Oncolytic virus hijacks GOT1 and pyrimidinosomes to fuel pyrimidine synthesis for replication in tumor cells.

Glioblastoma multiforme (GBM) is an aggressive brain tumor characterized by metabolic plasticity and resistance to therapy. Understanding the mechanisms underlying GBM's adaptability to metabolic stress is crucial for developing effective treatments. This study investigates the role of Brain Protein I3 (BRI3) in regulating lipid metabolism and autophagy in GBM, and its potential as a therapeutic target. We performed integrative bioinformatics analysis using TCGA-GBM and CGGA datasets to identify lipophagy-related gene signatures. BRI3's function was examined through in vitro studies using GBM cell lines and patient-derived samples. Lipid metabolism and autophagy were assessed under normal and oxygen-glucose deprivation (OGD) conditions in BRI3-knockdown and control GBM cells. Bioinformatics analysis revealed a lipophagy-related gene signature associated with poor prognosis in GBM. BRI3 emerged as a key upregulated gene in GBM, correlating with altered lipid homeostasis and enhanced autophagy. In vitro studies demonstrated that BRI3 knockdown led to lipid accumulation, impaired autophagy, reduced proliferation, and increased apoptosis in GBM cells. Under OGD conditions mimicking the tumor microenvironment, BRI3-depleted cells showed compromised lipid mobilization, autophagy induction, and cell survival compared to controls. Our findings suggest BRI3 as a critical regulator of lipophagy in GBM, enhancing tumor cell resilience to metabolic stress. This study provides insights into GBM's metabolic adaptability and identifies BRI3 as a potential therapeutic target for modulating tumor cell survival in the challenging glioblastoma microenvironment.

Reshaping the immunosuppressive niche in hepatocellular carcinoma: crosstalk networks, metabolic reprogramming, and therapeutic strategies.

Midkine and pleiotrophin in glioma: From mechanistic insights to therapeutic potential.

Non-coding RNAs as biomarkers and therapeutic targets in pancreatic cancer: Clinical implications and translational perspectives.

Cyanobacteria-driven morphology and adaptive microbial succession: Resilience mechanisms in algal-bacterial granular sludge under tripartite stress.

Chemical defense is a pivotal strategy for predator, pathogen, and parasite avoidance in amphibians. Although most defensive chemicals in amphibians are obtained through biosynthesis, poison frogs sequester dietary alkaloids, in some cases hydroxylating or N-methylating the ingested alkaloids to form more potent chemicals. Although more than 1200 lipophilic alkaloids have been isolated in anuran secretions, the mechanisms underlying alkaloid sequestration and biotransformation remain largely unknown. This study investigates the biochemical pathways employed by Adelphobates galactonotus to sequester and transform ingested alkaloids. Specifically, we focused on the hydroxylation of orally administered pumiliotoxin (+)-251D to form allopumiliotoxin (+)267A using ultra performance liquid chromatography - triple quadrupole mass spectrometry. We examined the distribution of these alkaloids across several organs, including the liver, skin, digestive tract, gallbladder, kidney, and fat bodies. Using a novel protocol for sample preparation via solid-phase extraction, our study elucidates the translocation patterns of these alkaloids, along with differences in their ratios. We detected pumiliotoxin (+)-251D, and its hydroxylated derivate in the liver, suggesting hepatic involvement in processing, while the skin was the primary site of storage for both alkaloids. Additionally, we report the presence of these alkaloids in the urine and fat bodies, suggesting a passive storage mechanism. This study advances our understanding of anuran chemical defense and metabolic adaptations.

Species- and salt-dependent Mg2+ handling during fermentation - Comparative responses of Saccharomyces boulardii and Lactobacilli.

The role of macrophage metabolic reprogramming in efferocytosis: A dual-edged sword in atherosclerosis and tumor progression.

The granuloma serves not only as a physical barrier to restrict the dissemination of intracellular pathogens but also functions as a complex immune microenvironment. However, the bioenergetics and regulatory mechanisms maintaining this architecture remain elusive in vertebrates. Here, integrating multi-tissue transcriptomics, single-cell RNA sequencing (scRNA-seq), ultrastructural imaging, and fluorescence in situ hybridization (FISH) in a largemouth bass (Micropterus salmoides)-Nocardia seriolae infection model, we resolved the metabolic and functional landscape of the granuloma. We found that across multiple tissues (head kidney, spleen, liver, kidney), the host initiates a synchronized transcriptional program that promotes macrophage differentiation into specialized epithelioid macrophages (E-Macs). Notably, E-Macs concurrently upregulated specific transporters and metabolic enzymes (e.g., laao, slc6a8), as well as oxidative phosphorylation (OXPHOS) and glycolysis genes, accompanied by mitochondrial proliferation. Functionally, E-Macs shifted from a pro-inflammatory to an immunoregulatory and pro-survival phenotype, characterized by high expression of protease inhibitors (e.g., csta) and anti-apoptotic factors (e.g., bcl2l14, ywhag1). Comparative analysis in zebrafish confirmed these metabolic and regulatory signatures are evolutionarily conserved. In conclusion, this study reveals a host survival strategy of immune regulation underpinned by metabolic adaptation, providing novel perspectives for controlling chronic granulomatous diseases in aquaculture.

