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.

Adolescence represents a developmental phase marked by profound and rapidly shifting emotional states. While some adolescents exhibit pronounced, day-to-day mood variability, others remain comparatively stable. Although emotional fluctuation has long been considered a core feature with implications for health and well-being, the determinants underlying these substantial individual differences remain insufficiently understood. To address this, we conducted a longitudinal study using daily app-based assessments, aiming to explore whether perceived stress and self-esteem dynamics help explain why some adolescents show greater mood variability than others. We asked N = 70 adolescents to rate their self-esteem, positive, and negative mood once per day for 15 days. For data analyses, we used path analytic mediation modeling. Fluctuation of self-esteem (FSE) significantly predicted both fluctuation of positive mood (FPM; b = 0.282, 95% CI [0.101, 0.464], p = .0.002) and fluctuation of negative mood (FNM; b = 0.395, 95% CI [0.147, 0.644], p = 0.002) indicating that greater variability in self-esteem is associated with greater mood fluctuation. Moreover, perceived stress (PS) significantly predicted FSE (b = 0.057, 95% CI [0.012, 0.102], p = 0.013), suggesting that higher perceived stress was associated with greater self-esteem fluctuation. Significant indirect effect emerged for PS on FPM (b = 0.016, 95% CI [0.003, 0.030], p = 0.019) and on FNM (b = 0.023, 95% CI [0.002, 0.043], p = 0 .028) via FSE, confirming a mediating role of self-esteem fluctuations. This study showed that perceived stress was associated with fluctuations in self-esteem, which were related to mood variability among adolescents. These findings suggest that stress reduction could be explored as a potential avenue for future interventions.

Intravenous ketamine and intranasal esketamine have shown rapid effects in reversing suicidality and improving depressive symptoms. In countries that allow psychiatric euthanasia and/or assisted suicide (EAS), we argue that potentially effective treatments for suicidal ideation and behaviour, such as ketamine, should be required before allowing patients to access psychiatric EAS. Ketamine can both help clarify patients' decision-making capacity and serve as a reasonable therapeutic alternative when determining irremediability. For patients who refuse potentially effective treatments such as ketamine, oversight bodies should establish a formal process through which they can petition for review of their EAS request-protecting their legal right to die while guarding against potentially preventable death.

Globally, parenting interventions have been shown to improve caregiving practices and child development. However, rigorous evidence from sub-Saharan Africa remains limited, particularly for programmes that leverage multiple community-based delivery platforms. We evaluated the effectiveness of the Moments that Matter (MTM) parenting programme delivered by community volunteers in partnership with faith leaders on child development and caregiving-related outcomes in Kenya.

We conducted a cluster-randomised controlled trial in two counties in western Kenya. Villages were randomly assigned to the MTM parenting programme or a standard-of-care waitlist control, stratified by county. Eligible participants were primary caregivers of children aged 0-18 months. The intervention consisted of monthly group sessions and home visits delivered over 18 months. Caregivers were surveyed at baseline and endline. The primary outcome was child development measured using the Caregiver Reported Early Development Instruments. Intervention effects were estimated using mixed-effects models with a difference-in-differences, intention-to-treat approach.

Between February and March 2023, 595 caregiver-child dyads in 46 villages were enrolled and randomly assigned to the intervention (n=310) or control (n=285). At endline, there were no overall intervention effects on child development outcomes. Moderate-to-large effects were observed across multiple secondary outcomes, including caregiver stimulation, harsh discipline, caregiver mental health, social support, intimate partner violence victimisation, child dietary diversity, and male caregiver engagement, as reported by female primary caregivers. Exploratory subgroup analyses revealed treatment heterogeneity by county, with small significant improvements in child language and socioemotional development in one county but null effects in the other.

A multicomponent parenting programme delivered in partnership between community volunteers and faith leaders improved multiple caregiving and family well-being outcomes but did not lead to overall improvements in child development. Findings highlight the potential of integrating multiple community-based platforms for delivering parenting programmes, while underscoring the need for implementation research to enhance impacts on child development at scale.

NCT05796934.