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Developing molecular approaches to the creation of robust and water-resistant adhesive materials promotes a fundamental understanding of interfacial adhesion mechanisms as well as future applications of biomedical adhesive materials. Here, we present a simple and robust strategy that combines natural thioctic acid and mussel-inspired iron-catechol complexes to enable ultra-strong adhesive materials that can be used underwater and simultaneously exhibit unprecedentedly high adhesion strength on diverse surfaces. Our experimental results show that the robust crosslinking interaction of the iron-catechol complexes, as well as high-density hydrogen bonding, are responsible for the ultra-high interfacial adhesion strength. The embedding effect of the hydrophobic solvent-free network of poly(disulfides) further enhances the water-resistance. The dynamic covalent poly(disulfides) network also makes the resulting materials reconfigurable, thus enabling reusability via repeated heating and cooling. This molecule-engineering strategy offers a general and versatile solution to the design and construction of dynamic supramolecular adhesive materials. [ABSTRACT FROM AUTHOR]

Background: The aerial parts of Peganum harmala L. (APP) is a well-known and effective herbal medicine in China, and has been commonly used for treating various ailments, including cough and asthma. Objectives: To evaluate the antitussive, expectorant, and bronchodilating effects of the quinazoline alkaloids ([+ or -])-vasicine(VAS), deoxyvasicine (DVAS) (both isolated from the alkaloid fraction of APP) and (±)- vasicinone (VAO) (synthesized from VAS). Methods: The three quinazoline alkaloids were tested as antitussive on cough models in mice and guinea pigs. VAO was synthesized from VAS via the oxidation of hydrogen peroxide. VAS, VAO, and DVAS were orally administered at dosages of 5,15, and 45 mg/kg. Cough in these models was induced by ammonia, capsaicin, and citric acid. Phenol red secretion experiments in mice were performed to evaluate the expectorant activity of the alkaloids. Bronchodilating effects were evaluated by using a bronchoconstrictive induced by acetylcholine chloride and histamine in guinea pigs. Results: In antitussive tests, VAS, VAO, and DVAS significantly inhibited coughing frequency and prolonged the cough latency period in animals. At the highest doses tested (45 mg/kg), they showed antitussive activities similar to codeine phosphate (30 mg/kg) in mice and guinea pigs. Expectorant evaluation showed that VAS, VAO, and DVAS could significantly increase phenol red secretion in mice by 0.54-, 0.79- and 0.97-fold, by 0.60-, 0.99-, and 1.06-fold, and by 0.46-, 0.73-, and 0.96-fold, respectively, at dosages of 5,15, and 45 mg/kg compared with the control (0.5% CMC-Na, 20 ml/kg). Ammonium chloride at 1500 mg/kg increased phenol red secretion in mice by 0.97-fold compared with the control. Bronchodilation tests showed that VAS, VAO, and DVAS prolonged the pre-convulsive time for 28.59%, 57.21%, and 29.66%, respectively, at a dose of 45 mg/kg in guinea pigs, whereas aminophylline prolonged the pre-convulsive time by 46.98% compared with pretreatment. Conclusions: Quinazoline alkaloids VAS, VAO, and DVAS have significant antitussive, expectorant, and bronchodilating activities. VAS, VAO, and DVAS are the active ingredients in APP, which can be used to treat respiratory disease. Keywords: Peganum harmala L Antitussive Expectorant Bronchodilating Quinazoline, Introduction Cough is among the common symptoms associated with many respiratory diseases, such as asthma, chronic bronchitis, and pneumonia (Ce et al., 2009; Irwing and Madison, 2000). These respiratory diseases [...]

Enabling dynamically tunable emissive systems offers opportunities for constructing smart materials. Clusteroluminescence, as unconventional luminescence, has attracted increasing attention in both fundamental and applied sciences. Herein, we report a supramolecular poly(disulfides) network with tunable clusteroluminescence. The reticular H‐bonds synergize the rigidity and mobility of dynamic networks, and endow the resulting materials with mechanical adaptivity and robustness, simultaneously enabling efficient clusteroluminescence and phosphorescence at 77 K. Orthogonally tunable luminescence are achieved in two manners, i.e. slow backbone disulfide exchange and fast side‐chain metal coordination. Further exploration of the reprocessability and chemical closed‐loop recycling of intrinsic dynamic networks for sustainable materials is feasible. We foresee that the synergistic strategy of dynamic chemistry offers a novel pathway and potential opportunities for smart emissive materials. [ABSTRACT FROM AUTHOR]

