AbstractThe cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) pathway has a crucial role in detecting tumour-derived DNA, whether the pathway is generated spontaneously or induced therapeutically. Activation of the cGAS–STING pathway triggers type I interferon signalling and pro-inflammatory responses in both tumour and immune cells...

AbstractThe clinical application of chimeric antigen receptor (CAR) T cell therapy in solid tumors remains limited due to significant safety concerns, particularly “on-target, off-tumor” toxicity and cytokine release syndrome (CRS). Here, we describe a class of CARs that employ disulfide-directed multicyclic peptides (DDMPs) as compact antigen-recognition domains targeting the tumor-associate...

AbstractINTRODUCTIONDigital biomarkers for detecting Alzheimer's disease (AD) remain controversial due to inconsistent accuracy and unclear relationships with AD core biomarkers.METHODSThis study recruited 428 Chinese older adults to determine the associations of artificial intelligence (AI)-assisted virtual reality (VR) cognitive scores with plasma amyloid beta (Aβ)42/Aβ40, phosphorylated ta...

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...