RNASE4 promotes malignant progression and chemoresistance in hypoxic glioblastoma via activation of AXL/AKT and NF-κB/cIAPs signaling pathways.

Glioblastoma (GBM) is the most malignant brain tumor frequently characterized by a hypoxic microenvironment. In this investigation, we unveiled unprecedented role of Ribonuclease 4 (RNASE4) in GBM pathogenesis through integrative methodologies. Leveraging The Cancer Genome Atlas (TCGA) dataset and clinical specimens from normal brain tissues, low- and high-grade gliomas, alongside rigorous and functional analyses, we identified a consistent upregulation of RNASE4 correlating with advanced GBM pathological stages and poor clinical survival outcomes.

Platinum-based metal complexes as chloride transporters that trigger apoptosis.

In this paper we demonstrate that Pt(ii) complexes can function as efficient transmembrane chloride transporters. A series of Pt(ii) metal complexes with urea-appended isoquinoline ligands were synthesised and operate classical hydrogen bonding interactions rather than ligand exchange. A number of the complexes exhibited potent transmembrane chloride activity in vesicle studies, while also showing strong antiproliferative activity in cisplatin-resistant cell lines induction of apoptosis and inhibition of intracellular ROS.

Discovery and heterologous biosynthesis of glycosylated polyketide luteodienoside A reveals unprecedented glucinol-mediated product offloading by a fungal carnitine -acyltransferase domain.

Luteodienoside A is a novel glycosylated polyketide produced by the Australian fungus MST-FP2246, consisting of an unusual 1--β-d-glucopyranosyl--inositol (glucinol) ester of 3-hydroxy-2,2,4-trimethylocta-4,6-dienoic acid. Mining the genome of identified a putative gene cluster for luteodienoside A biosynthesis (), harbouring a highly reducing polyketide synthase (HR-PKS, LtbA) fused at its C-terminus to a carnitine -acyltransferase (cAT) domain. Heterologous pathway reconstitution in , substrate feeding assays and gene truncation confirmed the identity of the cluster and demonstrated that the cAT domain is essential for offloading luteodienoside A from the upstream HR-PKS.

Ensuring the quality of clinical supervision: Stakeholder perceptions of pharmacy preceptor competence.

Introduction: Experiential education helps to integrate knowledge into practice, develops professionalism and understanding of a pharmacist's role in practice, and is a major component of pharmacy education. The role of the preceptor in experiential education is to model professional behaviours and provide feedback on student preceptee performance and competence. Little is known about how preceptors feel about their competency being assessed or the most appropriate way to assess competency.

Spatial Layouts of Low-Entropy Hydration Shells Guide Protein Binding.

Protein-protein binding enables orderly biological self-organization and is therefore considered a miracle of nature. Protein‒protein binding is driven by electrostatic forces, hydrogen bonding, van der Waals force, and hydrophobic interactions. Among these physical forces, only hydrophobic interactions can be considered long-range intermolecular attractions between proteins due to the electrostatic shielding of surrounding water molecules.

Application of multi-region input-output analysis to examine biosecurity risks associated with the global shipping network.

The vast majority of globally traded cargo is transported via maritime shipping. Whilst in port for loading and unloading, these ships can pick up local marine organisms with internal ballast water or as external biofouling assemblages and subsequently move these to destination far beyond their natural ranges. Over the past decades, this mechanism has led to the establishment of hundreds of non-indigenous species (NIS) around global coastlines.

Synthesis and antitumour evaluation of indole-2-carboxamides against paediatric brain cancer cells.

Paediatric glioblastomas are rapidly growing, devastating brain neoplasms with an invasive phenotype. Radiotherapy and chemotherapy, which are the current therapeutic adjuvant to surgical resection, are still associated with various toxicity profiles and only marginally improve the course of the disease and life expectancy. A considerable body of evidence supports the antitumour and apoptotic effects of certain cannabinoids, such as WIN55,212-2, against a wide spectrum of cancer cells, including gliomas.

Late-stage modification of peptides and proteins at cysteine with diaryliodonium salts.

