The Patent Foramen Ovale and Migraine: Associated Mechanisms and Perspectives from MRI Evidence

Migraine is a common neurological disease with a still-unclear etiology and pathogenesis. Patent foramen ovale (PFO) is a kind of congenital heart disease that leads to a right-to-left shunt (RLS). Although previous studies have shown that PFO has an effect on migraine, a clear conclusion about the link between PFO and migraine is lacking. We first summarized the PFO potential mechanisms associated with migraine, including microembolus-triggered cortical spreading depression (CSD), the vasoactive substance hypothesis, impaired cerebral autoregulation (CA), and a common genetic basis. Further, we analyzed the changes in brain structure and function in migraine patients and migraine patients with PFO. We found that in migraine patients with PFO, the presence of PFO may affect the structure of the cerebral cortex and the integrity of white matter, which is mainly locked in subcortical, deep white matter, and posterior circulation, and may lead to changes in brain function, such as cerebellum and colliculus, which are involved in the processing and transmission of pain. In summary, this paper provides neuroimaging evidence and new insights into the correlation between PFO and migraine, which will help to clarify the etiology and pathogenesis of migraine, and aid in the diagnosis and treatment of migraine in the future

Sequence Stratigraphy and Geochemistry of Oil Shale Deposits in the Upper Cretaceous Qingshankou Formation of the Songliao Basin, NE China: Implications for the Geological Optimization of In Situ Oil Shale Conversion Processing

The Songliao Basin contains some of the largest volumes of oil shales in China; however, these energy sources are located in areas covered by arable land, meaning that the best way of exploiting them is likely to be environmentally friendly in situ conversion processing (ICP). Whether the oil shales of the Songliao Basin in the Qingshankou Formation are suitable for ICP remain controversial. In this paper, through sequence stratigraphic correlations, three main thick oil shale layers (N1, N2, and N3) of the Sequence1 (Sq1) unit in the first member of Qingshankou Formation (K2qn1) are confirmed as consistently present throughout the Southeastern Uplift region of the basin. The spectral trend attributes reflect that the lake reached a maximum flood surface of the K2qn1 in N2 oil shale layer, and the total organic carbon (TOC) and Fischer assay (FA) oil yield are significantly increasing. The N2 and N3 oil shale layers were deposited in a high lake level environment associated with ingressions of ocean water. The oil shale in these layers with the characteristics of high TOC (maximum of 23.9 wt %; average of 7.2 wt %), abundance of aquatic organic matter (OM) (maximum hydrogen index (HI) of 1080.2 mg/g; average of 889.9 mg/g) and carbonate contents (maximum of 29.5%; average of 15.4%). The N2 and N3 oil shale layers have higher brittleness index (BI) values (generally 40–50%), larger cumulative thicknesses (maximum of 13.3 m; average of 12.0 m), and much higher source potential index (SPI) values (0.92 and 0.88 tHC/m2, respectively) than the N1 oil shale layer within Sq1 transgressive system tracts (TST), indicating that the N2 and N3 layers are prospective targets for ICP. In addition, oil shales buried to depths of <1000 m have strong hydrocarbon generation capacities that make them suitable for ICP

Codelivery of a miR-124 Mimic and Obatoclax by Cholesterol-Penetratin Micelles Simultaneously Induces Apoptosis and Inhibits Autophagic Flux in Breast Cancer in Vitro and in Vivo

Penetratin is a classical cell-penetrating peptide with the potential to assist in the transmembrane delivery of proteins or drugs. However, the synthesis and application of cholesterol-penetratin (Chol-P) conjugates as nonviral delivery systems for microRNAs or drugs have not previously been reported. In this study, the amphiphilic Chol-P was shown to self-assemble into micelles and efficiently deliver miR-124 and obatoclax. The codelivered miR-124-M-Oba had a homogeneous particle size and a positive zeta potential. Treatment with miR-124 mincreased cytotoxicity, and cell proliferation, was promoted by miR-124 inhibitor-loaded micelles in MCF-7 human breast cancer cells. Moreover, the inhibitory effects on cell proliferation, colony formation, and cell migration were increased in the miR-124-M-Oba group compared to the miR-124-M group. miR-124-M-Oba induced higher levels of mitochondrial apoptosis via Bax and caspase-9 activation. In addition, we found that the cationic Chol-P and miR-124-M could potently induce autophagy, and miR-124 was degraded in the corresponding autophagolysosomes. The obatoclax encapsulated in miR-124-M-Oba could inhibit the degradation of miR-124 and p62 in autophagolysosomes, which consequently maintained the concentration of miR-124 in breast cancer cells. Furthermore, miR-124-M-Oba potently inhibited tumor growth in subcutaneous xenograft breast cancer models. In summary, the miR-124-M-Oba prepared in this work showed improved apoptosis induction and autophagic flux inhibitory effects in MCF-7 cells, and miR-124-M-Oba may have potential applications in breast cancer therapy