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Nucleus pulposus (NP) cells play a critical role in maintaining intervertebral disc integrity through producing the components of extracellular matrix (ECM). NP cell dysfunction, including senescence and hyper-apoptosis, has been regarded as critical events during intervertebral disc degeneration development. In the present study, we found that Transcription Factor 7-Like 2 (TCF7L2) was overexpressed within degenerative intervertebral disc tissue samples, and TCF7L2 silencing improved lipopolysaccharide (LPS)-induced repression on NP cell proliferation, ECM synthesis, and LPS-induced NP cell senescence. miR-1260b directly targeted TCF7L2 and inhibited TCF7L2 expression. miR-1260b overexpression improved LPS-induced degenerative changes in NP cells; more importantly, TCF7L2 overexpression significantly reversed the effects of miR-1260b overexpression on LPS-stimulated degenerative changes within NP cells. For the first time, we demonstrated the function of the miR-1260b/TCF7L2 axis on the phenotypic maintenance of chondrocyte-like NP cells and ECM synthesis by NP cells under LPS stimulation.

Aim The co-expression network of long non-coding RNA ROR (lncRNA-ROR) and microRNA-185-3p (miR-185-3p) has not been focused on osteosarcoma. Therein, this work was initiated to uncover lncRNA-ROR and miR-185-3p functions in osteosarcoma. Methods LncRNA-ROR, miR-185-3p and Yes-associated protein 1 (YAP1) expression in osteosarcoma tissues and cells were detected. The screened cells (MG63 and U2OS) were transfected with decreased and/or increased lncRNA-ROR and miR-185-3p to explore osteosarcoma progression. Tumor growth was detected by tumor xenografts in mice. Results Up-regulated lncRNA-ROR and YAP1 and down-regulated miR-185-3p were found in osteosarcoma. LncRNA ROR knockdown or miR-185-3p overexpression inhibited osteosarcoma cell progression while lncRNA ROR elevation or miR-185-3p inhibition presented the opposite effects. Function of lncRNA ROR was rescued by miR-185-3p and regulated the growth and metastasis of osteosarcoma cells via modulating YAP1, the target gene of miR-185-3p. Conclusion This work illustrates that lncRNA-ROR down-regulation or miR-185-3p up-regulation inhibits osteosarcoma progression via YAP1 repression.

The switch between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a key role in aging-induced osteoporosis. In this study, miR-19a-3p was obviously downregulated in BMSCs from aged humans and mice. Overexpressed miR-19a-3p evidently reduced aging-induced bone loss in mice and promoted osteogenic differentiation of BMSCs, while silenced miR-19a-3p manifestly increased aging-induced bone loss in mice and repressed osteogenic differentiation of BMSCs. Hoxa5 was significantly downregulated in the BMSCs from aged mice and contribute to miR-19a-3p-induced osteoblast differentiation as a direct target gene of miR-19a-3p. Furthermore, lncRNA Xist was found as a sponge of miR-19a-3p to repress BMSCs osteogenic differentiation. In conclusion, our study reveals the critical role of the lncRNA Xist/miR-19a-3p/Hoxa5 pathway in aging-induced osteogenic differentiation of BMSCs, indicating the potential therapeutic target for osteoporosis.

Increasing salinity levels in marine and estuarine ecosystems greatly influence developmental, physiological and molecular activities of inhabiting fauna. Marine medaka (Oryzias melastigma), a euryhaline research model, has extraordinary abilities to survive in a wide range of aquatic salinity. To elucidate how marine medaka copes with salinity differences, the responses of Oryzias melastigma after being transferred to different salt concentrations [0 practical salinity units (psu), 15 psu, 30 psu (control), 45 psu] were studied at developmental, histochemical and transcriptome levels in the gill and liver tissues. A greater number of gills differentially expressed genes (DEG) under 0 psu (609) than 15 psu (157) and 45 psu (312), indicating transcriptomic adjustments in gills were more sensitive to the extreme hypotonic environment. A greater number of livers DEGs were observed in 45 psu (1,664) than 0 psu (87) and L15 psu (512), suggesting that liver was more susceptible to hypertonic environment. Further functional analyses of DEGs showed that gills have a more immediate response, mainly in adjusting ion balance, immune and signal transduction. In contrast, DEGs in livers were involved in protein synthesis and processing. We also identified common DEGs in both gill and liver and found they were mostly involved in osmotic regulation of amino sugar and nucleotide sugar metabolism and steroid biosynthesis. Additionally, salinity stresses showed no significant effects on most developmental and histochemical parameters except increased heartbeat with increasing salinity and decreased glycogen after transferred from stable conditions (30 psu) to other salinity environments. These findings suggested that salinity-stress induced changes in gene expressions could reduce the effects on developmental and histochemical parameters. Overall, this study provides a useful resource for understanding the molecular mechanisms of fish responses to salinity stresses.

