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The quinolone resistance crpP genes can mediate decreased susceptibility to quinolones. However, diversification and prevalence of crpP genes and crpP-carrying integrative and conjugative elements (ICEs) still need to be elucidated. In this study, genome sequencing was conducted for 200 Chinese Pseudomonas aeruginosa isolates, 16 of which were fully sequenced. All the 37 available CrpP variants were collected for phylogenetic analysis, 10 CrpP enzymes were chosen to conduct cloning and antimicrobial susceptibility test, and 22 crpP-carrying Tn6786-related ICEs were selected for detail genetic dissection analysis. Then, typing/nomenclature schemes for crpP variants and crpP-carrying ICEs were established for the first time. The 10 representative CrpP enzymes were confirmed to mediate decreased susceptibility to one to three quinolones. Tn6786-related ICEs displayed high-level diversification in both nucleotide sequences and modular structures. Mainly, massive gene acquisition/loss occurred across the whole genomes of Tn6786-related ICEs. 53.5% (107/200) of the tested clinical P. aeruginosa isolates from China carried crpP genes, which were exclusively located within chromosome-borne Tn6786-related ICEs. The crpP-carrying ICEs were at active stages of evolution and had the high potential to be an important vector for the dissemination of resistance genes besides crpP. The present study furthered the understanding of the bioinformatics and epidemiology of crpP genes and crpP-carrying ICEs. [ABSTRACT FROM AUTHOR]

• A total of 161 metallo-β-lactamase (MBL)-producing Enterobacteriaceae isolates were investigated for their in vitro sensitivity to aztreonam–avibactam. • Klebsiella pneumoniae (n = 73, 45.4%) and Escherichia coli (n = 53, 32.9%) were the most common species. • Pre-existing lung disease was associated with a hazard effect on worse disease outcomes among the patients with MBL- Enterobacteriaceae infections. • The resistance rate of aztreonam in these isolates was as high as 81.4%, and the MIC 90 of aztreonam–avibactam after adding avibactam was 1/4 μg/ml. • The results suggest that the combination of aztreonam–avibactam is highly potent against MBL-producing Enterobacteriaceae in China. To study the molecular epidemiology of clinical metallo-β-lactamase (MBL)-producing Enterobacteriaceae isolates in China and to evaluate the antimicrobial susceptibility of MBL- Enterobacteriaceae isolates to aztreonam–avibactam. Bacterial speciation was determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PCR was used to screen for common carbapenemase genes. Antimicrobial susceptibility testing of common clinical antibiotics and aztreonam–avibactam was performed using the standard broth microdilution method. A total of 161 MBL- Enterobacteriaceae isolates were included, with Klebsiella pneumoniae (n = 73, 45.4%) and Escherichia coli (n = 53, 32.9%) being the most common species. Among the 161 isolates, bla NDM (n = 151), bla IMP (n = 13), and bla VIM (n = 2) were detected, including five strains (3.1%) co-harboring two MBLs. MBL- Enterobacteriaceae isolates frequently contained two (n = 55, 34.2%) or more (n = 89, 55.3%) additional serine β-lactamase genes (bla KPC , bla CTX-M , bla TEM , or bla SHV). Antimicrobial susceptibility testing showed that 81.4% of isolates (n = 131) were resistant to aztreonam. The rates of resistance to cefazolin, ceftazidime, ceftriaxone, cefotaxime, ampicillin–sulbactam, amoxicillin–clavulanic acid, and piperacillin–tazobactam were all over 90%. The addition of avibactam (4 μg/ml) significantly reduced the minimum inhibitory concentrations (MICs) of the aztreonam-resistant isolates by more than 8-fold (range ≤0.125 to 4 μg/ml), with a MIC 50 /MIC 90 of ≤0.125/1 μg/ml among the 131 isolates. Overall, 96.9% (n = 156) of the total isolates were inhibited at an aztreonam–avibactam concentration of ≤1 μg/ml. Univariate and multivariate logistic regression analysis found that in patients with MBL- Enterobacteriaceae infections, the presence of pre-existing lung disease (adjusted odds ratio 8.267, 95% confidence interval 1.925–28.297; p = 0.004) was associated with a hazard effect on worse disease outcomes. The combined use of aztreonam–avibactam is highly potent against MBL- Enterobacteriaceae and may serve as a new candidate for the treatment of infections caused by MBL- Enterobacteriaceae in China. [ABSTRACT FROM AUTHOR]

