An Overview of In Vitro Models of Alcohol-Related Hepatocellular Carcinoma.

Background: Chronic and excessive alcohol consumption is the leading cause of death due to chronic liver disease. Alcohol-related liver disease (ALD) encompasses a broad spectrum of clinical and pathological features, ranging from asymptomatic and reversible pathologies to hepatocellular carcinoma (HCC), a highly prevalent and deadly liver cancer. Indeed, alcohol consumption is one of the main worldwide etiologies of HCC.

Design and validation of cell-based potency assays for frataxin supplementation treatments.

Friedreich's ataxia (FRDA) is a multisystem, autosomal recessive disorder caused by mutations in the frataxin () gene. As FRDA is considered an FXN deficiency disorder, numerous therapeutic approaches in development or clinical trials aim to supplement FXN or restore endogenous expression. These include gene therapy, protein supplementation, genome editing or upregulation of transcription.

Comparison: Imported and Indigenous HIV Fourth-generation immunodiagnostic kits.

Early detection of any disease is always a life-saving methodology for human beings likewise the detection of p24 antigen is always better than the detection of HIV antibodies. In the current era, p24 antigen is added additionally in HIV antibodies detection assays and called HIV fourth-generation immunodiagnostic kit. The different HIV fourth-generation kit having different capacities to pick up the low concentration of analyte as well as represent the detection values in different units.

A Phage-Based Approach to Identify Antivirulence Inhibitors of Bacterial Type IV Pili.

The increasing threat of antibiotic resistance underscores the urgent need for innovative strategies to combat infectious diseases, including the development of antivirulants. Microbial pathogens rely on their virulence factors to initiate and sustain infections. Antivirulants are small molecules designed to target virulence factors, thereby attenuating the virulence of infectious microbes.

Large-scale and long-term wildlife research and monitoring using camera traps: a continental synthesis.

Camera traps are widely used in wildlife research and monitoring, so it is imperative to understand their strengths, limitations, and potential for increasing impact. We investigated a decade of use of wildlife cameras (2012-2022) with a case study on Australian terrestrial vertebrates using a multifaceted approach. We (i) synthesised information from a literature review; (ii) conducted an online questionnaire of 132 professionals; (iii) hosted an in-person workshop of 28 leading experts representing academia, non-governmental organisations (NGOs), and government; and (iv) mapped camera trap usage based on all sources.

Multi-Targeting Macrocyclic Peptides as Nanomolar Inhibitors of Self- and Cross-Seeded Amyloid Self-Assembly of α-Synuclein.

Amyloid self-assembly of α-synuclein (αSyn) is linked to the pathogenesis of Parkinson's disease (PD). Type 2 diabetes (T2D) has recently emerged as a risk factor for PD. Cross-interactions between their amyloidogenic proteins may act as molecular links.

Phase-Engineered Bi-RuO Single-Atom Alloy Oxide Boosting Oxygen Evolution Electrocatalysis in Proton Exchange Membrane Water Electrolyzer.

Engineering nanomaterials at single-atomic sites can enable unprecedented catalytic properties for broad applications, yet it remains challenging to do so on RuO-based electrocatalysts for proton exchange membrane water electrolyzer (PEMWE). Herein, the rational design and construction of Bi-RuO single-atom alloy oxide (SAAO) are presented to boost acidic oxygen evolution reaction (OER), via phase engineering a novel hexagonal close packed (hcp) RuBi single-atom alloy. This Bi-RuO SAAO electrocatalyst exhibits a low overpotential of 192 mV and superb stability over 650 h at 10 mA cm, enabling a practical PEMWE that needs only 1.

Targeted sputum sequencing for rapid and broad drug resistance of Mycobacterium tuberculosis.

Purpose: Rapid detection of drug resistance in Mycobacterium tuberculosis (Mtb) from clinical samples facilitates the timely provision of optimal treatment regimens for tuberculosis (TB) patients.

Methods: In November, 2023, the WHO released its second catalogue of resistance-conferring mutations in Mtb. Utilizing this information, we developed a single 17-plex PCR assay covering 16 key resistance genes and modified thermo-protection buffer to amplify 30 kbp DNA directly from sputum samples for nanopore sequencing.

Humanized Candida and NanoBiT Assays Expedite Discovery of Bdf1 Bromodomain Inhibitors With Antifungal Potential.

