CD163+ macrophages in mantle cell lymphoma induce activation of pro-survival pathways and immune suppression.

Mantle cell lymphoma (MCL) is dependent on a supportive tumor immune microenvironment (TIME), where infiltration of CD163+ macrophages has a negative prognostic impact. This study explores how abundance and spatial localization of CD163+ cells are associated with the biology of the MCL TIME. This is achieved through spatial multi-omic investigations of tumor and infiltrating CD163+ and CD3+ cells, respectively. We analyzed diagnostic MCL tissue from 100 patients. Sixty-three proteins were measured by GeoMx® digital spatial profiling in tissue microarrays. Regions of interests (ROIs) were selected in tumor-rich and tumor-sparse tissue regions. Molecular profiling of CD163+ macrophage segments, CD20+ MCL tumor cell segments and CD3+ T-cell segments was performed. To validate protein profiles, 1811 mRNAs were measured in CD20+ cells and two subsets of T-cells. Image analysis was used to extract the phenotype and position of each targeted cell allowing exploration of cell frequencies and cellular neighborhoods. Proteomic investigations revealed that CD163+ cells modulate their immune profile depending on the localization and that the immune inhibitory molecules VISTA and B7-H3 have higher expression in tumor-sparse versus tumor-rich tissue regions and targeting should be explored. We show that MCL tissues with more abundant infiltration of CD163+ cells have a higher expression of key components of the mitogen-activated protein kinase (MAPK) pathway, which was validated by complementary mRNA analyses. Thus, the MAPK pathway may be a feasible therapeutic target in MCL patients with CD163+ cell infiltration. We further show the independent and combined prognostic value of CD11c and CD163 beyond established risk factors.

Quantification and Profiling of Early and Late Differentiation Stage T Cells in Mantle Cell Lymphoma Reveals Immunotherapeutic Targets in Subsets of Patients.

With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue (n = 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (TH) cells and cytotoxic (TC) cells of early (CD57-) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. TC and CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a higher expression of several key immune suppressive proteins, tentatively controlling T-cell expansion in regions close to the tumor. We revealed that T cells in late differentiation stages (CD57+) are enriched among MCL infiltrating T cells and are predictive of an increased expression of immune suppressive markers. CD47, IDO1 and CTLA-4 were identified as potential targets for patients with T-cell-rich MCL TIME, while GITR might be a feasible target for MCL patients with sparse T-cell infiltration. In subgroups of patients with a high degree of CD57+ TC-cell infiltration, several immune checkpoint inhibitors, including TIGIT, PD-L1 and LAG3 were increased, emphasizing the immune-suppressive features of this highly differentiated T-cell subset not previously described in MCL.

Mesenchymal stem cell secretome for regenerative medicine: Where do we stand?

BACKGROUND: Mesenchymal stem cell (MSC)-based therapies have yielded beneficial effects in a broad range of preclinical models and clinical trials for human diseases. In the context of MSC transplantation, it is widely recognized that the main mechanism for the regenerative potential of MSCs is not their differentiation, with in vivo data revealing transient and low engraftment rates. Instead, MSCs therapeutic effects are mainly attributed to its secretome, i.e., paracrine factors secreted by these cells, further offering a more attractive and innovative approach due to the effectiveness and safety of a cell-free product. AIM OF REVIEW: In this review, we will discuss the potential benefits of MSC-derived secretome in regenerative medicine with particular focus on respiratory, hepatic, and neurological diseases. Both free and vesicular factors of MSC secretome will be detailed. We will also address novel potential strategies capable of improving their healing potential, namely by delivering important regenerative molecules according to specific diseases and tissue needs, as well as non-clinical and clinical studies that allow us to dissect their mechanisms of action. KEY SCIENTIFIC CONCEPTS OF REVIEW: MSC-derived secretome includes both soluble and non-soluble factors, organized in extracellular vesicles (EVs). Importantly, besides depending on the cell origin, the characteristics and therapeutic potential of MSC secretome is deeply influenced by external stimuli, highlighting the possibility of optimizing their characteristics through preconditioning approaches. Nevertheless, the clarity around their mechanisms of action remains ambiguous, whereas the need for standardized procedures for the successful translation of those products to the clinics urges.

