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Food packaging films play a vital role in preserving and protecting food. The focus has gradually shifted to safety and sustainability in the preparation of functional food packaging materials. In this study, a bisquaternary ammonium salt of tannic acid (BQTA) was synthesized, and the bioplastics based on BQTA and polyvinyl alcohol (PVA) were created for packaging applications. The impact of BQTA on antibacterial effect, antioxidant capacity, opacity, ultraviolet (UV) protective activity, mechanical strength, thermal stability, and anti-fog of the resultant bioplastics was examined. In vitro antibacterial experiments confirmed that BQTA possesses excellent antimicrobial properties, and only a trace amount addition of BQTA in PVA composite film could inhibit about 100% of Escherichia coli and Staphylococcus aureus . Compared to BQTA/PVA bioplastics with pure PVA, the experiment findings demonstrate that BQTA/PVA bioplastics show strong antioxidant and UV protection action and the performance of fruit preservation. It also revealed a small improvement in thermal stability and tensile strength. The small water contact angle, even at low BQTA concentrations, gave BQTA/PVA bioplastics good anti-fog performance. Based on the findings, bioplastics of BQTA/PVA have the potential to be used to create packaging, and they can be applied as the second (inner) layer of the primary packaging to protect food freshness and nutrition due to their antioxidant activity and biocompatibility.

Sacran is a cyanobacterial supergiant polysaccharide with carboxylate and sulfate groups that exhibits antiallergic and antiinflammatory properties. However, its high anionic functions restrict cell compatibility. Quaternary ammonium groups were substituted to form sacran ampholytes, and the cell compatibility of the cationized sacran hydrogels was evaluated. The cationization process involved the reaction of N -(3-chloro-2-hydroxypropyl)trimethylammonium chloride with the primary amine or hydroxyl groups of sacran. The degree of cationization ranged from 32 to 87% for sugar residues. Hydrogels of sacran ampholytes were prepared by annealing their dried sheets by thermal cross-linking; these hydrogels exhibited anisotropic expansion properties. The water contact angle on the hydrogels decreased from 26.5 to 15.3° with an increase in the degree of cationization, thereby enhancing hydrophilicity. The IC 50 values of sacran ampholytes decreased with an increased degree of cationization, resulting in a reduction in cytotoxicity toward the L-929 mouse fibroblast cell line. This reduction was associated with an increase in the cell proliferation density after 3 days of incubation. Scanning electron microscopy images showed fibroblast intercellular connections. Therefore, the sacran ampholyte hydrogel exhibited increased hydrophilicity and cell compatibility, which is beneficial for various biomedical applications.

Glioblastoma (GBM) represents an aggressive brain tumor, characterized by intra- and inter-tumoral heterogeneity and therapy resistance, leading to unfavourable prognosis. An increasing number of studies pays attention on the regulation of ferroptosis, an iron-dependent cell death, as a strategy to reverse drug resistance in cancer. However, the debate on whether this strategy may have important implications for the treatment of GBM is still ongoing. In the present study, we used ferric ammonium citrate and erastin to evaluate ferroptosis induction effects on two human GBM cell lines, U-251 MG, with proneural characteristics, and T98-G, with a mesenchymal profile. The response to ferroptosis induction was markedly different between cell lines, indeed T98-G cells showed an enhanced antioxidant defence, with increased glutathione levels, as compared to U-251 MG cells. Moreover, using bioinformatic approaches and analysing publicly available datasets from patients' biopsies, we found that GBM with a mesenchymal phenotype showed an up-regulation of several genes involved in antioxidant mechanisms as compared to proneural subtype. Thus, our results suggest that GBM subtypes differently respond to ferroptosis induction, emphasizing the significance of further molecular studies on GBM to better discriminate between various tumor subtypes and progressively move towards personalized therapy., (© 2024. The Author(s).)

Dialkyldimethyl ammonium compound (DADMAC) is widely used in daily life as a typical disinfectant and often co-exists with the heavy metal zinc in sewage environments. This study investigated the effects of co-exposure to zinc (1 mg/L) and DADMAC (0.2-5 mg/L) on the performance, bacterial community, and resistance genes (RGs) in a partial sulfur autotrophic denitrification coupled with anaerobic ammonium oxidation (PSAD-Anammox) system in a sequencing batch moving bed biofilm reactor for 150 days. Co-exposure to zinc and low concentration (0.2 mg/L) DADMAC did not affect the nitrogen removal ability of the PASD-Anammox system, but increased the abundance and transmission risk of free RGs in water. Co-exposure to zinc and medium-to-high (2-5 mg/L) DADMAC led to fluctuations in and inhibition of nitrogen removal, which might be related to the enrichment of heterotrophic denitrifying bacteria dominated by Denitratisoma. Co-exposure to zinc and high concentration DADMAC (5 mg/L) stimulated the secretion of extracellular polymeric substances and increased the proliferation risk of intracellular RGs in sludge. This study provided insights into the application of PSAD-Anammox system and the ecological risks of wastewater containing zinc and DADMAC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Bitter taste receptors (TAS2Rs) and their downstream signaling pathways are expressed not only in the oral tissues but also in extraoral tissues. Emerging data has demonstrated the beneficial effect of ghrelin in neurodegenerative diseases. Gaining more insight into the interaction between TAS2Rs and gut hormones may expand their therapeutic applications. Herein, we aimed to assess the possible effect of TAS2R activation by denatonium benzoate (DB) in modulating functional and neurobiochemical alterations in a model of Parkinson's disease (PD)., Main Methods: PD model was induced by daily injection of rotenone (2 mg/kg). Rats received DB (5 mg/kg), atenolol (10 mg/kg), or both concomitantly with rotenone, daily for 28 days. Evaluation of the motor abnormalities and histological examination of brain tissues were conducted. In addition, striatal dopamine contents, immunohistochemical expression of tyrosine hydroxylase, plasma ghrelin level, and biochemical analysis of markers of inflammation and oxidative stress were assessed., Key Findings: Treatment with DB increased serum levels of ghrelin and striatal dopamine contents with consequent amelioration of oxidative stress and attenuation of inflammatory cytokines. Moreover, DB treatment significantly ameliorated motor disturbance and histological abnormalities compared to untreated rats. Atenolol inhibited ghrelin release and abolished the positive effect of DB suggesting the involvement of ghrelin on such effects., Significance: The current study suggests that TAS2Rs agonists are promising candidates for ameliorating rotenone-induced PD pathology in rats, an action that could be linked to the enhancement of ghrelin release with consequent antioxidant and anti-inflammatory activities., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Emerging resistance of Gram-negative bacteria, including Pseudomonas aeruginosa , to commonly used detergents and disinfectant is encountering us with hazard. Inappropriate use of disinfectants has forced bacteria to gain resistance. The ability of bacteria to extrude substrates from the cellular interior to the external environment has enabled them to persist in exposure to toxic compounds, which is due to existence of transport proteins. Efflux pumps, in Gram-negative bacteria, are proteins responsible for exporting molecules outside of the cell, by crossing the two membranes. In this study, 40 P. aeruginosa strains from hospitals, clinics, and burn center laundries and 40 P. aeruginosa strains from urban laundries were collected. This study evaluated the minimum inhibitory concentration (MIC) level of sodium dodecyl sulfate (SDS), didecyldimethylammonium chloride (DDAC), and octenidine dihydrochloride (Od) in P. aeruginosa strains. The real-time PCR was carried out to evaluate the expression of MexAB-OprM, MexCD-OprJ, and MexXY-OprM efflux system. The obtained results indicated a higher MIC level for SDS, DDAC, and Od in medical laundries. The sub-MIC level of DDAC and Od increased the expression level of MexAB-OprM, MexCD-OprJ, and MexXY-OprM in P. aeruginosa strains, suggesting that efflux pumps contribute to disinfectant resistance in P. aeruginosa .

