Myometrium infection decreases TREK1 through NHE1 and increases contraction in pregnant mice.

Intrauterine infection during pregnancy can enhance uterine contractions. A two-pore K+ channel TREK1 is crucial for maintaining uterine quiescence and reducing contractility, with its properties regulated by pH changes in cell microenvironment. Meanwhile, the sodium hydrogen exchanger 1 (NHE1) plays a pivotal role in modulating cellular pH homeostasis, and its activation increases smooth muscle tension. By establishing an infected mouse model of Escherichia coli (E. coli) and lipopolysaccharide (LPS), we used Western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence to detect changes of TREK1 and NHE1 expression in the myometrium, and isometric recording measured the uterus contraction. The NHE1 inhibitor cariporide was used to explore the effect of NHE1 on TREK1. Finally, cell contraction assay and siRNA transfection were performed to clarify the relationship between NHE1 and TREK1 in vitro. We found that the uterine contraction was notably enhanced in infected mice with E. coli and LPS administration. Meanwhile, TREK1 expression was reduced, whereas NHE1 expression was upregulated in infected mice. Cariporide alleviated the increased uterine contraction and promoted myometrium TREK1 expression in LPS-injected mice. Furthermore, suppression of NHE1 with siRNA transfection inhibited the contractility of uterine smooth muscle cells and activated the TREK1. Altogether, our findings indicate that infection increases the uterine contraction by downregulating myometrium TREK1 in mice, and the inhibition of TREK1 is attributed to the activation of NHE1.NEW & NOTEWORTHY Present work found that infection during pregnancy will increase myometrium contraction. Infection downregulated NHE1 and followed TREK1 expression and activation decrease in myometrium, resulting in increased myometrium contraction.

Hypoxia-induced autophagy inhibits myometrial proliferation in pregnant mice via the mTOR pathway in vitro.

In brief: During pregnancy and delivery, the myometrium was affected by hypoxia stress, which acts as a regulator of cell proliferation. The proliferation of uterine smooth muscle cells in pregnant mice was inhibited under hypoxia, which was related to the up-regulated autophagy through the mTOR pathway. Abstract: Hypoxia is closely associated with physiological and pathological conditions in the human body, and the myometrium is affected by hypoxic stress during pregnancy and delivery. Autophagy is a catabolic pathway involved in the regulation of apoptosis, proliferation, and migration of a variety of cells, which can be activated under hypoxia. However, the mechanism and function of autophagy in uterine smooth muscle cells remained unclear. The aim of this study was to investigate the changes in autophagy in pregnant uterine smooth muscle cells (pUSMCs) under hypoxia and the effect of autophagy on myometrial cellscell proliferation during pregnancy. In this study, primary uterine smooth muscle cells were isolated from mice in late pregnancy and cultured under normoxic and hypoxic conditions, respectively. Western blotting and immunofluorescence were used to detect the expression levels of autophagy-related proteins LC3B, P62, mTOR, and p-mTOR under different culture conditions. Cell proliferation was assessed by CCK-8 assay. In addition, 3-methyladenine (3-MA) was used to inhibit autophagy in hypoxia-treated pUSMCs, and MHY1485 was used to activate mTOR. Studies have confirmed that under hypoxic conditions, autophagy is enhanced and cell proliferative viability is reduced in pUSMCs. The autophagy inhibitor 3-MA restored cell proliferation inhibited by hypoxia. Furthermore, hypoxia in pUSMCs led to a downregulation of p-mTOR/mTOR levels. The mTOR activator MHY1485 inhibited autophagy by preventing the binding of autophagosomes to lysosomes and reversed the hypoxia-induced inhibition of cell proliferation. Collectively, our results indicate that hypoxia upregulates autophagy through the mTOR pathway in pUSMCs, thereby inhibiting cell proliferation during pregnancy.

Prolonged stretching of rat uteri causes hypoxia and inhibits contractility via potassium channel TREK1.

