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Journal articleLedesma Amaro R, 2026,
Single cell profiling framework reveals metabolic subpopulations as drivers of bioproduction heterogeneity
, Nature Communications, Vol: 17, ISSN: 2041-1723Heterogeneity within clonal cell populations remains a critical bottleneck within bioprocess engineering, notably by undermining bioproduction yields. Efforts to mitigate its impact have, however, been hampered by technological difficulties quantifying metabolism at the single-cell level. Here, we propose a framework based on single-cell biosensor analysis that enables robust characterisation of cell's metabolic states, leveraging it to detect and isolate isogeneic heterogeneity in response to environmental perturbations and within microbial cell factories. We identify acute and gradual glucose depletion to induce differentiation of metabolically distinct subpopulations and reveal these subpopulations to exhibit differential production capabilities, with lower intracellular pH subpopulations exhibiting enhanced product accumulation within violacein-producing strains but reduced yields within lycopene-producing strains. Lastly, we highlight galactose cultivation as a method to modulate subpopulation dynamics towards higher-producing lycopene phenotypes. Altogether, our research provides insights into subpopulation differentiation and establishes promising avenues for the engineering of more robust and higher-producing strains.
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Journal articleHowlett P, Durairaj A, Lesosky M, et al., 2026,
The diagnostic accuracy of chest Xray screening for silicosis: a systematic review, meta-analysis and modelling study
, Occupational and Environmental Medicine, ISSN: 1351-0711Objectives: Chest Xray (CXR) is widely used for silicosis diagnosis, despite concerns egarding sensitivity. We investigated the diagnostic accuracy of CXR for silicosis screening compared to computed tomography (CT), high-resolution CT (HRCT) and autopsy, and modelled the relationship between CXR sensitivity and disease severity. Methods: Medline, Embase, Scopus, and Web of Science databases were searched on 2nd July 2024 (Prospero registration: CRD42024513830). Meta-analyses were performed by reference standard and at increasing reference test severity cut-offs. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool assessed risk of bias. In scenarios of fixed and relative sensitivity, according to disease severity, we estimated missed silicosis cases and the number needed to screen (NNS) in hypothetical populations of low (5%), medium (15%) and high (30%) silicosis prevalence. Results: Twenty studies included 2156 participants and 1105 silicosis cases. CXR had moderate sensitivity (0.76; 95% confidence interval (CI): 0.63-0.86, I2=84%) and high specificity (0.89, 95% CI: 0.77-0.95, I2=57%) compared to HRCT in 12 studies, and low sensitivity (0.50, 95% CI: 0.45-0.55, I2=0%) and high specificity (0.91, 95% CI: 0.87-0.93, I2=20%) compared to autopsy in two studies. CXR sensitivity increased with higher reference test severity cut-offs. Clinically relevant numbers of cases were missed in fixed and relative sensitivity scenarios; increased prevalence and less severe disease resulted in more missed cases and a lower NNS.Conclusions: Silicosis severity and reference test type both plausibly influence CXR sensitivity. Assuming either fixed or relative sensitivity results in missed silicosis cases. Judicious HRCT screening is likely to improve case detection.
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Journal articleChen H, Peng H, Ellis T, et al., 2026,
Programmable cell–cell adhesion in synthetic yeast communities for improved bioproduction
, Nature Chemical Biology, ISSN: 1552-4450In multicellular systems, engineering-controlled cell–cell adhesion and metabolic interdependence are vital for developing complex functionalities. This study introduces a yeast synthetic toolbox for modular cell–cell adhesion and cocultures, aiming to overcome the limitations of existing approaches that lack genetic specificity and control. First, a model yeast strain 007Δ is created with seven main flocculation and agglutination genes removed, providing a clean background for synthetic adhesion systems. Then, three distinct adhesion pair systems—Strategy 1, Strategy 2.1 and Strategy 2.2—are established involving yeast flocculation and agglutination proteins and yeast surface display systems. In addition, a quantitative assessment is conducted on the adhesive specificity and strength, alongside the capability of synthetic adhesion to generate patterns. Finally, we successfully demonstrate enhanced bioproduction of the high-value food antioxidant, resveratrol, utilizing synthetic cocultures coupled with cell adhesion systems. We anticipate that this toolkit will emerge as a valuable resource for diverse applications in synthetic biology and biomanufacturing.
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Journal articleMcKenzie J, Carter C, Jackson MM, et al., 2026,
Mechanisms driving immunopathogenesis of viral exacerbations in chronic respiratory disease.
, ThoraxBACKGROUND: Exacerbations are major causes of morbidity in individuals with chronic respiratory diseases such as chronic obstructive pulmonary disease, asthma and bronchiectasis. Increasing evidence implicates respiratory viruses as predominant triggers, though the underlying immunopathogenic mechanisms remain poorly understood. NARRATIVE: This review synthesises current knowledge on the interplay between viral pathogens at the airway epithelial barrier, including structural and immunological mechanisms that may dysregulate antiviral immunity in chronic respiratory diseases. Furthermore, we discuss how perturbations in the respiratory microbiome, characterised by reduced microbial diversity, can modulate host antiviral immune defences. CONCLUSIONS: Collectively, these interconnected factors create a permissive environment predisposing to viral infection and exacerbations in chronic respiratory diseases. Understanding the complex interactions between airway structure, interferon-mediated antiviral responses, inflammation and microbiota is essential for developing targeted therapies to effectively manage virus-induced exacerbations and reduce disease burden.
