Associations of MTHFR Polymorphisms and Cytosine Modifications with Early-Gestational Diabetes Mellitus in Chinese Pregnant Women.

Early-Gestational Diabetes Mellitus (Early-GDM) is a complex condition that may cause complications in infants of affected mothers. The aim of this case-control study was to analyze the effects of genetic-epigenetic interaction on Early-GDM and fetal development with respect to cytosine modifications (i.e., 5mC, 5-methylcytosines; and 5hmC, 5-hydroxymethylcytosines) and single nucleotide polymorphisms (SNPs) of MTHFR, a key gene involving cytosine modifications. Peripheral blood samples were collected from 92 women in their first or second trimester of pregnancy (Early-GDM, n = 14; Controls, n = 78). Global DNA 5mC and 5hmC were quantified by HPLC-MS/MS, and MTHFR SNPs (rs1801133 C > T and rs1801131 A > C) were determined by TaqMan-qPCR. Association analysis suggested that MTHFR rs1801133 TT genotype was a risk factor of Early-GDM (OR [odds ratio] = 4.00; 95% CI [confidence interval]: 1.24, 12.86; p = 0.02). The C allele of rs1801131 appeared to be a protective factor for the 2-h OGTT (oral glucose tolerance test) (OR = -0.79; 95% CI: -1.48, -0.10; p = 0.03). Patients with Early-GDM had higher global 5mC and lower global 5hmC. The reduction of global 5hmC and the TT genotype of rs1801133 were associated with higher level of the 1st-FBG (fasting blood glucose in the first trimester) (p < 0.05). Additionally, global 5mC showed a positive correlation with birth weight, body length and head circumference of newborns, while global 5hmC showed a negative correlation with birth weight. The current study implicated MTHFR SNPs and cytosine modifications in the development of Early-GDM and potential complications in their newborns.

A unified framework of transformations based on the Jordan-Wigner transformation.

Quantum simulation of chemical Hamiltonians enables the efficient calculation of chemical properties. Mapping is one of the essential steps in simulating fermionic systems on quantum computers. In this work, a unified framework of transformations mapping fermionic systems to qubit systems is presented and many existing transformations-such as Jordan-Wigner, Bravyi-Kitaev, and parity transformations-are included in this framework. Based on this framework, the Multilayer Segmented Parity (MSP) transformation is proposed. The MSP transformation is a general mapping with an adjustable parameter vector, which can be viewed as a generalization of the above-mentioned mappings. Furthermore, the MSP transformation can adjust flexibly when dealing with different systems. Applying these mappings to the electronic structure Hamiltonians of various molecules, the MSP transformation is found to perform better on a number of Pauli operators and gates needed in the circuit of Hamiltonian simulation. The MSP transformation will reduce the qubit gate requirement for Hamiltonian simulation on noisy intermediate-scale quantum devices, and it will provide a much wider choice of mappings for researchers.

Associations between exposure to perfluoroalkyl substances and birth outcomes: A meta-analysis.

Although previous meta-analyses have shown that prenatal PFASs exposure is associated with reduction in birth weight, effects of prenatal PFASs exposure on birth outcomes have not been fully explored. We conducted a meta-analysis of 23 eligible studies searched from Embase, PubMed, and Web of Science before March 21, 2021 to analyze the association between prenatal PFASs exposure and birth outcomes, including premature birth (PTB), low birth weight (LBW), small for gestational age (SGA) and miscarriage. Odds ratio (OR) and corresponding confidence intervals were extracted for analysis. According to the heterogeneity of the included studies, fixed-effects (I2 ≤ 50%) and random-effects (I2 > 50%) models were applied respectively. The significant associations between PFOS and PTB (pooled OR = 1.54, 95% CI: 1.20-1.98), PFOA and miscarriage (pooled OR = 1.40, 95% CI: 1.15-1.70), and PFOS and LBW (pooled OR = 1.52, 95% CI: 1.19-1.94) were obtained. There were differences between included studies with different study regions, sampling time, and samples type used for PFASs assessment. These findings may provide insight in risk assessment and decision-making in producing products that contain PFASs.

Anion Induced Synthesis, Structural Characterization and Antibacterial Activity of Zinc(II) Complexes Derived from 5-Bromo-2-((2-(diethylamino)ethylimino)methyl)phenol.

