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Candida albicans is a common Candida species, responsible for infections in various anatomical sites under different environmental conditions, aggravated in the presence of its biofilms. As such, this study aimed to reveal the regulation of C. albicans biofilms under acidic conditions by the transcription factor Sfl1, whose role on biofilm formation is unclear. For that, microbiologic and transcriptomic analyses were performed with the knock-out mutant C. albicans sfl1/sfl1 and its parental strain SN76, grown in planktonic and biofilm lifestyles at pH 4 (vaginal pH). The results revealed that despite being a filamentation repressor Sf1 is required for maximal biofilm formation under acidic conditions. Additionally, Sfl1 was found to induce 275 and 126 genes in biofilm and planktonic cells, respectively, with an overlap of 19 genes. The functional distribution of Sfl1 targets was similar in planktonic and biofilm modes but an enrichment of carbohydrate metabolism function was found in biofilm cells, including some genes encoding proteins involved in the biofilm matrix production. Furthermore, this study shows that the regulatory network of Sfl1 in acidic biofilms is complex and include the positive and negative regulation of transcription factors involved in adhesion and biofilm formation, such as AHR1, BRG1, TYE7, TEC1, WOR1, and various of their targets. Overall, this study shows that Sfl1 is a relevant regulator of C. albicans biofilm formation in acidic environments and contributes to a better understanding of C. albicans virulence under acidic conditions., This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation [grant NORTE-01-0145-FEDER-000004] funded by the European Regional Development Fund under the scope of Norte2020 e Programa Operacional Regional do Norte. The authors also acknowledge the project funding by the “02/SAICT/2017 e Projetos de Investigação Científica e Desenvolvimento Tecnológico (IC&DT)”grant POCI-01-0145-FEDER-028893] [grant NORTE-01-0145-FEDER-031515]., info:eu-repo/semantics/publishedVersion

This work presents a new approach to the application of essential oils, exposure to the vapor phase, which can be considered a first approach for the development of a complementary or alternative form of vulvovaginal candidiasis (VVC) treatment. VVC is a significant infection caused by Candida species and remains a common disease that affects millions of women every year. Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases. The increasing incidence of drug-resistant Candida strains and the limited therapeutic options make the discovery of effective alternative therapies fundamental. Essential oils (EOs) have been suggested as a promising alternative, and interestingly, vapor-phase essential oils (VP-EOs) present more advantages than their direct application. Thus, this study aims to evaluate the effect of oregano VP-EO (VP-OEO) on biofilms of antifungal-resistant vaginal isolates of Candida species (Candida albicans and Candida glabrata) and determine its mode of action. CFU, membrane integrity, and metabolic activity were evaluated. Furthermore, a reconstituted vaginal epithelium was used to mimic vaginal conditions and evaluate the effect of VP-OEO on Candida species infection, analyzed by DNA quantification, microscopy, and lactate dehydrogenase activity. The results revealed high VP-OEO antifungal activity. There was a significant reduction (\>4 log CFU) in Candida species biofilms. Furthermore, the results show that the mechanisms of action of VP-OEO are related to membrane integrity and metabolic activity. The epithelium model confirms the effectiveness of VP-OEO. This study suggests that VP-EO can be considered a first approach for the development of an alternative form of VVC treatment. IMPORTANCE This work presents a new approach to the application of essential oils, exposure to the vapor phase, which can be considered a first approach for the development of a complementary or alternative form of vulvovaginal candidiasis (VVC) treatment. VVC is a significant infection caused by Candida species and remains a common disease that affects millions of women every year. The great difficulty in treating VVC and the extremely limited effective therapeutic options make the development of alternative treatments crucial. In this scope, this study aims to contribute to the development of effective, inexpensive, and nontoxic strategies for the prevention and treatment of this infectious disease, based on natural products. Moreover, this new approach has several advantages for women, such as lower costs, easy access, an easier mode of application, avoidance of skin contact, and, therefore, fewer negative impacts on womens health., This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of the UIDB/04469/2020 unit and grant 2020.05720.BD to L.F. Also, this study was supported by LABBELS-Associate Laboratory in Biotechnology, Bioengineering, and Microelectromechanical Systems LA/P/0029/2020, and M.E.R. thanks the FCT for funding through program DL 57/2016-Norma Transitoria. S.C.-D.-O. acknowledges national funds through the FCT, IP, within the scope of the project RISE-LA/P/0053/2020., info:eu-repo/semantics/publishedVersion

