Background: N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined. Methods: Quantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitro and in vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429. Results: KIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3′ UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as a cis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3. Conclusion: Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.

A novel bi-layered osteochondral scaffold, including of PVA/Gel/V layer for the cartilage and n-HA/PA6 layer for the subchondral bone, has been proposed to evaluate the potential of the engineered of osteochondral grafts in repairing articular osteochondral defects in rabbits. The two different layers of the scaffolds were seeded with allogenic bone marrow-derived stem cells (BMSCs), which were chondrogenically and osteogenically induced respectively. The critical-size osteochondral defects were created in the knees of adult rabbits. The defects were treated with cell-bi-layered constructs (Group A), bi-layered constructs (Group B) and untreated group C as control group. The adhesion, proliferation and differentiation of BMSCs were demonstrated by immunohistochemical staining and scanning electron microscopy (SEM) in vitro. Cell survival was tracked via fluorescent labeling in vivo. Overall, the porous PVA/Gel/V-n-HA/PA6 scaffold was compatible and had no negative effects on the BMSCs in vitro culture. The cell-bi-layered scaffolds showed superior repair results as compared to the control group using gross examination and histological assessment. With BMSCs implantation, the two different layers of the composite biomimetic scaffolds provided a suitable environment for cells to form respective tissue. Simultaneously, the RT-PCR results confirmed the expression of specific extracellular matrix (ECM) markers for cartilaginous or osteoid tissue. This investigation showed that the porous PVA/Gel/V-n-HA/PA6 scaffold is a potential matrix for treatment of osteochondral defects, and the method of using chondrogenically and osteogenically differentiated BMSCs as seed cells on each layer might be a promising strategy in repair of articular osteochondral defect due to enhanced chondrogenesis and osteogenesis.

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The group theoretical treatment of bound and scattering state problems is extended to include band structure. We show that one can realize Hamiltonians with periodic potentials as dynamical symmetries, where representation theory provides analytic solutions, or which can be treated with more general spectrum generating algebraic methods. We find dynamical symmetries for which we derive the transfer matrices and dispersion relations. Both compact and non-compact groups are found to play a role.

Temporomandibular joint (TMJ) ankylosis is a refractory disease that is difficult to predictably treat. This study evaluated the prognosis of using standard alloplastic TMJ prostheses for the treatment of TMJ ankylosis in Chinese patients with severe mandibular deficiency. Patients treated from 2013 to 2015 were reviewed. The computer-aided design and manufacture (CAD/CAM) technique was used to guide bony mass removal and locate the TMJ prosthesis (Biomet, USA). Eleven patients were included in this study. All prostheses were successfully installed and stabilized intraoperatively. In 4 patients with severe mandibular deficiency, their mandibular ramus was elongated by the TMJ prosthesis and 2 patients were combined with Le Fort I osteotomy guided by digital templates. Their mean chin advancement was 10.19 mm. Their SNB and ramus heights were also significantly improved after operation (P < 0.05). There was no prosthesis loosening, breakage, or infection leading to removal after a mean follow-up period of 22 months (range, 12-31mos.). Mouth opening was significantly improved from 5.5 mm preoperatively to 31.5 mm postoperatively. TMJ reconstruction with standard alloplastic prosthesis is a reliable treatment for ankylosis, especially in recurrent cases. By CAD/CAM technique, it can correct jaw deformities simultaneously and produce stable results.