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Journal articleMolyneaux PL, Hirani NA, Chia CCK, et al., 2026,
Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study.
, Nat Commun, Vol: 17Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited treatment options. LTI-03 promotes alveolar epithelial cell survival and reduces profibrotic protein expression in experimental models of IPF. In this Phase 1b, randomized, double-blind, placebo-controlled dose-escalation study, 24 participants with IPF were randomized 3:1 to inhaled LTI-03 5 mg/day (N = 9), LTI-03 10 mg/day (N = 9) or placebo (N = 6) for 14 days and included in all analyses (ClinicalTrials.gov: NCT05954988). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs). Exploratory analyses included pharmacokinetics and disease-related biomarkers. LTI-03 was well-tolerated, with no treatment-related discontinuations, no severe TEAEs, and no evidence of airway obstruction by spirometry and associated symptoms. In deep bronchial brushings, both LTI-03 doses significantly reduced interleukin-11 (p = 0.0406 at 5 mg/day; p = 0.044 at 10 mg/day) and thymic stromal lymphopoietin (p = 0.0256 at 5 mg/day; p = 0.0128 at 10 mg/day) versus placebo. The 10 mg/day dose suppressed collagen type 1 alpha chain 1 (p = 0.0248), CXC chemokine ligand 7 (p = 0.0248) and galectin-7 (p = 0.0332). Other measured biomarkers were not significantly changed. The favorable safety profile and reductions in disease-related biomarkers support further evaluation of inhaled LTI-03 for IPF. This study was fully funded by Rein Therapeutics, Inc.
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Journal articleLedesma Amaro R, 2026,
WASP: a pipeline for functional annotation prediction based on AlphaFold structural models
, Nature Communications, ISSN: 2041-1723Protein function annotation is crucial for understanding biological processes and mechanisms. Traditionally, annotations rely on sequence homology, providing valuable insights but often leaving gaps even in well-characterised organisms. With AlphaFold enabling rapid generation of protein structural models, we can now infer function from three-dimensional shape. Here, we present WASP, a pipeline leveraging structural homology to enhance protein annotation prediction at scale, providing a more comprehensive understanding of protein functions across various organisms. WASP relies on network topology for better accuracy and more robust statistical power. We show that WASP achieves superior F1 scores compared to state-of-the-art sequence-based tools when recovering hidden annotations. On 20 industrially relevant organisms, WASP retrieves annotations for 20-30% of previously uncharacterized proteins. We further demonstrate utility in genome-scale metabolic model curation, identifying native candidates for 75-100% of orphan reactions. WASP highlights how structural homology can systematically discover annotations missed by sequence-based approaches.
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Journal articleFranks PW, Lim L-L, Ramsay M, et al., 2026,
The Lancet Commission on precision health: equitable, data-driven health outcomes for all.
, Lancet, Vol: 408, Pages: 302-305 -
Journal articleBozkurt O, Ecevit A, Gunlemez A, 2026,
Noninvasive acoustic evaluation of oral feeding skills in preterm infants with bronchopulmonary dysplasia.
, Pediatr ResBACKGROUND: Oral feeding difficulties are common in infants with bronchopulmonary dysplasia (BPD) and contribute to delayed discharge. The aim was to evaluate oral feeding skills (OFS) and swallow-respiration coordination in infants with BPD using a bedside noninvasive signal-based device. METHODS: Prospective observational study. Forty-six infants with BPD and 51 stable preterm controls ( ≤ 32 weeks' gestation) underwent a two-minute oral feeding evaluation. Acoustic swallow and respiratory signals were synchronously recorded to derive total swallow count (TSwC), maximum rhythmic swallow count (MxRSwC), average time between rhythmic swallows (AvgTmBtwnRhSw), respiration rate, and swallowing apnea. RESULTS: Infants with BPD had fewer TSwC and MxRSwC, and a longer AvgTmBtwnRhSw (all p < 0.05). Oxygen desaturation events were more frequent and swallowing apnea was more common in BPD group (%39 vs %9.8, p = 0.001). Infants with BPD achieved full independent oral feeding at an older postmenstrual age than controls. CONCLUSION: Oral feeding skills in preterm infants with BPD are characterized by delayed progression and altered swallowing rhythmicity, suggesting impaired swallow-respiration coordination. Individualized noninvasive acoustic assessment provides a feasible and objective method for the evaluation of OFSs in infants with BPD. IMPACT: Infants with BPD often have delayed and less mature oral feeding skills mostly driven by impaired swallow-respiration coordination. This study demonstrates the feasibility of a simple, objective, noninvasive bedside approach for assessment of swallowing physiology and swallow-respiration coordination during oral feeding. Individualized evaluation of feeding readiness using noninvasive, easily accessible tools may support targeted feeding strategies in preterm infants with BPD.
