Neurodegenerative effects of air pollutant Particles: Biological mechanisms implicated for Early-Onset Alzheimer's disease.

BACKGROUND: Sporadic Alzheimer's disease (AD) occurs in 99% of all cases and can be influenced by air pollution such as diesel emissions and more recently, an iron oxide particle, magnetite, detected in the brains of AD patients. However, a mechanistic link between air pollutants and AD development remains elusive. AIM: To study the development of AD-relevant pathological effects induced by air pollutant particle exposures and their mechanistic links, in wild-type and AD-predisposed models. METHODS: C57BL/6 (n = 37) and APP/PS1 transgenic (n = 38) mice (age 13 weeks) were exposed to model pollutant iron-based particle (Fe0-Fe3O4, dTEM = 493 ± 133 nm), hydrocarbon-based diesel combustion particle (43 ± 9 nm) and magnetite (Fe3O4, 153 ± 43 nm) particles (66 µg/20 µL/third day) for 4 months, and were assessed for behavioural changes, neuronal cell loss, amyloid-beta (Aß) plaque, immune response and oxidative stress-biomarkers. Neuroblastoma SHSY5Y (differentiated) cells were exposed to the particles (100 µg/ml) for 24 h, with assessments on immune response biomarkers and reactive oxygen species generation. RESULTS: Pollutant particle-exposure led to increased anxiety and stress levels in wild-type mice and short-term memory impairment in AD-prone mice. Neuronal cell loss was shown in the hippocampal and somatosensory cortex, with increased detection of Aß plaque, the latter only in the AD-predisposed mice, with the wild-type not genetically disposed to form the plaque. The particle exposures however, increased AD-relevant immune system responses, including inflammation, in both strains of mice. Exposures also stimulated oxidative stress, although only observed in wild-type mice. The in vitro studies complemented the immune response and oxidative stress observations. CONCLUSIONS: This study provides insights into the mechanistic links between inflammation and oxidative stress to pollutant particle-induced AD pathologies, with magnetite apparently inducing the most pathological effects. No exacerbation of the effects was observed in the AD-predisposed model when compared to the wild-type, indicating a particle-induced neurodegeneration that is independent of disease state.

Nanoscale Titanium Surface Engineering via Low-Temperature Hydrothermal Etching for Enhanced Antimicrobial Properties.

Bioinspired nanotopography artificially fabricated on titanium surfaces offers a solution for the rising issue of postoperative infections within orthopedics. On a small scale, hydrothermal etching has proven to deliver an effective antimicrobial nanospike surface. However, translation to an industrial setting is limited by the elevated synthesis temperature (150 °C) and associated equipment requirements. Here, for the first time, we fabricate surface nanostructures using comparatively milder synthesis temperatures (75 °C), which deliver physicochemical properties and antimicrobial capability comparable to the high-temperature surface. Using a KOH etchant, the simultaneous formation of titania and titanate crystals at both temperatures produces a one-dimensional nanostructure array. Analysis indicated that the formation mechanism comprises dissolution and reprecipitation processes, identifying the deposited titanates as hydrated layered tetra-titanates (K2Ti4O9·nH2O). A proposed nanospike formation mechanism was confirmed through the identification of a core and outer shell for individual nanostructures, primarily comprised of titanates and titania, respectively. Etching conditions dictated crystalline formation, favoring a thicker titanate core for nanorods under higher synthesis temperatures and etchant concentrations. A bactericidal investigation showed the efficacy against Gram-negative bacteria for a representative low-temperature nanosurface (34.4 ± 14.4%) was comparable to the higher temperature nanosurface (34.0 ± 17.0%), illustrating the potential of low-temperature hydrothermal synthesis. Our results provide valuable insight into the applicability of low-temperature etching protocols that are more favorable in large-scale manufacturing settings.

Oxygen-vacancy-rich molybdenum carbide MXene nanonetworks for ultrasound-triggered and capturing-enhanced sonocatalytic bacteria eradication.