In brief: During pregnancy, uterine kept quiescence along with uterine overdistention before labor. Prolonged stretching induced uterus myometrial hypoxia, increased TREK1 expression, and relaxed the myometrium, which may contribute to uterine quiescence and atony during pregnancy. Abstract: The mechanisms underlying pre-labor uterine quiescence and uterine atony during overdistention are unclear. TREK1 (a two-pore domain potassium channel) and hypoxia-inducible factor-1α (HIF-1α) are activated by mechanical stretch, and their expression is upregulated by decreased uterine contractility. HIF-1α is a nuclear factor which regulates numerous target proteins, but whether it regulates TREK1 during the uterine stretch to cause uterine quiescence and/or atony is unclear. We investigated uterine contractility at different gestational stages in rats, as well as in non-pregnant uteri, which were induced by prolonged stretching and hypoxia. We also assessed the effects of incubating the uteri with or without echinomycin or l-methionine. Moreover, we analyzed HIF-1α and TREK1 expression levels in each group, as well as at various gestational stages of pregnant human uteri. We found that contractility was significantly decreased in pregnant uteri when compared with non-pregnant uteri, and this decrease was associated with increases in HIF-1α and TREK1 expression levels. HIF-1α and TREK1 expression levels in human uteri increased with the gestational length. Decreased uterine contractility and increased HIF-1α and TREK1 expression levels were also observed in non-pregnant rat uteri under 8 g of stretching tension or hypoxia. Inhibition of hypoxia with echinomycin restored normal uterine contractility, while HIF-1α and TREK1 protein expression remained reduced. TREK1 inhibition with l-methionine also restored uterine contractility under tension or hypoxia. In conclusion, we demonstrated that prolonged stretching induces myometrial hypoxia, increases TREK1 expression, and relaxes the myometrium, which may contribute to uterine quiescence and atony.

Optimal delivery time for patients with diet-controlled gestational diabetes mellitus: a single-center real-world study.

BACKGROUND: To determine the optimal delivery time for women with diet-controlled gestational diabetes mellitus by comparing differences in adverse maternal-fetal outcome and cesarean section rates. METHODS: This real-world retrospective study included 1,050 patients with diet-controlled gestational diabetes mellitus who delivered at 35-42 weeks' gestation. Data on patient characteristics, maternal-fetal outcomes, and cesarean section rate based on fetal gestational age were collected and analyzed. Differences between deliveries with and without iatrogenic intervention were also analyzed. RESULTS: The cesarean section rate at ≥ 41 weeks' gestation was significantly higher than that at 39-39 + 6 weeks (56% vs. 39%, p = 0.031). There were no significant differences in multiple adverse maternal or neonatal outcomes at delivery before and after 39 weeks. Vaginal delivery rates were increased significantly at 39-39 + 6 weeks due to iatrogenic intervention (p = 0.005) and 40-40 + 6 weeks (p = 0.003) in patients without and with spontaneous uterine contractions, respectively. CONCLUSIONS: It's recommended that optimal delivery time for patients with diet-controlled gestational diabetes mellitus should be between 39- and 40 + 6 weeks' gestation. Patients who have Bishop scores higher than 4 can undergo iatrogenic intervention at 39-39 + 6 weeks. However iatrogenic interventions are not recommended for patients with low Bishop scores.

First-principles study of phase-dependent carrier transport mechanism for MASnI3Sn-based halide perovskite.

Organic-inorganic hybrid perovskites have attracted tremendous attentions owing to their excellent properties as next-generation photovoltaic devices. With soft covalent framework, organic-inorganic hybrid perovskites exhibit different phases at different temperatures. The band-edge features of perovskites are mainly contributed by inorganic framework, which means the structural differences between these phases would lead to complex carrier transport. We investigated the carrier transport of Sn-based organic-inorganic hybrid perovskite CH3NH3SnI3(MASnI3), considering acoustic deformation potential scattering, ionized impurity scattering, and polar optical phonon scattering. It is found that the electron mobility of each phase of MASnI3is strongly correlated with the Sn-I-Sn bond angle and there is in-plane/out-of-plane anisotropy. The projected crystal orbital Hamilton population analysis suggested that the tilt and rotation of the [SnI6]4-octahedron influence the Sn(p)-I(p) orbital electron coupling and the electron transport, leading to different band-edge features in multiple phases. The carrier mobility with respect to temperature was further calculated for each phase of MASnI3in respective temperature intervals, showing lower carrier mobility in high temperature. Comparing the contribution of different scattering mechanisms, it was found that the dominant scattering mechanism is polar optical phonon scattering, while multiple scattering mechanisms compete in individual cases.

