Core Insights - The article discusses the revolutionary advancements in structural biology through the use of cryo-electron microscopy (cryo-EM) and AI tools like AlphaFold, enabling high-resolution observation and prediction of protein structures [3][6] - A paradigm shift is occurring in structural biology, moving from targeted structure determination to structure-guided discovery of previously uncharacterized biological entities [3][6] - The CryoSeek strategy, proposed by Yan Ning's team, combines cryo-EM with AI-assisted modeling and bioinformatics analysis to discover entirely new biological entities in nature [3][6] Summary by Sections CryoSeek Strategy - In October 2024, Yan Ning's team introduced CryoSeek, utilizing cryo-EM as an observational tool combined with AI for automatic modeling and bioinformatics analysis [3][6] - The strategy aims to identify unknown biological entities from any accessible source, showcasing its potential in discovering novel nanostructures [6] Discoveries in Glycobiology - In October 2025, the team published two papers detailing the discovery of new glycofibril structures using the CryoSeek strategy, highlighting the importance of sugars in biological assembly [4][11] - The research emphasizes that sugars can act as information molecules and structural scaffolds, opening new avenues in glycobiology [4][11] New Algorithms and Techniques - The team developed a new algorithm named Ahaha for determining the absolute handedness of glycofibrils, addressing a significant challenge in sugar science [12][14] - Ahaha has been deployed as an online service, facilitating global access for researchers to measure the absolute handedness of sugar fibers [16] Structural Insights - The research identified five new glycofibrils with varying compositions and structural assemblies, revealing a continuum from protein-dominant to sugar-dominant structures [8][9] - The findings indicate that glycan-mediated interactions are crucial for the assembly of these diverse fibers, challenging the traditional view that proteins are the primary builders of biological structures [11][12]