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Torque Teno Virus (TTV) is a single-stranded circular DNA virus which has been identified as a surrogate marker of immune competence in transplantation. In this study we investigated the dynamics of plasma TTV DNAemia in 79 adult patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory large B-cell lymphoma, also evaluating the impact of TTV on immunotoxicities, response and survival outcomes. After lymphodepleting therapy, TTV DNA load decreases slightly until reaching nadir around day 10, after which it increased steadily until reaching maximum load around day 90. TTV DNA load

Mass spectrometry (MS) can unlock crucial insights into the intricate world of glycosylation analysis. Despite its immense potential, the qualitative and quantitative analysis of isobaric glycopeptide structures remains one of the most daunting hurdles in the field of glycoproteomics. The ability to distinguish between these complex glycan structures poses a significant challenge, hindering our ability to accurately measure and understand the role of glycoproteins in biological systems. A few recent publications described the use of collision energy (CE) modulation to improve structural elucidation, especially for qualitative purposes. Different linkages of glycan units usually demonstrate different stabilities under CID/HCD fragmentation conditions. Fragmentation of the glycan moiety produces low molecular weight ions (oxonium ions) that can serve as a structure-specific signature for specific glycan moieties, however, specificity of these fragments has never been examined closely. Here, we investigated fragmentation specificity using synthetic stable isotope-labelled glycopeptide standards. These standards were isotopically labelled at the reducing terminal GlcNAc, which allowed us to resolve fragments produced by oligomannose core moiety and fragments generated from outer antennary structures. Our research identified the potential for false positive structure assignments due to the occurrence of “Ghost” fragments resulting from single glyco unit rearrangement or mannose core fragmentation within the collision cell. To mitigate this issue, we have established a minimal intensity threshold for these fragments to prevent the misidentification of structure-specific fragments in glycoproteomics analysis. Our findings provide a crucial step forward in the quest for more accurate and reliable glycoproteomics measurements.Graphical abstract

Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), with (cases) and without (control group) COVID-19 diagnosis, were paired to sex and age. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanic ventilation and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 269 axial SpA patients were included, of whom 165 (61.3%) with COVID-19 and 104 (38.7%) without COVID-19. Most of them were men (N = 153; 56.9%) with mean age of 46.3 ± 13.8 years and long-term disease (13.1 ± 9.9 years). There were no significant statistically differences concerning social distancing, smoking, BMI, waist circumference and comorbidities. Regarding b-DMARDs, 134 (75.3%) were on TNF inhibitors and 17 (9.6%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 45, 73.8% vs. n = 38, 73.1%, respectively; p = 0.93). In addition, disease activity was similar before and after the infection. On the other hand, the control group had significantly higher disease activity score, according to ASDAS-CRP (2.8 ± 1.8 vs. 1.8 ± 1.2, p = 0.03). Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.2 ± 3.6 days, with length of hospitalization quite similar between patients who died and those discharged (12.6 ± 7 and 13.9 ± 11.7, respectively). The global death estimation for COVID-19 was 1.9 (95%CI 0.6–4.3), regardless HLA-B27 status. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials – REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

The long-term clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has been little explored. A prospective multicenter registry-based cohort study conducted from December 2020 to July 2022 by the Spanish Transplant and Cell Therapy group, was used to analyze the relationship of antibody response over time after full vaccination (at 3-6 weeks, 3, 6 and 12 months) (2 doses) and of booster doses with breakthrough SARS-CoV-2 infection in 1551 patients with hematological disorders. At a median follow-up of 388 days after complete immunization, 266 out of 1551 (17%) developed breakthrough SARS-CoV-2 infection at median of 86 days (range 7-391) after full vaccination. The cumulative incidence was 18% [95% confidence interval (C.I.), 16-20%]. Multivariate analysis identified higher incidence in chronic lymphocytic leukemia patients (29%) and with the use of corticosteroids (24.5%), whereas female sex (15.5%) and more than 1 year after last therapy (14%) were associated with a lower incidence (p 0.05 for all comparisons). Median antibody titers at different time points were significantly lower in breakthrough cases than in non-cases. A serological titer cut-off of 250 BAU/mL was predictive of breakthrough infection and its severity. SARS-CoV-2 infection-related mortality was encouragingly low (1.9%) in our series. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant.

