The NOTCH gene was identified approximately 110 years ago. Classical studies have revealed that NOTCH signaling is an evolutionarily conserved pathway. NOTCH receptors undergo three cleavages and translocate into the nucleus to regulate the transcription of target genes. NOTCH signaling deeply participates in the development and homeostasis of multiple tissues and organs, the aberration of which results in cancerous and noncancerous diseases. However, recent studies indicate that the outcomes of NOTCH signaling are changeable and highly dependent on context. In terms of cancers, NOTCH signaling can both promote and inhibit tumor development in various types of cancer. The overall performance of NOTCH-targeted therapies in clinical trials has failed to meet expectations. Additionally, NOTCH mutation has been proposed as a predictive biomarker for immune checkpoint blockade therapy in many cancers. Collectively, the NOTCH pathway needs to be integrally assessed with new perspectives to inspire discoveries and applications. In this review, we focus on both classical and the latest findings related to NOTCH signaling to illustrate the history, architecture, regulatory mechanisms, contributions to physiological development, related diseases, and therapeutic applications of the NOTCH pathway. The contributions of NOTCH signaling to the tumor immune microenvironment and cancer immunotherapy are also highlighted. We hope this review will help not only beginners but also experts to systematically and thoroughly understand the NOTCH signaling pathway.

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This article focuses on the study of textural and protein characteristics of crisp grass carp (CGC) and grass carp (GC) fillets. The higher texture profile analysis (TPA) texture characteristics of CGC are related to a higher content of myofibrillar, sarcoplasmic, stromal proteins, sulfur amino acids and hydrophobic amino acids. Raman spectroscopy further revealed that the secondary and tertiary structural changes in the two fish meat proteins relate to the differences in TPA texture characteristics of the fillets. Lower α‐helix contents and higher β‐sheet contents are closely correlated to the special mastication properties of CGC fillets. More importantly, the disulfide bond content is another factor that affects the texture of CGC fillets. Furthermore, differential scanning calorimetry revealed that the special mastication properties of CGC fillets result from the greater stabilization afforded by proteins. Overall, the results show that the special texture characteristics of CGC fillet correlates positively with the protein characteristics found in fish muscle tissue. PRACTICAL APPLICATIONS Textural characteristics are an important quality for seafood products, which affects acceptability and mechanical processing of fillets. Crisp grass carps (CGCs), broadbean‐fed grass carp (GC), have special mastication. In previous studies, we have found that the differences of texture between both carp's muscles were highly significant. More importantly, the different texture correlated closely with their ultrastructures. Hence, CGC and GC muscles, as the objects for study, will be able to better reflect the relationship between texture and protein characteristics. The research aimed at revealing the mechanism of mastication in CGC muscle to resolve the mastication of CGC decreasing after freezing process.