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Additional file 1: Figure S1 (A) In vitro biocompatibility of O-CS-DOX NDs at varied concentrations for 24 h treatment. (B) In vitro biocompatibility of O-CS-DOX NDs at varied concentrations for 48 h treatment.

Supplemental Material for A novel strategy against hepatitis B virus: Glycyrrhetnic acid conjugated multi-component synergistic nano-drug delivery system for targeted therapy by QingXia Guan, XiaoYing Zhou, FangFang Yang, Xue Zhang, YanHong Wang, WeiNan Li and XiuYan Li in Journal of Biomaterials Applications

Purpose: Caffeic acid phenethyl ester (CAPE) is the main polyphenol extracted from honeybee propolis, which inhibits the growth of several kinds of tumor. This study aimed to assess the inhibitory effect of CAPE in nasopharyngeal carcinoma (NPC), evaluate the synergistic action of CAPE in radiotherapy sensitivity of NPC cell lines and further elucidate the possible molecular mechanism involved. Materials and methods: CCK-8 assay was used to analyze cell proliferation ability. Colony formation assay was used to evaluate the clonogenic ability and radio-sensitiveness of NPC cells by CAPE treatment. Wound-healing and transwell assay were used to assess the motility of cells. The expression of key molecules of the epithelial–mesenchymal transition (EMT) was determined by western blot analysis and changes in radiation sensitivity were measured by colony-formation assay. cDNA microarray analysis was used to determine differentially expressed genes with and without CAPE treatment, with Gene Ontology enrichment of gene function and KEGG pathways determined. Cell cycle and apoptosis were detected by flow cytometry and western blot analysis. Results: CAPE suppressed the viability of NPC cell lines time- and dose-dependently. It induced apoptosis in NPC cells along with decreased expression of Bcl-XL and increased cleavage of PARP and expression of Bax. G1 phase arrest was induced by CAPE with ower expression of CDK4, CDK6, Rb and p-Rb. The migratory and invasive ability of NPC cells was decreased by the EMT pathway. The irradiation sensitivity of NPC cells was enhanced with CAPE treatment. CAPE specifically inhibited nuclear factor κB (NF-κB) signaling pathway by suppressing p65 subunit translocation from cytoplasm to nucleus. CAPE treatment was synergistic with chemotherapy and radiotherapy. Conclusion: CAPE may inhibit the proliferation and metastasis of NPC cells but enhance radiosensitivity in NPC therapy by inhibiting the NF-κB pathway. CAPE could be a potential therapeutic compound for NPC therapy.

Objective To study the role of LOC339524 gene in mediating the expression of inflammatory cytokines in mouse microglia bv2 cell line induced by lipopolysaccharide (LPS). Methods Mouse microglia bv2 cells were treated with 100 ng/mL LPS for 3, 6, 9 or 12 h to determine the optimal time for observing the inflammatory response. The cells were then treated with 10, 100, 1 000, and 10 000 ng/mL LPS or with 100 ng/mL LPS for 3, 6, 9, and 12 h, and the changes in the expression of LOC339524 protein was investigated. The changes in the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in response to LPS challenge were detected in bv2 cells with siRNA-mediated LOC339524 gene silencing or lentivirus-mediated LOC339524 overexpression using qPCR and Western blotting. Results Compared with blank control, LPS treatment increased TNF-α, IL-6 mRNA and protein expression at different times (P < 0.05), and the expression was consistent at 12 hours. 12 hours were selected for subsequent inflammatory reaction studies; The expression of LOC339524 protein was increased viadifferent concentrations of LPS treatment(P < 0.05) when compared with 0 ng/mL, and that increase was in a time-dependent manner at 100 ng/mL LPS concentration (P < 0.05). After 12 hours of LPS treatment, the expression of TNF-α and IL-6 mRNA and protein was significantly up-regulated in the siRNA group compared with the unrelated fragment group (P < 0.05). Conversely the expression of TNF-α and IL-6 mRNA and protein in the over-expression group was significantly lower than that in the normal group (P < 0.05). Conclusion LOC339524 is an inflammatory response factor that promotes the inflammatory response of bv2 cells to LPS.

