Thymidine Phosphodiester Chemiluminescent Probe for Sensitive and Selective Detection of Ectonucleotide Pyrophosphatase 1.

ENPP-1 is a transmembrane enzyme involved in nucleotide metabolism, and its overexpression is associated with various cancers, making it a potential therapeutic target and biomarker for early tumor diagnosis. Current detection methods for ENPP-1 utilize a colorimetric probe, , which has significant limitations in sensitivity. Here, we present probe , the first nucleic acid-based chemiluminescent probe designed for rapid and highly sensitive detection of ENPP-1 activity.

Biocompatible Flash Chemiluminescent Assay Enabled by Sterically Hindered Spiro-Strained-Oxetanyl-1,2-Dioxetane.

Chemiluminescence is the emission of light that occurs as a result of a chemical reaction. Depending on the rate of chemiexcitation, light emission can occur as a long-lasting, low-intensity, glow-type reaction or a rapid, highly intense flash-type reaction. Assays using a flash-type mode of action provide enhanced detection sensitivity compared to those using a glow-type mode.

Divergent outcomes of anti-PD-L1 treatment coupled with host-intrinsic differences in TCR repertoire and distinct T cell activation states in responding versus non-responding tumors.

Differential responses to immune checkpoint inhibitors (ICI) may be attributed to tumor-intrinsic factors or environmental cues; however, these mechanisms cannot fully explain the variable ICI responses in different individuals. Here, we investigate the potential contribution of immunological heterogeneity with a focus on differences in T-cell receptor (TCR) repertoire to ICI responses, which has not been defined previously. To reveal additional factors underlying heterogeneous responses to ICI, we employed a squamous cell carcinoma (SCC) mouse model in which tumor-bearing recipients unambiguously diverged into responders (R) or non-responders (NR) upon anti-PD-L1 treatment.

High-Throughput Measurement and Machine Learning-Based Prediction of Collision Cross Sections for Drugs and Drug Metabolites.

Drug metabolite identification is a bottleneck of drug metabolism studies due to the need for time-consuming chromatographic separation and structural confirmation. Ion mobility-mass spectrometry (IM-MS), on the other hand, separates analytes on a rapid (millisecond) time scale and enables the measurement of collision cross section (CCS), a unique physical property related to an ion's gas-phase size and shape, which can be used as an additional parameter for identification of unknowns. A current limitation to the application of IM-MS to the identification of drug metabolites is the lack of reference CCS values.

Differential responses to immune checkpoint inhibitor dictated by pre-existing differential immune profiles in squamous cell carcinomas caused by same initial oncogenic drivers.

Background: While immune checkpoint inhibitors (ICI) were approved for head and neck squamous cell carcinomas (HNSCCs), the response rate remains relatively low. Mechanisms underlying ICI unresponsiveness versus sensitivity are not fully understood.

Method: To better delineate differential responses to ICI treatment, we employed mouse SCC models, termed KPPA tumors that were caused by deleting p53 and hyperactivating PIK3CA, two most frequently mutated genes in human HNSCCs.