Intestinal stem cells (ISCs) fuel the lifelong self‐renewal of the intestinal tract and are paramount for epithelial repair. In this context, the Wnt pathway component LGR5 is the most consensual ISC marker to date. Still, the effort to better understand ISC identity and regulation remains a challenge. We have generated a Mex3a knockout mouse model and show that this RNA‐binding protein is crucial for the maintenance of the Lgr5+ ISC pool, as its absence disrupts epithelial turnover during postnatal development and stereotypical organoid maturation ex vivo. Transcriptomic profiling of intestinal crypts reveals that Mex3a deletion induces the peroxisome proliferator‐activated receptor (PPAR) pathway, along with a decrease in Wnt signalling and loss of the Lgr5+ stem cell signature. Furthermore, we identify PPARγ activity as a molecular intermediate of MEX3A‐mediated regulation. We also show that high PPARγ signalling impairs Lgr5+ ISC function, thus uncovering a new layer of post‐transcriptional regulation that critically contributes to intestinal homeostasis.

Stroke is a leading cause of death and disability worldwide. Stroke prevention, early diagnosis, and efficient acute treatment are priorities to successfully impact stroke death and disability. Fluid biomarkers may improve stroke differential diagnostic, patient stratification for acute treatment, and post‐stroke individualized rehabilitation. In the present work, we characterized the use of stroke animal models in fluid biomarker research through a systematic review of PubMed and Scopus databases, followed by a literature review on the translation to the human stroke care setting and future perspectives in the field. We found increasing numbers of publications but with limited translation to the clinic. Animal studies are very heterogeneous, do not account for several human features present in stroke, and, importantly, only a minority of such studies used human cohorts to validate biomarker findings. Clinical studies have found appealing candidates, both protein and circulating nucleic acids, to contribute to a more personalized stroke care pathway. Still, brain tissue complexity and the fact that different brain pathologies share lesion biomarkers make this task challenging due to biomarker low specificity. Moreover, the study design and lack of validation cohorts may have precluded a formal integration of biomarkers in different steps of stroke diagnosis and treatment. To overcome such issues, recent pivotal studies on biomarker dynamics in individual patients are providing added value to diagnosis and anticipating patients' early prognosis. Presently, the most consistent protein biomarkers for stroke diagnosis and short‐ and long‐term prognosis are associated with tissue damage at neuronal (TAU), axonal (NFL), or astroglial (GFAP and S100β) levels. Most promising nucleic acids are microRNAs (miR), due to their stability in plasma and ease of access. Still, clinical validation and standardized quantitation place them a step behind compared protein as stroke biomarkers. Ultimately, the definition of clinically relevant biomarker panels and optimization of fast and sensitive biomarker measurements in the blood, together with their combination with clinical and neuroimaging data, will pave the way toward personalized stroke care.

Stroke is a leading cause of death and disability in the world. To address such a problem, early diagnosis and tailored acute treatment represent one of the major priorities in acute stroke care. Since the efficacy of reperfusion treatments is highly time-dependent, there is a critical need to optimize procedures for faster and more precise diagnosis. We provide a concise review of the most relevant and well-documented blood–protein biomarkers that exhibit greater potential for translational to clinical practice in stroke differential diagnosis and to differentiate ischemic stroke from hemorrhagic stroke, followed by an overview of the most recent point-of-care technological approaches to address this problem. The integration of fluid-based biomarker profiling, using point-of-care biosensors with demographic, clinical, and neuroimaging parameters in multi-dimensional clinical decision-making algorithms, will be the next step in personalized stroke care.

INTRODUCTIONWe investigated the effects of matrix type and reagent batch changes on diagnostic performances and longitudinal trajectories of brain‐derived tau (BD‐tau).METHODSWe evaluated (i) Cohort 1: paired EDTA plasma and serum from Alzheimer biomarker‐positive older adults versus controls (n = 26); and (ii) Cohort 2: n = 79 acute ischemic stroke patients with 265 longitudinal samples across four time points.RESULTSIn Cohort 1, plasma and serum BD‐tau were strongly correlated (rho = 0.96, p < 0.0001) with similar diagnostic performances (AUCs >99%) and correlations with CSF total‐tau (rho = 0.93–0.94, p < 0.0001). However, absolute concentrations were ∼40% higher in plasma versus serum. In Cohort 2, first and repeated BD‐tau measurements showed a near‐perfect correlation (rho = 0.96, p < 0.0001), with no significant between‐batch concentration differences. In longitudinal analyses, substituting ∼10% of the first‐run concentrations for the remeasured values showed overlapping estimated trajectories without significant differences at any time point.DISCUSSIONBD‐tau has equivalent diagnostic accuracies, but non‐interchangeable absolute concentrations, in plasma versus serum. Furthermore, the analytical robustness is unaffected by batch‐to‐batch reagent variations.Highlights Brain‐derived tau (BD‐tau) is a novel blood‐based biomarker that quantifies tau protein of CNS origin. Effects of preanalytical handling procedures on the quality and reproducibility of BD‐tau measures are unknown. In two cohorts of n = 105 participants, we compared BD‐tau concentrations and diagnostic performances in paired plasma and serum samples, and evaluated impacts of batch‐to‐batch reagent variations. Paired plasma and serum showed equivalent diagnostic performances to separate amyloid‐positive AD from amyloid‐negative controls, indicating both can be used independently. Repeated measurements and longitudinal trajectories of plasma BD‐tau were unaffected by batch‐to‐batch reagent variation.

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