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Journal articleJervis PA, Rosa GM, Bates KA, et al., 2026,
Early maturation of host antimicrobial peptide defences is associated with host-pathogen coexistence.
, Nat Chem BiolEpizootic outbreaks of invasive pathogens, such as the fungal pathogen Batrachochytrium dendrobatidis (Bd), are increasingly recognized as a global threat to biodiversity. However, not all susceptible host populations are equally impacted by these disease outbreaks. While some populations persist despite intense infections and high mortality rates, others can transition to enzootic coexistence with the pathogen. Here, we use comparative peptidomics to identify differences in antimicrobial peptide (AMP) maturation in Bd-susceptible common midwife toads (Alytes obstetricans) through metamorphosis. Here, we show that animals that metamorphose before AMP immune maturation display a low-diversity AMP phenotype deficient in anti-Bd AMPs. Where a high incidence of postmetamorphic animals occur with immature AMPs, populations are associated with epizootic disease dynamics. Conversely, populations associated with mature AMPs are stable following invasion of the pathogen. Our results show that even intrinsically susceptible amphibian species can possess the tools that allow populations to recover following a severe Bd epizootic.
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Journal articleKhor YH, Luppi F, Adegunsoye A, et al., 2026,
Acute exacerbation in fibrotic interstitial lung disease: An International Working Group Report.
, Am J Respir Crit Care MedAcute exacerbations (AEs) occur both in patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic interstitial lung disease (fILD). These events confer high morbidity and mortality, with a lack of proven effective therapeutic interventions. The objective of this state-of-the-art document is to summarize latest evidence since the 2016 international working group report on AE-IPF, expanding it across the spectrum of all fILDs. A comprehensive literature review on the epidemiology, associated and risk factors, prognosis, and management of AE-fILD is summarized. In addition to revising the AE definition and diagnostic criteria for broad application across different fILDs, a conceptual framework for acute respiratory worsening (ARW) has been proposed to encompass a variety of acute respiratory deteriorations, both related and unrelated to AE. This allows structured evaluation in both clinical and research settings. The proposed revised definition for AE-fILD is an acute respiratory event characterized by increased respiratory symptoms or signs and associated with radiologic or histologic features consistent with diffuse alveolar damage (with or without superimposed organizing pneumonia) in a patient with known or newly diagnosed fILD. On the other hand, ARW refers to a heterogeneous group of clinical events with acute symptom worsening not attributable to DAD in patients with fILD, such as pulmonary edema, bronchitis, and pneumonia, although severe pneumonia can trigger AE-fILD. Additionally, we discuss considerations for inclusion of AE as a clinical trial endpoint, as well as research priorities for advancing knowledge on the pathogenic mechanisms, event prediction, risk stratification, and development of drugs and supportive treatments.
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Journal articleGodson A, Eddie L, Schuster M, et al., 2026,
NbRD21 protease controls receptor kinase homeostasis in Nicotiana benthamiana.
, New PhytolRD21-like proteases are papain-like cysteine proteases with a C-terminal granulin domain that are abundant and ubiquitous in angiosperms and have often been implicated in immunity. We previously found that the activity of RD21 in Nicotiana benthamiana (NbRD21) is suppressed during infection with Pseudomonas syringae. Here, we studied the role of NbRD21 in immunity and proteome processing. NbRD21 was disrupted by genome editing and rd21 mutants were subjected to disease assays and shotgun proteomics. Dipeptide substrate zLR-AMC was used in protease assays and agroinfiltration was used to transiently express NbRD21 and candidate substrates. Genome-edited lines lacking NbRD21 develop normally but have drastically reduced zLRase activity and are significantly more susceptible to P. syringae. Shotgun proteomics revealed an increased accumulation of c. 20 diverse receptor-like kinases (RLKs) in untreated rd21 knockout lines, but their transcript levels are unaltered when compared to wild-type plants. 35S-driven GFP-tagged RLKs accumulate more upon transient expression in rd21 plants than in wild-type plants. These data indicate that NbRD21 post-translationally controls RLK homeostasis, either by directly degrading RLKs or indirectly by regulating endocytic RLK recycling.
