Multi-target antimicrobial agents are considered a viable alternative to target-specific antibiotics, resistance to which emerged as a global threat. Used centuries before the discovery of conventional antibiotics, metal(loid)-based antimicrobials (MBAs), which target multiple biomolecules within the bacterial cell, are regaining research interest. However, there is a significant limiting factor-the balance between cost and efficiency. In this article, we utilize a checkerboard assay approach to explore antimicrobial combinations of MBAs with commonly used quaternary ammonium compound (QAC) antiseptics in order to discover novel combinations with more pronounced antimicrobial properties than would be expected from a simple sum of antimicrobial effects of initial components. This phenomenon, called synergy, was herein demonstrated for several mixtures of Al3+with cetyltrimethylammonium bromide (CTAB) and TeO32- with benzalkonium chloride (BAC) and didecyldimethylammonium bromide (DDAB) against planktonic and biofilm growth of Pseudomonas aeruginosa ATCC27853. Biofilm growth of Escherichia coli ATCC25922 was synergistically inhibited by the Cu2 +and benzalkonium chloride (BAC) mixture. Multiple additive mixtures were identified for both organisms. The current study observed unexpected species and growth state specificities for the synergistic combinations. The benefit of synergistic mixtures will be captured in economy/efficiency optimization for antimicrobial applications in which MBAs and QACs are presently used.
OBJECTIVE: We are entering the antimicrobial resistance era (AMR), where resistance to antibiotics is becoming more and more prevalent. In order to address this issue, various approaches are being explored. In this article, we explore for synergy between two very different antimicrobials, the antiseptic class of quaternary ammonium compounds and antimicrobial metals. These two antimicrobials have very different actions. Considering a OneHealth approach to the problem, finding synergistic mixtures allows for greater efficacy at lower concentrations, which would also address antimicrobial pollution issues.

The use of disinfectants containing benzalkonium chloride (BAC) has become increasingly widespread in response to triclosan (TCS) restrictions and the COVID-19 pandemic, leading to the increasing presence of BAC in aquatic ecosystems. However, the potential environmental health impacts of BAC on fish remain poorly explored. In this study, we show that BAC and TCS can induce the gut dysbiosis in zebrafish (Danio rerio), with substantial effects on health. Breeding pairs of adult zebrafish were exposed to environmentally relevant concentrations of BAC and TCS (0.4-40 μg/L) for 42 days. Both BAC and TCS exposure perturbed the gut microbiota, triggering the classical NF-κB signaling pathway and resulting in downstream pathological toxicity associated with inflammatory responses, histological damage, inhibited ingestion, and decreased survival. These effects were dose-dependent and sex-specific, as female zebrafish were more susceptible than male zebrafish. Furthermore, we found that BAC induced toxicity to a greater extent than the restricted TCS at environmentally relevant concentrations, which is particularly concerning. Our results suggest that environmental exposure to antimicrobial chemicals can have ecological consequences by perturbing the gut microbiota, a previously underappreciated target of such chemicals. Rigorous ecological analysis should be conducted before widely introducing replacement antimicrobial compounds into disinfecting products.

