The glutathione S-transferase Gstt1 drives survival and dissemination in metastases.

Identifying the adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (pancreatic adenocarcinoma, PDA). A loss-of-function shRNA targeted screen in metastatic-derived cells identified Gstt1, a member of the glutathione S-transferase superfamily, as uniquely required for dissemination and metastasis, but dispensable for primary tumour growth. Gstt1 is expressed in latent disseminated tumour cells (DTCs), is retained within a subpopulation of slow-cycling cells within existing metastases, and its inhibition leads to complete regression of macrometastatic tumours.

Large Electromechanical Response in a Polycrystalline Alkali-Deficient (K,Na)NbO Thin Film on Silicon.

The demand for large electromechanical performance in lead-free polycrystalline piezoelectric thin films is driven by the need for compact, high-performance microelectromechanical systems (MEMS) based devices operating at low voltages. Here we significantly enhance the electromechanical response in a polycrystalline lead-free oxide thin film by utilizing lattice-defect-induced structural inhomogeneities. Unlike prior observations in mismatched epitaxial films with limited low-frequency enhancements, we achieve large electromechanical strain in a polycrystalline (K,Na)NbO film integrated on silicon.

Valorization of palm oil mill effluent via enhanced oil recovery as an alternative feedstock for biodiesel production.

Residual oil from palm oil mill effluent (POME) can be valorized into value-added products like biofuel. However, the complex structure in POME limits the full recovery of intracellular lipids. To address this challenge, low-frequency ultrasonication was used as a pre-treatment prior to oil recovery to improve the yield by liberating the entrapped oil via the cell disruption technique.

Accurate proteome-wide missense variant effect prediction with AlphaMissense.

The vast majority of missense variants observed in the human genome are of unknown clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on human and primate variant population frequency databases to predict missense variant pathogenicity. By combining structural context and evolutionary conservation, our model achieves state-of-the-art results across a wide range of genetic and experimental benchmarks, all without explicitly training on such data.

H3K36 methylation maintains cell identity by regulating opposing lineage programmes.

The epigenetic mechanisms that maintain differentiated cell states remain incompletely understood. Here we employed histone mutants to uncover a crucial role for H3K36 methylation in the maintenance of cell identities across diverse developmental contexts. Focusing on the experimental induction of pluripotency, we show that H3K36M-mediated depletion of H3K36 methylation endows fibroblasts with a plastic state poised to acquire pluripotency in nearly all cells.

Similar deamination activities but different phenotypic outcomes induced by APOBEC3 enzymes in breast epithelial cells.

APOBEC3 (A3) enzymes deaminate cytosine to uracil in viral single-stranded DNA as a mutagenic barrier for some viruses. A3-induced deaminations can also occur in human genomes resulting in an endogenous source of somatic mutations in multiple cancers. However, the roles of each A3 are unclear since few studies have assessed these enzymes in parallel.

Limited plasticity of monocyte fate and function associated with epigenetic scripting at the level of progenitors.

Myeloid cell heterogeneity is known, but whether it is cell-intrinsic or environmentally-directed remains unclear. Here, an inducible/reversible system pausing myeloid differentiation allowed the definition of clone-specific functions that clustered monocytes into subsets with distinctive molecular features. These subsets were orthogonal to the classical/nonclassical categorization and had inherent, restricted characteristics that did not shift under homeostasis, after irradiation, or with infectious stress.

Comparison of vegetable oils on the uptake of lutein and zeaxanthin by ARPE-19 cells.

Aim: To compare the effect of vegetable oils on the uptake of lutein and zeaxanthin by adult retinal pigment epithelial (ARPE)-19 cells .

Methods: ARPE-19 cells were cultured in Dulbecco's Modified Eagle Medium-F-12 supplemented with 10% foetal bovine serum and 1% penicillin-streptomycin in a humidified 5% CO incubator maintained at 37°C. Cells were treated with 247 µmol/L lutein, 49 µmol/L zeaxanthin and 1% (v/v) of either coconut oil, corn oil, peanut oil, olive oil, sunflower oil, soybean oil, castor oil, or linseed oil for 48h.

