Acute myeloid leukemia (AML) is a systemic, heterogeneous hematologic malignancy with poor overall survival. While some malignancies have seen improvements in clinical outcomes with immunotherapy, ...success of these agents in AML remains elusive. Despite limited progress, stem cell transplantation and donor lymphocyte infusions show that modulation of the immune system can improve overall survival of AML patients. Understanding the causes of immune evasion and disease progression will identify potential immune-mediated targets in AML. This review explores immunosuppressive mechanisms that alter T-cell-mediated immunity in AML.
•Maternal plasma PFAS levels are associated with cardiovascular development in children.•Short-chain PFAS levels are associated with decreased cardiac wall thickness.•Long-chain PFAS levels are ...associated with decreased vascular wall thickness.
High maternal plasma perfluoroalkyl substances (PFAS) concentrations has been associated with adverse birth outcomes, but data on early childhood cardiovascular health is limited. This study aimed to assess the potential association between maternal plasma PFAS concentrations during early pregnancy and cardiovascular development in offspring.
Cardiovascular development was assessed through blood pressure measurement, echocardiography and carotid ultrasound examinations among 957 children from the Shanghai Birth Cohort aged at 4 years old. Maternal plasma concentrations of PFAS were measured at mean gestational age of 14.4 (SD:1.8) weeks. The joint associations between PFAS mixture concentrations and cardiovascular parameters were analyzed using a Bayesian kernel machine regression (BKMR). The potential association of individual PFAS chemicals concentrations was explored using multiple linear regression.
In BKMR analyses, carotid intima media thickness (cIMT), interventricular septum thickness in diastole and systole, posterior wall thicknesses in diastole and systole, and relative wall thickness were significantly lower when all log10-transformed PFAS were fixed at 75th percentile in comparison to at their 50th percentileEstimated overall Risk:-0.31 (95%CI: −0.42, −0.20), −0.09 (95%CI: −0.11, −0.07), −0.21 (95%CI: −0.26, −0.16), −0.09 (95%CI: −0.11, −0.07), −0.07 (95%CI: −0.10, −0.04) and −0.005 (95%CI: −0.006, −0.004).Furthermore, maternal plasma concentrations of individual short-chain PFAS was associated with a decrease in left ventricular wall thickness, intraventricular septum thickness and enlarged chamber volume, and long-chain with a decrease in cIMT.
Our findings suggest that maternal plasma PFAS concentrations during early pregnancy was adversely associated with cardiovascular development in offspring, including thinner cardiac wall thickness and cIMT.
Aims
The association of maternal gestational diabetes mellitus (GDM) with childhood cardiovascular alterations is not well established. This study aims to test the hypothesis that prenatal exposure ...to GDM is associated with vascular and cardiac alterations in early childhood.
Methods
In a population‐based prospective cohort among 1094 mothers and their offspring, GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups criteria. Childhood blood pressure (BP) measurement, echocardiography and vascular ultrasound were performed using standardised methods at 4 years old. The associations between maternal GDM and childhood cardiovascular outcomes were modelled using linear regression and binary logistic regression. Mediation analysis was conducted to test the potential mediators.
Results
Maternal GDM was associated with higher systolic BP (SBP; β, 1.20; 0.11, 2.28), lower left ventricular end‐diastolic diameter (LVEDD; β, −0.36; −0.71, −0.01), lower end‐diastolic volume (EDV; β, −1.42; −2.71, −0.13) and increased risk of high blood pressure (HBP, OR = 1.522; 95% CI, 1.023 to 2.264) in offspring at the age of 4 years. After stratification by sex, the association remained strong only in male offspring (SBP: β, 1.94; 0.37, 3.51; LVEDD: β, −0.60; −1.09, −0.12; EDV: β, −2.09; −3.86, −0.31; HBP: OR = 1.797; 95% CI, 1.063 to 3.037) and was independent of maternal and child characteristics. However, carotid intima‐media thickness (cIMT) was not associated with maternal GDM. Mediation analysis showed that the effects on childhood cardiovascular alterations were attributable mostly to the direct effects of maternal GDM.
