PSMA-targeted delivery of docetaxel in prostate cancer using small-sized PDA-based micellar nanovectors.

In this study, we present the first comparative analysis of active and passive drug delivery systems for docetaxel (DTX) in prostate cancer using supramolecular self-assembled micellar nanovectors. Specifically, we developed two novel micelles based on polydiacetylenic amphiphiles (PDA) for passive and active targeting. The active targeting micelles were designed with a prostate-specific membrane antigen (PSMA) ligand, ACUPA, to facilitate recognition by PSMA-positive cancer cells.

N-glycosylation of ephrin B1 modulates its function and confers therapeutic potential in B-cell lymphoma.

Given the pivotal role of the Eph-Ephrin signaling pathway in tumor progression, agonists or antagonists targeting Eph/Ephrin have emerged as promising anticancer strategies. However, the implications of glycosylation modifications within Eph/Ephrin and their targeted protein therapeutics remain elusive. Here, we identify that N-glycosylation within the receptor-binding domain (RBD) of ephrin B1 (EFNB1) is indispensable for its functional repertoire.

A quantitative intracellular peptide binding assay reveals recognition determinants and context dependence of short linear motifs.

Transient protein-protein interactions play key roles in controlling dynamic cellular responses. Many examples involve globular protein domains that bind to peptide sequences known as Short Linear Motifs (SLiMs), which are enriched in intrinsically disordered regions of proteins. Here we describe a novel functional assay for measuring SLiM binding, called Systematic Intracellular Motif Binding Analysis (SIMBA).

Surveying helix 12 dynamics within constitutively active estrogen receptors using bipartite tetracysteine display.

Somatic Y537S and D538G mutations within the estrogen receptor alpha ligand-binding domain (ERα-LBD) have been linked to enhanced cell proliferation, survival, and metastases in ER-positive breast cancers. Such mutations are thought to confer ligand-independent receptor activation by increasing the flexibility of helix 12 (H12), a segment within the ERα-LBD that acts as a dynamic regulator of ERα activity. We employed bipartite tetracysteine display coupled with the biarsenical profluorophore FlAsH-EDT to monitor ligand-independent structural transitions of H12 in ERα-LBDs that include Y537S or D538G mutations.

TFII-I/GTF2I regulates globin gene expression and stress response in erythroid cells.

Transcription factor TFII-I/GTF2I is ubiquitously expressed and has been shown to play a role in the differentiation of hematopoietic cells and in the response to various cellular stressors. We previously demonstrated that TFII-I acts as a repressor of adult β-globin gene transcription and positively regulates expression of stress response proteins, including ATF3. Here we analyzed the function of TFII-I in TF-1 cells during erythroid differentiation and in response to cellular stress, including unfolded protein response, hypoxia, and oxidative stress.

Predicting metal-binding proteins and structures through integration of evolutionary-scale and physics-based modeling.

Metals are essential elements in all living organisms, binding to approximately 50% of proteins. They serve to stabilize proteins, catalyze reactions, regulate activities, and fulfill various physiological and pathological functions. While there have been many advancements in determining the structures of protein-metal complexes, numerous metal-binding proteins still need to be identified through computational methods and validated through experiments.

Development and applications of a machine learning model for an in-depth analysis of pentylenetetrazol-induced seizure-like behaviors in adult zebrafish.

Epilepsy, a neurological disorder causing recurring seizures, is often studied in zebrafish by exposing animals to pentylenetetrazol (PTZ), which induces clonic- and tonic-like behaviors. While adult zebrafish seizure-like behaviors are well characterized, manual assessment remains challenging due to its time-consuming nature, potential for human error/bias, and the risk of overlooking subtle behaviors. Aiming to circumvent these issues, we developed a machine learning model for automating the analysis of subtle abnormal and seizure-like behaviors in PTZ-exposed adult zebrafish.

Using Laboratory Test Results for Surveillance During a New Outbreak of Acute Hepatitis in 3-Week- to 5-Year-Old Children in the United Kingdom, the Netherlands, Ireland, and Curaçao: Observational Cohort Study.

