Caries is the most common and extensive oral chronic disease. Due to the lack of anti-caries properties, traditional caries filling materials can easily cause secondary caries and lead to treatment failure. Nanomaterials can interfere with the bacteria metabolism, inhibit the formation of biofilm, reduce demineralization, and promote remineralization, which is expected to be an effective strategy for caries management. The nanotechnology in anti-caries materials, especially nano-adhesive and nano-composite resin, has developed fast in recent years. In this review, the antibacterial nanomaterials, remineralization nanomaterials, and nano-drug delivery systems are reviewed. We are aimed to provide a theoretical basis for the future development of anti-caries nanomaterials.

Candida albicans , a critical pathogen listed on the WHO fungal priority pathogens list, is a major cause of candidiasis and candidemia, particularly in immunocompromised populations. The lack of novel antifungal drugs and the increasing prevalence of drug resistance underscore the urgent need for new therapeutic strategies. By screening compounds derived from Aloe vera using hyphal induction assays, we identified aloe emodin (AE) as a potent inhibitor of C. albicans hyphal development. We demonstrate for the first time that AE, at concentrations of 50–100 μg/mL that do not affect fungal growth, significantly inhibits C. albicans hyphal development and its infections to oral epithelial cells without cytotoxicity. The confocal observation and following transcriptome and metabolome analysis demonstrate that AE localizes to fungal mitochondria and chelates iron, thereby disrupting iron homeostasis. These effects lead to mitochondrial dysfunction and metabolic reprogramming, particularly by impairing succinate dehydrogenase 2 activity, thereby reducing ATP and cAMP production. The decrease in cAMP levels leads to downregulation of the cAMP–PKA signaling pathway, a central regulator of hyphal development, ultimately suppressing hyphal growth. Mitochondrial function and metabolic assays, together with validation using mutants of the cAMP–PKA pathway, further confirmed the mechanism underlying the anti-hyphal activity of AE. AE at 50–100 μg/mL administered via drinking water also significantly reduced fungal burden and tissue damage in an oropharyngeal candidiasis model, which is similar with clinical antifungal nystatin. Collectively, our findings indicate that AE is a promising candidate for development as a therapeutic agent for oral candidiasis. Key points: • Aloe emodin disrupts mitochondrial iron homeostasis to remodel metabolism in C. albicans. • Aloe emodin downregulates the cAMP-PKA pathway to inhibit C. albicans hyphae. • Aloe emodin functions as a novel candidate for treating infections caused by C. albicans. Graphical

Candida albicans is the most prevalent opportunistic pathogenic fungus in humans, and its extracellular vesicles (EVs) play crucial roles in its growth and pathogenesis. Previously, we found that C. albicans EVs at low levels could promote its growth. However, the effects of EVs when accumulated at high concentrations in C. albicans remain unclear. This study revealed that a high concentration of EVs inhibited hyphal development in C. albicans in a time-dependent manner. Transcriptome and RT-qPCR analyses showed that EVs significantly upregulated the transcription repressor NRG1 and downregulated hyphal-specific genes in a laboratory strain and five clinical isolates, while EVs failed to repress nrg1Δ/Δ hyphae. Further experiments confirmed that EVs upregulated the upstream transcription factor SKO1 (but downregulated BRG1) to increase NRG1 expression, thereby inhibiting hyphal formation. Cargo proteins in EVs were key components that inhibited C. albicans hyphal growth. Additionally, EV-treated C. albicans showed improved mouse survival and reduced organ fungal burden in candidemia, but EVs did not attenuate virulence in nrg1Δ/Δ-infected mice. These results reveal that C. albicans EVs at high levels play an important role in its pathogenicity and highlight the potential for novel therapeutic strategies.