Development of lycopene-based whole-cell biosensors for the visual detection of trace explosives and heavy metals.

Residual explosives in conflicting zones have caused irreversible damage to human safety and the environment. Whole-cell biosensors can to detect remnants of buried explosives, such as 2,4-dinitrotoluene (DNT), a stable and highly volatile compound in explosives. However, all the reported whole-cell biosensors utilize fluorescence or luminescence as the biological markers, making their detection difficult in real minefields. Here, we presented a lycopene-based whole-cell biosensor in Escherichia coli to output visible signals in response to DNT, which can help in the visual detection of buried explosives. To construct the whole-cell biosensor, the DNT-responsive promoter yqjF was used as the sensing element, and the lycopene synthetic gene cassette crtEBI was served as the reporting element. Then, the metabolic flux for lycopene production was enhanced to improve the output signal of the whole-cell biosensor, and a terminator was utilized to reduce the background interference. The optimized biosensor LSZ05 could perceive at least 1 mg/L DNT. The DNT-specificity and robust performance of the biosensor under different environmental factors were confirmed. Our results showed that converting the biosensor into a lyophilized powder was an effective storage method. The biosensor LSZ05 could effectively detect DNT in two kinds of soil samples. The lycopene-based whole-cell biosensor could also be used to visually detect heavy metals. Our findings laid the foundation for visually detecting buried explosives in minefields, which was a valuable supplement to the reported biosensors. The methods used for optimizing the lycopene-based whole-cell biosensor, including the improvement of the output signal and reduction of background interference, were quite effective.

M2 Macrophages Upregulated by Allergen Exposure in Seasonal Allergic Rhinitis.

INTRODUCTION: Macrophages play a central role in balancing the immune response by switching phenotypes between the M1 and M2 profiles according to a delicate equilibrium. Based on a previous clinical trial (NCT03649139), this study aimed to evaluate the change in M2 macrophages during pollen exposure in seasonal allergic rhinitis (SAR). METHODS: Nasal symptom scores were recorded. Peripheral M2 macrophages were investigated according to cell surface markers, and M2-associated cytokine/chemokine release in serum and nasal secretion were assessed. In vitro pollen stimulation tests were performed, and polarized macrophage subsets were analyzed by flow cytometry. RESULTS: Compared to baseline, the percentage of peripheral CD163+ M2 macrophages in CD14+ monocytes increased during the pollen season (p < 0.001) and at the end of treatment (p = 0.004) in the SLIT group. The percentage of CD206+CD86- M2 cells in M2 macrophages during the pollen season was higher than that at baseline and at the end of SLIT. On the other hand, the percentage of CD206-CD86+ M2 cells in M2 macrophages significantly increased at the end of treatment in the SLIT group compared to baseline (p = 0.049), the peak pollen period (p = 0.017), and the placebo group (p = 0.0023). M2-associated chemokines CCL26 and YKL-40 were significantly increased during the pollen season in the SLIT group and remained higher at the end of SLIT than at baseline. Correspondingly, in vitro study demonstrated that Artemisia annua promoted M2 macrophage polarization in pollen-induced AR patients. CONCLUSION: Significant M2 macrophage polarization was promoted when patients with SAR were exposed to the allergen, either naturally exposed in pollen seasons or subjectively continuously exposed during the course of SLIT.

Short-term postoperative efficacy of steroid-eluting stents for eosinophilic chronic rhinosinusitis with nasal polyps: A randomized clinical trial.

