Advances in the understanding of talaromycosis in HIV-negative patients (Especially in children and patients with hematological malignancies): A comprehensive review.

Talaromyces marneffei (T.marneffei) stands out as the sole thermobiphasic fungus pathogenic to mammals, including humans, within the fungal community encompassing Ascomycota, Eurotium, Eurotiumles, Fungiaceae, and Cyanobacteria. Thriving as a saprophytic fungus in its natural habitat, it transitions into a pathogenic yeast phase at the mammalian physiological temperature of 37°C. Historically, talaromycosis has been predominantly associated with HIV/AIDS, classified among the three primary opportunistic infections linked with AIDS, alongside tuberculosis and cryptococcosis. As advancements are made in HIV/AIDS treatment and control measures, the incidence of talaromycosis co-infection with HIV is declining annually, whereas the population of non-HIV-infected talaromycosis patients is steadily increasing. These patients exhibit diverse risk factors such as various types of immunodeficiency, malignant tumors, autoimmune diseases, and organ transplantation, among others. Yet, a limited number of retrospective studies have centered on the clinical characteristics and risk factors of HIV-negative talaromycosis patients, especially in children and patients with hematological malignancies, resulting in an inadequate understanding of this patient cohort. Consequently, we conducted a comprehensive review encompassing the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis, treatment, and prognosis of HIV-negative talaromycosis patients, concluding with a prospectus of the disease's frontier research direction. The aim is to enhance comprehension, leading to advancements in the diagnosis and treatment rates for these patients, ultimately improving their prognosis.

In this paper, we conducted a comprehensive review encompassing the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis, treatment, and prognosis of HIV-negative talaromycosis patients, concluding with a prospectus of the disease's frontier research direction. The aim is to enhance comprehension, leading to advancements in the diagnosis and treatment rates for these patients, ultimately improving their prognosis.

X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

A single gene mutation underpins metabolic adaptation and acquisition of filamentous competence in the emerging fungal pathogen Candida auris.

Filamentous cell growth is a vital property of fungal pathogens. The mechanisms of filamentation in the emerging multidrug-resistant fungal pathogen Candida auris are poorly understood. Here, we show that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, which forms elongated filamentous cells after a prolonged culture period. Whole-genome sequencing analysis reveals that all RL-FC isolates harbor a mutation in the C2H2 zinc finger transcription factor-encoding gene GFC1 (Gfc1 variants). Deletion of GFC1 leads to an RL-FC phenotype similar to that observed in Gfc1 variants. We further demonstrate that GFC1 mutation causes enhanced fatty acid ß-oxidation metabolism and thereby promotes RL-FC/filamentous growth. This regulation is achieved through a Multiple Carbon source Utilizer (Mcu1)-dependent mechanism. Interestingly, both the evolved RL-FC isolates and the gfc1Δ mutant exhibit an enhanced ability to colonize the skin. Our results reveal that glycerol-mediated GFC1 mutations are beneficial during C. auris skin colonization and infection.

Progress in the application of nanoparticles for the treatment of fungal infections: A review.

The burden of fungal infections on human health is increasing worldwide. Aspergillus, Candida, and Cryptococcus are the top three human pathogenic fungi that are responsible for over 90% of infection-related deaths. Moreover, effective antifungal therapeutics are lacking, primarily due to host toxicity, pathogen resistance, and immunodeficiency. In recent years, nanomaterials have proved not only to be more efficient antifungal therapeutic agents but also to overcome resistance against fungal medication. This review will examine the limitations of standard antifungal therapy as well as focus on the development of nanomaterials.

Phaeohyphomycosis caused by Corynespora cassiicola, a plant pathogen worldwide.

