Anti‐angiogenic therapy has long been considered a promising strategy for solid cancers. Intrinsic resistance to hypoxia is a major cause for the failure of anti‐angiogenic therapy, but the underlying mechanism remains unclear. Here, it is revealed that N4‐acetylcytidine (ac4C), a newly identified mRNA modification, enhances hypoxia tolerance in gastric cancer (GC) cells by promoting glycolysis addiction. Specifically, acetyltransferase NAT10 transcription is regulated by HIF‐1α, a key transcription factor of the cellular response to hypoxia. Further, acRIP‐sequencing, Ribosome profiling sequencing, RNA‐sequencing, and functional studies confirm that NAT10 in turn activates the HIF‐1 pathway and subsequent glucose metabolism reprogramming by mediating SEPT9 mRNA ac4C modification. The formation of the NAT10/SEPT9/HIF‐1α positive feedback loop leads to excessive activation of the HIF‐1 pathway and induces glycolysis addiction. Combined anti‐angiogenesis and ac4C inhibition attenuate hypoxia tolerance and inhibit tumor progression in vivo. This study highlights the critical roles of ac4C in the regulation of glycolysis addiction and proposes a promising strategy to overcome resistance to anti‐angiogenic therapy by combining apatinib with ac4C inhibition.

Introduction: There is limited basic research on carbon dioxide (CO 2 ) fractional laser, indicating blind spots in CO 2 fractional laser treatment of certain diseases. This study aimed to organize previous literature, summarize the current research, and speculate on possible future development. Methods: We searched document data on fractional CO 2 lasers from the Web of Science core collection database and retrieved 928 articles from 2004 to 2021. CiteSpace software was used to analyze the main institutions, authors, subject hotspots, and research frontiers in global CO 2 fractional laser research. Results: The results revealed that 928 related papers were published in the past 18 years (2004-2021), and the number has increased annually. The publications were written by 3239 authors from 626 institutions in 60 countries/regions. The United States (US) dominates this field (312 documents), followed by Italy (289), and South Korea (88). Lasers in Surgery and Medicine is the journal with the most publications and citations, and Uebelhoer is the central author. The main research hotspots include vulvovaginal atrophy, fractional photothermolysis, keloids, drug delivery, gene expressions, facial acne scarring, resurfacing, vitiligo, and photo damage. Conclusion: Using CiteSpace, this paper draws a map of authors, institutions, and keywords in fractional CO 2 laser from 2004 to 2021; summarizes the main authors, institutions, research hotspots, and cutting-edge topics of global fractional CO 2 laser technology in recent years; and summarizes the current application status of global fractional CO 2 laser in disease treatment. It also provides new ideas for the future application and research of fractional CO 2 lasers.