Incurable bacterial infection and intractable multidrug resistance remain critical challenges in public health. A prevalent approach against bacterial infection is phototherapy including photothermal and photodynamic therapy, which is unfortunately limited by low penetration depth of light accompanied with inevitable hyperthermia and phototoxicity damaging healthy tissues. Thus, eco-friendly strategy with biocompatibility and high antimicrobial efficacy against bacteria is urgently desired. Herein, we propose and develop an oxygen-vacancy-rich MoOxin situ on fluorine-free Mo2C MXene with unique neural-network-like structure, namely MoOx@Mo2C nanonetworks, in which their desirable antibacterial effectiveness originates from bacteria-capturing ability and robust reactive oxygen species (ROS) generation under precise ultrasound (US) irradiation. The high-performance, broad-spectrum microbicidal activity of MoOx@Mo2C nanonetworks without damaging normal tissues is validated based on systematic in vitro and in vivo assessments. Additionally, RNA sequencing analysis illuminates that the underlying bactericidal mechanism is attributed to the chaotic homeostasis and disruptive peptide metabolisms on bacteria instigated by MoOx@Mo2C nanonetworks under US stimulation. Considering antibacterial efficiency and a high degree of biosafety, we envision that the MoOx@Mo2C nanonetworks can serve as a distinct antimicrobial nanosystem to fight against diverse pathogenic bacteria, especially eradicating multidrug-resistant bacteria-induced deep tissue infection.

Insights from a Bibliometrics-Based Analysis of Publishing and Research Trends on Cerium Oxide from 1990 to 2020.

The purpose of this study is to evaluate the literature for research trends on cerium oxide from 1990 to 2020 and identify gaps in knowledge in the emerging application(s) of CeONP. Bibliometric methods were used to identify themes in database searches from PubMed, Scopus and Web of Science Core Collection using SWIFT-Review, VOSviewer and SciMAT software programs. A systematic review was completed on published cerium oxide literature extracted from the Scopus database (n = 17,115), identifying themes relevant to its industrial, environmental and biomedical applications. A total of 172 publications were included in the systematic analysis and categorized into four time periods with research themes identified; "doping additives" (n = 5, 1990-1997), "catalysts" (n = 32, 1998-2005), "reactive oxygen species" (n = 66, 2006-2013) and "pathology" (n = 69, 2014-2020). China and the USA showed the highest number of citations and publications for cerium oxide research from 1990 to 2020. Longitudinal analysis showed CeONP has been extensively used for various applications due to its catalytic properties. In conclusion, this study showed the trend in research in CeONP over the past three decades with advancements in nanoparticle engineering like doping, and more recently surface modification or functionalization to further enhanced its antioxidant abilities. As a result of recent nanoparticle engineering developments, research into CeONP biological effects have highlighted its therapeutic potential for a range of human pathologies such as Alzheimer's disease. Whilst research over the past three decades show the versatility of cerium oxide in industrial and environmental applications, there are still research opportunities to investigate the potential beneficial effects of CeONP in its application(s) on human health.

Development of Nanoparticle Adaptation Phenomena in Acinetobacter baumannii: Physiological Change and Defense Response.