Pregnancy involves profound endocrine and metabolic adaptations, such as the increase in maternal cortisol levels, which plays a central role in fetal maturation and appropriate fetal development. However, at high levels, evidence suggests that exposure to maternal cortisol can be harmful to fetal growth and subsequent infant neurodevelopment. This study examined the associations between maternal serum cortisol levels during gestation and fetal anthropometry, assessed by ultrasonography, both measured simultaneously in either the second or the third trimester of pregnancy. It also explored potential relationships between gestational cortisol and infant cognitive development at three months of age, evaluated using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). This study is nested within a larger project involving mother-child dyads from southern Brazil. The data presented here refers to 632 dyads with complete fetal anthropometric measurements, serum cortisol data, and last menstrual period information. Among the 632 included dyads, 520 infants were assessed for cognitive development at three months of age. In adjusted analyses, higher gestational cortisol levels remained significantly and positively associated with fetal head circumference (B = 0.12, 95% CI: 0.05; 0.19, p = 0.001), abdominal circumference (B = 0.09, 95% CI: 0.02; 0.16, p = 0.015), femur length (B = 0.02, 95% CI: 0.00; 0.04, p = 0.013), and biparietal diameter (B = 0.03, 95% CI: 0.01; 0.05, p = 0.005). No significant association was observed for estimated fetal weight. Additionally, higher maternal cortisol levels during pregnancy were significantly associated with lower infant cognitive scores at three months (B = -0.05, 95% CI: -0.09; -0.01, p = 0.038). These findings suggest that gestational cortisol may exert distinct influences on fetal growth and early cognitive functioning, highlighting the importance of understanding its underlying biological mechanisms.

Virus-host metabolic interaction: SGIV-induced protein lactylation suppresses viral propagation.

Metastatic castration‑resistant prostate cancer (mCRPC) remains a lethal disease due to universal resistance to androgen‑receptor pathway inhibitors (ARPI). Tumor progression is orchestrated by a spectrum of androgen‑receptor‑independent drivers, including genomic alterations in DNA damage repair pathways, epigenetic shifts promoting lineage plasticity, metabolic adaptations and an immunosuppressive tumor microenvironment. This evolving understanding has catalyzed the development of novel therapeutic strategies. These include PARP inhibitors for tumors with homologous recombination repair deficiencies, protein kinase B inhibitors for the phosphatase and tensin homolog‑loss subset, prostate‑specific membrane antigen (PSMA)‑targeted radioligand therapy, bispecific T‑cell engagers, antibody‑drug conjugates and immune checkpoint inhibitors. Furthermore, liquid biopsy profiling, PSMA‑positron emission tomography‑based radiomics and artificial intelligence platforms are enhancing real‑time patient selection and response assessment. The present review synthesized these recent preclinical and clinical advances to delineate biomarker‑driven, mechanism‑based therapeutic sequencing and combination strategies for mCRPC in the post‑ARPI era.19.

Metabolic and redox adaptations of the corneal endothelium: From metabolic plasticity to therapeutic opportunities.

Robust gut microbiota as a key protective barrier for Ruditapes philippinarum survival following an extreme-rainfall disturbance.

Effect of packaging-induced oxygen microenvironments on the viability and metabolism of Lactobacillus paracasei in yogurt.

Ketone body metabolism activates the immune response against Staphylococcus aureus infection by fueling the tricarboxylic acid cycle and affecting histone β-hydroxybutyrylation.

Targeting the xylosyltransferase TMEM5 in glioblastoma to modulate CLOCK and CRY1 expression and restore temozolomide sensitivity via the circadian signaling axis.

Gravity as a key player for the preservation of muscle mass and function in the era of anti-obesity therapies?

Chromodomain helicase DNA‑binding protein 4 (CHD4) is a core adenosine triphosphate (ATP)‑dependent chromatin‑remodeling factor of the nucleosome‑remodeling and deacetylase (NuRD) complex. It plays a crucial role in chromatin structure regulation, gene expression regulation, and DNA damage response. It has been demonstrated that CHD4 has context‑dependent functions in tumor development and progression. It can influence tumor progression via such mechanisms as regulating tumor‑related signaling pathways, maintaining the silencing of tumor suppressor genes, and promoting metabolic adaptation; it can also exert tumor‑suppressive effects in specific transcriptional regulatory environments. Additionally, during DNA damage response, CHD4 participates in chromatin remodeling at damage sites, in cell cycle recovery, and in repair pathway selection. It is also involved in the development of tumor treatment resistance through mechanisms that include regulation of DNA repair, cell cycle progression, drug efflux, the tumor immune microenvironment, and replication fork stability. It has also been shown that various non‑coding RNAs participate in the functional regulation of CHD4 by modulating its expression, localization, and protein stability. In summary, as a key node connecting chromatin regulation, genome stability, and tumor treatment response, CHD4 holds significant importance in tumor progression and treatment.