BACKGROUND: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory clinical phenotype with a high symptom burden and relapse rate. Steroid-eluting stents are safe and effective for reducing polyp size, symptom burden, and the need for revision sinus surgery. In this study we aimed to evaluate the efficacy and safety of steroid-eluting stent implantation on the surgical outcomes of patients with ECRSwNP. METHODS: This prospective, multicenter, randomized, intrapatient-controlled trial recruited patients 18 to 65 years of age with ECRSwNP who required surgery. Ninety-eight patients were enrolled and randomly implanted with absorbable steroid-eluting stents containing mometasone furoate in one sinus at the end of surgery. All patients received standard postoperative care and follow-up. The primary outcome was the Lund-Kennedy endoscopic score within 12 weeks postsurgery. Secondary outcomes included nasal symptoms scores, nasal resistance, acoustic rhinometry, nasal nitric oxide levels, 3-dimensional volumetric computed tomography scores, and eosinophil counts in the ethmoid mucosa. RESULTS: Ninety-five patients completed the trial. At postoperative weeks 4, 8, and 12, the Lund-Kennedy scores were significantly lower on the treatment side than on the control side (all p < 0.01). Compared with the treatment side, the control side exhibited higher tissue eosinophilia at week 4 and higher volumetric, nasal obstruction, and total nasal symptom scores at postoperative week 8 (p = 0.011, p = 0.011, p < 0.01, and p = 0.001, respectively). No adrenal cortical suppression or serious side effects were observed. CONCLUSION: Steroid-eluting stents reduce postoperative sinus mucosal edema, and eosinophilic inflammation, with persistent effects after stent disintegration, and are a good supplementary postsurgical treatment in patients with ECRSwNP.

Selenium-Enriched Cardamine violifolia Increases Selenium and Decreases Cholesterol Concentrations in Liver and Pectoral Muscle of Broilers.

BACKGROUND: Supernutrition of selenium (Se) in an effort to produce Se-enriched meat may inadvertently cause lipid accumulation. Se-enriched Cardamine violifolia (SeCv) contains >80% of Se in organic forms. OBJECTIVES: This study was to determine whether feeding chickens a high dose of SeCv could produce Se-biofortified muscle without altering their lipid metabolism. METHODS: Day-old male broilers were allocated to 4 groups (6 cages/group and 6 chicks/cage) and were fed either a corn-soy base diet (BD, 0.13-0.15 mg Se/kg), the BD plus 0.5 mg Se/kg as sodium selenite (SeNa) or as SeCv, or the BD plus a low-Se Cardamine violifolia (Cv, 0.20-0.21mg Se/kg). At week 6, concentrations of Se and lipid and expression of selenoprotein and lipid metabolism-related genes were determined in the pectoral muscle and liver. RESULTS: The 4 diets showed no effects on growth performance of broilers. Compared with the other 3 diets, SeCv elevated (P < 0.05) Se concentrations in the pectoral muscle and liver by 14.4-127% and decreased (P < 0.05) total cholesterol concentrations by 12.5-46.7% and/or triglyceride concentrations by 28.8-31.1% in the pectoral muscle and/or liver, respectively. Meanwhile, SeCv enhanced (P < 0.05) muscular α-linolenic acid (80.0%) and hepatic arachidonic acid (58.3%) concentrations compared with SeNa and BD, respectively. SeCv downregulated (P < 0.05) the cholesterol and triglyceride synthesis-related proteins (sterol regulatory element binding transcription factor 2 and diacylglycerol O-acyltransferase 2) and upregulated (P < 0.05) hydrolysis and ß-oxidation of fatty acid-related proteins (lipoprotein lipase, fatty acid binding protein 1, and carnitine palmitoyltransferase 1A), as well as selenoprotein P1 and thioredoxin reductase activity in the pectoral muscle and/or liver compared with SeNa. CONCLUSIONS: Compared with SeNa, SeCv effectively raised Se and reduced lipids in the liver and muscle of broilers. The effect was mediated through the regulation of the cholesterol and triglyceride biosynthesis and utilization-related genes.

Effect of polyfluoroalkyl chemicals on the occurrence of urge urinary incontinence: a population-based study.