The modification of peptides and proteins has emerged as a powerful means to efficiently prepare high value bioconjugates for a range of applications in chemical biology and for the development of next-generation therapeutics. Herein, we report a novel method for the chemoselective late-stage modification of peptides and proteins at cysteine in aqueous buffer with suitably functionalised diaryliodonium salts, furnishing stable thioether-linked synthetic conjugates. The power of this new platform is showcased through the late-stage modification of the affibody zEGFR and the histone protein H2A.

Versatile naphthalimide tetrazines for fluorogenic bioorthogonal labelling.

Fluorescent probes for biological imaging have revealed much about the functions of biomolecules in health and disease. Fluorogenic probes, which are fluorescent only upon a bioorthogonal reaction with a specific partner, are particularly advantageous as they ensure that fluorescent signals observed in biological imaging arise solely from the intended target. In this work, we report the first series of naphthalimide tetrazines for bioorthogonal fluorogenic labelling.

Cyclisation strategies for stabilising peptides with irregular conformations.

Cyclisation is a common synthetic strategy for enhancing the therapeutic potential of peptide-based molecules. While there are extensive studies on peptide cyclisation for reinforcing regular secondary structures such as α-helices and β-sheets, there are remarkably few reports of cyclising peptides which adopt irregular conformations in their bioactive target-bound state. In this review, we highlight examples where cyclisation techniques have been successful in stabilising irregular conformations, then discuss how the design of cyclic constraints for irregularly structured peptides can be informed by existing β-strand stabilisation approaches, new computational design techniques, and structural principles extracted from cyclic peptide library screening hits.

Cascade reaction engineering on zirconia-supported mesoporous MFI zeolites with tunable Lewis-Brønsted acid sites: a case of the one-pot conversion of furfural to γ-valerolactone.

Catalytic cascade reactions are strongly desired as a potential means of combining multistep reactions into a single catalytic reactor. Appropriate catalysts composed of multi-reactive sites to catalyze cascade reactions in a sequential fashion are central to such efforts. Here, we demonstrate a bifunctional zeolite catalyst with close proximity of Brønsted and Lewis acid sites through the synthesis of a mesoporous ZrO[Al]MFI nanosponge (NS).

The protein corona determines the cytotoxicity of nanodiamonds: implications of corona formation and its remodelling on nanodiamond applications in biomedical imaging and drug delivery.

The use of nanodiamonds for biomedical and consumer applications is growing rapidly. As their use becomes more widespread, so too do concerns around their cytotoxicity. The cytotoxicity of nanodiamonds correlates with their cellular internalisation and circulation time in the body.

Spontaneous S-Si bonding of alkanethiols to Si(111)-H: towards Si-molecule-Si circuits.

We report the synthesis of covalently linked self-assembled monolayers (SAMs) on silicon surfaces, using mild conditions, in a way that is compatible with silicon-electronics fabrication technologies. In molecular electronics, SAMs of functional molecules tethered to gold sulfur linkages dominate, but these devices are not robust in design and not amenable to scalable manufacture. Whereas covalent bonding to silicon has long been recognized as an attractive alternative, only formation processes involving high temperature and/or pressure, strong chemicals, or irradiation are known.

Regioselective convergent synthesis of 2-arylidene thiazolo[3,2-]pyrimidines as potential anti-chikungunya agents.

Convergent and convenient regioselective synthesis of novel thiazolo[2,3-]pyrimidine derivatives was accomplished using the one-pot reaction of 6-ethylthiouracil, bromoacetic acid, anhydrous sodium acetate, acetic anhydride, acetic acid and suitable aldehyde. X-ray crystallographic study reveals the presence of the configuration of only one regioisomer confirmed by computational studies as being the most likely isomer present.

A physician-initiated double-blind, randomised, placebo-controlled, phase 2 study evaluating the efficacy and safety of inhibition of NADPH oxidase with the first-in-class Nox-1/4 inhibitor, GKT137831, in adults with type 1 diabetes and persistently elevated urinary albumin excretion: Protocol and statistical considerations.

