Prostaglandin I2 (PGI2) signaling is vasoprotective. Further, PGI2 signaling exhibits immunomodulatory properties that largely promote an anti-inflammatory state. Inflammation and immune activity are associated with the development of hypertension. However, it remains unknown whether exogeneous PGI2 can restrain the immune and inflammatory responses in the context of hypertension. A phenome-wide association study evaluated  single-nucleotide polymorphisms (SNPs) in the receptor for PGI2, IP (gene name PTGIR), and the associated odds of developing cardiovascular pathologies. C57Bl/6J mice underwent one of two models to evaluate the effect of an exogenous PGI2 analog on aortic inflammation and hypertension. Mice were either administered the PGI2 analog, treprostinil (TPL), at the initiation of angiotensin II (Ang II) infusion to determine the effect of TPL on the development of inflammation and hypertension, or mice were administered TPL after 2 weeks of Ang II to determine the ability of TPL to reduce blood pressure and inflammation in established hypertension. Humans who were heterozygous for a SNP in IP had a significantly greater odds ratio for several vascular pathologies compared to controls. Mice that received TPL at the onset of Ang II infusion were protected from developing hypertension and exhibited reduced aortic inflammation. Mice that received TPL two weeks after initiation of Ang II infusion exhibited a significant reduction in their blood pressure, decreased aortic inflammation, diminished aortic fibrosis, and fewer splenic Th1 cells compared to vehicle treatment. Exogeneous PGI2 signaling protects against the development and/or maintenance of Ang II-induced hypertension, possibly through inhibition of Th1 cell function.

Genetic variation contributes substantially to interindividual and interpopulation differences in drug response, yet most pharmacogenomic studies remain biased toward European populations. Here, we systematically assessed pharmacogenomic variation across East Asians (EAS) and Europeans (EUR) using public genomic datasets and investigated the potential evolutionary forces shaping these differences. Our analyses revealed that EAS populations generally harbor a lower frequency of pharmacogenomic variants previously associated with reduced drug response compared with EUR populations, indicating population-level differences in the distribution of PGx variants. Drug-associated genes exhibited threefold higher population differentiation than the genome-wide background (FST = 0.18 vs. 0.06). Key transport genes such as SLCO1B3/SLCO1B7 showed striking differences in cumulative allele probability (EAS: 18.69% vs. EUR: 91.60%), suggesting population-level divergence in drug transport and pharmacokinetics. Population genetic analyses revealed stronger signals of positive selection on PGx variants in EAS populations, likely reflecting historical adaptations to pathogen and dietary pressures. For instance, the VKORC1-rs9923231-T allele, which enhances warfarin sensitivity, shows evidence of selection in EAS populations (XP-EHH = 3.58) and may relate to vitamin K intake. Conversely, the EUR-enriched SH2B3-rs3184504-T allele (AFEUR: 0.46 vs. AFEAS: 0.003) has been associated with selection related to blood pressure regulation. Collectively, these findings highlight the importance of incorporating population diversity into pharmacogenomic research and underscore the potential need for population-specific drug response guidelines to advance global precision medicine.

Clinical management of hypertension in patients with autoimmune rheumatic diseases (ARDs) is challenging. Firstly, the impact on blood pressure (BP) of several antirheumatic drugs varies and the available evidence points towards a wide range of effects. Secondly, management of hypertension in terms of diagnosis, BP thresholds and therapeutic targets currently follows the general recommendations, even though patients with ARDs present a markedly adverse cardiovascular profile. Thirdly, lifestyle interventions in terms of non-pharmaceutical management follow the general recommendations. Notably, it has been shown that they can improve autoimmune disease-specific endpoints, however, their intimate effect on BP has not been fully explored. Finally, the choice of anti-hypertensive medication currently complies with the general antihypertensive therapy recommendations, in the absence of appropriately designed studies in these populations. This review aims to summarize the impact of antirheumatic drugs on BP and present the available data regarding clinical management of hypertension in patients with ARDs.

