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Lignin-derived carbon nanofibers (LCNFs) formed via the solution blowing of a biopolymer are developed here as a promising replacement for polyacrylonitrile (PAN)-derived carbon nanofibers (PCNFs) formed via electrospinning for such applications as supercapacitor (SC) electrodes. Accordingly, it is demonstrated here that a biopolymer (kraft lignin, which is, essentially, a waste material) can substitute a petroleum-derived polymer (PAN). Moreover, this can be achieved using a much faster and safer fiber-forming method. The present work employs the solution blowing of lignin-derived nonwovens and their carbonization to form electrode materials. These materials are characterized and explored as the electrodes in supercapacitor prototypes. Given the porosity importance of carbon fibers in SC applications, N2 gas adsorption tests were performed for characterization. LCNFs revealed the specific surface area (SSA) and capacitance values as high as 1726 m2/g and 11.95 F/g, which are about one-half of those for PCNFs, 3624 m2/g and 25.5 F/g, respectively. The capacitance values of LCNFs are comparable with those reported in the literature, but the SSA observed here is much higher. Moreover, no further post-carbonization activation steps were performed here in comparison with those materials reported in the literature. It was also found here that fiber pre-oxidation in air prior to carbonization and the addition of zinc chloride affect the SSA and capacitance values of both LCNFs and PCNFs. The electrochemical tests of the SCs prototypes were used to evaluate their capacitance at different charging rates, voltage windows, and the number of cycles. The capacitance of PCNFs decreased by about 47% during fast charging, while the capacitance of LCNFs improved during fast charging, bringing them to the level of only 21% below that of PCNFs. These changes were correlated with the packing density of the electrodes. It should be emphasized that LCNFs revealed a much higher mass yield, which was 4–5 times higher than that of PCNFs. LCNFs also possess a higher packing density, a lower price, and cause a significantly lower environmental impact than PCNFs. The best cell supercapacitor delivered a maximum specific energy of 1.77 Wh/kg and a maximum specific power of 156 kW/kg, surpassing conventional electrochemical supercapacitors. Remarkably, it retained 95.2% of its initial capacitance after 10,000 GCD cycles at a current density of 0.25 A/g, indicating robust stability. Accordingly, kraft lignin, a bio-waste material, holds great promise as a raw material for supercapacitor electrodes.

Sulfonamides are a conventional class of antibiotics that are well-suited to combat infections. However, their overuse leads to antimicrobial resistance. Porphyrins and analogs have demonstrated excellent photosensitizing properties and have been used as antimicrobial agents to photoinactivate microorganisms, including multiresistant Staphylococcus aureus (MRSA) strains. It is well recognized that the combination of different therapeutic agents might improve the biological outcome. In this present work, a novel meso-arylporphyrin and its Zn(II) complex functionalized with sulfonamide groups were synthesized and characterized and the antibacterial activity towards MRSA with and without the presence of the adjuvant KI was evaluated. For comparison, the studies were also extended to the corresponding sulfonated porphyrin TPP(SO3H)4. Photodynamic studies revealed that all porphyrin derivatives were effective in photoinactivating MRSA (>99.9% of reduction) at a concentration of 5.0 μM upon white light radiation with an irradiance of 25 mW cm−2 and a total light dose of 15 J cm−2. The combination of the porphyrin photosensitizers with the co-adjuvant KI during the photodynamic treatment proved to be very promising allowing a significant reduction in the treatment time and photosensitizer concentration by six times and at least five times, respectively. The combined effect observed for TPP(SO2NHEt)4 and ZnTPP(SO2NHEt)4 with KI seems to be due to the formation of reactive iodine radicals. In the photodynamic studies with TPP(SO3H)4 plus KI, the cooperative action was mainly due to the formation of free iodine (I2).

Cancer is the second leading cause of death worldwide; therefore, there is an urgent need to find safe and effective therapies. Triple-negative breast cancer (TNBC) is diagnosed in ca. 15–20% of BC and is extremely aggressive resulting in reduced survival rate, which is mainly due to the low therapeutic efficacy of available treatments. Photodynamic therapy (PDT) is an interesting therapeutic approach in the treatment of cancer; the photosensitizers with good absorption in the therapeutic window, combined with their specific targeting of cancer cells, have received particular interest. This review aims to revisit the latest developments on chlorin-based photoactive molecules for targeted therapy in TNBC. Photodynamic therapy, alone or combined with other therapies (such as chemotherapy or photothermal therapy), has potential to be a safe and a promising approach against TNBC.

