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This study aims to develop and validate a novel prognostic model to estimate overall survival (OS) in nasopharyngeal carcinoma (NPC) patients based on clinical features and blood biomarkers. We assessed the model's incremental value to the TNM staging system, clinical treatment, and Epstein‐Barr virus (EBV) DNA copy number for individual OS estimation. We retrospectively analyzed 519 consecutive patients with NPC. A prognostic model was generated using the Lasso regression model in the training cohort. Then we compared the predictive accuracy of the novel prognostic model with TNM staging, clinical treatment, and EBV DNA copy number using concordance index (C‐index), time‐dependent ROC (tdROC), and decision curve analysis (DCA). Subsequently, we built a nomogram for OS incorporating the prognostic model, TNM staging, and clinical treatment. Finally, we stratified patients into high‐risk and low‐risk groups according to the model risk score, and we analyzed the survival time of these two groups using Kaplan–Meier survival plots. All results were validated in the independent validation cohort. Using the Lasso regression, we established a prognostic model consisting of 13 variables with respect to patient prognosis. The C‐index, tdROC, and DCA showed that the prognostic model had good predictive accuracy and discriminatory power in the training cohort than did TNM staging, clinical treatment, and EBV DNA copy number. Nomogram consisting of the prognostic model, TNM staging, clinical treatment, and EBV DNA copy number showed some superior net benefit. Based on the model risk score, we split the patients into two subgroups: low‐risk (risk score ≤ −1.423) and high‐risk (risk score > −1.423). There were significant differences in OS between the two subgroups of patients. Similar results were observed in the validation cohort. The proposed novel prognostic model based on clinical features and serological markers may represent a promising tool for estimating OS in NPC patients., 1. Currently, the TNM staging system is not adequate for prognosis without considering other clinicopathological factors or serum biomarkers. 2. In this study, we adopt a new algorithm to establish a novel prognostic model based on clinical features and blood biomarkers, which showed better predictive accuracy than traditional TNM staging, clinical treatment, and EBV DNA. 3. The prognostic model represents a promising signature for estimating OS in NPC patients.

The miglitol intermediate, 6-(N-hydroxyethyl)-amino-6-deoxy-α-l-sorbofuranose (6NSL), is catalyzed from N-2-hydroxyethyl glucamine (NHEG) by resting cells of Gluconobacter oxydans. One of the key factors limiting 6NSL production was the availability of oxygen during both cell cultivation and biotransformation of NHEG to 6NSL. Based on G. oxydans/pBBR1-sldAB-pqqABCDE-tldD (G. oxydans/AB-PQQ), the Vitreoscilla hemoglobin (VHb) was heterologously expressed in G. oxydans to enhance oxygen transfer efficiency and improve 6NSL production. The recombinant G. oxydans/AB-PQQ-VHb displayed higher biomass and NHEG oxidation activity than the control stain. The transcription levels of respiratory chain-related enzyme genes in G. oxydans/AB-PQQ-VHb exhibited up-regulation, indicating that the presence of VHb promoted the respiration. The dissolved oxygen (DO) concentration for cell cultivation was optimized in a 5-L stirred bioreactor. At a DO concentration of 20%, the maximum volumetric oxidation activity of NHEG of G. oxydans/AB-PQQ-VHb in the stirred bioreactor reached 168.3 ± 3.2 U/L. Furthermore, the biotransformation of NHEG to 6NSL using G. oxydans/AB-PQQ-VHb was carried out under different oxygen tensions to investigate the effect of oxygen on 6NSL production. Finally, up to 87.5 ± 5.9 g/L 6NSL was accumulated in the reaction mixture within 16 h when the DO was controlled at 30%.

Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract. Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and belongs to environmental endocrine disruptors (EDCs). It can be entered the human body which is harmful to health. The relationship between DEHP and AR is still inconclusive. This study aims to investigate the effect of environmental pollutants DEHP on AR. By examining DEHP metabolites in the urine of AR patients and building an AR model. 24 BALB/c mice were used as the study subjects, and ovalbumin (OVA) and DEHP (3 mg/kg/body) were used for intragastric administration. They were divided into control group, DEHP group, OVA group and OVA + DEHP group. Examination, behavioral scoring, inflammatory factor testing, oxidative stress testing, detection of aryl hydrocarbon receptor (AhR) and signaling pathways CYP1A1 and CYP1B1 related proteins and mRNA. The concentrations of 3 metabolites of DEHP (MEHHP, MEOHP, and MEHP) in urine of AR patients were higher. And HE-staining showed that for the control group, many chronic inflammatory cell infiltration and nasal mucosal destruction were observed in the OVA + DEHP group and were more severe than the OVA group. Allergic symptom scores were obtained from sneezing, scratching, number of scratching, and nose flow. The scores of the OVA group and the OVA + DEHP group were higher than 7 points. Serum ELISA and nasal mucosal oxidative stress tests are more serious in the OVA + DEHP group. The expression of AhR protein and its mRNA was increased in the DEHP group, OVA group and OVA + DEHP group. The OVA + DEHP group was more significant in the OVA group and DEHP group. And the mRNAs of the AhR-related signaling pathways CYP1A1 and CYP1B1 were also more prominent in the OVA + DEHP group. DEHP may aggravate its inflammatory response through the AhR pathway closely related to the environment. When combined with OVA, DEHP can further aggravate the OVA-induced nasal inflammatory response and make the nasal cavity have undergone severe changes, and many inflammatory cells have infiltrated. DEHP has shown an adjuvant effect, and the AhR-related signaling pathways CYP1A1 and CYP1B1 may be critical.

The chemoenzymatic synthesis of heparin, through a multienzyme process, represents a critical challenge in providing a safe and effective substitute for this animal-sourced anticoagulant drug. D-glucuronyl C5-epimerase (C5-epi) is an enzyme acting on a heparin precursor, N-sulfoheparosan, catalyzing the reversible epimerization of D-glucuronic acid (GlcA) to L-iduronic acid (IdoA). The absence of reliable assays for C5-epi has limited elucidation of the enzymatic reaction and kinetic mechanisms. Real time and offline assays are described that rely on 1D 1H NMR to study the activity of C5-epi. Apparent steady-state kinetic parameters for both the forward and the pseudo-reverse reactions of C5-epi are determined for the first time using polysaccharide substrates directly relevant to the chemoenzymatic synthesis and biosynthesis of heparin. The forward reaction shows unusual sigmoidal kinetic behavior, and the pseudo-reverse reaction displays nonsaturating kinetic behavior. The atypical sigmoidal behavior of the forward reaction was probed using a range of buffer additives. Surprisingly, the addition of 25 mM each of CaCl2 and MgCl2 resulted in a forward reaction exhibiting more conventional Michaelis–Menten kinetics. The addition of 2-O-sulfotransferase, the next enzyme involved in heparin synthesis, in the absence of 3′-phosphoadenosine 5′-phosphosulfate, also resulted in C5-epi exhibiting a more conventional Michaelis–Menten kinetic behavior in the forward reaction accompanied by a significant increase in apparent Vmax. This study provides critical information for understanding the reaction kinetics of C5-epi, which may result in improved methods for the chemoenzymatic synthesis of bioengineered heparin.

