Prenatal maternal stress, sleep quality, and neonatal birth weight: A prospective cohort study.

To assess if the impacts of prenatal maternal stress (PNMS) on neonatal physical development including birth weight and body length vary by trimesters, and to explore the mediating effect of sleep quality in the relationships. A total of 2778 pregnant women were included from the Shanghai Maternal-Child Pairs Cohort. PNMS and sleep quality were measured in the first trimester (12-16 gestational weeks) and third trimester (32-36 gestational weeks) using the Life Event Scale for Pregnant Women (LESPW) and Pittsburgh Sleep Quality Index, respectively. And total LESPW scores were classified into three groups: high stress (≥75th percentile), medium stress (≥25th and <75th percentile), and low stress (<25th percentile). Multiple linear and logistic regressions were employed to examine the associations between PNMS and birth weight, and bootstrap were utilized to explore the mediating effects of maternal sleep. Higher (adjusted odds ratio, aOR = 1.521; 95% confidence interval (CI), 1.104-2.096) and medium (aOR = 1.421; 95% CI, 1.071-1.885) PNMS and stress from subjective events (aOR = 1.334; 95% CI, 1.076-1.654) in the first trimester were significantly associated with elevated risk for large for gestational age. Maternal severe negative objective events stress (OE3) in the third trimester were negatively associated with birth weight (ß = -0.667; 95% CI, -1.047∼-0.287), and maternal sleep latency during this period acted as a mediator in the association (indirect effect: ß = -0.0144; 95% CI, -0.0427∼-0.0003). Besides, a significant negative correlation between total LESPW score (ß = -0.022; 95% CI, -0.038∼-0.006; per 100 score) and body length in the third trimester was also observed. The impact of PNMS on neonatal birth weight varies by stress types and exposure timing. Prolonged maternal sleep latency in the third trimester correlated with lower birth weight, and mediating the link of OE3 and birth weight, which might indicate a critical period of vulnerability to the effects of PNMS on neonatal physical development.

Systematic approaches to C-lignin engineering in Medicago truncatula.

BACKGROUND: C-lignin is a homopolymer of caffeyl alcohol present in the seed coats of a variety of plant species including vanilla orchid, various cacti, and the ornamental plant Cleome hassleriana. Because of its unique chemical and physical properties, there is considerable interest in engineering C-lignin into the cell walls of bioenergy crops as a high-value co-product of bioprocessing. We have used information from a transcriptomic analysis of developing C. hassleriana seed coats to suggest strategies for engineering C-lignin in a heterologous system, using hairy roots of the model legume Medicago truncatula. RESULTS: We systematically tested strategies for C-lignin engineering using a combination of gene overexpression and RNAi-mediated knockdown in the caffeic acid/5-hydroxy coniferaldehyde 3/5-O-methyltransferase (comt) mutant background, monitoring the outcomes by analysis of lignin composition and profiling of monolignol pathway metabolites. In all cases, C-lignin accumulation required strong down-regulation of caffeoyl CoA 3-O-methyltransferase (CCoAOMT) paired with loss of function of COMT. Overexpression of the Selaginella moellendorffii ferulate 5-hydroxylase (SmF5H) gene in comt mutant hairy roots resulted in lines that unexpectedly accumulated high levels of S-lignin. CONCLUSION: C-Lignin accumulation of up to 15% of total lignin in lines with the greatest reduction in CCoAOMT expression required the strong down-regulation of both COMT and CCoAOMT, but did not require expression of a heterologous laccase, cinnamyl alcohol dehydrogenase (CAD) or cinnamoyl CoA reductase (CCR) with preference for 3,4-dihydroxy-substituted substrates in M. truncatula hairy roots. Cell wall fractionation studies suggested that the engineered C-units are not present in a heteropolymer with the bulk of the G-lignin.

Ozone Exposure During Pregnancy and Risk of Gestational Hypertension or Preeclampsia in China.