Adherence to the Mediterranean Diet, Sodium and Potassium Intake in People at a High Risk of Dementia.

Adequate sodium and potassium intake, along with adherence to the Mediterranean diet (MedDiet), are key factors for preventing hypertension and cerebrovascular diseases. However, data on the consumption of these nutrients within the MedDiet are scarce. This cross-sectional study aims to assess the association between MedDiet adherence and sodium/potassium intake in the MIND-Matosinhos randomized controlled trial, targeting Portuguese adults at a high risk of dementia. Good adherence to the MedDiet was defined using the Portuguese Mediterranean Diet Adherence Screener questionnaire (≥10 points), and both sodium/potassium intakes were estimated from 24-hour urine collections. The association between MedDiet adherence and these nutrients' intake (dichotomized by the median) was quantified by calculating odds ratios (OR) and respective 95% confidence intervals (95% CI) using a logistic regression. A total of 169 individuals (60.9% female; median age: 70 years; range: 36-85 years) were included. Good adherence to the MedDiet was observed among 18.3% of the sample. After adjusting for sex, age, education and using antihypertensive drugs, good MedDiet adherence was associated with higher sodium (OR = 3.11; 95% CI: 1.27-7.65) and potassium intake (OR = 9.74; 95% CI: 3.14-30.26). Increased adherence to the MedDiet may contribute to a higher potassium intake but seems to have limited effects on the adequacy of sodium levels.

De Novo Biosynthesis of Curcumin in Saccharomyces cerevisiae.

Curcumin, a natural polyphenol derived from turmeric, has attracted immense interest due to its diverse pharmacological properties. Traditional extraction methods from Curcuma longa plants present limitations in meeting the growing demand for this bioactive compound, giving significance to its production by genetically modified microorganisms. Herein, we have developed an engineered Saccharomyces cerevisiae to produce curcumin from glucose. A pathway composed of the 4-hydroxyphenylacetate 3-monooxygenase oxygenase complex from Pseudomonas aeruginosa and Salmonella enterica, caffeic acid O-methyltransferase from Arabidopsis thaliana, feruloyl-CoA synthetase from Pseudomonas paucimobilis, and diketide-CoA synthase and curcumin synthase from C. longa was introduced in a p-coumaric acid overproducing S. cerevisiae strain. This strain produced 240.1 ± 15.1 µg/L of curcumin. Following optimization of phenylpropanoids conversion, a strain capable of producing 4.2 ± 0.6 mg/L was obtained. This study reports for the first time the successful de novo production of curcumin in S. cerevisiae.

dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe.

The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA-directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines. PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. PIAS2b depletion promotes mitotic catastrophe at prophase. High-throughput proteomics reveals the proteasome (PSMC5) and spindle cytoskeleton (TUBB3) to be direct targets of PIAS2b SUMOylation at mitotic initiation. These results identify PIAS2b-dsRNAi as a promising therapy for ATC and other aggressive anaplastic carcinomas.

TERRA ONTseq: a long-read-based sequencing pipeline to study the human telomeric transcriptome.

