Substrate Specificity of LACCASE8 Facilitates Polymerization of Caffeyl Alcohol for C-Lignin Biosynthesis in the Seed Coat of Cleome hassleriana.

Catechyl lignin (C-lignin) is a linear homopolymer of caffeyl alcohol found in the seed coats of diverse plant species. Its properties make it a natural source of carbon fibers and high-value chemicals, but the mechanism of in planta polymerization of caffeyl alcohol remains unclear. In the ornamental plant Cleome hassleriana, lignin biosynthesis in the seed coat switches from guaiacyl lignin to C-lignin at ∼12 d after pollination. Here we found that the transcript profile of the laccase gene ChLAC8 parallels the accumulation of C-lignin during seed coat development. Recombinant ChLAC8 oxidizes caffeyl and sinapyl alcohols, generating their corresponding dimers or trimers in vitro, but cannot oxidize coniferyl alcohol. We propose a basis for this substrate preference based on molecular modeling/docking experiments. Suppression of ChLAC8 expression led to significantly reduced C-lignin content in the seed coats of transgenic Cleome plants. Feeding of 13C-caffeyl alcohol to the Arabidopsis (Arabidopsis thaliana) caffeic acid o-methyltransferase mutant resulted in no incorporation of 13C into C-lignin, but expressing ChLAC8 in this genetic background led to appearance of C-lignin with >40% label incorporation. These results indicate that ChLAC8 is required for C-lignin polymerization and determines lignin composition when caffeyl alcohol is available.

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.

[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.

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.

Enzymatic basis for C-lignin monomer biosynthesis in the seed coat of Cleome hassleriana.

C-lignin is a linear polymer of caffeyl alcohol, found in the seed coats of several exotic plant species, with promising properties for generation of carbon fibers and high value chemicals. In the ornamental plant Cleome hassleriana, guaiacyl (G) lignin is deposited in the seed coat for the first 6-12 days after pollination, after which G-lignin deposition ceases and C-lignin accumulates, providing an excellent model system to study C-lignin biosynthesis. We performed RNA sequencing of seed coats harvested at 2-day intervals throughout development. Bioinformatic analysis identified a complete set of lignin biosynthesis genes for Cleome. Transcript analysis coupled with kinetic analysis of recombinant enzymes in Escherichia coli revealed that the switch to C-lignin formation was accompanied by down-regulation of transcripts encoding functional caffeoyl CoA- and caffeic acid 3-O-methyltransferases (CCoAOMT and COMT) and a form of cinnamyl alcohol dehydrogenase (ChCAD4) with preference for coniferaldehyde as substrate, and up-regulation of a form of CAD (ChCAD5) with preference for caffealdehyde. Based on these analyses, blockage of lignin monomer methylation by down-regulation of both O-methyltransferases (OMTs) and methionine synthase (for provision of C1 units) appears to be the major factor in diversion of flux to C-lignin in the Cleome seed coat, although the change in CAD specificity also contributes based on the reduction of C-lignin levels in transgenic Cleome with down-regulation of ChCAD5. Structure modeling and mutational analysis identified amino acid residues important for the preference of ChCAD5 for caffealdehyde.

Gene regulatory networks for lignin biosynthesis in switchgrass (Panicum virgatum).