BACKGROUND: The artificial fluorinated group of compounds polyfluoroalkyl chemicals (PFCs) has been applied extensively in daily life for decades, and is present in food, drinking water, and indoor dust. The nephrotoxicity of PFCs has been widely studied for its characteristics of being mainly excreted through passing urine and affecting urodynamics. This work aimed to investigate the relationship between PFCs and the occurrence of urge urinary incontinence (UUI) in the United States (US) population. METHODS: There were 3157 eligible female participants retrieved from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2014. A logistic regression model was used to examine the relationship between UUI and eight kinds of PFCs. The dose-response relationship was investigated through restricted cubic spline analysis in this retrospective study. RESULTS: Of the 3157 eligible female participants, 913 self-reported a history of UUI. Total PFCs, perfluorohexane sulfonic acid (PFHS), 2-(N-methyl-perfluorooctane sulfonamido) acetate (MPAH), and perfluorononanoic acid (PFNA) correlated positively with the occurrence of UUI after adjusting for age, race, education, vigorous recreational activities, hypertension, diabetes, body mass index (BMI), creatinine, and estimated glomerular filtration rate (eGFR). Based on the results of sub-group analysis, the increasing tertiles contained odds ratios [OR; 95% confidence intervals (CI)] of 1.25 (95% CI, 1.03-1.51, p = 0.026) and 1.56 (95% CI, 1.29-1.89, p < 0.001) for total PFCs compared with the lowest tertile. The OR for PFHS, MPAH, and PFNA were 1.75, 1.71, and 1.41 respectively, in the highest tertile. CONCLUSION: This study investigated the relationship between PFCs and UUI in female and found total PFCs, PFHS, MPAH, and PFNA were positively correlated with the risk of UUI. The results will contribute to developing individualized treatment for female patients suffering UUI.

Effects of deoxynivalenol on the porcine growth performance and intestinal microbiota and potential remediation by a modified HSCAS binder.

The objectives of this study were to determine the effects of deoxynivalenol (DON) on growth performance and intestinal microbiota in weaning piglets, and potential efficacy of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce DON toxicity. Four groups of 21-day-old male piglets (n = 7/group) were fed either a control diet, or diet containing 1.0 or 3.0 mg/kg DON, or 3.0 mg/kg DON plus 0.05% modified HSCAS for 28 d. Compared to the control, dietary DON at 1.0 and/or 3.0 mg/kg reduced (P < 0.05) the body weight gain (16.0-60.8%) and feed intake (18.1-38.7%) during the whole experiment, and increased (P < 0.05) the feed/gain ratio (12.8-33.8%) between d 1-28. The body weight gain and feed intake were further decreased (P < 0.05) in 3.0 mg/kg DON in comparison to 1.0 mg/kg DON during d 15-28. DON exposure reshaped gut microbial structure by drastically affecting the abundance of several bacterial phyla, families and genera, including dysbiosis of Actinobacteria, Cyanobacteria, Firmicutes, and Proteobacteria in small intestine. Notably, dietary Amdetox™ supplementation alleviated the adverse effects of DON on growth performance of piglets and improved the intestinal flora disorder. Therefore, the current study has revealed that Amdetox™, the modified HSCAS binder, can alleviate DON-induced negative effects and could be used as a promising countermeasure for reducing DON toxicity.

Artemisia annua-sublingual immunotherapy for seasonal allergic rhinitis: A randomized controlled trial.

BACKGROUND: Artemisia annua is an important autumnal pollen allergen for seasonal allergic rhinitis (SAR) in northern China. To date, no study has investigated allergen immunotherapy with A annua. We aimed to investigate the efficacy and mechanisms underlying A annua-sublingual immunotherapy (SLIT). METHODS: This was a randomized, double-blind, placebo-controlled phase III clinical trial involving 71 SAR patients, randomized to SLIT with A annua extract (n = 47) or placebo (n = 24) for 32 weeks. Total nasal symptom score (TNSS; primary clinical end point) was evaluated at baseline (peak pollen phase (PPP) in the previous year), initiation of A annua-SLIT, 1st PPP during SLIT, end of SLIT and 2nd PPP during follow-up. Blood samples and nasal secretions were collected at beginning and after SLIT for assessment of T cells and inflammatory mediators. Safety was assessed according to adverse events (AEs) reported. RESULTS: Artemisia annua-SLIT significantly reduced TNSS to a greater level from baseline (from 9.45 ± 1.68 to 6.16 ± 2.27) than placebo (from 9.29 ± 2.09 to 9.05 ± 2.40) at the 1st PPP (P < .001) and sustained the improvement in symptoms throughout to the 2nd PPP. Preseasonal A annua-SLIT for 16 weeks significantly decreased Th2 cells, increased nTreg and Tr1 cells in blood; and increased cystatin 1 (CST1) in nasal secretion after 16 and 32 weeks compared with pretreatment. Overall, 17/47 patients experienced mild local AEs and 2 patients mild systemic AEs, after A annua-SLIT. CONCLUSION: Artemisia annua-SLIT is an efficacious and safe treatment in patients with A annua SAR.

