Detecting Gene-Gene Interaction among DNA Repair Genes in Chinese non-Syndromic Cleft lip with or Without Palate Trios.

OBJECTIVE: The objective of this study is to investigate the gene-gene interactions associated with NSCL/P among DNA repair genes. DESIGN: This study included 806 NSCL/P case-parent trios from China. Quality control process was conducted for genotyped single nucleotide polymorphisms (SNPs) located in six DNA repair genes (ATR, ERCC4, RFC1, TYMS, XRCC1 and XRCC3). We tested gene-gene interactions with Cordell's method using statistical package TRIO in R software. Bonferroni corrected significance level was set as P = 4.24 × 10-4. We also test the robustness of the interactions by permutation tests. SETTING: Not applicable. PATIENTS/PARTICIPANTS: A total of 806 NSCL/P case-parent trios (complete trios: 682, incomplete trios: 124) with Chinese ancestry. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Not applicable. RESULTS: A total of 118 SNPs were extracted for the interaction tests. Fourteen pairs of significant interactions were identified after Bonferroni correction, which were confirmed in permutation tests. Twelve pairs were between ATR and ERCC4 or XRCC3. The most significant interaction occurred between rs2244500 in TYMS and rs3213403 in XRCC1(P = 8.16 × 10-15). CONCLUSIONS: The current study identified gene-gene interactions among DNA repair genes in 806 Chinese NSCL/P trios, providing additional evidence for the complicated genetic structure underlying NSCL/P. ATR, ERCC4, XRCC3, TYMS and RFC1 were suggested to be possible candidate genes for NSCL/P.

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.

Identification of genetic loci jointly influencing COVID-19 and coronary heart diseases.

BACKGROUND: Comorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks. METHODS: By leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs). FINDINGS: Briefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18-0.19) to 0.23 (95% CI 0.23-0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs → COVID-19 → CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks. INTERPRETATION: Five SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of 'Long COVID-19.'

Hg bioaccumulation in the aquatic food web from tributaries of the Three Gorges Reservoir, China and potential consumption advisories.

The Three Gorges Reservoir (TGR) holds the distinction of being China's largest reservoir, and the presence of pollutants in the fish from the reservoir have a direct impact on the health of local residents. Thus, 349 fish specimens of 21 species and 1 benthos (Bellamya aeruginosas) were collected from four typical tributaries of the TGR from 2019 to 2020. These specimens were analyzed for the concentrations of total mercury (THg) and methylmercury (MeHg), and some representative samples were tested for δ13C and δ15N values to reveal the characteristics of bioaccumulation and biomagnification. The maximum safe daily consumption was estimated based on the oral reference dose (0.1 µg kg-1 bw/day according to US-EPA, 2017). The results showed that the mean THg and MeHg concentrations in fish from the TGR tributaries were 73.18 ± 49.21 ng g-1 and 48.42 ± 40.66 ng g-1, respectively, with the trophic magnification factors (TMFs) of THg and MeHg being 0.066 and 0.060, respectively. Among all the fish species in the tributaries, the highest daily maximum safe consumption amount was 1253.89 g for S. asotus consumed by adults, while the lowest was 62.88 g for C. nasus consumed by children.

KCNQ1 rs2237892 polymorphism modify the association between short-term ambient particulate matter exposure and fasting blood glucose: A family-based study.

BACKGROUND: The association between particulate matter and fasting blood glucose (FBG) has shown conflicting results. Genome-wide association studies have shown that KCNQ1 rs2237892 polymorphism is associated with the risk of diabetes. Whether KCNQ1 rs2237892 polymorphism might modify the association between particulate matter and FBG is still uncertain. METHODS: Data collected from a family-based cohort study in Northern China, were used to perform the analysis. A generalized additive Gaussian model was used to examine the short-term effects of air pollutants on FBG. We further conducted interaction analyses by including a cross-product term of air pollutants by rs2237892 within KCNQ1 gene. RESULTS: A total of 4418 participants were included in the study. In the single pollutant model, the FBG level increased 0.0031 mmol/L with per 10 µg/m3 elevation in fine particular matter (PM2.5) for lag 0 day. After additional adjustments for nitrogen dioxide (NO2) and sulfur dioxide (SO2), similar results were observed for lag 0-2 days. As for particulate matter with particle size below 10 µm (PM10), the significant association between the daily average concentration of the pollutant and FBG level was observed for lag 0-3 days. Additionally, rs2237892 in KCNQ1 gene modified the association between PM and FBG level. The higher risk of FBG levels associated with elevations in PM10 and PM2.5 were more evident as the number of risk allele C increased. Individuals with a CC genotype had the highest risk of elevation in FBG levels. CONCLUSION: Short-term exposures to PM2.5 and PM10 were associated with higher FBG levels. Additionally, rs2237892 in KCNQ1 gene might modify the association between the air pollutants and FBG levels.