Background: Fosfomycin is an important broad-spectrum bactericidal antibiotic to treat multidrug-resistant bacteria infections. It is generally accepted that heteroresistant bacteria are an intermediate stage in the formation of drug resistance, but there are few studies on the formation mechanism underlying fosfomycin heteroresistance (FHR).Objectives: To reveal the characteristics and formation mechanisms of FHR in Escherichia coli isolates obtained from chickens.Methods: We identified the FHR according to the population analysis profile (PAP) test and in vitro time-kill assay. Growth curves for FHR E. coli and their subpopulations were measured. Also, the subpopulations were repeatedly cultured in fosfomycin-free medium for 5-20 overnight incubation periods. The formation mechanisms of FHR in E. coli isolates were identified through accumulation assay, carbohydrate utilization testing, real-time relative quantitative PCR analysis, DNA sequencing, transcriptomic analysis, intracellular ATP and cAMP-level assessment.Results: Four of six E. coli strains were confirmed to show FHR, with a total of six subpopulations. The subpopulations restored phenotypic susceptibilities to fosfomycin within 5-20 overnight incubation sessions, but four of six subpopulations still maintained FHR characteristics. Differing from their parental isolates, the uptake of fosfomycin in the subpopulations through GlpT was reduced remarkably. Further studies identified that the low expression of glpT was due to the decrease of intracellular cAMP levels in the subpopulations, which was caused by the decreased ATP levels in cells.Conclusions: Our findings revealed the formation mechanism of E. coli isolates showing FHR obtained from chicken in China and characterized the dynamic change traits in vitro of the subpopulations. [ABSTRACT FROM AUTHOR]

To characterize the formation mechanism and characteristics of two cointegrate plasmids in Salmonella enterica serotype Enteritidis strain S13, plasmids from strain S13 and three corresponding transconjugants were subjected to whole genome sequencing and analyzed using bioinformatics tools. The traits of two fusion plasmids in transconjugants were characterized by stability and conjugation experiments. Sequence analysis indicated that strain S13 contained four plasmids, including mcr-1 -bearing pS13-1, bla CTX–M–55-carrying pS13-2, tet (M)-bearing pS13-3, and floR -carrying pS13-4. IncN1-F33:A–:B– plasmid pS13-2, respectively, fused with IncFI:A–:B– plasmid pS13-3 and IncX1 plasmid pS13-4, which generated two cointegrate plasmids, designated pS13D and pS13F, which involved in two intermolecular replicative mechanisms mediated by IS 26 and the novel transposon Tn 6952 (Δ Tn AS3 -IS 26 - Δ IS Ecp1 - ramA - Δ IS 26 - Δ Tn AS1), respectively. This is the first report of the fusion of the IncN1-F33:A–:B– plasmid and IncFI:A–:B– plasmid mediated by IS 26 , and with IncX1 plasmid mediated by Tn 6952. The formation and evolution of cointegrate plasmids could expand the resistance and host spectrum of fusion plasmids. [ABSTRACT FROM AUTHOR]

