Filtration is an established water‐purification technology. However, due to low flow rates, the filtration of large volumes of water is often not practical. Herein, we report an alternative ...purification approach in which a magnetic nanoparticle composite is used to remove organic, inorganic, microbial, and microplastics pollutants from water. The composite is based on a polyoxometalate ionic liquid (POM‐IL) adsorbed onto magnetic microporous core–shell Fe2O3/SiO2 particles, giving a magnetic POM‐supported ionic liquid phase (magPOM‐SILP). Efficient, often quantitative removal of several typical surface water pollutants is reported together with facile removal of the particles using a permanent magnet. Tuning of the composite components could lead to new materials for centralized and decentralized water purification systems.
Clean machine: A three‐component composite allows the magnetic removal of organic, inorganic, microbial, and microplastic pollutants from water. Magnetic Fe2O3/SiO2 core–shell nanoparticles are functionalized with a polyoxometalate ionic liquid. The composite can be dispersed in water, binds multiple pollutants and can be fully recovered with a permanent magnet.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
New gold(
i
) complexes with coordination to 5-fluorouracil (5-FU), an anticancer drug with antibacterial properties, have been synthesised and characterised, and are the first reported examples of ...5-FU-Au compounds. These new complexes show high solution stability, even in the presence of a cysteine derivative, and so were evaluated as antibacterial compounds against model Gram-positive and Gram-negative bacteria. All the complexes show excellent antibacterial activity against Gram-positive
B. subtilis
, most of them improving the activity of 5-FU alone. Furthermore, these new complexes are also active against Gram-negative
E. coli
, where Au(5-FU)(PTA), the complex with the smallest phosphane, is the most bactericidal, 32 times more active than 5-FU on its own.
New gold(
i
)-phosphine complexes with coordination to 5-fluorouracil (5-FU), being the first reported examples of 5-FU-Au compounds, present antibacterial properties.
Gene expression dynamics have provided foundational insight into almost all biological processes. Here, we analyze expression of environmentally responsive genes and transcription factor genes to ...infer signals and pathways that drive pathogen gene regulation during invasive Candida albicans infection of a mammalian host. Environmentally responsive gene expression shows that there are early and late phases of infection. The early phase includes induction of zinc and iron limitation genes, genes that respond to transcription factor Rim101, and genes characteristic of invasive hyphal cells. The late phase includes responses related to phagocytosis by macrophages. Transcription factor gene expression also reflects early and late phases. Transcription factor genes that are required for virulence or proliferation in vivo are enriched among highly expressed transcription factor genes. Mutants defective in six transcription factor genes, three previously studied in detail (Rim101, Efg1, Zap1) and three less extensively studied (Rob1, Rpn4, Sut1), are profiled during infection. Most of these mutants have distinct gene expression profiles during infection as compared to in vitro growth. Infection profiles suggest that Sut1 acts in the same pathway as Zap1, and we verify that functional relationship with the finding that overexpression of either ZAP1 or the Zap1-dependent zinc transporter gene ZRT2 restores pathogenicity to a sut1 mutant. Perturbation with the cell wall inhibitor caspofungin also has distinct gene expression impact in vivo and in vitro. Unexpectedly, caspofungin induces many of the same genes that are repressed early during infection, a phenomenon that we suggest may contribute to drug efficacy. The pathogen response circuitry is tailored uniquely during infection, with many relevant regulatory relationships that are not evident during growth in vitro. Our findings support the principle that virulence is a property that is manifested only in the distinct environment in which host-pathogen interaction occurs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell ...exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fungal invasion of the oral epithelium is central to the pathogenesis of oropharyngeal candidiasis (OPC). Candida albicans invades the oral epithelium by receptor-induced endocytosis but this process ...is incompletely understood. We found that C. albicans infection of oral epithelial cells induces c-Met to form a multi-protein complex with E-cadherin and the epidermal growth factor receptor (EGFR). E-cadherin is necessary for C. albicans to activate both c-Met and EGFR and to induce the endocytosis of C. albicans. Proteomics analysis revealed that c-Met interacts with C. albicans Hyr1, Als3 and Ssa1. Both Hyr1 and Als3 are required for C. albicans to stimulate c-Met and EGFR in oral epithelial cells in vitro and for full virulence during OPC in mice. Treating mice with small molecule inhibitors of c-Met and EGFR ameliorates OPC, demonstrating the potential therapeutic efficacy of blocking these host receptors for C. albicans.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, ...and charge, and their chemical functional groups can be easily modified to match the needs of the final application and mode of administration. This review focuses on polysaccharidic nanocarriers based on chitosan and hyaluronic acid for small interfering RNA (siRNA) delivery, which are highly positively and negatively charged, respectively. The key properties, strengths, and drawbacks of each polysaccharide are discussed. In addition, their use as efficient nanodelivery systems for gene silencing applications is put into context using the most recent examples from the literature. The latest advances in this field illustrate effectively how chitosan and hyaluronic acid can be modified or associated with other molecules in order to overcome their limitations to produce optimized siRNA delivery systems with promising
and
results.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The photothermal response of plasmonic nanomaterials can be exploited for a number of biomedical applications in diagnostics (biosensing and optoacoustic imaging) and therapy (drug delivery and ...photothermal therapy). The most common cellular response to photothermal cancer treatment (ablation of solid tumors) using plasmonic nanomaterials is necrosis, a process that releases intracellular constituents into the extracellular milieu producing detrimental inflammatory responses. Here we report the use of laser-induced photothermal therapy employing gold nanoprisms (NPRs) to specifically induce apoptosis in mouse embryonic fibroblast cells transformed with the SV40 virus. Laser-irradiated “hot” NPRs activate the intrinsic/mitochondrial pathway of apoptosis (programmed cell death), which is mediated by the nuclear-encoded proteins Bak and Bax through the activation of the BH3-only protein Bid. We confirm that an apoptosis mechanism is responsible by showing how the NPR-mediated cell death is dependent on the presence of caspase-9 and caspase-3 proteins. The ability to selectively induce apoptotic cell death and to understand the subsequent mechanisms provides the foundations to predict and optimize NP-based photothermal therapy to treat cancer patients suffering from chemo- and radioresistance.
