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Pei Zhou,* Hongbo Guan,* Yanyan Guo, Liangliang Zhu, Xiaomei Liu Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaomei LiuKey Laboratory of Maternal-Fetal Medicine of Liaoning Province, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang, 110004, People’s Republic of ChinaTel +86-18940255055Email liuxm@cmu.edu.cnPurpose: Maternal obesity impairs kidney development and function of the offspring and leads to a greater risk of kidney disease in adulthood. The present study aimed to investigate the link between peroxisomes, oxidative stress (OS), and inflammasomes in the fetal kidney of maternal obesity rats and to explore the potential therapeutic effects of the antioxidant pyrroloquinoline quinone (PQQ).Methods: Maternal obesity rats were developed by administration of a high fat diet plus supplementation with PQQ (40 mg/kg body weight) as a potential therapy. Renal histology was observed by Periodic Acid-Schiff staining. The expression profiles of peroxins, fatty acid β-oxidation enzymes, antioxidants, and the regulators of the unfolded protein response (UPR) pathway and NLRP3 inflammasome were analyzed in the kidneys and tubular epithelial cells (TECs) from near-term fetuses (embryonic day 20).Results: The present work revealed that: 1) a maternal high fat diet (MHF) led to higher blood pressure in adult offspring; 2) MHF led to downregulation of peroxisome markers PEX3 and 14 in fetal kidneys; 3) the antioxidant SOD2 and catalase were decreased, and oxidative stress marker Ephx2 was increased; 4) MHF-induced activation of the UPR pathway; 5) the KEAP1-NRF2 pathway was activated; 6) activation of the NLRP3 inflammasome led to secretion of pro-inflammation factors; 7) in TECs, the changes in PEXs and NLRP3 are similar to tissues, but UPR and NRF2 pathways showed opposite trends; 8) and the antioxidant PQQ alleviated maternal lipotoxicity by decreasing ROS levels and inhibiting activation of ER stress and inflammasome in fetal kidney.Conclusion: A maternal high fat diet decreased the number of peroxisomes, subsequently activated OS and inflammasomes, resulting in pyroptosis and apoptosis in fetal kidney. The antioxidant PQQ served a protective role against the effects of lipotoxicity on kidney programming and, thus, is a potential candidate to prevent maternal obesity-induced renal programming.Keywords: maternal obesity, kidney, peroxisome, oxidative stress, inflammasome

Preeclampsia (PE) is an obstetric disorder. N6-methyladenosine (m6A) modification is related to PE trophoblast biological behaviors. This study explored the mechanism of m6A-modified circSETD2 in trophoblast biological behaviors. Chorionic trophoblast apoptosis and circSETD2 expression in PE rat models were detected. HTR8/SVneo cells were induced by CoCl

In this paper, an anisotropic bilinear finite element method is constructed for the elliptic boundary layer optimal control problems. Supercloseness properties of the numerical state and numerical adjoint state in a \begin{document}$ \epsilon $\end{document} -norm are established on anisotropic meshes. Moreover, an interpolation type post-processed solution is shown to be superconvergent of order \begin{document}$ O(N^{-2}) $\end{document} , where the total number of nodes is of \begin{document}$ O(N^2) $\end{document} . Finally, numerical results are provided to verify the theoretical analysis.

This paper presents a new numerical method and analysis for solving second-order elliptic interface problems. The method uses a modified nonconforming rotated Q1 immersed finite element (IFE) space to discretize the state equation required in the variational discretization approach. Optimal order error estimates are derived in L2-norm and broken energy norm. Numerical examples are provided to confirm the theoretical results.

In this paper, nonconforming finite element methods (FEMs) are proposed for the constrained optimal control problems (OCPs) governed by the nonsmooth elliptic equations, in which the popular $$EQ_1^{rot}$$ element is employed to approximate the state and adjoint state, and the piecewise constant element is used to approximate the control. Firstly, the convergence and superconvergence properties for the nonsmooth elliptic equation are obtained by introducing an auxiliary problem. Secondly, the goal-oriented error estimates are obtained for the objective function through establishing the negative norm error estimate. Lastly, the methods are extended to some other well-known nonconforming elements.

The existence of either eccentricity or slenderness has a significant effect on the mechanical properties of a structure or member. These properties can change the working mechanism, failure mode, and bearing capacity of the structure or member. A concrete-filled, glass fibre-reinforced, polymer tube composite column has the same problem. We carried out experiments on the influences of eccentricity and slenderness on the mechanical properties of concrete-filled, glass fibre-reinforced, polymer tube composite columns. The experimentally recorded stress–strain relationships are presented graphically, and the ultimate axial stresses and strains and the FRP tube hoop strains at rupture were tabulated. The results indicate that the influences of slenderness and eccentricity on the composite columns were significant with regard to the axial strain, hoop strain, ultimate bearing capacity, lateral displacement, and failure mode. Based on the existing research literature and the results reported in this paper, the bearing capacity formula of a composite slender column under an eccentric load was established. The theoretical results were in good agreement with the experimental results.

