Endometrial cancer (EC) is a prevalent gynecological malignancy worldwide, and 5-methylcytosine (m⁵C) modification of mRNA is a crucial epigenetic modification associated with the development and occurrence of several cancers. However, the precise function of m⁵C modification in EC remains elusive. This study aimed to investigate the expression and clinical significance of the primary m⁵C modification writer, NSUN2, in EC. Our findings indicated that NSUN2 exhibited a substantial up-regulation in EC as a result of an epigenetic augmentation in H3K4me3 levels within the promoter region, which was triggered by the down-regulation of KDM5A. Moreover, gain- and loss-of-function experiments revealed the role of NSUN2 in enhancing m⁵C modification of mRNA, thereby promoting EC cell proliferation. RNA bisulfite sequencing and transcriptomic sequencing were employed to elucidate the involvement of NSUN2 in the regulation of ferroptosis. Subsequent in vitro experiments confirmed that the knockdown of NSUN2 significantly up-regulated the levels of lipid peroxides and lipid ROS in EC cells, thereby augmenting the susceptibility of EC to ferroptosis. Mechanistically, NSUN2 stimulated the m⁵C modification of SLC7A11 mRNA, and the m⁵C reader YBX1 exhibited direct recognition and binding to the m⁵C sites on SLC7A11 mRNA via its internal cold shock domain (CSD), leading to an increase in SLC7A11 mRNA stability and elevated levels of SLC7A11. Additionally, rescue experiments showed that NSUN2 functioned as a suppressor of ferroptosis, which was dependent on SLC7A11. Overall, targeting the NSUN2/SLC7A11 axis inhibited tumor growth by increasing lipid peroxidation and ferroptosis of EC cells both in vitro and in vivo. Therefore, our study provides new insight into the role of NSUN2, suggesting that NSUN2 may serve as a prognostic biomarker and therapeutic target in patients with EC.

LINC00461, a long non-coding RNA, is important for the proliferation and migration of glioma cells LINC00461, a long non-coding RNA, is important for the proliferation and migration of glioma cells

Phagosome- and xenophagosome-lysosome systems play a critical role in the defense of pathogenic bacteria, such as Salmonella and S. aureus, in macrophages. A great part of the bacteria escapes from the digestion and can survive through some mechanisms that are still poorly understood and which require further exploration. Here we identified that Salmonella inhibited the expression and activation of TFEB to blunt the functions of lysosomes and defense of clearance by activating caspase-1. The expression and activation of TFEB were enhanced early under the infection of S. aureus, which was followed by shrinkage to weaken lysosomal functions due to the delayed activation of ERK, mTOR, and STAT3. Thus, we have identified novel escape mechanisms for Salmonella and S. aureus to deepen and strengthen our strategies fighting with pathogens.

Purkinje cells are critical for the function of cerebellum. The degeneration of Purkinje cells leads to defects in motion control. We have found that Purkinje cells specifically express Ankfy1 protein during development and in adult. This protein seems to play minor functions during development as Ankfy1 knockout mice appear normal till adult. However, at 9-month-old, knockout mice showed abnormal cerebellum with reduced vermis size and developed defective motor function. Further investigation demonstrated that the cerebellum of the mutant mouse has lost most of its Purkinje cells, while other cerebellar cells remained largely normal. Our data suggested that theAnkfy1might be important for the maintenance of cerebellar Purkinje cells.

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that is rare and highly aggressive and that may progressively involve many organs. CNS (central nervous system), BM (bone marrow) and skin are the most common systems involved. To date, only 2 cases of IVLBCL involving the thyroid have been reported. Here, we report a case of IVLBCL involving the thyroid and accompanied by bilateral nodular goiter. In this case, a thyroid mass was identified in a physical examination of a 68-year-old male who initially presented with dyspnea accompanied by intermittent headache for approximately 1 month. Computed tomography scans revealed that the left lobar thyroid was occupied by a large, slightly lower density mass (5.8 × 4.7 × 8.4 cm). However, the patient had no hyperthyroidism or hoarseness. Levels of thyroid hormones and anti-thyroid autoantibodies in the serum were normal preoperatively. Thyroid mass resection was performed to establish a diagnosis and to relieve symptoms. Pathological results of the surgical specimen revealed that large atypical lymphoma cells filled the capillaries in the lesion area. Immunohistochemical staining revealed that the large-sized tumor cells were positive for CD20, PAX-5, MUM-1 and BCL-2, and were negative for CD3, CD5, CD43, CD10, CD23, CyclinD1, CD138, CD30, ALK, CD56, MPO, S-100, TTF-1, TG (thyroglobulin) and CT (calcitonin). The Ki-67 index was estimated to be approximately 85%. The patient was subsequently diagnosed as “Classical” IVLBCL non-germinal center B-cell type. The patient declined chemotherapy and died in the fifth month after operation.