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  • Journal article
    Barkan-Öztürk H, Verdross P, Bismarck A, 2024,

    Macroporous lignin adsorbents: A bio-sourced tool kit to defuse the Cr(VI) threat in wastewater

    , Journal of Environmental Chemical Engineering, Vol: 12

    Amino-functionalised (triethylenetetramine) macroporous lignin monoliths were produced by curing an emulsion template containing untreated kraft black liquor with oxirane-crosslinkers. These lignin-based adsorbents were tested for the removal of Cr(VI) from water and synthetic waste water. A one-pot rout for their production is presented and their chemical and physical nature was investigated. Produced monoliths were tested in static and continuous adsorption experiments and chromium removal from water and synthetic wastewater was quantified via UV–vis spectroscopy. The nitrogen content of functionalised lignin monoliths reached up to 5.1 wt%, leading to adsorption capacities of up to 897 mg/g at pH = 2, as compared to non-functionalised lignin monoliths with a maximum adsorption capacity of 117 mg/g. The adsorption capacity of lignin monoliths produced is amongst the highest of bio-based materials presented in the literature.

  • Journal article
    sun M, Xiong Gao A, Liu X, Ledesma Amaro R, Bai Zet al., 2024,

    Microbial conversion of ethanol to high-value products: progress and challenges

    , Biotechnology for Biofuels and Bioproducts
  • Journal article
    Feary J, Devaraj A, Burton M, Chua F, Coker RK, Datta A, Hewitt RJ, Kokosi M, Kouranos V, Reynolds CJ, Ross CL, Smith V, Ward K, Wickremasinghe M, Szram Jet al., 2024,

    Artificial stone silicosis: a UK case series.

    , Thorax

    Silicosis due to artificial stone (AS) has emerged over the last decade as an increasing global issue. We report the first eight UK cases. All were men; median age was 34 years (range 27-56) and median stone dust exposure was 12.5 years (range 4-40) but in 4 cases was 4-8 years. One is deceased; two were referred for lung transplant assessment. All cases were dry cutting and polishing AS worktops with inadequate safety measures. Clinical features of silicosis can closely mimic sarcoidosis. UK cases are likely to increase, with urgent action needed to identify cases and enforce regulations.

  • Journal article
    Calamita E, Liu WH, Ogger PP, Griffin L, Michalaki C, Murphy F, Worrell J, McCarthy C, Agro A, Hertz M, Maher TM, Lloyd CM, Molyneaux P, Kumar V, Byrne AJet al., 2024,

    Type 1 Invariant Natural Killer T Cells Drive Lung Fibrosis.

    , Am J Respir Crit Care Med, Vol: 210, Pages: 521-523
  • Journal article
    Thillai M, Oldham JM, Ruggiero A, Kanavati F, McLellan T, Saini G, Johnson SR, Ble F-X, Azim A, Ostridge K, Platt A, Belvisi M, Maher TM, Molyneaux PLet al., 2024,

    Deep Learning-based Segmentation of Computed Tomography Scans Predicts Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis.

    , Am J Respir Crit Care Med, Vol: 210, Pages: 465-472

    Rationale: Despite evidence demonstrating a prognostic role for computed tomography (CT) scans in idiopathic pulmonary fibrosis (IPF), image-based biomarkers are not routinely used in clinical practice or trials. Objectives: To develop automated imaging biomarkers using deep learning-based segmentation of CT scans. Methods: We developed segmentation processes for four anatomical biomarkers, which were applied to a unique cohort of treatment-naive patients with IPF enrolled in the PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study and tested against a further United Kingdom cohort. The relationships among CT biomarkers, lung function, disease progression, and mortality were assessed. Measurements and Main Results: Data from 446 PROFILE patients were analyzed. Median follow-up duration was 39.1 months (interquartile range, 18.1-66.4 mo), with a cumulative incidence of death of 277 (62.1%) over 5 years. Segmentation was successful on 97.8% of all scans, across multiple imaging vendors, at slice thicknesses of 0.5-5 mm. Of four segmentations, lung volume showed the strongest correlation with FVC (r = 0.82; P < 0.001). Lung, vascular, and fibrosis volumes were consistently associated across cohorts with differential 5-year survival, which persisted after adjustment for baseline gender, age, and physiology score. Lower lung volume (hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.96-0.99]; P = 0.001), increased vascular volume (HR, 1.30 [95% CI, 1.12-1.51]; P = 0.001), and increased fibrosis volume (HR, 1.17 [95% CI, 1.12-1.22]; P < 0.001) were associated with reduced 2-year progression-free survival in the pooled PROFILE cohort. Longitudinally, decreasing lung volume (HR, 3.41 [95% CI, 1.36-8.54]; P = 0.009) and increasing fibrosis volume (HR, 2.23 [95% CI, 1.22-4.08]; P = 0.009) were associated with differen

