DNA starvation/stationary phase protection protein of Helicobacter pylori as a potential immunodominant antigen for infection detection.

BACKGROUND: Application of chicken egg yolk immunoglobulin Y (IgY) for Helicobacter pylori (H. pylori, HP) has gained much interest in recent years. Comparing with for treatment, IgY may be more advantageous when used for H. pylori detection. METHODS: Nine strains of H. pylori with different genetic backgrounds were inactivated and used to immunize hens, respectively, for the preparation of polyclonal anti-H. pylori immunoglobulin Y (anti-HP IgY). The proteins of H. pylori with reactivity to anti-HP IgY were detected by Western Blot. The five protein bands that can be well recognized by anti-HP IgY of each group, and were prevalent in all nine strains were excised from SDS-PAGE gel, digested and identified by Nano-HPLC-MS/MS analysis. The potential of these identified proteins as antigen detection targets was then assessed by sequence analysis. RESULTS: Anti-HP IgY derived from each group of specific strain immunized hens can recognize self-strain and non-self-strain antigens well. Five immunodominant antigens were identified as chaperonin GroEL, flagellin A, urease subunit alpha, peroxiredoxin and DNA starvation/stationary phase protection protein. Sequences analysis showed that both peroxiredoxin and DNA starvation/stationary phase protection protein were present in all 1000 strains of H. pylori queried, and the amino acid sequences were highly conserved. The highest sequence consistency between the DNA starvation/stationary phase protection protein of H. pylori and non-Helicobacter organisms was 52.59%, and the consistent sites were scattered and there was no continuous long fragment consensus sequence. CONCLUSION: DNA starvation/stationary phase protection protein was identified as an immunodominant antigen of H. pylori and sequence analysis indicated that it could serve as a potential antigen target for the diagnosis of H. pylori infection.

A Mechanochromic and Vapochromic Luminescent Cuprous Complex Based on a Switchable Intramolecular π···π Interaction.

An in-depth study on a stimuli-responsive tetranuclear cuprous luminescent complex is reported and gives new insights into the origin and possible use of the observed stimuli-responsive luminescence. Its crystalline polymorphs with two different shapes are obtained by using different crystallization solvents and show distinct emissions, with one being blue emissive and the other being yellow emissive. Upon grinding, only the blue-emitting polymorph has a marked change in the emission color from blue to yellow, and its ground sample exhibits a yellow emission similar to that of the yellow-emitting polymorph. Interestingly, the yellow-emitting polymorph after exposure to acetone vapor can emit a blue emission and display luminescence mechanochromism similar to that of the blue-emitting polymorph. Single-crystal structural analyses of the two different polymorphs reveal the relationship between the mechanochromic luminescence and the geometrical configuration of the {Cu(µ-dppm)2Cu} unit and intramolecular "pyridyl/phenyl" π···π interactions, supported as well by their PXRD, FT-IR, TGA, and PL studies in various states and by TD-DFT analyses. The results demonstrate the different roles of switchable intramolecular π···π interactions and the geometrical configuration of the {Cu(µ-dppm)2Cu} unit in this stimuli-responsive luminescence and potential applications of such stimuli-responsive luminescence in optical sensing and anticounterfeiting encryption technologies and deepen the understanding of such stimuli-responsive luminescence originating from switchable intramolecular π···π interactions. In addition, it is clearly suggested that the rational utilization of switchable intramolecular π···π interactions is a feasible route for developing stimuli-responsive intelligent luminescent materials and devices.

Thermo-, Mechano-, and Vapochromic Dinuclear Cuprous-Emissive Complexes with a Switchable CH3CN-Cu Bond.

