Microplastics as Trojan horses: Vectors of pathogens, pollutants, and antimicrobial resistance genes.

Critical minerals as a Trojan Horse: The political ecology of green extractivism in climate governance

Cyclodextrin-siderophore conjugates as a Trojan horse strategy for bacterial targeting.

Targeting bacterial metal dependence: material design with computational frontiers.

Nanobubbles alleviate iron-mediated cell death in algae-bacteria symbiotic systems under sulfamethoxazole stress: Insights into electron transfer and ferrikinetics.

The century-old vision of a "magic bullet" in oncology is being realized through the paradigm of precision theranostics, which formally integrates targeted delivery, cytotoxic action, and non-invasive imaging into a unified clinical feedback loop. This review synthesizes the cutting-edge convergence of three interdependent pillars: antibody-drug conjugates (ADCs), which act as Trojan horses delivering potent cytotoxic payloads; radioimmunotherapy (RIT), which harnesses the power of radionuclides for crossfire-mediated cytotoxicity; and advanced molecular imaging, which orchestrates patient stratification and early response assessment. We dissect the mechanistic innovations in ADC design, the renaissance of RIT with novel isotopes and targets, and the pivotal role of immuno-PET in enabling an "image-to-treat" paradigm. Furthermore, we explore the synergistic frontier of rationally combining ADCs and RIT to overcome resistance through multi-mechanistic attacks, leveraging radiation for payload activation, and priming the tumor microenvironment. Despite challenges in toxicity management, radiopharmaceutical supply, and regulatory frameworks, the integration of these modalities, guided by artificial intelligence and functional imaging, heralds a new era of dynamic, personalized, and adaptive cancer therapy. This integrative approach promises to convert tumor heterogeneity from a fundamental obstacle into a targetable vulnerability; however, this promise must be tempered by clinical examples in which heterogeneity undermined otherwise promising targeted approaches (for example, subclonal RAS mutations limiting benefit from anti-EGFR monoclonal antibodies in colorectal cancer). We therefore emphasize lesion-level imaging and adaptive, imaging-guided sequencing as realistic, evidence-based mechanisms by which theranostics can reduce the impact of intratumoral heterogeneity and improve the chance of durable benefit.

Micro/nanoplastic-induced gut dysbiosis: A key driver of systemic toxicity via the gut-organ axes in animals.

The formation of amide bonds is key to the biosynthesis of numerous natural products as well as to the industrial production of pharmaceuticals and valuable chemicals. As an alternative to the often inefficient and wasteful chemical syntheses of amides, emerging sustainable biocatalytic strategies rely on enzymes, such as amide bond synthetases (ABSs). Here we report the characterization of two distinct types of ABSs from the biosynthesis of the typically antibacterial and cytotoxic rubromycin polyketides, hyaluromycin and coumarubrin, which are produced by Streptomyces hyaluromycini and Lentzea tibetensis, respectively. These enzymes, ShRaABS and LtRaABS, are presumed to regiospecifically attach the aminocyclopentenone and aminocoumarin substituents (or their biosynthetic precursors) to the rubromycin backbone. Both ABSs were scrutinized for their substrate tolerance toward amino- and carboxy-donors, establishing LtRaABS as the more promising biocatalyst that allowed the generation of numerous unnatural rubromycins. These compounds include a "Trojan Horse" dopamine congener as the first known rubromycin with antibiotic activity against a Gram-negative Pseudomonas sp. by exploiting the strain's siderophore-uptake machinery. In addition, LtRaABS allowed the azide functionalization of rubromycins, thereby setting the stage for bioorthogonal click chemistry that can be employed in the future, for example, for the generation of antibody-drug conjugates.