New porphyrin–pyrrolidine/pyrroline conjugates were prepared by revisiting 1,3-dipolar cycloaddition reactions between a porphyrinic azomethine ylide and a series of dipolarophiles. Cationic conjugates obtained by alkylation of the pyrrolidine/pyrroline cycloadducts showed ability to generate singlet oxygen and to produce iodine in presence of KI when irradiated with visible light. Some of the cationic derivatives showed photobactericidal properties towards a Gram-negative bioluminescent E. coli. In all cases, these features were significantly improved using KI as coadjutant, allowing, under the tested conditions, the photoinactivation of the bacterium until the detection limit of the method with a drastic reduction of the required photosensitizer concentration and irradiation time. The obtained results showed a high correlation between the ability of the cationic porphyrin derivative to produce singlet oxygen and iodine and its E. coli photoinactivation profile.

Microbial infection is a severe concern, requiring the use of significant amounts of antimicrobials/biocides, not only in the hospital setting, but also in other environments. The increasing use of antimicrobial drugs and the rapid adaptability of microorganisms to these agents, have contributed to a sharp increase of antimicrobial resistance. It is obvious that the development of new strategies to combat planktonic and biofilm-embedded microorganisms is required. Photodynamic inactivation (PDI) is being recognized as an effective method to inactivate a broad spectrum of microorganisms, including those resistant to conventional antimicrobials. In the last few years, the development and biological assessment of new photosensitizers for PDI were accompanied by their immobilization in different supports having in mind the extension of the photodynamic principle to new applications, such as the disinfection of blood, water, and surfaces. In this review, we intended to cover a significant amount of recent work considering a diversity of photosensitizers and supports to achieve an effective photoinactivation. Special attention is devoted to the chemistry behind the preparation of the photomaterials by recurring to extensive examples, illustrating the design strategies. Additionally, we highlighted the biological challenges of each formulation expecting that the compiled information could motivate the development of other effective photoactive materials.

Background/objectives: In this article, we present a literature review of methods used to measure the shaping ability of endodontic rotary files, including the selection of endodontic sample type (extracted teeth versus simulated blocks) and an imaging evaluation method. This review was conducted as background research to identify concerns that arise when designing research studies in this domain and propose how the field can plan more systematic studies going forward., Methods: A literature search was conducted using PubMed, MEDLINE, Embase, ScienceDirect, Scopus, and e B-on databases, including studies published in English from January 2010 to June 2024. Only studies that specified in vitro or ex vivo methods for evaluating the endodontic performance of NiTi rotary files on canal transportation and centering ability were considered., Results: A total of 86 studies met the inclusion criteria from an initial pool of 651. Of these, 67 studies used extracted teeth, while 20 utilized simulated root canals in resin blocks. For evaluation methods, 55 studies employed Micro-Computed Tomography and Cone-Beam Computed Tomography (MCT + CBCT), 30 used Double Digital Images/Radiographs/Photographs (DDIR + DDIP) with software analysis, 1 used both DDIR and MCT, 1 used high-precision nano-CT, and 1 used a digital single-lens reflex (DSLR) camera., Conclusions: The findings indicate that the MCT method and its advanced variations appear superior in many cases for evaluating the quality of root canal instrumentation due to their ability to provide detailed three-dimensional images. We also discuss the pros and cons of other evaluation methods, including CBCT and DDIR. Finally, we identify important factors to consider for optimizing future cross-study comparisons. This work highlights the importance of being familiar with shaping ability assessment methods as new instruments are introduced to the market.

