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Chlorins are highly interesting compounds due to their spectroscopic properties in both UV-Vis and NIR regions. Upon coordination to a metal ion, the corresponding metallochlorins exhibit more valuable physicochemical properties that enable a broader range of applications, such as in photodynamic therapy (PDT), water splitting catalysis, optical sensor devices and dye-sensitized solar cells. Synthetic chemistry has been in a continuous quest to fulfil most green chemistry requirements through the development of efficient reactions. Being a heating process that does not depend on heat transfer to the reaction medium, ohmic heating accomplishes the mentioned requirements and allows a fast and uniform heating regime thanks to the ionic conductivity of the reaction medium. Herein, we report the metallation of pyrrolidine- and isoxazolidine-fused chlorins with Zn(II), Cu(II) and Pd(II) salts by ohmic heating, using non-toxic aqueous solutions, and their corresponding physico-chemical characterization. All pyrrolidine-fused chlorins showed higher yields, when compared with isoxazolidine ones. From the thermogravimetric analysis performed it is possible to infer that the metal enhances the steadiness of the macrocycle, making it easier to cause the thermal decomposition of the pyrrolidine- and isoxazolidine-fused chlorins. The Zn(II) complexes showed high absorption in the NIR spectral region, a low fluorescence quantum yield and a short excited singlet state, which indicate the high efficiency of intersystem crossing to the triplet state, making them very promising candidates as photosensitizers for PDT.

Serological assays are valuable tools to study SARS‐CoV‐2 spread and, importantly, to identify individuals that were already infected and would be potentially immune to a virus reinfection. SARS‐CoV‐2 Spike protein and its receptor binding domain (RBD) are the antigens with higher potential to develop SARS‐CoV‐2 serological assays. Moreover, structural studies of these antigens are key to understand the molecular basis for Spike interaction with angiotensin converting enzyme 2 receptor, hopefully enabling the development of COVID‐19 therapeutics. Thus, it is urgent that significant amounts of this protein became available at the highest quality. In this study, we produced Spike and RBD in two human derived cell hosts: HEK293‐E6 and Expi293F™. We evaluated the impact of different and scalable bioprocessing approaches on Spike and RBD production yields and, more importantly, on these antigens' quality attributes. Using negative and positive sera collected from human donors, we show an excellent performance of the produced antigens, assessed in serologic enzyme‐linked immunosorbent assay (ELISA) tests, as denoted by the high specificity and sensitivity of the test. We show robust Spike productions with final yields of approx. 2 mg/L of culture that were maintained independently of the production scale or cell culture strategy. To the best of our knowledge, the final yield of 90 mg/L of culture obtained for RBD production, was the highest reported to date. An in‐depth characterization of SARS‐CoV‐2 Spike and RBD proteins was performed, namely the antigen's oligomeric state, glycosylation profiles, and thermal stability during storage. The correlation of these quality attributes with ELISA performance show equivalent reactivity to SARS‐CoV‐2 positive serum, for all Spike and RBD produced, and for all storage conditions tested. Overall, we provide straightforward protocols to produce high‐quality SARS‐CoV‐2 Spike and RBD antigens, that can be easily adapted to both academic and industrial settings; and integrate, for the first time, studies on the impact of bioprocess with an in‐depth characterization of these proteins, correlating antigen's glycosylation and biophysical attributes to performance of COVID‐19 serologic tests., Spike and RBD were produced in human derived cells hosts. Shake flasks, stirred tank and wave bioreactors were compared. The impact of these different scalable bioprocessing approaches on Spike and RBD production yields and quality attributes was evaluated. An in‐depth characterization of SARS‐CoV‐2 Spike and RBD proteins was performed, namely the antigen s oligomeric state, glycosylation profiles and thermal stability during storage. The correlation of these quality attributes with ELISA performance is discussed.

Indomethacin is a potent non-steroidal anti-inflammatory drug (NSAID) with a strong selective inhibitor activity towards cyclooxygenase-2 (COX-2), an enzyme that is highly overexpressed in various tumour cells, being involved in tumourigenesis. Concomitantly, porphyrins have gained much attention as promising photosensitizers (PSs) for the non-invasive photodynamic therapy (PDT) of cancer. Herein, we report the design, and determine the singlet oxygen generation capacity and in vitro cellular toxicity of porphyrin- and chlorin-indomethacin conjugates (P2-Ind and C2-Ind). Both the conjugates were obtained in high yields and were characterized by 1H, 19F and 13C NMR as well as by high resolution mass spectrometry. The singlet oxygen generation properties were assessed by the 1,3-diphenylisobenzofuran singlet oxygen trap method, which showed that C2 and C2-Ind are the best singlet oxygen photosensitizers. In addition, it was found that the presence of indomethacin did not influence the singlet oxygen generation of porphyrin or chlorin. Cytotoxicity studies of the conjugate in human HEp2 cells revealed that the porphyrin- and chlorin-indomethacin conjugates have similar dark cytotoxicities, while chlorin C2 was shown to be the most phototoxic. Despite having lower cellular uptake than C2-Ind after 24 hours, chlorin C2 had a broad localization in HEp2 cells while the chlorin-indomethacin conjugate C2-Ind could be detected in the form of small aggregates. DFT calculations were performed to shed light on the reaction energy involved in the formation of the indomethacin conjugates and to compare the relative stability of selected isomers in solution. Moreover, the calculated energy of their first excited triplet state structures confirmed their use as suitable photosensitizers to generate singlet oxygen for PDT.

