The mechanisms underlying gut development, especially peristalsis, are widely studied topics. However, the causes of gut peristalsis-related diseases, especially Opioid-Induced Bowel Dysfunction (OIBD) disorder, have not been well defined. Therefore, our study used zebrafish, a popular model for studying both gut development and peristalsis, and DCFH-DA, a dye that clearly labels the live fish gut lumen, to characterize the formation process of gut lumen as well as the gut movement style in vivo. By applying Loperamide Hydrochloride (LH), the μ-opioid receptor-specific agonist, we established an OIBD-like zebrafish model. Our study found that acetylcholine (ACh) was a key transmitter that derepressed the phenotype induced by LH. Overall, the study showed that the antagonistic role of ACh in the LH-mediated opioid pathway was evolutionarily conserved; moreover, the OIBD-like zebrafish model will be helpful in the future dissection of the molecular pathways involved in gut lumen development and pathology.

Interferon regulatory factor (IRF)-8 is a critical transcription factor involved in the pathogenesis of myeloid neoplasia. However, the underlying mechanisms in vivo are not well known. Investigation of irf8-mutant zebrafish in this study indicated that Irf8 is evolutionarily conserved as an essential neoplastic suppressor through tight control of the proliferation and longevity of myeloid cells. Surviving irf8 mutants quickly developed a myeloproliferative neoplasm (MPN)-like disease with enhanced output of the myeloid precursors, which recurred after transplantation. Multiple molecules presented notable alteration and Mertk signaling was aberrantly activated in the hematopoietic cells in irf8 mutants. Transgenic mertk overexpression in Tg(coro1a:mertk) zebrafish recapitulated the myeloid neoplasia-like syndrome in irf8 mutants. Moreover, functional interference with Mertk, via morpholino knockdown or genetic disruption, attenuated the myeloid expansion phenotype caused by Irf8 deficiency. Therefore, Mertk signaling is a critical downstream player in the Irf8-mediated regulation of the progression of myeloid neoplasia. Our study extends the understanding of the mechanisms underlying leukemogenesis.

Microglia are derived from primitive myeloid cells and gain their early identity in the embryonic brains. However, the mechanism by which the brain milieu confers microglial maturation signature remains elusive. Here, we demonstrate that the baxcq55 zebrafish and Baxtm1Sjk mouse embryos exhibit similarly defective early microglial maturation. BAX, a typical pro-apoptotic factor, is highly enriched in neuronal cells and regulates microglial maturation through both pro-apoptotic and non-apoptotic mechanisms. BAX regulates dlb via the CaMKII-CREB axis calcium-dependently in living neurons while ensuring the efficient Notch activation in the immigrated pre-microglia by apoptotic neurons. Notch signaling is conserved in supporting embryonic microglia maturation. Compromised microglial development occurred in the Cx3cr1Cre/+Rbpjfl/fl embryonic mice; however, microglia acquire their appropriate signature when incubated with DLL3 in vitro. Thus, our findings elucidate a BAX-CaMKII-CREB-Notch network triggered by the neuronal milieu in microglial development, which may provide innovative insights for targeting microglia in neuronal disorder treatment.

PurposeThe objectives of this study are to: (1) investigate the extent of antagonistic and distal neighboring tooth migration in the maxillary posterior single tooth‐missing site during the healing period of bone augmentation and implant surgery; (2) identify factors associated with tooth migration.Materials and methodsOne hundred and forty‐three cases that lost the maxillary first molar were included, and their CBCT data during the edentulous period were obtained. Dentition models were reconstructed from CBCT, and superimpositions were performed, followed by measuring migration distances and calculating migration rates of antagonistic and distal neighboring teeth. Factors were analyzed using multivariate generalized estimating equations (GEE).ResultsThe mean migration distances were 208 ± 137 μm and 403 ± 605 μm for antagonistic teeth and distal teeth, and the mean migration rates were 26.8 ± 21.2 μm/month and 48.5 ± 76.7 μm/month, respectively. One hundred and nineteen out of 143 distal neighboring teeth migrated toward the edentulous site, and all antagonistic teeth migrated occlusally. Occlusal contact loss and chronic apical periodontitis both significantly accelerated antagonistic tooth migration (p < 0.05), the latter also accelerated distal tooth migration (p < 0.05). Besides, the displacement of the distal teeth was somewhat accelerated by the impacted adjacent third molar and root protrusion into the sinus.ConclusionsThe neighboring teeth tend to migrate toward the edentulous gap in the maxillary posterior region. Occlusal contact loss and chronic apical periodontitis are two significant risk factors for accelerating antagonistic tooth migration, and for distal teeth, chronic apical periodontitis is the risk factor. The impacted adjacent third molar and root protrusion into the sinus are also potential risk factors for accelerating the migration of the maxillary distal tooth. Thus, to prevent maxillary edentulous gap reduction, the factors mentioned above should be taken into consideration when planning treatment flow.

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