Smart Carbon Fiber-Reinforced Polymer Composites for Damage Sensing and On-Line Structural Health Monitoring Applications.

High electrical conductivity, along with high piezoresistive sensitivity and stretchability, are crucial for designing and developing nanocomposite strain sensors for damage sensing and on-line structural health monitoring of smart carbon fiber-reinforced polymer (CFRP) composites. In this study, the influence of the geometric features and loadings of carbon-based nanomaterials, including reduced graphene oxide (rGO) or carbon nanofibers (CNFs), on the tunable strain-sensing capabilities of epoxy-based nanocomposites was investigated. This work revealed distinct strain-sensing behavior and sensitivities (gauge factor, GF) depending on both factors. The highest GF values were attained with 0.13 wt.% of rGO at various strains. The stability and reproducibility of the most promising self-sensing nanocomposites were also evaluated through ten stretching/relaxing cycles, and a distinct behavior was observed. While the deformation of the conductive network formed by rGO proved to be predominantly elastic and reversible, nanocomposite sensors containing 0.714 wt.% of CNFs showed that new conductive pathways were established between neighboring CNFs. Based on the best results, formulations were selected for the manufacturing of pre-impregnated materials and related smart CFRP composites. Digital image correlation was synchronized with electrical resistance variation to study the strain-sensing capabilities of modified CFRP composites (at 90° orientation). Promising results were achieved through the incorporation of CNFs since they are able to form new conductive pathways and penetrate between micrometer-sized fibers.

Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes.

BACKGROUND: Auranofin is an approved anti-rheumatic drug that has a broad-range inhibitory action against several microorganisms, including human pathogenic fungi. The auranofin activity against Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, has not been properly addressed. Since there are few therapeutic options for this life-threatening systemic mycosis, this study evaluated the effects of auranofin on H. capsulatum growth and expression of virulence factors. METHODOLOGY/PRINCIPAL FINDINGS: Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) of auranofin against 15 H. capsulatum strains with distinct genetic backgrounds were determined using the yeast form of the fungus and a microdilution protocol. Auranofin activity was also assessed on a macrophage model of infection and on a Tenebrio molitor invertebrate animal model. Expression of virulence-related genes was compared between auranofin treated and untreated H. capsulatum yeast cells using a quantitative PCR assay. Auranofin affected the growth of different strains of H. capsulatum, with MIC and MFC values ranging from 1.25 to 5.0 µM and from 2.5 to >10 µM, respectively. Auranofin was able to kill intracellular H. capsulatum yeast cells and conferred protection against the fungus in the experimental animal model of infection. Moreover, the expression of catalase A, HSP70, superoxide dismutase, thioredoxin reductase, serine proteinase, cytochrome C peroxidase, histone 2B, formamidase, metallopeptidase, Y20 and YPS3 proteins were reduced after six hours of auranofin treatment. CONCLUSIONS/SIGNIFICANCE: Auranofin is fungicidal against H. capsulatum and reduces the expression of several virulence-related genes, which makes this anti-rheumatic drug a good candidate for new medicines against histoplasmosis.

Divergent Regioselective Synthesis of Functionalized 1,2,3-1H-Triazoles from Nitriles and Arylazides under Metal- and/or Solvent-free Conditions.

Highly selective and divergent syntheses, which are crucial in both organic synthesis and medicinal chemistry, involve significant advancements in compound accessibility. By modifying α-cyano esters into α-cyano ketones, the synthesis pathway broadens to include a diverse range of 4-CN, 5-amino, and 5-arylamino derivatives of 1,2,3-triazoles, which are achieved notably through the Dimroth rearrangement. This versatility extends further with the potential for a triple cascade reaction, leading to the production of carboximidamide compounds, which are facilitated by the Cornforth rearrangement. Advancements in compound accessibility not only expand the repertoire of synthesized molecules but also open new avenues for potential pharmacological agents. Building on these findings, we have developed an innovative and efficient method for the divergent synthesis of functionalized 1,2,3-triazoles. This method strategically utilizes α-cyanocarbonyls and arylazides by harnessing their reactivity and compatibility to orchestrate a variety of molecular transformations. By optimizing these substrates, our goal is to simplify synthetic routes, improve product yields, and accelerate the discovery and development of new chemical entities with promising biological activities.

