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Abstract Objective The aim of this study was to investigate the dynamic changes in QTc interval duration among patients with COVID-19 infection before, during, and after infection, in order to assess the short- and potential long-term impact of COVID-19 on cardiac electrophysiology. Methods A retrospective analysis was conducted on 303 inpatients diagnosed with COVID-19 who visited a tertiary Grade A hospital in China between August 2022 and December 2023. Inclusion criteria required patients to have at least two electrocardiogram (ECG) recordings at three specific time points: before COVID-19 infection, during acute infection, and after recovery (more than one month post-infection). Results The mean age of participants was 72.8 ± 14.7 years, with a male preponderance (62%, n = 188). A significant prolongation of QTc interval was observed during COVID-19 infection compared to pre-infection levels (438.3 ± 26.7 ms vs. 433.9 ± 26.6 ms, p = 0.025). QTc interval was positively correlated with age both before (r = 0.23, p = 0.001) and during infection (r = 0.19, p = 0.001). In short-term follow-up (≤ 6 months), QTc interval remained unchanged from the infectious period (p > 0.05), whereas it significantly decreased during long-term follow-up (> 6 months; 429.6 ± 32.5 ms vs. 437.5 ± 28.2 ms, p = 0.002). Additionally, P-wave duration significantly decreased from the infectious period to long-term follow-up (99.5 ± 14.8 ms to 96.4 ± 15.2 ms, p = 0.024). Conclusions COVID-19 infection demonstrated a significant correlation with prolonged QTc interval, persisting in the short term but gradually returning to normal in the long term. Similarly, P-wave duration shortened over time, suggesting potential cardiac electrophysiological recovery. Clinical trial number Not applicable.

BackgroundPerfluorinated and polyfluoroalkyl substances (PFAS), a large group of emerging pollutants, are ubiquitous in the ecological environment. Their multiple organ toxic effects on human body are reported. Understanding the exposure level of PFAS in cord serum and associated influencing factors can provide scientific evidence for studying maternal and newborn health effects and risk regulation.ObjectiveTo explore the exposure levels of PFAS in cord serum and potential impact factors.MethodsThis study was based on the maternal and infant database and the cord serum sample bank of the Sheyang Mini Birth Cohort Study (SMBCS) established in 2009. A self-designed questionnaire was used to collect information on sociodemographic characteristics, living environment, and lifestyle of mothers during pregnancy. A total of 1097 cord serum samples were measured utilizing ultra-high performance liquid chromatography-Q-Exactive Orbitrap high-resolution mass spectrometry. Multiple linear regression models were used to identify influencing factors related to PFAS exposure level in cord serum.ResultsA total of 38 types of PFAS were detected in the cord serum samples, including 20 perfluorocarboxylic acids (PFCA), 14 perfluorosulfonic acids (PFSA), and 4 other types of PFAS. The detection rates of 14 PFAS compounds were above 50%. The detection rates of perfluoro-1-hexanesulfonic acid (PFHxS), perfluoro-1-octanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA) were in the range of 99.18%-100.00%. The median concentrations of PFOA and 6∶2 chlorinated polyfluorinated ether sulfonic acid (6∶2CI-PFESA) were higher than those of the other compounds, which were 3.76 µg·L−1 and 2.61 µg·L−1, respectively. The correlation coefficients among cord serum PFAS were in the wide range of 0.0911-0.8429 (P < 0.05). The associations between PFHxS and perfluoro-1-heptanesulfonic acid (PFHpS) (r=0.8429, P < 0.05), PFOS and PFHpS (r=0.7012, P < 0.05), and PFUdA and perfluorododecanoic acid (PFDoA) (r=0.7875, P < 0.05) were positive. The proportions of PFCA and PFSA in the cord serum samples were 60.1% and 38.4%, respectively. PFOA and 6∶2 Cl-PFESA were the predominant compounds in the cord serum samples, whose proportions were 37.8% and 19.3%, respectively. The concentrations of specific types of cord serum PFAS had varied associations with the following demographic variables of pregnant women: age, parity, education level, gestational age, and occupation. The multiple linear regression analysis found that the concentrations of 8 PFAS (PFHxS, PFHpS, PFNA, PFOS, PFDA, PFUdA, PFDoA, and 6∶2 CI-PFESA) in umbilical cord serum were lower in pregnant women aged 25 years and older than in those under the age of 25 years; compared to pregnant women with education levels at or below junior middle school, those with education levels at or above high school had lower concentrations of perfluoroheptanoic acid (PFHpA); the concentration of PFHpA in cord serum was negatively correlated with household annual income; multiparous women had higher concentrations of PFNA, PFUdA, and PFDoA than primiparous women; compared to mothers engaged in manual labor, the concentration of perfluoro-1-butanesulfonic acid (PFBS) in umbilical cord serum was lower in mothers engaged in mental labor, while the concentrations of PFBS and PFOA were lower and the concentrations of perfluorotridecanoic acid (PFTrDA) and 8∶2 chlorinated polyfluorinated ether sulfonic acid (8∶2CI-PFESA) were higher in mothers of other occupational types; the concentrations of umbilical cord serum PFOA, PFOS, PFUdA, and PFDoA were positively correlated with the gestational age of pregnant women, while N-methylperfluoro-1-octanesulfonamido acetic acid (N-MeFOSAA) was negatively correlated with the gestational age of pregnant women; PFTrDA was negatively correlated with the birth weight of newborns; compared with those with insufficient gestational weight gain, those with adequate gestational weight gain had lower PFDoA, while those with excess gestational weight gain had higher N-MeFOSAA.ConclusionPFAS compounds exposure is common in the mothers and infants in the study area. PFOA and 6∶2 CI-PFESA are the two main compounds in cord serum. Cord serum PFAS are associated with several demographic characteristics of the pregnant women. Future research needs to pay more attention to PFAS alternatives and other emerging contaminants.