The present work describes the evolution of a resistance phenotype to a multitargeting antimicrobial agent, namely, silver nanoparticles (nanosilver; NAg), in the globally prevalent bacterial pathogen Acinetobacter baumannii. The Gram-negative bacterium has recently been listed as a critical priority pathogen requiring novel treatment options by the World Health Organization. Through prolonged exposure to the important antimicrobial nanoparticle, the bacterium developed mutations in genes that encode the protein subunits of organelle structures that are involved in cell-to-surface attachment as well as in a cell envelope capsular polysaccharide synthesis-related gene. These mutations are potentially correlated with stable physiological changes in the biofilm growth behavior and with an evident protective effect against oxidative stress, most likely as a feature of toxicity defense. We further report a different adaptation response of A. baumannii to the cationic form of silver (Ag+). The bacterium developed a tolerance phenotype to Ag+, which was correlated with an indicative surge in respiratory activity and changes in cell morphology, of which these are reported characteristics of tolerant bacterial populations. The findings regarding adaptation phenomena to NAg highlight the risks of the long-term use of the nanoparticle on a priority pathogen. The findings urge the implementation of strategies to overcome bacterial NAg adaptation, to better elucidate the toxicity mechanisms of the nanoparticle, and preserve the efficacy of the potent alternative antimicrobial agent in this era of antimicrobial resistance. IMPORTANCE Several recent studies have reported on the development of bacterial resistance to broad-spectrum antimicrobial silver nanoparticles (nanosilver; NAg). NAg is currently one of the most important alternative antimicrobial agents. However, no studies have yet established whether Acinetobacter baumannii, a globally prevalent nosocomial pathogen, can develop resistance to the nanoparticle. The study herein describes how a model strain of A. baumannii with no inherent silver resistance determinants developed resistance to NAg, following prolonged exposure. The stable physiological changes are correlated with mutations detected in the bacterium genome. These mutations render the bacterium capable of proliferating at a toxic NAg concentration. It was also found that A. baumannii developed a "slower-to-kill" tolerance trait to Ag+, which highlights the unique antimicrobial activities between the nanoparticulate and the ionic forms of silver. Despite the proven efficacy of NAg, the observation of NAg resistance in A. baumannii emphasises the potential risks of the repeated overuse of this agent on a priority pathogen.

Systematic and Bibliometric Analysis of Magnetite Nanoparticles and Their Applications in (Biomedical) Research.

Recent reports show air pollutant magnetite nanoparticles (MNPs) in the brains of people with Alzheimer's disease (AD). Considering various field applications of MNPs because of developments in nanotechnology, the aim of this study is to identify major trends and data gaps in research on magnetite to allow for relevant environmental and health risk assessment. Herein, a bibliometric and systematic analysis of the published magnetite literature (n = 31 567) between 1990 to 2020 is completed. Following appraisal, publications (n = 244) are grouped into four time periods with the main research theme identified for each as 1990-1997 "oxides," 1998-2005 "ferric oxide," 2006-2013 "pathology," and 2014-2020 "animal model." Magnetite formation and catalytic activity dominate the first two time periods, with the last two focusing on the exploitation of nanoparticle engineering. Japan and China have the highest number of citations for articles published. Longitudinal analysis indicates that magnetite research for the past 30 years shifted from environmental and industrial applications, to biomedical and its potential toxic effects. Therefore, whilst this study presents the research profile of different countries, the development in research on MNPs, it also reveals that further studies on the effects of MNPs on human health is much needed.

Variants of Tn6924, a Novel Tn7 Family Transposon Carrying the blaNDM Metallo-ß-Lactamase and 14 Copies of the aphA6 Amikacin Resistance Genes Found in Acinetobacter baumannii.

Carbapenem resistance in Acinetobacter baumannii is primarily due to the global spread of two main clones that carry oxa23, oxa24, and oxa58. However, new carbapenem-resistant clones are emerging that are also resistant to a wide range of antibiotics. Strains belonging to ST85IP (Institut Pasteur) carry the blaNDM metallo-ß-lactamase carbapenem resistance gene. Here, we completed the genome sequence of an ST85IP strain, Cl300, recovered in 2015 in Lebanon, using a combination of Illumina MiSeq and Oxford Nanopore sequencing and a hybrid assembly approach. Cl300 is highly resistant to meropenem and amikacin, and consistent with this, a copy of the blaNDM carbapenem and 14 copies of the aphA6 amikacin resistance genes were found in the genome. Cl300 also contains the sul2 sulfonamide and the msr(E) macrolide resistance genes. All aphA6 copies and blaNDM are in a novel 76-kb Tn7 family transposon designated Tn6924. Like Tn7, Tn6924 is bounded by 29-bp inverted repeats with additional TnsB binding sites at each end. Several variants of Tn6924 were found in a set of diverse strains, including ST85IP strains as well as members of global clones 1 and 2. sul2 and msr(E) are in a 13.0-kb pseudocompound transposon (PCT) bounded by IS1008. ST85s represent a diverse group of strains, particularly in their antibiotic resistance gene content and the K and OC surface polysaccharide loci. Acquisition of Tn6924 by members of global clones indicates the significance of this transposon in spreading two clinically significant resistance genes, blaNDM and aphA6. IMPORTANCE To date, efforts to study the resistance mechanisms of carbapenem-resistant Acinetobacter baumannii have been largely focused on the two major globally distributed clones (GC1 and GC2). ST85 is an emerging sequence type, and unlike other clones, it is associated with the carriage of the blaNDM gene. Here, we completed the genome sequence of an ST85 strain and showed that blaNDM and 14 copies of the aphA6 amikacin resistance genes are in Tn6924, a novel Tn7 family transposon. Analysis of all publicly available ST85s predicted that all strains in the main lineage carry a variant of Tn6924. Variants of Tn6924 were also found in other clones, including GC1 and GC2. Tn6924 is an important mobile element given that it carries two clinically important resistance genes (blaNDM and aphA6) and has spread to other clones. Therefore, outbreaks caused by ST85s should be studied and tracked.

