Dongpu Shao, Lei Shi, and Honglei Ji. Mol. Cells 2023;46:414-6. https://doi.org/10.14348/molcells.2023.0060

Studies have reported that prenatal exposure to fine particulate matter (PM_2.5) might be associated with adverse birth outcomes in offspring. However, evidence with regard to the effects of prenatal exposure to PM_2.5 and, especially, its main chemical constituents on offspring's weight in childhood is limited and inconsistent. The present study aimed to examine associations of prenatal exposure to PM_2.5 total mass and its chemical constituents in each trimester with children's weight from birth to 6 years of age using data from Shanghai-Minhang Birth Cohort Study. A total of 1,084 mother-infant pairs were included with both PM_2.5 exposure data and at least one measurement of weight and height. Weight-for-Length (WLZ), BMI-for-Age (BMIz), and Weight-for-Age (WAZ) z-scores were generated according to the World Health Organization guidelines. Exposure to PM_2.5 total mass and its chemical constituents [organic carbon (OC), black carbon (BC), ammonium (NH₄⁺), nitrate (NO₃^-), sulfate (SO₄^2-), and soil dust (SOIL)] during pregnancy was estimated from a satellite based modelling framework. We used multiple informant model to estimate the associations of trimester-specific PM_2.5 total mass and its specific constituents concentrations with WLZ/BMIz and WAZ of offspring at birth and 1, 4, and 6 years of age. In multiple informant model, we observed consistent patterns of associations between exposure to PM_2.5 total mass, OC, BC, NH₄⁺, NO₃^-, and SO₄^2- during the 2^nd and 3^rd trimesters and decreased WLZ/BMIz and WAZ at 1, 4, and 6 years of age in boys. We observed associations between prenatal exposure to PM_2.5 total mass, NH₄⁺, and NO₃^- during the 1^st and 2^nd trimesters and increased WLZ/BMIz and WAZ in girls at birth. However, there were null associations at 1 and 4 years of age and inverse associations at 6 years of age. Prenatal exposure to PM_2.5 total mass and its main chemical constituents was associated with decreased weight in boys from 1 to 6 years of age, with increased weight at birth and decreased weight at 6 years of age in girls. Our findings suggest that prenatal exposure to PM_2.5 and its chemical constituents may have a lasting effect on offspring's weight in childhood.

Background: Early revascularization of the culprit vessel is the most effective treatment for reducing the risk of mortality from acute STEMI with and without cardiogenic shock. However, the most recent trends and impact of multivessel percutaneous coronary intervention (PCI) during the index hospitalization on in-hospital outcomes are unknown.Methods: The National Inpatient Sample was queried from October 2015 to 2019 for hospitalizations with STEMI. The impact of multivessel PCI on in-hospital outcomes of patients with and without cardiogenic shock was evaluated.Results: Of 624,605 STEMI hospitalizations treated with PCI, 12.5% were complicated by cardiogenic shock. Among hospitalizations without cardiogenic shock, 15.7% were treated by multivessel PCI, which declined from 20.8% in 2015 to 13.9% in 2019 (P_trend < 0.001). Multivessel and culprit-only PCI had similar rates of In-hospital mortality (2.4 vs. 2.3%, p = 0.027) and major adverse cardiac and cerebrovascular events (MACCE; 7.4 vs. 7.2%, p = 0.072). Among hospitalizations with cardiogenic shock, 22.1% were treated by multivessel PCI, which declined from 29.2% in 2015 to 19.4% in 2019 (P_trend < 0.001). Multivessel PCI was associated with higher rates of in-hospital mortality (30.9 vs. 28.4%, p < 0.001) and MACCE (39.9 vs. 36.5%, p < 0.001) than culprit-only PCI.Conclusion: The frequency of multivessel PCI for STEMI with and without cardiogenic shock is declining. Multivessel PCI is associated with worse in-hospital outcomes for STEMI with cardiogenic shock but not for STEMI without cardiogenic shock.

Disulfidptosis, a newly identified form of cell death, holds significant biological relevance; however, its role in cardiovascular diseases remains poorly characterized. To investigate this, disulfide bond formation was evaluated using non-reducing Western blot, while cytoskeletal alterations were assessed via phalloidin staining. In vivo experiments using a rat model of myocardial infarction (MI) and in vitro experiments using H9c2 cardiomyocytes subjected to oxygen‑glucose deprivation (OGD) both demonstrated upregulation of SLC7A11, NADPH depletion, and cystine accumulation under OGD or MI conditions. Notably, increased disulfide bonds in actin cytoskeletal proteins were observed, leading to cytoskeletal collapse. Inhibition of SLC7A11 rescued disulfidptosis across all models. Cellular knockdown of Nckap1 (a core component of the Rac1-WRC-Arp2/3 pathway) suppressed disulfidptosis, whereas overexpression of Rac1, Nckap1, or Wave2 promoted it. Spatial transcriptomic analysis of human infarcted myocardium further validated the concurrent upregulation of SLC7A11 and Rac1-WRC-Arp2/3 pathway components. Collectively, these findings indicate that MI induces disulfidptosis-a novel cell death modality mediated by activation of the SLC7A11 and Rac1-WRC-Arp2/3 signaling pathways.

FGR proto-oncogene (Fgr), a member of the Src family kinases, has garnered attention for its potential involvement in apoptotic signaling, yet its role in cardiovascular diseases, particularly acute myocardial infarction (AMI), remains unexplored. This study sought to investigate whether elevated left ventricular Fgr expression alleviates myocardial injury in the infarcted area and whether this protective mechanism is mediated by modulating phosphoinositide 3-kinase (PI3K)/Akt phosphorylation. The transcriptome-wide association study was initially utilized to screen for susceptibility genes in the left ventricle, with findings validated using bulk-RNA sequencing data from a rat model of left anterior descending coronary artery (LAD) ligation; subsequently, human spatial transcriptomics combined with single-nucleus RNA sequencing data confirmed differential expression of Fgr and PI3K/Akt in the infarcted region. Fgr knockdown via siRNA in H9C2 cells and pharmacological inhibition with TL02-59 in rats were conducted to assess cellular survival and cardiac function, respectively. Fgr emerged as a common candidate gene identified through multi-omics data analysis, with its up-regulation confirmed both in vivo and in vitro. Fgr silencing in an in vitro oxygenglucose deprivation model significantly reduced cell survival and suppressed PI3K/Akt phosphorylation, whereas TL02-59 administration in rats subjected to LAD ligation impaired post-infarction cardiac function while concurrently inhibiting PI3K/Akt phosphorylation levels. This study demonstrates that Fgr is markedly up-regulated in AMI and exerts cardioprotective effects, possibly through modulation of PI3K/Akt signaling phosphorylation, thereby underscoring its potential as a therapeutic target.