Exposure to perfluorooctane sulfonate (PFOS) has been associated with lower bone density and the occurrence of osteoporosis in human studies, but the effects and mechanisms of PFOS induces bone loss is not well understood. Our research is aimed at examining the effects of PFOS on osteoblastic activity and investigating the toxicological mechanisms of PFOS-induced bone loss. Cell proliferation, ALP activity, bone nodule formation, ROS levels, and cell apoptosis were assessed after treating osteoblasts with different concentrations of PFOS. Through transcriptome analysis, the differentially expressed genes (DEGs) were screened and the biofunctions were elucidated by Kyoto Encyclopedia of Genes and Genomes (KEGG) and The Gene Set Enrichment Analysis (GSEA). Vation of important genes and protein expression was accomplished using RT-PCR and Western blot methods, respectively. The results show that PFOS can reduce bone formation markers and improve oxidative stress and cell apoptosis. The DEGs in PFOS-treated groups were involved in multiple pathways, including FoxO, HIF-1, Rap1, Hippo, and sphingolipid signaling. FoxO1 was validated as the key gene which regulates osteogenic differentiation and redox status. Our findings suggest that PFOS reduces bone formation through FoxO1-mediated oxidative stress and apoptosis, as well as inhibition of the OPG/RANKL and FoxO1/β-catenin pathways. It will be beneficial for early intervention or treatment of PFOS-induced bone loss, highlighting the importance of regulatory measures to limit human exposure to PFOS.

Background: Pesticides may impact children’s neurodevelopment. As children’s metabolic function and neural plasticity change throughout their growth and development, the effects of pesticide exposure may also vary. Objectives: We aimed to identify the trajectories of combined pesticide exposure during childhood, and to examine the associations of the exposure trajectories with children’s neurobehavior at the age of 10. Methods: We involved repeated measurements of three pesticide metabolites [Pentachlorophenol (PCP), 3,5,6-Trichloro-2-pyridinol (TCPy), and Carbofuran phenol (CFP)], in urine samples collected from children in a cohort study at ages 1, 2, 3, 6, 7, 8, 9, and 10 years. The group-based multi-trajectory model (GBMT) and latent class analysis (LCA) were separately utilized to describe the distinct trajectories and patterns of pesticide mixture exposure during childhood. Meanwhile, the Strengths and Difficulties Questionnaire (SDQ) and attention deficit hyperactivity disorder (ADHD) Criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) list were applied to assess behavioral disorders in children. The associations between exposure trajectories and behavioral problem scores were then examined. Results: The GBMT model delineated three distinct trajectories of combined pesticide exposure among children: consistently low, higher levels in early childhood transitioning to lower levels during pre-school age, and lower levels in early childhood followed by higher levels in the middle childhood. The LCA model identified three similar longitudinal exposure patterns. Further, the children in the second trajectory group identified by GBMT, characterized by higher early childhood exposure levels, exhibited significantly elevated hyperactivity/inattention scores of the SDQ compared to the other two groups (β = 0.46, 95 %CI: 0.11, 0.81; β = 0.44, 95 %CI: 0.02, 0.86). Conclusions: Our study revealed that exposure to pesticides during early childhood (especially before the age of two), rather than other age periods, was linked to hyperactivity/inattention problems in children aged 10 years. We also provided a novel perspective on characterizing the fluctuation in repeated measurements of multiple environmental chemicals and identifying the potential critical windows.

