Trio fatale: Neutrophils, NETs, and necrosis.

In a recent issue of Nature, Adrover et al. report a neutrophil subset that induces pleomorphic tumor necrosis through neutrophil extracellular trap (NET)-mediated vascular occlusion. This process drives epithelial-to-mesenchymal transition (EMT) and metastasis of perinecrotic cancer cells, reframing necrosis as an active process and uncovering targetable mechanisms to combat cancer dissemination.

Emerging strategies, applications and challenges of targeting NAD in the clinic.

Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD-related clinical trials, focusing on aging and neurodegenerative diseases.

Predicting loaf volume of white bread by near infrared spectroscopy on wheat flour. Comparative application: NIR reflection, NIR transmission and portable NIR reflection.

White bread is a worldwide consumed food product with significant nutritional value. The loaf volume of bread is a crucial parameter that influences its texture, appearance and consumer acceptability. Near Infrared Spectroscopy (NIRS) has shown significant potential in predicting the loaf volume of white bread, providing a faster and potentially more accurate alternative to time consuming traditional methods.

Adjusting the management of the Antarctic krill fishery to meet the challenges of the 21st century.

Antarctic krill () is the central prey species in the Southern Ocean food web, supporting the largest and fastest-growing fishery in the region, managed by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR). Climate change is threatening krill populations and their predators, while current catch limits do not take into account climate variability or krill population dynamics. In 2024, CCAMLR was unable to renew its spatial catch limits, highlighting the urgent need for improved management of the krill fishery to prevent any harm to the Southern Ocean ecosystem.

Artificial Intelligence and Network Medicine: Path to Precision Medicine.

Over the past two decades, network medicine (NM) has evolved to help define disease mechanisms, identify drug targets, and guide increasingly precise therapies. In recent years, the integration of NM with artificial intelligence (AI), particularly deep learning techniques, has evolved with increasing applications. AI techniques help elucidate complex disease mechanisms and define precise therapies.

Optimization of 2,3-dihydrophthalazine-1,4-dione PARP inhibitor scaffold for nanomolar potency and specificity towards human PARP10.

PARP10 is a potential drug target due to its overexpression in several cancer types and its roles in DNA repair mechanisms and tumorigenesis. In this study, we performed an optimization campaign on our earlier compounds based on a 2,3-dihydrophthalazine-1,4-dione scaffold which emerged with dual PARP10 and PARP15 inhibitory activity. The specific aim was to improve the potency and selectivity towards PARP10.

Target RNA recognition drives PIWI complex assembly for transposon silencing.

PIWI-clade Argonaute proteins and their associated PIWI-interacting RNAs (piRNAs) are essential guardians of genome integrity, silencing transposable elements through distinct nuclear and cytoplasmic pathways. Nuclear PIWI proteins direct heterochromatin formation at transposon loci, while cytoplasmic PIWIs cleave transposon transcripts to initiate piRNA amplification. Both processes rely on target RNA recognition by PIWI-piRNA complexes, yet how this leads to effector recruitment is unclear.

Autophagy and Bacterial infections.

Autophagy is an evolutionarily conserved cellular process that is prominent during bacterial infections. In this review article, we discuss how direct pathogen clearance via xenophagy and regulation of inflammatory products represent dual functions of autophagy that coordinate an effective antimicrobial response. We detail the molecular mechanisms of xenophagy, including signals that indicate the presence of an intracellular pathogen and autophagy receptor-mediated cargo targeting, while highlighting pathogen counterstrategies, such as bacterial effector proteins that inhibit autophagy initiation or exploit autophagic membranes for replication.

tRNA as an assembly chaperone for a macromolecular transcription-processing complex.

Transfer RNAs (tRNAs) are widely recognized for their role in translation. Here, we describe a previously unidentified function of tRNA as an assembly chaperone. During poxviral infection, tRNA lacking the anticodon mcmsU34 modification is specifically sequestered from the cellular tRNA pool to promote formation of a multisubunit poxviral RNA polymerase complex (vRNAP).

Safeguarding nocturnal pollinators for food security in sub-Saharan Africa.

Nocturnal pollinators are vital for food security in sub-Saharan Africa, yet they face numerous threats, including habitat loss, light pollution, and climate change. Understanding these combined risks and implementing targeted management strategies to protect them is essential for ensuring sustainable agriculture, food security, and biodiversity in the region.

Relationships between anterior cruciate ligament elastic and viscoelastic properties and cartilage degeneration in osteoarthritic human knee joints.

Knee joint osteoarthritis (OA) is characterized by alterations in articular cartilage and subchondral bone, but concurrent biomechanical changes in the bundles of human anterior cruciate ligament are poorly known. This study aimed at characterizing the anteromedial (AM) and posterolateral (PL) bundles' elastic and viscoelastic properties and relate them to knee joint OA. Small dogbone-shaped samples were cut from mid-substance of AM and PL bundles of human knees (n = 18 knees, N = 9 cadavers) and subjected to tensile sinusoidal and multi-step stress-relaxation testing.

An ancient and essential miRNA family controls cellular interaction pathways in .

The transition from unicellular to multicellular life required the acquisition of coordinated and regulated cellular behaviors, including adhesion and migration. In metazoans, this involves adhesion proteins, signaling systems, and an elaborate extracellular matrix (ECM) that contributes to adhesion and signaling interactions. Innovations that enabled complex multicellularity occurred through new genes in these pathways, novel functions for existing genes, and regulatory changes.

