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Glioblastoma (GBM) is the most malignant brain tumor with unmet therapeutic demand. The blood‐brain‐barrier (BBB) and tumor heterogeneity limit the treatment effectiveness of various interventions. Here, an ultrasound augmented chemo/immuno therapy for GBM using a neutrophil‐delivered nanosensitizer, is developed. The sensitizer is composed of a ZnGa2O4:Cr3+ (ZGO) core for persistent luminescence imaging and a hollow sono‐sensitive TiO2 shell to generate reactive oxygen species (ROS) for controlled drug release. Immune checkpoint inhibitor (Anti‐PD‐1 antibody) is trapped in the interior of the porous ZGO@TiO2 with paclitaxel (PTX) loaded liposome encapsulation to form ZGO@TiO2@ALP. Delivered by neutrophils (NEs), ZGO@TiO2@ALP‐NEs can penetrate through BBB for GBM accumulation. After intravenous injection, ultrasound irradiation at GBM sites initiates ROS generation from ZGO@TiO2@ALP, leading to liposome destruction for PTX and anti‐PD‐1 antibody release to kill tumors and induce local inflammation, which in‐turn attractes more ZGO@TiO2@ALP‐NEs to migrate into tumor sites for augmented and sustained therapy. The treatment enhances the survival rate of the GBM bearing mice from 0% to 40% and endows them with long‐term immuno‐surveillance for tumor recurrence, providing a new approach for precision therapy against GBM and other cancers. [ABSTRACT FROM AUTHOR]

G-quadruplexes (G4s) are a kind of non-canonical nucleic acid secondary structures, which involve in various biological processes in living cells. The relationships between G4s and human diseases, such as tumors, neurodegenerative diseases, and viral infections, have attracted great attention in the last decade. G4s are considered as a promising new target for disease treatment. For instance, G4 ligands are reported to be potentially effective in SARS-COV-2 treatment. However, because of the lack of analytical methods with high performance for the identification of intracellular G4s, the detailed mechanisms of the biofunctions of G4s remain elusive. Meanwhile, through demonstrating the principles of how the G4s systematically modulate the cellular processes with advanced detection methods, biochemical targeting of G4s in living cells can be realized by chemical and biological tools and becomes useful in biomedicine. This review highlights recent methodological advances about intracellular G4s and provides an outlook on the improvement of the bioanalysis and biochemical targeting tools of G4s., Competing Interests: The authors declare no competing financial interests., (© 2022 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.)

Immune cell heterogeneity due to the differential expression of RNA splicing variants still remains unexplored. This is mainly because single-cell imaging technologies of splicing variants with precise sequence or base resolution are now not readily available. Herein, we design a splice-junction anchored padlock-probe-mediated rolling circle amplification assay (SpliceRCA) for single-cell imaging of splice isoforms of essential regulatory immune gene (CD45) upon T-cell activation. Two recognition regions in the padlock probe can target the splice-junction sequence, resulting in a close proximity for triggering in situ one-target-one-amplicon amplification. With the read length of ∼30 nucleotides, this method allows discrimination of isoforms with single-base precision and quantification of isoforms with single-molecule resolution. We applied SpliceRCA to single-cell image splice variants of essential regulatory immune gene (CD45) upon T-cell activation. It is found that CD45RO isoform presents a distal nuclear spatial distribution and is coregulated with CD45RB upon activation. Our strategy provides a single-cell analysis platform to investigate the mechanism of complex immune responses and may further guide immunotherapy., Competing Interests: The authors declare no competing financial interest.