Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei.

Mycoses are one of the major causes of morbidity/mortality among immunocompromised individuals. Considering the importance of these infections, the World Health Organization (WHO) defined a priority list of fungi for health in 2022 that include Candida albicans as belonging to the critical priority group and Pichia kudriavzevii (Candida krusei) to the medium priority group. The existence of few available antifungal drugs, their high toxicity, the acquired fungal resistance, and the appearance of new species with a broader spectrum of resistance, points out the need for searching for new antifungals, preferably with new and multiple mechanisms of action. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 was previously tested against several fungi and revealed an interesting activity, with minimal inhibitory concentration (MIC) values of 8 µg/mL for C. krusei and of 128 µg/mL for C. albicans. The main objective of the present work was to deeply understand the mechanisms involved in its antifungal activity. The effects of the cyclam salt on yeast metabolic viability (resazurin reduction assay), yeast mitochondrial function (JC-1 probe), production of reactive oxygen species (DCFH-DA probe) and on intracellular ATP levels (luciferin/luciferase assay) were evaluated. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 induced a significant decrease in the metabolic activity of both C. albicans and C. krusei, an increase in Reactive Oxygen Species (ROS) production, and an impaired mitochondrial function. The latter was observed by the depolarization of the mitochondrial membrane and decrease in ATP intracellular levels, mechanisms that seems to be involved in the antifungal activity of H4[H2(4-CF3PhCH2)2Cyclam]Cl4. The interference of the cyclam salt with human cells revealed a CC50 value against HEK-293 embryonic kidney cells of 1.1 µg/mL and a HC10 value against human red blood cells of 0.8 µg/mL.

Plasmatic MicroRNAs and Treatment Outcomes of Patients with Metastatic Castration-Resistant Prostate Cancer: A Hospital-Based Cohort Study and In Silico Analysis.

Prostate cancer (PCa) is one of the most common malignancies among men worldwide. Inevitably, all advanced PCa patients develop metastatic castration-resistant prostate cancer (mCRPC), an aggressive phase of the disease. Treating mCRPC is challenging, and prognostic tools are needed for disease management. MicroRNA (miRNA) deregulation has been reported in PCa, constituting potential non-invasive prognostic biomarkers. As such, this study aimed to evaluate the prognostic potential of nine miRNAs in the liquid biopsies (plasma) of mCRPC patients treated with second-generation androgen receptor axis-targeted (ARAT) agents, abiraterone acetate (AbA) and enzalutamide (ENZ). Low expression levels of miR-16-5p and miR-145-5p in mCRPC patients treated with AbA were significantly associated with lower progression-free survival (PFS). The two miRNAs were the only predictors of the risk of disease progression in AbA-stratified analyses. Low miR-20a-5p levels in mCRPC patients with Gleason scores of <8 were associated with worse overall survival (OS). The transcript seems to predict the risk of death regardless of the ARAT agent. According to the in silico analyses, miR-16-5p, miR-145-5p, and miR-20a-5p seem to be implicated in several processes, namely, cell cycle, proliferation, migration, survival, metabolism, and angiogenesis, suggesting an epigenetic mechanism related to treatment outcome. These miRNAs may represent attractive prognostic tools to be used in mCRPC management, as well as a step further in the identification of new potential therapeutic targets, to use in combination with ARAT for an improved treatment outcome. Despite the promising results, real-world validation is necessary.

Antitumor Effect of Chalcone Derivatives against Human Prostate (LNCaP and PC-3), Cervix HPV-Positive (HeLa) and Lymphocyte (Jurkat) Cell Lines and Their Effect on Macrophage Functions.