Existing industrial fermentations for Gluconobacter oxydans require a rich nitrogen source, which results in a relatively high production cost. In present study, amino acids utilization from yeast extract (YE) (20 g·L−1) was investigated, revealing that glutamate is disproportionately utilized, and consequently becomes a rate-limiting factor for the activity of membrane-bound sorbitol dehydrogenase (mSLDH). Additional supplementation of glutamate (0.1%) improved the abundance of coenzyme pyrroloquinoline quinone (PQQ) by 1.51-fold. Meanwhile, enzyme activity of mSLDH was improved by 1.21-fold, which was mainly dependent on the induction of PQQ. Partial substitution of YE (15 g·L−1) with glutamate (2 g·L−1) as nitrogen source was tested in G. oxydans fermentations and the thus-obtained resting-cells exhibited an high mSLDH activity towards the miglitol precursor N-2-hydroxyethyl-glucamine with an increased productivity (59.2 vs. 42.1 mg· (g DCW)-1 h-1) and an equally high yield (81.56% vs. 80.35%) compared with cells fermented with 25 g·L−1 YE. Taken together, the results provide a feasible strategy for economical fermentation of G. oxydans in achieving high mSLDH activity for biotransformation applications in large-scale.

Background Relaxin is a small peptide hormone that regulates extracellular matrix remodeling and reduces fibrosis in a number of organs. Little is known about its impact on chronic rhinosinusitis with nasal polyps (CRSwNP); thus, we aimed to determine the expression of human H2 relaxin (relaxin-2) and its role in tissue remodeling in CRSwNP. Methods Patients were enrolled and divided into the following groups: CRS with NP (CRSwNP; n = 20), CRS without NP (CRSsNP; n = 20), and controls (n = 15). Tissue samples were analyzed by Masson trichrome staining for collagen, while the location and expression of relaxin-2, transforming growth factor beta 1 (TGF-β1), and phosphorylated (p) Smad2/Smad3 were analyzed by immunohistochemistry and Western blot. The expression of relaxin-2, Smad2, Smad3, and TGF-β1 mRNA was tested by quantitative polymerase chain reaction (qPCR). Ex vivo NP were treated with relaxin-2 (n = 15) or TGF-β1 (n = 15). Collagen type I (collagen I), relaxin-2, and TGF-β1 levels in the culture supernatants were examined by enzyme-linked immunosorbent assay, while pSmad2/Smad3 in culture pellets was analyzed by Western blot, and the expression of Smad2 and Smad3 mRNA was tested by qPCR. Results The collagen, relaxin-2, TGF-β1, and pSmad2/Smad3 protein expression levels were significantly decreased in the CRSwNP group compared with the CRSsNP group ( P Conclusions The antifibrotic effects of relaxin-2 may play a role in tissue remodeling in CRSwNP, but the detailed mechanism deserves further study.

Allergic rhinitis (AR) is a common upper airway allergic disease caused by allergens triggering a type 2 immune response. The imbalance of CD4+ T cell subsets is the essential immunological feature of AR, which is mainly characterized by the predominance of T helper (Th) 2 cells. Recent studies indicated that the anti-inflammatory factor interleukin (IL)-37 is involved in the immune regulation of AR. However, the mechanism of IL-37 acts on AR has not been fully elucidated. Thus, we sought to assess the protective role of IL-37 in AR and further explore the possible mechanism. An ovalbumin (OVA)-induced AR murine model was established. After IL-37 treatment, the allergic symptoms (sneezes and nasal rubbings), nasal mucosal infiltration with eosinophils, and serum IgE production were found significantly attenuated. For CD4+ T cell subsets, the proliferation and differentiation of Th2 and Th17 cells were restrained. The relevant effector cytokines of IL-4, IL-5, IL-6, and IL-17a protein expression and transcription factors GATA3 and RORγt mRNA levels were obviously decreased. However, IL-37 had no significant effect on Th1 and Treg response including in IFN-γ, IL-10, T-bet, and Foxp3 expression. Furthermore, IL-37 was found down-regulated the STAT6, STAT3, phospho-STAT6, and phospho-STAT3 expression. In conclusion, IL-37 alleviates allergic inflammation in AR possibly through repressing STAT6 and STAT3 signaling pathways.

Although vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulate the 3D structures and predict the B cell epitopes on the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches and validate epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induce antibody production, six of these are immunodominant epitopes in individuals, and 23 are conserved within SARS-CoV-2, SARS-CoV, and bat coronavirus RaTG13. We find that the immunodominant epitopes of individuals with domestic (China) SARS-CoV-2 are different from those of individuals with imported (Europe) SARS-CoV-2, which may be caused by mutations on the S (G614D) and N proteins. Importantly, we find several epitopes on the S protein that elicit neutralizing antibodies against D614 and G614 SARS-CoV-2, which can contribute to vaccine design against coronaviruses., Graphical Abstract, Highlights • B cell epitopes of SARS-CoV-2 are obtained using structure-based approaches • The predicted epitopes effectively induce robust antibody responses • D614 and G614 SARS-CoV-2 display different immunodominant epitopes • Epitopes on S protein elicit D614 and/or G614 SARS-CoV-2-neutralizing antibodies, Lu et al. predict and validate B cell epitopes on the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches. The immunodominant epitopes vary between D614 and G614 SARS-CoV-2. The epitopes on the S protein elicit neutralizing antibodies against D614 and G614 SARS-CoV-2.

Traditional composting of kitchen waste (KW) is cost- and time-intensive, requiring procedures of collection, transport and composing. Consequently, the direct in-situ reduction of KW via treatment at the point of collection is gaining increasing attention. However, high oil content of KW causes separation and degradation issues due to its low bioavailability and the hydrophobicity, and therefore greatly limiting the direct application of in-situ methods for mass reduction. To overcome this, a bacterial consortium of Pseudomonas putida and Bacillus amyloliquefaciens was constructed, which exhibited a synergistically improved oil degrading ability for lipase-catalyzed hydrolysis, fatty acids β-oxidation, biosurfactant production and surface tension reduction, and the degradation ratio reached 58.96% within 48 h when the initial KW oil concentration was 8.0%. The in-situ aerobic digestion of KW was further performed in a 20-L stirred-tank reactor, the content of KW oil (34.72 ± 2.05% of total solids, w/w) was rapidly decreased with a simultaneous increase in both lipase activity and in microbial cell numbers, and the degradation ratio reached 57.38%. The synergetic effect of the two strains including B. amyloliquefaciens and P. putida promoted the decomposition process of KW oil, which also paved the way for an efficient degradation strategy to support the application potential of in-situ microbial reduction of KW.