The fungal Bromodomain and Extra-Terminal (BET) protein Bdf1 is a potential antifungal target against invasive fungal infections. However, the need to selectively inhibit both Bdf1 bromodomains (BDs) over human orthologs and the lack of molecular tools to assess on-target antifungal efficacy hamper efforts to develop Bdf1 BD inhibitors as antifungal therapeutics. This study reports a phenyltriazine compound that inhibits both Bdf1 BDs from the human fungal pathogen Candida glabrata with selectivity over the orthologous BDs from the human BET protein Brd4.

Individualization of piperacillin dosage based on therapeutic drug monitoring with or without model-informed precision dosing: a scenario analysis.

Background: Model-informed precision dosing (MIPD) combines population pharmacokinetic knowledge with therapeutic drug monitoring (TDM) to optimize dosage adjustment. It could improve target concentration attainment over empirical TDM, still widely practised for broad-spectrum antibiotics.

Objectives: To evaluate the respective performance of TDM and MIPD in achieving target piperacillin exposure.

CAR T access and outcomes in large B-cell lymphoma according to ethnicity and socioeconomic deprivation in the UK.

Data on the impact of ethnic and socioeconomic factors on Chimeric antigen receptor (CAR) T-cell therapy (access and outcomes are limited, but key to understand whether results from the registration trials are generalizable to real-world patient populations. Here, we analysed ethnicity, socioeconomic deprivation and referral patterns in a cohort of 314 large B-cell lymphoma patients approved for third-line CD19 CAR-T across three large UK CAR-T centres. Patients from deprived areas had a lower infusion rate compared to low deprivation areas (73% vs.

Phytic Acid-Induced Gradient Hydrogels for Highly Sensitive and Broad Range Pressure Sensing.

Ionic conductive hydrogels have emerged as an excellent option for constructing dielectric layers of interfacial iontronic sensors. Among these, gradient ionic hydrogels, due to the intrinsic gradient elastic modulus, can achieve a wide range of pressure responses. However, the fabrication of gradient hydrogels with optimal mechanical and sensing properties remains a challenge.

Ultrasmall α-MnO with Low Aspect Ratio: Applications to Electrochemical Multivalent-Ion Intercalation Hosts and Aerobic Oxidation Catalysts.

Hollandite-type α-MnO exhibits exceptional promise in current industrial applications and in advancing next-generation green energy technologies, such as multivalent (Mg, Ca, and Zn) ion battery cathodes and aerobic oxidation catalysts. Considering the slow diffusion of multivalent cations within α-MnO tunnels and the catalytic activity at edge surfaces, ultrasmall α-MnO particles with a lower aspect ratio are expected to unlock the full potential. In this study, ultrasmall α-MnO (<10 nm) with a low aspect ratio (c/a ≈ 2) is synthesized using a newly developed alcohol solution process.

Harnessing Multi-Center-2-Electron Bonds for Carbene Metal-Hydride Nanocluster Catalysis.

N-Heterocyclic carbene (NHC) ligands possess the ability to stabilize metal-based nanomaterials for a broad range of applications. With respect to metal-hydride nanomaterials, however, carbenes are rare, which is surprising if one considers the importance of metal-hydride bonds across the chemical sciences. In this study, we introduce a bottom-up approach leveraging preexisting metal-metal m-center-n-electron (mc-ne) bonds to access a highly stable cyclic(alkyl)amino carbene (CAAC) copper-hydride nanocluster, [(CAAC)6Cu14H12][OTf]2 with superior stability compared to Stryker's reagent, a popular commercial phosphine-based copper hydride catalyst.

Integration of unpaired single cell omics data by deep transfer graph convolutional network.

The rapid advance of large-scale atlas-level single cell RNA sequences and single-cell chromatin accessibility data provide extraordinary avenues to broad and deep insight into complex biological mechanism. Leveraging the datasets and transfering labels from scRNA-seq to scATAC-seq will empower the exploration of single-cell omics data. However, the current label transfer methods have limited performance, largely due to the lower capable of preserving fine-grained cell populations and intrinsic or extrinsic heterogeneity between datasets.

A generative model for inorganic materials design.