The long noncoding RNA TERRA is transcribed from telomeres in virtually all eukaryotes with linear chromosomes. In humans, TERRA transcription is driven in part by promoters comprising CpG dinucleotide-rich repeats of 29 bp repeats, believed to be present in half of the subtelomeres. Thus far, TERRA expression has been analyzed mainly using molecular biology-based approaches that only generate partial and somehow biased results. Here, we present a novel experimental pipeline to study human TERRA based on long-read sequencing (TERRA ONTseq). By applying TERRA ONTseq to different cell lines, we show that the vast majority of human telomeres produce TERRA and that the cellular levels of TERRA transcripts vary according to their chromosomes of origin. Using TERRA ONTseq, we also identified regions containing TERRA transcription start sites (TSSs) in more than half of human subtelomeres. TERRA TSS regions are generally found immediately downstream from 29 bp repeat-related sequences, which appear to be more widespread than previously estimated. Finally, we isolated a novel TERRA promoter from the highly expressed subtelomere of the long arm of Chromosome 7. With the development of TERRA ONTseq, we provide a refined picture of human TERRA biogenesis and expression and we equip the scientific community with an invaluable tool for future studies.

Risk of chronic kidney disease in 260 patients with lupus nephritis-analysis of a nationwide multicentre cohort with up to 35 years of follow-up.

OBJECTIVES: To compare proliferative (PLN) and membranous (MLN) lupus nephritis (LN) regarding clinical and laboratory presentation and long-term outcomes; To investigate predictors of progression to chronic kidney disease (CKD). METHODS: Multicentre observational study, with retrospective analysis of a prospective cohort, using data from the Rheumatic Diseases Portuguese Registry-Reuma.pt. Patients with biopsy-proven PLN, MLN and mixed LN were included. Cox regression survival analysis was used to investigate predictors of CKD. RESULTS: 260 patients were included. Median follow-up was 8 years (IQR 11; minimum 1, maximum 35 years). MLN patients presented with significantly lower serum creatinine (0.70 (IQR 0.20; minimum 0.50, maximum 1.30) mg/dl vs 0.80 (IQR 0.31; minimum 0.26, maximum 2.60) in PLN, p= 0.003). Proteinuria levels did not differ between groups (p= 0.641). Levels of complement were reduced in PLN but nearly normal in MLN patients, and there were fewer patients with positive anti-dsDNA antibodies in the MLN group (p< 0.001). One year after the beginning of treatment, 62% of the patients achieved EULAR/ERA-EDTA complete response, with further 5% achieving partial response. Patients with lower proteinuria at diagnosis were more likely to achieve a complete renal response at one year, however, proteinuria at diagnosis or at one year did not predict long term CKD. Estimated glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 at one year was the strongest predictor of progression to CKD (HR 23 [95% CI 8-62], p< 0.001). Other possible predictors included the use of azathioprine for induction of remission, older age at diagnosis and male sex. CONCLUSION: Proteinuria levels did not predict LN histologic class in our cohort. eGFR cutoff of 75 mL/min/1.73 m2 after one year of treatment was strongly predictive of progression to CKD.

The impact of digital media on sexuality: a descriptive and qualitative study.

The beliefs about Digital Information and Communication Media (DM) impact on sexuality by people from the community are an essential field to understanding people's sexual behaviours and their response to others' sexuality. This cross-sectional, online, descriptive, qualitative study, developed in the context of the celebration of National Sexual Health Day in Portugal, intended to identify the reasons and the activities using DM related to sexuality and explore participant's beliefs about the impact of DM on sexuality. In August 2021, a convenience sample of 167 people (M = 40.01; SD = 14.67; range 19-75 years old) completed an online survey that was disseminated through social networks and that included two closed questions about internet use and an open question about their personal beliefs about the impact of DM on sexual health. The results showed that most participants were motivated to use DM to search for erotic content (51.5%). DMs are also regularly used for educational purposes, such as seeking information about sexual pleasure and satisfaction (46.1%). Regarding qualitative data, three themes were identified concerning the impact of DM on sexuality: YES, IT'S SEX, SO WHAT?, I'M MORE VULNERABLE NOW! and SEXUAL EXPANSION. DM is an indisputable resource in sexual health, like in other dimensions of health. Still, it may facilitate exposure to contexts of aggression with a harmful impact on mental health, especially for younger people. Taken together, our results reveal that sexuality is part of DM use, and people share beliefs that indicate they may be actively involved in diminishing its hazards and benefiting from its potential.