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IJS, KILJ, NUK, PNG, UL, UM
Microorganisms offer an alternative green and scalable technology for the synthesis of value added products. Fungi secrete high quantities of bioactive substances, which play dual-functional roles as ...both reducing and stabilizing agents in the synthesis of colloidal metal nanoparticles such as silver nanoparticles, which display potent antimicrobial properties that can be harnessed for a number of industrial applications. The aim of this work was the production of silver nanoparticles using the extracellular cell free extracts of
, and to evaluate their activity as antimicrobial and antibiofilm agents. The 45-nm diameter silver nanoparticles synthesized using this methodology possessed a high negative surface charge close to -30 mV and showed colloidal stability from pH 3-9 and under conditions of high ionic strength (
= 10-500 mM). A combination of environmental SEM, TEM, and confocal Raman microscopy was used to study the nanoparticle-
interactions to gain a first insight into their antimicrobial mechanisms. Raman data demonstrate a significant decrease in the fatty acid content of
cells, which suggests a loss of the cell membrane integrity after exposure to the PchNPs, which is also commensurate with ESEM and TEM images. Additionally, these biogenic PchNPs displayed biofilm disruption activity for the eradication of
and
biofilms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We describe why the cyclic heteropolyanion P8W48O18440– (abbreviated as {P8W48}) is an ideal building block for the construction of intrinsically porous framework materials by classifying and ...analyzing >30 coordination polymers incorporating this polyoxometalate (POM) ligand. This analysis shows that the exocyclic coordination of first-row transition metals (TMs) to {P8W48} typically yields frameworks which extend through {W–O–TM–O–W} bridges in one, two, or three dimensions. However, despite the rich structural diversity of such compounds, the coordination of TMs to the {P8W48} ring is poorly understood, and therefore largely unpredictable, and had not until now been present with any structural classification that could allow rational design. Herein, not only do we present a new approach to understand and classify this new class of materials, we also present three {P8W48}-based frameworks which complement those frameworks which have previously been described. These new compounds help us postulate a new taxonomy of these materials. This is possible because the TM coordination sites of the {P8W48} ring are found, once fully mapped, to lead to well-defined classes of connectivity. Together, analysis provides insight into the nature of the building block connectivity within each framework, to facilitate comparisons between related structures, and to fundamentally unite this family of compounds. Hence we have tentatively named these compounds as “POMzites” to reflect the POM-based composition and zeolitic nature of each family member, although crucially, POMzites differ from zeolites in the modular manner of their preparation. As the synthesis of further POMzites is anticipated, the classification system and terminology introduced here will allow new compounds to be categorized and understood in the context of the established materials. A better understanding of TM coordination to the {P8W48} ring may allow the targeted synthesis of new frameworks rather than the reliance on serendipity apparent in current methods.
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IJS, KILJ, NUK, PNG, UL, UM
During hematogenously disseminated candidiasis, blood borne fungi must invade the endothelial cells that line the blood vessels to infect the deep tissues. Although
Candida albicans
, which forms ...hyphae, readily invades endothelial cells, other medically important species of
Candida
are poorly invasive in standard in vitro assays and have low virulence in immunocompetent mouse models of disseminated infection. Here, we show that
Candida glabrata
,
Candida tropicalis
,
Candida parapsilosis
, and
Candida krusei
can bind to vitronectin and high molecular weight kininogen present in human serum. Acting as bridging molecules, vitronectin and kininogen bind to αv integrins and the globular C1q receptor (gC1qR), inducing human endothelial cells to endocytose the fungus. This mechanism of endothelial cell invasion is poorly supported by mouse endothelial cells but can be restored when mouse endothelial cells are engineered to express human gC1qR or αv integrin. Overall, these data indicate that bridging molecule-mediated endocytosis is a common pathogenic strategy used by many medically important
Candida spp
. to invade human vascular endothelial cells.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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