6-(N-hydroxyethyl)-amino-6-deoxy- l -sorbofuranose (6NSL), a key precursor in the synthesis of miglitol, is produced from N-2-hydroxyethyl-glucamine (NHEG) by the regioselective oxidation of Gluconobacter oxydans. The limitation of PQQ biosynthesis became a bottleneck for improvement of PQQ-dependent D -sorbitol dehydrogenase (mSLDH) activity. Five expression plasmids were constructed for the co-expression of the pqqABCDE gene cluster and the tldD gene on the basis of pBBR1-gHp0169-sldAB in G. oxydans to increase the biosynthesis of PQQ. The G. oxydans/pGA004, in which pqqABCDE and tldD were expressed as a cluster under the control of gHp0169 promoter, showed the optimal performance. The intracellular PQQ concentration and specific activity of mSLDH in cells increased by 79.3 % and 53.7 %, respectively, compared to that in G. oxydans/pBBR-sldAB. Then, the repeated batch biotransformation of NHEG to 6NSL by G. oxydans/pGA004 was carried out. Up to 75.0 ± 3.0 g/L of 6NSL production with 94.5 ± 3.6 % of average conversion rate of NHEG to 6NSL was achieved after four cycles of run. These results indicated that G. oxydans/pGA004 with high productivity had great potential for 6NSL production in industrial bioprocess.

Asthma is a chronic and heterogeneous disease characterised by airway inflammation and intermittent airway narrowing. The key obstacle in the prevention and treatment of asthma has been our incomplete understanding of its aetiology and biological mechanisms. The ras homolog family member A (RhoA) of the Rho family GTPases has been considered to be one of the most promising and novel therapeutic targets for asthma. It is well known that RhoA/Rho‐kinases play an important role in the pathophysiology of asthma, including airway smooth muscle contraction, airway hyper‐responsiveness, β‐adrenergic desensitisation and airway remodelling. However, recent advances have suggested novel roles for RhoA in regulating allergic airway inflammation. Specifically, RhoA has been shown to regulate allergic airway inflammation through controlling Th2 or Th17 cell differentiation and to regulate airway remodelling through regulating mesenchymal stem cell (MSC) differentiation. In this review, we evaluate the literature regarding the recent advances in the activation of RhoA/Rho‐kinase, cytokine and epigenetic regulation of RhoA/Rho‐kinase, and the role of RhoA/Rho‐kinase in regulating major features of asthma, such as airway hyper‐responsiveness, remodelling and inflammation. We also discuss the importance of the newly identified role of RhoA/Rho‐kinase signalling in MSC differentiation and bronchial epithelial barrier dysfunction. These findings indicate the functional significance of the RhoA/Rho‐kinase pathway in the pathophysiology of asthma and suggest that RhoA/Rho‐kinase signalling may be a promising therapeutic target for the treatment of asthma., We evaluate recent advances in cytokine and epigenetic regulation of RhoA/Rho‐kinase and the role of RhoA/Rho‐kinase in regulating major clinical features of asthma, such as airway hyper‐responsiveness, remodelling and inflammation. The newly identified roles of RhoA/Rho‐kinase signalling in mesenchymal stem cell differentiation and bronchial epithelial barrier dysfunction are also discussed. We suggest that RhoA/Rho‐kinase signalling may be a promising therapeutic target for the treatment of asthma.

An extremely halophilic archaeon, strain ZY8T, was isolated from a rock salt of Yunnan salt mine. It was able to grow at 12–30% (w/v) NaCl (optimum, 15–20%), pH 7.0–9.0 (optimum, pH 8.5), and 20–45 °C (optimum, 42 °C). Sequence similarity search of its 16S rRNA gene showed that strain ZY8T belonged to the genus Halorubrum, and it is closely related to species of H. aethiopicum SAH-A6T (98.6%), H. aquaticum EN-2T (98.6%), and H. halodurans Cb34T (98.5%), respectively. Strain ZY8T contained phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and phosphatidylglycerol sulfate as its major phospholipids, and a sulfated diglycosyl diether as its major glycolipid. The DNA G+C content was 66.7 mol%. DNA–DNA relatedness between strains ZY8T and closely related species were far below 70%. Based on the phenotypic and phylogenetic analyses, it is proposed that strain ZY8T represents a novel species of the genus Halorubrum, for which the name Halorubrum glutamatedens sp. nov. is proposed. The type strain is ZY8T (=CGMCC 1.16026T=NBRC 112866T).

Objectives Allergic rhinitis (AR), a common chronic inflammatory disease in the upper airways. The prevalence of AR in children seems to be increasing recently, and the most significant causes of the increase are thought to be changes in environmental factors, especially air pollution. However, we could not find any meta-analysis on the risk of air pollution exposure on the prevalence of AR in childhood. The aim of this research was to carry out a meta-analysis on the results of recent studies (21 s t century) to present valid information about exposure to air pollution and risk of prevalence of childhood AR. Methods PubMed, Science, Google Scholar, Elsevier and MDPI web database were searched up to January 1, 2000 to February 28, 2018. Including of air pollution and AR in childhood related to the observation of literature. Meta-analysis, study quality assessment, heterogeneity analysis and publication bias test were using Stata-MP 14.1 and Review Manager version 5.3 software. Results 13 studies will be included in the meta-analysis (8 cross-sectional studies, 5 cohort studies). Exposure to NO2 (OREurope = 1.031, 95%CI [1.002,1.060], P = 0.033; ORAsia = 1.236, 95%CI [1.099,1.390], P = 0.000; ORoverall = 1.138, 95%CI [1.052,1.231], P = 0.001); Exposure to SO2 (OREurope = 1.148, 95%CI [1.030,1.279], P = 0.012; ORAsia = 1.044, 95%CI [0.954,1.142], P = 0.352; ORoverall = 1.085, 95%CI [1.013,1.163], P = 0.020); Exposure to PM10 (OREurope = 1.190, 95%CI [1.092,1.297], P = 0.000; ORAsia = 1.075, 95%CI [0.995,1.161], P = 0.066; ORoverall = 1.125, 95%CI [1.062,1.191], P = 0.000); Exposure to PM2.5 (OREurope = 1.195, 95%CI [1.050,1.360], P = 0.007; ORAsia = 1.163, 95%CI [1.074,1.260], P = 0.000; ORoverall = 1.172, 95%CI [1.095,1.254], P = 0.000). Conclusions Exposed to air pollution probable is a risk of prevalence of childhood AR. And the prevalence of AR will be increase when exposed to NO2, SO2, PM10 and PM2.5, but maybe the relationship between SO2/PM10 and prevalence of AR are not closely in Asia.

Allergic rhinitis (AR) is a chronic inflammatory airway disease that is caused by an abnormal T cell response. T helper (Th)-17 cells and Th2 cells are the CD4+ T cell subsets implicated in the pathogenesis of AR. The suppression of excessive responses of these Th17 and Th2 cells has been reported to be an effective therapeutic approach to treat AR patients, and continuous efforts are being undertaken to find new methods to modulate the function of these cells. Recent studies have shown that IL-1R8 and its ligand IL-37 negatively regulate the immune response. In this study, we investigated the immunomodulatory the roles of IL-37/IL-1R8 axis in AR patients. We found that IL-1R8 expression was very low on dendritic cells (DCs) and resting CD4+ T cells but increased strongly on CD4+ T cells following T cell activation. Furthermore, IL-1R8 expression on CD4+ T cells was markedly higher in AR patients than in healthy controls. The IL-1R8 ligand IL-37 could act on CD4+ T cells to inhibit IL-17 and IL-4 production but could not influence DC-induced IL-17- and IL-4-producing CD4+ T cell responses. Meanwhile, recombinant IL-37 (rIL-37) did not influence IL-6, IL-1β, and IL-10 production by DCs and expression of co-stimulatory molecules (including CD80, CD40, CD86 and HLA-DR) in DCs. Thus, IL-37 may regulate aberrant T cell immune response of allergic rhinitis mainly through CD4+ T cells, not DCs. The immunomodulatory roles of the IL-37/IL-1R8 axis indicate the therapeutic potential of this axis in AR.