Leptin is an adipose tissue hormone that acts as energy sensor and reproductive function regulator. Recent reports suggest that leptin is involved in mitochondrial biogenesis in different tissue cells. Herein, we hypothesized that leptin could also affect Sertoli cells mitochondrial dynamics and biogenesis. Human Sertoli cells (hSCs) were cultured in the presence of different leptin concentrations (5, 25 and 50 ng/mL) or vehicle for 24 h. The three different leptin concentrations were selected to mimic the circulating levels found either in normal weight, obese, and morbidly obese individuals, respectively. Leptin receptor (LEPR) expression was evaluated as well as mitochondrial membrane potential, complexes levels, complex II activity and basal respiration. Moreover, mitochondrial DNA copy number and expression of mitochondrial biogenesis markers were assessed. In hSCs, leptin concentrations similar to those found both in lean men decreased mitochondrial complex II protein levels, but no changes in its activity were observed. This is in agreement with basal respiration and mitochondrial membrane potential assessments, which indicate no alterations in mitochondrial fitness. Furthermore, no changes in mitochondrial biogenesis markers were observed upon leptin exposure, although SIRT1/3 levels were increased after exposure to the highest leptin concentration. Overall, the increase in SIRT1/3 levels suggests a role for leptin in glycolysis, which given the relevance of SCs glycolytic flux for germ cells nutritional support further reinforces that this mechanism can be linked to obesity-related subfertility/infertility.

The brain cholinergic system comprises two main recognized subdivisions, the basal forebrain and the brainstem cholinergic systems. The effects of chronic alcohol consumption on the basal forebrain cholinergic nuclei have been investigated extensively, but there is only one study that has examined those effects on the brainstem cholinergic nuclei. The last one comprises the pedunculopontine tegmental (PPT) and the laterodorsal tegmental (LDT) nuclei, which are known to give origin to the main cholinergic projection to the ventral tegmental area, a key brain region of the neural circuit, the mesocorticolimbic system, that mediates several behavioral and physiological processes, including reward. In the present study, we have examined, using stereological methods, the effects of chronic alcohol consumption (6 months) and subsequent withdrawal (2 months) on the total number and size of PPT and LDT choline acetyltransferase (ChAT)-immunoreactive neurons. The total number of PPT and LDT ChAT-immunoreactive neurons was unchanged in ethanol-treated and withdrawn rats. However, ChAT-immunoreactive neurons were significantly hypertrophied in ethanol-treated rats, an alteration that did not revert 2 months after ethanol withdrawal. These results show that prolonged exposure to ethanol leads to long-lasting, and potentially irreversible, cytoarchitectonic and neurochemical alterations in the brainstem cholinergic nuclei. These alterations suggest that the alcohol-induced changes in the brainstem cholinergic nuclei might play a role in the mechanisms underlying the development of addictive behavior to alcohol.

The specific demands of supply chains built upon large and complex IoT systems, make it a must to design a coordinated framework for cyber resilience provisioning, intended to guarantee trusted supply chains of ICT systems, built upon distributed, dynamic, potentially insecure, and heterogeneous ICT infrastructures. As such, the solution proposed in this paper is envisioned to deal with the whole supply chain system components, from the IoT ecosystem to the infrastructure connecting them, addressing security and privacy functionalities related to risks and vulnerabilities management, accountability, and mitigation strategies, as well as security metrics and evidence-based security assurance. In this paper, we present FISHY as a preliminary architecture that is designed to orchestrate existing and beyond state-of-the-art security appliances in composed ICT scenarios. To this end, the FISHY architecture leverages the capabilities of programmable networks and IT infrastructure through seamless orchestration and instantiation of novel security services, both in real-time and proactively. The paper also includes a thorough business analysis to go far beyond the technical benefits of a potential FISHY adoption, as well as three real-world use cases highlighting the envisioned benefits of a potential FISHY adoption., This research was funded by H2020 FISHY Project, grant number 952644, and for UPC authors by the Spanish Ministry of Science, Innovation and Universities and FEDER, grant number RTI2018-094532-B-I00.

Functional organic dyes play a key role in many fields, namely in biotechnology and medical diagnosis. Herein, we report two novel 2,3- and 3,4-dihydroxyphenyl substituted rosamines (3 and 4, respectively) that were successfully synthesized through a microwave-assisted protocol. The best reaction yields were obtained for rosamine 4, which also showed the most interesting photophysical properties, specially toward biogenic amines (BAs). Several amines including n- and t-butylamine, cadaverine, and putrescine cause spectral changes of 4, in UV–Vis and fluorescence spectra, which are indicative of their potential application as an effective tool to detect amines in acetonitrile solutions. In the gas phase, the probe response is more expressive for spermine and putrescine. Additionally, we found that methanolic solutions of rosamine 4 and n-butylamine undergo a pink to yellow color change over time, which has been attributed to the formation of a new compound. The latter was isolated and identified as 5 (9−aminopyronin), whose solutions exhibit a remarkable increase in fluorescence intensity together with a shift toward more energetic wavelengths. Other 9-aminopyronins 6a, 6b, 7a, and 7b were obtained from methanolic solutions of 4 with putrescine and cadaverine, demonstrating the potential of this new xanthene entity to react with primary amines., Financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e a Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the project PTDC/QUI-QOR/29426/2017. The research team would like to thank the projects UIDB/50006/2020, PTDC/QUI-QIN/28142/2017 and Grant BU263P18 (from the Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo). F. M. -S. gratefully acknowledges FCT (Portugal’s Foundation for Science and Technology) within grant DFA/BD/9136/2020. A.M.G.S. and A.L. thank FCT for the program DL 57/2016 – Norma transitória.