OBJECTIVE: This systematic review aims to evaluate the potential benefits and underlying mechanisms of combining SDF with light curing, based on available studies.
METHODS: A systematic search of publications was conducted with the keywords \"silver diamine fluoride\" or \"silver fluoride\" and \"dental light curing,\" \"LED curing,\" \"dental laser,\" and \"dental polymerization\" in 4 databases: PubMed, EBSCO, Scopus, and Google Scholar to identify English-language articles published up to March 2023. Duplicate publications were deleted. Two reviewers screened the titles and abstracts and excluded irrelevant publications. The full text of the remaining publications was retrieved. Studies investigating the effect of light-curing on SDF-treated carious lesions were included.
RESULTS: The 175 publications initially found included 5 laboratory studies investigating the effects of light curing on 38% SDF-treated dentine carious lesions, but no clinical study was found. Four of these studies were conducted on extracted primary teeth, and one was on extracted permanent teeth. SDF with light curing increased microhardness (n = 3, p < .05) showed a higher mineral density (n = 1, p < .041) and had more silver ion precipitation in infected dentine (n = 1, p < .016) compared to SDF without light curing. Moreover, no significant differences in the antibacterial activity were observed between SDF with light curing and SDF alone (n = 1, p > .05).
CONCLUSIONS: Drawing from the limited number of laboratory studies, incorporating light curing subsequent to the SDF application yields potential favorable outcomes that include augmented microhardness, elevated mineral density, and heightened silver ion precipitation within infected dentine. Future clinical research is required to confirm or refute the benefit of light curing on SDF-treated carious lesions.

In this work, liposomes loaded with the fungicide, Fludioxonil (FLUD), for the containment of fungal diseases in agriculture were developed. Three types of vesicles with different compositions were compared: (I) plain vesicles, composed of soy phosphatidylcholine and cholesterol; (II) PEG-coated vesicles, with an additional polyethylene glycol coating; and (III) cationic vesicles, containing didodecyldimethylammonium bromide. Nanometric-sized vesicles were obtained both by the micelle-to-vesicle transition method and by the extrusion technique, and encapsulation efficiency, drug loading content, and Zeta potential were determined for all the samples. The extruded and PEGylated liposomes were the most stable over time and together with the cationic ones showed a significant prolonged FLUD release capacity. The liposomes\' biological activity was evaluated on conidial germination, germ tube elongation and colony radial growth of the ascomycete Botrytis cinerea, a phytopathogenic fungus affecting worldwide many important agricultural crops in the field as well as in the postharvest phase. The extruded and PEGylated liposomes showed greater effectiveness in inhibiting germ tube elongation and colony radial growth of the fungal pathogen, even at 0.01 µg·mL-1, the lowest concentration assessed.

Quaternary ammonium compounds (QACs) are widely detected in the aquatic environment due to their extensive use in a wide array of antibacterial products during the pandemic. In the current study, UV/monochloramine (UV/NH2Cl) was used to degrade three typical QACs, namely benzalkonium compounds (BACs), dialkyl dimethyl ammonium compounds (DADMACs), and alkyl trimethyl ammonium compounds (ATMACs). This process achieved high efficiency in removing BACs from water samples. The transformation products of QACs treated with UV/NH2Cl were identified and characterized using a high-resolution mass spectrometer, and transformation pathways were proposed. The formation of N-nitroso-N-methyl-N-alkylamines (NMAs) and N-nitrosodimethylamine (NDMA) were observed during QAC degradation. The molar formation yield of NDMA from C12-BAC was 0.04 %, while yields of NMAs reached 1.05 %. The ecotoxicity of NMAs derived from QACs was predicted using ECOSAR software. The increased toxicity could be attributed to the formation of NMAs with longer alkyl chains; these NMAs, exhibited a one order of magnitude increase in toxicity compared to their parent QACs. This study provides evidence that QACs are the specific and significant precursors of NMAs. Greater attention should be given to NMA formation and its potential threat to the ecosystem, including humans.

Disorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder. In organ bath experiments, the bitter tastants denatonium, quinine, dextromethorphan, and noscapine, dose-dependently relaxed the pre-contracted gallbladder. Utilizing gene-deficient mouse strains, neither transient receptor potential family member 5 (TRPM5), nor the Tas2r143/Tas2r135/Tas2r126 gene cluster, nor tuft cells proved to be required for this relaxation, indicating direct action upon smooth muscle cells (SMC). Accordingly, denatonium, quinine and dextromethorphan increased intracellular calcium concentration preferentially in isolated gallbladder SMC and, again, this effect was independent of TRPM5. RT-PCR revealed transcripts of Tas2r108, Tas2r126, Tas2r135, Tas2r137, and Tas2r143, and analysis of gallbladders from mice lacking tuft cells revealed preferential expression of Tas2r108 and Tas2r137 in tuft cells. A TAS2R143-mCherry reporter mouse labeled tuft cells in the gallbladder epithelium. An in silico analysis of a scRNA sequencing data set revealed Tas2r expression in only few cells of different identity, and from in situ hybridization histochemistry, which did not label distinct cells. Our findings demonstrate profound tuft cell- and TRPM5-independent relaxing effects of bitter tastants on gallbladder smooth muscle, but do not support the concept that these effects are mediated by bitter receptors.