Although rare, trans-kingdom infection features an interesting infection biology concept, in which highly versatile pathogenic attributes allow successful infections in evolutionarily highly divergent species. Corynespora cassiicola is a phytopathogenic fungus and occasionally causes human infections. Herein, we report a phaeohyphomycosis case caused by C. cassiicola. Given that sporadic reports may contribute to a lack of awareness of the transmission route, clinical manifestations, and diagnostic and clinical management, we systematically reviewed the cases reported thus far. Nine patients were identified and included in the pooled analysis, 88.9% (8/9) of whom were reported after 2010. All patients were from Asian, African, and Latin American countries, among whom 77.8% (7/9) were farmers or lived in areas with active agriculture. Exposed body parts were the major affected infection area, and clinical manifestations were mainly non-specific inflammatory reactions. Although biochemical and morphological examinations confirmed the presence of fungal infection, molecular analysis was used for the final diagnosis, with 77.8% (7/9) being identified by internal transcribed spacer sequencing. Whereas voriconazole, terbinafine, and AmB, either alone or in combination, resulted in successful infection resolution in most cases (5/9; 55.5%), those suffering from invasive facial infections and CARD9 deficiency showed poor outcomes. Our patient is the third case of invasive facial infection caused by C. cassiicola and was successfully treated with intravenous LAmB followed by oral voriconazole combined with topical antifungal irrigation. Molecular identification of fungus and prompt antifungal treatment is pivotal in the clinical success of patients suspected to have phaeohyphomycosis. Moreover, as evidenced by our data, itraconazole treatment is not recommended.

Galleria mellonella in vitro model for chromoblastomycosis shows large differences in virulence between isolates.

BACKGROUND: Chromoblastomycosis is the World Health Organization (WHO)-recognized fungal implantation disease that eventually leads to severe mutilation. Cladophialophora carrionii (C. carrionii) is one of the agents. However, the pathogenesis of C. carrionii is not fully investigated yet. METHODS: We investigated the pathogenic potential of the fungus in a Galleria mellonella (G. mellonella) larvae infection model. Six strains of C. carrionii, and three of its environmental relative C. yegresii were tested. The G. mellonella model was also applied to determine antifungal efficacy of amphotericin B, itraconazole, voriconazole, posaconazole, and terbinafine. RESULTS: All strains were able to infect the larvae, but virulence potentials were strain-specific and showed no correlation with clinical background of the respective isolate. Survival of larvae also varied with infection dose, and with growth speed and melanization of the fungus. Posaconazole and voriconazole exhibited best activity against Cladophialophora, followed by itraconazole and terbinafine, while limited efficacy was seen for amphotericin B. CONCLUSION: Infection behavior deviates significantly between strains. In vitro antifungal susceptibility of tested strains only partly explained the limited treatment efficacy in vivo.

Educational Mismatch and Workers' Fertility Intentions: Evidence from China.

This paper focuses on the impact of the educational mismatch on workers' fertility intentions and explores the underlying mechanisms. Empirical research based on the China Family Panel Survey (CFPS) data shows that undereducation has a negative effect on the fertility intentions of women aged 18-35, whereas overeducation reports no effect, a finding that remains stable in the robustness test and the IV model. An explanation for this phenomenon is that undereducated female workers have a wage premium and higher expectations of career development, which implies a greater opportunity cost of fertility. The heterogeneity analysis shows that women with low socio-economic status, especially those who are less educated, from low-income households, and who are employed in the private sector, are more affected. It is therefore necessary to reduce the substitution risk in the labor market for this group and to lighten the fertility burden and pressure on women.

XB130 inhibits healing of diabetic skin ulcers through the PI3K/Akt signalling pathway.

