UNASSIGNED: Cervical cancer, primarily driven by high-risk human papillomavirus (HR-HPV) infection, ranks as the second most common cancer globally. Understanding combined infections\' role, including Cervical fungi, is crucial in cervical carcinogenesis. This study aims to explore the potential correlation between HR-HPV, cervical fungi, and cervical cancer, while adjusting for various factors.
UNASSIGNED: The study population comprised patients undergoing colposcopy and conization due to abnormal cervical screening results. Clinical data including age, gravidity, HPV (human papillomavirus) genotypes, cervical pathology, and p16/Ki67 expression were extracted. Cervical TCT (ThinPrep Pap Test) and HPV testing are utilized for screening cervical lesions, with fungal presence suggested by TCT results. 5,528 participants were included in this study. Statistical analyses investigated associations between HPV/fungi co-infection and cervical lesions, employing multinomial logistic regression and interaction analysis.
UNASSIGNED: Co-infection with fungi and HPV may decrease the risk of cervical lesions compared to HPV infection alone. In the co-infection group, compared with HPV infection alone, the risk of low-grade squamous intraepithelial lesions (LSIL) was reduced by 27% (OR = 0.73, 95% CI: 0.59-0.90), the risk of high-grade squamous intraepithelial lesions (HSIL) was reduced by 35% (OR = 0.65, 95% CI: 0.51-0.82), and the risk of cervical cancer was reduced by 43% (OR = 0.57, 95% CI: 0.35-0.92). The interaction analysis revealed a negative interaction between fungal and HPV infections in the development of cervical cancer (RERI = -6.25, AP = -0.79, SI = 0.52), HSIL (RERI = -19.15, AP = -0.37, SI = 0.72) and LSIL (RERI = -1.87, AP = -0.33, SI = 0.71), suggesting a sub-additive effect, where the combined effect of the two infections was less than the sum of their individual effects. This indicates that fungal infection may attenuate the promoting effect of HPV on cervical lesions. In exploring the potential mechanism, we found that the co-infection group had significantly lower p16 positivity (54.6%) compared to the HPV-only group (60.2%) (p = 0.004), while there was no statistically significant difference in Ki67 positivity.
UNASSIGNED: This study unveils the intricate relationship between cervical fungi and HPV in cervical lesions. Co-infection with fungi and HPV against cervical lesions compared to HPV infection alone, indicating a novel clinical interaction. Lower p16 positivity in co-infection hints at a protective mechanism, urging further exploration.

UNASSIGNED: The prevalence of invasive fungal infections (IFI) has risen in the past three decades, attributed to advancements in immune-modulatory therapies employed in transplantation, rheumatology, and oncology.
RESULTS: Organisms that cause IFI evade the host\'s natural defenses or at opportunities of immunologic weakness. Infections occur from inhalation of potentially pathogenic organisms, translocation of commensal organisms, or reactivation of latent infection. Organisms that cause IFI in immunocompromised populations include Candida spp., Cryptococcus spp., environmental molds, and endemic fungi. Diagnosis of these infections is challenging due to slow organism growth and fastidious culture requirements. Moreover, fungal biomarkers tend to be non-specific and can be negatively impacted by prophylactic antifungals. Antibody-based tests are not sensitive in immunocompromised hosts making antigen-based testing necessary. Prevention of IFI is guided by pathogen avoidance, removal or minimization of immune-suppressing factors, and pharmacologic prophylaxis in select hosts.
CONCLUSIONS: Understanding the complex interplay between the immune system and opportunistic fungal pathogens plays a key role in early diagnosis and prevention.