We report on hydrogen-bonded layer-by-layer (LbL) films as a robust, reusable platform for temperature-triggered “on-demand” release of drugs. Films with high drug loading capacity, temperature-controlled on–off drug release, and stability at physiological conditions were enabled by assembly of tannic acid (TA) with temperature-responsive block copolymer micelles (BCMs), which were pre-formed by heating solutions of a neutral diblock copolymer, poly(N-vinylpyrrolidone)-b-poly(N-isopropylacrylamide) (PVPON-b-PNIPAM), to a temperature above the lower critical solution temperature (LCST) of PNIPAM. The BCM/TA films exhibited temperature-triggered swelling/deswelling transitions at physiological conditions (swelling ratios of 1.75 and 1.2 at 37°C and 20°C, respectively). A model drug, doxorubicin (DOX) was incorporated into the film at a high drug-to-matrix ratio (~9.3wt.% of DOX per film mass), with a total loading capacity controlled by the film thickness. At 37°C, DOX was efficiently retained within the hydrophobic BCM cores of BCM/TA films, whereas exposure to a lower temperature (20°C) triggered fast DOX release. While neither bare BCM-containing films nor films loaded with DOX showed cytotoxicity at 37°C, drug released from films at lower temperature exhibited high potency against breast cancer cells. Repeated on/off drug release was demonstrated with 1.5-μm-thick DOX-loaded films, allowing at least three 30-min cooling cycles with consistent DOX (~12–16% of loaded DOX released for each cycle) released over a 4-day period. Despite significant stress associated with multiple swelling/deswelling cycles, films maintained their structural integrity in PBS, and each film could be repeatedly loaded with drug and used more than 15 times with only ~7% loss in film thickness and no obvious changes in reloading capacity or release profiles. This work presents the first proof-of-concept utility of temperature-responsive BCM-containing films for repeated on-demand release of a drug. [ABSTRACT FROM AUTHOR]

Abstract: We report on construction of hydrogen-bonded monolayers and multilayers of micelles of the poly(2-(diethylamino)ethyl methacrylate)-block-poly(N-isopropyl acrylamide) (PDEA-b-PNIPAM) with PNIPAM-corona and polybasic PDEA cores. Films were constructed at pH 7.5 and 25°C to assure the deposition of PDEA-b-PNIPAM in the micellar form. When monolayers of block copolymer micelles (BCMs) were exposed to moderately acidic pH values, micellar cores dissolved, while PDEA-b-PNIPAM remained adsorbed at the surface as unimers. In contrast to reversible micellization of PDEA-b-PNIPAM in solution, micelle-to-unimer transition was irreversible at the surface. Adsorption of a layer of tannic acid (TA) or polyethacrylic acid (PEAA) on top of BCM monolayers inhibited pH-triggered morphological changes within adsorbed BCMs. By taking advantage of the high pK a values of TA and PEAA, we were also able to construct multilayers of PDEA-b-PNIPAM micelles through hydrogen bonding interactions between micellar PNIPAM coronas and TA or PEAA. Similar to BCM monolayers coated with TA or PEAA, dissolution of BCMs was also inhibited when incorporated within hydrogen-bonded multilayers. Such inhibition of dissolution is due to enhanced hydrogen bonding interactions between coronal PNIPAM chains and protonated TA molecules or PEAA chains at decreasing pH values restricting the pH-induced conformational changes of the micellar core chains within the adsorbed layer. Films of responsive BCMs are attractive coatings for controlled delivery of functional molecules from surfaces due to a combination of stimuli-response properties with the relatively high loading capacity for functional molecules. [ABSTRACT FROM AUTHOR]

In the development of dendritic cell (DC) vaccines, the maturation of DCs is a critical stage. Adjuvants play a pivotal role in the maturation of DCs, with a major concern being to ensure both efficacy and safety. This study introduces an innovative approach that combines high efficacy with safety through the synthesis of micro‐adjuvants grafted with copolymers of 2‐(methacrylamido) glucopyranose (MAG) and methacryloxyethyl trimethyl ammonium chloride (DMC). The utilization of metal‐free surface‐initiated atom transfer radical polymerization enables the production of safe and recyclable adjuvants. These micrometer‐sized adjuvants surpass the optimal size range for cellular endocytosis, enabling the retrieval and reuse of them during the ex vivo maturation process, mitigating potential toxicity concerns associated with the endocytosis of non‐metabolized nanoparticles. Additionally, the adjuvants exhibit a "micro‐ligand‐mediated maturation enhancement" effect for DC maturation. This effect is influenced by the shape of the particle, as evidenced by the distinct promotion effects of rod‐like and spherical micro‐adjuvants with comparable sizes. Furthermore, the porous structure of the adjuvants enables them to function as cargo‐carrying "micro‐shuttles", releasing antigens upon binding to DCs to facilitate efficient antigen delivery. [ABSTRACT FROM AUTHOR]

