Browse Articles

Performance analysis of a solar desalination system operated by humidification–dehumidification technique

Abstract The humidification–dehumidification desalination system represents a thermal-based technology primarily intended for small-scale water desalination applications. It facilitates the production of distilled water from saline seawater at sub-boiling temperatures by employing low-grade heat sources, such as solar energy or waste heat, which are both readily available and characterized by low operational costs. This study aims to enhance the yield of distilled water from actual seawater (Suez Canal water) while simultaneously reducing production costs under the climatic conditions of Cairo, Egypt. To achieve this, an experimental, economic, and environmental evaluation was conducted on a closed-air open-water humidification–dehumidification desalination system, which is recognized for its superior energy efficiency. The pilot plant was constructed, and experimental trials were performed during the months of February and March. The investigation focused on assessing the effects of varying the seawater mass flow rate for a range of 0.39–0.63 kg/s and the air velocity during daytime operation hours. A constant flow of city water was supplied to the dehumidifier coil to condense the water vapor from the moist air. System performance was monitored from 9 AM to 5 PM daily. The findings indicate that the maximum distilled water production reached 17.04 kg/day at a seawater flow rate of 0.63 kg/s and an air velocity of 13.2 m/s. The estimated cost of distilled water production was approximately 0.017 $ per liter, while the CO 2 emission was reduced by 6 tons annually for the same amount of distilled water.

Tunable and nonlinearity-enhanced dispersive-plus-dissipative coupling in photon-pressure circuits

Abstract Photon-pressure circuits are the circuit implementation of the cavity optomechanical Hamiltonian and discussed for qubit readout, low-frequency quantum photonics and dark matter axion detection. Due to the enormous design flexibility of superconducting circuits, photon-pressure systems provide fascinating possibilities to explore unusual parameter regimes of the optomechanical Hamiltonian. Here, we report the realization of a photon-pressure platform, in which a GHz circuit interacts with a MHz circuit via a magnetic-flux-tunable combination of dispersive and dissipative photon-pressure. In addition, both coupling rates are considerably enhanced by nonlinearities of the GHz-mode, which leads to the multi-photon coupling rates scaling stronger with the pump photon number n c than the usual $$\sqrt{{n}_{\mathrm{c}}}$$ n c dependence. We demonstrate that interference of the two interaction paths leads to a Fano-like response in photon-pressure induced transparency, and that the dynamical backaction is considerably modified compared to the dispersive case, including a parametric instability caused by a red-detuned pump tone.

Abstract MPTH77: Genome-wide Characterization of Fourteen Circulating Metals and Possible Contribution to Cardiovascular-Kidney-Metabolic Syndrome

Introduction: Trace metals, both essential and non-essential, can be toxic at abnormally high or low concentrations and may contribute to cardiovascular-kidney-metabolic (CKM) syndrome. Limited genomic studies have examined trace metals in multi-ethnic populations. Hypothesis: We hypothesize that common genetic variants are associated with circulating trace metal levels in a multi-ethnic population, and metal-related genetic variants may contribute to CKM. Methods: Metal data were rank-based inverse-norm transformed and missingness imputed as LOD by √2. We conducted genome-wide association analysis of fourteen trace metals in the Atherosclerosis Risk in Communities Study (ARIC) separately for Black and White participants. The results summaries were then meta-analyzed with results from prior genetic studies of European and Asian cohorts for each metal. To elucidate potential biological mechanisms and phenotypic consequences, we performed downstream analyses including phenome-wide association analyses (PheWAS) by leveraging UK Biobank and FinnGen genetic summaries, colocalization with GTEx v8 expression data, and two-sample Mendelian Randomization (MR) with CKM traits. Results: Among 15,054 multi-ethnic participants, 38 genetic loci (18 novel) were associated with 14 circulating metal levels (p<5×10 -8 , Figure A). For example, rs130107325, a missense variant on SLC39A8 , previously linked to systolic and diastolic blood pressure, was associated with manganese. A novel locus, rs11939299 ( PALLD ), was associated with nickel, a gene previously linked to coronary artery disease. A novel intronic variant, rs41353851 ( CARD11), previously associated with congenital cardiovascular anomalies, was associated with arsenic. In the PheWAS,111 significant associations were identified (p<2.7x10 -10 ), including cardiovascular traits such as mean arterial, systolic, and diastolic blood pressure. Fourteen out of 38 identified loci showed evidence of colocalization (PP.H4>0.8) with gene expression in tissues, such as strontium with heart atrial appendages. In the MR, 31 significant associations showed modest to moderate effects on CKM traits (p<0.05, Figure B), including iron and barium with coronary atherosclerosis and barium with ischemic heart disease. Conclusion: We identified novel loci associated with circulating trace metal concentrations in multi-ethnic populations. The observed associations in the downstream analysis provided biological plausibility of metal on CKM health effects.