In this study, three types of dodecyl chitosan quaternary ammonium salts, each with different spacer groups were synthesized. These chitosan derivatives are N',N'-dimethyl-N'-dodecyl-ammonium chloride-N-amino-acetyl chitosan (DMDAC), N'-dodecyl-N-isonicotinyl chitosan chloride (DINCC) and N',N'-dimethyl-N'-dodecyl-ammonium chloride-N-benzoyl chitosan (DMDBC). The synthesized products were characterized using Fourier transform infrared spectrometers, nuclear magnetic resonance, thermogravimetric analysis, and elemental analysis. The antibacterial and antibiofilm activities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were investigated. The experimental results indicated that the introduction of hydrophobic groups of spacer groups could enhance the antibacterial and antibiofilm activities of the chitosan derivatives. The antibacterial rates of the chitosan derivatives were over 90 % for both E. coli and S. aureus at a concentration of 0.5 mg/mL. The chitosan derivatives removed >50 % of the mature biofilm of E. coli and over 90 % of the mature biofilm of S. aureus at a concentration of 2.5 mg/mL. Further, the synthesized chitosan derivatives were determined to be non-toxic to L929 cells. Among them, DMDBC exhibited the most promising overall performance and show potential for wide-ranging applications in food preservation, disinfectants, medical, and other fields., Competing Interests: Declaration of competing interest We declare that we have no financial or personal relationships with any individuals or organizations that could inappropriately influence our work. We have no professional or personal interest in any product, service, or company that could be seen as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, O-quaternary ammonium chitosan (O-HTCC) containing bicationic antibacterial active groups was synthesized to develop an O-HTCC/PVA porous nanofibrous film to enhance antibacterial activity, leveraging surface modification and nano-porous structure design. Uniform and smooth nanofibrous structures (average diameter: 72-294 nm) were successfully obtained using a simple and feasible electrospinning method. A response surface model via Box-Behnken design (BBD) was used to clarify the interaction relationship between O-HTCC fiber diameter and three critical electrospinning parameters (O-HTCC concentration, applied voltage, feed flow rate), predicting that the minimum O-HTCC fiber diameter (174 nm) could be achieved with 7 wt% of O-HTCC concentration, 14 kV of voltage, and 0.11 mL/h of feed flow rate. Linear regression (R 2  = 0.9736, Radj 2  = 0.9716) and the Anderson Darling test demonstrated the excellent fit of the RSM-BBD model. Compared to N-HTCC/PVA nanofibrous film, the O-HTCC/PVA version showed increased growth inhibition and more effective antibacterial efficacies against Escherichia coli (E. coli) (~;86.34 %) and Staphylococcus aureus (S. aureus) (~;99.99 %). DSC revealed improved thermal stability with an increased melting temperature (238 °C) and endothermic enthalpy (157.7 J/g). This study holds potential for further development of antibacterial packaging to extend food shelf-life to reduce bacterial infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A new, more effective vaccine against tuberculosis (TB) is urgently needed to curtail the current TB problem. The only licensed vaccine, BCG, has been shown to have highly variable protective efficacy in several clinical trials ranging from zero to 80 % against TB disease. We have previously reported that BCG formulated in dimethyl dioctadecyl-ammonium bromide (DDA) with D-(+)-Trehalose 6,6'-Dibehenate (TDB) adjuvant (BCG + Adj) is significantly more protective than BCG alone following murine aerosol Mycobacterium tuberculosis infection. Here we investigate the immunological basis for this improved efficacy by examining expression of different immune markers and cytokines in the lungs of vaccinated mice after M. tuberculosis aerosol challenge. We found significantly greater numbers of pulmonary IL-17A-expressing CD4 + T cells in mice immunized with BCG+Adj as compared to nonvaccinated and BCG-immunized mice at one-month post-challenge and that the enhanced protection was abrogated in IL-17A-deficient mice. Furthermore, we found significantly higher levels of IL-17A, IL-12p40 and IL-33 expression in the lungs of BCG + Adj immunized animals relative to nonvaccinated mice after M. tuberculosis challenge. These results demonstrate that the DDA/TDB adjuvant increases expression of IL-17A in response to the BCG vaccine and that these augmented IL-17A levels enhance control of M. tuberculosis infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: Despite cisplatin's long history as a cornerstone in cancer therapy, both acquired chemoresistance and significant impacts on healthy tissues limit its use. Hepatotoxicity is one of its side effects. Adjunct therapies have shown promise in not only attenuating liver damage caused by cisplatin but also in enhancing the efficacy of chemotherapy. In this context, a new quaternary ammonium chitosan Schiff base (QACSB) was synthesized and applied as an encapsulating agent for the in-situ synthesis of QACSB-ZnO nanocomposite., Material and Methods: Thirty male albino rats were classified into Group 1 (control) distilled water, Group 2 (Cisplatin-treated) (12 mg/kg, i.p), and Group 3 (QACSB-ZnO NCs/cisplatin-treated) (150 mg/kg/day QACSB-ZnO NCs, i.p) for 14 days + a single dose of cisplatin. Liver functions, tissue TNF-α, MDA, and GSH were measured as well as histopathological and immunohistochemical studies were performed., Results: The QACSB-ZnO NCs significantly restore liver functions, tissue TNF-α, MDA, and GSH levels (p < 0.001). Histopathological examination showed patchy necrosis in the cisplatin-treated group versus other groups. The QACSB-ZnO NCs showed a weak TGF-β1 (score = 4) and a moderate Bcl-2 immunohistochemistry expression (score = 6) versus the CP group., Conclusions: QACSB-ZnO NCs have been shown to protect the liver from cisplatin-induced hepatotoxicity., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Heat stroke (HS) generated liver injury is a lethal emergency that occurs when the body is exposed to temperatures up to 40 °C for a few hours., Purpose: This study aimed to evaluate the therapeutic prospects of Catalpol (CA) from the blood-cooling herb Rehamanniae Radix on liver injury by HS., Study Design and Methods: A murine HS model (41 ± 0.5 °C, 60 ± 5 % relative humidity) and two cell lines (lipopolysaccharide + 42 °C) were used to assess the protective effects of CA on physiological, pathological, and biochemical features in silico, in vivo, and in vitro., Results: CA treatment significantly improved survival rates in vivo and cell viability in vitro over those of the untreated group. Additionally, CA treatment reduced core body temperature, enhanced survival time, and mitigated liver tissue damage. Furthermore, CA treatment also reduced the activities of AST and ALT enzymes in the serum samples of HS mice. Molecular docking analysis of the 28 overlapping targets between HS and CA revealed that CA has strong binding affinities for the top 15 targets. These targets are primarily involved in nine major signaling pathways, with the JAK-STAT pathway being highly associated with the other eight pathways. Our findings also indicate that CA treatment significantly downregulated the expression of proinflammatory cytokines both in vivo and in vitro while upregulating the expression of anti-inflammatory cytokines. Moreover, CA treatment reduced the levels of JAK2, phospho-STAT5, and phospho-STAT3 both in vivo and in vitro, which is consistent with its inhibition of the apoptotic markers p53, Bcl2, and Bax., Conclusions: Heat stroke-induced liver injury was inhibited by CA through the downregulation of JAK/STAT signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

