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Background: Mast cell activation is an important driver of abdominal pain in irritable bowel syndrome (IBS). While evidence supports the role of IgE-mediated mast cell activation in visceral pain development in IBS, the role of pseudoallergic MRGPRX2-mediated mast cell activation in this process remains unknown., Objective: We investigated whether MRGPRX2-mediated mast cell activation plays a role in abdominal pain development in patients with IBS., Design: MRGPRX2 expression in mast cells and other immune cells was characterised across colon layers using flow cytometry. We evaluated whether MRGPRX2 agonists trigger mast cell degranulation and transient receptor potential vanilloid 1 (TRPV1) sensitisation in healthy human colonic submucosal plexus samples using live imaging. Rectal biopsies were then collected from patients with IBS and healthy volunteers (HV) and MRGPRX2 + mast cell frequency, MRGPRX2 expression per cell, mast cell degranulation kinetics in response to MRGPRX2 agonists, MRGPRX2 agonistic activity and presence of MRGPRX2 agonists in biopsy supernatants were assessed., Results: MRGPRX2 + mast cells are enriched in the submucosa and muscularis of the healthy human colon. MRGPRX2 agonists induce mast cell degranulation and TRPV1 sensitisation in the healthy colon submucosa. While the frequency of rectal MRGPRX2 + mast cells was unaltered in IBS, submucosal mast cells showed increased degranulation in response to MRGPRX2 agonists in IBS compared with HV. MRGPRX2 agonistic activity was increased in IBS rectal biopsy supernatant compared with HV, which was associated with increased levels of substance P., Conclusion: The MRGPRX2 pathway is functionally upregulated in the colon of patients with IBS, supporting its role in abdominal pain in IBS., Competing Interests: Competing interests: Part of this study is supported by Takeda Pharmaceutical Company Limited (Osaka, Japan). GB is an Editorial Board Member of Gut. All remaining authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: There is increasing interest in the use of home-based monitoring in people with chronic lung diseases to improve access to care, support patient self-management, and facilitate the collection of information for clinical care and research. However, integration of home-based monitoring into clinical and research settings requires careful consideration of test performance and other attributes. There is no published guidance from professional respiratory societies to advance the science of home-based monitoring for chronic lung disease. Methods: An international multidisciplinary panel of 32 clinicians, researchers, patients, and caregivers developed a multidimensional framework for the evaluation of home-based monitoring in chronic lung disease developed through consensus using a modified Delphi survey. We also present an example of how the framework could be used to evaluate home-based monitoring using spirometry and pulse oximetry in adults with asthma, bronchiectasis/cystic fibrosis, chronic obstructive pulmonary disease, and interstitial lung disease. Results: The PANACEA framework includes seven domains (test Performance, disease mANAgement, Cost, patient Experience, clinician Experience, researcher Experience, and Access) to assess the degree to which home-based monitoring assessments meet the conditions for clinical and research use in chronic lung disease. Knowledge gaps and recommendations for future research of home spirometry and pulse oximetry in asthma, bronchiectasis/cystic fibrosis, chronic obstructive pulmonary disease, and interstitial lung disease were identified. Conclusions: The development of the PANACEA framework allows standardized evaluation of home-based monitoring in chronic lung diseases to support clinical application and future research.

Electronic and vibrational relaxation processes can be optimized and tuned by introducing alternative pathways that channel excess energy more efficiently. An ensemble of interacting molecular systems can help overcome the bottlenecks caused by large energy gaps between intermediate excited states involved in the relaxation process. By employing this strategy, catenanes composed of mechanically interlocked carbon nanostructures show great promise as new materials for achieving higher efficiencies in electronic devices. Herein, we perform nonadiabatic excited state molecular dynamics on different all-benzene catenanes. We observe that catenanes experience faster relaxations than individual units. Coupled catenanes present overlapping energy manifolds that include several electronic excited states spatially localized on the different moieties, increasing the density of states that ultimately improve the efficiency in the energy relaxation. This result suggests the use of catenanes as a viable strategy for tuning the internal conversion rates in a quest for their utilization for new optoelectronic applications., (© 2024 Wiley Periodicals LLC.)