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Mono (2-ethylhexyl) phthalate (MEHP) is a major metabolite of di (2-ethylhexyl) phthalate (DEHP). This study aimed to observe the toxic effect of MEHP on human endometrial microvascular endothelial cells (HEMECs) and its potential molecular mechanism. HEMECs were exposed to different concentrations of MEHP (0, 50, 100, and 200 nM). NEO2734 in vivo Cell viability and apoptosis were assessed by cell counting kit-8 (CCK-8) and flow cytometry assays. Western blot was performed to examine the expression of apoptosis-related proteins (Bcl-2, Bax, and Caspase-3). Moreover, the expression of pyroptosis-related Caspase-1 was detected by western blot and immunofluorescence assays. Lactate dehydrogenase (LDH) release levels were evaluated in HEMECs treated with MEHP and/or Caspase-1 inhibitor Ac-YVAD-CHO. After exposure to MEHP, NLRP3 expression was examined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. LDH release and apoptosis levels were tested in HEMECs induced by MEHP and/or siNLRP3. MEHP significantly induced cell viability and inhibited apoptosis for HEMECs, with a concentration-dependent manner. Furthermore, Bcl-2/Bax ratio was distinctly reduced and Caspase-3 expression was increased in HEMECs after exposure to MEHP. Western blot and immunofluorescence results confirmed that MEHP markedly augmented Caspase-1 expression in HEMECs. Furthermore, LDH release levels were fortified in HEMECs treated with MEHP, which were improved following cotreatment with Ac-YVAD-CHO. At the mRNA and protein levels, NLRP3 expression was prominently increased in HEMECs exposed to MEHP. NLRP3 knockdown markedly ameliorated the increase in LDH release and apoptosis induced by MEHP exposure in HEMECs. Our findings suggested that exposure to MEHP facilitates apoptosis and pyroptosis of HEMECs through NLRP3 inflammasome.Simulation models represent soil organic carbon (SOC) dynamics in global carbon (C) cycle scenarios to support climate-change studies. It is imperative to increase confidence in long-term predictions of SOC dynamics by reducing the uncertainty in model estimates. We evaluated SOC simulated from an ensemble of 26 process-based C models by comparing simulations to experimental data from seven long-term bare-fallow (vegetation-free) plots at six sites Denmark (two sites), France, Russia, Sweden and the United Kingdom. The decay of SOC in these plots has been monitored for decades since the last inputs of plant material, providing the opportunity to test decomposition without the continuous input of new organic material. The models were run independently over multi-year simulation periods (from 28 to 80 years) in a blind test with no calibration (Bln) and with the following three calibration scenarios, each providing different levels of information and/or allowing different levels of model fitting (a) calibrating decomposition parameters separately at each experimental site (Spe); (b) using a generic, knowledge-based, parameterization applicable in the Central European region (Gen); and (c) using a combination of both (a) and (b) strategies (Mix). We addressed uncertainties from different modelling approaches with or without spin-up initialization of SOC. Changes in the multi-model median (MMM) of SOC were used as descriptors of the ensemble performance. On average across sites, Gen proved adequate in describing changes in SOC, with MMM equal to average SOC (and standard deviation) of 39.2 (±15.5) Mg C/ha compared to the observed mean of 36.0 (±19.7) Mg C/ha (last observed year), indicating sufficiently reliable SOC estimates. Moving to Mix (37.5 ± 16.7 Mg C/ha) and Spe (36.8 ± 19.8 Mg C/ha) provided only marginal gains in accuracy, but modellers would need to apply more knowledge and a greater calibration effort than in Gen, thereby limiting the wider applicability of models.Blood biomarkers of multiple sclerosis (MS) can provide a better understanding of pathophysiology and enable disease monitoring. Here, we performed quantitative shotgun lipidomics on the plasma of a unique cohort of 73 monozygotic twins discordant for MS. We analyzed 243 lipid species, evaluated lipid features such as fatty acyl chain length and number of acyl chain double bonds, and detected phospholipids that were significantly altered in the plasma of co-twins with MS compared to their non-affected siblings. Strikingly, changes were most prominent in ether phosphatidylethanolamines and ether phosphatidylcholines, suggesting a role for altered lipid signaling in the disease.
Mother-child pairs may separate during early life, yet the health impacts thereof are unclear. We explored the patterns and impact of separation among women living with HIV (WLHIV) and their children in South Africa.
WLHIV who had initiated antiretroviral therapy (ART) during pregnancy received HIV viral load (VL) testing and completed a timeline questionnaire of mother-child separation since delivery at 3-5years post-partum. Health care usage was abstracted from routine medical records. We examined associations between separation and (a) maternal health outcomes (engagement in HIV care and HIV viral suppression, [VS]) and (b) child health outcomes (post-breastfeeding HIV testing and immunisation completion), using logistic regression.
Of 346 mother-child pairs (median maternal age at antenatal ART initiation, 28years), 24% were ever separated (median time to first separation 20months, interquartile range [IQR] 9, 31). Most separated children were living with their grandmothers (65/83, 78%). Mothers who ever separated were younger, and more likely to be employed, and to reside in informal housing than those who never separated. Any separation reduced the odds of VS≤50 copies/mL at four years post-partum (odds ratio 0.57; 95% CI 0.34-0.93); associations were similar for VL≤1000 copies/mL and maternal engagement in care. No association was found between separation and child confirmatory HIV testing or immunisation completion.
In this setting, mother-child separation is common in the first four years of life and appears associated with suboptimal maternal outcomes. Further research is required to understand the drivers and implications of mother-child separation.
In this setting, mother-child separation is common in the first four years of life and appears associated with suboptimal maternal outcomes. Further research is required to understand the drivers and implications of mother-child separation.
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