Background Covid-19 is associated with an increased risk of pulmonary embolism (PE) therefore, should the cut off d-dimer value be adjusted for these patients? Material and methods Retrospective and observational study to understand if there is a d-dimer cut-off that could guide clinics to perform a thoracic computed tomography angiography (CTA) in patients with covid-19. The population was covid-19 patients admitted to covid-19 dedicated wards of a University Hospital Centre for one year. Results and conclusions 725 (52%) patients with covid-19 had a d-dimer value dosed during the first 5 days of the disease. Those, 63 (9%) did a CTA with a diagnosis of 16 (25%) PE. Gender was equally represented, median age was 70 years (ID = 3.49) and the majority (94%) survived. Thirteen (81%) patients with PE had a d-dimer value above 2500 ng/mL (OR = 9.244, 95% CI 2.248–9.837), with 7 (54%) with values over 10000 ng/mL, but in 3 (9%) it was under 1500 ng/mL. Seventy-three (63%) of patients with a d-dimer over 1500 ng/mL did not had a thoracic CTA performed. In our population PE was not a frequent outcome. The results are influenced by the low number of thoracic CTA performed because, even tough the cut-off d-dimer value used at our hospital to perform a thoracic CTA to exclude PE is 1500 ng/mL, most patients with that d-dimer value did not take the exam and so PE could not be excluded. Although in most PE cases the d-dimer value was above 2500 ng/mL, the results of our study cannot verify if that is a better cut-off value.

The large production and widespread daily consumption of plastic materials—which began in the last century—together with the often-inadequate collection and recycling systems, have made plastics and, consequently, microplastics (MPs) ubiquitous pollutants [...]

Sleep is one of the most ubiquitous but also complex animal behaviors. It is regulated at the global, systems level scale by circadian and homeostatic processes. Across the 24-h day, distribution of sleep/wake activity differs between species, with global sleep states characterized by defined patterns of brain electric activity and electromyography. Sleep patterns have been most intensely investigated in mammalian species. The present review begins with a brief overview on current understandings on the regulation of sleep, and its interaction with aging. An overview on age-related variations in the sleep states and associated electrophysiology and oscillatory events in humans as well as in the most common laboratory rodents follows. We present findings observed in different studies and meta-analyses, indicating links to putative physiological changes in the aged brain. Concepts requiring a more integrative view on the role of circadian and homeostatic sleep regulatory mechanisms to explain aging in sleep are emerging.

espanolObjetivo: Realizar un estudio comparativo del proceso de clarificacion de un humedal natural usando dos coagulantes, sulfato de aluminio y cascara de papa (Solanum tuberosum L). Metodologia: Inicialmente se recolecto el residuo agroindustrial de diferentes establecimientos de comidas rapidas y restaurantes de la ciudad de Barranquilla donde, habitualmente, es descartado. La cascara de papa se sometio a lavado, secado y molienda. El polvo obtenido se tamizo y envaso hermeticamente en un frasco de vidrio para ser utilizado como coagulante. El sulfato de aluminio se obtuvo en el comercio. Las muestras de agua se recolectaron de la cienaga de Malambo mediante un muestreo simple. Para remover su turbidez se realizo un ensayo de jarras que simulo los procesos de coagulacion, floculacion y sedimentacion, teniendo como referencia los parametros establecidos en la NTC 3903 de 2010, usando cada coagulante. Resultados: El agua objeto de estudio tuvo una turbidez inicial de 59,60 UNT. La mayor remocion de este parametro se obtuvo con una dosis de 40 mg/L de sulfato de aluminio (92,51%); mientras que el coagulante natural removio 81,32% al emplear una dosis de 10 mg/L. Conclusiones: Se determino que las dosis de los coagulantes, sulfato de aluminio y cascara de papa, utilizados en esta investigacion influyeron sobre la turbidez del agua de la cienaga, impulsando al estudio y aprovechamiento de la cascara de papa como alternativa viable en el tratamiento de las aguas. EnglishObjective: Conduct a comparative study of the clarification process of a natural wetland using two coagulants, aluminum sulfate and potato peel (Solanum tuberosum L). Methodology: Initially, the agroindustrial waste was collected from different fast-food establishments and restaurants in the city of Barranquilla, where it is usually discarded. Potato peel is washed, dried and ground. The powder obtained was screened and packed tightly in a glass jar to be used as a coagulant. Aluminum sulfate was obtained commercially. Water samples are collected from the Cienaga de Malambo by simple sampling. To remove its turbidity, a jug test was performed that simulated the coagulation, flocculation and sedimentation processes, taking as a reference the parameters established in NTC 3903 of 2010, using each coagulant. Results: The water under study had an initial turbidity of 59.60 UNT. The greatest removal of this parameter was obtained with a dose of 40 mg / L aluminum sulfate (92.51%); while the natural coagulant removed 81.32% when using a dose of 10 mg / L. Conclusions: It was determined that the doses of coagulants, aluminum sulfate and potato peel, used in this investigation influenced the turbidity of the water of the swamp, impulse to the study and use of the potato peel as a viable alternative in the treatment of water.

