Volatile organic compounds (VOCs) in exhaled breath reflect biological processes in the lungs. Exploring VOC profiles in severe asthma patients starting biologics may reveal treatment-related biological changes over time. This study aimed to assess the performance and feasibility of applying a sparse partial least squares-discriminant analysis (sPLS-DA) analytical approach in detecting longitudinal changes in exhaled VOCs of patients with severe asthma initiating biologic treatment. Exhaled breath was collected in the 3TR-ABC study, a multicenter observational prospective cohort study, at baseline and 4 months after starting biologics (benralizumab or dupilumab). VOCs were trapped on thermal desorption tubes and analyzed by gas chromatography-mass spectrometry. Paired sPLS-DA was used to distinguish baseline from post-treatment VOC profiles, and Kendall rank correlation assessed associations with clinical parameters at baseline. Data from two sites (Amsterdam and Copenhagen) were available of 25 severe asthma patients. The sPLS-DA resulted in a model containing five VOCs (methyl isobutyl ketone, 2-ethyl-1-hexanol, 5-methyl octadecane, 2-methylundecane and 1,1'-oxybis(decane)) with an area under the receiver operating characteristic curve of 0.89 (95% confidence interval: 0.79-0.99) for distinguishing baseline and 4 months post treatment. At baseline, a positive correlation was observed between 2-ethyl-1-hexanol and asthma control (Asthma Control Questionnaire); τ = 0.40, p < 0.01. A negative correlation was found between 1,1'- oxybis(decane) and blood eosinophil counts (τ = -0.30, p=0.04). Based on our results, the proposed analytical approach appears feasible for analyzing longitudinal data in patients with severe asthma initiating biologics. Further validation in larger cohorts is warranted to confirm robustness and generalizability.

Obesity is a modifiable risk factor for atrial fibrillation (AF), but its relationship with acute procedural response and long-term rhythm durability after ablation for persistent AF (PeAF) remains incompletely defined.

To evaluate the association of body mass index (BMI) with acute AF termination and long-term atrial arrhythmia recurrence after first-time radiofrequency catheter ablation for PeAF.

We analyzed prospective data from 7,559 consecutive patients with clinically documented PeAF undergoing first-time radiofrequency catheter ablation between January 2018 and March 2025. Patients were classified according to World Health Organization BMI categories. The primary outcome was atrial arrhythmia recurrence after a 3-month blanking period.

During a median follow-up of 41 months, atrial arrhythmia recurrence occurred in 3,494 patients (46.2%). In the fully adjusted model, higher BMI was associated with recurrence as a continuous variable (HR 1.03, 95% CI 1.02-1.04). Compared with normal-weight patients, overweight and obese patients had higher recurrence risks (HR 1.15, 95% CI 1.06-1.24; and HR 1.31, 95% CI 1.18-1.45, respectively). Acute AF termination occurred in 832 patients (11.0%) and decreased with increasing BMI. Higher BMI was associated with lower odds of acute AF termination (OR 0.95, 95% CI 0.93-0.97). Findings were consistent across sensitivity analyses.

In patients with PeAF undergoing first-time radiofrequency ablation, higher BMI was associated with lower acute AF termination and increased long-term recurrence. BMI may serve as a practical marker for preprocedural risk stratification.

Cardiovascular diseases are the leading cause of mortality in Spain, yet there is no systematic population-based cardiovascular screening program. This study evaluated the feasibility of a nurse-led, single-visit cardiovascular screening program in primary care (PreveCardio), and identified the prevalence of modifiable cardiovascular risk factors, their associated socioeconomic factors, and the translation of pilot findings into regional health policy.

We conducted a cross-sectional study across 42 primary care centers in a Spanish region (January-March 2023). A random sample of 8491 individuals aged 50 to 75 years was invited to participate. Trained nurses performed a single 30-minute visit with point-of-care measurements (blood pressure, lipid profile, HbA1c) and validated questionnaires. Multivariable logistic regression models were fitted with Benjamini-Hochberg correction.

