Bioinformatics analysis of gene bhsA and its role in Ca2+ -treated Escherichia coli.

One of the commonly employed methods in molecular biology is to utilize calcium chloride to treat Escherichia coli for the preparation of competent cells to facilitate foreign gene expression. However, the molecular mechanisms underlying Ca2+ mediation of competent cell formation and identification of the key genes involved in the process remain unclear. In previous studies, the combined analysis of transcriptomics and proteomics revealed bhsA as one of the crucial genes. The gene ontology functional annotation of bhsA identified it as a member of the YhcN family encoding an outer membrane protein that confers resistance to various stresses. The IPR0108542 domain found within the protein plays a significant role in stress response and biofilm formation in E. coli. Analysis of the STRING database showed that the proteins interacting with bhsA are primarily involved in biofilm formation and stress resistance. Using the RED homologous recombination method, a bhsA deletion strain was constructed to verify its role in E. coli genetic transformation. Although the mutant strain showed no significant differences in morphology or growth trend when compared to the wild-type strain, its transformation efficiency decreased by 1.14- and 1.64-fold with plasmids pUC19 and pET-32a. Furthermore, the 1-N-phenylnaphthylamine assay indicated a 1.71-fold reduction in cell membrane permeability in the mutant strain.

Epigenome-wide perspective of cadmium-associated DNA methylation and its mediation role in the associations of cadmium with lipid levels and dyslipidemia risk.

BACKGROUND: Studies demonstrated the associations of cadmium (Cd) with lipid levels and dyslipidemia risk, but the mechanisms involved need further exploration. OBJECTIVES: We aimed to explore the role of DNA methylation (DNAM) in the relationship of Cd with lipid levels and dyslipidemia risk. METHODS: Urinary cadmium levels (UCd) were measured by inductively coupled plasma mass spectrometry, serum high-density lipoprotein (HDL), total cholesterol, triglyceride, and low-density lipoprotein were measured with kits, and DNAM was measured using the Infinium MethylationEPIC BeadChip. Robust linear regressions were conducted for epigenome-wide association study. Multivariate linear and logistic regressions were performed to explore the associations of UCd with lipid levels and dyslipidemia risk, respectively. Mediation analyses were conducted to explore potential mediating role of DNAM in the associations of Cd with lipid levels and dyslipidemia risk. RESULTS: UCd was negatively associated with HDL levels (p = 0.01) and positively associated with dyslipidemia (p < 0.01). There were 92/11 DMPs/DMRs (FDR<0.05) associated with UCd. Cd-associated DNAM and pathways were connected with cardiometabolic diseases and immunity. Cg07829377 (LINC01060) mediated 42.05%/22.88% of the UCd-HDL/UCd-dyslipidemia associations (p = 0.02 and 0.01, respectively). CONCLUSIONS: Cadmium caused site-specific DNAM alterations and the associations of UCd with lipid levels and dyslipidemia risk may be partially mediated by DNAM.

Associations of essential trace elements with epigenetic aging indicators and the potential mediating role of inflammation.

BACKGROUND: Essential trace elements (ETEs) play essential roles in vital functions, but their effects on epigenetic aging remain poorly understood. OBJECTIVES: This study aimed to investigate the associations of ETEs with four epigenetic aging indicators and assess the potential mediating role of inflammation. METHODS: We recruited 93 individuals from hospitals between October 2018 and August 2019. Plasma levels of cobalt, copper, iron, manganese, molybdenum, selenium, and zinc were measured by ICP-MS, and leukocyte DNA methylation levels were measured using Illumina MethylationEPIC beadchip. Linear regression was used to estimate the association between seven plasma ETEs and epigenetic aging indicators. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to evaluate the effect of ETEs mixtures. Inflammatory status was assessed using four systemic inflammation indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII)) and three cytokines (IL-4, IL-6, and IL-13). Mediation analysis was performed to explore the role of inflammation in the above associations. RESULTS: Plasma Se levels were significantly negatively associated with DunedinPACE, whereas Cu levels were significantly positively associated with it. Both WQS regression and BKMR models suggested that Se and Cu dominate the effect of the ETEs mixture. MLR and interleukin 6 were significantly and positively associated with DunedinPACE. Further mediation analysis indicated that inflammation partially mediated the association between ETEs and DunedinPACE. DISCUSSION: Plasma Se and Cu levels are closely associated to epigenetic aging, and inflammation might be a potential mechanism underlying this relationship. These findings contribute to the prevention of health hazards associated with population aging.