Background Lung branching morphogenesis is characterized by epithelial-mesenchymal interactions that ultimately define the airway conducting system. Throughout this process, energy and structural macromolecules are necessary to sustain the high proliferative rates. The extensive knowledge of the molecular mechanisms underlying pulmonary development contrasts with the lack of data regarding the embryonic lung metabolic requirements. Here, we studied the metabolic profile associated with the early stages of chicken pulmonary branching. Methods In this study, we used an ex vivo lung explant culture system and analyzed the consumption/production of extracellular metabolic intermediates associated with glucose catabolism (alanine, lactate, and acetate) by 1H-NMR spectroscopy in the culture medium. Then, we characterized the transcript levels of metabolite membrane transporters (glut1, glut3, glut8, mct1, mct3, mct4, and mct8) and glycolytic enzymes (hk1, hk2, pfk1, ldha, ldhb, pdha, and pdhb) by qPCR. ldha and ldhb mRNA spatial localization was determined by in situ hybridization. Proliferation was analyzed by directly assessing DNA synthesis using an EdU-based assay. Additionally, we performed western blot to analyze LDHA and LDHT protein levels. Finally, we used a Clark-Type Electrode to assess the lung explant's respiratory capacity. Results Glucose consumption decreases, whereas alanine, lactate, and acetate production progressively increase as branching morphogenesis proceeds. mRNA analysis revealed variations in the expression levels of key enzymes and transporters from the glycolytic pathway. ldha and ldhb displayed a compartment-specific expression pattern that resembles proximal–distal markers. In addition, high proliferation levels were detected at active branching sites. LDH protein expression levels suggest that LDHB may account for the progressive rise in lactate. Concurrently, there is a stable oxygen consumption rate throughout branching morphogenesis. Conclusions This report describes the temporal metabolic changes that accompany the early stages of chicken lung branching morphogenesis. Overall, the embryonic chicken lung seems to shift to a glycolytic lactate-based metabolism as pulmonary branching occurs. Moreover, this metabolic rewiring might play a crucial role during lung development.

The present research reports the efficient synthesis of mono- and di-(aminophenyl)porphyrins and their metalation with Zn(II) using microwave irradiation. The subsequent reaction of amino-functionalized porphyrins with siloxane moieties bearing epoxy or carboxyl functional groups provided four new porphyrin-modified siloxanes. The structure of the resulting derivatives was established by 1H-NMR and MALDI-TOF-MS. The optical properties of the porphyrin chromophores were preserved, as proven by comparing the absorption and emission spectra of the initial porphyrins to those of the porphyrin-modified siloxanes.

Cytokinesis completes cell division by constriction of an actomyosin contractile ring that separates the two daughter cells. Here we use the early Caenorhabditis elegans embryo to explore how the actin filament network in the ring and the surrounding cortex is regulated by the single cytokinesis formin CYK-1 and the ARP2/3 complex, which nucleate nonbranched and branched filaments, respectively. We show that CYK-1 and the ARP2/3 complex are the predominant F-actin nucleators responsible for generating distinct cortical F-actin architectures and that depletion of either nucleator affects the kinetics of cytokinesis. CYK-1 is critical for normal F-actin levels in the contractile ring, and acute inhibition of CYK-1 after furrow ingression slows ring constriction rate, suggesting that CYK-1 activity is required throughout ring constriction. Surprisingly, although the ARP2/3 complex does not localize in the contractile ring, depletion of the ARP2 subunit or treatment with ARP2/3 complex inhibitor delays contractile ring formation and constriction. We present evidence that the delays are due to an excess in formin-nucleated cortical F-actin, suggesting that the ARP2/3 complex negatively regulates CYK-1 activity. We conclude that the kinetics of cytokinesis are modulated by interplay between the two major actin filament nucleators.

Assessment is a regulatory and fundamental element of the teaching-learning process (Dutra et al., 2018), which in the perspective of the Assessment for Learning allows fostering the learning (Broadfoot et al., 1999). This study aimed to analyse students’ involvement and motivation in the Assessment for Learning processes and the impact on learning. The participants were 21 students of a class of the 11th grade of the Scientific- Humanistic Course of Science and Technology, with an average age of 17.23. The instruments used were focus group interviews, audio recordings of teacher feedbacks, several self and peer assessment moments and the teacher’s diary. Auto evaluation data were analyzed using descriptive measures (average and mode) and the information from pear observations, focus group interview and teacher board diary were analyzed using the content analysis procedures (Bardin, 2008).The data showed that students raised their level of involvement and motivation for the sessions, especially in the construction of the gymnastic scheme. In addition, the application of this methodology has enhanced learning in the acquisition of knowledge, as well as in the dynamics of the different groups.