This article describes the molecular mechanism by which tetraalkylammonium chloride ([R 4 N]Cl: R- = methyl (Me), ethyl (Et), propyl (Pr),butyl (Bu)) modulates the stability, folding, and dynamics of cytochrome c (Cyt c). Analysis of [R 4 N]Cl effects on thermal/chemical denaturations, millisecond refolding/unfolding kinetics, and slow CO-association kinetics of Cyt c without and with denaturant providing some significant results: (i) [R 4 N]Cl decreasing the unfolding free energy estimated by thermodynamic and kinetic analysis of thermal/chemical denaturation curves and kinetic chevrons (Log k obs -[GdmCl]) of Cyt c, respectively (ii) hydrophobicity of R-group of [R 4 N]Cl, preferential inclusion of [R 4 N]Cl at the protein surface, and destabilizing enthalpic attractive interactions of [Me 4 N]Cl and steric entropic interactions of [Et 4 N]Cl,[Pr 4 N]Cl and [Bu 4 N]Cl with protein contribute to [R 4 N]Cl-induced decrease thermodynamic stability of Cyt c (iii) [R 4 N]Cl exhibits an additive effect with denaturant to decrease thermodynamic stability and refolding rates of Cyt c (iv) low concentrations of [R 4 N]Cl (≤ 0.5 M) constrain the motional dynamics while the higher concentrations (>0.75 M [R 4 N]Cl) enhance the structural-fluctuations that denture protein (v) hydrophobicity of R-group of [R 4 N]Cl alters the [denaturant]-dependent conformational stability, refolding-unfolding kinetics, and CO-association kinetics of Cyt c. Furthermore, the MD simulations depicted that the addition of 1.0 M of [R 4 N]Cl increased the conformational fluctuations in Cyt c leading to decreased structural stability in the order [Me 4 N]Cl < [Et 4 N]Cl < [Pr 4 N]Cl < [Bu 4 N]Cl consistent with the experimental results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Treated or coated sutures promise to prevent contamination of wounds., Purpose: The purpose of the study was to coat surgical sutures with a new quaternary ammonium silane (QAS) antimicrobial compound at two different application temperatures and then to evaluate the resulting structural, physical, mechanical, and biological properties., Study Design, Setting, Sample: In vitro and in vivo studies were conducted using male albino Wistar rats approved by the Joint Ethical Committee of IMU and Postgraduate Medical Institute, Lahore. Only suture samples, coated uniformly with verified presence of the compound and of adequate length were used. Samples which were not coated uniformly and with inadequate length or damaged were excluded., Predictor Variable: Predictor variables were sutures with and without QAS coatings and different temperatures. Sutures were coated with QAS at 0.5 and 1.0% wt/vol using the dip coating technique and sutures with and without QAS coating were tested at 25 and 40 °C temperatures., Main Outcome Variable(s): Outcome variables of structural and physico-mechanical properties of QAS-coated and non-coated sutures were measured using Fourier transform infrared spectroscopy (for structural changes), confocal laser and scanning electron (for diameter changes), and tensile strength/modulus (for mechanical testing). Biologic outcome variables were tested (bacterial viability); macrophage cultures from Wistar rats were tested (M1/M2 polarization detecting IL-6 and IL-10). Macrophage cells were analyzed with CD80+ (M1) and CD163+ (M2). Chemotaxis index was calculated as a ratio of quantitative fluorescence of cells., Covariates: Not applicable., Analyses: Ordinal data among groups were compared using the Wilcoxon Mann-Whitney U test along with the comparison of histological analysis using the Wilcoxon Sign-rank test (P < .05)., Results: Fourier transform infrared spectroscopy peak at 1490 cm -1 confirmed the presence of QAS on suture's surfaces with a significant increase (P < .05) in diameter (0.99 ± 0.5-mm) and weight (0.77 ± 0.02-mg) observed for 1% QAS groups treated at 40 °C. Non-coated samples heated at 25 °C had significantly (P < .05) less diameters (0.22 ± 0.03-mm) and weights (0.26 ± 0.06-mg). Highest tensile strength/modulus was observed for 0.5% QAS-coated samples which also had significantly higher antibacterial characteristics than other sutures (P < .05). QAS-coated sutures significantly increased M1 and M2 markers., Conclusion and Relevance: QAS coating conferred antibacterial action properties without compromising the physical and mechanical properties of the suture., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Dental caries (DC) is one of the most common oral diseases and is mainly caused by Streptococcus mutans ( S. mutans ). The use of antibiotics against S. mutans usually has side effects, including developing resistance. N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC), a natural product, has great potential utility in antibacterial agents owing to its low toxicity and good biocompatibility. Thus, the purpose of the present study was to explore the antimicrobial activity of N-2-HACC against S. mutans through the permeability of the cell wall, integrity of cell membrane, protein and nucleic acid synthesis, respiratory metabolism, and biofilm formation. Our results confirmed that the MIC of N-2-HACC against S. mutans was 0.625 mg/mL with a 90.01 ± 1.54% inhibition rate. SEM observed the formation of cavities on the surface of S. mutans after 12 h N-2-HACC treatment. The level of alkaline phosphatase (AKP) activity was higher in the N-2-HACC treatment group than in the control group, indicating that N-2-HACC can improve the permeability of the cell wall. Also, N-2-HACC treatment can destroy the cell membrane of S. mutans by increasing conductivity and absorbance at 260 nm, decreasing cell metabolic activity, and enhancing the fluorescence at 488 nm. Respiratory metabolism revealed that the activities of the Na + -K + -ATP enzyme, pyruvate kinase (PK), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were decreased after N-2-HACC treatment, revealing that N-2-HACC can inhibit glycolysis and the tricarboxylic acid cycle (TCA cycle) of S. mutans . Moreover, N-2-HACC can also decrease the contents of the nucleic acid and solution protein of S. mutans , interfere with biofilm formation, and decrease the mRNA expression level of biofilm formation-related genes. Therefore, these results verify that N-2-HACC has strong antibacterial activity against S. mutans , acting via cell membrane integrity damage, increasing the permeability of cell walls, interfering with bacterial protein and nucleic acid synthesis, perturbing glycolysis and the TCA cycle, and inhibiting biofilm formation. It is suggested that N-2-HACC may represent a new potential synthetically modified antibacterial material against S. mutans .

This comprehensive literature review examines the use of silver diamine fluoride (SDF) for the prevention and treatment of enamel carious lesions. SDF has been approved by different international drug associations as a caries-preventing agent to be used on deep carious lesions (dentin). However, SDF can cause staining of exposed tooth structures. Furthermore, the effect of SDF on the bond of adhesives to the tooth structure is still being determined. This review explores various studies on the use of SDF to treat enamel carious lesions, highlighting its effectiveness and preventive action. The literature suggests that SDF inhibits bacterial growth, promotes remineralization, and does not negatively affect adhesive retentions. Potassium iodide (KI) or glutathione (GSH) can reduce staining and discoloration. However, the reviewed studies have limitations. Further research, including well-designed clinical trials, is necessary to validate the findings and evaluate the long-term implications of SDF treatment. Conclusion: Despite the above-mentioned limitations, SDF shows potential as a therapy for enamel caries prevention, remineralization, and use as an adjuvant to other dental treatments, warranting further investigation and the refinement of application methods., Competing Interests: The author declares they have no competing interests., (©2024 AlSheikh.)

A new antibacterial system (HG) based on the host-guest chemistry between pillar[5]arene and a zwitterionic guest was fabricated. The HG complex displayed excellent antibacterial and biofilm formation inhibition and dispersal activities against E. coli , S. aureus and MRSA.

Stimuli-responsive supramolecular chemotherapy, particularly in response to cancer biomarkers, has emerged as a promising strategy to overcome the limitations associated with traditional chemotherapy. Spermine (SPM) is known to be overexpressed in certain cancers. In this study, we introduced a novel supramolecular chemotherapy system triggered by SPM. The system featured pyridine salts of a diphenylanthracene derivative (PyEn) and a complementary water-soluble pillar[5]arene (WP5C5) with long alkyl chains. The diphenylanthracene unit of PyEn is effectively encapsulated within the long alkyl chains of WP5C5, resulting in a substantial reduction in the cytotoxicity of PyEn towards normal cells. The therapeutic effect of PyEn is selectively triggered intracellularly through SPM, leading to the endosomal release of PyEn and concurrent in situ cytotoxicity. This supramolecular chemotherapy system exhibits notable tumor inhibition against SPM-overexpressed cancers with reduced side effects on normal tissues. The supramolecular strategy for intracellular activation provides a novel tool with potential applications in chemotherapeutic interventions, offering enhanced selectivity and reduced cytotoxicity to normal cells.

Herein, we report a new strategy for the design of antibiotic agents based on the electrostatic interaction and hydrogen bonding, highlighting the significance of hydrogen bonding and the increased recognition sites in facilitating the interaction with bacterial cell membranes and DNA. A series of quaternary ammonium functionalized urea-based anion receptors were studied. While the monodentate mono-urea M1 , bisurea M2 , and trisurea M3 failed to break through the cell membrane barrier and thus could not kill bacteria, the extended bidentate dimers D1 - D3 presented gradually increased membrane penetrating capabilities, DNA conformation perturbation abilities, and broad-spectrum antibacterial activities against E. coli , P. aeruginosa , S. aureus , E. faecalis , and S. epidermidis .