Carbon Dots: A Bright Future as Anticounterfeiting Encoding Agents.

Counterfeit products and data vulnerability present significant challenges in contemporary society. Hence, various methods and technologies are explored for anticounterfeiting encoding, with luminescent tracers, particularly luminescent carbon dots (CDs), emerging as a notable solution. CDs offer promising contributions to product security, environmental sustainability, and the circular economy. This critical review aims to highlight the luminescence responsiveness of CDs to physical and chemical stimuli, achieved through nanoengineering their chemical structure. The discussion will delve into the various tunable luminescence mechanisms and decay times of CDs, investigating preferential excitations such as up-conversion, delayed fluorescence, fluorescence, room temperature phosphorescence, persistent luminescence, energy and charge transfer, as well as photo-chemical interactions. These insights are crucial for advancing anticounterfeiting solutions. Following this exploration, a systematic review will focus on the research of luminescent CDs' smart encoding applications, encompassing anticounterfeiting, product tracing, quality certification, and information encryption. Finally, the review will address key challenges in implementing CDs-based technology, providing specific insights into strategies aimed at maximizing their stability and efficacy in anticounterfeiting encoding applications.

MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation and TP53/p53 - a Nordic Lymphoma Group study.

The transcription factor MYC is a well-described oncogene with an important role in lymphomagenesis, but its significance for clinical outcome in mantle cell lymphoma (MCL) remains to be determined. We performed an investigation of the expression of MYC protein in a cohort of 251 MCL patients complemented by analyses of structural aberrations and mRNA, in a sub-cohort of patients. Fourteen percent (n=35) of patients showed high MYC protein expression with >20% positive cells (MYChigh), among whom only one translocation was identified, and 86% (n=216) of patients showed low MYC protein expression. Low copy number gains of MYC were detected in ten patients, but with no correlation to MYC protein levels. However, MYC mRNA levels correlated significantly to MYC protein levels with a R2 value of 0.76. Patients with a MYChigh tumor had both an independent inferior overall survival and an inferior progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.2-3.4 and HR=2.2, 95% CI: 1.04-4.6, respectively) when adjusted for additional high-risk features. Patients with MYChigh tumors also tended to have additional high-risk features and to be older at diagnosis. A subgroup of 13 patients had concomitant MYChigh expression and TP53/p53 alterations and a substantially increased risk of progression (HR=16.9, 95% CI: 7.4-38.3) and death (HR=7.8, 95% CI: 4.4-14.1) with an average overall survival of only 0.9 years. In summary, we found that at diagnosis a subset of MCL patients (14%) overexpressed MYC protein, and had a poor prognosis but that MYC rearrangements were rare. Tumors with concurrent MYC overexpression and TP53/p53 alterations pinpointed MCL patients with a dismal prognosis with a median overall survival of less than 3 years. We propose that MYC needs to be assessed beyond the current high-risk factors in MCL in order to identify cases in need of alternative treatment.

Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony.

Arsenic and antimony are metalloids with profound effects on biological systems and human health. Both elements are toxic to cells and organisms, and exposure is associated with several pathological conditions including cancer and neurodegenerative disorders. At the same time, arsenic- and antimony-containing compounds are used in the treatment of multiple diseases. Although these metalloids can both cause and cure disease, their modes of molecular action are incompletely understood. The past decades have seen major advances in our understanding of arsenic and antimony toxicity, emphasizing genotoxicity and proteotoxicity as key contributors to pathogenesis. In this review, we highlight mechanisms by which arsenic and antimony cause toxicity, focusing on their genotoxic and proteotoxic effects. The mechanisms used by cells to maintain proteostasis during metalloid exposure are also described. Furthermore, we address how metalloid-induced proteotoxicity may promote neurodegenerative disease and how genotoxicity and proteotoxicity may be interrelated and together contribute to proteinopathies. A deeper understanding of cellular toxicity and response mechanisms and their links to pathogenesis may promote the development of strategies for both disease prevention and treatment.

