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Background: Anthracycline‐related cardiotoxicity has a poor prognosis; therefore, early detection of any change in LV function is critical. Objective: The aim of this study was to evaluate the two‐dimensional speckle tracking technique for the early detection of cardiac toxicity after low‐dose anthracycline chemotherapy in the Chinese population. Methods: Forty breast cancer patients were treated by chemotherapy using anthracycline for 4–6 cycles. Patients were examined by echocardiography before chemotherapy (T0) and after the second (T2), fourth (T4), and sixth (T6) cycle. LV ejection fraction (LVEF), LV global longitudinal strain (GLS) and endocardium, mid‐myocardium, and epicardium global longitudinal strain (GLS‐Endo, GLS‐Mid, and GLS‐Epi). Additionally, global circumferential strain (GCS), RV global longitudinal strain (RVGLS), and LA global longitudinal strain (LAGLS) were evaluated. Results: Left ventricular ejection fraction was significantly reduced at T4 (P < 0.05). Compared with T0, GLS, GLS‐Endo, GLS‐Mid, and GLS‐Epi were significantly reduced at T2, T4, and T6 (P < 0.05 for all), the apical septum wall (AS) was also reduced significantly at T2 (P < 0.05), and the apical anterior wall (AA) and the basal anterior wall (BA) longitudinal strains were significantly reduced at T4 (P < 0.05). GCS, RVGLS, and LAGLS were not significantly changed after treatment (P > 0.05). Conclusions: LV stratified strains and strain of the segments supplied by the left anterior descending coronary artery are more sensitive to the cardiac toxicity of anthracycline. [ABSTRACT FROM AUTHOR]

DNA methylation is one of the key epigenetic regulatory mechanisms in development and spermatogenesis. However, the dynamic regulatory mechanisms of genome-wide DNA methylation during testicular development remain largely unknown. Herein, we generated a single-base resolution DNA methylome and transcriptome atlas of precocious porcine testicular tissues across three developmental stages (1, 75, and 150 days old). The results showed that the dynamic methylation patterns were directly related to the expression of the DNMT3A gene. Conjoint analysis revealed a negative regulatory pattern between promoter methylation and the positive regulation of 3′-untranslated region (3′UTR) methylation. Mechanistically, the decrease in promoter methylation affected the upregulation of meiosis-related genes, such as HORMAD1 , SPO11 , and SYCE1. Demethylation in the 3′UTR induced the downregulation of the INHBA gene and knockdown of INHBA inhibited cell proliferation by reducing the synthesis of activin A. These findings contribute to exploring the regulatory mechanisms of DNA methylation in testicular development. • The atlas of DNA methylomes and transcriptome during porcine testicular development. • DNA methylation in promoter and 3′UTR negatively and positively regulated gene expression, respectively. • The key genes regulated by DNA methylation in promoter and 3′UTR involved in spermatogenesis and testicular development were identified. • The dynamic DNA methylation patterns of porcine testis was related to DNMT3A. • Demethylation in 3′UTR induced INHBA inhibition repressed the immature Sertoli cell proliferation through impeding activin A synthesis process. [ABSTRACT FROM AUTHOR]

The integrated stress response (ISR), a pivotal protein homeostasis network, plays a critical role in the formation of long-term memory (LTM). The precise mechanism by which the ISR controls LTM is not well understood. Here, we report insights into how the ISR modulates the mnemonic process by using targeted deletion of the activating transcription factor 4 (ATF4), a key downstream effector of the ISR, in various neuronal and non-neuronal cell types. We found that the removal of ATF4 from forebrain excitatory neurons (but not from inhibitory neurons, cholinergic neurons, or astrocytes) enhances LTM formation. Furthermore, the deletion of ATF4 in excitatory neurons lowers the threshold for the induction of long-term potentiation, a cellular model for LTM. Transcriptomic and proteomic analyses revealed that ATF4 deletion in excitatory neurons leads to upregulation of components of oxidative phosphorylation pathways, which are critical for ATP production. Thus, we conclude that ATF4 functions as a memory repressor selectively within excitatory neurons. [ABSTRACT FROM AUTHOR]