Methoxychlor induces oxidative stress and impairs early embryonic development in pigs.

Introduction: Methoxychlor (MXC) is an organochlorine pesticide (OCP) that was formerly used worldwide as an insecticide against pests and mosquitoes. However, MXC is not biodegradable and has lipophilic characteristics; thus, it accumulates in organisms and affects reproductive function. MXC, as an estrogenic compound, promotes oxidative stress, induces oxidative stress damage to ovarian follicles, and causes miscarriages and stillbirths in females. In this research endeavor, our primary objective was to explore the ramifications of MXC regarding the developmental processes occurring during the initial stages of embryogenesis in pigs. Methods: In this study, we counted the blastocyst rate of early embryos cultured in vitro. We also examined the reactive oxygen species level, glutathione level, mitochondrial membrane potential, mitochondrial copy number and ATP level in four-cell stage embryos. Finally, apoptosis and DNA damage in blastocyst cells, as well as pluripotency-related and apoptosis-related genes in blastocyst cells were detected. The above experiments were used to evaluate the changes of MXC damage on early parthenogenetic embryo development. Results and Discussion: The results showed that early embryos exposed to MXC had a significantly lower cleavage rate, blastocyst rate, hatching rate, and total cell count compared with the control group. It was also of note that MXC not only increased the levels of reactive oxygen species (ROS), but also decreased the mitochondrial membrane potential (ΔΨm) and mitochondrial copy number during the development of early embryos. In addition, after MXC treatment, blastocyst apoptosis and DNA damage were increased, decreased cell proliferation, and the expression of pluripotency-related genes SOX2, NANOG, and OCT4 was down-regulated, while the expression of apoptosis-related genes BAX/BCL-2 and Caspase9 was up-regulated. Our results clearly show that MXC can have deleterious effects on the developmental processes of early porcine embryos, establishing the toxicity of MXC to the reproductive system. In addition, the study of this toxic effect may lead to greater concern about pesticide residues in humans and the use of safer pesticides, thus potentially preventing physiological diseases caused by chemical exposure.

Salidroside Supplementation Affects In Vitro Maturation and Preimplantation Embryonic Development by Promoting Meiotic Resumption.

Salidroside (Sal) possesses several pharmacological activities, such as antiaging, and anti-inflammatory, antioxidant, anticancer activities, and proliferation-promoting activities, but the effects of Sal on oocytes have rarely been reported. In the present study, we evaluated the beneficial effects of Sal, which is mainly found in the roots of Rhodiola. Porcine cumulus oocyte complexes were cultured in IVM medium supplemented (with 250 µmol/L) with Sal or not supplemented with Sal. The maturation rate in the Sal group increased from 88.34 ± 4.32% to 94.12 ± 2.29%, and the blastocyst rate in the Sal group increased from 30.35 ± 3.20% to 52.14 ± 7.32% compared with that in the control group. The experimental groups showed significant improvements in the cumulus expansion area. Sal reduced oocyte levels of reactive oxygen species (ROS) and enhanced intracellular GSH levels. Sal supplementation enhanced the mitochondrial membrane potential (MMP), ATP level, and mtDNA copy number, which shows that Sal enhances the cytoplasmic maturation of oocytes. Oocytes in the Sal group exhibited slowed apoptosis and reduced DNA breakage. Cell cycle signals and oocyte meiosis play important roles in oocyte maturation. The mRNA expressions of the MAPK pathway and MAPK phosphorylation increased significantly in the Sal group. The mRNA expression of the oocyte meiosis gene also increased significantly. These results show that Sal enhances the nuclear maturation of oocytes. Moreover, Sal increased the number of blastocyst cells, the proliferation of blastocysts, and the expressions of pluripotency genes. Sal down-regulated apoptosis-related genes and the apoptotic cell rate of blastocysts. In summary, our results demonstrate that Sal is helpful to improving the quality of porcine oocytes in vitro, and their subsequent embryonic development.

Hydroxysafflor yellow A inhibits endothelial cell ferroptosis in diabetic atherosclerosis mice by regulating miR-429/SLC7A11.

