Disruptive Agent Research Articles

Revolutionizing Finance: Decentralized Finance as a Disruptive Challenge to Traditional Finance

This paper examines the emergence and impact of Decentralized Finance (DeFi), between 2019 and 2024, as a disruptive agent opposing traditional finance (TradFi). By using blockchain technology to offer decentralized, open, and readily available financial services, the DeFi industry has seen explosive expansion Emphasizing DeFi's competitive advantage over TradFi, this study aims to investigate notable trends, developments, and market drivers in the toolkit. The main conclusions are the fast and significant rise in Total Value Locked (TVL), the clear increase in user adoption, the expansion in the number of transactions and trading volume on decentralized exchanges (DEXs), and the development of creative financial products. DeFi constantly changes the financial scene despite regulatory oversight and market volatility, so posing major problems and opportunities for established financial institutions.

The power of MXene-based materials for emerging contaminant removal from water - A review

The rise of MXenes in water purification and environmental remediation is a remarkable leap forward in tackling various emerging pollutants. With their unique 2D designs and flexible surface characteristics, MXenes have shown excellent efficiency in eliminating various emerging contaminants such as metals, pharmaceutical residues, per- and poly-fluoroalkyl substances (PFAS), microplastics, and emerging pathogens. Their high conductivity and multifunctionality provide them an increased surface area, promoting robust physical and electrostatic interactions that enhance the adsorption of contaminants. Furthermore, the versatile utility of MXenes in a range of water treatment systems highlights their promising role in advancing methods for purification. This review addresses MXene-based materials' effectiveness in removing emerging contaminants via several innovative techniques including adsorption, membrane separation, disinfection, and photocatalysis. Additionally, it discusses the techno-economic and MXene feasibility in emerging contaminants removal at the industrial scale. This review aims to shed light on the great potential of MXenes and their composites as disruptive agents in emerging contaminants removal and offer guidance for future research endeavors leveraging their capabilities in addressing emerging challenges related to water pollutants.

Exploring bio-oil aqueous phase (BOAP) from seaweed biomass as biofilm disruptive agents against foodborne pathogens

Proper preservation of nutrient-rich raw food from microbial contamination is a major challenge faced by the food industry. The use of antibiotics and chemicals to address the issue of contamination in fresh produce and meat has led to antibiotic-resistant pathogens. In the current study, the anti-biofilm effect of bio-oil aqueous phase (BOAP) collected during pyrolysis of seaweed was evaluated against some major food-borne pathogens for its biofilm inhibition and eradication potential in mono- and dual-species biofilms. The results showed that BOAP could eradicate almost 75% of dual-species biofilms. Further, the preservative effect of the BOAP was examined using appropriate food samples (pineapple and prawns). There was profound reduction in the bacterial load in the food samples which shows that BOAP has effective food preservation property. SEM analysis also revealed the drastic reduction in biofilm in BOAP treated food samples. In future, natural preservatives and BOAP can be combined to increase shelf-life of the above food samples.

Endocrine disruptor-induced epimutagenesis in vitro : Insight into molecular mechanisms.