Exploring the molecular pathways of the activation process in PPARγ recurrent bladder cancer mutants.

The intricate involvement of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in glucose homeostasis and adipogenesis is well-established. However, its role in cancer, particularly luminal bladder cancer, remains debated. The overexpression and activation of PPARγ are implicated in tumorigenesis. Specific gain-of-function mutations (M280I, I290M, and T475M) within the ligand-binding domain of PPARγ are associated with bladder cancer and receptor activation. The underlying molecular pathways prompted by these mutations remain unclear. We employed a dual-basin structure-based model (db-SBM) to explore the conformational dynamics between the inactive and active states of PPARγ and examined the effects of the M280I, I290M, and T475M mutations. Our findings, consistent with the existing literature, reveal heightened ligand-independent transcriptional activity in the I290M and T475M mutants. Both mutants showed enhanced stabilization of the active state compared to the wild-type receptor, with the I290M mutation promoting a specific transition route, making it a prime candidate for further study. Electrostatic analysis identified residues K303 and E488 as pivotal in the I290M activation cascade. Biophysical assays confirmed that disrupting the K303-E488 interaction reduced the thermal stabilization characteristic of the I290M mutation. Our study demonstrates the predictive capabilities of combining simulation and cheminformatics methods, validated by biochemical experiments, to gain insights into molecular activation mechanisms and identify target residues for protein modulation.

A Cluster of Diutina catenulata Funguria in Patients with Coronavirus Disease 2019 (COVID-19) Hospitalized in a Tertiary Reference Hospital from Rio de Janeiro, Brazil.

During the COVID-19 pandemic, fungal infections, especially pulmonary aspergillosis, mucormycosis, and invasive candidiasis, have emerged as a significant health concern. Beyond Candida albicans, the most common cause of invasive candidiasis, other rare ascomycetous yeast species have been described in tertiary care units, potentially posing a broader health threat. We have isolated, from September 2020 to June 2021, nine Diutina catenulata strains from urine samples of six patients. This was intriguing as this fungus had not been previously identified in our institution, nor after June 2021. Therefore, we decided to outline the clinical features of the patients with this rare pathogen, to describe phenotypic characteristics, including antifungal susceptibility profiles, of this yeast species and to identify the genetic makeup through whole-genome sequencing analysis to evaluate if this was a cluster of genetically similar D. catenulata isolates in our institution. The strains were identified through MALDI-TOF MS analyses and Sanger sequencing of two rDNA regions. All patients yielding D. catenulata from urine samples needed ventilator support and used urinary catheters during hospitalization for treatment of COVID-19. None of them had received COVID-19 vaccines. Morphological and biochemical profiles of the nine strains were largely consistent, although fluconazole susceptibility varied, ranging from 4 to 32 µg/mL. Phylogenomic analysis revealed minimal genetic variation among the isolates, with low intrapopulation variation, supported by the identification of only 84 SNPs across all strains. Therefore, we propose that the yeast strains isolated were part of a cluster of D. catenulata funguria in the context of COVID-19.

Non-Zoonotic Transmission of Sporotrichosis: A Translational Study of Forty-Three Cases in a Zoonotic Hyperendemic Area.