Revisiting Oral Antiseptics, Microorganism Targets and Effectiveness.

A good oral health status is mostly dependent on good oral hygiene habits, which knowingly impacts systemic health. Although controversial, chemical oral antiseptics can be useful in adjunct use to mechanical dental plaque control techniques in the prevention and management of local and overall health and well-being. This review aims to revisit, gather and update evidence-based clinical indications for the use of the most popular oral antiseptics, considering different types, microorganism targets and effectiveness in order to establish updated clinical recommendations.

[The Impact of CFTR Modulating Therapy on Chronic Lung Infection in Patients with Cystic Fibrosis]. / O Impacto da Terapêutica Moduladora da CFTR na Infeção Pulmonar Crónica em Doentes com Fibrose Quística.

Cystic fibrosis is the most common lethal genetic disease in the white population, affecting approximately 80 000 people worldwide. It is an autosomal recessive, monogenic, and multisystemic disease, with over 2000 mutations described in the CFTR protein gene. The dysfunction of this protein leads to a decrease in the secretion of chlorine and bicarbonate, sodium hyperabsorption, and consequent water absorption, resulting in the thickening of secretions and accumulation of pathogens. These changes culminate in inflammation, chronic pulmonary infection, and recurrent exacerbations, with lung disease being the main cause of morbidity and mortality. In the early stages of the disease, Staphylococcus aureus is generally the agent responsible for chronic infection. Over time, Pseudomonas aeruginosa becomes more prevalent, being the most frequent bacteria in adults. However, in up to 70% of patients, colonization is polymicrobial, with frequent isolation of S. aureus and P. aeruginosa, associated with Haemophilus influenzae or Streptococcus pneumoniae, as well as isolation of other bacterial agents, viruses, or fungi. In recent years, drugs modulating CFTR have been developed which have shown a positive effect on lung function, body mass index, exacerbation rate, chlorine concentration, and quality of life. Currently, four drugs are approved that act by improving the function or increasing the amount of protein produced and consequently the ion transport. [...].

A fibrose quística é a doença genética letal mais comum na população branca, afetando aproximadamente 80 000 pessoas em todo o mundo. É uma doença autossómica recessiva, monogenética e multissistémica, estando descritas mais de 2000 mutações no gene da proteína CFTR. A disfunção desta proteína leva à diminuição da secreção de cloro e de bicarbonato, hiperabsorção de sódio e consequentemente de água, resultando no espessamento das secreções e acumulação de agentes patogénicos. Estas alterações culminam em inflamação, infeção pulmonar crónica e agudizações recorrentes, sendo a doença pulmonar a principal causa de morbilidade e mortalidade. Nas fases iniciais da doença, o Staphylococcus aureus é, geralmente, o agente responsável pela infeção crónica. Com o tempo, a Pseudomonas aeruginosa vai adquirindo um papel mais preponderante, sendo a bactéria mais frequente nos adultos. Contudo, em até 70% dos doentes, a colonização é polimicrobiana, sendo frequente o isolamento de S. aureus e P. aeruginosa, associado a Haemophilus influenzae ou Streptococcus pneumoniae, bem como o isolamento de outros agentes bacterianos, vírus ou fungos. Nos últimos anos foram desenvolvidos fármacos moduladores da CFTR, que demonstraram efeito positivo na função pulmonar, índice de massa corporal, taxa de exacerbações, concentração de cloro e qualidade de vida. Atualmente, estão aprovados quatro fármacos que atuam melhorando a função ou aumentando a quantidade de proteína produzida e consequentemente o transporte dos iões. [...].

C-N linked donor type porphyrin derivatives: unrevealed hole-transporting materials for efficient hybrid perovskite solar cells.