Endocrine disrupting chemicals (EDCs) such as bisphenol S (BPS) are xenobiotic compounds that can disrupt endocrine signaling following exposure due to steric similarities to endogenous hormones within the body. EDCs have been shown to induce disruptions in normal epigenetic programming (epimutations) that accompany dysregulation of normal gene expression patterns that appear to predispose disease states. Most interestingly, the prevalence of epimutations following exposure to many different EDCs often persists over multiple subsequent generations, even with no further exposure to the causative EDC. Many previous studies have described both the direct and prolonged effects of EDC exposure in animal models, but many questions remain about molecular mechanisms by which EDCs initially induce epimutations or contribute to the propagation of EDC-induced epimutations either within the exposed generation or to subsequent generations. Additional questions remain regarding the extent to which there may be differences in cell-type specific susceptibilities to various EDCs, and whether this susceptibility is correlative with expression of relevant hormone receptors and/or the location of relevant hormone response elements (HREs) in the genome. To address these questions, we exposed cultured mouse pluripotent (induced pluripotent stem [iPS]), somatic (Sertoli and granulosa), and germ (primordial germ cell like [PGCLC]) cells to BPS and measured changes in DNA methylation levels at the epigenomic level and gene expression at the transcriptomic level. We found that there was indeed a difference in cell-type specific susceptibility to EDC-induced epimutagenesis and that this susceptibility correlated with differential expression of relevant hormone receptors and, in many cases, tended to generate epimutations near relevant HREs within the genome. Additionally, however, we also found that BPS can induce epimutations in a cell type that does not express relevant receptors and in genomic regions that do not contain relevant HREs, suggesting that both canonical and non-canonical signaling mechanisms can be disrupted by BPS exposure. Most interestingly, we found that when iPS cells were exposed to BPS and then induced to differentiate into PGCLCs, the prevalence of epimutations and differentially expressed genes (DEGs) initially induced in the iPSCs was largely retained in the resulting PGCLCs, however, >90% of the specific epimutations and DEGs were not conserved but were rather replaced by novel epimutations and DEGs following the iPSC to PGCLC transition. These results are consistent with a unique concept that many EDC-induced epimutations may normally be corrected by germline and/or embryonic epigenetic reprogramming but that due to disruption of the underlying chromatin architecture induced by the EDC exposure, many novel epimutations may emerge during the reprogramming process as well. Thus, it appears that following exposure to a disruptive agent such as an EDC, a prevalence of epimutations may transcend epigenetic reprogramming even though most individual epimutations are not conserved during this process.

Antibody-Loading of Biological Nanocarrier Vesicles Derived from Red-Blood-Cell Membranes.

Antibodies, disruptive potent therapeutic agents against pharmacological targets, face a barrier in crossing immune systems and cellular membranes. To overcome these, various strategies have been explored including shuttling via liposomes or biocamouflaged nanoparticles. Here, we demonstrate the feasibility of loading antibodies into exosome-mimetic nanovesicles derived from human red-blood-cell membranes, which can act as nanocarriers for intracellular delivery. Goat-antichicken antibodies are loaded into erythrocyte-derived nanovesicles, and their loading yields are characterized and compared with smaller dUTP-cargo molecules. Applying dual-color coincident fluorescence burst analyses, the loading yield of nanocarriers is rigorously profiled at the single-vesicle level, overcoming challenges due to size-heterogeneity and demonstrating a maximum antibody-loading yield of 38-41% at the optimal vesicle radius of 52 nm. The achieved average loading yields, amounting to 14% across the entire nanovesicle population, with more than two antibodies per loaded vesicle, are fully comparable to those obtained for the much smaller dUTP molecules loaded in the nanovesicles after additional exosome-spin-column purification. The results suggest a promising new avenue for therapeutic delivery of antibodies, potentially encompassing also intracellular targets and suitable for large-scale pharmacological applications, which relies on the exosome-mimetic properties, biocompatibility, and low-immunogenicity of bioengineered nanocarriers synthesized from human erythrocyte membranes.

Armed actor interventions in humanitarian and public health crises: examining perspectives of crisis-affected community members

BackgroundDespite frequently providing non-military services in times of crisis, little systematic research has examined the perspectives of crisis-affected community members on the role of armed actors responding to humanitarian crises and public health emergencies.MethodsTo address this research gap, 175 interviews were conducted (2020–2021) amongst humanitarian and public health practitioners; armed actors; and crisis-affected community members across three country and four crisis contexts. Specifically, this effort included an Ebola outbreak in the Democratic Republic of the Congo; a refugee crisis on the Jordanian-Syrian border; and a volcanic eruption and COVID-19 outbreak in the Philippines. Data was analysed using grounded theory principles.ResultsCrisis-affected community members held diverse views. Non-state armed groups (NSAGs) and government armed actors were characterised as antagonists by some but supportive by others; gender issues were central to perceptions of armed actors, in ways that were both prejudicing and favourable. Overall perception was most closely linked to armed actor roles rather than the relative amount of conflict in a given area.ConclusionsFindings nuance the relevant literature characterizing NSAGs as disruptive agents, and also the relevant literature that does not fully consider the nuances of gender and armed actor roles as deeply relevant to crisis-affected community perspectives on armed actors. These findings have important implications for both policy and academic discourse on militarization and localization.

