Targeting the mevalonate pathway potentiates NUAK1 inhibition-induced immunogenic cell death and antitumor immunity.

The induction of immunogenic cell death (ICD) impedes tumor progression via both tumor cell-intrinsic and -extrinsic mechanisms, representing a robust therapeutic strategy. However, ICD-targeted therapy remains to be explored and optimized. Through kinome-wide CRISPR-Cas9 screen, NUAK family SNF1-like kinase 1 (NUAK1) is identified as a potential target.

-Loaded Easily Injectable Hydrogel Promotes Endometrial Repair via Long-Term Retention and Microenvironment Modulation.

Regeneration of the injured endometrium, particularly the functional layer, is crucial for the prevention of uterine infertility. At present, clinical treatment using sodium hyaluronate hydrogel injection is limited by its relatively low fluidity, short-term retention, and insufficient bioactive ingredients, so it is necessary to develop an advanced healing-promoting hydrogel. The modulation of the microenvironment by presents a bioactive component that can facilitate the regeneration of the functional layer.

Deciphering transcription activity of mammalian early embryos unveils on/off of zygotic genome activation by protein translation/degradation.

Quantification of transcription activities in mammalian preimplantation embryos is challenging due to a huge amount of maternally stored transcripts and paucity of research materials. Here, we investigate genome-wide transcription activities of mouse and human preimplantation embryos by quantifying elongating RNA polymerase II. Two transcriptional waves are identified in early mouse embryos, with summits at the 2-cell and 8-cell stages.

Maternal ELL3 loss-of-function leads to oocyte aneuploidy and early miscarriage.

Up to an estimated 10% of women experience miscarriage in their lifetimes. Embryonic aneuploidy is a leading cause for miscarriage, infertility and congenital defects. Here we identify variants of ELL3, a gene encoding a transcription elongation factor, in couples who experienced consecutive early miscarriages due to embryonic aneuploidy.

Chemical proteomic profiling of lysine crotonylation using minimalist bioorthogonal probes in mammalian cells.

Protein lysine crotonylation has been found to be closely related to the occurrence and development of various diseases. Currently, site identification of crotonylation is mainly dependent on antibody enrichment; however, due to the cost, heterogeneity, and specificity of antibodies, it is desired to develop an alternative chemical tool to detect crotonylation. Herein, we report an alkynyl-functionalized bioorthogonal chemical probe, Cr-alkyne, for the detection and identification of protein lysine crotonylation in mammalian cells.