Conclusions
Our results provide evidence that maternal GDM is associated with offspring cardiovascular adaptations at preschool age. Further studies are needed to replicate our results and the long‐term effect of these adaptations on later cardiovascular risks needs further investigation.
Previous research investigating the correlation between prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and subsequent blood pressure (BP) in offspring has yielded limited and ...contradictory findings. This study was conducted to investigate the potential relationship between maternal PFAS levels during pregnancy and subsequent BP in early childhood. A total of 129 expectant mothers from the Shanghai Birth Cohort were included in the study. Using high-performance liquid chromatography/tandem mass spectrometry, we measured ten PFAS compounds in maternal plasma throughout the pregnancy. When the children reached the age of 4, we examined their systolic BP (SBP) and diastolic BP (DBP), along with mean arterial pressure (MAP) and pulse pressure (PP). Data interpretation employed multiple linear and logistic regression models, complemented by Bayesian kernel machine regression (BKMR).We found that the majority of PFAS concentrations remained stable during pregnancy. The linear and BKMR models indicated a positive relationship between the PFAS mixture in maternal plasma and offspring's DBP and MAP, with perfluorohexanesulphonic acid (PFHxS) having the most significant influence (PFHxS and DBP first trimester:β=3.03, 95%CI: (1.01,5.05); second trimester: β=2.35, 95%CI: (0.94,3.75); third trimester: β=2.57, 95%CI:(0.80,4.34); MAP first trimester:β=2.55, 95%CI: (0.64,4.45); second trimester: β=2.28, 95%CI: (0.95,3.61); third trimester: β=2.35, 95%CI:(0.68,4.01)). Logistic regression highlighted an increased risk of prehypertension and hypertension in offspring with higher maternal PFHxS concentrations during all three trimesters first trimester: OR=2.53, 95%CI:(1.11,5.79), second trimester: OR=2.05, 95%CI:(1.11,3.78), third trimester: OR=3.08, 95%CI:(1.40,6.79). A positive correlation was identified between the half-lives of PFAS and the odds ratio (OR) of prehypertension and hypertension in childhood (β=0.139, P=0.010). In conclusion, this research found maternal plasma PFAS concentrations to be positively associated with BP in offspring, with PFHxS showing the most significant influence. This correlation remained consistent throughout pregnancy, and this effect was proportional to the half-lives of PFAS.
Display omitted
•The levels of PFAS in maternal plasma were positively linked to offspring's BP.•PFHxS showed the most significant influence in maternal PFAS and offspring's BP.•The correlation of PFAS and BP remained consistent throughout pregnancy.•Effect of PFAS on BP was proportional to the half-lives of PFAS.
Atrioventricular septal defects (AVSD) are a complicated subtype of congenital heart defects for which the genetic basis is poorly understood. Many studies have demonstrated that the transcription ...factor SOX7 plays a pivotal role in cardiovascular development. However, whether
SOX7
single nucleotide variants are involved in AVSD pathogenesis is unclear. To explore the potential pathogenic role of
SOX7
variants, we recruited a total of 100 sporadic non-syndromic AVSD Chinese Han patients and screened
SOX7
variants in the patient cohort by targeted sequencing. Functional assays were performed to evaluate pathogenicity of nonsynonymous variants of
SOX7
. We identified three rare SOX7 variants, c.40C > G, c.542G > A, and c.743C > T, in the patient cohort, all of which were found to be highly conserved in mammals. Compared to the wild type, these
SOX7
variants had increased mRNA expression and decreased protein expression. In developing hearts, SOX7 and GATA4 were highly expressed in the region of atrioventricular cushions. Moreover, SOX7 overexpression promoted the expression of GATA4 in human umbilical vein endothelial cells. A chromatin immunoprecipitation assay revealed that SOX7 could directly bind to the
GATA4
promoter and luciferase assays demonstrated that SOX7 activated the
GATA4
promoter. The SOX7 variants had impaired transcriptional activity relative to wild-type SOX7. Furthermore, the SOX7 variants altered the ability of GATA4 to regulate its target genes. In conclusion, our findings showed that deleterious
SOX7
variants potentially contribute to human AVSD by impairing its interaction with GATA4. This study provides novel insights into the etiology of AVSD and contributes new strategies to the prenatal diagnosis of AVSD.