Quaternary ammonium compound (QAC) disinfectants represent one of our first lines of defense against pathogens. Their inhibitory and bactericidal activities are usually tested through minimum inhibitory concentration (MIC) and time-kill assays, but these assays can become cumbersome when screening many compounds. We investigated how the dynamic surface tension (DST) measurements of QACs correlate with these antimicrobial activities by testing a panel of potent and structurally varied QACs against the gram-positive Staphylococcus aureus and the gram-negative Pseudomonas aeruginosa. We found that DST values correlated well with bactericidal activity in real-world disinfection conditions but not with MIC values. Moreover, no correlation between these two antimicrobial activities of QACs (bactericidal and inhibition) was observed. In addition, we observed that the bactericidal activity of our QAC panel against the gram-negative P. aeruginosa was severely affected in the presence of hard water. Interestingly, we found that the counterion of the QAC affects the killing of bacteria in these conditions, a phenomenon not observed in most MIC assessments. Moreover, some of our best-in-class QACs show enhanced bactericidal activity when combined with a commercially available QAC. In conclusion, we determined that an intrinsic physical property of QACs (DST) can be used as a technique to screen for bactericidal activity of QACs in conditions that mimic real-world disinfection conditions., (© 2024 Wiley-VCH GmbH.)

In this paper, a hydrogel material with efficient antibacterial, hemostatic, self-healing, and injectable properties was designed for the treatment of diabetic wounds. Firstly, quaternary ammonium salts were grafted with oxidized sodium alginate, and quaternized oxidized sodium alginate (QOSA) was synthesized. Due to the introduction of quaternary ammonium group it has antibacterial and hemostatic effects, at the same time, due to the presence of aldehyde group it can be reacted with carboxymethyl chitosan (CMCS) to form a hydrogel through the Schiff base reaction. Furthermore, deer antler blood polypeptide (DABP) was loaded into the hydrogel (QOSA&CMCS&DABP), showing good swelling ratio and bacteriostatic effect. In vitro and in vivo experiments demonstrated that the hydrogel not only quickly inhibited hepatic hemorrhage in mice and reduced coagulation index and clotting time in vitro, but also significantly enhanced collagen deposition at the wound site, accelerating wound healing. This demonstrates that the multifunctional hydrogel materials (QOSA&CMCS&DABP) have promising applications in the acceleration of skin wound healing and antibacterial promotion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: This systematic review aims to evaluate the potential benefits and underlying mechanisms of combining SDF with light curing, based on available studies., Materials and 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)., Conclusion: 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Min et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2024. The Author(s).)

The adherence of pathogenic microorganisms to surfaces and their association to form antibiotic-resistant biofilms threatens public health and affects several industrial sectors with significant economic losses. For this reason, the medical, pharmaceutical and materials science communities are exploring more effective anti-fouling approaches. This review focuses on the anti-fouling properties, structure-activity relationships and environmental toxicity of quaternary ammonium salts (QAS) and, as a subclass, ionic liquid compounds. Greener alternatives such as QAS-based antimicrobial polymers with biocide release, non-fouling (i.e., PEG, zwitterions), fouling release (i.e., poly(dimethylsiloxanes), fluorocarbon) and contact killing properties are highlighted. We also report on dual-functional polymers and stimuli-responsive materials. Given the economic and environmental impacts of biofilms in submerged surfaces, we emphasize the importance of less explored QAS-based anti-fouling approaches in the marine industry and in developing efficient membranes for water treatment systems.

Nano-assemblies based on perphenazine modified pillar[5]arene were constructed successfully for synergistic photothermal and photodynamic (I&II) cancer therapy.