N6-methyladenosine (m6A) regulators are involved in the progression of various cancers via regulating m6A modification. However, the potential role and mechanism of the m6A modification in osteosarcoma remains obscure. In this study, WTAP was found to be highly expressed in osteosarcoma tissue and it was an independent prognostic factor for overall survival in osteosarcoma. Functionally, WTAP, as an oncogene, was involved in the proliferation and metastasis of osteosarcoma in vitro and vivo. Mechanistically, M6A dot blot, RNA-seq and MeRIP-seq, MeRIP-qRT-PCR and luciferase reporter assays showed that HMBOX1 was identified as the target gene of WTAP, which regulated HMBOX1 stability depending on m6A modification at the 3′UTR of HMBOX1 mRNA. In addition, HMBOX1 expression was downregulated in osteosarcoma and was an independent prognostic factor for overall survival in osteosarcoma patients. Silenced HMBOX1 evidently attenuated shWTAP-mediated suppression on osteosarcoma growth and metastasis in vivo and vitro. Finally, WTAP/HMBOX1 regulated osteosarcoma growth and metastasis via PI3K/AKT pathway. In conclusion, this study demonstrated the critical role of the WTAP-mediated m6A modification in the progression of osteosarcoma, which could provide novel insights into osteosarcoma treatment.

Background A modified prone cervical spine surgical position using a body-shape plaster bed with skull traction (BSPST) was compared with the traditional prone surgical position with horseshoe headrests. Methods Forty-seven patients undergoing posterior cervical spine surgery for cervical spine fracture were retrospectively classified into two groups, BSPST group (n = 24) and traditional group (n = 23) and underwent posterior instrumented fusion with or without decompression. Multiple indicators were used to evaluate the advantages of the BSPST compared with the traditional position. Results All the operations went smoothly. The mean recovery rate was 56.30% in the BSPST group and 48.55% in the traditional group, with no significant difference. Intraoperative blood loss and total incidence of complications were significantly less in the BSPST group than in the traditional group. In addition, the BSPST position provided greater comfort level for the operators and allowed convenient intraoperative radiography. Conclusions This is the first study to describe a combined body-shape plaster bed and skull traction as a modified cervical spine prone surgical position that is simple, safe and stable, adjustable during surgery, reproducible and economical for posterior cervical spine fracture surgery and potentially other cervical and upper dorsal spine surgeries in the prone position. Additionally, this position provides surgeons a comfortable surgical field and can be easily achieved in most orthopedic operation rooms.

Background: N6-methyladenosine (m6A) regulators are involved in the progression of various cancers via regulating m6A modification. However, the potential role and mechanism of the m6A modification in osteosarcoma (OS) remains obscure. Methods: The expression of m6A regulators were detected using qPCR and western blot. Cell proliferation, colony formation, wound healing and transwell invasion assays were used to reveal the role of WTAP in the progression of OS. The mechanism of WTAP-mediated m6A modification was explored using M6A dot blot, RNA-seq and MeRIP-seq, MeRIP-qRT-PCR and luciferase reporter assays. Results: Here, WTAP was found to be high expression in OS tissue and it was an independent prognostic factor for OS patients . Functionally, WTAP, as an oncogene, was involved in the proliferation and metastasis of OS. Mechanistically, M6A dot blot, RNA-seq and MeRIP-seq, MeRIP-qRT-PCR and luciferase reporter assays showed that HMBOX1 is the target gene of WTAP, which regulated HMBOX1 stability in an m6A-dependent manner by targeting to the 3’UTR of HMBOX1 mRNA. In addition, HMBOX1 expression was downregulated in OS and negatively linked to WTAP expression in OS patients. Silenced HMBOX1 evidently attenuated shWTAP-mediated suppression on OS growth and metastasis in vivo and vitro. Finally, WTAP/HMBOX1 regulated OS growth and metastasis via PI3K/AKT pathway. Interpretation: The study demonstrates the critical role of the WTAP-mediated m6A modification in the progression of OS, which could provide novel insights into therapy of OS. Funding Statement: This study was supported by National Natural Science Foundation of China (Grant Nos. 81772866); National Natural Science Foundation of China (Grant Nos. 81502331); Natural Science Foundation of Hunan Province (Grant Nos. 2018JJ2617); Natural Science Foundation of Hunan Province (Grant Nos. 2016JJ3176); National Key Research and Development Program of China (No. 2016YFC1201800) ; Natural Science Foundation of Hunan Province (No. 2018SK2090). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Informed consent was obtained from each patient or their guardians, and the study were approved by the Ethics Committee of The Third Xiangya Hospital of Central South University. All animal care and handling procedures were approved by the Institutional Animal Care and Use Committee of The Third Xiangya Hospital of Central South University, Changsha, China.

Chromium is toxic to marine animals and can cause damage to many of their organs, including the liver. To test the toxicity of chromium on marine organisms, we exposed the liver of the marine medaka (Oryzias melastigma) with hexavalent chromium [Cr(VI)]. Our results show that Cr enrichment in the liver demonstrates a positive correlation to the exposure concentration. With the increase of Cr(VI) concentration, pathological changes including nuclear migration, cell vacuolization, blurred intercellular gap, nuclear condensation, become noticeable. To further study changes in gene expression in the liver after Cr(VI) exposure, we used RNA-seq to compare expression profiles before and after Cr(VI) exposure. After acute Cr(VI) exposure (2.61 mg/l) for 96 h, 5862 transcripts significantly changed. It is the first time that the PPAR pathway was found to respond sensitively to Cr(VI) exposure in fish. Finally, combined with other published study, we found that there may be some difference between Cr(VI) toxicity in seawater fish and freshwater fish, due to degree of oxidative stress, distribution patterns and detailed Cr(VI) toxicological mechanisms. Not only does our study explore the mechanisms of Cr(VI) toxicity on the livers of marine medaka, it also points out different Cr(VI) toxicity levels and potential mechanisms between seawater fish and freshwater fish.