Salicornia ramosissima J.Woods is an edible halophyte, widely distributed in the Portuguese salt marsh that has been under valorized. The aim of this study is to expand the knowledge regarding S. ramosissima bioactive composition and safety, highlighting its potential use as nutraceutical ingredient. Therefore, extracts obtained by conventional (CE) and microwave-assisted extraction (MAE) were characterized regarding phenolic profile, antioxidant activity, radical scavenging capacity and intestinal cell effects. Moreover, organic pesticides were screened to guarantee the consumers safety. The highest phenolic and flavonoid contents were observed for the CE, as well as the scavenging capacity of O2•− (IC50 = 979.36 µg/mL) and HOCl (IC50 = 90.28 µg/mL). In contrast, the best antioxidant and antiradical activities were achieved by MAE (65.56 µmol FSE/g dw and 17.74 µg AAE/g dw for FRAP and ABTS assays, respectively). The phenolic composition was similar for both extracts, being characterized by the presence of phenolic acids, flavonols, flavanols, flavones and flavanones. The predominant compound for both extracts was myricetin. None of the extracts were cytotoxic in intestinal cell lines. Vestigial levels of β-endosulfan and p,p’-DDE were identified in MAE. These results support that S. ramosissima could be a source of bioactive compounds for nutraceutic industry.

The specific demands inherent to supply chains built upon large IoT systems, make a must the design of a coordinated framework for cyber resilience provisioning intended to guaranteeing trusted supply chains of ICT systems, built upon distributed, dynamic, potentially insecure and heterogeneous ICT infrastructures. As such, the proposed solution is envisioned to deal with the whole supply chain system components, from the IoT ecosystem to the infrastructure connecting them, addressing security and privacy functionalities related to risks and vulnerabilities management, accountability and mitigation strategies as well as security metrics and evidence-based security assurance. In this paper we present FISHY, as a preliminary designed architecture, designed to orchestrate both existing and beyond state-of-the-art security appliances in composed ICT scenarios and also leveraging capabilities of programmable network and IT infrastructure through seamless orchestration and instantiation of novel security services, both in real-time and proactively. The paper also includes a thorough business analysis to go far beyond the technical benefits of a potential FISHY adoption as well as three real-world use cases where to strongly support the envisioned benefits of a FISHY adoption.

Fresh fish is a highly perishable food characterized by a short shelf-life, and for this reason, it must be properly handled and stored to slow down its deterioration and to ensure microbial safety and marketable shelf-life. Modern consumers seek fresh-like, minimally processed foods due to the raising concerns regarding the use of preservatives in foods, as is the case of fresh fish. Given this, emergent preservation techniques are being evaluated as a complement or even replacement of conventional preservation methodologies, to assure food safety and extend shelf-life without compromising food safety. This paper reviews the main mechanisms responsible for fish spoilage and the use of conventional physical methodologies to preserve fresh fish, encompassing the main effects of each methodology on microbiological and chemical quality aspects of this highly perishable food. In this sense, conventional storage procedures (refrigeration and freezing) are counterpointed with more recent cold-based storage methodologies, namely chilling and superchilling. In addition, the use of novel food packaging methodologies (edible films and coatings) is also presented and discussed, along with a new storage methodology, hyperbaric storage, that states storage pressure control to hurdle microbial development and slow down organoleptic decay at subzero, refrigeration, and room temperatures.

The development of straightforward reproducible methods for the preparation of new photoluminescent coordination polymers (CPs) is an important goal in luminescence and chemical sensing fields. Isophthalic acid derivatives have been reported for a wide range of applications, and in addition to their relatively low cost, have encouraged its use in the preparation of novel lanthanide-based coordination polymers (LnCPs). Considering that the photoluminescent properties of these CPs are highly dependent on the existence of water molecules in the crystal structure, our research efforts are now focused on the preparation of CP with the lowest water content possible, while considering a green chemistry approach. One- and two-dimensional (1D and 2D) LnCPs were prepared from 5-aminoisophthalic acid and Sm3+/Tb3+ using hydrothermal and/or microwave-assisted synthesis. The unprecedented LnCPs were characterized by single-crystal X-ray diffraction (SCRXD), powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM), and their photoluminescence (PL) properties were studied in the solid state, at room temperature, using the CPs as powders and encapsulated in poly(methyl methacrylate (PMMA) films, envisaging the potential preparation of devices for sensing. The materials revealed interesting PL properties that depend on the dimensionality, metal ion, co-ligand used and water content.

Human populations and natural ecosystems are bound to be exposed to ionizing radiation from the deposition of artificial radionuclides resulting from nuclear accidents, nuclear devices or radiological dispersive devices (“dirty bombs”). On the other hand, Naturally Occurring Radioactive Material industries such as phosphate production or uranium mining, contribute to the on site storage of residuals with enhanced concentrations of natural radionuclides. Therefore, in the context of the European agreements concerning nuclear energy, namely the European Atomic Energy Community Treaty, monitoring is an essential feature of the environmental radiological surveillance. In this work, we obtain 3D maps from outdoor scenarios, and complete such maps with measured radiation levels and with its radionuclide signature. In such scenarios, we face challenges such as unknown and rough terrain, limited number of sampled locations and the need for different sensors and therefore different tasks. We propose a radiological solution for scouting, monitoring and inspecting an area of interest, using a fleet of drones and a controlling ground station. First, we scout an area with a Light Detection and Ranging sensor onboard a drone to accurately 3D-map the area. Then, we monitor that area with a Geiger–Müller Counter at a low-vertical distance from the ground to produce a radiological (heat)map that is overlaid on the 3D map of the scenario. Next, we identify the hotspots of radiation, and inspect them in detail using a drone by landing on them, to reveal its radionuclide signature using a Cadmium–Zinc–Telluride detector. We present the algorithms used to implement such tasks both at the ground station and on the drones. The three mission phases were validated using actual experiments in three different outdoor scenarios. We conclude that drones can not only perform the mission efficiently, but in general they are faster and as reliable as personnel on the ground.

