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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.

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.

Development and validation of a single-step and accurate reverse transcriptase loop-mediated isothermal amplification technique (RT-LAMP) for rapid identification of SARS-CoV-2 relative to commercial quantitative reverse transcriptase real-time PCR (qRT-PCR) assays to allow prompt initiation of proper medical care and containment of virus spread. Primers showing optimal features were subjected to analytical sensitivity and specificity to assess the limit of detection (LOD) and cross-reaction with closely- and distantly-related viral species, and clinically prominent bacterial and fungal species. In order to evaluate the clinical utility, our RT-LAMP was subjected to a large number of clinical samples, including 213 negative and 47 positive patients, relative to two commercial quantitative RT-PCR assays. The analytical specificity and sensitivity of our assay was 100% and 500 copies/ml when serial dilution was performed in both water and sputum. Subjecting our RT-LAMP assay to clinical samples showed a high degree of specificity (99.5%), sensitivity (91.4%), positive predictive value (97.7%), and negative predictive value (98.1%) when used relative to qRT-PCR. Our RT-LAMP assay was two times faster than qRT-PCR and is storable at room temperature. A suspected case that later became positive tested positive using both our RT-LAMP and the two qRT-PCR assays, which shows the capability of our assay for screening purposes. We present a rapid RT-LAMP assay that could extend the capacity of laboratories to process two times more clinical samples relative to qRT-PCR and potentially could be used for high-throughput screening purposes when demand is increasing at critical situations.

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 C 2 H 2 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 β-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 gfc1 Δ 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.

Cryptococcus neoformans is a significant fungal pathogen that poses a serious threat to immunocompromised individuals, particularly those with HIV/AIDS. In the study, we found that the very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase, Phs1, was important for melanin formation, growth at 39 °C, maintenance of cell wall integrity, and virulence in murine models. Through RNA sequencing, we examined transcriptomic alterations and discovered that the deletion of PHS1 resulted in the upregulation of 169 genes and downregulation of 540 genes, many of which are associated with critical metabolic and cellular functions. Notably, the PHS1 -deficient mutant exhibited a significant reduction in ATP-dependent activities compared to wild-type cells at mRNA level. Furthermore, metabolomic data indicated considerable disruptions in oxidative phosphorylation and the TCA cycle following PHS1 deletion. Collectively, our findings underscore the potential role of Phs1 in cellular energy regulation and its contribution to the virulence of C. neoformans .

Background Candida albicans , Candida glabrata , and Candida parapsilosis are three prevalent causes of candidiasis, worldwide. These species are considered as nine medically important complex species. Limited knowledge about these newly recognized species prompted us to develop a one-step, multiplex PCR to detect and identify them in clinical settings. Methods Primers targeting Hyphal Wall Protein I gene for the C. albicans, C. dubliniensis, C. africana , Intergenic Spacer for the C. glabrata, C. nivariensis, C. bracarensis , and Intein and ITS rDNA for the C. parapsilosis, C. orthopsilosis, and C. metapsilosis were designed. Using 168 CBS reference strains and 280 clinical isolates, the specificity and reproducibility of the developed assay were evaluated. Results Our developed assay successfully identified and distinguished all the nine species. No cross-reaction with closely- and distantly-related yeast species, Aspergillus species and human DNA was observed, resulting in 100% specificity. The ambiguous results obtained by MALDI-TOF for C. albicans and C. africana were corrected by our 9-plex PCR assay. This assay identified all the cryptic complex species from two test sets from Iran and China, correctly. Conclusions Our developed multiplex assay is accurate, specific, cost/time-saving, and works without the tedious DNA extraction steps. It could be integrated into routine clinical laboratories and as a reliable identification tool and has the potential to be implemented into epidemiological studies to broaden the limited knowledge of cryptic species complexes.

Aspergillus species are the most common causative agents involved in otomycosis. In this study, 45 Aspergillus isolates were obtained from patients with otomycosis in western China during 2013–2016. The aim of this study is to identify the Aspergillus isolates to the species level by using β-tubulin gene sequencing and to evaluate their in vitro susceptibility to nine antifungal drugs: amphotericin B, itraconazole, voriconazole, posaconazole, ravuconazole, isavuconazole, caspofungin, micafungin and anidulafungin according to CLSI M38-A2. Our results indicate that A. tubingensis (18/45) is the predominant Aspergillus species causing ear infections in western China, which is three times more than its sibling species A. niger (6/45) and A. welwitschiae (2/45). Other detected species were A. fumigatus ( n  = 8), A. terreus ( n  = 7) and A. flavus ( n  = 4). Antifungal susceptibility data indicate that triazoles and echinocandins are active against the most Aspergillus isolates. There are no significant differences in the susceptibility among A. niger, A. tubingensis and A. welwitschiae to each of the antifungals tested. One azole-resistant A. fumigatus isolate with a TR34/L98H mutation in the CYP51A gene and one posaconazole-resistant A. terreus isolate presented among the studied isolates. In conclusion, A. tubingensis is the most prevalent Aspergillus species causing otomycosis in western China. Posaconazole and echinocandins are potential drugs for treatment of otomycosis due to Aspergillus ; however, in vivo efficacy remains to be determined.