The increasing frequency and duration of marine heatwaves (MHWs) due to climate change pose severe threats to aquaculture, causing drastic physiological and growth impairments in farmed fish, undermining their resilience against additional environmental pressures. To ensure sustainable production that meets the global seafood demand and animal welfare standards, cost-effective and eco-friendly strategies are urgently needed. This study explored the efficacy of the red macroalga Asparagopsis taxiformis on juvenile white seabream Diplodus sargus reared under optimal conditions and upon exposure to a MHW. Fish were fed with four experimental diets (0%, 1.5%, 3% or 6% of dried powdered A. taxiformis ) for a prophylactic period of 30 days (T30) and subsequently exposed to a Mediterranean category II MHW for 15 days (T53). Biometric data and samples were collected at T30, T53 and T61 (8 days post-MHW recovery), to assess performance indicators, biomarker responses and histopathological alterations. Results showed that A. taxiformis supplementation improved catalase and glutathione S-transferase activities and reduced lipid peroxidation promoted by the MHW, particularly in fish biofortified with 1.5% inclusion level. No histopathological alterations were observed after 30 days. Additionally, fish biofortified with 1.5% A. taxiformis exhibited increased citrate synthase activity and fish supplemented with 1.5% and 3% showed improved digestive enzyme activities (e.g., pepsin and trypsin activities). Overall, the present findings pointed to 1.5% inclusion as the optimal dosage for aquafeeds biofortification with A. taxiformis , and confirmed that this seaweed species is a promising cost-effective ingredient with functional properties and great potential for usage in a climate-smart context.

The Brazilian Atlantic Forest, renowned for its exceptional species richness and high endemism, acts as a vital reservoir of terrestrial biodiversity, often referred to as a biodiversity hotspot. Consequently, there is an urgent need to restore this forest to safeguard certain species and to unravel the ecophysiological adaptations of others. This study aims to integrate some physiological parameters, including gas exchange and chlorophyll a fluorescence, with anatomical and metabolic techniques to elucidate how five different native species ( Paubrasilia echinata , Chorisia glaziovii , Clusia nemorosa , Licania tomentosa , and Schinus terebinthifolius ), each occupying distinct ecological niches, respond to seasonal variations in rainfall and their consequences. Our investigation has revealed that C. nemorosa and P. echinata exhibit robust mechanisms to mitigate the adverse effects of drought. In contrast, others demonstrate greater adaptability (e.g., S. terebinthifolia and C. glaziovii ). In this context, exploring metabolic pathways has proven invaluable in comprehending the physiological strategies and their significance in species acclimatization. This study provides a comprehensive overview of the impact of water restrictions and their consequential effects on various species, defining the strategies each species uses to mitigate water privation during the dry season.

Water deficiency has been recognized as a major abiotic stress that causes losses in maize crops around the world. The maize crop is very important due to the range of products that are derived from this plant. A potential way to reduce the damages caused by water deficiency in maize crops is through the association with plant growth-promoting bacteria (PGPB) and arbuscular mycorrhizal fungi (AMF). To define the mechanisms developed by associative PGPB and AMF in maize that are involved in protection against moderate drought (MD), this study evaluated the biometrical, anatomical, biochemical, and physiological parameters of maize grown under MD and inoculated with different PGPB ( Azospirillum brasilense strain Ab-V5 and Bacillus sp. strain ZK) and with AMF. The relative water content did not change in the treatments. The association with ZK increased the shoot:total ratio, total dry weight, maximum quantum yield of photosystem II, vascular cylinder thickness, and vascular cylinder area. The Ab-V5 inoculation led to an increment in root dry weight, the area of metaxylem vessel elements, and nitrate reductase activity. The AMF association did not lead to changes in the measured parameters. The results indicate that the association with PGPB is a relevant alternative to contribute to reducing losses in maize crops under drought. However, AMF is not indicated for this crop under drought.