Han Chen,1,2,* Xiaoying Zhou,1,2,* Xinyu Tang,2,3 Shuo Li,1,2 Guoxin Zhang1,2 1Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2The First Clinical Medical College, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoxin ZhangDepartment of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, People’s Republic of ChinaEmail guoxinz@njmu.edu.cnBackground or Purpose: It is important to predict nodal metastases in patients with early esophageal cancer to stratify patients for endoscopic resection or esophagectomy. This study was to establish a novel artificial neural network (ANN) and assess its ability by comparing it with a traditional logistic regression (LR) model for predicting lymph node (LN) metastasis in patients with superficial esophageal squamous cell carcinoma (SESCC).Methods: A primary cohort was established, composed of 733 patients who underwent esophagectomy for SESCC from December 2012 to December 2019. The following steps were applied: (i) predictor selection; (ii) development of an ANN and a LR model, respectively; (iii) cross-validation; and (iv) evaluation of performance between the two models. The diagnostic assessment was performed with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: The established ANN model had 6 significant predictors: a past habit of alcohol taking, tumor size, submucosal invasion, histologic grade, lymph-vessel invasion, and preoperative CT result. The ANN model performed better than the LR model in specificity (91.20% vs 72.59%, p=0.006), PPV (56.49% vs 39.78%, p=0.020), accuracy (90.72% vs 74.49%, p< 0.0001), C-index (91.5% vs 86.8%, p< 0.001), and IDI (improved by 23.3%, p< 0.001). There were no differences between these two models in sensitivity (87.06% vs 83.21%, p=0.764), NPV (98.17% vs 95.21%, p=0.627), and NRI (improved by − 1.1%, p=0.824).Conclusion: This ANN model is superior to the LR model and may become a valuable tool for the prediction of LN metastasis in patients with SESCC.Keywords: superficial esophageal squamous cell carcinoma, lymph node metastasis, neural network, machine learning

Xiao Sun,1 Lu Guo,1 Mengmeng Shang,1 Dandan Shi,1 Ping Liang,2 Xuanxuan Jing,1 Dong Meng,1 Xinxin Liu,1 Xiaoying Zhou,1 Yading Zhao,1 Jie Li1 1Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jie LiDepartment of Ultrasound, Qilu Hospital of Shandong University, Wenhua Western Road, 107#, Jinan Tel/Fax +86-531-82166101Email jieli301@163.comPurpose: To synthesize and evaluate a novel folate-conjugated ultrasonic nanobubble (HA-FOL-NB) loading low-molecular-weight hyaluronic acid (LMW-HA) for specific tumor-associated macrophages (TAMs) targeting and reeducation.Methods: The characteristics, cytotoxicity, contrast-enhanced ultrasound imaging (CEUS), and targeting ability to TAMs of HA-FOL-NBs were investigated. The TAMs reprogramming function of HA-FOL-NBs combining ultrasound targeted nanobubble destruction was assessed as well.Results: HA-FOL-NBs (about 342nm) showed remarkable contrast enhancement images, and higher targeting ability due to the folate to folate receptor interactions. Combined with ultrasound targeted nanobubble destruction, HA-FOL-NBs could specifically deliver LMW-HA into TAMs, thus exhibited stronger reeducation effect compared with free LMW-HA.Conclusion: These folate-conjugated and LMW-HA-loaded nanobubbles, with targeted CEUS imaging and TAMs reeducation, are expected to be a potential approach for tumor therapy based on TAMs, especially folate receptor-positive ones.Keywords: ultrasound contrast agent, ultrasonic nanobubble, tumor-associated macrophage, tumor microenvironment, contrast-enhanced ultrasound imaging

Mengmeng Shang,1 Xiao Sun,1 Lu Guo,1 Dandan Shi,1 Ping Liang,2 Dong Meng,1 Xiaoying Zhou,1 Xinxin Liu,1 Yading Zhao,1 Jie Li1 1Department of Ultrasound, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China; 2Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Jie LiDepartment of Ultrasound, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan 250012, People’s Republic of ChinaTel +86-531-82166101Fax +86-531-86927544Email jieli301@163.comBackground: Synergistic chemoradiotherapy (CRT) has become a primary effective curative approach for many solid cancers. However, CRT is still associated with several obstacles, including the increases in side effects and systemic toxicity. Incorporating nanocarriers into CRT is a new and exciting approach to solve these obstacles. The purpose of the present study was to design a unique pH- and ultrasound-responsive perfluoropentane-encapsulated, paclitaxel (PTX)-loaded carboxymethyl chitosan nanodroplets (NDs) for combined imaging and synergistic CRT.Materials and Methods: The NDs were prepared by a homogenization/emulsion method. Their physicochemical properties, echogenicity and biocompatibility were evaluated. PTX-loaded NDs with a high loading efficiency and encapsulation efficiency were prepared and their pH-responsive drug release profile was determined by dialysis sack method. Then, PC3 cells were exposed to (1) PTX (4 μg/mL), (2) NDs (30 μg/mL), (3) PTX-loaded NDs (34 μg/mL), (4) RT (6 Gy), (5) RT (10 Gy), (6) combination of PTX (4 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy), (7) combination of NDs (30 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6Gy), (8) combination of PTX-loaded NDs (30 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy). 24 hrs later, CCK-8 assay, flow cytometry and migration assay were carried out to evaluate their therapeutic effects in CRT.Results: The desired NDs were successfully prepared, which were with round, spherical shapes, relatively smooth surfaces, core-shell structures and uniform in sizes (< 300 nm with PDI< 0.3 when at pH≧6.0). The NDs exhibited good abilities in pH-dependent charge conversion, biocompatibility and ultrasound contrast echogenicity. The in vitro drug release from PTX-loaded NDs (the highest loading efficiency and encapsulation efficiency were 20.35% and 91.58%) was pH dependent and exhibited an initial burst followed by a sustained drug release. The results of the CCK-8 assay, flow cytometry and migration assay all showed PTX-loaded NDs combined ultrasound and RT significantly enhanced cell responses in CRT.Conclusion: The pH- and ultrasound-responsive PTX-loaded NDs, which exhibited a high echogenicity, drug delivery ability and radiosensitization ability, could be a feasible option for combined imaging and novel enhancing approach in synergistic CRT.Keywords: nanodroplets, ultrasound contrast agents, chemoradiotherapy, radiosensitizer, paclitaxel, chitosan