The discussion of inequality has been an enduring topic in sociology and economics. With the intensification of inequality, an increasing amount of research has begun to focus on the impact of inequality on various aspects of the economy and society. However, research on how inequality affects families’ education investment behavior currently remains relatively scarce. This study contributes to filling this gap by presenting one of the first analyses of the effect of intergenerational mobility-based opportunity inequality on family education investment. Specifically, based on a Chinese population sample survey conducted in 2015 and the China Family Panel Studies survey conducted in 2018, this paper measures the intergenerational mobility of regions using an index of intergenerational educational rank correlation, and it uses extracurricular tutoring expenses to measure families’ investment in their children’s education. The benchmark regression results show that intergenerational mobility significantly negatively impacts family education investment, with the average family education investment decreasing by 25.75 percent for every 0.1-unit increase in intergenerational mobility. This negative effect remains significant after robustness tests, such as replacing the explanatory variables and dependent variables, considering the influence of important omitted variables, evaluating the impact of unobservable factors, and introducing an instrumental variable for two-stage least squares regression analysis. In addition, this negative impact is more prevalent among families with high socioeconomic status, while it is not significant in families with low socioeconomic status. The reason is that families with low socioeconomic status face greater credit constraints and intergenerational mobility incentives. Furthermore, an examination of the mechanisms involved reveals that although the improvement in intergenerational mobility may increase people’s confidence in investing, it ultimately reduces family education investment by lowering excessive anxiety and the extent of status-seeking behavior among families. According to the analysis, promoting equality of opportunity could mitigate China’s negative educational competition and facilitate the realization of the “Double Reduction” policy.

Pressure ulcer formation depends on various factors among which repetitive ischaemia/reperfusion(I/R) injury plays a vital role. Molecular hydrogen (H2) was reported to have protective effects on I/R injuries of various internal organs. In this study, we investigated the effects of H2 inhalation on pressure ulcer and the underlying mechanisms. H2 inhalation significantly reduced wound area, 8‐oxo‐dG level (oxidative DNA damage) and cell apoptosis rates in skin lesions. H2 remarkably decreased ROS accumulation and enhanced antioxidant enzymes activities by up‐regulating expression of Nrf2 and its downstream components in wound tissue and/or H2O2‐treated endothelia. Meanwhile, H2 inhibited the overexpression of MCP‐1, E‐selectin, P‐selectin and ICAM‐1 in oxidant‐induced endothelia and reduced inflammatory cells infiltration and proinflammatory cytokines (TNF‐α, IL‐1, IL‐6 and IL‐8) production in the wound. Furthermore, H2 promoted the expression of pro‐healing factors (IL‐22, TGF‐β, VEGF and IGF1) and inhibited the production of MMP9 in wound tissue in parallel with acceleration of cutaneous collagen synthesis. Taken together, these data indicated that H2 inhalation suppressed the formation of pressure ulcer in a mouse model. Molecular hydrogen has potentials as a novel and alternative therapy for severe pressure ulcer. The therapeutic effects of molecular hydrogen might be related to its antioxidant, anti‐inflammatory, pro‐healing actions.

Cryptococcus neoformans is a significant human fungal pathogen, particularly concerning for immunocompromised individuals. Key kinases, Hsl101 and Urk1, are critical for crossing the blood-brain barrier, although the specific mechanisms by which they do so remain undefined. In this study, we systematically investigate the impact of HSL101 or URK1 deletion on the proteomic and metabolomic profiles of C. neoformans . By generating a deletion mutant for HSL101 , we observed profound alterations in the expression levels of 366 proteins and 421 metabolites, highlighting significant disruptions in key biological processes, such as oxidative phosphorylation and ATP synthesis, which are vital for energy production in the cell. Similarly, the deletion of URK1 resulted in significant changes in the expression of 236 proteins and 366 metabolites, particularly affecting pathways related to steroid biosynthesis and starch and sucrose metabolism, which are critical for cellular function and adaptation. These findings shed light on the regulatory roles of Hsl101 and Urk1 in the metabolic pathways of C. neoformans .