Lifestyle Factors, Genetic Risk, and Cardiovascular Disease Risk among Breast Cancer Survivors: A Prospective Cohort Study in UK Biobank.

BACKGROUND: Evidence is limited regarding the association between lifestyles and cardiovascular disease (CVD), and the extent to which healthy lifestyles could offset the genetic risk of CVD in females with breast cancer (BC). METHODS: Females diagnosed as BC, who were free of CVD at baseline, from UK Biobank were included. Five modifiable lifestyle factors were considered to calculate the healthy lifestyle score, namely body mass index (BMI), smoking, alcohol drinking, dietary habits, and physical activity. The polygenetic risk score (PRS) was derived for coronary heart disease (CHD), ischemic stroke (IS), and heart failure (HF). RESULTS: In 13,348 female BC survivors, there were 986 CVD events (736 CHD, 165 IS, and 353 HF) over a median of 8.01 years of follow-up. Participants with 4-5 healthy lifestyle components were associated with a decreased risk of incident CVD (HR: 0.50; 95%CI: 0.37, 0.66), CHD (HR: 0.49; 95%CI: 0.35, 0.69), IS (HR: 0.35; 95%CI: 0.19, 0.65), and HF (HR: 0.59; 95%CI: 0.36, 0.97), compared with those with 0-1 lifestyle components. Evidence for the genetic-lifestyle interaction was observed for CHD (p = 0.034) and HF (p = 0.044). Among participants at high genetic risk, a healthy lifestyle was associated with a lower risk of CHD (HR: 0.37; 95%CI: 0.24, 0.56), IS (HR: 0.37; 95%CI: 0.15, 0.93) and HF (HR: 0.39; 95%CI: 0.21, 0.73). CONCLUSIONS: Our findings suggest that BC survivors with a high genetic risk could benefit more from adherence to a healthy lifestyle in reducing CVD risk.

Geopolymer composite spheres derived from graphene-modified fly ash/slag: Facile synthesis and removal of lead ions in wastewater.

Geopolymer composite spheres derived from potassium-activated graphene-modified slag/fly ash powder were produced in a polyethylene glycol (PEG 400) solvent. The effect of graphene type (graphene oxide (GO) and few-layered graphene (GNP)) on the pore structure and lead ions (Pb2+) removal performance of the spheres were evaluated. The results showed that the composite spheres modified with GOs (0.1-0.4 wt%) and GNPs (1-4 wt%) could be spheroidized with an improved performance to adsorb Pb2+ in solution. The graphene-containing spheres reached a maximum BET surface area of 68.85 m2/g. Pseudo-second-order and Langmuir isotherm models could express the adsorption process, which was controlled by both monolayer adsorption and chemisorption. The obtained spheres also showed high adsorption capacities for Ni2+, Cu2+, Zn2+ and Cd2+ ions. Chemical, physical, electrostatic, ion exchange and cation-π interaction were attributed to the adsorption mechanism of the spheres. The spheres showed good cycling ability compared to those without graphene, which had potential application in heavy metal wastewater treatment.

Synergism of cell adhesion regulatory genes and instant air pollutants on blood pressure elevation.