  • Journal article
    Fu J, Zaghen S, Lu H, Konzock O, Poorinmohammad N, Kornberg A, Ledesma-Amaro R, Koseto D, Wentzel A, Di Bartolomeo F, Kerkhoven EJet al., 2024,

    Reprogramming Yarrowia lipolytica metabolism for efficient synthesis of itaconic acid from flask to semipilot scale.

    , Sci Adv, Vol: 10

    Itaconic acid is an emerging platform chemical with extensive applications. Itaconic acid is currently produced by Aspergillus terreus through biological fermentation. However, A. terreus is a fungal pathogen that needs additional morphology controls, making itaconic acid production on industrial scale problematic. Here, we reprogrammed the Generally Recognized As Safe (GRAS) yeast Yarrowia lipolytica for competitive itaconic acid production. After preventing carbon sink into lipid accumulation, we evaluated itaconic acid production both inside and outside the mitochondria while fine-tuning its biosynthetic pathway. We then mimicked the regulation of nitrogen limitation in nitrogen-replete conditions by down-regulating NAD+-dependent isocitrate dehydrogenase through weak promoters, RNA interference, or CRISPR interference. Ultimately, we optimized fermentation parameters for fed-batch cultivations and produced itaconic acid titers of 130.1 grams per liter in 1-liter bioreactors and 94.8 grams per liter in a 50-liter bioreactor on semipilot scale. Our findings provide effective approaches to harness the GRAS microorganism Y. lipolytica for competitive industrial-scale production of itaconic acid.

  • Journal article
    Heggie A, Thurston TLM, Ellis T, 2024,

    Microbial messengers: nucleic acid delivery by bacteria.

    , Trends Biotechnol

    The demand for diverse nucleic acid delivery vectors, driven by recent biotechnological breakthroughs, offers opportunities for continuous improvements in efficiency, safety, and delivery capacity. With their enhanced safety and substantial cargo capacity, bacterial vectors offer significant potential across a variety of applications. In this review, we explore methods to engineer bacteria for nucleic acid delivery, including strategies such as engineering attenuated strains, lysis circuits, and conjugation machinery. Moreover, we explore pioneering techniques, such as manipulating nanoparticle (NP) coatings and outer membrane vesicles (OMVs), representing the next frontier in bacterial vector engineering. We foresee these advancements in bacteria-mediated nucleic acid delivery, through combining bacterial pathogenesis with engineering biology techniques, as a pivotal step forward in the evolution of nucleic acid delivery technologies.

  • Journal article
    Howlett P, Gan J, Lesosky M, Feary Jet al., 2024,

    Relationship between cumulative silica exposure and silicosis: a systematic review and dose-response meta-analysis.

    , Thorax

    BACKGROUND: Silicosis, a chronic respiratory disease caused by crystalline silica exposure, is a persistent global lung health issue. No systematic review of the relationship between cumulative respirable crystalline silica (RCS) exposure and silicosis exists. UK exposure limits are currently under review. We therefore performed a systematic review and dose-response meta-analysis of this relationship. METHODS: Web of Science, Medline and Embase were searched on 24 February 2023. Studies of radiographic, autopsy or death certificate silicosis, with an estimated average follow-up of over 20 years since first employment, were included. Cumulative silicosis risk methods were compared. The relative risks (RR) of silicosis at increasing cumulative exposures were calculated and used to estimate the absolute risk reduction (ARR). RESULTS: Eight eligible studies, including 10 cohorts, contributed 8792 cases of silicosis among 65 977 participants. Substantial differences in cumulative risk estimates between methodologies exist. Using the same method, we observed higher cumulative silicosis risks among mining compared with non-mining cohorts. A reduction from 4 to 2 mg/m³-years in cumulative RCS exposure corresponded to substantial risk reductions among miners (RR 0.23 (95% CI 0.18 to 0.29, I2=92.9%) with an ARR of 323 (95% CI 298 to 344) per 1000) and non-miners (RR 0.55 (95% CI 0.36 to 0.83, I2=77.0%) with an ARR of 23 (95% CI 9 to 33) per 1000). CONCLUSION: Despite significant heterogeneity, our findings support a reduction in permissible exposure limits from 0.1 mg/m3 to 0.05 mg/m³, particularly among mining populations. Further research is needed among non-miners as only two studies were eligible.

