Browse Articles

Transiently amplified fluctuations assemble dissipative materials

Chemical reactions assemble supramolecular materials with finite lifetimes, responsiveness to stimuli, and the capacity to self-heal after perturbation. These dynamic behaviors arise from a reaction cycle that switches a molecule between associating and nonassociating states via two independent pathways, each driven by a distinct chemical reagent. Here, we show that this same network architecture can transiently amplify small concentration fluctuations, leading to a pronounced, spontaneous increase in the yield of assembled material. Following a small perturbation in reagent supply, the chemical kinetics do not immediately relax toward a steady state; instead, they initially evolve farther from equilibrium and promote the assembly of thermodynamically unstable products. For a model supramolecular system, this dynamical effect produces a strong transient amplification of assembled material above its steady-state level. By analyzing the conditions for transient growth and its maximum, we find that steady states farther from detailed balance can exhibit stronger amplification and higher transient yields. Although these excursions are short-lived, accumulating experimental evidence suggests that analogous dynamics already occur in chemically active supramolecular materials. The mathematically precise conditions identified here suggest opportunities to amplify fluctuations in the design of responsive materials.

Abstract 10: Online food pantries as a novel setting for behavioral nudge interventions to improve diet and reduce cardiovascular risk in households facing food insecurity

Background: Individuals facing food insecurity have higher cardiovascular risks, partly due to unhealthy diets. Healthy food nudges harness heuristics to increase selection of healthier options and their use in charitable food programs can help reach food insecure families while maximizing resources. In this qualitative study, we explored the decision environment of online food pantries, including decision-making factors of the shoppers, to inform nudge development. Methods: We recruited adults who were shoppers or workers of online food pantries in metro Chicago in a 2:1 distribution, respectively. We conducted semi-structured interviews that covered several topic areas, including the online pantry experience and decision-making factors when shopping the pantry. All interviews were transcribed, translated (for Spanish interviews), and underwent content analysis to describe the decision environment and key determinants of food choices. Results: Interviews were conducted with 32 participants, of which 69% were shoppers. Instead of pre-planned grocery lists, most shoppers described making decisions as they scrolled through the online site, which presented the opportunity for nudges to influence the decision-making moment. Also, most shoppers (77%) ordered as regularly as allowed, demonstrating the potential for repeat exposure to behavioral interventions. Specific characteristics of a food item or social factors influenced decision making about food choices (Figure). Item-specific factors were the item’s market value, ability to combine with other pantry offerings to make a meal, ability to be prepared in multiple ways, healthfulness (both in supporting general good health and chronic disease management), freshness (as opposed to nonperishables), and novelty. Major social factors were taste preferences and dietary restrictions of the household, size of household, and consideration of other shoppers’ needs and waste reduction. Conclusions: We identified decision-making patterns and processes of individuals who utilize online pantries; this information can be used to design and implement healthy food nudges in online food pantries. While health is a major decision-making factor, other food-related and social factors are also involved in the heuristics of choosing groceries in online food pantries. Nudges that bundle healthy pantry offerings may further increase healthy food selection while helping shoppers to meal-plan a variety of dishes for their households.

Abstract 33: Equivalence of Algorithm- and Log-guided Sleep Estimates within GGIR: The REasons for Geographic and Racial Differences in Stroke 24-hour Activity Cycles (REGARDS 24H-ACT) Study

Introduction: A best practice for sleep actigraphy assessment includes concurrent participant completion of a daily sleep log, which poses additional burden on both the participant (~3 minutes [min]/day) and research staff (~30 min/participant for data entry and verification steps). The Heuristic algorithm looking at the Distribution of Change in Z-angle (HDCZA), the default GGIR algorithm in R, estimates the rest interval by detecting sleep onset and wake-up times from raw acceleration data, without a sleep log. This study examined equivalence in HDCZA versus log-guided sleep parameters. Methods: Data are from an initial sub-set of 1,059 REGARDS 24H-ACT ancillary study participants (aged 77.7 ± 6.9 years, 56.9% female, 23.2% Black, and 52.6% from the Stroke Belt region). Participants were asked to wear a GENEActiv device (Activinsights Ltd.; Kimbolton, UK) on their non-dominant wrist for 24 hours/day over 8 consecutive days. Raw acceleration data were processed in GGIR using HDCZA- and log-guided approaches. A set of primary sleep parameters, including sleep onset and wake-up times (hh:mm ± min; 24H time) and rest and sleep intervals (min), were averaged across nights and compared between the two scoring methods using paired t-tests and two one-sided equivalence tests with ± 30 min equivalent zones. Results: The (mean ± standard deviation) sleep onset time was (HDCZA: 22:54 ± 106.5 min vs log: 22:50 ± 94.0 min), wake-up time was (HDCZA: 7:07 ± 103.4 min vs log: 7:18 ± 91.9 min), rest interval was (HDCZA: 493.5 ± 101.2 min vs log: 507.7 ± 88.6 min), and sleep interval was (HDCZA: 411.6 ± 91.7 min vs log: 366.8 ± 79.5 min). The mean difference in sleep onset time was statistically null; however, wake-up time, rest, and sleep interval durations significantly differed between the scoring methods (all p<0.001). The sleep interval duration was not statistically equivalent between scoring methods; however, the remaining sleep parameters were statistically equivalent within ± 30 min (Figure). Conclusion: While statistical equivalence was found with some sleep parameters, the HDCZA method did not yield precise estimates for the sleep interval. Given the importance of accurate sleep interval estimation for public health recommendations and analytic techniques based on sleep duration (e.g., compositional data analysis), using only the HDCZA-detected method may lead to misclassification of overall sleep health. Funding: RF1AG077707 and R01AG077707 (to KMD, KPG, and PP)