Underwater physical signal collection is crucial for helping athletes evaluate health and optimize training methods. However, it is difficult for existing underwater devices to simultaneously collect stable and accurate subtle pulse signals and large motions in complex water environments. Herein, a flexible, waterproof, and stable underwater human physical signal collection system based on a flexible micropillar double-layer pressure sensor was proposed. The developed sensor is integrated with a micropillar sensing layer and packaging layer, which exhibit a dual-mode sensing range that includes subtle and high pressure with a rapid response. The sensing layer provides wide-range deformation for improving the sensing performance; the packaging layer reduces the influence of water flow on the sensor when sensing subtle pressure underwater, which provides support for the microstructure when it senses high pressure to enhance the sensing performance. The sensor can accurately recognize both subtle pulse vibrations and large-scale muscle expansion-contraction signals in water. Therefore, an underwater physical signal collection device (UPCD) was constructed with a micropillar sensor and an information storage circuit board. The status of an underwater athlete can be estimated through a machine learning method by analyzing the data collected from the UPCD, which can recognize the training and physical conditions and further assist in optimizing the training method.

Childhood obesity manifests metabolic heterogeneity, and differentiating metabolically unhealthy obesity (MUO) from metabolically healthy obesity (MHO) provides a refined framework for early cardiometabolic risk stratification than obesity status alone. However, the effects of multiple bisphenol A (BPA) analogues exposure on MUO in obese children remained understudied. This study investigated the associations between multiple urinary BPA analogues and metabolic obesity phenotypes in 290 obese Chinese children aged 6-7 years. Individual analogue associations were evaluated using logistic regression, while joint exposure effects were characterized using weighted quantile sum regression (WQS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR). Urinary trace elements underwent principal components reduction and were incorporated into sensitivity analyses to address co-exposure confounding. Continuous metabolic phenotypes and selected pairwise interaction patterns were additionally examined as complementary analyses. In single-pollutant models, BPAF was identified as the most consistent positive association signal for MUO, maintaining directional stability following batch adjustment and trace-element principal component correction. Although the mixture models did not demonstrate a robust overall joint effect, component-weight and contribution analyses consistently highlighted BPAF as a leading positive contributor, with several analogues exhibiting weaker or antagonistic effects. Phenome-wide analyses showed modest, exploratory signals mainly for blood pressure- and adiposity-related traits. Overall, these findings establish BPAF as a higher-priority candidate exposure for pediatric metabolic dysfunction and indicate that BPA analogue co-exposure manifests through heterogeneous component-specific contributions rather than uniform cumulative effects.

BackgroundAlzheimer's disease (AD) is characterized by a neuropathological cascade that begins with amyloid-β (Aβ) deposition. The recent success of disease-modifying drugs targeting Aβ has demonstrated that modulating amyloidopathy can yield clinical benefits, underscoring the need for additional drugs affecting amyloid pathology.ObjectiveTo identify novel drug targets associated with Aβ accumulation in AD using Mendelian randomization (MR) analysis of the druggable genome.MethodsWe performed MR analysis on expression quantitative trait loci (eQTLs) of the druggable genome in relation to Aβ accumulation using summary-data-based MR (SMR). Blood eQTL data were obtained from the eQTLGen consortium, and brain eQTL data from BrainMeta and PsychENCODE, while Aβ positron emission tomography (PET) genome-wide association study data were derived from 11,816 non-Hispanic White participants across 13 cohorts. Co-localization analysis was conducted to enhance the reliability of the MR results, and additional validation was performed using blood and brain protein quantitative trait loci (pQTLs) as instrumental variables.ResultsThe SMR and co-localization analyses revealed causal associations between the druggable genome and Aβ accumulation, with APH1B identified in blood eQTL data and ACE, APH1B, and CR1 identified in brain eQTL data. Further analysis using pQTL data confirmed causal associations for ACE and CR1, with ACE showing a negative association with Aβ PET uptake.ConclusionsThese findings highlight potential target genes for AD treatment, and the protective effect of ACE against amyloid pathology suggests that alternative medications to ACE inhibitors may be preferred for blood pressure management in the context of AD. Overall, our study demonstrates the potential of MR to facilitate drug repurposing for AD.

Cardiac magnetic resonance imaging (CMR) is increasingly used for detailed evaluation of cardiac structures and function. Its wide field of view also allows identification of extracardiac abnormalities, some of which may significantly impact clinical management.