The low endosomal escape efficiency of endocytosis-based delivery has become a key barrier restricting therapeutic biomacromolecule applications in biomedicine. A review published in Biomedical Analysis highlights emerging non-endocytic transmembrane delivery strategies that bypass conventional cellular uptake pathways and enable direct cytosolic delivery of proteins, nucleic acids, and gene-editing tools. Led by Dr. Yang Liu from Hefei Comprehensive National Science Center, the review summarizes recent advances in physical, biomimetic, and bioengineered delivery platforms and discusses their potential for gene therapy, drug delivery, and cellular engineering.

Remodeling may draw to mind images of construction crews and scaffolding, but the process is far from unique to buildings. In fact, even molecules can be remodeled. Pandorachelins, newly-discovered molecules produced by Pandoraea bacterial species, are one such example. These new findings from researchers at the Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute (Leibniz-HKI) and Cluster of Excellence “Balance of the Microverse” at the University of Jena were published in Angewandte Chemie International Edition.

T-cell engagers (TCEs) are an emerging class of immunotherapeutics that have demonstrated considerable clinical efficacy across a range of tumor types. However, their clinical application remains constrained by the challenge of balancing antitumor activity with acceptable safety, which is particularly prominent in solid malignancies. Multiple strategies have been explored to address this trade-off, including molecular engineering, dosing regimens, and patient selection. Nonetheless, within molecular design efforts, activity and toxicity are still largely optimized in isolation.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a non-canonical neurotrophic factor broadly expressed throughout the brain. Previous work has shown that MANF modulates neuronal functions in various disease contexts; however, its cell-type-specific roles within the brain remain incompletely understood. Notably, clinical data link MANF deficiency to microcephaly in humans, yet traditional rodent models fail to replicate this pathology.

Researchers at Kyushu University have discovered a compound called lipoic acid trisulfide (LASSS) that strengthens HGF, a protein that drives muscle repair but can lose its function with age. LASSS protects HGF from this age-related damage while also enhancing its ability to trigger repair. The team hopes the findings could lead to treatments for age-related muscle loss in humans and companion animals, supporting longer, healthier lives.

Plant-infecting fungi have evolved sophisticated strategies to overcome natural barriers and colonize their hosts. A new study investigates the biology of Colletotrichum fungi, among the world’s most destructive plant pathogens, to better understand the mechanisms that drive their success. By exploring how these pathogens interact with plant hosts, researchers uncover new insights into fungal adaptation and provide valuable knowledge that could help develop new strategies for protecting crops from devastating diseases.

Researchers from Zhejiang University and The Chinese University of Hong Kong have discovered that silk sericin—long considered a mere glue coating silk fibers—actively orchestrates the self-assembly of silk fibroin into ordered nanofibrils. Published in Science Bulletin, the study shows that sericin drives liquid-liquid phase separation to create dynamic micro-compartments that concentrate, stabilize, and guide fibroin proteins through a multi-stage maturation process. The findings provide a new mechanistic framework for silk fiber formation and offer design principles for bioinspired programmable materials.