Extrachromosomal circular DNA (eccDNA) is a type of double-stranded circular DNA that is derived and free from chromosomes. It has a strong heterogeneity in sequence, length, and origin and has been identified in both normal and cancer cells. Although many studies suggested its potential roles in various physiological and pathological procedures including aging, telomere and rDNA maintenance, drug resistance, and tumorigenesis, the functional relevance of eccDNA remains to be elucidated. Recently, due to technological advancements, accumulated evidence highlighted that eccDNA plays an important role in cancers by regulating the expression of oncogenes, chromosome accessibility, genome replication, immune response, and cellular communications. Here, we review the features, biogenesis, physiological functions, potential functions in cancer, and research methods of eccDNAs with a focus on some open problems in the field and provide a perspective on how eccDNAs evolve specific functions out of the chaos in cells.

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If you would like to write for this, or any other Emerald publication, then please use our Emerald for Authors service information about how to choose which publication to write for and submission guidelines are available for all. Please visit www.emeraldinsight.com/authors for more information. About Emerald www.emeraldinsight.comEmerald is a global publisher linking research and practice to the benefit of society. The company manages a portfolio of more than 290 journals and over 2,350 books and book series volumes, as well as providing an extensive range of online products and additional customer resources and services.Emerald is both COUNTER 4 and TRANSFER compliant. The organization is a partner of the Committee on Publication Ethics (COPE) and also works with Portico and the LOCKSS initiative for digital archive preservation. AbstractPurpose -The purpose of this paper is to present key points relating to the development of micro drill bits with high aspect ratios and to provide a solution for high aspect ratio hole drilling. Design/methodology/approach -Based on the analysis of challenges in high aspect ratio hole drilling, key points for the development of micro drills bit with high aspect ratio are discussed. A design example of a micro drill bit with 0.3 mm diameter and a 7.2 mm flute length is presented. Experiments are conducted to verify the performance of the developed micro drill bit. Findings -Helix angle, web thickness and flute land ratio are three key parameters that significantly influence the behaviour of micro drill bits with high aspect ratios. Large helix angle, web thickness and flute land ratio are beneficial in terms of improving the performance of high aspect ratio micro drill bits.Step drilling is essential to prevent drill breakage and to ensure smooth debris evacuation. Meanwhile, proper steps and drilling parameters are of great importance to complete high aspect ratio hole drilling. Originality/value -The paper highlights key points relating to the development of micro drill bits with high aspect ratios that can provide a satisfactory solution for high aspect ratio micro drill bit design.

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