Trojan Horse Research Articles

Cellular Trojan Horse initiates bimetallic Fe-Cu MOF-mediated synergistic cuproptosis and ferroptosis against malignancies.

Disruptions in metal balance can trigger a synergistic interplay of cuproptosis and ferroptosis, offering promising solutions to enduring challenges in oncology. Here, we have engineered a Cellular Trojan Horse, named MetaCell, which uses live neutrophils to stably internalize thermosensitive liposomal bimetallic Fe-Cu MOFs (Lip@Fe-Cu-MOFs). MetaCell can instigate cuproptosis and ferroptosis, thereby enhancing treatment efficacy. Mirroring the characteristics of neutrophils, MetaCell can evade the immune system and not only infiltrate tumors but also respond to inflammation by releasing therapeutic components, thereby surmounting traditional treatment barriers. Notably, Lip@Fe-Cu-MOFs demonstrate notable photothermal effects, inciting a targeted release of Fe-Cu-MOFs within cancer cells and amplifying the synergistic action of cuproptosis and ferroptosis. MetaCell has demonstrated promising treatment outcomes in tumor-bearing mice, effectively eliminating solid tumors and forestalling recurrence, leading to extended survival. This research provides great insights into the complex interplay between copper and iron homeostasis in malignancies, potentially paving the way for innovative approaches in cancer treatment.

Drive Bunch Train for the Dielectric Trojan Horse Experiment at the Argonne Wakefield Accelerator

The recently demonstrated concept of the plasma photocathode, whereby a high-brightness bunch is initialized by laser ionization within a plasma wakefield acceleration bubble, is informally referred to as Trojan Horse wakefield acceleration. In a similar vein, the dielectric Trojan Horse concept incorporates a dielectric-lined waveguide to support a charged particle beam-driven accelerating mode and uses laser initiated ionization of neutral gas within the waveguide to generate a witness beam. One of the advantages of the dielectric Trojan Horse concept is the reduced requirements in terms of timing precision due to operation at a lower frequency. In this paper, we present experimental results on the generation and characterization of a four-bunch drive train for resonant excitation of wakefields in a cylindrical dielectric waveguide conducted at the Argonne Wakefield Accelerator facility. The results lay the foundation for the demonstration of a plasma photocathode scheme within a dielectric wakefield accelerating structure. Modifications to improve capture efficiency with improved beam transmission are suggested as well.

Surface wettability control and electron transport regulation in zerovalent iron for enhanced removal of emerging polystyrene microplastics-heavy metal contaminants

Emerging microplastics-heavy metal (MPs-HM) contaminants in wastewaters pose an emerging health and environmental risk due to their persistence and increasing ecological risks (e.g., “Trojan horse” effect). Hence, removing MPs in solution and preventing secondary releases of HM has become a key challenge when tackling with MPs pollution. Leveraging the hydrophobic nature of MPs and the electron transfer efficiency from Fe0 to HM, we demonstrate an alkylated and sulfidated nanoscale zerovalent iron (AS-nZVI) featuring a delicate “core-shell-hydrophobic film” nanostructure. Exemplified by polystyrene (PS) MPs-Pb(II) removal, the three nanocomponents offer synergistic functions for the rapid separation of MPs, as well as the reduction and stabilization of Pb(II). The outmost hydrophobic film of AS-nZVI greatly improves the anticorrosion performance of nanoscale zerovalent iron and the enrichment abilities of hydrophilic MPs, achieving a maximum removal capacity of MPs to 2725.87 mgMPs·gFe−1. This MPs enrichment promotes the subsequent reductive removal of Pb(II) through the electron transfer from the iron core of AS-nZVI to Pb(II), a process further strengthened by the introduced sulfur. When considering the inevitable aging of MPs in wastewaters due to mechanical wear or microbial degradation, our study concurrently examines the efficiencies and behaviors of AS-nZVI in removing virgin-MPs-Pb(II) and aged-MPs-Pb(II). The batch results reveal that AS-nZVI has an exceptional ability to remove above 99.6 % Pb(II) for all reaction systems. Overall, this work marks a pioneering effort in highlighting the importance of MPs-toxin combinations in dealing with MPs contamination and in demonstrating the utility of nZVI techniques for MPs-contaminated water purification.