  • Journal article
    Chen W, Park Y-K, Studená L, Bell D, Hapeta P, Fu J, Nixon PJ, Ledesma-Amaro Ret al., 2024,

    Synthetic, marine, light-driven, autotroph-heterotroph co-culture system for sustainable β-caryophyllene production.

    , Bioresour Technol, Vol: 410

    Applying low-cost substrate is critical for sustainable bioproduction. Co-culture of phototrophic and heterotrophic microorganisms can be a promising solution as they can use CO2 and light as feedstock. This study aimed to create a light-driven consortium using a marine cyanobacterium Synechococcus sp. PCC 7002 and an industrial yeast Yarrowia lipolytica. First, the cyanobacterium was engineered to accumulate and secrete sucrose by regulating the expression of genes involved in sucrose biosynthesis and transport, resulting in 4.0 g/L of sucrose secretion. Then, Yarrowia lipolytica was engineered to efficiently use sucrose and produce β-caryophyllene that has various industrial applications. Then, co- and sequential-culture were optimized with different induction conditions and media compositions. A maximum β-caryophyllene yield of 14.1 mg/L was obtained from the co-culture. This study successfully established an artificial light-driven consortium based on a marine cyanobacterium and Y. lipolytica, and provides a foundation for sustainable bioproduction from CO2 and light through co-culture systems.

  • Journal article
    Meldrum OW, Donaldson GC, Narayana JK, Xaverius Ivan F, Jaggi TK, Mac Aogáin M, Finney LJ, Allinson JP, Wedzicha JA, Chotirmall SHet al., 2024,

    Accelerated Lung Function Decline and Mucus-Microbe Evolution in Chronic Obstructive Pulmonary Disease.

    , Am J Respir Crit Care Med, Vol: 210, Pages: 298-310

    Rationale: Progressive lung function loss is recognized in chronic obstructive pulmonary disease (COPD); however, no study concurrently evaluates how accelerated lung function decline relates to mucus properties and the microbiome in COPD. Objectives: Longitudinal assessment of mucus and microbiome changes accompanying accelerated lung function decline in patients COPD. Methods: This was a prospective, longitudinal assessment of the London COPD cohort exhibiting the greatest FEV1 decline (n = 30; accelerated decline; 156 ml/yr FEV1 loss) and with no FEV1 decline (n = 28; nondecline; 49 ml/yr FEV1 gain) over time. Lung microbiomes from paired sputum (total 116 specimens) were assessed by shotgun metagenomics and corresponding mucus profiles evaluated for biochemical and biophysical properties. Measurements and Main Results: Biochemical and biophysical mucus properties are significantly altered in the accelerated decline group. Unsupervised principal component analysis showed clear separation, with mucus biochemistry associated with accelerated decline, whereas biophysical mucus characteristics contributed to interindividual variability. When mucus and microbes are considered together, an accelerated decline mucus-microbiome association emerges, characterized by increased mucin (MUC5AC [mucin 5AC] and MUC5B [mucin 5B]) concentration and the presence of Achromobacter and Klebsiella. As COPD progresses, mucus-microbiome shifts occur, initially characterized by low mucin concentration and transition from viscous to elastic dominance accompanied by the commensals Veillonella, Gemella, Rothia, and Prevotella (Global Initiative for Chronic Obstructive Lung Disease [GOLD] A and B) before transition to increased mucus viscosity, mucins, and DNA concentration together with the emergence of pathogenic microorganisms including Haemophilus, Moraxella, and Pseudomonas (GOLD E). Conclusions: Mucus-microbiome associations evolve over time wi

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