Heterosis, or hybrid vigor, describes the superior performance of F1 hybrids compared to parental inbreds. While soil microbiomes are proposed to influence heterosis, it remains unclear how heterotic plants shape their microbiomes and how interactions relate to stress responses. Here, we investigate the role of rhizosheath formation—the soil tightly adhering to roots—in maize heterosis under nitrogen deprivation. Across sterilization, inoculation, and transplantation experiments, hybrids develop larger rhizosheaths than inbreds, and rhizosheath size associates with biomass heterosis. Rhizosheath-enriched genus Massilia correlates with lateral root density, rhizosheath size, and growth. Untargeted metabolomics and flavone-deficient mutants reveal links between Massilia and flavonoid pathways, while growth promotion by Massilia can also occur independently of host flavones. Metagenomic analysis shows that larger rhizosheaths recruit microbial functions related to nutrient cycling and stress adaptation. These findings identify rhizosheath formation as an integrative trait associated with heterosis and a promising target for breeding resilient crops. This study shows that maize hybrids form larger rhizosheaths than inbreds, which are linked with beneficial microbes such as Massilia. These interactions support root growth, nutrient uptake, and reduced nitrogen loss under stress.

Ribosomal frameshifting is an important, albeit rare, mRNA decoding mechanism that generally allows the synthesis of a single protein from two different reading frames. +1 frameshifting is commonly presumed to involve re-pairing of the P-site tRNA with the +1 codon. However, in several occurrences in the yeast Saccharomyces cerevisiae, P-site tRNA re-pairing with the +1 codon is impossible. In one model, +1 frameshifting occurs according to a common mechanism involving P-site tRNA movement without re-pairing with the +1 codon. The alternative is a distinct mechanism allowing A-site tRNA acceptance at the +1 codon in the absence of P-site tRNA movement. Here, we experimentally compared all known +1 ribosomal frameshifting sites in S. cerevisiae, including a novel case discovered during this study in LLP1. We identified a conserved RNA secondary structure upstream of the ABP140 frameshifting site that increases frameshifting efficiency. The location of the structure suggests that it creates an mRNA-pulling effect favoring +1 codon in the P-site. Placing the stimulator upstream of various known frameshifting sites revealed that its stimulatory action is selective to those frameshifting sites where P-site tRNA re-pairing is possible, reinforcing the idea of two distinct mechanisms of +1 ribosomal frameshifting.

Exogenous natural products (NPs) undergo complex metabolic transformations both in vivo and in vitro, generating structurally diverse metabolites. Due to the involvement of host enzymes and gut microbiota, as well as the structural complexity of NPs themselves, their metabolic processes exhibit unique characteristics. However, existing metabolic transformation information remains fragmented, limiting systematic understanding of their metabolic mechanisms. To address this gap, MetabFlow (https://bddg.hznu.edu.cn/metabflow/), a comprehensive database dedicated to the metabolism of exogenous NPs, was developed. MetabFlow is distinguished by: (a) systematic integration of 7294 curated metabolic reactions covering both in vivo and in vitro transformations, providing a complete knowledge map of exogenous NP metabolism; (b) unique integration of enzyme-catalyzed and microbiota-mediated reactions, highlighting the distinctive metabolic features of NPs; (c) establishment of a structured metabolic network by constructing upstream-downstream reaction relationships, elucidating how exogenous NPs evolve across different metabolic pathways; (d) inclusion of approximately 3200 compounds not indexed in mainstream databases, with detailed structural information, annotations, and complete metabolic profiles. MetabFlow is designed to support research in NP metabolism, drug discovery, and related fields.

Bacteria constantly adapt to changing environmental conditions through diverse processes that involve numerous regulator and effector proteins. In this regard, small proteins play a significant role in promoting stress adaptation in bacteria. Although they were largely overlooked in early genome annotations, recent technological advances and a growing recognition of their significance have paved the way for the increasing identification and characterization of this intriguing class of proteins. Many small proteins contain a transmembrane domain and are integral to the cytoplasmic membrane. Others interact with and modulate membrane protein complexes. In this review, we focus on the current knowledge of these small membrane proteins, with an emphasis on their interactions, membrane insertion pathways, and toxicity.