Background : Post-thrombotic syndrome (PTS) is a common and debilitating sequela of lower limb deep vein thrombosis (DVT). There is significant heterogeneity in reported PTS incidence due to lack of standardised diagnostic criteria. This review aimed to develop diagnostic criteria for PTS and subsequently refine the reported incidence and severity. Methods : PRISMA principles were followed; however, the review was not registered. The Cochrane CENTRAL database, MEDLINE, Embase, the NHS NICE Healthcare Databases Advanced Search interface, and trial registers including isrctn.com and clinicaltrials.gov were searched for studies addressing areas of interest (PTS definition, epidemiology, assessment). An experienced Clinical Librarian undertook the systematic searches, and two independent reviewers agreed on the relevance of the papers. Conflicts were resolved through panel review. Evidence quality was assessed using a modified Coleman scoring system and weighted according to their relevance to the aforementioned areas of interest. Results : A total of 339 abstracts were retrieved. A total of 33 full-text papers were included in this review. Following qualitative analysis, four criteria were proposed to define PTS: (1) a proven thrombotic event on radiological assessment; (2) a minimum 24-month follow-up period after an index DVT; (3) assessment with a validated score; and (4) evidence of progression of venous insufficiency from baseline. Four papers conformed to our PTS definition criteria, and the incidence of mild to moderate PTS ranged from 7 to 36%. On reviewing the studies which utilised the recommended Villalta scale, PTS incidence narrowed further to 23-36%. Incidence and severity reached a plateau at 24 months. Conclusions : Four diagnostic criteria were developed from qualitative synthesis. When these criteria were applied to the literature, the range of reported PTS incidence narrowed. These four criteria may standardise PTS diagnosis in future studies, facilitating the pooling of data for meta-analysis and synthesis of higher levels of evidence.

Colour assessment using digital methods can yield varying results, and it is important for clinicians to recognize the potential variability intra and inter-device. This study aimed to compare the L*a*b* values of VITA Classical (VC) and VITA Toothguide 3D-MASTER (VM) guides using two methods, SpectroShade (SS) and eLAB. Thirty-four measurements per tab were performed by a single operator across three batches of each guide. Intraclass correlation coefficients (ICC) between batches were calculated. Values <0.5, 0.5-0.75, 0.75-0.9, and >0.90 were classified as poor, moderate, good, and excellent reliability, respectively. Results were reported as mean and standard deviation of the L*a*b* values and respective colour differences (ΔE 00 ) for each tab and method. Statistical analyses were performed with an independent t -test, α = 0.05. ICC values between batches were excellent for all L*a*b*, except for a* component in eLAB. There were statistically significant differences between methods in most L*a*b* values. The intra-device mean ΔE 00 was 0.5 ± 0.6 for VC, 0.5 ± 0.8 for VM in SS, 1.1 ± 0.8 for VC, 1.1 ± 0.9 for VM in eLAB. The mean ΔE 00 inter-device was 4.9 ± 1.7 for VC, 5.0 ± 1.7 for VM. Both methods demonstrated good internal consistency, with high ICC values and low intra-device colour differences, but exhibited high variability between methods, higher for a* the component.

In recent years, cocoa and dark chocolate have attracted the interest of consumers not only for their sensory characteristics but also for their nutritional properties and positive impact on health. The baobab is a fruit of African origin with a sour and slightly sweet flavour, widely consumed by local communities due to its unique nutritional features. The aim of this work was to evaluate the impact of the concentration of baobab flour in the development of functional dark chocolate, including physical, chemical, nutritional and sensory evaluations. The results presented a positive correlation between the incorporation of baobab flour and the antioxidant activity (up to 2297 mmol TE/100 g), vitamin C content (up to 49.7 mg/100 g), calcium (up to 1052 mg/kg), potassium (up to 10,175 mg/kg), phosphorus (up to 795.9 mg/kg), chlorine (up to 235.4 mg/kg) and sulphur (up to 1158 mg/kg). The sensory evaluation of dark chocolate with 3% baobab presented the highest evaluation on the parameters "texture" and "overall flavour", while the parameter "overall flavour" presented the lowest evaluation on chocolate with 9% baobab. No influence was observed on fatty acid profile, protein, fat and hardness.

Ageing beer in contact with wood is a common technological procedure that has been used for centuries to improve colour, structure, and certain flavours. Herein, the impact of the addition of French and American oak wood to two beer styles, pale and dark, on beer phenolic composition (total phenolics, total flavonoids, and HPLC-DAD) and bioactivity (FRAP, DPPH, anti-inflammatory activity in RAW 264.7, and antiproliferative in Caco-2 cells) was assessed. Thirteen phenolics were quantified with values according to previous reports. Dark malt resulted in higher values of total phenolics, to which m-hydroxybenzoic, syringic, p-coumaric acids, and xanthohumol contributed considerably; the exception was (+)-catechin and salicylic acid, which were found to be higher in pale beers. American oak significantly increased 3,4-dihydroxyphenylacetic, vanillic, and syringic acids up to roughly 3, 2, and 10 times, respectively, when compared with French wood. FRAP and DPPH values varied between pale and dark beers, with a less pronounced effect after wood addition. All samples presented considerable cellular antioxidant and anti-inflammatory as well as antiproliferative activity, but differences were found only for the antiproliferative activity, which was higher for the dark beers, which reached about 70% inhibition. Overall, the influence of malts was more pronounced than that of wood, in the studied conditions, highlighting the overwhelming impact of malts on the bioactivity of beer.

