N 6 -methyladenosine (m 6 A) is a commonly present modification of mammalian mRNAs and plays key roles in various cellular processes. m 6 A modifiers catalyze this reversible modification. However, the underlying mechanisms by which these m 6 A modifiers are regulated remain elusive. Here we show that expression of m 6 A demethylase ALKBH5 is regulated by chromatin state alteration during leukemogenesis of human acute myeloid leukemia (AML), and ALKBH5 is required for maintaining leukemia stem cell (LSC) function but is dispensable for normal hematopoiesis. Mechanistically, KDM4C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing H3K9me3 levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m 6 Adependent way. Thus, our findings link chromatin state dynamics with expression regulation of m 6 A modifiers and uncover a selective and critical role of ALKBH5 in AML that might act as a therapeutic target of specific targeting LSCs.

Background: Ewing sarcoma is the second most common malignant bone tumor in children, but it rarely originates from extra-skeletal sites. The commonly involved sites of soft tissue include paravertebral spaces, lower extremities, the pelvis, head, and neck, while primary extra-skeletal Ewing sarcoma (EES) located in the genitals is extremely rare.Case Presentation: We report a young patient who presented to our hospital with a painful erection of the penis and limited motion of the left hip. Magnetic resonance imaging showed a hyperintense mass with invasion of adjacent tissue in the penis and a heterogeneously high signal lesion in the left proximal femur. 18F-fluorodeoxyglucose positron-emission tomography detected widespread metastatic lesions in the bilateral lung and multiple skeletons. An incisional biopsy of the penis was performed; the histopathological findings and EWS gene translocation identified by molecular analysis confirmed the diagnosis of Ewing sarcoma. Subsequently, the punch-biopsy specimen from the left femur showed undifferentiated small round cells, a finding consistent with the microscopic presence of Ewing sarcoma metastasis. However, after the first course of multiagent chemotherapy, the penile mass did not obtain stabilization but instead grew progressively with surface ulceration and multidrug resistant bacteria infection. Despite receiving antibiotics and maximal supportive therapy, the patient died from sepsis and lung metastasis complications in the intensive care unit 2 months later.Conclusion: This case indicates that although EES as a subtype of Ewing sarcoma is rare, it can occur virtually in any soft tissue site, even in the genitals. Therefore, clinicians need to distinguish this entity from other soft tissue sarcomas with rapid progression since early diagnosis and timely treatment of EES are pivotal for a favorable prognosis.

An ultraviolet light emitting diode (UV-LED) array chip as irradiation source for nano-TiO2 catalyzed photochemical vapor generation (PCVG) was combined with a hollow electrode point discharge microplasma optical emission spectrometer...

Nonalcoholic fatty liver disease (NAFLD) includes a series of hepatic manifestations, starting with liver steatosis and potentially evolving towards nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis or even hepatocellular carcinoma (HCC). Its incidence is increasing worldwide. Several factors including metabolic dysfunction, oxidative stress, lipotoxicity contribute to the liver inflammation. Several immune cell-mediated inflammatory processes are involved in NAFLD in which T cells play a crucial part in the progression of the disease. In this review, we focus on the role of different subsets of both conventional and unconventional T cells in pathogenesis of NAFLD. Factors regarding inflammation and potential therapeutic approaches targeting immune cells in NASH are also discussed.