Ammonium and hexyltrimethylammonium thiomolybdates (ATM and ATM-C6) and thiotungstates (ATT and ATT-C6) were synthesized. Their toxicity was evaluated using both in vitro and in vivo approaches via the zebrafish embryo acute toxicity assay (ZFET), while the copper-thiometallate interaction was studied using cyclic voltammetry, as well as in an in vivo assay. Cyclic voltammetry suggests that all thiometallates form complexes with copper in a 2:1 Cu:thiometallate ratio. Both in vitro and in vivo assays demonstrated low toxicity in BALB/3T3 cells and in zebrafish embryos, with high IC 50 and LC 50 values. Furthermore, the hexyltrimethylammonium ion played a crucial role in enhancing viability and reducing toxicity during prolonged treatments for ATM and ATT. In particular, the ZEFT assay uncovered the accumulation of ATM in zebrafish yolk, averted by the incorporation of the hexyltrimethylammonium ion. Notably, the copper-thiometallate interaction assay highlighted the improved viability of embryos when cultured in CuCl 2 and ATM-C6, even at high CuCl 2 concentrations. The hatching assay further confirmed that copper-ATM-C6 interaction mitigates inhibitory effects induced by thiomolybdates and CuCl 2 when administered individually. These results suggest that the incorporation of the hexyltrimethylammonium ion in ATM increase its ability to interact with copper and its potential application as a copper chelator., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: to investigate whether baseline mineral distribution modulates the ability of silver diammine fluoride (SDF) to remineralize and stain enamel caries lesions., Methods: This laboratory study followed a 3 [treatment: SDF/fluoride varnish (FV)/deionized water (DIW)] ×3 [lesion protocol: methylcellulose (MeC)/hydroxyethylcellulose (HEC)/Carbopol 907 (C907)] factorial design. Lesions were created in bovine enamel specimens (n = 20). Treatments were applied and lesions remineralized in artificial saliva. Digital transverse microradiography (TMR-D) was used to analyze lesions. Lesion color was monitored spectrophotometrically. The effects of lesion protocol and treatment on changes in lesion depth (ΔLD), mineral loss (ΔΔZ), maximum mineral density at the surface zone (ΔSZ max ), and color changes related to remineralization (ΔL* remin ) were analyzed using two-way ANOVA., Results: The treatment×lesion protocol interaction was significant for ΔΔZ (p < 0.01) and ΔL* remin (p < 0.01), however not for ΔLD (p = 0.23) or ΔSZ max (p = 0.91). There were no differences in ΔΔZ between treatments in HEC and C907 lesions. However, DIW resulted in more remineralization than both SDF (p < 0.01) and FV (p = 0.01) in MeC lesions. Considering changes from lesion baseline after remineralization in MeC lesions, SDF treatment resulted in the highest mineral gain in the surface zone. However, DIW revealed the highest mineral gain after remineralization in the lesion body. SDF stained lesions with the intensity increasing after remineralization in C907 lesions, whereas staining decreased in MeC and HEC lesions., Conclusion: High fluoride treatments can interfere with continuous remineralization of caries lesions due to partial arrest. Baseline lesion mineral distribution affects SDF's ability to enhance remineralization and the staining caused by SDF., Clinical Significance: SDF is being used to arrest active caries lesions extending into dentin and to treat dentin hypersensitivity. This study shed light on SDF's effect on an isolated process in dental caries only, remineralization. It achieved this by examining enamel caries lesions with differing mineral distributions and assessing their staining properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: This study aims to evaluate antibacterial effects of silver diamine fluoride (SDF), SDF/potassium iodide (KI), and nanosilver fluoride (NSF)., Methods: Antimicrobial activity of sterile saline, 5% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX), SDF, SDF/KI, NSF, and KI solutions against Streptococcus mutans and Lactobacillus casei was assessed through disc diffusion tests. A dual-species biofilm of S. mutans-L. casei was formed on 48 enamel samples, divided into six groups (n = 8). Group 1 was treated with sterile saline, Group 2 with 5% NaOCl, Group 3 with 2% CHX, Group 4 with SDF, Group 5 with SDF/KI, and Group 6 with NSF. The samples were analysed using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Statistical analysis utilized Shapiro-Wilk and Kruskal-Wallis tests and multiple comparisons were conducted using Dunn test., Results: SDF, SDF/KI, and NaOCl displayed significantly higher antibacterial activity against dual-species biofilm compared to NSF and CHX (p < 0.050)., Conclusions: In conclusion, SDF and SDF/KI demonstrated greater antibacterial activity than NSF. SDF's antibacterial activity was unaffected by KI. Further research is needed to determine the appropriate content and concentration for achieving effective antibacterial activity with NSF., Clinical Significance: The use of silver-containing materials is increasing in popularity within pediatric dentistry. In this study, an endeavor has been made to assist pediatric dentists in determining which solution might be more advantageous for preventing caries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Cotton has attracted considerable attention due to its functional characteristics. The focus of research on cotton has shifted in recent years towards designing multi-functional and modified media for cotton fibers, which can be firmly combined with textiles, giving them reusability and extending their service life. This study constructed a synergistic antibacterial layer of quaternary ammonium compounds (QACs) and N-halamine (Hals) using an in-situ free radical copolymerization method in water, named QACs/Hals@cotton-Cl. The route significantly increases the number of antibacterial active centers. FTIR, XPS, and SEM were used to systematically analyze the product's chemical structure, surface morphology, and other characteristics. The modified fabric's antibacterial efficiency, wound healing, renewability, and durability were also evaluated. The chlorinated modified cotton fabric could completely eradicate S. aureus and E. coli within 10 min. Compared with pure cotton, it notably promoted the healing rate of infected wounds in mice. The modification method imparted excellent hydrophobicity to the cotton fabric, with a contact angle exceeding 130°, making it easy to remove surface stains. After 30 days of regular storage and 24 h of UV irradiation, the active chlorine concentration (Cl + %) only decreased by 25 % and 39 %, respectively, and the reduced Cl + % was effectively recharged via simple re-chlorination. The hydrophobicity and antimicrobial properties of QACs/Hals@cotton-Cl remained stable even after 20 cycles of friction. This simple synthesis technique provides a convenient approach for the scalable fabrication of multifunctional and rechargeable antibacterial textiles, with potential applications in medical devices and personal hygiene protection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: In community settings with limited dental personnel and equipment, and in an era when the aerosol transmission of infectious agents is on the rise, a non-invasive approach to caries management is critical. To provide information on non-invasive material selection, the aim of this study was to compare the remineralization effect of commonly used fluoride-containing materials, adjunctive to the everyday use of fluoride toothpaste (F-toothpaste), on primary tooth natural dentin caries., Methods: Fifty-five specimens were randomly divided into five groups: 38% silver diamine fluoride (SDF), 5% fluoride varnish (F-varnish), glass-ionomer cement (GIC), deionized water (DW) with F-toothpaste slurry, and DW as a control group (n = 11). The lesion depth and mineral density were measured before and after bacterial pH-cycling using micro-computed tomography. The percentage of mineral density change (%MDchange) was quantified. The dependent t-test, Wilcoxon-Signed-Rank Test, and one way ANOVA with Bonferroni correction were used to analyse the data., Results: SDF application reduced lesion depth from 844.6 to 759.1 μm (p < 0.045) while increasing mineral density from 551.4 to 763.0 mgHA/cm 3 (p < 0.003). Only mineral density rose from 600.2 to 678.4 mgHA/cm 3 (p < 0.013) when GIC was used. The other groups showed no difference. The highest %MDchange was also found after SDF treatment (49.7%, p < 0.05), whereas GIC (17.2%, p < 0.05) presented a higher percentage than the F-varnish (2.0%), F-toothpaste (-1.1%) and no-treatment groups (-1.4%)., Conclusion: In this in vitro study, where the pH of cycling was almost neutral, using SDF as an adjunct to F-toothpaste resulted in the highest remineralization compared with other remineralizing materials., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Alzheimer's disease (AD) is associated with brain accumulation of amyloid-beta (Aβ) and neurofibrillary tangle formation, in addition to reduced brain docosahexaenoic acid (DHA) and increased brain iron levels. DHA requires access across the blood-brain barrier (BBB) to enter the brain, and iron has been shown to affect the expression and function of a number of BBB transporters. Therefore, this study aimed to assess the effect of iron on the expression and function of fatty acid binding protein 5 (FABP5) and fatty acid transport protein 1 (FATP1), both which mediate brain endothelial cell trafficking of DHA., Methods: The mRNA and protein levels of FABP5 and FATP1 in human cerebral microvascular endothelial (hCMEC/D3) cells was assessed by RT-qPCR and Western blot, respectively following ferric ammonium citrate (FAC) treatment (up to 750 µM, 72 h). The function of FABP5 and FATP1 was assessed via uptake and efflux of radiolabelled 3 H-oleic acid and 14 C-DHA., Results: FAC (500 µM, 72 h) had no impact on the expression of FABP5 at the protein and mRNA level in hCMEC/D3 cells, which was associated with a lack of effect on the uptake of 14 C-DHA. FAC led to a 19.7% reduction in FATP1 protein abundance in hCMEC/D3 cells with no impact on mRNA levels, and this was associated with up to a 32.6% reduction in efflux of 14 C-DHA., Conclusions: These studies demonstrate a role of iron in down-regulating FATP1 protein abundance and function at the BBB, which may have implications on fatty acid access to the brain., (© 2024. The Author(s).)

The widespread use of disinfectants and antiseptics, and consequently their release into the environment, determines the relevance of studying their potential impact on the main producers of organic matter on the planet-photosynthetic organisms. The review examines the effects of some biguanides and quaternary ammonium compounds, octenidine, miramistin, chlorhexidine, and picloxidine, on the functioning of the photosynthetic apparatus of various organisms (Strakhovskaya et al. in Photosynth Res 147:197-209, 2021; Knox et al. in Photosynth Res 153:103, 2022; Paschenko et al. in Photosynth Res 155:93-105, 2023a, Photosynth Res 2023b). A common feature of these antiseptics is the combination of hydrophobic and hydrophilic regions in the molecules, the latter carrying a positive charge(s). The comparison of the results obtained with intact bacterial membrane vesicles (chromatophores) and purified pigment-protein complexes (photosystem II and I) of oxygenic organisms allows us to draw conclusions about the mechanisms of the cationic antiseptic action on the functional properties of the components of the photosynthetic apparatus., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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.

This study aimed to compare the effect of silver diamine fluoride (SDF) and fluoride varnish (NaF) on the Vickers microhardness (VHN) of enamel and dentin after radiotherapy and pH-cycling. Human premolars were cut longitudinally, embedded and serially polished. The VHN of enamel/dentin and irradiated enamel/dentin were evaluated. The irradiated specimens were treated with either NaF or SDF, subjected to pH-cycling then VHN test for 4 days. Consequently, they were subjected to energy-dispersive X-ray (EDX) analysis. Radiation adversely affect enamel VHN (p<0.05), whereas dentin VHN was not affected (p>0.05). After pH-cycling, a significant decrease in dentin VHN was observed on day 2 for all groups, whereas enamel VHN was significantly decreased in the control group on day 4. SDF-treated enamel demonstrated higher VHN than that of NaF on day 3. Caries prevention effect of SDF and NaF were observed on enamel, where SDF was proved to be superior to NaF.

Background: Silver diamine fluoride (SDF) is becoming more widely recognized as a simple, cost-effective approach to minimize sensitivity and arrest caries. However, SDF results in caries that are stained black. Potassium iodide (KI) treatment with SDF may minimize or lessen the staining. However, the effectiveness of KI on staining has not been investigated. Studies demonstrating that potassium iodide reduces the black staining are still insufficient. This paper presents the study protocol for Healthy Smiles, a randomized controlled trial implemented to compare the staining propensity of SDF and SDF+KI., Objective: This study, Healthy Smiles, aims to evaluate the staining propensity of SDF and SDF+KI using a Nix Mini color sensor among children aged 4 to 6 years. Another objective of the study is to evaluate the caries-arresting effect of SDF and SDF+KI in the treatment of carious primary teeth., Methods: This study is a randomized controlled trial. A total of 60 children with caries that meet the criteria of the International Caries Detection and Assessment System (code 1 or above) will be randomly assigned to treatment groups, where group 1 will be treated with SDF and group 2 will be treated with SDF+KI. Discoloration of treated lesions will be assessed digitally using a Nix Mini color sensor. Participants will be followed up at 1, 3, and 6 months after treatment to digitally record the ∆L and ∆E values using the Nix Mini color sensor. Data will be analyzed using SPSS (version 28; IBM Corp). Independent sample t tests and the Mann-Whitney U test will be used to compare the 2 groups., Results: Enrollment started in October 2023. It is estimated that the enrollment period will be 12 months. Data collection is planned to be completed in 2024., Conclusions: The presented paper describes Happy Smiles, a project that provides an opportunity to address the aesthetic inconvenience of patients without compromising the effectiveness of the SDF treatment. The trial findings will contribute to the limited evidence base related to discoloration after SDF intervention to improve aesthetic appearances in child oral health. If the results from the trial are promising, it will lead to the development of a model for child oral health and pave the way for further research in child oral health., International Registered Report Identifier (irrid): PRR1-10.2196/51087., (©Praveena Navaneethan, Imran Pasha Mohammed, Rekha P Shenoy, Junaid Junaid, Supriya Amanna, Zeyad Alsughier, Shaul Hameed Kolarkodi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.07.2024.)