Treatment with the Bifidobacterium longum Strain DSM 32947 Increases Bone Mineral Density in Female Mice.

Previous studies have shown that the gut microbiota regulates bone mass and that certain strains of Bifidobacterium longum prevent bone loss in ovariectomized (ovx) mice. A novel strain of Bifidobacterium longum (B. longum subsp.

Recombinant cathepsins B and L promote α-synuclein clearance and restore lysosomal function in human and murine models with α-synuclein pathology.

Unlabelled: The autophagy-lysosomal pathway is crucial for maintaining homeostasis and survival of neurons, hence defects in this system have been associated with neurodegeneration, including Parkinson's disease (PD). The cysteine proteases cathepsin B (CTSB) and cathepsin L (CTSL) are involved in the clearance of various neurodegenerative disease-related proteins such as amyloid-[Formula: see text], huntingtin and the prion protein. While there are studies implicating CTSB and CTSL as mediators of α-synuclein/SNCA clearance, their exact roles remain unclear.

A novel feedback loop between DYRK2 and USP28 regulates cancer homeostasis and DNA damage signaling.

Posttranslational modifications, such as ubiquitination and phosphorylation, play pivotal roles in regulating protein stability in response to cellular stress. Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) and ubiquitin-specific peptidase 28 (USP28) are critical regulators of cell cycle progression, DNA damage response, and oncogenic signaling. However, their functional interplay remains largely unexplored.

Hepatic Expression of ACBP Is a Prognostic Marker for Weight Loss After Bariatric Surgery.

The incidence and prevalence of obesity and related cardio-metabolic diseases are on the rise, posing a critical health care challenge to systems across the globe. Bariatric surgery is a therapeutic cornerstone for morbidly obese patients, besides novel medical treatments, partly by ameliorating metabolic inflammation, a hallmark of metabolic diseases. Acyl-CoA Binding Protein (ACBP), also known as diazepam-binding inhibitor (DBI), is a regulator of autophagy and metabolism, and has recently been shown to increase in individuals undergoing voluntary fasting and in patients with cancer cachexia-induced malnutrition.

Functional transitions of the Aspergillus fumigatus iron regulator HapX are governed by conserved domains cooperatively binding [2Fe-2S] clusters.

Accurate sensing of cellular iron levels is vital, as this metal is essential but toxic in excess. The iron-sensing transcription factor HapX is crucial for virulence of Aspergillus fumigatus, the predominant human mold pathogen. Its absence impairs growth under iron limitation and excess, but not under moderate iron availability, suggesting that HapX switches between three states to adapt to varying iron availability.

Mitochondrial ROS drive foam cell formation via STAT5 signaling in atherosclerosis.

Macrophage-to-foam cell transition is an integral part of atherosclerotic plaque progression. Particularly, oxidized low-density lipoprotein (oxLDL) is a driving factor in foam cell formation, altering macrophage function and metabolism. The aim of our research was to understand the impact of oxLDL-induced mitochondrial reactive oxygen species on macrophage-to-foam cell differentiation.

Roles of protein-protein interactions and monolayer mechanics in tricellulin localization to tricellular tight junctions.

Tricellular tight junctions (tTJs) seal the space between three or more cells in epithelial monolayers. These specialized tight junctions have distinct protein components, including a transmembrane protein tricellulin. However, the mechanisms by which tricellulin localizes specifically to tTJs are incompletely understood.

Structural and Functional Characterization of the Pro64Ser Leptin Mutant: Implications for Congenital Leptin Deficiency.

Congenital leptin deficiency or dysfunction is a form of monogenic childhood obesity. The disease is primarily caused by mutations in the LEP gene, which encodes for the expression of a hormone called leptin. The mutations typically impair leptin synthesis, secretion, or binding to the leptin receptor (LepR).

A split-site E3 ligase mechanism enables ZNFX1 to ubiquitinate and cluster single-stranded RNA into ubiquitin-coated nucleoprotein particles.

Eukaryotic cells use a multi-layered immune response to combat intracellular pathogens. The ubiquitin ligase ZNFX1 has emerged as a crucial yet little understood player that regulates the immune response while protecting against RNA viruses. Our study unveils the molecular mechanism of ZNFX1, mediated by the joint activity of a helicase serving as a nucleic acid sensor and a non-conventional E3 module featuring a split active site.

Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.

Eukaryotic cells have evolved sophisticated quality control mechanisms to eliminate aggregation-prone proteins that compromise cellular health. Central to this defense is the ubiquitin-proteasome system, where UBR4 acts as an essential E4 ubiquitin ligase, amplifying degradation marks on defective proteins. Cryo-electron microscopy analysis of UBR4 in complex with its cofactors KCMF1 and CALM1 reveals a massive 1.

Virgin Coconut Oil and Its Lauric Acid, Between Anticancer Activity and Modulation of Chemotherapy Toxicity: A Review.

Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty acid in VCO and has been associated with several pharmacological activities. The literatures show the pharmacological effects of VCO and LA on chronic pathologies, infectious diseases, and metabolic disorders.

Quantitative profiling of human brain organoid cell diversity across four protocols and multiple cell lines.

Human brain organoids are powerful in vitro models for brain development and disease. However, protocol and pluripotent cell line choices influence organoid variability and cell-type representation, complicating their use in biomedical research. Here, we systematically analyze the cellular and transcriptional landscape of brain organoids across multiple cell lines using four protocols aimed at recapitulating dorsal and ventral forebrain, midbrain, and striatum.