ICE Hpa1 was identified in the genome of a serovar 8 Haemophilus parasuis ST288 isolate YHP170504 from a case of swine lower respiratory tract infection. The aim of the present study was to characterize the integrative conjugative element ICE Hpa1 and its multiresistance region. Susceptibility testing was determined by broth microdilution and the complete ICE Hpa1 was identified by WGS analysis. The full sequence of ICE Hpa1 was analyzed with bioinformatic tools. The presence of ICE Hpa1 , its circular intermediate and integration site were confirmed by PCR and sequence analysis. Transfer of ICE Hpa1 was confirmed by conjugation. ICE Hpa1 has a size of 68,922 bp with 37.42% GC content and harbors 81 genes responsible for replication and stabilization, transfer, integration, and accessory functions, as well as seven different resistance genes [ bla Rob–3, tet (B), aphA1 , strA , strB , aac(6)′-Ie-aph(2′)-Ia , and sul2 ]. Conjugation experiments showed that ICE Hpa1 could be transferred to H. parasuis V43 with frequencies of 6.1 × 10–6. This is the first time a multidrug-resistance ICE has been reported in H. parasuis. Seven different resistance genes were located on a novel integrative conjugative element ICE Hpa1 , which suggests that the ICE Hpa1 is capable of acquiring foreign genes and serving as a carrier for various resistance genes. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the genetic and biological features of the tet (M)-harboring plasmid pTS14 in Salmonella enterica strain S14 isolated from a chicken fecal sample. Plasmid pTS14 was identified by conjugation, S1-pulsed-field gel electrophoresis (PFGE), Southern hybridization, and plasmid sequencing. The biological characteristics of pTS14 were assessed via stability, growth kinetics, and starvation survival experiments. Strain S14, belonging to ST3007, harbored a 119-kb tet (M)-bearing IncF2:A1:B1 conjugative plasmid pTS14. The plasmid pTS14 contained a novel transposon Tn 6709 with the genetic structure IS 26 - tnpA1 - tnpA2 -Δ orf13 - LP - tet (M)- tnpX -Δ tnpR -IS 26 , and the resistance genes tet (B), tet (D), strAB , sul2 , and bla TEM–1b. In addition, pTS14 was found to be highly stable in the recipient strain E. coli J53. The transconjugant TS14 exhibited a higher survival ratio than E. coli J53 under permanent starvation-induced stress. The tet (M)-bearing IncF2 epidemic plasmid lineage may accelerate the dissemination of tet (M) and other genes by coselection, which could constitute a potentially serious threat to clinical treatment regimens. [ABSTRACT FROM AUTHOR]

Tet(M)-type proteins confer resistance to tetracycline and related antibiotics by interacting with the ribosome. Genes encoding Tet(M) have been found in a range of bacteria, including Escherichia coli. In the current study, conjugation experiments were performed between seven different tetracycline-resistant, azide-susceptible E. coli strains isolated from ducks and tetracycline-sensitive, azide-resistant E.coli J53. Transconjugants were obtained from two of the strains at a frequency of 1.2 × 10−8. PCR, southern blotting and sequencing demonstrated that tet (M) in the transconjugants was located on a ~50 kb IncHI2-type plasmid and was part of a composite transposon, designated Tn6539. This transposon is flanked by two IS26 elements in opposite orientation and contains the Tn3Δ tnpA +Δ orf13 - lp - tet (M)+gamma delta+ tnpX +Δ tnpR sequences. The Δ orf13 - lp - tet (M) sequence was a highly conserved genetic fragment in E. coli harboring tet (M) and mainly located in the composite transposons flanked by IS6-family elements. In summary, Tn6539 is a new composite transposon capable of horizontal transfer of tet (M) among E. coli isolates. [ABSTRACT FROM AUTHOR]

Objective:Curcumin being used to treat various chronic diseases while its poor bioavailability issue limited its wide clinical application as a therapeutic agent. The aim of this work was to prepare curcumin-loaded self-assembled micelles using soluplus and solutol®HS15 (SSCMs) to enhance curcumin’s solubility and thus oral bioavailability. Methods:Optimum formulation was investigated and the optimized ratio of drugs and excipients was obtained and the SSCMs were prepared via ethanol solvent evaporation method. The optimal SSCMs were characterized by transmission electron microscopy, drug content analysis including loading efficiency (LE%) and entrapment efficiency (EE%), and the cumulative amount of curcumin released from the micelles were all calculated using HPLC method. The in vitro cytotoxicity and the permeability of SSCMs were measured by Caco-2 cell monolayers and the oral bioavailability was evaluated by SD rats. Key findings:The solubility of curcumin in self-assembled micelles was dramatically increased by 4200 times as compared to free curcumin. Caco-2 cells transport experiment exhibited that while soluplus and solutol®HS15 were self-assembled into micelles, it could not only promote the permeability of curcumin across membrane for better absorption, but also could restrain the curcumin pumped outside due to the role of P-gp efflux mechanism of soluplus and solutol®HS15. Furthermore, the prepared SSCMs formulation was almost nontoxic and had safety performance on Caco-2 cells model. Moreover, curcumin’s oral bioavailability of SSCMs formulation in SD rats had doubled than that of free curcumin. Conclusions:The prepared SSCMs were characterized by PS, PDI, LE%, EE% data analysis. After the soluplus and solutol®HS15 were self assembled into micelles, both the solubility and membrane permeability of curcumin were evaluated to have been enhanced, as well as the effect of efflux pump of curcumin was inhibited, hence to promote oral absorption and generate an increased bioavailability. [ABSTRACT FROM AUTHOR]