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Background: Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N6-methyladenosine (m6A) is an important post-transcriptional modification in RNAs that regulates cell fate determinant and progression of diseases. However, whether m6A methylation participates in the process of periodontitis with diabetes is unclear. Thus, we aimed to investigate the effects of AGEs on bone marrow mesenchymal stem cells (BMSCs), elucidate the m6A modification mechanism in diabetes-associated periodontitis. Methods: Periodontitis with diabetes were established by high-fat diet/streptozotocin injection and silk ligation. M6A modifications in alveolar bone were demonstrated by RNA immunoprecipitation sequence. BMSCs treated with AGEs, fat mass and obesity associated (FTO) protein knockdown and sclerostin (SOST) interference were evaluated by quantitative polymerase chain reaction, western blot, immunofluorescence, alkaline phosphatase and Alizarin red S staining. Results: Diabetes damaged alveolar bone regeneration was validated in vivo. In vitro experiments showed AGEs inhibited BMSCs osteogenesis and influenced the FTO expression and m6A level in total RNA. FTO knockdown increased the m6A levels and reversed the AGE-induced inhibition of BMSCs differentiation. Mechanically, FTO regulated m6A modification on SOST transcripts, and AGEs affected the binding of FTO to SOST transcripts. FTO knockdown accelerated the degradation of SOST mRNA in presence of AGEs. Interference with SOST expression in AGE-treated BMSCs partially rescued the osteogenesis by activating Wnt Signaling. Conclusions: AGEs impaired BMSCs osteogenesis by regulating SOST in an m6A-dependent manner, presenting a promising method for bone regeneration treatment of periodontitis with diabetes. [ABSTRACT FROM AUTHOR]

Background: The exact cerebral structural and functional mechanisms under the auditory verbal hallucinations (AVHs) in schizophrenia are still unclear. The Deutsch "high-low" word illusion might trigger attentional responses mimicking those under AVHs., Methods: We therefore have invited 16 patients with first-episode, paranoid schizophrenia, and 16 age- and gender-matched healthy volunteers to undergo the "oddball" event-related potentials elicited by the illusion. The clinical characteristics of patients were measured with the positive and negative symptom scale., Results: Besides the longer reaction time to the illusion, the standard P2 latency was shortened, the N2 latency was prolonged, and both N1 and P3 amplitudes were reduced in patients. The P3 source analyses showed the activated bilateral temporal lobes, parietal lobe and cingulate cortex in both groups, left inferior temporal gyrus in controls, and left postcentral gyrus in schizophrenia. Moreover, the N1 amplitude was positively correlated with the paranoid score in patients., Conclusions: Our results were in line with previous neurophysiological and neuroimaging reports of hallucination or auditory processing in schizophrenia, and illustrated a whole process of cerebral information processing from N1 to P3, indicating this illusion had triggered a dynamic cerebral response similar to that of the AVHs had engaged.