Cell wall recalcitrance is the major challenge to improving saccharification efficiency in converting lignocellulose into biofuels. However, information regarding the transcriptional regulation of secondary cell wall biogenesis remains poor in switchgrass (Panicum virgatum), which has been selected as a biofuel crop in the United States. In this study, we present a combination of computational and experimental approaches to develop gene regulatory networks for lignin formation in switchgrass. To screen transcription factors (TFs) involved in lignin biosynthesis, we developed a modified method to perform co-expression network analysis using 14 lignin biosynthesis genes as bait (target) genes. The switchgrass lignin co-expression network was further extended by adding 14 TFs identified in this study, and seven TFs identified in previous studies, as bait genes. Six TFs (PvMYB58/63, PvMYB42/85, PvMYB4, PvWRKY12, PvSND2 and PvSWN2) were targeted to generate overexpressing and/or down-regulated transgenic switchgrass lines. The alteration of lignin content, cell wall composition and/or plant growth in the transgenic plants supported the role of the TFs in controlling secondary wall formation. RNA-seq analysis of four of the transgenic switchgrass lines revealed downstream target genes of the secondary wall-related TFs and crosstalk with other biological pathways. In vitro transactivation assays further confirmed the regulation of specific lignin pathway genes by four of the TFs. Our meta-analysis provides a hierarchical network of TFs and their potential target genes for future manipulation of secondary cell wall formation for lignin modification in switchgrass.

The value of ultrasound in predicting isolated inter-twin discordance and adverse perinatal outcomes.

PURPOSE: To investigate the value of ultrasound approaching delivery to predict isolated inter-twin discordance and adverse perinatal outcomes. METHODS: We retrospectively included twin pregnancies with sonography approaching delivery in ten maternal-foetal medicine centres in China from 2013 to 2014. Estimated foetal weight (EFW) and inter-twin EFW disparity (EFWD) were calculated based on biometry parameters. Percentage errors between EFW and actual birthweight or between EFWD and actual inter-twin disparity were calculated. ROC curves and multiple logistic regression were applied to evaluate the ability of EFWD to predict inter-twin disparity ≥ 25%, stillbirth, asphyxia and admission to a neonatal intensive unit (NICU). Chorionicity-stratified analysis was further performed. RESULTS: Two hundred sixty-six monochorionic and 760 dichorionic twin pregnancies were analysed. The percentage errors in foetal weight estimations were 7-13%, whereas percentage errors in the estimation of inter-twin disparity were nearly 100%. Among eight formulas, Hadlock1 performed best, with a detectable rate of 65% and a false positive rate of 5% when predicting inter-twin disparity ≥ 25%. EFWD ≥ 22% was strongly associated with stillbirth (OR = 4.17, 95% CI 1.40-12.40) and NICU admission (OR = 3.48, 95% CI 2.03-5.97) after adjustment for gestational age, parity and abnormal umbilical systolic/diastolic ratio. Ultrasound had better predictive ability in monochorionic twins. CONCLUSION: The predictive value of ultrasound for isolated inter-twin discordance and adverse perinatal outcomes was limited, which was possibly due to the magnifying of systematic errors in the disparity estimation compared with weight estimation. Despite this, abnormal biometry was an independent contributor for the poor prognosis of neonates.

The Transcriptional Repressor MYB2 Regulates Both Spatial and Temporal Patterns of Proanthocyandin and Anthocyanin Pigmentation in Medicago truncatula.

Accumulation of anthocyanins and proanthocyanidins (PAs) is limited to specific cell types and developmental stages, but little is known about how antagonistically acting transcriptional regulators work together to determine temporal and spatial patterning of pigmentation at the cellular level, especially for PAs. Here, we characterize MYB2, a transcriptional repressor regulating both anthocyanin and PA biosynthesis in the model legume Medicago truncatula. MYB2 was strongly upregulated by MYB5, a major regulator of PA biosynthesis in M. truncatula and a component of MYB-basic helix loop helix-WD40 (MBW) activator complexes. Overexpression of MYB2 abolished anthocyanin and PA accumulation in M. truncatula hairy roots and Arabidopsis thaliana seeds, respectively. Anthocyanin deposition was expanded in myb2 mutant seedlings and flowers accompanied by increased anthocyanin content. PA mainly accumulated in the epidermal layer derived from the outer integument in the M. truncatula seed coat, starting from the hilum area. The area of PA accumulation and ANTHOCYANIDIN REDUCTASE expression was expanded into the seed body at the early stage of seed development in the myb2 mutant. Genetic, biochemical, and cell biological evidence suggests that MYB2 functions as part of a multidimensional regulatory network to define the temporal and spatial pattern of anthocyanin and PA accumulation linked to developmental processes.

