Etrinabdione (VCE-004.8), a B55α activator, promotes angiogenesis and arteriogenesis in critical limb ischemia.

Background: Vasculogenic therapies explored for the treatment of peripheral artery disease (PAD) have encountered minimal success in clinical trials. Addressing this, B55α, an isoform of protein phosphatase 2A (PP2A), emerges as pivotal in vessel remodeling through activation of hypoxia-inducible factor 1α (HIF-1α). This study delves into the pharmacological profile of VCE-004.

Chemotherapy Enriches for Proinflammatory Macrophage Phenotypes that Support Cancer Stem-Like Cells and Disease Progression in Ovarian Cancer.

High-grade serous ovarian cancer remains a poorly understood disease with a high mortality rate. Although most patients respond to cytotoxic therapies, a majority will experience recurrence. This may be due to a minority of drug-resistant cancer stem-like cells (CSC) that survive chemotherapy and are capable of repopulating heterogeneous tumors.

Usefulness of vancomycin treatment individualization via Bayesian algorithms: a 5-year study in critical patients.

Compare two vancomycin dosing strategies in critical patients with methicillin-resistant (MRSA) infections, considering the heterogeneity of the dosing regimens administered and their implications for toxicity and efficacy. Longitudinal retrospective observational study in two patient cohorts (standard dosing vs dosing via Bayesian algorithms). The group of Bayesian algorithms received substantially higher and significantly heterogeneous doses, with an absence of nephrotoxicity.

Transcriptomic profiling of an evolved Yarrowia lipolytica strain: tackling hexanoic acid fermentation to increase lipid production from short-chain fatty acids.

Background: Short-chain fatty acids (SCFAs) are cost-effective carbon sources for an affordable production of lipids. Hexanoic acid, the acid with the longest carbon chain in the SCFAs pool, is produced in anaerobic fermentation of organic residues and its use is very challenging, even inhibiting oleaginous yeasts growth.

Results: In this investigation, an adaptive laboratory evolution (ALE) was performed to improve Yarrowia lipolytica ACA DC 50109 tolerance to high hexanoic acid concentrations.

Transcriptomic profiles and diagnostic biomarkers in the Mediterranean seagrasses Posidonia oceanica and Cymodocea nodosa reveal mechanistic insights of adaptative strategies upon desalination brine stress.

Seawater desalination by reverse osmosis is growing exponentially due to water scarcity. Byproducts of this process (e.g.

Understanding political divisiveness using online participation data from the 2022 French and Brazilian presidential elections.

Digital technologies can augment civic participation by facilitating the expression of detailed political preferences. Yet, digital participation efforts often rely on methods optimized for elections involving a few candidates. Here we present data collected in an online experiment where participants built personalized government programmes by combining policies proposed by the candidates of the 2022 French and Brazilian presidential elections.

Traction-related complications in hip arthroscopy for 26 years. A systematic review.

The primary aim of the study is to determine the rate of traction-related complications in hip arthroscopy (HA) including perineal compression and distraction injuries, and the secondary objective is to report the incidence of complications in HA found on the studies selected by a systematic review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for data extraction from the PubMed and Cochrane databases obtained in February 2022. Reviewers extracted the title, author, date of publication, number of hips treated and number of complications describing the affected area, nerve and soft tissue injury related to traction.

Open (non-sterile) cultivations of Debaryomyces hansenii for recombinant protein production combining industrial side-streams with high salt content.

The halotolerant non-conventional yeast Debaryomyces hansenii can grow in media containing high concentrations of salt (up to 4 M), metabolize alternative carbon sources than glucose, such as lactose or glycerol, and withstand a wide range of temperatures and pH. These inherent capabilities allow this yeast to grow in harsh environments and use alternative feedstock than traditional commercial media. For example, D.

Stepwise emergence of the neuronal gene expression program in early animal evolution.

The assembly of the neuronal and other major cell type programs occurred early in animal evolution. We can reconstruct this process by studying non-bilaterians like placozoans. These small disc-shaped animals not only have nine morphologically described cell types and no neurons but also show coordinated behaviors triggered by peptide-secreting cells.

Fear-Avoidance Beliefs Are Associated with Pain Intensity and Shoulder Disability in Adults with Chronic Shoulder Pain: A Cross-Sectional Study.

Shoulder pain is one of the most common musculoskeletal conditions, and for people over 40 years old, it represents the musculoskeletal pain with the greatest impact on quality of life. Psychological factors, such as fear-avoidance beliefs, are associated with musculoskeletal pain, and several studies suggest that they can influence various treatment outcomes. Our objective was to explore the cross-sectional association between fear-avoidance beliefs and shoulder pain intensity and disability in subjects with chronic shoulder pain.

A risk assessment on Zostera chilensis, the last relict of marine angiosperms in the South-East Pacific Ocean, due to the development of the desalination industry in Chile.