A thermo-, mechano-, and vapochromic bimetallic cuprous-emissive complex has been reported, and the origin and application of its tri-stimuli-responsive luminescence have been explored. As revealed by single-crystal structure analysis, thermo- and vapochromic luminescence adjusted by heating at 60 °C and CH3CN vapor fuming, accompanied by a crystalline-to-crystalline transition, is due to the breaking and rebuilding of the CH3CN-Cu bond, as supported by 1H nuclear magnetic resonance (NMR), Fourier-transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), thermogravimetry (TG), and time-dependent density functional theory (TD-DFT) analyses of the CH3CN-coordinated species [Cu2(µ-dppa)2(µ-η1(N)η2(N,N)-fptz)(CH3CN)](ClO4)·H2O (1) and its CH3CN-removed derivative [Cu2(µ-dppa)2(µ-η1(N)η2(N,N)-fptz)](ClO4)·H2O (2). Luminescence mechanochromism, mixed with a crystalline-to-amorphous transition where the initial crystalline is different for 1 and 2, is mainly assigned as the destruction of the CH3CN-Cu bonding and/or the O···HNdppa and OH···Ntriazolyl hydrogen bonds. It is also suggested that a rational use of switchable coordination such as weak metal-solvent bonding is a feasible approach to develop multi-stimuli-responsive luminescent materials and devices.

Rapid Identification of Four Fusarium spp. Complex by High-Resolution Melting Curve Analysis and their Antifungal Susceptibility Profiles.

Fusarium species are globally distributed filamentous ascomycete fungi that are frequently reported as plant pathogens and opportunistic human pathogens, leading to yield loss of crops, mycotoxin contamination of food and feed products as well as damage to human and livestock. Human infections of Fusarium spp. are difficult to treat due to broad antifungal resistance by members of this genus. Their role as disease-causing agents in crops and humans suggests a need for antifungal resistance profiles as well as a simple, rapid, and cost effective identification method. Fusarium strains were isolated from food and clinical samples. High-resolution melting curve (HRM) analysis was performed using specific primers targeting internal transcribed spacer (ITS) region, followed with evaluation of specificity and sensitivity. The antifungal susceptibility of four Fusarium species was studied using the Sensititre YeastOne method. HRM analysis revealed reproducible, unimodal melting profiles specific to each of the four Fusarium strains, while no amplification of the negative controls. The minimum detection limits were 100-120 copies based on a 2 µl volume of template. Clear susceptibility differences were observed against antifungal agents by different Fusarium isolates, with amphotericin B and voriconazole displayed strongest antifungal effects to all the tested strains. We developed a simple, rapid, and low-cost qPCR-HRM method for identification of four Fusarium spp. (F. oxysporum, F. lateritium, F. fujikuroi, and F. solani). The antifungal susceptibility profiles supplied antifungal information of foodborne and clinical Fusarium spp. and provided guidance for clinical treatment of human infections.

Astragalus polysaccharide (APS) attenuated PD-L1-mediated immunosuppression via the miR-133a-3p/MSN axis in HCC.

CONTEXT: Astragalus polysaccharide (APS) is a new tumour therapeutic drug, that has an inhibitory effect on a variety of solid tumours. Tumour cell immunosuppression is related to the up-regulation of programmed death ligand 1 (PD-L1). However, whether APS exerts its antitumor effect by regulating PD-L1 remains unclear. OBJECTIVE: To explore whether APS exerts its antineoplastic effect via regulating PD-L1-mediated immunosuppression in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: SMMC-7721 cells were subcutaneous injected into BALB/C mice for HCC model establishment. Mice were intraperitoneally injected with 100, 200 and 400 mg/kg APS for 12 days. Immunohistochemistry (IHC) was performed to assess CD8+ T cells' rate and PD-L1 level in HCC tissues. HCC cells were pre-treated with 0.1, 0.5 and 1 mg/mL APS for 4 h, then were treated with 10 ng/mL IFN-γ 24 h. PD-L1 level and cell apoptosis was detected by flow cytometry. PD-L1 and Moesin (MSN) proteins were measured by western blot. MiR-133a-3p and MSN mRNA levels were assessed by qRT-PCR. The targets of miR-133a-3p were predicted by starBase, and which was verified by dual-luciferase reporter assay. RESULTS: Our findings illustrated that APS dose-dependently inhibited HCC growth tested with IC50 values of 4.2 mg/mL, and IFN-γ-induced PD-L1 expression and attenuated PD-L1-mediated immunosuppression in HCC cells. APS attenuated PD-L1-mediated immunosuppression via miR-133a-3p in HCC cells. Besides, miR-133a-3p targeted to MSN, and MSN inhibited the antitumor effect of APS by maintaining the stability of PD-L1. Moreover, APS attenuated PD-L1-mediated immunosuppression via the miR-133a-3p/MSN axis. CONCLUSIONS: APS attenuated PD-L1-mediated immunosuppression via miR-133a-3p/MSN axis to develop an antitumor effect. APS may be an effective drug for HCC treatment.

