SummarySynaptic loss is a hallmark of Alzheimer’s disease (AD) but lacks robust blood-based biomarkers. We investigate growth-associated protein 43 (GAP-43), previously identified as a synaptic candidate in the cerebrospinal fluid (CSF). Postmortem proteomic profiling of brain-derived extracellular vesicles (n= 21) highlights GAP-43 as a central hub within synaptic protein networks co-depleted...

AbstractChromatin bridges experience significant tension due to spindle fiber pulling and cell migration. Uncontrolled breakage of chromatin bridges by actomyosin contractile forces leads to detrimental consequences. The existence of specialized mechanisms that process chromatin bridges to prevent catastrophic rupture remains uncertain. Here, we uncover a unique property of ANKLE1, a midbody-te...

AbstractItaconate accumulates in macrophages upon bacterial infection, and manifests antibacterial activity. Convincing evidence substantiates that itaconate is transported across the plasma membrane and vacuolar membrane, but the molecular bases underlying bidirectional transport of itaconate across membranes and its effects on intracellular bacterial replication are less known. Here, we ident...

AbstractTransmembrane and extracellular proteins play crucial roles in diverse cellular functions and communication, affecting the progression and treatment of various diseases by mediating vital cellular processes. Whereas targeted protein degradation (TPD) represents an advancing therapeutic modality that leverages cellular degradation machinery to eliminate proteins of interest, present stra...

AbstractTotal neoadjuvant therapy (TNT) is a standard care for locally advanced rectal cancer (LARC), yet the immune remodeling mechanisms underlying its efficacy remain unclear. Using single-cell RNA, T cell receptor, and spatial transcriptome sequencing of matched pre- and post-treatment samples, we depicted the tumor microenvironment (TME) dynamics induced by different neoadjuvant therapies....

AbstractThe development of lipid nanoparticle (LNP) systems has largely advanced RNA therapeutics, particularly mRNA-based cancer immunotherapy. Conventional amine-LNPs, designed for hepatic RNA delivery, face challenges in targeting lymphoid organs effectively and maximize antigen presentation. In this study, we present the development of pH-responsive ionizable guanidine-LNPs (G-LNPs). Our ch...

AbstractThe immunosuppressive tumor microenvironment enables immune evasion through mechanisms beyond canonical immune checkpoints. While phosphatidylserine (PS) externalization coordinates apoptotic clearance under physiological conditions, tumors hijack this mechanism through apoptotic mimicry to subvert antitumor immunity. Here, we identify TMEM16F, a calcium-activated phospholipid scramblas...