Serpa is a protected designation of origin (PDO) cheese produced with raw ewes' milk and coagulated with Cynara cardunculus . Legislation does not allow for milk pasteurization and starter culture inoculation. Although natural Serpa's rich microbiota allows for the development of a unique organoleptic profile, it also suggests high heterogeneity. This raises issues in the final sensory and safety properties, leading to several losses in the sector. A possible solution to overcoming these issues is the development of an autochthonous starter culture. In the present work, some Serpa cheese Lactic acid bacteria (LAB)-isolated microorganisms, previously selected based on their safety, technological and protective performance, were tested in laboratory-scale cheeses. Their acidification, proteolysis (protein and peptide profile, nitrogen fractions, free amino acids (FAA)), and volatiles generation (volatile fatty acids (VFA) and esters) potential was investigated. Significant differences were found in all parameters analyzed, showing a considerable strain effect. Successive statistical analyses were performed to compare cheese models and Serpa PDO cheese. The strains L. plantarum PL1 and PL2 and the PL1 and L. paracasei PC mix were selected as the most promising, resulting in a closer lipolytic and proteolytic profile of Serpa PDO cheese. In future work, these inocula will be produced at a pilot scale and tested at the cheese level to validate their application.

The baobab tree ( Adansonia digitata L.) is found widely in the forests and savannas of sub-Saharan Africa. The baobab fruit has a sour and slightly sweet taste and is widely consumed by the natives, thus containing a high nutritional value and providing a source of income for rural people. This study aimed to compare the nutritional composition of baobab fruit pulp from different localities in the Namibe province (Angola). Twenty samples of baobab pulp were collected in markets of the four municipalities of Namibe. The results obtained showed that there is some geographic location dependence on nutritional and functional composition. The municipality of Camucuio showed samples with higher fibre content (56.62 g/100 g) and vitamin C (288.9 mg/100 g). Samples from the Virei municipality stood out for their antioxidant activity (1936 mmol TE/100 g), high K content (42.4 mg/g) and higher values of protein (2.42 g/100 g). The samples collected in the municipality of Bibala stood out for their high contents of carbohydrates (28.1 g/100 g), total phenolic compounds (972 mg GAE/100 g) and Ca (3.80 mg/g). Despite the differences in origin, the high nutritional value of baobab fruit has the potential to improve the diet of thousands of people in Africa qualitatively.

Serpa is a protected designation of origin cheese produced with a vegetable coagulant ( Cynara cardunculus L.) and raw ovine milk. Despite the unique sensory profile of raw milk cheeses, numerous parameters influence their sensory properties and safety. To protect the Serpa cheese quality and contribute to unifying their distinctive features, some rheologic and physicochemical parameters of cheeses from four PDO producers, in distinct seasons and with different sensory scores, were monitored. The results suggested a high chemical diversity and variation according to the dairy, month and season, which corroborates the significant heterogeneity. However, a higher incidence of some compounds was found: a group of free amino acids (Glu, Ala, Leu, Val and Phe), lactic and acetic acids, some volatile fatty acids (e.g., iC4, iC5, C6 and C12) and esters (e.g., ethyl butanoate, decanoate and dodecanoate). Through the successive statistical analysis, 13 variables were selected as chemical markers of Serpa cheese specificity: C 3 , C 4 , iC 5 , C 12 , Tyr, Trp, Ile, 2-undecanone, ethyl isovalerate, moisture content on a fat-free basis, the nitrogen-fractions (maturation index and non-protein and total nitrogen ratio) and G' 1 Hz . These sensory markers' identification will be essential to guide the selection and development of an autochthonous starter culture to improve cheese quality and safety issues and maintain some of the Serpa authenticity.

