Antibacterial peptides (ABPs) represent a promising alternative strategy for combating antimicrobial resistance. Graph neural networks and their variants have shown substantial potential in ABP identification. However, most existing graph-based methods focus on node features while neglecting edge features. Edge features play an important role in characterizing peptide conformation and spatial stability, thereby directly influencing interactions with bacterial membranes and antibacterial activity. Moreover, node and edge features extracted by heterogeneous encoders reside in disparate feature spaces, making their effective integration nontrivial. These challenges highlight the need for an explicit alignment mechanism to bridge heterogeneous representations. In this study, we propose CLABP, a contrastive learning-based framework for ABP identification that integrates edge features. Specifically, backbone dihedral angles, ProtT5 embeddings, and Define Secondary Structure of Proteins-derived secondary structures were employed as node features, while inter-residue distance, motion vectors, and rotation quaternions were used to construct edge features. Node and edge representations were independently extracted using dedicated encoders and subsequently aligned into a shared latent space via contrastive learning, which minimizes the distance between paired representations derived from the same peptide. The aligned features were then fused through a dual cross-attention mechanism for downstream prediction. CLABP outperforms other state-of-the-art methods, achieving an accuracy of 92.6% and a Matthews correlation coefficient of 0.853. Ablation studies further confirm that both edge features and the alignment mechanism are critical to model performance. 

The skin microbiome maintains cutaneous homeostasis through colonization resistance and immune modulation, targeted prebiotic interventions however remain largely unexplored. The present study addresses this lacuna effectively demonstrating the ability of plant-derived prebiotics to selectively modulate key skin commensals and pathogenic bacteria thereby unraveling a new dimension to use of prebiotics in skin care. Linum usitatissimum (flaxseed) and Allium sativum (garlic) extracts used herein exhibited complete growth inhibition of Staphylococcus aureus within 6 h, while Curcuma amada (mango ginger) rapidly halted the growth of Cutibacterium acnes within 15 min. Gas chromatography-mass spectrometry was carried out to unveil the bioactive constituents in plant-prebiotics as well as the exposed organisms. Field emission gun-scanning electron microscopy validated bacterial cell membrane disruption correlating with antimicrobial efficacy. Remarkably, Allium cepa (onion) and Tinospora cordifolia (guduchi) selectively enhanced the proliferation of Staphylococcus epidermidis while simultaneously inhibiting pathogenic species. Metabolomic profiling revealed that prebiotic-stimulated S.epidermidis produced elevated levels of butyric and succinic acids that are documented to have anti-bacterial activity. Plant-based prebiotics can thus be strategically reinforced to benefit skin microbiota with simultaneous inhibition of skin pathogens, providing a scientific foundation for microbiome-targeted cosmeceuticals.

Microgravity is a condition that may affect gastrointestinal function and metabolism during spaceflight. Despite attempts to keep normal dietary habits at the ISS, the food selection and meal timing may also be perturbed during the confinement. To understand the impact of spaceflight on human metabolism, we characterized the plasma metabolome of astronauts (n = 52) before, during, and after missions on board the International Space Station (ISS) using liquid chromatography coupled with mass spectrometry. Here we show that spaceflight affected around 40 circulating compounds. In this longitudinal assessment, the metabolic changes were already observed shortly after launch and subsided within a few days after landing. The flight-induced changes in metabolites reflected increased protein fermentation by the gut microbiota, possibly reflecting prolonged intestinal transit time caused by microgravity. Minor diet-related changes related to intakes of caffeine, fish, and some fats were also observed but affected less than one third of all metabolites responding to spaceflight. We did not observe major sex-specific differences in metabolism. Increasing the consumption of slow-fermented carbohydrates at ISS to reduce protein fermentation might improve gastrointestinal health in astronauts in future human long-term spaceflights. Here, by metabolomics profiling of blood samples collected before, during and after spaceflight in 52 astronauts, the authors identify changes in gut microbial metabolites indicative of slower gut transit during microgravity.

Myxobacteria are renowned producers of structurally diverse bioactive natural products. Motivated by a comprehensive inventory of myxobacterial biosynthetic gene clusters (BGCs), we develop efficient genetic toolkits and construct a robust heterologous expression chassis. We identify a pair of Myxococcus-derived recombinases, designated MxRecET, that enables efficient genome editing in the model strain Myxococcus xanthus DK1622. The synergistic combination of MxRecET recombineering with the transposon-associated nuclease TnpB (ISDra2) enables versatile genetic manipulations, including seamless deletion of large DNA fragments (up to 200 kb), tandem editing of dual loci, and flexible single-nucleotide substitutions within a streamlined two-week workflow. This integrated technology, termed MxDIRECT, facilitates the rational engineering of DK1622 into a plug-and-play chassis designated MxPKS, featuring enhanced growth properties, elimination of competing pathways, an improved precursor supply, and increased robustness. The effectiveness of MxPKS is demonstrated through heterologous expression of four polyketide synthase BGCs, leading to the discovery of multiple unknown polyketides. This work establishes a foundation for accelerated bioprospecting of myxobacteria. Myxobacteria are renowned producers of structurally diverse bioactive natural products but are difficult to engineer. Here the authors create a robust heterologous expression chassis and develop MxDIRECT, a recombineering strategy for scarless marker-free expression of biosynthetic gene clusters.