Cl415, a carbapenem-resistant Acinetobacter baumannii isolate containing four AbaR4 and a new variant of AbGRI2, represents a novel global clone 2 strain.

OBJECTIVES: To determine the genetic context of genes conferring antibiotic resistance on the carbapenem-resistant Acinetobacter baumannii Cl415, recovered in 2017 at El Youssef Hospital Centre in Akkar Governorate, North Lebanon. METHODS: Antibiotic resistance phenotype for 22 antibiotics was determined using disc diffusion or MIC determination. The whole-genome sequence of Cl415 was determined using a combination of the Illumina MiSeq and Oxford Nanopore (MinION) platforms. Complete genome was assembled using Unicycler and antibiotic resistance determinants and ISs were identified using ResFinder and ISFinder, respectively. RESULTS: Cl415 is a global clone 2 (GC2) strain and belongs to the most common STs of this clone, ST2IP and ST218OX. Cl415 is resistant to several antibiotics, including aminoglycosides and carbapenems to a high level. Genomic analysis of Cl415 revealed that it carries four chromosomal AbaR4 copies. One copy was found in the comM gene replacing the AbGRI1 island. Cl415 also contains a novel variant of AbGRI2, herein called AbGRI2-15, carrying only the blaTEM and aphA1 resistance genes. Cl415 belongs to a subclade of GC2 strains that appear to have diverged recently with a wide geographical distribution. CONCLUSIONS: The resistance gene complement of Cl415 was found in the chromosome with four oxa23 located in AbaR4 copies and the remaining genes in a novel variant of the AbGRI2 resistance island. Cl415 was isolated in Lebanon, but phylogenetic analysis suggests that Cl415 represents a new lineage with global distribution within GC2.

The impact of silver nanoparticles on microbial communities and antibiotic resistance determinants in the environment.

Nanosilver (NAg) is currently one of the major alternative antimicrobials to control microorganisms. With its broad-spectrum efficacy and lucrative commercial values, NAg has been used in medical devices and increasingly, in consumer products and appliances. This widespread use has inevitably led to the release and accumulation of the nanoparticle in water and sediment, in soil and even, wastewater treatment plants (WWTPs). This Article describes the physical and chemical transformations of NAg as well as the impact of the nanoparticle on microbial communities in different environmental settings; how the nanoparticle shifts not only the diversity and abundance of microbes, including those that are important in nitrogen cycles and decomposition of organic matters, but also their associated genes and in turn, the key metabolic processes. Current findings on the microbiological activity of the leached soluble silver, solid silver particulates and their respective transformed products, which underpin the mechanism of the nanoparticle toxicity in environmental microbes, is critically discussed. The Article also addresses the emerging evidence of silver-driven co-selection of antibiotic resistance determinants. The mechanism has been linked to the increasing pools of many antibiotic resistance genes already detected in samples from different environmental settings, which could ultimately find their ways to animals and human. The realized ecological impact of NAg calls for more judicial use of the nanoparticle. The generated knowledge can inform strategies for a better 'risks versus benefits' assessment of NAg applications, including the disposal stage.