Chalcones are synthetic and naturally occurring compounds that have been widely investigated as anticancer agents. In this work, the effect of chalcones 1-18 against the metabolic viability of cervical (HeLa) and prostate (PC-3 and LNCaP) tumor cell lines was tested, to compare the activity against solid and liquid tumor cells. Their effect was also evaluated on the Jurkat cell line. Chalcone 16 showed the highest inhibitory effect on the metabolic viability of the tested tumor cells and was selected for further studies. Recent antitumor therapies include compounds with the ability to influence immune cells on the tumor microenvironment, with immunotherapy being one actual goal in cancer treatment. Therefore, the effect of chalcone 16 on the expression of mTOR, HIF-1α, IL-1ß, TNF-α, IL-10, and TGF-ß, after THP-1 macrophage stimulation (none, LPS or IL-4), was evaluated. Chalcone 16 significantly increased the expression of mTORC1, IL-1ß, TNF-α, and IL-10 of IL-4 stimulated macrophages (that induces an M2 phenotype). HIF-1α and TGF-ß were not significantly affected. Chalcone 16 also decreased nitric oxide production by the RAW 264.7 murine macrophage cell line, this effect probably being due to an inhibition of iNOS expression. These results suggest that chalcone 16 may influence macrophage polarization, inducing the pro-tumoral M2 macrophages (IL-4 stimulated) to adopt a profile closer to the antitumor M1 profile.

Effect of 1-Carbaldehyde-3,4-dimethoxyxanthone on Prostate and HPV-18 Positive Cervical Cancer Cell Lines and on Human THP-1 Macrophages.

Xanthone derivatives have shown promising antitumor properties, and 1-carbaldehyde-3,4-dimethoxyxanthone (1) has recently emerged as a potent tumor cell growth inhibitor. In this study, its effect was evaluated (MTT viability assay) against a new panel of cancer cells, namely cervical cancer (HeLa), androgen-sensitive (LNCaP) and androgen-independent (PC-3) prostate cancer, and nonsolid tumor derived cancer (Jurkat) cell lines. The effect of xanthone 1 on macrophage functions was also evaluated. The effect of xanthone 1-conditioned THP-1 human macrophage supernatants on the metabolic viability of cervical and prostate cancer cell lines was determined along with its interference with cytokine expression characteristic of M1 profile (IL-1 ≤ ß; TNF-α) or M2 profile (IL-10; TGF-ß) (PCR and ELISA). Nitric oxide (NO) production by murine RAW264.7 macrophages was quantified by Griess reaction. Xanthone 1 (20 µM) strongly inhibited the metabolic activity of the cell lines and was significantly more active against prostate cell lines compared to HeLa (p < 0.05). Jurkat was the cell most sensitive to the effect of xanthone 1. Compound 1-conditioned IL-4-stimulated THP-1 macrophage supernatants significantly (p < 0.05) inhibited the metabolic activity of HeLa, LNCaP, and PC-3. Xanthone 1 did not significantly affect the expression of cytokines by THP-1 macrophages. The inhibiting effect of compound 1 observed on the production of NO by RAW 264.7 macrophages was moderate. In conclusion, 1-carbaldehyde-3,4-dimethoxyxanthone (1) decreases the metabolic activity of cancer cells and seems to be able to modulate macrophage functions.

Prevalence of Neisseria gonorrhoeae and Trichomonas vaginalis in Portuguese women of childbearing age.

The purpose of this study was to evaluate the prevalence of Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) in Portuguese women of childbearing age. Cervicovaginal self-collected samples of 680 childbearing-age women (15-44 years) were tested for NG and TV by polymerase chain reaction. Sociodemographic, clinical and behavioural data were assessed through an anonymous self-administered questionnaire. NG and TV prevalence was 1.3% (95% confidence interval (CI) 0.7-2.5%) and 1.0% (95% CI 0.5-2.1%), respectively. The prevalence of TV was significantly higher in women aged >22 years (p = .003), with >6 years after sexual intercourse (p = .003), and who reported previous pregnancy (p = .004). Our study suggests that NG and TV are rare in Portuguese women of childbearing age. However, larger epidemiological studies with a nationally representative sample of female subjects are warranted, to clarify the need for screening of these microorganisms in Portuguese women, since its prevalence is probably underestimated.IMPACT STATEMENTWhat is already known on this subject? Studies on the prevalence of NG and TV have been performed in several developed and developing countries. However, limited data is available in Portuguese women. The detection of NG and TV is necessary because, beside the risk of transmission to sex partners, these STIs may be associated with an increased risk of HIV acquisition and transmission, and ultimately with reproductive, pregnancy and perinatal complications.What do the results of this study add? Our study adds new findings to the body of knowledge on NG and TV prevalence in Portuguese women of reproductive age. As so, we found a low prevalence of both NG (1.3%) and TV (1.0%) in the studied population.What are the implications of these findings for clinical practice and/or further research? Our results may be a step ahead to encourage future nationally representative studies evaluating the prevalence of NG and TV genital infection and, consequently, to clarify the need for screening of these microorganisms. In clinical practice, it should be highlighted the appropriate management of NG and TV infection in specific situations, such as pregnancy. Also, sexual partners must be treated to prevent the recurrences in the index cases and reduce transmission to other partners.