With the advent of personalized medicine, there is a movement to develop “smaller” and “smarter” microdevices that are able to distinguish similar cancer subtypes. Tumor cells display major differences when compared to their natural counterparts, due to alterations in fundamental cellular processes such as glycosylation. Glycans are involved in tumor cell biology and they have been considered to be suitable cancer biomarkers. Thus, more selective cancer screening assays can be developed through the detection of specific altered glycans on the surface of circulating cancer cells. Currently, this is only possible through time-consuming assays. In this work, we propose the “intelligent” Lab on Fiber (iLoF) device, that has a high-resolution, and which is a fast and portable method for tumor single-cell type identification and isolation. We apply an Artificial Intelligence approach to the back-scattered signal arising from a trapped cell by a micro-lensed optical fiber. As a proof of concept, we show that iLoF is able to discriminate two human cancer cell models sharing the same genetic background but displaying a different surface glycosylation profile with an accuracy above 90% and a speed rate of 2.3 seconds. We envision the incorporation of the iLoF in an easy-to-operate microchip for cancer identification, which would allow further biological characterization of the captured circulating live cells. This work was partially funded by the projects NanoSTIMA and NORTE-01-0145-FEDER-000029, both supported by the North Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF); and by the Portuguese Foundation for Science and Technology, within the scope of the PhD grant PD/BD/135023/2017 and the projects: PTDC/BBB-EBI/0567/2014 (to CAR) and UID/BIM/04293/2013. It was also funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274; PPBI-POCI-01-0145-FEDER-022122). MB acknowledges the Marie Sklodowska-Curie grant agreement No. 748880.

