Palmitate potentiates the SMAD3-PAI-1 pathway by reducing nuclear GDF15 levels.

Nuclear growth differentiation factor 15 (GDF15) reduces the binding of the mothers' against decapentaplegic homolog (SMAD) complex to its DNA-binding elements. However, the stimuli that control this process are unknown. Here, we examined whether saturated fatty acids (FA), particularly palmitate, regulate nuclear GDF15 levels and the activation of the SMAD3 pathway in human skeletal myotubes and mouse skeletal muscle, where most insulin-stimulated glucose use occurs in the whole organism.

Compositional data analysis enables statistical rigor in comparative glycomics.

Comparative glycomics data are compositional data, where measured glycans are parts of a whole, indicated by relative abundances. Applying traditional statistical analyses to these data often results in misleading conclusions, such as spurious "decreases" of glycans when other structures increase in abundance, or high false-positive rates for differential abundance. Our work introduces a compositional data analysis framework, tailored to comparative glycomics, to account for these data dependencies.

Simplified acid extraction and quantification of histones in human tumor cells.

Histones are essential nuclear proteins that package eukaryotic DNA into chromosomes, play a vital role in gene regulation, DNA replication, DNA repair and chromosome condensation. Understanding histone modifications is crucial for grasping biological and disease-related processes. Specific alterations in histone modifications serve as sensitive and selective biomarkers for conditions like cancer, impacting both tumor and immune cells and affecting their interactions.

Microfluidics-enabled core/shell nanostructure assembly: Understanding encapsulation processes via particle characterization and molecular dynamics.

In the realm of hybrid nanomaterials, the construction of core/shell nanoparticles offer an effective strategy for encompassing a particle by a polymeric or other suitable material, leading to a nanocomposite with distinct features within its structure. The polymer shell can be formed via nanoprecipitation, optimized by manipulating fluid flow, fluid mixing, modulating device features in microfluidics. In addition to the process optimization, success of polymer assembly in encapsulation strongly lies upon the favorable molecular interactions originating from the diverse chemical environment shared between core and shell materials facilitating formation of core/shell nanostructure.

Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancer.

Sirtuin 7 (SIRT7), a member of the sirtuin family of NAD+-dependent deacetylases, plays a vital role in cancer, exhibiting context-dependent functions across various malignancies. Our study investigates the role of SIRT7 depletion in head and neck squamous cell carcinoma (HNSCC) progression. In vitro and 3D organotypic models demonstrated that SIRT7 knock-out attenuates cancer cell viability, proliferation, and motility as well as induces downregulation of migration- and epithelial-mesenchymal transition (EMT)-related gene expression.

Discovery of (3-Phenylcarbamoyl-3,4-dihydro-2-pyrrol-2-yl)phosphonates as Imidazoline Receptor Ligands with Anti-Alzheimer and Analgesic Properties.

Imidazoline receptors (I-IRs) are altered in Alzheimer's disease (AD) patients and are associated with analgesia. I-IRs are not structurally described, and their pharmacological characterization relies on their modulation by highly affine ligands. Herein, we describe the synthesis of (3-phenylcarbamoyl-3,4-dihydro-2-pyrrol-2-yl)phosphonates endowed with relevant affinities for I-IRs in human brain tissues.

The human patellar tendon is mechanically homogenous at its mid-substance.

The human patellar tendon contains distinct fascicle bundles across its mediolateral and anteroposterior regions. Studies have suggested region-specific behaviour during in vivo actions, but it is unclear whether such regional differences result from localized variation in composition and mechanical properties within the tendon itself. Furthermore, the viscoelastic properties of any region of the human patellar tendon have not been well described previously.

Identification of SETD4 as an Onco-Immunological Biomarker Encompassing the Tumor Microenvironment, Prognoses, and Therapeutic Responses in Various Human Cancers.