BackgroundPer- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants that possess potential toxicity to the human body. The production and utilization of diverse emerging PFAS have resulted in widespread human exposure. Therefore, it is imperative to establish a quantitative methodology encompassing a wide range of PFAS for a comprehensive assessment of human exposure to these compounds. ObjectiveTo establish a high-throughput quantitative method for the simultaneous determination of 53 PFAS in human serum based on ultra-high-performance liquid chromatography-Q Exactive high resolution mass spectrometry (UPLC-Q Exactive HRMS). MethodsThe extraction recoveries of hydrophilic-lipophilic balance (HLB) column, weak anionexchange (WAX) column, and 96-well WAX μElution plate were compared to select the SPE column with the highest recovery. The retention time and peak shape of the target compounds were compared between ACQUITY UPLC BEH C18 column and Accucore aQ column, and the more cost-effective column was chosen. The effects of adding different levels of ammonium formate (0, 2, 5 and 10 mmol·L−1) in mobile phase on peak shape and target response were compared to determine the optimal buffer salt concentration. The optimal spray voltage was obtained by comparing −2 kV and −4 kV. The proposed method was validated from the aspects of selectivity, standard curve, limits of detection, precision, accuracy, and matrix effect. The method was applied to 142 umbilical serum samples. ResultsThe best recovery rate (64%-118%) was achieved by using 96-well WAX μElution plate. The optimal separation and peak shape were obtained by utilizing Accucore aQ column with H2O-methanol (containing 5 mmol·L−1 ammonium formate) as the mobile phase. Less in-source collision and better target response were observed when the spray voltage was set to −2 kV. All target analytes had a good linearity, with R2 > 0.99. The limits of detection ranged from 0.01 to 0.50 μg·L−1, and the recovery ranged from 69% to 127% with the precision less than 26%. A total of 31 PFAS were detected in the 142 actual samples, among which 14 PFAS had a detection frequency over 50%. Perfluorooctanoic acid showed the highest median concentration of 4.16 μg·L−1, followed by 6:2 chlorinated polyfluorinated ether sulfonate and perfluorooctane sulfonates (3.50 μg·L−1 and 1.59 μg·L−1, respectively). ConclusionIn this study, we establish a UPLC-Q Excative HRMS method for simutanious determination of 53 PFAS concentrations in serum. This method has the advantages of wide coverage of PFAS, good selectivity, and easy operation, and is suitable for biological detection with a large sample size.

Abstract Aims Previous studies have shown a significant reduction in skeletal muscle content in patients with chronic heart failure (CHF). The present study focused on the erector spinae muscle (ESM) to determine whether ESM content is associated with the development and severity of CHF. Methods and results A total of 652 patients were included in this trial for the study. According to the diagnostic criteria of CHF, 652 patients were divided into two groups, namely, the control group (268 patients) and the CHF group (384 patients). Meanwhile, to assess whether the ESM is associated with the severity of CHF, patients in the CHF group were divided into two groups according to left ventricular ejection fraction (LVEF) values: heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%, 256 patients) and heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%, 68 patients). Receiver operating curve analysis was performed to assess whether ESM content could predict CHF and determine its severity. Compared with the control group, the patients in the CHF group were older, the prevalence of coronary heart disease (CHD) and atrial fibrillation was higher, the colour ultrasound results showed that LVEF decreased significantly, and the left ventricular end‐diastolic internal diameter and left ventricular end‐systolic internal diameter increased significantly. Besides, patients in the CHF group had significantly lower ESM content, and ESM is an independent predictor of heart failure, with an odds ratio of 0.713 (CHF group vs. control group, 95% confidence interval 0.626–0.811, P