Evolution of biofilm-forming pathogenic bacteria in the presence of nanoparticles and antibiotic: adaptation phenomena and cross-resistance.

BACKGROUND: Treatment of bacterial biofilms are difficult and in many cases, expensive. Bacterial biofilms are naturally more resilient to antimicrobial agents than their free-living planktonic counterparts, rendering the community growth harder to control. The present work described the risks of long-term use of an important alternative antimicrobial, silver nanoparticles (NAg), for the first time, on the dominant mode of bacterial growth. RESULTS: NAg could inhibit the formation as well as eradicating an already grown biofilm of Pseudomonas aeruginosa, a pathogen notorious for its resilience to antibiotics. The biofilm-forming bacterium however, evolved a reduced sensitivity to the nanoparticle. Evidence suggests that survival is linked to the development of persister cells within the population. A similar adaptation was also seen upon prolonged exposures to ionic silver (Ag+). The persister population resumed normal growth after subsequent passage in the absence of silver, highlighting the potential risks of recurrent infections with long-term NAg (and Ag+) treatments of biofilm growth. The present study further observed a potential silver/antibiotic cross-resistance, whereby NAg (as well as Ag+) could not eradicate an already growing gentamicin-resistant P. aeruginosa biofilm. The phenomena is thought to result from the hindered biofilm penetration of the silver species. In contrast, both silver formulations inhibited biofilm formation of the resistant strain, presenting a promising avenue for the control of biofilm-forming antibiotic-resistant bacteria. CONCLUSION: The findings signify the importance to study the nanoparticle adaptation phenomena in the biofilm mode of bacterial growth, which are apparently unique to those already reported with the planktonic growth counterparts. This work sets the foundation for future studies in other globally significant bacterial pathogens when present as biofilms. Scientifically based strategies for management of pathogenic growth is necessary, particularly in this era of increasing antibiotic resistance.

Emerging Concern for Silver Nanoparticle Resistance in Acinetobacter baumannii and Other Bacteria.

The misuse of antibiotics combined with a lack of newly developed ones is the main contributors to the current antibiotic resistance crisis. There is a dire need for new and alternative antibacterial options and nanotechnology could be a solution. Metal-based nanoparticles, particularly silver nanoparticles (NAg), have garnered widespread popularity due to their unique physicochemical properties and broad-spectrum antibacterial activity. Consequently, NAg has seen extensive incorporation in many types of products across the healthcare and consumer market. Despite clear evidence of the strong antibacterial efficacy of NAg, studies have raised concerns over the development of silver-resistant bacteria. Resistance to cationic silver (Ag+) has been recognised for many years, but it has recently been found that bacterial resistance to NAg is also possible. It is also understood that exposure of bacteria to toxic heavy metals like silver can induce the emergence of antibiotic resistance through the process of co-selection. Acinetobacter baumannii is a Gram-negative coccobacillus and opportunistic nosocomial bacterial pathogen. It was recently listed as the "number one" critical level priority pathogen because of the significant rise of antibiotic resistance in this species. NAg has proven bactericidal activity towards A. baumannii, even against strains that display multi-drug resistance. However, despite ample evidence of heavy metal (including silver; Ag+) resistance in this bacterium, combined with reports of heavy metal-driven co-selection of antibiotic resistance, little research has been dedicated to assessing the potential for NAg resistance development in A. baumannii. This is worrisome, as the increasingly indiscriminate use of NAg could promote the development of silver resistance in this species, like what has occurred with antibiotics.

We Are One: Multispecies Metabolism of a Biofilm Consortium and Their Treatment Strategies.