Rapeseed is a very important oil crop in China; however, its production is challenging due to the absence of effective weed management strategies. This is predominantly because of a shortage of herbicide resistance genes. Acetohydroxyacid synthase (AHAS) herbicides inhibit AHAS, a key enzyme involved in branched-chain amino acid synthesis that is required for plant growth. A rapeseed line designated M342 with AHAS herbicide resistance was developed through seed mutagenesis and was studied to assess the level and mode of inheritance of the resistance and to identify the molecular basis of resistance. M342 possessed a high level of cross-resistance to sulfonylureas (SUs) and imidazolinones (IMIs). This resistance was due to AHAS insensitivity to these herbicides and was inherited as a dominant trait conferred by a single nuclear-encoded gene. Molecular analysis revealed the presence of a Trp574Leu mutation in M342, and an allele-specific cleaved amplified polymorphic sequence (AS-CAPS) marker was developed and cosegregated with herbicide resistance in the F2, BC1, and BC2 populations. This mutation altered the transcript levels of BnAHAS1 and BnAHAS3 in M342 compared with those in the wild type, but it did not affect the agronomic or quality traits. The simple genetic inheritance of this mutation and the availability of the cleaved amplified polymorphic sequence (CAPS) marker and herbicide resistance gene should facilitate the development of herbicide-resistant rapeseed cultivars for effective weed control in China.

We analytically study the electronic structures and optical properties of zigzag-edged black phosphorene nanoribbons (ZPNRs) utilizing the tight-binding (TB) Hamiltonian and Kubo formula. By solving the discrete Schordinger equation directly, we obtain the energy spectra and wavefunctions for a $N$-ZPNR with $N$ number of transverse zigzag atomic chains, and classify the eigenstates according to the lattice symmetry. We then obtain the optical transition selection rule of ZPNRs based on the symmetry analysis and the analytical expressions of the optical transition matrix elements. Under an incident light linearly-polarized along the ribbon, importantly, we find that the optical transition selection rule for the $N$-ZPNR with even- or odd-$N$ is qualitatively different. In specification, for even-$N$ ZPNRs the inter- (intra-) band selection rule is $\Delta n=$odd (even), since the parity of the wavefunction corresponding to the $n$th subband in the conduction (valence) band is $(-1)^{n}[(-1)^{(n+1)}]$ due to the presence of the $C_{2x}$ symmetry. In contrast, all optical transitions are possible among all subbands due to the absence of the $C_{2x}$ symmetry. Our findings provide a further understanding on the electronic states and optical properties of ZPNRs, which are useful in the explanation of the optical experiment data on ZPNR samples., Comment: 13 pages, 9 figures

