AbstractProtein detection is a cornerstone of life science research. Here, we present Cell Lysate Fluorescence Anisotropy (CFAST), a versatile and accessible alternative cellular protein detection method. CFAST measures cellular protein levels through changes in fluorescence anisotropy of a long lifetime triangulenium dye-labeled nanobody probe. The minimal steps of centrifugation and nuclease ...

AbstractEpigenetic editing, particularly N6-methyladenosine (m6A) modification, represents a promising therapeutic strategy by silencing genes without altering DNA sequence. However, in vivo epigenetic intervention of neuroinflammation remains challenging and has rarely been explored. Here we developed a hybrid epigenetic nanomodulator, siMETTL3-hNVs, by integrating natural microglia-derived na...

AbstractObjective. Positron emission tomography (PET) detectors that encode depth-of-interaction (DOI) while achieving high timing and energy resolution are essential for long axial field-of-view (FOV) clinical PET systems. In this work, we propose an optically coupled hybrid semi-monolithic detector design, in which a pixelated scintillator array is coupled to a monolithic scintillator slab us...

AbstractAlternative tandem transcription initiation is a pervasive mechanism of gene regulation, yet its genetic impact on human disease remains largely unknown. Here, we systematically quantify the genetic regulation of alternative tandem transcription initiation across 25,859 samples from 49 normal human tissues and 33 tumor tissues. We identify approximately 0.4 million genetic variants asso...

AbstractUltrasound-mediated blood-brain barrier (BBB) opening enables non-invasive and targeted brain drug delivery. However, the underlying mechanisms are poorly understood. We resolve how ultrasound pulse regulates microbubble dynamics, endothelial bioeffects and BBB opening characteristics in real-time and at a cross-scale manner. High speed imaging revealed coalescence and heterogenous bubb...

AbstractThe 3D architecture of the eukaryotic genome is largely shaped by cohesin complexes containing either STAG1 or STAG2 subunits. Yet, their roles in post-mitotic genome refolding remain unclear. Here, we establish STAG2 as the predominant paralog and primary orchestrator of this process. We find that upon mitotic exit, STAG1 depletion imposes negligible effects on genome refolding or tran...

AbstractMass spectrometry-based chemical proteomics enables unbiased assessment of ligand potency and selectivity across the proteome. However, current approaches remain limited by the low throughput of single-compound screening and reliance on pre-synthesized libraries. Here we devise a mechanism-driven “library-versus-proteome” platform that couples dynamic combinatorial libraries with acti...