Phytochemical Profiling Studies of Alkaloids and Coumarins from the Australian Plant Geijera parviflora Lindl. (Rutaceae) and Their Anthelmintic and Antimicrobial Assessment.

Phytochemical profiling followed by antimicrobial and anthelmintic activity evaluation of the Australian plant Geijera parviflora, known for its customary use in Indigenous Australian ceremonies and bush medicine, was performed. In the present study, seven previously reported compounds were isolated including auraptene, 6'-dehydromarmin, geiparvarin, marmin acetonide, flindersine, and two flindersine derivatives from the bark and leaves, together with a new compound, chlorogeiparvarin, formed as an artefact during the isolation procedure and isolated as a mixture with geiparvarin. Chemical profiling allowed for a qualitative and quantitative comparison of the compounds in the leaves, bark, flowers, and fruit of this plant. Subsequently, a subset of these compounds as well as crude extracts from the plant were evaluated for their antimicrobial and anthelmintic activities. Anthelmintic activity assays showed that two of the isolated compounds, auraptene and flindersine, as well as the dichloromethane and methanol crude extracts of G. parviflora, displayed significant activity against a parasitic nematode (Haemonchus contortus). This is the first report of the anthelmintic activity associated with these compounds and indicates the importance of such fundamental explorations for the discovery of bioactive phytochemicals for therapeutic application(s).

Development of endothelial-targeted CD39 as a therapy for ischemic stroke.

BACKGROUND: Ischemic stroke is characterized by a necrotic lesion in the brain surrounded by an area of dying cells termed the penumbra. Salvaging the penumbra either with thrombolysis or mechanical retrieval is the cornerstone of stroke management. At-risk neuronal cells release extracellular adenosine triphosphate, triggering microglial activation and causing a thromboinflammatory response, culminating in endothelial activation and vascular disruption. This is further aggravated by ischemia-reperfusion injury that follows all reperfusion therapies. The ecto-enzyme CD39 regulates extracellular adenosine triphosphate by hydrolyzing it to adenosine, which has antithrombotic and anti-inflammatory properties and reverses ischemia-reperfusion injury. OBJECTIVES: The objective off the study was to determine the efficacy of our therapeutic, anti-VCAM-CD39 in ischaemic stroke. METHODS: We developed anti-VCAM-CD39 that targets the antithrombotic and anti-inflammatory properties of recombinant CD39 to the activated endothelium of the penumbra by binding to vascular cell adhesion molecule (VCAM)-1. Mice were subjected to 30 minutes of middle cerebral artery occlusion and analyzed at 24 hours. Anti-VCAM-CD39 or control agents (saline, nontargeted CD39, or anti-VCAM-inactive CD39) were given at 3 hours after middle cerebral artery occlusion. RESULTS: Anti-VCAM-CD39 treatment reduced neurologic deficit; magnetic resonance imaging confirmed significantly smaller infarcts together with an increase in cerebrovascular perfusion. Anti-VCAM-CD39 also restored blood-brain barrier integrity and reduced microglial activation. Coadministration of anti-VCAM-CD39 with thrombolytics (tissue plasminogen activator [tPA]) further reduced infarct volumes and attenuated blood-brain barrier permeability with no associated increase in intracranial hemorrhage. CONCLUSION: Anti-VCAM-CD39, uniquely targeted to endothelial cells, could be a new stroke therapy even when administered 3 hours postischemia and may further synergize with thrombolytic therapy to improve stroke outcomes.

A Review of the Ethnobotanical Use, Chemistry and Pharmacological Activities of Constituents Derived from the Plant Genus Geijera (Rutaceae).

Geijera Schott is a plant genus of the Rutaceae Juss. (rue and citrus) family, comprising six species which are all native to Oceania. Of the plants belonging to this genus, the most significant species that has a customary use is Geijera parviflora, which was used by Indigenous Australians, primarily as a pain reliever. Herein, a comprehensive review of the literature published on the genus Geijera from 1930 to 2023 was conducted. This is the first review for this plant genus, and it highlights the chemical constituents reported to date, together with the range of pharmacological properties described from the various species and different parts of the plant. These properties include anti-inflammatory, anti-microbial, anti-parasitic, insect repellent, analgesic, neuroactive, and anti-cancer activities. Finally, a reflection on some of the important areas for future focused studies of this plant genus is provided.