In the development of dendritic cell (DC) vaccines, the maturation of DCs is a critical stage. Adjuvants play a pivotal role in the maturation of DCs, with a major concern being to ensure both efficacy and safety. This study introduces an innovative approach that combines high efficacy with safety through the synthesis of micro‐adjuvants grafted with copolymers of 2‐(methacrylamido) glucopyranose (MAG) and methacryloxyethyl trimethyl ammonium chloride (DMC). The utilization of metal‐free surface‐initiated atom transfer radical polymerization enables the production of safe and recyclable adjuvants. These micrometer‐sized adjuvants surpass the optimal size range for cellular endocytosis, enabling the retrieval and reuse of them during the ex vivo maturation process, mitigating potential toxicity concerns associated with the endocytosis of non‐metabolized nanoparticles. Additionally, the adjuvants exhibit a "micro‐ligand‐mediated maturation enhancement" effect for DC maturation. This effect is influenced by the shape of the particle, as evidenced by the distinct promotion effects of rod‐like and spherical micro‐adjuvants with comparable sizes. Furthermore, the porous structure of the adjuvants enables them to function as cargo‐carrying "micro‐shuttles", releasing antigens upon binding to DCs to facilitate efficient antigen delivery. [ABSTRACT FROM AUTHOR]

[Display omitted] • A dynamic self-polishing and self-renewing antibacterial surface was developed. • The functionalized surface has good biocompatibility, enzymatic biodegradable properties and excellent bactericidal properties. • This strategy provides a promising and new route to design and fabricate multifunctional surfaces with long-term antibacterial activity for biomaterials and implantable devices. To meet the development of multifunctional surfaces with long-term antibacterial activity for biomaterials and implantable devices, herein, a novel self-polishing antibacterial surface was developed. The functionalized surface was prepared by first surface-initiated ring-opening grafting polymerization (SI-ROP) of a cyclic carbonate monomer 4′-(fluorosulfonyl)benzyl-5-methyl-2-oxo-1,3-dioxane-5-carboxylate (FMC) containing a sulfonyl fluoride group in the side chain onto the material surface and then by a "sulfur(IV)-fluorine" exchange (SuFEx) postclick modification reaction to link the imidazolium salt ionic liquid to the polyFMC (PFMC) brush. In vitro experimental results showed that the functionalized surface has good biocompatibility, enzymatic biodegradable properties and excellent bactericidal properties, which can effectively kill E. coli (∼94%) and S. aureus (∼93%). In addition, the functionalized surface can release the killed bacteria (∼90%) several times efficiently under the action of lipase enzymatic degradation, restoring the original bactericidal function of the surface, thus forming a dynamic self-polishing and self-renewing antibacterial surface. Therefore, this method for the fabrication of self-polishing antibacterial surfaces may offer innovative insights into applications of biomedical implant materials. [ABSTRACT FROM AUTHOR]

R2931 --> Nucleic acid aptamers are emerging as the new generation molecular recognition elements for diagnostics based on their synthetic nature, stability under a wide range of temperatures and amenability to different sensing platforms. Aptamers can further be modified in sequence and chemically to increase their specificities and affinities for their target molecule and to enhance their stabilities in the presence of nucleases. Such characteristics are compatible with the small electrochemical aptasensor that we are developing for point of care diagnosis of infectious virus species. Ebola virus, which kills up to 90% of those it infects, is one of the deadliest known viruses. Being highly contagious, the Ebola virus calls for rapid diagnosis for isolation of infected individuals to prevent viral outbreak. For this purpose, we have selected DNA aptamers with high affinities and specificities for Ebola virus (EBOV) soluble glycoprotein (sGP). The presence of sGP in abundance into the blood stream of infected individuals even during the early stages of infection, makes it an excellent biomarker for diagnosis. The selected aptamers functioned well on a portable nanoporous aluminum oxide (NAAO) sensor to detect sGP in Ebola infected macaque serum samples. This NAAO sensor which allows label free detection of ebola infected serum samples, now being tested against many samples for accuracy of reporting, has the potential to greatly accelerate EBOV diagnosis on site and to automatically relay that information to central authorities, thereby preventing the spread of this highly contagious virus and saving thousands of lives. [ABSTRACT FROM AUTHOR]