Abstract TH982: Proteomic Profiles and Pathways of Ischemic Stroke Risk in Women from the Nurses’ Health Study

Background: Ischemic stroke (IS) is a major global cause of death and disability, especially affecting women, who have a 20% higher lifetime risk and poorer recovery. Despite its prevalence, reliable biomarkers that predict IS risk remain limited, impeding early detection and prevention efforts. Methods: We examined proteomic data from 450 incident IS cases, with a median time-to-event of 5.5 yrs (IQR: 2.8 yrs), and 450 matched controls in a nested case-control study within women with a median age of 65.8 (IQR: 10.1 yrs) in the Nurses’ Health Study. We used the Olink Explore HT platform to measure 5,440 proteins in plasma. Conditional logistic regression models were fitted for each protein with IS as the outcome, adjusting for established cardiometabolic, lifestyle, and hormonal IS risk factors. The false discovery rate was controlled using the q value method. Weighted co-expression network analysis (WCNA) was applied to the subset of proteins nominally associated with stroke ( p value < 0.05) to identify modules of highly correlated proteins. Functional gene set enrichment analysis (FGSEA) was conducted using eight established protein sets from MSigDB to characterize biological pathways represented within these modules. Results: Fourteen proteins were significantly associated with IS risk ( q value < 0.05). A total of 274 proteins had a p value < 0.05 and were used in WCNA analyses. Four distinct protein clusters were associated with IS. The cluster most positively correlated with IS risk ( r = 0.16) was characterized by proteins related to aging and inflammation. Its hub protein, follistatin-like 3, has been linked to vascular remodeling and endothelial dysfunction. Conversely, the cluster with the strongest negative association with IS risk ( r = -0.14) had a metabolic and anti-inflammatory profile. Its hub protein, dentin matrix acidic phosphoprotein 1, regulates phosphate and mineral metabolism, inhibits vascular calcification, and maintains metabolic homeostasis. FGSEA revealed neutrophil degranulation as the top pathway positively associated with IS, highlighting the role of immune activation. Conclusions: This large-scale proteomic analysis identified novel circulating proteins and networks associated with IS risk in women. These findings highlight biologically distinct metabolic pathways that may inform the development of targeted interventions to lower stroke risk. Subsequent work will validate these findings in external cohorts like the UK Biobank.

Sequence of events that led to the South Lhonak lake outburst flood in Sikkim, India

Mitochondrial metabolic imbalance drives diploidization in mouse haploid embryonic stem cells via NADPH overload

Abstract 60: Effect of Multivitamin Reduces Within-Visit Blood Pressure Variability in Older Adults: Findings from the COSMOS Randomized Controlled Trial

Background: Within-Visit Blood Pressure Variability (WVBPV) reflects short-term fluctuations in BP readings. Although less studied than mean blood pressure, WVBPV is an independent predictor of cardiovascular events and mortality. The effect of multivitamin-multimineral (MVM) supplementation on WVBPV is unknown. We examined the two-year impact of MVM use on WVBPV in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS). Methods: COSMOS is a randomized, double-blind, placebo-controlled, 2×2 factorial trial testing daily MVM (Centrum Silver) and cocoa extract (CE) supplements for 2 years in women aged ≥65 years and men aged ≥60 years without major cardiovascular diseases (CVD) or recent cancer. In the COSMOS-Clinic subcohort with clinic-based measurements, WVBPV was assessed at baseline and 2 years follow-up using variability independent of the mean (VIM) and average real variability (ARV) of systolic BP (SBP). Treatment effects were estimated with mixed-effects models, adjusting for CE, age, sex, and recruitment source. Results: Among 529 participants (mean age 69.7 ± 5.4 years; 48.8% women), baseline characteristics were similar by MVM treatment group. MVM supplementation reduced both VIM (−0.72; 95% CI: −1.38 to −0.06; p = 0.033) and ARV (−1.07 mmHg; 95% CI: −1.94 to −0.20; p = 0.016) over two years, without changing mean BPs. Reductions in ARV were greater females compared with men (−2.14 mmHg; 95% CI −3.35 to −0.92; p_interaction = 0.018). Conclusions: This study provides the first randomized trial evidence that daily MVM supplementation improves WVBPV in older adults. Benefits appear to be more pronounced in women. Given the strong association between WVBPV and cardiovascular risk, these findings suggest a potential novel role for MVM in cardiovascular prevention strategies, warranting further evaluation of its clinical relevance. Registration: URL: https://clinicaltrials.gov unique identifier NCT02422745