Dissertação de mestrado em Genética Molecular, O grande impacto económico proveniente de danos nas culturas agrícolas causados por fungos fitopatogénicos leva, por vezes, ao uso exacerbado e continuado de fungicidas sintéticos na agricultura convencional. Alguns destes fungicidas, caracterizados pela alta especificidade do seu mecanismo de ação, resultaram no surgimento de estirpes resistentes e também efeitos prejudiciais para o ambiente. Estudos recentes abordam os extratos de plantas como potenciais antifúngicos naturais a serem usados na agricultura orgânica, pela sua complexidade e biodegradabilidade intrínseca, contudo ainda é necessário descobrir novos extratos com atividade antifúngica e de que forma é que estes atuam. Assim, com este trabalho pretendeu-se estudar a atividade antifúngica e possíveis mecanismos de ação de extratos de plantas com potencial aplicação em práticas agrícolas sustentáveis. Através de ensaios de viabilidade foi demostrado que, dos quatro extratos etanólicos testados, Callistemon citrinus (CC), Cistus ladanifer (CL), Fraxinus angustifolia (FA) e Pistacia terebinthus (PT), Saccharomyces cerevisiae é sensível ao extrato CL em todos os tempos avaliados, em particular, após 2 h de tratamento com 400 µg/ml de CL, a percentagem de viabilidade da celular foi 71,20 % ± 4,16. Além disso, foi determinada a percentagem de inibição do crescimento do micélio (%ICM) após 9 dias de incubação com o extrato CL em fungos fitopatogénicos. Concretamente, a %ICM de Colletotrichum acutatum, C. gloeosporioides e Diplodia corticola foi 38,09 % ± 4,00; 30,32 % ± 4,00 e 37,4 2% ± 8,76, respetivamente, após 9 dias de incubação com o extrato CL em fungos fitopatogénicos. O estudo de possíveis mecanismos de toxicidade envolvidos nas vias de biossíntese de ergosterol, integridade da parede celular e no processo de apoptose foi realizado através de ensaios de viabilidade com as estirpes mutantes de S. cerevisiae erg2, bck1, mkk1/mkk2 e yca1 e através da análise do potencial de membrana interna mitocondrial por citometria de fluxo. As mutantes erg2, bck1 e mkk1/mkk2 foram mais sensíveis e a mutante yca1 mais resistente ao extrato CL, comparativamente à estirpe selvagem. Segundo os resultados preliminares de citometria, CL desencadeia a despolarização da membrana mitocondrial. Assim, os resultados sugerem que o extrato CL apresenta atividade antifúngica e afeta estas vias. Contudo, novos estudos, com outras mutantes, por exemplo, devem ser realizados para confirmar os resultados obtidos, sobretudo o efeito do extrato no processo de apoptose, uma vez que os resultados de citometria sugerem despolarização da membrana mitocondrial após a exposição de S. cerevisiae ao extrato CL., The great economic impact arising from damage to agricultural crops caused by phytopathogenic fungi sometimes leads to the exacerbated and continued use of synthetic fungicides in conventional agriculture. Some of these fungicides, characterized by the high specificity of their mechanism of action, have resulted in the emergence of resistant strains and harmful effects to the environment. Recent studies approach plant extracts as potential natural antifungals to be used in organic agriculture, due to their complexity and intrinsic biodegradability, however it is still necessary to discover new extracts with antifungal activity and how they act. Thus, with this work it is intended to study the antifungal activity and possible mechanisms of action of plant extracts with potential application in sustainable agricultural practices. Through viability assays it was demonstrated that, of the four ethanolic extracts tested, Callistemon citrinus (CC), Cistus ladanifer (CL), Fraxinus angustifolia (FA) and Pistacia terebinthus (PT), Saccharomyces cerevisiae was sensitive to the extract CL in all the evaluated times, in particular, after 2h of treatment with 400 µg/ml CL (71.20 % ± 4.16 viability). Furthermore, the percentage of mycelium growth inhibition (%ICM) after 9 days of incubation with the CL extract on phytopathogenic fungi was determined. Specifically, the %ICM of Colletotrichum acutatum, C. gloeosporioides and Diplodia corticola were 38.09 % ± 4.00; 30.32 % ± 4.00 e 37.42 % ± 8.76, respectively, after 9 days of incubation with 500 µg/ml CL extract. The study of possible toxicity mechanisms involved in ergosterol biosynthesis pathways, cell wall integrity and apoptosis process was performed by viability assays with the erg2, bck1, mkk1/mkk2 and yca1 mutant S. cerevisiae strains and by analysis of mitochondrial inner membrane potential by flow cytometry. The erg2, bck1 and mkk1/mkk2 mutants were more sensitive and the yca1 mutant more resistant to the CL extract compared to the wild type strain. Additionally, according to preliminary cytometry results, CL triggers mitochondrial membrane depolarization. Thus, the results suggest that CL extract exhibits antifungal activity and affects these pathways. However, further studies with other mutants, for example, should be performed to confirm the results obtained, especially the effect of the extract on the apoptosis process, since cytometry results suggest mitochondrial membrane depolarization after exposure of S. cerevisiae to CL extract.

