Generation of human and murine exhausted CD8 T cells in vitro.

T cell exhaustion is a state of dysfunction that can occur due to persistent exposure to antigens, such as in the tumor microenvironment. The progressive loss of effector functions in exhausted T cells can lead to resistance to immune checkpoint inhibitors and adoptive cell immunotherapies. Improving our understanding of the exhaustion process is thus crucial for optimizing the clinical outcomes of immunotherapy.

Discovery of a potential open ocean nursery for the endangered shortfin mako shark in a global fishing hotspot.

Populations of large pelagic sharks are declining worldwide due to overfishing. Determining the overlap between shark populations and fishing activities is important to inform conservation measures. However, for many threatened sharks the whereabouts of particularly vulnerable life-history stages - such as pregnant females and juveniles - are poorly known.

Carbon-carbon bond formation and cleavage at redox active bis(pyridylimino)isoindole (BPI) germylene compounds.

Redox-active ligands provide alternative reaction pathways by facilitating redox events. Among these, tridentate bis(piridylimino)isoindole (BPI) fragments offer great potential, though their redox-active behaviour remains largely underdeveloped. We describe herein a family of BPI germanium(II) complexes and the study of their redox properties.

Cyclodehydrogenation of molecular nanographene precursors catalyzed by atomic hydrogen.

Atomically precise synthesis of graphene nanostructures on semiconductors and insulators has been a formidable challenge. In particular, the metallic substrates needed to catalyze cyclodehydrogenative planarization reactions limit subsequent applications that exploit the electronic and/or magnetic structure of graphene derivatives. Here, we introduce a protocol in which an on-surface reaction is initiated and carried out regardless of the substrate type.

It's all about scale: The landscape effect on avian haemosporidians.

Environmental characteristics drastically shape the host-parasite associations under natural conditions. This is the case of parasites such as avian haemosporidians which naturally infect birds and are transmitted by insect vectors. Landscape characteristics are known to determine the epidemiology of transmission of these parasites in the wild, but the strength of these factors may differ at different spatial scales.

Estimating SARS-CoV-2 Omicron XBB.1.5 Spike-Directed Functional Antibody Levels From an Anti-Receptor Binding Domain Wuhan-Hu-1-Based Commercial Immunoassay Results.

We investigated whether antibody concentrations measured in plasma using the Roche Elecsys® Anti-SARS-CoV-2 S assay (targeting the receptor binding domain, RBD) could estimate levels of Wuhan-Hu-1 and Omicron XBB.1.5 spike-directed antibodies with neutralizing ability (NtAb) or those mediating NK-cell activity.

Roles for the long non-coding RNA / in pancreatic beta cell function.

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of beta cell function. Here, we show that an lncRNA-transcribed antisense to Pax6, annotated as Pax6os1/PAX6-AS1, was upregulated by high glucose concentrations in human as well as murine beta cell lines and islets. Elevated expression was also observed in islets from mice on a high-fat diet and patients with type 2 diabetes.

Strong legacies of emerging trends in winter precipitation on the carbon-climate feedback from Arctic tundra.

Changes in winter precipitation accompanying emerging climate trends lead to a major carbon-climate feedback from Arctic tundra. However, the mechanisms driving the direction, magnitude, and form (CO and CH) of C fluxes and derived climate forcing (i.e.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

Staple principles for the definition of front-of-pack nutritional labels.

Front-of-pack nutrition labels (FOPNLs) have been developed since 1989 to curb the increasing prevalence of obesity and non-communicable diseases (NCDs) and to promote healthy consumption choices. While several countries have introduced their own labeling schemes on a voluntary basis, the European Commission aims to harmonize a FOPNL system that will be mandatory for all member states. This paper summarizes a contribution to the current debate on FOPNLs from Italian and Spanish researchers working in the fields of human nutrition, nutritional epidemiology and public health education and communication policy before the final decision on FOPNLs to become mandatory in Europe is taken.