Background: In March 2022, a concerning rise in cases of unexplained pediatric hepatitis was reported in multiple countries. Cases were defined as acute hepatitis with serum transaminases >500 U/L (aspartate transaminase [AST] or alanine transaminase [ALT]) in children aged 16 years or younger. We explored a simple federated data analytics method to search for evidence of unreported cases using routinely held data.

Development of a versatile system for evaluating the target protein degradation activity of novel ubiquitin ligases utilizing existing PROTACs.

Proteolysis-Targeting Chimeras (PROTAC) are a bifunctional molecule that binds to a protein of interest (POI) and a ubiquitin ligase, thereby inducing the ubiquitination and degradation of POI. Many PROTACs currently utilize a limited number of ubiquitin ligases, such as von Hippel-Lindau (VHL) and Cereblon. Because these ubiquitin ligases are widely expressed in normal tissues, unexpected side effects can occur.

Sub-organellar mitochondrial hydrogen peroxide observed using a SNAP tag targeted coumarin-based fluorescent reporter.

Mitochondria are major sites of reactive oxygen species (ROS) production within cells. ROS are important signalling molecules, but excessive production can cause cellular damage and dysfunction. It is therefore crucial to accurately determine when, how and where ROS are produced within mitochondria.

Autophagic flux measurement: Cargo degradation versus generation of degradation products.

Autophagy is the cellular processes that transport cytoplasmic components to lysosomes for degradation. It plays essential physiological roles, including in adaptation to environmental changes such as starvation and maintaining intracellular quality control. Recently, its links to aging and disease have garnered substantial attention.

Major advances in protein function assignment by remote homolog detection with protein language models - A review.

There is an ever-increasing need for accurate and efficient methods to identify protein homologs. Traditionally, sequence similarity-based methods have dominated protein homolog identification for function identification, but these struggle when the sequence identity between the pairs is low. Recently, transformer architecture-based deep learning methods have achieved breakthrough performances in many fields.

Effects of exercise and transient estradiol exposure in middle-aged female rats.

The benefits of estrogen treatment on cognition in middle-aged and older women are dependent on many factors, including the timing of treatment. Moreover, the potential interactive effects with other lifestyle factors, such as exercise, are poorly understood. In this study, we tested for lasting benefits of independent and combined treatment with estrogen and voluntary exercise initiated in midlife, using a rat model of menopause.

Association of Epstein-Barr Virus and its clinical relevance in Human Papillomavirus-negative oral squamous cell carcinoma: A cohort study from South India.

Objective: The study assessed the prevalence and clinical implications of Epstein Barr Virus (EBV)-positive but Human Papillomavirus (HPV)-negative oral squamous cell carcinoma (OSCC) in a tertiary care hospital setting. The overall goal was to elucidate the potential impact of EBV on OSCC disease progression and prognosis.

Design: A total of 134 surgically resected and histopathologically confirmed OSCC tumor biopsies were collected from a tertiary care hospital.

Cost-effective production of meaty aroma from porcine cells for hybrid cultivated meat.

Cultivated meats are typically hybrids of animal cells and plant proteins, but their high production costs limit their scalability. This study explores a cost-effective alternative by hypothesizing that controlling the Maillard and lipid thermal degradation reactions in pure cells can create a meaty aroma that could be extracted from minimal cell quantities. Using spontaneously immortalized porcine myoblasts and fibroblasts adapted to suspension culture with a 1 % serum concentration, we developed a method to isolate flavor precursors via freeze-thawing.

Development of a comprehensive food glycomic database and its application: Associations between dietary carbohydrates and insulin resistance.

Carbohydrates are an integral part of a healthy diet. The molecular compositions of carbohydrates encompass a very broad range of unique structures with many being ill-defined. This vast structural complexity is distilled into vague categories such as total carbohydrates, sugars, starches, and soluble/insoluble fibers.

Pylb-based overexpression of cytochrome P450 in Bacillus subtilis 168.