A total of 3545 individuals participated (41.8%; mean age 61.2 ± 7.3 years; 56.7% women). The completeness of clinical data exceeded 99%. Elevated blood pressure was identified in 40.4%, obesity in 29.5%, nonoptimal low-density lipoprotein cholesterol in 48.7%, prediabetes in 30.7%, and active smoking in 19.5%. Smoking showed the steepest socioeconomic gradient (aOR, 3.25; 95%CI, 2.09-5.03). The direct cost per participant was euro11.75.

A nurse-led, single-visit cardiovascular screening program is operationally feasible in Spanish primary care, revealing a high burden of modifiable cardiovascular risk factors and significant socioeconomic disparities. Smoking showed the steepest income-associated gradient. This pilot study led to the approval of the first systematic cardiovascular screening program in a Spanish autonomous community.

Agingis characterized by chronic low-grade inflammation ("inflammaging"), a key driver of functional decline and age-related diseases. The cGAS-STING pathway, which senses cytosolic DNA, has emerged as a central mediator of this sterile inflammation. Here, we systematically review the mechanisms of cGAS-STING activation in aging-including mitochondrial DNA leakage, nuclear envelope disruption, and retrotransposon activation-and its role in driving cellular senescence and the senescence-associated secretory phenotype (SASP). We examine the pathway's pathological contributions across multiple systems, including the nervous, cardiovascular, musculoskeletal, metabolic, reproductive, and sensory systems. We also discuss therapeutic strategies targeting cGAS-STING, encompassing small-molecule inhibitors, natural products, nanomedicine, and gene therapy. Furthermore, we integrate AlphaFold3-based structural modeling and CB-DOCK2 molecular docking analyses to characterize the binding modes and affinities of key inhibitors (e.g., H-151, RU.521, VBIT-4, Mdivi-1) to cGAS, STING, VDAC1, and DRP1, providing a structural rationale for their therapeutic potential. Finally, we address current challenges, including tissue-specific effects and pathway complexity, and highlight future directions for translating these insights into clinical interventions for aging and age-associated disorders.

Myotonic dystrophy type 1 (DM1) is a progressive, multisystemic disorder in which gastrointestinal (GI) involvement is prevalent but frequently underestimated in routine clinical care. This study aimed to evaluate the GI manifestations and symptom burden in patients with adult-onset DM1. We performed a retrospective study in patients with genetically confirmed adult-onset DM1. GI symptom burden was assessed through three sources: (1) patient-reported outcome measures (PROMs), specifically the Gastrointestinal Symptom Rating Scale (GSRS) and the Sydney Swallow Questionnaire (SSQ), (2) an open-ended question asking patients to name their five most bothersome symptoms, and (3) GI symptoms and diagnoses documented in their medical records. Associations between GI symptoms and sex, age, disease duration, Body Mass Index (BMI), and CTG repeat size were analysed. Ninety-five patients with adult-onset DM1 were included (57% female; mean age 44.2±11.8 years). GI symptoms imposed a substantial burden, as 54% of patients exceeded the GSRS clinical threshold and 53% exceeded the SSQ threshold. In open-ended reporting, 31% of patients named a gastrointestinal problem among their most bothersome symptoms, ranking it fourth among all complaints, 13% named swallowing difficulties. In line with the PROM findings, medical record review demonstrated a high prevalence of GI manifestations, including dysphagia (59%), diarrhoea (35%), and constipation (33%). Female sex was strongly associated with higher odds of constipation (OR 9.25,p<0.01), diarrhoea (OR 3.45,p=0.02), and abdominal pain (OR 7.40,p<0.01). Increasing age and longer disease duration were associated with higher odds of constipation, dysphagia, cholelithiasis, and non-alcoholic liver steatosis (p<0.05). No associations were observed for CTG repeat size or BMI. GI symptoms are highly prevalent and burdensome in adult-onset DM1. Female sex, longer disease duration, and older age were associated with a higher symptom prevalence. Structured screening using PROMs should be integrated into multidisciplinary care to ensure that these symptoms are detected promptly and addressed adequately.

