Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden.

Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer's response to Fulvestrant (Fulv) treatment. Using in vitro cell lines and in vivo xenograft metastasis mouse models, we examined the molecular mechanisms of combining ER targeting with a ketogenic diet.

Motor cortical neuronal hyperexcitability associated with α-synuclein aggregation.

ΑBSTRACT: In Parkinson's disease (PD), Lewy pathology deposits in the cerebral cortex, but how the pathology disrupts cortical circuit integrity and function remains poorly understood. To begin to address this question, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. We reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern.

Intelligent in-cell electrophysiology: Reconstructing intracellular action potentials using a physics-informed deep learning model trained on nanoelectrode array recordings.

Intracellular electrophysiology is essential in neuroscience, cardiology, and pharmacology for studying cells' electrical properties. Traditional methods like patch-clamp are precise but low-throughput and invasive. Nanoelectrode Arrays (NEAs) offer a promising alternative by enabling simultaneous intracellular and extracellular action potential (iAP and eAP) recordings with high throughput.

DAMPs, PAMPs, NLRs, RIGs, CLRs and TLRs - Understanding the Alphabet Soup in the Context of Bone Biology.

Purpose Of Review: The purpose of this review is to summarize the current understanding of cell-autonomous innate immune pathways that contribute to bone homeostasis and disease.

Recent Findings: Germ-line encoded pattern recognition receptors (PRRs) are the first line of defense against danger and infections. In the bone microenvironment, PRRs and downstream signaling pathways, that mount immune defense, interface intimately with the core cellular processes in bone cells to alter bone formation and resorption.

Aminoguanidine hemisulfate improves mitochondrial autophagy, oxidative stress, and muscle force in Duchenne muscular dystrophy via the AKT/FOXO1 pathway in mdx mice.

Background: Duchenne muscular dystrophy (DMD) is a prevalent, fatal degenerative muscle disease with no effective treatments. Mdx mouse model of DMD exhibits impaired muscle performance, oxidative stress, and dysfunctional autophagy. Although antioxidant treatments may improve the mdx phenotype, the precise molecular mechanisms remain unclear.

A phase 2 randomized, placebo-controlled trial of inulin for the prevention of gut pathogen colonization and infection among patients admitted to the intensive care unit for sepsis.

Background: Patients admitted to the intensive care unit (ICU) often have gut colonization with pathogenic bacteria and such colonization is associated with increased risk for death and infection. We conducted a trial to determine whether a prebiotic would improve the gut microbiome to decrease gut pathogen colonization and decrease downstream risk for infection among newly admitted medical ICU patients with sepsis.

Methods: This was a randomized, double-blind, placebo-controlled trial of adults who were admitted to the medical ICU for sepsis and were receiving broad-spectrum antibiotics.

Mitochondrial dysfunction is a major cause of thromboinflammation and inflammatory cell death in critical illnesses.

Background: Mitochondria generate the adenosine triphosphate (ATP) necessary for eukaryotic cells, serving as their primary energy suppliers, and contribute to host defense by producing reactive oxygen species. In many critical illnesses, including sepsis, major trauma, and heatstroke, the vicious cycle between activated coagulation and inflammation results in tissue hypoxia-induced mitochondrial dysfunction, and impaired mitochondrial function contributes to thromboinflammation and cell death.

Methods: A computer-based online search was performed using the PubMed and Web of Science databases for published articles concerning sepsis, trauma, critical illnesses, cell death, mitochondria, inflammation, coagulopathy, and organ dysfunction.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

Endothelial Gsα deficiency promotes ferroptosis and exacerbates atherosclerosis in apolipoprotein E-deficient mice via the inhibition of NRF2 signaling.

The importance of ferroptosis in the occurrence and progression of atherosclerosis is gradually being recognized. The stimulatory G protein α subunit (Gsα) plays a crucial role in the physiology of endothelial cells (ECs). Our previous study showed that endothelial Gsα could regulate angiogenesis and preserve endothelial permeability.

Shallow-water mussels (Mytilus galloprovincialis) adapt to deep-sea environment through transcriptomic and metagenomic insights.

Recent studies have unveiled the deep sea as a rich biosphere, populated by species descended from shallow-water ancestors post-mass extinctions. Research on genomic evolution and microbial symbiosis has shed light on how these species thrive in extreme deep-sea conditions. However, early adaptation stages, particularly the roles of conserved genes and symbiotic microbes, remain inadequately understood.

Spermine driven water deficit tolerance in early growth phases of sweet corn genotypes under hydroponic cultivation.

Sweet corn is highly susceptible to water deprivation, making it crucial to identify effective strategies for enhancing its tolerance to water deficit conditions. This study investigates the novel application of Spermine as a bio-stimulant to improve sweet corn (Zea mays L. var.

Green synthesized FeNPs ameliorate drought stress in Spinacia oleracea L. through improved photosynthetic capacity, redox balance, and antioxidant defense.

The present study was designed to highlight the ameliorative role of iron nanoparticles (FeNPs) against drought stress in spinach (Spinacia oleracea L.) plants. A pot experiment was performed in two-way completely randomize design with three replicates.

Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology.

Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion.

Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans.

