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Computational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFA robust transfer learning approach for high-dimensional linear regression to support integration of multi-source gene expression data.
PLoS Comput Biol
January 2025
Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China.
Transfer learning aims to integrate useful information from multi-source datasets to improve the learning performance of target data. This can be effectively applied in genomics when we learn the gene associations in a target tissue, and data from other tissues can be integrated. However, heavy-tail distribution and outliers are common in genomics data, which poses challenges to the effectiveness of current transfer learning approaches.
View Article and Find Full Text PDFThread-Filler: A Standardized Combination Therapy.
J Craniofac Surg
January 2025
Department of Plastic, Reconstructive, and Aesthetic Surgery, Bilkay Clinic, Izmir, Turkey.
Advanced technology and increasing knowledge about aging faces have combined to create the illusion of thread lifting to replace surgical interventions. However, results that came far beyond expectations led to a heavy suspicion of these tools. However, combined treatments with fillers would have better outcomes with a synergetic effect.
View Article and Find Full Text PDFTheoretical Understanding of Photoluminescence and Singlet Oxygen Quantum Yields in a Few Halogenated Fluorescein Dyes.
Chem Asian J
December 2024
Department of Chemistry, Indian Institute of Technology Tirupati, Tirupati, A.P 517619, India.
Visible-light absorbing metal-free organic dyes are of increasing demand for various optoelectronic applications because of their great structure-function tunability through chemical means. Several dyes also show huge potential in triplet photosensitization, generating reactive singlet oxygen. Understanding the structure-property relationships of many well-known fluorescein dyes is of paramount importance in designing next-generation energy efficient dyes, which is currently limited.
View Article and Find Full Text PDFDynamic Phosphorescence Behavior of Carbene-Metal-Amide Complexes from the Perspective of Excited State Modulation.
Angew Chem Int Ed Engl
January 2025
Beijing Institute of Technology, School of Chemistry and Chemical Engineering, CHINA.
Carbene-metal-amide (CMA) complexes have diverse applications in luminescence, imaging and sensing. In this study, we designed and synthesized a series of CMA complexes, which were subsequently doped into a PMMA host. These materials demonstrate light-induced dynamic phosphorescence, attributed to their long intrinsic triplet state lifetime (τP,int, in the μs-ms scale), high intersystem crossing (ISC) rate constant (kISC, up to 107 s-1), and bright phosphorescence.
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