Reversible Mechanochromic Luminescence of Tetranuclear Cuprous Complexes.

Mechanochromic luminescence materials have attracted rapidly growing interest. Nevertheless, the designed synthesis of such materials remains a challenge, and there have been few examples based on weak intramolecular interactions. Herein, we report a new approach for preparing mechanochromic luminescence materials of Cu(I) complexes, i.e., constructing a photoluminescence system that bears a large coplanar multinuclear Cu(I) unit showing weak intramolecular π···π interactions with the planar rings of the coordinated ligands in the molecule. Using it, a series of novel mechanochromic luminescent tetranuclear Cu(I) complexes have been successfully designed and synthesized. As revealed by single-crystal X-ray crystallography, these Cu(I) complexes share an identical {Cu4[µ3-η2(N,N),η1(N),η1(N)-pyridyltetrazole]2}2+ planar fragment whose coplanar pyridyl rings exhibit weak intramolecular π···π interactions with the phenyl rings of the coordinated phosphine ligands in the molecule. All of these Cu(I) complexes exhibit reversible mechanochromic luminescence, which can be attributed to the change in the rigidity of the molecular structure resulting from the disruption and restoration of intramolecular π···π interactions between the pyridyl and phenyl rings triggered by grinding and CH2Cl2 vapor, as supported by powder X-ray diffraction and Fourier transform infrared spectrometry. In addition, the results might provide a new route for developing mechanochromic luminescence materials of Cu(I) complexes for intelligent responsive luminescent devices.

Rapid identification of the Candida glabrata species complex by high-resolution melting curve analysis.

BACKGROUND: Candida glabrata is a common pathogen that causes invasive candidiasis. Among non-albicans Candida infections, C glabrata infections are associated with the highest fatality rates. Candida glabrata sensu stricto, Candida nivariensis, and Candida bracarensis have been identified and together form the C glabrata species complex. It is difficult to detect the two rare species by traditional laboratory methods. This study established a method for the rapid identification of members of the C glabrata species complex based on high-resolution melting curve (HRM) analysis and evaluated its practical application. METHODS: The internal transcribed spacer (ITS) region was used as target gene region to design specific primers. HRM analysis was performed with three subspecies of the C glabrata species complex and negative controls to test its specificity and sensitivity. To evaluate its practical application, the HRM technique was tested with clinical isolates, and the results were compared with the DNA sequencing results. RESULTS: Differences were detected among the melting profiles of the members of the C glabrata species complex. The negative controls were not amplified, indicating the high specificity of the method. The minimum detection limits of C glabrata sensu stricto, C nivariensis, and C bracarensis were approximately 1 × 101  copies/µL or less. The results of the HRM analysis of the clinical isolates were consistent with the DNA sequencing results. CONCLUSIONS: The HRM method is sensitive and can be used to rapidly identify the members of the C glabrata species complex. The method can allow early and targeted treatment of patients with invasive candidiasis.

Factors Associated With Colonoscopy Compliance Based on Health Belief Model in a Community-Based Colorectal Cancer Screening Program Shanghai, China.

Screening can help early detection of colorectal cancer (CRC) in the general population. However, colonoscopy compliance in screening program is low in China. The study aimed to identify factors associated with colonoscopy compliance based on Health Belief Model (HBM). An investigation was conducted in Huangpu District, Shanghai in 2015. High-risk individuals of CRC received an in-person interview with physicians to fill out a questionnaire. The questionnaires assessing predictors of colonoscopy compliance were collected, and status of colonoscopy participation was determined. Univariate and multiple logistic regression analyses were conducted. Among 2,568 high-risk population (20.68%), 531 subjects underwent colonoscopy. Participants with both risk assessment and fecal immunochemical test positive were most likely to undergo colonoscopy. Based on HBM, colonoscopy compliance was positively associated with higher perceived severity (odds ratio [OR] = 1.05, 95% confidence interval [CI] = [1.00, 1.10]). Higher perceived barriers (OR = 0.97, 95% CI = [0.94, 0.99]), without prior colonoscopy (OR = 0.35, 95% CI = [0.26, 0.47]), not knowing anyone who underwent colonoscopy before (OR = 0.74, 95% CI = [0.58, 0.96]), without health-care provider recommendation on colonoscopy (OR = 0.58, 95% CI = [0.44, 0.77]), and without psychosocial support from someone for colonoscopy (OR = 0.27, 95% CI = [0.21, 0.35]) were shown to be associated with colonoscopy noncompliance. The colonoscopy compliance was low in this CRC screening program in Shanghai, China. The influencing factors were positive results in primary screening, perceived severity, perceived barriers, personal or others' experiences in colonoscopy, health-care provider recommendation, and psychosocial supports. Effective education campaign and facilitated communication between health-care providers and high-risk population were suggested in the future interventions.