Cancer treatment mediated by bacteria, also known as Bacteria-mediated cancer therapy (BMCT), has emerged as a promising strategy that overcomes several limitations of conventional cancer treatments by exploiting the natural tumor-targeting ability of bacteria. Among them, Salmonella typhimurium has gained particular attention due to its intrinsic capacity to colonize hypoxic and nutrient-deprived regions of tumors, secrete cytotoxins, and activate host immune responses. This review, along with summarizing these mechanisms, uniquely integrates the diverse anticancer mechanisms of S. typhimurium, such as apoptosis and autophagy induction, immune modulation, nutrient competition, and tumor colonization, which collectively contribute to tumor regression. We discuss the recent advances in metabolic engineering and synthetic biology to provide a unified perspective on how engineered strains achieve enhanced specificity, biosafety, and controlled intratumoral payload delivery. We also critically evaluate the current limitations and translational challenges of BMCT, emphasizing that bacteria-based therapies only complement and not replace existing cancer treatments.

RNA-targeted degradation technologies offer significant promise for treating diseases by selectively disrupting gene expression. However, a robust method to specifically, efficiently, and programmability degrade targeted RNAs in mammalian cells is still in demand. Here, we present a versatile platform, dCas13d-directed chaperone-mediated autophagy (dCasCMA), which integrates the precise targeting capabilities of dCas13/CRISPR with the degradation efficiency of chaperone-mediated autophagy (CMA) to achieve efficient degradation of specific RNAs. By combining dCas13d with a CMA-targeting motif and customizable guide RNA (gRNA), the platform allows for accurate targeting of both exogenous and endogenous RNAs in cells. Moreover, the incorporation of multiplexed gRNA expression arrays enables the simultaneous degradation of multiple RNA targets during viral pathogenesis in live cells and in vivo. Our findings emphasize the platform’s modular design, which enables flexible combinations of dCCTM components with user-defined gRNA sequences. This versatility positions it as a promising tool for developing innovative therapies for various diseases. RNA-targeted degradation holds therapeutic potential but still needs more efficient tools. Here, authors develop dCasCMA, a platform that combines CRISPR targeting with a cellular degradation mechanism to efficiently degrade specific RNAs in live cells and in vivo, enabling multi-target therapies.

Chemical Entities of Biological Interest (ChEBI) is a high-quality, manually curated, and open-access database and ontology of chemical entities available online at https://www.ebi.ac.uk/chebi/. The chemical entities in question are either naturally occurring compounds or synthetic compounds that play a vital role in the processes of living organisms. ChEBI was launched in 2004, and over the years the original codebase has become increasingly difficult to maintain. Here, we describe the complete overhaul and modernization of ChEBI’s infrastructure, including its codebase and associated tools (website, web services, and submission tool) to ensure the continued availability and growth of this critical resource for the global bioinformatics community and beyond. The infrastructure overhaul also enabled us to introduce new features and capabilities into ChEBI as well as to update or deprecate redundant ones.

IscB, as the putative ancestor of Cas9, possesses a compact size, making it suitable for in vivo delivery. OgeuIscB is the first IscB protein known to function in eukaryotic cells but requires a complex TAM (NWRRNA). Here, we characterize a CRISPR-associated IscB system, named DelIscB, which recognizes a flexible TAM (NAC). Through systematically engineering its protein and sgRNA, we obtain enDelIscB with an average 48.9-fold increase in activity. By fusing enDelIscB with T5 exonuclease (T5E), we find that enDelIscB-T5E displays robust efficiency comparable to that of enIscB-T5E in human cells. Moreover, by fusing cytosine or adenosine deaminase with enDelIscB nickase, we establish efficient miniature base editors (ICBE and IABE). Finally, we efficiently generate mouse models by microinjecting mRNA/sgRNA of enDelIscB and enDelIscB-T5E into mouse embryos. Collectively, our work presents a set of enDelIscB-based miniature genome-editing tools with great potential for diverse applications in vivo. Cas9-based genome editing tools face challenges for efficient in vivo delivery due to their large size. Here, the authors present a set of compact genome-editing tools engineered from a CRISPR-associated IscB system which exhibit robust editing efficiency in human cells and mouse embryos.