Synthesis and antimicrobial activity of novel 5-aminoimidazole-4-carboxamidrazones.

A mild and simple method was developed to prepare a series of fifteen 5-aminoimidazole 4-carboxamidrazones, starting from the easily accessible 5-amino-4-cyanoformimidoyl imidazoles. The antimicrobial activity of these novel amidrazones was screened against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and Candida sp. (Candida albicans, Candida krusei, Candida parapsilosis). Only a subset of compounds displayed fair-moderate activity against S. aureus and E. coli but all exhibited activity against Candida sp. The three most potent antifungal compounds were further tested against Cryptococcus neoformans, Aspergillus fumigatus and three dermatophytes (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum gypseum). These three hit compounds strongly inhibited C. krusei and C. neoformans growth, although their activity on filamentous fungi was very weak when compared to the activity on yeasts.

Chlamydia trachomatis infection: implications for HPV status and cervical cancer.

Genital Chlamydia trachomatis (CT) infections have been identified as a major health problem concern. CT is associated with adverse effect on women reproduction and also associated with cervical hypertrophy and induction of squamous metaplasia, providing a possible relationship with human papillomavirus (HPV) infection. Infection by high-risk HPV types is crucial to the pathogenesis of invasive cervical cancer (ICC), but other co-variants/cofactors must be present for the development of malignancy. CT biological effect may damage the mucosal barrier, improving HPV infection, or may interfere in immune response and viral clearance supporting the persistence of HPV infection. Moreover, CT-related chronic cervical inflammation, decrease of lower genital tract antigen-presenting cells, inhibition of cell-mediated immunity, and anti-apoptotic capacity may influence the natural history of HPV infection, namely persistence progression or resolution. Although several epidemiological studies have stated a positive association involving CT and HPV-related cervical neoplastic lesions and/or cervical cancer (CC), the specific role of this bacterium in the pathogenesis of cervical neoplasia has not been completely clarified. The present review summarizes several studies on CT role in cervical cancer and suggests future research directions on HPV and CT interaction.

A Cyclam Salt as an Antifungal Agent: Interference with Candida spp. and Cryptococcus neoformans Mechanisms of Virulence.

The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells.

Is Chlamydia trachomatis related to human papillomavirus infection in young women of southern European population? A self-sampling study.

BACKGROUND: It is well established the role of human papillomavirus (HPV) in cervical cancer (CC) etiology. Chlamydia trachomatis (CT) infection seems to synergize with HPV in CC multistage process. The aim of this study was to assess the correlation of HPV and CT infection in young student women. MATERIAL AND METHODS: Cervicovaginal samples were obtained by self-sampling method from young women (n = 432; mean age 18.0 ± 2.46 years) recruited among the student community and tested for HPV and CT DNA by polymerase chain reaction. RESULTS: In CT positive cases, there is an increased risk of HPV detection [odds ratio (OR) 2.4, 95 % confidence interval (CI) 1.03-6.27, p < 0.037]. The highest rate of coinfection with HPV and CT were observed in the mean age of 20.6 years, and all coinfection cases were found in young women who referred no previous history or symptoms of sexually transmitted infections. Within HPV-positive young women, there was no significant difference between CT and high-risk HPV. CONCLUSIONS: Our results suggest a causal association between HPV and CT infection in young women; infection with this bacterium may be a predisposing factor for subsequent infection with HPV, or vice versa, due to similar mode of sexual transmission, inferring the promising role of CT in CC development. However, the specific question on multistage process of HPV-associated carcinogenesis, which may be affected by CT, remains unclear.

