ARC Centre of Excellence in Advanced Molecular Imaging

For 50years poly(ethylene glycol) (PEG) has been regarded as the gold standard of biocompatible, hydrophilic, and stealthy nanomedicine excipients. PEG has demonstrated improved pharmacokinetic profile, improved physical stability, and reduced toxicity for a variety of therapeutic molecules. PEG and PEG derivatives are ubiquitous, present in nearly all lipid nanoparticle vaccines, oncology nanomedicines, and over a third of solid oral dosage forms. PEG is also frequently used as a stabiliser in food and PEGylated surfactants dominate in cosmetic products. However, there is a growing body of research in which PEG immunogenicity is observed not only through repeated doses of PEGylated therapeutics, but also in so-called PEG-naïve individuals who have not yet been exposed to PEGylated drugs or formulations. Due to the potential overuse of PEG and the apparent subsequent sensitization that arises in individuals, research into PEG alternatives has garnered significant attention. Poly(cyclic imino ether)s (PCIE) are a promising family of biocompatible synthetic polymers, including poly(2-oxazoline)s (POx) and poly(2-oxazine)s (POz), which have attracted significant attention due to their potential for broad functionalisation, and tuneable physicochemical properties. Hydrophilic PCIEs have been presented as PEG alternatives with the aim of providing an alternative to PEG in nanomedicine and reducing the potential for adverse events in an increasingly PEG-sensitized population. Reports of preclinical studies involving PCIE nanomedicines are growing and show promise in terms of their application in the medical field, however, instances of clinical translation for this class of nanomedicines are disproportionately few. This review discusses the general motivation for developing PEG alternatives and their potential benefits using PCIEs as an example. It encompasses a critical appraisal of the preclinical research space surrounding PCIEs, with a view to understanding the lack of a preclinical-to-clinical translation pipeline. In reviewing the development, application and translation challenges of PCIE nanomedicines, we aim to highlight the promise of these materials for the next decade of PCIE nanomedicine research.

Australia's native fauna is unique through millions of years of isolated evolution resulting in a significant divergence of marsupial brain anatomy, and thus neural pathways, from eutherian mammals. This study provides a morphometric description of a mature female koala (Phascolarctos cinereus) through segmentation of high-resolution magnetic resonance images. As the availability of brain specimens of the endangered koala is scarce, brain segmentation has been performed on a single specimen. The brain of a naturally deceased koala was removed and fixed in 10% neutral buffered formaldehyde (pH 7.0). The MRI was acquired on a 9.4 T Bruker Biospec MR system with Paravision 7.0 software, using a 3D multigradient echo sequence, with TR/TE = 70 msec/ (8 echoes 4-32 msec), a field of view = 7.0 × 6.4 × 4.0 cm3. AMIRA post image processing software was used to create three-dimensional volume reconstruction of different brain structures, allowing for the calculation of their volumes. The koala brain is lissencephalic and has a volume of 15720.98 mm3. It was found that the olfactory bulbs of the koala were 418 mm3 or 2.66% of the total brain volume (tbv). The cerebral hemispheres were 9336.92 mm3 (59.39% of the tbv). The interhemispheric connections were 148 mm3 (0.94% of tbv). The combined volume of the anterior commissure and fasciculus aberrans, which is specific to marsupials, has also been labeled and segmented. The ventricular system was 172 mm3 (1.09% of tbv). The brainstem was 1874 mm3 (11.92% of tbv). The cerebellum was 2304.69 mm3 (14.66% of tbv). This study can be used as a basis for clinical imaging of koalas and as baseline data for future research into brain development of koalas and other marsupials.

Molecular interactions are crucial to improving the efficiency and stability of perovskite solar cells, yet current solution-based approaches relying on molecular incorporation or surface passivation show inherent limitations in separately controlling these interactions. Here we reveal an intrinsic interfacial interaction that arises from simple contact between individually crystallized two-dimensional and three-dimensional perovskites without mixing or permanent bonding. We define this contact-triggered cationic interaction (CCI), which reversibly constrains molecular degrees of freedom, suppresses phase transitions, enhances carrier lifetimes and induces a unique recrystallization of the three-dimensional framework. This CCI-driven recrystallization produces refined FAPbI3 with improved cation homogeneity, reduced lattice disorder and superior optoelectronic properties. Devices using CCI-driven FAPbI3 achieve 26.25% efficiency (25.61% certified) and retain a projected operational lifetime exceeding 20,000 h. Our findings provide the first quantitative evidence that intrinsic interfacial cationic interactions can directly influence perovskite material quality and device performance. Solution processing of 2D/3D perovskite structures for solar cells offers limited control over layer formation. Lee et al. propose a dry approach, bringing the 2D and 3D perovskite layers into physical contact, to enhance the quality of the perovskite film.

Abstract. The increasing release of Antarctic meltwater represents one of the most profound, yet uncertain, consequences of global climate change. The absence of interactive ice sheets in state-of-the-art climate models prevents the direct calculation of ice–ocean feedbacks, leaving significant uncertainty in the global and regional consequences of meltwater discharge. This study leverages results from the Southern Ocean Freshwater Input from Antarctica (SOFIA) initiative to assess the ocean response to a 0.1 Sv meltwater perturbation and infer the feedback on ice shelf basal melting across 10 CMIP6 models. We analyze meltwater-induced temperature anomalies across distinct continental shelf regimes and compare them with SSP5-8.5 warming-induced anomalies. We then translate these anomalies into basal melt rates using a parameterization calibrated with a new observational climatology, which reveals strongly regional melt sensitivities that cannot be captured with an Antarctic-wide coefficient. Although the meltwater feedback is generally thought to amplify basal melting, our results demonstrate large regional differences, with implied enhanced ice shelf mass loss in some sectors but suppressed basal melting in others. The model ensemble indicates a warming feedback on the continental shelf in most East Antarctic regions, whereas in West Antarctica, most models simulate either cooling or reduced warming, suggesting a negative feedback. This regional contrast implies that East Antarctica may play an increasingly dominant role in future ice shelf mass loss. Simulations support existing hypotheses linking these asymmetric temperature responses to strong regional connectivity and shelf-break dynamics, including a strengthened Antarctic Slope Front, an accelerated Antarctic Slope Current, and reduced dense shelf water formation.