Progress in magnetic particle imaging signal and iron quantification methods in vivo - application to long circulating SPIONs.

The strengths of Magnetic Particle Imaging (MPI) lay in its sensitivity, quantitative nature, and lack of signal attenuation for Superparamagnetic Iron Oxide Nanoparticles (SPION). These advantages make MPI a powerful tool for the non-invasive monitoring of tracer behaviour over time. With more MPI studies emerging, a standardized method for determining the boundaries of a region of interest (ROI) and iron quantification is crucial. The current approaches are inconsistent, making it challenging to compare studies, hindering MPI progression. Here we showcase three different ROI selection methods for the quantification of iron in vivo and ex vivo. Healthy mice were intravenously administered a long circulating tracer, never before applied in MPI, and the ROI methods were tested for their ability to accurately quantify the total signal present, in addition to the accumulation of the tracer in individual organs. We discuss how the quantified iron amount can be vastly altered based on the choice of ROI, the importance of the standard curve and the challenges associated with each method. Lastly, the user variability and accuracy of each method was compared by 3 independent users to ensure their consistency and lack of bias.

Serum neurofilament light as a biomarker of vulnerability to a second mild traumatic brain injury.

A second mild traumatic brain injury (mTBI) sustained prior to neuropathological recovery can lead to exacerbated effects. Without objective indicators of this neuropathology, individuals may return to activities at risk of mTBI when their brain is still vulnerable. With axonal injury recognized as a neuropathological hallmark of mTBI, we hypothesized that serum levels of neurofilament light (NfL), a highly sensitive biomarker of axonal injury, may be predictive of vulnerability to worse outcomes in the event of a second mTBI. Given this hypothesis is difficult to test clinically, we used a two-hit model of mTBI in rats and staggered inter-injury intervals by 1-, 3-, 7-, or 14-days. Repeat-mTBI rats were dichotomized into NfLhigh (NfL>median at the time of re-injury) and NfLlow (NfL

Targeted Isolation of Antibiotic Brominated Alkaloids from the Marine Sponge Pseudoceratina durissima Using Virtual Screening and Molecular Networking.

Many targeted natural product isolation approaches rely on the use of pre-existing bioactivity information to inform the strategy used for the isolation of new bioactive compounds. Bioactivity information can be available either in the form of prior assay data or via Structure Activity Relationship (SAR) information which can indicate a potential chemotype that exhibits a desired bioactivity. The work described herein utilizes a unique method of targeted isolation using structure-based virtual screening to identify potential antibacterial compounds active against MRSA within the marine sponge order Verongiida. This is coupled with molecular networking-guided, targeted isolation to provide a novel drug discovery procedure. A total of 12 previously reported bromotyrosine-derived alkaloids were isolated from the marine sponge species Pseudoceratina durissima, and the compound, (+)-aeroplysinin-1 (1) displayed activity against the MRSA pathogen (MIC: <32 µg/mL). The compounds (1−3, 6 and 9) were assessed for their central nervous system (CNS) interaction and behavioral toxicity to zebrafish (Danio rerio) larvae, whereby several of the compounds were shown to induce significant hyperactivity. Anthelmintic activity against the parasitic nematode Haemonchus contorutus was also evaluated (2−4, 6−8).

Phytochemical Profiling and Biological Testing of the Constituents of the Australian Plant Haemodorum brevisepalum.

