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Abstract Background Chrysanthemum morifolium ‘HangBaiJu’, a popular medicinal and edible plant, exerts its biological activities primarily through the presence of flavones and caffeoylquinic acids (CQAs). However, the regulatory mechanism of flavone and CQA biosynthesis in the chrysanthemum capitulum remains unclear. Results In this study, the content of flavones and CQAs during the development of chrysanthemum capitulum was determined by HPLC, revealing an accumulation pattern with higher levels at S1 and S2 and a gradual decrease at S3 to S5. Transcriptomic analysis revealed that CmPAL1/2, CmCHS1/2, CmFNS, CmHQT, and CmHCT were key structural genes in flavones and CQAs biosynthesis. Furthermore, weighted gene co-expression correlation network analysis (WGCNA), k-means clustering, correlation analysis and protein interaction prediction were carried out in this study to identify transcription factors (TFs) associated with flavone and CQA biosynthesis, including MYB, bHLH, AP2/ERF, and MADS-box families. The TFs CmERF/PTI6 and CmCMD77 were proposed to act as upstream regulators of CmMYB3 and CmbHLH143, while CmMYB3 and CmbHLH143 might form a complex to directly regulate the structural genes CmPAL1/2, CmCHS1/2, CmFNS, CmHQT, and CmHCT, thereby controlling flavone and CQA biosynthesis. Conclusions Overall, these findings provide initial insights into the TF regulatory network underlying flavones and CQAs accumulation in the chrysanthemum capitulum, which laid a theoretical foundation for the quality improvement of C. morifolium ‘HangBaiJu’ and the high-quality development of the industry.

Abstract To exhaustively explore the association of infant genetic polymorphisms of methionine synthase (MTR) gene with the risk of non-syndromic congenital heart disease (CHD). A hospital-based case–control study involving 620 CHD cases and 620 health controls was conducted from November 2017 to March 2020. Eighteen SNPs were detected and analyzed. Our date suggested that the genetic polymorphisms of MTR gene at rs1805087 (GG vs. AA: aOR = 6.85, 95% CI 2.94–15.96; the dominant model: aOR = 1.77, 95% CI 1.35–2.32; the recessive model: aOR = 6.26, 95% CI 2.69–14.54; the addictive model: aOR = 1.81, 95% CI 1.44–2.29) and rs2275565 (GT vs. GG: aOR = 1.52, 95% CI 1.15–1.20; TT vs. GG: aOR = 4.93, 95% CI 1.93–12.58; the dominant model: aOR = 1.66, 95% CI 1.27–2.17; the recessive model: aOR = 4.41, 95% CI 1.73–11.22; the addictive model: aOR = 1.68, 95% CI 1.32–2.13) were significantly associated with the higher risk of CHD. And three haplotypes of G-A-T (involving rs4659724, rs95516 and rs4077829; OR = 5.48, 95% CI 2.58–11.66), G-C-A-T-T-G (involving rs2275565, rs1266164, rs2229276, rs4659743, rs3820571 and rs1050993; OR = 0.78, 95% CI 0.63–0.97) and T-C-A-T-T-G (involving rs2275565, rs1266164, rs2229276, rs4659743, rs3820571 and rs1050993; OR = 1.60, 95% CI 1.26–2.04) were observed to be significantly associated with risk of CHD. Our study found that genetic polymorphisms of MTR gene at rs1805087 and rs2275565 were significantly associated with higher risk of CHD. Additionally, our study revealed a significant association of three haplotypes with risk of CHD. However, the limitations in this study should be carefully taken into account. In the future, more specific studies in different ethnic populations are required to refine and confirm our findings. Trial registration: Registration number: ChiCTR1800016635; Date of first registration: 14/06/2018.

Background The purpose of this study was to explore the association between anaemia during early pregnancy and the risk of neonatal outcomes.Methods We collected clinical data from pregnant women (≥18 years) who received their first antenatal care between 8 and 14 weeks of gestation in Hunan Provincial Maternal and Child Health Care Hospital. Multiple logistic regression models and restricted cubic spline regression models were used to analyse the association between anaemia during early pregnancy and the risk of neonatal outcomes. In addition, sensitivity analysis was further performed to assess the robustness of the results.Results The prospective cohort study ultimately included 34 087 singleton pregnancies. In this study, the rate of anaemia during early pregnancy was 16.3%. Our data showed that there was a positive relationship between the rate of preterm birth, low birth weight as well as small for gestational age (SGA) and the severity of maternal anaemia (Ptrend