BackgroundParabens, a widely used class of preservatives, are suspected to be potential obesogens as emerging endocrine disrupting chemicals with reproductive and developmental toxicity. ObjectiveTo analyze five urinary parabens (PBs) and estimate the associations of exposure to PBs with adiposity measures in 10-year-old school-age children. MethodsA total of 471 school-age children aged 10 years from the Sheyang Mini Birth Cohort were enrolled in this study. A questionnaire survey was conducted to collect socio-demographic information, physical activity, and dietary intake. Weight, height, and waist circumference of children were measured, and age- and sex-adjusted body mass index (BMI-Z score) was calculated. Spot urine samples were collected during the follow-up visits. Urinary concentrations of five PBs including methyl-paraben (MeP), ethyl-paraben (EtP), propyl-paraben (PrP), butyl-paraben (BuP), and benzyl-paraben (BzP) were detected by gas chromatography-tandem mass spectrometry (GC-MS/MS). Generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR) models were applied to estimate associations of individual/overall urinary PBs concentrations with BMI Z-score and waist circumference. ResultsThe positive rates of selected five urinary PBs were in the range from 78.98% to 98.94%. The urinary PBs concentrations (geometric mean) were in the range of 0.31-5.43 μg·L−1. The children's BMI Z-score and waist circumference (mean ± standard deviation) were (0.56±1.40) and (67.62±10.07) cm respectively. The GLMs results showed that the urinary BzP concentration was negatively associated with waist circumference (b=−0.08, 95%CI: −0.14, −0.02; P=0.01). In sex-stratified analysis, the urinary concentration of BzP was negatively associated with BMI-Z score (b=−0.59, 95%CI: −0.88, −0.30; P

Abstract Nonalcoholic steatohepatitis (NASH) is a rapidly developing pathology around the world, with limited treatment options available. Some farnesoid X receptor (FXR) agonists have been applied in clinical trials for NASH, but side effects such as pruritus and low‐density lipoprotein elevation have been reported. Intestinal FXR is recognized as a promising therapeutic target for metabolic diseases. Glycine‐β‐muricholic acid (Gly‐MCA) is an intestine‐specific FXR antagonist previously shown to have favorable metabolic effects on obesity and insulin resistance. Herein, we identify a role for Gly‐MCA in the pathogenesis of NASH, and explore the underlying molecular mechanism. Gly‐MCA improved lipid accumulation, inflammatory response, and collagen deposition in two different NASH models. Mechanistically, Gly‐MCA decreased intestine‐derived ceramides by suppressing ceramide synthesis–related genes via decreasing intestinal FXR signaling, leading to lower liver endoplasmic reticulum (ER) stress and proinflammatory cytokine production. The role of bile acid metabolism and adiposity was excluded in the suppression of NASH by Gly‐MCA, and a correlation was found between intestine‐derived ceramides and NASH severity. This study revealed that Gly‐MCA, an intestine‐specific FXR antagonist, has beneficial effects on NASH by reducing ceramide levels circulating to liver via lowering intestinal FXR signaling, and ceramide production, followed by decreased liver ER stress and NASH progression. Intestinal FXR is a promising drug target and Gly‐MCA a novel agent for the prevention and treatment of NASH.

Abstract We investigated the alteration of gut microbiota and the associated metabolic risks in hypertensive patients with obstructive sleep apnea (OSA) comorbidity. Fecal and blood samples were collected from 52 hypertensive patients, who were divided into three groups: A (controls, apnea‐hypopnea index[AHI] 20, n = 20). The composition of the gut microbiota was studied through 16s RNA sequencing of variable regions 3–4. Analysis of the results revealed that group C had a significant higher concentration of total cholesterol, low‐density lipoprotein, and IL‐1β compared with group A. The Shannon index showed that bacterial biodiversity was lower in OSA patients. At the phylum level, the ratio of Firmicutes to Bacteroidetes (F/B) was significantly higher in group C than in groups A and B. At the genus level, the relative abundance of short‐chain fatty acids (SCFA)‐producing bacteria (e.g., Bacteroides and Prevotella) was lower while the number of inflammation‐related bacteria (e.g., Lactobacillus) was increased in patients with OSA. We found that the IL‐1β level was negatively correlated with Bacteroidetes. The area under the receiver operating characteristic curve was .672 for F/B ratio in determining hypertensive patients with OSA. In patients with hypertension, OSA was associated with worse gut dysbiosis, as evidenced by decreased levels of short‐chain fatty acids‐producing bacteria and increased number of inflammation‐related bacteria. The differences in gut microbiota discriminate hypertensive patients with OSA from those without and may result in an enhanced inflammatory response and increase the risk of metabolic diseases.