Duck Tembusu virus (DTMUV) is a pathogenic flavivirus that causes a substantial drop in egg production and severe neurological disorders in domestic waterfowl. Self-assembled ferritin nanoparticles ...with E protein domains I and II (EDI-II) of DTMUV (EDI-II-RFNp) were prepared, and its morphology was observed. Two independent experiments were conducted. First, Cherry Valley ducks aged 14 days were vaccinated with EDI-II-RFNp, EDI-II, and phosphate buffered solution (PBS, pH 7.4), and special and virus neutralization (VN) antibodies, interleukin 4 (IL-4) and interferon gamma (IFN-γ) in serum, and lymphocyte proliferation were detected. Second, the vaccinated ducks with EDI-II-RFNp, EDI-II, and PBS were injected with virulent DTMUV, clinical signs at 7 days postinfection (dpi) were observed, and mRNA levels of DTMUV in the lungs, liver, and brain at 7 and 14 dpi were detected. The results showed near-spherical nanoparticles EDI-II-RFNp with a 16.46 ± 4.70 nm diameters. The levels of specific and VN antibodies, IL-4 and IFN-γ, and lymphocyte proliferation in the EDI-II-RFNp group were significantly higher than those in the EDI-II and PBS groups. In the DTMUV challenge test, clinical signs and mRNA levels in tissue were used to evaluate protection of EDI-II-RFNp. EDI-II-RFNp-vaccinated ducks showed milder clinical signs and lower levels of DTMUV RNA in the lungs, liver, and brain. These results indicate that EDI-II-RFNp effectively protects ducks against the DTMUV challenge and could be a vaccine candidate to provide an effective and safe method for preventing and controlling DTMUV infection.
Current evidence relating birthweight and gestational age to cardiovascular risk is conflicting. Whether these factors have independent or interactive impacts on cardiovascular parameters during ...early childhood remains unclear. The goal of this study was to explore whether there were any independent and interactive effects of gestational age and birthweight on blood pressure, left ventricle (LV) structure, and function in 4 years old.
This study included 1194 children in the Shanghai Birth Cohort from 2013 to 2016. Information about the mothers and children was recorded at time of birth using a questionnaire. Follow-up measurements, including anthropometric, blood pressure, and echocardiography, were taken between 2018 and 2021, when the children were 4 years old. Multiple linear or logistic regressions and restricted cubic spline were used to explore the association of birthweight and gestational age with cardiovascular measurements.
Gestational age had a significant negative correlation with both systolic blood pressure β = - 0.41, 95% CI: (- 0.76, - 0.07) and mean arterial pressure β = - 0.36, 95%CI: (- 0.66, - 0.07). The risk of prehypertension decreased with increased gestational age OR = 0.54, 95% CI: (0.32, 0.93). The relationship between birthweight with blood pressure was U-shape (P for non-linear < 0.001). The wall thickness, volume, mass, and cardiac output of LV increased with birthweight, though the ejection fraction β = - 1.02, 95% CI: (- 1.76, - 0.27) and shorten fraction β = 0.72, 95% CI: (- 1.31, - 0.14) decreased with birthweight. The risk of LV hypertrophy was not associated with birthweight OR = 1.59, 95% CI: (0.68, 3.73).
In this study, we found different associations of birthweight and gestational age with cardiovascular measurements in the offspring at 4 years old. Gestational age influenced blood pressure independent of birthweight. Heart size and function at 4 years old was influenced mostly by birthweight and not by gestational age.
