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Background: Bisphenol A (BPA), a common endocrine-disrupting chemical (EDC), has been revealed to be closely associated with the induction of abnormal heart development, obesity, prediabetes, and other metabolic disorders. However, the underlying mechanism of maternal BPA exposure on fetal heart development abnormalities is not clear. Methods: To explore the adverse effects of BPA and its potential mechanism on heart development, C57BL/6 J mice and human cardiac AC-16 cells were used to conduct in vivo and in vitro studies. For the in vivo study, mice were exposed to low-dose BPA (40 mg/(kg·bw)) and high-dose BPA (120 mg/(kg·bw)) for 18 d during pregnancy. In vitro study, human cardiac AC-16 cells were exposed to BPA of various concentrations (0.01, 0.1, 1, 10, and 100 µM) for 24 h. Cell viability and ferroptosis were evaluated using 2,5-diphenyl-2 H-tetrazolium bromide (MTT), immunofluorescence staining, and western blotting. Results: In BPA-treated mice, the alterations of fetal cardiac structure were observed. Increased NK2 homeobox 5(Nkx2.5) was detected in vivo with the induction of ferroptosis, revealing that BPA induced abnormal fetal heart development. Furthermore, the results showed that SLC7A11 and SLC3A2 decreased in low- and high-dose BPA-treated groups, suggesting that system Xc- mediated BPA-induced abnormal fetal heart development via inhibiting the expression of GPX4. Observing AC-16 cells confirmed that cell viability declined significantly with various concentrations of BPA. Moreover, BPA exposure suppressed GPX4 expression by inhibiting System Xc- (the decrease of SLC3A2 and SLC7A11). Collectively, system Xc- modulating cell ferroptosis might play important in abnormal fetal heart development induced by BPA exposure.

The filamentous temperature‐sensitive (Fts) protein FtsEX plays a pivotal role in Escherichia coli (E. coli) cell division by facilitating the activation of peptidoglycan hydrolysis through the adaptor EnvC. FtsEX belongs to the type VII ATP‐binding cassette (ABC) transporter superfamily, which harnesses ATP energy to induce mechanical force, triggering a cascade of conformational changes that activate the pathway. However, the precise mechanism by which FtsEX initiates mechanotransmission remains elusive. Due to the inherent instability of this type of ABC transporter protein in vitro, the conformation of FtsEX has solely been determined in the stabilized ATP‐bound state. To elucidate the dynamics of FtsEX, we characterized FtsEX and EnvC of various functional structures through cryo‐electron microscopy (cryo‐EM) and homology modeling. We validated the structures by molecular dynamics simulations. By site‐directed mutagenesis and phenotype screening, we also identified the functional residues involved in allosteric communication between FtsE and FtsX as well as FtsX and EnvC. Additionally, we discovered a potential role of phospholipids in stabilizing the complex conformation during mechanotransmission. This comprehensive exploration significantly enhances our understanding of the intricate mechanisms governing bacterial cell division and unveils potential molecular targets for developing innovative antimicrobial drugs to combat antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background: This study investigates the association between dietary flavonoid intake and the incidence of mild cognitive impairment (MCI) through a matched case-control design. Methods: Dietary intake was assessed using a food frequency questionnaire, comparing the intake of flavonoids between individuals with MCI and those with normal cognitive function. Logistic regression analysis was employed to evaluate the correlation between dietary flavonoid intake and the risk of MCI. Additionally, blood concentrations of S100β, a marker of the blood-brain barrier (BBB) integrity, were measured using electrochemiluminescence immunoassay, and Pearson correlation analysis was conducted to explore the relationship between dietary flavonoid intake and blood S100β levels. Results: Compared to participants with normal cognition, those with MCI had significantly lower dietary intakes of total flavonoids, isoflavones, daidzein, glycitein, genistein, kaempferol, myricetin, flavonols, and anthocyanidins, while the intake of peonidin was significantly higher. Univariate logistic regression analysis indicated that high dietary intake of total flavonoids, isoflavones, daidzein, glycitein, genistein, kaempferol, myricetin, and flavonols was negatively correlated with MCI, whereas peonidin intake was positively correlated with MCI. Multivariate logistic regression analysis confirmed these findings. Pearson correlation analysis revealed a significant negative correlation between dietary intake of kaempferol and myricetin and blood S100β levels. Conclusion: Increasing the dietary intake of total flavonoids, isoflavones, daidzein, glycitein, genistein, and flavonols appears to be a protective factor against MCI, while higher intake of peonidin is associated with an increased risk of MCI. The protective or adverse effects of these flavonoids may not be related to the permeability of the BBB. Myricetin and kaempferol intake may protect cognitive function by maintaining BBB integrity. Plain language and summary: Brief highlights: More attention to neurons Previous studies on the cognitive effects of flavonoid intake have mainly focused on their direct effects on central neurons and glial cells. Less attention to BBB damage Few studies have investigated the effects of flavonoid intake on the BBB, which indirectly affects cognitive function. Negative correlation between BBB damage and Myricetin and Kaempferol It was found that Myricetin and Kaempferol, two components of flavonoids, were negatively correlated with the risk of MCI and negatively correlated with blood levels of the BBB integrity marker S100β. They may protect cognitive function in middle-aged and elderly people by preserving the integrity of the BBB. [ABSTRACT FROM AUTHOR]