Guardians of the vault: unmasking online threats and fortifying e-banking security, a systematic review

Purpose The purpose of this paper is to investigate and analyze the adoption of digital technologies in the banking industry and its impact on the rise of digital fraudulent activities, specifically focusing on online banking frauds. This paper aims to provide insights into the current technologies implemented by banks to secure their online banking systems and explores the methods used by cybercriminals to exploit security vulnerabilities in these systems. Design/methodology/approach In order to understand how digital technologies in banking can be secured against online fraud, this research conducted a systematic literature review (SLR) on digital banking, online banking fraud, and security measurements. The review encompasses a variety of sources from online databases such as Emerald Insight, Google Scholar, IEEE, JSTOR, Springer and Science Direct. Findings The key finding of the paper is that the adoption of digital technologies in the banking industry has led to a significant increase in digital fraudulent activities, particularly in the form of online banking frauds. This paper emphasizes that these frauds have become a global concern and have evolved into an industry where cybercriminals use sophisticated tools such as phishing attacks, denial-of-service attacks, Trojan horses, malware infections, identity theft and computer viruses. Research limitations/implications This study relies solely on a literature review without incorporating primary data or case studies; therefore, it might miss out on the firsthand experiences and perspectives of banks and cybersecurity professionals. Practical implications This study emphasizes the need for banks to adopt advanced security measures to safeguard their online banking systems. Social implications This study underscores the importance of ongoing training and awareness programs for both bank employees and customers. Originality/value This study specifically addresses the adoption of digital technologies in the banking industry and its correlation with the increase in digital fraudulent activities. This focus on the intersection of technology and fraud in the banking sector is a distinctive aspect. This study conducts a SLR to examine the current technologies implemented by banks to safeguard their online banking systems. This comprehensive approach provides insights into the diverse security measures used by banks to protect against various types of cyber threats.

Using decision tree classifier to detect Trojan Horse based on memory data

Using decision tree classifier to detect Trojan Horse based on memory data

When the Trojan horse is unable to reach inside the city: investigation of the mechanism of resistance behind the first reported cefiderocol-resistant E. coli in Canada.

Gram-negative metallo-β-lactamase-producing bacteria can be extremely problematic, especially when found to be extensively drug-resistant (XDR). Cefiderocol is a novel antimicrobial that has been shown to overcome most carbapenemases, with very rare resistance reported to date. Within our institution, two multidrug-resistant and one XDR strains were isolated from a patient who recently emigrated from India. Each isolate underwent whole-genome sequencing to resolve plasmids and determine phylogenetics, strain typing, and mechanisms of resistance. The XDR E. coli was ST167, harbored NDM-5, cirA and PBP3 mutations, consistent with cefiderocol resistance. Our study suggests that the NDM region is required in conjunction with cirA and PBP3 mutations. It is not clear why; however, our study did determine a potential novel iron-transport region unique to the cefiderocol-resistant isolate. This is the first characterized cefiderocol-resistant E.coli reported from Canada. Health centers should be on alert for this clone.IMPORTANCEThe development of cefiderocol, a novel siderophore cephalosporin, has provided additional options to the treatment of extensively drug-resistant (XDR) Gram-negative bacteria. Resistance to cefiderocol is poorly understood and only recently described. Here, we describe a case of a patient with recent travel to India harboring three Escherichia coli isolates, one resistant and two susceptible to cefiderocol. Two isolates are highly similar genetically, allowing the mechanism of resistance to be described more closely. The importance of this manuscript contributes both globally to the understanding of cefiderocol resistance in E. coli as well as nationally as this is the first resistant case reported in Canada. This is especially concerning as cefiderocol is not currently approved in Canada. The implications of reporting emerging resistance to new antimicrobials for XDR Gram negatives are impactful to infectious disease specialists, clinical microbiologists, physicians, and public health.

