Correlation of Differentially Expressed lncRNAs with Intestinal Flora Imbalance, Small Intestinal Permeability, and Glucose Uptake in T2DM Mice.

Diabetes is a major global health concern. This study aimed to investigate the correlation between differentially expressed lncRNAs in mice with type 2 diabetes mellitus (T2DM) and alterations in the intestinal flora and intestinal pathology. A T2DM mouse model was constructed by feeding mice a high-fat diet. Serum fat metabolism-related indices and insulin levels were biochemically detected. Serum inflammatory factors (IL-1ß, IL-6, TNF-α, IL-10) and endotoxin (LPS) were measured by ELISA. Histopathological changes in the small intestines of mice were observed by HE. The short-chain fatty acid (SCFA) content was analyzed using GC-MS. Analysis of altered intestinal flora in T2DM mice was performed using a 16sRNA sequencing assay. Differences in lncRNA expression profiles in small intestinal tissues were analyzed using RNA-seq assays. Spearman's correlation analysis was used to correlate the expression of candidate lncRNAs with changes in differential gut flora. Spearman's correlation analysis was used to analyze the correlation between the expression of candidate differentially expressed lncRNAs, small intestinal permeability, and glucose absorption. We found that serum levels of LPS, BUN, Scr, TC, TG, LDL-C, IL-1ß, IL-6, and TNF-α were elevated and levels of HDL-C, insulin, and IL-10 were decreased in T2DM mice. The ileal enterochromes of T2DM mice were disorganized and broken, the number of enterochromes was reduced, the local epithelial cells were necrotic, and the plasma membrane layer was locally absent. In addition, the protein expression of ZO-1 and occludin was decreased, and the protein expression of SGLT-1 and GLUT-2 was elevated in the model group compared to the control group. The levels of Acetic acid, Propionic acid and Butyric acid were decreased and the levels of Isobutyric acid and Isovaleric acid were increased, the abundance of beneficial bacteria was decreased and the abundance of harmful bacteria was increased in the feces of T2DM mice. RNA-seq identified nine differentially expressed lncRNAs (LINC00675, Gm33838, Gm11655, LOC6613926, LOC6613788, LOC6613791, LOC6613795, Arhgap27os3, and A330023F24Rik). In addition, we found significant correlations between differentially expressed lncRNAs and a variety of intestinal flora, as well as between small intestinal permeability and glucose absorption. A significant correlation was observed between differentially expressed lncRNAs in the intestinal tissues of T2DM mice and intestinal flora imbalance, small intestinal permeability, and glucose absorption.

Flexible molecularly imprinted fiber library for the metabolic analysis of bisphenol F and ecological risk evaluation.

Bisphenol F (BPF) has evoked global attentions due to its ubiquity and detrimental effects. Herein, a flexible molecularly imprinted fiber library was firstly proposed for the metabolic analysis of BPF in aquatic ecosystems. The library includes flexible single fibers and fiber arrays to precisely identify BPF and its metabolites with a wide range of polarities. Compared to commercial polyacrylate, the performance increased 11.56-570.98-fold. The adsorption capacity and the LogKow value were positively related. These arrays were used for the acquisition of environmental metabolomics data from aquatic ecosystems. In-depth data analysis showed that risk quotient was lower than 0.76, and bioaccumulation factor was lower than 2000 L/kg. Distribution concentration of BPF and its metabolites changed seasonally, and accumulation in sediment was much larger than that in surface water and hydrobionts. The risk is gradually increasing in sediment, but it does not reach high risk. The likelihood of bioaccumulation of parent compounds was greater than its metabolites. The library can be used in the metabolic diagnosis of pollutants with a broad range of polarities, providing a new method to acquire data for further ecological risk assessment, and offering a revolutionary strategy for environmental metabolomics investigation in aquatic ecosystems.

Post-imprinting modification of molecularly imprinted polymer for proteins detection: A review.