The ecological and medical significance of bacterial biofilms have been well recognized. Biofilms are harder to control than their planktonic free-living counterparts and quite recently, the focus of the study has shifted to the multispecies consortia, which represent the vast majority of real-case infection scenarios. Studies have begun to explore the complex interspecies interactions within these biofilms. However, only little attention is currently given to the role of cellular metabolites in the cell-to-cell communication. The concentration gradients of metabolic substrates and products affect the spatial growth of bacteria in multispecies biofilm. This, if looked into more deeply, can lead to identification of potential therapies targeting the specific metabolites and hence the coordinated protection in the bacterial community. Herein, we review the interspecies communications, including their metabolic cross-talking, in multispecies biofilm, to signify the importance of such interactions on the initial formation and subsequent growth of these biofilms. Multispecies biofilms with their species heterogeneity are more resilient to antimicrobial agents than their single species biofilm counterparts and this characteristic is of particular interest when dealing with pathogenic bacteria. In this Review, we also discuss the treatment options available, to include current and emerging avenues to combat pathogenic multispecies biofilms in the clinical, environmental, as well as industrial settings.

In vitro coronal protein signatures and biological impact of silver nanoparticles synthesized with different natural polymers as capping agents.

Biopolymer-capped particles, sodium alginate-, gelatin- and reconstituted silk fibroin-capped nanosilver (AgNPs), were synthesized with an intention to study, simultaneously, their in vitro and in vivo haemocompatibility, one of the major safety factors in biomedical applications. Solid state characterization showed formation of spherical nanoparticles with 5 to 30 nm primary sizes (transmission electron microscopy) and X-ray photoelectron spectroscopy analysis of particles confirmed silver bonding with the biopolymer moieties. The degree of aggregation of the biopolymer-capped AgNPs in the synthesis medium (ultrapure water) is relatively low, with comparable hydrodynamic size with those of the control citrate-stabilized NPs, and remained relatively unchanged even after 6 weeks. The polymer-capped nanoparticles showed different degrees of aggregation in biologically relevant media - PBS (pH 7.4) and 2% human blood plasma - with citrate- (control) and alginate-capped particles showing the highest aggregation, while gelatin- and silk fibroin-capped particles revealed better stability and less aggregation in these media. In vitro cytotoxicity studies revealed that the polymer-capped particles exhibited both concentration and (hydrodynamic) size-dependent haemolytic activity, the extent of which was higher (up to 100% in some cases) in collected whole blood samples of healthy human volunteers when compared to that in the washed erythrocytes. This difference is thought to result from the detected protein corona formation on the nanoparticle surface in the whole blood system, which was associated with reduced particle aggregation, causing more severe cytotoxic effects. At the tested particle concentration range in vitro, we observed a negligible haemolysis effect in vivo (Balb/c mice). Polymer-capped particles did accumulate in organs, with the highest levels detected in the liver (up to 422 µg per g tissue), yet no adverse behavioural effects were observed in the mice during the duration of the nanoparticle exposure.

Nanosilver Targets the Bacterial Cell Envelope: The Link with Generation of Reactive Oxygen Radicals.

The work describes the interactions of nanosilver (NAg) with bacterial cell envelope components at a molecular level and how this associates with the reactive oxygen species (ROS)-mediated toxicity of the nanoparticle. Major structural changes were detected in cell envelope biomolecules as a result of damages in functional moieties, such as the saccharides, amides, and phosphodiesters. NAg exposure disintegrates the glycan backbone in the major cell wall component peptidoglycan, causes complete breakdown of lipoteichoic acid, and disrupts the phosphate-amine and fatty acid groups in phosphatidylethanolamine, a membrane phospholipid. Consistent with the oxidative attacks, we propose that the observed cell envelope damages are inflicted, at least in part, by the reactive oxygen radicals being generated by the nanoparticle during its leaching process, abiotically, without cells. The cell envelope targeting, especially those on the inner membrane phospholipid, is likely to then trigger the rapid generation of lethal levels of cellular superoxide (O2•-) and hydroxyl (OH•) radicals herein seen with a model bacterium. The present study provides a better understanding of the antibacterial mechanisms of NAg, whereby ROS generation could be both the cause and consequence of the toxicity, associated with the initial cell envelope targeting by the nanoparticle.

