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Journal articleSun M, Gao AX, Ye B, et al., 2026, , Synthetic and Systems Biotechnology, Vol: 13, Pages: 37-49, ISSN: 2405-805X
Membraneless organelles (MLOs) formed through liquid-liquid phase separation (LLPS) constitute crucial dynamic microenvironments within cells, capable of selectively concentrating specific molecules and regulating biochemical reactions. Based on the working mechanisms of natural MLOs, researchers have designed and constructed various synthetic MLOs. These MLOs have been applied in regulating enzyme activity, optimizing metabolic pathways, regulating gene expression, producing recombinant proteins, and developing functional biomaterials. Here, we systematically summarized the design strategies, characterization techniques, and client protein recruitment methods for synthetic MLOs, and categorically reviewed their application progress in the biotechnology field. We also discussed current challenges faced in the practical applications of synthetic MLOs and future research directions. This review aims to provide theoretical guidance and practical reference for the design and application of LLPS-driven synthetic MLOs, thereby promoting their innovative development in synthetic biology and biotechnology.
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Journal articleZhao A, Jüstel JPM, Jones MP, et al., 2026, , Cleaner Materials, Vol: 21, Pages: 100407-100407, ISSN: 2772-3976
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Journal articleZhang B, Murali GG, Quitéria TFH, et al., 2026, , Composites Part B: Engineering, Vol: 323, ISSN: 1359-8368
An interleaving strategy for polymer matrix composite laminates is proposed to create a mechanical fuse allowing interlaminar damage to be localised in the interleaf, which can subsequently be repaired. To create the mechanical fuse, the laminates are interleaved with thermoplastic polymer films with suitable mechanical properties to act as a repairable weak link. Carbon fibre/epoxy laminates interleaved with polystyrene (PS) were investigated by three-point flexure and static indentation tests. In the three-point bending tests, shear–driven damage was observed in the interleaved region, and this damage was subsequently repaired by application of heat and pressure. After two damage-repair cycles, the stiffness was virtually fully recovered, and the shear strength restored to 88% of the pristine value. In the static indentation tests, the stiffness and damage onset force of the specimens recovered to 84% and 70% of the pristine values, respectively, after three damage-repair cycles.
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Journal articleYu Y, Lu R, Sun M-L, et al., 2026, , Metab Eng, Vol: 96, Pages: 80-91
Ricinoleic acid, an industrially high-value hydroxy fatty acid traditionally sourced from castor seed oil. However, plant-based production is plagued by challenges such as inherent toxicity, environmental risks, and unstable supply. Microbial biosynthesis provides a safer and more sustainable alternative, eliminating the need for land cultivation, shortens production cycles, and mitigates the toxicity risks associated with castor seed harvesting. Furthermore, microbial production of ricinoleic acid in the form of single cell oil (SCO) confers significant advantages over free fatty acid, including enhanced stability and reduced cytotoxicity. In this study, the oleaginous yeast Yarrowia lipolytica was metabolically rewired via a multi-pronged strategy: boosting the synthesis of oleoyl-CoA (the precursor of ricinoleic acid), mimicking plant acyl editing to refine phosphatidylcholine pool precursors, promoting the assembly of ricinoleic acid into storage triacylglycerols, and suppressing competing degradation pathways. Employing this integrated engineering approach, the final engineered strain YY-20 accumulated 729.4 mg/L of ricinoleic acid in shake flask cultures, accounting for 28.3% of total fatty acids. More notably, fed-batch fermentation in a bioreactor achieved a record-high ricinoleic acid titer of 6.0 g/L (comprising 26.1% of total fatty acids), accompanied by 22.8 g/L of SCO and a lipid content of 37.3% dry cell weight. These results demonstrate the efficacy of coordinated lipid pathway engineering in establishing Y. lipolytica as a robust microbial cell factory for hydroxy fatty acid production. The high SCO titer and efficient ricinoleic acid synthesis underscore the potential of this platform for the scalable industrial biomanufacturing of ricinoleic acid and other high-value unusual fatty acids.