Over the past two decades, zoonotic sporotrichosis transmitted by naturally infected cats has become hyperendemic in Rio de Janeiro, Brazil. Sporothrix brasiliensis is the main agent involved. However, there are other forms of transmission of sporotrichosis. The aim of this study was to evaluate and associate the epidemiological, clinical and therapeutic data and the susceptibility of Sporothrix spp. to antifungal drugs in 43 non-zoonotic sporotrichosis cases. Forty-three clinical strains of Sporothrix were identified by partial sequencing of the calmodulin gene. An antifungal susceptibility test of amphotericin B, terbinafine, itraconazole, posaconazole and isavuconazole was performed according to the broth microdilution method. Most patients were male (55.8%). Regarding the source of infection, 21 patients (48.8%) reported trauma involving plants and/or contact with soil. Sporothrix brasiliensis was the predominant species (n = 39), followed by S. globosa (n = 3) and S. schenckii (n = 1). Sporothrix brasiliensis was associated with all the sources of infection, reinforcing previous data showing the presence of this species in environmental sources, as well as with all the clinical forms, including severe cases. One clinical strain of Sporothrix brasiliensis was classified as a non-wild-type strain for amphotericin B and another for itraconazole. S. schenckii was classified as non-WT for all the antifungals tested. In this context, it is important to emphasize that non-zoonotic sporotrichosis still occurs in the state of Rio de Janeiro, with S. brasiliensis as the main etiological agent, primarily associated with infections acquired after traumatic inoculation with plants and/or soil contact, followed by S. globosa and S. schenckii. In addition, non-WT strains were found, indicating the need to monitor the antifungal susceptibility profile of these species. It is crucial to investigate other natural sources of S. brasiliensis to better understand this fungal pathogen and its environment and host cycle.

Lung Ultrasound as an Adjunct to Pulse Oximetry and Respiratory Symptoms in the Diagnosis of Freediving-Induced Pulmonary Syndrome.

INTRODUCTION: B-lines on lung ultrasound have been found in asymptomatic competitive breath-hold divers, but their significance and time to resolution are not well understood. We sought to investigate the relationship between B-lines, oxygen saturation, and respiratory symptoms after competitive dives to diagnose pulmonary injury. METHODS: We performed lung ultrasounds before (predive), immediately after (postdive), and within 1 h (follow-up) of a competitive dive. B-lines were counted in each intercostal space in the anterior, lateral, and posterior lung fields, and the highest number of B-lines within a space was recorded for each lung region. At follow-up, each diver's oxygen saturation and respiratory symptoms were recorded. Statistical analysis included the Kruskal-Wallis test, Spearman's correlation, and sensitivity and specificity calculations. RESULTS: Forty-four divers completed 143 individual dives of four different disciplines. The median number of B-lines was 0 (IQR inclusive=0) predive, 1 (IQR=3) postdive, and 0 (IQR=1) at follow-up. There was a significant difference in total B-lines between measurement times (p<0.001). Sensitivity and specificity of hypoxemia, clinically significant B-lines, and both measures in tandem in detecting respiratory symptomatology were 52% and 76%, 24% and 92%, and 24% and 95%, respectively. CONCLUSIONS: B-lines are a common phenomenon in competitive breath-hold divers on surfacing and decrease within 1 h, suggesting a physiologic fluid shift. B-lines are negatively correlated with oxygen saturation, indicating that extravascular fluid impairs gas exchange in the lung. Neither hypoxemia nor clinically significant B-lines were found to be reliable indicators for respiratory symptomatology, suggesting that there may be multiple phenotypes of freediving-induced pulmonary syndrome.

Evaluation of enteral and parenteral hyaluronic acid in induced ischemic skin flaps in rats: a double-blinded and randomized study.

PURPOSE: To evaluate exogenous hyaluronic acid (HA) derived from bacterial fermentation through enteral and parenteral routes in ischemic skin flaps induced in rats, using clinical and histological exams; and interleukins (IL) as tissue inflammatory biomarkers. METHODS: Sixty-four male adults Wistar rats with ischemic skin flaps on the dorsum were randomized into four groups, based on the treatment protocol: subcutaneous administration of saline solution (0.9%) (GI); oral administration of distilled water (GII); subcutaneous administration of HA (0.3%) (GIII); and oral administration of HA (1%) (GIV). Flaps of all groups were comparable regarding clinical and macroscopic evaluation, histological examination, pro-inflammatory cytokines (IL-1ß, IL-6, and tumor necrosis factor-α) and anti-inflammatory cytokine IL-10. RESULTS: A lower percentage of necrosis was identified in flaps treated with subcutaneous administration of HA (0.3%). The pro- and anti-inflammatory cytokines, epidermis thickness, blood vessels, and inflammatory cells showed statistically significant inter-group and intra-group differences (p < 0.05). CONCLUSIONS: High molecular HA (1,400 ~ 2,000 kDa) administrated by subcutaneous or oral route exhibited beneficial effects in ischemic skin flaps of rats. However, subcutaneous administration of HA (0.3%) showed better results in terms of the percentage of necrosis and epithelialization.