BACKGROUND: Diabetic skin ulcers, a significant global healthcare burden, are mainly caused by the inhibition of cell proliferation and impaired angiogenesis. XB130 is an adaptor protein that regulates cell proliferation and migration. However, the role of XB130 in the development of diabetic skin ulcers remains unclear. AIM: To investigate whether XB130 can regulate the inhibition of proliferation and vascular damage induced by high glucose. Additionally, we aim to determine whether XB130 is involved in the healing process of diabetic skin ulcers, along with its molecular mechanisms. METHODS: We conducted RNA-sequencing analysis to identify the key genes involved in diabetic skin ulcers. We investigated the effects of XB130 on wound healing using histological analyses. In addition, we used reverse transcription-quantitative polymerase chain reaction, Western blot, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, immunofluorescence, wound healing, and tubule formation experiments to investigate their effects on cellular processes in human umbilical vein endothelial cells (HUVECs) stimulated with high glucose. Finally, we performed functional analysis to elucidate the molecular mechanisms underlying diabetic skin ulcers. RESULTS: RNA-sequencing analysis showed that the expression of XB130 was up-regulated in the tissues of diabetic skin ulcers. Knockdown of XB130 promoted the healing of skin wounds in mice, leading to an accelerated wound healing process and shortened wound healing time. At the cellular level, knockdown of XB130 alleviated high glucose-induced inhibition of cell proliferation and angiogenic impairment in HUVECs. Inhibition of the PI3K/Akt pathway removed the proliferative effects and endothelial protection mediated by XB130. CONCLUSION: The findings of this study indicated that the expression of XB130 is up-regulated in high glucose-stimulated diabetic skin ulcers and HUVECs. Knockdown of XB130 promotes cell proliferation and angiogenesis via the PI3K/Akt signalling pathway, which accelerates the healing of diabetic skin ulcers.

Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study.

Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1ß and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.

The Epidemiology and Clinical Characteristics of Fungemia in a Tertiary Hospital in Southern China: A 6-Year Retrospective Study.

Knowledge of the epidemiology and clinical characteristics of fungemia in southern China is limited. We conducted a six-year retrospective descriptive study to analyze the epidemiological and clinical characteristics of fungemia at the largest tertiary hospital in Guangxi, southern China. Data were obtained from the laboratory registry of patients with fungemia between January 2014 and December 2019. Demographic characteristics, underlying medical conditions, and outcomes for each case were analyzed. A total of 455 patients with fungemia were identified. Unexpectedly, Talaromyces marneffei (T. marneffei) was the most frequently isolated agent causing fungemia in the region (149/475, 31.4%), and Candida albicans (C. albicans) was the most commonly isolated Candida spp. (100/475, 21.1%). We identified that more than 70% of talaromycosis fungemia developed in AIDS patients, whereas candidemia was most commonly associated with a history of recent surgery. Notably, the total mortality rate of fungemia and the mortality rate in patients with T. marneffei and Cryptococcus neoformans (C. neoformans) fungemia were significantly higher in HIV-uninfected patients than in HIV-infected patients. In conclusion, the clinical pattern of fungemia in Guangxi is different from that in previous studies. Our study may provide new guidance for the early diagnosis and prompt treatment of fungemia in similar geographic regions.

Diagnosis of invasive fungal infections: challenges and recent developments.

BACKGROUND: The global burden of invasive fungal infections (IFIs) has shown an upsurge in recent years due to the higher load of immunocompromised patients suffering from various diseases. The role of early and accurate diagnosis in the aggressive containment of the fungal infection at the initial stages becomes crucial thus, preventing the development of a life-threatening situation. With the changing demands of clinical mycology, the field of fungal diagnostics has evolved and come a long way from traditional methods of microscopy and culturing to more advanced non-culture-based tools. With the advent of more powerful approaches such as novel PCR assays, T2 Candida, microfluidic chip technology, next generation sequencing, new generation biosensors, nanotechnology-based tools, artificial intelligence-based models, the face of fungal diagnostics is constantly changing for the better. All these advances have been reviewed here giving the latest update to our readers in the most orderly flow. MAIN TEXT: A detailed literature survey was conducted by the team followed by data collection, pertinent data extraction, in-depth analysis, and composing the various sub-sections and the final review. The review is unique in its kind as it discusses the advances in molecular methods; advances in serology-based methods; advances in biosensor technology; and advances in machine learning-based models, all under one roof. To the best of our knowledge, there has been no review covering all of these fields (especially biosensor technology and machine learning using artificial intelligence) with relevance to invasive fungal infections. CONCLUSION: The review will undoubtedly assist in updating the scientific community's understanding of the most recent advancements that are on the horizon and that may be implemented as adjuncts to the traditional diagnostic algorithms.

