The totipotent 2C-like state safeguards genomic stability of mouse embryonic stem cells.

Mouse embryonic stem cells (mESCs) sporadically transition to a transient totipotent state that resembles blastomeres of the two-cell (2C) embryo stage, which has been proposed to contribute to exceptional genomic stability, one of the key features of mESCs. However, the biological significance of the rare population of 2C-like cells (2CLCs) in ESC cultures remains to be tested. Here we generated an inducible reporter cell system for specific elimination of 2CLCs from the ESC cultures to disrupt the equilibrium between ESCs and 2CLCs. We show that removing 2CLCs from the ESC cultures leads to dramatic accumulation of DNA damage, genomic mutations, and rearrangements, indicating impaired genomic instability. Furthermore, 2CLCs removal results in increased apoptosis and reduced proliferation of mESCs in both serum/LIF and 2i/LIF culture conditions. Unexpectedly, p53 deficiency results in defective response to DNA damage, leading to early accumulation of DNA damage, micronuclei, indicative of genomic instability, cell apoptosis, and reduced self-renewal capacity of ESCs when devoid of 2CLCs in cultures. Together, our data reveal that transition to the privileged 2C-like state is a major component of the intrinsic mechanisms that maintain the exceptional genomic stability of mESCs for long-term self-renewal.

FOXD2-AS1 promotes migration and invasion of head and neck squamous cell carcinoma and predicts poor prognosis.

Aim: To investigate the role of long noncoding RNA FOXD2-AS1 in head and neck squamous cell carcinoma (HNSCC). Materials & methods: The expression and clinical significance of FOXD2-AS1 were analyzed using data from public databases. Transwell assays were used to examine the function of FOXD2-AS1 in HNSCC. The molecular mechanism of FOXD2-AS1 was probed by western blotting. Results: The expression of FOXD2-AS1 was upregulated in HNSCC; it was positively related with the pathological stage as well as with poor prognosis in HNSCC patients. FOXD2-AS1 silencing inhibited HNSCC cell migration and invasion, also influenced the expression of epithelial-mesenchymal transition-related molecules. Conclusion: FOXD2-AS1 was a prognostic marker in patients with HNSCC and may be a favorable novel treatment target for HNSCC.

Analysis of heaping-induced decline in olive quality: insights from integrated analysis between phenotypic traits and gene expression profiles.

Heaping is an unavoidable process before olive milling, and its duration significantly affects the olive quality. However, there is limited research on the quality changes of olive fruits on a short-time scale. To gain a better understanding of the molecular mechanisms underlying postharvest deterioration of olives, this study piled olives at room temperature and extracted oil at 0 h, 8 h, 24 h, 48 h and 72 h to analyze oil quality parameters. GC/LC-MS techniques were employed to investigate variations in metabolite contents. Concurrently, the transcriptional profiles of olives during heaping were examined. As piling time progressed, quality indicators declined, and stored fruit were categorized into three groups based on their quality characters: '0 h' belongs to the first category, '8 h' and '24 h' to the second category, and '48 h' and '72 h' to the third category. Metabolite changes were consistent with the expression patterns of genes related to their synthesis pathways. Additionally, ethylene was identified as a crucial factor influencing fruit senescence. These findings establish a foundation for further research on olive deterioration after harvesting and offer insights for optimizing olive oil production.

Transition of the Type of Band Alignments for All-Inorganic Perovskite van der Waals Heterostructures CsSnBr3/WS2(1-x)Se2x.

In general, two-dimensional semiconductor-based van der Waals heterostructures (vdWHs) can be modulated to achieve the transition of band alignments (type-I, type-II, and type-III), which can be applied in different applications. However, it is rare in three-dimensional perovskite-based vdWHs, and it is challenging to achieve the tunable band alignments for a single perovskite-based heterostructure. Here, we systematically investigate the electronic and optical properties of all-inorganic perovskite vdWHs CsSnBr3/WS2(1-x)Se2x based on density functional theory (DFT) calculation. The calculated results show that the transitions of band alignment from type-II to type-I and type-III to type-II are achieved by modulating the doping ratio of the Se atom in the WS2(1-x)Se2x monolayer for SnBr2/WS2(1-x)Se2x and CsBr/WS2(1-x)Se2x heterostructures, respectively, in which the CsBr and SnBr2 represent two different terminated surfaces of CsSnBr3. The change of band alignments can be attributed to the conduction band minimum (CBM) transforming from the W 5d to Sn 5p orbital in SnBr2/WS2(1-x)Se2x vdWHs, and the valence band maximum (VBM) and CBM change from an overlapped state to a separated one in CsBr/WS2(1-x)Se2x vdWHs. This work can provide a theoretical basis for the dynamic modulation of band alignments in perovskite-based vdWHs.

Hypomethylated SPANXA1/A2 promotes the metastasis of head and neck squamous cell carcinoma.