Inspired by protein post-translational modification (PTM), post-imprinting modification (PIM) has been proposed and developed to prepare novel molecularly imprinted polymers (MIPs), which are similar to functionalized biosynthetic proteins. The PIM involves site-directed modifications in the imprinted cavity of the MIP, such as introducing high-affinity binding sites and introducing fluorescent signal molecules. This modification makes the MIP further functionalized and improves the shortcomings of general molecular imprinting, such as single function, low selectivity, low sensitivity, and inability to fully restore the complex function of natural antibodies. This paper describes the characteristics of PIM strategies, reviews the latest research progress in the recognition and detection of protein biomarkers such as lysozyme, prostate-specific antigen, alpha-fetoprotein, human serum albumin, and peptides, and further discusses the importance, main challenges, and development prospects of PIM. The PIM technology has the potential to develop a new generation of biomimetic recognition materials beyond natural antibodies. It can be used in bioanalysis and other multitudinous fields for its unique features in molecule recognition.

Advances in Molecular Imprinting Technology for the Extraction and Detection of Quercetin in Plants.

Quercetin is a kind of flavonoid compound, which has antioxidative, anti-aging and anti-cancer effects, so it is of great importance to study the efficient extraction and highly sensitive detection of quercetin. Molecular imprinting technology has remarkable selectivity and resistance to complex matrix interference, which is often used for extracting quercetin. The methods of molecular imprinted solid phase extraction, molecularly imprinted microsphere extraction, molecularly imprinted electrochemical sensor recognition and molecularly imprinted composite material extraction of quercetin from plant samples were discussed in detail. This review provides valuable information on efficient and sensitive methods for separating and purifying quercetin in plants. It also provides a technical reference for further investigation of the separation and analysis of active ingredients in natural products.

State-of-the-art molecular imprinted colorimetric sensors and their on-site inspecting applications.

Molecular imprinted colorimetric sensors can realize visual semi-quantitative analysis without the use of any equipment. With the advantages of low cost, fast response, ease of handling, and excellent recognition ability, the molecular imprinted colorimetric sensor shows great application potential in the field of sample rapid assay. Molecular imprinted colorimetric sensors can be prepared in various forms to meet the needs of different sample determination, such as film, hydrogel, strip, and adsorption coating. In this review, the preparation methods for various types of molecularly imprinted colorimetric sensors are systematically introduced. Their applications in the field of on-site biological sample detection, drug detection, disease treatment, chiral substance detection and separation, environmental analysis, and food safety detection are introduced. The limitations encountered in the practical application are presented, and the future development directions prospect.

Paper-Based Molecular-Imprinting Technology and Its Application.

Paper-based analytical devices (PADs) are highly effective tools due to their low cost, portability, low reagent accumulation, and ease of use. Molecularly imprinted polymers (MIP) are also extensively used as biomimetic receptors and specific adsorption materials for capturing target analytes in various complex matrices due to their excellent recognition ability and structural stability. The integration of MIP and PADs (MIP-PADs) realizes the rapid, convenient, and low-cost application of molecular-imprinting analysis technology. This review introduces the characteristics of MIP-PAD technology and discusses its application in the fields of on-site environmental analysis, food-safety monitoring, point-of-care detection, biomarker detection, and exposure assessment. The problems and future development of MIP-PAD technology in practical application are also prospected.