1H-1,2,3-triazol-1,4-naphthoquinone Derivatives: Novel Inhibitors Targeting Pyocyanin Biosynthesis for P. Aeruginosa Infection Treatment Advances.

BACKGROUND: This study investigates the potential of eleven 1H-1,2,3-triazol-1,4-naphthoquinone conjugates as virulence factor inhibitors (like Pyocyanin) and their affinity for PhzM, a crucial enzyme for Pyocyanin biosynthesis in Pseudomonas aeruginosa infections. METHODS: A straightforward synthetic pathway enabled the production of these compounds, which were characterized and structurally confirmed through spectroscopic analyses. Evaluation of their impact on PhzM thermal stability identified promising candidates for PhzM binders. RESULTS: Concentration-response behavior elucidated their binding affinity, revealing them as the first reported micromolar affinity ligands for PhzM. Structure-activity relationship analysis emphasized the role of specific molecular moieties in binding affinity modulation, paving the way for future advanced inhibitors' development. CONCLUSION: These findings highlight the potential of naphthoquinone-triazole derivatives as leads for novel therapeutics against P. aeruginosa infections.

Immunomodulatory Effects of Anadenanthera colubrina Bark Extract in Experimental Autoimmune Encephalomyelitis.

This study aimed to evaluate the efficacy of the ethanolic extract of Anadenanthera colubrina in modulating the immune response in the Experimental Autoimmune Encephalomyelitis (EAE) model. The ethanolic extract of the dried bark was analyzed by ESI (+) Orbitrap-MS to obtain a metabolite profile, demonstrating a wide variety of polyphenols, such as flavonoids and phenolic acids. Various parameters were evaluated, such as clinical signs, cytokines, cellular profile, and histopathology in the central nervous system (CNS). The ethanolic extract of A. colubrina demonstrated significant positive effects attenuating the clinical signs and pathological processes associated with EAE. The beneficial effects of the extract treatment were evidenced by reduced levels of pro-inflammatory cytokines, such as IL1ß, IL-6, IL-12, TNF, IFN-γ, and a notable decrease in several cell profiles, including CD8+, CD4+, CD4+IFN-γ, CD4+IL-17+, CD11c+MHC-II+, CD11+CD80+, and CD11+CD86+ in the CNS. In addition, histological analysis revealed fewer inflammatory infiltrates and demyelination sites in the spinal cord of mice treated with the extract compared to the control model group. These results showed, for the first time, that the ethanolic extract of A. colubrina exerts a modulatory effect on inflammatory processes, improving clinical signs in EAE, in the acute phase of the disease, which could be further explored as a possible therapeutic alternative.

[Management of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients]. / Abordagem à Infeção pelo Vírus Citomegálico em Doentes Submetidos a Transplante Alogénico de Progenitores Hematopoiéticos.

Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.