Phytochemical profiling was undertaken on the crude extracts of the bulbs, stems, and the fruits of Haemodorum brevisepalum, to determine the nature of the chemical constituents present. This represents the first study to investigate the fruits of a species of Haemodorum. In total, 13 new and 17 previously reported compounds were isolated and identified. The new compounds were of the phenylphenalenone-type class, with a representative of a novel structural form, named tentatively "oxabenzochromenone" (1), a compound akin to an intermediate in a recently proposed phenylphenalenone metabolic network (2), seven new phenylphenalenones (4-10), four new phenylbenzoisochromenones (11-14), and a new phenylbenzoisochromenone derivative (18). The previously reported compounds identified were of the following structure classes: oxabenzochrysenone (3, 23-26), flavonol (15, 16), phenylbenzoisochromenone (17, 21, 22, 27-30), and phenylphenalenone (19, 20). Compounds 2-4, 6-9, 15-18, 21, 22, and 26 were subjected to antimicrobial evaluation with moderate activity observed against Staphylococcus aureus MRSA and slight activity against Pseudomonas aeruginosa and Candida albicans. Compounds 4, 6-9, 17, and 21 were also evaluated for anthelminthic activity against larvae of the blood-feeding parasitic nematode Haemonchus contortus.

Application of Networking Approaches to Assess the Chemical Diversity, Biogeography, and Pharmaceutical Potential of Verongiida Natural Products.

This study provides a review of all isolated natural products (NPs) reported for sponges within the order Verongiida (1960 to May 2020) and includes a comprehensive compilation of their geographic and physico-chemical parameters. Physico-chemical parameters were used in this study to infer pharmacokinetic properties as well as the potential pharmaceutical potential of NPs from this order of marine sponge. In addition, a network analysis for the NPs produced by the Verongiida sponges was applied to systematically explore the chemical space relationships between taxonomy, secondary metabolite and drug score variables, allowing for the identification of differences and correlations within a dataset. The use of scaffold networks as well as bipartite relationship networks provided a platform to explore chemical diversity as well as the use of chemical similarity networks to link pharmacokinetic properties with structural similarity. This study paves the way for future applications of network analysis procedures in the field of natural products for any order or family.

Structural and Morphological Analysis of Cellulose Pulp Produced from the Fractionation of Eucalyptus obliqua Sawdust Using γ-Valerolactone.

Organic solvents offer promising methods for the fractionation of Eucalyptus obliqua lignocellulosic biomass. This study investigated the impact of γ-valerolactone (GVL) fractionation on the morphology of cellulose and its internal structure using scanning electron microscopy (SEM), nuclear magnetic resonance (NMR) and Fourier-transform infrared (FT-IR) spectroscopy. The solubilized lignin precipitated on the macrofibril surface as lignin spheres. GVL fractionation significantly increased the crystallinity of the recovered pulps from 0.29 for the sawdust to an average of 0.53 and a maximum of 0.66. The main states of cellulose that were susceptible to hydrolysis during the fractionation were amorphous and surface cellulose, both of which were reduced significantly, while paracrystalline and pure crystalline fractions in the pulp increased. It was concluded that GVL fractionation can produce a crystalline cellulose pulp of high quality suitable for further processing.

Phytochemical Profiling and Biological Activity of the Australian Carnivorous Plant, Drosera magna.

Phytochemical profiling was undertaken on the crude extracts of Drosera magna to determine the nature of the chemical constituents present. In total, three new flavonol diglycosides (1-3), one new flavan-3-ol glycoside (4), and 12 previously reported compounds of the flavonol (5, 9), flavan-3-ol (15), flavanone (8), 1,4-napthoquinone (6, 7, 13, 14), 2,3-dehydroxynapthalene-1,4-dione (10-12), and phenolic acid (16) structure classes were isolated and identified. Compounds 1-9, 13, 17, and 18 were assessed for antimicrobial activity, with compounds 6, 7, 8, and 9 showing significant activity. Compounds 1, 2, and 6 were also evaluated for anthelmintic activity against larval forms of Hemonchus contortus, with compound 6 being active.

Assessment of interfacial interactions between starch and non-isocyanate polyurethanes in their hybrids.

Manufacturing of multifunctional materials through blending is a promising route for improving performance of biopolymers including starch. Non-isocyanate polyurethanes (NIPUs) are an emerging group of green materials. Understanding the mechanism of interaction between starch and NIPU not only highlights underlying chemistry but also offers an opportunity to tailor the properties and functions of starch-NIPU hybrids. We investigated the interfacial interactions between starch and NIPU to pave the way towards development of high-performance green materials. Multiple analyses revealed that NIPU interacted effectively with starch chains via intermolecular hydrogen bonds. We showed that NIPU domains can efficiently interact with the small portion of starch skeleton at interfacial region and they are only moderately miscible. Incorporation of either component above certain ratio resulted in a phase separation. This work contributes towards understanding of interfacial chemistry between starch and NIPUs and enables tailoring the interface for facile engineering of starch-NIPU hybrids.