Gut Microbiota Interacts with Dietary Habits in Screenings for Early Detection of Colorectal Cancer.

Background/objectives: Gut microbiota interacts with nutrients, which may be relevant to assigning a microbial signature to colorectal cancer (CRC). We aim to evaluate the potential of gut microbiota combined with dietary habits in the early detection of pathological findings related to CRC in the course of a screening program.

Methodology: The colonoscopy performed on 152 subjects positive for fecal occult blood test showed that 6 subjects had adenocarcinoma, 123 had polyps, and 23 subjects had no pathological findings.

Valorization of Coffee Cherry By-Products Through Fermentation by Human Intestinal Lactobacilli in Functional Fermented Milk Beverages.

During coffee production, the removal and disposal of the coffee bean-surrounding layers pose an environmental problem. In this work, we examined the effects of several aqueous coffee cherry extracts on the growth and metabolism, biofilm formation, antioxidant capacity and antimicrobial activity of six lactobacilli from the INIA collection and a commercial probiotic GG strain. Growth medium supplementation with different coffee cherry extracts (at 40%) stimulated strain growth and metabolism.

Optimization of a Pressurized Extraction Process Based on a Ternary Solvent System for the Recovery of Neuroprotective Compounds from Leaves.

Green chemistry focuses on reducing the environmental impacts of chemicals through sustainable practices. Traditional methods for extracting bioactive compounds from leaves, such as hydro-distillation and organic solvent extraction, have limitations, including long extraction times, high energy consumption, and potential toxic solvent residues. This study explored the use of supercritical fluid extraction (SFE), pressurized liquid extraction (PLE), and gas-expanded liquid (GXL) processes to improve efficiency and selectivity.

Aptamer-conjugated gold nanoparticles enable oligonucleotide delivery into muscle stem cells to promote regeneration of dystrophic muscles.

Inefficient targeting of muscle stem cells (MuSCs), also called satellite cells, represents a major bottleneck of current therapeutic strategies for muscular dystrophies, as it precludes the possibility of promoting compensatory regeneration. Here we describe a muscle-targeting delivery platform, based on gold nanoparticles, that enables the release of therapeutic oligonucleotides into MuSCs. We demonstrate that AuNPs conjugation to an aptamer against α7/β1 integrin dimers directs either local or systemic delivery of microRNA-206 to MuSCs, thereby promoting muscle regeneration and improving muscle functionality, in a mouse model of Duchenne Muscular Dystrophy.

Effects of Repeated Cisplatin and Monosodium Glutamate on Visceral Sensitivity in Rats.

Cisplatin, a chemotherapeutic drug, is known for causing gastrointestinal disorders and neuropathic pain, but its impact on visceral sensitivity is unclear. Monosodium glutamate (MSG) has been shown to improve gastrointestinal dysmotility and neuropathic pain induced by cisplatin in rats. This study aimed to determine if repeated cisplatin treatment alters visceral sensitivity and whether dietary MSG can prevent these changes.

Genetic Diversity and Relationships Among Tunisian Wild and Cultivated L. Species.

Assessing and determining genetic diversity in rose species is a crucial step for conservation efforts, the establishment of a core collection, and the development of new varieties. This study represents the first investigation of genetic diversity among various rose species at different ploidy levels in Tunisia, with the aim of elucidating the genetic structure of the genus. It encompasses both spontaneous and cultivated accessions, featuring local and introduced species recognized for their adaptability, ornamental value, and fragrance.

Acrylamide Exposure and Cardiovascular Risk: A Systematic Review.

Acrylamide is a food contaminant formed during high-temperature cooking processes, leading to unintentional human exposure. Diet is the primary source for non-smokers, with potatoes, cereals, and coffee being the main contributors. While animal studies have demonstrated that acrylamide is neurotoxic, genotoxic, mutagenic, and cardiotoxic, its effects on human cardiovascular health remain poorly understood.