Seagrasses, which are considered among the most ecologically valuable and endangered coastal ecosystems, have a narrowly limited distribution in the south-east Pacific, where Zostera chilensis is the only remaining relict. Due to water scarcity, desalination industry has grown in the last decades in the central-north coasts of Chile, which may be relevant to address in terms of potential impacts on benthic communities due to their associated high-salinity brine discharges to subtidal ecosystems. In this work, we assessed ecophysiological and cellular responses to desalination-extrapolable hypersalinity conditions on Z.

VCE-005.1, an hypoxia mimetic betulinic acid derivative, induces angiogenesis and shows efficacy in a murine model of traumatic brain injury.

One of the main global causes of mortality and morbidity is traumatic brain injury (TBI). Neuroinflammation and brain-blood barrier (BBB) disruption play a pivotal role in the pathogenesis of acute and chronic TBI onset. The activation of the hypoxia pathway is a promising approach for CNS neurodegenerative diseases, including TBI.

Ghost-arc geochemical anomaly at a spreading ridge caused by supersized flat subduction.

The Southern Atlantic-Southwest Indian ridges (SASWIR) host mid-ocean ridge basalts with a residual subduction-related geochemical fingerprint (i.e., a ghost-arc signature) of unclear origin.

Levels of Pro-Inflammatory and Bone-Resorptive Mediators in Periodontally Compromised Patients under Orthodontic Treatment Involving Intermittent Forces of Low Intensities.

During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended.

Mobile-phone text messaging to promote ideal cardiovascular health in women.

Objective: Ideal cardiovascular health (CVH) was developed to promote CVH as a key component of primordial prevention. Mobile short message service (SMS) is useful for improving health behaviours. We aim to test the effectiveness of SMS intervention in women to improve CVH.

Utilization of salt-rich by-products from the dairy industry as feedstock for recombinant protein production by Debaryomyces hansenii.

The dairy industry processes vast amounts of milk and generates high amounts of secondary by-products, which are still rich in nutrients (high Chemical Oxygen Demand (COD) and Biochemical Oxygen Demand (BOD) levels) but contain high concentrations of salt. The current European legislation only allows disposing of these effluents directly into the waterways with previous treatment, which is laborious and expensive. Therefore, as much as possible, these by-products are reutilized as animal feed material and, if not applicable, used as fertilizers adding phosphorus, potassium, nitrogen, and other nutrients to the soil.

Daily changes on seasonal ecophysiological responses of the intertidal brown macroalga : Implications of climate change.

Global climate change is expected to have detrimental effects on coastal ecosystems, with impacts observable at the local and regional levels, depending on factors such as light, temperature, and nutrients. Shifts in dominance between primary producers that can capitalize on carbon availability for photosynthesis will have knock-on effects on marine ecosystems, affecting their ecophysiological responses and biological processes. Here, we study the ecophysiological vulnerability, photoacclimation capacity, and tolerance responses as ecophysiological responses of the intertidal kelp (Phaeophyceae, Laminariales) during a year through different seasons (autumn, winter, spring, and summer) in the Pacific Ocean (central Chile).

Adar-mediated A-to-I editing is required for embryonic patterning and innate immune response regulation in zebrafish.

Adenosine deaminases (ADARs) catalyze the deamination of adenosine to inosine, also known as A-to-I editing, in RNA. Although A-to-I editing occurs widely across animals and is well studied, new biological roles are still being discovered. Here, we study the role of A-to-I editing in early zebrafish development.

Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency.

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V).

A cannabidiol aminoquinone derivative activates the PP2A/B55α/HIF pathway and shows protective effects in a murine model of traumatic brain injury.

Background: Traumatic brain injury (TBI) is characterized by a primary mechanical injury and a secondary injury associated with neuroinflammation, blood-brain barrier (BBB) disruption and neurodegeneration. We have developed a novel cannabidiol aminoquinone derivative, VCE-004.8, which is a dual PPARγ/CB agonist that also activates the hypoxia inducible factor (HIF) pathway.

Brain lesions associated with eosinophilia. A useful clue for neurotoxocariasis. Report of one case.

Neurotoxocariasis is uncommon. Its manifestations include events of meningitis, encephalitis and less frequently vasculitis, which manifest as headache, seizures, focalization, confusion, cognitive alterations and /or fever. Peripheral eosinophilia with clinical and neurological imaging elements, allow its early suspicion.

A phylogenetic and proteomic reconstruction of eukaryotic chromatin evolution.

Histones and associated chromatin proteins have essential functions in eukaryotic genome organization and regulation. Despite this fundamental role in eukaryotic cell biology, we lack a phylogenetically comprehensive understanding of chromatin evolution. Here, we combine comparative proteomics and genomics analysis of chromatin in eukaryotes and archaea.

Debaryomyces hansenii: an old acquaintance for a fresh start in the era of the green biotechnology.

The halophilic yeast Debaryomyces hansenii has been studied for several decades, serving as eukaryotic model for understanding salt and osmotic tolerance. Nevertheless, lack of consensus among different studies is found and, sometimes, contradictory information derived from studies performed in very diverse conditions. These two factors hampered its establishment as the key biotechnological player that was called to be in the past decade.