Abstract TH874: The Platelet-to-HDL Ratio Partially Mediates the Association Between Lipoprotein(a) and Abdominal Aortic Aneurysm: A Single Center Retrospective Study

Background: Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease, but its mechanistic role in abdominal aortic aneurysm (AAA) remains uncertain. Given that inflammation plays a central role in both vascular remodeling and aneurysm progression, we hypothesized that systemic inflammation mediates the relationship between Lp(a) and AAA. Methods: This retrospective study included 468 hospitalized patients between 2022 and 2024, consisting of 148 with AAA and 320 with valvular heart disease as control. Serum Lp(a) levels and routine hematologic indices were measured, and seven derived inflammatory indices (e.g., neutrophil-to-HDL ratio, monocyte-to-HDL ratio, lymphocyte-to-HDL ratio, platelet-to-HDL ratio [PHR]) were calculated. Mediation analyses adjusted for clinical covariates assessed direct and indirect effects of Lp(a) on AAA. Results: Multivariable logistic regression analysis revealed that both Lp(a) and PHR were independently associated with AAA (Lp(a): OR = 1.002 [1.001, 1.003]; PHR: OR = 1.006 [1.003, 1.006]). Mediation analysis showed that only PHR demonstrated a statistically significant mediating effect between Lp(a) and AAA (average causal mediation effect = 0.0002, [0.0000, 0.0004]). The total effect of Lp(a) on AAA was 0.0018, with a direct effect of 0.0017 and an indirect effect via PHR of 0.0001. Conclusions: Elevated Lp(a) was independently associated with the presence of AAA, and part of this association was mediated through platelet-related inflammatory activation, as reflected by PHR. This suggests a role for platelet-related inflammation in the underlying mechanism, which may inform future therapeutic strategies.

Subcellular calcium dynamics and organelle perturbations in resistosome-mediated cell death

Plant nucleotide-binding domain leucine-rich repeat-containing (NLR) proteins act as intracellular immune receptors that assemble into resistosomes to execute immune responses. However, the subcellular processes during cell death following resistosome activation remain unclear. Here, we visualized the changes in calcium signaling and organelle behavior after activation of the NRC4 (NLR required for cell death 4) resistosome. We found that NRC4 membrane enrichment coincided with calcium influx. This is followed by sequential mitochondria and plastid disruption, endoplasmic reticulum fragmentation, and cytoskeleton depolymerization. Subsequent loss of plasma membrane integrity, nuclear shrinkage, and vacuolar collapse mark the terminal stage of cell death. Our findings reveal a spatiotemporally resolved cascade of subcellular events downstream of resistosome activation, providing mechanistic insight into the execution phase of plant immune cell death.

The psychological impact of first-time childbirth on parents

The psychological effects of first-time childbirth on parents have long been a focal point in social science research. This study provides a new perspective by applying demographic transition theory to explore how the experience of having a first child influences parents’ mental health. Our findings indicate that the arrival of a first child not only increases family size but also brings about significant psychological and emotional adjustments in parents. These changes are often driven by pressures associated with financial stability, career development, and shifts in personal identity, which prompt parents to reconsider their life goals and values. Moreover, the psychological effects of first-time childbirth vary notably across different socioeconomic backgrounds. This paper offers empirical insights that can guide policymakers and social organizations in developing targeted support and intervention strategies to enhance parental well-being during the transition to parenthood.