Dual antiplatelet therapy (DAPT), alongside percutaneous coronary intervention (PCI), is central to the prevention of ischemic events following acute coronary syndrome (ACS). However, response to therapy can vary due to several factors including CYP2C19 gene variation, which shows increased prevalence in East Asian populations. DAPT responsiveness can be assessed using techniques such as light transmission aggregometry (LTA), VerifyNow ® and thromboelastography with the PlateletMapping ® assay, and there is increasing focus on the utility of platelet function testing to guide individualized treatment. This systematic literature review of one English and three Chinese language databases was conducted to evaluate the evidence for the utility of thromboelastography in ACS/PCI in East Asia. The search identified 42 articles from the English language and 71 articles from the Chinese language databases which fulfilled the pre-determined inclusion criteria, including 38 randomized controlled trials (RCTs). The identified studies explored the use of thromboelastography compared to LTA and VerifyNow in monitoring patient responsiveness to DAPT, as well as predicting ischemic risk, with some studies suggesting that thromboelastography is better able to detect low DAPT response than LTA. Other studies, including one large RCT, described the use of thromboelastography in guiding the escalation of DAPT, with some evidence suggesting that such protocols reduce ischemic events without increasing the risk of bleeding. There was also evidence suggesting that thromboelastography can be used to identify individuals with DAPT hyporesponsiveness genotypes and could potentially guide treatment by adjusting therapy in patients depending on responsiveness.

The risk assessment of pesticide residues in food is a key priority in the area of food safety. Most jurisdictions have implemented pre-marketing authorization processes, which are supported by prospective risk assessments. These prospective assessments estimate the expected residue levels in food combining results from residue trials, resembling the pesticide use patterns, with food consumption patterns, according to internationally agreed procedures. In addition, jurisdictions such as the European Union (EU) have implemented large monitoring programs, measuring actual pesticide residue levels in food, and are supporting large-scale human biomonitoring programs for confirming the actual exposure levels and potential risk for consumers. The organophosphate insecticide chlorpyrifos offers an interesting case study, as in the last decade, its acceptable daily intake (ADI) has been reduced several times following risk assessments by the European Food Safety Authority (EFSA). This process has been linked to significant reductions in the use authorized in the EU, reducing consumers' exposure progressively, until the final ban in 2020, accompanied by setting all EU maximum residue levels (MRL) in food at the default value of 0.01 mg/kg. We present a comparison of estimates of the consumer's internal exposure to chlorpyrifos based on the urinary marker 3,5,6-trichloro-2-pyridinol (TCPy), using two sources of monitoring data: monitoring of the food chain from the EU program and biomonitoring of European citizens from the HB4EU project, supported by a literature search. Both methods confirmed a drastic reduction in exposure levels from 2016 onwards. The margin of exposure approach is then used for conducting retrospective risk assessments at different time points, considering the evolution of our understanding of chlorpyrifos toxicity, as well as of exposure levels in EU consumers following the regulatory decisions. Concerns are presented using a color code, and have been identified for almost all studies, particularly for the highest exposed group, but at different levels, reaching the maximum level, red code, for children in Cyprus and Israel. The assessment uncertainties are highlighted and integrated in the identification of levels of concern.

The aim of this study was to evaluate the impact of high-pressure processing (HPP) on the long-term storage of chocolate fillings at room temperature, compared with conventional storage at lower temperatures. Dark chocolate fillings were treated at different pressure levels, holding times and stored at 20 °C for 12 months. Unprocessed batches were stored at 4 °C and at -12 °C. Moisture, water activity (aw), pH, colour, G' 1Hz and indigenous microflora were measured at 2, 4, 6, 8, 10 and 12 months of storage. Results showed that 600 MPa/20 min processing was the most effective controlling mesophilic group, presenting 3.8 log cfu/g after 12 months of storage, and inactivating moulds and yeasts after HPP treatment. Colour was affected by storage, including a reduction in the L* parameter in all conditions to final values between 37.8 and 39.3, while the a* parameter increased during storage time at -12 °C and 4 °C to final values of around 12, and parameter b* decreased at storage temperature 20 °C to 5.3. Storage time affected the rheological behaviour of HPP-treated samples, increasing G' 1Hz from the 2nd to 12th month of storage time to the final values between 1603 kPa and 2139 kPa. Moisture, aw and pH were not affected by HPP treatment nor storage time.

