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Abstract Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients’ blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.

Grouting material is the core force transfer medium of grouting sealing and anchorage reinforcement methods for cracks in earthen sites; the performance of grouting slurry is the key to affecting the reinforcement effect. To solve the problems of poor flexural strength, easy shrinkage and cracking of existing grouting slurry, using Glutinous Rice Pulp, Calcined Ginger Nuts, and Loess Soil as substrates, and choosing the content and length of basalt fiber (BF) as control variables, 13 groups of specimens were designed by orthogonal test method to explore the influence of mixed fiber on the mobility, shrinkage, compressive, and flexural strength. The microstructure was analyzed by SEM to explain the strengthening mechanism from physical and chemical perspectives. The results show that the mobility decreases linearly with the increase in BF content and length; after mixing BF, the shrinkage rate is significantly reduced, but when the fiber length and content are relatively high, the surface is prone to cracking. The excellent bridging ability of BF can effectively improve the compressive and flexural strength of the specimen. When the fiber length and content are high, the specimen shows certain ductile failure characteristics, and the fracture energy increases more than 10 times.

Intracranial primary chondrosarcomas are rare, accounting for <0.15% of all intracranial tumors, but exhibit a high risk of recurrence. Due to the rarity of this condition, it has proven difficult to establish efficacy-based treatment guidelines. The present study details a case of clivus chondrosarcoma exhibiting no recurrence following surgical resection using an endoscopic transsphenoidal approach and postoperative adjuvant radiotherapy. A 41-year-old female presented with primary symptoms of left eye esotropia, scotoma of the left nasal visual field and double vision. Preoperative cranial magnetic resonance imaging revealed a lesion on the clivus, which was initially diagnosed as chordoma. However, clivus chondrosarcoma was ultimately diagnosed based on intraoperative findings and postoperative histopathology. The tumor was totally resected and 25 doses of adjuvant radiotherapy with planning gross tumor volume (60 Gy) and planning clinical target volume (50 Gy) were administered for 5 weeks. The patient was discharged at 12 days post-surgery with no obvious postoperative complications. Over the 28-month follow-up period, there was no evidence of recurrence, which may be due to the successful use of combined gross total resection and adjuvant radiotherapy. Therefore, surgical resection using an endoscopic transsphenoidal approach and postoperative adjuvant radiotherapy is an effective method for treating intracranial clivus chondrosarcoma. [ABSTRACT FROM AUTHOR]