O vírus citomegálico (CMV) é um tipo de vírus de ácido desoxirribonucleico de dupla cadeia que pertence à família herpesviridae. Após uma infeção primária, o vírus torna-se latente em vários tipos de glóbulos brancos. A infeção por CMV pode permanecer latente ou tornar-se ativa, especialmente em indivíduos imunodeprimidos, como aqueles submetidos a transplantes de células progenitoras hematopoiéticas (TPH), onde a reativação do CMV pode ocorrer. Neste contexto, a infeção por CMV é comum e associada a elevadas taxas de morbilidade e mortalidade. A pneumonite é uma das complicações mais graves, com taxas de mortalidade superiores a 50%. Além disso, mesmo na ausência de doença específica do órgão, a infeção por CMV está relacionada com um aumento da mortalidade não relacionada com a recidiva da neoplasia hematológica. Dada a frequência e gravidade desta infeção em doentes submetidos a TPH, é crucial implementar estratégias eficazes de monitorização, prevenção e tratamento. Este protocolo foi desenvolvido para identificar os grupos de doentes que se beneficiam de uma abordagem sistematizada para a infeção por CMV e definir a estratégia mais adequada para cada grupo. A monitorização da carga viral de CMV no sangue periférico é fundamental, especialmente em doentes com risco moderado a elevado de infeção ativa. A profilaxia primária com letermovir (fármaco antiviral) é recomendada para reduzir a incidência de infeção ativa, especialmente em doentes com alto risco. A profilaxia secundária com valganciclovir (fármaco antiviral) é recomendada após um episódio de infeção ativa, enquanto o tratamento de antecipação e de doença é baseado na monitorização da carga viral e na resposta clínica. Este protocolo visa melhorar a abordagem da infeção por CMV em doentes submetidos a TPH, garantindo uma abordagem preventiva e terapêutica eficaz e segura.

Anti-inflammatory and anti-oxidant action of tadalafil in testicular regeneration process after heat stress.

Tadalafil, a potent phosphodiesterase inhibitor 5 (PDE-5), is commonly used for the management of erectile dysfunction. However, its therapeutic potential extends beyond this indication. This study aimed to investigate the impact of tadalafil on the recovery of testicular parenchyma in male Wistar rats exposed to testicular thermal stress. Fifty-four Wistar rats were subjected to testicular thermal stress and randomly assigned to receive either tadalafil treatment (TAD) or no treatment (control). TAD was administered intraperitoneally at a dose of either 0.9 mg/kg or 1.8 mg/kg. Biometric parameters, histopathological assessment of the testis, serum testosterone levels, oxidative stress, and interleukin levels were evaluated on days 7, 15, and 30 after thermal shock. The animals were euthanized at the end of each experimental period, and samples were collected. TAD treatment maintained testicular weight and reduced the testicular degenerative process up to day 7 post-injury. However, despite TAD therapy, serum testosterone levels were decreased in the treated groups at days 7 and 15 post-thermal stress. TAD also decreased TNF-α and NO levels at different doses but had no effect on IL-6. The treatment with TAD after heat shock demonstrated anti-inflammatory and antioxidant properties but did not prevent the aggravation of testicular lesions in subsequent periods, even with the systematic reduction in TNF-α and NO levels. Therefore, this selective PDE-5 inhibitor, at the dosages used, did not have a positive impact on testosterone levels during the post-thermal stress period, which could compromise the resumption of the spermatogenic process.

Expanding geographic distribution knowledge of Galerinamarginata (Batsch) Kühner (Agaricales, Hymenogastraceae) with a novel Antarctic record.

Background: The investigation of Agaricales diversity in the Antarctica is limited, with only seven genera reported for the region. Galerina stands out as the genus with the highest species diversity, including 12 species in Antarctica. This research reports the presence of G.marginata in the region, providing the first complete morphological description for the specimen developing in Antarctica. Sampling was conducted during the Austral summer of 2022/2023 as part of the XLI Brazilian Antarctic Operation in Point Smellie, Byers Peninsula, Livingston Island, South Shetland Archipelago, Antarctica. Phylogenetic relationships reconstructed by Maximum Likelihood demonstrate that G.marginata forms a monophyletic clade with over 60% bootstrap support in most branches. The isolate in this study was found to be internal to the main cluster. Evolutionary reconstructions using the Maximum Likelihood method indicate that the branches correspond to the Antarctic isolate being an internal clade within the marginata group. Recording fungal populations in polar regions offers information about their adaptation and survival in inhospitable environments. Understanding the species' distribution in Antarctica encourages future investigations into its ecology and interactions with other organisms. Here, data are presented to establish an initial foundation for monitoring the G.marginata population in Antarctica and assessing the potential impacts of climate change on its development and survival in the forthcoming years. New information: We report the third occurrence of Galerinamarginata (Batsch) Kühner in Antarctica and provide, for the first time, a comprehensive morphological description of an individual of the species for the Antarctic continent, accompanied by phylogenetic analyses and comprehensive discussions regarding its diversity and global distribution.