Abstract Introduction Physical activity (PA) is believed to play an important part in many aspects during childhood and adolescence, especially cardiorespiratory fitness and cardiometabolic health. ...However, whether different levels of PA in daily life influence the structure or function of heart in school-aged children remains unknown. We aimed to investigate the association between PA and cardiovascular parameters in 7-year-old children. Methods Follow-up data from the Shanghai Prenatal Cohort Study and the Shanghai Birth Cohort was analyzed. Perinatal information including both maternal and offspring datum was recorded. A refined questionnaire was used to evaluate the frequency and duration of children’s PA levels. Blood pressure, echocardiography, and anthropometry assessment were conducted during the follow-up of 7-year-old children. Results Overall, high PA level was associated with higher left ventricle posterior wall thickness in diastole (LVPWd, β coefficient: 0.36, 95% CI: 0.12, 0.61), higher left ventricle mass index (LVMI, β = 0.28, 95% CI: 0.07, 0.48), mitral E/a ratio (β = 0.47, 95% CI: 0.22, 0.71) and slower heart rate (β = -0.32, 95% CI: -0.57, -0.07), compared to low PA level. Medium PA level was associated with lower diastolic blood pressure (DBP, β = -0.18, 95% CI: -0.35, -0.01). In subgroup analysis, increased relative wall thickness (RWT) was found in high PA level boys (β = 0.36, 95% CI: 0.05, 0.67), and systolic blood pressure (SBP) showed a significant decrease in high PA level girls (β = -0.42, 95% CI: -0.78, -0.06). Conclusions This study suggested non-athlete children having higher PA level were associated with thicker left ventricle (LV) walls and better LV diastolic function, as well as slower heart rate and DBP at the age of 7. Furthermore, disparity in the association between PA level with morphological heart patterns and blood pressure existed in different sex category.
This experiment demonstrated the resonance asymmetry phenomenon in the resonant fiber optic gyro. The asymmetry of resonant curve affects the system open-loop bias and its stability, which directly ...affects the accuracy of angular velocity measurement. In this paper, a new mathematic model is established. The influence of the coupler normal mode loss difference (the phase difference between the coupler cross port output optical field and direct port is less than the ideal π/2) on the symmetry of resonant curve, the resonant signal modulated by the triangular wave, and the demodulation curve are analyzed. Moreover, the asymmetry of the resonant curve leads to the asymmetry of the resonant signal, as modulated by the triangular wave and the demodulation curve from the theoretical simulation and the experiment.
Abstract
Background
Humans are widely exposed to perfluoroalkyl substances (PFAS), which have been found to be associated with various adverse birth outcomes. As blood pressure (BP) is an important ...parameter reflecting cardiovascular health in early life, it is necessary to investigate the association of PFAS exposure during early lifetime and BP in childhood. Therefore, we investigated the potential association between PFAS levels in umbilical cord blood and BP of the offspring at 4 years of age in a prospective cohort study.
Methods
PFAS in umbilical cord blood samples after birth were measured with high-performance liquid chromatography/tandem mass spectrometry in the Shanghai Birth Cohort. BP was measured at 4 years of age in the offspring. Multiple linear regression model was used to investigate the association between individual PFAS level and BP of the offspring. Bayesian kernel machine regression (BKMR) was used to analyze the relationship between the PFAS mixture and BP of the offspring, while weighted quantile sum (WQS) regression was utilized for sensitivity analysis.
Results
A total of 129 mother-child pairs were included in our analysis. In multiple linear regressions, we observed that long-chain PFAS, mainly including perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUA), was negatively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP). BKMR showed that an increase in umbilical cord blood PFAS mixture levels was significantly associated with a decrease in SBP, DBP and MAP Estimated differences (SD): -0.433 (0.161); -0.437 (0.176); -0.382 (0.179), respectively. The most important component in the association with SBP, DBP, and MAP was PFUA. PFDoA was found to be positively associated with SBP, DBP and MAP in both models. Sensitivity analysis with WQS regression showed consistent results.
Conclusion
Our findings suggested that umbilical blood PFAS exposure was negatively associated with BP in offspring at 4 years of age, including SBP, DBP, and MAP.
PDF