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Journal articleHowlett P, Durairaj A, Gan J, et al., 2026,
Adjusting for the diagnostic accuracy of CXR in the dose-response relationship between cumulative silica exposure and silicosis in miners.
, Occup Environ MedINTRODUCTION: A recent meta-analysis confirmed that chest X-ray (CXR) has low sensitivity for diagnosing silicosis. We re-estimated previously published dose-response relationships between cumulative respirable crystalline silica (RCS) exposure and silicosis risk, under the assumptions that sensitivity was either fixed or relative to the population proportion of severe silicosis. METHODS: We combined unpublished logistic regression models from Scottish coal miners with meta-analysis results to model how CXR sensitivity changed according to cumulative RCS exposure. We assumed specificity was 0.95. Among mining cohorts, we calculated the difference in the cumulative risk of silicosis between the unadjusted and fixed and relative scenarios. Finally, we re-estimated a published dose-response meta-analysis and associated absolute risk reductions (ARR). RESULTS: The cumulative risk of silicosis was substantially higher in both the fixed and relative sensitivity scenarios compared with the unadjusted estimate in all mining cohorts. This was most pronounced in the relative scenario and when cumulative RCS exposures were below approximately 6 mg/m³-years. A reduction in cumulative RCS exposure from 4 to 2mg/m³-years corresponded to larger ARRs in the fixed and relative scenarios than the unadjusted scenario; 382 (95% CI 361 to 399) and 529 (95% CI 353 to 592) cases per 1000 miners compared with 313 (95% CI 288 to 333) cases per 1000 miners, respectively. DISCUSSION: We relied on a single estimate of the proportion of severe disease to link sensitivity and cumulative RCS exposure. Nevertheless, adjusting for the reduced diagnostic accuracy of CXR for silicosis suggests the burden of silicosis is underestimated in published mining cohorts.
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Journal articleShah A, 2026,
PRESIDE protocol: a global registry of antimicrobial resistance in chronic lung disease
, ERJ Open Research, ISSN: 2312-0541Antimicrobial resistance (AMR) is an escalating global health threat. Chronic lung diseases (CLDs) represent a key area in which AMR poses unique and often underestimated challenges, yet high-quality epidemiological data remain scarce. To address this gap, the European Respiratory Society Clinical Research Collaboration on AMR in Lung Infections (AMR-Lung CRC) has developed PRESIDE, an international prospective observational registry designed to evaluate the prevalence and burden of AMR in patients with CLD. PRESIDE is a global, multicentre study recruiting paediatrics and adults with CLD who have undergone respiratory microbiological testing as part of routine clinical care within the year prior to data collection. Participating centres enroll patients during two-week recruitment periods, held twice yearly over five years from 2025 to 2030. The registry captures a comprehensive set of core variables, including demographics and smoking history, CLD type and aetiology, microbiological history, comorbidities, clinical characteristics, therapeutic exposures, and respiratory microbiology results.This registry aims to generate robust, prospective, real-world evidence on AMR epidemiology in CLD, enabling comparison across regions and disease phenotypes. Findings are expected to inform clinical decision-making, support antimicrobial stewardship, and guide the development of context-specific guidelines and public health strategies. Ultimately, PRESIDE seeks to strengthen global efforts to address AMR in chronic respiratory infections and improve outcomes for patients with CLD.
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Journal articleGao C, Meng X, Chen X, et al., 2026,
Surface immune signaling unlocks NLR activation through mRNA alternative splicing.
, Science, Vol: 393, Pages: 65-70Plants activate pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) to combat pathogens. However, how these systems coordinate immune activation while preventing autoimmunity remains poorly understood. In this study, we uncovered a regulatory mechanism in which surface immune signaling unlocks nucleotide-binding leucine-rich repeat (NLR) immune receptor activation through mRNA splicing. We identified an N-terminal prodomain in the potato late blight resistance protein Rpi-vnt1.1 that inhibits resistosome formation, preventing potential autoactivation of this NLR. Upon pathogen perception, PTI signaling induced alternative splicing of Rpi-vnt1.1 mRNA, removing this inhibitory element. This primed Rpi-vnt1.1 for activation by the Phytophthora infestans effector AVRvnt1, enabling resistosome assembly and immune signaling. The widespread conservation of N-terminal extensions in coiled coil-type NLRs points to a common regulatory mechanism in preventing potential autoactivation while preserving pathogen sensitivity.
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