[Gene-gene/gene-environment interaction of transforming growth factor-ß signaling pathway and the risk of non-syndromic oral clefts].

OBJECTIVE: To explore the association between polymorphisms of transforming growth factor-ß (TGF-ß) signaling pathway and non-syndromic cleft lip with or without cleft palate (NSCL/P) among Asian populations, while considering gene-gene interaction and gene-environment interaction. METHODS: A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium, which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P. After stringent quality control measures, 343 single nucleotide polymorphism (SNP) spanning across 10 pivotal genes in the TGF-ß signaling pathway were selected from the original genome-wide association study(GWAS) dataset for further analysis. The transmission disequilibrium test (TDT) was used to test for SNP effects. The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction. Environmental factors collected for the study included smoking during pregnancy, passive smoking during pregnancy, alcohol intake during pregnancy, and vitamin use during pregnancy. Due to the low rates of exposure to smoking during pregnancy and alcohol consumption during pregnancy (<3%), only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed. The threshold for statistical significance was rigorously set at P =1.46×10-4, applying Bonferroni correction to account for multiple testing. RESULTS: A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P (P<0.05), but none of these associations was statistically significant after Bonferroni' s multiple test correction. However, there were 6 pairs of SNPs rs4939874 (SMAD2) and rs1864615 (TGFBR2), rs2796813 (TGFB2) and rs2132298 (TGFBR2), rs4147358 (SMAD3) and rs1346907 (TGFBR2), rs4939874 (SMAD2) and rs1019855 (TGFBR2), rs4939874 (SMAD2) and rs12490466 (TGFBR2), rs2009112 (TGFB2) and rs4075748 (TGFBR2) showed statistically significant SNP-SNP interaction (P<1.46×10-4). In contrast, the analysis of gene-environment interactions did not yield any significant results after being corrected by multiple testing. CONCLUSION: The comprehensive evaluation of SNP associations and interactions within the TGF-ß signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations. However, the significant gene-gene interactions identified suggest that the genetic architecture influencing NSCL/P risk may involve interactions between genes within the TGF-ß signaling pathway. These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

[A ssociations of short-term ambient particulate matter exposure and MTNR1B gene with triglyceride-glucose index: A family-based study].

OBJECTIVE: To explore the effects of short-term particulate matter (PM) exposure and the melatonin receptor 1B (MTNR1B) gene on triglyceride-glucose (TyG) index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China (FISSIC). METHODS: Probands and their relatives from 9 rural areas in Fangshan District, Beijing, were included in the study. PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System. TyG index was calculated by fasting triglyceride and glucose concentrations. The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models, in which covariates such as age, sex, and lifestyles were adjusted for. Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index. RESULTS: A total of 4 395 participants from 2 084 families were included in the study, and the mean age of the study participants was (58.98±8.68) years, with 53. 90% females. The results of association analyses showed that for every 10 µg/m3 increase in PM2.5 concentration, TyG index increased by 0.017 (95%CI: 0.007-0.027), while for per 10 µg/m3 increment in PM10, TyG index increased by 0.010 (95%CI: 0.003-0.017). And the associations all had lagged effects. In addition, there was a positive association between the rs10830963 polymorphism and the TyG index. For per increase in risk allele G, TyG index was elevated by 0.040 (95%CI: 0.004-0.076). The TyG index was 0.079 (95%CI: 0.005-0.152) higher in carriers of the GG genotype compared with carriers of the CC genotype. The interaction of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study. CONCLUSION: Short-term exposure to PM2.5 and PM10 were associated with higher TyG index. The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Short-Term Exposure to Nitrogen Dioxide Modifies Genetic Predisposition in Blood Lipid and Fasting Plasma Glucose: A Pedigree-Based Study.

(1) Background: Previous studies suggest that exposure to nitrogen dioxide (NO2) has a negative impact on health. But few studies have explored the association between NO2 and blood lipids or fasting plasma glucose (FPG), as well as gene-air pollution interactions. This study aims to fill this knowledge gap based on a pedigree cohort in southern China. (2) Methods: Employing a pedigree-based design, 1563 individuals from 452 families participated in this study. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and FPG were measured. We investigated the associations between short-term NO2 exposure and lipid profiles or FPG using linear mixed regression models. The genotype-environment interaction (GenoXE) for each trait was estimated using variance component models. (3) Results: NO2 was inversely associated with HDLC but directly associated with TG and FPG. The results showed that each 1 µg/m3 increase in NO2 on day lag0 corresponded to a 1.926% (95%CI: 1.428-2.421%) decrease in HDLC and a 1.400% (95%CI: 0.341-2.470%) increase in FPG. Moreover, we observed a significant genotype-NO2 interaction with HDLC and FPG. (4) Conclusion: This study highlighted the association between NO2 exposure and blood lipid profiles or FPG. Additionally, our investigation suggested the presence of genotype-NO2 interactions in HDLC and FPG, indicating potential loci-specific interaction effects. These findings have the potential to inform and enhance the interpretation of studies that are focused on specific gene-environment interactions.

