Background: Cardiac aging represents an independent risk factor for aging‐associated cardiovascular diseases. Although evidence suggests an association between NOD‐, LRR‐, and pyrin domain–containing protein 3 (NLRP3) inflammasome formation and numerous cardiovascular diseases, its role in cardiac aging remains largely unclear. Methods and Results: The longevity of mice with wild‐type and NLRP3 knockout (NLRP3 ^−/− ) genotypes was assessed, with or without d ‐galactose treatment. Cardiac function was evaluated using echocardiography, and cardiac histopathology was examined through hematoxylin and eosin and Masson's trichrome staining. Senescence‐associated β‐galactosidase (SA‐β‐gal) staining was employed to detect cardiac aging. Western blotting was used to assess aging‐related proteins (p53, p21) and pyroptosis‐related proteins. Additionally, dihydroethidium staining, lactate dehydrogenase release, and interleukin‐1β ELISA assays were performed, along with measurements of total superoxide dismutase and malondialdehyde levels. In vitro, H9c2 cells were exposed to d ‐galactose for 24 hours in the absence or presence of N ‐acetyl‐ l ‐cysteine (reactive oxygen species inhibitor), BAY‐117082 (nuclear factor κ‐light‐chain enhancer of activated B cells inhibitor), MCC950 (NLRP3 inhibitor), and VX‐765 (Caspase‐1 inhibitor). Immunofluorescence staining was employed to detect p53, gasdermin D, and apoptosis‐associated speck‐like protein proteins. Intracellular reactive oxygen species levels were assessed using fluorescence microscopy and flow cytometry. Senescence‐associated β‐galactosidase staining and Western blotting were also employed in vitro for the same purpose. The results showed that NLRP3 upregulation was implicated in aging and cardiovascular diseases. Inhibition of NLRP3 extended life span, mitigated the aging phenotype, improved cardiac function and blood pressure, ameliorated lipid metabolism abnormalities, inhibited pyroptosis in cardiomyocytes, and ultimately alleviated cardiac aging. In vitro, the inhibition of reactive oxygen species, nuclear factor κ‐light‐chain enhancer of activated B cells, NLRP3, or caspase‐1 attenuated NLRP3 inflammasome‐mediated pyroptosis. Conclusions: The reactive oxygen species/nuclear factor κ‐light‐chain enhancer of activated B cells/NLRP3 signaling pathway loop contributes to d ‐galactose–treated cardiomyocyte senescence and cardiac aging.

Background: Coronary artery calcification (CAC) is a crucial indicator of subclinical atherosclerotic cardiovascular disease. The relationship between long‐term insulin resistance (IR) trajectory and CAC has been explored in few studies. Therefore, this study aimed to investigate whether the long‐term IR time series of young adults are associated with the incidence of CAC in midlife. Methods and Results: In a cohort study comprising 2777 participants from the CARDIA (Coronary Artery Risk Development in Young Adults) study, the homeostasis model assessment for IR was used to measure IR levels, and group‐based trajectory modeling was used to fit three 25‐year homeostasis model assessments for IR trajectories. Logistic regression was used to estimate the association between the 3 homeostasis model assessments for IR trajectories and CAC events at year 25. The results showed that among 2777 participants (mean age, 50.10±3.58 years; 56.2% women; 46.4% Black), there were 780 incident CAC events after a 25‐year follow‐up. After full adjustment, the prevalence of CAC was higher in the moderate‐ (odds ratio [OR], 1.40 [1.10–1.76]) and the high‐level homeostasis model assessments for IR trajectories (OR, 1.84 [1.21–2.78]) than in the low‐level trajectory. This association was observed in obese individuals despite the negative interaction between IR and different types of obesity (all P interactions >0.05). Conclusions: Our study revealed that young adults with a higher level of IR were more likely to develop CAC in middle age. Furthermore, this association persisted in obese individuals. These findings highlight the importance of identifying subclinical cardiovascular risk factors and implementing primary prevention measures.

The role of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and triglyceride-glucose index (TyG index) in predicting all-cause and cause-specific mortalities remains elusive. This study included 384,420 adults from the Shanghai cohort and the UK Biobank (UKB) cohort. After multivariable adjustment in the Cox models, FPG ≥7.0 mmol/L or HbA1c ≥ 6.5% increased the risk of all-cause mortality, FPG ≥5.6 mmol/L or HbA1c ≥ 6.5% increased CVD-related mortality, and higher or lower TyG index increased all-cause and CVD-related mortalities in the Shanghai cohort; FPG ≥5.6 mmol/L, HbA1c ≥ 5.7%, TyG index <8.31 or ≥9.08 increased the risks of all-cause, CVD-related, and cancer-related mortalities in the UKB cohort. FPG or HbA1c increased the discrimination of the conventional risk model in predicting all-cause and CVD-related mortalities in both cohorts. Thus, increased levels of FPG and HbA1c and U-shaped TyG index increase the risks of all-cause especially CVD-related mortalities.

The global rise of multidrug-resistant pathogens, particularly Methicillin-resistant Staphylococcus aureus (MRSA), has become a critical public health concern, necessitating the urgent discovery of new antimicrobial agents. Griseorhodin C, a hydroxyquinone compound isolated from Streptomyces, has demonstrated significant inhibitory effects against MRSA. In this study, we employed a comprehensive approach combining transcriptome and metabolome analyses to investigate the underlying antimicrobial mechanism of Griseorhodin C. Our findings reveal that Griseorhodin C interferes with multiple bacterial metabolic pathways, including those essential for the biosynthesis and metabolism of amino acids, purine metabolism and energy metabolism, ultimately leading to bacterial growth inhibition and cell death. Notably, Griseorhodin C showed superior inhibitory effects compared to the clinical standard, vancomycin, both in vivo and vitro. These results highlight the potential of Griseorhodin C as a promising candidate for the development of new therapeutic strategies aimed at combating MRSA infections. The study underscores the importance of exploring natural products as sources of novel antibiotics in the ongoing fight against antimicrobial resistance.