Competition for DNA binding between the genome protector replication protein A and the genome modifying APOBEC3 single-stranded DNA deaminases.

The human APOBEC family of eleven cytosine deaminases use RNA and single-stranded DNA (ssDNA) as substrates to deaminate cytosine to uracil. This deamination event has roles in lipid metabolism by altering mRNA coding, adaptive immunity by causing evolution of antibody genes, and innate immunity through inactivation of viral genomes. These benefits come at a cost where some family members, primarily from the APOBEC3 subfamily (APOBEC3A-H, excluding E), can cause off-target deaminations of cytosine to form uracil on transiently single-stranded genomic DNA, which induces mutations that are associated with cancer evolution.

Farnesysltransferase Inhibitor Prevents Burn Injury-Induced Metabolome Changes in Muscle.

Burn injury remains a significant public health issue worldwide. Metabolic derangements are a major complication of burn injury and negatively affect the clinical outcomes of severely burned patients. These metabolic aberrations include muscle wasting, hypermetabolism, hyperglycemia, hyperlactatemia, insulin resistance, and mitochondrial dysfunction.

Epigenetic reader SP140 loss of function drives Crohn's disease due to uncontrolled macrophage topoisomerases.

How mis-regulated chromatin directly impacts human immune disorders is poorly understood. Speckled Protein 140 (SP140) is an immune-restricted PHD and bromodomain-containing epigenetic "reader," and SP140 loss-of-function mutations associate with Crohn's disease (CD), multiple sclerosis (MS), and chronic lymphocytic leukemia (CLL). However, the relevance of these mutations and mechanisms underlying SP140-driven pathogenicity remains unexplored.

Atorvastatin favorably modulates a clinical hepatocellular carcinoma risk gene signature.

Lipophilic but not hydrophilic statins have been shown to be associated with reduced risk for hepatocellular carcinoma (HCC) in patients with chronic viral hepatitis. We investigated differential actions of lipophilic and hydrophilic statins and their ability to modulate a clinical prognostic liver signature (PLS) predicting HCC risk in patients with liver disease. Hepatitis C virus (HCV)-infected Huh7.

Simulation-Based Mastery Learning to Facilitate Transition to Nursing Practice.

Background: Simulation-based mastery learning (SBML) was developed and implemented to facilitate nursing students' transition to clinical practice.

Purpose: To evaluate nursing students' perspectives on the impact of SBML on their transition to clinical practice.

Method: A descriptive qualitative study using focus group discussions was conducted with final-year nursing students who had completed their clinical practicum and SBML.

Brain motor and fear circuits regulate leukocytes during acute stress.

The nervous and immune systems are intricately linked. Although psychological stress is known to modulate immune function, mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood. Here we show that distinct brain regions shape leukocyte distribution and function throughout the body during acute stress in mice.

Human enteric viruses autonomously shape inflammatory bowel disease phenotype through divergent innate immunomodulation.

Altered enteric microorganisms in concert with host genetics shape inflammatory bowel disease (IBD) phenotypes. However, insight is limited to bacteria and fungi. We found that eukaryotic viruses and bacteriophages (collectively, the virome), enriched from non-IBD, noninflamed human colon resections, actively elicited atypical anti-inflammatory innate immune programs.

Galvanic corrosion protection of Al-alloy in contact with carbon fibre reinforced polymer through plasma electrolytic oxidation treatment.

Al-alloy/carbon fibre reinforced polymer (CFRP) joint systems offer exceptionally lightweight, superior fatigue behaviour and impact resistance for aerospace applications. Nevertheless, the galvanic corrosion at the joint interfaces accelerates the adhesive failure and strength damage. In this work, oxidation of Al 7075 alloy was studied by employing plasma electrolytic oxidation (PEO) and thin film sulphuric acid anodizing (TFSAA) methods, addressing their galvanic corrosion (GC) protection performance in contact with CFRP.