Efficacy and Safety of Bifidobacterium longum Supplementation in Infants: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Strategies to stabilize and support overall infant health by increasing the number of Bifidobacterium longum in the infant gut are of interest, but few studies have systematically addressed this issue. We aimed to evaluate the efficacy and safety of Bifidobacterium longum use in infants using meta-analysis. METHODS: We searched PubMed, EMBASE, Cochrane Library of Systematic Reviews, and SinoMed for publications until 27 July 2022. The main outcomes of interest were weight gain, risk of necrotizing enterocolitis (NEC), and adverse events. Two authors independently performed study screening, risk of bias assessment, and data extraction. Outcome data were extracted from each included study and combined using mean difference (MD) or risk ratio (RR) and finally combined using a fixed-effect model or random-effect model. RESULTS: A total of 4481 relevant studies were identified, of which 15 were found to be eligible for randomized controlled trials and were included in the meta-analysis. The combined extracted data showed that the intervention group containing Bifidobacterium longum had a significantly lower risk of NEC (RR = 0.539, 95% CI: 0.333, 0.874) compared to the control group. There was no statistical difference between the intervention and control groups regarding weight gain (MD = 0.029, 95% CI: -0.032, 0.090), the occurrence of adverse events (RR = 0.986, 95% CI: 0.843, 1.153), and serious adverse events (RR = 0.881, 95% CI: 0.493, 1.573). CONCLUSIONS: Bifidobacterium longum may significantly reduce the risk of NEC in infants as well as being safe; thus, further research evidence is needed on whether there is a benefit on weight gain.

Unprecedented hetero-coordinated Ir(C

By using 2-(9-phenanthryl)pyridine (phpyr) and its derivatives as cyclometalated ligands, we synthesized a set of isomeric red-emitting complexes Ir(phpyr-R)2tmd (R = -H, -CF3, -F and -CH3, tmd = 2,2,6,6-tetramethylheptane-3,5-dione) with different coordinated modes, including bis-five-membered and five- + six-membered Ir-(C^N) ring chelating modes. The latter are the first examples of hetero-coordinated Ir(C^N)2(L^X)-type complexes containing both five- and six-membered Ir-(C^N) metallocycles. Their coordination geometries were distinctly determined using X-ray crystallographic analysis. Compared to typical bis-five-membered ring-chelated complexes, these novel hetero-coordinated isomers show bathochromic emission and lower quantum yields. On careful analysis of their electrochemical behavior and DFT calculations, it has been found that the regulatory effects of the solitary six-membered metallocycles in Ir(phpyr-R)2tmd could not only stabilize the LUMO but also destabilize the HOMO, leading to a narrower energy gap. More importantly, DFT calculations of the relative energies of these isomeric complexes demonstrated that bis-five-membered and five- + six-membered chelating modes are more stable compared to bis-six-membered rings, consistent with experiments. This work provides guidance for the structural design of Ir(C^N)2(L^X)-type complexes.

The study of a novel high selectivity pyrenyl-based fluorescence probe with aggregation-induced emission characteristics for Fe3+ detection designed by a structure modulation strategy.

The past decades have witnessed the feat of fluorescent probes for Fe3+ detection, where eliminating the interference by other metal ions plays a pivotal role in its detection by probes in complex environments. Herein, by taking advantage of the substituent effects, the electron-withdrawing group (EWG) -CF3 and electron-donating group (EDG) -CH3 were introduced to 2-(1-pyrenyl)pyridine (pypyr) to prepare two turn-off fluorescence probes, 5-trifluoromethyl-2-(1-pyrenyl)pyridine (pypyr-CF3) and 5-methyl-2-(1-pyrenyl)pyridine (pypyr-CH3). Intriguingly, both probes displayed novel aggregation-induced emission (AIE) characteristics in MeCN/H2O mixtures and the size and morphology of the aggregated particles were studied via DLS and TEM. By the modulation strategy, pypyr-CF3 can detect Fe3+ in the presence of 29 different metal ions without interference. Comparatively, pypyr-CH3 experienced serious interference from other metal ions such as Hg2+ and Zr4+. Besides, pypyr-CF3 not only demonstrated a higher photoluminescence quantum yield (PLQY) of 65.25% and wider pH adaptability but is also capable of Fe3+ detection over a wide pH range of 2-11 with a short response time (5 seconds). A plausible quenching mechanism based on the inner filter effect has also been demonstrated. More importantly, the versatile applications of pypyr-CF3, such as the quantitative analysis of Fe3+ in actual water samples, anti-forgery ink, fingerprint identification, etc., further corroborate its superb capabilities. This study aims to lend concrete support to the design and selectivity modulation of probes.

Cobalt Metal-Organic Frameworks with Aggregation-Induced Emission Characteristics for Fluorometric/Colorimetric Dual Channel Detection of Nitrogen-Rich Heterocyclic Compounds.