[Efficacy of weight management combined with uvulopalatopharyngoplasty for obesityrelated obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To evaluate the clinical efficacy of weight management combined with pharyngoplasty for treatment of obesity-related obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Sixty obese patients with OSAHS were randomly assigned into the combined treatment group and control group (n=30) and received treatment with uvulopalatopharyngoplasty (UPPP) combined with cognitive-behavioral-psychological intervention for family weight management and uvulopalatopharyngoplasty with conventional management. At 3 and 6 months of the treatment, the patients were examined for changes in body mass index (BMI), neck circumference, waist circumference, Epworth Sleepiness Scale (ESS) scores, apnea-hypopnea index (AHI), the lowest oxygen saturation (LSaO2) and the percentage of time with oxygen saturation below 90% (CT90). RESULTS: After 6 months of treatment, the patients receiving the combined treatment showed significant reductions of BMI, neck circumference and waist circumference as compared with the measurements before treatment and with those in the control group (P < 0.01); these parameters showed no significant changes in the control group (P > 0.05). In the combined treatment group, the ESS score, CT90, AHI, and LSaO2 at 6 months were all superior to those in the control group (P < 0.01) and differed significantly cross different time points during the treatment, and their improvements were the most obvious after 6 months (P < 0.01). After 6 months of treatment, the combined treatment group had a similar cure rate with the control group (6.6% vs 7.1%; χ2=1.66, P > 0.05) but a significantly higher good response (defined as an AHI < 20 h-1 and an AHI reduction by ≥50%) rate (60% vs 35.7%; χ2=8.71, P < 0.01) and a higher overall response (a AHI reduction ≥50%) rate (83.3% vs 53.6%; χ2=10.62, P < 0.01). CONCLUSIONS: Weight management combined with uvulopalatopharyngoplasty can produce a good clinical efficacy for treatment of OSAHS with obesity, and the patients should have strengthened continuous family weight management while receiving surgical treatment.

Yeast ß-glucan alleviates cognitive deficit by regulating gut microbiota and metabolites in Aß1-42-induced AD-like mice.

Alzheimer's disease (AD) is a neurodegenerative disease that remarkably imposes a huge global public health burden. Yeast ß-glucans have been incorporated in functional foods and used in prophylactic applications owing to their biological effects. However, few studies had investigated the effects of yeast ß-glucans on neurodegenerative diseases. Here, gut microbiota and metabolites SCFAs were analyzed through high-throughput 16S rRNA gene sequencing and GC-MS, respectively. Results indicated that yeast ß-glucans could prominently shape the intestinal flora and produce SCFAs. Aß1-42-induced AD mice treated with small-molecular yeast ß-glucan (S-ß-Glu) or macro-molecular yeast ß-glucan (M-ß-Glu) exhibited evident alterations of the composition of the gut microbiota, especially in some beneficial bacteria and inflammatory-related bacteria such as Lactobacillus, Bifidobacterium, Desulfovibrio, Oscillibacter, Mucispirillum, Alistipes, Anaerotruncus, and Rikenella. M-ß-Glu regulated gut microbiota act as prebiotics better than S-ß-Glu. Correlation analysis demonstrated the key microbiota closely associated with AD-related pathologies and cognition. Moreover, M-ß-Glu and S-ß-Glu ameliorated neuroinflammation and brain insulin resistance (IR), which played a central role in the process of AD pathology. This study broadened the underlying applications of yeast ß-glucans as a novel dietary supplementation to prevent early-stage pathologies associated with AD by regulating gut microbiota and the potential mechanism might be ameliorating brain IR.

Association of plasma ß-amyloid 40 and 42 concentration with type 2 diabetes among Chinese adults.

