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Fusobacterium nucleatum (Fn) is a Gram-negative oral commensal, prevalent in various human diseases. It is unknown how this common commensal converts to a rampant pathogen. We report that Fn secretes an adhesin (FadA) with amyloid properties via a Fap2-like autotransporter to enhance its virulence. The extracellular FadA binds Congo Red, Thioflavin-T, and antibodies raised against human amyloid β42. Fn produces amyloid-like FadA under stress and disease conditions, but not in healthy sites or tissues. It functions as a scaffold for biofilm formation, confers acid tolerance, and mediates Fn binding to host cells. Furthermore, amyloid-like FadA induces periodontal bone loss and promotes CRC progression in mice, with virulence attenuated by amyloid-binding compounds. The uncleaved signal peptide of FadA is required for the formation and stability of mature amyloid FadA fibrils. We propose a model in which hydrophobic signal peptides serve as "hooks" to crosslink neighboring FadA filaments to form a stable amyloid-like structure. Our study provides a potential mechanistic link between periodontal disease and CRC and suggests anti-amyloid therapies as possible interventions for Fn-mediated disease processes.

White matter dysplasia (WMD) in preterm infants due to intrauterine inflammation is caused by excessive apoptosis of oligodendrocyte precursor cells (OPCs). In recent years, studies have found that excessive autophagy and apoptosis are highly interconnected and important in infection and inflammatory diseases in general. Therefore, in this study, we aimed to confirm whether regulation of autophagy by using the Akt phosphorylation agonist SC79 can inhibit abnormal apoptosis of OPCs and promote myelin maturation and white matter development in neonatal rats with WMD. We investigated the effect of inflammation on oligodendrocyte development in P0 neonatal rats by intracerebellar injection of LPS, and collected brain tissue at P2 and P5. Immunohistochemical and immunofluorescence staining were used to evaluate white matter damage, while immunofluorescence staining, terminal deoxynucleotidyl transferase dUTP nick end labeling analysis (TUNEL), and western blotting were used to evaluate autophagy and apoptosis. First, we observed that white matter development was arrested and white matter fiber maturation was impaired in LPS-inflicted pups compared with those in the sham-operated group. Second, treatment with SC79 reduced the levels of LC3II, caspase 3, caspase 9, and Bax/Bcl-2 and increased the levels of p62, p-Akt, and p-mTOR in the brain tissue of neonatal rats. Finally, SC79 treatment inhibited OPC apoptosis by increasing the binding of Beclin 1 to Bcl-2, which promoted OPC differentiation and maturation. However, the opposite results were observed after rapamycin administration. Taken together, our results suggest that SC79 can inhibit the abnormal apoptosis of OPCs caused by excessive autophagy through the Akt/mTOR pathway and that SC79 is a potential therapeutic agent for WMD in preterm infants. [ABSTRACT FROM AUTHOR]

Linguistic q-rung orthopair fuzzy numbers (Lq-ROFNs) are composed of a set of q-rung orthopair fuzzy numbers (q-ROFNs) with membership and nonmembership degrees of linguistic variables, which can be regarded as an extension of linguistic intuitionistic fuzzy numbers (LIFNs) and linguistic Pythagorean fuzzy numbers (LPFNs). Compared with LIFNs and LPFNs, Lq-ROFNs have a wider range of applicability because the value of q can have a wider range, thus allowing to handle more multiattribute group decision making (MAGDM) problems. Based on Lq-ROFS, this paper first proposes the Chebyshev distance metric, then develops the Chebyshev distance entropy for deriving objective solution of decision makers' (DMs') weight vector and attribute weight vector by combining the metric and entropy measure. The TODIM method has been widely valued by the society and has achieved good results in many MAGDM problems. Subsequently, the TODIM decision method in Lq-ROFS is presented and combined with the Chebyshev distance entropy model as a new decision method (CDE-TODIM) to solve the MAGDM problems. This method process is objective and direct and takes into account the decision maker's preferences, and the decision results are more persuasive. Finally, the effectiveness and rationality of this MAGDM method are illustrated by a case as well as comparisons. [ABSTRACT FROM AUTHOR]