Background: SET domain-containing protein 4 (SETD4) is a histone methyltransferase that has been shown to modulate cell proliferation, differentiation, and inflammatory responses by regulating histone H4 trimethylation (H4K20me3). Previous reports have demonstrated its function in the quiescence of cancer stem cells as well as drug resistance in several cancers. A limited number of systematic studies have examined SETD4's role in the tumor microenvironment, pathogenesis, prognosis, and therapeutic response.

Renal-Clearable Biomass-Derived Carbon Dots with Red Fluorescence for Masked Cryptic Kidney Injury Imaging.

Masked cryptic kidney injury (MCKI), an early stage of acute kidney injury (AKI), is challenging to detect and diagnose, especially in the modern context where toxic substances, such as surfactants, are increasingly misused. Consequently, there is an urgent need for methods for the visual diagnosis of MCKI. In this study, we synthesized environmentally friendly spirulina-derived carbon dots (SpiCDs) using spirulina as a biobased raw material through a simple hydrothermal process.

Eugenol inhibits NEAT1 as a ceRNA in pre-cancerous breast lesions.

Objective: Eugenol (EU) from cloves is highly effective against different tumors. The long noncoding ribonucleic acids (lncRNAs), which play a role of competing endogenous RNAs (ceRNAs), suppress microRNAs (miRNAs) involved in post-transcriptional regulatory networks. The present work focused on analyzing how EU affected pre-cancerous breast lesions (PBL).

Metabolic and inflammatory status in prepuberty and early adulthood for individuals with a history of extrauterine growth restriction: a cohort study.

Background: Perinatal growth and nutrition have been shown to be determinants in the programming of different tissues, such as adipose tissue, predisposing individuals to metabolic alterations later in life. Previous studies have documented an increased risk of metabolic disturbances and low-grade inflammation in prepubertal children with a history of extrauterine growth restriction (EUGR). The aim of this study was to evaluate possible alterations resulting from impaired growth during early childhood and their impact on young adult health.

Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants.

Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications.

Independent effect of body fat content on inflammatory biomarkers in children and adolescents: The GENOBOX study.

Background And Aims: To assess the relationship between body composition indicators and inflammatory biomarkers in children and adolescents of the GENOBOX study.

Methods And Results: Anthropometry data from 264 subjects from the subsample of Zaragoza (Spain) included: weight, height, waist circumference, body mass index and triponderal index. Body composition was determined by Dual-energy X-ray Absorptiometry (DXA), obtaining visceral adipose tissue, fat mass index and lean mass index.

Central Downregulation of S-Resistin Alleviates Inflammation in EWAT and Liver and Prevents Adipocyte Hypertrophy.

The hypothalamus integrates peripheral signals and modulates food intake and energy expenditure by regulating the metabolic function of peripheral tissues, including the liver and adipose tissue. In a previous study, we demonstrated that s-resistin, an intracellular resistin isoform highly expressed in the hypothalamus and upregulated during aging, is important in the central control of energy homeostasis, affecting mainly the peripheral response to insulin by still unknown mechanisms. Herein, using an intracerebroventricular injection of a specific lentiviral RNAi against s-resistin, we assessed, in the Wistar rat, the effects of central s-resistin downregulation on the expression and phosphorylation levels of intermediates involved in insulin signaling and the inflammatory response in epididymal white adipose tissue (eWAT) and liver.

Epidemiology of New Psychoactive Substances in Relation to Traditional Drugs of Abuse in Clinical Oral Fluid Samples.

New psychoactive substances (NPS) are health-hazardous through unpredictable toxicity and effects and largely unknown epidemiology, motivating studies of the latter. Up to 138 NPS were retrospectively identified using liquid chromatography-high resolution mass spectrometry data from all 34 183 oral fluid drug samples collected in one Swedish health care region 2019-2020 representing 9468 psychiatric and addiction care patients. In total, 618 findings representing 58 NPS were detected in 481 samples from 201 patients.

The mutational landscape of Staphylococcus aureus during colonisation.

Staphylococcus aureus is an important human pathogen and a commensal of the human nose and skin. Survival and persistence during colonisation are likely major drivers of S. aureus evolution.

Self-Reported Performance and Hormonal-Cycle-Related Symptoms in Competitive Female Athletes.

