Identification and functional characterization of CXCL17 in cartilaginous fishes reveals an ancient origin of the CXCL17-GPR25 signaling pathway

This study identifies functional CXCL17 orthologs in cartilaginous fishes through integrated genomic and experimental approaches, demonstrating their high-affinity interaction with GPR25 and establishing that the CXCL17-GPR25 signaling pathway originated in ancient cartilaginous fish ancestors or earlier.

Yu, J., Wang, J.-J., Li, H.-Z. + 2 more2026-03-06⚗️ biochemistry

Systematic assessment of the impact of targeted selection methods and environment-mimicking culture conditions on fungal natural product libraries

This study systematically evaluates how fungal selection strategies, phylogenetic classification, and environment-mimicking culture conditions influence chemical diversity in natural product libraries, providing practical guidelines to optimize library design for more efficient drug discovery.

Ness, M., Wendt, K., Peramuna, T. + 4 more2026-03-06⚗️ biochemistry

Bleb formation induced by acidic mixing buffers improves liquid stability of mRNA-LNPs

This study demonstrates that inducing bleb formation during mRNA-LNP preparation using high ionic strength acidic citrate buffers significantly enhances liquid shelf-life by reducing mRNA degradation and lipid-mRNA adduct formation, offering a universal, chemistry-independent strategy to enable extended refrigerated storage without modifying the mRNA or lipid components.

Grundler, J., Chertok, B., Nilam, A. + 6 more2026-03-06⚗️ biochemistry

Non-coding RNA RsaE regulates biofilm thickness, viability and dissemination in methicillin-resistant Staphylococcus aureus

This study identifies the non-coding RNA RsaE as a critical regulator in MRSA that, in conjunction with RNase Y, fine-tunes phenol-soluble modulin (PSM) expression through post-transcriptional and transcriptional mechanisms, thereby controlling biofilm architecture, cell viability, and systemic dissemination during infection.

Chauhan, M., Ivanova, I., Sudnick, E. G. + 10 more2026-03-06⚗️ biochemistry

MUTYH cancer-associated variants within the interdomain connector differentially impact glycosylase activity and cellular DNA repair

This study demonstrates that cancer-associated MUTYH variants within the interdomain connector exhibit differential functional impacts, with some impairing lesion recognition and others disrupting downstream repair steps, highlighting the necessity of combining in vitro and cellular assays for accurate variant classification.

Khuu, C., Malek, M., Conlon, S. + 3 more2026-03-04⚗️ biochemistry

Molecular mechanisms of immune evasion by host protein glycosylation of a bacterial immunogen used in nucleic acid vaccines

This study reveals that host-derived N-glycosylation of the Mycobacterium tuberculosis Ag85B antigen in nucleic acid vaccines creates a physical and biochemical shield that occludes immune epitopes and recruits inhibitory Siglec-9 receptors, thereby explaining the vaccine's lack of efficacy and highlighting the need for glycosylation-aware immunogen engineering.

Cinar, M. S., Adams, T. M., Nawaz, Z. + 7 more2026-03-03⚗️ biochemistry

Investigating the versatility of cytochalasan cytochrome P450 monooxygenases using combinatorial biosynthesis reveals stereochemical restrictions

This study utilizes combinatorial biosynthesis and genome mining to characterize cytochalasan cytochrome P450 monooxygenases, revealing that while these enzymes exhibit intrinsic promiscuity toward structurally related analogues, their activity on non-native substrates is strictly governed by the stereochemistry of functional groups rather than macrocycle size.

Li, L., Ali, T., Goralczyk, J. + 5 more2026-03-03⚗️ biochemistry

Structure of the human KEOPS/tRNA complex and characterization of pathogenic variants responsible for the Galloway Mowat syndrome.

This study presents the first cryo-EM structure of the complete human KEOPS complex bound to its tRNA substrate and demonstrates that Galloway-Mowat syndrome pathogenic variants retain partial t6A modification activity in vitro and in yeast, indicating that the disease arises from suboptimal rather than total loss of t6A pathway function.

Cirio, C., Auxilien, S., Liger, D. + 13 more2026-03-03⚗️ biochemistry

Synthesis and Assembly of a New-generation Bifunctional Lipid Nanoparticle for Selective Delivery of mRNA to Antigen Presenting Cells

This paper describes the development of mRNA-BLNP3, a novel bifunctional lipid nanoparticle that combines CD1d and mannose receptor targeting to achieve superior antigen-presenting cell delivery, reduced liver accumulation, and enhanced humoral and cellular immune responses compared to previous generations.

Chen, C.-Y., Wang, S.-W., Wong, C.-H.2026-03-02⚗️ biochemistry

Proteasome Inhibition Enhances Lysosome-mediated Targeted Protein Degradation

This study demonstrates that combining proteasome inhibitors with an autophagy-targeting chimera (AUTAC) synergistically enhances lysosome-mediated degradation of the anti-apoptotic protein Mcl1 by exploiting the NRF1-driven adaptive autophagy response, thereby overcoming drug resistance and promoting cell death in multiple myeloma and lung cancer models.

Elshazly, A. M., Hosseini, N., Vangala, J. R. + 7 more2026-03-02⚗️ biochemistry

The structure of Egalitarian in complex with the K10 mRNA localization signal reveals a modular binding surface required for function

This study elucidates the crystal structure of the Drosophila adaptor protein Egalitarian bound to the K10 mRNA localization signal, revealing a modular binding mechanism that is essential for asymmetric mRNA transport and validated by functional deficits in genome-edited flies with mutations in the identified RNA-recognition residues.

Hong, Z., Jin, L., Muehle, J. + 1 more2026-03-02⚗️ biochemistry