Asymmetric nanocapsules via elongated liposome templated polymerization (ELTP) mediated by RAFT polymerization.

Polymeric nanocapsules comprised of hydrophobic shells and hollow aqueous interiors are an extremely useful class of nanomaterial, particularly in the encapsulation and controlled delivery of hydrophilic cargo. Generally prepared via droplet or latex templation approaches, polymeric nanocapsules are mostly spherical. Controlling the morphology of hollow nanocapsules is an intriguing design challenge.

Significant risk of venous thromboembolism associated with targeted anti-myeloma immunomodulatory drugs. Comment on: Targeted anti-cancer agents and risk of venous thromboembolism.

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Fab-Induced Stabilization of an Ion Channel Receptor Enables Mechanistic Characterization of Small-Molecule Therapeutics.

Developing small-molecule (SM) therapeutics that target membrane proteins (MPs) is often challenging, because few biophysical methods can handle the detergents required to maintain target stability. Here, we report a surface plasmon resonance (SPR)-based methodology that enables the characterization of interactions between SMs and an ion channel receptor (MP1) in complex with a stabilizing antibody fragment (Fab) and surfactant. Briefly, a stable MP1-Fab complex was formed by coimmobilizing MP1 with an anti-MP1-Fab within the hydrogel film to study the interactions of MP1 with SMs.

Cholesterol-terminated cationic lipidated oligomers (CLOs) as a new class of antifungals.

Infections caused by fungal pathogens are a global health problem, and have created an urgent need for new antimicrobial strategies. This report details the synthesis of lipidated 2-vinyl-4,4-dimethyl-5-oxazolone (VDM) oligomers an optimized Cu(0)-mediated reversible-deactivation radical polymerization (RDRP) approach. Cholesterol-Br was used as an initiator to synthesize a library of oligo-VDM (degree of polymerisation = 5, 10, 15, 20, and 25), with an α-terminal cholesterol group.

Combining Fundamental Kinetics and Standard Alkylation Assays to Prioritize Lead-Like KRAS G12C Inhibitors.

We measure the fundamental rate constants of internally discovered KRAS G12C inhibitors to demonstrate how kinetic analyses can be integrated with standard biochemical and cell-based assays for more optimal biophysical compound prioritization. In this proof-of-principle study, we characterize three irreversible covalent inhibitors targeting the mutant cysteine at the switch II binding pocket. We estimate the three fundamental kinetic rate constants ( , , ) that define the contributions of affinity and inactivation to the overall alkylation rate for a more complete biophysical characterization.

Neonatal Outcomes following 2 Cases of Maternal CAR-T Therapy for High-Grade B-Cell Lymphoma.

Introduction: Chimeric antigen receptor T cells (CAR-Ts) targeting CD19 represent a significant advance in treatment for patients with relapsed/refractory B-cell malignancies. Although a significant minority of recipients are women during their reproductive years, there is a paucity of data regarding pregnancy and neonatal outcomes in women previously treated with CAR-T. This is important as maternal T cells are known to cross the placenta and into breastmilk during pregnancy and breastfeeding, respectively.

Evaluation of the Interdisciplinary Care Home-bAsed Reablement Program (I-CHARP) for People Living With Cognitive Impairment and Dementia in Care Homes.

Background: Major knowledge and practice gaps exist in aged care home services to support independence of older people with dementia. This research evaluates an adaptation of a community-based rehabilitation model for care homes, namely Interdisciplinary Care Home-bAsed Reablement Program (I-CHARP), by examining whether (and, if so, how) I-CHARP produces its intended effects and how this programme can be practicably implemented, sustained and scaled up across care homes in Australia.

Methods: I-CHARP is a 4-month bio-behavioural-environmental rehabilitation model of care, integrated in care home services, supported through the deployment of an implementation strategy, the Research Enabled Aged Care Homes (REACH) network.

Manipulating a host-native microbial strain compensates for low microbial diversity by increasing weight gain in a wild bird population.

