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Background Recent ancient DNA studies uncovering large-scale demographic events in Iberia have presented very limited data for Portugal, a country located at the westernmost edge of continental Eurasia. Here, we present the most comprehensive collection of Portuguese ancient genome-wide data, from 67 individuals spanning 5000 years of human history, from the Neolithic to the nineteenth century. Results We identify early admixture between local hunter-gatherers and Anatolian-related farmers in Neolithic Portugal, with a northeastern–southwestern gradient of increasing Magdalenian-associated ancestry persistence in Iberia. This profile continues into the Chalcolithic, though Bell Beaker-associated sites reveal Portugal’s first evidence of Steppe-related ancestry. Such ancestry has a broader demographic impact during the Bronze Age, despite continuity of local Chalcolithic genetic ancestry and limited Mediterranean connections. The village of Idanha-a-Velha emerges in the Roman period as a site of significant migration and interaction, presenting a notably diverse genetic profile that includes North African and Eastern Mediterranean ancestries. The Early Medieval period is marked by the arrival of Central European genetic diversity, likely linked to migrations of Germanic tribes, adding to coeval local, African, and Mediterranean influences. The Islamic and Christian Conquest periods show strong genetic continuity in northern Portugal and significant additional African admixture in the south. The latter remains stable during the post-Islamic period, suggesting enduring African influences. Conclusions We reveal dynamic patterns of migration in line with cultural exchange across millennia, but also the persistence of local ancestries. Our findings integrate genetic information with historical and archeological data, enhancing our understanding of Iberia’s biological and cultural heritage.

The increasing demand for sustainable meat alternatives has driven research into edible insects as a protein source. This study developed and characterized hybrid hams using pork meat with 10% of Tenebrio molitor, 10% of Alphitobius diaperinus, or 5% of A. diaperinus plus 5% of T. molitor powders. The hybrid hams were analyzed for color, texture, nutritional composition, amino acid profile, antioxidant activity, and consumer acceptance. Results indicated that adding insect powder led to a darker color in hybrid hams. The protein content increased, reaching 49% in the 10% T. molitor and 46% in the 10% A. diaperinus formulations, compared to 35% in the control (without insect powder). Amino acid analysis of the 10% A. diaperinus formulation revealed higher concentrations of essential amino acids compared to the control, with threonine increasing by 185%, valine by 24% and histidine by 27%. Also, the inclusion of insect powders enhanced the mineral profile, mainly sodium, potassium, phosphorus, and sulfur. The total polyphenol content nearly doubled in the 10% A. diaperinus and mixed formulations. Additionally, sensory evaluation revealed that these formulations were well-accepted. These findings support the potential of edible insects as a sustainable and nutritious protein source for innovative food products.

In around 716 AD, the city of Santarém, Portugal, was conquered by the Berber and Arab armies that swept the Iberian Peninsula and went on to rule the region until the 12 th century. Archaeological excavations in 2007/08 discovered an Islamic necropolis (Avenida 5 de Outubro #2–8) that appears to contain the remains of an early Muslim population in Santarém (8 th – 10 th century). In this study, skeletal material from 58 adult individuals was analysed for stable carbon ( δ 13 C col ; δ 13 C ap ), nitrogen ( δ 15 N) and sulphur ( δ 34 S) isotope ratios in bones, and stable oxygen ( δ 18 O), carbon ( δ 13 C en ) and radiogenic strontium ( 87 Sr/ 86 Sr) isotopes in tooth enamel. The results of this study revealed a dietary pattern of predominantly C 3 -plant and domestic C 3 -fed herbivore consumption during adulthood ( δ 13 C col and δ 15 N, respectively) but a higher proportion of C 4 -plant input during childhood ( δ 13 C en ) for some individuals—interpreted as possible childhood consumption of millet porridge, a common practice in North Africa—in those with unorthodox burial types (Groups 1 and 2) that was not practiced in the individuals with canonical burials (Group 3). In this first mobility study of a medieval Muslim population in Portugal, δ 18 O DW values revealed greater heterogeneity in Groups 1 and 2, consistent with diverse origins, some in more humid regions than Santarém when compared to regional precipitation δ 18 O data, contrasting the more homogenous Group 3, consistent with the local precipitation δ 18 O range. Ancient DNA analysis conducted on three individuals revealed maternal (mtDNA) and paternal (Y-chromosome) lineages compatible with a North African origin for (at least) some of the individuals. Additionally, mobility of females in this population was higher than males, potentially resulting from a patrilocal social system, practiced in Berber and Arab communities. These results serve to offer a more detailed insight into the ancestry and cultural practices of early Muslim populations in Iberia.