AIMS/HYPOTHESIS: There is evidence for a bidirectional association between type 2 diabetes and Alzheimer's disease. Plasma ß-amyloid (Aß) is a potential biomarker for Alzheimer's disease. We aimed to investigate the association of plasma Aß40 and Aß42 with risk of type 2 diabetes. METHODS: We performed a case-control study and a nested case-control study within a prospective cohort study. In the case-control study, we included 1063 newly diagnosed individuals with type 2 diabetes and 1063 control participants matched by age (±3 years) and sex. In the nested case-control study, we included 121 individuals with incident type 2 diabetes and 242 matched control individuals. Plasma Aß40 and Aß42 concentrations were simultaneously measured with electrochemiluminescence immunoassay. Conditional logistic regression was used to evaluate the association of plasma Aß40 and Aß42 concentrations with the likelihood of type 2 diabetes. RESULTS: In the case-control study, the multivariable-adjusted ORs for type 2 diabetes, comparing the highest with the lowest quartile of plasma Aß concentrations, were 1.97 (95% CI 1.46, 2.66) for plasma Aß40 and 2.01 (95% CI 1.50, 2.69) for plasma Aß42. Each 30 ng/l increment of plasma Aß40 was associated with 28% (95% CI 15%, 43%) higher odds of type 2 diabetes, and each 5 ng/l increment of plasma Aß42 was associated with 37% (95% CI 21%, 55%) higher odds of type 2 diabetes. Individuals in the highest tertile for both plasma Aß40 and Aß42 concentrations had 2.96-fold greater odds of type 2 diabetes compared with those in the lowest tertile for both plasma Aß40 and Aß42 concentrations. In the nested case-control study, the multivariable-adjusted ORs for type 2 diabetes for the highest vs the lowest quartile were 3.79 (95% CI 1.81, 7.94) for plasma Aß40 and 2.88 (95% CI 1.44, 5.75) for plasma Aß42. The multivariable-adjusted ORs for type 2 diabetes associated with each 30 ng/l increment in plasma Aß40 and each 5 ng/l increment in plasma Aß42 were 1.44 (95% CI 1.18, 1.74) and 1.47 (95% CI 1.15, 1.88), respectively. CONCLUSIONS/INTERPRETATION: Our findings suggest positive associations of plasma Aß40 and Aß42 concentration with risk of type 2 diabetes. Further studies are warranted to elucidate the underlying mechanisms and explore the potential roles of plasma Aß in linking type 2 diabetes and Alzheimer's disease.

Single-Chain Variable Fragment Antibody of Vascular Cell Adhesion Molecule 1 as a Molecular Imaging Probe for Colitis Model Rabbit Investigation.

Vascular cell adhesion molecule-1 (VCAM-1) can be a promising target for colitis study because of its critical role in inflammation development. Single-chain variable fragment (scFv) antibody presents fast blood clearance when served as an imaging probe. We applied the probe of 99mTc-scFv-VCAM-1 to colitis rabbit to examine its imaging performance. The colitis model rabbit was prepared, and a typical inflammatory lesion was confirmed in the colon. The probe of 99mTc-scFv-VCAM-1 was synthesized and injected into the model animal before imaging examination. Scintigraphy detected colitis lesions in both SPECT planar and SPECT/CT fused images, with higher target-to-nontarget ratios in the model group (2.71 ± 0.31) than those in the control group (1.12 ± 0.10). Biodistribution study determined tracer uptake in different organs, and autoradiography (ARG) confirmed probe accumulation in colon lesions. The uptake ratio of the model colon to the control colon was 4.71 ± 0.61 in quantitative analysis of the ARG regions of interest. Stronger VCAM-1 expression in the model colon than that in the control colon was confirmed by western blotting and immunohistochemistry. Our imaging study indicates molecular imaging with scFv-VCAM-1 as a promising way for inflammatory bowel disease diagnosis and evaluation.

Interaction of estrogen receptor ß5 and interleukin 6 receptor in the progression of non-small cell lung cancer.

Numerous studies have shown that the estrogen receptor beta (ERß) and interleukin 6 receptor (IL-6R) had interaction in many tumors, including lung cancer. Previous studies found that ERß5 exhibits a different biological function compared with the other subtypes of ERß. Therefore, this study mainly explores the interaction between ERß5 and IL-6R in the progression of lung cancer. We found that the expression of ERß5, IL-6 and glycoprotein 130 (GP130) were significantly increased (P < 0.001) and the 5-year survival rate with the co-expression of ERß5 and GP130 is significantly lower (P = 0.0315) in non-small cell lung cancer (NSCLC) patients. The cell proliferation, invasion, and cell cycle were markedly increased, and the cell apoptotic was markedly inhibited with the concurrent action of ERß5 and IL-6 in A549 cells (P < 0.05). In addition, the expression of ERß5, GP130, p-AKT, and p-44/42 MAPK was also significantly increased in A549 cells (P < 0.05). These results indicate that ERß5 and GP130 can synergistically promote the progression of NSCLC and maybe combined as an independent prognostic factor in patients. In addition, these results also provide a theoretical basis for the combined targeting therapy of ERß5 and GP130 in NSCLC.