In this paper, we propose a modified Polak–Ribière–Polyak (PRP) conjugate gradient method for solving large-scale nonlinear equations. Under weaker conditions, we show that the proposed method is globally convergent. We also carry out some numerical experiments to test the proposed method. The results show that the proposed method is efficient and stable.

An adverse intrauterine environment impairs the development of pancreatic islets in the fetus and leads to insufficient β cell mass and β cell dysfunction. We previously reported that Pex14, a peroxin protein involved in the biogenesis and degradation of peroxisomes, is markedly reduced in the pancreas of an intrauterine growth restriction fetus and last into adulthood. Peroxisomes function in a wide range of metabolic processes including fatty acid oxidization, ROS detoxification, and anti-inflammatory responses. To elucidate the impact of downregulation of the Pex14 gene on β cell, Pex14 was knocked down by siRNA in INS-1 cells. Pex14 knockdown disturbed peroxisomal biogenesis and dysregulated fatty acid metabolism and lipid storage capability, thereby increased ROS level and blunted insulin secretion. Moreover, Pex14 knockdown upregulated inflammation factors and regulators of endoplasmic reticulum stress. The lipotoxicity of fatty acid (including palmitic acid and linoleic acid) in β cells was exacerbated by knockdown of Pex14, as indicated by H2O2 accumulation and increased programmed cell death. The present results demonstrate the vital role of Pex14 in maintaining normal peroxisome function and β cell viability and highlight the importance of a functional peroxisomal metabolism for the detoxification of excess FAs in β cells.

Preeclampsia (PE) is a leading cause of maternal and perinatal death. Accumulated evidence suggests that many long non-coding RNAs (lncRNAs) are abnormally expressed in placentas from PE patients, and they may play functional roles in the development of PE. The present study aimed to investigate the functional role TUG1 in PE and explore the potential molecular mechanisms. Clinically, the expression of TUG1 in placental tissues from PE and normal controls was determined. In vitro, human trophoblast HTR-8/SVneo and JAR cells were employed for loss or gain-of-function assays. Our results demonstrate that TUG1 was downregulated in PE placental tissues compared with normal controls. Moreover, downregulation of TUG1 inhibited the migration and invasion of trophoblast-like cells. Bioinformatics analysis and functional assays showed that TUG1 interacted with miR-204-5p and negatively regulated the expression and function of miR-204-5p in trophoblast cells. Furthermore, TUG1-mediated migration and invasion of trophoblast cells was regulated by miR-204-5p. Together, our results suggested that TUG1 regulates trophoblast migration and invasion partly through sponging miR-204-5p, and the TUG1/miR-204-5p axis could be a potential therapeutic target for the treatment of PE.

To analyze existing cohort studies and provide evidence for the use of prenatal selective serotonin reuptake inhibitor (SSRI) monotherapy and the associated risk of gestational hypertension and preeclampsia.A comprehensive search of English language articles published before 30th April 2017 was conducted on PubMed, EMBASE, and the Web of Science databases. Using data acquired, we summarized the relative risks (RRs) and 95% confidence intervals (CIs) of gestational hypertension and preeclampsia using the random-effects model. Heterogeneity between studies was also assessed with the ISeven cohort studies with 1,108,261 individuals were included for analysis. Compared with nonusers, those undertaking prenatal SSRI monotherapy were more likely to develop gestational hypertension or preeclampsia (summarized RR = 1.21, 95% CI: 1.05-1.40, IWomen who receive SSRI monotherapy during pregnancy are at increased risk of gestational hypertension and preeclampsia.

Mesenchymal stem cells (MSCs), which exhibit the property of immune-modulation, have been shown to treat various diseases, including pulmonary hypertension. There is a functional similarity between the pulmonary circulation and the placenta, but it remains to be elucidated whether MSCs can be applied to treat endotoxin-induced hypertension during pregnancy; therefore, the aim of the present study was to investigate the therapeutic effect of a human umbilical cord-derived MSC infusion on endotoxin-induced hypertension during pregnancy. Rats were randomly divided into three groups (n=7 per group): Control, endotoxin-treated and endotoxin + MSCs. The model of preeclampsia (PE) was established via the intravenous injection of endotoxin. In the endotoxin + MSCs group, MSCs at 2×106 cells/rat were injected via the vena caudalis. The blood pressure, urine protein and number of white blood cells were measured. In addition, the protein expression levels of the pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) and the anti-inflammatory cytokine IL-10 were examined by ELISA. The blood pressure, levels of urine protein and number of white blood cells in the endotoxin-treated group were significantly higher than those in the control group (P

A new stable nonconforming mixed finite element (MFE) scheme is proposed for the constrained optimal control problem (OCP) governed by elliptic equations. The nonconforming FEs are employed to approximate the co-state, the piecewise constant element for the state and control, respectively. The corresponding optimal order error estimates are derived by full use of the distinguish properties of the nonconforming element, i.e.,?(a) the divergence of the function in the FE space is a constant; (b) the consistency error is one order higher than its interpolation error in the broken energy norm. Finally, some numerical results are carried out to verify the theoretical analysis.