Bacillus cereus is a food-borne pathogen that can produce cereulide in the growth period, which causes food poisoning symptoms. Due to its resistance to heat, extreme pH, and proteolytic enzymes, cereulide poses a serious threat to food safety. Temperature, pH, and aw can influence cereulide production, but there is still a lack of research with multi-environmental impacts. In this study, the effects of temperature (15~45 °C), pH (5~8), and aw (0.945~0.996) on the emetic reference strain B. cereus F4810/72 growth, cereulide production, relevant ces genes (cesA, cesB, cesP), and transcription regulators genes (codY and abrB) expression at transcription level were studied. B. cereus survived for 4~53 h or grew to 6.85~8.15 log10 CFU/mL in environmental combinations. Cereulide accumulation was higher in mid-temperature, acidic, or high aw environments. Increased temperature resulted in a lower cereulide concentration at pH 8 or aw of 0.970. The lowest cereulide concentration was found at pH 6.5 with an increased aw from 0.970 to 0.996. Water activity had a strong effect on transcriptional regulator genes as well as the cesB gene, and temperature was the main effect factor of cesP gene expression. Moreover, environmental factors also impact cereulide synthesis at transcriptional levels thereby altering the cereulide concentrations. The interaction of environmental factors may result in the survival of B. cereus without growth for a period. Gene expression is affected by environmental factors, and temperature and pH may be the main factors influencing the correlation between B. cereus growth and cereulide formation. This study contributed to an initial understanding of the intrinsic link between the impact of environmental factors and cereulide formation and provided valuable information for clarifying the mechanism of cereulide synthesis in combined environmental conditions.

Abstract Background Arterial stiffness index (ASI) is closely related to coronary atherosclerosis. This study aims to explore whether ASI can predict coronary heart disease (CHD) and its severity. Methods In this study, a total of 726 patients with suspected CHD were recruited. Based on coronary angiography results, the subjects were assigned into three groups: the control group (without obvious coronary artery disease), single-vessel disease group, and multi-vessel disease group (the number of vessels diseased ≥ 2). At the same time, according to the results of angiography, myocardial enzyme spectrum, electrocardiogram, color Doppler echocardiography and clinical manifestations, these patients were divided into four groups: the control group, stable angina (SA) Group, unstable angina (UA) group, and acute myocardial infarction (AMI) group. We have compared whether there were differences in ASI and related baseline data between groups. Receiver operating curve (ROC) analysis was conducted to determine whether ASI could predict CHD and evaluate the severity. Results ASI was positively correlated with the number of diseased branches of coronary artery. The value of ASI was increased as the number of the diseased branches increased. The ASI value in the SA group was significantly higher compared with the control group. Furthermore, the ASI value in the UA and AMI groups was remarkably increased compared with the control and SA groups. The results of ROC analysis indicated that the sensitivity and specificity of ASI was 71.0% and 85.4% in diagnosing CHD, respectively. While ASI was used in predicting the severity of CHD, the sensitivity was 72.1% and specificity 57.9%. Conclusion ASI is of great value in the diagnosis of coronary heart disease and the prediction of its severity.

Background: Urinary para-nitrophenol (PNP), an exposure biomarker of ethyl parathion (EP) and methyl parathion (MP) pesticides, was still pervasively detected in the general population even after global restriction for years. And the concern whether there is an association of PNP level with child development of the nervous system is increasing. The current study aimed to evaluate the maternal urinary PNP concentrations during late pregnancy and the associations of PNP levels with cognitive and motor function of their children at the age of 2 years. Methods: 323 mother-child pairs from the Sheyang Mini Birth Cohort Study were included in the current study. Gas chromatography-tandem mass spectrometry was used to measure concentrations of PNP, the specific metabolite of EP and MP, in maternal urine samples during pregnancy. Developmental quotients (DQs) scores measured with Gesell Developmental Scales were employed to evaluate cognitive and motor function of children aged 2 years. Generalized linear models were performed to analyze the associations of PNP concentrations in pregnant women’s urine samples with cognitive and motor function of their children. Results: Maternal PNP was detected in all urine samples with a median of 4.11 μg/L and a range from 0.57 μg/L to 109.13 μg/L, respectively. Maternal urinary PNP concentrations showed a negative trend with DQ of motor area [regression coefficient (β) = − 1.35; 95 % confidence interval (95 %CI): − 2.37, − 0.33; P