Investigation of inflammatory bowel disease risk factors in 4 families in central China.

The prevalence of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing markedly in China. The present study performed pedigree analysis of 4 families with a history of IBD and investigated the association of genetic and environmental factors with susceptibility to IBD. A total of 10 IBD patients (8 CD patients and 2 UC patients) and 90 family members were included in the present study. The clinical characteristics of familial subjects were compared with those of patients with sporadic IBD. Previously reported mutations, namely interleukin-10 receptor (IL10R)-A Thr84Ile, IL10RA Gly141Arg, IL10RB Trp159X, X-linked inhibitor of apoptosis (XIAP) Cys203Tyr, nucleotide-binding oligomerization domain-containing protein 2 (NOD2) Arg702Trp, NOD2 Gly908Arg and NOD2 Leu1007fsinsC, were screened in the patients with IBD, and selected demographic factors were compared between the patients and their unaffected family members. It was observed that single-gene and multi-gene inheritance patterns contributed to IBD in Chinese families. Based on data from the registry system, the ratio of patients with a family history of IBD was 1.25%, which was lower than that in the Western population. First-degree relatives were found to be more susceptible to IBD, and siblings were affected more frequently. Furthermore, the median age of diagnosis was younger in familial patients than in sporadic patients (29.0 vs. 36.0 for CD; 35.5 vs. 41.0 for UC). However, none of the 7 susceptibility loci were present in any of the familial patients. Immigration was a significant risk factor of IBD (odds ratio: 4.667; 95% confidence interval: 1.165-18.690; P=0.021). In conclusion, genetic heterogeneity exits between Chinese families with IBD and the Western population. The present findings suggest that genetic background and environmental factors serve a role in the pathogenesis of IBD.

Tumor necrosis factor-related apoptosis inducing ligand gene polymorphisms are correlated with gastric cancer in central China.

PURPOSE: To investigate the association of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) gene polymorphisms with gastric cancer in Chinese Han population in central China. METHODS: A total of 304 patients with gastric cancer confirmed by histopathology and 421 unrelated healthy controls were studied. Gene polymorphisms of TRAIL (G1525A and C1595T) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The frequency of the genotype carriers of TRAIL 1525A (GA + AA) and 1595T (CT + TT) was significantly lower in gastric cancer than in healthy controls (37.2% vs. 61.5%, P < 0.001, OR = 0.581, 95% CI 0.442 ~ 0.764; 36.2% vs. 62.0%, P < 0.001, OR = 0.570, 95% CI 0.433 ~ 0.750, respectively). Stratification analysis showed that both TRAIL 1525A (GA + AA) and 1595T (CT + TT) carriers were associated with poorly-differentiated gastric cancer compared to 1525GG genotype and 1595CC genotype (OR = 0.516, 95%CI 0.279 ~ 0.957, P = 0.026; OR = 0.395, 95%CI 0.207 ~ 0.753, P = 0.004, respectively). CONCLUSIONS: TRAIL G1525A and C1595T gene polymorphisms were significantly correlated with the susceptibility to gastric cancer in Chinese Han population in central China.

CCL25/CCR9 interactions regulate the function of iNKT cells in oxazolone-induced colitis in mice.

BACKGROUND: Natural killer T (NKT) cells share phenotypic and functional properties with both conventional natural killer cells and T cells. These cells might have an important role in the pathogenesis of ulcerative colitis (UC). The interaction of chemokine ligand 25 (CCL25) with chemokine receptor 9 (CCR9) is involved in gut-specific migration of leukocytes and induces regulatory T cells (Tregs) to migrate to the intestine in chronic ileitis. METHODOLOGY/FINDINGS: In UC patients, NKT receptor CD161, CCL25, and CCR9 expression levels were evaluated by qRT-PCR. A murine model of oxazolone-induced colitis was induced in BALB/c mice. The mRNA levels of NK1.1, CCL25 and CCR9, and pro-inflammatory cytokines in mice were evaluated. The CCR9 expression on Type I or invariant NKT (iNKT) cells, and the iNKT cells chemotaxis are observed according to flow cytometry. NKT receptor CD161, CCL25 and CCR9 expression levels were significantly increased in UC patients. And, the mRNA expression levels of NK1.1, CCL25 and CCR9 were increased in oxazolone-induced colitis in mice. The production of pro-inflammatory cytokines was significantly increased, especially interleukin 4 (IL-4), IL-10 and IL-13. We observed significantly increased CCR9 expression on iNKT cells. Furthermore, we found an increased iNKT population and enhanced chemotaxis during oxazolone-induced colitis. CONCLUSIONS/SIGNIFICANCE: Our study suggests that CCL25/CCR9 interactions may promote the induction and function of iNKT cells during oxazolone-induced colitis. These findings may have important implications for UC treatment and suggest a role for CCR9 inhibitors.