Map of thrombogenesis in viral infections and viral-driven tumours.

Viruses are pathogenic agents responsible for approximately 10% of all human cancers and significantly contribute to the global cancer burden. Until now, eight viruses have been associated with the development of a broad range of malignancies, including solid and haematological tumours. Besides triggering and promoting oncogenesis, viral infections often go hand-in-hand with haemostatic changes, representing a potential risk factor for venous thromboembolism (VTE). Conversely, VTE is a cardiovascular condition that is particularly common among oncological patients, with a detrimental impact on patient prognosis. Despite an association between viral infections and coagulopathies, it is unclear whether viral-driven tumours have a different incidence and prognosis pattern of thromboembolism compared to non-viral-induced tumours. Thus, this review aims to analyse the existing evidence concerning the association of viruses and viral tumours with the occurrence of VTE. Except for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection, which are associated with a high risk of VTE, little evidence exists concerning the thrombogenic potential associated with oncoviruses. As for tumours that can be induced by oncoviruses, four levels of VTE risk are observed, with hepatocellular carcinoma (HCC) and gastric carcinoma (GC) associated with the highest risk and nasopharyngeal carcinoma (NPC) associated with the lowest risk. Unfortunately, the incidence of cancer-related VTE according to tumour aetiology is unknown. Given the negative impact of VTE in oncological patients, research is required to better understand the mechanisms underlying blood hypercoagulability in viral-driven tumours to improve VTE management and prognosis assessment in patients diagnosed with these tumours.

FAAH rs324420 Polymorphism: Biological Pathways, Impact on Elite Athletic Performance and Insights for Sport Medicine.

Gene variation linked to physiological functions is recognised to affect elite athletic performance by modulating training and competition-enabling behaviour. The fatty acid amide hydrolase (FAAH) has been investigated as a good candidate for drug targeting, and recently, its single-nucleotide polymorphism (SNP) rs324420 was reported to be associated with athletic performance. Given the implications, the biological pathways of this genetic polymorphism linked to elite athletic performance, considering sport type, psychological traits and sports injuries, need to be dissected. Thus, a narrative review of the literature concerning the biological mechanisms of this SNP was undertaken. In addition to its role in athletic performance, FAAH rs324420 is also involved in important mechanisms underlying human psychopathologies, including substance abuse and neural dysfunctions. However, cumulative evidence concerning the C385A variant is inconsistent. Therefore, validation studies considering homogeneous sports modalities are required to better define the role of this SNP in elite athletic performance and its impact on stress coping, pain regulation and inflammation control.

Association of FAAH rs324420 (C385A) Polymorphism with High-Level Performance in Volleyball Players.

Genetic variants are recognized to affect athletic performance, partially by modulating competition-facilitating behavior. In this study, the role of three genetic variants previously linked to athlete status was investigated among elite volleyball players. A total of 228 players (26.7 ± 8.1 years old) participating in the Portuguese championship and with multiple medalists in national and international competitions were evaluated in terms of anthropometrics, training regime, sports experience, and a history of sports lesions. SNP genotyping was conducted by means of TaqMan® Allelic Discrimination Methodology. Volleyball players showed significantly different anthropometric indicators and training habits according to sex (p < 0.05). The A allele of the genetic variant Fatty Acid Amide Hydrolase (FAAH) rs324420 (C385A) was shown to be significantly associated with superior athletic achievements under a dominant genetic model (AA/AC vs. CC, odds ratio (OR) = 1.70; 95% Cl, 0.93-3.13; p = 0.026; p < 0.001 after Bootstrap), which was corroborated by a multivariable analysis (AA/AC vs. CC adjusted OR = 2.00; 95% Cl, 1.04-3.82; p = 0.037). Age and hand length were also found to be independently associated with high-level performance (p < 0.05). Our results confirm the role of FAAH in athletic performance. More investigation into this polymorphism's potential impact on stress coping, pain, and inflammation regulation in sport, particularly in the scope of lesions prevention and treatment, is required.