Serum levels of human epididymis protein 4 are more stable than cancer antigen 125 in early and mid-term pregnancy.

AIM: Previous studies have shown serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) levels could serve as predictive markers in the diagnosis of ovarian cancer. However, HE4 levels have been less well studied during pregnancy, especially in threatened abortion, while CA125 levels were fluctuated. Our study aimed to assess the stability of HE4 and CA125 levels through trimesters and in cases of threatened abortion. METHODS: Forty-six nonpregnant women (control), 167 healthy pregnant women and 46 pregnant threatened abortion (TA; 8-12 weeks pregnancy) women who visited the Obstetrics and Gynecology Hospital of Fudan University from September to December 2017 were recruited. The healthy pregnant women group included 57 women in the first trimester (T1), 55 in the second (T2) and 55 in the third (T3). Serum levels of HE4 and CA125 were measured by electrochemiluminescent immunoassay. RESULTS: Both HE4 and CA125 levels in the T3 group were significantly higher than in the control group (P < 0.001). There was no difference in HE4 between the control, T1 and T2 groups, while levels of CA125 in T1 group were elevated (P < 0.001). There was no difference in HE4 levels between the TA, control and T1 groups. However, the levels of CA125 in the TA group were much higher (P < 0.05). CONCLUSION: The level of HE4 was found to be more stable than that of CA125 in early and mid-pregnancy and in cases of threatened abortion.

Torsion of normal-sized ovary during late pregnancy: A case report and review of the literature.

Adnexal torsion is one of the most common gynecologic surgical emergencies. All age groups can be affected, but torsion of normal-sized ovary that happens during late pregnancy is rare and challenging to be diagnosed. The objective of this article is to present a case of adnexal torsion in a normal-sized ovary suspected by magnetic resonance imaging (MRI) in the third trimester of pregnancy. A 36-year-old woman at 32 + 5 weeks gestational age was admitted to hospital due to recurrent severe left lower abdominal pain. Doppler ultrasound failed to demonstrate the ovarian diseases, while MRI scan suspected the diagnosis of adnexal torsion. The patient received emergent exploratory laparotomy, and the left adnexa with a necrotic ovary was removed. Tocolytic therapy was used before and after surgery. Finally, she delivered a healthy full-term infant via cesarean section. Adnexal torsion occurring in a normal-sized ovary was quite rare in the third trimester pregnancy. MRI might be better than ultrasound in the early diagnosis of ovarian torsion.

A genomics approach to deciphering lignin biosynthesis in switchgrass.

It is necessary to overcome recalcitrance of the biomass to saccharification (sugar release) to make switchgrass (Panicum virgatum) economically viable as a feedstock for liquid biofuels. Lignin content correlates negatively with sugar release efficiency in switchgrass, but selecting the right gene candidates for engineering lignin biosynthesis in this tetraploid outcrossing species is not straightforward. To assist this endeavor, we have used an inducible switchgrass cell suspension system for studying lignin biosynthesis in response to exogenous brassinolide. By applying a combination of protein sequence phylogeny with whole-genome microarray analyses of induced cell cultures and developing stem internode sections, we have generated a list of candidate monolignol biosynthetic genes for switchgrass. Several genes that were strongly supported through our bioinformatics analysis as involved in lignin biosynthesis were confirmed by gene silencing studies, in which lignin levels were reduced as a result of targeting a single gene. However, candidate genes encoding enzymes involved in the early steps of the currently accepted monolignol biosynthesis pathway in dicots may have functionally redundant paralogues in switchgrass and therefore require further evaluation. This work provides a blueprint and resources for the systematic genome-wide study of the monolignol pathway in switchgrass, as well as other C4 monocot species.