Extensive critique of the evidence-based policy paradigm has led to new ways of considering the role of evidence; for example Katherine Smith suggests that "ideas" rather than evidence mediate "the relationship between research and policy". In this paper, we used Smith's typology on "ideas" to explore how this can be applied to a case of Australian policy making: a police diversion scheme for simple possession of drugs. We aimed to analyse the idea's journey into policy in one Australian jurisdiction (New South Wales) and assess its fit with the four different types of ideas outlined by Smith. Qualitative case study analysis using data from New South Wales, Australia, over the period 2018 to 2024. Multiple data sources were used: interviews with stakeholders (n = 26), documents [reports, non-governmental organization (NGO) advocacy documents], media and official reports of a Drug Summit. Each data source was searched for narration/text concerned with police diversion in addition to decriminalisation, extracted and analysed against Smith's typology. Features of 'institutionalised ideas' suggest that police diversion is not an institutionalised idea. It appears in this case to be a 'chameleonic idea' inasmuch as its characteristics change and are malleably deployed by different stakeholders with different interests. 'Flexian policy actors' (including police, government officials, advocates and researchers) are able to interpret, transform and shape the meaning of police diversion to suit their interests and commitments. Despite evidence synthesis and expert review recommending police diversion as a second-best option to decriminalisation, it was taken up into policy. We suggest this is because of its chameleonic nature, serving simultaneously at the hands of different policy actors as a roadblock to decriminalisation and as a Trojan horse for decriminalisation reform whilst also obscuring tensions between police diversion and decriminalisation. Applying Katherine Smith's typology of ideas to an Australian police diversion scheme for simple possession of drugs shows that the scheme is not an institutionalised idea but rather a chameleonic idea. Smith's typology of ideas adds another layer to policy process frameworks, enhancing analysis seeking to understand the uptake of ideas into policy.

The development of next-generation nanotheranostics is increasingly challenged by the dual imperatives of environmental sustainability and the urgent need to overcome complex biological barriers, particularly multidrug resistance (MDR) in hepatocellular carcinoma (HCC). Herein, we bridge the gap between circular economy principles and precision nanomedicine by upcycling discarded eggshell membranes (ESM) into a hierarchical metabolic therapeutic platform. Utilizing the protein fiber network of ESM as a natural biotemplate, we orchestrated the anisotropic growth of calcium carbonate (CaCO3) into unique yolk-shell nanostructures (YSNs) via interfacial molecular recognition. This bioinspired architecture features a high specific surface area, enabling the efficient coloading of the chemotherapeutic cisplatin (CDDP) and ultrathin vanadium carbide (V4C3) MXene nanozymes, stabilized by a biotinylated carboxymethyl chitosan (Biotin-CMCS) targeting shell. Mechanistically, this "Trojan Horse" system exploits the acidic tumor microenvironment (TME) to trigger a rapid cascade of disassembly, releasing a surge of Ca2+ ions and MXene-driven reactive oxygen species (ROS). Crucially, we demonstrate that the resulting mitochondrial calcium overload instigates a catastrophic "bioenergetic crisis," characterized by the irreversible opening of mitochondrial permeability transition pores (mPTP) and the precipitous depletion of intracellular adenosine triphosphate (ATP). This metabolic collapse effectively deactivates ATP-dependent DNA repair machineries (e.g.,poly(ADP-ribose) polymerase 1 (PARP1) and excision repair cross-complementation group 1 (ERCC1)), thereby reversing cisplatin resistance and sensitizing tumor cells to DNA damage. In vivo evaluations in HCC xenografts confirm potent tumor regression with minimal systemic toxicity, facilitated by the renal clearance of biodegradable calcium metabolites. This work presents a paradigm shift in material design, transforming biowaste into a metabolic reprogramming weapon for sustainable and effective cancer therapy.

Mutualistic symbioses are potentially vulnerable to exploitation, particularly in hosts that acquire symbionts from the environment, where harmful exploiters inhabit. The independent evolution and persistence of intricate partner-choice mechanisms in many symbioses testify the threat by specialized exploiters of mutualisms, although only few have been documented in nature. We report here a lethal "Trojan horse" pathogen, Burkholderia sp. SJ1, exploiting the stinkbug-Caballeronia gut symbiosis. This bacterium resembles symbionts by using wrapping motility to traverse the host's sorting organ, inducing symbiotic organ morphogenesis and colonizing it. Unlike mutualists, however, it resists host digestion for nutrient acquisition, breaches the gut epithelium, and causes sepsis, rapidly killing the host. Colonization of the symbiotic organ is essential for its lethality. This case shows how pathogens can exploit mutualisms, highlighting the evolutionary pressures shaping partner-choice mechanisms and the fragility of even highly specialized mutualisms.

Beyond hepatitis D virus: the discovery of animal deltaviruses, their diversity, helpers and their position in an expanding world of circular RNA replicons.