The Blockchain: Opportunities for Research in Information Technology

Blockchain technology has come to be seen as a radically different kind of information technology due to its role as a disruptive agent that challenges incumbent actors and their assumptions. With this research paper, I cover the basics and benefits of blockchain technology as well as its possible industries residing, organization and even changing. The blockchain is a decentralized database technology, which had brought the rise and the existence of cryptocurrencies. Similar to Bitcoin, the magnitude of its operation is wielded not only for digital currency. This article will be carrying on the matter of blockchain systems type diversity with public, private, and consortium chains detailed, and the role of the network nodes in achieving consensus being specified. Keywords: - Cryptocurrencies (e.g., Bitcoin, Ethereum), Smart contracts, Digital Signatures, Supply chain applications, Blockchain applications, Blockchain in finance and healthcare

Opinion Dynamics on Directed Complex Networks

We propose and analyze a mathematical model for the evolution of opinions on directed complex networks. Our model generalizes the popular DeGroot and Friedkin-Johnsen models by allowing vertices to have attributes that may influence the opinion dynamics. We start by establishing sufficient conditions for the existence of a stationary opinion distribution on any fixed graph, and then provide an increasingly detailed characterization of its behavior by considering a sequence of directed random graphs having a local weak limit. Our most explicit results are obtained for graph sequences whose local weak limit is a marked Galton-Watson tree, in which case our model can be used to explain a variety of phenomena, for example, conditions under which consensus can be achieved, mechanisms in which opinions can become polarized, and the effect of disruptive stubborn agents on the formation of opinions. Funding: This work was supported by the National Science Foundation [Grants NSF-DMS-1929298 and CMMI-2243261].

Epistemic outsiders: Unpacking and utilising the epistemic dimension of disruptive agency in sustainability transformations

Disruptions (systemic disturbances) are crucial to initiate and accelerate sustainability transformations of large-scale social systems (be they socio-ecological, socio-technical, or socio-institutional). Their emergence, characteristics and effects strongly relate to the role of agents who aim to disrupt and transform the status quo, and which thus possess what we call disruptive agency. In this paper, we highlight the epistemic dimension of disruptive agency in social transformations, first by conceptualizing disruptive agents as epistemic outsiders with respect to the social system that they intend to disrupt and transform, and second by connecting this conceptualization to notions of belief, social practices, social networks, discourses, or institutions. We identify five advantages of this approach. Firstly, it informs and conceptually enables various promising interdisciplinary avenues to explore and potentially influence transformative change towards sustainability. Secondly, an epistemic conception of disruptive agency offers a key for an integrated analysis of the individual and collective levels of agency involved in sustainability transformations. Thirdly, the notion of epistemic outsiders conceptually connects agent positions across system boundaries that are understood to be of crucial importance for sustainability transformations respectively (e.g., “niche innovators” or “regime intermediaries”) but which lack an integrated understanding. Fourthly, an epistemic perspective additionally highlights the changing requirements and challenges resulting in two principal stages of transformations unfolding over time, namely before/after a new epistemic layout is shared by a majority of agents. Finally, the above features allow to derive and conceive of new intervention formats and strategies.

