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Journal articleCastets J, Buridan M, Toboso Moreno I, et al., 2026,
A dual phospholipase system instructs membrane hydrolysis during the final stages of plant autophagy.
, Nat Commun, Vol: 17Autophagy is a conserved intracellular catabolic process, critical for plant stress tolerance. Upon their delivery in the vacuole, how autophagic bodies containing cargo are hydrolyzed to warrant autophagy degradation remains unclear in multicellular organisms. Here, we found that two Arabidopsis phospholipases, LCAT4 and LCAT3, traffic to the vacuolar lumen and converge on autophagic bodies through fundamentally different routes. While LCAT4 directly binds ATG8 and uses autophagy as a transport system to reach the vacuole prepackaged within autophagosomes, LCAT3 traffics to the lytic compartment independently of autophagosome formation. Knocking out both genes causes an accumulation of autophagic bodies accompanied with a reduction in autophagy degradation. In vivo reconstitution demonstrated that LCAT3 can hydrolyse the membrane of autophagic bodies, enabling the activity of LCAT4 to enhance this process. Together, this work sheds light on the vacuolar stages of autophagy, showing that plants have evolved a multi-component pathway for the efficient disruption of autophagosomal membranes as a critical step for the completion of the autophagy pathway.
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Journal articleTan WY, Lee TY, Tan KB, et al., 2026,
Developing and validating an electronic health record-embedded AI model for managing multimorbid hospitalisation risk in patients with chronic RESpiratory disease (AiRES): a study protocol.
, BMJ Open, Vol: 16BACKGROUND: Chronic respiratory diseases (CRDs), such as asthma and chronic obstructive pulmonary disease (COPD), are heterogeneous conditions with a high multimorbidity burden. However, existing risk assessment instruments prioritise physiological measures while overlooking systemic comorbidities. We aim to develop and validate an electronic health record (EHR)-embedded artificial intelligence (AI) model-AiRES (AI in patients with RESpiratory disease)-to predict the 30-day, 90-day and 180-day risks of all-cause and index-disease hospitalisations. This model represents a first step towards a clinical decision support tool for personalised multimorbidity management in patients with CRD. METHOD AND ANALYSIS: Patients aged ≥18 years with a validated case definition of asthma and COPD will be identified from Singapore health administrative data (2012-2020). Candidate predictors will include age, sex, ethnicity, housing type, and comorbidities, measured across multiple care settings as visit frequency, grouped at quarterly intervals in Year 1 and annually for Years 2 and 3 over a 3-year lookback window. We will predict 30-day, 90-day, and 180-day risks of (1) all-cause and (2) asthma/COPD-specific hospital admissions using up to five randomly selected index dates per individual. Three machine learning algorithms-logistic regression (LR) with Lasso regularisation, eXtreme Gradient Boosting, and Categorical Boosting-will be trained using 10-fold cross-validation (CV) with an ensemble feature selection strategy. The optimal model, selected based on performance and feature importance, will be benchmarked against two reference models: a full LR and a Zero-Inflated Negative Binomial regression with hospitalisation history as the sole predictor. Discrimination and calibration will be assessed using internal-external cluster-based and temporal CV. Clinical utility will be evaluated using decision curve analysis. ETHICS AND DISSEMINATION: This study obtained ethics approval fr
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Journal articleMak J, Feary J, Amaral A, et al., 2026,
Mortality in a cohort of Transport for London workers
, Scientific Reports, Vol: 16, ISSN: 2045-2322Transport workers face various occupational hazards, however long-term effects on mortality are less understood. Transport for London (TfL) employs almost 30,000 workers across a wide range of transport-based jobs and working environments. This study aimed to characterise mortality among TfL employees, and investigate long-term health outcomes.A retrospective cohort was formed using cause of death data from the TfL pension fund for employees working between 1960 and 2010. Workers were grouped by job title and Cox proportional hazard models were used to assess all-cause, respiratory, cardiovascular, and cancer mortality. Bus (hazard ratio HR: 1.17, 95% confidence interval CI 1.09-1.25) and London Underground (LU) (HR: 1.23, 95% CI 1.15-1.32) workers had significantly higher risks of all-cause, as well as respiratory, cardiovascular, and cancer mortality when compared to office workers. Mortality rates did not differ significantly between bus and LU workers, potentially due to shared occupational or lifestyle risk factors.In this large subway cohort study, mortality rates over 50 years were greater among bus and LU workers compared to office employees. However, findings should be interpreted cautiously due to limitations in data availability and unmeasured confounders. Future prospective studies should address these limitations by collecting detailed health and exposure data.