A new series of Zn(II) and Cu(II)-based porphyrin complexes 5a and 5b doubly functionalised with carbazole units were developed to be used as hole-transporting materials (HTMs) in perovskite solar cells (PSCs). These complexes were obtained via a nucleophilic substitution reaction mediated by PhI(OAc)2/NaAuCl4·2H2O, or using C-N transition metal-assisted coupling. The hole extraction capability of 5a and 5b was assessed using cyclic voltammetry; this study confirmed the better alignment of the Zn(II) complex 5a with the perovskite valence band level, compared to the Cu(II) complex 5b. The optimised geometry and molecular orbitals of both complexes also corroborate the higher potential of 5a as a HTM. Photoluminescence characterisation showed that the presence of 5a and 5b as HTMs on the perovskite surface resulted in the quenching of the emission, matching the hole transfer phenomenon. The photovoltaic performance was evaluated and compared with those of reference cells made with the standard HTM spiro-OMeTAD. The optimised 5-based devices showed improvements in all photovoltaic characteristics; their open circuit voltage (Voc) reached close to 1 V and short-circuit current density (Jsc) values were 13.79 and 9.14 mA cm-2 for 5a and 5b, respectively, disclosing the effect of the metallic centre. A maximum power conversion efficiency (PCE) of 10.01% was attained for 5a, which is 65% of the PCE generated by using the spiro-OMeTAD reference. This study demonstrates that C-N linked donor-type porphyrin derivatives are promising novel HTMs for developing efficient and reproducible PSCs.

HDAC-6 inhibition ameliorates the early neuropathology in a mouse model of Krabbe disease.

Introduction: In Krabbe disease (KD), mutations in ß-galactosylceramidase (GALC), a lysosomal enzyme responsible for the catabolism of galactolipids, leads to the accumulation of its substrates galactocerebroside and psychosine. This neurologic condition is characterized by a severe and progressive demyelination together with neuron-autonomous defects and degeneration. Twitcher mice mimic the infantile form of KD, which is the most common form of the human disease. The Twitcher CNS and PNS present demyelination, axonal loss and neuronal defects including decreased levels of acetylated tubulin, decreased microtubule stability and impaired axonal transport. Methods: We tested whether inhibiting the α-tubulin deacetylase HDAC6 with a specific inhibitor, ACY-738, was able to counteract the early neuropathology and neuronal defects of Twitcher mice. Results: Our data show that delivery of ACY-738 corrects the low levels of acetylated tubulin in the Twitcher nervous system. Furthermore, it reverts the loss myelinated axons in the sciatic nerve and in the optic nerve when administered from birth to postnatal day 9, suggesting that the drug holds neuroprotective properties. The extended delivery of ACY-738 to Twitcher mice delayed axonal degeneration in the CNS and ameliorated the general presentation of the disease. ACY-738 was effective in rescuing neuronal defects of Twitcher neurons, stabilizing microtubule dynamics and increasing the axonal transport of mitochondria. Discussion: Overall, our results support that ACY-738 has a neuroprotective effect in KD and should be considered as an add-on therapy combined with strategies targeting metabolic correction.

Interactive effects of palladium (Pd) and microplastics (MPs) on metal bioaccumulation and biological responses in the Mediterranean mussel, Mytilus galloprovincialis.

This study investigates the potential of MPs as carriers of pollutants as they can strengthen bioaccumulation of toxic metals on marine organisms. For the first time, the interaction of the metal palladium (Pd) with the widespread MPs, both with increasing concentrations in water environments from anthropogenic sources, was tested. Mytilus galloprovincialis, an important seafood product, was exposed to Pd (24 h) in two ways: water-dissolved and MPs-adsorbed, with depuration followed for 144 h. Quantification of Pd in tissues shown an accumulation 2-3 times higher (59 % of initial Pd) for mussels exposed to MPs-adsorbed Pd and higher in digestive gland than when exposed to water-dissolved Pd (25 %; higher in gills). Additionally, it was demonstrated that Pd induced oxidative stress and altered the feeding behavior of mussels. Therefore, this work support MPs as being vectors of metals (i.e. Pd) to enhance their bioaccumulation on marine organisms which highlights ecological risk of these emerging pollutants.

