所有项目
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摘要: Background. Positron Emission Tomography (PET) is a vital medical imaging tool for studying in vivo metabolism. However, conventional PET systems are limited in their inability to image during free movement. Therefore, we have developed a wearable brain PET system for real-time imaging, called SmartBrain. Methods. The SmartBrain used 192 detectors and the detector consists of a 6 × 6...
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The landscape of catalytic RNA in complex eukaryotes remains poorly charted. Although self- cleaving ribozymes are widespread in microbial and viral genomes, their existence and functional roles in humans remain limited. Here, we introduce a generalizable, genome-wide discovery platform that integrates high-throughput signals from two complementary adapter ligation assays— 3P-seq and...
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Deubiquitinases (DUBs) orchestrate ubiquitin homeostasis, yet their compartment-specific activities remain underexplored. We developed a genetically encoded strategy to assembly activity-based ubiquitin probes in cellulo via sortase A (SrtA)-mediated transpeptidation. Co-targeting SrtA and its ubiquitin substrate to the outer mitochondrial membrane reduced off-target transpeptidation and enabled...
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Severe fever with thrombocytopenia syndrome virus (SFTSV) poses a growing global health threat with substantial mortality and no effective treatments. We report the discovery of ZS1C5, a human antibody that neutralizes SFTSV with subnanomolar potency by targeting a previously unknown interdomain epitope on glycoprotein Gn, mediated by an elongated CDRH3. A single dose of ZS1C5 conferred robust...
现已发表于 Vita. doi: 10.15302/vita.2025.12.0002 -
摘要: Background: Variants in the dynamin 1-like (DNM1L) gene, which encodes dynamin-related protein 1 (Drp1), can cause encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1) and optic atrophy 5 (OPA5), two neurodevelopmental disorders with distinct symptoms. Given the critical role of Drp1 in mitochondrial fission, it is believed that disrupted mitochondrial fission is key to...
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The 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-associated antigens...
现已发表于 Journal of the American Chemical Society. doi: 10.1021/jacs.5c13642 -
摘要:
With CryoSeek, a structure-first paradigm for discovery, we have determined high resolution 3D structures of a number of glycofibrils, in which well-ordered glycans either form a thick shell coating various protein cores or constitute the entire fibril. To improve the throughput of CryoSeek, we hereby report two methods. The recursive bisection clustering (RBC) strategy has been designed to...
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Genome instability drives tumor evolution through incremental mutations and catastrophic events such as chromothripsis. Despite significant advances, the diversity and underlying mechanisms of genome instability remain insufficiently understood. Here, we identify a previously unrecognized form of genome instability termed "chromocytosis", in which chromosome bridge breakage during mitosis causes...
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摘要:
Alternative tandem transcription initiation (ATI) is a pervasive mechanism of gene regulation, yet its genetic impact on human disease remains largely unknown. Here, we systematically quantified genetic regulation of ATI across 25,859 samples from 49 human normal tissues and 33 tumor tissues. We identified ~0.4 million 5′ UTR ATI quantitative trait loci (5′aQTLs) in 5,295 genes, with 32%...
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摘要:
SUN1/2, core components of the linker of nucleoskeleton and cytoskeleton (LINC) complex, transmit extracellular mechanical forces to nuclear lamina and chromatin. However, their role in regulating peripheral chromatin in mechanosensing and mechanoadaptation remains unclear. Using CRISPR/Cas9-mediated knockout of Sun1 or Sun2 in myoblasts, we identified a SUN1/2-dependent mechano-feedback loop....