In vitro and in silico studies of enterobactin-inspired Ciprofloxacin and Fosfomycin first generation conjugates on the antibiotic resistant E. coli OQ866153

BackgroundThe emergence of antimicrobial resistance in bacterial pathogens is a growing concern worldwide due to its impact on the treatment of bacterial infections. The "Trojan Horse" strategy has been proposed as a potential solution to overcome drug resistance caused by permeability issues.ObjectiveThe objective of our research was to investigate the bactericidal activity and mechanism of action of the "Trojan Horse" strategy using enterobactin conjugated with Ciprofloxacin and Fosfomycin against the antibiotic-resistant Escherichia coli strain OQ866153.MethodologyEnterobactin, a mixed ligand of E. coli OQ866153, was conjugated with Ciprofloxacin and Fosfomycin individually to aid active absorption via specific enterobactin binding proteins (FepABCDG). The effectiveness of the conjugates was assessed by measuring their bactericidal activity against E. coli OQ866153, as well as their ability to inhibit DNA gyrase enzyme and biofilm formation.ResultsThe Fe+3-enterobactin-Ciprofloxacin conjugate effectively inhibited the DNA gyrase enzyme (Docking score = -8.597 kcal/mol) and resulted in a lower concentration (25 μg/ml) required to eliminate supercoiled DNA plasmids compared to the parent drug (35 μg/ml; Docking score = -6.264 kcal/mol). The Fe+3-Enterobactin-Fosfomycin conjugate showed a higher inhibition percentage (100%) of biofilm formation compared to Fosfomycin (21.58%) at a concentration of 2 mg/ml, with docking scores of -5.481 and -3.756 kcal/mol against UDP-N acetylglucosamine 1-carboxyvinyltransferase MurA.ConclusionThe findings of this study suggest that the "Trojan Horse" strategy using enterobactin conjugated with Ciprofloxacin and Fosfomycin can effectively overcome permeability issues caused by efflux proteins and enhance the bactericidal activity of these drugs against antibiotic-resistant strains of E. coli.

Cajaninstilbene acid derivatives conjugated with siderophores of 3-hydroxypyridin-4(1H)-ones as novel antibacterial agents against Gram-negative bacteria based on the Trojan horse strategy

The low permeability of the outer membrane of Gram-negative bacteria is a serious obstacle to the development of new antibiotics against them. Conjugation of antibiotic with siderophore based on the “Trojan horse strategy” is a promising strategy to overcome the outer membrane obstacle. In this study, series of antibacterial agents were designed and synthesized by conjugating the 3-hydroxypyridin-4(1H)-one based siderophores with cajaninstilbene acid (CSA) derivative 4 which shows good activity against Gram-positive bacteria by targeting their cell membranes but is ineffective against Gram-negative bacteria. Compared to the inactive parent compound 4, the conjugates 45c or 45d exhibits significant improvement in activity against Gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae and especially P. aeruginosa (minimum inhibitory concentrations, MICs = 7.8–31.25 μM). The antibacterial activity of the conjugates is attributed to the CSA derivative moiety, and the action mechanism is by disruption of bacterial cell membranes. Further studies on the uptake mechanisms showed that the bacterial siderophore-dependent iron transport system was involved in the uptake of the conjugates. In addition, the conjugates 45c and 45d showed a lower cytotoxic effects in vivo and in vitro and a positive therapeutic effect in the treatment of C. elegans infected by P. aeruginosa. Overall, our work describes a new class and a promising 3-hydroxypyridin-4(1H)-one-CSA derivative conjugates for further development as antibacterial agents against Gram-negative bacteria.

Mechanistic insight into the intensification of arsenic toxicity to rice (Oryza sativa L.) by nanoplastic: Phytohormone and glutathione metabolism modulation

In this study, nanoplastic (NPs) at environmentally relevant concentration (0.001% w/w) had no effect on the growth of rice, while significantly elevated the phytotoxicity of As (III) by 9.4–22.8% based on the endpoints of biomass and photosynthesis. Mechanistically, NPs at 0.001% w/w enhanced As accumulation in the rice shoots and roots by 70.9% and 24.5%, respectively. Reasons of this finding can was that (1) the co-exposure with As and NPs significantly decreased abscisic acid content by 16.0% in rice, with subsequent increasing the expression of aquaporin related genes by 2.1- to 2.7-folds as compared with As alone treatment; (2) the presence of NPs significantly inhibited iron plaque formation on rice root surface by 22.5%. We firstly demonstrated that “Trojan horse effect” had no contribution to the enhancement of As accumulation by NPs exposure. Additionally, NPs disrupted the salicylic acid, jasmonic acid, and glutathione metabolism, which subsequently enhancing the oxidation (7.0%) and translocation (37.0%) of in planta As, and reducing arsenic detoxification pathways (e.g., antioxidative system (28.6–37.1%), As vacuolar sequestration (36.1%), and As efflux (18.7%)). Our findings reveal that the combined toxicity of NPs and traditional contaminations should be considered for realistic evaluations of NPs.