Conventional clinical monitoring of anesthetic agents predominantly relies on indirect physiological indicators, which fail to accurately quantify the actual anesthetic concentrations in circulating blood. We report a surface-enhanced Raman spectroscopy (SERS) sensing platform based on TiO₂@Ag nanocomposites, coupled with optimized solid-phase extraction pretreatment, for the semi-quantitative trend monitoring of anesthetic drugs in complex blood matrices. This platform achieves reliable detection across the clinically relevant concentration range (nanomolar to micromolar levels), enabling concentration-dependent detection of four widely used clinical anesthetic agents with excellent reproducibility. Validation with authentic clinical blood samples further confirms a significant correlation between recorded SERS signals and LC-MS/MS-determined laudanosine concentrations, together with physiologically consistent trends in pharmacodynamic responses. Collectively, these proof-of-concept findings support the preliminary feasibility of SERS-based intraoperative anesthetic monitoring, warranting further validation toward future perioperative drug monitoring applications.

Accurate detection of acetylcholinesterase (AChE) activity and its inhibitors is indispensable for the early diagnosis and drug discovery of neurodegenerative diseases. In nanozyme-based assays, the sensing mechanism relies on thiocholine (TCh), the product of AChE-catalyzed acetylthiocholine hydrolysis, which specifically inhibits the peroxidase (POD)-like activity of the nanozyme, thereby reducing the oxidation of 10-acetyl-3,7-dihydroxyphenoxazine (ADHP) to the fluorescent and chromogenic product resorufin, enabling indirect quantification of AChE activity. However, conventional nanozyme-based AChE assays are fundamentally limited by a long-standing paradigm conflict: highly active nanozymes typically require acidic conditions for optimal catalysis, whereas AChE and biological systems function exclusively at near-neutral physiological pH. This incompatibility forces tedious pH-switching protocols, which inevitably cause AChE inactivation, signal distortion, and poor reproducibility. Here, we address this incompatibility by engineering an amphiphilic osmium (Os)-ruthenium (Ru) bimetallic polymeric nanozyme (polymer@OsRu) that exhibits robust POD-like activity at neutral pH, achieving high catalytic efficiency without compromising biocompatibility. This work delivers two key advances: (i) materials innovation-the polymer and the Os-Ru bimetallic synergy enable robust catalytic activity under physiological conditions, overcoming the limitations of conventional nanozymes; (ii) platform innovation-the integration of dual-mode (colorimetric and fluorescent) readouts provides intrinsic cross-validation, significantly enhancing detection reliability. The platform achieves ultrasensitive acetylcholinesterase (AChE) detection (LOD = 0.0297 mU mL^-1 for colorimetry and 0.0856 mU mL^-1 for fluorometry) and reliable inhibitor analysis (IC₅₀ = 0.716 µM and 0.92 µM for the clinical drug rivastigmine tartrate), outperforming most reported neutral-pH AChE assays. Beyond analytical performance, this study establishes a generalizable design principle for decoupling nanozyme catalytic efficiency from pH constraints, establishing a versatile framework for physiologically adaptive, multimodal biosensing with broad implications in neurodegenerative diagnostics and drug discovery.