Reconstitution of a selective demethylation system for lanosterol is desperately needed for more efficient synthesis of steroidal drugs. Sterol 14α-demethylase cytochrome P450 (CYP51) has been confirmed to catalyze sterol 14α-demethylation, an essential reaction in sterol biosynthesis. Herein, a putative CYP51 gene (RtCYP51) was mined from the complete genome sequence of Rhodococcus triatomae BKS 15-14. Its amino acid sequence showed 25–68% identity to other sterol 14α-demethylases, and contained a novel alanine-rich sequence at the C-terminus. Heterologous expression of the RtCYP51 gene in Escherichia coli (E. coli) yielded a ∼54 kDa recombination protein that exhibited a typical reduced CO-difference spectrum and a dissociation constant (Kd) of 2.93 μM for lanosterol. Furthermore, three exogenous electron donor systems, including Fdx-FdR (Acinetobacter sp.OC4 ferredoxin and ferredoxin reductase), Fld-FdR2 (E. coli flavodoxin and flavodoxin reductase) and NfFdR (Nocardia farcinica iron-sulfur containing NADPH-P450 reductase) were selected for coupling the electron-transfer from the coenzyme to RtCYP51. Fdx-FdR was found to be the most efficient electron donor and was also confirmed to support the lanosterol demethylation activity of RtCYP51 in vitro. Under the optimum molar ratio of RtCYP51/FdR/Fdx (1:2:10), RtCYP51 exhibited a relatively high turnover number of 0.63 min−1 (nmol metabolized lanosterol/min/nmol RtCYP51), compared with known bacterial CYP51s.

Introduction Endoscopic sinus surgery (ESS) has had many complications, e.g., synechia formation. This meta-analysis investigated the effect of a novel chitosan-based dressing on prevention of synechia and wound healing after ESS. Methods We systematically searched various medical literature data bases and included the randomized controlled trials (RCT) regarding the effect of novel chitosan-based dressing on ESS. The study outcomes included synechia, granulations, hemostasis, crusting scores, and infection. Results Six RCTs, which involved 337 patients, were included in the meta-analysis. Compared with control intervention after ESS, chitosan-based gel dressing substantially inhibited synechia (risk ratio [RR] 0.28 [95% confidence interval {CI}, 0.15–0.54]; p = 0.0001), improved granulations (RR 1.47 [95% CI, 1.07–2.03]; p = 0.02), and hemostasis (RR 1.47 [95% CI, 1.07–2.03]; p = 0.02) but demonstrated no effect on crusting scores (standard mean difference -0.41 [95% CI, -1.06 to 0.23]; p = 0.21) and infection (RR 0.88 [95% CI, 0.51–1.52]; p = 0.64). Conclusion Compared with control intervention, chitosan-based dressing was associated with significantly reduced synechia and with increased granulations and hemostasis but showed no influence on crusting and infection after ESS.

Gram-negative, spiral or curved rod-shaped cells of a bacterial strain, designated ZC80T, were isolated from a rock salt sample collected at Yunnan salt mine, China. Analysis of the strain's 16S rRNA gene sequence revealed a clear affiliation of this novel strain within the family Rhodospirillaceae . Strain ZC80T formed a robust cluster with Pelagibius litoralis CL-UU02T at a 16S rRNA gene sequence similarity level of 88.1 %. Strain ZC80T shared no more than 91.0 % 16S rRNA gene sequence similarity with the type strains of other species in the family Rhodospirillaceae . Strain ZC80T was able to grow in the presence of 2–15 % (w/v) NaCl, and grew at 10–50 °C and pH 6.0–10.0. The major fatty acids were C19 : 0 cyclo ω8c (41.3 %). The major isoprenoid quinone was ubiquinone 10 (Q-10). The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol and an unidentified aminolipid. The DNA G+C content of strain ZC80T was 60.8 mol%. On the basis of phylogenetic analyses and chemotaxonomic and physiological data, strain ZC80T is considered to represent a novel species of a new genus in the family Rhodospirillaceae , for which the name Marivibrio halodurans gen. nov., sp. nov. is proposed. The type strain of Marivibrio halodurans is ZC80T (=CGMCC 1.15697T=NBRC 112461T).

A non-motile, spherical or oval extremely halophilic archaeon, strain Y69T, was isolated from a brine of the Yunnan salt mine, China. Colonies on JCM 168 agar plate were round (1-2 mm in diameter), moist, and orange-pigmented. Phylogenetic analysis of the almost-complete 16S rRNA gene sequence showed that the isolate belonged to the species of the genus Halorubrum, with a close relationship to Halorubrum aidingense 31-hongT (98.5%), Halorubrum lacusprofundi ATCC 49239T (98.2%), and Halorubrum kocurii BG-1T (98.0%). The major polar lipids of strain Y69T were phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and a sulfated diglycosyl diether. Strain Y69T grew in 15-30% (w/v) NaCl. The temperature and pH ranges for growth were 25-50 °C and 6.5-9.0, respectively. Optimal growth occurred at 20% (w/v) NaCl, 42 °C, and pH 8.0. Mg2+ was required for growth. The DNA G+C content was determined to be 65.1 mol% by the thermal denaturation method. DNA-DNA hybridization values between strain Y69T and the closely related species were lower than 70%. Based on the data presented in this study, strain Y69T represents a novel species for which the name Halorubrum salsamenti sp. nov. is proposed. The type of the strain is Y69T (=CGMCC 1.15455T = JCM 31270T).

Allergic rhinitis (AR) is a common inflammatory disease of the upper airway. Recent evidence suggests that gene‑gene interactions between tumor necrosis factor receptor superfamily 4 (TNFSF4) and B cell lymphocyte kinase (BLK) may have a synergistic effect on T and B cells in determining immunologic aberration, via the nuclear factor‑κB pathway. The present study was performed to evaluate the potential association between specific single nucleotide polymorphisms (SNPs) in the TNFSF4 and BKL genes with susceptibility to AR in Chinese subjects. A population‑based case‑control study was performed in 600 Chinese AR patients and 700 controls. Blood was drawn for DNA extraction, and 9 SNPs (6 in TNFSF4 and 3 in BKL genes) were selected and genotyped. The TNFSF4 SNPs rs1234314 and rs1234315, and the BLK SNPs rs13277113 and rs1600249 were observed to occur in different frequencies between the AR patients and the controls. The CC (rs1234314, rs1234315) and AA (rs1600249, rs13277113) genotypes provided protective effects against AR, whereas the AG (rs13277113) genotype presented a risk factor for AR. The haplotypes ACC in the rs1234313‑rs1234314‑rs1234315 block and GA in the rs2254546‑rs13277113 block significantly decreased the risk of AR, whereas the GGT and AG haplotypes served protective roles. SNP interaction analysis further indicated that there may be synergistic effects among the selected sets of polymorphisms. The present study suggests a novel association between specific TNFSF4 and BLK gene polymorphisms and AR risk, highlighting their potential utility as genetic biomarkers for AR susceptibility in a Chinese Han population.