Importance: Although certain air pollutants have been associated with adverse obstetric outcomes, evidence regarding the association of ozone (O3) exposure with the risk of hypertensive disorders in pregnancy (HDP) is limited and inconsistent. Objectives: To evaluate the association between gestational O3 exposure and HDP (ie, gestational hypertension and preeclampsia) risk, and to explore the window of susceptibility for O3 exposure during pregnancy. Design, Setting, and Participants: This cohort study recruited pregnant patients from the Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China, from March 2017 to December 2018. Participants were older than 18 years, had no infectious diseases or chronic noncommunicable diseases before pregnancy, were Shanghai residents with intent to participate in the study, and had plans to give birth in Shanghai. Gestational hypertension and preeclampsia were diagnosed according to the diagnostic criteria of the Chinese Society of Obstetrics and Gynecology during the study period. Data on residential addresses, demographic characteristics, and household living environments were collected from participants through a questionnaire survey. Data were analyzed from December 10, 2021, to May 10, 2022. Exposures: A high temporospatial resolution model was applied to predict individual levels of daily O3 exposure during pregnancy. Main Outcomes and Measures: The outcomes were gestational hypertension and preeclampsia, and data on these diagnoses were extracted from the hospital's information system. A logistic regression model was used to estimate the associations between O3 exposure and risk of gestational hypertension or preeclampsia. Exposure-response associations were confirmed by restricted cubic spline functions. Distributed lag models were used to identify the O3 exposure window of susceptibility. Results: Among the 7841 participants (all females; mean [SD] age, 30.4 [3.8] years), 255 (3.2%) had gestational hypertension and 406 (5.2%) had preeclampsia. Pregnant individuals with HDP had considerably higher prepregnancy body mass indexes and lower educational levels. The mean (SD) O3 exposure levels were 97.66 (25.71) µg/m3 in the first trimester and 106.13 (22.13) µg/m3 in the second trimester. Each 10-µg/m3 increment of O3 exposure during the first trimester was associated with higher gestational hypertension risk (relative risk, 1.28; 95% CI, 1.04-1.57). However, gestational O3 exposure was not associated with the risk of preeclampsia. The restricted cubic spline function analysis revealed an exposure-response association between O3 exposure and risk of gestational hypertension. Conclusions and Relevance: Results of this study showed an association between increased gestational hypertension risk and O3 exposure during the first trimester. Furthermore, gestational weeks 1 to 9 were identified as the window of susceptibility for O3 exposure and elevated gestational hypertension risk. Sustainable O3 control is needed to reduce the disease burden of gestational hypertension.

Prospective associations between various prenatal exposures to maternal psychological stress and neurodevelopment in children within 24 months after birth.

BACKGROUND: There is increasing evidence that prenatal exposure to maternal psychological distress may be a factor influencing offspring neurodevelopment, but stress type-dependent effects of maternal psychological distress on offspring neurodevelopment in early childhood have yet to be fully elucidated. Additionally, although positive maternal mental health exerts potential effects in protecting against adverse health outcomes, few investigators have considered the effects of positive maternal mental health on offspring neurodevelopment in early childhood. AIMS: To determine the associations between various prenatal exposures to maternal psychological distress and positive life-event experiences and offspring neurodevelopment within 24 months of age. METHODS: A total of 4412 mother-child dyads were recruited from the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC). Maternal perceived stress, negative life-event stress, positive life-event experiences around the time of conception (i.e., three months prior to and after conception) were assessed at 12-16 gestational weeks, and maternal anxiety and depressive symptoms were assessed at 32-36 gestational weeks. We measured children's neurodevelopment using the Ages and Stages Questionnaire, Third Edition (ASQ-3) at two, six, 12, and 24 months postnatally. We then exploited generalized linear models to estimate the associations between prenatal maternal psychological distress and positive life-event experiences and children's neurodevelopment at the above periods, and generalized linear mixed models were applied to assess the associations between maternal psychological distress and positive life-event experiences and suspected developmental delay (SDD) in children within 24 months after birth based on a longitudinal design. RESULTS: Maternal perceived stress and negative life-event stress around the time of conception, and anxiety and depressive symptoms during late pregnancy were negatively associated with scores of children's neurodevelopment at two, six, 12, and 24 months of age; while maternal life-event experiences were positively associated with scores of children's neurodevelopment. Longitudinal analysis revealed that higher levels of maternal negative life-event stress and depressive symptoms augmented the risk of SDD in personal-social (OR = 1.435, 1.681). Mothers who experienced higher levels of positive life-event experiences exhibited a reduced risk of SDD in gross motor and personal-social domains (OR = 0.373, 0.350). CONCLUSIONS: Prenatal exposure to maternal psychological distress is negatively associated with children's neurodevelopment in early childhood depending upon the type of distress. Maternal positive life-event experiences around the time of conception appeared to present potential benefits for child neurodevelopment.

Associations of ozone exposure with gestational diabetes mellitus and glucose homeostasis: Evidence from a birth cohort in Shanghai, China.