Accumulating evidence suggests that an instant exposure to particulate matter (PM) may elevate blood pressure (BP), where cell-adhesion regulatory genes may be involved in the interplay. However, few studies to date critically examined their interaction, and it remained unclear whether these genes modified the association. To assess the association between instant PM exposure and BP, and to examine whether single-nucleotide polymorphisms (SNPs) mapped in four cell adhesion regulatory genes modify the relationship, a cross-sectional study was performed, based on the baseline of an ongoing family-based cohort in Beijing, China. A total of 4418 persons from 2089 families in Northern China were included in the analysis. Four tagged SNPs in cell adhesion regulatory genes were selected among ZFHX3, CXCL12, RASGRP1 and MIR146A. A generalized additive model (GAM) with a Gaussian link was adopted to estimate the change in blood pressure after instant PM2.5 or PM10 exposure. A cross-product term of PM2.5/PM10 and genotype was incorporated into the GAM model to test for interaction. The study observed that an instant exposure to either PM2.5 or PM10 was found to be associated with elevated systolic blood pressure (SBP). On average, a 10 µg/m3 increase in instant exposure to PM2.5 and PM10 concentration corresponded to 0.140% (95% CI: 0.014%-0.265%, P = 0.029) and 0.173% (95% CI: 0.080%-0.266%, P < 0.001) higher SBP. However, diastolic blood pressure (DBP) was not elevated as the PM2.5 or PM10 concentration increased (P > 0.05). A synergetic interaction on SBP was observed between SNPs in four cell adhesion regulatory genes (rs2910164 in MIR146A, rs2297630 in CXCL12, rs7403531 in RASGRP1, and rs7193343 in ZFHX3) and instant PM2.5 exposure (Pfor interaction <0.05). Briefly, as carriers of risk alleles in each of these four genes increased, an enhanced association was found between instant PM2.5 exposure and SBP.

Nonalcoholic fatty liver disease and cardiovascular diseases: A Mendelian randomization study.

BACKGROUND: Evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with cardiovascular diseases (CVDs). However, the results are inconsistent, and the causality remains to be established. OBJECTIVE: We aimed to investigate the potential causal relationship between NAFLD and CVDs, including arterial stiffness, coronary artery disease, heart failure, stroke, ischemic stroke and its subtypes using two-sample Mendelian randomization (MR). METHODS: Genetic instruments were used as proxies for NAFLD. Publicly available summary-level data were obtained from the UK Biobank, the CARDIoGRAMplusC4D Consortium, the MEGASTROKE Consortium, and other consortia. Six complementary MR methods were performed, including inverse variance weighted method (IVW), MR-Egger, weighted median, weighted mode, MR-PRESSO, and MR-RAPS. RESULTS: NAFLD was significantly associated with arterial stiffness (ß = 0.04 [95%CI, 0.02-0.06], P = 5.53E-04). Moreover, the results remained consistent and robust in the sensitivity analysis. As for heart failure, the IVW method suggested that NAFLD was significantly associated with heart failure (OR = 1.08, 95%CI: 1.02-1.14, P = 0.005) in the absence of pleiotropy. However, there were no significant associations of NAFLD with coronary artery disease, stroke, ischemic stroke, or any ischemic stroke subtype. CONCLUSION: The MR study supported the causal effect of NAFLD on arterial stiffness. However, the study did not provide enough evidence suggesting the causal associations of NAFLD with heart failure, coronary artery disease, and any stroke subtypes.

Wound complications and bleeding with new oral anticoagulants in patients undergoing total joint arthroplasty: A systematic review and meta-analysis of randomized controlled trials.

AIMS: The results of associations between new oral anticoagulants (NOACs) and wound complications after total joint arthroplasty remain inconsistent. We conducted a systematic review and meta-analysis of randomized controlled trials to make comparisons with low molecular weight heparins (LMWH) on the clinical outcomes of total wound complications, together with other efficacy and safety endpoints to further evaluate the safety and efficacy of NOACs. METHODS: This meta-analysis was conducted based on a published protocol (PROSPERO: CRD42019140841). We searched for available articles in PubMed, Embase and Cochrane Library through Jun 62 021. Random-effects meta-analyses, including subgroup analyses, were conducted to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for specific doses of NOACs. RESULTS: We retrieved 1683 studies, of which 20 were eligible for inclusion. We found that apixaban was associated with a lower incidence of total wound complications compared with LMWH (RR = 0.81; 95% CI: 0.65-1.00), while dabigatran and rivaroxaban did not increase the risk of total wound complications. In addition, apixaban was associated with a reduction in the risk of major/clinically relevant nonmajor bleeding events compared to LMWH (RR = 0.80, 95% CI: 0.65-0.99), while rivaroxaban increased the risk for major/clinically relevant nonmajor bleeding events (RR = 1.23, 95% CI: 1.02-1.50). Moreover, all 4 NOACs were associated with lower incidences of major venous thromboembolism compared with LMWH. CONCLUSION: A lower risk of wound complications was detected for apixaban, while dabigatran and rivaroxaban did not increase the risk when compared with LMWH. The efficacy of 4 NOACs was broadly similar.