Jiaxiang Ye,1 Junqi Huang,2 Qian He,3 Weilin Zhao,4 Xiaoying Zhou,5 Zhe Zhang,4 Yongqiang Li,1 Jiazhang Wei,6 Jinyan Zhang1 1Department of Medical Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 2Department of Pathology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 3Institute for the Advancement of Higher Education, Hokkaido University, Sapporo, Japan; 4Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 5Life Science Institute, Guangxi Medical University, Nanning 530021, People’s Republic of China; 6Department of Otolaryngology and Head and Neck Oncology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China Background: Epstein–Barr virus (EBV) actively contributes to the pathological process of nasopharyngeal carcinoma (NPC) by enabling NPC cells to acquire various capacities required for their malignant biological actions. Our earlier works demonstrated that EBV-encoded latent membrane protein 1 (LMP1) enhanced vascular endothelial growth factor (VEGF)-mediated angiogenesis by boosting store-operated Ca2+ entry (SOCE) upon extracellular epidermal growth factor (EGF) stimulation. However, the antagonistic effects of SOCE blockage on EBV-promoted angiogenesis must be appropriately evaluated in vivo, and the global effect of EBV infection on the EGF-elicited cytosolic Ca2+ signaling, which regulates VEGF-mediated angiogenesis remains to be further clarified. Materials and methods: Two EBV-infected NPC cell lines, CNE2-EBV and HK1-EBV, along with their parental cell lines were employed in the present study. Dynamic cytosolic Ca2+ changes were measured in individual fluorescent Ca2+ indicator-loaded cells. Amounts of VEGF production were determined by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs)-formed tube networks were quantitatively evaluated as an in vitro angiogenesis assay. A mouse model concurrently bearing EBV-positive/negative xenografts was utilized to evaluate the tumor growth and angiogenesis in vivo. Results: EBV infection reliably promoted transplanted tumor growth while enhancing angiogenesis. Introduction of EBV into EBV-negative NPC cells increased the EGF-stimulated VEGF production while amplifying the EGF-evoked Ca2+ responses. Inhibition of the EBV-boosted Ca2+ signaling using 2-aminoethyl diphenylborinate (2-APB), a specific SOCE inhibitor, effectively antagonized the EBV-promoted VEGF production and endothelial tube formation in vitro. Pharmacological blockage of SOCE exhibited anti-angiogenic effect in the EBV-positive xenografts. Conclusion: SOCE can serve as a candidate pharmacological target for treating NPC, as blockage of the Ca2+ signaling via SOCE is a feasible strategy to suppress the EBV-driven malignant profiles in NPC cells. Keywords: nasopharyngeal carcinoma, store-operated Ca2+ entry, angiogenesis, Epstein–Barr virus, vascular endothelial growth factor

In this study, ten trace elements in Ziziphora clinopodioides Lam., Lamiaceae, from different regions, periods and parts in Xinjiang were determined by atomic absorption spectrometry following microwave-assisted acid digestion. The decreasing sequence of elements levels was K > Ca > Mg > Fe > Cu > Zn > Na > Mn > Cd > Pb. Chemometric approaches, such as correlation analysis, principal component analysis, and hierarchical cluster analysis were applied to classify Z. clinopodioides according to its elements contents. Principal component analysis revealed 83.51% of the variance with the first four principal component variables. Hierarchical cluster analysis indicated five groups from the eighteen regions, and the result of classification can correspond to the geographical distribution for the most regions. Variation in the elements exhibited a decreasing trend, but of different types in the studied periods. Elemental contents distributed in leaves were higher than those in flowers and stems. Therefore, chemometric approaches could be used to analyze data to accurately classify Z. clinopodioides according to origins. This study provided some elemental information on chemotaxonomy, diversity, changing pattern, distribution, and metabolism of Z. clinopodioides at spatial and temporal levels, and could be used as a reference of planting and quality standards. Keywords: Ziziphora clinopodioides, Trace elements, Atomic absorption spectrometry, Chemometric approaches, Diversity, Variation and distribution

Background The fatty acid composition of B. napus’ seeds determines the oil’s nutritional and industrial values, and affects seed germination. Many studies have reported correlations among C16:0, C18:0, C18:1, C18:2 and C18:3 based on phenotypic data; however, the genetic basis of the fatty acid composition in B. napus is still not well understood. Results In this study, unconditional and conditional quantitative trail locus (QTL) mapping analyses were conducted using a recombinant inbred line in six environments. In total, 21 consensus QTLs each for C16:0, C18:0 and C18:2, 16 for C18:1 and 22 for C18:3 were detected by unconditional mapping. The QTLs with overlapping confidence intervals were integrated into 71 pleiotropically unique QTLs by meta-analysis. Two major QTLs, uuqA5–6 and uuqA5–7, simultaneously affected the fatty acids, except C18:0, in most of environments, with the homologous genes fatty acid desaturase 2 (FAD2) and glycerol-3-phosphate sn-2-acyltransferase 5 (GPAT5) occurring in the confidence interval of uuqA5–6, while phosphatidic acid phosphohydrolase 1 (PAH1) was assigned to uuqA5–7. Moreover, 49, 30, 48, 60 and 45 consensus QTLs were detected for C16:0, C18:0, C18:1, C18:2 and C18:3, respectively, by the conditional mapping analysis. In total, 128 unique QTLs were subsequently integrated from the 232 conditional consensus QTLs. A comparative analysis revealed that 63 unique QTLs could be identified by both mapping methodologies, and 65 additional unique QTLs were only identified in conditional mapping. Conclusions Thus, conditional QTL mapping for fatty acids may uncover numerous additional QTLs that were inhibited by the effects of other traits. These findings provide useful information for better understanding the genetic relationships among fatty acids at the QTL level. Electronic supplementary material The online version of this article (10.1186/s12870-018-1268-7) contains supplementary material, which is available to authorized users.