The Modified Messenger RNA Platform and the Creation of Unintended Proteins: A Genocidal Trojan Horse

The Modified Messenger RNA Platform and the Creation of Unintended Proteins: A Genocidal Trojan Horse

Conformity poses a double-edged sword effect on the evolution of cooperation within heterogeneous endowment populations

Understanding the emergence and maintenance of cooperation is crucial for social development, particularly in the context of contemporary wealth inequality. However, the prevalent phenomenon of individual conformity in humans and social animals is often overlooked in the presence of heterogeneous endowments. Motivated by these considerations, we investigate the impact of conformists on cooperation within the population characterized by binary heterogeneous endowments. Our results reveal that the presence of conformists in a population can influence payoff-driven individuals. These conformists can catalyze the establishment of cooperation across rich and poor individuals, enhancing network reciprocity when the multiplication factor is high (i.e., the degree of cooperation synergy is high), but act as Trojan horses eroding cooperation clusters centered around rich cooperators under a low multiplication factor, thus exhibiting a double-edged sword impact on cooperation. Furthermore, consistent results are observed when accounting for individual conformity biases and multiplayer public goods game. Our research findings reveal the impact of conformity-driven behavior on cooperation in the context of heterogeneous endowments, contributing to a more comprehensive understanding of cooperative evolution amidst inequality.

Insect chitosan/pullulan/gallium photo-crosslinking hydrogels with multiple bioactivities promote MRSA-infected wound healing

Methicillin-resistant Staphylococcus aureus (MRSA) and other drug-resistant bacteria have become more common in recent years, which has made it extremely difficult to treat and heal many different kinds of wounds and caused enormous financial losses. Because of its unique “Trojan horse” function, Ga3+ has been recognized as a new possible candidate for inhibiting and eradicating drug-resistant bacteria. Furthermore, natural polysaccharide materials with outstanding biological characteristics, such as insect chitosan (CS) and pullulan (PUL), have attracted significant interest. In this study, we used quaternized-catechol chitosan (QDCS-PA), methacrylate-dialdehyde pullulan (DPUL-GMA), and gallium ion (Ga) to create a multi-crosslinked photo-enhanced hydrogel (Q-D/Ga/UV) with antimicrobial, hemostatic, self-healing, and injectable properties for promoting MRSA-infected wound healing. In vitro, the Q-D/Ga/UV hydrogels demonstrated good mechanical properties, antioxidant capabilities, biocompatibility, hemostatic properties, and antibacterial activity. The addition of gallium ions enhanced the hydrogels' mechanical properties, hemostatic capabilities, antibacterial activity, and ability to induce wound healing. Q-D/Ga/UV hydrogel significantly promoted wound contraction, collagen deposition, and angiogenesis while also suppressing inflammation in a whole-skin wound model of MRSA-infected rats. In conclusion, Q-D/Ga/UV hydrogels demonstrate significant promise for healing wounds infected with drug-resistant bacteria.

A Zombie Macrophage‐Based “Trojan horse” Enhances the Effect of Efferocytosis Through Immune Regulation for Atherosclerosis Treatment

AbstractVarious immune cell‐mediated drug delivery systems have been reported for precision medicine, but the proinflammatory differentiation of immunocyte vehicles can exacerbate disease progression, resulting in a formidable obstacle to efficacious pharmacotherapy. The progression of atherosclerosis is closely related to the recruitment of blood immunocytes into the plaques, as the migrated macrophages can differentiate into harmful foam cells, leading to dysregulation of macrophage immunity. In this study, a “Trojan horse” based on zombie macrophages (denoted as Z‐Møs) as a biomimetic drug delivery system (denoted as ZARMs) is constructed to regulate macrophage immunity inside plaques. Reactive oxygen species‐responsive nanoparticles (denoted as AR‐NPs) loaded with atorvastatin (denoted as ATT) are encapsulated into Z‐Møs to construct ZARMs. After intravenous administration, ZARMs selectively migrate into plaques, and insusceptible biological characteristics are kept even in the presence of high levels of ROS within the plaques, which simultaneously triggers ATT release from AR‐NPs loaded in Z‐Møs. Treatment assessments indicate that ZARMs can efficiently boost macrophage immunity to reduce the inflammatory burden by inhibiting the expression of CD47 on foam cells without the risk of detrimental domestication of immunocytes in the plaques. This Z‐Møs‐mediated drug delivery system may arouse an advanced therapeutic strategy for preventing atherosclerotic cardiovascular disease.

