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Journal articleSun T, Sun M-L, Lin L, et al., 2026,
Combining multiplex metabolic engineering with adaptive evolution strategies for high-level succinic acid production in Yarrowia lipolytica
, Synthetic and Systems Biotechnology, Vol: 11, Pages: 48-58, ISSN: 2405-805XSuccinic acid, an essential platform chemical with extensive utility in biodegradable materials, pharmaceuticals, and the food industry, faces challenges of high energy consumption and environmental pollution in traditional chemical synthesis. Here, we employed multiplex metabolic engineering and adaptive laboratory evolution to enhance succinic acid biosynthesis in Yarrowia lipolytica. By attenuating succinate dehydrogenase (Sdh) activity, mitigating by-product accumulation, and enhancing the succinate synthesis pathway, engineered strains showed efficient succinic acid production from glycerol. The titer reached 130.99 g/L under unregulated pH conditions, translating to a yield of 0.35 g/g and a productivity of 0.70 g/(L·h). Subsequently, transporter engineering and adaptive evolution strategies were applied to enhance glucose utilization for succinic acid synthesis, yielding an evolved strain that eliminated the growth lag phase and produced 106.68 g/L succinic acid from glucose, which translated to a yield of 0.32 g/g and a productivity of 0.64 g/(L·h). Additionally, transcriptomic analysis and inverse metabolic engineering revealed that 4-hydroxyphenylpyruvate dioxygenase (4-Hppd) in the tyrosine degradation pathway partially restored the growth of Sdh-deficient strains on glucose, offering new insights for subsequent succinic acid biomanufacturing using Y. lipolytica.
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Journal articleRafieenia R, Fu J, Hapeta P, et al., 2026,
Advancing arabinose-based bioproduction in Yarrowia lipolytica by integrating metabolic engineering and adaptive laboratory evolution
, Metabolic Engineering, Vol: 94, Pages: 15-23, ISSN: 1096-7176The oleaginous yeast, Yarrowia lipolytica has gained interest as a biotechnological chassis to produce foods, chemicals, pharmaceuticals, and biofuels. To reduce production costs and sustainability, inexpensive and abundant feedstocks such as lignocellulose must be used for bioproduction. Since lignocellulosic biomass contains components that cannot be utilised by Y. lipolytica, it is important to use engineering biology to enable their utilisation. L-arabinose is the second most abundant pentose in lignocellulose after xylose. However, it has received much less attention than xylose as a bioresource. In the present study, we first engineered Y. lipolytica to grow on L-arabinose as the sole carbon source. We used several wild-type and engineered strains to express the multigene arabinose cassette. Second, we used adaptive laboratory evolution to improve the utilisation of arabinose by the engineered strains. Third, we enabled the production of β-carotene from arabinose by expressing a β-carotene cassette in the evolved strain. Using minimal YNB medium supplemented with 20 g/l of arabinose as the sole carbon source resulted in the complete utilisation of L-arabinose within 120 h. In bioreactors, a β-carotene production of 418.89 mg/l was achieved with the complete utilisation of 60 g/l of L-arabinose. This study is the first to engineer L-arabinose utilisation in Y. lipolytica, opening new avenues for biomanufacturing using alternative carbon sources.