The design of functional materials with desired properties is essential in driving technological advances in areas like energy storage, catalysis, and carbon capture. Generative models provide a new paradigm for materials design by directly generating novel materials given desired property constraints, but current methods have low success rate in proposing stable crystals or can only satisfy a limited set of property constraints . Here, we present MatterGen, a model that generates stable, diverse inorganic materials across the periodic table and can further be fine-tuned to steer the generation towards a broad range of property constraints.

The Microenvironment in DCIS and Its Role in Disease Progression.

Ductal carcinoma in situ (DCIS) accounts for ~20% of all breast cancer diagnoses but whilst known to be a precursor of invasive breast cancer (IBC), evidence suggests only one in six patients will ever progress. A key challenge is to distinguish between those lesions that will progress and those that will remain indolent. Molecular analyses of neoplastic epithelial cells have not identified consistent differences between lesions that progressed and those that did not, and this has focused attention on the tumour microenvironment (ME).

A Guide to Breast Cancer Research: An Introduction.

"A Guide to Breast Cancer Research: From Cells and Molecular Mechanisms to Therapy" is designed as a comprehensive reference for early career investigators and postgraduate students. This book aims to provide a broad overview of contemporary breast cancer research. It covers key areas including development and cancer, metastasis and immunology, subtypes, signalling, therapy, and resistance.

Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy.

The complex nature of the immunosuppressive tumor microenvironment (TME) requires multi-agent combinations for optimal immunotherapy. Here we describe multiplex universal combinatorial immunotherapy via gene silencing (MUCIG), which uses CRISPR-Cas13d to silence multiple endogenous immunosuppressive genes in the TME, promoting TME remodeling and enhancing antitumor immunity. MUCIG vectors targeting four genes delivered by adeno-associated virus (AAV) (Cd274/Pdl1, Lgals9/Galectin9, Lgals3/Galectin3 and Cd47; AAV-Cas13d-PGGC) demonstrate significant antitumor efficacy across multiple syngeneic tumor models, remodeling the TME by increasing CD8 T-cell infiltration while reducing neutrophils.

Unlocking the potential of azide-phosphine Staudinger reaction for the synthesis of poly(arylene iminophosphorane)s and materials therefrom.

Iminophosphoranes with the general formula (RP═NR') have great potential in synthetic chemistry as valuable precursors/intermediates in organic synthesis or as building blocks for various organic compounds. However, the synthetic approaches and conditions to prepare iminophosphoranes are still poorly understood, limiting the utility of this chemistry for organic materials. In this article, a simple and efficient synthesis of previously unattainable poly(arylene iminophosphoranes) is reported.

Enhanced sensitivity and scalability with a Chip-Tip workflow enables deep single-cell proteomics.

Single-cell proteomics (SCP) promises to revolutionize biomedicine by providing an unparalleled view of the proteome in individual cells. Here, we present a high-sensitivity SCP workflow named Chip-Tip, identifying >5,000 proteins in individual HeLa cells. It also facilitated direct detection of post-translational modifications in single cells, making the need for specific post-translational modification-enrichment unnecessary.

Spatio-temporal risk prediction of leptospirosis: A machine-learning-based approach.

Background: Leptospirosis is a neglected zoonotic disease prevalent worldwide, particularly in tropical regions experiencing frequent rainfall and severe cyclones, which are further aggravated by climate change. This bacterial zoonosis, caused by the Leptospira genus, can be transmitted through contaminated water and soil. The Pacific islands bear a high burden of leptospirosis, making it crucial to identify key factors influencing its distribution.

Barriers to early diagnosis and treatment of cervical cancer in Addis Ababa, Ethiopia: qualitative study.

Objective: Cervical cancer remains the most diagnosed and deadly cancer among women in low and middle income countries, including Ethiopia, although it can be controlled if detected and treated early. However, research on contextual barriers to early diagnosis and treatment of cervical cancer is limited in Ethiopia. This study aimed to describe the lived experience of the patients and to explore the barriers to early diagnosis and treatment of cervical cancer.

Metabolomics identifies plasma biomarkers of localized radiation injury.

A radiological accident may result in the development of a local skin radiation injury (LRI) which may evolve, depending on the dose, from dry desquamation to deep ulceration and necrosis through unpredictable inflammatory waves. Therefore, early diagnosis of victims of LRI is crucial for improving medical care efficiency. This preclinical study aims to identify circulating metabolites as biomarkers associated with LRI using a C57BL/6J mouse model of hind limb irradiation.