A Sublimable Dinuclear Cuprous Complex Showing Selective Luminescence Vapochromism in the Crystalline State.

A new sublimable dicopper(I) complex bearing 1,2-bis(diphenylphosphino)ethane and 5-trifluoromethyl-3-(2'-pyridyl)pyrazolate ligands has been designed and synthesized, and its crystalline solvated and nonsolvated compounds have also been obtained and investigated. It is shown that only the crystalline solvated compound exhibits reversible and selective luminescence vapochromism, arising from its unique "pyridyl/CH2Cl2/pyridyl" organic sandwich-like stacking arrangement revealed by X-ray crystallography, as supported by time-dependent density functional theory calculations. Additionally, the neutral Cu(I) complex has excellent thermal stability and sublimability, good solid-state luminescence properties, and TADF character, and it is suggested to be a good emitter for vapor-deposited organic light-emitting diodes.

Transport stress induces pig jejunum tissue oxidative damage and results in autophagy/mitophagy activation.

Pig transportation is associated with intestinal oxidative stress and results in destruction of intestinal integrity. Autophagy has been contributed to maintain cell homeostasis under stresses. The purpose of this study was to evaluate the effects of transport stress on morphology, intestinal mucosal barrier and autophagy/mitophagy levels in pig jejunum. A total of 16 finishing pigs were randomly divided into two groups. The control group was directly transported to the slaughterhouse and rested for 24 hr. The experimental groups were transported for 5 hr and slaughtered immediately. The results showed that transportation induced obvious stress responses with morphological and histological damage in jejunum accompanying with an elevated level of malondialdehyde (MDA; p < .05), endotoxin (LPS; p < .05), lactic dehydrogenase (LDH; p < .05) and a decreased level of serum superoxide dismutase (SOD; p < .05). Also, hemeoxy genase 1 (HO-1; p < .01) as well as tight junction protein (claudin-1 [p < .001], occludin [p < .05] and zonula occludens 1 [ZO-1; p < 0.05]) levels were attenuated in jejunum tissue, and NADPH oxidase 1 (NOX1; p < .01) mRNA expression was up-regulated. Further research indicated that transport stress could induce autophagy through increasing microtubule-associated protein light chain 3 (LC3; p < .05) and autophagy-related gene 5 (ATG5; p < .01) levels and suppressing p62 expression. Additionally, transport stress increased the protein levels of PTEN-induced putative kinase 1 (PINK1; p < .05) and Parkin (p < .05) which was associated with mitophagy. In conclusions, transport stress could induce the destruction of intestinal integrity and involve in the intestinal mucosal barrier oxidative damage, and also contribute to activation of autophagy/mitophagy.

Cryo-EM Visualization of an Active High Open Probability CFTR Anion Channel.

The cystic fibrosis transmembrane conductance regulator (CFTR) anion channel, crucial to epithelial salt and water homeostasis, and defective due to mutations in its gene in patients with cystic fibrosis, is a unique member of the large family of ATP-binding cassette transport proteins. Regulation of CFTR channel activity is stringently controlled by phosphorylation and nucleotide binding. Structural changes that underlie transitions between active and inactive functional states are not yet fully understood. Indeed the first 3D structures of dephosphorylated, ATP-free, and phosphorylated ATP-bound states were only recently reported. Here we have determined the structure of inactive and active states of a thermally stabilized CFTR, the latter with a very high channel open probability, confirmed after reconstitution into proteoliposomes. These structures, obtained at nominal resolution of 4.3 and 6.6 Å, reveal a unique repositioning of the transmembrane helices and regulatory domain density that provide insights into the structural transition between active and inactive functional states of CFTR. Moreover, we observe an extracellular vestibule that may provide anion access to the pore due to the conformation of transmembrane helices 7 and 8 that differs from the previous orthologue CFTR structures. In conclusion, our work contributes detailed structural information on an active, open state of the CFTR anion channel.