Black phosphorus (BP) has emerged as a promising material candidate for next generation electronic and optoelectronic devices due to its high mobility, tunable band gap and highly anisotropic properties. In this work, polarization resolved ultrafast mid-infrared transient reflection spectroscopy measurements are performed to study the dynamical anisotropic optical properties of BP under magnetic fields up to 9 T. The relaxation dynamics of photoexcited carrier is found to be insensitive to the applied magnetic field due to the broadening of the Landau levels and large effective mass of carriers. While the anisotropic optical response of BP decreases with increasing magnetic field, its enhancement due to the excitation of hot carriers is similar to that without magnetic field. These experimental results can be well interpreted by the magneto-optical conductivity of the Landau levels of BP thin film, based on an effective k*p Hamiltonian and linear response theory. These findings suggest attractive possibilities of multi-dimensional controls of anisotropic response (AR) of BP with light, electric and magnetic field, which further introduces BP to the fantastic magnetic field sensitive applications.

The anterior communicating artery (ACoA) is the most common site of cerebral aneurysms, accounting for as much as 36% of aneurysms. Microsurgical clipping and coil embolization are treatment modalities for ruptured and nonruptured cerebral aneurysms. Compared with surgical clipping, coil embolization has a relatively lower mortality and incidence of cognitive impairment in patients. However, successful management of the patient with twice ruptured ACoA aneurysm is facing critical challenges.This article has described a case of twice ruptured aneurysm with the first rupture occurring when the patient was admitted and the second rupture occurring during coil embolization. Perioperative nursing assessment, monitoring, intervention, patient teaching, and the nurse's role are discussed from a nursing perspective.

In this paper, a polarization maintaining fiber (PMF) is used as the sensing element for microfluidic velocity measurement. The proposed fiber microfluidic velocity sensor adopts the Sagnac loop structure, where the PMF is incorporated in the fiber loop. The microfluidic velocity measurement is realized by monitoring the output spectrum of the Sagnac loop. Different microfluidic velocity causes different pressure on the side of the PMF, which leads to the wavelength shift of the output spectrum of the Sagnac loop. Experimental results show that a quadratic relationship between the microfluidic velocity and the dip shift of the output spectrum has been observed with the microfluidic velocity range from 0∼900um/min. The proposed microfluidic velocity fiber sensor owns significant behavior in various applications such as chemical engineering and medical equipment technology.

Supplemental Digital Content is available in the text, Background: Cancer has become a major public concern all over the world and early diagnosis of cancer is of great benefit for treatment and prognosis. Several studies have investigated the association between abnormal circulating microRNA-126 (miR-126) expression and the risk of various cancers, but the results are inconsistent. Therefore, this meta-analysis was carried out to assess the potential diagnostic value of miR-126 for cancer. Methods: Relevant studies were searched from PubMed, Embase, and Web of Science and we calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operator characteristic curve (AUC) to assess the diagnostic value of miR-126 for cancer detection. Results: A total of 745 cancer patients and 749 controls from 11 studies of 7 papers were included in this meta-analysis. The summary estimates revealed that the pooled sensitivity was 68% (95% confidence interval [CI]: 60–75%), the specificity was 76% (95% CI: 65–85%), the PLR was 2.87 (95% CI: 1.96–4.21), the NLR was 0.42 (95% CI: 0.35–0.52), the DOR was 7 (95% CI: 4–11), and the AUC was 0.77 (95%CI: 0.73–0.80). Moreover, the sample type, cancer type, sample size, and quality score might be sources of heterogeneity. Conclusion: This systematic review and meta-analysis suggests that miR-126 has great potential to be a noninvasive biomarker in the diagnosis of cancer. However, more well-designed studies with larger sample size on the diagnostic value of miR-126 for cancer are needed in the future.

FZD6 plays crucial roles in human tumorigenesis. However, its mechanism in regulating cancers has not been fully elucidated. In the study, we found that FZD6 repressed gastric cancer cell proliferation and migration via activating non-canonical wnt pathway. In addition, non-canonical wnt pathway ameliorated expression of canonical wnt pathway. We also demonstrated that the FZD6 was involved in miR-21-dependent effects in the canonical and non-canonical wnt pathways in gastric cancer. These findings provide a better understanding of the development and progression of gastric cancer and may be an important implication for future therapy.