Cryptococcus neoformans, a global threat to human health.

BACKGROUND: Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL, Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections. METHODS: We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keyword Cryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance of C. neoformans to approved antifungal drugs. RESULTS: There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden. CONCLUSION: The rising threat of C. neoformans is compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.

TREM2 as a Potential Immune-Related Biomarker of Prognosis in Patients with Skin Cutaneous Melanoma Microenvironment.

Background: The skin cutaneous melanoma (SKCM) is a devastating form of skin cancer triggered by genetic and environmental factors, and the incidence of SKCM has rapidly increased in recent years. Immune infiltration of the tumor microenvironment is positively associated with overall survival in many tumors. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although numerous evidences suggest a crucial role for TREM2 in tumorigenesis of some tumors, no systematic SKCM analysis of TREM2 is available. Mehods. The relationship between TREM2 expression and diagnostic and prognostic value of SKCM patients via using The Cancer Genome Atlas (TCGA) data. The expression level of TREM2 and clinical characteristic correlation in SKCM patients were assessed by the Wilcoxon rank sum test. The cox regression methods, Kaplan-Meier (KM), and log-rank test were used to assess the impact of TREM2 expression on the overall survival (OS). Furthermore, the Gene Set Enrichment Analysis (GSEA) and TIMER were performed to evaluate the enrichment pathways and potential functions and quantify the immune cell infiltration level for TREM2 expression. Results: The TREM2 in SKCM sample expression levels was significantly higher than in normal tissues. Moreover, this expression level of TREM2 was also associated with the BMI of SKCM patients. KM overall survival analysis and OS curve displayed that a high-level TREM2 expression was significantly correlated with a better SKCM prognosis of patients as compared with a low level of TREM2 expression. The GSEA analysis also revealed that TREM2 was associated with immune functions, such as neutrophil activation. Conclusion: TREM2 played a crucial role in SKCM, which might be a prognostic biomarker and correlated with immune infifiltrates in SKCM patients.

Genotypic diversity and antifungal susceptibility of Scedosporium species from clinical settings in China.

BACKGROUND: Scedosporium species have drawn significant interest as inhabitants of polluted soil and water and as cause of high mortality in near-drowning patients. So far, most cases have been reported from Europe and Australia, while knowledge on their prevalence and genotypic diversity from Asia is scant. OBJECTIVES: To increase the knowledge of the genetic diversity and in vitro antifungal susceptibility of Scedosporium species involved in human infections from China. METHODS: Here, we applied the ISHAM-MLST consensus scheme for molecular typing of Scedosporium species and revealed both high species diversity and high genotypic diversity among 45 Chinese clinical Scedosporium isolates. RESULTS: Among the five species, Scedosporium boydii (n = 22) was the most common, followed by S. apiospermum (n = 18), S. aurantiacum (n = 4) and S. dehoogii (n = 1). S. aurantiacum was reported for the first time from clinical samples in China. The predominant sequence types (STs) were ST17 in S. apiospermum, ST4 in S. boydii and ST92 in S. aurantiacum, including four novel STs (ST40, ST41, ST42 and ST43) in S. apiospermum. Based on the CLSI-M38 A2 criterion, voriconazole was the only antifungal compound with low MIC values (MIC90 ≤ 1 µg/ml) for all Scedosporium isolates in our study. CONCLUSIONS: The genetic diversity of clinical isolates of Scedosporium species from China is extremely high, with S. boydii being predominant and S. aurantiacum being firstly reported here. VOR was the only antifungal compound with low MIC values for all Scedosporium isolates in our study, which should be recommended as the firstline antifungal treatment against scedosporiosis in China.