Exome sequencing identifies DLG1 as a novel gene for potential susceptibility to Crohn's disease in a Chinese family study.

BACKGROUND: Genetic variants make some contributions to inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). More than 100 susceptibility loci were identified in Western IBD studies, but susceptibility gene has not been found in Chinese IBD patients till now. Sequencing of individuals with an IBD family history is a powerful approach toward our understanding of the genetics and pathogenesis of IBD. The aim of this study, which focuses on a Han Chinese CD family, is to identify high-risk variants and potentially novel loci using whole exome sequencing technique. METHODS: Exome sequence data from 4 individuals belonging to a same family were analyzed using bioinformatics methods to narrow down the variants associated with CD. The potential risk genes were further analyzed by genotyping and Sanger sequencing in family members, additional 401 healthy controls (HC), 278 sporadic CD patients, 123 UC cases, a pair of monozygotic CD twins and another Chinese CD family. RESULTS: From the CD family in which the father and daughter were affected, we identified a novel single nucleotide variant (SNV) c.374T>C (p.I125T) in exon 4 of discs large homolog 1 (DLG1), a gene has been reported to play multiple roles in cell proliferation, T cell polarity and T cell receptor signaling. After genotyping among case and controls, a PLINK analysis showed the variant was of significance (P<0.05). 4 CD patients of the other Chinese family bore another non-synonymous variant c.833G>A (p.R278Q) in exon 9 of DLG1. CONCLUSIONS: We have discovered novel genetic variants in the coding regions of DLG1 gene, the results support that DLG1 is a novel potential susceptibility gene for CD in Chinese patients.

Identification of Homer1 as a potential prognostic marker for intrahepatic cholangiocarcinoma.

BACKGROUND: The aim of the present study was to analyze whether Homer1 is a potential prognostic marker for intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: The expression of Homer1 in ICC tissue was detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated by Western blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. RESULTS: Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant difference between ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologic differentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion (p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1 revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expression of Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was an independent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63- 21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC. CONCLUSIONS: Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The current study shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection, and it provides an important basis for screening/treating high-risk patients.

Elevated risk of opportunistic viral infection in patients with Crohn's disease during biological therapies: a meta analysis of randomized controlled trials.

BACKGROUND: Biological agents have been widely used in the treatment of Crohn's disease (CD). These drugs carry the risk of excessive immunosuppression, indicating possible opportunistic infections including opportunistic viral infections, but no meta analysis has ever focused on this issue. PURPOSE: To evaluate whether there is an association between biological agents therapy and the risk of opportunistic viral infections and serious infections in patients with CD. METHODS: A search of online databases was performed and literature selection was carried out according to the inclusion and exclusion criteria by reading titles, abstracts and full texts. Study heterogeneity and publication bias were assessed. Whether to choose a fixed effects model or a random effects model depended on the result of heterogeneity test. RESULTS: There was a statistical significance in opportunistic viral infection events between the biological agents group and the placebo group. However, our analysis didn't observe statistically significant differences between the two groups when combined analyses were carried out for herpes zoster and herpes simplex separately. A risk trend in the biological agents group was observed in the analysis for herpes zoster. More analyses aimed at the outcome measures and including influenza and serious infection were carried out separately, but no statistical significance was found in them. CONCLUSION: Biological agents use might increase the risk of opportunistic viral infections in patients with CD, but not the risk of herpes simplex and serious infections. More randomized controlled trials (RCTs) are needed to draw the conclusion of whether they could elevate the risk of herpes zoster.