Exercising regularly promotes health, but these benefits are complicated by acute inflammation induced by exercise. A potential source of inflammation is cell-free DNA (cfDNA), yet the cellular origins, molecular causes, and immune system interactions of exercise-induced cfDNA are unclear. To study these, 10 healthy individuals were randomized to a 12-wk exercise program of either high-intensity tactical training (HITT) or traditional moderate-intensity training (TRAD).

Exploring the regulatory role of small RNAs in modulating host-pathogen interactions: implications for bacterial and viral infections.

MicroRNAs (miRNAs) and transfer RNA-derived stress-induced RNAs (tiRNAs) have emerged as crucial players in the post-transcriptional regulation of gene expression in various cellular processes, including immunity and host defense against infections. In recent years, increasing evidence has highlighted their complex role in influencing the host response during viral and bacterial infections. miRNAs have been shown to play multiple roles in host-pathogen interaction like TLR activation and altered disease virulence during bacterial infections.

[Advances in the study of viruses inhibiting the production of advanced autophagy or interferon through Rubicon to achieve innate immune escape].

The innate immune response is the first line of defense for the host against viral infections. Targeted degradation of pathogenic microorganisms through autophagy, in conjunction with pattern recognition receptors synergistically inducing the production of interferon (IFN), constitutes an important pathway for the body to resist viral infections. Rubicon, a Run domain Beclin 1-interacting and cysteine-rich domain protein, has an inhibitory effect on autophagy and IFN production.

Description and Classification of Training Drills, Based on Biomechanical and Physiological Load, in Elite Basketball.

The aim of this study was to understand and describe the physiological and biomechanical demands of various tasks used in basketball training and, subsequently, to provide a practical application of these tasks in a typical training week. Twelve basketball players had their external load variables monitored across 179 training sessions (2896 samples) using local positioning system technology. These variables included total distance covered, distance covered at various intensity levels, accelerations, decelerations, PlayerLoad™, and explosive efforts.

Synergistic Effects of Omega-3 Fatty Acids and Physical Activity on Oxidative Stress Markers and Antioxidant Mechanisms in Aged Rats.

Background: Aging induces degenerative processes in the body, contributing to the onset of various age-associated diseases that affect the population. Inadequate dietary habits and low physical activity are major contributors to increased morbidity during aging. This study aimed to investigate the combined effects of omega-3 fatty acid supplementation and physical activity on the markers of oxidative stress and antioxidant defense mechanisms in aged male Wistar rats (23-24 months).

Genome-Wide Identification and Functional Characterization of Gene Family Reveal Its Involvement in Response to Stress in Cotton.

SKP1 constitutes the Skp1-Cullin-F-box ubiquitin E3 ligase (SCF), which plays a role in plant growth and development and biotic and abiotic stress in ubiquitination. However, the response of the gene family to abiotic and biotic stresses in cotton has not been well characterized. In this study, a total of 72 genes with the conserved domain of SKP1 were identified in four Gossypium species.

Enhancement Strategy for Protocatechuic Acid Production Using with Focus on Continuous Fermentation Scale-Up and Cytotoxicity Management.

Protocatechuate acid (PCA) is a phenolic acid naturally synthesized by various organisms. Protocatechuic acid is synthesized by plants for physiological, metabolic functions, and self-defense, but extraction from plants is less efficient compared to the microbial culture process. The microbial synthesis of protocatechuic acid is sustainable and, due to its high yield, can save energy consumption when producing the same amount.

Light Quality Plays a Crucial Role in Regulating Germination, Photosynthetic Efficiency, Plant Development, Reactive Oxygen Species Production, Antioxidant Enzyme Activity, and Nutrient Acquisition in Alfalfa.

Light is a vital regulator of photosynthesis, energy production, plant growth, and morphogenesis. Although these key physiological processes are well understood, the effects of light quality on the pigment content, oxidative stress, reactive oxygen species (ROS) production, antioxidant defense systems, and biomass yield of plants remain largely unexplored. In this study, we applied different light-emitting diode (LED) treatments, including white light, red light, blue light, and a red+blue (1:1) light combination, to evaluate the traits mentioned above in alfalfa ( L.

Almond Grafting for Plum Pox Virus Resistance Triggers Significant Transcriptomic and Epigenetic Shifts in Peaches.

Sharka disease, caused by the plum pox virus (PPV), negatively impacts stone fruit production, resulting in economic losses. It has been demonstrated that grafting the almond ( (Miller) D.A.

Long-Term 5-HT Receptor Agonist NLX-112 Treatment Improves Functional Recovery After Spinal Cord Injury.

Spinal cord injury (SCI) results in functional deficits below the injured spinal level. The descending serotonergic system in the spinal cord is critically involved in the control of motor and autonomic functions. Specifically, SCI damages the projections of serotonergic fibers, which leads to reduced serotonin inputs and increased amounts of spinal serotonergic receptors.

Exploring the Role of Carbon Monoxide in Seed Physiology: Implications for Stress Tolerance and Practical Uses.

Carbon monoxide (CO) is recognized as a signaling molecule in plants, inducing various physiological responses. This article briefly examines the physiological functions of CO in seed biology and seedlings' responses to environmental stresses. The activity of heme oxygenase (HO), the main enzyme responsible for CO synthesis, is a key factor controlling CO levels in plant cells.