Serpentina goat is an autochthonous breed from the Alentejo region in Southern Portugal. Meat from kids is a low‐fat protein food that meets consumer demand for healthier and leaner meat options. However, meat from older and heavier animals is less appreciated and often sold at low prices or processed. To promote adult goat meat value, a dry aging process in a bag permeable to water vapor was applied. Effects of aging on cooking loss and of aging and cooking on nutritional properties (minerals, protein, ashes, water content, fatty acids and total fat), pH, color, water activity, nutritional claims, reference intakes and nutrition declaration were investigated. Longissimus thoracis et lumborum from five female goats at the end of productive life (8–12 years) were aged 46 days at 2°C ± 2°C and 60%–90% relative humidity. Samples were analyzed after aging, trimming, and cooking in an oven at 150°C until core temperature reached 68°C. Both aging (yield of 72.61% ± 15.2%) and thermal processing led to increased pH values. Aged meat exhibited higher lightness and redness values than regular meat, but cooking increased brightness. In what concerns minerals, potassium content decreased significantly with aging (from 339 to 258 mg/100 g fresh weight), but did not significantly change when cooking the aged meat. The same was observed for magnesium, decreasing only with aging (from 24.7 to 15.2 mg/100 g fresh weight). Minerals like Ca, S and Cu did not change significantly with both processes. A higher concentration of total fatty acids was observed in aged meat, but cooking equalized values between meat samples, with 18:1c9 being the predominant. The n‐6/n‐3 ratio remained within recommended limits (< 4), generally recognized to have a positive impact on the human diet. Regarding nutritional claims, according to the Regulation (EC) n° 1924 (2006), Serpentina chevon can be considered as “high protein” and as “low saturated fat” food, with exception for the raw aged meat, slightly above the regulatory limit of 1.5/100 g of meat (1.645/100 g of meat). Both aging and cooking processes affected meat attributes, providing important information to optimize meat quality and consumer demands. Effects of dry aging‐in‐bag and thermal processes on the nutritional profile of Serpentina chevon were investigated. The results revealed significant differences in pH, color, mineral content and fatty acid composition, with the aged and cooked meat showing a profile within the recommended nutritional reference values. Results highlight the potential of dry aging to enhance the underused goat meat, promoting consumer acceptance and increasing nutritional quality.

Small extracellular vesicles (sEVs) have ∼30–200 nm diameter size and may act as carriers of different cargoes, depending on the cell of origin or on the physiological/pathological condition. As endogenous nanovesicles, sEVs are important in intercellular communication and have many of the desirable features of an ideal drug delivery system. sEVs are naturally biocompatible, with superior targeting capability, safety profile, nanometric size, and can be loaded with both lipophilic and hydrophilic agents. Because of their biochemical and physical properties, sEVs are considered a promising strategy over other delivery vehicles in the central nervous system (CNS) since they freely cross the blood-brain barrier and they can be directed to specific nerve cells, potentiating a more precise targeting of their cargo. In addition, sEVs remain stable in the peripheral circulation, making them attractive nanocarrier systems to promote neuroregeneration. This review focuses on the recent progress in methods for manufacturing, isolating, and engineering sEVs that can be used as a therapeutic strategy to overcome neurodegeneration associated with pathologies of the CNS, with particular emphasis on Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis diseases, as well as on brain tumors.

Background Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI). Methods A prospective, case–control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed. Results A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7–7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence rate of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences rates, respectively). Conclusion We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.

