Esophageal squamous cell carcinoma (ESCC) remains a major health burden, particularly in Asia, with poor patient prognosis despite advancements in radiotherapy, chemotherapy, and immunotherapy. The marked interpatient and intratumor heterogeneity of ESCC underscores the need for molecularly informed diagnostic and therapeutic strategies. Recent high-throughput omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, have substantially advanced our understanding of ESCC biology. Genomic profiling has revealed recurrent alterations such as TP53 and NOTCH1 mutations, as well as actionable targets including PIK3CA, FGFR1, and SOX2 amplifications, which provide new opportunities for precision therapy. Epigenomic and transcriptomic analyses have identified methylation-based early detection markers (e.g., PAX9, SIM2) and immune-related transcriptomic subtypes associated with prognosis and immunotherapy responsiveness. Proteomic and metabolomic studies have further uncovered cell cycle and spliceosome pathway activation and altered lactate metabolism, offering additional biomarker and therapeutic insights. In this review, we synthesize these multi-omics advances and highlight how they collectively inform improved diagnostic, prognostic, and therapeutic strategies for ESCC. Despite these developments, the clinical translation of multi-omics findings remains limited due to the lack of standardized analytical pipelines, insufficient multicenter validation, and the high cost and technical complexity of integrating multi-omics data into routine clinical workflows. Future research integrating artificial intelligence with multi-omics data holds promise for enhancing diagnostic accuracy and enabling more precise therapeutic decision-making in ESCC.

Chromosome substitution strains (CSS) are critical tools for dissecting complex traits, although iterative breeding steps and intraspecific compatibility requirements limit conventional approaches. Here, we developed a Targeted chromosome Elimination And Microcell-mediated chromosome transfer platform (TEAM) for chromosome replacement combining CRISPR/Cas9-mediated chromosome elimination with microcell-mediated chromosome transfer (MMCT). Using this approach, we substituted the endogenous mouse Y chromosome (chrY) with either the mouse or human Y chromosome. Intraspecies substitutions yielded karyotypically stable embryonic stem cells that supported development into adult males. By contrast, in interspecies CSS, human chrY displayed severe instability and progressive DNA damage. Despite partial transcription of human chrY genes, recipient animals exhibited systemic inflammation, high rates of neonatal death, and poor growth. Reduced CENP-A levels were observed at human chrY centromeres, leading to segregation errors, micronuclei formation, and widespread chromosome rearrangements. This technology enables programmable construction of chromosome substitution models for investigating chromosomal function, genome evolution, and synthetic karyotype design in mammals.

Genome-wide off-target effect poses a safety risk for clinical use of adenine base editor (ABE), among which ABE8e is one of the most efficient. Genome-wide off-target analysis by two-cell embryo injection (GOTI) analysis showed that the rate of genome-wide single-nucleotide variants (SNVs) in ABE8e-edited cells was ∼30-fold higher than that of spontaneous SNVs in control cells, indicating prevalent off-target effects of ABE8e, but no off-target effect for ABE7.10, from which ABE8e was derived. We performed saturation mutagenesis of eight amino acid sites of the deaminase (TadA8e) within ABE8e and obtained ABE8e^Y149V that exhibited high editing efficiency without detectable off-target effect. Furthermore, TadA8e^Y149V could be fused with other Cas homologs (PAM-relaxed SpRY, hypercompact SaKKH, or IscB) to expand its target range. Finally, ABE8e^Y149V editing of hydroxyphenylpyruvate dioxygenase (Hpd) gene prevented lethality in hereditary tyrosinemia type I mice. The high efficiency and fidelity of ABE8e^Y149V suggest its potential application in ABE-based gene therapies.

Antibodies have emerged as central components of therapeutic strategies against viral infectious diseases, functioning as key effectors in both prevention and treatment. While traditional antibody discovery has relied heavily on high-throughput screening, the field is now shifting toward rational antibody design, which requires integrative insights into sequence–structure–function relationships. However, existing resources provide a valuable foundation but remain limited in scope, highlighting the need for a standardized and well-annotated antibody database that integrates multidimensional features to further support systematic exploration, cross-pathogen comparison, and rational antibody design. Here, we introduce the Multidimensional Antiviral Antibody Database (MAAD; raabmd.org/raab/index), a curated platform dedicated to antibody, nanobody and single-chain variable fragment targeting three high-impact RNA virus families, Coronaviridae (SARS-CoV-1, SARS-CoV-2, MERS-CoV), Orthomyxoviridae (influenza virus), and Pneumoviridae (respiratory syncytial virus, human metapneumovirus), which were selected due to the large, high-quality datasets accumulated in recent years. MAAD further incorporates a suite of interactive analysis modules, including CDR and germline annotation, similarity-based sequence analysis, sequence-based clustering and structure-guided identification of antigen–antibody interface residues, complemented by per-site entropy and mutation rate profiling. These features enable in-depth exploration of antibody sequence characteristics, thereby facilitating functional and structural insights for rational antibody design. Together, by bridging antibody sequence, structure, and function, MAAD offers an open and standardized platform that advances comparative antiviral research and supports therapeutic antibody discovery.