Synergistic Antimicrobial Activity of Silver Nanoparticles with an Emergent Class of Azoimidazoles.

The combination of two or more agents capable of acting in synergy has been reported as a valuable tool to fight against pathogens. Silver nanoparticles (AgNPs) present a strong antimicrobial action, although their cytotoxicity for healthy cells at active concentrations is a major concern. Azoimidazole moieties exhibit interesting bioactivities, including antimicrobial activity. In this work, a class of recently described azoimidazoles with strong antifungal activity was conjugated with citrate or polyvinylpyrrolidone-stabilized AgNPs. Proton nuclear magnetic resonance was used to confirm the purity of the compounds before further tests and atomic absorption spectroscopy to verify the concentration of silver in the prepared dispersions. Other analytical techniques elucidate the morphology and stability of AgNPs and corresponding conjugates, namely ultraviolet-visible spectrophotometry, scanning transmission electron microscopy and dynamic light scattering analysis. The synergistic antimicrobial activity of the conjugates was assessed through a checkerboard assay against yeasts (Candida albicans and Candida krusei) and bacteria (Staphylococcus aureus and Escherichia coli). The conjugates showed improved antimicrobial activity against all microorganisms, in particular towards bacteria, with concentrations below their individual minimal inhibitory concentration (MIC). Furthermore, some combinations were found to be non-cytotoxic towards human HaCaT cells.

Red-shifted and pH-responsive imidazole-based azo dyes with potent antimicrobial activity.

A novel route is described to obtain 2-aminoimidazole azo dyes with a unique substituent pattern in the heteroaryl unit that provides halochromic properties, exhibiting vibrant colours that change from magenta to deep blue. Potent antimicrobial properties against infectious yeasts were demonstrated. No cytotoxicity was detected for concentrations lower than 16 µg mL-1.

Nanostructured Lipid Carriers Enriched Hydrogels for Skin Topical Administration of Quercetin and Omega-3 Fatty Acid.

Chronic skin exposure to external hostile agents (e.g., UV radiation, microorganisms, and oxidizing chemicals) may increase oxidative stress, causing skin damage and aging. Because of their well-known skincare and protective benefits, quercetin (Q) and omega-3 fatty acids (ω3) have attracted the attention of the dermocosmetic and pharmaceutical sectors. However, both bioactives have inherent properties that limit their efficient skin delivery. Therefore, nanostructured lipid carriers (NLCs) and enriched PFC® hydrogels (HGs) have been developed as a dual-approach vehicle for Q and/or ω3 skin topical administration to improve bioactives' stability and skin permeation. Two NLC formulations were prepared with the same lipid composition but differing in surfactant composition (NLC1-soy lecithin and poloxamer 407; NLC2-Tween® 80 and dioctyl sodium sulfosuccinate (DOSS)), which have an impact on physicochemical properties and pharmaceutical and therapeutic performance. Despite both NLCs presenting high Q loading capacity, NLC2's physicochemical properties make them more suitable for topical skin administration and ensure longer colloidal stability. Additionally, NLC2 demonstrated a more sustained Q release, indicating higher bioactive storage while improving permeability. The occlusive effect of NLCs-enriched HGs also has a positive impact on skin permeability. Q-loaded NLC2, with or without ω3, -enriched HGs demonstrated efficacy as antioxidant and photoprotective formulations as well as effective reduction in S. aureus growth, indicating that they constitute a promising approach for topical skin administration to prevent skin aging and other damaging cutaneous processes.

Halochromic Silk Fabric as a Reversible pH-Sensor Based on a Novel 2-Aminoimidazole Azo Dye.