Improving food sustainability by converting orange peel waste products into hydrogels using stirred media milling

There is a need for natural gelling ingredients within the food industry. We have shown that orange peel suspensions (OPS) form hydrogels when treated with a stirred media mill. Gels were formed when an aqueous 3% OPS was milled for longer than 60 min. Their gel strength increased with milling time, which was attributed to progressive disruption of the plant cell tissues and release of pectin and other polysaccharides. The water holding capacity and amount of bound water in the orange peel gels increased with milling time. Shear rheology experiments showed that the gels exhibited shear thinning and were predominantly elastic-like materials. FTIR analysis and addition of bond disruptive agents suggested that hydrophobic interactions between methoxy groups on the pectin were mainly responsible for crosslinking and gelation. Overall, our results suggest that stirred media milling may improve the utilization of orange peel as a functional ingredient in the food industry.

Interactions of Choline and Geranate (CAGE) and Choline Octanoate (CAOT) Deep Eutectic Solvents with Lipid Bilayers

AbstractMixtures between choline and geranic acid (CAGE) have previously been shown to insert into lipid bilayers. This may be useful for the transdermal delivery of larger pharmaceuticals, however, little is known about the mechanism of activity. By comparing the interactions between CAGE and lipid bilayers with those of a less‐active, yet closely‐related analogue, choline octanoic acid (CAOT), a chemical basis can be investigated. Overall, six systems are studied here by neutron reflectivity, where d54‐1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine (DMPC) solid‐supported phospholipid bilayers are first formed on SiO2 substrates before exposure to the deep eutectic solvent (DES). Components of the DES could be identified within the bilayer by exploiting contrast variation and selective deuteration. CAGE is shown to be a mild disruptive agent, free to insert and diffuse across the bilayer, preserving much of the bilayer integrity. Experiments identify co‐mingling of geranate ions inhibits the efficient packing of lipid tails, increasing hydration across the bilayer. Conversely, CAOT is found to both exchange and remove lipid molecules to achieve incorporation, inducing swelling and the formation of solvent patches. It appears these behaviors derive from the structures of the anions and thus amphiphilicity of the DES, laying the foundations for the rational design and optimization of these candidates toward transdermal delivery.

Performance assessment and root-cause analysis of a deteriorating On-Grid Industrial PV System for the identification of newly originating power degrading defect

Solar modules deployed in industrial areas have the potential to conserve a significant quantity of national grid electricity; nevertheless, the accessibility of industrial contaminants and emissions creates an unusual surrounding environment for industrial PV plants. Thus, evaluating the performance of industrial solar power plants and highlighting any disruptive agent is crucial for their reliable and feasible operation. The current study investigates the deterioration of a 101 kW On-Grid PV system installed in the aluminum industry that has a newly discovered degrading defect, namely the localised partial cell soiling on industrial PV system, which hasn't been seen or identified in classic studies specifically on industrial PV systems operating on ideal conditions. The underperformance of a solar power plant is identified using comparison between PVsyst simulation results and real plant performance metrics. Moreover, assessment analysis is presented by using characterization techniques such as FESEM, EDX, XRD, and FTIR. The results show that the actual yield (57,807 kWh DC and 56,031 kWh AC), array captured losses (12.257 h/day Lc), array system losses (0.57 h/day Ls), and performance ratio (51 %) all differ from the projected yield (89,637 DC and 86,392 kWh AC), array captured losses (6.256 h/day Lc), array system losses (1.067 h/day Ls), and performance ratio (79 %). Additionally, the performance analysis of the strings connected to both inverters demonstrates that the underperformance is caused by the newly originating defect since the PV-defected inverter strings perform worse than the other one. According to the characterization techniques, the industrial residue material of a specific section of the aluminum industry and the material accumulated on specific cells of panels have similar chemical, morphological, and elemental compositions. BaSO4 is found to be the common compound in both materials. Future PV designs, particularly those aimed at the industrial sector, will benefit from the knowledge of the industrial PV system's defect-originating material characteristics and underperformance.

Iron and copper on Botrytis cinerea: new inputs in the cellular characterization of their inhibitory effect.