Shift work has become a common practice across many sectors during the past decades as a result of the growing demands of human life. There are many possibilities to organize shift schedules, however, all of them, some more than others, impose serious impacts on the individual´s health, social life and organization level. Thus, we conducted a review using Scopus, Science Direct and Web of Science, and using the keywords and criteria deemed appropriate, with the main objective of identifying the main consequences that have been positively associated with shift work at several domains to this day. The results of this review indicated that shift work and everything that this type of work implies, can lead to severe health consequences, namely sleep disorders, psychiatric disorders, gastrointestinal disturbances, metabolic disorders, cardiovascular disease, urologic disorders and even some types of cancer. These health consequences arise due to the disruption of the circadian clock system, which is associated with alterations at genetic level. Moreover, shift work also causes impacts in social life, as the individual may experience more difficulties in socializing with family and friends, which may lead to isolation and organization level, as excessive sleepiness, stress and dissatisfaction may lead to a detriment of the performance and alertness, which may result in more accidents. In conclusion, considering the nefarious effects that this type of organization of working time can impose, primarily for the worker, but also for the worker’s family and also organization in which this works, it is crucial that the organization seek to protect the worker safety and health, which can be achieved by consultation the working physician but also with the use of tools that allow monitoring the worker health and general cognitive state.

Cytokinesis is the last step of cell division that physically partitions the mother cell into two daughter cells. Cytokinesis requires the assembly and constriction of a contractile ring, a circumferential array of filamentous actin (F-actin), non-muscle myosin II motors (myosin), and actin-binding proteins that forms at the cell equator. Cytokinesis is accompanied by long-range cortical flows from regions of relaxation toward regions of compression. In the C. elegans one-cell embryo, it has been suggested that anterior-directed cortical flows are the main driver of contractile ring assembly. Here, we use embryos co-expressing motor-dead and wild-type myosin to show that cortical flows can be severely reduced without major effects on contractile ring assembly and timely completion of cytokinesis. Fluorescence recovery after photobleaching in the ingressing furrow reveals that myosin recruitment kinetics are also unaffected by the absence of cortical flows. We find that myosin cooperates with the F-actin crosslinker plastin to align and compact F-actin bundles at the cell equator, and that this cross-talk is essential for cytokinesis. Our results thus argue against the idea that cortical flows are a major determinant of contractile ring assembly. Instead, we propose that contractile ring assembly requires localized concerted action of motor-competent myosin and plastin at the cell equator. The research leading to these results was funded by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement 640553 – ACTOMYO). AXC and RG hold Principal Investigator positions from the Portuguese Foundation for Science and Technology (FCT) (CEECIND/01967/2017 and CEECIND/00333/2017, respectively). F-YC and AMS hold FCT junior researcher positions (DL 57/2016/CP1355/CT0013 and DL 57/2016/CP1355/CT0017, respectively). AFS holds an FCT Ph.D. scholarship (SFRH/BD/121874/2016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background and Aims Transthyretin (TTR) amyloidosis is a disease characterized by destabilization of the native TTR tetramer. It can be caused by aging or due to pathogenic mutations, and its diagnosis is often missed. Hereditary transthyretin amyloidosis (ATTRv), due to Val50Met mutation, is frequently linked with polyneuropathy but it can cause nephropathy too, causing wide range levels of albuminuria and renal dysfunction. Tafamidis, a TTR tetramer stabilizer, has been associated with significant decrease of albuminuria in ATTRv. However, TTR nephropathy is not an approved indication for its use. Plus, the renal effects of chronic oral administration of this TTR stabilizer are yet to be understood. This study evaluated longitudinal changes of eGFR-EPI within 72 months of therapy with tafamidis and identified factors associated with these changes. Method A retrospective cohort, single centre study was conducted. We have followed consecutive ATTRv Val50Met patients on tafamidis therapy from July 2012 to March 2019. Men and women aged 18-85 years were eligible if they had neuropathy stage I, were anti-amyloid treatment-naïve patients that accomplished at least 60 months of tafamidis therapy and had eGFR over 45 ml/min/1.73m2 with any grade of albuminuria. Exclusion criteria were: pregnancy, malignancies, diabetes and concurrent etiologies for nephropathy. Statistical analyses included Mann-Whitney test and linear mixed models to analyze the longitudinal changes in eGFR of the two groups of patients (albumunuric/ non-albuminuric at baseline), by controlling for variables that could be associated with eGFR EPI Cystatin C course. Results From 366 patients, biopsy-proven ATTR amyloidosis, treated with tafamidis, 122 patients met our criteria (56 males, 66 females) and had a median age of 36 (IQR: 32-46) years old. Twenty-eight had pathological urinary albumin-to-creatinine ratio (ACR), defined by ACR >30 mg/dL, and ACR >300 mg/dL was only found in females. In univariate analysis no significant differences were found between median eGFR decline in albuminuric versus non-albuminuric patients (p=0.330). At all time points, mean eGFR levels were significantly lower in baseline albuminuric patients. According to our estimation, eGFR at baseline was 11.2 mL/min/1.73 m2 lower in baseline albuminuric patients, adjusted for age at the disease onset and time between symptom onset and tafamidis initiation. Baseline albuminuria status (p=0,005), age at the disease onset (p Conclusion This study represents a real-life experience of oral chronic administration of tafamidis and its effects on ATTR nephropathy, concerning albuminuria reduction and renal function decline. Our analysis had shown similar decline rates in eGFR, irrespectively the degree of albuminuria at baseline, differently from what would be expected, since higher grades of albuminuria are related with more rapidly kidney function deterioration. Besides its capacity of stabilizing TTR tetramers, tafamidis could have an enhancing role in the podocyte regeneration process through potential cofactors for amyloid fibrils toxic effect, that could be present in the glomerular basement membrane and mesangium. This nephroprotector effect should be considered when a switch of therapy is demanded by the neuropathy status and a second line treatment is considered. Presence of renal disease may be an indication for tafamidis maintenance and combined therapy.