CONTEXT: Ferroptosis may play an essential role in lipid peroxidation and endothelial dysfunction of aortic endothelial cells (ECs) in type 2 diabetes mellitus (T2DM) with atherosclerosis (AS). Hydroxysafflor yellow A (HSYA) has shown substantial antioxidant stress and anti-ferroptosis. OBJECTIVE: This study confirms whether HSYA improves symptoms in a mouse model of T2DM/AS and elucidates the underlying mechanisms. MATERIALS AND METHODS: ApoE-/- mice were fed with high fat combined with 30 mg/kg streptozotocin to establish a T2DM/AS model. Then mice were treated with intraperitoneal injections of 2.25 mg/kg HSYA for 12 weeks. Human Umbilical Vein Endothelial cells (HUVEC) induced by 33.3 mM d-glucose +100 µg/mL ox-LDL were used to construct a high lipid and high glucose cell model treated with 25 µM HSYA. The changes in oxidative stress- and ferroptosis-related markers were detected, and the regulatory effect of HSYA on the miR-429/SLC7A11 was also verified. Normal ApoE-/- mice or HUVEC cells were used as the control group. RESULTS: HSYA effectively reduced atherosclerotic plaque formation in the T2DM/AS mouse model and inhibited HUVEC ferroptosis, such as upregulating GSH-Px, SLC7A11 and GPX4, but inhibited ACSL4. Furthermore, HSYA also downregulated the expression of miR-429, which further regulated SLC7A11 expression. After miR-429 mimic or SLC7A11 siRNA transfection in the HUVEC, the antioxidative stress and anti-ferroptosis effects of HSYA were significantly abolished. CONCLUSIONS: HSYA is expected to become an important health drug to prevent the occurrence and development of T2DM/AS.

Distributed MPC of vehicle platoons with guaranteed consensus and string stability.

Control of vehicle platoon can effectively reduce the traffic accidents caused by fatigue driving and misoperation, reduce air resistance by eliminating the inter-vehicle gap which will effectively reduce fuel consumption and exhaust emissions. A hierarchical control scheme for vehicle platoons is proposed in this paper. Considering safety, consistency, and passengers' comfort, a synchronous distributed model predictive controller is designed as an upper-level controller, in which a constraint guaranteeing string stability is introduced into the involved local optimization problem so as to guarantee that the inter-vehicle gap error gradually attenuates as it propagates downstream. A terminal equality constraint is added to guarantee asymptotic consensus of vehicle platoons. By constructing the vehicle inverse longitudinal dynamics model, a lower-level control scheme with feedforward and feedback controllers is designed to adjust the throttle angle and brake pressure of vehicles. A PID is used as the feedback controller to eliminate the influence of unmodeled dynamics and uncertainties. Finally, the performance of longitudinal tracking with the proposed control scheme is validated by joint simulations with PreScan, CarSim, and Simulink.

Retrospective Analysis of the Safety and Efficacy of AngioJet Rheolytic Thrombectomy for Acute Pulmonary Embolism: A Single-Center Study.

BACKGROUND: To investigate the efficacy, safety, and feasibility of AngioJet Rheolytic Thrombectomy (ART) in the treatment of acute pulmonary embolism (APE). METHODS: Twelve patients with intermediate- or high-risk APE received ART and were followed up for 6-32 months. The technical success rate, clinical success rate, mortality, complication, and ancillary and laboratory tests before and after operation were analyzed retrospectively. RESULTS: The technical and clinical success rates of ART were both 91.67% (11/12). Except for the patient who died of heart failure during the operation, the rest of patients had no serious complications. After operation, arterial oxygen partial pressure increased while hemoglobin and troponin decreased (P < 0.05). All patients were free of recurrence of APE after 6-32 months of follow-up. Pulmonary artery thrombosis significantly reduced or disappeared. CONCLUSIONS: ART is an effective treatment for intermediate- and high-risk APE. It quickly clears the main pulmonary artery thrombus, relieves pulmonary hypertension, and improves the long-term prognosis of patients.

Analysis for global characteristics of Lyapunov exponents in vehicle plane motion system.

In the field of vehicle system dynamics, it is significant to propose an appropriate quantitative indicator for system stability or dynamics characteristics. Lyapunov exponents method is an excellent quantitative indicator for analysing nonlinear system characteristics. It was used to studied the stable region of nonlinear vehicle plane motion system. However, the effect of Lyapunov exponents method in revealing the global dynamics characteristics has not been fully studied. Aiming at this key problem, this paper analyses the global characteristics of Lyapunov exponents with different degrees of freedom nonlinear models. The results show that Lyapunov exponents can well reflect the global layer characteristics for vehicle system. However, the value characteristic under different DOF models is not unified. The research and analysis in this paper supplement the quantitative analysis theory for vehicle system dynamics.

The perturbed expression of m6A in parthenogenetic mouse embryos.

