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Background: Although immune checkpoint blockade (ICB) therapy has brought survival benefits to patients with specific cancer types, most of cancer patients remain refractory to the ICB therapy, which is largely attributed to the immunosuppressive tumor microenvironment. Thereby, it is urgent to profile key molecules and signal pathways responsible for modification of tumor microenvironment. Methods: Multiple databases of esophageal squamous cell carcinoma (ESCC) were integratively analyzed to screen candidate genes responsible for infiltration of CD8+ T cells. Expression of pescadillo ribosomal biogenesis factor 1 (PES1) in clinical ESCC samples was examined by qRT-PCR, western blotting, and immunohistochemistry. The mechanisms of PES1 were investigated via RNA sequencing and mass spectrometry followed by immunoprecipitation and proximity ligation assay. The clinical and therapeutic significance of PES1 in ESCC was comprehensively investigated using ESCC cells and mouse model. Results: PES1 was significantly upregulated and correlated with poor prognosis in ESCC patients. PES1 knockdown decreased ESCC cell growth in vitro and in vivo and enhanced the efficacy of ICB therapy in mouse model, which was established through subcutaneous inoculation with ESCC cells. Analyses on RNA sequencing and mass spectrometry suggested that PES1 expression was negatively correlated with IL15 and ILF3 was one of the PES1-associated proteins. It has been known that ILF3 interacts with and stabilizes IL15 mRNA to increase IL15 protein level. Our data further indicated that PES1 interfered with the interaction between ILF3 and IL15 mRNA and impaired ILF3-mediated stabilization of IL15 mRNA, which eventually reduced the protein level of IL15. Interestingly, the inhibitory effect of ICB therapy boosted by PES1 knockdown dramatically antagonized by knockdown of IL15, which suppressed the tumor-infiltrated CD8+ T cells in ESCC. Finally, we confirmed the relationships among PES1, IL15, and CD8+ T cell infiltration in 10 locally advanced ESCC patients receiving ICB neoadjuvant therapy and demonstrated that ICB therapy would be more effective in those with low expression of PES1. Conclusions: Altogether, our findings herein provided novel insights on biological function and clinical significance of PES1 and suggested that high expression of PES1 could suppress ILF3-IL15 axis-mediated immunosurveillance and promote resistance to ICB through restraining tumor-infiltrated CD8+ T cells. [ABSTRACT FROM AUTHOR]

A new hybrid organic–inorganic perovskite, (R-3AQ)KI3 [R-3AQ2+ = (R)-(+)-3-aminoquinuclidine], has been synthesized and comprehensively characterized by experimental approaches and density functional theory calculations. Our experimental results demonstrate that (R-3AQ)KI3 has a typical perovskite structure and exhibits a reversible order–disorder phase transition at temperatures of 457 and 443 K on heating and cooling, respectively. Under ultraviolet irradiation, a clear yellowish-green emission peaked at 556 nm was observed for (R-3AQ)KI3. The calculated electronic structure shows that (R-3AQ)KI3 possesses a typical direct bandgap with a value of 3.74 eV and its valence band maximum and conduction band minimum primarily arise from the I-5p and I-5s orbitals, respectively. In addition, the elastic calculations indicate that (R-3AQ)KI3 displays a relatively large structure stiffness, relatively small elastic anisotropy, and fairly low acoustic velocity, owing to the rigid K–I bonds and the strong hydrogen bond interactions between the [KI3]2− perovskite framework and R-3AQ2+ cations. These results suggest that the mechanical robustness of this multifunctional (R-3AQ)KI3 makes it a good candidate material for sensing applications. [ABSTRACT FROM AUTHOR]

Vitamin E (VE) can effectively prevent occurrence of lung cancer caused by passive smoking in mice. However, whether VE prevents smoking-induced cytotoxicity remains unclear. In this study, a primary culture of embryonic lung cells (ELCs) was used to observe the cytotoxic effects of cigarette smoke extract (CSE), including its influence on cell survival, cell cycle, apoptosis, and DNA damage, and also to examine the effects of VE intervention on CSE-induced cytotoxicity. Our results showed that CSE could significantly inhibit the survival of ELCs with dose- and time-dependent effects. Furthermore, CSE clearly disturbed the cell cycle of ELCs by decreasing the proportion of cells at the S and G2/M phases and increasing the proportion of cells at the G0/G1 phase. CSE promoted cell apoptosis, with the highest apoptosis rate reaching more than 40%. CSE also significantly caused DNA damage of ELCs. VE supplementation could evidently inhibit or reverse the cytotoxic effects of CSE in a dose- and time-dependent manner. The mechanism of CSE effects on ELCs and that of VE intervention might involve the mitochondrial pathway of cytochrome c-mediated caspase activation. Our study validate that VE plays a clearly protective effect against CSE-induced cytotoxicity in mouse embryonic lung cells.

• Set up a non-uniform Lidar system based on non-uniform sampling strategy. • Design non-uniform image object detection model with mAP50 of 69.4%. • System imaging speed increased by 66.57%. LiDAR (Light Laser Detection and Ranging) is a potential technology that can acquire multi-dimensional and multi-wavelength imaging information. A non-uniform sampling strategy is implemented to enhance the imaging speed, but this system's data can't be efficiently processed and detected. In this paper, we introduce a novel method for object detection in non-uniform imaging, aiming to improve scene analysis and enhance the object detection effect. We use the KITTI dataset with a non-uniform sampling strategy to generate a simulation dataset and design and train NU-YOLO (Non-uniform YOLO) to detect the object in non-uniform images. We build a non-uniform LiDAR system to verify the object detection performance in real scenarios and the speed boost of the LiDAR system. The simulation and experimental results show that NU-YOLO can detect objects in non-uniform images with a higher mAP50 of 7.4% than YOLO (You Only Look Once) v8. By using a non-uniform sampling strategy, NU-YOLO performs 3% better on the mAP50 metric than the model trained using a uniform sampling dataset with the same counts of sampling points. Notably, the non-uniform imaging system increases in speed compared to its uniform sampling counterpart without compromising imaging quality in critical areas. This work opens new application prospects for more intelligent in LiDAR. [ABSTRACT FROM AUTHOR]