BACKGROUND: Associations between individual exposure to ozone (O3) and gestational diabetes mellitus (GDM) have rarely been investigated, and critical windows of O3 exposure for GDM have not been identified. OBJECTIVES: We aimed to explore the associations of gestational O3 exposure with GDM and glucose homeostasis as well as to identify the potential critical windows. METHODS: A total of 7834 pregnant women were included. Individual O3 exposure concentrations were evaluated using a high temporal-spatial resolution model. Each participant underwent an oral glucose tolerance test (OGTT) to screen for GDM between 24 and 28 gestational weeks. Multiple logistic and multiple linear regression models were used to estimate the associations of O3 with GDM risks and with blood glucose levels of OGTT, respectively. Distributed lag nonlinear models (DLNMs) were used to estimate the critical windows of O3 exposure for GDM. RESULTS: Nearly 13.29 % of participants developed GDM. After controlling for covariates, we observed increased GDM risks per IQR increment of O3 exposure in the first trimester (OR = 1.738, 95 % CI: 1.002-3.016) and the first two trimesters (OR = 1.576, 95 % CI: 1.005-2.473). Gestational O3 exposure was positively associated with increased fasting blood glucose (the first trimester: ß = 2.964, 95 % CI: 1.529-4.398; the first two trimesters: ß = 1.620, 95 % CI: 0.436-2.804) and 2 h blood glucose (the first trimester: ß = 6.569, 95 % CI: 1.775-11.363; the first two trimesters: ß = 6.839, 95 % CI: 2.896-10.782). We also observed a concentration-response relationship of gestational O3 exposure with GDM risk, as well as fasting and 2 h blood glucose levels. Additionally, 5-10 gestational weeks was identified as a critical window of O3 exposure for GDM development. CONCLUSION: In summary, we found that gestational O3 exposure disrupts glucose homeostasis and increases the risk of GDM in pregnant women. Furthermore, 5-10 gestational weeks could be a critical window for the effects of O3 exposure on GDM.

[Latest Findings on Prediction and Prevention of Preeclampsia].

Preeclampsia, a progressive disease involving multiple systems, afflicts pregnancy specifically. It contributes to severe maternal and perinatal morbidity and mortality. It has been reported that preeclampsia initiates from a mismatch between the utero-placental supply and demand, which subsequently triggers the release of placental syncytiotrophoblast stress-derived factors and an imbalance of proangiogenic/antiangiogenic factors, eventually causing maternal systemic endothelial lesions and systemic inflammatory response. Currently, treatments available for preeclampsia are very limited in number. Hence, prediction and prevention carry special significance. Herein, we reviewed the current understanding of preeclampsia, especially findings on the prediction and prevention of preeclampsia published within the past 5 years. We discussed the Fetal Medicine Foundation (FMF) screening model based on placental growth factor (PlGF) and the effects of aspirin, calcium, exercise, and termination of pregnancy in preventing preeclampsia. The efficacy and safety of other new preventive measures still need further validation.

Trophoblast Exosomal UCA1 Induces Endothelial Injury through the PFN1-RhoA/ROCK Pathway in Preeclampsia: A Human-Specific Adaptive Pathogenic Mechanism.

Preeclampsia is regarded as an evolution-related disease that has only been observed in humans and our closest relatives, and the important factor contributing to its pathogenesis is endothelial dysregulation secondary to a stressed placenta. Hypoxia-inducible factor 1 subunit alpha (HIF1α), a highly conserved molecule in virtually all mammals, is regarded as a crucial regulator of the hypoxia adaptation and evolution. Persistent high expression of HIF1α in the placenta is one of the pathogenic mechanisms of preeclampsia. Therefore, human-specific molecules should link increased HIF1α to preeclampsia. We reported that urothelial cancer associated 1 (UCA1) is a potential mediator because it is a human-specific long noncoding RNA (lncRNA) that is upregulated in placental tissues and maternal serum from women with preeclampsia and is regulated by HIF1α. The cellular HIF1α-UCA1 pathway promoted the adaptation of trophoblasts to hypoxia by inducing vascular endothelial growth factor (VEGF) secretion and changes in the levels of key enzymes in glycolysis. On the other hand, circulating exosomal UCA1 secreted from stressed trophoblasts induced vascular endothelial dysfunction, especially excess ROS production, as measured by exosome extraction and a coculture system. At the molecular level, UCA1 physically bound to ubiquitin-specific peptidase 14 (USP14), which is a deubiquitinating enzyme, and UCA1 functioned as a scaffold to recruit USP14 to profilin 1 (PFN1), an actin-binding protein contributing to endothelial abnormalities and vascular diseases. This ternary complex inhibited the ubiquitination-dependent degradation of PFN1 and prolonged its half-life, further activating the RhoA/Rho-kinase (ROCK) pathway to induce ROS production in endothelial cells. Taken together, these observations suggest a role for the evolution-related UCA1 in the HIF1α-induced adaptive pathogenic mechanism of preeclampsia, promoting the survival of hypoxic trophoblasts and injuring maternal endothelial cells.