Abstract 40: Risk of Incident Chronic Kidney Disease Among Subtypes of Prevalent and Incident Cardiovascular Disease: UK Biobank

Introduction: Cardiovascular disease (CVD) and chronic kidney disease (CKD) are interconnected through shared risk factors and vascular pathology. CKD is a well-established driver of cardiovascular morbidity and mortality, but risk for the development of new-onset CKD after CVD remains poorly defined. Current CVD guidelines lack recommendations for kidney function or albuminuria screening and thus it is rarely performed in clinical settings. We aimed to estimate the risk of incident CKD among individuals with subtypes of prevalent CVD and following incident CVD events. Methods: We analyzed 394,344 participants from the UK Biobank, excluding individuals with baseline CKD (estimated glomerular filtration rate <60mL/min/1.73m2 or urine albumin-to-creatinine ratio >30mg/g). Participants were stratified by prevalent CVD subtype—heart failure (HF), myocardial infarction, stroke, atrial fibrillation, or peripheral artery disease (PAD)—using diagnostic codes. Multivariable Cox regression models estimated hazard ratios (HR) for incident CKD adjusting for demographics, socioeconomic status, comorbidities, laboratory values, medications, and study site. Adjusted 5- and 10-year cumulative CKD incidences were derived from the models. Analyses were repeated for incident CKD following incident CVD events. Results: The sample was 54.4% female with mean age 56.7 years. Over a median follow-up of 13.5 years, all subtypes of prevalent CVD were independently associated with increased risk of incident CKD. Incidence rates were highest for HF (10.6/1000 person years) and PAD (12.4/1000 person years), in the absence of other CVD. Participants with HF and PAD had the highest relative and absolute risks for incident CKD compared to no CVD (HF: HR 1.51, 95%CI 1.31–1.74; PAD: HR 1.51, 95%CI 1.30–1.75). The 10-year adjusted cumulative CKD incidences were 5.6% (95%CI 4.9–6.4) for HF and 5.3% (95%CI 4.9–5.7) for PAD. The lowest risk was observed for prevalent stroke (HR 1.24, 95%CI 1.13–1.36). Among incident CVD events, incident HF was associated with the highest risk (HR 3.03, 95%CI 2.89–3.17) of subsequent CKD, corresponding to a 10-year adjusted cumulative incidence of 9.7% (95%CI 9.3–10.1). Conclusions: Both prevalent and incident CVD are associated with substantially increased risk of developing CKD. These findings support incorporating CKD screening into post-CVD care pathways, particularly following HF or PAD, to facilitate early identification and prevention of CKD progression.

Abstract TH823: Gut microbiome correlates of CGM metrics and progression toward diabetes in adults without diabetes

Gut microbial composition has been linked to type 2 diabetes (T2D) and prediabetes. Continuous glucose monitoring (CGM) provides dynamic measures of glycemic regulation and may detect early dysglycemia. However, it is unclear how CGM metrics may relate to the gut microbiome among individuals without T2D. We included 790 participants from the Framingham Heart Study (FHS) Third Generation cohorts without T2D who underwent stool shotgun metagenomics at baseline (2016-2019) and had ≥3 days of Dexcom G6 Pro CGM data (2022-2025). We examined associations of gut microbial species with eight CGM metrics, fasting blood glucose (FG), and HbA1c using multivariable models (MaAslin 2, FDR q <0.05). We created separate microbial composite scores for CGM related species and FG/HbA1c related species, each summed and weighted by their respective beta coefficients. Among individuals without T2D at baseline (n=826), we examined the prospective association of each microbial score with T2D using multivariable logistic regression models. We repeated analysis among individuals without prediabetes at baseline (n=570) to assess prediabetes upon follow up. Multivariable logistic regression models were adjusted for age, sex, education, diet quality, medication use, and other lifestyle factors. FHS participants (mean age at baseline 55 y, 58% female) had an average age of 61 years at follow-up, FG of 94mg/dL, and 31% had prediabetes at baseline. We observed 44 associations of 19 unique microbial species with glycemic outcomes, including 35 negative and four positive associations with CGM metrics (% time above 140, continuous overall net glycemic action over 24 hours, coefficient of variation, mean glucose, and glycemic risk assessment diabetes equation), 5 species associations with FG, and no associations with HbA1c ( Figure 1 ). Over a median follow up of 6.2 years, there were 36 new cases of T2D and 171 cases of prediabetes. In multivariable adjusted models, a CGM microbial score was associated with a 37% (OR 0.63, [95% CI 0.43, 0.91]) lower odds of T2D and a 19% (OR 0.81, [95% CI 0.65, 0.99]) lower odds of prediabetes ( Figure 2 ). Results for T2D were similar with adjustment for FG but were attenuated for prediabetes. There were no significant associations of an FG microbial score with T2D or prediabetes in fully adjusted models. CGM related microbial features are associated with lower odds of T2D and may provide insight between microbial communities and progression of dysglycemia.