Transitions in Metabolic Health Status and Obesity Over Time and Risk of Diabetes: The Dongfeng-Tongji Cohort Study.

CONTEXT: Evidence regarding the association between metabolically healthy overweight or obesity (MHOO) and diabetes is controversial, and mostly ignores the dynamic change of metabolic health status and obesity. OBJECTIVE: To explore the association between transitions of metabolic health status and obesity over 5 years and diabetes incidence. METHODS: We examined 17 309 participants derived from the Dongfeng-Tongji cohort and followed from 2008 to 2018 (median follow-up 9.9 years). All participants were categorized into 4 phenotypes based on body mass index (BMI) and metabolic health status: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), MHOO, and metabolically unhealthy overweight or obesity (MUOO). The associations of changes in BMI-metabolic health status (2008-2013) with diabetes incidence (2018) were performed among 12 206 individuals with 2 follow-up examinations. RESULTS: Compared with stable MHNW, stable MHOO (hazard ratio [HR] 1.76; 95% CI 1.26, 2.45) and transition from MHOO to metabolically unhealthy phenotypes were associated with higher risk for diabetes (HR 2.97; 95% CI 1.79, 4.93 in MHOO to MUNW group and HR 3.38; 95% CI 2.54, 4.49 in MHOO to MUOO group). Instead, improvements to metabolic healthy phenotypes or weight loss occurring in MUOO reduced the risk of diabetes compared with stable MUOO, changing from MUOO to MHNW, MUNW, and MHOO resulted in HRs of 0.57 (95% CI 0.37, 0.87), 0.68 (95% CI 0.50, 0.93), and 0.45 (95% CI 0.34, 0.60), respectively. CONCLUSION: People with MHOO, even stable MHOO, or its transition to metabolically unhealthy phenotypes were at increased risk of diabetes. Metabolic improvements and weight control may reduce the risk of diabetes.

Plasma PFOA and PFOS Levels, DNA Methylation, and Blood Lipid Levels: A Pilot Study.

Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) is associated with blood lipids in adults, but the underlying mechanisms remain unclear. This pilot study aimed to investigate the associations between PFOA or PFOS and epigenome-wide DNA methylation and assess the mediating effect of DNA methylation on the PFOA/PFOS-blood lipid association. We measured plasma PFOA/PFOS and leukocyte DNA methylation in 98 patients enrolled from the hospital between October 2018 and August 2019. The median plasma PFOA/PFOS levels were 0.85 and 2.29 ng/mL. Plasma PFOA and PFOS levels were significantly associated with elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels. There were 63/87 CpG positions and 8/11 differentially methylated regions (DMRs) associated with plasma PFOA/PFOS levels, respectively. In addition, 5 CpG positions (annotated to AFF3, CREB5, NRG2, USF2, and intergenic region) and one DMR annotated to IRF6 may mediate the association between plasma PFOA/PFOS and LDL levels (mediated proportion from 7.29 to 46.77%); two CpG positions may mediate the association between plasma PFOA/PFOS and TC levels (annotated to CREB5 and USF2, mediated proportion is around 30%). The data suggest that PFOA/PFOS exposure alters DNA methylation. More importantly, the association of PFOA/PFOS with lipid indicators was partly mediated by DNA methylation changes in lipid metabolism-related genes.

Association of serum bisphenol A levels with incident overweight and obesity risk and the mediating effect of adiponectin.