This study introduces a highly selective and sensitive luminescent sensor based on simply mixing a Tb(III)-based luminescent Metal–Organic Framework with polymethyl-methacrylate enabling to detect sub-ppb range of nitroaromatic vapours, properly. To the best of our knowledge, this is the first report on the use of this material for detecting gaseous analytes. Meanwhile, the present sensor dispels previous doubts about the selectivity and sensitivity of this material for the detection of nitroaromatic explosives in liquid media along with its applicability in the presence of potential interferences.

A fluorescent NO2 gas sensor using the metal–organic framework (MOF) Tb(BTC) (BTC = benzene-1,3,5-tricarboxylate) as an active material is reported here. The lanthanide MOF crystals have been immobilized in transparent films of two different inert and non-emissive polymers i.e. polymethylmethacrylate (PMMA) and polydimethylsiloxane (PDMS) by spin coating Tb(BTC) suspended in the corresponding polymer organic solution onto solid substrates. The presence of the MOF particles in the resulting fluorescent films has been further confirmed by SEM and optical microscopy images. The sensing films exhibit fast and sensitive responses (fluorescence quenching) when exposed to a low concentration of NO2. The dependence of the sensor response on the analyte concentration fitted a two-site Stern–Volmer quenching model from which good calibration curves were obtained. These properties, along with recovery of the sensor emission after gentle heating (50 °C), make these materials realistic candidates for the development of luminescent sensing films based on MOFs.

The introduction of a carboxylate function into porphyrins allows a variety of modifications, including coordination and conjugation, which are central to enhance the efficiency of macrocycles in photonic materials and biological applications. Herein, a synthetic strategy to obtain 5-(4′-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin and its pyrrolidine-fused chlorin derivative was developed by the 1,3-dipolar cycloaddition of a carbomethoxyphenyl substituted porphyrin with an azomethine ylide, followed by hydrolysis under thermal acidic conditions. The 1,3-dipolar cycloaddition of the carbomethoxyphenyl porphyrin with N-methyl nitrone was also performed to give an isomeric mixture of isoxazolidine-fused chlorins, revealing lower selectivity and lower yields; in addition, retrocycloaddition of the isoxazolidine-fused chlorins was observed under the hydrolysis conditions. The resulting carboxyphenyl macrocycles were characterized using 1H and 19F NMR, ESI-MS and SC-XRD for 5-(4′-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin. In order to study the influence of coordination to a metal ion on the electronic properties of carboxyphenyl substituted porphyrins, a series of metal complexes of 5-(4′-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin and its pyrrolidine-fused chlorin derivative were synthesized by microwave-mediated metallation with Fe(III), Cu(II) and Zn(II) salts. EPR spectroscopy was particularly relevant to the characterization of the Cu(II) complexes of both macrocycles and to study the coordination chemistry of these ligands with Cu(II) ions.

We describe the synthesis and characterization of a new N-methylpyrrolidine-fused meso-tetracarboxyphenylchlorin with highly emissive features. The synthetic approach to obtain the fluorescent chlorin involves the microwave-assisted synthesis of meso-tetrakis (4-methoxycarbonylphenyl)porphyrin, followed by a 1,3-dipolar cycloaddition reaction of this porphyrin with azomethine ylide and, finally, ester hydrolysis under basic conditions. The incorporation and anchoring of the chlorin to a nanostructured porous TiO2 matrix is achieved and optimized for its use as a fluorescent sensor. In particular, we found an efficient detection of the explosive triacetone triperoxide (TATP) in the gas phase. The optical response after analyte exposure is selective and fast, with response time t50 values of less than 10 min under exposure to TATP saturated vapours.