In the wake of the COVID-19 pandemic, respiratory tract infections have emerged as a significant global threat, yet their impact on public health was previously underappreciated. This study investigated the antiviral efficacy of the nano-coating agent BARRIER90, composed of silicon-quaternary ammonium compound and a naturally derived biopolymer, against three distinct respiratory viruses: Influenza A (H1N1), Adenovirus Type 1, and Enterovirus-Coxsackie B1. BARRIER90 exhibited robust and sustained virucidal activity, persisting up to 90 days post-coating, against the enveloped virus, Influenza A, with significant reduction in viral plaques. Contrastingly, its efficacy against non-enveloped viruses revealed transient activity against Enterovirus-Coxsackie B1, with almost no antiviral activity observed against Adenovirus Type 1. These findings indicate the potential of antimicrobial coatings in mitigating viral transmission through contaminated surfaces (fomites), which harbour pathogenic viruses for longer periods. Antimicrobial coatings may facilitate infection control in various settings, including healthcare facilities and shared workspaces.

Perchlorate (ClO4-) mainly exists in the form of ammonium perchlorate in industrial production. However, the degradation mechanisms of different concentrations of ammonium nitrogen (NH4+-N) and ClO4- mixed pollutants in the environment are not well understood. This study aims to explore the potential of different types of carbon sources for ClO4- and NH4+-N biodegradation. Experimental results showed that the concentration and type of carbon sources are decisive to simultaneous removal of NH4+-N and ClO4-. Under condition of C(COD)/C(ClO4-) ratio of 21.15 ± 4.40, the simultaneously removal efficiency of ClO4- and NH4+-N in acetate (Ace) was relatively higher than that in methanol (Met). C(NH4+-N)/C(ClO4-) ratio of 9.66 ± 0.51 and C(COD)/C(ClO4-) ratio of 2.51 ± 0.87 promoted ClO4- reduction in glucose-C (Glu-C). However, high concentration of Glu could cause pH decrease (from 7.57 to 4.59), thereby inhibiting ClO4- reduction. High-throughput sequencing results indicated that Proteobacteria and Bacteroidetes have made a major contribution to the simultaneous removal of NH4+-N and ClO4-. They are two representative bacterial phyla for participating in both ClO4- reduction and denitrification. Notably, the abundance of main ClO4- degrading bacteria (such as Proteobacteria, Chloroflexi, and Firmicutes) significantly increased by 528.57 % in Glu-C. It can be inferred that the concentration of carbon source and NH4+-N were the most important factors determining the removal efficiency of ClO4- by influencing changes in the core microbial community. This study will provide new techniques and mechanistic insights for the simultaneous removal of mixed ClO4- and nitrogen pollutants, which can also provide theoretical support for innovation in future biological treatment processes.