Establishment of a laboratory colony of Pressatia choti (Diptera: Psychodidae), a suspected vector of Leishmania braziliensis.

BACKGROUND: Pressatia choti is a common sand fly found in the Atlantic Forest of Brazil, which is suspected to be involved in the transmission of Leishmania braziliensis. Herein, we aimed to establish a Pr. choti laboratory colony. METHODS: Wild-caught female sand flies were blood fed on hamsters and maintained under controlled conditions (temperature: 26 °C; relative humidity: 70%). RESULTS: Of the 301 collected female sandflies, 288 were identified as Pr. choti. The life cycle duration ranged from 31 to 56 days. CONCLUSIONS: We successfully established a Pr. choti colony, whose biological parameters were similar to those of other neotropical sand flies.

Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition.

Crovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low-volume self-administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open-label, multicenter, phase 3 trial evaluating the non-inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor-naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 2:1 to crovalimab or eculizumab. Co-primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT-Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non-inferior to eculizumab in the co-primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, -2.8 [-15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, -3.9 [-14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [-11.4, 16.3]). A clinically meaningful improvement in FACIT-Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit-risk profile of crovalimab.

Adherence to mediterranean diet and aromatic plants intake are related with gustatory function: A case-study from a Portuguese region.

The Mediterranean Diet has been recognized as one of the healthiest and most sustainable dietary patterns and is flavor rich due to the use of different seasonings, such as aromatic plants, in dish confection. Based on the hypotheses that: 1) gustatory function will affect food choices; 2) seasoning flavors may be differently accepted according to individuals' gustatory functions; the aim of the present study was to assess the association between taste sensitivity and/or preference with Mediterranean Diet adherence and seasoning consumption. A total of 383 adults (18-59 years old; 198 female, 185 male) from North Alentejo region of Portugal were enrolled in this study, with 291 (145 female and 146 male) also evaluated for gustatory function. Recognition thresholds were obtained for four tastes (sweet, sour, salty, and bitter) and astringency, as well as preference level for the highest concentration of each stimulus tested. A validated Food Frequency Questionnaire was filled out, and MD adherence was extrapolated from the answers of the Food Frequency Questionnaire according to the Mediterranean Diet Adherence Screener (MEDAS) score. In total, 20.8% of the individuals presented low, 58.2% medium, and 21.0% high adherence. Adherence was higher in women than men and in older individuals than younger adults. Adherence to the Mediterranean Diet was positively correlated with aromatic plants consumption but not spices. Seasonings were associated with gustatory function, and the cluster with higher consumption presented higher preferences for bitter and salty tastes. Total sodium intake was also higher in this cluster, suggesting that these individuals prefer stronger oral sensations. In conclusion, this study shows that MD adherence is not high, even in regions with rural characteristics. The observed association of MD and seasoning intake with gustatory function do underline the usefulness of this information in strategies aimed at promoting healthy and sustainable eating patterns.

Determination of Inhibitory Effect of PKM2 Enzyme and Antitumoral Activity of Novel Coumarin-Naphthoquinone Hybrids.

BACKGROUND: Oral squamous cell carcinoma (OSCC) represents the primary form of oral cancer, posing a significant global health threat. The existing chemotherapy options are accompanied by notable side effects impacting patient treatment adherence. Consequently, the exploration and development of novel substances with enhanced anticancer effects and fewer side effects have become pivotal in the realms of biological and chemical science. OBJECTIVE: This work presents the pioneering examples of naphthoquinone-coumarin hybrids as a new category of highly effective cytotoxic substances targeting oral squamous cell carcinoma (OSCC). METHODS: Given the significance of both naphthoquinones and coumarins as essential pharmacophores/ privileged structures in the quest for anticancer compounds, this study focused on the synthesis and evaluation of novel naphthoquinones/coumarin hybrids against oral squamous cell carcinoma. RESULTS: By several in vitro, in silico, and in vivo approaches, we demonstrated that compound 6e was highly cytotoxic against OSCC cells and several other cancer cell types and was more selective than current chemotherapeutic drugs (carboplatin) and the naphthoquinone lapachol. Furthermore, compound 6e was non-hemolytic and tolerated in vivo at 50 mg/kg with an LD50 of 62.5 mg/kg. Furthermore, compound 6e did not induce apoptosis and cell cycle arrest but led to intracellular vesicle formation with LC3 aggregation in autophagosomes, suggesting an autophagic cell death. Additionally, 6e had a high-affinity potential for PKM2 protein, higher than the known ligands, such as lapachol or shikonin, and was able to inhibit this enzyme activity in vitro. CONCLUSION: We assert that compound 6e shows promise as a potential lead for a novel chemotherapeutic drug targeting OSCC, with potential applicability to other cancer types.

