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.

Delocalisation enables efficient charge generation in organic photovoltaics, even with little to no energetic offset.

Organic photovoltaics (OPVs) are promising candidates for solar-energy conversion, with device efficiencies continuing to increase. However, the precise mechanism of how charges separate in OPVs is not well understood because low dielectric constants produce a strong attraction between the charges, which they must overcome to separate. Separation has been thought to require energetic offsets at donor-acceptor interfaces, but recent materials have enabled efficient charge generation with small offsets, or with none at all in neat materials.

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.

Predicting molecular vibronic spectra using time-domain analog quantum simulation.

Spectroscopy is one of the most accurate probes of the molecular world. However, predicting molecular spectra accurately is computationally difficult because of the presence of entanglement between electronic and nuclear degrees of freedom. Although quantum computers promise to reduce this computational cost, existing quantum approaches rely on combining signals from individual eigenstates, an approach whose cost grows exponentially with molecule size.

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.

Plasmonic enhancement of aqueous processed organic photovoltaics.

Sodium tungsten bronze (Na WO) is a promising alternative plasmonic material to nanoparticulate gold due to its strong plasmonic resonances in both the visible and near-infrared (NIR) regions. Additional benefits include its simple production either as a bulk or a nanoparticle material at a relatively low cost. In this work, plasmonic Na WO nanoparticles were introduced and mixed into the nanoparticulate zinc oxide electron transport layer of a water processed poly(3-hexylthiophene):phenyl-C-butyric acid methyl ester (P3HT:PCBM) nanoparticle (NP) based organic photovoltaic device (NP-OPV).

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.

Health literacy, pain-related interference and pain-related distress of patients with musculoskeletal pain.

The present study aimed to compare pain-related interference and pain-related distress in patients with musculoskeletal pain and differing levels of health literacy. A cross-sectional study was conducted among 243 patients with chronic musculoskeletal pain. Short Test of Functional Health Literacy in Adults classified the level of health literacy.

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.

Analog quantum simulation of chemical dynamics.

Ultrafast chemical reactions are difficult to simulate because they involve entangled, many-body wavefunctions whose computational complexity grows rapidly with molecular size. In photochemistry, the breakdown of the Born-Oppenheimer approximation further complicates the problem by entangling nuclear and electronic degrees of freedom. Here, we show that analog quantum simulators can efficiently simulate molecular dynamics using commonly available bosonic modes to represent molecular vibrations.

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.

Delocalised kinetic Monte Carlo for simulating delocalisation-enhanced charge and exciton transport in disordered materials.

Charge transport is well understood in both highly ordered materials (band conduction) or highly disordered ones (hopping conduction). In moderately disordered materials-including many organic semiconductors-the approximations valid in either extreme break down, making it difficult to accurately model the conduction. In particular, describing wavefunction delocalisation requires a quantum treatment, which is difficult in disordered materials that lack periodicity.

Optimisation of bacterial release from a stable microfluidic-generated water-in-oil-in-water emulsion.

Application of droplet microfluidics for the encapsulation of bacteria in water-in-oil-in-water (W/O/W) emulsion allows for production of monodisperse droplets with controllable size. In this study the release of bacteria from W/O/W emulsion, the effect of the double emulsion structure on bacterial growth and metabolic activity, and the stability and mechanism of bacterial release were investigated. W/O/W emulsions were formed using a double flow-focusing junction microfluidic device under controlled pressure to produce droplets of approximately 100 μm in diameter containing an inner aqueous phase (W) of about 40-50 μm in diameter.

Outcomes and endpoints reported in studies of pulmonary exacerbations in people with cystic fibrosis: A systematic review.

Background: There is no consensus about which outcomes should be evaluated in studies of pulmonary exacerbations in people with cystic fibrosis (CF). Outcomes used for evaluation should be meaningful; that is, they should capture how people feel, function or survive and be acknowledged as important to people with CF, or should be reliable surrogates of those outcomes. We aimed to summarise the outcomes and corresponding endpoints which have been reported in studies of pulmonary exacerbations, and to identify those which are most likely to be meaningful.

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.