Two extremely halophilic archaea, strains D90T and D93, were isolated from underground salt deposits of Yunnan salt mine, China. Both strains were pleomorphic or short rods, non-motile, Gram-negative and required 1.7 M NaCl for growth, with optimum at 3.4 M. Mg2+ was not required for growth. Multiple copies of the 16S rRNA gene were obtained for both strains. Sequence similarity analysis of 16S rRNA genes revealed that strains D90T and D93 were closely related to Halobaculum magnesiiphilum MGY-184T and Halobaculum gomorrense DSM 9297T with the sequence similarity between 96.2–98.1 %. The sequence similarity of the rpoB′ gene between strain D90T and Halobaculum gomorrense JCM 9908T was 94.1 %. The DNA G+C contents of strains D90T and D93 were 65.9 and 67.6 mol%, respectively. The major polar lipids of both strains were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and glycolipid. The DNA–DNA relatedness value between strains D90T and D93 was 90.1±0.5 %, while that between strain D90T and Halobaculum gomorrense JCM 9908T was 30.0±0.7 %. The comparison of physiological and biochemical characteristics, including the requirements of NaCl, Mg2+, pH, etc., differentiated strains D90T and D93 from Halobaculum magnesiiphilum MGY-184T and Halobaculum gomorrense JCM 9908T. Therefore, strains D90T and D93 represent a novel species of the genus Halobaculum , for which the name Halobaculum roseum sp. nov. is proposed. The type strain is D90T (=CGMCC 1.15501T=JCM 31273T).

Summary The prevalence of allergic rhinitis (AR) and asthma has been increasing, and the comorbidity rates of these diseases are very high. Here, 176 AR patients, 124 patients with comorbid AR and asthma (AR-A) and 206 healthy Chinese children as controls were included in a case–control study. Six single-nucleotide polymorphisms (SNPs), miR-146a (rs2910164, rs57095329 and rs6864584), miR-196a2 (rs11614913), miR-499 (rs3746444) and miR-149 (rs2292832), were genotyped. The prevalence of homozygous miR-149 (rs2292832) CC genotype and C allele were considerably increased in AR and AR-A patients, compared with the controls. AR-A group showed higher frequencies of CC genotype and C allele of rs2292832 than AR group. No significant difference in the genotypic and allelic frequencies of other miRNA SNPs was found between the groups. MiR-149 levels in peripheral blood mononuclear cells (PBMCs) were significantly lower in CC (variant type) cases compared with TT (wild-type) cases. In further experiments, PBMCs obtained from the healthy controls with CC, CT and TT genotypes were stimulated by house dust mite extracts, which led to a significant decrease in the levels of miR-149 in PBMCs obtained from CC and TT individuals. This decrease was more pronounced in CC compared with TT cases. Our results demonstrate that miR-149 rs2292832 variant is not only strongly associated with AR and AR-A, but it may lead to an increase in the susceptibility to allergies following the stimulation with an allergen, through the changes in miR149 expression. Additionally, AR patients with CC genotypes were shown to be more susceptible to asthma.

Objective: This study aimed to determine the aryl hydrocarbon receptor (AhR) and transforming growth factor beta 1 (TGF-β1) expression levels in chronic rhinosinusitis (CRS) and their possible correlation with allergic state and tissue remodeling. Methods: Patients were enrolled and divided into the following groups: CRS without nasal polyps (NP) without allergic rhinitis (AR) (CRSsNPsAR; n = 20), CRS with NP with AR (CRSwNPwAR; n = 20), CRS with NP without AR (CRSwNPsAR; n = 20), and controls (n = 15). Tissue samples were analyzed by Masson trichrome staining for collagen, while the location and expression of AhR and TGF-β1 were analyzed by immunohistochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blotting. Results: The collagen amounts as well as AhR and TGF-β1 mRNA and protein expression levels were significantly increased in the CRSsNPsAR group compared with the CRSwNP (CRSwNPsAR and CRSwNPwAR) samples (p < 0.01). However, higher collagen amounts (p < 0.05) and higher TGF-β1 (p < 0.05) but lower AhR expression levels (p < 0.05) were detected in the CRSwNPwAR versus the CRSwNPsAR patients. Both AhR and TGF-β1 expression were positively correlated with the collagen level in CRS samples (p < 0.01). Conclusions: Elevated AhR expression may be involved in the progression of tissue remodeling in CRSsNPsAR similar to TGF-β1 expression. Conversely, lower AhR expression may be involved in allergic reactions in CRSwNPwAR.

miR-511-3p, encoded by CD206/Mrc1, was demonstrated to reduce allergic inflammation and promote alternative (M2) macrophage polarization. Here, we sought to elucidate the fundamental mechanism by which miR-511-3p attenuates allergic inflammation and promotes macrophage polarization. Compared with WT mice, the allergen-challenged Mrc1(–/–) mice showed increased airway hyperresponsiveness (AHR) and inflammation. However, this increased AHR and inflammation were significantly attenuated when these mice were pretransduced with adeno-associated virus–miR-511-3p (AAV–miR-511-3p). Gene expression profiling of macrophages identified Ccl2 as one of the major genes that was highly expressed in M2 macrophages but antagonized by miR-511-3p. The interaction between miR-511-3p and Ccl2 was confirmed by in silico analysis and mRNA-miR pulldown assay. Further evidence for the inhibition of Ccl2 by miR-511-3p was given by reduced levels of Ccl2 in supernatants of miR-511-3p–transduced macrophages and in bronchoalveolar lavage fluids of AAV–miR-511-3p–infected Mrc1(–/–) mice. Mechanistically, we demonstrated that Ccl2 promotes M1 macrophage polarization by activating RhoA signaling through Ccr2. The interaction between Ccr2 and RhoA was also supported by coimmunoprecipitation assay. Importantly, inhibition of RhoA signaling suppressed cockroach allergen–induced AHR and lung inflammation. These findings suggest a potentially novel mechanism by which miR-511-3p regulates allergic inflammation and macrophage polarization by targeting Ccl2 and its downstream Ccr2/RhoA axis.

Asthma and allergic rhinitis (AR) frequently occur as comorbid diseases of the upper airways. Single-nucleotide polymorphisms (SNPs) in the TNFSF4 and FAM167A-BLK genes have recently been shown to be associated with various immune-related disorders.Our aim was to determine whether TNFSF4 or FAM167A-BLK polymorphisms confer genetic susceptibility to asthma and AR in a Han Chinese population.We performed a case-control study of 290 asthmatic children and 252 healthy controls. Nine SNPs in the TNFSF4 region (rs1234313, rs1234314, rs1234315, rsl 2039904, rs844648 and rsl 0912580) and the FAM167A-BLK region (rs2254546, rs13277113 and rs1600249) were detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.This study revealed that three SNPs in TNFSF4 (rsl 234313, rsl 234314 and rsl 234315) and two SNPs in FAM167A-BLK (rs2254546 and rsl 600249) were significantly correlated with asthma and AR, while SNP rsl600249 was associated with asthma without allergic rhinitis as a risk factor. Further, we demonstrated synergistic effects between the TNFSF4 and FAM167A-BLK SNPs.This study supports that the SNPs in TNFSF4 and FAM167A-BLK may be involved in asthma and AR gene risk in the Han Chinese cohort.