Functionalization of Nanomaterials for Skin Cancer Theranostics.

Skin cancer has drawn attention for the increasing incident rates and high morbidity worldwide. Timely diagnosis and efficient treatment are of paramount importance for prompt and effective therapy. Thus, the development of novel skin cancer diagnosis and treatment strategies is of great significance for both fundamental research and clinical practice. Recently, the emerging field of nanotechnology has profoundly impact on early diagnosis and better treatment planning of skin cancer. In this review, we will discuss the current encouraging advances in functional nanomaterials for skin cancer theranostics. Challenges in the field and safety concerns of nanomaterials will also be discussed.

Invasive infections due to Magnusiomyces capitatus: case report and review of its prevalence in China.

Magnusiomyces capitatus is an emerging opportunistic yeast, thus far mainly reported from the Western world where fungemia is the most frequent presentation in immunocompromised patients with high mortality. We described a rare case of Magnusiomyces capitatus infection from our hospital in China and reviewed six further cases published to date in Chinese literature. It is noted that half more of the cases (4/7) presented with fungemia in younger, immunosuppressed patients, whereas the remaining cases were with pneumonia in elderly, immunocompetent patients. All seven Chinese cases had favourable outcome with antifungal therapy. Based on the limited in vitro and clinical data, a combination of amphotericin B either with 5-fluorocytosine or voriconazole for fungemia in immunocompromised patients, and although fluconazole is not recommended as first-line therapy in the guideline, in our study, fluconazole alone or with 5-fluorocytosine for local pulmonary infection in immunocompetent patients is effective with good outcome.

Characteristics and Prognosis of Talaromyces marneffei Infection in HIV-positive Children in Southern China.

Knowledge about the clinical characteristics and prognostic factors of Talaromyces marneffei infection in children is limited, especially in HIV-positive children. We performed a retrospective study of all HIV-positive pediatric inpatients with T. marneffei infection in a tertiary hospital in Southern China between 2014 and 2019 and analyzed the related risk factors of poor prognosis using logistic regression. Overall, 28 cases were enrolled and the prevalence of talaromycosis in AIDS children was 15.3% (28/183). The median age of the onset was 8 years (range: 1-14 years). The typical manifestation of skin lesion with central umbilication was not common (21.4%). All the children had very low CD4+ cell counts (median 13.5 cells/µL, range: 3-137 cells/µL) on admission. 92.9% children were misdiagnosed and talaromycosis was only noted after positivity for HIV infection. 89.3% diagnoses of T. marneffei infections were based on positive blood cultures, with a long culture time (median 7 days, range from 3-14 days). The sensitivity of fungus 1,3-ß-D-glucan assay was 63.2%. Amphotericin B was superior to itraconazole in the induction antifungal therapy of talaromycosis in HIV-positive children. A six-month follow-up revealed a 28.6% mortality. Lower ratio of CD4+/CD8+ and amphotericin B treatment not over 7 days predicted poor prognosis. Our retrospective study provided an overview and update on the current knowledge of talaromycosis in HIV-positive children. Pediatricians in endemic areas should be aware of mycoses to prevent misdiagnosis. 1,3-ß-D-glucan assay did not show optimal sensitivity. Amphotericin B treatment over 7 days can improve poor prognosis.

Genotyping and Drug Resistance Profile of Clinical Isolates of Candida albicans from Vulvovaginal Candidiasis in the Eastern China.