Prenatal fine particulate matter exposure associated with placental small extracellular vesicle derived microRNA and child neurodevelopmental delays.

BACKGROUND AND AIMS: Prenatal fine particulate matter (PM2.5) exposure has been linked to adverse neurodevelopment. However, epidemiological evidence remains inconclusive and little information about the effects of various PM2.5 components on child neurodevelopment is currently known. The underlying mechanism was also not elucidated. The study aimed to evaluate the effects of PM2.5 and components exposure on child neurodevelopmental delays and the role of placental small extracellular vesicles (sEVs)-derived miRNAs in the associations. METHODS: We included 267 mother-child pairs in this analysis. Prenatal PM2.5 and components (i.e. elements, water-soluble ions, and PAHs) exposure during three trimesters were monitored through personal PM2.5 sampling. Child neurodevelopment at 2, 6, and 12 months old were evaluated by Ages and Stages Questionnaire (ASQ). We isolated sEVs from placental tissue to analyze the change of sEVs-derived miRNAs in response to PM2.5. Associations between the PM2.5-associated miRNAs and child neurodevelopment were evaluated using multivariate linear regression models. RESULTS: The PM2.5 exposure levels in the three trimesters range from 2.51 to 185.21 µg/m3. Prenatal PM2.5 and the components of Pb, Al, V and Ti exposure in the second and third trimester were related to decreased ASQ scores communication, problem-solving and personal-social domains in children aged 2 or 6 months. RNA sequencing identified fifteen differentially expressed miRNAs. The miR-101-3p and miR-520d-5p were negatively associated with PM2.5 and Pb component. miR-320a-3p expression was positively associated with PM2.5 and V component. Meanwhile, the miR-320a-3p was associated with decreased ASQ scores, as reflected by ASQ-T (ß: -2.154, 95 % CI: -4.313, -0.516) and problem-solving domain (ß: -0.605, 95 % CI: -1.111, -0.099) in children aged 6 months. CONCLUSION: Prenatal exposure to PM2.5 and its Pb, Al, V & Ti component were associated with infant neurodevelopmental delays. The placenta sEVs derived miRNAs, especially miR-320a-3p, might contribute to an increased risk of neurodevelopmental delays.

Associations of maternal prenatal emotional symptoms with neurodevelopment of children and the neonatal meconium microbiota: A prospective cohort study.

BACKGROUND: Maternal emotional symptoms during pregnancy increase the risk of neurodevelopmental problems in offspring, and microbiota have been shown to be a potential mechanism underlying the link. However, the associations among maternal prenatal emotional symptoms, the meconium microbiota, and offspring neurodevelopment have yet to be fully elucidated. The aim of this prospective cohort study was to assess the relationship between maternal prenatal emotional symptoms and neurodevelopment of the child at 24 months of age, and to investigate the potential role of the neonatal meconium microbiota in the relationship. METHODS: A total of 410 mother-child pairs (152 women in the Symptoms group vs. 258 women in the No-symptoms group) were recruited from the ongoing Shanghai Maternal-Child Pairs Cohort. This study included a subgroup of women who were assessed for maternal anxiety and depressive symptoms at 32-36 weeks of gestation. Neonatal meconium samples were collected after birth for 16 S sequencing. Children's neurodevelopment was measured using the Ages and Stages Questionnaire, Third Edition (ASQ-3) and Strengths and Difficulties Questionnaire (SDQ) at 24 months postnatally (n = 287). RESULTS: Compared with the No-symptoms group, children in the Symptoms group had a higher degree of hyperactivity and total difficulties at 24 months of age. Increases in alpha diversity, distinct overall composition, enriched relative abundance of Proteobacteria, and different predicted microbial functions were observed in the meconium of neonates exposed to maternal prenatal emotional symptoms. The neonatal gut microbiota alpha diversity and relative abundance of genera from the Proteobacteria phylum and Lactobacillus were negatively correlated with children's degree of prosocial behavior, tendency toward hyperactivity, and poor fine motor development. In addition, mediating effects of neonatal meconium microbial richness and the relative abundance of Lactobacillus were observed between maternal emotional symptoms and children's prosocial behavior. CONCLUSIONS: Maternal prenatal emotional symptoms are associated with alterations in the offspring meconium microbiota and children's neurodevelopment at 24 months of age, and the microbial richness indices and Lactobacillus may play a mediating role. Future research is needed to identify and understand the biological pathways and metabolisms linking the relationships among maternal emotional symptoms, meconium microbiota, and neurodevelopment of children.