Transcriptional regulation of neural stem cell expansion in the adult hippocampus.

Experience governs neurogenesis from radial-glial neural stem cells (RGLs) in the adult hippocampus to support memory. Transcription factors (TFs) in RGLs integrate physiological signals to dictate self-renewal division mode. Whereas asymmetric RGL divisions drive neurogenesis during favorable conditions, symmetric divisions prevent premature neurogenesis while amplifying RGLs to anticipate future neurogenic demands.

Surface Treatment and Bioinspired Coating for 3D-Printed Implants.

Three-dimensional (3D) printing technology has developed rapidly and demonstrates great potential in biomedical applications. Although 3D printing techniques have good control over the macrostructure of metallic implants, the surface properties have superior control over the tissue response. By focusing on the types of surface treatments, the osseointegration activity of the bone-implant interface is enhanced.

Low NCOR2 levels in multiple myeloma patients drive multidrug resistance via MYC upregulation.

MYC upregulation is associated with multidrug refractory disease in patients with multiple myeloma (MM). We, isolated patient-derived MM cells with high MYC expression and discovered that NCOR2 was down-regulated in these cells. NCOR2 is a transcriptional coregulatory protein and its role in MM remains unknown.

Type I, II, and III Interferon Signatures Correspond to Coronavirus Disease 2019 Severity.

We analyzed plasma levels of interferons (IFNs) and cytokines, and expression of IFN-stimulated genes in peripheral blood mononuclear cells in patients with coronavirus disease 2019 of varying disease severity. Patients hospitalized with mild disease exhibited transient type I IFN responses, while intensive care unit patients had prolonged type I IFN responses. Type II IFN responses were compromised in intensive care unit patients.

Massively parallel characterization of CYP2C9 variant enzyme activity and abundance.

CYP2C9 encodes a cytochrome P450 enzyme responsible for metabolizing up to 15% of small molecule drugs, and CYP2C9 variants can alter the safety and efficacy of these therapeutics. In particular, the anti-coagulant warfarin is prescribed to over 15 million people annually and polymorphisms in CYP2C9 can affect individual drug response and lead to an increased risk of hemorrhage. We developed click-seq, a pooled yeast-based activity assay, to test thousands of variants.

Transversus Abdominis Plane Block Versus Intraperitoneal Local Anesthetics in Bariatric Surgery: A Systematic Review and Network Meta-analysis.

Background: Transversus abdominis plane (TAP) block and intraperitoneal local anesthetics (IPLA) are widely investigated techniques that potentially improve analgesia after bariatric surgery. The analgesic efficacy of TAP block has been shown in previous studies, but the performance of TAP block can be difficult in patients with obesity. We performed a systematic review and meta-analysis to compare the analgesic efficacy of TAP block and IPLA.

Astrocytic interleukin-3 programs microglia and limits Alzheimer's disease.

Communication within the glial cell ecosystem is essential for neuronal and brain health. The influence of glial cells on the accumulation and clearance of β-amyloid (Aβ) and neurofibrillary tau in the brains of individuals with Alzheimer's disease (AD) is poorly understood, despite growing awareness that these are therapeutically important interactions. Here we show, in humans and mice, that astrocyte-sourced interleukin-3 (IL-3) programs microglia to ameliorate the pathology of AD.

Wow, woo, win"- Healthcare students' and facilitators' experiences of interprofessional simulation in three-dimensional virtual world: A qualitative evaluation study.

Background: In an age disrupted by COVID-19 pandemic, three-dimensional virtual world (3DVW) offers an opportunity for healthcare students from different higher education institutions to participate in interprofessional education. Despite its growing evidence, there is a need to unravel the complex learning process in order to ensure high quality of interprofessional education delivery.

Aim: This study aimed to explore the experiences of healthcare students and facilitators on the use of 3DVW for interprofessional team-based virtual simulation.