Salivary mycobiome dysbiosis and its potential impact on bacteriome shifts and host immunity in oral lichen planus

The biodiversity of the mycobiome,an important component of the oral microbial community,and the roles of fungal–bacterial and fungal–immune system interactions in the pathogenesis of oral lichen planus (OLP) remain largely uncharacterized.In this study,we sequenced the salivary mycobiome and bacteriome associated with OLP.First,we described the dysbiosis of the microbiome in OLP patients,which exhibits lower levels of fungi and higher levels of bacteria.Significantly higher abundances of the fungi Candida and Aspergillus in patients with reticular OLP and of Alternaria and Sclerotiniaceae_unidentified in patients with erosive OLP were observed compared to the healthy controls.Aspergillus was identified as an “OLP-associated” fungus because of its detection at a higher frequency than in the healthy controls.Second,the co-occurrence patterns of the salivary mycobiome–bacteriome demonstrated negative associations between specific fungal and bacterial taxa identified in the healthy controls,which diminished in the reticular OLP group and even became positive in the erosive OLP group.Moreover,the oral cavities of OLP patients were colonized by dysbiotic oral flora with lower ecological network complexity and decreased fungal–Firmicutes and increased fungal–Bacteroidetes sub-networks.Third,several keystone fungal genera (Bovista,Erysiphe,Psathyrella,etc.) demonstrated significant correlations with clinical scores and IL-17 levels.Thus,we established that fungal dysbiosis is associated with the aggravation of OLP.Fungal dysbiosis could alter the salivary bacteriome or may reflect a direct effect of host immunity,which participates in OLP pathogenesis.

Electric field-driven building blocks for introducing multiple gradients to hydrogels

Gradient biomaterials are considered as preferable matrices for tissue engineering due to better simulation of native tissues.The introduction of gradient cues usually needs special equipment and complex process but is only effective to limited biomaterials.Incorporation of multiple gradients in the hydrogels remains challenges.Here,betasheet rich silk nanofibers(BSNF)were used as building blocks to introduce multiple gradients into different hydrogel systems through the joint action of crosslinking and electric field.The blocks migrated to the anode along the electric field and gradually stagnated due to the solution-hydrogel transition of the systems,finally achieving gradient distribution of the blocks in the formed hydrogels.The gradient distribution of the blocks could be tuned easily through changing different factors such as solution viscosity,which resulted in highly tunable gradient of mechanical cues.The blocks were also aligned under the electric field,endowing orientation gradient simultaneously.Different cargos could be loaded on the blocks and form gradient cues through the same crosslinking-electric field strategy.The building blocks could be introduced to various hydrogels such as Gelatin and NIPAM,indicating the universality.Complex niches with multiple gradient cues could be achieved through the strategy.Silk-based hydrogels with suitable mechanical gradients were fabricated to control the osteogenesis and chondrogenesis.Chondrogenic-osteogenic gradient transition was obtained,which stimulated the ectopic osteochondral tissue regeneration in vivo.The versatility and highly controllability of the strategy as well as multifunction of the building blocks reveal the applicability in complex tissue engineering and various interfacial tissues.