Inducer-free expression systems are promising tools for biorefinery because they can reduce the reliance on inducers, reducing production costs and simplifying processes. Owing to their broad range of substrate structures and catalytic reactions, cytochrome P450s are promising biocatalysts to produce value-added compounds. However, unsuitable levels of cytochrome P450 expression could result in cell stress, affecting the efficiency of the biocatalyst.

Silica Nanoparticle-Protein Aggregation and Protein Corona Formation Investigated with Scattering Techniques.

Protein-nanoparticle interactions and the resulting corona formation play crucial roles in the behavior and functionality of nanoparticles in biological environments. In this study, we present a comprehensive analysis of protein corona formation with superfolder green fluorescent protein (sfGFP) and bovine serum albumin in silica nanoparticle dispersions using small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS). For the first time, we subtracted the scattering of individual proteins in solution and individual nanoparticles from the protein-nanoparticle complexes.

Mina53 catalyzes arginine demethylation of p53 to promote tumor growth.

Arginine methylation is a common post-translational modification that plays critical roles in many biological processes. However, the existence of arginine demethylases that remove the modification has not been fully established. Here, we report that Myc-induced nuclear antigen 53 (Mina53), a member of the jumonji C (JmjC) protein family, is an arginine demethylase.

Structural insights into HIV-2 CA lattice formation and FG-pocket binding revealed by single-particle cryo-EM.

One of the striking features of human immunodeficiency virus (HIV) is the capsid, a fullerene cone comprised of pleomorphic capsid protein (CA) that shields the viral genome and recruits cofactors. Despite significant advances in understanding the mechanisms of HIV-1 CA assembly and host factor interactions, HIV-2 CA assembly remains poorly understood. By templating the assembly of HIV-2 CA on functionalized liposomes, we report high-resolution structures of the HIV-2 CA lattice, including both CA hexamers and pentamers, alone and with peptides of host phenylalanine-glycine (FG)-motif proteins Nup153 and CPSF6.

Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.

The developmental lipidome of Nippostrongylus brasiliensis.

Background: Nippostrongylus brasiliensis-a nematode of rodents-is commonly used as a model to study the immunobiology of parasitic nematodes. It is a member of the Strongylida-a large order of socioeconomically important parasitic nematodes of animals. Lipids are known to play essential roles in nematode biology, influencing cellular membranes, energy storage and/or signalling.

Non-thermal atmospheric plasma treatments enhance the growth, photosynthesis, metabolite accumulation, and nutritional value of geranium (Pelargonium graveolens L'Herit) leaves.

This study investigated the effects of non-thermal atmospheric plasma (NTAP) treatment on the growth, chemical composition, and biological activity of geranium (Pelargonium graveolens L'Herit) leaves. NTAP was applied at a frequency of 13.56 MHz, exposure time of 15 s, discharge temperature of 25 °C, and power levels (T1 = 50, T2 = 80, and T3 = 120 W).

Synergistic anticancer effects of cisplatin and phenolic aglycones of the aerial part of Rumex dentatus L. in tongue squamous cell carcinoma: insights from network pharmacology and biological verification.

Background: Oral squamous cell carcinoma (OSCC) ranks as the sixth most common malignancy globally. Cisplatin is the standard chemotherapy for OSCC, but resistance often reduces its efficacy, necessitating new treatments with fewer side effects. Rumex dentatus L.

Unveiling the omics tapestry of B-acute lymphoblastic leukemia: bridging genomics, metabolomics, and immunomics.

Acute B-lymphoblastic leukemia (B-ALL) is a highly heterogeneous hematologic malignancy, characterized by significant molecular differences among patients as the disease progresses. While the PI3K-Akt signaling pathway and metabolic reprogramming are known to play crucial roles in B-ALL, the interactions between lipid metabolism, immune pathways, and drug resistance remain unclear. In this study, we performed multi-omics analysis on different patient cohorts (newly diagnosed, relapsed, standard-risk, and poor-risk) to investigate the molecular characteristics associated with metabolism, signaling pathways, and immune regulation in B-ALL.