Generation of an isogenic gene-corrected iPSC line (OGHFUi001-A-1) from a type 1 early infantile epileptic encephalopathy (EIEE1) patient with a hemizygous R330L mutation in the ARX gene.

Type 1 early infantile epileptic encephalopathy (EIEE1) is a rare X-link neurodevelopmental disorder caused by mutations in the ARX gene. The mechanism remains unclear due to the lack of cellular models for the disease. We previously have generated an iPSC line (OGHFUi001-A) from a male EIEE1 patient with a hemizygous R330L mutation in the ARX gene. Here we corrected the R330L mutation genetically using CRISPR/Cas9 technology to generate an isogenic control, which was an ideal control to investigate the pathogenesis of the mutation in this disease.

Prenatal ultrasound measurements of mild congenital pulmonary airway malformation and long-term prognosis: A retrospective cohort study.

OBJECTIVE: To investigate the relationship between mild congenital pulmonary airway malformation (CPAM) and its long-term prognosis in childhood and to explore whether surgery is necessary. METHODS: We conducted a retrospective cohort of fetuses with mild CPAM diagnosed prenatally with available long-term outcomes in childhood from 2004 to 2016. The patients were divided into two groups according to the fetal CPAM-to-volume ratio (CVR) of less than 1.0 and 1.0-1.6. The primary outcome was a postnatal composite outcome including CPAM-associated respiratory symptoms and surgical resection of the lesion. The secondary outcomes included neonatal asphyxia, perinatal morbidity and mortality. RESULTS: Forty-two fetuses were identified as having CVR <1.0 or CVR-1.0-1.6 respectively (n = 37 vs n = 5; 88.1% vs 11.9%), with the median duration of follow up 2.15 years (0.3-10.8 years). Of 42 patients, 32 (76%) remained asymptomatic without recurrent respiratory symptoms or surgical resection; the other 10 with CVR <1.0 had respiratory symptoms. Of 10 symptomatic cases, five recovered after expectant treatment, and five underwent resection, for an increase in lesion size and recurrent respiratory infection. CONCLUSION: Patients with CVR <1.0 still need to be closely observed after birth. Conservative management is a reasonable option in asymptomatic cases, but surgery might be necessary in some.

Early-Pregnancy Intermediate Hyperglycemia and Adverse Pregnancy Outcomes Among Women Without Gestational Diabetes.

CONTEXT: Universal early-pregnancy screening for overt diabetes reveals intermediate hyperglycemia (fasting plasma glucose [FPG] [5.1-6.9 mM]). OBJECTIVE: We evaluated the association between early-pregnancy intermediate hyperglycemia and adverse pregnancy outcomes among women without gestational diabetes. METHODS: This retrospective cohort study was conducted at the Obstetrics and Gynecology Hospital, Shanghai, China, from 2013 to 2017. All singleton pregnancies with FPG less than or equal to 6.9 mM in early pregnancy and receiving a 75-g oral glucose tolerance test (OGTT) were included. Women with prepregnancy diabetes were excluded. Individuals with normal OGTT were analyzed. Pregnancy outcomes for FPG less than 5.1 mM and intermediate hyperglycemia were evaluated. The primary outcomes were large for gestational age (LGA) and primary cesarean delivery. Multivariate logistic regressions were conducted. Statistical significance was defined as P less than .05. RESULTS: In total, 24 479 deliveries were included, of which 23 450 (95.8%) had normal OGTTs later in pregnancy (NGT). There were 807 (3.4%) women who had an FPG of 5.1 to 6.9 mM in early pregnancy. Compared to the NGT group with an FPG of less than 5.1 mM in early pregnancy (N = 20692), the intermediate hyperglycemia NGT group (N = 693) had a higher age and body mass index (BMI), and significantly higher rates of LGA, primary cesarean delivery, preterm birth, preeclampsia, and neonatal distress. The rates of primary cesarean delivery (adjusted odds ratio [AOR] 1.24; 95% CI, 1.05-1.45), preterm birth (AOR 1.75; 95% CI, 1.29-2.36), and neonatal distress (AOR 3.29; 95% CI, 1.57-6.89) remained statistically significantly higher after adjustments for maternal age, BMI, and other potential confounding factors. CONCLUSION: Women with intermediate hyperglycemia in early pregnancy are at an increased risk for adverse maternal-fetal outcomes, even with normal future OGTTs.