Abstract TU153: Demographic and Geographic Disparities in Ischemic Stroke Mortality with Comorbid Hypertension: A Nationwide Analysis, 2000–2020

Background: Ischemic stroke (IS) and hypertension are closely linked cardiovascular conditions, with hypertension being the most significant modifiable risk factor for the development of IS. While stroke-related mortality has been widely studied, the burden of IS mortality with comorbid hypertension remains insufficiently characterized. Hypothesis: We hypothesized that mortality from IS with comorbid hypertension has increased over the past two decades and varies significantly by sex, race, and geographic region. Methods: We analyzed national mortality data from the CDC WONDER database for individuals aged > 35 years from 2000 to 2020. IS was defined as the underlying cause of death (ICD-10: I63, I69.3) with hypertensive disease (I10–I15) listed as a contributing cause. Age-adjusted mortality rates (AAMRs) per 1,000,000 were calculated. Joinpoint regression was used to evaluate temporal trends and annual percent change (APC). Results: A total of 61,595 deaths were attributed to IS with comorbid hypertension. AAMRs declined from 20.8 (95% CI, 20.1–21.6) in 2000 to 10.7 (95% CI, 10.2–11.1) in 2012 (APC = –6.9%; p<0.001), followed by a marked increase to 30.3 (95% CI, 29.6–31.1) in 2020 (APC = 16.5%; p<0.001). Cumulatively, females had slightly higher AAMRs than males (16.7 [95% CI, 16.6–16.9] vs. 16.5 [95% CI, 16.3–16.7]). Racial disparities were substantial: African Americans had the highest AAMR (25.7 [95% CI, 25.1–26.3]), followed by White (16.0 [95% CI, 15.9–16.1]), Asian (15.6 [95% CI, 14.9–16.2]), and American Indian (13.4 [95% CI, 11.8–15.0]) populations. AAMRs were highest in micropolitan rural areas (19.1 [95% CI, 18.6–19.5]) and lowest in large fringe metropolitan regions (14.0 [95% CI, 13.7–14.3]). Regionally, the West had the highest AAMR (19.5 [95% CI, 19.2–19.9]), followed by the South (18.7 [95% CI, 18.5–18.9]), the Midwest (16.1 [95% CI, 15.9–16.4]), and the Northeast (12.0 [95% CI, 11.7–12.2]). Conclusions: While IS mortality with comorbid hypertension declined from 2000 to 2012, the sharp increase observed in subsequent years represents a concerning shift in national trends. This burden disproportionately affects African Americans, rural residents, and those living in the Western and Southern United States. These findings underscore the need for targeted public health and clinical strategies focused on hypertension control, early stroke prevention, and the reduction of disparities across vulnerable, marginalized populations.

Human recognition of feline stress-related behavioral states from visual cues depends on observer characteristics

Structural transitions in the stepwise assembly of proteasome core particles

Abstract 20S catalytic core particles (CP) of eukaryotic 26S proteasomes are composed of two identical halves comprising 14 distinct subunits. 15S precursor complexes (PC) represent detectable half-CPs assembly intermediates lacking the β7-subunit but containing assembly chaperones Ump1 and Pba1-Pba2. Incorporation of β7 drives 15S-PC dimerisation and further CP maturation. Our cryo-EM structures of the yeast 15S-PC and all 13S-PC-derived intermediates suggest that assembly in yeast is not restricted to a single trajectory, but instead involves alternative, and potentially simultaneous pathways. Comparison of the intermediates reveals how Ump1 and β-subunits become structured with each additionally incorporated β-subunit, and how this prepares peptidase sites for auto-activation. We identify two transient interactions of Pba1 with the α-ring, which are important for an ordered progression of maturation. Pba1 loop 81-117 intercalates between subunits α3 and α4 in 13S-15S-PCs and is displaced upon 15S-PC dimerisation. The second interaction involves the α1 N-terminus, deletion of which leads to a defect in Pba1-Pba2 release. These findings indicate how changes in α-ring subunit conformations coordinate CP maturation with Pba1‑Pba2 release.