Abstract 18: Association of Serum Metabolic Profiles with Mortality and Longevity: The Trans-Omics for Precision Medicine (TOPMed) Study

Introduction: All-cause and cause-specific mortality remain major measures of public health burden, despite the rising number of individuals achieving longevity (≥85 years). Although many mortality-related metabolites have been identified, metabolite predictors of long-term mortality and longevity across diverse populations remain understudied. We aim to identify novel metabolites associated with mortality and longevity. Methods: Circulating metabolite profiling was performed across seven cohorts in the Trans-Omics for Precision Medicine project. Cox models were used to examine the associations of 1,121 metabolites with all-cause, cardiovascular (CV), cancer, and respiratory mortality. Logistic regression was used to assess longevity, defined as living past 85 years at the end of follow-up, adjusting for clinical risk factors (CRF). Random-effects meta-analysis was used to estimate joint effects, and subgroup analyses were conducted by sex and race. Replication was performed using independent samples. Results: During an average follow-up of ten years among 26,091 participants (57% women, 41% Whites), there were 6,315 deaths, including 1,649 (26%), 1,387 (22%), and 314 (5%) from CV, cancer, and respiratory diseases, and 4,216 participants achieved longevity. A total of 183, 101, 12, and 23 metabolites were discovered and replicated (FDR < 0.05) for all-cause, CV, cancer, and respiratory mortality, with a range of 20% to 98% risk difference per SD increase of the metabolite. Nearly half of the metabolites were novel, and carnitines, glycerophospholipids, ceramides, and sphingolipids were leading pathways. A metabolite risk score derived from all-cause mortality-related metabolites improved the prediction of all-cause mortality by an average of 3.3%, using Harrell’s C, beyond CRF across participating cohorts. In the longevity analyses, 38 metabolites were discovered and replicated, and 31 were shared with all-cause mortality (correlation r = -0.97). Among the seven metabolites uniquely linked to longevity, taurocholate, glycocholate, and glycoursodeoxycholate suggested distinct bile acid metabolism, possibly driven by enterohepatic or microbiome-related processes. Subgroup analyses of all-cause mortality and longevity by sex and race revealed no significant heterogeneity across strata. Conclusions: We identified circulating metabolites associated with mortality and longevity, providing insight into slowing aging and the identification of at-risk populations.

A nematode-built conduit for cross kingdom biotrophic interaction

Traffic conflict identification method on curved road based on Frenet coordinate system

Aiming at the TTC (Time to Collision) and derivative indicators’ problems of unclear definition and missed/wrong judgments of traffic conflicts on curved road in the traditional Cartesian coordinate system, a new method that can better identify the conflicts on curved road is proposed. The method first establishes the Frenet coordinate system according to the road centerline (i.e., the reference line), and obtains the vehicle trajectory coordinates in the Frenet coordinate system. The Frenet coordinate system can simplify the calculation difficulty of vehicle trajectory and conflict under the curve road. Then determine the vehicle state in the Frenet coordinate system, and then use TTC to calculate rear-end and lane-change conflicts according to the state of the vehicle (non-lane-change/lane-change). Finally, a total of 4 hours of video data were collected based on the K283 of the lane-switch work zone of the Jiqing Highway. Subsequently, the continuous high-precision conflict data in the region was obtained through the video and conflict identification program, and the traditional method was compared with the new method. The results show that different methods have a significant impact on the identification of the number of serious conflicts. The new method can reduce the missed judgments of serious rear-end conflicts on curved road, especially at the junctions of curved and straight segments (segment 3/4/7/8/9), and can also reduce wrong judgments of serious lane-change conflicts. In addition, among the 125 added serious rear-end conflicts identified by the new method, the maximum deceleration of 10 conflicting vehicles during the conflict exceeds the dangerous state −4/-1.5m/s 2 , which explain that the new method can help us better identify the risks of curved road. The new method combines the Frenet coordinate system, vehicle state determination and TTC, which can reduce the missed/wrong judgments of conflicts on curved road, and expand the traffic conflict identification from previous straight road to full-line road alignment.