The use of a portable X-ray fluorescence spectrometer for measuring nickel in plants: sample preparation and validation.

X-ray fluorescence is a fast, cost-effective, and eco-friendly method for elemental analyses. Portable X-ray fluorescence spectrometers (pXRF) have proven instrumental in detecting metals across diverse matrices, including plants. However, sample preparation and measurement procedures need to be standardized for each instrument. This study examined sample preparation methods and predictive capabilities for nickel (Ni) concentrations in various plants using pXRF, employing empirical calibration based on inductively coupled plasma optical emission spectroscopy (ICP-OES) Ni data. The evaluation involved 300 plant samples of 14 species with variable of Ni accumulation. Various dwell times (30, 60, 90, 120, 300 s) and sample masses (0.5, 1.0, 1.5, 2.0 g) were tested. Calibration models were developed through empirical and correction factor approaches. The results showed that the use of 1.0 g of sample (0.14 g cm-2) and a dwell time of 60 s for the study conditions were appropriate for detection by pXRF. Ni concentrations determined by ICP-OES were highly correlated (R2 = 0.94) with those measured by the pXRF instrument. Therefore, pXRF can provide reliable detection of Ni in plant samples, avoiding the digestion of samples and reducing the decision-making time in environmental management.

Continuous UV-C/H2O2 and UV-C/Chlorine applied to municipal secondary effluent and nanofiltration retentate: Removal of contaminants of emerging concern, ecotoxicity, and reuse potential.

As global effects of water scarcity raise concerns and environmental regulations evolve, contemporary wastewater treatment plants (WWTPs) face the challenge of effectively removing a diverse range of contaminants of emerging concern (CECs) from municipal effluents. This study focuses on the assessment of advanced oxidation processes (AOPs), specifically UV-C/H2O2 and UV-C/Chlorine, for the removal of 14 target CECs in municipal secondary effluent (MSE, spiked with 10 µg L-1 of each CEC) or in the subsequent MSE nanofiltration retentate (NFR, no spiking). Phototreatments were carried out in continuous mode operation, with a hydraulic retention time of 3.4 min, using a tube-in-tube membrane photoreactor. For both wastewater matrices, UV-C photolysis (3.3 kJ L-1) exhibited high efficacy in removing CECs susceptible to photolysis, although lower treatment performance was observed for NFR. In MSE, adding 10 mg L-1 of H2O2 or Cl2 enhanced treatment efficiency, with UV-C/H2O2 outperforming UV-C/Chlorine. Both UV-C/AOPs eliminated the chronic toxicity of MSE toward Chlorella vulgaris. In the NFR, not only was the degradation of target CECs diminished, but chronic toxicity to C. vulgaris persisted after both UV-C/AOPs, with UV-C/Chlorine increasing toxicity due to potential toxic by-products. Nanofiltration permeate (NFP) exhibited low CECs and microbial content. A single chlorine addition effectively controlled Escherichia coli regrowth for 3 days, proving NFP potential for safe reuse in crop irrigation (<1 CFU/100 mL for E. coli; <1 mg L-1 for free chlorine). These findings provide valuable insights into the applications and limitations of UV-C/H2O2 and UV-C/Chlorine for distinct wastewater treatment scenarios.