higher prevalence of abnormal vitamin B 12 levels than those without prior resection (n=6/16, n=23/179; P =0.018). A disease duration within 5 years was a risk factor of abnormal folate levels in CD patients., Conclusions: This study showed that vitamin B 12 and folate deficiencies were more common in patients with CD than in UC patients and controls. Prior ileal or ileocolonic resection was a risk factor of serum vitamin B 12 abnormalities, and a disease duration within 5 years was a risk factor of low serum folate levels in CD patients., Competing Interests: Conflict of interest: None.

Two mutants isolated from a tagging library of Synechocystis sp. strain PCC 6803 were sensitive to high light and had a tag in sll1471 encoding CpcG2, a linker protein for photosystem I (PSI)-specific antenna. Both mutants demonstrated strongly impaired NDH-1-dependent cyclic electron transport. Blue native-polyacrylamide gel electrophoresis followed by immunoblotting and mass spectrometry analyses of the wild type and a mutant containing CpcG2 fused with yellow fluorescent protein-histidine6 indicated the presence of a novel NDH-1L-CpcG2-PSI supercomplex, which was absent in the cpcG2 deletion mutant, the PSI-less mutant, and several other strains deficient in NDH-1L and/or NDH-1M. Coimmunoprecipitation and pull-down analyses on CpcG2-yellow fluorescent protein-histidine6, using antibody against green fluorescent protein and nickel column chromatography, confirmed the association of CpcG2 with the supercomplex. Conversely, the use of antibodies against NdhH or NdhK after blue native-polyacrylamide gel electrophoresis and in coimmunoprecipitation experiments verified the necessity of CpcG2 in stabilizing the supercomplex. Furthermore, deletion of CpcG2 destabilized NDH-1L as well as its degradation product NDH-1M and significantly decreased the number of functional PSI centers, consistent with the involvement of CpcG2 in NDH-1-dependent cyclic electron transport. The CpcG2 deletion, however, had no effect on respiration. Thus, we propose that the formation of an NDH-1L-CpcG2-PSI supercomplex in cyanobacteria facilitates PSI cyclic electron transport via NDH-1L., (© 2016 American Society of Plant Biologists. All Rights Reserved.)

Although current vaccination strategies have been successful at preventing a variety of human diseases, attempts at vaccinating against some pathogens such as AIDS and tuberculosis (TB) have been more problematic, largely in that abnormally high numbers of antigen specific CD8+ T cells are required for protection. This study assessed the effect of temporarily dampening the chemokine receptor CXCR3 and CCR5 after vaccination on host immune responses by the administration of TAK-779, a small molecule CXCR3 and CCR5 antagonists commonly used to inhibit HIV infection. Our results showed that the use of TAK-779 enhanced memory CD8+ T cell immune responses both qualitatively and quantitatively. Treatment with TAK-779 following vaccination of an influenza virus antigen resulted in enhanced memory generation with more CD8+CD127+ memory precursor and fewer terminally differentiated effector CD8+CD69+ T cells. These memory T cells were able to become IFN-γ-secreting effector cells when re-encountered the same antigen, which can further enhance the efficacy of vaccination. The mice vaccinated in the presence of TAK-779 were better protected upon influenza virus challenge than the control. These results showed that vaccination while temporarily inhibiting chemokine receptor CXCR3 and CCR5 by TAK-779 could be a promising strategy to generate large number of protective memory CD8+ T cells.

The role of microRNA bantam, one of the most abundant microRNAs in Sf9 cells, was studied for its role in baculovirus infection in vitro and in vivo. The expression level of bantam was increased after AcMNPV infection in Sf9 cells and in Spodoptera litura larvae. In Sf9 cells, application of bantam inhibitor or mimic altered the expression of many virus genes, the most affected gene being lef8, gp41 and p10, the expression level of which was increased by 8, 10 and 40 times, respectively, in the presence of bantam inhibitor. Virus DNA replication was decreased in the presence of bantam mimic and increased in the presence of bantam inhibitor in a dose dependent manner. However, the production of budded virus did not change significantly. Feeding the larvae of S. litura and Spodoptera exigua with bantam antagomiR, a more stable form of the inhibitor, resulted in an abnormal larval growth and a decreased pupation rate. In S. litura, larvae died 3.5 days sooner than the control when bantam antagomiR was applied, together with AcMNPV. In infected S. exigua, larval mortality increased from 47% without antagomiR to 80% with it. The results suggest that microRNA bantam plays an important role in insect growth, as well as in baculovirus-insect interaction.