A fiber sphere-embedded long-period fiber grating (LPFG) sensor has been proposed and fabricated for curvature measurement with high sensitivity. Compared with the normal LPFG, the embedded fiber sphere excites cladding modes and two dips of the output spectrum have been observed. The curvature measurement can be realized by monitoring the shift of the two dips. Experimental results show that the highest curvature sensitivity is up to −104.642 nm/m − 1 with the curvature ranging from 0 to 0.71 m − 1. The temperature response of the sensor has also been studied and a quadratic linear relationship between the dip shift and the temperature has been observed. The highest temperature sensitivity is 0.36 nm / ° C with the temperature range between 20°C and 90°C.

BackgroundDiarrhoea-predominant irritable bowel syndrome (IBS-D) is a common outcome after inflammation due to bacterial gastroenteritis. Several studies have shown ongoing immune activation in the mucosa of patients with IBS-D and a number of studies have suggested that mesalazine slow-release granule formulation (2?g; PENTASA®, Ferring Pharmaceuticals Ltd) may provide benefit including a reduction in stool frequency.ObjectivesOur primary aim was to compare the effect of mesalazine with placebo on stool frequency. Our secondary aims were to assess the effect of mesalazine on abdominal pain, stool consistency, urgency and satisfactory relief of irritable bowel syndrome (IBS) symptoms.Design/participants/interventionWe performed a double-blind, randomised placebo-controlled trial of 2?g mesalazine twice daily compared with placebo for 3 months in Rome III criteria patients with IBS-D.SettingsParticipants were recruited from the primary care research network and secondary care hospitals. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’. Those recruited in Nottingham had sigmoid biopsies and/or magnetic resonance imaging of the abdomen at the start and end of the trial.ResultsA total of 136 patients with IBS-D (82 female, 54 male) were randomised; 10 patients withdrew from each group. Analysis by intention to treat showed that the mean daily average stool frequency during weeks 11 and 12 was 2.8 [standard deviation (SD) 1.2] in the mesalazine group and 2.7 (SD 1.9) in the placebo group, with a group difference of 0.1 (95% confidence interval –0.33 to 0.53); p?=?0.66.ConclusionsMesalazine did not improve abdominal pain, stool consistency or percentage with satisfactory relief compared with placebo during the last 2 weeks’ follow-up. A post hoc analysis in 13 postinfectious patients with IBS appeared to show benefit but this needs confirmation in a larger group. More precise subtyping based on underlying disease mechanisms may allow more effective targeting of treatment in IBS.Trial registrationCurrent Controlled Trials ISRCTN76612274.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

Introduction: Immune activation has been reported in the mucosa of irritable bowel syndrome patients with diarrhoea (IBS-D) and some small studies have suggested that Mesalazine may reduce symptoms. We performed a double blind, randomised placebo controlled trial of 2g Mesalazine twice daily versus placebo for 3 months in Rome III criteria IBS-D patients. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. Methods: Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of “satisfactory relief of IBS symptoms”. Results: 136 patients with IBS-D (82 F, 54 M) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in Mesalazine and 2.7 (1.9) in placebo group with no significant group difference (95% confidence interval) 0.1 (-0.33,0.53); p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared to placebo during the last 2 weeks follow up. Conclusion: This study does not support any clinically meaningful benefit or harm of Mesalazine compared with placebo in unselected IBS with diarrhoea. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. (ClinicalTrials.gov number NCT01316718)

To investigate the effectiveness of pedicled superior gluteal artery perforator bilateral quadrilobed flaps for repairing large sacrococcygeal pressure sores.Between June 2003 and August 2011, 6 paraplegia patients with large sacrococcygeal pressure sores were repaired with the pedicled superior gluteal artery perforator bilateral quadrilobed flaps. There were 2 males and 4 females with an average age of 45.6 years (range, 37-62 years). The mean disease duration was 8.4 months (range, 3-26 months). According to National Pressure Ulcer Advisory Panel (NPUAP) standard, 6 cases rated as degree IV. The size of pressure sores ranged from 15 cm x 13 cm to 18 cm x 16 cm. The size of flaps ranged from 18 cm x 14 cm to 21 cm x 15 cm.After operation, all flaps survived successfully. The wounds healed by first intention in 5 cases; partial dehiscence of incision occurred in 1 case, which was cured after dressing change for 26 days. Six patients were followed up 6-24 months (mean, 12.5 months). The appearance and texture of the flaps were smooth and soft with good elasticity and no ulceration.Pedicled superior gluteal artery perforator bilateral quadrilobed flaps can repair large sacrococcygeal pressure sores. The appearance of flaps is smooth and has good compression-resistance effect.

