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Human cancers induce a chaotic, dysfunctional vasculature that promotes tumor growth and blunts most current therapies; however, the mechanisms underlying the induction of a dysfunctional vasculature have been unclear. Here, we show that split end (SPEN), a transcription repressor, coordinates rRNA synthesis in endothelial cells (ECs) and is required for physiological and tumor angiogenesis. SPEN deficiency attenuated EC proliferation and blunted retinal angiogenesis, which was attributed to p53 activation. Furthermore, SPEN knockdown activated p53 by upregulating noncoding promoter RNA (pRNA), which represses rRNA transcription and triggers p53-mediated nucleolar stress. In human cancer biopsies, a low endothelial SPEN level correlated with extended overall survival. In mice, endothelial SPEN deficiency compromised rRNA expression and repressed tumor growth and metastasis by normalizing tumor vessels, and this was abrogated by p53 haploinsufficiency. rRNA gene transcription is driven by RNA polymerase I (RNPI). We found that CX-5461, an RNPI inhibitor, recapitulated the effect of Spen ablation on tumor vessel normalization and combining CX-5461 with cisplatin substantially improved the efficacy of treating tumors in mice. Together, these results demonstrate that SPEN is required for angiogenesis by repressing pRNA to enable rRNA gene transcription and ribosomal biogenesis and that RNPI represents a target for tumor vessel normalization therapy of cancer., Introduction Angiogenesis, the growth of new vessels from existing ones, is required for vascularization of both physiological and pathological tissues (1). Tumor angiogenesis, however, is driven by abnormally high level [...]

Molybdenum trioxide (MoO3) shows promise as an anode material for Li/Na-ion batteries due to its low cost and high capacity. However, it suffers from poor cycling stability and volume expansion during charging and discharging, which affects its performance. To overcome these issues, researchers have developed a unique hybrid composite by coating MoO3 nanorods with TiO2, creating MoO3@TiO2 core–shell nanorods. The TiO2 coating significantly improves the composite's cycling stability, rate capability, and overall electrochemical performance in Li/Na-ion batteries. The optimized electrode (MoO3@TiO2-2) achieves an impressive capacity of 1259.4 mA h g–1 after 500 cycles at 200 mA g–1 and a discharge capacity of 693.3 mA h g–1 after 1000 cycles at 2000 mA g–1 in lithium-ion batteries. In sodium-ion batteries, they show high reversible discharge capacities of 499.1 and 389.3 mA h g–1 after 500 cycles at 100 and 200 mA g–1, respectively. Moreover, even after 1200 cycles at 2 A g–1, the electrode retains a capacity of 300.2 mA h g–1. When combined with an NMC811 cathode in a full-cell Li-ion battery, the composite exhibits excellent cycling performance, lasting over 150 cycles with a capacity of 200 mA h g–1. This research has significant implications for the development of high-performance rechargeable batteries for various electrochemical energy applications. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of H+/K+ATPase in the proliferation of pepsin‐induced vocal cord leukoplakia (VCL) cells. Study Design: Translation research. Setting: Affiliated Hospital of University. Methods: Immunohistochemistry was used to detect pepsin, H+/K+ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+/K+‐ATPase distribution of VCL cells were investigated. Results: The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate‐to‐severe dysplasia than in normal tissue (p <.05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p <.01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning‐ and autophagy‐promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+/K+‐ATPase and lysosomes in VCL cells; it also mediated lysosome acidification. Conclusion: Pepsin and H+/K+‐ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+/K+‐ATPase. [ABSTRACT FROM AUTHOR]