Droplet Digital PCR-Based Detection of Clarithromycin Resistance in Helicobacter pylori Isolates Reveals Frequent Heteroresistance.

Chronic infection with Helicobacter pylori causes peptic ulcers and stomach cancer in a subset of infected individuals. While standard eradication therapy includes multiple antibiotics, treatment failure due to resistance is an increasing clinical problem. Accurate assessment of H. pylori antimicrobial resistance has been limited by slow growth and sampling of few isolates per subject. We established a method to simultaneously quantify H. pylori clarithromycin-resistant (mutant) and -susceptible (wild-type) 23S rRNA gene alleles in both stomach and stool samples using droplet digital PCR (ddPCR). In 49 subjects, we assessed the performance of these assays alongside clarithromycin MIC testing of up to 16 H. pylori isolates per subject and included both cancer (25 subjects) and noncancer (24 subjects) cases. Gastric ddPCR and H. pylori culture showed agreement with urea breath test (UBT) detection of infection in 94% and 88% of subjects, respectively, while stool ddPCR showed agreement with UBT in 92% of subjects. Based on MIC testing of 43 culture-positive cases, 20 subjects had only susceptible isolates, 14 had a mix of susceptible and resistant isolates, and 9 had only resistant isolates. ddPCR of gastric samples indicated that 21 subjects had only wild-type alleles, 13 had a mixed genotype, and 9 had only mutant alleles. Stool ddPCR detected mutant alleles in four subjects for which mutant alleles were not detected by stomach ddPCR, and no resistant isolates were cultured. Our results indicate that ddPCR detects H. pylori clarithromycin resistance-associated genotypes, especially in the context of heteroresistance.

Transmembrane helical interactions in the CFTR channel pore.

Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene affect CFTR protein biogenesis or its function as a chloride channel, resulting in dysregulation of epithelial fluid transport in the lung, pancreas and other organs in cystic fibrosis (CF). Development of pharmaceutical strategies to treat CF requires understanding of the mechanisms underlying channel function. However, incomplete 3D structural information on the unique ABC ion channel, CFTR, hinders elucidation of its functional mechanism and correction of cystic fibrosis causing mutants. Several CFTR homology models have been developed using bacterial ABC transporters as templates but these have low sequence similarity to CFTR and are not ion channels. Here, we refine an earlier model in an outward (OWF) and develop an inward (IWF) facing model employing an integrated experimental-molecular dynamics simulation (200 ns) approach. Our IWF structure agrees well with a recently solved cryo-EM structure of a CFTR IWF state. We utilize cysteine cross-linking to verify positions and orientations of residues within trans-membrane helices (TMHs) of the OWF conformation and to reconstruct a physiologically relevant pore structure. Comparison of pore profiles of the two conformations reveal a radius sufficient to permit passage of hydrated Cl- ions in the OWF but not the IWF model. To identify structural determinants that distinguish the two conformations and possible rearrangements of TMHs within them responsible for channel gating, we perform cross-linking by bifunctional reagents of multiple predicted pairs of cysteines in TMH 6 and 12 and 6 and 9. To determine whether the effects of cross-linking on gating observed are the result of switching of the channel from open to close state, we also treat the same residue pairs with monofunctional reagents in separate experiments. Both types of reagents prevent ion currents indicating that pore blockage is primarily responsible.

Luminescent Three- and Four-Coordinate Dinuclear Copper(I) Complexes Triply Bridged by Bis(diphenylphosphino)methane and Functionalized 3-(2'-Pyridyl)-1,2,4-triazole Ligands.