Natural Compounds from the Marine Brown Alga Caulocystis cephalornithos with Potent In Vitro-Activity against the Parasitic Nematode Haemonchus contortus.

Eight secondary metabolites (1 to 8) were isolated from a marine sponge, a marine alga and three terrestrial plants collected in Australia and subsequently chemically characterised. Here, these natural product-derived compounds were screened for in vitro-anthelmintic activity against the larvae and adult stages of Haemonchus contortus (barber's pole worm)-a highly pathogenic parasitic nematode of ruminants. Using an optimised, whole-organism screening system, compounds were tested on exsheathed third-stage larvae (xL3s) and fourth-stage larvae (L4s). Anthelmintic activity was initially evaluated on these stages based on the inhibition of motility, development and/or changes in morphology (phenotype). We identified two compounds, 6-undecylsalicylic acid (3) and 6-tridecylsalicylic acid (4) isolated from the marine brown alga, Caulocystis cephalornithos, with inhibitory effects on xL3 and L4 motility and larval development, and the induction of a "skinny-straight" phenotype. Subsequent testing showed that these two compounds had an acute nematocidal effect (within 1-12 h) on adult males and females of H. contortus. Ultrastructural analysis of adult worms treated with compound 4 revealed significant damage to subcuticular musculature and associated tissues and cellular organelles including mitochondria. In conclusion, the present study has discovered two algal compounds possessing acute anthelmintic effects and with potential for hit-to-lead progression. Future work should focus on undertaking a structure-activity relationship study and on elucidating the mode(s) of action of optimised compounds.

Inter-relationship between lactose crystallization and surface free fat during storage of infant formula.

Inter-relationship between lactose crystallization (LC), the amount and composition of surface free fat (SFF); and their effect on physico-chemical properties of infant formula (IF) containing hydrolyzed and intact (non-hydrolyzed) whey protein in their composition were investigated at two temperatures (25 and 45 °C) and five RH (11-65%) conditions. Results varied with compositional variation of IF. LC increased exponentially with SFF in non-hydrolyzed IF powders. IF composition influenced LC and caused selective migration of triglycerides, resulting in higher proportion of unsaturated fats in SFF of powders with large lactose crystals and vice-versa. Increase in SFF with increased proportion of saturated fats in their composition, resulted in reduced wettability of powders. Overall, IF composition affects LC which influences the amount and type of fat migration to particle surface resulting in varying wettability of IF powders.

Natural Products of Marine Macroalgae from South Eastern Australia, with Emphasis on the Port Phillip Bay and Heads Regions of Victoria.

Marine macroalgae occurring in the south eastern region of Victoria, Australia, consistingof Port Phillip Bay and the heads entering the bay, is the focus of this review. This area is home toapproximately 200 different species of macroalgae, representing the three major phyla of the greenalgae (Chlorophyta), brown algae (Ochrophyta) and the red algae (Rhodophyta), respectively. Overalmost 50 years, the species of macroalgae associated and occurring within this area have resultedin the identification of a number of different types of secondary metabolites including terpenoids,sterols/steroids, phenolic acids, phenols, lipids/polyenes, pheromones, xanthophylls andphloroglucinols. Many of these compounds have subsequently displayed a variety of bioactivities.A systematic description of the compound classes and their associated bioactivities from marinemacroalgae found within this region is presented.

Exploring resveratrol dimers as virulence blocking agents - Attenuation of type III secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa.