PurposeThe incidence of primary liver cancer is increasing year by year, with environmental factors playing a non-negligible role. At present, many studies are still disputing whether air pollution is associated with primary liver cancer incidence, and it is difficult to draw causal inferences. Therefore, in this study, we used two-sample Mendelian randomization (MR) to assess the causal relationship between air pollution (including PM2.5, PM2.5–10, PM10, nitrogen dioxide and nitrogen oxides) and primary liver cancer risk and its related biomarkers (Alpha-fetoprotein, Osteopontin, Glypican-3 and Arginase-1).Patients and methodsWe used large-scale publicly available genome-wide association studies (GWAS) summary data to conduct MR analyses of European and East Asian populations. Inverse variance weighted (IVW) method was used as the main analysis method, and weighted median model, MR-Egger, simple model and weighted model methods were selected for quality control. Heterogeneity was checked by the Cochran’s Q test. The MR-Egger regression and the MR-PRESSO global test detect pleiotropy. The sensitivity analysis was performed using the leave-one-out method.ResultsBetween air pollution and primary liver cancer in either European (PM2.5: p = 0.993; PM2.5–10: p = 0.833; PM10: p = 0.257; nitrogen dioxide: p = 0.215; nitrogen oxides: p = 0.614) or East Asian (PM2.5: p = 0.718; PM2.5–10: p = 0.362; PM10: p = 0.720; nitrogen dioxide: p = 0.101; nitrogen oxides: p = 0.760) populations were found no statistical association. Notably, there was a causal relationship between nitrogen oxides and Arginase-1, a biomarker associated with hepatocellular differentiation, statistically significant associations remained after deletion for single nucleotide polymorphisms (SNPs) associated with alcohol intake frequency, Body mass index (BMI) and cancers (Beta: 4.46; 95%CI: 0.83–8.08; p = 0.015). There was no heterogeneity or pleiotropy in the results.ConclusionThis MR study found no evidence to support a causality between air pollution and primary liver cancer in European and East Asian populations, but nitrogen oxides may affect hepatocellular differentiation.

ObjectiveThe real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D.MethodsWe leveraged publicly available genome-wide association study (GWAS) summary data to perform MR analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen were used. The summary statistic data for T1D (n = 264,137) were obtained from the latest release from the FinnGen consortium as the outcome of interest. The selection of instrumental variables conformed strictly to a series of preset inclusion and exclusion criteria. MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods were used to assess the causal association. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy.ResultsAt the phylum level, only Bacteroidetes was indicated to have causality on T1D (OR = 1.24, 95% CI = 1.01-1.53, P = 0.044) in the IVW analysis. When it comes to their subcategories, Bacteroidia class (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, PFDR = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, PFDR = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10-4, PFDR = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected.ConclusionsThe present study reports that Bacteroidetes phylum, Bacteroidia class, and Bacteroidales order causally increase T1D risk, whereas Eubacterium eligens group genus, which belongs to the Firmicutes phylum, causally decreases T1D risk. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa’s role in the pathophysiology of T1D.

Introduction To investigate the independent and combined effects of advanced maternal age and pre-pregnancy body mass index (BMI) on the risk of pre-eclampsia and gestational diabetes mellitus (GDM).Research design and methods Logistic regression models were used to estimate the OR and 95% CIs of pre-eclampsia and GDM with advanced maternal age and pre-pregnancy BMI, respectively, and the interaction between advanced maternal age and pre-pregnancy BMI. We also used causal mediation analysis to assess the mediating role of pre-pregnancy BMI on maternal age–pre-eclampsia/GDM associations.Results In this study, 788 cases (2.31%) were diagnosed with pre-eclampsia and 5430 cases (15.92%) were diagnosed with GDM. We found that advanced maternal age was associated with a higher risk for pre-eclampsia and GDM, with adjusted ORs (aORs) of 1.74 (95% CI 1.49–2.05) and 1.76 (95% CI 1.65–1.89) after adjusting for potential confounders, respectively. In addition, maternal pre-pregnancy overweight/obesity was associated with the risk of pre-eclampsia and GDM, with the corresponding aORs of 3.64 (95% CI 3.12–4.24) and 1.71 (95% CI 1.60–1.85), respectively. We also observed the interaction between maternal age and pre-pregnancy BMI for the risk of pre-eclampsia/GDM (all p for interaction