Abstract TU109: Sex Differences in Frailty Phenotypes among Older Adults with Cardiovascular Disease

Introduction: Frailty is highly prevalent and prognostically significant among older adults with cardiovascular disease (CVD). Studies have shown that women are more likely to be frail compared with men; however, sex differences in frailty phenotypes remain underexplored in CVD. Purpose: We quantified sex differences in frailty phenotypes among community-dwelling older adults with CVD. Methods: We used data from participants in Round 12 of the National Health and Aging Trends Study (NHATS) with a reported history of CVD (history of heart disease and myocardial infarction). The Frailty Phenotype Criteria were used to assess frailty: unintentional weight loss, weakness, slowness, physical exhaustion, and low physical activity. To determine if participants met these criteria, we 1) applied original operationalized definitions for NHATS data (Original NHATS), and 2) replaced the weakness (based on 5-repeat chair stands, not grip strength) and slowness criteria with measures from the Short Physical Performance Battery (SPPB). Weighted descriptive and comparative statistics were used to compare frailty phenotypes between women and men. Results: Of the 1477 community-dwelling older adults in Round 12 with a reported history of CVD, the average age (±standard error) was 76.4±0.2 years, 45.3% were female, and 81.3% were non-Hispanic White (Table 1). Using the original NHATS criteria measures (N=1080), 15.6% were frail, but there was no significant sex difference (p = 0.064). Replacing weakness and slowness criteria with the SPPB measures (N=1289), 46.8% were frail, and women were significantly more likely to be frail compared with men (p < 0.001). Conclusions: The prevalence of frailty among older adults with CVD varies depending on the criteria for weakness and slowness; however, using the SPPB measures augmented our sample size. Moreover, observed sex differences in frailty may depend on the criteria used.

Abstract MPTH57: Racial disparities in accelerated hypertension onset among women and the role of neighborhood disinvestment: the REasons for Geographic and Racial Differences in Stroke Study

Background: Although Black women are known to have higher hypertension rates than White women, longitudinal investigations of racial disparities in accelerated hypertension onset and the role of neighborhood factors in shaping these differences are severely limited. Methods: We used data on 15,354 women in the REasons for Geographic and Racial Differences in Stroke (REGARDS) national longitudinal cohort study to quantify racial disparities in accelerated hypertension onset and to examine the degree to which these disparities vary across levels of neighborhood (i.e. census tract) socioeconomic disinvestment. Participants were recruited between 2003-2007 (mean age=64 years, SD=9.5) and followed prospectively. Age of hypertension onset was based on age at self-reported physician diagnosis or measured high blood pressure (≥140mm/Hg systolic or ≥90mm/Hg diastolic). Neighborhood disinvestment (low, moderate, high) was determined using a summary score of six socioeconomic indicators from U.S. Census Bureau data. We used Weibull accelerated failure time models with age as the time-scale accounting for left, interval, and right censoring to estimate racial differences in age of hypertension onset. We adjusted our estimates for individual-level sociodemographic factors, health-related behaviors, and neighborhood clustering. Results: We found that Black women acquired hypertension a median of 9.4 years earlier than White women (95% Confidence Interval (CI): -10.0, -8.9), independent of individual-level sociodemographic factors. Black-White inequities in accelerated hypertension onset persisted across levels of neighborhood disinvestment. After additionally accounting for census-tract clustering, in neighborhoods with low disinvestment, Black women had hypertension a median of 9.1 years earlier than White women (95% CI: -10.1, -8.0). Within highly disinvested neighborhoods, hypertension occurred a median of 7.7 years earlier (95% CI: -8.8, -6.6) in Black compared to White women. Conclusion: Our findings highlight that accelerated hypertension onset experienced by Black women persists regardless of neighborhood contexts, underscoring the need to investigate structural determinants earlier in the life-course to address health inequities more effectively.