Background/aims: Amiodarone, a thyroid hormone-like molecule, can induce dyslipidemia and thyroid dysfunction. However, the effects of dronedarone on lipid metabolism and of both dronedarone and amiodarone on thyroid function and lipid metabolism remain unknown., Methods: Fifty male Sprague-Dawley rats were randomly divided into 5 groups (10 in each group): normal control (NC), amiodarone-treated (AMT), dronedarone-treated (DRT), rats treated with amiodarone combined with polyene phosphatidylcholine (AC), and rats treated with dronedarone combined with polyene phosphatidylcholine (DC). Rats were given amiodarone (120 mg/kg/d), dronedarone (120 mg/kg/d), and polyene phosphatidylcholine (200 mg/kg/d) for 13 weeks. At the end of weeks 4, 8, 12, and 13, plasma-free triiodothyronine (FT3), free thyroxine (FT4), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were determined. At the end of this protocol, rats were sacrificed and the thyroid glands were isolated, weighed, and examined histopathologically. The protein expression of Bcl-2 was measured by immunochemical staining. The mRNA expression of thyroglobulin (Tg), type-1 deiodinase (D1), and thyroid peroxidase (TPO) were detected by polymerase chain reaction (PCR)., Results: Compared with the NC group, FT3 and FT4 levels in the DRT and DC groups significantly increased at week 4 but declined thereafter. The AMT and AC groups had lower FT3 levels but comparable FT4 levels. The levels of TG, LDL-c, and HDL-c in the NC group were lower than those in the other groups whereas the LDL-c/HDL-c ratio was lowest in the AMT group. Bcl-2 expression significantly increased in the DRT group. The mRNA expression of Tg increased whereas the mRNA expression of D1 decreased. Dronedarone induced hyperthyroidism at the early stage and hypothyroidism at the late stage whereas amiodarone only caused hypothyroidism., Conclusion: Both dronedarone and amiodarone can induce dyslipidemia and increase the levels of TC, LDL-c, and HDL-c, and these effects may be associated with thyroid dysfunction., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Lipopolysaccharide (LPS), the major component of the outer cell wall of Gram-negative bacteria, activates the immune system and threatens the health of livestock and poultry. However, little is known about the genes and pathways involved in the immune response of ducklings to LPS. To elucidate the genes involved in the response of 7-day-old duckling spleens treated with LPS, RNA from LPS-treated and control duckling spleens was analyzed by RNA-Seq. The results showed 11,095 and 10,840 genes with >10 clean reads in the LPS-treated and control groups, respectively. Among these genes, 89 were differentially expressed (log2 ratio ≥ 1, P ≤ 0.01, false discovery rate ≤ 0.001); 67 of these were upregulated and 22 were downregulated in the LPS-treated group compared to the control. GO and GO-rich analysis showed that differentially expressed genes were enriched in 13 functional categories (P < 0.05). Pathway analysis and pathway richness analysis showed that differentially expressed genes were enriched in six pathway categories (P < 0.05). Further analysis showed that some immune system-related signaling pathways, such as the hematopoietic cell lineage, Toll-like receptor signaling pathway, T cell receptor signaling pathway, T cell receptor signaling pathway, complement and coagulation cascades, antigen processing and presentation, and chemokine signaling pathway, are active during the immune response. To confirm the RNA-Seq results, we detected CCL4, LBP, CD71, and STEAP3 expression using real-time PCR analysis, and the results were consistent with the RNA-Seq results. Our results provide new information on the genes involved in the immune response of duckling spleens to LPS.

Background: Intestinal intraepithelial lymphocytes that reside within the epithelium of the intestine form one of the main branches of the immune system. A majority of IELs express CD8α homodimer together with other molecules associated with immune regulation. Growing evidence points to the WNT signaling pathway as a pivotal piece in the immune balance and focuses on its direct regulation in intestinal epithelium. Therefore we decided to investigate its role in IELs' immune status determination., Method: DSS colitis was induced in male C57BL mice. IELs were isolated from colon samples using mechanical dissociation followed by percoll gradient purification and Magnetic-activated cell sorting. Phenotype and cytokine production and condition with Wnts were analyzed by flow cytometry, real-time PCR or ELISA. Proliferation of lymphocytes were evaluated using CFSE dilution. Cell responses after WNT pathway interference were also evaluated., Results: Non-canonical WNT pathway elements represented by FZD5, WNT5A and NFATc1 were remarkably elevated in colitis IELs. The non-canonical WNT5A skewed them into a pro-inflammatory category as measured by inhibitory cell surface marker LAG3, LY49E, NKG2A and activated marker CD69 and FASL. Gaining of a pro-inflammatory marker was correlated with increased IFN-γ production but not TNF whilst decreased TGF-β and IL-10. Both interrupting WNT5A/PKC pathway and adding canonical WNT stimulants could curtail its immune-activating effect., Conclusion: Canonical and non-canonical WNT signals act in opposing manners concerning determining CD8αα(+) IELs immune status. Targeting non-canonical WNT pathway may be promising in tackling inflammatory bowel disease.