There are conflicting data regarding the relationship between high-sensitivity cardiac Troponin I (Hs-cTnI) and the ablation effectiveness quotient (AEQ) with arrhythmia recurrence following atrial fibrillation (AF) ablation. Our goals were to evaluate the impact of the Ablation Index (AI) software on Hs-cTnI and AEQ levels and to assess whether these markers are predictors of arrhythmia recurrence.Prospective single-center study of 75 consecutive patients referred for paroxysmal AF ablation from October 2017 to January 2019. Procedural endpoints and 2-year outcomes were assessed and compared to those of 75 propensity score-matched patients submitted to non-AI-guided pulmonary vein isolation (PVI) [control group].Compared to the control group, patients having AI-guided PVI had lower Hs-cTnI values (1580 [IQR 1180-2140] ng/L vs. 2600 [IQR 1840 - 3900], p 0.001) and a lower AEQ (0.9 [IQR 0.6-1.2] ng/L/s vs. 1.4 [0.8-1.6] ng/L/s, p 0.001). After a median follow-up of 26 (IQR 20-32) months, there was a significant reduction in arrhythmia recurrence in the AI group (15% vs. 31%, HR 0.67 [95% CI, 0.32-1.40], p = 0.02). However, neither Hs-cTnI nor AEQ was predictors of arrhythmia recurrence in AI-guided PVI.The use of the AI software led to reduced levels of Hs-cTnI and lower AEQ in AF patients submitted to PVI. However, none of these markers predicted arrhythmia recurrence.

Several studies have shown that ingestion of microplastics causes adverse effects in aquatic organisms, including sediment-dwelling invertebrates. Most studies focus on evaluating the effects of plastic particles alone without testing the mediating effects of different natural stressors and thus lacking realistic exposure scenarios. The present study addresses the interactive effects of exposure to polyethylene microplastics (PE-MPs; 2.5 g/kg) in the midge Chironomus riparius life history traits under different temperatures (15, 20 and 25 °C), a salinity gradient (0, 1 and 3 g L

Chlorination is one of the most important stages in the treatment of drinking water due to its effectiveness in the inactivation of pathogenic organisms. However, the reaction between chlorine and natural organic matter (NOM) generates harmful disinfection by-products (DBPs), such as trihalomethanes (THMs). In this research, drinking water quality data was collected from the distribution networks of 19 rural and semi urban systems that use water sources as: springs, surfaces, and a mixture of both, in three provinces of the Pacific slope of Costa Rica during April 2018 to September 2019. Twelve models were developed from four data sets: all water sources, spring, surface, and mixture of spring and surface waters. Linear, logarithmic, and exponential multivariate regression models were developed for each data set to predict the concentration of total trihalomethanes (TTHMs) in the distribution networks. Concentrations of TTHMs were found between < 0.20 to 91.31 µg/L, with chloroform being the dominant species accounting for 62% of TTHMs on average. Turbidity, free residual chlorine, total organic carbon (TOC), dissolved organic carbon (DOC) and ultraviolet absorbance at 254 nm (UV254) showed a significant correlation with TTHMs. In all the data sets the linear models presented the best goodness-of-fit and were moderately robust. Four models, the best of each data set, were validated with data from the same systems, and, according to the criteria of R2, SE, MSE and MAE, spring water and mixed spring/surface water models showed a satisfactory level of explanation of the variability of the data. Moreover, the models seem to better predict TTHMs concentrations below 30 µg/L. These models were satisfactory and could be useful for decision-making in drinking water supply systems and be considered in possible modifications in current legislation.

BACKGROUND: The organosolv process promotes biomass delignification at relatively high temperatures using a wide variety of organic solvent solutions. Nevertheless, previous studies on organosolv processes have not dealt with the use of ethyl lactate as organic solvent. Thus the aim of the present contribution was to determine and to validate if the use of ethyl lactate has a positive influence on lignin recovery for organosolv processes whose feedstock is the solid waste from a wheat straw‐based biorefinery. The effect of operating conditions (temperature and time) on lignin recovery was also studied. RESULTS: A mixed design of experiments was proposed as the strategy to maximize lignin recovery. The mathematical model derived from a multiple linear regression applied to the mixed design results indicates that 190 °C and a non‐aqueous solution containing ethyl lactate and ethanol (81.2% w/w ethyl lactate) could provide a maximum lignin recovery of 75.9% w/w. This theoretical maximum was validated. Thus the proposed model adequately describes the behavior of lignin recovery. Moreover, Fourier transform infrared (FTIR) characterization of the resultant lignin suggested that its structure is a function of the organic solvent solution used during the organosolv process. CONCLUSION: The evidence from this study indicates that lignin recovery from the solid waste of a wheat straw‐based biorefinery in an organosolv process depends on temperature and ethyl lactate presence in the reaction medium. These findings enhance the understanding of organosolv processes and could be applied if eventual lignin valorization is desired. © 2019 Society of Chemical Industry

This review provides insights on the impact of glycosylation in cancer biology and its influence in the current approaches of targeted cancer therapies in the clinical setting. The roles of glycosylation in cancer signaling, tumor progression, and metastasis are reviewed as well as glycans and glycan-binding proteins in tumor immunomodulation. Moreover, the latest reports on glycans influencing targeted therapeutic approaches in cancer are summarized. Finally, we discuss the future challenges of the field, outlining potential applications of glycan-based biomarkers for patient stratification and strategies for improving personalized cancer treatment.