Nanoparticle-based photothermal therapy (PTT) provides localized tumor ablation but remains limited by off-target accumulation and the need for high systemic doses. To address these challenges, we developed gold nanorods (AuNRs) coated with a multivalent glucose ligand (mvGlu-AuNR) that engages glucose transporter type 1 (GLUT1) for selective tumor delivery. This design leverages the Warburg effect, using GLUT1 as a metabolic Trojan horse to enter glycolytic cancer cells. In 4T1 breast cancer models, mvGlu-AuNR showed an 8-fold increase in gold content and a 3-fold rise in photoacoustic signal compared to nontargeted controls. Notably, mvGlu-AuNRs converted light to heat more efficiently than mPEG-AuNRs under identical irradiation conditions. ICP-MS analysis confirmed tumor-to-liver ratios ranging from 1.56 to 4.88, which is consistent with strong tumor localization and minimal hepatic uptake. At a systemic dose of 1 mg/kg, mvGlu-AuNRs enabled efficient tumor heating and slowed tumor growth without signs of off-target toxicity. These findings establish metabolic targeting as an effective strategy to enhance PTT specificity, reduce off-target exposure, and enable markedly lower gold dosing.

Plastic and its degradation products are growing and becoming a global emergency. In the "Plasticene era" the degradation of plastic, exacerbated by climate change, generates microplastics (MP) and nanoplastics (NP). Due to their small size, they are transported everywhere, and therefore we find them increasingly in the air, in the sea and in fresh water, in the soil, and bioconcentrated in the food chain. Food consumption is one of the most important human exposure pathways to MPs that have been found in all food. MPs, due to their oxidative stress and inflammatory effects, are a growing concern for human health. Furthermore, due to their hydrophobic surface, they act as a Trojan horse for other types of environmental contaminants that are known to be toxic and endocrine disruptors. MPs and NPs enter the human body mainly through ingestion of food, water and other beverages, as well as through inhalation and direct contact with the skin. They have been found in the placenta, urine, follicular fluid, atheromatous plaques, seminal fluid as well as in blood which transports them throughout our body. Several studies in mammals indicate that MPs smaller than 10 μm can cross cell membranes, posing potential health risks through oxidative stress, inflammation, immune dysfunction, neurotoxicity, altered metabolism, impaired cell proliferation, alteration of the gut microbiota, abnormal tissue development and carcinogenicity. Our studies on human populations have highlighted the negative role of MPs in male and female fertility, in dialysis subjects, in groups with bowel diseases and colorectal cancer and in subjects with major depression. The topic in question is currently at the centre of scientific research, posing an urgent need for prevention interventions at all levels and requiring legislative and cultural interventions to reduce plastics from production to consumption according to a One Health perspective in a Planetary Heart vision.

Current research often overlooks the polymer-specific aging behaviors of polar (PA6) versus non-polar (PP) microplastics during advanced oxidation processes (AOPs). Addressing this gap, this study establishes a synergistic ultraviolet-persulfate (UV-PS) oxidation system to contrast the degradation mechanisms of PA6 against the natural photodegradation of PP, specifically examining their carrier effects for Doxycycline (DOX). The research has found that the sulfate radicals generated by the UV-PS system can efficiently attack the amide bonds in the PA6 molecule, resulting in a degradation level of the aging process being several times that of PP. Quantitative analysis reveals that the inherent polarity of the PA6 framework increases due to the oxidation-induced increase in active sites, resulting in an adsorption capacity for DOX that is 12 times that of non-polar PP and 27 times that of pure UV aging. However, this excellent enrichment ability aggravates its biological risk, and in vitro simulated digestion experiments confirm the "Trojan Horse" effect of aging PA6. The adsorbed DOX was not permanently sealed, but the complete release of ~ 100% was achieved under the synergistic action of gastric fluid proton attack (about 70% of burst release) and increased solubility of intestinal bile salts. This study confirms that PS-PA6 as a high-risk "supercarrier" for antibiotics, highlighting the critical need for differentiated risk assessment for specific polymers in complex water treatment environments.