Abstract WE574: Systematic Review and Meta-Analysis of Left-Sided Valvular Involvement in Intravenous Drug Use–Associated Infective Endocarditis

Background: Right-sided infective endocarditis is classically linked to intravenous drug use (IVDU), yet contemporary reports suggest substantial left-sided and multivalvular disease. The true burden across valves and its clinical implications have not been quantified in a comprehensive synthesis. Hypothesis: We hypothesize that left-sided valve involvement represents a significant and underrecognized proportion of IVDU-associated infective endocarditis and is associated with higher rates of surgery and death compared with isolated right-sided disease. Methods: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD420251010004), we searched PubMed, Embase, Scopus, and Web of Science (January 2021–December 2025) for studies enrolling adults (≥18 years) with echocardiography-confirmed IVDU-associated infective endocarditis. Random-effects meta-analysis (DerSimonian–Laird) estimated pooled prevalence and relative risk (RR) with 95% confidence intervals (CIs). Heterogeneity was assessed with I 2 , risk of bias with ROBINS-E, and small-study effects with funnel plots and sensitivity analyses. When reported, side-specific prevalences allowed both-sided cases to contribute to each side. Results: Fourteen studies (n=1,783 patients) met eligibility criteria. Pooled prevalence was 61% (95% confidence interval (CI)=57–65) for right-sided involvement, 41% (95% CI=35–47) for left-sided involvement, and 7% (95% CI=5–10) for both-sided disease. Valve-level involvement was tricuspid 61%, mitral 23%, aortic 17%, and pulmonic 1%. Compared with left-sided disease, right-sided involvement was more frequent (relative risk (risk ratio)=1.49; 95% CI=1.15–1.95; p=0.008). Staphylococcus aureus was the leading pathogen (73%), including methicillin-resistant strains in 17%. Valve surgery occurred in 21% and all-cause mortality in 17%. Findings were robust in leave-one-out and subgroup analyses with minimal evidence of publication bias. Conclusions: Left-sided valve involvement occurs in approximately two in five cases of IVDU-associated infective endocarditis, which is far higher than traditionally appreciated, and frequently affects the mitral and aortic valves. These data challenge the assumption of predominantly right-sided disease and support routine transesophageal echocardiography, early surgical evaluation, and integrated addiction care to improve outcomes in this high-risk population.

Abstract TH938: Association between AHA’s Life’s Essential 8 and Coronary Artery Plaque Burden in the VA Million Veteran Program

Background: While AHA’s Life’s Essential 8 (LE8) metric predicts cardiovascular events, its association with coronary plaque measured by invasive angiography and interaction with genetic risk are unknown. We examined associations between LE8, plaque burden, and genetically predicted coronary artery disease (CAD) in U.S. veterans. Methods: This cohort study included VA Million Veteran Program (MVP) participants who underwent invasive angiography (2000-2021) and completed the MVP Lifestyle Survey to derive the exposure LE8 score (0-100; higher = better cardiovascular health). The outcome was plaque severity (normal = reference, non-obstructive, 1-vessel, 2-vessel, 3-vessel/left main disease). Multinomial regression was used to assess associations between LE8 and plaque severity, adjusting for age at angiogram, sex, race, and ethnicity. We also examined whether the effects of LE8 on plaque severity are independent of genetically predicted CAD estimated by a polygenic risk score. Results: We included 22,234 veterans (mean [SD] age, 67.4 [8.4] years; 21,447 [96.5%] male); 18,304 (82.3%) self-identified as White and 2,186 [9.8%] as Black. Median [IQR] LE8 score was 54 [45-63]. LE8 score was inversely associated with prevalence of any plaque, with larger effect sizes observed with increasing plaque burden: OR per 10 points increase in LE8 score was 0.86 (P = 9.2×10 -15 ) for non-obstructive, 0.84 (P = 5.8×10 -20 ) for 1-vessel, 0.81 (P = 6.7×10 -24 ) for 2-vessel, and 0.74 (P = 1.6×10 -50 ) for 3-vessel/left main disease. Cholesterol, glucose, and smoking were the LE8 components most strongly associated with plaque burden. Among 15,015 participants of genetically inferred European ancestry (EUR) and 1,825 of African ancestry (AFR), LE8 score remained inversely associated with plaque burden independent of genetically predicted CAD. We did not detect a significant interaction between LE8 and genetic risk for CAD, but we observed a trend towards attenuated LE8 effects for those with high genetic risk among EUR (P interaction = 0.095). Conclusions: Higher LE8 score is associated with lower odds of developing coronary artery plaque, with stronger associations across greater plaque burden, independent of genetically predicted CAD. Among individuals with lower genetic risk for CAD, LE8 was more strongly associated with plaque burden. These findings highlight the value of lifestyle-based interventions to mitigate plaque accumulation even in those with genetic predisposition.