A total of 244 Candida albicans isolates recovered from vulvovaginal candidiasis (VVC) patients in Suzhou, Eastern China, were investigated. According to CLSI documents M27-A4 and M59-3ed/M60-2ed, the MIC geometric means of nine antifungals in increasing order were micafungin (0.048 mg/L), anidulafungin (0.132 mg/L), caspofungin (0.19 mg/L), itraconazole (0.23 mg/L), posaconazole (0.25 mg/L), voriconazole (0.28 mg/L), 5-flucytosine (0.44 mg/L), amphotericin B (0.49 mg/L) and fluconazole (2.01 mg/L) respectively. Of note, 6.5% (16/244) C. albicans isolates showed resistance mainly to anidulafungin (mono-echinocandin resistance), while voriconazole had the lowest susceptibility rate of 34.8% (85/244), followed by fluconazole 59.4% (145/244), respectively. All isolates were genotyped by allelic combination of 3 microsatellite markers (CEF3, CAIII and LOC4). A total of 129 different allelic genotypes were identified, in which seven different clades were recognized with a discriminatory power of 0.96. Genotypes A-D were present in 35% of the isolates. In conclusion, decrease in antifungal drug susceptibility to C. albicans isolates from VVC is alarming. Our findings revealed the genetic diversity of C. albicans isolates among VVC patients and provided insights into the molecular epidemiology of Candida infections in China.

Multi-kingdom microbiota analyses identify bacterial-fungal interactions and biomarkers of colorectal cancer across cohorts.

Despite recent progress in our understanding of the association between the gut microbiome and colorectal cancer (CRC), multi-kingdom gut microbiome dysbiosis in CRC across cohorts is unexplored. We investigated four-kingdom microbiota alterations using CRC metagenomic datasets of 1,368 samples from 8 distinct geographical cohorts. Integrated analysis identified 20 archaeal, 27 bacterial, 20 fungal and 21 viral species for each single-kingdom diagnostic model. However, our data revealed superior diagnostic accuracy for models constructed with multi-kingdom markers, in particular the addition of fungal species. Specifically, 16 multi-kingdom markers including 11 bacterial, 4 fungal and 1 archaeal feature, achieved good performance in diagnosing patients with CRC (area under the receiver operating characteristic curve (AUROC) = 0.83) and maintained accuracy across 3 independent cohorts. Coabundance analysis of the ecological network revealed associations between bacterial and fungal species, such as Talaromyces islandicus and Clostridium saccharobutylicum. Using metagenome shotgun sequencing data, the predictive power of the microbial functional potential was explored and elevated D-amino acid metabolism and butanoate metabolism were observed in CRC. Interestingly, the diagnostic model based on functional EggNOG genes achieved high accuracy (AUROC = 0.86). Collectively, our findings uncovered CRC-associated microbiota common across cohorts and demonstrate the applicability of multi-kingdom and functional markers as CRC diagnostic tools and, potentially, as therapeutic targets for the treatment of CRC.

Gut microbiota associated with cryptococcal meningitis and dysbiosis caused by anti-fungal treatment.

The gut microbiota is a dynamic and highly diverse microbial ecosystem that affects many aspects of the host's physiology. An improved understanding of the gut microbiota could lead to better strategies for the diagnosis and therapy of cryptococcal meningitis (CM), but the impact of Cryptococcus infection and anti-fungal treatment on the gut microbiota has rarely been studied. We characterized the diversity and composition of the gut microbiota in CM patients at diagnosis and healthy controls (HCs) using metagenomic sequencing and determined the effects of anti-fungal drugs. We found that CM patients had distinct bacterial and fungal compositions compared with HCs, with eight differentially abundant fungal and 72 differentially abundant bacterial species identified between the two groups. CM patients showed an increased abundance of Enterococcus avium, Leuconostoc mesenteroides, and Weissella cibaria, and a decreased abundance of Prevotella spp. compared with HCs. However, anti-fungal treatment only led to minor changes in the intestinal microbiota. Moreover, both positive and negative correlations existed in fungal, bacterial, and clinical indicators. Our study suggests that the Cryptococcus neoformans infection caused a distinct dysbiosis of the gut microbiota and contributes valuable information implying potential links between the CM and gut microbiota.