Identification of Candida albicans and non-MRSA Staphylococcus aureus in free-living amoebae isolated from the hospital wards; an alarm for distribution of nosocomial infections via FLA

ABSTRACT Free-living amoebae (FLA) are isolated from the hospital environments and known as Trojan horses for medical essential microorganisms. This study aimed to investigate the prevalence and the presence of FLA and two critical agents of nosocomial infections, in the hospital wards. Sixty samples were collected from four communities and cultured onto non-nutrient agar (NNA). After total DNA extraction, FLA were characterized using PCR and sequencing. The presence of Candida albicans and Staphylococcus aureus was evaluated using real-time and conventional PCR, respectively. Acanthamoeba sp. was characterized in 30 (50%) samples. Two (6.6%) and one (3.3%) samples were positive for Vahlkampfiidae and Vermamoeba vermiformis, respectively . S. aureus was detected in 13 (43.3%) of samples, while none of them were positive for methicillin-resistant gene. C. albicans DNA was detected in one (3.3%) FLA-positive sample. The isolation of FLA from hospital suggests an essential role these eukaryotes in the inter-ward circulation of nosocomial infections.

Nanoplastics increase in vitro oestrogenic activity of neurotherapeutic drugs.

Environmental pollution with plastic nanoparticles (PNPs) has rendered hazard assessment of unintentional human exposure to neurotherapeutic drugs through contaminated water and food ever more complicated. Due to their small size, PNPs can easily enter different cell types and cross different biological barriers, while their high surface-to-volume ratio enables higher adsorption of chemicals. This is how PNPs take the role of a Trojan horse as they enhance bioaccumulation of many different pollutants. One of the health concerns related to water pollution with neurotherapeutic drugs is endocrine disruption, already evidenced for the anticonvulsant drug carbamazepine (Cbz) and antidepressant fluoxetine (Flx). Our study aimed to evaluate endocrine disrupting effects of Cbz and Flx in mixtures with polystyrene nanoparticles (PSNPs) using the in vitro luciferase assay to measure oestrogen receptor activity in T47D-KBluc cells treated with Cbz-PSNPs or Flx-PSNPs mixtures and compare it with the activities observed in cells treated with individual mixture components (Cbz, Flx, or PSNPs). Dose ranges used in the study were 0.1-10 mg/L, 1-100 µmol/L, and 0.1-10 µmol/L for PSNPs, Cbz, and Flx, respectively. Our findings show that none of the individual components activate oestrogen receptors, while the mixtures induce oestrogen receptor activity starting with 0.1 mg/L for PSNPs, 10 µmol/L for Cbz, and 0.5 µmol/L for Flx. This is the first study to evidence that PSNPs increase oestrogen receptor activity induced by neurotherapeutic drugs at their environmentally relevant concentrations and calls for urgent inclusion of complex mixtures in health hazard assessments to inform regulatory response.

Mirizzi syndrome: The Trojan horse of gallbladder disease

BackgroundThe incidence of Mirizzi Syndrome ranges from 0.05 to 5.7 % of patients who undergo cholecystectomy. The purpose of this study is to examine the preoperative workup and postoperative outcomes for patients diagnosed with Mirizzi Syndrome. MethodsRetrospective chart review was conducted between January 2018 and January 2022 at a single institution. All adult patients who underwent cholecystectomy were included. Results1628 patients underwent cholecystectomy of which 47 were diagnosed with Mirizzi Syndrome. The majority of patients had type 1 Mirizzi Syndrome. Preoperative studies were often nondiagnostic and 81 % of cases were diagnosed intraoperatively. 66 % of cases were performed laparoscopically, an open approach was required for type V Mirizzi Syndrome. The complication rate was 25 %; most commonly a bile leak requiring ERCP. ConclusionMirizzi syndrome is more common than previously expected and related to patient's ability to seek timely medical care. Most cases can be completed laparoscopically however there is a high rate of complications. Key messageThis study presents an additional cohort of patients found to have Mirizzi syndrome and supports the hypothesis that it is difficult to diagnose preoperatively. Cases should be attempted laparoscopically but there remains a high complication rate.