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Journal articleFerrando-Marco M, Berger S, Barkoulas M, 2026, , Genetics
Asymmetric cell division in the epidermal stem cells of Caenorhabditis elegans, known as seam cells, relies on the Wnt/β-catenin asymmetry pathway to generate daughter cells with distinct fates. However, whether components of this pathway components are transcriptionally regulated during these divisions remains unclear. Here, we employ single molecule fluorescence in situ hybridisation to quantify mRNA distributions of key Wnt pathway components during L2 symmetric and asymmetric seam cell divisions. We find that transcripts encoding the negative regulators pry-1/Axin and apr-1/APC are enriched in posterior daughter cells, while those encoding the positive regulators sys-1/β-catenin, wrm-1/β-catenin, and lit-1/NLK, along with the transcription factor pop-1/TCF, are enriched in anterior daughter cells. Strikingly, molecular asymmetries are already evident following the L2 symmetric division, with anterior and posterior daughters exhibiting distinct levels of Wnt component expression and Wnt pathway activation. These mRNA distributions are surprising considering the established protein localisations that underpin the Wnt asymmetry model and suggest extensive post-divisional transcriptional regulation. We further demonstrate that pop-1 and pry-1 asymmetric expression partly depends on Wnt signalling activity. Investigation of protein distributions using knock-in reporters for PRY-1 and CAM-1 showed that protein accumulation patterns at L2 are consistent with transcript levels. Our findings uncover transcriptional feedback within the Wnt pathway that may reinforce robust fate specification and reveal molecular heterogeneity in seam cells with potential functional consequences for lineage behaviour.
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Journal articleArmstrong-James D, 2026,
Describing the burden and characteristics of Aspergillus- related chronic lung disease at ³Ô¹ÏºÚÁÏ College Healthcare Trust: a 10-year retrospective study
, BMJ Open Respiratory Research, ISSN: 2052-4439Background: The epidemiology of Aspergillus-related chronic lung disease remains poorly defined. We aimed to characterise the local burden at ³Ô¹ÏºÚÁÏ College Healthcare NHS Trust (ICHT), London, across a 10-year period (2014-2024). Methods: Electronic health records were reviewed to identify individuals tested for serological markers of Aspergillus species infection after which thoracic CT scans were reviewed for features of Aspergillus-related chronic lung disease. Patients were classified into diagnostic categories based on definitions provided in the recent British Thoracic Society (BTS) Clinical Statement. Results: In total, 334 individuals met criteria for serologic Allergic Bronchopulmonary Aspergillosis (sABPA), 145 for Allergic Bronchopulmonary Aspergillosis (ABPA), 74 for Chronic Pulmonary Aspergillosis (CPA), 38 for Simple Aspergilloma and 11 with CPA-ABPA overlap. Serological responses varied: ABPA patients had higher median Aspergillus fumigatus-specific IgE titres (7.52 kUA/L, vs 1.94 kUA/L, p<0.05) and a greater proportion were positive for Aspergillus antibody (IgG) or precipitins (62.5% vs 32.9%, p<0.05) compared with sABPA. CPA patients had lower median total IgE (94 vs 1494 IU/mL, p<0.05) and A. fumigatus-specific IgE (2.24 vs 7.52 kUA/L, p<0.05) than ABPA patients. The was a wide spectrum of radiological presentations across diagnostic categories.Conclusions: While case numbers are likely underestimated, our findings highlight a substantial and heterogenous local burden. This improved understanding of local epidemiology will inform our local service development.
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Journal articleMadhuprakash J, Toghani A, Pai H, et al., 2026, , Sci Adv, Vol: 12
Pathogens counteract central nodes of NLR immune receptor networks to suppress immunity. However, the mechanisms by which pathogens hijack helper NLR pathways are poorly understood. We show that an effector from the late blight pathogen Phytophthora infestans interacts with the host protein NbTOL9a and a helper NLR to suppress immunity. We solved the crystal structure of the RXLR-LWY effector AVRcap1b in complex with the ENTH domain of NbTOL9a. The structure revealed that, unlike other RXLR-LWY effectors, AVRcap1b has a previously unidentified L-shaped fold that defines a distinct structural family of effectors in the genus Phytophthora. We defined the AVRcap1b/NbTOL9a binding interface and designed effector mutants that do not bind NbTOL9a, impairing immune suppression. This suggests that ENTH binding is required for full virulence activity. Last, we show that AVRcap1b associates specifically with activated NbNRC2 independently of NbTOL9a binding. We propose a model in which the effector interconnects NbNRC2 with the NbTOL9a pathway. Our results illustrate a previously uncharacterized pathogen mechanism to hijack NLR pathways and suppress immunity.
