As a systemic disease, osteoporosis (OP) results in bone density loss and fracture risk, particularly in the hip and vertebrae. However, the underlying molecular mechanisms of OP development have not been fully illustrated. N6-Methyladenosine (m6A) is the most abundant modification of mRNAs, which is involved in many of pathological processes in aging disease. However, its role and regulatory mechanism in OP remains unknown. Here, we aimed to investigate the roles of m6A and its demethylase FTO in OP development. The results showed that m6A methylated RNA level was up-regulated in the bone marrow mesenchymal stem cells (BMSCs) from patients with OP. The level of N6-methyladenosine demethylase FTO was consistently decreased in the BMSCs from patients with OP. Functionally, lentivirus-mediated FTO overexpression in normal BMSCs to compromised osteogenic potential. Mechanism analysis further suggested that FTO overexpression decreased the m6A methylated and total level of runt related transcription factor 2 (Runx2) mRNA, subsequently inhibited osteogenic differentiation. We found that FTO inhibition could effectively improve the bone formation in ovariectomized osteoporotic mice in vivo . Together, these results reveal that RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating runx2 mRNA and inhibiting osteogenic differentiation.

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Highlights METTL3 is highly expressed in osteosarcoma. METTL3 downregulation inhibits metastases of osteosarcoma cells. m6A regulates osteosarcoma cell activity. METTL3 modifies TRAF6 activity via m6A. TRAF6 inhibits the repressive effects of sh-METTL3 on osteosarcoma metastases.

Metastatic spinal cord compression (SCC) secondary to small cell lung cancer (SCLC) is a disastrous oncological emergency, but it is poorly understood due to the small numbers of patients and their short survival times. Whether patients suffered from SCC caused by metastatic SCLC benefit from spinal surgery remains unknown. The aim of this study was to evaluate the role of surgical treatment and prognostic factors in patients with SCC caused by metastatic SCLC. Methods: From 2009 to 2019, 30 consecutive patients surgically treated for metastatic SCC from SCLC were enrolled in this retrospective analysis. Kaplan-Meier method and Cox regression analysis were used to estimate overall survival (OS) and identify prognostic factors. Quality of life (QoL) was assessed by the three-level EuroQol-five-Dimensions (EQ-5D-3L) instrument and compared using Student's t test. Results: The median OS time was 9 months in our series. Relief of pain, preservation of neurological function, and improvement of performance status were achieved after surgical intervention. The mean EQ-5D-3L utility score showed a significant improvement after surgery (0.3394 preoperatively vs 0.5884 postoperatively). According to Cox regression analysis, postoperative ECOG-PS and immunotherapy were identified to be independent prognostic factors for patients with SCC caused by metastatic SCLC. Conclusion: Despite the short life expectancy, prompt surgical decompression is extremely necessary for patients with SCC caused by SCLC, for surgery played a critical role in improving patients' QoL. Better performance status after surgery and receiving immunotherapy were associated with a longer OS.

Skin cancer has drawn attention for the increasing incident rates and high morbidity worldwide. Timely diagnosis and efficient treatment are of paramount importance for prompt and effective therapy. Thus, the development of novel skin cancer diagnosis and treatment strategies is of great significance for both fundamental research and clinical practice. Recently, the emerging field of nanotechnology has profoundly impact on early diagnosis and better treatment planning of skin cancer. In this review, we will discuss the current encouraging advances in functional nanomaterials for skin cancer theranostics. Challenges in the field and safety concerns of nanomaterials will also be discussed.