Age-dependent alterations of TRPA1 and urocortin 1 signaling in the Edinger–Westphal nucleus in a mouse model of Alzheimer’s disease

Abstract Cholinergic neurons of the preganglionic Edinger–Westphal nucleus (EW) are involved in Alzheimer’s disease (AD), however, the role of urocortin 1 (UCN1) positive peptidergic neurons of the centrally projecting EW (EWcp) remains unclear. EWcp cells exclusively express transient receptor potential ankyrin 1 (TRPA1) ion channels, implicated in neurodegenerative disorders. We hypothesized that the EWcp/UCN1 /Trpa1 neurons may be involved in AD-related pathologies. Age-dependent (2, 6, 9, 12 and 18 months) Trpa1 mRNA expression (RNAscope in situ hybridization) and UCN1 peptide (immunostaining) content of the EWcp were examined in male triple transgenic mouse (3xTg-AD) model of AD. 1 H-MRI spectroscopy was performed in the hippocampus at 6, 12 and 18 months to evaluate the taurine and N-acetylaspartate levels, metabolites reflecting neuroprotection and neuronal integrity as AD prognostic markers. Trpa1 expression was lower in 2 and 6-months-old 3xTg-AD than controls. Later the genotype differences disappeared due to the progressive, age-related reduction of Trpa1 mRNA transcripts in the controls. In contrast, the Trpa1 expression of transgenic mice remained persistently low. Similarly, the UCN1 peptide content was also lower in the 2 and 6-months-old 3xTg-AD compared to controls. However, UCN1 level increased with age, which was more pronounced in 3xTg-AD than controls abolishing the genotype differences. Age-dependent decrease in taurine level was detected in transgenic animals leading to significantly lower taurine/creatine ratio in 12 and 18-months-old 3xTg-AD animals compared to the controls. This age-related dynamics of Trpa1 and UCN1 expression of 3xTg-AD mice suggests that altered UCN1 signaling may contribute to AD-associated mood disorders and memory decline.

Linking photoelectron circular dichroism to the asymmetric total photoemission yield measured in aerosol nanoparticles of tyrosine

Abstract Spectroscopic techniques that are sensitive to molecular chirality are important analytical tools to quantitatively determine enantiomeric excess and purity of chiral molecular samples. Many chiroptical processes however produce weak enantio-specific asymmetries due to their origin relying on weak magnetic dipole or electric quadrupole effects. Photoelectron circular dichroism (PECD) in contrast, is an intense effect, that is fully contained in the electric dipole description of light matter interaction and creates a chiral asymmetry in the photoelectron angular distribution. Here, we demonstrate that this chiral signature in the angular distribution of emitted electrons can be translated into the total photoemission yield for particulate matter. The resulting chiral asymmetry of the photoemission yield (CAPY), mediated by the attenuation of light within condensed particles, can be detected experimentally without requiring high vacuum systems and electron spectrometers. This effect can be exploited as an analytical tool with high sensitivity to chirality and enantiopurity for studies of chiral organic and hybrid submicron particles in environmental, biomedical or catalytic applications.

Abstract WE550: Impact of the Mindfulness-Based Blood Pressure Reduction (MB-BP) Program on Cardiovascular Health: A Randomized Clinical Trial

Background: Mindfulness-based interventions may improve cardiovascular health (CVH) by supporting behavioral change across multiple risk factors. This study evaluated the impact of Mindfulness-Based Blood Pressure Reduction (MB-BP), a mindfulness program targeting hypertension-related behaviors ( Image 1 ), on CVH using the American Heart Association’s Life’s Essential 8 framework. Methods: This secondary analysis of parallel-group, phase 2 randomized clinical trial evaluated the effects of MB-BP on CVH in 201 participants with elevated office BP (≥120/80 mmHg). The MB-BP group (n=101) received an 8-week program focused on mindfulness training and education targeting diet, physical activity, medication adherence, alcohol use, and stress, whereas the control group (n=100) received enhanced usual care ( Image 2 ). CVH was assessed using available Life’s Essential 8 components: systolic blood pressure, body mass index (BMI), diet (DASH adherence), physical activity, smoking, and sleep duration. Generalized estimating equations evaluated intervention effects through six months. Results: At six months follow-up, MB-BP participants significantly improved composite CVH scores compared to controls (standardized mean difference: 0.144; 95% CI: 0.023, 0.266) ( Image 3 ). MB-BP influenced most CVH components in healthier directions at trend levels, with the strongest responses for physical activity (47.9 MET min/week; 95% CI: -16.5, 112.3), sleep (0.34 hours/night; 95% CI: -0.10, 0.78), systolic blood pressure (-4.95 mmHg; 95% CI: -10.34, 0.44) and DASH diet score (0.27, 95% CI: -0.15, 0.69). Conclusions: MB-BP led to modest but clinically significant improvements in CVH, driven by multiple Life’s Essential 8 components. These findings suggest that MB-BP may be an effective behavioral intervention to support CVH and reduce risk for cardiovascular disease. ClinicalTrials.gov Preregistration Identifiers: NCT03256890, NCT03859076