Genetic manipulation of lignin reduces recalcitrance and improves ethanol production from switchgrass.

Switchgrass is a leading dedicated bioenergy feedstock in the United States because it is a native, high-yielding, perennial prairie grass with a broad cultivation range and low agronomic input requirements. Biomass conversion research has developed processes for production of ethanol and other biofuels, but they remain costly primarily because of the intrinsic recalcitrance of biomass. We show here that genetic modification of switchgrass can produce phenotypically normal plants that have reduced thermal-chemical (≤180 °C), enzymatic, and microbial recalcitrance. Down-regulation of the switchgrass caffeic acid O-methyltransferase gene decreases lignin content modestly, reduces the syringyl:guaiacyl lignin monomer ratio, improves forage quality, and, most importantly, increases the ethanol yield by up to 38% using conventional biomass fermentation processes. The down-regulated lines require less severe pretreatment and 300-400% lower cellulase dosages for equivalent product yields using simultaneous saccharification and fermentation with yeast. Furthermore, fermentation of diluted acid-pretreated transgenic switchgrass using Clostridium thermocellum with no added enzymes showed better product yields than obtained with unmodified switchgrass. Therefore, this apparent reduction in the recalcitrance of transgenic switchgrass has the potential to lower processing costs for biomass fermentation-derived fuels and chemicals significantly. Alternatively, such modified transgenic switchgrass lines should yield significantly more fermentation chemicals per hectare under identical process conditions.

Trophoblast fusion in fetal growth restriction is inhibited by CTGF in a cell-cycle-dependent manner.

Fetal growth restriction (FGR) is a relatively common complication of pregnancy, and insufficient syncytialization in the placenta may play an important role in the pathogenesis of FGR. However, the mechanism of impaired formation of the syncytiotrophoblast layer in FGR patients requires further exploration. In the present study, we demonstrated that the level of syncytialization was decreased in FGR patient placentas, while the expression of connective tissue growth factor (CTGF) was significantly upregulated. CTGF was found to inhibit trophoblast fusion via regulating cell cycle progress of BeWo cells. Furthermore, we found that CTGF negatively regulates cell cycle arrest in a p21-dependent manner as overexpression of p21 could rescue the impaired syncytialization induced by CTGF-overexpression. Besides, we also identified that CTGF inhibits the expression of p21 through ITGB4/PI3K/AKT signaling pathway. Our study provided a new insight for elucidating the pathogenic mechanism of FGR and a novel idea for the clinical therapy of FGR.

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.

Docosahexaenoic acid insufficiency impairs placental angiogenesis by repressing the methylene-bridge fatty acylation of AKT in preeclampsia.

INTRODUCTION: Preeclampsia (PE), characterised by hypertension in pregnancy, is regarded as a placental metabolism-related syndrome affecting 5-8% of pregnancies worldwide. The insufficiency of polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), is a causative factor of PE pathogenesis. However, its molecular aetiology is yet to be comprehensively elucidated. METHODS: CRISPR/Cas9 was used to construct Fads2 knockout mice. Gas chromatography-mass spectrometry was used to detect placental fatty acid levels. Gene Expression Omnibus was used to analyze placental FADS2 mRNA levels. CCK-8 assay was used to assess cell growth capacity. Cell migration and invasion abilities were measured by transwell and wound healing assay. Tube forming assay was used to test angiogenesis ability. The co-immunoprecipitation assay was used to validate interactions between two proteins. AKT inhibitor MK-2206 and methylene-bridge fatty acylation inhibitor tryptophan were used to rescue experiments. RESULTS: Compared to those in women with normal pregnancies, the DHA levels in the placentas of patients with PE decreased with the downregulation of FADS2, the key desaturase in the synthesis of PUFAs. Pregnant Fads2+/- mice exhibited PE-like symptoms, including proteinuria and elevated systolic arterial blood pressure, due to defective placental angiogenesis. Mechanistically, FADS2 knockdown in trophoblasts decreased cellular DHA levels and repressed the methylene-bridge fatty-acylation of AKT, inhibiting AKT-VEGFA signalling, which is crucial for angiogenesis. DISCUSSION: Our results suggest that placental DHA insufficiency downregulates placental angiogenesis via inhibiting fatty acylating AKT and AKT-VEGFA signalling, a novel insight into abnormal fatty acid metabolism in PE.