Heritable nanosilver resistance in priority pathogen: a unique genetic adaptation and comparison with ionic silver and antibiotics.

The past decade has seen the incorporation of antimicrobial nanosilver (NAg) into medical devices, and, increasingly, in everyday 'antibacterial' products. With the continued rise of antibiotic resistant bacteria, there are concerns that these priority pathogens will also develop resistance to the extensively commercialized nanoparticle antimicrobials. Herein, this work reports the emergence of stable resistance traits to NAg in the WHO-listed priority pathogen Staphylococcus aureus, which has previously been suggested to have no, or very low, capacity for silver resistance. With no native presence of genetically encoded silver defence mechanisms, the work showed that the bacterium is dependent on mutation of physiologically essential genes, including those involved in nucleotide synthesis and oxidative stress defence. While some mutations were uniquely associated with resistance to NAg, the study also found common mutations that could be protective against both NAg and ionic silver. This is consistent with the observation of NAg/ionic silver cross-resistance. These mutations were detected following withdrawal of the silver exposure, denoting heritable characteristics that allow for spread of the resistance traits even with discontinued silver use. Heritable silver resistance in priority pathogen cautions that these nanoparticle antimicrobials should only be used as needed, to preserve their efficacy for treating infections.

Oxygen-Vacancy Engineering of Cerium-Oxide Nanoparticles for Antioxidant Activity.

To address an important challenge in the engineering of antioxidant nanoparticles, the present work devised a surface-to-bulk migration of oxygen vacancies in the oxygen radical-scavenging cerium-oxide nanoparticles. The study highlights the significance of surface oxygen vacancies in the intended cellular internalization and, subsequently, the radical scavenging activity of the nanoparticles inside the cells. The findings advise future development of therapeutic antioxidant nanomaterials to also include engineering of the particles for enhanced surface defects not only for the accessibility of their oxygen vacancies but also, equally important, rendering them bioavailable for cellular uptake.

Anti-amoebic activity of acyclic and cyclic-samarium complexes on Acanthamoeba.

This work investigated the anti-amoebic activity of two samarium (Sm) complexes, the acyclic complex [bis(picrato)(pentaethylene glycol)samarium(III)] picrate-referred to as [Sm(Pic)2(EO5)](Pic)-and the cyclic complex [bis(picrato)(18-crown-6)samarium(III)] picrate-referred to as [Sm(Pic)2(18C6)](Pic). Both Sm complexes caused morphological transformation of the protozoa Acanthamoeba from its native trophozoite form carrying a spine-like structure called acanthopodia, to round-shaped cells with loss of the acanthopodia structure, a trademark response to environmental stress. Further investigation, however, revealed that the two forms of the Sm complexes exerted unique cytotoxicity characteristics. Firstly, the IC50 of the acyclic complex (0.7 µg/mL) was ~ 10-fold lower than IC50 of the cyclic Sm complex (6.5 µg/mL). Secondly, treatment of the Acanthamoeba with the acyclic complex caused apoptosis of the treated cells, while the treatment with the cyclic complex caused necrosis evident by the leakage of the cell membrane. Both treatments induced DNA damage in Acanthamoeba. Finally, a molecular docking simulation revealed the potential capability of the acyclic complex to form hydrogen bonds with profilin-a membrane protein present in eukaryotes, including Acanthamoeba, that plays important roles in the formation and degradation of actin cytoskeleton. Not found for the cyclic complex, such potential interactions could be the underlying reason, at least in part, for the much higher cytotoxicity of the acyclic complex and also possibly, for the observed differences in the cytotoxicity traits. Nonetheless, with IC50 values of < 10 µg/mL, both the acyclic and cyclic Sm complexes feature a promising potential as cytotoxic agents to fight amoebic infections.

Nanosilver and the microbiological activity of the particulate solids versus the leached soluble silver.

