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Journal articleSun M, Gao AX, Ye B, et al., 2026,
Advances in engineering and applications of synthetic phase-separated membraneless organelles in biotechnology
, Synthetic and Systems Biotechnology, Vol: 13, Pages: 37-49, ISSN: 2405-805XMembraneless 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 articleMac Aogáin M, Gilmour A, Chalmers JD, et al., 2026,
Targeting Inflammation in Bronchiectasis.
, Drugs, Vol: 86, Pages: 797-812Bronchiectasis is defined by chronic infection, dysregulated inflammation and impaired mucociliary clearance underpinning progressive structural lung injury. While airway infection remains a clinical hallmark, numerous studies demonstrate that excessive neutrophil-dominated inflammation is a key determinant of disease severity, exacerbation risk and quality of life. Recent developments have transformed our understanding of inflammatory drivers uncovering distinct inflammatory endotypes defined by dominant microbial species, pattern-recognition receptor activation, inflammasome signalling, Th17-associated cytokine networks and failures of mucosal immunity. The emerging roles of viral-bacterial interactions, fungi, pathobionts and the broader microbiome challenge the conventional infection-only paradigm and highlight gaps in current therapeutic strategies. Such developments underpin the rationale behind anti-inflammatory strategies in bronchiectasis, ranging from suppression of neutrophil-driven injury through direct neutrophil elastase or upstream dipeptidyl peptidase-1 (DPP-1) inhibition, to immunomodulatory macrolides, toward therapies aimed at recalibrating epithelial and mucosal homeostasis. While several antibacterial and anti-infective trials have produced mixed results, this is likely to reflect unresolved heterogeneity in microbiome composition and host immune signalling. In contrast, emerging anti-inflammatory strategies show strong positive signals, reinforcing the need for better endotyping and biomarker-guided patient selection. Here we synthesize recent mechanistic and clinical insights to propose a more integrated framework for understanding and ultimately targeting airway inflammation in bronchiectasis.
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Journal articleWang H-Y, Yuen ELH, Chen Y-F, et al., 2026,
A hydrophobic core in the coiled-coil domain is essential for NRC resistosome function.
, New Phytol, Vol: 250, Pages: 3247-3263The nucleotide-binding leucine-rich repeat protein (NLR) required for cell death (NRC) family represents a group of helper NLRs that are required by sensor NLRs to execute hypersensitive cell death during pathogen infection. NRCs contain an N-terminal coiled-coil (CC) domain essential for their function, yet our knowledge of how this domain contributes to NRC function remains limited. Using site-directed mutagenesis and transient expression in Nicotiana benthamiana, we screened conserved hydrophobic residues among NRCs and identified seven required for NRC4-mediated cell death, revealing a hydrophobic feature within the CC domain that contributes to NRC-mediated immunity. Structural analysis revealed that four of these residues form a hydrophobic core in the CC domain. This hydrophobic core is important for NRC4 subcellular localization, oligomerization, and phospholipid association, but not for NRC4 focal accumulation at the extrahaustorial membrane during Phytophthora infestans infection. Sequence analysis and functional assays revealed that this core is highly conserved in NRCs and some singleton NLRs but has degenerated in NRC-dependent sensor NLRs. Our study identifies a hydrophobic feature in the CC domain of NRCs and reveals its contribution to NLR-mediated immunity.