A new series of bimetallic Cu(I) complexes 1-5 triply bridged by a monoanionic or charge-neutral functionalized 3-(2'-pyridyl)-1,2,4-triazole in a µ-η1(N),η2(N,N) tridentate binding mode and two bis(diphenylphosphino)methane (dppm) ligands have been synthesized. Complexes 1-5 are singly or doubly charged dinuclear Cu(I) species with an eight-membered Cu2C2P4 ring of {Cu(µ-dppm)2Cu} unit, in which 3 and 4 adopt the boat-boat conformation, while 1, 2, and 5 display the chair-boat form. In these dimeric copper(I) complex cations, one of the two Cu(I) ions is four-coordinated, in a highly distorted N2P2 tetrahedral environment and the other is three-coordinated, in a distorted NP2 trigonal planar arrangement. All these Cu(I) complexes exhibit a comparatively weak low-energy absorption in CH2Cl2 solution, ascribed to the charge-transfer transitions with appreciable 1MLCT contribution, as suggested by time-dependent density functional theory (TDDFT) analyses. Complexes 1-5 display good emission properties in both solution and solid states at ambient temperature, which are well-modulated via structural modification of 3-(2'-pyridyl)-1,2,4-triazole, including the alteration of the substituent type (-CF3, -H, -CH3, and -C(CH3)3) and position (ortho-, meta-, and para-position). Furthermore, the variation of the substituent (-CF3 and -C(CH3)3) on the 5-site of the 1,2,4-triazolyl ring markedly influences the proton activity of the 1,2,4-triazolyl-NH, thus leading to the formation of both singly and doubly charged bimetallic Cu(I) species regulated by the NH ↔ N- conversion, resulting from NH deprotonation of the 1,2,4-triazolyl ring.

Gastric Juice-Based Real-Time PCR for Tailored Helicobacter Pylori Treatment: A Practical Approach.

A gastric juice-based real-time polymerase chain reaction (PCR) assay was established to identify Helicobacter pylori infection, clarithromycin susceptibility and human CYP2C19 genotypes and to guide the choice of proton pump inhibitor (PPI), clarithromycin and amoxicillin treatment for tailored H. pylori eradication therapy. From January 2013 to November 2014, 178 consecutive dyspeptic patients were enrolled for collection of gastric biopsy samples and gastric juice by endoscopy at the Peking University Third Hospital; 105 and 73 H. pylori-positive and -negative patients, respectively, were included in this study. H. pylori infection was defined as samples with both a strongly positive rapid urease test (RUT) and positive H. pylori histology. A series of primers and probes were distributed into four reactions for identifying the H. pylori cagH gene coupled with an internal control (Rnase P gene), A2142G and A2143G mutants of the H. pylori 23S rRNA gene, and single-nucleotide polymorphisms (SNPs) G681A of CYP2C19*2 and G636A of CYP2C19*3. The E-test and DNA sequencing were used to evaluate the H. pylori clarithromycin susceptibility phenotype and genotype. The SNPs CYP2C19*2 and CYP2C19*3 were also evaluated by nucleotide sequencing. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of this gastric juice-based real-time PCR assay were evaluated by comparing with the same measures obtained through gastric biopsy-based PCR and culture. The H. pylori diagnostic sensitivities of the culture, PCR, and gastric biopsy- and gastric juice-based real-time PCR assays were 90.48% (95/105), 92.38% (97/105), 97.14% (102/105) and 100% (105/105), respectively; the specificities of the above methods were all 100%. Higher false-negative rates were found among the gastric biopsy samples assessed by culture (10.48%, 11/105), PCR (7.62%, 8/105) and real-time PCR (2.86%, 3/105) than in gastric juice by real-time PCR. Regarding clarithromycin susceptibility, a concordance of 82.98% (78/94) and discordance of 17.02% (16/94) were observed among the different methods, discrepancies that mainly represent differences between the H. pylori clarithromycin susceptibility phenotype and genotype. Three coinfections of susceptible and resistant strains were detected, with resistant-to-susceptible ratios of 1.16, 3.44, and 8.26. The CYP2C19 genotyping results from gastric juice by real-time PCR were completely in accordance with those obtained from biopsy samples by conventional PCR. This gastric juice-based real-time PCR assay is a more accurate method for detecting H. pylori infection, clarithromycin susceptibility and CYP2C19 polymorphisms. The method may be employed to inform the choice of proton pump inhibitor (PPI), clarithromycin and amoxicillin treatment for tailored H. pylori eradication therapy.