The aberrant expression of SPANXA1/A2 (sperm protein associated with the nucleus on the X-chromosome, family members A1/A2) has been observed in multi types of cancers. However, the roles of SPANXA1/A2 in head and neck squamous cell carcinoma (HNSCC) remain largely unknown. The expression of SPANXA1/A2 was evaluated via analyzing UCSC XENA and GEO databases. To dissect the underlying cause of silencing SPANXA1/A2-mediated suppression, cell migration and invasion were detected in SPANXA1/A2 manipulated cell lines. Western blot was performed to evaluate EMT-related factors. The methylation microarray data of SPANXA1/A2 in HNSCC from the UCSC XENA database were used to identify whether aberrant overexpressed SPANXA1/A2 is induced by aberrant DNA methylation. SPANXA1/A2 was highly expressed in tumor tissues and associated with poor survival of patients with HNSCC. Knockdown of SPANXA1/A2 inhibited migration and invasion abilities in both Cal-27 and SCC-9 cells through epithelial-mesenchymal transition (EMT) suppression. The SPANXA1/A2 expression negatively related to its DNA methylation level. SPANXA1/A2 DNA hypomethylation was associated with metastatic stage and poor survival of patients with HNSCC. A dose-dependent increase of SPANXA1/A2 mRNA was observed in both cal-27 and SCC-9 cells after treatment with 5-AZA-2'-deoxycytidine (5-AZA-CdR). We demonstrated that knockdown of SPANXA1/A2 obviously inhibited tumor cell migration and invasion through EMT suppression. DNA hypomethylation might be responsible for the aberrant SPANXA1/A2 overexpressing. SPANXA1/A2 may be used as a diagnosed and independent prognosis indicator of HNSCC, and knockdown of SPANXA1/A2 may present a new gene-based therapy for HNSCC.

[Diagnostic value of chronotropic incompetence in coronary heart disease].

OBJECTIVE: To determine the diagnostic value of chronotropic incompetence (CI) in coronary heart disease (CHD). METHODS: Two hundred thirty three patients who underwent the electrocardiogram treadmill exercise test (TET) and coronary angiography (CAG) were included in this study. CAG was used as the standard of diagnosing CHD. The sensitivity, specificity, and accuracy of CI were compared with the traditional index of TET. RESULTS: There was no significant difference between the sensitivity, specificity and accuracy of CI (81.7%, 64.3%, and 71.2% respectively) and those of the traditional index (73.1%, 69.3%, and 70.8% respectively, P> 0.05), while the specificity (87.9%) and accuracy (79.4%) were significantly higher after combining CI and the traditional index than that of the traditional index alone (P<0.05). There was no significant difference in the sensitivity (P> 0.05). CONCLUSION: CI was a usefull index in diagnosing CHD. CI combined with the traditional index of TET can significantly improve the specificity and accuracy of TET for CHD.

[Different left ventricular geometric patterns and ambulatory pulse pressures in essential hypertensive patients].

OBJECTIVE: To explore the relationship between different left ventricular geometric patterns and ambulatory pulse pressures in essential hypertension patients. METHODS: Left ventricular geometric patterns were identified according to the results of left ventricular mass index and relative left ventricular thickness assessed by echocardiography in 130 hypertension patients. The average levels of 24-hour pulse pressure, daytime pulse pressure, and nighttime pulse pressure were analyzed by ambulatory blood pressure monitoring. The method of multiple stepwise regression analysis was applied to identify the independent determinants of ambulatory pulse pressures. After controlling or adjusting the effects of agr and the 24-hour mean arterial pressure, the average levels of 24-hour, daytime, and nighttime pulse pressure among different left ventricular geometric patterns were compared. Forty normotensive subjects served as controls. RESULTS: The age and the level of 24-hour mean arterial pressure were the independent determinants of 24-hour, daytime, and nighttime pulse pressure. After adjusting the effects of age and 24-hour mean arterial pressure, the average levels of 24-hour pulse pressure and daytime pulse pressure in concentric remodeling, concentric hypertrophy, and eccentric hypertrophy pattern groups were higher than those in the control group and normal geometric pattern group, whereas there were not significant differences among different left ventricular remodeling patterns at the average levels of 24-hour, daytime, and nighttime pulse pressure. CONCLUSION: Pulse pressure is an important risk factor in the development of cardiac remodeling in essential hypertension.

Quadruple atrioventricular nodal pathways: involved in orthodromic atrioventricular reentrant tachycardia.

Supraventricular tachycardia can be caused by multiple atrioventricular nodal pathways or atrioventricular accessory pathways. Herein, we report the case of a patient who was diagnosed with an orthodromic atrioventricular reentrant tachycardia that was caused by an unusual combination of quadruple atrioventricular nodal pathways and an atrioventricular accessory pathway. Radiofrequency catheter ablation of the accessory pathway successfully eliminated the arrhythmias and the patient's symptoms. Careful analysis of complete electrophysiologic studies can help in the diagnosis of such rare clinical presentations.