Abstract WE456: Cumulative Social Risk and Sex Differences in Hypertension Severity Among U.S. Adults: NHANES 2005–2023

Background: Social determinants of health contribute to hypertension disparities, yet the cumulative effects of multiple social risks and potential sex differences remain poorly understood. Methods: We analyzed National Health and Nutrition Examination Survey (NHANES) 2005–2023 data for adults ≥18 years. Hypertension was defined per the 2025 American College of Cardiology/American Heart Association guidelines as elevated (120–129/<80 mmHg), Stage 1 (130–139 or 80–89 mmHg), Stage 2 (140–159 or 90–109 mmHg), and severe (≥160 or ≥110 mmHg). A cumulative social risk index (0–≥4) included poverty, education, marital status, employment, insurance, and minority status. Survey-weighted multinomial logistic regression estimated adjusted relative risk ratios (aRRR) and 95% confidence interval (CIs), adjusting for age and Life’s Essential 8 behavior scores (diet, sleep, physical activity, and smoking). Analyses were stratified by sex, and temporal trends were evaluated across NHANES cycles using ≥2 social risks as the threshold, reflecting the population median. Results: Among 194.6 million adults (N = 39,358), mean age was 47.7 years, and 44% had ≥2 social risks (46% females, 41% males). In the total population, cumulative social risk was not associated with elevated, Stage 1, or Stage 2 hypertension; however, ≥4 risks were associated with severe hypertension (aRRR = 3.73, 95% CI 1.61–8.61). Among males, associations appeared only at advanced stages: Stage 2 (aRRR = 1.36, 95% CI 1.10–1.66) and severe hypertension (aRRR = 3.78, 95% CI 2.34–6.10). Among females, cumulative social risk showed a progressive pattern: Stage 1 hypertension was lower at three risks (aRRR = 0.82, 95% CI 0.70–0.96), while Stage 2 risk emerged at three risks (aRRR = 1.29, 95% CI 1.03–1.59), and at four or more risks, both elevated BP (aRRR = 1.29, 95% CI 1.01–1.63) and severe hypertension (aRRR = 4.33, 95% CI 2.56–7.32) were significantly higher. Over time, adults with ≥2 social risks showed widening disparities—males experienced rising Stage 2 and severe hypertension in later cycles, while females demonstrated earlier, sustained increases beginning at Stage 1. Conclusions: Cumulative social disadvantage was independently associated with more severe hypertension, with stronger and earlier effects among females. Despite stable national hypertension trends, persistent social and sex inequities underscore the need for upstream interventions to achieve equitable blood pressure control in the U.S.

Novel explainable deep learning based drug sensitivity prediction for early treatment of breast cancer

Bispecific GLP-1/GLP-2 agonism in advanced type 2 diabetes: preclinical characterization and a randomized, double-blind, placebo-controlled phase I trial

Abstract PG-102 is a potency-optimized bispecific Fc fusion protein targeting GLP-1 and GLP-2 receptors. In db/db mouse models of advanced diabetes characterized by uncontrolled hyperglycemia and catabolic weight loss, PG-102 achieved superior and sustained glycemic control compared with semaglutide or tirzepatide while preserving body weight, uncoupling glycemic control from catabolic weight loss. Mechanistic studies indicated that these effects were not driven by acute insulinotropic activity, but by β-cell preservation and enhanced glucose uptake. These benefits required dual GLP-1R/GLP-2R engagement, as PG-102 outperformed monospecific Fc fusion agonists or their combination and promoted coordinated receptor trafficking with delayed internalization. We conducted a randomized, double-blind, placebo-controlled multiple ascending dose phase 1 study at a single center in the Republic of Korea in adults with overweight (BMI 25–30 kg/m²). Twenty-four participants were randomized within three weekly dose cohorts (15 mg, 30 mg, and 30/60 mg; n  = 6 per cohort) in a 6:2 ratio to receive PG-102 ( n  = 18) or placebo ( n  = 6). All randomized participants (PG-102 n  = 18; placebo n  = 6) received at least one dose and were included in the safety analysis. Safety and tolerability were predefined as the primary endpoint and assessed by treatment-emergent adverse events (TEAEs). TEAEs occurred in 5/6 (83.3%) participants in each PG-102 cohort and 4/6 (66.7%) in placebo; treatment-related AEs occurred in 5/6 (83.3%) and 3/6 (50.0%), respectively. No serious adverse events or discontinuations due to adverse events occurred. Gastrointestinal events were mild to moderate. These findings support bispecific GLP-1/GLP-2 agonism as a mechanistically distinct incretin strategy in advanced T2D. ClinicalTrials.gov identifier: NCT06309667.