Empirical studies from laboratory systems and humans show that the gut microbiota is linked to host health. Similar evidence for effects on traits linked to fitness in nature is rare, not least because experimentally manipulating the gut microbiota is challenging. We isolated, characterized, and cultured a bacterial strain, APC4233, directly from a wild bird (the great tit ) and provided it as a self-administered dietary supplement.

Gender-different effect of Src family kinases antagonism on photophobia and trigeminal ganglion activity.

Background: Src family kinases (SFKs) contribute to migraine pathogenesis, yet its role in regulating photophobia behaviour, one of the most common forms of migraine, remains unknown. Here, we addressed whether SFKs antagonism alleviates photophobia behavior and explored the underlying mechanism involving hypothalamus and trigeminal ganglion activity, as measured by the alteration of neuropeptide levels and transcriptome respectively.

Methods: A rapid-onset and injury-free mouse model of photophobia was developed following intranasal injection of the TRPA1 activator, umbellulone.

NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations.

Background: Commercial genome-wide genotyping arrays have historically neglected coverage of genetic variation across populations.

Objective: We aimed to create a multi-ancestry genome-wide array that would include a wide range of neuro-specific genetic content to facilitate genetic research in neurological disorders across multiple ancestral groups, fostering diversity and inclusivity in research studies.

Methods: We developed the Illumina NeuroBooster Array (NBA), a custom high-throughput and cost-effective platform on a backbone of 1,914,934 variants from the Infinium Global Diversity Array and added custom content comprising 95,273 variants associated with more than 70 neurological conditions or traits, and we further tested its performance on more than 2000 patient samples.

A comparative study on surface-engineered nanoceria using a catechol copolymer design: colloidal stability antioxidant activity.

Nanoceria (NC) are widely studied as potent nanozyme antioxidants, featuring unique multifunctional, self-regenerative, and high-throughput enzymatic functions. However, bare NC are reported to show poor colloidal stability in biological media. Despite this, the nexus between colloidal stability and antioxidant activity has rarely been assessed.

Enhancing Prehospital Care During the Conflict in Ukraine: NATO's Role in Global Health Engagement.

Introduction: The conflict in Ukraine, ongoing since 2014 and escalating with the Russian invasion in 2022, has unveiled profound challenges in prehospital care essential for the survival and recovery of warfighters and civilians alike, necessitating a detailed examination of the current medical response mechanisms and their effectiveness.

Materials And Methods: This study provides an overview of these challenges and examines how these critical vulnerabilities have impacted the delivery of medical care in war-torn regions. It also explores the role of NATO and its member states in addressing these challenges, focusing on the efforts to standardize prehospital care, enhance training, and foster interoperability among medical services.

Blood Cancer Network Ireland (BCNI) and National Cancer Registry Ireland (NCRI) collaboration: challenges and utility of an Enhanced Blood Cancer Outcomes Registry (EBCOR) pilot.

Background: The Blood Cancer Network Ireland and National Cancer Registry Ireland worked to create an Enhanced Blood Cancer Outcomes Registry (EBCOR). Enhanced data in acute myeloid leukaemia (AML) included an extensive data dictionary, bespoke software and longitudinal follow-up.

Aims: To demonstrate the utility of the database, we applied the data to examine a clinically relevant question: Charlson comorbidity index (CCI) usefulness in predicting AML patients' survival.

Validation and Comparison of Common Thoracolumbar Injury Classification Treatment Algorithms and a Novel Modification.

Background And Objectives: The most common thoracolumbar trauma classification systems are the Thoracolumbar Injury Classification and Severity Score (TLICS) and the Thoracolumbar AO Spine Injury Score (TL AOSIS). Predictive accuracy of treatment recommendations is a historical limitation. Our objective was to validate and compare TLICS, TL AOSIS, and a modified TLICS (mTLICS) that awards 2 points for the presence of fractured vertebral body height loss >50% and/or spinal canal stenosis >50% at the fracture site.

