Qian Wang

BACKGROUND: Mechanosensitive nuclear signaling contributes to myocardial ischemia-reperfusion injury, but the substrates and mechanisms of NUAK1 (AMPK-related kinase 5) remain unclear. We investigated whether NUAK1 regulates SYNE1 (Nesprin-1)/linker of nucleoskeleton and cytoskeleton-dependent nuclear gating of YAP1 (Yes-associated protein 1) during hypoxia/reoxygenation and ischemia-reperfusion injury. METHODS AND RESULTS: Quantitative phosphoproteomics identified a conserved NUAK1-dependent phosphorylation site in striated muscle-enriched Nesprin1-α2/SYNE1 (S434; S8284 in nesprin-1 giant). Coimmunoprecipitation and in vitro kinase assays supported direct SYNE1 phosphorylation by NUAK1. In neonatal mouse ventricular myocytes, genetic or pharmacological inhibition of NUAK1 decreased apoptotic signaling, reduced SYNE1 stability, enhanced YAP1 nuclear localization, and altered nuclear YAP1 dynamics. SYNE1 phosphosite mutants and nuclear/cytoplasmic fractionation supported a NUAK1-SYNE1 axis that restrains YAP1 nuclear accumulation under stress. Atomic force microscopy linked this pathway to nuclear mechanical remodeling. In a mouse model of ischemia-reperfusion injury, NUAK1 inhibition reduced acute myocardial damage and improved remodeling indices. CONCLUSIONS: NUAK1-dependent SYNE1 phosphorylation shapes nuclear mechanosignaling during ischemic stress. NUAK1 downregulation promotes cardiomyocyte YAP1 nuclear activity and attenuates injury responses.

Background: Left atrial appendage (LAA) patency after catheter ablation and LAA closure (LAAC) is a key determinant of postprocedure stroke. The effect of LAA electrical isolation (LAAEI) on LAA patency after LAAC in patients with atrial fibrillation (AF) remains unknown. Our objective was to explore the effect of LAAEI on LAA patency after catheter ablation and LAAC in patients with AF. Methods: Patients with persistent AF who underwent combined catheter ablation and LAAC were enrolled. LAA patency was detected by cardiac computed tomographic angiography at 3 months after the procedure. Results: A total of 686 patients with persistent AF with 3‐month device surveillance by cardiac computed tomographic angiography were included initially. Propensity score matching analysis was conducted on the basis of clinical features, echocardiographic parameters and procedural characteristics, and 469 patients were matched, including 363 with non‐LAAEI and 106 with LAAEI. Patients in matched groups showed 53.7% complete closure (no patency). Of the 46.3% of cases with LAA patency, visible peridevice leak was seen in 72.8%, and 27.2% had patency without visible peridevice leak. Compared with the non‐LAAEI group, the LAAEI group had a lower rate of LAA patency (49.6% versus 34.9%; adjusted odds ratio, 0.69 [95% CI, 0.48–0.98]; P =0.040). LAAEI was protective against LAA patency with an odds ratio of 0.68, and the other predictor of contrast leak into the LAA was maximum diameter of LAA orifice (odds ratio, 1.04 [95% CI, 1.00–1.08]; P =0.046). Conclusions: LAAEI is an effective strategy for reducing LAA patency in patients with persistent AF undergoing combined catheter ablation and LAAC. Registration: URL: clinicaltrials.gov ; Unique Identifier: NCT03788941.

Myocardial inflammation plays a critical role in the progression of injury following myocardial infarction (MI), yet the transcriptional mechanisms regulating cardiomyocyte inflammation to mitigate post‐ischemic injury remain poorly understood. This study elucidated the role of Estrogen‐Related Receptor Gamma (ERRγ) in modulating the inflammatory response post‐MI, demonstrating that ERRγ expression was downregulated in ischemic tissue and hypoxic neonatal mouse ventricular myocytes (NMVMs). Cardiomyocyte‐specific overexpression of ERRγ reduced infarct size, improved cardiac function, and suppressed excessive myocardial inflammation and pyroptosis by binding to the GBP5 promoter, thereby inhibiting GBP5 transcription and reducing NLRP3 inflammasome assembly. The protective effects of ERRγ overexpression were reversed by overexpressing GBP5, and the ERRγ agonist DY131 also improved cardiac function after MI. These findings suggest that ERRγ activation reduces myocardial ischemic injury by regulating cardiomyocyte inflammation and pyroptosis, highlighting ERRγ as a potential novel therapeutic target for attenuating post‐MI injury.

This study examined whether the Theory of Planned Behavior (TPB) constructs were differentially related to quit intention and past-year quit attempt in Chinese young adult smokers, and whether these relationships varied by gender and number of other household smokers. Throughout June of 2021, 757 smokers (mean age = 25.95, SD = 3.23) completed an online survey. TPB constructs assessed included affective and instrumental attitude, injunctive and descriptive norms, and perceived control. Moderation effects were assessed via interaction terms. Multivariate analyses revealed that quit intention was associated with instrumental attitude and perceived control, while past-year quit attempt was associated with affective attitude, injunctive norm, and perceived control. Male smokers' quit intention was linked to affective attitude, and female smokers' quit intention was linked to instrumental attitude. Quit intention increased with age only when other household smokers were few (i.e., two or less). The association between perceived control and past-year quit-attempt was more pronounced in female than in male smokers. Quit intention and quit attempt may be governed by partially distinct TPB constructs. TPB constructs were robust to the effect of the number of other household smokers. Male and female smokers may not differ in their quit intention or past-year quit attempt, but may diverge in how TPB constructs drive these outcomes.

Cannabis sativa, commonly known as marijuana, has been cultivated for its industrial, medicinal, and psychotropic properties for centuries. Its primary psychoactive compound – delta-9-tetrahydrocannabinol (THC) – produces effects such as euphoria, relaxation, and changes in perceptions [1]. According to the 2021 United Nations Office on Drugs and Crime (UNODC) World Drug Report, cannabis was the […]

The aims of this study were to: 1) validate the factor structure of the short-form smoking consequences questionnaire (S-SCQ) in Chinese young adults; 2) assess measurement invariance of the S-SCQ across smokers and never-smokers; 3) examine factors of the S-SCQ in relation to smoking-related variables. Data from 1,540 respondents (757 smokers, 783 never-smokers) were collected anonymously via an online survey in June, 2021. All respondents completed the S-SCQ and other smoking-related items. Confirmatory factor analysis (CFA) was conducted to validate the factor structure of S-SCQ. Measurement invariance of the S-SCQ was examined across smoking status. Relations between outcome expectancies and other smoking-related variables were further examined. CFA results supported the four-factor structure of the S-SCQ. Measurement invariance tests supported configural, metric, partial scalar, and strict invariance of the S-SCQ across smoking status. Never-smokers exposed to household SHS or intending to smoke had weight control and reinforcement expectancies. Smokers exposed to moderate household SHS or scored higher on the FTND had greater positive reinforcement expectancies. For never-smokers, household SHS exposure and future smoking intentions may be key constructs to target in smoking prevention efforts. For smokers, smoking-induced sensory satisfaction may be a key construct to transform in expectancy-based interventions.