Abstract 35: Sleep Differences in Elementary-Age Children by Household Income During School Vs. Summer: Findings from the What’s UP (Undermining Prevention) with Summer Observational Cohort Study

Purpose: Children experience excessive weight gain during the summer months, and changes in sleep behaviors may contribute. Children in low-income families are at elevated risk of engaging in poorer health behaviors and health outcomes and may be exposed to greater changes in sleep during summer. The purpose of this study was to assess differences in school-aged children’s sleep health by household income separately while in school and summer. Methods: Children (n=1,007, age range: 5-14yrs, 49% female) wore an Actigraph GT9X for 24 hours per day over 14 days in spring and summer across a maximum of 3 years (6 timepoints). Sleep duration, bedtime, and waketime were calculated using the GGIR (v3.1.2) R package and HDCZA algorithm. Variability of these metrics was calculated as the individual standard deviation across days at each timepoint. Income groups were determined as parent-report of household income, categorized as low-income (<2.0 income-to-poverty ratio), middle-income (2.0-3.0 income-to-poverty ratio), or high-income (>3.0 income-to-poverty ratio). We utilized mixed effects models to examine mean levels and variability of sleep metrics to compare income groups in school and summer. Results: Analyses included 34,767 days of accelerometer data. Children had similar sleep duration and timing during school and summer across income groups. However, children in low-income families went to bed significantly later in summer than children in middle (+13.2mins, 95%CI: 5.3, 21.1) and high-income (+21.0mins, 95%CI: 10.1, 31.9) families. Children in low-income families also woke up significantly later in summer than children in high-income families (+12.1mins, 95%CI: 2.4, 21.9). Bedtime was more variable in summer (low vs. middle: +5.2mins; 95%CI: 2.5, 7.9; low vs. high: +8.5mins; 95%CI: 4.8, 12.3), while waketime was more variable in school (low vs. middle: +10.3mins; 95%CI: 7.8, 12.8; low vs. high-income: +13.1mins; 95%CI: 9.6, 16.6) and in summer (low vs. middle: +12.0mins; 95%CI: 9.4, 14.5; low vs. high: +18.7mins; 95%CI: 15.3, 22.2). Conclusions: Children from low-income households had later sleep timing and more sleep variability as compared to their middle and high-income counterparts. Future studies should examine the contextual and behavioral time-use factors associated with sleep health in children across income groups, especially in low-income families, to identify where or when to intervene for effective sleep intervention.

Electroacupuncture-based vagal stimulation attenuates epileptic seizures through a body–brain circuit

Vagus nerve stimulation offers a promising strategy for seizure control but remains limited by its invasive delivery. Here, we reveal electroacupuncture (EA), an ancient neuromodulatory technique rooted in traditional Chinese medicine, at specific somatic acupoints linked to the vagal–brain axis to treat epilepsy and delineate the precise underlying neural mechanisms. We demonstrate that EA at the Dazhui (GV14) acupoint exhibits broad-spectrum antiseizure efficacy across multiple seizure models. Anatomical and functional analyses reveal that GV14 activates the vagal afferents and recruits neurons in the caudal nucleus of the solitary tract (cNTS), which are essential for seizure suppression. Using targeted recombination in active populations and chemogenetic manipulation, we show that GV14 EA suppresses seizures via the recruitment of a defined cNTS–locus coeruleus–amygdala circuit. Furthermore, through vagal afferent activity screening, we identify Yaoqi (EXB9) as an alternative therapeutic acupoint that activates a shared neural pathway to robustly attenuate seizures. Importantly, thread-embedding acupuncture at GV14 or EXB9 produces sustained seizure reduction in a chronic epilepsy model. Together, these findings elucidate a functional vagal–brain circuit underlying EA-induced seizure control and support its translational potential as a minimally invasive neuromodulatory strategy to replace vagal stimulation for epilepsy treatment.

