Advancements in nanobody generation: Integrating conventional, in silico, and machine learning approaches.

Nanobodies, derived from camelids and sharks, offer compact, single-variable heavy-chain antibodies with diverse biomedical potential. This review explores their generation methods, including display techniques on phages, yeast, or bacteria, and computational methodologies. Integrating experimental and computational approaches enhances understanding of nanobody structure and function. Future trends involve leveraging next-generation sequencing, machine learning, and artificial intelligence for efficient candidate selection and predictive modeling. The convergence of traditional and computational methods promises revolutionary advancements in precision biomedical applications such as targeted drug delivery and diagnostics. Embracing these technologies accelerates nanobody development, driving transformative breakthroughs in biomedicine and paving the way for precision medicine and biomedical innovation.

Dual-energy CT evaluation of gastrointestinal bleeding.

Gastrointestinal bleeding is a common cause for hospital admissions and is an important cause of morbidity and mortality. Although endoscopy is accepted as the standard initial diagnostic modality for the evaluation of gastrointestinal bleeding, multiphasic computed tomography (CT) imaging has become an alternative diagnostic tool. Dual-energy CT with post-processing techniques may have additional advantages over single-energy computed tomography in evaluation of gastrointestinal bleeding. In this article, we discuss the role of dual-energy CT in the evaluation of gastrointestinal bleeding with potential advantages over conventional CT and limitations.

Multicyclic Peptides as Scaffolds for the Development of Tumor Targeting Agents.

The lack of specificity of traditional cytotoxic drugs triggers the development of anticancer agents with high selectivity to tumor-specific proteins. The unveiling of target structures such as EGFR or Her2 allows the focused development of novel therapies and has strongly advanced tumor treatment. Tumor-specific high-affinity ligands can be identified by using display techniques such as phage, yeast surface, ribosome and mRNA display. These techniques enable the screening of huge libraries, consequently providing a valuable alternative to rational drug development. In recent years, miniproteins and multicyclic peptides have become the preferred ligands expressed by these libraries. Due to their favorable pharmacokinetics and the ease of their synthesis, peptidic ligands overcome disadvantages of antibody derived therapeutics. Peptides that are structurally defined by a rigid scaffold are ideally suited for the use in display techniques. These molecules feature high stability and excellent affinities while offering the opportunity to randomize partial sequences to be used as binding sites. Structurization of the peptide scaffold can be achieved by different approaches, of which cyclization is one of the most commonly used. The favored cyclization strategies are based on amide or disulfide bridging and the use of synthetic braces or chemical linkers. The use of multicyclic peptides allows the simultaneous presentation of several different binding loops. Semisynthetic approaches enable the introduction of unnatural amino acids, increasing the diversity of the resulting peptide libraries. Given that, miniprotein scaffolds offer a wide range of potential applications and facilitate efficient screening of novel high-affinity ligands to be used in precise diagnosis and highly efficient cancer therapy.