Purpose: Kidney disease caused by type 1 diabetes can progress to end stage renal disease and can increase mortality risk. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) plays a major role in producing oxidative stress in the kidney in diabetes, and its activity is attenuated by GKT137831, an oral Nox inhibitor with predominant inhibitory action on Nox-1 and Nox - 4. Previous studies have demonstrated renoprotective effects with GKT137831 in various experimental models of type 1 diabetes-related kidney disease.

Unravelling the effects of size, volume fraction and shape of nanoparticle additives on crystallization of nanocomposite polymers.

We conducted large scale molecular dynamics simulations to understand the effects of size, shape and volume fraction of additive nanoparticles on the crystallization of nanocomposite polymers. We used spherical and cubic gold nanoparticles of various sizes ranging from 2 to 8 nm to create hexacontane (CH)-gold nanocomposites at various volume fractions of 0.84-19.

Complementary medicine products information-seeking by pregnant and breastfeeding women in Australia.

Objective: Complementary medicine product use in pregnancy and lactation is common but little is known about women's health literacy and information-seeking regarding this. The objectives of this study were to identify and explore pregnant or breastfeeding women's sources of, and rationale for seeking complementary medicine products information, the types of information sought, and how women felt their health care practitioners can help them receive information that meets their needs.

Design: A qualitative research design consisting of in-depth interviews and focus group discussions was conducted.

Neuronal regulates motor circuit integrity and controls motor function and lifespan.

Neuronal aging involves a progressive decline in cognitive abilities and loss of motor function. Mutations in human genes () lead to a wide-range of diseases including muscular dystrophy, peripheral neuropathy and progeria. Here we investigate the role of neuronal in regulating age-related phenotypes.

Cellulose Fibers Enable Near-Zero-Cost Electrical Sensing of Water-Soluble Gases.

We report an entirely new class of printed electrical gas sensors that are produced at near "zero cost". This technology exploits the intrinsic hygroscopic properties of cellulose fibers within paper; although it feels and looks dry, paper contains substantial amount of moisture, adsorbed from the environment, enabling the use of wet chemical methods for sensing without manually adding water to the substrate. The sensors exhibit high sensitivity to water-soluble gases (e.

Measurement of redox states of the β3 integrin disulfide bonds by Mass Spectrometry.

Functional disulfide bonds mediate a change in protein function in which they reside when cleaved or formed. To elucidate how a functional disulfide bond controls protein activity, it is critical that the redox state of the bond in the population of protein molecules is known. Measurement of changes in disulfide bond redox state relies on thiol probes and immunoblotting.

Myeloperoxidase in the inflamed colon: A novel target for treating inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a debilitating disorder involving inflammation of the gastrointestinal tract. The incidence of IBD is increasing worldwide. Immunological responses in the gastrointestinal (GI) tract to altered gut microbiota, mucosal injury and loss of intestinal epithelial cell function all contribute to a complex mechanism underlying IBD pathogenesis.

Intake of free sugars and micronutrient dilution in Australian adults.

Background: The negative health effect of excessive intake of free sugars has been gaining increasing public awareness.

Objective: This secondary analysis aimed to evaluate the impact of free-sugar intake on micronutrient dilution, and estimate a threshold level of free-sugar intake at which a decrease in micronutrient intake becomes evident, based on data from the Australian Health Survey 2011-2012.

Design: Dietary data from adult respondents (weighted n = 6150) who had completed two 24-h recalls were analyzed.

Development of an All Solid State Battery Incorporating Graphene Oxide as Proton Conductor.

Graphene oxide (GO) shows high proton conductivity (≈10 Scm), excellent mechanical stability, and electrical insulation property, which makes it an ideal candidate for use as a proton conducting solid state electrolyte. The prospects of using GO as single phase solid electrolyte in an all solid battery is presented herein. A battery with the cell configuration: Zn + ZnSO•7HO + graphite (anode) || GO (electrolyte) || MnO + graphite (cathode) is fabricated.