Introduction : Vulvovaginal candidiasis is a disease that affects millions of women worldwide. Oral formulations, topical creams or ointments are the conventional dosage forms, with an increase in drug administration through vaginal via. The use of simulated biological fluids (e.g. vaginal fluid) in the evaluation of antifungal therapies may better mimic the real biological environments and therefore provide a better understanding of the behavior of the antifungal. Methods : The main objective of this work was to compare planktonic growth and biofilm formation of Candida species, on common growth medium, Sabouraud Dextrose Broth (SDB) and on vaginal simulation conditions, Simulated Vaginal Fluid (SVF), through the optical density determination, colony-forming units and scanning electron microscopy. In addition, under the same conditions this study also evaluated the ability of vapor phase of oregano and white thyme essential oils (VP-EOs), potential alternative treatment, to inhibit biofilm formation and to destroy mature biofilms of vaginal isolates, through the colony-forming units determination. Results : Candida isolates maintained the same biofilm formation capacity and morphology in both media (SVF and SDB). Furthermore, the results obtained in this work related with VP-EOs effect agree with results acquired, previously, with SDB. This means that the effect of VP-EOs is not affected by the SVF medium, and that this fluid allows the dissolution of the volatile and bioactive compounds. Conclusions : These results can predict the in vivo behaviour, suggesting a potential effective application of VP-EOs as prophylactic or therapeutic treatment for biofilm-related vulvovaginal candidiasis., This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and grant ref 2020.05720.BD for Liliana Fernandes. Also, this study was supported by LABBELS — Associate Laboratory in Biotechnology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020 and Maria Elisa Rodrigues thanks FCT for funding through program DL 57/2016—Norma transitória, info:eu-repo/semantics/publishedVersion

The constant financial scandals and the recent world economic crises have intensified the debate on Audit Quality and the reliability of financial reporting in the capital markets. More robust banking supervision and efficient risk management contribute to better capital adequacy in banks and, consequently, promote financial stability in the banking sector. The present study aims to analyse the relationship between the Risk-Weighted Assets of several European banks and their respective market value, in order to identify the influence of audit quality on this practice. For this purpose, a sample of 94 banks from 22 European countries is used, covering the period from 2007 to 2020. The variables under analysis take the form of bank-specific, institutional, and macroeconomic variables. The results show that Risk-Weighted Assets, the size of banks, and Non-performing loans have a negative influence on the market value. On the other hand, Profitability and Audit Quality have a positive influence. Os constantes escândalos financeiros e as recentes crises económicas mundiais, têm vindo a pôr em causa a Qualidade de Auditoria e a confiabilidade do relato financeiro no mercado de capitais. Uma supervisão bancária mais robusta e uma eficiente gestão de risco contribuem para uma melhor adequação de capital nos bancos e, consequentemente, promovem a estabilidade financeira no setor bancário. O presente estudo tem como objetivo analisar a relação entre o Risk-Weighted Assets de vários bancos Europeus e o seu respectivo valor de mercado, a fim de identificar a influência da qualidade da auditoria nesta relação. Para o efeito, é utilizada uma amostra de 94 bancos de 22 países europeus, entre o período de 2007 a 2020. As variáveis em análise assumem a forma de variáveis específicas do banco, institucionais e macroeconómicas. Os resultados demonstram que o Risk-Weighted Assets, a dimensão dos bancos e os empréstimos em incumprimento têm uma influência negativa no valor de mercado. Por outro lado, a rendibilidade e a qualidade de auditoria têm uma influência positiva.