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Journal articleBoo A, Mehta H, Ledesma-Amaro R, et al., 2026,
Burden-aware feedback control of microbial consortia
, Nature Communications, Vol: 17, ISSN: 2041-1723Engineered microbial consortia are emerging as programmable systems capable of sensing and responding to their environment. However, maintaining defined community composition over time remains challenging, particularly in bioprocesses where growth conditions and metabolic burdens continuously shift. Here, we develop a burden-aware multicellular RNA-based feedback control system that stabilises coculture composition by coupling gene expression burden to growth regulation. The system integrates three modules: quorum sensing-based communication, an RNA-based comparator computing deviations from a target ratio, and tuneable growth regulation via heterologous expression burden or CRISPRi-mediated knockdowns. In a two-strain E. coli coculture, this architecture maintains stable coculture ratios over 24-hour batch cultures, recovers growth rates by up to 90% following burden-induced growth reduction, and increases protein production yields by up to 81% in the slower-growing strain. We achieve tuneability by adjusting RNA binding strength and quorum-sensing signal production. This work demonstrates that burden-driven growth control can be used to stabilise and tune synthetic microbial consortia.
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Journal articleJiang Q, Normand C, Beauchamp F, et al., 2026,
Structural composite battery: Reinforced carbon fibre electrodes within a porous polyethersulfone matrix
, Composites Science and Technology, Vol: 278, ISSN: 0266-3538A method to produce multifunctional structural battery composites comprising carbon fibre reinforced anodes and cathodes, and electrolyte filled bicontinuous polymer matrix is disclosed. Lithium iron phosphate (LFP) and lithium titanate (LTO) were deposited onto carbon fibres by electrophoretic deposition (EPD) to produce multifunctional cathodes and anodes, respectively. EPD allowed for an even coating of individual carbon fibres depositing 30 wt% of active materials with respect to carbon fibre current collectors. Carbon fibre reinforced cathode (LFP@CF), separator and anode (LTO@CF) were stacked and impregnated using polyethersulfone (PES) in N-methyl-2-pyrrolidone (NMP) solution; the PES was subsequently precipitated by non-solvent induced phase separation forming a porous high-performance polymer matrix within the stack. The porous matrix binds the carbon fibres and separator while providing sufficient openness for the electrochemical interface. The LFP@CF | separator | LTO@CF/PES assembly had an average Young's modulus of 27 ± 10 GPa and tensile strength of 282 ± 65 MPa. Structural battery composites possessed an energy density of 63 Wh/kg<inf>LFP</inf> or 2 Wh/kg<inf>battery</inf> at charge rate of 0.1C and were able to be cyclically dis/charged for more than 400 h.
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Journal articleZhao Y, Gu H, Ledesma-Amaro R, et al., 2026,
Magnetically actuated β-glucosidase immobilized on oak chips for enhanced wine aroma release.
, Food Res Int, Vol: 231β-Glucosidase (BGL) plays a key role in wine aroma enhancement by hydrolyzing glycosidic precursors; however, its application is limited by instability under harsh winemaking conditions. To address this, we developed an integrated biocatalytic system by immobilizing an acid-tolerant BGL onto functionalized magnetic oak chips (NFOak) via oriented Ni2+-histidine coordination. Comprehensive characterization confirmed the fabrication of a porous, magnetic cellulose scaffold. The immobilized BGL exhibited significantly enhanced stability against winemaking stresses (low pH, high ethanol) compared to the free enzyme. Furthermore, magnetic actuation of the biocomposite improved its hydrolytic performance, likely attributed to enhanced mass transfer. When applied to Chardonnay and Marselan wines, the magnetically actuated system effectively hydrolyzed glycosidic precursors, markedly increasing the concentrations of key volatile compounds-such as linalool and ethyl benzoate associated with fruity and floral aroma profiles. The treatment also induced subtle modulations in wine color and phenolic composition. Safety assessments confirmed no nickel leaching and oenologically acceptable iron levels. This work provides a sustainable and efficient strategy for controllable aroma modulation, combining the oenological benefits of a natural oak carrier with the operational controllability of magnetic actuation.