Candida auris (C. auris) has caused notable outbreaks across the globe in last decade and emerged as a life-threatening human pathogenic fungus. Despite significant advances in antifungal research, the drug resistance mechanisms in C. auris still remain elusive. Under such pressing circumstances, research on identification of new antifungal compounds is of immense interest. Thus, our studies aimed at identifying novel drug candidates and elucidate their biological targets in C. auris. After screening of several series of synthetic and hemisynthetic compounds from JUNIA chemical library, compounds C4 (butyl 2-(4-chlorophenyl)hydrazine-1-carboxylate) and C13 (phenyl 2-(4-chlorophenyl) hydrazine-1-carboxylate), belonging to the carbazate series, were identified to display considerable antifungal activities against C. auris as well as its fluconazole resistant isolates. Elucidation of biological targets revealed that C4 and C13 lead to changes in polysaccharide composition of the cell wall and disrupt vacuole homeostasis. Mechanistic insights further unravelled inhibited efflux pump activities of ATP binding cassette transporters and depleted ergosterol content. Additionally, C4 and C13 cause mitochondrial dysfunction and confer oxidative stress. Furthermore, both C4 and C13 impair biofilm formation in C. auris. The in vivo efficacy of C4 and C13 were demonstrated in Caenorhabditis elegans model after C. auris infection showing reduced mortality of the nematodes. Together, promising antifungal properties were observed for C4 and C13 against C. auris that warrant further investigations. To summarise, collected data pave the way for the design and development of future first-in-class antifungal drugs.

The quality and sensory attributes of juices are influenced by their natural microbiota and the microorganisms found on filtration membranes. This study aimed to assess the influence of natural microbiota and specific contaminants, including Candida krusei, Rhodotorula mucilaginosa, Debaryomyces prosopidis, Ralstonia insidiosa, and Lactiplantibacillus paraplantarum, isolated from cranberry juice and its associated industrial filtration membranes, on the characteristics of cranberry juice. Their growth kinetics and impacts on total phenols, total anthocyanins, total proanthocyanins, total organic acids, pH, titratable acidity, and volatile compounds were assessed. During the 42 h fermentation period, Candida krusei and Ralstonia insidiosa exhibited significant growth, increasing by 1-log and 3-log, respectively. The natural microbiota led to a 7% and 6% reduction in anthocyanins and proanthocyanidins, while Candida krusei and Rhodotorula mucilaginosa caused losses of 10% and 7% in proanthocyanidins, respectively. Organic acid content remained stable, except for an 8% decrease caused by Ralstonia insidiosa. Volatile compounds underwent significant increases, particularly in green (703%), winey (100%), mushroom (306%), and fusel (2678%) notes. These findings underscore the rapid impact of microorganisms from natural microbiota and filtration membranes on cranberry juice characteristics, highlighting the importance for beverage industries to prioritize customer safety and satisfaction.

OBJECTIVE: This experimental study aimed to examine the effectiveness of transdermal antimicrobial photodynamic therapy (APDT) with and without antimicrobial lock therapy (ALT), on catheter biofilms.
METHODS: S. epidermidis and C. orthopsilosis biofilms were formed within peripheral venous catheters positioned in the marginal ear veins of New Zealand white rabbits. Biofilm formation was confirmed with scanning electron microscopy in two catheters. 24 catheters with staphylococcal biofilms and 24 with fungal biofilms were treated with APDT, ALT or \"APDT plus ALT\" for five days. Six catheters were separated as controls. APDT was applied with a red colored LED lamp and methylene blue as the photosensitizer. Vancomycin lock solutions were used as ALT for staphylococcal biofilms and amphotericin B for fungal biofilms. The effect of treatment procedures was evaluated by intraluminal biofilm viability testing based on spectrophotometric evaluation, and a quantitative (OD) value was obtained for each catheter.
RESULTS: The mean OD values obtained by 600 nm spectrophotometric reading at 24 h (biofilm viability) after \"ALT\", \"APDT\" and \"ALT plus APDT\" procedures were 0.363, 0.151 and 0.128 for S. epidermidis and 0.092, 0.104 and 0.227 for C. orthopsilosis, respectively. All these OD values obtained after treatment procedures were lower than controls for both S. epidermidis (OD: 0,802) and C. orthopsilosis (OD: 0,315), although there were large fluctuations in our results.
CONCLUSIONS: Our results suggest that transdermal APDT may be an effective method for treating staphylococcal and candida biofilms formed within intravenous catheters in our rabbit ear model. The combined use of APDT and ALT might be beneficial in these staphylococcal biofilms.