Synthetic polymer surfaces provide an excellent opportunity for developing materials with inherent antimicrobial and/or biocidal activity, therefore representing an answer to the increasing demand for antimicrobial active medical devices. So far, biologists and material scientists have identified a few features of bacterial cells that can be strategically exploited to make polymers inherently antimicrobial. One of these is represented by the introduction of cationic charges that act by killing or deactivating bacteria by interaction with the negatively charged parts of their cell envelope (lipopolysaccharides, peptidoglycan, and membrane lipids). Among the possible cationic functionalities, the antimicrobial activity of polymers with quaternary ammonium centers (QACs) has been widely used for both soluble macromolecules and non-soluble materials. Unfortunately, most information is still unknown on the biological mechanism of action of QACs, a fundamental requirement for designing polymers with higher antimicrobial efficiency and possibly very low toxicity. This mini-review focuses on surfaces based on synthetic polymers with inherently antimicrobial activity due to QACs. It will discuss their synthesis, their antimicrobial activity, and studies carried out so far on their mechanism of action.

Iron is often accumulated in the liver during pathological conditions such as cirrhosis and cancer. Elevated expression of glucose transporters GLUT1 and GLUT3 is associated with reduced overall survival in patients with hepatocellular carcinoma. However, it is not known whether iron can regulate glucose transporters and contribute to tumor proliferation. In the present study, we found that treatment of human liver cell line HepG2 with ferric ammonium citrate (FAC) resulted in a significant upregulation of GLUT3 mRNA and protein in a dose-dependent manner. Similarly, iron accumulation in mice fed with high dietary iron as well as in mice injected intraperitoneally with iron dextran enhanced the GLUT3 expression drastically in the liver. We demonstrated that iron-induced hepatic GLUT3 upregulation is mediated by the LKB1/AMPK/CREB1 pathway, and this activation was reversed when treated with iron chelator deferiprone. In addition, inhibition of GLUT3 using siRNA prevented iron-mediated increase in the expression of cell cycle markers and cellular hyperproliferation. Furthermore, exogenous sodium beta-hydroxybutyrate treatment prevented iron-mediated hepatic GLUT3 activation both in vitro and in vivo. Together, these results underscore the importance of iron, AMPK, CREB1 and GLUT3 pathways in cell proliferation and highlight the therapeutic potential of sodium beta-hydroxybutyrate in hepatocellular carcinoma with high GLUT3 expression.

Adjuvants are effective tools to enhance vaccine efficacy and control the type of immune responses such as antibody and T helper 1 (Th1)- or Th2-type responses. Several studies suggest that interferon (IFN)-γ-producing Th1 cells play a significant role against infections caused by intracellular bacteria and viruses; however, only a few adjuvants can induce a strong Th1-type immune response. Recently, several studies have shown that lipid nanoparticles (LNPs) can be used as vaccine adjuvants and that each LNP has a different adjuvant activity. In this study, we screened LNPs to develop an adjuvant that can induce Th1 cells and antibodies using a conventional influenza split vaccine (SV) as an antigen in mice. We observed that LNP with 1,2-di-O-octadecenyl-3-trimethylammonium-propane (DOTMA) as a component lipid (DOTMA-LNP) elicited robust SV-specific IgG1 and IgG2 responses compared with SV alone in mice and was as efficient as SV adjuvanted with other adjuvants in mice. Furthermore, DOTMA-LNPs induced robust IFN-γ-producing Th1 cells without inflammatory responses compared to those of other adjuvants, which conferred strong cross-protection in mice. We also demonstrated the high versatility of DOTMA-LNP as a Th1 cell-inducing vaccine adjuvant using vaccine antigens derived from severe acute respiratory syndrome coronavirus 2 and Streptococcus pneumoniae . Our findings suggest the potential of DOTMA-LNP as a safe and effective Th1 cell-inducing adjuvant and show that LNP formulations are potentially potent adjuvants to enhance the effectiveness of other subunit vaccines.

Introduction: Caries in primary teeth rapidly advances owing to its thin structure, thereby requiring restoration. However, restorations often fail due to various causes such as secondary caries and reduced microtensile bond strength (μTBS), which calls for the use of antimicrobial agents such as silver diamine fluoride (SDF)., Aim: This study aims to measure and analyse the effect of SDF application on the μTBS of three regularly used restorative materials to dentin of primary teeth as well as compare the types of bond failure interfaces under SEM., Materials and Methods: The study comprised 60 samples equally divided into six groups among three restorative materials, namely, glass ionomer cement (GIC, Groups I and II), resin-modified glass ionomer cement (RMGIC, Groups III and IV), and composite resin (Groups V and VI) with subdivisions of A and B, where A represented samples with SDF application and B represented samples without SDF application., Results and Observations: It was observed that μTBS of RMGIC to sound and carious dentin irrespective of SDF application was found to be statistically significant (P < 0.05), and when GIC, RMGIC, and composite resins were compared to both sound and carious dentin irrespective of SDF application, it was statistically significant (P < 0.05). SEM analysis revealed predominantly cohesive failures among all the groups., Conclusion: Based on the results, it was concluded that SDF has no adverse effect on the μTBS of GIC, RMGIC, and composite resin to both carious and sound dentin of primary teeth., (Copyright © 2024 Copyright: © 2024 Journal of Indian Society of Pedodontics and Preventive Dentistry.)