Parthenogenetically activated oocytes cannot develop to term in mammals owing to abnormal epigenetic modifications. Methylation of the N6 position of adenosine (m6A) is a post-transcriptional epigenetic modification of RNA. To investigate the role of m6A methylation in parthenogenetic (PA) embryonic development, we analyzed METTL3, METTL14, FTO, ALKBH5, YTHDF2, IGF2BP1, and IGF2BP2 expression by quantitative real-time PCR. These genes were found dynamically expressed during the 2-cell, 4-cell, 8-cell, and blastocyst stages of the embryo. Compared to normally fertilized embryos, the expression of these genes was perturbed in PA embryos, especially at the 8-cell stage. Furthermore, immunofluorescence was used to detect m6A expression. The results demonstrated that m6A expression decreased in the 2-cell stage, whereas it increased in the 8-cell stage of PA embryos. Taken together, these results suggest that the expression of RNA methylation-related genes was perturbed, leading to abnormal m6A modification during early development in PA embryos.

The expression of TET3 regulated cell proliferation in HepG2 cells.

Ten-eleven translocation (TET) proteins have been shown to be abnormally expressed in different cancers. To investigate the expression pattern of TET proteins in HepG2 cells, sodium ascorbate was used to treat HepG2 cells. Our results showed that TET1, TET2 and TET3 expression was increased after sodium ascorbate treatment. The TET proteins catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thus, 5mC and 5hmC levels were examined. The results suggested that 5hmC was increased after sodium ascorbate treatment. To further determine the biological function of the TET proteins, si-TET1, si-TET2 and si-TET3 were transfected into HepG2 cells. The results showed that a knock down of TET3 expression stimulated cell proliferation of HepG2 cells. To further understand the effects of TET3 expression on cell proliferation, sodium ascorbate was added to the cells after transfection with si-TET3. The results demonstrated that sodium ascorbate could rescue TET3 expression and inhibit cell proliferation. Taken together, these results indicate that TET3 expression regulated cell proliferation, which is associated with 5hmC in HepG2 cells.

Imbalance between proliferation and apoptosis-related impaired GPR30 expression is involved in preeclampsia.

The proliferation and apoptosis of cells in the placenta play a critical role in preeclampsia (PE) in which estrogen has been implicated via estrogen receptors (ERs). A novel ER, G-protein-coupled receptor 30 (GPR30), has recently been shown to be involved in PE. We investigated the basic levels of proliferation and apoptosis in normal placentae and placentae with PE and compared GPR30 expression levels between the two groups. We demonstrated that low GPR30 expression levels, more apoptosis, and less proliferation were associated with PE. Moreover, our in vitro study showed that both the selective GPR30 agonist G1 and the general ER agonist 17-ß-estradiol were able to protect the placenta from hypoxia-reoxygenation injuries, resulting in decreased apoptosis and increased proliferation. Furthermore, this protective effect was abolished by the addition of the selective GPR30 inhibitor G15. These results provide evidence that (1) GPR30 is involved in regulating cell proliferation and apoptosis; (2) pharmacologic upregulation of GPR30 is beneficial for PE management; (3) GPR30 may therefore be an interventional target for pregnancies complicated by PE.

G protein-coupled receptor 30 regulates trophoblast invasion and its deficiency is associated with preeclampsia.

BACKGROUND: Preeclampsia is known to be associated with reduced circulating levels of estrogen. The effects of estrogen in preeclampsia are normally mediated by the classical estrogen receptors. Intriguingly, a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), has been recently found to play an important role in several estrogenic effects. However, the mechanisms by which GPR30 may mediate the development of preeclampsia remain unknown. METHOD: We observed that the expression of GPR30 in placental trophoblast cells is lower in preeclamptic placentas compared with normotensive controls. We then investigated the role of GPR30 in trophoblast cell invasion by utilizing placental explants and the immortalized human trophoblast cell line (HTR8/SVneo). RESULTS: The selective GPR30 agonist G1 and a general estrogen receptors agonist 17-ß-estradiol (E2) both improved trophoblast cells invasion by upregulating MMP9 expression and the PI3K-Akt signaling pathway. This effect was abolished by a selective GPR30 inhibitor G15, implying that GPR30 may be involved in regulating trophoblast invasion, and that down-regulation of this receptor may result in the development of preeclampsia. CONCLUSION: The present study suggests that GPR30 is a critical regulator of trophoblast cell invasion, and as such may be a potential therapeutic interventional target for preeclampsia and other pregnancy complications resulting from impaired trophoblast invasion.