Introduction: The present scientific consensus is that the menstrual cycle (MC) and hormonal contraceptive (HC) cycle only influence performance trivially. Nevertheless, athletes perceive changes in performance that they associate with different phases of their hormonal cycle.

Methods: A total of 959 female athletes completed a questionnaire, of which 750 were included in the present analysis.

Corrigendum to: "High prevalence of hepatitis E and rat hepatitis E viruses in wastewater in Gothenburg, Sweden" [One Health, volume 19, article number 100882].

[This corrects the article DOI: 10.1016/j.onehlt.

Locus coeruleus signal intensity and emotion regulation in agitation in Alzheimer's disease.

Hyperphosphorylated tau accumulation is seen in the noradrenergic locus coeruleus from the earliest stages of Alzheimer's disease onwards and has been associated with symptoms of agitation. It is hypothesized that compensatory locus coeruleus-noradrenaline system overactivity and impaired emotion regulation could underlie agitation propensity, but to our knowledge this has not previously been investigated. A better understanding of the neurobiological underpinnings of agitation would help the development of targeted prevention and treatment strategies.

Impact of Daytime and Nighttime Blood Pressure and Nocturnal Blood Pressure Fall on Heart Failure Risk in Treated Hypertension.

Background: To evaluate the impact of daytime, nighttime and nocturnal blood pressure (BP) fall on heart failure (HF).

Methods: We analyzed data of five cohorts including 15,526 treated hypertensive patients, experiencing 625 HF events, by study-level meta-analysis. The pooled hazard ratios (HR) and 95% confidence intervals (CI) for 1-SD increase in BP parameters or per group were calculated.

Prospective association of changes in (poly)phenol intake, body weight and physical activity with inflammatory profile.

Backgrounds And Aim: To prospectively evaluate the associations between changes in (poly)phenol intake, body weight(BW), and physical activity(PA) with changes in an inflammatory score after 1-year.

Methods And Results: This is a prospective observational analysis involving 484 participants from the PREDIMED-Plus with available inflammatory measurements. (Poly)phenol intake was estimated using a validated semi-quantitative food frequency questionnaire and the Phenol-Explorer database.

Validity of the MED4CHILD tool for assessing adherence to the Mediterranean diet in preschool children.

Unlabelled: Most of the available tools to assess adherence to Mediterranean diet (MedDiet) were constructed for adults, having limited applicability to children and adolescents. The aim of this study is to validate a specific questionnaire to assess adherence to MedDiet in children aged 3 to 6 years (MED4CHILD questionnaire). The validation was performed in a baseline examination of a cohort of children who were recruited in schools in seven cities.

Synthesis of New Promising BNCT Agents Based on Conjugates of -Dodecaborate Anion and Aliphatic Diamino Acids.

In this work, a series of boronated amidines based on the -dodecaborate anion and amino acids containing an amino group in the side chain of the general formula [BHNHC(NH(CH)CH(NH)COOH)CH], where n = 2, 3, 4, were synthesized. These derivatives contain conserved α-amino and α-carboxyl groups recognized by the binding centers of the large neutral amino acid transporter (LAT) system, which serves as a target for the clinically applied BNCT agent para-boronophenylalanine (BPA). The paper describes several approaches to synthesizing the target compounds, their acute toxicity studies, and tumor uptake studies in vivo in two tumor models.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Modeling Musculoskeletal Disorders in Zebrafish: Advancements in Muscle and Bone Research.

Zebrafish () have emerged as a valuable model organism for investigating musculoskeletal development and the pathophysiology of associated diseases. Key genes and biological processes in zebrafish that closely mirror those in humans, rapid development, and transparent embryos make zebrafish ideal for the in vivo studies of bone and muscle formation, as well as the molecular mechanisms underlying musculoskeletal disorders. This review focuses on the utility of zebrafish in modeling various musculoskeletal conditions, with an emphasis on bone diseases such as osteoporosis and osteogenesis imperfecta, as well as muscle disorders like Duchenne muscular dystrophy.