Nano-sized outer membrane vesicles (OMV) are lipid-bilayered structures that primarily encapsulate periplasmic components, with minor inclusion of cytoplasmic materials. Rather than passive byproducts of cellular damage, OMVs are now understood as active mediators of bacterial physiology, environmental adaptation, and host interaction. Recent evidence identifies envelope instability as a key mechanistic driver of OMV biogenesis. Disruptions in outer membrane–peptidoglycan connectivity, imbalances in periplasmic homeostasis, and alterations in lipid asymmetry collectively promote vesicle formation as a regulated adaptive response. Under stress conditions, OMVs acquire specialized functional roles, selectively enriching specific cargo and exhibiting surface properties that enable them to sequester host-derived antimicrobial factors. OMV-associated biomolecules further influence vesicle uptake into host cells through distinct endocytic pathways, shaping intracellular trafficking and downstream functional outcomes. Following internalization, pathogen-derived OMVs disrupt host signaling pathways and are exploited to promote immune evasion, whereas commensal-derived OMVs contribute to microbiota homeostasis and immune modulation. In parallel, growing efforts to harness OMVs as vaccine platforms highlight their potential as innovative tools for both therapeutic and prophylactic applications. Collectively, these insights position OMVs as critical mediators of bacterial pathogenicity and as promising targets for anti-infective strategies. A review summarizes recent insights into outer membrane vesicles (OMVs) in Gram negative bacteria, including their biogenesis mechanisms, stress-associated cargo remodeling, host-cell interactions, immunomodulatory roles, and therapeutic applications.

The influence of plate tectonics on microbial distributions remains poorly understood. Here, we demonstrate that the global biogeography of hydrothermal vent-endemic chemoautotrophic microbiota is structured by the tectonic history of the global major oceans. These microbiota, particularly anaerobic ones, are significantly more abundant in early-origin Pacific, Arctic, and Mediterranean oceans, whereas they are notably scarce in late-formed Atlantic and Indian Oceans. This pattern was attributed to the timing of ocean formation and its interplay with global redox evolution. Fully oxygenated conditions in the Phanerozoic during the formation of the latter two oceans imposed a dual-dispersal barrier among oceans: toxicity of molecular oxygen to anaerobes and depletion of energy sources (especially reduced chemicals) for aerobes, but such a barrier didn’t exist before the Phanerozoic, when the former three oceans started. These results integrate microbial biogeography into a geodynamic framework, revealing that even microbial life is subject to planetary-scale geological constraints. The links between deep-time geologic processes and microbial distribution remain poorly understood. This paper reveals that tectonic and geochemical evolution shapes the global biogeography of hydrothermal bacteria by limiting their dispersal to the oceans formed after oxygenation.

Circular RNA (circRNA) exhibits extended stability and enhanced protein expression, and its translational efficiency and immunogenicity can be improved through nucleoside modification and rolling circle translation (RCT). However, it remains challenging to produce protein-encoding circRNA with modified nucleosides. Here we identified a cap-independent translation enhancer (CITE) element from black beetle virus, termed BBV, which could drive the translation of nucleoside-modified RNA and RCT of engineered circRNA. In addition, we developed a system to produce ‘scarless’ circRNA via in vitro transcription (IVT). The resulting circRNA vaccine outperformed m1ψ-mRNA vaccine in inhibiting tumor growth in mice. With nucleoside modification, circRNA exhibited reduced expression of pro-inflammatory cytokines. Further, nucleoside-modified circRNA encoding glucagon-like peptide-1 (GLP-1) peptides reduced blood glucose levels with efficacy comparable to that of commercial semaglutide, and ameliorated liver damage in obese mice. Moreover, nucleoside-modified circRNA encoding myelin oligodendrocyte glycoprotein (MOG35–55) peptides induced immune tolerance and alleviated disease progression in an experimental autoimmune encephalomyelitis (EAE) murine model. Collectively, we established a nucleoside-modified circRNA platform that facilitated efficient translation with minimal immunogenicity, expanding the application scenarios of circRNA beyond vaccines. A suite of tools to improve translation and immunogenicity of circular RNAs, including nucleoside modification and rolling circle translation, for applications in cancer vaccines, protein replacement and autoimmune therapies.