Conservative management or cesarean hysterectomy for placenta accreta spectrum in middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Cesarean hysterectomy is a dominant and effective approach during delivery in patients with placenta accreta spectrum (PAS). However, as hysterectomy results in a loss of fertility, conservative management is an alternative approach. However, management selection may be affected by a country's overall economic level. Thus the preferred treatment for PAS generates controversy in middle-income countries. OBJECTIVES: We aimed to compare conservative management and cesarean hysterectomy for managing PAS in middle-income countries. SEARCH STRATEGY: China National Knowledge Infrastructure, Wanfang Med Online Databases, Cochrane Library, Ovid MEDLINE, PubMed, Web of Science, EMBASE, clinicaltrials.gov, and Scopus were searched from inception through to October 1, 2022. SELECTION CRITERIA: We included studies that evaluated at least one complication comparing conservative management and hysterectomy. All cases were diagnosed with PAS prenatally and intraoperatively. DATA COLLECTION AND ANALYSIS: The primary outcomes were blood loss, adjacent organ damage, and the incidence of hysterectomy. Descriptive analyses were conducted for studies that did not meet the meta-analysis criteria. A fixed-effects model was used for studies without heterogeneity and a random-effects model was used for studies with statistical heterogeneity. MAIN RESULTS: In all, 11 observational studies were included, with 975 and 625 patients who underwent conservative management and cesarean hysterectomy, respectively. Conservative management was significantly associated with decreased blood loss and lower risks of adjacent organ injury and hysterectomy. Conservative management significantly reduced blood transfusions, hospitalization duration, operative time, intensive care unit admission rates, and infections. There were no significant differences in the risks of coagulopathy, thromboembolism, or reoperation. CONCLUSION: Given short-term complications and future fertility preferences for patients, conservative management appears to effectively manage PAS in middle-income countries. Owing to low levels of evidence, high heterogeneity and insufficient long-term follow-up data, further detailed studies are warranted.

First-principles predictions of enhanced thermoelectric properties for Cs2SnI2Cl2and Cs2PbI2Cl2monolayers with spin-orbit coupling.

Inspired by the exceptional charge transport properties and ultra-low thermal conductivity of halide perovskite, we investigate the electronic nature, thermal transport, and thermoelectric properties for Ruddlesden-Popper all-inorganic perovskite, Cs2SnI2Cl2and Cs2PbI2Cl2monolayers, using first-principles calculations. During the calculations, spin-orbit coupling has been considered for electronic transport as well as thermoelectric properties. The results show that the Cs2SnI2Cl2and Cs2PbI2Cl2monolayers exhibit high carrier mobility and low thermal conductivity. Stronger phonon-phonon interaction is responsible for the fact that thermal conductivity of Cs2SnI2Cl2monolayer is much lower than that of Cs2PbI2Cl2monolayer. At 700 K, the values of the figure of merit (ZT) for the n-type doped Cs2SnI2Cl2and Cs2PbI2Cl2monolayers are about 1.05 and 0.32 at the optimized carrier concentrations 5.42 × 1012cm-2and 9.84 × 1012cm-2. Moreover, when spin-orbit coupling is considered, the correspondingZTvalues are enhanced to 2.73 and 1.98 at 5.27 × 1011cm-2and 6.16 × 1011cm-2. These results signify that Cs2SnI2Cl2and Cs2PbI2Cl2monolayers are promising thermoelectric candidates.

High glucose induced HIF-1α/TREK1 expression and myometrium relaxation during pregnancy.

Background: The incidence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM patients have a significantly higher rate of cesarean section and postpartum hemorrhage, suggesting changes in uterine contractility. TWIK-1-related potassium channel (TREK1) expressed in the pregnant uterus and its role in uterine contraction. In this study, we examined the expression of HIF-1α and TREK1 proteins in GDM uterine and investigated whether high glucose levels are involved in the regulation of human uterine smooth muscle cells (HUSMCs) contraction through TREK1, and verified the role of HIF-1α in this process. Methods: Compared the uterine contractility between GDM and normal patients undergoing elective lower segment cesarean section. The HUSMCs were divided into normal glucose group, high glucose group, normal glucose with CoCl2 group, CoCl2 with echinomycin/L-Methionine group, and high glucose with echinomycin/L-Methionine group; Compare the cell contractility of each group. Compared the expression of hypoxia-inducible factor-1α (HIF-1α) and TREK1 protein in each group. Results: The contractility of human uterine strips induced by both KCl and oxytocin was significantly lower in patients with GDM compared with that in normal individuals, with increased TREK1 and HIF-1α protein expression. The contractility of cultured HUSMCs was significantly decreased under high glucose levels, which was consistent with increased expression of HIF-1α and TREK1 proteins. The contractility of HUSMCs was decreased when hypoxia was induced by CoCl2 and increased when hypoxia was inhibited by echinomycin. The TREK1 inhibitor L-methionine also recovered the decreased contractility of HUSMCs under high glucose levels or hypoxia. Discussion: The high glucose levels decreased the contractility of the myometrium, and increased expression of HIF-1a and TREK1 proteins play a role in changes in uterus contractility.