Loss of a major toxin gene cluster defines a metabolic schism and host-specific virulence in Botrytis pseudocinerea

Botrytis pseudocinerea is a cryptic fungal species, sympatric with the notorious plant pathogen Botrytis cinerea , yet possessing distinct ecological traits including intrinsic fungicide resistance. Despite this advantage, B. pseudocinerea rarely dominates agricultural ecosystems, presenting an ecological paradox. This study resolves this paradox by defining the unique pathogenic identity of B. pseudocinerea isolate VD165. We demonstrate that VD165 exhibits superior vegetative growth and stress tolerance compared to B. cinerea B05.10, coupled with heightened virulence on solanaceous hosts (tomato, tobacco) but reduced virulence on grape. A comprehensive bio-guided chemical investigation reveals a fundamental metabolic schism: the constitutive and infection-induced upregulation of botcinin polyketides (via Bcboa6 / Bcboa9 ) contrasted with the complete functional loss of the botrydial sesquiterpene pathway. This loss is biochemically confirmed by the significant accumulation of the upstream precursor mevalonolactone. This chemotype, loss of botrydial and compensatory super-activation of botcinins, phenocopies B. cinerea Δ Bcbot2 mutants, establishing B. pseudocinerea as a “natural knockout” model that validates the inverse regulation of these major toxin families. We propose that this “evolution by subtraction” is a lineage-specific adaptation shared with the sister species B. fabae , driving host specialization and defining the ecological niche of B. pseudocinerea .

Abstract WE412: Androgenic Profile and Cardiometabolic Health among Post-Menopausal Women: the Buffalo OsteoPerio Study

Objective: Postmenopausal women have relatively higher testosterone than estradiol. We aim to use traditional and data-driven approaches to explore how such an androgenic hormone milieu of multiple correlated sex steroids may be associated with cardiometabolic health in postmenopausal women. Methods: We measured serum testosterone, estradiol, sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEA-S) among 599 postmenopausal women from the Buffalo OsteoPerio Study. Using a traditional approach, we created an androgenicity profile index (API) from biomarker z-scores (z testosterone + z DHES-S − z estradiol − z SHBG ). We used linear regression and quantile regression to assess associations of the API and its individual components with the calculated Framingham 10-year coronary heart diseases (CHD) risk score and homeostasis model assessment for insulin resistance (HOMA-IR), adjusting for potential confounding factors. Effect modification by age, exogenous menopausal hormonal use, and body fat was also assessed. To further assess the combined effects of androgenic hormone milieu on predicted CHD risk and HOMA-IR, we used Bayesian Kernel Machine Regression, an emerging data-driven, non-parametric Bayesian framework that estimates nonlinear, interactive mixture effect among multiple correlated biomarkers. Results: Each unit increase in the API was significantly associated with a 4% (95% CI: 1% to 6%) higher predicted CHD risk and a 5% (95% CI: 1% to 8%) higher HOMA-IR. A similar association was observed for SHBG, but not for other API components. The biomarker mixture were also positively associated with predicted CHD risk and HOMA-IR (Figure 1). The significant associations of API with predicted CHD risk and HOMA-IR were more pronounced among those with lower high density lipoprotein cholesterol, poorer adiposity measures, and those without exogenous hormone therapy (Figure 2). From quantile regression, the association of the API with CHD risk was strongest in those with higher percentiles of CHD risk (i.e., > 90 th percentile, Figure 3). Conclusions: Traditional and data-driven approaches concorded that an androgenic hormone milieu were positively associated with CHD risk and HOMA-IR in postmenopausal women and more pronounced in those at higher risk for cardiometabolic conditions.

Abstract TH834: Novel Pharmacist-Led Shared Care Program Improved Lipid Control In Stable Ischemic Heart Disease Patients.

Introduction: The Ischemic Heart Disease (IHD) Shared Care programme (SC) was conceptualised to facilitate the joint management of patients with stable ischemic heart disease between the cardiac specialist and primary care providers with a focus on aggressive secondary cardiovascular risk reduction. During the first year, patients under the SC programme were reviewed by clinical pharmacists in primary care every 4 months with an annual review by the primary cardiologist. Aims: We aimed to evaluate the cardiovascular risk factor control (CVRF) of IHD patients under SC as compared with patients under standard care. Methodology: A retrospective analysis of patients enrolled under SC from 1 st July 2024 to 31 st March 2025 was conducted with events monitored until 1 st October 2025. Participants in SC were compared with other IHD patients undergoing standard care. The primary outcome was control of cardiovascular risk factors. Results: Figure 1 outlines the SC model compared with standard care. A total of 51 patients under the Shared Care programme and 433 patients in the standard care were analysed in the study. Table 1 describes the characteristics of the study populations. Patient in both groups were similarly matched in age, gender, previous acute coronary syndromes and cardiovascular risk factors. Table 2 depicts the CVRF control and safety signals at follow-up. Patients under SC had a significantly lower LDL level (1.55 ± 0.357 mmol/L vs 1.90 ± 0.810mmol/L, p= 0.003) with similar HbA1c levels and blood pressure control. Patients in SC had a higher visit frequency (2.94 ± 1.54 vs 1.05 ± 1.28, p < 0.001). No increase in safety signals of unplanned specialist clinic review or hospitalisation were observed. Conclusion: Patients under pharmacy-led shared care programme had better management lipid management compared with standard care with no safety signals observed.