Conventional thrombolytic agents exhibit significant limitations in treating thrombotic disorders characterized by narrow therapeutic windows and persistent vascular injury, failing to meet clinical requirements in terms of precision, timeliness, and treatment durability. To address these challenges, we have developed a blood cell membrane-camouflaged probiotic-powered micro-robot system (EcN-PN/rt-PA). This innovative system utilizes natural probiotics as biological carriers functionalized with drug-loaded hybrid membrane nanovesicles possessing dual-targeting capabilities against thrombus. By harnessing the rapid motility of probiotics and the active targeting properties of the hybrid membranes, the system achieves rapid and precise delivery of thrombolytic drugs to thrombotic tissues. Capitalizing on the innate rod-shaped structure and self-propelling capacity of probiotics, this micro-robot demonstrates enhanced penetration depth into thrombotic tissues, significantly improving thrombolytic efficiency. Experimental results reveal that this thrombolytic micro-robot, which combines thrombus targeting, deep penetration, and prolonged circulation characteristics, not only rapidly and accurately targets and penetrates thrombotic tissues but also extends the biological half-life of thrombolytic drugs approximately 193-fold, enabling sustained thrombolytic effects while effectively inhibiting secondary thrombus formation. This novel dual-targeting thrombolytic strategy provides an important scientific solution for treating thrombotic diseases with narrow therapeutic windows caused by vascular injury.

Globally, births to women in their early thirties have become more prevalent. The current study aimed to examine the association of maternal age (30-34 years) with adverse perinatal outcomes, especially congenital birth defects and stillbirth.

A literature search was conducted using PubMed, Web of Science, and Google Scholar for relevant studies published between July 1989 and August 2025. The primary outcomes were congenital birth defects (i.e., composite of Down syndrome and structural birth defects) and stillbirth. The secondary outcomes were preterm birth, low birthweight (LBW), neonatal mortality, small-for-gestational age (SGA), and intrauterine growth restriction (IUGR). Adverse perinatal outcomes were examined in women aged 30-34 compared with younger cohorts aged 18-29 years. The quality of the included studies and potential publication bias were evaluated. For the meta-analysis, forest plots were created for each outcome, and heterogeneity was assessed using the I² statistic. Data were synthesized employing both random- and mixed-effects models.

Sixty studies were included in this meta-analysis. Maternal age (30-34 years) was associated with a significantly higher risk of overall congenital birth defects (OR, 1.10; 95% CI, 1.03, 1.17; P = 0.007; I ² = 92) compared with a reference age group of 18-29 years. The pooled subgroup analysis revealed that maternal age (30-34 years) showed a significant association with Down syndrome (OR, 1.97; 95% CI, 1.79, 2.16; P < 0.00001; I ² = 0) but a non-significant association with structural birth defects (OR, 0.99; 95% CI, 0.94, 1.05; P = 0.8; I ² = 84). Moreover, maternal age (30-34 years) showed a non-significant association with stillbirth (OR, 1.07; 95% CI, 0.94, 1.23; P = 0.3; I ² = 100), preterm birth, LBW, neonatal mortality, SGA, and IUGR.

Maternal age 30-34 years was associated with a significantly higher risk of congenital birth defects, especially Down syndrome, but was not associated with other adverse perinatal outcomes, when compared to the 18-29 age group.

https://www.crd.york.ac.uk/prospero/, identifier CRD420251105683.

Clearance of dead cells by efferocytosis is a critical process for homeostasis, notably by limiting inflammation. Defective efferocytosis has been associated with autoimmune, neurodegenerative, and cardiovascular diseases, as well as chronic infections, making its regulation a potential therapeutic target. Here, we identify circulating cochlin LCCL (Limulus factor C, Cochlin, and Lgl1) domain as a regulator of efferocytosis. Using cell binding assay for recombinant cochlin LCCL domain, we establish its tropism for dead or dying cells of both immune and non-immune lineages from murine and human origins. By three independent functional assays, we demonstrate that endogenous and exogenous cochlin LCCL domain enhances macrophage efferocytosis in vitro and in vivo in lipopolysaccharide (LPS)-induced inflammation and intranasal Pseudomonas aeruginosa infection, to a similar extent as the efferocytosis promoter GAS6. Our findings provide a role of cochlin LCCL domain in the regulation of efferocytosis, alongside its already described pro-inflammatory role, as an immunomodulator for host response and homeostasis.