Endotypes of chronic rhinitis: A cluster analysis study.

BACKGROUND: Chronic rhinitis (CR) is currently regarded as a syndrome, which presents as several endotypes. The aim of this study was to identify the CR endotype clusters and investigate the inflammatory patterns associated with the different endotypes. METHODS: A total of 259 CR patients and 20 control subjects were enrolled in this prospective study. Twelve clinical variables were analyzed using cluster analysis and five inflammatory variables were measured to investigate the inflammatory patterns associated with the different clusters. RESULTS: Six endotype clusters of CR were defined in the Chinese CR patients. Patients in cluster 1 (38.6%) were diagnosed as allergic rhinitis (AR) without asthma, and in cluster 2 (13.5%) as AR with asthma, with all demonstrating positive results for local eosinophils and high levels of local and serum IgE. Similarly, patients in cluster 3 (18.6%) were diagnosed as nonallergic rhinitis with eosinophilia syndrome (NARES) without asthma and in cluster 5 (5.0%) as NARES with asthma, with all demonstrating positive results for local eosinophils, and negative results for both local and serum IgE. Patients in cluster 4 (4.6%) were diagnosed as local allergic rhinitis and showed positive results for local eosinophils and local IgE, but negative results for serum IgE, whereas patients in cluster 6 (19.7%) were diagnosed as idiopathic rhinitis because of high symptoms scores, but negative findings for local eosinophils, local IgE, and serum IgE. CONCLUSIONS: Chinese CR patients may be clustered into six endotypes with different inflammatory patterns, which may help in delivering individualized treatment.

The impact of metformin use on survival in prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Metformin has been implicated to reduce the risk of prostate cancer (PCa) beyond its glucose-lowering effect. However, the influence of metformin on prognosis of PCa is often controversial. RESULTS: A total of 13 cohort studies encompassing 177,490 individuals were included in the meta-analysis. Data on overall survival (OS) and cancer-specific survival (CSS) was extracted from 8 and six studies, respectively. Comparing metformin users with non-metformin users, the pooled hazard ratios (HRs) for OS and CSS were 0.79 (95% confidence interval [CI] 0.63-0.98) and 0.76 (95% CI 0.57-1.02), respectively. Subgroup analyses stratified by baseline charcteristics indicated significant CSS benefits were noted in studies conducted in USA/Canada with prospective, large sample size, multiple-centered study design. Five studies reported the PCa prognosis for recurrence-free survival (RFS) and metformin use was significantly associated with patient RFS (HR 0.74, 95% CI, 0.58-0.95). METHODS: Relevant studies were searched and identified using PubMed, Embase and Cochrane databases from inception through January 2017, which investigated associations between the use of metformin and PCa prognosis. Combined HRs with 95% CI were pooled using a random-effects model. The primary outcomes of interest were OS and CSS. CONCLUSIONS: Our findings provide indication that metformin therapy has a trend to improve survival for patients with PCa. Further prospective, multi-centered, large sample size cohort studies are warranted to determine the true relationship.

Involvement of erbB4 and tumor marker genes in renal carcinoma regulatory network.

BACKGROUND: Renal carcinoma is a common urologic tumor, and there is no ideal tumor marker for clinical diagnosis except for imaging diagnosis. This study aims to screen the serum tumor markers closely related with the benign and malignant of renal carcinoma out and chart out the regulatory network that involves renal carcinoma-related genes. METHODS: Based on 96 pathologically diagnosed renal cancer patients, factors strongly linked to renal carcinoma character were selected using Fisher discriminant analysis. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to manipulate function annotation of erbB4 and the selected genes and pathway analysis. RESULTS: Four essential tumor markers CYFRA21-1, CA125, VHL and HIF-1ß were successfully screened out. Using GO and KEGG databases, the regulatory network of renal cancer cell escaping apoptosis was charted out on the basis of erbB4 signaling pathway. CONCLUSION: Serum tumor marker genes play a certain part in the genesis and development of renal carcinoma. We preliminarily illustrated the molecular mechanism of these markers to predict tumor, laying a foundation for further exploration in renal carcinoma.