Textiles are important components for the development of lightweight and flexible displays useful in smart materials. In particular, halochromic textiles are fibrous materials with a color-changing ability triggered by pH variations mainly based on pH-sensitive dye molecules. Recently, a novel class of 2-aminoimidazole azo dyes was developed with distinct substituent patterns. In this work, silk fabric was functionalized through exhaustion for the first time with one of these dyes (AzoIz.Pip). The halochromic properties of the dye were assessed in an aqueous solution and after silk functionalization. The solutions and the fabrics were thoroughly analyzed by ultraviolet-visible (UV-vis) spectra, color strength (K/S), color difference (∆E), CIE L*a*b* coordinates, and the ultraviolet protection factor (UPF). The dyeing process was optimized, and the halochromic performance (and reversibility) was assessed in universal Britton-Robinson buffers (ranging from pH 3 to 12) and artificial body fluids (acid and alkaline perspiration, and wound exudate). AzoIz.Pip showed vibrant colors and attractive halochromic properties with a hypsochromic shift from blue (557 nm) to magenta (536 nm) in aqueous buffered solutions. Similarly, the functionalized silk showed a shift in wavelength of the maximum K/S value from 590 nm to 560 nm when pH increases. The silk fabric showed a high affinity to AzoIz.Pip, and promoted additional color stabilization of the dye, avoiding color loss as observed when the dye is in solution at alkaline pH after 24 h. The color reversibility was effective up to the fourth cycle and the fastness tests denoted suitable results, except washing fastness. The cytotoxicity of the silk fabric extracts was assessed, depicting reduced viability of HaCaT cells to <70% only when the dye concentration in the fabric is higher or equal to 64 µg·mL-1. Nevertheless, lower concentrations were also very effective for the halochromic performance in silk. These materials can thus be a helpful tool for developing sensors in several sectors such as biomedicine, packaging, filtration, agriculture, protective apparel, sports, camouflage, architecture, and design.

FAAH rs324420 Polymorphism Is Associated with Performance in Elite Rink-Hockey Players.

Genetic factors are among the major contributors to athletic performance. Although more than 150 genetic variants have been correlated with elite athlete status, genetic foundations of competition-facilitating behavior influencing elite performances are still scarce. This is the first study designed to examine the distribution of genetic determinants in the athletic performance of elite rink-hockey players. A total of 116 of the world's top best rink-hockey players (28.2 ± 8.7 years old; more than 50% are cumulatively from the best four world teams and the best five Portuguese teams), who participated at the elite level in the National Rink-Hockey Championship in Portugal, were evaluated in anthropometric indicators/measurements, training conditions, sport experience and sport injuries history. Seven genetic polymorphisms were analyzed. Polymorphism genotyping was performed using the TaqMan® Allelic Discrimination Methodology. Rink-hockey players demonstrated significantly different characteristics according to sex, namely anthropometrics, training habits, sports injuries and genetic variants, such as Vitamin D Receptor (VDR) rs731236 (p < 0.05). The Fatty Acid Amide Hydrolase (FAAH) rs324420 A allele was significantly associated with improved athletic performance (AA/AC vs. CC, OR = 2.80; 95% Cl, 1.23−6.35; p = 0.014; p = 0.008 after Bootstrap) and confirmed as an independent predictor among elite rink-hockey players (adjusted OR = 2.88; 95% Cl, 1.06−7.80; p = 0.038). Our results open an interesting link from FAAH-related biology to athletic performance.

Genomic profile in association with sport-type, sex, ethnicity, psychological traits and sport injuries of elite athletes.

