Progressive systemic inflammation precedes decompensation in compensated cirrhosis.

Background & Aims: Systemic inflammation is a driver of decompensation in cirrhosis with unclear relevance in the compensated stage. We evaluated inflammation and bacterial translocation markers in compensated cirrhosis and their dynamics in relation to the first decompensation.

Methods: This study is nested within the PREDESCI trial, which investigated non-selective beta-blockers for preventing decompensation in compensated cirrhosis and clinically significant portal hypertension (CSPH: hepatic venous pressure gradient ≥10 mmHg).

Lateral Atrial Expression Patterns Provide Insights into Local Transcription Disequilibrium Contributing to Disease Susceptibility.

Background: Transcriptional dysregulation, possibly affected by genetic variation, contributes to disease development. Due to dissimilarities in development, function, and remodeling during disease progression, transcriptional differences between the left atrial (LA) and right atrial (RA) may provide insight into diseases such as atrial fibrillation.

Methods: Lateral differences in atrial transcription were evaluated in CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) using a 2-stage discovery and replication design.

The CC motif chemokine ligand 11 contributes to alcoholic liver disease.

Aims: Alcoholic liver disease (ALD) is characterized by aberrant lipid metabolism and chronic inflammation that eventually give rise to cirrhosis and hepatocellular carcinoma. In the present study we investigated the contribution of CC motif chemokine ligand 11 (CCL11) to ALD pathogenesis.

Methods And Materials: ALD was induced in mice by binge ethanol gavage or chronic ethanol feeding.

Cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions.

Prion diseases, particularly sporadic cases, pose a challenge due to their complex nature and heterogeneity. The underlying mechanism of the spontaneous conversion from PrPC to PrPSc, the hallmark of prion diseases, remains elusive. To shed light on this process and the involvement of cofactors, we have developed an in vitro system that faithfully mimics spontaneous prion misfolding using minimal components.

Detection of clinically relevant variants in the gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL.

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.

AlphaFold-Based AI Docking Reveals AMPK/SIRT1-TFEB Pathway Modulation by Traditional Chinese Medicine in Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD) is a chronic, progressive disorder characterized by hepatic steatosis and excessive lipid accumulation. Its high global adult prevalence (approximately 50.7%), however, FDA-approved therapeutic drugs remains lacking.

Timing of exercise differentially impacts adipose tissue gain in male adolescent rats.

Circadian rhythms of metabolic, hormonal, and behavioral fluctuations and their alterations can impact health. An important gap in knowledge in the field is whether the time of the day of exercise and the age of onset of exercise exert distinct effects at the level of whole-body adipose tissue and body composition. The goal of the present study was to determine how exercise at different times of the day during adolescence impacts the adipose tissue transcriptome and content in a rodent model.

Promoting Angiogenesis/Osteogenesis by a New Copper/Magnesium Hydroxide Hybrid Nanoparticle: In Vitro and In Vivo Investigation.

In this study, a new hybrid nanoparticle composed of magnesium hydroxide and copper oxide (Mg(OH)/CuO) with an optimized ratio of magnesium (Mg) to copper (Cu) was designed and incorporated into a 3D-printed scaffold made of polycaprolactone (PCL) and gelatin. These hybrid nanostructures (MCNs) were prepared using a green, solvent-free method. Their topography, surface morphology, and structural properties were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS).

Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study.

Background: Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24 h of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19.

Dual modes of DNA N-methyladenine maintenance by distinct methyltransferase complexes.

Stable inheritance of DNA N-methyladenine (6mA) is crucial for its biological functions in eukaryotes. Here, we identify two distinct methyltransferase (MTase) complexes, both sharing the catalytic subunit AMT1, but featuring AMT6 and AMT7 as their unique components, respectively. While the two complexes are jointly responsible for 6mA maintenance methylation, they exhibit distinct enzymology, DNA/chromatin affinity, genomic distribution, and knockout phenotypes.

Quantitative proteomic analysis unveils a critical role of VARS1 in hepatocellular carcinoma aggressiveness through the modulation of MAGI1 expression.

Background: Hepatocellular carcinoma (HCC) genetic/transcriptomic signatures have been widely described. However, its proteomic characterization is incomplete. We performed non-targeted quantitative proteomics of HCC samples and explored its clinical, functional, and molecular consequences.

Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis.

Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples.

Post-testicular spermatozoa of a marine teleost can conduct cytoplasmic and mitochondrial translation.

Translational silence of spermatozoa has long been considered the norm in animals. However, studies in mammals have shown that the mitochondrial ribosomal machinery is selectively activated during capacitation in the female reproductive tract, while cytosolic ribosomes remain inactive. Here, using quantitative proteomics in a piscine model species, we show that proteins involved in mRNA processing and cytoplasmic translation are predominantly accumulated in immature spermatozoa within the extratesticular excurrent ducts, while those related to flagellar motility are enriched in ejaculated (mature) sperm.