Magnetic resonance imaging evaluation of foetal intracranial haemorrhage and the correlation with ultrasound findings and postnatal outcomes.

OBJECTIVES: The aim of the study was to compare the magnetic resonance imaging (MRI) findings of intracranial haemorrhage (ICH) in the middle- and late trimesters and to explore the relationship between the MRI features of foetal ICH and postnatal outcomes. METHODS: This was a retrospective study which recruited foetal ICH diagnosed by MRI in one tertiary centre from 2015 to 2019. The prenatal and postnatal medical records were reviewed. RESULTS: Of 39 ICH cases, 82.1% (32) had germinal matrix intraventricular haemorrhage (GM-IVH), and 18.9% (7) were diagnosed with non-GM-IVH. The cerebellum, corpus callosum and subdural space were affected in 5, 1 and 1 non-GM-IVH cases, respectively. MRI confirmed possible ICH on sonogram in 10 cases (35.7%) and the remaining 19 added ICH diagnoses that were not obtained on initial ultrasound imaging. Pregnancy outcome data were available in 82.1% of (32) cases, of which 21 were terminated pregnancies, 1 was foetal demise and 10 were delivered. One neonate died after birth and one infant suffered from hearing loss. The remaining eight patients had favourable outcome. CONCLUSION: In our study, evaluation of the relationship between MRI findings and outcomes remains challenging, depending on the timing of examination and the hematoma itself. MRI was an adjunct to US in diagnosing ICH in utero which helps to assess postnatal development.

PM2.5 exposure and maternal glucose metabolism in early pregnancy: Associations and potential mediation of 25-hydroxyvitamin D.

Gestational diabetes mellitus (GDM) has become a new global epidemic with a rapidly increasing prevalence. Previous studies have suggested that air pollution is associated with GDM risk, but the results are inconsistent, and mechanistic studies are limited. Based on a hospital-based cohort, a total of 6374 participants were included in this study. Individual daily PM2.5 exposure at a 1-km resolution was predicted using a full-spatiotemporal-coverage model. The results of multiple linear regression showed that glycated hemoglobin (HbA1c) was significantly associated with PM2.5 both in the 1-month preconception and in the first trimester of pregnancy. Additionally, HbA1c decreased 0.437% (95% CI: -0.629, -0.244) as the serum 25-hydroxyvitamin D (25(OH)D) increased by one interquartile range (IQR) (9.2 ng/ml). An IQR increase in PM2.5 exposure was also negatively associated with serum 25(OH)D (estimated change% and 95% CI: -7.249 (-9.054, -5.408) in the 1-month preconception and - 13.069 (-15.111, -10.979) in the first trimester of pregnancy). Mediation analysis showed that serum 25(OH)D status mediated the association between HbA1c and PM2.5 exposure both in the preconception and in the first trimester (mediated percent: 2.00% and 4.05% (Sobel p＜0.001), respectively). The result suggested a vicious cycle among PM2.5 exposure, lower serum VD status and a higher HbA1c. More studies are warranted since the protective effect of 25(OH)D against glucose disorders associated with air pollution in this study was limited.

Generation of an induced pluripotent stem cell line (OGHFUi001-A) from a type 1 early infantile epileptic encephalopathy with ARX mutation.

Type 1 early infantile epileptic encephalopathy (EIEE1) is a severe early-onset epileptic encephalopathy with arrest of psychomotor development caused by hemizygous mutations in the ARX gene, which encodes a transcription factor in fundamental brain developmental processes. A human induced pluripotent stem cell (iPSC) line, termed as OGHFUi001-A, was generated using non-integrating episomal vector technique from peripheral blood mononuclear cells (PBMCs) of a 7-year-old male EIEE1 patient, who had a hemizygous (c.989G > T: p.R330L) mutation in the ARX gene. OGHFUi001-A offers a useful cell resource to investigate pathogenic mechanisms in EIEE1, as well as a cell-based model for drug development for EIEE1.

FGF21 Serum Levels in the Early Second Trimester Are Positively Correlated With the Risk of Subsequent Gestational Diabetes Mellitus: A Propensity-Matched Nested Case-Control Study.