Pseudomonas aeruginosa is a common Gram-negative bacterium in hospital infections and one of the main pathogens causing opportunistic infections in humans. In recent years, the drug resistance of P. aeruginosa has become increasingly severe. Therefore, it is urgent to explore new targets for antibacterial therapy. In P. aeruginosa, iron is an essential element not only for cell growth but also for successful infection. Two siderophores are produced by P. aeruginosa: pyoverdine and pyochelin. They help P. aeruginosa to obtain iron and play an important role in interspecific competition, anti-oxidative stress, and virulence. Furthermore, siderophores have been used to design "Trojan horse" antibiotics. These antibiotic-siderophore conjugates enter the cytoplasm of P. aeruginosa via siderophore uptake systems for pyoverdine and pyochelin, releasing antibacterial substances and exerting corresponding effects against P. aeruginosa. This review discusses the synthesis, secretion, and uptake of siderophores in P. aeruginosa as well as the role of the "Trojan horse" strategy in treating P. aeruginosa infections.

The management of chronic rhinosinusitis (CRS) is frequently complicated by treatment recalcitrance, a phenomenon primarily driven by the persistence of microbial biofilms. Beyond their traditional role as a physical barrier against antibiotics, recent evidence positions biofilms as sophisticated immune modulators that actively perpetuate mucosal dysbiosis. This review synthesizes the pathological continuum of biofilm-associated CRS, elucidating how biofilm derived pathogen associated molecular patterns (PAMPs) trigger the release of epithelial alarmins (TSLP, IL-33, IL-25), thereby fueling a maladaptive Type 2 inflammatory loop. We further examine bacterial survival strategies, such as the formation of small colony variants (SCVs) and intracellular "Trojan Horse" reservoirs, which render conventional functional endoscopic sinus surgery (FESS) and antimicrobial monotherapies insufficient for complete eradication. Crucially, we discuss the current diagnostic disconnect where standard cultures fail to detect biofilm burdens. Finally, we propose a therapeutic paradigm shift from a purely bactericidal approach to one of ecological restoration. By integrating cutting-edge strategies, including matrix-degrading enzymes, bacteriophage cocktails, and Nasal Microbiota Transplantation (NMT), we construct a multi-dimensional framework aiming to restore sinonasal homeostasis. Together, these emerging strategies support a shift from pathogen suppression alone toward ecological and immunologic rebalancing of the sinonasal mucosa, offering a more durable conceptual framework for overcoming treatment recalcitrance.

The emergence of extensively drug-resistant Enterobacterales, particularly carbapenemase-producing Klebsiella pneumoniae, poses a serious global health threat. Cefiderocol (FDC), a sideromycin antibiotic, employs a 'Trojan horse' strategy by using bacterial iron transport systems to enter the cell and inhibit cell wall synthesis. Although initially promising, resistance to FDC has rapidly emerged in the clinics and in the environment, necessitating a comprehensive understanding of the underlying resistance mechanisms. In this study, we used transposon-directed insertion-site sequencing in an extensively drug-resistant FDC-susceptible K. pneumoniae ST258 strain to systematically identify genetic networks that modulate FDC resistance. Our transposon-directed insertion-site sequencing analysis revealed 299 chromosomal genes significantly impacting FDC resistance, with 143 identified as conditionally resistant modulators (CRMs) and 156 as conditionally essential genes. CRMs notably included genes associated with FDC influx, such as the siderophore uptake genes cirA and tonB, and porin channels such as ompK36 and tolB. Importantly, we identified several CRMs involved in bacterial capsule synthesis and expression (e.g. csrD and glnD), suggesting that capsule overexpression is a novel resistance mechanism. Phenotypic characterization of cirA, csrD and glnD knockout mutants confirmed increased FDC resistance. Furthermore, disruption of csrD and glnD resulted in enhanced capsule production, increased resistance to human serum and, in particular, increased virulence in a Galleria mellonella infection model. These results emphasize the multifactorial nature of FDC resistance, involving both impaired drug entry and capsule-mediated protection, with potentially pleiotropic effects on bacterial virulence. Our study elucidates key genetic determinants of FDC resistance and highlights the complex interplay between antibiotic resistance and bacterial pathogenicity.

Molecular PET imaging of tumor-associated macrophages in precision oncology.

Natural metal-containing nanoparticles as an important form of metals in their biogeochemical cycle and biological effect.