The formation of zygote is the beginning of mammalian life, and dynamic epigenetic modifications are essential for mammalian normal development. H3K27 di-methylation (H3K27me2) and H3K27 tri-methylation (H3K27me3) are marks of facultative heterochromatin which maintains transcriptional repression established during early development in many eukaryotes. However, the mechanism underlying establishment and regulation of epigenetic asymmetry in the zygote remains obscure. Here we show that maternal EZH2 is required for the establishment of H3K27me3 in mouse zygotes. However, combined immunostaining with ULI-NChIP-seq (ultra-low-input micrococcal nuclease-based native ChIP-seq) shows that EZH1 could partially safeguard the role of EZH2 in the formation of H3K27me2. Meanwhile, we identify that EHMT1 is involved in the establishment of H3K27me2, and that H3K27me2 might be an essential prerequisite for the following de novo H3K27me3 modification on the male pronucleus. In this work, we clarify the establishment and regulatory mechanisms of H3K27me2 and H3K27me3 in mouse zygotes.

Precise regulation of chromosome segregation during oocyte meiosis is of vital importance to mammalian reproduction. Anaphase promoting complex/cyclosome (APC/C) is reported to play an important role in metaphase‐to‐anaphase transition. Here we report that cell division cycle 23 (Cdc23, also known as APC8) plays a critical role in regulating the oocyte chromosome separation. Cdc23 localized on the meiotic spindle, and microinjection of Cdc23 siRNA caused decreased ratios of metaphase‐to‐anaphase transition. Loss of Cdc23 resulted in abnormal spindles, misaligned chromosomes, errors of homologous chromosome segregation, and production of aneuploid oocytes. Further study showed that inactivation of spindle assembly checkpoint and degradation of Cyclin B1 and securin were disturbed after Cdc23 knockdown. Furthermore, we found that inhibiting spindle assembly checkpoint protein Msp1 partly rescued the decreased polar body extrusion and reduced the accumulation of securin in Cdc23 knockdown oocytes. Taken together, our data demonstrate that Cdc23 is required for the chromosome segregation through regulating the spindle assembly checkpoint activity, and cyclin B1 and securin degradation in meiotic mouse oocytes.

N6-methyladenosine (m6A) is one of the most common and well-known internal RNA modifications that occur on mRNAs or ncRNAs. It affects various aspects of RNA metabolism, including splicing, stability, translocation, and translation. An abundance of evidence demonstrates that m6A plays a crucial role in various pathological and biological processes, especially in tumorigenesis and tumor progression. In this article, we introduce the potential functions of m6A regulators, including “writers” that install m6A marks, “erasers” that demethylate m6A, and “readers” that determine the fate of m6A-modified targets. We have conducted a review on the molecular functions of m6A, focusing on both coding and noncoding RNAs. Additionally, we have compiled an overview of the effects noncoding RNAs have on m6A regulators and explored the dual roles of m6A in the development and advancement of cancer. Our review also includes a detailed summary of the most advanced databases for m6A, state-of-the-art experimental and sequencing detection methods, and machine learning-based computational predictors for identifying m6A sites.

Treating central nervous system (CNS) infections caused by extensively drug-resistant (XDR) gram-negative bacilli, such as carbapenem-resistant Klebsiella pneumoniae, represents a significant clinical challenge. Polymyxin is occasionally used as a salvage treatment for this severe CNS infection. We report here a rare case of polymyxin-resistant Klebsiella pneumoniae ventriculitis, which was successfully treated with ventricular injections and intravenous antibiotics. A 53-year-old male underwent a decompressive craniectomy and was referred to our hospital with cerebrospinal fluid incisional leakage and persistent fever. The minimum inhibitory concentration of polymyxin B in this patient increased from 2 to 4 μg/mL during the course of treatment. He was diagnosed with polymyxin-resistant XDR Klebsiella pneumoniae ventriculitis. We successfully treated the infection with intravenous ceftazidime/avibactam (CAZ/AVI) combined with ventricular injection of tigecycline according to cerebrospinal fluid microbiological culture. CAZ/AVI combined with tigecycline may be an effective salvage treatment for CNS infections caused by polymyxin-resistant XDR Klebsiella pneumoniae.