ABSTRACT IgA nephropathy (IgAN), the most common primary glomerular disease, involves mucosa–kidney axis dysregulation, with gut dysbiosis increasingly implicated in its pathogenesis. Certain Escherichia coli ( E. coli ) strains harbour virulence‐associated features that promote intestinal colonization, barrier disruption and immune activation. Recent microbiome and metagenomic studies have reported an enrichment of E. coli in patients with IgAN, suggesting a potential link to the mucosa–kidney axis. Nevertheless, E. coli may contribute to IgAN through two major pathways. First, sustained LPS exposure may induce aberrant production of galactose‐deficient IgA1 (Gd‐IgA1) by stimulating B cells and activate the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages, thereby amplifying systemic and renal inflammation. Second, metabolic reprogramming is associated with increased circulating sphingosine‐1‐phosphate (S1P) and altered production of indole and trimethylamine (TMA); S1P may promote mesangial proliferation and fibrosis, whereas indole‐ and TMA‐related pathways may contribute to tubulointerstitial injury and chronic kidney disease (CKD) progression. Beyond conventional gut microbiota‐targeted interventions, emerging precision therapeutic strategies offer promising new directions for the etiological treatment of IgAN. This review summarizes E. coli virulence factors, pathogenesis, and host, environmental, and ecological factors driving its gut expansion in IgAN patients and outlines corresponding therapeutic strategies.
ABSTRACT The contemporary home remains trapped in a mechanistic paradigm of twentieth‐century resource consumption, where metabolic biological presence is considered irrelevant to the functioning of a building. Presenting the home as a conceptual vehicle for metabolically optimised living spaces in dense urban environments, this paper develops a conceptual framework of metabolic design patterns that enables the staged retrofit of bioreactors, from composters and fermenters to bioelectrical systems, into human‐occupied living spaces. By bringing circular resource processing into the heart of domestic life the principles for regenerative homes are established. Bioelectrical systems are given particular attention because they provide real‐time, connectable data through electricity as a medium for information, power, and chemical transformation simultaneously, forming a connective backbone for generating the metabolic design patterns. Three patterns are developed: Toilet as Hearth, Kitchen Garden, and Greywater Wetland, each integrating bioelectrical systems into the habitation programme to provide the respective architectural affordances. The framework proposes a staged retrofit pathway to implementation from passive sensing to neighbourhood metabolic exchange, supported by a conceptual anatomical atlas for diagnosing metabolic failures in established metabolic systems. This revaluation positions metabolic presence as a generative resource rather than a cost, directly addressing SDGs 6, 7, 9, 11 and 12.
ABSTRACT The filamentous fungus Penicillium rubens is well known as an industrial host for producing penicillin and also used as a promising chassis for secondary metabolite biosynthesis. Chromosomal position effect significantly influences the functional implementation of exogenous genetic modules, but it remains underexplored in filamentous fungi such as P. rubens . In this study, a PiggyBac ( PB ) transposon‐mediated mutagenesis library was constructed in P. rubens . High‐throughput sequencing confirmed a broadly distributed with moderate local hopping of PB insertions across this fungal genome. To characterize the genome position effect, two genomic loci libraries including low‐expression (P4) and high‐expression (P7) positions were obtained respectively by flow cytometry. Heterologous biosynthesis of the plant‐derived anthraquinone physcion in P. rubens , via targeted integration of its biosynthetic gene cluster (BGC) into the P7 genomic loci, substantially boosted the titre to a level significantly higher than that achieved via integration at the P4 loci, demonstrating a direct correlation between the integration locus and the secondary metabolite output. To our knowledge, this is the first systematic elucidation of chromosomal position effect on heterologous biosynthesis of secondary metabolites in P. rubens and it also provides an insight for rational selection of integration sites in filamentous fungi.
The Pseudomonas syringae complex (Psc) is a group of globally distributed phytopathogens responsible for substantial agricultural losses. Although bacteriophage-based biocontrol has shown promise against Psc, no studies have examined phages targeting blueberry-tropic Psc lineages. Here, we isolated phages infecting Psc strains from diseased highbush blueberry (Vaccinium corymbosum), and evaluated their suitability for biocontrol using a multi-stage screening pipeline incorporating host-range analysis, comparative genomics, environmental stability testing, in vitro antibacterial efficacy assays and ex planta validation. Twelve of the isolated phages exhibited favourable host-range characteristics. Genomic analyses revealed substantial phylogenetic diversity among these candidates but simultaneously identified multiple clonal groups, reducing the collection to eight non-redundant phages spanning five distinct genera. Candidate phages generally retained infectivity under environmentally relevant conditions and exhibited heterogeneous but largely favourable stability profiles. Planktonic killing assays uncovered considerable variation in antibacterial efficacy, but phage performance appeared to be driven by infection compatibility and host-specific factors rather than properties intrinsic to individual phages. Notably, the jumbo phage φ CB10 emerged as a particularly promising candidate due to its strong antibacterial activity (median GRC = 0.943), favourable environmental stability and unique genomic features. Cocktails containing the most effective candidates produced substantial and longitudinally sustained reductions in epiphytic colonization of detached blueberry leaves by Psc, exceeding five orders of magnitude at peak efficacy and demonstrating robust activity in a biologically relevant ex planta system. Importantly, in vitro antibacterial efficacy was predictive of performance in our ex planta model (r = 0.67; p = 0.0003), supporting the utility of tiered screening approaches for candidate selection. Taken together, these findings establish a framework for the systematic identification and evaluation of phages targeting Psc, and support the development of phage-based interventions for managing plant diseases.