This study investigates the volumetric 3D printing of thermoplastic materials using xolography. Employing the Hoftyzer and Van Krevelen model to estimate solubility parameters, we explored various factors influencing the printing process, including resin viscosity and polarity, and polymer solubility in the resins. Three strategies were implemented to increase printing resolution in xolography by increasing the resin viscosity, enhancing the resin polarity, and incorporating monomers with strong hydrogen-bonding capabilities. These strategies promoted polymer precipitation at lower monomer conversions, enabling the fabrication of high-resolution thermoplastic 3D structures via xolography. Importantly, the printed materials demonstrated solubility in selected solvents, highlighting their potential for further processing or recycling.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with global distribution and documented risks to human and environmental health. Sorbent-based technologies are widely explored for PFAS removal, yet the advancement of this field is impeded by inconsistent and incomplete experimental reporting, hindering reproducibility and comparative analysis.In this perspective, a structured framework is presented to guide the comprehensive characterization when reporting of new PFAS sorbents. The proposed framework defines three essential domains for experimental evaluation: i) sorbent characterization, ii) water matrix specification and PFAS details, and iii) sorption and regeneration performance, including flow-through packed-bed evaluation (both bench- and pilot-scales). General guidelines are provided for each domain to promote consistency, transparency, and comparability across studies. This Perspective aims to facilitate rigorous cross-study comparison and accelerate the development of effective PFAS sorbents.

<strong class="journal-contentHeaderColor">Abstract.</strong> The increasing release of Antarctic meltwater represents one of the most profound, yet uncertain, consequences of global climate change. The absence of interactive ice sheets in state-of-the-art climate models prevents the direct calculation of ice-ocean feedbacks, leaving significant uncertainty in the global and regional consequences of meltwater discharge. This study leverages results from the Southern Ocean Freshwater Input from Antarctica (SOFIA) initiative to assess the ocean response to a 0.1 Sv meltwater perturbation and to infer the resulting feedback on ice shelf basal melting across 10 CMIP6 models. We analyze meltwater-induced temperature anomalies across distinct continental shelf regimes, compare them with SSP5-8.5 global warming-induced anomalies, and translate these into basal melt rates using a parameterization calibrated with a new observational climatology. Although the meltwater feedback is generally thought to amplify basal melting, our results demonstrate large regional differences, with implied enhanced ice shelf mass loss in some sectors but suppressed basal melting in others. The model ensemble indicates a warming feedback on the continental shelf in most East Antarctic regions, whereas in West Antarctica, the region with the greatest observed ice shelf mass loss in recent decades, most models simulate cooling or reduced warming, suggesting a negative feedback. This regional contrast implies that East Antarctica may play an increasingly dominant role in future ice shelf mass loss. Simulations support existing hypotheses linking these asymmetric temperature responses to strong regional connectivity and shelf break dynamics, including a strengthened Antarctic Slope Front, an accelerated Antarctic Slope Current, and reduced dense shelf water formation.

Parkinson's disease is one of the fastest-growing neurodegenerative disorders, with no effective treatments to modify its progression. Microglial-driven neuroinflammation, mediated by NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome activation, plays a key role in disease onset and progression. The NLRP3 inflammasome is upregulated in microglia from Parkinson's disease patients and activated by oxidative stress and α-synuclein aggregates, triggering the release of pro-inflammatory mediators that contribute to neuroinflammation and neuronal death. MCC950, the first described specific NLRP3 inhibitor, has shown promise in Parkinson's disease models but is limited by suboptimal pharmacokinetics and safety, hindering its clinical development. Here, we developed a novel NLRP3 inflammasome inhibitor, MCC7840 (also known as Inzomelid or Emlenoflast), and utilized clinically relevant PET-MRI imaging biomarkers to assess its therapeutic efficacy in preclinical models of Parkinson's disease. MCC7840 inhibited NLRP3 in human and mouse microglia with nanomolar potency, while demonstrating improved systemic exposure, half-life, brain permeability and bioavailability compared with MCC950. In a murine NLRP3 gain-of-function model of Muckle-Wells syndrome, MCC7840 effectively inhibited mortality and demonstrated superior potency compared with MCC950. Chronic oral administration of MCC7840 protected against neuroinflammation, motor deficits and dopamine loss in both 6-hydroxydopamine and preformed α-synuclein fibril mouse models of Parkinson's disease. Radiotracer imaging of multiple PET markers in the same mouse revealed that MCC7840 attenuated neuroinflammation (translocator protein ligand; 18F-DPA-714), preserved dopamine uptake (fluorodopa; 18F-FDOPA), mitigated dopamine transporter (DAT) loss (DAT ligand; 18F-FBCTT) and reduced blood-brain barrier leakage (gadolinium contrast MRI). Notably, MCC7840 was effective in a slowly progressing 12-month α-synuclein model, even when administered after symptom onset, 4 months post-α-synuclein injection. These findings highlight the utility of PET/MRI as a non-invasive tool to evaluate drug efficacy and support MCC7840, and other brain-penetrant NLRP3 inhibitors, as promising disease-modifying therapies for Parkinson's disease, warranting future clinical investigation.