In the last few years, some inherited determinants have been associated with elite athletic performance, but its polygenic trait character has limited the correct definition of elite athlete's genomic profile. This qualitative descriptive study aims to summarize the current understanding about genetic and epigenetic factors in elite athletes, as well as their genomic profile in association with sport-type, sex, ethnicity, psychological traits and sport injuries. A narrative review of the literature across a broad cross-section of the elite athletes' genomic profile was undertaken. Elite performance relies on rare gene variants within a great interface between molecular, cellular and behavioral sport-related phenotypes and the environment, which is still poorly understood. ACTN3 rs1815739 and ACE I/D polymorphisms appear to be associated to specific sprint phenotypes and influence the athletic status, i.e., the rs1815739 variant is more influential to 200-m performance and the ACE ID polymorphism is more involved in the longer, 400-m sprint performance. Generally, athletes show endurance-based sports characteristics or power-based sports characteristics, but some studies have reported some genes associations to both sports-based characteristics. Furthermore, genetic studies with larger cohorts of single-sport athletes might be preferable than studies combining athletes of different sports, given the existence of distinct athlete profiles and sport demands. Athletic performance may be influenced by the serotonergic pathway and the potential injury risk (namely stress fracture) might be associated to a genetic predisposition associated to the mechanical loading from the intense physical exercise. The study of gene variants associated to sex and ethnicity-related to athletic performance needs further investigation. The combination of genome-wide association studies addressing the genetic architecture of athletes and the subsequent replication and validation studies might for additional genetic data is mandatory.

Gelation Behavior and Stability of Multicomponent Sterol-Based Oleogels.

Novel fat mimetic materials, such as oleogels, are advancing the personalization of healthier food products and can be developed from low molecular weight compounds such as γ-oryzanol and ß-sitosterol. Following molecular assembly, the formation of a tubular system ensues, which seems to be influenced by elements such as the oleogelators' concentration and ratio, cooling rates, and storage periods. Sterol-based oleogels were formulated under distinct environmental conditions, and a comprehensive study aimed to assess the effects of the mentioned factors on oleogel formation and stability, through visual observation and by using techniques such as small-angle X-ray scattering, X-ray diffraction, confocal Raman spectroscopy, rheology, and polarized microscopy. The long, rod-like conformations, identified by small-angle X-ray scattering, showed that different cooling rates influence oleogels' texture. Raman spectra showed that the stabilization time is associated with the interfibrillar aggregation, which occurred differently for 8 and 10 wt%, with a proven relationship between ferulic acid and the tubular formation. This report gives fundamental insight into the critical point of gelation, referring to the time scale of the molecular stabilization. Our results verify that understanding the structuring mechanisms of oleogelation is decisive for the processing and manufacturing of novel foods which integrate oleogels in their structure.

Optimizing PMMA solutions to suppress contamination in the transfer of CVD graphene for batch production.

Mass production and commercial adoption of graphene-based devices are held back by a few crucial technical challenges related to quality control. In the case of graphene produced by chemical vapor deposition, the transfer process represents a delicate step that can compromise device performance and reliability, thus hindering industrial production. In this context, the impact of poly(methyl methacrylate) (PMMA), the most common support material for transferring graphene from the Cu substrate to any target surface, can be decisive in obtaining reproducible sample batches. Although effective in mechanically supporting graphene during the transfer, PMMA solutions needs to be efficiently designed, deposited, and post-treated to serve their purpose while minimizing potential contaminations. Here, we prepared and tested PMMA solutions with different average molecular weight (AMW) and weight concentration in anisole, to be deposited by spin coating. Optical microscopy and Raman spectroscopy showed that the amount of PMMA residues on transferred graphene is proportional to the AMW and concentration in the solvent. At the same time, the mechanical strength of the PMMA layer is proportional to the AMW. These tests served to design an optimized PMMA solution made of a mixture of 550,000 (550k) and 15,000 (15k) AMW PMMA in anisole at 3% concentration. In this design, PMMA-550k provided suitable mechanical strength against breakage during the transfer cycles, while PMMA-15k promoted depolymerization, which allowed for a complete removal of PMMA residues without the need for any post-treatment. An XPS analysis confirmed the cleanness of the optimized process. We validated the impact of the optimized PMMA solution on the mass fabrication of arrays of electrolyte-gated graphene field-effect transistors operating as biosensors. On average, the transistor channel resistance decreased from 1860 to 690 Ω when using the optimized PMMA. Even more importantly, the vast majority of these resistance values are distributed within a narrow range (only ca. 300 Ω wide), in evident contrast with the scattered values obtained in non-optimized devices (about 30% of which showed values above 1 MΩ). These results prove that the optimized PMMA solution unlock the production of reproducible electronic devices at the batch scale, which is the key to industrial production.