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Journal articleYang H, Yuen FW, Ryan MJ, et al., 2026,
Pathogenicity of Fusarium xylarioides, the Causal Pathogen of Coffee Wilt Disease, in Coffee Seedlings and an Alternate Host, Tomato Fruit
, Plant Pathology, Vol: 75, ISSN: 0032-0862Widespread crop cultivation has offered more opportunity for pathogens to evolve resulting in the emergence of new virulence and lifestyle patterns. Alternate hosts surrounding a crop field can also help pathogens survive, spread and provide inoculum for subsequent growing seasons. Examining pathogen hosts under laboratory conditions can explain disease emergence mechanisms. Here, we studied four strains of Fusarium xylarioides, a soil-borne, vascular fungal pathogen that causes coffee wilt disease collected over several decades and preserved in the CABI culture collection. We observed that these fungi can colonise tomato fruits as an alternate host to coffee and used these to test the pathogenicity of historic F. xylarioides and F. oxysporum f. sp. lycopersici strains. Expression of effector genes in F. xylarioides was compared in both the primary (coffee) and an alternate plant host (tomato). We used pathogenicity assays on coffee seedlings and tomato fruits by fungal staining, diagnostic end-point PCRs and real-time quantitative PCRs to verify the infection of both plant hosts. Passaging through coffee seedlings (infection followed by re-isolation of the pathogen) resulted in increased effector gene expression and enhanced pathogenicity. These findings indicate that alternate hosts may act as reservoirs for the pathogen, with implications for disease persistence and spread. A clearer understanding of plant disease cycles is therefore essential for the development of effective management strategies aimed at mitigating impacts on global food production.
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Journal articleSingh S, Darawshy F, Erlandson K, et al., 2026,
Lower airway dysbiosis in nontuberculous mycobacteria-positive bronchiectasis is associated with neutrophil extracellular trap-predominant severe phenotypes.
, Am J Respir Crit Care Med, Vol: 212, Pages: 936-951RATIONALE: The discoveries of neutrophilic inflammation and Pseudomonas-dominant pulmonary dysbiosis have helped pave the way for host-directed therapy in bronchiectasis. Substantial knowledge gaps still remain about the interplay between neutrophilic signatures and microbes in nontuberculous mycobacterial lung disease (NTM-LD), a phenotypically diverse lung infection that is increasingly prevalent in the United States and other parts of the world. OBJECTIVES: To evaluate the lower airway microbiota and neutrophilic traits in NTM-negative (NTM-) and NTM-positive (NTM+) bronchiectasis. METHODS: 16S rRNA gene sequencing, cell counts, and neutrophil extracellular trap (NET) immunoassays were performed on bronchoscopic lower airway samples in 200 bronchiectasis subjects (108 NTM-, 92 NTM+). A preclinical model of oral commensal microaspiration and NTM infection was used to profile the murine lower airways with flow cytometry and a NET assay. MEASUREMENTS AND MAIN RESULTS: Lower airways of NTM+ bronchiectasis patients were enriched with Mycobacterium and oral commensals (eg, Veillonella, Prevotella, and Streptococcus). NET levels were higher in NTM+ BAL fluid. Mycobacterium and oral commensals co-occurred with NET and neutrophils in network studies. Distinct oral commensal taxa were associated with severe disease phenotypes such as cavitary disease and exacerbators. In a murine microaspiration model, the combination of oral commensals and Mycobacterium led to a sustained proinflammatory immune response marked by an increase in Th17 cells, γδT cells, and PD-1+ T lymphocytes as well as higher NET levels. CONCLUSIONS: Our analyses showed that distinct microbiome features beyond the primary pathogen can contribute to neutrophilic inflammation and severe disease phenotypes in bronchiectasis/NTM-LD.
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Journal articleButler L, Awan AR, Ellis T, et al., 2026,
Engineering non-ribosomal peptide synthesis: tuning the antibiotics engine of the microbial world.
, Crit Rev Biotechnol, Vol: 46, Pages: 501-521Non-Ribosomal Peptide Synthetases produce chemically diverse peptides in nature, many of which have antimicrobial properties, providing an opportunity to use synthetic biology to fine tune them for pharmaceutical applications. Major challenges remain with total and semi-synthesis of these complex peptides with specific bioengineering methodologies being developed to increase low yields and enhance bioactivity. Here we review major advances in engineering non-ribosomal peptides with a focus on improvements made to achieve better yield and bioactivity. This can be achieved through: engineering precursor metabolites, altering metabolic flux, introducing strong promoters and regulators, and redirecting metabolism to biosynthetic gene clusters which can then be expressed natively or heterologously. We also review glycopeptide antibiotics as a promising opportunity for engineering through synthetic biology for the biosynthesis of novel non-ribosomal peptides.
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Journal articleVerweij PE, Alastruey-Izquierdo A, Amilon K, et al., 2026,
Closing the gap on antifungal resistance.
, Nat Med, Vol: 32, Pages: 1586-1591
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