Mosaic phenotypic evolution underlies the adaptive success of water-surface colonization in Gerromorpha

Understanding how the remarkable phenotypic diversity observed in organisms arises through shifts in macroevolutionary patterns and tempos is a fundamental challenge in evolutionary biology. Phenotypes often evolve in a mosaic pattern during adaptive transitions. For organisms that have invaded highly specialized habitats, such as the unique two-phase interface habitats (water surfaces), the macroevolutionary history of their phenotypic diversification remains only superficially understood. Semiaquatic bugs (Insecta: Heteroptera: Gerromorpha), which exhibit extensive habitat diversification and unparalleled phenotypic innovation, represent one of the most successful extant adaptive groups at this interface and provide an excellent system for study. By analyzing their adaptive transitions and phenotypic macroevolutionary history, we demonstrate that Gerromorpha experienced a single major adaptive transition from land to the water surface. Subsequently, semiaquatic bugs successfully colonized a wide range of distinct water-surface habitats. During this process, phenotypic space was explored under strong constraints and along pronounced mosaic trajectories; i.e., different body regions exhibited markedly distinct patterns of phenotypic space occupation and partitioning, as well as markedly different evolutionary rates. Furthermore, we showed that this mosaic pattern of phenotypic space occupation and rates of exploration had complex and critical effects on the invasion and colonization of water-surface habitats. Our study provides a typical case of macroevolutionary dynamics in species adapted to specialized air–water interface habitats, emphasizing the complex and significant roles of environmental context and functional demands in shaping patterns of phenotypic evolution.

Abstract TU117: Ecological momentary assessment of sleep disturbances, fatigue, and physical activity among Thai older adults receiving hemodialysis

Background: Older adults receiving hemodialysis in Thailand frequently experience sleep disturbances, fatigue, and low physical activity (PA). Although prior studies have described daily and diurnal variations in these symptoms, they have not investigated how hemodialysis treatment itself influences symptom patterns throughout the day. This study aimed to (1) compare sleep, fatigue, and PA between dialysis and non-dialysis days and (2) examine associations between ultrafiltration volume and these behaviors. Method: Time-based ecological momentary assessment sampling was performed over 7 days. Participants wore an ActiGraph continuously and responded to four daily text-message prompts assessing sleep (modified Brief Pittsburgh Sleep Quality Index) and fatigue (0–10 scale). Hemodialysis treatment data, including ultrafiltration volume, were collected after each session. Descriptive statistics and generalized estimating equations were used for analysis. Results: Thirty-five participants (69% male; mean age = 66.2 ± 7.4 years) completed 895 of 980 possible fatigue assessments (91.3%) and provided 228 days and 233 nights of ActiGraph data (93.1% and 95.1% of possible observations, respectively). Compared with non-hemodialysis days, participants reported significantly higher fatigue in the afternoon (β = 1.15, p < 0.001), evening (β = 3.00, p < 0.001), and night (β = 2.73, p < 0.001) of dialysis days, but not in the morning (β = –0.30, p = 0.153). On dialysis days, total sleep time, step count, and moderate-to-vigorous PA were significantly lower than on non-dialysis days after adjusting for age and BMI (p < 0.05). Higher ultrafiltration volume was associated with self-reported poorer sleep quality (β = -0.35, p < 0.05) and higher morning fatigue (β = 0.55, p < 0.01). Conclusion: This study demonstrates that older adults receiving hemodialysis experience a marked day-to-day and diurnal symptom burden, characterized by increased afternoon, evening, and nighttime fatigue, shorter sleep duration, and reduced PA on dialysis days compared with non-dialysis days. Ultrafiltration volume was independently associated with poorer self-reported sleep quality and greater morning fatigue, though it was not related to PA. These findings highlight the importance of tailoring fluid management strategies and developing interventions that mitigate fatigue and sleep disruption to improve daily PA in this population.