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Journal articleWang Y, Jiang Q, Vorlaufer D, et al., 2026,
Application of vitrimer-based sizing agent onto carbon fibres through thiol-ene photo-polymerisation
, COMPOSITES PART A-APPLIED SCIENCE AND MANUFACTURING, Vol: 202, ISSN: 1359-835X -
Journal articleAlmousa HA, De Luca HG, Anthony DB, et al., 2026,
Uniform and scalable carbon nanotube growth on carbon fibers: insights from experimental dynamic snapshots and computational fluid dynamics
, Carbon, Vol: 248, ISSN: 0008-6223Carbon nanotube (CNT) grafted carbon fibers (CFs) are promising for multifunctional composites (CFRPs) but remain limited by scalability, non-uniform growth, and degradation of fiber tensile strength. This paper reports a continuous spool-to-spool chemical vapor deposition (CVD) process that achieves uniform CNT growth throughout 12k CF tows while preserving fiber tensile properties. The uniformity of CNT coverage, over meters of length and across thousands of fibers, was objectively established via a multi-length scale characterization protocol, combining machine learning-based SEM classification with macroscopic measurements of BET-based specific surface area (SSA) and gravimetric CNT content. Microscopic and macroscopic measurements are independently self-consistent. To understand and optimize CNT growth, a new dynamic snapshot method was developed and combined with steady-state computational fluid dynamics (CFD) modelling to resolve the spatial evolution of catalyst activation, nucleation, and CNT growth kinetics as a function of reactor temperature and species concentrations. These insights informed targeted modifications to gas flow and temperature conditions, enabling reproducible CNT growth at 550 °C. Under optimized CVD conditions, the CFs were grafted with a CNT corona of 850 nm in length, corresponding to a loading of 2.9 wt% on the fibers, which led to a ten-fold increase in SSA (5.35 m2 g−1). The process was shown to be stable for extended lengths (>50 m) and reproducible across multiple runs, establishing a scalable route for integrating CNT-grafted CFs into conventional manufacturing. This experimental-computational framework provides a rational approach toward high-performance multifunctional, hierarchical CFRPs.
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Journal articleStewart I, John A, Bin L, et al., 2026,
Residual lung abnormality following COVID-19 hospitalisation is characterised by biomarkers of epithelial injury
, EBioMedicine, Vol: 124, ISSN: 2352-3964Some survivors of acute COVID-19 infection have long-term symptoms that could suggest ongoing lung impairment. Searches performed in MEDLINE and Embase for SARS-COV-2 studies with radiological lung follow-up estimated that 50% of participants had inflammatory patterns and 29% had fibrotic patterns at a median of 3 months post infection. Analysis of the UK nationwide Post-hospitalisation COVID-19 Study at 5-months follow-up suggested that up to 11% of people discharged from hospital following COVID-19 infection were at-risk of radiological residual lung abnormalities, such as ground glass opacity and reticulation. In people with pulmonary fibrosis, these radiological patterns are often consistent with persistent epithelial lung injury. Biomarker studies have identified associations with COVID-19 severity, however there are few studies that explore the relationship between biomarkers of epithelial injury and parenchymal lung abnormalities post-hospitalisation.
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Journal articleGreenland JR, Perch M, Halloran K, et al., 2026,
Considerations for Endpoints in Lung Transplant Clinical Trials: Perspective on the ISHLT Consensus Statement.
, J Heart Lung Transplant, Vol: 45, Pages: 168-171 -
Journal articleGreenland JR, Perch M, Halloran K, et al., 2026,
Considerations for Endpoints in Lung Transplant Clinical Trials: An ISHLT Consensus Statement.
, J Heart Lung Transplant, Vol: 45, Pages: e104-e128Clinical trials in lung transplantation have been hindered by a lack of clarity on the formulation and significance of endpoints for evaluating therapeutic efficacy. To address this challenge, a multidisciplinary working group from the International Society for Heart and Lung Transplantation developed consensus recommendations on endpoints beyond mortality. These endpoints include primary graft dysfunction (PGD), chronic lung allograft dysfunction (CLAD), acute cellular rejection (ACR), antibody-mediated rejection (AMR), immunosuppression-related complications, patient-reported outcomes (PROs), and pediatric-specific considerations. For each endpoint, a subgroup reviewed measurement best practices, assessed links to clinical benefit, and evaluated the evidence supporting their utility in clinical trial settings. Consensus was established through a Delphi process involving three rounds of voting. This document provides practical guidance for operationalizing these endpoints and outlines their optimal use in clinical trials. By standardizing trial design, these recommendations aim to accelerate the development of urgently needed therapies to improve lung transplantation outcomes.