Traditional ewe's cheese producers face certain challenges caused by fluctuating environmental parameters inside the ripening room, which lead to lack of homogeneity in the final product. The present research discusses the application of computer fluid dynamics for simulating the distribution of environmental parameters, predicting the airflow pattern, and identifying critical areas where such parameters could cause reduced cheese quality. A new monitoring system was developed including presence sensors, temperature and humidity dataloggers, pneumatic actuators, microcontrollers, and microcomputers connected remotely for control, data visualization, and processing. The validation of the computer simulation and monitoring system was made with a batch of 40 ewe's cheeses distributed in three different zones inside a prototype ripening room and ripened for 35 days. At 35 days, a physical, chemical, and microbiological characterization of cheeses was made for evaluation of the influence of environmental conditions on cheese quality. The comparison between simulated and local measurements showed close agreement, especially concerning air velocity inside the stacks of cheese. The results of Pearson's correlation analysis and PCA concluded that temperature affected the appearance of the rind, hardness, number and area occupied by holes. Humidity affected a w and mFeret. Air velocity affected pH and the circularity of gas holes.

Neurotransmitter depletion and mitochondrial dysfunction are among the multiple pathological events that lead to neurodegeneration. Following our previous studies related with the development of multitarget mitochondriotropic antioxidants, this study aims to evaluate whether the π-system extension on the chemical scaffolds of AntiOXCIN2 and AntiOXCIN3 affects their bioactivity and safety profiles. After the synthesis of four triphenylphosphonium (TPP + ) conjugates (compounds 2 - 5 ), we evaluated their antioxidant properties and their effect on neurotransmitter-metabolizing enzymes. All compounds were potent equine butyrylcholinesterase ( eq BChE) and moderate electric eel acetylcholinesterase ( ee AChE) inhibitors, with catechols 4 and 5 presenting lower IC 50 values than AntiOXCIN2 and AntiOXCIN3, respectively. However, differences in the inhibition potency and selectivity of compounds 2 - 5 towards non-human and human cholinesterases (ChEs) were observed. Co-crystallization studies with compounds 2 - 5 in complex with human ChEs ( h ChEs) showed that these compounds exhibit different binging modes to h AChE and h BChE. Unlike AntiOXCINs, compounds 2 - 5 displayed moderate human monoamine oxidase ( h MAO) inhibitory activity. Moreover, compounds 4 and 5 presented higher ORAC-FL indexes and lower oxidation potential values than the corresponding AntiOXCINs. Catechols 4 and 5 exhibited broader safety windows in differentiated neuroblastoma cells than benzodioxole derivatives 2 and 3. Compound 4 is highlighted as a safe mitochondria-targeted antioxidant with dual ChE/MAO inhibitory activity. Overall, this work is a contribution for the development of dual therapeutic agents addressing both mitochondrial oxidative stress and neurotransmitter depletion.

Vasopressins are evolutionarily conserved peptide hormones. Mammalian vasopressin functions systemically as an antidiuretic and regulator of blood and cardiac flow essential for adapting to terrestrial environments. Moreover, vasopressin acts centrally as a neurohormone involved in social and parental behavior and stress response. Vasopressin synthesis in several cell types, storage in intracellular vesicles, and release in response to physiological stimuli are highly regulated and mediated by three distinct G protein coupled receptors. Other receptors may bind or cross-bind vasopressin. Vasopressin is regulated spatially and temporally through transcriptional and post-transcriptional mechanisms, sex, tissue, and cell-specific receptor expression. Anomalies of vasopressin signaling have been observed in polycystic kidney disease, chronic heart failure, and neuropsychiatric conditions. Growing knowledge of the central biological roles of vasopressin has enabled pharmacological advances to treat these conditions by targeting defective systemic or central pathways utilizing specific agonists and antagonists.