Certain metals play key roles in infection by the gray mold fungus, Botrytis cinerea. Among them, copper and iron are necessary for redox and catalytic activity of enzymes and metalloproteins, but at high concentrations they are toxic. Understanding the mechanism requires more cell characterization studies for developing new, targeted metal-based fungicides to control fungal diseases on food crops. This study aims to characterize the inhibitory effect of copper and iron on B. cinerea by evaluating mycelial growth, sensitivity to cell wall perturbing agents (congo red and calcofluor white), membrane integrity, adhesion, conidial germination, and virulence. Tests of copper over the range of 2 to 8 mM and iron at 2 to 20 mM revealed that the concentration capable of reducing mycelial growth by 50% (IC50) was 2.87 mM and 9.08 mM for copper and iron, respectively. When mixed at equimolar amounts there was a significant inhibitory effect mostly attributable to copper. The effect of Cu50, Fe50, and Cu50-Fe50 was also studied on the mycelial growth of three wild B. cinerea strains, which were more sensitive to metallic inhibitors. A significant inhibition of conidial germination was correlated with adhesion capacity, indicating potential usefulness in controlling disease at early stages of crop growth. Comparisons of the effects of disruptive agents on the cell wall showed that Cu, Fe, and Cu-Fe did not exert their antifungal effect on the cell wall of B. cinerea. However, a relevant effect was observed on plasma membrane integrity. The pathogenicity test confirmed that virulence was correlated with the individual presence of Cu and Fe. Our results represent an important contribution that could be used to formulate and test metal-based fungicides targeted at early prevention or control of B. cinerea.

Estrogen receptor α mediates alternariol-induced apoptosis and modulation of the invasiveness of ovarian cancer cells

Mycotoxins are secondary metabolites of fungi that may affect both human and animal health. Some of them possess estrogenic activity, due to direct binding to estrogen receptors (ERs) and hence disturb the hormonal balance of the organism. Alternariol (AOH) was previously reported as genotoxic, estrogenic and immunomodulatory agent. However, detailed mechanism of its action has not been fully elucidated. Estrogen receptor α (ERα) was previously reported to modulate the proliferation and invasiveness of ovarian cancer cells. Thus, we decided to verify whether estrogenic-like mycotoxin may affect ovarian cancer cells via ERα. The results showed that AOH induces apoptosis and oxidative stress and that these effects are partially modulated by ERα. Moreover, AOH decreases the invasion and migration of ovarian cancer cells and promotes changes in the expression of genes and proteins that are associated with the invasiveness of cancer i.e. MMP9, SNAIL1/2, ZEB1/2, VIM, CDH1 and CDH2. In conclusion, we postulate that AOH might significantly affect the viability and invasiveness of ovarian cancer cells via modulation of ERα and therefore possibly act as an endocrine disruptive agent in ovarian cancer cells.

Development, systematic optimisation and biofilm disruption activity of eugenol-based nanosized emulsions stabilised with Tween 80

The aims of this study were to systematically optimise a formula for eugenol emulsions via face-centered central composite design and to assess the activity against two-different bacterial strains (Staphylococcus aureus and Propionibacterium acnes) present at planktonic and biofilm forms. The molecular interaction of excipients, mean particle size (MPS) including zeta potential (ZP), drug entrapment efficiency (DEE) and in vitro drug release of optimised emulsions was done using FT-IR, Malvern Zetasizer, ultracentrifugation technique and membrane-free dissolution model, respectively. The emulsions consisted of 151.3 ± 1.45 nm MPS, −21.3 ± 1.25 mV ZP and 93.98 ± 1.41% DEE values. On storage of emulsions at 25 °C for 3 months, the value of DEE was found to be 72.12 ± 2.82%. The Tween 80 emulsifier film coverage onto the dispersed eugenol droplets of emulsions delayed significantly the drug release (12%–19%) compared to the drug release occurred from pure eugenol. The treatment of planktonic S. aureus and P. acnes with diluted eugenol emulsions showed the minimum inhibitory concentration and minimum bactericidal concentration values at 1.25–2.5 mg/ml whereas it occurred at 10 mg/ml for pure eugenol. Treating the biofilms with eugenol emulsions (1–2 mg/ml) yielded 59–70% minimum biofilm eradication concentration but 10 mg/ml pure eugenol showed 60%. Hence, the eugenol emulsions displayed antibacterial activity and could be projected as an antibiofilm or biofilm disruption agent.

Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma

Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment.Graphical

Flavonoids as omnipotent candidates for cancer management

The development of the cancer is a complex process as it proliferates, alters the signaling pathways, and ultimately reduced the patient's survival. The altered cellular events and compromised cellular apoptosis restricts the sensitization of cancer cells to the existing chemotherapeutics. Hence, cancer therapy needs to focus on the development of novel, cost effective, and potent therapeutics approaches which can even overcome the chemo resistance. Plant-based secondary metabolites, such as flavonoids, and their versatile use in health benefits as well as research interest pertaining to their therapeutic benefits are increasing. Flavonoids are used as dietary supplements and are involved in several biological functions and activities. Flavonoids are polyphenolic compounds composed of a 15-carbon skeleton. Due to their diverse pharmacological activities, flavonoids are used for the management of several diseases via oxidative stress and the induction/regression of proteins, enzymes, genes and signaling pathways. The present review aims to extensively discuss the mechanism of flavonoids and their potential utility in inducing programmed cell death. The role of flavonoids as anti-angiogenic, vascular disruption agent and overcoming drug resistance are also discussed. Presently, we have reviewed the various studies on different types of flavonoids, the working mechanism of flavonoids, pharmacological effects, targeting pathways and clinical studies of flavonoids related to multiple cancers. This review offers a prospect for scientists worldwide to understand the potential of flavonoids in the management of cancer.

A tri-level optimization model for facility location-protection problem considering design and redesign decisions under disruption

PurposeFortification-interdiction models provide system designers with a broader perspective to identify and protect vital components. Based on this concept, the authors examine how disruptions impact critical supply systems and propose the most effective protection strategies based on three levels of decision-makers. This paper aims to investigate location and fortification decisions at the first level. Moreover, a redesign problem is presented in the third level to locate backup facilities and reallocate undisrupted facilities following the realization of the disruptive agent decisions at the second level.Design/methodology/approachTo address this problem, the authors develop a tri-level planner-attacker-defender optimization model. The model minimizes investment and demand satisfaction costs and alleviates maximal post-disruption costs. While decisions are decentralized at different levels, the authors develop an integrated solution algorithm to solve the model using the column-and-constraint generation (CCG) method.FindingsThe model and the solution approach are tested on a real supply system consisting of several hospitals and demand areas in a region in Iran. Results indicate that incorporating redesign decisions at the third level reduces maximum disruption costs.Originality/valueThe paper makes the following contributions: presenting a novel tri-level optimization model to formulate facility location and interdiction problems simultaneously, considering corrective measures at the third level to reconfigure the system after interdiction, creating a resilient supply system that can fulfill all demands after disruptions, employing a nested CCG method to solve the model.

Probing the drivers of Staphylococcus aureus biofilm protein amyloidogenesis and disrupting biofilms with engineered protein disaggregases.