Although rare in the general population, pulmonary fungal infections usually occur in immunocompromised patients. The mainstay of pulmonary fungal infection treatment is prolonged intravenous antifungal therapy. However, surgical management may be required in cases of complex disease, resistance to medical therapy or percutaneous procedures, or associated complications such as fungal empyema and massive hemoptysis. In this series, we present three patients with complicated thoracic fungal infections who underwent individualized surgical management over a 3-month period in 2022 at our institution. Complicated pulmonary fungal infections require surgical intervention to ensure complete resolution. The choice of operation is dependent on several factors, and surgeons operating on these patients must be privy to the various surgical modalities that may be required to successfully treat these patients.

SUMMARYThe ability to overcome metabolic stress is a major determinant of outcomes during infections. Pathogens face nutrient and oxygen deprivation in host niches and during their encounter with immune cells. Immune cells require metabolic adaptations for producing antimicrobial compounds and mounting antifungal inflammation. Infection also triggers systemic changes in organ metabolism and energy expenditure that range from an enhanced metabolism to produce energy for a robust immune response to reduced metabolism as infection progresses, which coincides with immune and organ dysfunction. Competition for energy and nutrients between hosts and pathogens means that successful survival and recovery from an infection require a balance between elimination of the pathogen by the immune systems (resistance), and doing so with minimal damage to host tissues and organs (tolerance). Here, we discuss our current knowledge of pathogen, immune cell and systemic metabolism in fungal infections, and the impact of metabolic disorders, such as obesity and diabetes. We put forward the idea that, while our knowledge of the use of metabolic regulation for fungal proliferation and antifungal immune responses (i.e., resistance) has been growing over the years, we also need to study the metabolic mechanisms that control tolerance of fungal pathogens. A comprehensive understanding of how to balance resistance and tolerance by metabolic interventions may provide insights into therapeutic strategies that could be used adjunctly with antifungal drugs to improve patient outcomes.

We describe for the first time, a high-quality genome for a rare human yeast pathogen Candida mucifera, from a patient with chronic suppurative otitis media. This pathogen exhibited reduced azole susceptibility, similar to its close relatives within the Trichomonascus ciferrii species complex.

Invasive candidiasis (IC) is an increasingly prevalent, costly, and potentially fatal infection brought on by the opportunistic yeast, Candida. Previously, IC has predominantly been caused by C. albicans which is often drug susceptible. There has been a global trend towards decreasing rates of infection secondary to C. albicans and a rise in non-albicans species with a corresponding increase in drug resistance creating treatment challenges. With advances in management of malignancies, there has also been an increase in the population at risk from IC along with a corresponding increase in incidence of breakthrough IC infections. Additionally, the emergence of C. auris creates many challenges in management and prevention due to drug resistance and the organism\'s ability to transmit rapidly in the healthcare setting. While the development of novel antifungals is encouraging for future management, understanding the changing epidemiology of IC is a vital step in future management and prevention.

Candida species are common human pathogens that cause a wide range of diseases ranging from superficial to invasive candidiasis. However, basic studies focusing on the mechanisms underlying these diseases are limited. This article reviews our previous research on the mechanisms of superficial and invasive candidiasis, the virulence of Candida species, and Candida species fitness to hosts. Regarding invasive candidiasis, we focused on two types of infections: ocular candidiasis and endogenous candidiasis from the gastrointestinal tract. Using an established ocular candidiasis mouse model, along with retrospective epidemiological research, we found a strong association between Candida albicans and ocular candidiasis. Regarding endogenous candidiasis, research using Candida auris indicated that invasive strains had a higher capability for gastrointestinal tract colonization and showed greater dissemination compared with non-invasive strains. In terms of superficial candidiasis, we focused on the defense mechanism in vulvovaginal candidiasis. The results suggested that stimulated invariant natural killer T cells played a protective role against C. albicans vaginal infection and might be a therapeutic target for vulvovaginal candidiasis. Concerning Candida species fitness, we focused on environmental factors, particularly oxygen concentration, and evaluated biofilm formation under various oxygen concentrations, revealing that each Candida species favored different oxygen concentrations. In particular, Candida tropicalis showed greater biofilm formation under hypoxic conditions. Our research revealed several insights for understanding the exact mechanisms of candidiasis, which might lead to better control of Candida species infections and appropriate treatment.