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Journal articleMolyneaux PL, Mogulkoc N, Gunen H, et al., 2026,
Oral Nalbuphine in Idiopathic Pulmonary Fibrosis-Associated Cough: The CORAL Randomized Clinical Trial.
, JAMAIMPORTANCE: For patients with idiopathic pulmonary fibrosis (IPF), cough impairs quality of life; effective treatments for IPF-associated cough are needed. OBJECTIVE: To determine if nalbuphine extended release (ER), a κ opioid receptor agonist and μ-opioid receptor antagonist, decreases cough compared with placebo in patients with IPF-associated cough. DESIGN, SETTING, AND PARTICIPANTS: In this randomized, double-blind, placebo-controlled phase 2b trial conducted at 52 sites in 10 countries, patients with IPF, chronic cough for at least 8 weeks, and a Cough Severity Numerical Rating Scale (0, no cough; 10, worst possible cough) score of 4 or higher were enrolled from February 2024 to February 2025, with last follow-up in April 2025. Statistical analyses were conducted from May to August 2025. INTERVENTION: Patients were randomized 1:1:1:1 to receive nalbuphine ER at doses of 27 mg, 54 mg, or 108 mg or placebo twice daily for 6 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the relative change from baseline in 24-hour cough frequency (coughs/h), measured with a digital cough monitor, for nalbuphine ER compared with placebo at week 6. The key secondary outcome was the relative change from baseline in the patient-reported cough frequency (Evaluating Respiratory Symptoms in IPF cough subscale; scores range from 0-4, lower scores indicate lesser cough frequency) at week 6. RESULTS: Of the 223 patients screened, 165 were randomized (42, 43, 40, and 40 to receive nalbuphine ER 27 mg, 54 mg, and 108 mg, and placebo, respectively) and 160 were included in the primary analysis (median age, 71 [range, 51-85] years; 28.5% female). The baseline mean (SD) cough count was 28.3 (27.4) coughs/h. In the nalbuphine ER 27 mg, 54 mg, and 108 mg twice-daily groups, the mean relative decrease in the cough count and the absolute decrease in coughs/h were 47.9% (from 24.6 to 11.9; P = .008), 53.4% (from 28.0 to 14.9; P < .001), and 60.2%
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Journal articleYousefi N, Tao H, Anthony DB, et al., 2026,
Scale matters: a perspective on structural hierarchical carbon fibre composites incorporating carbon nanotubes
, Composites Science and Technology, ISSN: 0266-3538Composites have long played a vital role in material science due to their lightweight, stiff, strong, and durable construction. Composites consist of at least two complementary materials, typically comprising reinforcing elements, prominently carbon or glass fibres, held in place by a surrounding polymer matrix. Conventional fibre composites already display a structural hierarchy from fibres within tows, to plies, to laminates forming large-scale structures. The term “hierarchical composites” specifically refers to materials that integrate reinforcements spanning additional length scales, down to the molecular range, most notably nanoscale reinforcements that complement microscale fibres. Natural structural materials rely extensively on hierarchical motifs to maximise performance, though using constituents limited by abundance and ambient aqueous processing. Technical hierarchical composites are broadly inspired by natural multiscale systems, sometimes implementing specific mechanisms from nature in new material classes. In hierarchical composites, the largest reinforcement, fibres, dominate in-plane mechanical properties. In contrast, nanoscale reinforcements may address matrix-dominated responses by, for example, improving shear properties that control stress transfer and kink band initiation, introducing additional toughening mechanisms to limit debonding or delamination, and providing direct reinforcement, particularly through-thickness. Nanomaterials can provide other benefits, such as improved fatigue life, acoustic damping, and solvent/fire resistance. The addition of nanomaterials may also imbue composites with multifunctionality, obviating other constituents or components and reducing system weight. We critically discuss the progress in developing hierarchical fibre reinforced carbon nanotube composites over the past decade and provide insight into manufacturing and their structural and functional performance.
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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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