BACKGROUND: Existing cross-sectional studies indicated a positive association of bisphenol A (BPA) with overweight and obesity. However, the relationship and potential mechanisms underlying this association remain to be elucidated in prospective studies. OBJECTIVE: This study was designed to investigate whether serum BPA is associated with incident overweight and obesity risk, and to further explore whether adiponectin plays a mediating role in the association. METHODS: We measured blood BPA and adiponectin in Chinese populations. The association of serum BPA with overweight and obesity risk was evaluated using multivariable logistic regression models. We further examined the mediating effect of adiponectin by causal mediation analysis. RESULTS: Among 796 participants free of overweight and obesity at baseline, 133 individuals developed overweight and obesity during the follow-up period. Compared with those in the lowest quartile of serum BPA, those in the second and third quartiles were positively associated with incident overweight and obesity risk adjusting for covariates (all P-values < 0.05), whereas this association was not observed in the fourth quartile. Further spline analysis showed an inverted U-shaped dose-response relationship (Pnon-linear = 0.04). Furthermore, each unit of serum log10-transformed BPA levels was associated with higher changes in waist-to-height ratio and body roundness index (all P-values < 0.05). Mediation analysis indicated significant indirect effects of adiponectin on the associations of BPA with overweight and obesity prevalence (mediation proportion: 46.08%; P = 0.02), and BMI levels (mediation proportion: 30.32%; P = 0.03). CONCLUSION: Serum BPA displayed a positive association with incident overweight and obesity risk in a non-monotonic pattern, and adiponectin might mediate the association. Further mechanistic studies are warranted.

Association of serum BPA levels with changes in lipid levels and dyslipidemia risk in middle-aged and elderly Chinese.

Previous evidences exploring the associations of BPA with lipid changes and dyslipidemia did not obtain consistent results. To evaluate whether serum BPA concentration was associated with changes in blood lipid levels and incident dyslipidemia risk in middle-elderly Chinese adults, we conducted a prospective study with 1093 participants (average 62.65 years old) derived from the Dongfeng-Tongji cohort which was founded in 2008 and followed up each 5 years. Serum BPA levels were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Changes in lipid levels were named as Δ lipids which equal to Lipid2013 - Lipid2008. The diagnosis of dyslipidemia was according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in 2016. We used multivariable linear regression and Logistic regression to explore the relations between serum BPA levels and changes in lipid levels and incident dyslipidemia risk, respectively. Besides, restricted cubic splines were used to explore the dose-response relations. After 5 years' follow-up, 51 individuals developed with hypercholesterolemia, 87 with hypertriglyceridemia, 34 with high-LDL-cholesterolemia, 74 with low-HDL-cholesterolemia, and 199 with dyslipidemia. At baseline serum BPA levels were positively related to TC, LDL-c, and Non-HDL-c levels. In the prospective study, each Ln-BPA increase was associated with 0.05 (95% CI: 0.02, 0.09) mmol/L increase in Δ TC, 0.07 (95% CI:0.03, 0.11) mmol/L increase in Δ Non-HDL-c, 0.05 (95% CI: 0.01, 0.08) increase in Δ TC/HDL-c, and 0.05 (95% CI: 0.01, 0.08) increase in Δ Non-HDL-c/HDL-c. We only observed significant associations in females but not in males. Besides, serum BPA levels were positively associated with hypercholesterolemia (OR=1.12, 95% CI: 1.01, 1.25). The restricted cubic splines obtained similar results. In conclusion, serum BPA was associated TC and Non-HDL-c changes, and BPA was also associated with increased risk of hypertriglyceridemia. Further prospective studies with large sample size are warranted to validate our findings.

Associations of serum PFOA and PFOS levels with incident hypertension risk and change of blood pressure levels.

Evidence on the associations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with hypertension or blood pressure (BP) levels was limited and inconsistent. The present prospective study aims to evaluate the longitudinal associations of serum levels of PFOA and PFOS with incident hypertension risk and change of blood pressure levels. At baseline 1080 participants (mean age 62 years, 58.9% females) free of hypertension, cardiovascular disease, diabetes, and cancer were followed up for nearly 5 years. Baseline serum levels of PFOA and PFOS were measured with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Hypertension was defined as any of (1) self-reported physician-diagnosed hypertension (2) use of hypotension drugs (3) measured systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Change of BP was evaluated as a difference between twice measurements (BP at follow-up visit－BP at baseline). After adjustment for multiple covariates, serum PFOS levels were negatively correlated with risk of hypertension [RR per lg-unit = 0.94 (95% CI: 0.88, 0.99)] and change of systolic BP [ß = -1.48 (95% CI: -2.56, -0.41)]. The highest vs lowest quartiles of PFOS concentration was negatively associated with hypertension risk. Compared with Q1, the RRs (95% CIs) for Q2, Q3, and Q4 were 0.83 (0.67-0.98), 0.81 (0.67-0.97), and 0.81(0.67-0.97), respectively (p for trend = 0.016). The negative associations remained in females but not in males (p for interaction = 0.44). No significant association of PFOA with hypertension risk was observed. Further studies are needed to validate our findings.