Due to its characteristics, fresh fish is a highly perishable food with a very short shelf-life under refrigeration. Several methods have been introduced to slow down its deterioration, such as by means of oxygen depletion of the food package (vacuum packaging), or by changing the natural atmosphere that is in contact with the fresh fish (modified atmosphere packaging), or by the use of chemicals generally recognized as safe: such compounds can be directly applied (by dipping or spraying) or incorporated into packaging materials and slowly migrate to the product, exerting a hurdle effect against microbial development and lipid oxidation (active packaging). This review aims to cover the most recent advances in chemical-based approaches for fresh fish preservation, applied either singly or in combination. Vacuum packaging, modified atmosphere, and active packaging preservation methodologies are presented, along with the inclusion of chemical additives, such as organic acids and natural extracts, and their combination with icing systems. Advantages and disadvantages of these methodologies and their impact on fresh fish quality and shelf-life are discussed, reaching the conclusion that both are positively influenced overall. Indeed, the contribution of chemical-based strategies for fresh fish preservation is undeniable, and is expected to be a research topic of increasing interest in the future.

While public intervention in Research and Development (R&D) is generally supported by economic theory and R&D subsidies are being implemented in most OECD countries, evidence on their effectiveness fails to reveal conclusive results. Exploring data from approved and rejected applicants to two R&D funding instruments in Portugal, we provide further evidence on R&D subsidy programmes directed to firms and S&T organisations, by identifying the determinants of grant decisions by the public agency. The results show that subsidies to firms are mainly aimed at large R&D projects by manufacturing firms, in both high- and low-technology sectors. Subsidies to S&T organisations show a higher degree of selectivity, targeting mainly universities and premium public research centres, and favouring R&D projects in exact sciences and engineering and cooperation projects. The subsidy allocation process in Portugal presents distinctive features in line with its status of an innovation follower country.

The 1,3-dipolar cycloaddition reaction of meso-tetraarylporphyrins with nitrones gives isoxazolidine-fused chlorins. Depending on the substitution pattern on the meso-aryl groups and the nitrone, the chlorins can be obtained in high yields (up to 91%). Bacteriochlorin-type bisadducts are also obtained, although in low yield, from the reaction of meso-tetrakis(pentafluorophenyl)porphyrin with N-methyl, N-cyclohexyl or N-benzyl nitrone. The structure of a bis(N-benzyl isoxazolidine-fused) bacteriochlorin was determined by single-crystal X-ray diffraction and rationalized by DFT calculations. To further explore the nature of site selectivity in the formation of bisadducts, isomeric mixed bacteriochlorins and isobacteriochlorins were synthesized by two complementary routes that involved the sequential addition of two types of 1,3-dipoles to the porphyrin macrocycle: a nitrone and an azomethine ylide. The photophysical properties of the mixed bacteriochlorins were evaluated and the results were compared with the reported data for other meso-tetraarylbacteriochlorins.

Luminescent metal–organic frameworks (LMOFs) are promising materials for lighting and sensing applications. Herein, exposure of the highly luminescent Zn2(bpdc)2(bpee) MOF (H2bpdc = 4,4′-biphenyldicarboxylic acid and bpee = 1,2-bipyridylethene) to subppm amine contents turns on a new absorption band unambiguously ascribed to free bpee molecules concomitant with the gradual appearance of a new photoluminescence band at shorter wavelengths. These findings combined with Fourier-transform infrared spectra, powder X-ray diffraction and thermogravimetric analysis of exposed LMOF powders confirm that bpee ligands are exchanged by amines and released inside the LMOF, triggering absorption and luminescence features which can be exploited for highly sensitive amine recognition. This principle was demonstrated in mixed matrix membranes (MMMs) prepared by a simple solvent-free method consisting of mixing Zn2(bpdc)2(bpee) with dimethylvinyl-terminated dimethylsiloxane and dimethylhydrogen siloxane. This method enabled...

Introdução: O resveratrol é uma fitoalexina natural cujos principais benefícios devem-se às suas propriedades anti-inflamatórias e antioxidantes. Os seus efeitos sugerem que este é um suplemento útil para a redução da inflamação, podendo desempenhar um papel fundamental na prevenção das doenças cardiovasculares. Este promove a vasodilatação pela indução da síntese de óxido nítrico (NO), possui atividade antitrombótica e evita a agregação plaquetária. O fator de crescimento endotelial vascular ( VEGF) é responsável pela angiogénese, sendo a sua expressão infuenciada pelo resveratrol. Objetivos: Avaliar o efeito do resveratrol no perfl vascular pela determinação da pressão arterial e dos biomarcadores interleucina-6 (IL-6), proteína C reativa (PCR), VEGF e NO. Material e Métodos: 27 alunos com idades compreendidas entre os 18 e os 22 anos foram divididos em grupo controlo (GC) e grupo de intervenção (GI), que consumiram placebo e 100 mg de resveratrol por dia, respetivamente, durante 1 mês. A pressão arterial foi medida com aparelho automático validado. Os níveis de PCR foram obtidos por imunoturbidimetria, os de IL-6 e VEGF por slot blot e a quantifcação de NO por espectrofotometria. Resultados: Entre os grupos observou-se uma diminuição da pressão arterial braquial e central (ρ˂0.05). A variação negativa no NO apresentou-se superior no GC apesar das diferenças não serem signifcativas (p>0,05). Nos restantes marcadores avaliados não se observaram diferenças signifcativas. Conclusões: A ingestão regular de resveratrol parece ser uma abordagem preventiva a nível vascular, dado que modula positivamente o perfl vascular, reduzindo a pressão arterial. A variação nos níveis de NO poderá ajudar a explicar os benefícios verifcados. info:eu-repo/semantics/publishedVersion