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Journal articleWorland AM, Xu VA, Duran MF, et al., 2026,
Staying productive under pressure: systems evaluations of β-carotene production in Yarrowia lipolytica under continuous fermentation
, Trends in Biotechnology, Vol: 44, Pages: 154-169, ISSN: 0167-7799Scaling biomanufacturing from laboratory to industrial scale poses significant challenges, especially for continuous fermentation. This study investigates these challenges using a β-carotene-producing Yarrowia lipolytica strain. Through fermentation experiments and proteomics, we have assessed how fermentation modes, carbon sources, dissolved O2, and media composition influence long-term bioproduction. In shaking flask subcultures, the strain maintained β-carotene production for over ~30 generations. However, in continuous fermentations, subpopulation shifted toward faster-growing low-producers, leading to significant production losses within just ~18 growth generations. This process was accelerated by O2 limitation and high bioreactor dilution rates. Using canola oil as a carbon source increases population heterogeneity but enhances β-carotene biosynthesis and prolongs production compared with glucose-based media. Kinetic modeling suggests that strains optimized for the highest production in laboratory settings may be less robust in industrial environments, where suboptimal yet faster-growing variants gain a competitive edge under prolonged stress and ultimately shape overall continuous fermentation performance.
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Journal articleXu C, Wang Z, Sun L, et al., 2026,
Sustainable bioprocess for D-chiro-inositol production via metabolic engineering of <i>Saccharomyces cerevisiae</i>
, CHEMICAL ENGINEERING JOURNAL, Vol: 527, ISSN: 1385-8947 -
Journal articleMaher T, Jenkins G, Saini G, et al., 2026,
Prospective study of fibrosis in the lung endpoints (PROFILE): characteristics of an incident cohort of patients with idiopathic pulmonary fibrosis
, BMJ Open Respiratory Research, Vol: 13, ISSN: 2052-4439Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease. The PROFILE study was a prospective, observational cohort study designed to better define the natural history of IPF, understand disease biology and identify biomarkers to support disease management and enhance clinical trial design.Methods: Individuals with an incident diagnosis of IPF were recruited between 2010 and 2017 across two co-ordinating centres in the UK. Demographics, clinical measurements and blood samples were obtained at baseline, and 1, 3, 6, 12, 24, 36 months. Disease progression events were defined as death or relative FVC decline>10% at 12 months. Survival estimates were modelled using cox proportional hazards; longitudinal lung function decline was estimated using mixed effect models, specified with restricted cubic splines, a random intercept for participant and random effect for study visit. All models were adjusted for baseline age, sex and continuous baseline percent predicted forced vital capacity (ppFVC).Results: A total of 632 participants were recruited, 77.1% were male and mean age at enrolment was 70.4 years (SD 8.4). Mean baseline ppFVC was 79.5% (SD 19.2), mean percent predicted DLCO (ppDLCO) was 45.7% (SD 15.1). A total of 304 (48.1%) participants met disease progression criteria at 1 year. Median survival was 3.7 years (95%CI 3.3; 4.0). More severe baseline physiology, 12-month relative lung function decline ≥10%, older age, and short telomeres were independent risk factors for mortality. Twelve-month estimated change in ppFVC was -5.28% (95%CI -6.34; -4.22) with an average FVC decline of 186.9ml (95%CI -225.4.0; -148.5), 12-month estimated change in ppDLCO was -3.35% (95%CI -4.30; -2.40).Conclusion: The PROFILE cohort confirms that untreated, IPF is inexorable progressive and inevitably fatal with a poor median survival from diagnosis.
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Journal articleMartin AK, Mercier O, Bottiger B, et al., 2026,
ISHLT Consensus Statement on the Perioperative use of ECLS in Lung Transplantation: Part III: Postoperative Considerations
, JOURNAL OF HEART AND LUNG TRANSPLANTATION, Vol: 45, Pages: e63-e81, ISSN: 1053-2498- Cite
- Citations: 3
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Journal articleNarayana JK, Chotirmall SH, 2026,
Reply: Methodological clarifications of AI-powered research trend analytics in bronchiectasis.
, Eur Respir J, Vol: 67 -
Journal articleReed AK, Mercier O, Behr J, et al., 2026,
ISHLT Consensus Statement on the Perioperative use of ECLS in Lung Transplantation: Part I: Preoperative Considerations
, JOURNAL OF HEART AND LUNG TRANSPLANTATION, Vol: 45, Pages: e1-e34, ISSN: 1053-2498- Cite
- Citations: 1
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