By changing the anions of zinc salts, three different zinc(II) complexes, [Zn2(HL)2(NCS)4]·2CH3OH (1), [Zn2L(µ2-η1:η1-CH3COO)2(NCS)] (2) and [Zn(HL)I2]·CH3OH (3), where L = 5-bromo-2-((2-(diethylamino)ethylimino)methyl)phenolate, HL = 5-bromo-2-((2-(diethylammonio)ethylimino)methyl)phenolate, have been synthesized and characterized by IR and UV-Vis spectroscopy, as well as single-crystal X-ray diffraction. X-ray analysis indicates that the Zn atoms in the complexes are in trigonal bipyramidal, square pyramidal and tetrahedral coordination. The anions of the zinc salts lead to the formation of different structures of the complexes. Antibacterial activity of the complexes against Staphylococcus aureus, Escherichia coli, Klebsielle pneumoniae and Candida albicans strains was studied.

Transient Early Fine Motor Abnormalities in Infants Born to COVID-19 Mothers Are Associated With Placental Hypoxia and Ischemia.

Background: Long-term effects of Coronavirus Disease 2019 (COVID-19) on infants born to infected mothers are not clear. Fine motor skills are crucial for the development of infant emotional regulation, learning ability and social skills. Methods: Clinical information of 100 infants born to 98 mothers (COVID-19 n = 31, non-COVID-19 n = 67) were collected. Infants were follow-up up to 9 months post-partum. The placental tissues were examined for SARS-CoV-2 infection, pathological changes, cytokines, and mtDNA content. Results: Decreased placental oxygen and nutrient transport capacity were found in infected pregnant women. Increased IL-2, IL-6, TNF-α, and IFN-γ were detected in trophoblast cells and maternal blood of COVID-19 placentas. Elevated early fine motor abnormal-ities and increased serum TNI (troponin I) levels at delivery were observed in infants born to mothers with COVID-19. Increased abnormal mitochondria and elevated mtDNA content were found in the placentas from infected mothers. The placental mtDNA content of three infants with abnormal DDST were increased by 4, 7, and 10%, respectively, compared to the mean of the COVID-19 group. The Maternal Vascular Malperfusion (MVM), elevated cytokines and increased placental mtDNA content in mothers with COVID-19 might be associated with transient early fine motor abnormalities in infants. These abnormalities are only temporary, and they could be corrected by daily training. Conclusions: Babies born to COVID-19 mothers with mild symptoms appeared to have little or no excess long-term risks of abnormal physical and neurobehavioral development as compared with the infants delivered by non-COVID-19 mothers.

Maternal Folic Acid Supplementation Mediates Offspring Health via DNA Methylation.

The clinical significance of periconceptional folic acid supplementation (FAS) in the prevention of neonatal neural tube defects (NTDs) has been recognized for decades. Epidemiological data and experimental findings have consistently been indicating an association between folate deficiency in the first trimester of pregnancy and poor fetal development as well as offspring health (i.e., NTDs, isolated orofacial clefts, neurodevelopmental disorders). Moreover, compelling evidence has suggested adverse effects of folate overload during perinatal period on offspring health (i.e., immune diseases, autism, lipid disorders). In addition to several single-nucleotide polymorphisms (SNPs) in genes related to folate one-carbon metabolism (FOCM), folate concentrations in maternal serum/plasma/red blood cells must be considered when counseling FAS. Epigenetic information encoded by 5-methylcytosines (5mC) plays a critical role in fetal development and offspring health. S-adenosylmethionine (SAM), a methyl donor for 5mC, could be derived from FOCM. As such, folic acid plays a double-edged sword role in offspring health via mediating DNA methylation. However, the underlying epigenetic mechanism is still largely unclear. In this review, we summarized the link across DNA methylation, maternal FAS, and offspring health to provide more evidence for clinical guidance in terms of precise FAS dosage and time point. Future studies are, therefore, required to set up the reference intervals of folate concentrations at different trimesters of pregnancy for different populations and to clarify the epigenetic mechanism for specific offspring diseases.

Oxidovanadium(V) and Dioxidomolybdenum(VI) Complexes of N'-(3,5-Dichloro-2-hydroxybenzylidene)-4-fluorobenzohydrazide: Synthesis, Characterization, Crystal Structures and Catalytic Property.

N'-(3,5-Dichloro-2-hydroxybenzylidene)-4-fluorobenzohydrazide (H2L) was used to prepare oxidovanadium(V) complex [VOL(OEt)(MeOH)] (1) and dioxidomolybdenum(VI) complex [MoO2L(OH2)]·[MoO2L(EtOH)] (2). The complexes were characterized by IR, UV-Vis, NMR spectroscopy, and single crystal X-ray diffraction. X-ray analysis indicates that the complexes are mononuclear species with the metal atoms in octahedral coordination. The complexes were studied for catalytic oxidation property on some olefins with tert-butyl hydroperoxide as oxidant.

B-RCA revealed circulating miR-33a/b associates with serum cholesterol in type 2 diabetes patients at high risk of ASCVD.