In order to acquire the information about the insertion copy number and integration site of T-DNA in the genome of transgenic high oleic acid rapeseed ( Brassica napus L.), we isolated the genomic DNA from the transgenic line W-4, the T2 generation plants, then the transgenic genomic DNA was digested with Bam HI prior to conducting Southern bolt with the probe of a segment of NPT II labeled with Dig. The results showed that only one copy of T-DNA was detected to be integrated into the genome of transgenic line W-4. To isolate the flanking sequence of both right border and left border of T-DNA insertion in the genome, the thermal asymmetric interlaced PCR (TAIL-PCR) was employed by using three or four nested specific primers designed based on the sequence of the vector pCNFIRnos and a short arbitrary degenerate primer (AD1 or AD2) , respectively. The PCR products corresponding to flanking sequences of the right and left border were specifically amplified. The flanking sequence of right border is 470 bp in length which includes a 290 bp genomic sequence and a 180 bp vector sequence based on analysis of VecScreen, while the left border flanking sequence is 641 bp in length including a 365 bp genomic sequence and a 276 bp vector sequence. Further sequence alignment analysis revealed that the 180 bp sequence is identical to the RB border of pCNFIRnos vector, which exists a 62 bp deletion, whereas the later of 276 bp is better identical to the left border of pCNFIRnos vector besides a change from G to A happened. Therefore, it was suggested that the integration of the T-DNA in the genome of transgenic line W-4 should be a kind of vector backbone-free integration. Furthermore, there is no any information about homologous sequence of acquired flanking sequences found in the genome based on the Blastn analysis, which implied that the T-DNA should be integrated into non-coding region of the genome. In conclusion, we considered that the information about the T-DNA insertion copy number, integration site and flanking sequences in the genome of the transgenic rapeseed W-4 might be very useful for the biosafety assessment of genetically modified rapeseed and for the indentification of the transgenic high oleic acid rapeseed.

A simple and sensitive rapid resolution liquid chromatography method with a short run time was developed for the simultaneous determination of caffeic acid and rosmarinic acid in Ziziphora clinopodioides Lam. A good chromatographic separation was obtained on an XDB-C18 reversed-phase analytical column (50 mm × 4.6 mm, 1.8 μm) by gradient elution with methanol and water containing 1 % acetic acid (v/v) at 0.9 mL/min flow rate. The detection wavelength was set at 330 nm. The mean recoveries of the two compounds were 101.6 % for caffeic acid and 104.2 % for rosmarinic acid. The method was successfully applied to determine the two compounds in 10 Z. clinopodioides Lam. samples of different origins. A significant variation in the contents of the two compounds among the 10 samples was observed. Therefore, this method provides a new basis for the overall routine quality control assessment of Z. clinopodioides Lam., Colegio de Farmacéuticos de la Provincia de Buenos Aires

The interaction between extracellular matrix (ECM) and hepatic stellate cells (HSC) is the major event in liver fibrosis and recovery. The integrins, as a family of cell surface adhesion molecules, mediate adhesion of HSC to ECM and regulate a variety of cellular functions. In this thesis, I have examined the hypothesis that the ECM regulated HSC phenotype in liver fibrosis and recovery is mediated by integrins; and that integrin avb3 plays a role in HSC activation, proliferation and apoptosis. These were examined by 1) investigating the correlations of ECM remodelling with HSC activation, proliferation or apoptosis in-vivo and in-vitro; 2) evaluating the regulation of integrin expression and adhesion affinities by different substrata in-vitro; 3) investigating the function of integrin avb3 on extracellular and intracellular signalling mechanisms that regulate cell survival or apoptosis. To do so, rat CCl4 liver fibrosis/recovery models and human liver biopsies were employed. In-vitro substrata-HSC cell models, integrin avb3 agonists (vitronectin, fibronectin, collagen I), and antagonists (matrigel, echistatin and integrin specific antibodies), and various biochemical techniques were used. In-vivo studies demonstrated that as fibrosis progressed in liver, collagen I, MMP-2, MT1-MMP, TIMP-1, CTGF, TGF-b1 expression were increased and collagenase activity was suppressed. As spontaneous recovery occurred, the expression of these fibrotic effectors declined and returned to normal, whereas collagenase activity was increased to normal. The change of a-SMA expression, a HSC activation marker, was associated with fibrogenesis or spontaneous recovery, indicating HSC as a key cell in liver fibrosis. In-vitro studies using substrata-HSC cell models demonstrated that substrata in ECM regulate HSC activation, proliferation, arrest and apoptosis, which were associated with cell morphology change and altered integrin expression. This study is first reporting that integrin avb3 is expressed by activated HSC and involved in HSC proliferation and survival in a fibrotic microenvironment.