Health and Liver Diagnostic Markers Influencing Glycemia in Subjects with Prediabetes: Preview Study.

Introduction: Glucose homeostasis may be dependent on liver conditions and influence health-related markers and quality of life (QoL) objective measurements. This study aimed to analyze the interactions of glycemia with liver and health status in a prediabetic population.

Subjects And Methods: This study included 2220 overweight/obese prediabetics from the multinational PREVIEW project.

Neuroinflammation in Age-Related Neurodegenerative Diseases: Role of Mitochondrial Oxidative Stress.

A shared hallmark of age-related neurodegenerative diseases is the chronic activation of innate immune cells, which actively contributes to the neurodegenerative process. In Alzheimer's disease, this inflammatory milieu exacerbates both amyloid and tau pathology. A similar abnormal inflammatory response has been reported in Parkinson's disease, with elevated levels of cytokines and other inflammatory intermediates derived from activated glial cells, which promote the progressive loss of nigral dopaminergic neurons.

Evaluation of a nanostructured CpG-ODN/ascorbyl palmitate as a safe and effective adjuvant for anticrotalic PLA2 serum.

Background: The WHO states that antivenom is the only safe and effective treatment to neutralize snake venom. Snakebite antivenom typically involves horse hyperimmunization with crude venom and Freund's adjuvant.

Methods: In the current work, we analyzed the ascorbyl palmitate liquid crystal structure with snake protein or PLA2, the carrier charge capacity, and we evaluated the immune response induced by the enzyme P9a(Cdt-PLA2) formulated in a nanostructure using CpG-ODN, determining the titer of IgG antibodies.

Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation: Rationale and Design for PRESTIGE-AF Trial.

Adequate secondary prevention in survivors of intracerebral hemorrhage (ICH) who also have atrial fibrillation (AF) is a long-standing clinical dilemma because these patients are at increased risk of recurrent ICH as well as of ischemic stroke. The efficacy and safety of oral anticoagulation, the standard preventive medication for ischemic stroke patients with AF, in ICH patients with AF are uncertain. PRESTIGE-AF is an international, phase 3b, multi-center, randomized, open, blinded end-point assessment (PROBE) clinical trial that compared the efficacy and safety of direct oral anticoagulants (DOACs) with no DOAC (either no antithrombotic treatment or any antiplatelet drug).

Mechanisms of recalcitrant fucoidan breakdown in marine Planctomycetota.

Marine brown algae produce the highly recalcitrant polysaccharide fucoidan, contributing to long-term oceanic carbon storage and climate regulation. Fucoidan is degraded by specialized heterotrophic bacteria, which promote ecosystem function and global carbon turnover using largely uncharacterized mechanisms. Here, we isolate and study two Planctomycetota strains from the microbiome associated with the alga Fucus spiralis, which grow efficiently on chemically diverse fucoidans.

Global Relative Importance of Denitrification and Anammox in Microbial Nitrogen Loss Across Terrestrial and Aquatic Ecosystems.

Denitrification and anaerobic ammonium oxidation (anammox) are the major microbial processes responsible for global nitrogen (N) loss. Yet, the relative contributions of denitrification and anammox to N loss across contrasting terrestrial and aquatic ecosystems worldwide remain unclear, hampering capacities to predict the human alterations in the global N cycle. Here, a global synthesis including 3240 observations from 199 published isotope pairing studies is conducted and finds that denitrification governs microbial N loss globally (79.

A multi-residue method based on solid phase extraction followed by HPLC-HRMS/MS analysis for the determination of dyes and additives released from polyester fibres after degradation.

Microfibres released from textiles are one of the most common types of microplastics (MPs) found in the environment. Whether they are synthetic or natural, they can undergo degradation in different environmental matrices. This may result in the leaching of a variety of chemicals, mainly textile dyes and additives of high toxicity that need to be regulated.