Visual search strategies and game knowledge in junior Australian rules football players: testing potential in talent identification and development.

This study explored video-based decision-making and eye-movement behavior as a complementary method to assess the decision-making skills and knowledge of elite junior Australian Rules (AR) Football players. Performance was measured twice over an 18-month period. This approach tested a practical and reliable assessment of decision-making and game knowledge that does not contribute to physical training load.

Potent activity of polymyxin B is associated with long-lived super-stoichiometric accumulation mediated by weak-affinity binding to lipid A.

Polymyxins are gram-negative antibiotics that target lipid A, the conserved membrane anchor of lipopolysaccharide in the outer membrane. Despite their clinical importance, the molecular mechanisms underpinning polymyxin activity remain unresolved. Here, we use surface plasmon resonance to kinetically interrogate interactions between polymyxins and lipid A and derive a phenomenological model.

Potency-Enhanced Peptidomimetic VHL Ligands with Improved Oral Bioavailability.

The von Hippel-Lindau (VHL) protein plays a pivotal role in regulating the hypoxic stress response and has been extensively studied and utilized in the targeted protein degradation field, particularly in the context of bivalent degraders. In this study, we present a comprehensive peptidomimetic structure-activity relationship (SAR) approach, combined with cellular NanoBRET target engagement assays to enhance the existing VHL ligands. Through systematic modifications of the molecule, we identified the 1,2,3-triazole group as an optimal substitute of the left-hand side amide bond that yields 10-fold higher binding activity.

Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson's disease progression.

SINE-VNTR-Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a human-specific SVA, termed SVA_67, correlated with the progression of Parkinson's disease (PD). In the present study, we demonstrate that SVA_67 acts as expression quantitative trait loci, thereby exhibiting a strong regulatory effect across the genome using whole genome and transcriptomic data from the Parkinson's progression markers initiative cohort.

Lipid sulfoxide polymers as potential inhalable drug delivery platforms with differential albumin binding affinity.

Inhalable nanomedicines are increasingly being developed to optimise the pharmaceutical treatment of respiratory diseases. Large lipid-based nanosystems at the forefront of the inhalable nanomedicines development pipeline, though, have a number of limitations. The objective of this study was, therefore, to investigate the utility of novel small lipidated sulfoxide polymers based on poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA) as inhalable drug delivery platforms with tuneable membrane permeability imparted by differential albumin binding kinetics.

Controlling nanoparticle-induced endothelial leakiness with the protein corona.

Understanding nanoparticle-cell interaction is essential for advancing research in nanomedicine and nanotoxicology. Apart from the transcytotic pathway mediated by cellular recognition and energetics, nanoparticles (including nanomedicines) may harness the paracellular route for their transport by inducing endothelial leakiness at cadherin junctions. This phenomenon, termed as NanoEL, is correlated with the physicochemical properties of the nanoparticles in close association with cellular signalling, membrane mechanics, as well as cytoskeletal remodelling.

Providing insight into the mechanism of action of cationic lipidated oligomers using metabolomics.

The increasing resistance of clinically relevant microbes against current commercially available antimicrobials underpins the urgent need for alternative and novel treatment strategies. Cationic lipidated oligomers (CLOs) are innovative alternatives to antimicrobial peptides and have reported antimicrobial potential. An understanding of their antimicrobial mechanism of action is required to rationally design future treatment strategies for CLOs, either in monotherapy or synergistic combinations.

Forest, climate, and policy literature lacks acknowledgement of environmental justice, diversity, equity, and inclusion.

Forests boast essential resources and potential to mitigate climate change, meriting the development of conservation policies on all governmental scales. Ecosystem services provided by forests, including biodiversity, air quality, and food and fuel production, make forests valuable assets for climate-vulnerable communities that often lack the means to cope with ecosystem service degradation resulting from climate change. Historically, these vulnerable communities are previously marginalized and socio-economically limited, and climate change augments already-existing injustices.