Background: Recently accumulated evidence suggests that Raf kinase inhibitor protein (RKIP) participates in regulation of many signaling pathways and plays an important role in tumorigenesis and tumor metastasis. However, studies investigating the role of RKIP in colorectal cancer have not been reported. The aim of this study was to investigate the role of RKIP on colorectal cancer cell differentiation, progression and its correlation with chemosensitivity., Results: Immunohistochemical analysis revealed that RKIP expression was higher in non-neoplastic colorectal tissue (NCRCT) and colorectal cancer tissue (CRCT) than that in metastatic lymph node tissue (MLNT) (P <0.05). P-ERK protein expression was higher in MLNT and CRCT than that in NCRCT (P = 0.02). Immunocytochemical analysis further revealed that RKIP expression was higher in the well differentiated cell line SW1116 as compared to that in the poorly differentiated cell line LoVo. Matrigel invasive assay demonstrated that the inhibition of RKIP by short hairpin RNA (shRNA) 271 transfection significantly increased the number of migrated cells (90.67 ± 4.04 vs. 37.33 ± 2.51, P <0.05), whereas over-expression of RKIP by PEBP-1 plasmid transfection significantly suppressed the number of migrated cells (79.24 ± 5.18 vs. 154.33 ± 7.25, P <0.05). Meanwhile, down-regulation of RKIP induced an increase in the cell survival rate by inhibiting apoptosis induced by hydroxycamptothecine., Conclusions: RKIP was also found to be associated with cell differentiation, with a higher activity in well differentiated colorectal cancer cells than in poorly differentiated ones. The upregulated expression of RKIP in colorectal cancer cells inhibited cell invasion and metastasis, while downregulation of RKIP reduced chemosensitivity by inhibiting apoptosis induced by HCPT.

Unlabelled: Influenza B virus (IBV) causes seasonal epidemics in humans. Although IBV has been isolated from seals, humans are considered the primary host and reservoir of this important pathogen. It is unclear whether other animal species can support the replication of IBV and serve as a reservoir. Swine are naturally infected with both influenza A and C viruses. To determine the susceptibility of pigs to IBV infection, we conducted a serological survey for U.S. Midwest domestic swine herds from 2010 to 2012. Results of this study showed that antibodies to IBVs were detected in 38.5% (20/52) of sampled farms, and 7.3% (41/560) of tested swine serum samples were positive for IBV antibodies. Furthermore, swine herds infected with porcine reproductive and respiratory syndrome virus (PRRSV) showed a higher prevalence of IBV antibodies in our 2014 survey. In addition, IBV was detected in 3 nasal swabs collected from PRRSV-seropositive pigs by real-time RT-PCR and sequencing. Finally, an experimental infection in pigs, via intranasal and intratracheal routes, was performed using one representative virus from each of the two genetically and antigenically distinct lineages of IBVs: B/Brisbane/60/2008 (Victoria lineage) and B/Yamagata/16/1988 (Yamagata lineage). Pigs developed influenza-like symptoms and lung lesions, and they seroconverted after virus inoculation. Pigs infected with B/Brisbane/60/2008 virus successfully transmitted the virus to sentinel animals. Taken together, our data demonstrate that pigs are susceptible to IBV infection; therefore, they warrant further surveillance and investigation of swine as a potential host for human IBV., Importance: IBV is an important human pathogen, but its ability to infect other species, for example, pigs, is not well understood. We showed serological evidence that antibodies to two genetically and antigenically distinct lineages of IBVs were present among domestic pigs, especially in swine herds previously infected with PRRSV, an immunosuppressive virus. IBV was detected in 3 nasal swabs from PRRSV-seropositive pigs by real-time reverse transcription-PCR and sequencing. Moreover, both lineages of IBV were able to infect pigs under experimental conditions, with transmissibility of influenza B/Victoria lineage virus among pigs being observed. Our results demonstrate that pigs are susceptible to IBV infections, indicating that IBV is a swine pathogen, and swine may serve as a natural reservoir of IBVs. In addition, pigs may serve as a model to study the mechanisms of transmission and pathogenesis of IBVs., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)