Gestational diabetes mellitus: The optimal time of delivery.

Gestational diabetes mellitus (GDM) is a common pregnancy complication strongly associated with poor maternal-fetal outcomes. Its incidence and prevalence have been increasing in recent years. Women with GDM typically give birth through either vaginal delivery or cesarean section, and the maternal-fetal outcomes are related to several factors such as cervical level, fetal lung maturity, the level of glycemic control still present, and the mode of treatment for the condition. We categorized women with GDM based on the latter two factors. GDM that is managed without medication when it is responsive to nutrition- and exercise-based therapy is considered diet- and exercise-controlled GDM, or class A1 GDM, and GDM managed with medication to achieve adequate glycemic control is considered class A2 GDM. The remaining cases in which neither medical nor nutritional treatment can control glucose levels or patients who do not control their blood sugar are categorized as class A3 GDM. We investigated the optimal time of delivery for women with GDM according to the classification of the condition. This review aimed to address the benefits and harms of giving birth at different weeks of gestation for women with different classes of GDM and attempted to provide an analytical framework and clearer advice on the optimal time for labor.

Preserved oxytocin-induced myometrium contraction and sensitivity to progesterone inhibition following rat uterus thermal insult. Impact on fertility.

Women seeking improved fertility often undergo diagnostic hysteroscopy that could cause uterine thermal injury with unclear impact on uterine contraction, embryo implantation and fertility. We tested whether uterine thermal insult adversely affects myometrium function and contraction related receptors, channels, junctional proteins and remodeling enzymes. Female Sprague-Dawley rats were anesthetized, the left uterine horn was infused with 85 ℃ hot saline (thermal Insult) and the right horn was infused with 25℃ warm saline (control) for 3 min. After 7-days recovery, uterine strips were prepared for tissue histology and measurement of contraction, and mRNA and protein levels of oxytocin receptor, progesterone (P4) receptor A (PR-A), membrane K+ channel TREK-1, junctional protein connexin-43 (CX-43) and matrix metalloproteinases MMP-2 and MMP-9. Uterine tissue histology showed cellular swelling and inflammatory cell infiltration immediately following thermal insult, and recovery with no difference from control 7-days later. KCl (96 mM) and oxytocin (10-13-10-7 M) caused significant contraction that was not different in thermal insult vs control uterine strips. Pretreatment with P4 (10-5 M) for 1 h caused marked inhibition of KCl and oxytocin contraction that was insignificantly greater in thermal vs control uterus. RT-PCR showed decreases in oxytocin receptor, PR-A, TREK-1, CX-43, MMP-2 and MMP-9 mRNA in thermal vs control uterus. Western blots showed decreases in oxytocin receptor, no change in TREK-1 and increased PRA, CX-43, MMP-2, and MMP-9 protein levels in thermal vs control uterus. To assess the impact on fertility, female rats were housed with male rats, and on gestational day 19, the litter size, pup weight and crown-rump length, and placenta weight were not different in thermal vs control uterus. Thus, after thermal insult-induced immediate inflammation and reduced heat-sensitive mRNA expression, the uterus undergoes a recovery and adaptation process involving preserved oxytocin-induced contraction, P4 inhibition and TREK-1 channels. The uterus self-healing process appears to require improved PR-A signaling, intercellular communication via CX-43 and tissue remodeling by MMP-2 and MMP-9. The uterine thermal recovery processes could be essential for maintaining fertility and future pregnancy outcome.

[Effects of Organic Carbon Content on the Residue and Migration of Polycyclic Aromatic Hydrocarbons in Soil Profiles].

The effects of total organic carbon content (TOC) on the migration of polycyclic aromatic hydrocarbons (PAHs) in the soil were investigated. This study analyzed the vertical properties of the concentrations and distributions of PAHs and TOC at various soil profiles from functionally different environmental regions including nature reserves, ploughs, orchards, farmlands, metropolitan areas, and industrial parks. The vertical migration properties of PAHs in soils were examined by conducting leaching experiments in soil columns. The concentrations of PAHs varied from region to region and showed strong, positive correlations with TOC in the same region. Furthermore, based on the leaching experiments, the transport abilities of PAHs were significantly influenced by TOC, although they could all be transported to the deep layers by TOC in soil columns. The downward migration of PAHs decreased with the increase in TOC and vice versa. The properties of the composition and structure of PAHs also had an obvious influence on their residues and migration in soil profiles at the same TOC conditions. In addition, the transport of PAHs was related to the amount of leaching water, the leaching time, and the additional PAHs.