The variability and heterogeneity found in Évora cheeses, Protected Designation of Origin (PDO), can affect consumers' choices. Assessing the ripening conditions and their effect can be helpful. To study the effect of ripening duration in Évora cheese PDO, sensory and chemical analyses were performed in cheese samples subjected to 30, 60, and 120 days of ripening under controlled conditions (temperature 14 to 15 °C and humidity 65 to 70%). Sensory analysis was conducted with a homogenous panel previously familiarized with the product after a short training period, and chemical analyses including pH, moisture, NaCl content, a w , and salt-in-moisture were determined. Panelists were able to distinguish the differences in the organoleptic characteristics of the three cheese stages, and chemical determinations showed significant differences between stages. Interrater agreement was higher in the sensory evaluation of cheeses with a longer maturation period. As expected, cheeses in the 120 days ripening period presented lower pH, moisture, and water activity and had higher salt-in-moisture content. This stage received the highest scores in hardness and color of the crust, intensity, pungency of the aroma, intensity of taste and piquancy, and firmness and granular characteristics of texture. Overall acceptance of cheese samples was positive, regardless of the ripening stage, which probably reflects both the homogeneity of taster profiles and the previous knowledge of this particular product. The degree of ripeness influences the physical, chemical, and sensory characteristics but does not affect the acceptance of this product by the consumer.

Due the implementation of nanotechnologies in the pharmaceutical industry over the last few decades, new type of cutting-edge formulations-nanopharmaceutics-have been proposed. These comprise pharmaceutical products at the nanoscale, developed from different types of materials with the purpose to, e.g., overcome solubility problems of poorly water-soluble drugs, the pharmacokinetic and pharmacodynamic profiles of known drugs but also of new biomolecules, to modify the release profile of loaded compounds, or to decrease the risk of toxicity by providing site-specific delivery reducing the systemic distribution and thus adverse side effects. To succeed with the development of a nanopharmaceutical formulation, it is first necessary to analyze the type of drug which is to be encapsulated, select the type matrix to load it (e.g., polymers, lipids, polysaccharides, proteins, metals), followed by the production procedure. Together these elements have to be compatible with the administration route. To be launched onto the market, the selected production method has to be scaled-up, and quality assurance implemented for the product to reach clinical trials, during which in vivo performance is evaluated. Regulatory issues concerning nanopharmaceutics still require expertise for harmonizing legislation and a clear understanding of clinically compliant production methods. The first part of this study addressing "Nanopharmaceutics: Part I-Clinical trials legislation and Good Manufacturing Practices (GMP) of nanotherapeutics in the EU" has been published in Pharmaceutics. This second part complements the study with the discussion about the production scales and clinically compliant production methods of nanopharmaceutics., Competing Interests: The authors declare no conflicts of interest.

The incidence of neglected diseases in tropical countries, such as Leishmaniasis and Chagas's disease, is attributed to a set of biological and ecological factors associated with the socioeconomic context of developing countries and with a significant burden to health care systems. Both Leishmaniasis and Chagas's disease are caused by different protozoa and develop diverse symptoms, which depend on the specific species infecting man. Currently available drugs to treat these disorders have limited therapeutic outcomes, frequently due to microorganisms' drug resistance. In recent years, significant efforts have been made towards the development of innovative drug delivery systems aiming to improve bioavailability and pharmacokinetic profiles of classical drug therapy. This paper discusses the key facts of Leishmaniasis and Chagas's disease, the currently available pharmacological therapies and the new drug delivery systems for conventional drugs.

Nanoemulsions are pharmaceutical formulations composed of particles within a nanometer range. They possess the capacity to encapsulate drugs that are poorly water soluble due to their hydrophobic core nature. Additionally, they are also composed of safe gradient excipients, which makes them a stable and safe option to deliver drugs. Cancer therapy has been an issue for several decades. Drugs developed to treat this disease are not always successful or end up failing, mainly due to low solubility, multidrug resistance (MDR), and unspecific toxicity. Nanoemulsions might be the solution to achieve efficient and safe tumor treatment. These formulations not only solve water-solubility problems but also provide specific targeting to cancer cells and might even be designed to overcome MDR. Nanoemulsions can be modified using ligands of different natures to target components present in tumor cells surface or to escape MDR mechanisms. Multifunctional nanoemulsions are being studied by a wide variety of researchers in different research areas mainly for the treatment of different types of cancer. All of these studies demonstrate that nanoemulsions are efficiently taken by the tumoral cells, reduce tumor growth, eliminate toxicity to healthy cells, and decrease migration of cancer cells to other organs.