The lowest order P1-nonconforming triangular finite element method (FEM) for elliptic and parabolic interface problems is investigated. Under some reasonable regularity assumptions on the exact solutions, the optimal order error estimates are obtained in the broken energy norm. Finally, some numerical results are provided to verify the theoretical analysis.

Summary Insufficient trophoblast invasion often occurs in patients experiencing preeclampsia. The 67-kDa laminin receptor (LR1) is a multifunctional protein that binds to laminin and interacts with the extracellular matrix. We recently demonstrated that LR1 is implicated in trophoblast migration and invasion. However, whether LR1 is involved in hypoxia-mediated trophoblastic invasion remains unclear and requires further investigation. This study demonstrates that two trophoblast-like cell lines (JEG3 and BeWo cells) cultured at 3% oxygen exerted enhanced migratory and invasive capabilities as compared with their counterparts exposed to 20% oxygen. LR1 expression was increased in hypoxic JEG3 cells but decreased after transfection with hypoxia-inducible factor 1 alpha (HIF-1α) specific siRNA. Moreover, shRNA targeting LR1 mRNA significantly inhibited hypoxia-induced increase in matrix metalloproteinase (MMP)-9 activity in JEG3 cells. Forced overexpression of LR1 augmented JEG3 cell migration and invasion, and enhanced MMP-9 expression and activity. Additionally, the blockade of the MMP-9 effect with its neutralizing antibody reduced LR1 elevation-promoted trophoblastic invasion. In summary, this study demonstrates that LR1 contributes to hypoxia-induced migration and invasion of trophoblast cells at least partly by mediating MMP-9 in vitro.

In this paper, we study the problem about the stochastic stabilization for a class of discrete-time singular systems involved constant time delay and the Markovian jump parameters. We pay attention to designing a dynamic feedback controller such that the resultant closed-loop system is regular, impulsive-free and stable. A condition that ensures that the dynamic feedback controller exists is obtained. Finally, we presents a numerical example to verify the effectiveness of the obtained result.

To test the effects of human umbilical cord mesenchymal stem cell (HU-MSC) transplantation on reversing preeclampsia (PE) symptoms in a lipopolysaccharide (LPS)-induced rat PE model.Human umbilical cord MSCs were detected, isolated, and cultured. Human umbilical cord MSC transplantation was conducted. Expressions of inflammatory cytokines in serum and placental tissue were measured by enzyme-linked immunosorbent assay. Changes in inflammatory cytokines, peroxisome proliferator-activated receptor γ (PPARγ), laminin receptor 1 (LR1), matrix metalloproteinase (MMP) 2, and MMP-9 messenger RNA (mRNA) levels in placental tissue were recorded by quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blotting were performed for PPARγ detection.The LPS group exhibited increased blood pressure and proteinuria and decreased fetal weight compared to the normal pregnancy (NP) group (all P.05). The LPS + MSC group presented lowered blood pressure and higher fetal weight than the LPS group (P.05). The levels of interferon γ, tumor necrosis factor α (TNF-α), interleukin (IL) 1β, IL-6, IL-8, IL-12, and intercellular adhesion molecule 1 (ICAM-1) increased and the levels of IL-4 and IL-10 levels decreased in the LPS group compared to the NP group (all P.05). Tumor necrosis factor α, IL-6, IL-12, and ICAM-1 levels decreased and IL-10 level increased in the LPS + MSC group compared to the LPS group (all P.05). The LPS-MSC group showed lower mRNA expressions of TNF-α, IL-6, MMP-2, MMP-9, and ICAM-1 and higher mRNA expressions of IL-10, PPARγ, and LR1 than the LPS group (all P.05).In summary, HU-MSC transplantation may be extremely beneficial for PE therapy.

Preeclampsia is a devastating pregnancy-related syndrome characterized by the onset of hypertension, proteinuria and edema. Insufficient invasion of trophoblasts is well-known to be correlated with preeclampsia development. The present study was performed to investigate the functional role microRNA (miRNA)-204 in trophoblastic invasion in vitro. We here found that the invasive capabilities of BeWo and JEG3 trophoblast-like cells were suppressed by miR-204 mimics, whereas enhanced by its inhibitor. Matrix metalloproteinase-9 (MMP9) was first confirmed to play a role in regulating trophoblast invasion through loss- or gain-of-function experiment. Notably, we demonstrated MMP9 as a direct target of miR-204 in BeWo cells by using the dual-luciferase assay. Moreover, forced overexpression of MMP9 was noted to partly attenuate the inhibitory effects of miR-204 on BeWo cell invasion. Taken together, our study indicates that miR-204 may contribute to the development of preeclampsia by inhibiting trophoblastic invasion, and that MMP9 is involved in miR-204-mediated trophoblast cell invasion. Our study suggests miR-204 as a novel therapeutic target for preeclampsia.