Organic UV-filters are emergent contaminants continuously released into the aquatic ecosystems. These compounds are persistent showing potential for bioaccumulation. Partial life-cycle tests may underestimate the toxicity of UV-filters especially since these compounds have shown to act as endocrine disruptors. In the present study, the benthic aquatic insect Chironomus riparius was exposed to a gradient of Benzophenone-3 (BP3) concentrations over two generations to assess effects over a full life cycle from the first-instar larvae in the parental (P) generation (emergence, fecundity and fertility) until emergence in the subsequent generation (filial - F1). Recovery from exposure was also assessed after one generational exposure. Our results showed that concentrations of up to 8mg BP3/kg, elicited no effects regarding emergence rate and development time of C. riparius in the P generation. Our results also showed that C. riparius fecundity was not affected by BP3 exposure, but a strong dose-response relationship was observed for fertility with none of the egg ropes hatching at 8mg BP3/kg. Regarding effects observed in the F1 generation, emergence and development time were impaired by continuous exposure to BP3. Moreover, reduced emergence and changes in development time were observed in the F1 generation maintained in control/clean conditions but whose parents were exposed to BP3. Results found in this two-generational study clearly show reproductive effects of BP3 on C. riparius that would not be detected using standard tests. Full life cycle and multigenerational assays are critical to properly evaluate the population level effects of endocrine disrupting compounds such as organic UV-filters. published

Increasing salinity levels in freshwaters due to natural and anthropogenic sources pose risk to exposed aquatic organisms. However, there is a paucity of information on how salinity may influence the effects of other chemical stressors especially psychiatric pharmaceuticals. Freshwater planarians which have been suggested as bioindicator species in aquatic habitats were used in this study to evaluate toxic effects of sodium chloride (NaCl) used here as a surrogate for increasing salinity, and its influence on the effects of the antidepressant, fluoxetine. Effects of NaCl on Schmidtea mediterranea were evaluated using survival, regeneration, locomotion, feeding, and reproduction as endpoints. Subsequently, combined effects of NaCl and fluoxetine on planarians’ locomotion and reproduction were also evaluated. Result showed that exposure to increased NaCl concentrations is toxic to planarians with 48 and 96 h LC50 of 9.15 and 7.55 g NaCl L−1 respectively and exposure to sub-lethal concentrations led to reductions in feeding (LOEC of 0.75 g NaCl L−1 or 1906 μS cm−1 at 20 °C) and reproduction (LOEC 3.0 g NaCl L−1 or 5530 μS cm−1 at 20 °C), delayed head regeneration (LOEC of 1.5 g NaCl L−1 or 3210 μS cm−1 at 20 °C), and also slight decreases in locomotor activity. Moreover, some developmental malformations were observed in regenerating planarians, as well as delayed or inhibition of wound healing and degeneration after fissioning and during head regeneration. A significant interaction between fluoxetine and NaCl was observed for locomotor activity and unlike planarians exposed to fluoxetine alone, fissioned planarians and their pieces from the combined exposure treatments were also unable to regenerate missing portions. Results show that S. mediterranea can be highly sensitive to low NaCl concentrations and that this stressor can alter the effects of fluoxetine. The implication of these effects for planarian populations in the natural habitat is discussed as well as the need for more research on the effects of neuroactive pharmaceuticals under relevant exposure scenarios.