The linkage between biocides and antibiotic resistance has been widely suggested in laboratories and various environments. However, the action mechanism of biocides on antibiotic resistance genes (ARGs) spread is still unclear. Thus, 6 quaternary ammonium biocides (QACs) with different bonded substituents or alkyl chain lengths were selected to assess their effects on the conjugation transfer of ARGs in this study. Two conjugation models with the same donor (E. coli DH5α (RP4)) into two receptors, E. coli MG1655 and pathogenic S. sonnei SE6-1, were constructed. All QACs were found to significantly promote intra- and inter-genus conjugative transfer of ARGs, and the frequency was highly impacted by their structure and receptors. At the same environmental exposure level (4 × 10 -1 mg/L), didecyl dimethyl ammonium chloride (DDAC (C10)) promoted the most frequency of conjugative transfer, while benzathine chloride (BEC) promoted the least. With the same donor, the enhanced frequency of QACs of intra-transfer is higher than inter-transfer. Then, the acquisition mechanisms of two receptors were further determined using biochemical combined with transcriptome analysis. For the recipient E. coli, the promotion of the intragenus conjugative transfer may be associated with increased cell membrane permeability, reactive oxygen species (ROS) production and proton motive force (PMF)-induced enhancement of flagellar motility. Whereas, the increase of cell membrane permeability and decreased flagellar motility due to PMF disruption but encouraged biofilm formation, maybe the main reasons for promoting intergenus conjugative transfer in the recipient S. sonnei. As one pathogenic bacterium, S. sonnei was first found to acquire ARGs by biocide exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Quaternary ammonium salts (QAS) are widely used in medicine, industry and agriculture as disinfectants, biocides, and fungicides. QAS have the ability to coat various surfaces, prevent adhesion of microorganisms to them and inhibit the formation of biofilm. A group of surfactants derived from benzoic acid with different chemical structures was tested: monomeric QAS with different alkyl chain lengths (C 12 , C 14 , C 16 ), gemini QAS containing 12-carbon alkyl chains and linkers of various lengths (3,4,6 methylene groups), as well as multifunctional QAS. Among the tested surfactants, monomeric QAS showed the highest bactericidal and fungicidal activity. All three groups of tested compounds inhibited the filamentation of C. albicans. The best antimicrobial activity was demonstrated by the monomeric surfactant C 12 AA, while the multifunctional equivalent (2xC 12 AA) was characterized by good anti-adhesive activity. All tested compounds are non-mutagenic and cause low hemolysis of sheep erythrocytes. Multifunctional and gemini surfactants are also non-toxic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is a substantially ascending demand for nonantibiotic strategies to overcome the resistance of bacterial infections. Here, the discovery of a distinctive antibacterial structure is reported. The novel structure of nanoparticle strategy is proposed for appreciable bacteria killing by the smart design of the delayed addition of crosslinkers into the reaction mixture. [2-(methacryloyloxy)ethyl]trimethylammonium chloride solution (MTCl), a water-soluble ionic liquid (IL), has narrow-size material distribution, good whiteness, and high weather resistance. The quaternary ammonium salt is utilized to efficiently permeate cell membranes through electrostatic interaction, accordingly, boasting a beneficiary of antibacterial properties. More importantly, it allows bacteria to attach the nanomaterials easily, especially the double-shelled nanosphere. In light of the introduction of 9-amino(9-deoxy)ep-quinine (QNNH 2 ) on its inner shell, it blocks the nucleic acid and glucose metabolism in bacteria, which is betterment of the antibacterial activity of double-shelled structure nanoparticle compared to other structure of nanomaterials. This physical/chemical/biological triple antibacterial process eliminates the need for traditional antibiotics, and the fabrication strategies and material properties described here provide insights into the design of antibacterial nanomaterials based on chemical and physical effects., (© 2024 Wiley‐VCH GmbH.)

The paper reports new hydrogels based on quaternary ammonium salts of chitosan designed as biocidal products. The chitosan derivative was crosslinked with salicylaldehyde via reversible imine bonds and supramolecular self-assemble to give dynamic hydrogels which respond to environmental stimuli. The crosslinking mechanism was demonstrated by 1 H NMR and FTIR spectroscopy, and X-ray diffraction and polarized light microscopy. The hydrogel nature, self-healing and thixotropy were proved by rheological investigation and visual observation, and their morphology was assessed by scanning electron microscopy. The relevant properties for application as biocidal products, such as swelling, dissolution, bioadhesiveness, antimicrobial activity and ex-vivo hemocompatibility and in vivo local toxicity and biocompatibility on experimental mice were measured and analyzed in relationship with the imination degree and the influence of each component. It was found that the hydrogels are superabsorbent, have good adhesivity to skin and various surfaces and antimicrobial activity against relevant gram-positive and gram-negative bacteria, while being hemocompatible and biocompatible. Besides, the hydrogels are easily biodegraded in soil. All these properties recommend the studied hydrogels as ecofriendly biocidal agents for living tissues and surfaces, but also open the perspectives of their use as platform for in vivo applications in tissue engineering, wound healing, or drug delivery systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