Background: As an important endocrine hormone regulating glucose metabolism, fibroblast growth factor 21 (FGF21) is increased in individuals with gestational diabetes mellitus (GDM) after 24 gestational weeks. However, it is unknown whether the increase in FGF21 precedes the diagnosis of GDM. Methods: In this nested case-control study, 133 pregnant women with GDM and 133 pregnant women with normal glucose tolerance (NGT) were identified through propensity score matching, and serum FGF21 levels were measured at 14 to 21 gestational weeks, before GDM is routinely identified. The differences in FGF21 levels were compared. The association between FGF21 and the occurrence of GDM was evaluated using logistic regression models with adjustment for confounders. Results: The serum FGF21 levels of the GDM group at 14 to 21 gestational weeks were significantly higher than those of the NGT group overall (P < 0.001), with similar results observed between the corresponding BMI subgroups (P < 0.05). The 2nd (OR 1.224, 95% CI 0.603-2.485), 3rd (OR 2.478, 1.229-5.000), and 4th (OR 3.419, 95% CI 1.626-7.188) FGF21 quartiles were associated with greater odds of GDM occurrence than the 1st quartile after multivariable adjustments. Conclusions: The serum FGF21 levels in GDM groups increased in the early second trimester, regardless of whether participants were stratified according to BMI. After adjusting for confounding factors, the FGF21 levels in the highest quartile were associated with more than three times higher probability of the diagnosis of GDM in the pregnancy as compared to levels in the first quartile.

A rapid thioacidolysis method for biomass lignin composition and tricin analysis.

BACKGROUND: Biomass composition varies from plant to plant and greatly affects biomass utilization. Lignin is a heterogeneous phenolic polymer derived mainly from p-coumaryl, coniferyl, and sinapyl alcohols and makes up to 10-25% of lignocellulosic biomass. Recently, tricin, an O-methylated flavone, was identified as a lignin monomer in many grass species. Tricin may function as a nucleation site for lignification and is advocated as a novel target for lignin engineering to reduce lignin content and improve biomass digestibility in grasses. Thioacidolysis is an analytical method that can be adapted to analyze both lignin monomeric composition and tricin content in the lignin polymer. However, the original thioacidolysis procedure is complex, laborious, and time consuming, making it difficult to be adopted for large-scale screening in biomass research. In this study, a modified, rapid higher throughput thioacidolysis method was developed. RESULTS: In combination with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), the modified thioacidolysis method can be used to simultaneously characterize the lignin composition and tricin content using 2-5 mg of dry samples. The modified method eliminates the solvent extraction and drastically improves the throughput; 80 samples can be processed in one day per person. Our results indicate that there is no significant difference in the determination of lignin S/G ratio and tricin content between the original and modified methods. CONCLUSIONS: A modified thioacidolysis protocol was established. The results demonstrate that the modified method can be used for rapid, high-throughput, and reliable lignin composition and tricin content analyses for screening transgenic plants for cell wall modifications or in large-scale genome-wide association studies (GWAS).

Early Versus Routine Oral Glucose Tolerance Test in Women With Intermediate Hyperglycemia at First Prenatal Visit: A Retrospective Cohort Study in China.

Background and Objectives: Intermediate hyperglycemia in the first half of pregnancy, defined as a fasting plasma glucose level between 5.1- 6.9 mM, increases the risk of gestational diabetes mellitus, but clinical evidence for further management is lacking. We aim to evaluate the effectiveness of an early oral glucose tolerance test (OGTT) followed by the identification of intermediate hyperglycemia on pregnancy outcomes in real world setting. Subjects and Methods: A retrospective cohort study was conducted at the Obstetrics and Gynecology Hospital, Shanghai, China, between 2013 and 2017. Women with intermediate hyperglycemia at the first prenatal visit were identified and underwent an immediate (within one week) or a routine OGTT (24-28 gw) according to their wishes and received nutrition and exercise advice. Women diagnosed of gestational diabetes (GDM) were managed by standard interventions. Primary outcome was larger for gestational age (LGA). Secondary outcomes were primary cesarean delivery, preterm birth, shoulder dystocia or forceps delivery, preeclampsia, neonatal hypoglycemia, hyperbilirubinemia, and low Apgar score. Logistic regressions with or without a further propensity score-matched analysis were performed. Results: Among 42406 women involved, 1104 (2.6%) with intermediate hyperglycemia at the first prenatal visit were identified, of whom 176 (15.9%) underwent an early OGTT and 741 (67.1%) received a routine OGTT. Logistic regression showed that an early OGTT was not significantly associated with an altered risk of LGA (adjusted OR 1.13, 95% CI 0.73-1.75) but was related to an increased odds for neonatal hyperbilirubinemia (adjusted OR 2.89; 95% CI 1.55-5.37). No significant associations were observed for other secondary outcomes. These trends remained consistent in propensity score-matched models. Conclusions: Our data from a real-world setting did not support that an early OGTT among women with intermediate hyperglycemia at the first prenatal visit improved pregnancy outcomes.