Mutual growth-promoting effect between Bifidobacterium bifidum WBBI03 and Listeria monocytogenes CMCC 54001.

In this study, Bifidobacterium bifidum WBBI03 and Listeria monocytogenes CMCC 54001 were selected to detect the changes in their growth pattern after mutual interaction between them. The proteomic changes after the interaction between the 2 bacteria were detected by the isobaric tags for relative and absolute quantitation method. The proteins related to the biosynthesis and cell reproduction were selected, and their changes at the transcriptional level were monitored by fluorescent quantitative PCR. Also, 3 other types of probiotic organisms and opportunistic pathogens were used to verify the results mentioned above. The results showed that growing the 2 organisms together could promote the growth of each other, resulting in earlier entry into the logarithmic phase. The results also showed that the expression of these proteins mostly tended to be upregulated at the translational and transcriptional level. The increase in the expression of these proteins might help promote the growth and reproduction of B. bifidum WBBI03 and L. monocytogenes CMCC 54001. One aspect of the biological significance of their presence in the normal intestine may be that the opportunistic pathogens promote the growth of the probiotics.

Hybrid Therapy as First-Line Regimen for Helicobacter pylori Eradication in Populations with High Antibiotic Resistance Rates.

BACKGROUND: Hybrid therapy has recently attracted widespread attention. However, many issues require further exploration. For example, research in regions with high antibiotic resistance rates is limited, and the correlation between eradication efficacy and antibiotic resistance remains unclear. The aim of this study was to determine the efficacy, compliance, safety, and risk factors of hybrid therapy as first-line regimen in a region with high antibiotic resistance rates. MATERIALS AND METHODS: This prospective study was conducted in a tertiary hospital between January 2014 and June 2015. A total of 196 patients with dyspepsia but without prior eradication therapy received hybrid regimen (esomeprazole 20 mg and amoxicillin 1000 mg twice daily for 14 days with the addition of clarithromycin 500 mg and tinidazole 500 mg twice daily for the final 7 days). All patients underwent Helicobacter pylori culture, antibiotic susceptibility testing and cytochrome P450 isoenzyme 2C19 polymorphism testing. RESULTS: Hybrid therapy achieved eradication rates of 77.0% (95% confidence interval (CI), 70.9-83.7%) in intention-to-treat (ITT), 83.9% (78.9-88.9%) in modified ITT and 86.0% (80.2-91.3%) in per-protocol analyses in a setting with high antibiotic resistance rates (amoxicillin 2.0%, clarithromycin 44.9%, metronidazole 67.3% and dual clarithromycin and metronidazole 33.3%). Adverse reactions occurred in 31.9% patients and 2.7% discontinued medications due to adverse reactions. Good compliance was achieved by 92.0%. Multivariate analyses identified clarithromycin resistance (odds ratio, 3.494; 95% CI, 1.237-9.869), metronidazole resistance (3.012; 1.013-12.054) and poor compliance (5.840; 1.126-30.296) as independent predictors of treatment failure. The eradication rate with dual clarithromycin and metronidazole resistance (70.2%) was markedly decreased compared to isolated clarithromycin resistance (87.5%), isolated metronidazole resistance (88.6%), or dual susceptibility (96.4%) (p = .014). CONCLUSIONS: Despite good compliance and safety, hybrid therapy as first-line regimen in populations with high antibiotic resistance rates had unsatisfactory efficacy, primarily due to dual clarithromycin and metronidazole resistance.

Tailored versus Triple plus Bismuth or Concomitant Therapy as Initial Helicobacter pylori Treatment: A Randomized Trial.