THE GAZA CONFLICT WITHIN INTERNATIONAL LAW

Israel came under brutal attack on October 7, 2023, culminated in a long festering all out conflict against the Hamas perpetrators in the Gaza Strip. All parties to conflict must act in accordance with international law. This article examines whether Israel’s subsequent use of force to rescue and defend its nationals, abides by the right of self-defense under the UN Charter and is in accordance with the law of armed conflict and international humanitarian law. Keywords: Gaza Conflict, Right of Self-Defense, Law of Armed Conflict, International Humanitarian Law

Efficient dynamic quantum secret sharing in pre-measurement and post-measurement phases

This study introduces a novel dynamic quantum secret sharing (DQSS) protocol that utilizes entanglement swapping, Bell measurements, and single-particle measurements to enable agent addition and revocation in both the pre-measurement and post-measurement phases. Since the dealer is only required to prepare Bell states for execution, the proposed DQSS offers greater flexibility and practicality compared to other existing protocols that rely on multiparticle entangled states and are limited to agent modifications in one phase. Furthermore, the proposed DQSS not only exhibits superior qubit efficiency to other related protocols but also demonstrates resilience against several notable attack methods, including Trojan horse and collusion attacks.

Cryptanalysis and improvement of quantum secure multi-party summation using single photons

A previous study [Entropy 25.4 (2023): 590] proposed a quantum secure multi-party summation protocol wherein n participants could obtain the modulo-2 summation result using single photons and single-particle operations. Owing to the absence of an entanglement state, this protocol was more practical than other quantum summation protocols that used entanglement properties. Thus, this study investigated the claim that this proposed protocol prevented the participants’ secret inputs from being disclosed. It was found that the previously proposed protocol was vulnerable to a quantum Trojan horse attack owing to the circular qubit transmission mode. Using a security loophole, this study proposed an attack strategy that allowed an outside attacker to steal any participant’s secret input without being detected by a third party and participants. In addition, a simulation experiment was conducted to demonstrate the feasibility of the proposed attack and evaluate the number of quantum Trojan horse probes that the attacker must inject into regular qubit sequences. Finally, a solution was proposed by modifying the protocol to securely prevent quantum Trojan horse attacks.

Piezocatalytic Schottky Junction Treats Atherosclerosis by a Biomimetic Trojan Horse Strategy.

The atherosclerotic vulnerable plaque is characterized by thefoamy macrophage burden, involving impaired cholesterol efflux and deficient efferocytosis. Correspondingly, piezocatalytic therapy is an emerging solution for eliminating the foamy macrophage burden with satisfactory spatiotemporal controllability and deep penetration depth. Herein, a biomimetic Trojan horse (Au-ZnO@MM) is engineered by coating the macrophage membrane (MM) onto the surface of a rod-like Au-ZnO Schottky Junction to effectively relieve the atherosclerotic progression. These Trojan horses with the coating of MM are actively transported into subsistent foamy macrophages and generate abundant reactive oxygen species (ROS) via ultrasound-activated piezocatalysis. ROS-initiated autophagy and mitochondrial dysfunction induce substantial cell apoptosis, alleviating the burden of subsistent foamy macrophages. The resulting apoptotic fragments further significantly facilitate cholesterol excretion and trigger efferocytosis of intraplaque fresh macrophages. Ultimately, the biomimetic Au-ZnO@MM piezocatalyst not only inhibits the foaming capacity of macrophages, but also improves the function of removing cell debris, which can stabilize atherosclerotic vulnerable plaque. Meanwhile, the plasmon resonance effect of integrated gold nanoparticles enables favorable photoacoustic molecular imaging for real-time image-guided atherosclerotic therapy. This proposed biomimetic Trojan horse strategy provides the paradigm of employing ultrasound-activated piezocatalytic methodology for enhanced atherosclerotic theranostics.