Nitrogen-rich heterocyclic compounds (NRHCs) are an emerging type of explosive, and their quantification is important in national security inspection and environmental monitoring. Up until now, designing an efficient NRHCs sensing strategy was still in the early stages. Herein, a new metal-organic framework (MOF) with aggregation-induced emission (AIE) characteristics is synthesized with fluorometric/colorimetric responses for rapid and selective detection of NRHCs. The nonemissive probe is designed with tetraphenylethylene derivative as the linker and Co as the node, quencher, and color-changing agent. Cobalt AIE-MOF exhibits a turn-on emission enhancement due to the competitive coordination substitution between NRHCs and the scaffold as well as the following AIE process of the liberative linkers. Meanwhile, the color appearance of the probe changes from blue to yellow based on the dissociation of the original Co coordinating system. Using this dual-mode probe, single- and dual-ring NRHCs are successfully detected from 5 µM to 7.5 mM within 25 s. The cobalt AIE-MOF exhibits excellent selectivity of NRHCs against a variety of interferences, providing a promising tool for designing a multichannel detection strategy.

Three novel topologically different metal-organic frameworks built from 3-nitro-4-(pyridin-4-yl)benzoic acid.

The design and synthesis of metal-organic frameworks (MOFs) have attracted much interest due to the intriguing diversity of their architectures and topologies. However, building MOFs with different topological structures from the same ligand is still a challenge. Using 3-nitro-4-(pyridin-4-yl)benzoic acid (HL) as a new ligand, three novel MOFs, namely poly[[(N,N-dimethylformamide-κO)bis[µ2-3-nitro-4-(pyridin-4-yl)benzoato-κ3O,O':N]cadmium(II)] N,N-dimethylformamide monosolvate methanol monosolvate], {[Cd(C12H7N2O4)2(C3H7NO)]·C3H7NO·CH3OH}n, (1), poly[[(µ2-acetato-κ2O:O')[µ3-3-nitro-4-(pyridin-4-yl)benzoato-κ3O:O':N]bis[µ3-3-nitro-4-(pyridin-4-yl)benzoato-κ4O,O':O':N]dicadmium(II)] N,N-dimethylacetamide disolvate monohydrate], {[Cd2(C12H7N2O4)3(CH3CO2)]·2C4H9NO·H2O}n, (2), and catena-poly[[[diaquanickel(II)]-bis[µ2-3-nitro-4-(pyridin-4-yl)benzoato-κ2O:N]] N,N-dimethylacetamide disolvate], {[Ni(C12H7N2O4)2(H2O)2]·2C4H9NO}n, (3), have been prepared. Single-crystal structure analysis shows that the CdII atom in MOF (1) has a distorted pentagonal bipyramidal [CdN2O5] coordination geometry. The [CdN2O5] units as 4-connected nodes are interconnected by L- ligands to form a fourfold interpenetrating three-dimensional (3D) framework with a dia topology. In MOF (2), there are two crystallographically different CdII ions showing a distorted pentagonal bipyramidal [CdNO6] and a distorted octahedral [CdN2O4] coordination geometry, respectively. Two CdII ions are connected by three carboxylate groups to form a binuclear [Cd2(COO)3] cluster. Each binuclear cluster as a 6-connected node is further linked by acetate groups and L- ligands to produce a non-interpenetrating 3D framework with a pcu topology. MOF (3) contains two crystallographically distinct NiII ions on special positions. Each NiII ion adopts an elongated octahedral [NiN2O4] geometry. Each NiII ion as a 4-connected node is linked by L- ligands to generate a two-dimensional network with an sql topology, which is further stabilized by two types of intermolecular OW-HW...O hydrogen bonds to form a 3D supramolecular framework. MOFs (1)-(3) were also characterized by powder X-ray diffraction, IR spectroscopy and thermogravimetic analysis. Furthermore, the solid-state photoluminescence of HL and MOFs (1) and (2) have been investigated. The photoluminescence of MOFs (1) and (2) are enhanced and red-shifted with respect to free HL. The gas adsorption investigation of MOF (2) indicates a good separation selectivity (71) of CO2/N2 at 273 K (i.e. the amount of CO2 adsorption is 71 times higher than N2 at the same pressure).

2,4,4,6,8,8-Hexanitro-2,6-diazaadamantane: A High-Energy Density Compound with High Stability.

A novel high-performance energetic compound of the polynitroazaadamantane family, 2,4,4,6,8,8-hexanitro-2,6-diazaadamantane, was designed and synthesized from 1,5-cyclooctadiene by two routes. Based on the experimental and calculated results, it exhibits a surprisingly high density (1.959 g cm-3), high thermal stability (onset decomposition temperature of 235 °C), high positive heat of formation, and excellent detonation properties. These fascinating properties, which are comparable to those of CL-20, show great promise for potential applications as a high-energy density material.