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Radical difunctionalization of aliphatic alkynes provides direct access to valuable multi‐substituted alkenes, but achieving a high level of chemo‐ and stereo‐control remains a formidable challenge. Herein a novel photoredox neutral alkyne di‐functionalization is reported through functional group migration followed by a radical‐polar crossover and energy transfer‐enabled stereoconvergent isomerization of alkenes. In this sequence, a hydroxyalkyl and an aryl group are incorporated concomitantly into an alkyne, leading to diversely functionalized E‐allyl alcohols. The scope of alkynes is noteworthy, and the reaction tolerates aliphatic alkynes containing hydrogen donating C─H bonds that are prone to intramolecular hydrogen atom transfer. The protocol features broad functional group compatibility, high product diversity, and exclusive chemo‐ and stereoselectivity, thus providing a practical strategy for the elusive radical di‐functionalization of unactivated alkynes. [ABSTRACT FROM AUTHOR]

Traumatic heterotopic ossification (THO) represents one of the most prominent contributors to post‐traumatic joint dysfunction, which currently lacks an effective and definitive preventative approach. Inflammatory activation due to immune dyshomeostasis during the early stages of trauma is believed to be critical in initiating the THO disease process. This study proposes a dual‐homeostatic modulation (DHM) strategy to synergistically prevent THO without compromising normal trauma repair by maintaining immune homeostasis and inducing stem cell homeostasis. A methacrylate‐hyaluronic acid‐based hydrogel spray device encapsulating a curcumin‐loaded zeolitic imidazolate framework‐8@ceric oxide (ZIF‐8@CeO2, CZC) nanoparticles (CZCH) is designed. Photo‐crosslinked CZCH is used to form hydrogel films fleetly in periosteal soft tissues to achieve sustained curcumin and CeO2 nanoparticles release in response to acidity and reactive oxygen species (ROS) in the inflammatory microenvironment. In vitro experiments and RNA‐seq results demonstrated that CZCH achieved dual‐homeostatic regulation of inflammatory macrophages and stem cells through immune repolarization and enhanced efferocytosis, maintaining immune cell homeostasis and normal differentiation. These findings of the DHM strategy are also validated by establishing THO mice and rat models. In conclusion, the CZCH hydrogel spray developed based on the DHM strategy enables synergistic THO prevention, providing a reference for a standard procedure of clinical operations. [ABSTRACT FROM AUTHOR]

High‐throughput gene sequencing has identified various genetic variants as the culprits for some common hereditary cancers. However, the heritability of a substantial proportion of cancers remains unexplained, which may result from rare deleterious mutations hidden in a myriad of nonsense genetic variations. This poses a great challenge to the understanding of the pathology and thus the rational design of effective treatments for affected patients. Here, whole genome sequencing is employed in a representative case in which one monozygotic twin is discordant for lung inflammatory myofibroblastoma to disclose rare tumor‐related mutations. A missense single nucleotide variation rs61955126 T>C in the lysine methyltransferase SETD8 (accession: NM_020382, SETD8C302R) is exposed. It is shown that SETD8 is vital for genomic integrity by promoting faithful DNA replication, and its C302R mutation downregulates the p53/p21 pathway. Importantly, the SETD8C302R mutation significantly increases the sensitivity of cancer cells to WEE1 inhibition. Given that WEE1 inhibitors have shown great promise for clinical approval, these results impart a potential therapeutic approach using WEE1 inhibitor for cancer patients carrying the same mutation, and indicate that genome sequencing and genetic functional studies can be integrated into individualized therapies. [ABSTRACT FROM AUTHOR]