Quaternary ammonium salt bactericides are broad-spectrum bactericides often used in oral care products because of their high antibacterial efficacy, strong penetration, and low toxicity. However, the excessive use of quaternary ammonium salt bactericides may cause contact dermatitis, scalding poisoning, and even death. Existing methods to determine quaternary ammonium salt bactericides are unable to meet current requirements owing to the lack of determination components. Therefore, establishing a simple and accurate method for the simultaneous detection of more quaternary ammonium salt bactericides is necessary. In this study, a method that couples sample pretreatment with high performance liquid chromatography-evaporative light-scattering detection (HPLC-ELSD) was developed for the simultaneous determination of quaternary ammonium salt bactericides in oral care products, including dodecyltrimethylammonium chloride, dodecyldimethylbenzylammonium chloride, benzethonium chloride, tetradecyl trimethyl ammonium chloride, tetradecyldimethylbenzylammonium chloride, N-hexadecyltrimethylammonium chloride, benzyldimethylhexadecylammonium chloride, trimethylstearylammonium chloride, stearyldimethylbenzylammonium chloride, and docosyltrimethylammonium chloride. Some of these bactericides do not absorb ultraviolet light, so a universal evaporative light-scattering detector was used owing to testing cost and stability concerns. The paste samples contained thickening agents, which are highly soluble in water but insoluble in organic solvents; these agents can seriously affect the results of sample pretreatment and damage the chromatographic column. Hence, sample dehydration was necessary. In this study, four dehydration methods were compared. Anhydrous sodium sulfate (Na2SO4) was selected, and the amount of Na2SO4 was optimized. Based on the solubility of the 10 target compounds and extraction efficiency, three extraction solvents were compared, and ethanol was selected. Ultrasonic extraction was the primary extraction process used in this study. The effects of different ultrasonication times, temperatures, and powers on the extraction recoveries were also investigated. Ultimately, the optimized conditions were as follows: extraction of the dehydrated paste and powder samples using ethanol at room temperature (25 ℃) for 20 min under 100 W ultrasound power, and dilution of the liquid sample with ethanol. After extraction, the samples were separated on an Acclaim Surfactant column (150 mm×4.6 mm, 5 μm) with 50 mmol/L ammonium acetate aqueous solution (pH=5.5) (A) and acetonitrile (B) as mobile phases. The gradient elution program were as follows: 0-5.0 min, 75%A-35%A, 5.0-15.0 min, 35%A-20%A, 15.0-20.0 min, 20%A, 20.0-21.0 min, 20%A-75%A, 21.0-25.0 min, 75%A. An external standard method was used for quantitative determination. The 10 compounds were analyzed within 25 min. Linear equations, correlation coefficients, and linear ranges were obtained by analyzing a series of mixed standard working solutions. The limits of detection (LODs, S/N=3) and quantification (LOQs, S/N=10) of the 10 components were determined. Stearyldimethylbenzylammonium chloride and docosyltrimethylammonium chloride showed good linear relationships in the range of 10-200 mg/L, while the other compounds demonstrated good linear relationships in the range of 5-100 mg/L. In all cases, correlation coefficients (R2) of no less than 0.9992 were obtained. The LODs and LOQs were in the range of 1.42-3.31 mg/L and 4.25-9.94 mg/L, respectively. Ten analytes were spiked in blank matrices, such as toothpaste (paste), mouthwash (liquid), and dentifrice powder (powder) at three levels, and the recoveries and precisions were calculated. The average recoveries were 87.9%-103.1%, and the corresponding relative standard deviations (RSDs) did not exceed 5.5% (n=6). The developed method was used to detect 109 oral care products. Benzyldimethylhexadecylammonium chloride and stearyldimethylbenzylammonium chloride revealed high detection rates. Moreover, the amount of stearyldimethylbenzylammonium chloride in one toothpaste sample exceeded regulatory requirements. Given its advantages of good precision and accuracy, the developed method is suitable for the quantitative analysis of the 10 aforementioned compounds in typical oral care products. The study findings can serve as a reference for the quality and safety monitoring of oral care products.

•The use of quaternary ammonium compounds (QACs) as disinfectants has increased exponentially due to the COVID-19 pandemic.•There is, thus, a corresponding increase in human exposure to these compounds.•New studies reveal important human health concerns.•A re-evaluation of the use of these compounds is in order.•A change over to newer and safer products may bode well for the future.