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Journal articleChen SY, Patranabish S, Weiland K, et al., 2026,
Scalable structural supercapacitors with graphene-modified high-surface-area electrodes
, Composites Science and Technology, Vol: 279, ISSN: 0266-3538Electrification, including emerging technologies such as structural supercapacitors, is critical in realizing carbon-neutral transportation. A fundamental challenge is the trade-off between mechanical properties and energy storage capabilities. We report the fabrication of structural supercapacitors with a novel fibre-fibre interface to improve the interlaminar strength and encapsulation while considering the effect of structural resin on energy storage performance. The synthesized graphene nanoplatelets-modified electrodes attain a high specific surface area of ∼231 m<sup>2</sup> g<sup>−1</sup> - outperforming comparable carbon-based electrodes. We learned that the use of a gel-polymer electrolyte (GPE) separator containing 60 wt% Li-salt eliminates the requirement of electrolyte infusion and showed the highest values for conductivity for the cell produced using GPE. The implementation of glass fabrics (GFs) into the GPE improved the flexural modulus by ∼22%, while retaining the mechanical strength of the cells. The multifunctional performance of the produced SSCs were on par or even outperformed the performances of SSCs reported in literature. A proof-of-concept prototype demonstrates that gel-polymer electrolyte cells can retain charges for longer than those with a glass fibre separator. Cumulatively, these offer the possibility of conventional composite manufacturing techniques to scale-up and eliminate delamination issues arising from different thermal expansion coefficients which also addresses the balance between mechanical stability and electrochemical performance. Our findings support the advancement of durable, lightweight energy storage and delivery systems for sustainable transportation, with potential applications in robotics and wearable technologies.
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Journal articleChin D, Hernandez-Beeftink T, Donoghue L, et al., 2026,
Genome-wide association study of Idiopathic Pulmonary Fibrosis susceptibility using clinically-curated European-ancestry datasets.
, Eur Respir J -
Journal articleGrover M, Ippolito D, Barkoulas M, 2026,
Worming out defence strategies: mechanisms of immunity through the lens of genetic screens in C. elegans
, Heredity, ISSN: 0018-067XSince Sydney Brenner's foundational work in 1974, Caenorhabditis elegans has served as an impactful model for biological discovery primarily driven by genetic approaches, including mutagenesis-based screens and RNAi-based functional genomics. We discuss here how genetic screens in C. elegans have advanced our understanding of innate immunity mechanisms by comparing signalling pathways and responses to a wide range of bacteria, viruses, and eukaryotic pathogens including oomycetes, and microsporidia. Screens have uncovered both evolutionarily conserved pathways and species-specific mechanisms of nematode immunity across multiple functional categories. These include mediators of pathogen recognition that specifically detect microbial patterns or infection-associated damage, surveillance immunity systems that sense pathogen-induced cellular dysfunction, and regulatory mechanisms that control the activation of immune signalling or balance it with physiological costs. A major theme emerging from these studies is the importance of cross tissue immune communication, as C. elegans coordinates responses between multiple tissues including neurons, intestine, and epidermis through complex signalling networks. Powerful genetic approaches, coupled with the continued development of new tools in the community, position C. elegans as an attractive whole-animal model for understanding fundamental principles of host-pathogen interactions and the evolutionary origins of innate immunity.
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Journal articleLedesma Amaro R, 2026,
PromoterAtlas: decoding regulatory sequences across Gammaproteobacteria using a transformer model
, Nature Communications, ISSN: 2041-1723Recent advances in deep learning, particularly transformer architectures, have improved computational approaches for biological sequence analysis. Despite these advances, computational models for bacterial promoter prediction have remained limited by small datasets, species-specific training, and binary classification approaches rather than comprehensive annotation frameworks. We present PromoterAtlas, a 1.8M parameter transformer model trained on 9M regulatory sequences from 3,371 gammaproteobacterial species. The model demonstrates recognition of various regulatory elements across different species, including ribosomal binding sites, various types of bacterial promoters, transcription factor binding sites, and terminators. Using this model, we developed a whole-genome promoter annotation tool for Gammaproteobacteria, with various levels of validation that support the predictions of promoters associated with different sigma (σ) factors. Furthermore, we show that the model embeddings reflect cross-species evolutionary relationships, clustering promoters by σ factor identity rather than species-specific sequence features. Finally, we show that model embeddings encode regulatory sequence information that enables effective prediction of transcription and translation levels. PromoterAtlas can contribute to our understanding of and ability to engineer bacterial regulatory sequences with potential applications in bacterial biology, synthetic biology, and comparative genomics.
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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 CommunAutophagy 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 articleDavies JC, Wilson G, Hughes D, 2026,
Variability: the law of life?
, Thorax, Vol: 81, Pages: 511-513 -
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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