A series of pyridyl analogues of rosamines was prepared by employing two methodologies: (i) the conventional-heating condensation of a pyridinecarboxaldehyde with 3-(diethylamino)phenol in propionic acid, and (ii) the novel ohmic-heating assisted condensation under "on water" conditions, followed by oxidation. The 4-pyridyl substituted rosamine was further converted into the N-methylpyridinium derivative through N-alkylation using methyl iodide. The influence of the position and cationization of the nitrogen atom of the pyridyl ring in the physicochemical properties of fluorophores was investigated by 1 H, 13 C, 15 N NMR spectral analysis, UV/Vis and fluorescence spectroscopy, single-crystal X-ray diffraction (4-pyridyl and N-methylpyridinium derivatives) and thermal-behavior analysis. Curiously, for ethanolic solutions of 4-pyridyl and N-methylpyridinium derivatives an extinction of color and fluorescence over time was observed. This phenomenon was further studied and the data revealed that it is the result of nucleophilic addition of ethoxide ion to the central 9-position of the xanthene. The kinetics of the process is slower for the 4-pyridyl rosamine, which emphasizes the importance of the charge in the N-methylpyridinium analogue in the reactivity of the molecule towards a nucleophile agent. This phenomenon is reversible, meaning that the compounds can be rapidly recovered by decreasing the pH, opening new avenues in the sensing applications of this class of rosamines.

In this work, we report the synthesis and characterization of three novel copper(II) complexes of naphthyl derived 3-hydroxy-4-pyridinone chelators. Their antibacterial activity against several Gram-positive and Gram-negative reference strains and multidrug-resistant clinical isolates was assessed through determination of the minimum inhibitory concentration (MIC). The complex Cu(naph1pp)2 shows the highest antibacterial activity, including against multidrug-resistant isolates, nonetheless, being more active against Gram-positive than Gram-negative bacteria. Cu(naph1pp)2 was further explored in combinatorial tests with ciprofloxacin against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). The combination of Cu(naph1pp)2 and ciprofloxacin is considered additive, i.e., the effect of the two compounds combined is stronger than that of the individual compounds in the equivalent concentration.

Three new hydrophilic 3-hydroxy-4-pyridinone chelators containing ether-derived substituents were prepared by a more sustainable synthetic protocol that involves the use of microwave heating and commercially available amines, allowing the successful production of highly water soluble chelators with improved reaction yields and reaction times. Compared with parent 3-hydroxy-4-pyridinone ligands, the new compounds were obtained faster and in higher amounts, facilitating the scale up of the synthesis, which is crucial to produce these ligands and their respective iron(III) complexes for many biological, analytical and agricultural applications. Ligands were fully characterized by 1H and 13C Nuclear Magnetic Resonance, High Resolution Mass Spectrometry and Single Crystal X-ray Diffraction and their performance in the analytical determination of iron(III) in water samples was evaluated by sequential injection methods. The results obtained are scientifically relevant, pointing out the potential of the new and straightforwardly synthesized ligands as analytical reagents for determination of iron(III).

Information provided by geotagged photos allow us to know where and when people have been, supporting a better understanding about tourist’s movement patterns across a destination. The aim of this paper is to study tourists’ movement patterns during their staying in Porto through the analysis of geotagged photos in order to fulfill marketing segmentation in an innovative way. For that purpose, the SPADE algorithm was used to find sequence patterns of tourists paths based on the time and location of the photos collected. Then, the K-Mode clustering algorithm was applied to these sequences in order to find identical behaviors in terms of paths followed by tourists. At the same time, in order to understand the influence of the different attractions on tourists’ paths, we performed a Social Network Analysis of the touristic attractions (spots, museums, streets, monuments, etc.). Based on the time and location of the photos collected, along with personal information, it was possible to understand tourists’ frequent movements across the city and to identify market segments based on a hybrid strategy.

The purpose of this chapter is to analyze the effect that corporate governance measures have in external audit fees in two countries where this matter is not much developed: Portugal and Spain. The analysis includes a sample of 39 listed companies on the Portuguese Stock Exchange and 104 listed companies on the Spanish Stock Exchanges for the years 2013 to 2015 using an OLS regression model. For the Spanish sample, the results show that the capital hold by the Board of Directors influence negatively external audit fees. The results are in accordance with the supplier perspective which states that better corporate governance practices decrease the control risk and, consequently, audit fees. On the other hand, the Board of Directors' diligence also affected external audit fees but positively, that is, the greater the number of meetings the greater the demand for an audit with quality which result in higher fees charged (demand perspective). For the Portuguese sample it can be observed that corporate governance characteristics do not affect external audit fees.

The main purpose of this chapter is to analyze the relationship between internal and external audit and its effect on external audit fees, through a questionnaire addressed to the external auditors of Portugal and Spain. It obtained 131 answers for Portugal and 149 answers for Spain. According to the results, the competencies and characteristics of internal auditors, as well as the type of activities performed by them and the communication between internal and external auditors, have a significant influence on the decision of using the internal audit work. However, the Portuguese external auditors do not consider this influence to be so significant that it affects the number of substantive tests, the quality of external audit, and external audit fees. However, for Spanish auditors using internal audits decreases the planned hours, the number of control and substantive tests, and improves external audit quality, but does not reflect in the fees to be charged to the client.