Prenatal fine particulate matter exposure, placental DNA methylation changes, and fetal growth.

This study was designed to examine the impact of prenatal fine particulate matter (PM2.5) exposure on fetal growth and the underlying placental epigenetic mechanism in a cohort of Chinese women. Within the prospective Shanghai Mother-Child Pairs cohort (Shanghai MCPC), 329 women carrying singleton pregnancy with a due date in 2018 were recruited between 2017 and 2018. Maternal PM2.5 exposure levels were estimated using gestational exposure prediction model combining satellite-driven ambient concentrations and personal air sampling. Fetal growth characteristics were evaluated by prenatal ultrasound examinations and anthropometric measurements at birth. In a discovery phase, whole-genome DNA methylation analysis was performed using the Infinium 850 K array. In a validation phase, placental DNA methylation was measured using bisulfite pyrosequencing for five candidate genes that showed the most significant alterations and function relevance in our methylation array screen, including BID (BH3 interacting domain death agonist), FOXN3 (Forkhead box N3), FOXP1 (Forkhead box P1), IGF2 (Insulin-like growth factor 2) and HSD11B2 (Hydroxysteroid 11-beta dehydrogenase 2). Multivariate linear regression models were applied to examine the associations among PM2.5 exposure, fetal growth characteristics and DNA methylation on placental candidate genes. Sobel tests were used to evaluate the mediating role of DNA methylation in multivariable models. After excluding women who withdrew or failed to provide placenta, a total of 287 pregnant women with an average age of 30 entered the final analysis. Increased PM2.5 exposure was significantly associated with reduced biparietal diameter (BPD) (ß: -0.136 mm, 95% CI: -0.228 to -0.043), head circumference (HC) (ß: -0.462 mm, 95% CI: -0.782 to -0.142), femur length (FL) (ß: -0.113 mm, 95% CI: -0.185 to -0.041) and abdominal circumference (AC) (ß: -0.371 mm, 95% CI: -0.672 to -0.071) in the second trimester and birth length (ß: -0.013 cm, 95% CI: -0.025 to -0.001). Prenatal PM2.5 exposure could lead to aberrant changes in DNA methylation profile of placenta genome, which were mainly enriched in reproductive development, energy metabolism and immune response. DNA methylation of IGF2 and BID showed significant associations with PM2.5 exposures during all exposure windows. In addition, BID methylation was negatively correlated with HC (ß: -1.396 mm, 95% CI: -2.582 to -0.209) and BPD (ß: -0.330 mm, 95% CI: -0.635 to -0.026) in the second trimester. Further mediation analysis indicated that BID methylation mediated about 30% of the effects of PM2.5 exposure on HC. These findings collectively suggested that prenatal PM2.5 exposure may cause adverse effects on fetal growth by modifying placental DNA methylation.

Differentially expressed circular RNAs and the competing endogenous RNA network associated with preeclampsia.

INTRODUCTION: Circular RNAs (circRNAs) are non-coding RNAs that are implicated in preeclampsia (PE) pathogenesis; however, their expression and functions in PE remain unclear. In this study, we aimed to investigate the expression of circRNAs in PE and construct a competing endogenous RNA (ceRNA) network, and analyze the associated pathways in PE pathogenesis. METHODS: We performed circRNA sequencing to identify the differential expression profile of circRNAs in PE as compared to normal pregnancy. The circRNA candidates were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Subsequently, we used datasets from the GEO database to generate the interaction network between circRNAs, microRNAs (miRNAs), and mRNAs. GO and KEGG enrichment analyses were performed to understand the functional significance of the differentially expressed circRNAs in PE. RESULTS: We identified 361 differentially expressed circRNAs (252 upregulated and 109 downregulated) in preeclamptic placentas. Within the selected 31 circRNAs, 6 of them were verified by qRT-PCR. GO and KEGG analyses revealed the potential pathways affected by these circRNAs, e.g., T cell receptor signaling and MAP kinase pathways. A total of 134 miRNAs and 199 mRNAs were revealed to be differentially expressed in PE by analyzing datasets from the GEO database. The circRNA-miRNA-mRNA network comprised 206 circRNAs, 50 miRNAs, and 38 mRNAs. KEGG analysis of the 38 mRNAs included pathways involved in AMPK and PI3K-Akt signaling. DISCUSSION: Our results reported the differential expression profile of circRNAs and the circRNA-miRNA-mRNA network in PE, which provides potential therapeutic targets for this disease.