High intestinal and systemic levels of interleukin-23/T-helper 17 pathway in Chinese patients with inflammatory bowel disease.

Interleukin-23/T-helper 17 (IL-23/Th17) pathway plays a key role in the pathogenesis of inflammatory bowel disease (IBD), but little is known about its expression in Chinese population. In this study, we investigated the mRNA and protein levels of IL-12p40, tumor necrosis factor-like cytokine 1A (TL1A), Janus kinase 2 (JAK2), and IL-23R both locally and systemically in Chinese IBD patients. Our results indicated that the mRNA levels of IL-12p40 and TL1A were increased in ulcerative colitis (UC) patients. Furthermore, serum IL-12p40 and TL1A levels were higher in active UC patients, especially in patients with disease course less than 1.25 years or initial onset. No correlation was found between the genotype and serum levels of IL-12p40 or TL1A in UC patients. Additionally, the mRNA and protein expression of JAK2 and IL-23R were increased in UC and Crohn's disease (CD) patients. Taken together, our results provided evidence that IL-23/Th17 pathway genes may represent important biomarkers of active stage of IBD and serve as novel therapeutic targets for IBD in Chinese population.

Fusion to chicken C3d enhances the immunogenicity of the M2 protein of avian influenza virus.

BACKGROUND: Current vaccines to avian influenzae virus (AIV), a highly contagious disease of birds, need to be constantly updated due to the high level of variation in the target antigens. Therefore, a vaccine that could induce broad cross protection against AIV is required. The M2 membrane protein is structurally conserved amongst AIV subtypes but tends in induce a poor immune response, whereas C3d has been shown in many species to enhance immunogenicity. In this study, we investigated the potential of M2-avian C3d fusion proteins to provide effective immunity. RESULTS: We fused chicken complement C3d to sM2 (M2 protein with the transmembrane region deleted) of AIV and expressed four fusion proteins, GST (Glutathione S-transferase tagged proteins in pGEX expression vector) -C3d-sM2, GST-C3d-L2-sM2, GST-C3d-L1-C3d-sM2 and GST-C3d-L1-C3d-L2-sM2 were used to immunize mice. In addition, Specific pathogen free (SPF) chickens were inoculated with the plasmids pcDNA-sM2, pcDNA-C3d-L1-C3d-L2-sM2, GST-sM2 and GST-C3d-L1-C3d-L2-sM2. The immune response was monitored by an enzyme-linked immunosorbent assay (ELISA) for sM2 antibody, and all the test animals were challenged with A/chicken/Bei Jing/WD9/98 (H9N2) virus. Results revealed that the anti-sM2 antibody in mice and chickens vaccinated with these proteins was higher than the nonfused forms of sM2, the GST-C3d-L1-C3d-L2-sM2 groups have conferred the highest 30% and 20% protection ratio in mice and chickens respectively. In addition, the pcDNA-C3d-L1-C3d-L2-sM2 also enhances the antibody responses to sM2 compared to pcDNA-sM2 in chickens, and acquired 13.3% protection ratio. CONCLUSION: These results indicated that chicken C3d enhanced the humoral immunity against AIV M2 protein either fused proteins expressed by the prokaryotic system or with the DNA vaccine. Nevertheless, in view of the poor protection ratio for these animals, we speculated that this is not a worthy developing of vaccine in these constructs.

A detection statistic for random-valued impulse noise.

This paper proposes an image statistic for detecting random-valued impulse noise. By this statistic, we can identify most of the noisy pixels in the corrupted images. Combining it with an edge-preserving regularization, we obtain a powerful two-stage method for denoising random-valued impulse noise, even for noise levels as high as 60%. Simulation results show that our method is significantly better than a number of existing techniques in terms of image restoration and noise detection.