Associations of plasma metal levels with type 2 diabetes and the mediating effects of microRNAs.

The present study aims to determine the associations of multiple plasma metal levels and plasma microRNAs (miRNAs) with diabetes risk, and further explore the mediating effects of plasma miRNAs on the associations of plasma metal with diabetes risk. We detected plasma levels of 23 metals by inductively coupled plasma mass spectrometry (ICP-MS) among 94 newly diagnosed and untreated diabetic cases and 94 healthy controls. The plasma miRNAs were examined by microRNA Array screening and Taqman real-time PCR validation among the same study population. The multivariate logistic regression models were employed to explore the associations of plasma metal and miRNAs levels with diabetes risk. Generalized linear regression models were utilized to investigate the relationships between plasma metal and plasma miRNAs, and mediation analysis was used to assess the mediating effects of plasma miRNAs on the relationships between plasma metals and diabetes risk. Plasma aluminum (Al), titanium (Ti), copper (Cu), zinc (Zn), selenium (Se), rubidium (Rb), strontium (Sr), barium (Ba), and Thallium (Tl) levels were correlated with elevated diabetic risk while molybdenum (Mo) with decreased diabetic risk (P < 0.05 after FDR multiple correction). MiR-122-5p and miR-3141 were positively associated with diabetes risk (all P < 0.05). Ti, Cu, and Zn were positively correlated with miR-122-5p (P = 0.001, 0.028 and 0.004 respectively). Ti, Cu, and Se were positively correlated with miR-3141 (P = 0.003, 0.015, and 0.031 respectively). In addition, Zn was positively correlated with miR-193b-3p (P = 0.002). Ti was negatively correlated with miR-26b-3p (P = 0.016), while Mo and miR-26b-3p were positively correlated (P = 0.042). In the mediation analysis, miR-122-5p mediated 48.0% of the association between Ti and diabetes risk. The biological mechanisms of the association are needed to be explored in further studies.

Associations between serum PFOA and PFOS levels and incident chronic kidney disease risk in patients with type 2 diabetes.

Chronic kidney disease (CKD) is a common comorbidity among patients with type 2 diabetes. Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been linked to poorer kidney function in general population, but the related studies in individuals with diabetes were very limited. We aimed to examine the longitudinal associations of PFOA and PFOS exposure and CKD incidence among diabetes patients. Baseline levels of PFOA and PFOS were measured in serum in 967 diabetes patients from the Dongfeng-Tongji cohort. Multivariable logistic regression models were used to characterize the relationship between serum PFOA and PFOS levels and incident CKD risk (defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2). During 10-years follow-up, 267 incident CKD cases were identified. Only PFOS level was significantly associated with lower risk of CKD incidence (adjusted OR: 0.67; 95%CI: 0.51, 0.88). Such inverse association was only observed among participants with lower eGFR levels (< 70 mL/min/1.73 m2), although the interaction did not achieve statistical significance. Notably, an inverted U-shaped relationship between eGFR and serum PFOS level (Pfor nonlinearity < 0.001) was observed based on the 1825 subjects with available data at baseline. PFOS exposure was negatively associated with CKD incidence in patients with diabetes, especially in those with baseline eGFR levels < 70 mL/min/1.73 m2. This may be explained by the implication of baseline kidney function on the serum PFAS concentrations which in turn affect the relationship between PFOS exposure and the incident CKD risk among diabetes.

Particle size and surfactant effects on chemical mechanical polishing of glass using silica-based slurry.

This study explores the effect of particle size and surfactant on the chemical mechanical polishing (CMP) of glass using colloidal silica-based slurry. It was found that the material removal rate strongly depends on the particle size and the types of surfactants and that the rms roughness was independent of particle size and correlated to surfactants. On the basis of polishing results, it was concluded that the main polishing mechanism was changed from indentation mechanism to surface-area mechanism, with the variation of particle size. In addition, the molecular structure, charge type, and lubricating effect of the surfactants play an important role in the dispersion of abrasive particles and in the CMP performance.