Nanosilver (Ag NPs) is currently one of the most commercialized antimicrobial nanoparticles with as yet, still unresolved cytotoxicity origins. To date, research efforts have mostly described the antimicrobial contribution from the leaching of soluble silver, while the undissolved solid Ag particulates are often considered as being microbiologically inert, serving only as source of the cytotoxic Ag ions. Here, we show the rapid stimulation of lethal cellular oxidative stress in bacteria by the presence of the undissolved Ag particulates. The cytotoxicity characteristics are distinct from those arising from the leached soluble Ag, the latter being locked in organic complexes. The work also highlights the unique oxidative stress-independent bacterial toxicity of silver salt. Taken together, the findings advocate that future enquiries on the antimicrobial potency and also importantly, the environmental and clinical impact of Ag NPs use, should pay attention to the potential bacterial toxicological responses to the undissolved Ag particulates, rather than just to the leaching of soluble silver. The findings also put into question the common use of silver salt as model material for evaluating bacterial toxicity of Ag NPs.

Ferrous ion as a reducing agent in the generation of antibiofilm nitric oxide from a copper-based catalytic system.

The work found that the electron-donating properties of ferrous ions (Fe2+) can be used for the conversion of nitrite (NO2-) into the biofilm-dispersing signal nitric oxide (NO) by a copper(II) complex (CuDTTCT) catalyst, a potentially applicable biofilm control technology for the water industries. The availability of Fe2+ varied depending on the characteristics of the aqueous systems (phosphate- and carbonate-containing nitrifying bacteria growth medium, NBGM and phosphate buffered saline, PBS at pH 6 to 8, to simulate conditions typically present in the water industries) and was found to affect the production of NO from nitrite by CuDTTCT (casted into PVC). Greater amounts of NO were generated from the CuDTTCT-nitrite-Fe2+ systems in PBS compared to those in NBGM, which was associated with the reduced extent of Fe2+-to-Fe3+ autoxidation by the iron-precipitating moieties phosphates and carbonate in the former system. Further, acidic conditions at pH 6.0 were found to favor NO production from the catalytic system in both PBS and NBGM compared to neutral or basic pH (pH 7.0 or 8.0). Lower pH was shown to stabilize Fe2+ and reduce its autoxidation to Fe3+. These findings will be beneficial for the potential implementation of the NO-generating catalytic technology and indeed, a 'non-killing' biofilm dispersal activity of CuDTTCT-nitrite-Fe2+ was observed on nitrifying bacteria biofilms in PBS at pH 6.

Antimicrobial activity of T4 bacteriophage conjugated indium tin oxide surfaces.

We report the antimicrobial activity of bare and surface functionalized indium tin oxide (ITO) conjugated with T4 bacteriophage towards E. coli. A ∼ 103-fold reduction (99.9%) in the bacterial concentration was achieved within 2 h exposure of E. coli to the bare as well as the amine, carboxylic and methyl functionalized ITO/T4 surfaces. Despite the known differences in bacteriophage loading of these ITO/T4 systems, the almost identical extent of antimicrobial activity of all of the ITO/T4 systems resulted from the release of a comparable amount of infective T4 from the systems. As anticipated, a single dose of immobilized bacteriophage was sufficient to eliminate further surge of bacterial population. Upon the 2 h eradication of the '1st batch' of E. coli population, all of the ITO/T4 systems, each system with 102-fold more suspended bacteriophage (due to propagation of the phage at the expense of the '1st batch' E. coli death), reduced the '2nd batch' of E. coli concentration by ∼104-fold in just 30 min, suggesting the potential of immobilized bacteriophage systems as solution to the issues of antimicrobial agent depletion. All of the ITO/T4 systems maintained their antimicrobial activity in the presence of model food components. The antimicrobial activity was however, affected by pH; at pH 5 whereby the bacteria's growth was physiologically inhibited, generally no reduction in E. coli concentration was detected. The present work provides an understanding of the mode of antimicrobial activity exhibited by an immobilized bacteriophage based substrate and demonstrates efficacy in the presence of food components.