N6-methyladenosine dynamics in placental development and trophoblast functions, and its potential role in placental diseases.

N6-methyladenosine (m6A) is the most abundant modification controlling RNA metabolism and cellular functions, but its roles in placental development are still poorly understood. Here, we characterized the synchronization of m6A modifications and placental functions by mapping the m6A methylome in human placentas (n = 3, each trimester), revealing that the dynamic patterns of m6A were associated with gene expression homeostasis and different biological pathways in placental development. Then, we generated trophoblast-specific knockout mice of Wtap, a critical component of methyltransferase complex, and demonstrated that Wtap was essential for trophoblast proliferation, placentation and perinatal growth. Further in vitro experiments which includes cell viability assays and series molecular binding assays demonstrated that WTAP-m6A-IGF2BP3 axis regulated the RNA stability and translation of Anillin (ANLN) and VEGFA, promoting trophoblast proliferation and secretion. Dysregulation of this regulatory axis was observed in placentas from pregnancies with fetal growth restriction (FGR) or preeclampsia, revealing the pathogenic effects of imbalanced m6A modifications. Therefore, our findings provide novel insights into the functions and regulatory mechanisms of m6A modifications in placental development and placental-related gestational diseases.

A hidden proteome encoded by circRNAs in human placentas: Implications for uncovering preeclampsia pathogenesis.

BACKGROUND: CircRNA-encoded proteins (CEPs) are emerging as new players in health and disease, and function as baits for the common partners of their cognate linear-spliced RNA encoded proteins (LEPs). However, their prevalence across human tissues and biological roles remain largely unexplored. The placenta is an ideal model for identifying CEPs due to its considerable protein diversity that is required to sustain fetal development during pregnancy. The aim of this study was to evaluate circRNA translation in the human placenta, and the potential roles of the CEPs in placental development and dysfunction. METHODS: Multiomics approaches, including RNA sequencing, ribosome profiling, and LC-MS/MS analysis, were utilised to identify novel translational events of circRNAs in human placentas. Bioinformatics methods and the protein bait hypothesis were employed to evaluate the roles of these newly discovered CEPs in placentation and associated disorders. The pathogenic role of a recently identified CEP circPRKCB119aa in preeclampsia was investigated through qRT-PCR, Western blotting, immunofluorescence imaging and phenotypic analyses. RESULTS: We found that 528 placental circRNAs bound to ribosomes with active translational elongation, and 139 were translated to proteins. The CEPs showed considerable structural homology with their cognate LEPs, but are more stable, hydrophobic and have a lower molecular-weight than the latter, all of which are conducive to their function as baits. On this basis, CEPs are deduced to be closely involved in placental function. Furthermore, we focused on a novel CEP circPRKCB119aa, and illuminated its pathogenic role in preeclampsia; it enhanced trophoblast autophagy by acting as a bait to inhibit phosphorylation of the cognate linear isoform PKCß. CONCLUSIONS: We discovered a hidden circRNA-encoded proteome in the human placenta, which offers new insights into the mechanisms underlying placental development, as well as placental disorders such as preeclampsia. Key points A hidden circRNA-encoded proteome in the human placenta was extensively identified and systematically characterised. The circRNA-encoded proteins (CEPs) are potentially related to placental development and associated disorders. A novel conserved CEP circPRKCB119aa enhanced trophoblast autophagy by inhibiting phosphorylation of its cognate linear-spliced isoform protein kinase C (PKC) ß in preeclampsia.

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.

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.

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.