AIMS: Type 2 diabetes (T2D) is a complex metabolic disease with high incidence throughout the world. Dyslipidemia is the leading cause of atherosclerotic cardiovascular diseases (ASCVD) in T2D patients. hsa-miR-33 (miR-33) serves as a regulator in lipid metabolism. We hypothesized that blood miR-33 associates with serum lipids in T2D patients at high risk of ASCVD events. METHODS: We developed a branched rolling circle amplification (B-RCA) method and assessed its sensitivity and specificity with miR-33a/b standards by traditional TaqMan assay. Circulating miR-33a/b level was then determined with B-RCA in 30 T2D patients at high risk for developing ASCVD and 33 healthy controls. Pearson correlation coefficient was used to evaluate the correlation between circulating miR-33a/b and serum cholesterol. RESULTS: Compared with TaqMan assay, B-RCA method showed a similar specificity and a 100-fold higher sensitivity for miR-33a detection. Circulating miR-33a/b level is positively correlated with serum total cholesterol (TC) (r = 0.364, p = 0.048) and low-density lipoprotein cholesterol (LDL-C) (r = 0.383, p = 0.037) in T2D patients at high risk for developing ASCVD. CONCLUSIONS: Our B-RCA method provided an alternative strategy with specificity and high sensitivity for circulating miRNAs detection, and the results demonstrated that miR-33a/b might play an important role in cholesterol regulation.

FTO Genotype and Type 2 Diabetes Mellitus: Spatial Analysis and Meta-Analysis of 62 Case-Control Studies from Different Regions.

Type 2 diabetes mellitus (T2DM) is a global health problem that results from the interaction of environmental factors with genetic variants. Although a number of studies have suggested that genetic polymorphisms in the fat mass and obesity-associated (FTO) gene are associated with T2DM risk, the results have been inconsistent. To investigate whether FTO polymorphisms associate with T2DM risk and whether this association is region-related, we performed this spatial analysis and meta-analysis. More than 60,000 T2DM patients and 90,000 controls from 62 case-control studies were included in this study. Odds ratios (ORs), 95% confidence intervals (CIs) and Moran's I statistic were used to estimate the association between FTO rs9939609, rs8050136, rs1421085, and rs17817499, and T2DM risk in different regions. rs9939609 (OR = 1.15, 95% CI 1.11-1.19) and rs8050136 (OR = 1.14, 95% CI 1.10-1.18) conferred a predisposition to T2DM. After adjustment for body mass index (BMI), the association remained statistically significant for rs9939609 (OR = 1.11, 95% CI 1.05-1.17) and rs8050136 (OR = 1.08, 95% CI 1.03-1.12). In the subgroup analysis of rs9939609 and rs8050136, similar results were observed in East Asia, while no association was found in North America. In South Asia, an association for rs9939609 was revealed but not for rs8050136. In addition, no relationship was found with rs1421085 or rs17817499 regardless of adjustment for BMI. Moran's I statistic showed that significant positive spatial autocorrelations existed in rs9939609 and rs8050136. Studies on rs9939609 and rs8050136 focused on East Asia and South Asia, whereas studies on rs1421085 and rs17817499 were distributed in North America and North Africa. Our data suggest that the associations between FTO rs9939609, rs8050136 and T2DM are region-related, and the two single-nucleotide polymorphisms contribute to an increased risk of T2DM. Future studies should investigate this issue in more regions.

Polymorphisms in FADS1 and FADS2 alter plasma fatty acids and desaturase levels in type 2 diabetic patients with coronary artery disease.

BACKGROUND: To explore whether plasma fatty acids and SNPs in the fatty acid desaturase (FADS) gene associated with type 2 diabetes (T2D) and coronary artery disease (CAD). METHODS: In this cross-sectional study, we utilized gas chromatography-mass spectrometric analysis and the high-resolution melting method to detect plasma fatty acids and SNPs respectively (rs174537G>T, rs174616C>T, rs174460T>C, and rs174450A>C) in 234 T2D, 200 CAD, 185 T2D&CAD patients, and 253 healthy controls. RESULTS: We found that T2D&CAD patients had the highest plasma arachidonic acid, dihomo-gamma-linolenic acid and delta-6 desaturase, and the lowest stearic acid, linolenic acid, and saturated fatty acids; plasma eicosapentaenoic acid and docosahexaenoic acid elevated in T2D patients, but significantly reduced in CAD patients. Moreover, T2D patients with rs174537 GG genotype were at risk of developing T2D&CAD (odds ratio (OR) 1.763; 95 % CI 1.143-2.718; p = 0.010), with elevated plasma LDL-cholesterol, arachidonic acid, and delta-6 desaturase. CONCLUSIONS: Our results show that SNPs in FADS gene (particularly rs174537) associate with plasma fatty acids and desaturase levels in patients with both T2D and CAD, which maybe increases the risk of CAD in diabetic patients.