With increasing health awareness of the pathogenic effects of disease-causing microorganisms, interest in and use (of medical textiles, disinfectants in medical devices, etc.) of antimicrobial substances have increased in various applications, such as medical textiles and disinfectants (alcohol-based and nonalcoholic), in medical devices There are several concerns with alcohol-based disinfectants, such as surface deformation of medical devices due to high alcohol content and damage to skin tissue caused by lipid and protein denaturation of cell membranes. Quaternary ammonium compounds (quats) were preferred because they have the potential to prepare water-based disinfectants. In this study, novel (3-chloropropyl)triethoxysilane (CPTMO) and (3-chloropropyl)triethoxysilane (CPTEO) based quaternary ammonium silane compounds (silane-quats) were developed using quats with carbon chain lengths of C12, C14, C16 and C18. Titration (ASTM D2074) was used to calculate the yield of the synthesis and the structures of the products were characterised by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy ( 13 C NMR, 1 H NMR) and gas chromatography-mass spectrometry (GC-MS).The in vitro antimicrobial activity of the synthesized samples was evaluated against Gram-positive (Staphylococcus aureus (S. aureus), Enterococcus hirae (E. hirae)) and Gram-negative (Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa)) bacteria and fungi (Candida albicans (C. albicans), Aspergillus brasiliensis (A. brasiliensis)) using the minimum inhibitory concentration (MIC) test. According to MIC tests, the silane-quats with the highest antimicrobial effects were dimethylhexadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (SQ3), which had an MIC of < 16 μg/ml (ppm) against E. coli, S. aureus, E. hirae, C. albicans, and A. brasiliensis and 32 μg/ml against P. aeruginosa. The MIC test results also showed antimicrobial activity at least 2 times greater than that of the commercially available disinfectant benzalkonium chloride (BAC). Findings suggest that SQ3 (C16) holds promise as an effective medical disinfectant, presenting a novel approach to combating microbial infections in healthcare settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Since the discovery of antimicrobial agents, the misuse of antibiotics has led to the emergence of bacterial strains resistant to both antibiotics and common disinfectants like quaternary ammonium compounds (QACs). A new class, 'gemini' QACs, which contain two polar heads, has shown promise. Octenidine (OCT), a representative of this group, is effective against resistant microorganisms but has limitations such as low solubility and high cytotoxicity. In this study, we developed 16 novel OCT derivatives. These compounds were subjected to in silico screening to predict their membrane permeation. Testing against nosocomial bacterial strains (G + and G - ) and their biofilms revealed that most compounds were highly effective against G + bacteria, while compounds 7, 8, and 10-12 were effective against G - bacteria. Notably, compounds 6-8 were significantly more effective than OCT and BAC standards across the bacterial panel. Compound 12 stood out due to its low cytotoxicity and broad-spectrum antimicrobial activity, comparable to OCT. It also demonstrated impressive antifungal activity. Compound 1 was highly selective to fungi and four times more effective than OCT without its cytotoxicity. Several compounds, including 4, 6, 8, 9, 10, and 12, showed strong virucidal activity against murine cytomegalovirus and herpes simplex virus 1. In conclusion, these gemini QACs, especially compound 12, offer a promising alternative to current disinfectants, addressing emerging resistances with their enhanced antimicrobial, antifungal, and virucidal properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jan Marek reports financial support was provided by Ministry of Health of the Czech Republic. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate caries preventive effects of 38 % silver diamine fluoride (SDF) pretreatment on neighboring tooth proximal to glass ionomer cement (GIC), including conventional GIC (CGIC) and resin-modified GIC (RMGIC) restorations in an in vitro model., Methods: HUMAN TOOTH BLOCKS WERE RESTORED WITH: SDF+CGIC (Group 1), CGIC (Group 2), SDF+RMGIC (Group 3) or RMGIC (Group 4). Enamel specimen simulating proximal surface of neighboring tooth was placed in proximity to the restorations. The specimen underwent cariogenic challenge with cross-kingdom biofilm of Streptococcus mutans, Lacticaseibacillus casei and Candida albicans. After cariogenic challenge, the biofilm's growth kinetics, viability, and morphology were evaluated by propidium monoazide-quantitative polymerase chain reaction (PMA-qPCR), confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), respectively. The enamel lesion depth, surface morphology and crystal characteristics were determined by micro-computed tomography (micro-CT), SEM and X-ray diffraction (XRD), respectively., Results: PMA-qPCR demonstrated lower microbial growth in Group 1 and 3 compared with Group 2 and 4 (p < 0.05). CLSM showed the dead-to-live ratio in Groups 1-4 were 1.15±0.12, 0.53±0.13, 1.10±0.24 and 0.63±0.10, respectively (Group 1,3 > 2,4, p < 0.05). SEM revealed Groups 1 and 3 had scattered biofilm whereas Group 2 and 4 had confluent biofilm. Micro-CT showed the enamel lesion depths (µm) were 98±9, 126±7, 103±6 and 128±7 for Group 1 to 4, respectively (Group 1,3 < 2,4, p < 0.05). SEM revealed oriented and ordered enamel prismatic patterns in Group 1 and 3, not in Group 2 and 4. XRD showed the reflections of hydroxyapatite in Groups 1 and 3 were sharper than Groups 2 and 4., Conclusion: SDF pretreatment enhances the preventive effect of GIC on proximal enamel surface on neighboring tooth through inhibiting cariogenic biofilm, reducing enamel demineralization and promoting enamel remineralization., Clinical Significance: SDF pretreatment of GIC restorations can help prevent caries on neighboring teeth, particular for patients with high caries risk., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The off-target loss of pesticide formulations caused by volatilization and leaching has reduced effective utilization and increased risks to the ecological environment and human health. Self-assembly of pesticides has been widely concerned due to the improved bioactivity and environmental compatibility. Herbicidal ionic liquids (HILs) could effectively decrease off-target loss and increase efficacy and environmental safety by improving the physicochemical properties of herbicides. Herein, HILs were prepared by pairing dicamba with quaternary ammonium salts containing different alkyl chain lengths and aromatic groups and subsequently self-assembled into spherical nanoparticles (HIL NPs) via electrostatic interaction and hydrophobic effect. Compared with dicamba, the obtained HIL NPs with an average particle size of 6-55 nm exhibited improved physicochemical properties, including high zeta potential values (+20.3 to +27.8 mV), low volatilization rate (2.4-3.9 %) and surface tension (22.83-33.07 mN m -1 ), decreased contact angle (32.25-41.55°) and leaching potential (76.2-86.5 %), and high soil adsorption (12.1-23.8 %), suggesting low risks to the environment. The control efficacy against Amaranthus retroflexus of HIL3 NPs pairing dicamba with octadecyl-trimethyl ammonium chloride was better than that of dicamba sodium salt at different concentrations. Therefore, the ionic liquid self-assembly developed by a facile and green preparation approach to reduce the volatility and leaching of pesticides would have enormous potential in sustainable agriculture., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To compare the prevention of enamel erosion and discolouring effect with a single and two weekly topical applications of silver diamine fluoride (SDF) solution., Methods: Human enamel blocks were divided into four groups. Group 1 (SDF2) received two weekly applications of SDF solution (Advantage Arrest: 260,000 ppm Ag, 44,300 ppm F, pH 9.1). Group 2 (SDF1) received a single application of SDF solution. Group 3 (SNF, Positive Control) received daily application of stannous-chloride/amine-fluoride/sodium-fluoride solution (Elmex® Enamel professional: 800 ppm Sn(II), 500 ppm F, pH 4.5). Group 4 (DW, Negative Control) received daily application of deionised water. The treated blocks were subjected to a 14-day erosive challenge. Crystal characteristics, elemental composition, surface morphology, percentage of surface microhardness loss (%SMHL), surface loss, and total colour change (ΔE) of the blocks were investigated using X-ray diffraction (XRD), energy-dispersive spectrometry (EDS) and scanning electron microscopy (SEM), Vickers' hardness testing, non-contact profilometry, and digital spectrophotometry, respectively., Results: XRD and EDS revealed precipitates of silver for SDF2 and SDF1 and tin for SNF. SEM showed prominent etched enamel pattern on DW than the other three groups. The%SMHL (%) of SDF2, SDF1, SNF, and DW were 26.6 ± 2.9, 33.6 ± 2.8, 38.9 ± 2.9, and 50.5 ± 2.8 (SDF2SDF1=SNF>DW, p < 0.05)., Conclusion: Two weekly applications was more effective than a single application of SDF in preventing enamel erosion, though it caused more discolouration., Clinical Significance: Topical application of 38 % SDF with two weekly applications protocol is effective in preventing enamel erosion., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Selecting the appropriate disinfectant to control and prevent healthcare-associated infections (HAIs) is a challenging task for environmental health experts due to the large number of available disinfectant products. This study aimed to develop a label-free flow cytometry (FCM) method for the rapid evaluation of bactericidal activity and to compare its efficacy with that of standard qualitative/quantitative suspension tests. The bactericidal efficiency of eight commercial disinfectants containing quaternary ammonium compounds (QACs) was evaluated against four strains recommended by EN 13727 ( Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus , Enterococcus hirae ) and four multidrug-resistant pathogens. The proposed FCM protocol measures changes in scattered light and counts following disinfectant exposure, neutralization, and culture steps. Unlike other available FCM-based methods, this approach does not rely on autofluorescence measurements, impedance cytometry, or fluorescent dyes. The FCM scattered light signals revealed both decreased count rates and morphological changes after treatment with minimum inhibitory concentrations (MICs) and higher concentrations for all tested bacteria. The results from the FCM measurements showed excellent correlation with those from standard assays, providing a rapid tool for monitoring the susceptibility profile of clinical, multidrug-resistant pathogens to chemical disinfectants, which could support infection prevention and control procedures for healthcare environments. This label-free FCM protocol offers a novel and rapid tool for environmental health experts, aiding in the optimization of disinfectant selection for the prevention and control of HAIs.

Background: The desirable properties of silver diamine fluoride (SDF) make it an effective agent for managing dental caries and tooth hypersensitivity. There are several clinical instances that SDF application might precede the placement of direct tooth-colored restorations. On the other hand, SDF stains demineralized/carious dental tissues black, which might affect the esthetic outcomes of such restorations. Color is a key parameter of esthetics in dentistry. Therefore, this study aims to systematically review dental literature on color/color change of tooth-colored restorations placed following the application of SDF on dentine., Methods: Comprehensive search of PubMed, Embase, Scopus and ISI Web of Science databases (until August 2023) as well as reference lists of retrieved studies was performed. In vitro studies reported color or color change of tooth-colored restorative materials applied on SDF-treated dentine were included. Methodological quality assessment was performed using RoBDEMAT tool. Pooled weighted mean difference (WMD) and 95% confidence interval (95% CI) was calculated., Results: Eleven studies/reports with a total of 394 tooth-colored restorations placed following a) no SDF (control) or b) SDF with/without potassium iodide (KI)/glutathione dentine pre-treatments were included. Color change was quantified using ∆E formulas in most reports. The pooled findings for the comparison of resin-based composite (RBC) restorations with and without prior 38% SDF + KI application revealed no statistically significant differences in ∆E values at short- and long-term evaluations (~ 14 days: WMD: -0.56, 95% CI: -2.09 to 0.96; I 2 : 89.6%, and ~ 60 days: WMD: 0.11; 95% CI: -1.51 to 1.72; I 2 : 76.9%). No studies provided sufficient information for all the items in the risk of bias tool (moderate to low quality)., Conclusions: The limited evidence suggested comparable color changes of RBC restorations with and without 38% SDF + KI pre-treatment up to 60 days. The included studies lacked uniformity in methodology and reported outcomes. Further studies are imperative to draw more definite conclusions., Protocol Registration: The protocol of this systematic review was registered in PROSPERO database under number CRD42023485083., (© 2024. The Author(s).)

Dental caries, a chronic infectious disease characterized by tooth mineral loss caused by plaque, is one of the major global public health problems. Silver diamine fluoride (SDF) has been proven to be a highly effective anti-caries drug due to its high bacterial inhibition and remineralization ability. However, the SDF solution is unstable, which immensely limits its clinical application. Therefore, new silver-load clay named AgF@Hec was designed by replacing the NH 3 with hectorite in this study. Fourier transform infrared spectroscopy and x-ray diffraction spectroscopy were employed to confirm the structure of AgF@Hec. Dynamic light scattering analysis was used to reveal the effect of different hectorite concentrations on the stability of AgF@Hec. Moreover, AgF@Hec exhibits significant remineralization and hardness recovery of the initial carious lesions. Bacteriostatic experiments also proved that it has a significant inhibitory effect on A. Viscosus, S. mutans, S. sanguinis, S. salivarius, Lactobacillus sp. and both gram-positive and gram-negative bacteria. We therefore believed that AgF@Hec should be a promising biomaterial that can be applied in the prevention of dental caries., (© 2024 IOP Publishing Ltd.)