BackgroundLow birth weight (LBW) is one of the most common adverse pregnancy outcomes. Previous studies have consistently shown that maternal body mass index (BMI) status before and during pregnancy is associated with LBW. However, previous studies lacked an association between paternal BMI and the conjunction effect of a couple's BMI and LBW in the offspring. Therefore, we established a cohort of pre-pregnancy couples to prospectively assess the relationship between maternal and paternal pre-pregnancy BMI and offspring LBW, very low birth weight (VLBW), and extremely low birth weight (ELBW).MethodsA prospective cohort study was established in Central China. A total of 34,104 pregnant women with singleton pregnancies at 8–14 gestational weeks and their husbands were finally enrolled and followed to 3 months postpartum. The multivariate logistic regression and restrictive cubic spline model were used to explore the relationship between parental pre-pregnancy BMI and the risk of LBW, VLBW, and ELBW in offspring.ResultsOf the 34,104 participants, maternal pre-pregnancy overweight and obesity were associated with a higher risk of LBW (overweight: OR = 1.720, 95% CI = 1.533 ~ 1.930; obesity: OR = 1.710, 95% CI = 1.360 ~ 2.151), VLBW (overweight: OR = 2.283, 95% CI = 1.839 ~ 2.834; obesity: OR = 4.023, 95% CI = 2.855 ~ 5.670), and ELBW (overweight: OR = 3.292, 95% CI = 2.151 ~ 5.036; obesity: OR = 3.467, 95% CI = 1.481 ~ 8.115), while underweight was associated with a higher risk of LBW (OR = 1.438, 95% CI = 1.294 ~ 1.599) and a lower risk of ELBW (OR = 0.473, 95% CI = 0.236 ~ 0.946). Paternal pre-pregnancy overweight and obesity were associated with a higher risk of LBW (overweight: OR = 1.637, 95% CI = 1.501 ~ 1.784; obesity: OR = 1.454, 95% CI = 1.289 ~ 1.641) and VLBW (overweight: OR = 1.310, 95% CI = 1.097 ~ 1.564; obesity: OR = 1.320, 95% CI = 1.037 ~ 1.681), while underweight was associated with a lower risk of LBW (OR = 0.660, 95% CI = 0.519 ~ 0.839). Parents who were both excessive-weights in pre-pregnancy BMI, as well as overweight mothers and normal-weight fathers before pre-pregnancy, were more likely to have offspring with LBW, VLBW, and ELBW. Dose-response relationship existed between parental pre-pregnancy and LBW, VLBW, and ELBW, except for paternal BMI and ELBW.ConclusionsParental pre-pregnancy BMI was associated with the risk of LBW in offspring. Management of weight before pregnancy for couples might help reduce their adverse pregnancy outcomes in future intervention studies.

BackgroundTo systematically evaluate the association of MTHFR genetic polymorphisms, maternal folic acid intake, and the time when folic acid intake was started with the risk of congenital heart disease (CHD) and investigated the role of their interaction on infant CHD risk in Chinese populations.MethodsA case–control study involving 592 CHD cases, 617 health controls, and their mothers was performed. The exposures of interest were single nucleotide polymorphisms (SNPs) of the MTHFR gene, maternal folic acid use, and the time when folic acid use was started. We applied the logistic regression model to explore the strength of association.ResultsOur findings showed that mothers lacking folic acid intake had a significantly higher risk of CHD in offspring (aOR = 2.00; 95%CI: 1.34–2.98). Mothers who started to use folic acid from the first trimester of the fetation (aOR = 1.65; 95% CI: 1.22–2.23) or from the second trimester of the fetation (aOR = 7.77; 95% CI: 2.52–23.96), compared with those starting to use folic acid from 3 months previous to the conception, were at a significantly higher risk of CHD in offspring. Genetic variants at rs2066470 (AA vs. GG: aOR = 5.09, 95%CI: 1.99–13.03), rs1801133 (AA vs. GG: aOR = 2.49, 95%CI: 1.58–3.93), and rs1801131 (TG vs. TT: aOR = 1.84, 95%CI: 1.36–2.50; GG vs. TT: aOR = 3.58, 95%CI: 1.68–7.63) were significantly associated with the risk of CHD based on the multivariate analysis. Additionally, statistically significant interactions between maternal folic acid intake and genetic variants of the MTHFR gene at rs1801133 and rs1801131 were observed.ConclusionAn association of maternal folic acid intake and the time when intake was started with the risk of CHD in offspring was found. What's more, maternal folic acid fortification may help counteract partial of the risks of CHD in offspring attributable to MTHFR genetic mutations.Registration numberhttp://www.chictr.org.cn/edit.aspx?pid=28300&htm=4, identifier: ChiCTR1800016635.