Chemical and Bioactive Screening of Green Polyphenol-Rich Extracts from Chestnut By-Products: An Approach to Guide the Sustainable Production of High-Added Value Ingredients.

Opportunities for the valorisation of agro-industrial residues of the chestnut (Castanea sativa Mill.) production chain have been fostered with the production of multifunctional polyphenol-rich extracts with the potential to be introduced as natural additives or active components in several products. Nonetheless, it is crucial to explore the feasibility of different extracts from the various by-products for these applications through the exhaustive study of their composition and bioactivities without losing sight of the sustainable character of the process. This work aimed at the screening of the phenolic compound composition and bioactivities of different green extracts of chestnut burs, shells and leaves, as the first step to establish their potential application as natural ingredients, primarily as food preservatives. To this end, maceration (MAC) as a conventional extraction method besides ultrasound and microwave-assisted extractions (UAE and MAE) was employed to obtain the extracts from chestnut by-products using water (W) and hydroethanolic solution (HE) as solvents. Phenolic compounds were analysed by HPLC-DAD-(ESI-)MS/MS; the antioxidant capacity was assessed by colourimetric assays, and the antimicrobial activity was evaluated against several strains of food-borne bacteria and fungi. The leaf extracts obtained by MAC-HE and UAE-HE presented the highest concentration of phenolic compounds (70.92 ± 2.72 and 53.97 ± 2.41 mg.g-1 extract dw, respectively), whereas, for burs and shells, the highest recovery of total phenolic compounds was achieved by using UAE-HE and UAE-W (36.87 ± 1.09 and 23.03 ± 0.26 mg.g-1 extract dw, respectively). Bis-HHDP-glucose isomers, chestanin and gallic acid were among the most abundant compounds. Bur extracts (MAC-HE and UAE-HE) generally presented the highest antioxidant capacity as measured by TBARS, while the best results in DPPH and reducing power assays were found for shell extracts (MAE-W and MAC-HE). Promising antibacterial activity was noticed for the aqueous extracts of burs, leaves and hydroethanolic extracts of shells, with emphasis on the MAE-W extract of burs that showed bactericidal activity against E. cloacae, P. aeruginosa and S. aureus (MBC 5 mg.mL-1). Overall, it can be concluded that chestnut by-products, including burs, shells and leaves, are sources of polyphenolic compounds with significant antioxidant and antimicrobial activities. The choice of extraction method and solvent greatly influenced the composition and bioactivity of the extracts. These findings highlight the potential of chestnut by-products for the development of natural additives, particularly for food preservation, while also emphasizing the importance of sustainable utilization of agricultural waste materials. Further research is warranted to optimize extraction techniques and explore additional applications for these valuable bioactive compounds.

Metal(oid)s in plastic debris, with distinct features, from Spanish Mediterranean beaches with different anthropogenic pressure: Are these particles potential monitors for metal pollution?

Metal(oid)s concentrations have been quantified in plastic pieces collected from four beaches located in the Mediterranean coast of Spain with different characteristics (i.e. anthropogenic pressure, zone). Metal(oid)s content was also related to selected plastic criteria (i.e. color, degradation status, polymer). The selected elements were quantified with mean concentrations in the sampled plastics with the following order: Fe > Mg > Zn > Mn > Pb > Sr > As > Cu > Cr > Ni > Cd > Co. Moreover, black, brown, PUR, PS, and coastal line plastics concentrated the higher metal(oid)s levels. Local of sampling (influence of mining exploitation) and severe degradation were key factors for uptake of metal(oid)s from water by plastics as modification of surfaces strengths their adsorption capacity. Determined high levels of Fe, Pb and Zn in plastics reflected the pollution degree of the marine areas. Therefore, this study is a contribution for the potential use of plastics as pollution monitors.