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Journal articleHemmings S, Varaden D, Barnes J, et al., 2026, , The Lancet Microbe, ISSN: 2666-5247
BackgroundLong-term exposure to indoor fungal bioaerosols is a recognised risk factor for respiratory illness, particularly in damp and poorly ventilated housing. However, the diversity and seasonal variability of these fungal communities are poorly understood. As part of the West London Healthy Home and Environment Study (WellHome), this study aimed to characterise the composition, diversity, and temporal dynamics of indoor fungal bioaerosols in urban UK homes, as compared with outdoor air, to inform future exposure baselines and policy development.MethodsIn this prospective, community-based observational study, 118 households were recruited across West London, UK, via community networks and partner organisations, prioritising families with children aged 5–17 years with asthma or allergies, from diverse socioeconomic backgrounds. Sampling occurred between Oct 3, 2022, and June 14, 2024. Participant data were collected via questionnaires completed by household members, capturing demographics, building characteristics, and respiratory health. Passive-air samplers were used in living rooms for 28 days during two seasonal campaigns, with concurrent outdoor sampling at four fixed community sites. Fungal bioaerosols were identified by ITS2 amplicon sequencing and quantified using broad-range quantitative PCR targeting the 18S rRNA gene. Diversity indexes and temporal dynamics were analysed using ecological statistics and generalised additive models.Findings118 households were enrolled, comprising 504 residents (263 women, 237 men, and four not reported). Among 504 participants who self-identified, the largest groups comprised individuals identifying as Black African (n=47), Somali (n=46), White British (n=42), and African (n=38), with additional representation from mixed race ethnic backgrounds (n=29), Black British (n=27), White (n=22), and Black Caribbean (n=18), alongside several other ethnicities each represented at lower frequencies. Of 118 households, 104 com
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Journal articleShort C, Semple T, Abkir M, et al., 2026, , Thorax
INTRODUCTION: The current cystic fibrosis (CF) care era, while hugely welcome, raises new challenges, particularly the need for more sensitive pulmonary outcome measures. Seeking further optimisation, we previously developed a Short extension to multiple breath washout measure (MBWShX) which captures previously overlooked, under-ventilated lung units but lacks regional information. Functional lung MRI addresses this limitation. We hypothesised these measures would be more sensitive to change in tracking CF lung disease than usual clinical respiratory function tests. METHODS: Forty-six people with (pw)CF, median age 15 (range 6-55) years were recruited to a single-centre study. While clinically stable, pwCF performed OE-MRI, MBW+/-ShX and spirometry at baseline and at 6 monthly intervals over 18 months of follow-up. A subgroup of pwCF (n=20) and age-matched healthy controls (HC, n=20) performed two repeatability visits within 6 weeks. RESULTS: OE-MRI/MBWShX were well tolerated, differentiated HC and CF groups, and were repeatable with negligible differences between two visits <6 weeks apart. OE-MRI/MBWShX parameters worsened at 12 months (p<0.05) and 18 months (p<0.01). In contrast, conventional measures of pulmonary function (FEV1+ LCI2.5) did not change significantly. CONCLUSIONS: OE-MRI/MBWShX are novel, sensitive tools to track progression of abnormalities in lung structure/function. Such progression may not be detected by conventional outcome measures. CF transmembrane conductance regulator (CFTR) modulators have been transformative for many pwCF and generally lead to substantial improvements in lung health. Stable FEV1 over longer time periods and, during mucoactive treatment withdrawal, may give false reassurance. OE-MRI/MBWShX reveal the likely less welcome reality that lung-disease progresses despite CFTR modulators. These measures could be considered in future studies when enhanced sensitivity is required.
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Journal articleSakamachi Y, Wiley E, Trempus CS, et al., 2026, , Sci Transl Med, Vol: 18
Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation that results from maladaptive responses to lung epithelial injury; however, the underlying mechanisms remain unclear, and treatment options are limited. Here, we showed that deficiency in the innate immune receptor toll-like receptor 5 (TLR5) is associated with IPF in humans and with increased susceptibility to bleomycin-induced pulmonary fibrosis in mice and that activation of lung epithelial TLR5 through a synthetic flagellin analog protected mice from experimental fibrosis. Mechanistically, epithelial TLR5 activation induced antimicrobial gene expression and ameliorated lung dysbiosis after injury. In contrast, TLR5 deficiency in mice and patients with IPF was associated with lung dysbiosis. Elimination of the microbiome in mice through administration of antibiotics abolished the protective effect of TLR5, and reconstitution of the microbiome by fecal microbiota transplantation rescued the observed phenotype. In conclusion, these studies revealed that TLR5 protects against pulmonary fibrosis through effects on the lung microbiota, providing insight into therapeutic approaches that may ultimately benefit patients with IPF.
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