Dengue virus serotype 2 (DENV2) alone undergoes structural expansion at 37 °C (associated with host entry), despite high sequence and structural homology among the four known serotypes. The basis for this differential expansion across strains and serotypes is unknown and necessitates mapping of the dynamics of dengue whole viral particles to describe their coordinated motions and conformational changes when exposed to host-like environments. Here we capture the dynamics of intact viral particles of two serotypes, DENV1 and DENV2, by amide hydrogen/deuterium exchange mass spectrometry (HDXMS) and time resolved Förster Resonance Energy Transfer. Our results show temperature-dependent dynamics hotspots on DENV2 and DENV1 particles with DENV1 showing expansion at 40 °C but not at 37 °C. HDXMS measurement of virion dynamics in solution offers a powerful approach to identify potential epitopes, map virus-antibody complex structure and dynamics, and test effects of multiple host-specific perturbations on viruses and virus-antibody complexes.
In microwave (MW) thermotherapy, it is challenging to regulate the temporal and spatial distribution of the temperature at the nanoscale. Herein, we report a nanothermometer for simultaneous MW heating and temperature distribution measurement. The nanothermometer was prepared by free radical polymerization with vinylbenzyl trimethylammonium chloride (VBTMACl) as the MW thermosensitizer and isopropylacrylamide (NIPAM) as the thermoresponsive unit, followed by anion exchange with fluorophore sodium 3-(4-(1,2,2-triphenylvinyl)phenoxy)propane-1-sulfonate (TPESONa).
Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, Institute of Developmental Biology and Regenerative Medicine, College of Chemistry and Chemical Engineering, Southwest University Chongqing 400715 P. R. China
Utilizing the cGAS-STING pathway to combat immune evasion is one of the most promising strategies for enhancing cancer immunotherapy. However, current techniques for activating the cGAS-STING pathway often face a dilemma, mainly due to the balance between efficacy and safety. Here, we develop a uracil base lesion-gated dumbbell DNA nanodevice (UBLE) that allows on-demand activation and termination of the cGAS-STING pathway in tumor cells, thereby enhancing cancer immunotherapy.
Herein, we present a strategy to access a novel class of pH-responsive, dual-state emissive (DSE), highly fluorescent pyrrole-based chromophores diformylation of dipyrroethenes (DPE) followed by condensation with various aniline derivatives. The DPE-based chromophores exhibit a large Stokes shift and maintain good fluorescence quantum yields. Remarkably, these chromophores demonstrate reversible colourimetric changes and a fluorometric 'on-off-on' switch in response to pH variations.
Cancer progression involves genetic and epigenetic changes that disrupt chromatin 3D organization, affecting enhancer-promoter interactions and promoting growth. Here, we provide an integrative approach, combining chromatin conformation, accessibility, and transcription analysis, validated by in silico and CRISPR-interference screens, to identify relevant 3D topologies in pediatric T cell leukemia (T-ALL and ETP-ALL). We characterize 3D hubs as regulatory centers for oncogenes and disease markers, linking them to biological processes like cell division, inflammation, and stress response.
State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center of Biological Structure, Tsinghua University, Beijing 100084, China; School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China. Electronic address:
PIEZO1 is a mechanically activated cation channel that undergoes force-induced activation and inactivation. However, its distinct structural states remain undefined. Here, we employed an open-prone PIEZO1-S2472E mutant to capture an intermediate open structure.