Exposure to cockroach allergen is a strong risk factor for developing asthma. Asthma has been associated with allergen-induced airway epithelial damage and heightened oxidant stress. In this study, we investigated cockroach allergen–induced oxidative stress in airway epithelium and its underlying mechanisms. We found that cockroach extract (CRE) could induce reactive oxygen species (ROS) production, particularly mitochondrial-derived ROS, in human bronchial epithelial cells. We then used the RT2 Profiler PCR array and identified that cyclooxygenase-2 (COX-2) was the most significantly upregulated gene related to CRE-induced oxidative stress. miR-155, predicted to target COX-2, was increased in CRE-treated human bronchial epithelial cells, and was showed to regulate COX-2 expression. Moreover, miR-155 can bind COX-2, induce COX-2 reporter activity, and maintain mRNA stability. Furthermore, CRE-treated miR-155−/− mice showed reduced levels of ROS and COX-2 expression in lung tissues and PGE2 in bronchoalveolar lavage fluid compared with wild-type mice. These miR-155−/− mice also showed reduced lung inflammation and Th2/Th17 cytokines. In contrast, when miR-155−/− mice were transfected with adeno-associated virus carrying miR-155, the phenotypic changes in CRE-treated miR-155−/− mice were remarkably reversed, including ROS, COX-2 expression, lung inflammation, and Th2/Th17 cytokines. Importantly, plasma miR-155 levels were elevated in severe asthmatics when compared with nonasthmatics or mild-to-moderate asthmatics. These increased plasma miR-155 levels were also observed in asthmatics with cockroach allergy compared with those without cockroach allergy. Collectively, these findings suggest that COX-2 is a major gene related to cockroach allergen–induced oxidative stress and highlight a novel role of miR-155 in regulating the ROS–COX-2 axis in asthma.

In our continuous chemical investigation on the marine-derived fungus Dichotomomyces cejpii F31-1, two new polyketides dichocetides B-C (1, 2), two new alkaloids dichotomocejs E-F (3, 4), and three known fumiquinozalines: scequinadoline A (5), quinadoline A (6), and scequinadoline E (7) were discovered from the culture broth and the mycelium in the culture medium, by the addition of l-tryptophan and l-phenylalanine. Their chemical structures were established by one dimensional (1D), two dimensional (2D) nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-MS) data. Among them, scequinadoline A (5) exhibited significant inhibitory activity against dengue virus serotype 2 production by standard plaque assay, equivalent to the positive control andrographlide. Scequinadoline A (5) possesses the potential for further development as a dengue virus inhibitor.

Objectives Asthma and allergic rhinitis (AR) frequently occur as comorbid diseases of the upper airways. Single-nucleotide polymorphisms (SNPs) in the FCRL3 and FCRL5 genes have recently been shown to be associated with various immune-related disorders. This study evaluated the association of FCRL3 and FCRL5 polymorphisms with asthma and allergic rhinitis (AR) in a Han Chinese population. Methods Seven single nucleotide polymorphisms (SNPs) of the FCRL3 and FCRL5 were genotyped in 300 asthmatic children, and 206 healthy unrelated individuals using PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Genotyping was validated by direct sequencing. Results Our results showed that the frequencies of the rs6692977 CT genotype and T allele within FCRL5 were significantly higher in asthma with comorbid AR compared to healthy controls (Bonferroni-corrected p (Pc) = 3.75 × 10−6; Pc = 0.006, respectively), whereas these of the CC genotype and C allele were significantly lower (Pc = 4.15 × 10−5; Pc = 0.006, respectively). The frequencies of the rs7528684 A allele (Pc = 1.80 × 10−3) and the rs10489678 G allele (Pc = 0.04) within FCRL3 were higher in asthma with comorbid AR than in controls. However, no differences in the tested genetic polymorphisms were detected between asthma and healthy individuals. Conclusion This study identified novel SNPs in FCRL3 and FCRL5 significantly associated with the risk for asthma with comorbid AR in the Chinese population. The genetic variants may play role in the development of the asthma phenotype in children with asthma.

Particulate matter (PM) is one of the most important environmental issues in China. This study aimed to explore the correlation between PM2.5 and airway inflammation in healthy rats. The PM2.5 group was given an intranasal instillation of PM2.5 suspension on 15 consecutive days, and each received oral saline from day 16 to 90. The BV intervention group was treated as the PM2.5 exposure group, except that BV instead of saline was given daily. A histopathologic examination was performed to evaluate the airway inflammation. The prevalence and function of Th1/Th2/Treg/Th17 cells were detected by flow cytometry and ELISA. The expression of AhR was detected by western blot and real-time PCR. We found that epithelial damage and increased infiltration of inflammatory cell were present in the airways after PM2.5 exposure; there was an immune imbalance of Th cells in the PM2.5 group; the expression of AhR was increased in the airways after PM2.5 exposure. In the PM2.5 + BV group, we demonstrated alleviated immune imbalance and reduced inflammatory cell infiltration in the airways. Our study showed that exposure to PM2.5 induced airway inflammation. The imbalance of Th1/Th2/Treg/Th17 in PM2.5-induced airway inflammation might be associated with activation of the AhR pathway. Oral BV reduces PM2.5-induced airway inflammation and regulates systemic immune responses in rats.

Adaptable exploitation of the catalytic potential of membrane-bound d-sorbitol dehydrogenase (mSLDH) from Gluconobacter oxydans is desperately needed in the industrial-scale production of miglitol. In the present study, a carbonyl group-dependent colorimetric quantification method was developed for the assay of miglitol key intermediate 6-(N-hydroxyethyl)-amino-6-deoxy-α-l-sorbofuranose (6NSL), and a high-throughput screening process of positive mutants was processed. Combined with several rounds of ultraviolet irradiation mutagenesis and screening procedure, a positive mutant strain G. oxydans ZJB16009 was obtained with significant increase in mSLDH catalytic activity by 1.5-fold, which exhibited an extremely accelerated uptake rate of d-sorbitol, and the fermentation time was significantly shortened from 22 to 11 h. In a 5-L biotransformation system, 60 g/L substrate N-2-hydroxyethyl glucamine (NHEG) was catalyzed by the resting cells of the mutant strain within 36 h and accumulated 53.6 g/L 6NSL, showing a 33.6% increase in the product yield. Therefore, it was indicated that the established high-throughput screening method could provide a highly efficient platform for the breading of G. oxydans strain for the industrial biosynthesis of miglitol intermediate 6NSL.