Upon interactions with its specific ligand hepatocyte growth factor (HGF), the c-Met signal is relayed to series of downstream pathways, exerting essential biological roles. Dysregulation of the HGF-c-Met signaling pathway has been implicated in the onset, progression and metastasis of various cancers, making the HGF-c-Met axis a promising therapeutic target. Both c-Met and HGF undergo glycosylation, which appears to be biologically relevant to their function and structural integrity. Different types of glycoconjugates in the local cellular environment can also regulate HGF/c-Met signaling by distinct mechanisms. However, detailed knowledge pertaining to the glycosylation machinery of the HGF-c-Met axis as well as its potential applications in oncology research is yet to be established. This mini review highlights the significance of the HGF-c-Met signaling pathway in physiological and pathological context, and discusses the molecular mechanisms by which affect the glycosylation of the HGF-c-Met axis. Owing to the crucial role played by glycosylation in the regulation of HGF/c-Met activity, better understanding of this less exploited field may contribute to the development of novel therapeutics targeting glycoepitopes.

This study aimed to explore the association of maternal diet, infant MTHFR gene polymorphisms, and their interactions with the risk of ventricular septal defects (VSDs). This case–control study recruited 448 mothers of VSD children and 620 mothers of healthy counterparts. Multivariableadjusted logistic regression models were constructed to examine the association between maternal dietary habits during the first trimester of gestation, MTHFR gene polymorphisms, and VSD. Gene–environment interaction effects were analyzed through logistic regression models, with false discovery rate p-value (FDR_p) < 0.05. Maternal excessive intake of fermented bean curd (OR = 2.00, 95%CI: 1.59–2.52), corned foods (OR = 2.23, 1.76–2.84), fumatory foods (OR = 1.75, 1.37–2.23), grilled foods (OR = 1.34, 1.04–1.72), and fried foods (OR = 1.80, 1.42–2.27) was associated with an increased risk of VSD. Regular intake of fish and shrimp (OR = 0.42, 0.33–0.53), fresh eggs (OR = 0.58, 0.44–0.75), soy products (OR = 0.69, 0.56–0.85), and dairy products (OR = 0.71, 0.59–0.85) was found to reduce the occurrence of VSD. Moreover, MTHFR gene polymorphisms at rs2066470 (homozygous: OR = 4.28, 1.68–10.90), rs1801133 (homozygous: OR = 2.28, 1.39–3.74), and rs1801131 (heterozygous: OR = 1.75, 1.24–2.47; homozygous: OR = 3.45, 1.50–7.95) elevated offspring susceptibility to VSDs. Furthermore, significant interactions of MTHFR polymorphisms with maternal dietary habits were observed, encompassing corned foods, fermented bean curd, fried foods, and grilled foods. Maternal dietary habits; MTHFR polymorphisms at rs2066470, rs1801131, and rs1801133; and their interactions were significantly associated with the occurrence of VSDs in offspring. [ABSTRACT FROM AUTHOR]

Background On May 31, 2021, the Chinese authorities announced that couples can have up to three children, aiming to stimulate a rise in fertility levels. However, there is limited research on second and third birth intentions of the childbearing-age population under China's three-child policy, and the existing results are inconsistent. Methods A cross-sectional survey was performed in Central China from June to August 2022. A total of 13 479 respondents aged 20-49 were enrolled in the study through a multi-stage sampling method. Data on the intentions to have a second or third child were collected using anonymized questionnaires. Descriptive statistics were performed to assess fertility intentions. Multivariate logistic regression analyses were used to assess the associations between fertility intentions and the related factors. Results Among families with a single child, 29.7% (1444 / 4859) of the respondents intended to have a second child, while among two-child families, 10.6% (750 / 7056) respondents intended to have a third child. Overall, participants indicated that the ideal number of children was 1.85 ± 0.52. The age-specific fertility intentions of the one-child families were always higher than those of two-child families; however, based on couples' age groups, the number of ideal children reported by two-child families was always higher than that of one-child families. Fertility intentions were influenced by the respondents' gender, age, residence, marital status, educational level, average working time, childcare support, marital satisfaction, accessibility of educational resources, health condition of both spouses, loan situation, size of living house and the gender of the first child or second child. Conclusions The general prevalence of the second and third birth intention of the childbearing-age population in Central China is not high. To increase the birth rate, it is necessary to create a favourable fertility context and offer supportive measures. [ABSTRACT FROM AUTHOR]