Editor's summaryAnti–PD-1 immunotherapies benefit certain patients with mismatch repair–deficient or microsatellite unstable colorectal cancer (CRC), yet mismatch repair–proficient tumors typically show poor responses. Zhang et al. report that responsive high-microsatellite instability tumors feature specific spatial niches containing T helper 1 (TH1)–like cells, immunostimulatory macrophag...

AbstractGPR88 is an orphan GPCR with genetic variants associated with multiple neuropsychiatric conditions. GPR88 exhibits enriched expression in the striatum, olfactory tubercle, and inferior olive. Despite these functional associations, its endogenous ligand and its downstream molecular pathways remain unresolved. Here, we found that climbing fiber (CF)–localized GPR88 regulates CF-Purkinje ...

AbstractIonotropic receptors (IRs) are essential for insect olfaction, enabling the detection of carboxylic acids, amines, moisture, and temperature cues that mediate critical behaviors, including mosquito host-seeking 1,2. However, the structural mechanisms underlying ligand specificity and channel activation in these receptors remain unclear. Here, we report cryo-electron microscopy (cryo-EM)...

AbstractThe gut microbiota plays a pivotal part in human health, yet the molecular mechanisms that underlie its effects are largely unexplored. Bacteroides, a dominant genus in the human gut microbiota, is depleted in patients with atherosclerosis, but its causal relationship with disease remains unclear. Here, using a mouse model, we show that administration of Bacteroides uniformis alleviates...

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...