Ergosterol is the predominant nature sterol constituent of plasma membrane in Saccharomyces cerevisiae. Herein, the biosynthetic pathway of ergosterol was proposed to be metabolically engineered for the efficient production of ergosta-5,7-dien-3β-ol, which is the precursor of vitamin D4. By target disruption of erg5, involved in the end-steps of post-squalene formation, predominantly accumulated ergosta-5,7-dien-3β-ol (4.12 mg/g dry cell weight). Moreover, the rate-limiting enzymes of ergosta-5,7-dien-3β-ol biosynthesis were characterized. Overexpression of Hmg1p led to a significant accumulation of squalene, and induction of Erg1p/Erg11p expression raised the yield of both total sterols and ergosta-5,7-dien-3β-ol with no obvious changes in growth behavior. Furthermore, the transcription factor allele upc2-1 was overexpressed to explore the effect of combined induction of rate-limiting enzymes. Compared with an obviously enhanced yield of ergosterol in the wild-type strain, decreases of both the ergosta-5,7-dienol levels and the total sterol yield were found in Δerg5-upc2-1, probably due to the unbalanced NADH/NAD+ ratio observed in the erg5 knockouts, suggesting the whole-cell redox homeostasis was also vital for end-product biosynthesis. The data obtained in this study can be used as reference values for the production of sterol-related intermediates involved in the post-squalene biosynthetic pathway in food-grade S. cerevisiae strains.

Background Numbers of mesenchymal stem cells (MSCs) are increased in the airways after allergen challenge. Ras homolog family member A (RhoA)/Rho-associated protein kinase 1 (ROCK) signaling is critical in determining the lineage fate of MSCs in tissue repair/remodeling. Objectives We sought to investigate the role of RhoA/ROCK signaling in lineage commitment of MSCs during allergen-induced airway remodeling and delineate the underlying mechanisms. Methods Active RhoA expression in lung tissues of asthmatic patients and its role in cockroach allergen–induced airway inflammation and remodeling were investigated. RhoA/ROCK signaling–mediated MSC lineage commitment was assessed in an asthma mouse model by using MSC lineage tracing mice (nestin-Cre; ROSA26-EYFP). The role of RhoA/ROCK in MSC lineage commitment was also examined by using MSCs expressing constitutively active RhoA (RhoA-L63) or dominant negative RhoA (RhoA-N19). Downstream RhoA-regulated genes were identified by using the Stem Cell Signaling Array. Results Lung tissues from asthmatic mice showed increased expression of active RhoA when compared with those from control mice. Inhibition of RhoA/ROCK signaling with fasudil, a RhoA/ROCK inhibitor, reversed established cockroach allergen–induced airway inflammation and remodeling, as assessed based on greater collagen deposition/fibrosis. Furthermore, fasudil inhibited MSC differentiation into fibroblasts/myofibroblasts but promoted MSC differentiation into epithelial cells in asthmatic nestin-Cre; ROSA26-EYFP mice. Consistently, expression of RhoA-L63 facilitated differentiation of MSCs into fibroblasts/myofibroblasts, whereas expression of RhoA-19 switched the differentiation toward epithelial cells. The gene array identified the Wnt signaling effector lymphoid enhancer–binding factor 1 (Lef1) as the most upregulated gene in RhoA-L63–transfected MSCs. Knockdown of Lef1 induced MSC differentiation away from fibroblasts/myofibroblasts but toward epithelial cells. Conclusions These findings uncover a previously unrecognized role of RhoA/ROCK signaling in MSC-involved airway repair/remodeling in the setting of asthma.

The Erg28p protein is localized to the endoplasmic reticulum, where it acts as a scaffold to tether the C-4 demethylase complex involved in the sterol biosynthesis pathway of Saccharomyces cerevisiae. However, due to the challenges involved in characterizing the interactions of membrane proteins, the precise region of Erg28p that is responsible for the assembly of this enzyme complex remains unknown. To address this question, mutants with serial truncations in the C-terminus of Erg28p were constructed based on a topology prediction of its transmembrane domain. Sterol profiles demonstrated that intermediates involved in the stepwise removal of the two C-4 methyl groups from the tetracyclic sterol ring were accumulated in the ERG28Δ135-447 strain. Homologous alignment of Erg28p further identified a highly conserved 10-amino acid sequence (63LS/QARTFGT/LWT72) within the truncated region of ERG28Δ136-273. Complementation of the BY4741/erg28 strain with the ScERG28Δ175-204 plasmid resulted both in a significant growth inhibition and a reduction of ergosterol biosynthesis compared with the plasmid without the Δ175-204 truncation. Furthermore, homology modeling of the Erg28p mutant indicated that the deletion of residues 63-72 significantly disrupted the 3D structure of the four parallel helices in Erg28p. Taken together, the data indicate that the region spanning amino acids 63-72 constitutes a key consensus motif within Erg28p that is required for sterol C-4 demethylation during ergosterol biosynthesis in S. cerevisiae.

Changes of circulating Follicular helper T (cTfh) cells existed in allergic rhinitis (AR) patients, and the severity of disease was associated with a more severe change of cTfh milieu. These results imply that cTfh cells may play a crucial role in the pathology of AR in Chinese patients.The aim of this study was to investigate the changes in cTfh cells in Chinese AR patients.Fifty-two patients were studied (32 in the AR group and 20 in the control group) for this research. The cTfh cell frequency and mRNA levels of transcription factor Bcl-6, B lymphocyte induced maturation protein 1 (BLIMP-1), and related cytokine IL-21 (IL-21 protein was also measured) were analyzed. Clinical severity was evaluated by total serum IgE levels, visual analog scale scores (VAS), and rhino-conjunctivitis quality-of-life questionnaires (RQLQ).The frequency of cTfh cells were elevated in AR groups vs healthy controls (p 0.05). Levels of IL-21 mRNA, Bcl-6 mRNA and the level of IL-21 protein were also significantly higher in the AR groups (p 0.05), whereas BLIMP-1 mRNA was decreased (p 0.05). Furthermore, positive correlations were identified between the frequency of cTfh cells and indicators of clinical severity (p 0.01).

BACKGROUND: Complex I is the first enzyme complex in the mitochondrial respiratory chain, responsible for generating a large fraction of energy during oxidative phosphorylation. Recently, it has been identified that complex I deficiency can result in increased inflammation due to the generation of reactive oxygen species by innate immune cells. As a reduction in complex I activity has been demonstrated in human stomachs with atrophic gastritis, we investigated whether complex I deficiency could influence Helicobacter pylori pathogenesis. MATERIALS AND METHODS: Ndufs6gt/gt mice have a partial complex I deficiency. Complex I activity was quantified in the stomachs and immune cells of Ndufs6gt/gt mice by spectrophotometric assays. Ndufs6gt/gt mice were infected with H. pylori and bacterial colonization assessed by colony-forming assay, gastritis assessed histologically, and H. pylori -specific humoral response quantified by ELISA. RESULTS: The immune cells and stomachs of Ndufs6gt/gt mice were found to have significantly decreased complex I activity, validating the model for assessing the effects of complex I deficiency in H. pylori infection. However, there was no observable effect of complex I deficiency on either H. pylori colonization, the resulting gastritis, or the humoral response. CONCLUSIONS: Although complex I activity is described to suppress innate immune responses and is decreased during atrophic gastritis in humans, our data suggest it does not affect H. pylori pathogenesis.