Background: Changes in glycosylation are known to play critical roles during gastric carcinogenesis. Expression of truncated O-glycans, such as the Sialyl-Tn (STn) antigen, is a common feature shared by many cancers and is associated with cancer aggressiveness and poor-prognosis. Methods: Glycoengineered cell lines were used to evaluate the impact of truncated O-glycans in cancer cell biology using in vitro functional assays, transcriptomic analysis and in vivo models. Tumor patients ‘samples and datasets were used for clinical translational significance evaluation. Findings: In the present study, we demonstrated that gastric cancer cells expressing truncated O-glycans display major phenotypic alterations associated with higher cell motility and cell invasion. Noteworthy, the glycoengineered cancer cells overexpressing STn resulted in tumor xenografts with less cohesive features which had a critical impact on mice survival. Furthermore, truncation of O-glycans induced activation of EGFR and ErbB2 receptors and a transcriptomic signature switch of gastric cancer cells. The disclosed top activated genes were further validated in gastric tumors, revealing that SRPX2 and RUNX1 are concomitantly overexpressed in gastric carcinomas and its expression is associated with patients’ poor-survival, highlighting their prognosis potential in clinical practice. Interpretation: This study discloses novel molecular links between O-glycans truncation frequently observed in cancer and key cellular regulators with major impact in tumor progression and patients’ clinical outcome. This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE ( POCI-01-0145-FEDER-016585 ; POCI-01-0145-FEDER-007274 ; POCI-01-0145-FEDER-028489 ) and National Funds through the Foundation for Science and Technology (FCT) , under the projects: PTDC/BBB-EBI/0567/2014 (to CAR), PTDC/MED-ONC/28489/2017 (to AM) and UID/BIM/04293/2013 ; and the project NORTE-01-0145-FEDER-000029 , supported by Norte Portugal Regional Programme ( NORTE 2020 ), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The authors acknowledge the support by Gastric Glyco Explorer Initial Training Network (European Union Seventh Framework Programme GastricGlycoExplorer project, grant number 316929 ). DF acknowledges the FCT PhD Programmes and Programa Operacional Potencial Humano (POPH), specifically the BiotechHealth Programe (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences), with the reference PD/0016/2012 funded by FCT . Grants were received from FCT, POPH and FSE (Fundo Social Europeu): SFRH/BD/110636/2015 to DF and SFRH/BPD/115730/2016 to FP. We thank Catharina Steentoft and Henrik Clausen for the cell line models and helpful scientific discussions. We are grateful for Nuno Mendes's technical support. The authors acknowledge the support of José Luis Costa and Mafalda Rocha from the i3S Genomics Platform (GenCore), and Maria G Lazaro from the Bioimaging I3S Scientific Platform , member of the PPBI ( PPBI-POCI-01-0145-FEDER-022122 ).

Herein, sixteen priority sixteen priority polycyclic aromatic hydrocarbons (PAHs) and seven polychlorinated biphenyls (PCBs), considered seawater quality indicators, were quantified in four beaches of the Iberian (Portuguese) northwest coastline, including one ornithological reserve. These seashores are close to an important industrial region and a harbour. Water samples were extracted for PAHs and PCBs in their aqueous phase (DAP) and suspended particulate matter (SPM) and analysed by GC-MS/MS. Annual average concentrations reached ∼8 ng/L (DAP) and ∼100 ng/g dw (SPM) for PAHs and ∼3 ng/L (DAP) and ∼19 ng/g dw (SPM) for PCBs. PAHs and PCBs had fluctuations suggestive of seasonality. The possible origins of PAHs point to pyrogenic (forest fires) and petrogenic activities linked to maritime transports. The source(s) of PCBs appear to be related with leaks from waste sorting centres located in the vicinity of the sampling sites, together with the burning of contaminated materials. Toxic equivalents (TEQs) suggested a low carcinogenic potential for PAHs in seawater samples (∼0.3 ng/L and ∼4 ng/g dw, for DAP and SPM). Evaluation of risk coefficients for Σ16 PAHs revealed "Low-risk" of both matrices in all sampling areas. PCBs thyroid toxicity equivalents (TEQs-TH), suggested a low impact on biota (∼7.0E-05 ng/L and ∼5.2E-04 ng/g dw, for DAP and SPM). However, in vivo acute assays with Artemia salina exposed to environmental concentrations of PAHs, PCBs, and mixtures, confirmed the theoretical approach, showing that this coastline is not "Risk-free". This fact calls for further toxicological approaches to fully understand the risks posed by these compounds locally.