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.

Sex Differences in Gut Microbiota and Their Relation to Arterial Stiffness (MIVAS Study).

Background: Recent research highlights the potential role of sex-specific variations in cardiovascular disease. The gut microbiome has been shown to differ between the sexes in patients with cardiovascular risk factors.

Objectives: The main objective of this study is to analyze the differences between women and men in the relationship between gut microbiota and measures of arterial stiffness.

Advancements in the fight against globally distributed OXA-48 carbapenemase: evaluating the new generation of carbapenemase inhibitors.

Carbapenemase OXA-48 and its variants pose a serious threat to the development of effective treatments for bacterial infections. OXA-48-producing Enterobacterales are the most prevalent carbapenemase-producing bacteria in large parts of the world. Although these bacteria exhibit low-level carbapenem resistance , the infections they cause are challenging to treat with conventional therapies, owing to their spread and complex detection in clinical settings.

Impact of functional re-education and environmental adaptation in cancer patients with respiratory pathology: Study protocol.

Background: In recent years, cancer survival rates have increased exponentially. However, this rise in survival comes with a significant drawback. As the number of treatment lines has grown, so too have the side effects, which can severely impact patients' functionality and quality of life.

Dry eye disease and morphological changes in the anterior chamber in people with cystic fibrosis.

Background: Cystic fibrosis (CF) is caused by variants in a gene that encodes a protein essential for water and ion transport in the epithelial cells of exocrine organs. Given the possible relationship of this protein and conjunctival and corneal epithelium, the aim of this study was to evaluate ophthalmologic alterations in people with CF.

Methods: Forty-five people with CF underwent pulmonary evaluation including inflammatory score (IS).

Selenoprotein-Mediated Redox Regulation Shapes the Cell Fate of HSCs and Mature Lineages.

The maintenance of cellular redox balance is crucial for cell survival and homeostasis and is disrupted with aging. Selenoproteins, comprising essential antioxidant enzymes, raise intriguing questions about their involvement in hematopoietic aging and potential reversibility. Motivated by our observation of mRNA downregulation of key antioxidant selenoproteins in aged human hematopoietic stem cells (HSCs) and previous findings of increased lipid peroxidation in aged hematopoiesis, we employed tRNASec gene (Trsp) knockout (KO) mouse model to simulate disrupted selenoprotein synthesis.

Unveiling the photocatalytic and antimicrobial activities of star-shaped gold nanoparticles under visible spectrum.

This study reports on the facile development of star-shaped gold nanoparticles via seed-mediated growth protocol. Gold nanostars (AuNSTs) demonstrated average particle size of 48 nm using transmission electron microscopy (TEM). Chemical composition of AuNSTs was verifired using energy dispersive X-ray spectroscopy (EDX) mapping.

Assessment of Humoral Response at SARS-CoV-2 Infection by Multipronged Functional Proteomics Approaches.

In the past decade, a major goal in biomedical research has been to understand why individuals differ in disease susceptibility, disease dynamics, and progression. In many pathologies, this variability stems from evolved immune mechanisms that resist inflammatory stress from various diseases that have been encountered throughout life. These may provide advantages against other diseases, reduce comorbidities, and enhance longevity.

Impact of Omega-3 on Endocannabinoid System Expression and Function, Enhancing Cognition and Behavior in Male Mice.

: Omega-3 long-chain polyunsaturated fatty acids (PUFAs) support brain cell membrane integrity and help mitigate synaptic plasticity deficits. The endocannabinoid system (ECS) is integral to synaptic plasticity and regulates various brain functions. While PUFAs influence the ECS, the effects of omega-3 on the ECS, cognition, and behavior in a healthy brain remain unclear.

Fetal Isolated Single Umbilical Artery (ISUA) and Its Role as a Marker of Adverse Perinatal Outcomes.

Single umbilical artery (SUA) is considered an ultrasound marker of anomalies. Although it may be present in about 0.5% to 6% of normal pregnancies, it has been linked with an increased risk of fetal growth restriction (FGR), as well as cardiac, genitourinary and gastrointestinal malformations and chromosomal anomalies such as trisomies 21 and 18.

Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer's Disease Implications.

Sex differences in brain metabolism and their relationship to neurodegenerative diseases like Alzheimer's are an important emerging topic in neuroscience. Intrinsic anatomic and metabolic differences related to male and female physiology have been described, underscoring the importance of considering biological sex in studying brain metabolism and associated pathologies. The hippocampus is a key structure exhibiting sex differences in volume and connectivity.