Alzheimer's disease (AD), a complex neurodegenerative disease associated with ageing, is the leading cause of dementia. Few people with early AD are eligible for the novel Food and Drug Administration (FDA)-approved drug treatments. Accordingly, new tools and early diagnosis markers are required to predict subtypes, individual stages, and the most suitable personalized treatment. We previously demonstrated that the regulation of microRNA (miR)-124 is crucial for proper neuronal function and microglia reshaping in human AD cell models. The aim of this study was to develop an efficient miR-124-3p-loaded exosome strategy and validate its therapeutic potential in using a multi-compartment microfluidic device of neuron-glia that recapitulates age-AD pathological features. Using cortical microglia from mouse pups, separated from glial mixed cultures and maintained for 2 days (stressed microglia), we tested the effects of SH-SY5Y-derived exosomes loaded with miR-124-3p mimic either by their direct transfection with Exo-Fect™ (ET124) or by their isolation from the secretome of miR-124 transfected cells (CT124). ET124 revealed better delivery effciency and higher potent effects in improving the stressed microglia status than CT124. Tricultures of human SH-SY5Y neuroblastoma cells (SH- ) were established in the presence of the human microglia cell line (HMC3) and immortalized human astrocytes (IM-HA) in tricompartmentalized microfluidic devices. Replacement of SH- cells with those transfected with APP695 (SH- ) in the tricultures and addition of low doses of hydrogen peroxide were used to simulate late-onset AD. The system mimicked AD-associated neurodegeneration and neuroinflammation processes. Notably, ET124 exhibited neuroprotective properties across the three cell types in the AD model by preventing neuronal apoptosis and neurite deficits, redirecting microglial profiles towards a steady state, and attenuating the inflammatory and miRNA fingerprints associated with astrocyte reactivity. To the best of our knowledge, this is the first study supporting the neuro- and immunoprotective properties of miR-124-engineered exosomes in a microfluidic triculture platform, recapitulating age-related susceptibility to AD. Our system offers potential to develop personalized medicines in AD patient subtypes.

Severe bacterial infections (SBI) have become less frequent in children with sickle cell disease (SCD) in the last decades. However, because of their potential risk of SBI, they usually receive empirical therapy with broad-spectrum antibiotics when they develop fever and are hospitalized in many cases. We performed a prospective study including 79 SCD patients with fever [median age 4.1 (1.7–7.5) years, 78.5% males; 17 of the episodes were diagnosed with SBI and 4 of them were confirmed] and developed a risk score for the prediction of SBI. The optimal score included CRP > 3 mg/dl, IL-6 > 125 pg/ml and hypoxemia, with an AUC of 0.91 (0.83–0.96) for the prediction of confirmed SBI and 0.86 (0.77–0.93) for possible SBI. We classified the patients in 3 groups: low, intermediate and high risk of SBI. Our risk-score-based management proposal could help to safely minimize antibiotic treatments and hospital admissions in children with SCD at low risk of SBI.

Microbial flora of portuguese chouriço (Alentejano (A) and Ribatejano (R)) with abnormal sensorial characteristics along shelf life was studied. Mesophilic anaerobic bacteria, enterococci, mesophilic sporeformers, coliforms, coagulase-positive staphylococci, sulphite reducing clostridia, Clostridium perfringens, moulds and yeasts were the most representative in both types of chouriço.

The intracellular mechanisms involved in the early phase of dendritic cell (DC) activation upon contact with chemical sensitizers are not well known. The strong skin sensitizer 2,4‐dinitrofluorobenzene (DNFB) was shown to induce the activation of mitogen‐activated protein kinases (MAPK) in DC. In the present study, we investigated a putative role for oxidative stress in DNFB‐induced MAPK activation and upregulation of the costimulatory molecule CD40. In a DC line generated from fetal mouse skin, DNFB induced a significant increase in protein oxidation, measured by the formation of carbonyl groups, while it had almost no effect on lipid peroxidation. The antioxidants glutathione and vitamin E, which inhibit protein and lipid oxidation, respectively, were used to assess the role of oxidative stress in DNFB‐induced MAPK activation. Glutathione, but not vitamin E, inhibited DNFB‐induced p38 MAPK and ERK1/2 phosphorylation, whereas none of the antioxidants interfered significantly with the DNFB‐induced upregulation of CD40 protein levels. Taken together, these results indicate that DNFB activates p38 MAPK and ERK1/2 via production of reactive oxygen species, and that protein oxidation plays an important role in MAPK activation.