Regulation of Hydrophobic Structures of Antibacterial Guanidinium-Based Amphiphilic Polymers for Subcutaneous Implant Applications.

Antimicrobial peptide mimics have been used to kill bacteria and construct antibacterial materials. Precise design and construction of chemical structure are essential for easy access to highly effective antimicrobial peptide mimics. Herein, cationic guanidinium-based polymers (PGXs) with varying hydrophobic structures were synthesized to explore the structure and antibacterial activity relationship of antimicrobial peptide mimics and to construct antibacterial implants. The effect of the hydrophobic chemical structure, including carbon chain length and configuration, on the antimicrobial activities against both Escherichia coli and Staphylococcus aureus was investigated. The antibacterial activities of PGXs improved with increasing alkyl chain length, and PGXs with a straight-chain hydrophobic structure exhibited better bactericidal activities than those with cyclic alkane and aromatic hydrocarbon. Furthermore, PGXs grafted with poly(dimethylsiloxane) (PDMS-PGXs) showed a similar bactericidal change tendency of PGXs in solution. Additionally, the PDMS-PGXs showed potent antibiofilm performance in vitro, which can inhibit bacterial infection in vivo as subcutaneous implants. This study may propose a basis for the precise design and construction of antibacterial materials and provide a promising way of designing biomedical devices and implants with bacterial infection-combating activities.

Metal-Free Atom Transfer Radical Polymerization to Prepare Recylable Micro-Adjuvants for Dendritic Cell Vaccine.

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.

Optimizing the Bacteriostatic and Cytocompatibility Properties of Poly(hexamethylene guanidine) Hydrochloride (PHMG) via the Guanidine/Alkane Ratio.

The emergence of "superbugs" is not only problematic and potentially lethal for infected subjects but also poses serious challenges for the healthcare system. Although existing antibacterial agents have been effective in some cases, the side effects and biocompatibility generally present difficulties. The development of new antibacterial agents is therefore urgently required. In this work, we have adapted a strategy for the improvement of poly(hexamethylene guanidine) hydrochloride (PHMG), a common antibacterial agent. This involves copolymerization of separate monomer units in varying ratios to find the optimum ratio of the hydrocarbon to guanidine units for antibacterial activity. A series of these copolymers, designated as PGB, was synthesized. By varying the guanidine/hydrophobic ratio and the copolymer molecular weight, a structure-optimized PGB was identified that showed broad-spectrum antibacterial activity and excellent biocompatibility in solution. In an antibacterial assay, the copolymer with the optimum composition (hydrophobic unit content 25%) inhibited >99% Staphylococcus aureus and was compatible with mammalian cells. A polyurethane emulsion containing this PGB component formed transparent, flexible films (PGB-PU films) on a wide range of substrate surfaces, including soft polymers and metals. The PGB-PU films showed excellent bacteriostatic efficiency against nosocomial drug-resistant bacteria, such as Pseudomonas aeruginosa and methicillin-resistant S. aureus (MRSA). It is concluded that our PGB polymers can be used as bacteriostatic agents generally and in particular for the design of antibacterial surfaces in medical devices.

Mucor indicus and Rhizopus oryzae co-culture to improve the flavor of Chinese turbid rice wine.

BACKGROUND: One of the most important species used to ferment Chinese turbid rice wine (CTRW) at an industrial-scale level is Rhizopus oryzae, although the flavor of CTRW fermented by pure R. oryzae is inferior to that of traditional CTRW. RESULTS: Mucor indicus was used as a cooperative species to improve the flavor of CTRW presented by R. oryzae. The flavor compounds in different fermentation stages were determined by headspace solid-phase microextraction-gas chromatography-mass spectrometry and high-performance liquid chromatography. It was noted that the M. indicus and R. oryzae co-culture changed the profiles of flavor compounds in CTRW, including esters, higher alcohols, amino acids and organic acids, and also significantly enhanced the concentration of sweet amino acids, fruity and floral esters, and higher alcohols. Sensory evaluation demonstrated that the CTRW fermented by M. indicus and R. oryzae had a more intense aroma, harmonious taste, continuation and full body mouth-feel because of more abundant flavor compounds. CONCLUSION: Mucor indicus is a promising species for co-culture with R. oryzae to improve the flavor of CTRW. © 2019 Society of Chemical Industry.

The Controversy of Pepsinogen A/Pepsin A in Detecting Extra-Gastroesophageal Reflux.

BACKGROUND: Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux. METHODS: PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples. RESULTS: Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring. CONCLUSIONS: Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.

Robust, anti-biofouling 2D nanogel films from poly(N-vinyl caprolactam-co-vinylimidazole) polymers.

In analogy with adsorbed protein films, we have fabricated a family of 2D nanofilms composed of poly(N-vinyl caprolactam-co-vinylimidazole) (PNVCL) nanogels. NVCL was copolymerized with 1-vinylimidazole (VIM), and then cross-linked with α,ω-dibromoalkanes with 2 to 8 carbons via quaternization to form the nanogels. The swelling ratio of the gels was precisely controlled by regulating the inter-chain spacing of the polymers at the level of the carbon atom chain length of the cross-linker. The short-chain alkanes used are relatively rigid and their dimensions provide an accurate estimate of the chain spacing in the nanogels. It was shown that small differences in the carbon atom number of the cross-linking agent led to significant differences in the mechanical properties of the nanogels, in particular in the softness, deformability, and contact area (in film form), all of which increased with increasing carbon number. Films of the softer gels not only showed good adhesion to a number of substrates, but were also mechanically robust. In addition, the films showed excellent light transmission and nontoxicity to L929 cells. Nanogels of intermediate softness were shown to inhibit the adhesion of bacteria and human umbilical vein smooth muscle cells (HUVSMCs), and to be resistant to the adsorption of the plasma protein fibrinogen, indicating strong anti-biofouling properties. Gels that were either too stiff or too soft showed somewhat weaker anti-fouling activity in terms both of HUVSMCs adhesion and protein adsorption.