Abstract TH972: Pulmonary Artery Pulsatility Measured by Cardiac Magnetic Resonance Imaging in Over 42,000 Participants Reveals Novel Genetic Risk Loci

Background: Pulmonary artery (PA) hemodynamics are predictors of mortality, yet genetic mechanisms underlying increased PA stiffness in diseases such as pulmonary hypertension are poorly understood, and targeted therapies are limited. Evaluation of PA hemodynamics frequently requires invasive right heart catheterization, limiting large-scale studies. Our investigation leveraged cardiac magnetic resonance (CMR) imaging to non-invasively determine and characterize PA pulsatility, an established measure of pulmonary vascular compliance. Methods: A deep learning model measured CMR-derived PA pulsatility in 42,774 UK Biobank participants. Associations of PA pulsatility with demographics and comorbidities were assessed using multivariate logistic regression models, and its association with all-cause mortality was evaluated using a multivariate Cox proportional hazards model. A genome-wide association study (GWAS) was performed, followed by genomic and in vitro functional characterization of candidate effector genes. Results: The mean (SD) PA pulsatility was 0.36 (0.11), and pulsatility decreased by 0.035 for every decade increase in age. We observed an inverse association between PA pulsatility and odds of congestive heart failure (odds ratio [OR] 1.55; 95% CI 1.37-1.76), chronic obstructive pulmonary disease (OR 1.41; 95% CI 1.29-1.53), diabetes (OR 1.18; 95% CI 1.13-1.23), and age- and sex-adjusted mortality (hazard ratio [HR] 1.13; 95% CI 1.03-1.23). A genome-wide association study of 40,496 participants identified loci on chromosome 2 (top SNP: rs6738973) and chromosome 10 (rs2077218) associated with PA pulsatility at genome-wide significance (p < 5x10 -8 ). Multiple lines of evidence from integrative fine-mapping analyses identified PKDCC and PLCE1 among likely effector genes. Using mass spectrometry, differential binding on electrophoretic mobility shift assays of two factors, NONO and SFPQ, at the lead loci were identified and shown to regulate downstream expression of PKDCC and PLCE1. Conclusions: This is the first large-scale, population-based epidemiologic and genomics study of PA pulsatility. Lower PA pulsatility is associated with older age, higher rates of comorbidities, and higher mortality odds. The genes PKDCC and PLCE1 are among likely effectors of PA pulsatility and warrant further functional characterization.

Structural basis for substrate specificity and MSMEG_0435-0436 binding by the mycobacterial long-chain acyl-CoA carboxylase complex

The presence of mycolic acid is a defining feature of the mycobacterial cell wall, which provides a highly impermeable barrier to many antibiotics. Biosynthesis of this fatty acid, as well as tuberculostearic acid, requires precursor molecules produced by the essential long-chain acyl-coenzyme A (CoA) carboxylase (LCC) complex. The LCC complex catalyzes carboxylation of the α-carbon of long-chain acyl-CoA, but also short-chain acetyl-CoA and propionyl-CoA. The complex includes the subunits AccA3, which contains a biotin carboxylase (BC) domain and a biotin carboxyl carrier protein (BCCP) domain, the long-chain acyl-CoA carboxyltransferase AccD4, the short-chain acyl-CoA carboxyltransferase AccD5, and the incompletely characterized protein AccE. We used electron cryomicroscopy (cryo-EM) to determine structures of the LCC complex from Mycobacterium smegmatis . In the structures, two AccE subunits tether eight AccA3 subunits to an AccD4 2 AccD5 4 heterohexamer core. Cryo-EM of the enzyme during catalysis reveals how AccD4 and AccD5 achieve substrate specificity, with AccD5 binding tightly to CoA and AccD4 binding long acyl chains. The BCCP domains of AccA3 undergo long-distance translocation to transfer a carboxyl group from the BC domain of AccA3 to the acyl-CoA substrate bound in AccD5. Further, we find that two copies of a protein complex formed from MSMEG_0435 and MSMEG_0436 can bind the LCC complex, sequestering the biotin moiety of BCCP domains near AccD5 and decreasing propionyl-CoA carboxylase activity. Rv0263c, the Mycobacterium tuberculosis ortholog of MSMEG_0435, has a role in bacterial survival during transmission, suggesting that these proteins may regulate production of branched fatty acid precursors for the mycobacterial cell wall.