Origanum vulgare L., Lamiaceae, from six different production areas of China and Pakistan were analyzed via gas chromatography equipped with a flame ionization detector (GC-FID) and examined for their volatile constituents by gas chromatography-mass spectroscopy (GC-MS). This procedure allowed the identification of 11 to 46 components among six production areas, representing 98.5% to 99.9% of the total oil extracted. The yields of the essential oil of the six production areas of O. vulgare ranged from 0.1 to 0.7%. The class of oxygenated monoterpenes was predominant in all the essential oils. However, samples S5 and S6 have high content of sesquiterpene hydrocarbons (33.7 and 43.7%); while sample S6 is high on oxygenated sesquiterpene (32.9%). The principal component analysis of O. vulgare was employed to provide a comprehensive evaluation of essential oil components. The cluster analysis of O. vulgare was classified into three subsets, characterized according to the major essential oil components. The current study investigated the composition differences of essential oil among six production areas offering foundation for quality control, resource optimization, and clinical treatments. Keywords: Essential oil, Origanum vulgare, GC-MS, Principal component analysis, Cluster analysis

BackgroundAsthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear.ObjectiveWe performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients.MethodsSixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed.ResultsSignificant heterogeneity of T-cell phenotypes was observed, with levels of IL-13–secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and ??-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine–high) and nonatopic forms.ConclusionThe evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies.

Background: DNA methylation of CpG sites on genetic loci has been linked to increased risk of asthma in children exposed to elevated ambient air pollutants (AAPs). Further identification of specific CpG sites and the pollutants that are associated with methylation of these CpG sites in immune cells could impact our understanding of asthma pathophysiology. In this study, we sought to identify some CpG sites in specific genes that could be associated with asthma regulation (Foxp3 and IL10) and to identify the different AAPs for which exposure prior to the blood draw is linked to methylation levels at these sites. We recruited subjects from Fresno, California, an area known for high levels of AAPs. Blood samples and responses to questionnaires were obtained (n = 188), and in a subset of subjects (n = 33), repeat samples were collected 2 years later. Average measures of AAPs were obtained for 1, 15, 30, 90, 180, and 365 days prior to each blood draw to estimate the short-term vs. long-term effects of the AAP exposures. Results: Asthma was significantly associated with higher differentially methylated regions (DMRs) of the Foxp3 promoter region (p = 0.030) and the IL10 intronic region (p = 0.026). Additionally, at the 90-day time period (90 days prior to the blood draw), Foxp3 methylation was positively associated with NO2, CO, and PM2.5 exposures (p = 0.001, p = 0.001, and p = 0.012, respectively). In the subset of subjects retested 2 years later (n = 33), a positive association between AAP exposure and methylation was sustained. There was also a negative correlation between the average Foxp3 methylation of the promoter region and activated Treg levels (p = 0.039) and a positive correlation between the average IL10 methylation of region 3 of intron 4 and IL10 cytokine expression (p = 0.030). Conclusions: Short-term and long-term exposures to high levels of CO, NO2, and PM2.5 were associated with alterations in differentially methylated regions of Foxp3. IL10 methylation showed a similar trend. For any given individual, these changes tend to be sustained over time. In addition, asthma was associated with higher differentially methylated regions of Foxp3 and IL10.

Background: Gastrointestinal symptoms have been reported to occur frequently in diabetes, but their prevalence in Chinese community-dwelling individuals with diabetes is unknown. The present study aimed to address this issue and explore the risk factors for gastrointestinal symptoms. Methods: A total of 1304 community-dwelling participants (214 with diabetes, 360 with prediabetes and 730 with normoglycemia) were surveyed for gastrointestinal symptoms using the Diabetes Bowel Symptom Questionnaire. Logistic regression analyses were applied to identify risk factors for gastrointestinal symptoms. Results: Of the overall study population, 18.6% reported at least one gastrointestinal symptom, without a significant difference between subjects with normoglycemia (17.7%), prediabetes (19.7%) and diabetes (20.1%). In all three groups, lower gastrointestinal symptoms, particularly diarrhea and constipation, were the most frequent. There was an interaction between age (≥65 years) and diabetes on the prevalence of at least one gastrointestinal symptom (p = 0.01) and of constipation (p = 0.004), with these being most frequent in subjects with diabetes aged ≥ 65 years. After multivariable adjustment, female gender and older age were associated with increased odds of at least one gastrointestinal symptom, specifically lower gastrointestinal symptoms. Older age was also associated with an increase in upper gastrointestinal symptoms. Conclusions: Gastrointestinal symptoms are common in Chinese community-dwelling adults with and without diabetes. Females, and the elderly with diabetes, are at an increased risk of symptoms. Refereed/Peer-reviewed