Bacterial infections continue to threaten humankind and the rapid spread of antibiotic resistant bacteria is alarming. Current antibiotics target essential bacterial processes and thereby apply a strong selective pressure on pathogenic and non-pathogenic bacteria alike. One alternative strategy is to block bacterial virulence systems that are essential for the ability to cause disease but not for general bacterial viability. We have previously show that the plant natural product (-)-hopeaphenol blocks the type III secretion system (T3SS) in the Gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. (-)-Hopeaphenol is a resveratrol tetramer and in the present study we explore various resveratrol dimers, including partial structures of (-)-hopeaphenol, as T3SS inhibitors. To allow rapid and efficient assessment of T3SS inhibition in P. aeruginosa, we developed a new screening method by using a green fluorescent protein reporter under the control of the ExoS promoter. Using a panel of assays we showed that compounds with a benzofuran core structure i.e. viniferifuran, dehydroampelopsin B, anigopreissin A, dehydro-δ-viniferin and resveratrol-piceatannol hybrid displayed significant to moderate activities towards the T3SS in Y. pseudotuberculosis and P. aeruginosa.

Bromophenolics from the Red Alga Polysiphonia decipiens.

The isolation and the structure determination of a new bromophenolic compound, polysiphonol (10), as well as five previously reported compounds, (4-8), from the red alga Polysiphonia decipiens is reported. In addition, the absolute configuration of the natural product rhodomelol (8) could be unequivocally confirmed for the first time, and on biosynthetic grounds, the absolute configuration of polysiphonol (10) was tentatively suggested. Compounds 4-8 were evaluated for their antibacterial activity against both Gram-positive and Gram-negative bacteria, but none of the compounds showed any appreciable activity.

Physicochemical properties and surface composition of infant formula powders.

Compositional difference in infant formula (IF) tends to influence its functionality and storage behaviour. The aim was to study the composition and physico-chemical properties of different stages of two commercial IF (A and B). Lactose crystallization measured by X-ray diffraction ranged between 2 and 32 % and was observed to decrease with increasing IF stages, which directly correlates with their composition. Scanning electron microscopy confirmed the presence of crystalline lactose which significantly (p < 0.05) increased the powder particle size. On the contrary, a negative correlation was observed between surface fat and lactose crystallization in all samples. Bulk and surface-free fat composition was significantly (p < 0.05) different for all samples. Surface free-fat analysis showed restricted presence (5-10% of surface fat) of unsaturated fatty acids (C18:1 and C18:2) in IF with higher crystalline lactose as opposed to >40% in others, suggesting a possible role of lactose crystallization in preferential migration of triglycerides to particle surface.

Optimisation of grafted phosphorylcholine-based polymer on additively manufactured titanium substrate for hip arthroplasty.

Despite the tremendous acceptance of additively manufactured (AM) Titanium alloys (Ti6Al4V) in the field of biomedical engineering, the high surface roughness due to partially-melted particles (fabricated in selective laser melting (SLM) process), limits their uses as hip implants. The objective of this study, therefore, is to modify the SLM fabricated Ti6Al4V implant interfaces with 2-Methacryloyloxyethyl phosphorylcholine (MPC) polymer, in the hope of enhancing surface properties and preventing the attachment of the cell simultaneously without affecting the mechanical properties significantly. Three different monomer concentrations were examined to determine the influence of monomer concentrations on polymerisation rate, chain length, and surface properties of the implants. Samples grafted with 0.6 M monomer concentration showed more uniform surface and less surface roughness in comparison with other samples and untreated Ti6Al4V surfaces. 0.6 M monomer concentration was found to be the best option for grafting PMPC to the hip implant interfaces because of its improved surface morphology, surface roughness, polymerisation rate, penetration depth and hardness results. Moreover, cell study on optimal surfaces revealed that PMPC grafted surfaces prevent the implant interfaces from uncontrollable cell attachment which is of utmost importance in smoothing the motion of the hip implant under cyclic loading. Overall, the PMPC grafting demonstrated the potentiality of its application on SLM Ti6Al4V substrate for improved hip arthroplasty performance.

Publisher Correction: Room temperature CO2 reduction to solid carbon species on liquid metals featuring atomically thin ceria interfaces.

The original version of this Article contained errors in the author affiliations. Affiliation 1 incorrectly read 'School of Chemical Engineering, University of New South Wales (UNSW), Sydney, NSW 2031, Australia' and affiliation 4 incorrectly read 'School of Engineering, RMIT University, Melbourne, VIC 3001, Australia.' This has now been corrected in both the PDF and HTML versions of the Article.