BACKGROUND: With markedly increased antibiotic resistance and unsatisfactory efficacies of common empiric eradication regimens in the mainland of China, tailored therapy may be the best choice to achieve good efficacy. This study compared the eradication rates, safety, and compliance of tailored therapy to those of triple therapy plus bismuth and concomitant therapy in the naïve patients with Helicobacter pylori infection. MATERIALS AND METHODS: Between September 2013 and April 2014, 1050 patients with H. pylori infection at three tertiary hospitals were randomly assigned to 10-day treatment with tailored, triple plus bismuth, or concomitant regimens. In tailored therapy, medications were adjusted according to clarithromycin sensitivity and cytochrome P450 isoenzyme 2C19 genotype. The antimicrobial susceptibility testing (E test) was performed. Eradication status was assessed 4-12 weeks after treatment. RESULTS: The eradication rate was significantly higher in tailored group than in triple plus bismuth and concomitant groups in both intention-to-treat (88.7 vs 77.4 vs 78.3%, p < .001) and per-protocol (93.3 vs 87.0 vs 87.4%, p = .021) analyses in a setting with high antibiotic resistance (clarithromycin 48.8%, metronidazole 65.7%, and dual resistance 35.3%). Significantly, fewer adverse effects occurred in tailored group than in concomitant group (22.0 vs 31.7%, p = .018). The eradication rates of dual clarithromycin and metronidazole resistance, isolated clarithromycin resistance, isolated metronidazole resistance, and dual susceptible were 78.7, 82.4, 94.8, and 94.4% in triple therapy plus bismuth and 75.9, 87.2, 92.9, and 95.2% in concomitant therapy, respectively. CONCLUSIONS: First-line tailored therapy achieves significantly higher eradication rates and fewer side effects, compared to triple therapy plus bismuth and concomitant therapy in a setting with high rates of clarithromycin and metronidazole resistance.

Cation-Induced Variation of Micromorphology and Luminescence Properties of Tungstate Phosphors by a Hydrothermal Method.

Eu3+-doped MWO4 (M = Zn, Cd, Ca, Sr, or Ba) nanorods and rodlike, spherical, dumbbell-like, and double-tapter-like grains have been obtained via a hydrothermal method. The distinct differences in cationic radius lead to a special morphology, which is attributed to the symmetry of the crystal structure and the differences in the growth rates of various crystals, and it further leads to the variation of luminescence. It was found that the charge transfer band of MWO4:0.04Eu3+ exhibits a blue shift with an increasing cationic radius, and the shift is ascribed to less covalency being caused by an increase in the cationic radius. The emission intensity obviously increases with cationic radius, increasing for the samples with a monoclinic phase; however, it is the opposite for the samples with a tetragonal phase, and CaWO4:0.04Eu3+ exhibits an optimal emission intensity. In addition, the possible reasons for the decay lifetime are also discussed in detail. Our results indicate that cations can effectively control the crystal structure, micromorphology, and luminescence in tungstate phosphors, and thus, our approach is effective for obtaining materials with the desired morphology and crystal structure.

Genetic variation in EYA4 on the risk of noise-induced hearing loss in Chinese steelworks firm sample.

OBJECTIVES: Noise-induced hearing loss is one of the most serious occupational diseases worldwide. It is caused by interactions between environmental and genetic factors. The purpose of this study was to examine the association between the genetic susceptibility of the eye absent homolog 4 (EYA4) gene and the risk of developing noise-induced hearing loss in China. METHODS: A case-control association study was carried out with 326 hearing loss cases and 326 controls matched with age and duration of noise exposure, drawn from a cohort of steel workers. Five single nucleotide polymorphisms (SNPs) in the EYA4 were selected and genotyped. Logistic regression was performed to analyse the main effect of genotypes and interactions between genotypes and individual/environmental factors adjusted for confounding factors. Moreover, generalised multiple dimensionality reduction was applied to further detect interaction among the 5 selected SNPs. RESULTS: Analysis revealed that locus polymorphism of rs3813346 was associated with the risk of developing noise-induced hearing loss in the dominance model, the codominance model and the addictive model (p=0.004, 0.009 and 0.003, respectively). A significant interaction between rs9321402 and cumulative noise exposure was found (p=0.002). A significant main effect p value (p=0.006) was obtained in the high-level exposure group (cumulative noise exposure ≥98 dB(A)). Generalised multiple dimensionality reduction indicated that the combined interaction of the 2 loci-rs3813346 and rs9493627-significantly affected the incidence of noise-induced hearing loss. CONCLUSIONS: The research suggests that EYA4 genetic variant and its interaction with noise levels may modify the susceptibility to develop noise-induced hearing loss in Chinese population.