A novel, extremely halophilic archaeon, strain Y73T, was isolated from a salt mine in Yunnan, China. Colonies formed on solid medium were circular (2–3 mm in diameter), smooth, orange, glistening and convex (~1 mm in elevation). Cells were Gram-stain-negative, non-motile and pleomorphic. Mg2+ was required for growth (optimum at 0.05 M). Optimal growth was observed at 20 % (w/v) NaCl, 42–45 °C and pH 7.5–8.5 under aerobic conditions. 16S rRNA gene sequence comparison showed that strain Y73T was closely related to Halorubrum halophilum B8T (similarity: 98.1 %), Halorubrum lipolyticum 9-3T (97.9 %) and Halorubrum saccharovorum JCM 8865T (97.6 %). Levels of rpoB′ gene sequence similarity between strain Y73T and H. halophilum B8T, H. lipolyticum 9-3T and H. saccharovorum JCM 8865T were 93.6, 93.8 and 94.7 %, respectively. DNA–DNA relatedness between strain Y73T and H. halophilum B8T was 38.7±0.5 %, while that between strain Y73T and H. saccharovorum JCM 8865T was 31.0±0.9 % . The DNA G+C content of strain Y73T was 61.9 mol%. The major polar lipids of strain Y73T were phosphatidic acid, phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and phosphatidylglycerol sulfate as phospholipids, and sulfated diglycosyl diether-1 as glycolipid. The phenotypic, chemotaxonomic and phylogenetic properties suggest that strain Y73T represents a novel species, for which the name Halorubrum trueperi sp. nov is proposed. The type strain is Y73T (=CGMCC 1.15503T=JCM 31271T).

Interleukin‑37 (IL‑37), a novel member of the IL‑1 cytokine family has been identified as a natural suppressor of innate immunity and inflammatory responses. The present study aimed to determine the expression of IL‑37 in peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis (AR), and examine the possible immunosuppressive effect of IL‑37 on inflammatory mediators and CD4+ T cells in the pathogenesis of AR. The expression levels of IL‑37 were determined in PBMCs from 39 patients with AR and 43 controls using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis and flow cytometry. Cytokines in the supernatants of the PBMCs and CD4+ T cells, which were stimulated with lipopolysaccharide in the presence or absence of IL‑37, were assayed using enzyme‑linked immunosorbent assays and RT‑qPCR analysis. The results showed that the patients with AR exhibited significantly decreased expression of IL‑37, and increased expression levels of interleukin (IL)‑1β and IL‑6 in PBMCs. Recombinant IL‑37 (rIL‑37) inhibited the production of IL‑1p and IL‑6, and enhanced the production of IL‑27 in PBMCs from the patients with AR and the control individuals. rIL‑37 also markedly decreased the expression of IL‑17 by CD4+ T cells in the patients with AR and controls. These results suggested that IL‑37 may be an important cytokine in the pathogenesis of AR. It may have a protective role in AR by inhibiting the production of proinflammatory cytokines and through suppressive regulation of the Th17 response.

Objectives: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Janus kinase 1(JAK1), a member of JAK family, has recently been found to participate in the immune response and the development of allergic airway disease. This study was performed to evaluate the potential association of JAK1 polymorphisms with AR in a Chinese Han population. Design and Methods: A case-control study was performed in 450 Chinese AR patients and 615 healthy controls. Three SNPs in the JAK1 gene, including rs3790532, rs310241 and rs2780815, were detected using a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Results: An association between SNPs rs310241 inthe JAK1 gene and AR in a Chinese Han population. However, no significant association was observed between rs3790532, rs2780815 polymorphisms and AR. For rs310241, the CC genotype and the C allele significantly increased the risk of AR. Furthermore, we found that the ACG haplotype in JAK1 gene was positively correlated with AR, while the GTG haplotype was associated with a significantly decreased risk of AR. Conclusion: This study indicates that JAK1 rs310241 C-related genotype and allele are likely involved in AR susceptibility, making them potentially useful genetic biomarkers for AR susceptibility in the Chinese Han population. DOI 10.12932/AP0630.34.2.2016

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with mast cell–mediated inflammation and heightened oxidant stress. Kynurenine (KYN), an endogenous tryptophan metabolite, can promote allergen-induced mast cell activation through the aryl hydrocarbon receptor (AhR). Objectives We sought to determine the role of the KYN/AhR axis and oxidant stress in mast cell activation and the development of CRSwNP. Methods We measured the expression of indoleamine 2,3-dioxygenase 1, tryptophan 2,3-dioxygenase, KYN, and oxidized calmodulin-dependent protein kinase II (ox-CaMKII) in nasal polyps and controls. KYN-potentiated ovalbumin (OVA)-induced ROS generation, cell activation, and ox-CaMKII expression were investigated in wild-type and AhR-deficient (AhR −/− ) mast cells. The role of ox-CaMKII in mast cell activation was further investigated. Results Nasal polyps in CRSwNP showed an increased expression of indoleamine 2,3-dioxygenase 1, tryptophan2,3-dioxygenase, and KYN compared with controls. AhR was predominantly expressed in mast cells in nasal polyps. Activated mast cells and local IgE levels were substantially increased in eosinophilic polyps compared with noneosinophilic polyps and controls. Furthermore, KYN potentiated OVA-induced ROS generation, intracellular Ca 2+ levels, cell activation, and expression of ox-CaMKII in wild-type, but not in AhR −/− mast cells. Compared with noneosinophilic polyps and controls, eosinophilic polyps showed increased expression of ox-CaMKII in mast cells. Mast cells from ROS-resistant CaMKII MMVVδ mice or pretreated with CaMKII inhibitor showed protection against KYN-promoted OVA-induced mast cell activation. Conclusions These studies support a potentially critical but previously unidentified function of the KYN/AhR axis in regulating IgE-mediated mast cell activation through ROS and ox-CaMKII in CRSwNP.

Background Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Protein tyrosine phosphatase non-receptor 22 encoded by PTPN22 gene and cytotoxic T-lymphocyte associated 4 encoded by Ctla4 gene are associated with autoimmune diseases. Purpose This study was performed to evaluate the potential association of PTPN22 and Ctla4 single nucleotide polymorphisms (SNPs) with AR in a Chinese Han population. Methods A case-control study was performed in 783 Chinese AR patients and 811 healthy controls. Three SNPs in PTPN22 gene (rs2488457, rs1310182, and rs3789604) and 6 SNPs in Ctla4 gene (rs3087243, rs231779, rs11571302, rs11571315, rs231725, and rs35219727) were detected using a polymerase chain reaction–restriction fragment length polymorphism assay (PCR-RFLP). Results For PTPN22 gene, a significantly decreased prevalence of the rs2488457 CC genotype and C allele was found in AR patients. The frequencies of the rs1310182 CC genotype, CT genotype, and C allele were significantly associated with the risk of AR. For Ctla4 gene, a significantly increased prevalence of the rs11571302 AA genotype, CA genotype and A allele was noted in AR patients. Conclusion SNPs of PTPN22 and Ctla4 genes are significantly associated with the risk of AR in the Chinese Han population.