Phenol-soluble modulins (PSMs) are the primary proteinaceous component of Staphylococcus aureus biofilms. Residence in the protective environment of biofilms allows bacteria to rapidly evolve and acquire antimicrobial resistance, which can lead to persistent infections such as those caused by methicillin-resistant S. aureus (MRSA). In their soluble form, PSMs hinder the immune response of the host and can increase the virulence potential of MRSA. PSMs also self-assemble into insoluble functional amyloids that contribute to the structural scaffold of biofilms. The specific roles of PSM peptides in biofilms remain poorly understood. Here, we report the development of a genetically tractable yeast model system for studying the properties of PSMα peptides. Expression of PSMα peptides in yeast drives the formation of toxic insoluble aggregates that adopt vesicle-like structures. Using this system, we probed the molecular drivers of PSMα aggregation to delineate key similarities and differences among the PSMs and identified a crucial residue that drives PSM features. Biofilms are a major public health threat; thus, biofilm disruption is a key goal. To solubilize aggregates comprised of a diverse range of amyloid and amyloid-like species, we have developed engineered variants of Hsp104, a hexameric AAA+ protein disaggregase from yeast. Here, we demonstrate that potentiated Hsp104 variants counter the toxicity and aggregation of PSMα peptides. Further, we demonstrate that a potentiated Hsp104 variant can drive the disassembly of preformed S. aureus biofilms. We suggest that this new yeast model can be a powerful platform for screening for agents that disrupt PSM aggregation and that Hsp104 disaggregases could be a promising tool for the safe enzymatic disruption of biofilms. IMPORTANCE Biofilms are complex mixtures secreted by bacteria that form a material in which the bacteria can become embedded. This process transforms the properties of the bacteria, and they become more resistant to removal, which can give rise to multidrug-resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA). Here, we study phenol-soluble modulins (PSMs), which are amyloidogenic proteins secreted by S. aureus, that become incorporated into biofilms. Biofilms are challenging to study, so we have developed a new genetically tractable yeast model to study the PSMs. We used our system to learn about several key features of the PSMs. We also demonstrate that variants of an amyloid disaggregase, Hsp104, can disrupt the PSMs and, more importantly, dissolve preformed S. aureus biofilms. We propose that our system can be a powerful screening tool and that Hsp104 disaggregases may be a new avenue to explore for biofilm disruption agents.

A264 ORAL IRON SUPPLEMENTATION SHAPES THE RECOVERY OF GUT THE MICROBIOTA AND PROMOTES CARCINOGENESIS IN THE APCMIN/+ MOUSE MODEL

Abstract Background Colorectal cancer (CRC) induces anemia in a large proportion of patients and is usually treated with oral iron supplementation. Surgery, the main treatment for CRC, is routinely accompanied by prophylactic antibiotics to avoid infection. Moreover, the concomitance of oral iron supplementation and antibiotics treatment is highly prevalent in general population. However, the combined effect of antibiotics and high luminal iron concentration in the gut on the microbiota and intestinal homeostasis remains unknown. Purpose This study sought to identify possible deleterious effects of the recovery from antibiotics exposure of the gut microbiota under oral iron supplementation. Method In order to assess the effects of luminal iron on the recovery of the gut microbiota, WT mice were subjected to antibiotic treatment with different concentrations of dietary iron. Then, to explore potential deleterious effects of this setup on CRC promotion and progression mediated by the human CRC gut microbiota, CRC model ApcMin/+ mice were subjected to antibiotics prior to gavage with fecal samples from anemic CRC patients, then fed different concentrations of dietary iron. The composition of the gut microbiota and its recovery after these interventions were assessed in stool samples by 16S rRNA. Gut microbiota functions were inferred by using the PICRUSt2, and short chain fatty acid (SCFA) concentration in feces were assessed by liquid-chromatography mass spectrometry. CRC progression and promotion were assessed by tumour counts and immunohistochemistry. Result(s) Recovery from antibiotics under high luminal iron concentration shifted the gut microbiota toward a Bacteroidetes phylum-dominant composition. Three bacterial species characterized as CRC initiators were significantly more abundant. Nitrogen, pentose phosphate, cyanoamino acid metabolisms were higher after recovery under oral iron supplementation. Antibiotic exposure induced a long-term increase in SCFAs linked to gut inflammation, propionate and succinate. For mice under high luminal iron concentration, they showed a lack of recovery in baseline levels of butyrate, a SCFA that inhibits cancer cell proliferation in the gut. In addition, an increase in CRC burden and progression were found in ApcMin/+ mice receiving fecal sample from patients and oral iron supplementation. Conclusion(s) Gut microbiota recovery from antibiotic exposure under oral iron supplementation is frequent in CRC patients, but is also common in the general population. This study identifies possible deleterious effects of the concomitance of these two disruptive agents of the gut microbiota on the CRC progression. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; NSERC, ICM Disclosure of Interest None Declared