Flurochloridone (FLC), a wildly used herbicide, could induce hepatotoxicity after long-term exposure to male rat, in addition to its reactive oxygen species (ROS)-dependent reproductive toxicity. The hepatotoxicity effect and mechanism was investigeted using 1, 10 and 100 μmol L−1 FLC treated BRL-3A liver cell in this study. The function of mitochondrial respiration, glycolysis rate and real time ATP production rate are determined by seahorse XF analyzer, and the bio-transformers of FLC, intermediates of TCA cycle and glycolysis, and related amino acids are determined and identified by [U-13C] Glucose metabolic flux technology based on UPLC-HRMS. The mRNA expression of cytochrome P450s and the key regulatory enzymes of glucose metabolism and γ- glutamyl cycle pathway. The protein expressions of protein kinase B (AKT) and glycogen synthase kinase-3 beta (GSK-3β) were determined. The results show dechlorination and glutathione (GSH) conjugate products of FLC are predominant bio-transformmers after 24 h treatment in BRL-3A cell. FLC could enhance glycolysis function and inhibit mitochondrial aerobic respiratory, which is accompanied by the decreased total ATP level and ATP produced rate. Increased glucose-6-phosphate, fructose-6-phosphate, pyruvate and lactate levels, and elevated level of GSH and its precursor 5-glutamate-cysteine (γ-Glu-Cys) are observed in FLC treated cells, which indicates that energy metabolism dysfunction and GSH accumulation could be potentially mediated by activating γ- Glutamyl cycle pathway. Conclusively, FLC induced hepatotoxicity could be potentially related to some free radical reactions, including inhibiting mitochondrial function, glucose metabolism via glycolysis, regulating γ- glutamyl cycle pathway to promote reactive oxygen species (ROS) level, and then induced cell apoptosis by inhibiting AKT/GSK-3β signal.

Atrial fibrillation (AF) is characterized by high morbidity and disability rate. The incidence of AF has rapidly increased due to increased aging population, causing a serious burden on society and patients. Therefore, it is necessary to determine the prevention and treatment of AF. Several studies have assessed the occurrence, development mechanism, and intervention measures of AF. The human gut has several non-pathogenic microorganisms forming the gut flora. The human gut microbiota plays a crucial role in the construction and operation of the metabolic system and immune system. Emerging clinical studies and basic experiments have confirmed that intestinal flora and its metabolites have a role in some metabolic disorders and chronic inflammatory diseases. Moreover, the gut microbiota has a role in cardiovascular diseases, such as hypertension and heart failure. However, the relationship between AF and gut microbiota is unclear. This review summarizes the relevant literature on the relationship between AF and intestinal flora with its metabolites, including Trimethylamine N-Oxide, short-chain fatty acids, lipopolysaccharide and bile acids. Therefore, this review may enhance further development of related research.

Background: Carbamate pesticides are widely used in agriculture and cause widespread human exposure. The health effect of carbamates on physical development remains unclear. The current study aimed to explore the carbamate’s health effect on physical development. Methods: Prenatal, 3-year-old, 7-year-old urinary carbofuranphenol concentration was measured by gas chromatography tandem mass spectrometry and adjusted by creatinine. Anthropometric indices were measured by standard method and z-score standardized. Generalized linear models (GLM) were using to assess associations between exposure measurements and anthropometric indices. The generalized estimate equation (GEE) was applied to analyze the association between multiperiod exposure and anthropometric indices, and time-interaction terms were used to exam health effect consistency of exposure in each period. Gender-stratified analysis were conducted according to results of gender-interaction terms to identify gender-specific effects. Results: The gender-interaction term of prenatal exposure with height z-score was significant (β = -0.057; 95% CI: −0.113, −0.001; p = 0.045). The 3-year-old carbofuranphenol level showed negative associations with weight z-score (β = -0.019; 95% CI: −0.038, −0.000; p = 0.040), height z-score (β = -0.015; 95% CI: −0.028, −0.001; p = 0.026), chest circumference (β = -0.086; 95% CI: −0.171, −0.001; p = 0.046), and waist circumference (β = -0.128; 95% CI: −0.230, −0.026; p = 0.014). No statistically significant trend was found for prenatal and 7-year-old carbofuranphenol levels. In GEEs, carbofuranphenol level was negatively associated with weight z-score (β = -0.103; 95% CI: −0.195, −0.011; p = 0.027), height z-score (β = -0.087; 95% CI: −0.152, −0.022; p = 0.008), and chest circumference (β = -0.472; 95% CI: −0.918, −0.026; p = 0.037). Boy’s height z-score was inversely associated with carbamate exposure (β = -0.140; 95% CI: −0.227, −0.053; p = 0.001). Conclusions: Prenatal and postnatal carbamate exposure may affect physical developmental process.

Background: Early-life carbamate exposure during developmental period has been linked with adverse health effects and attracted attention. Methods: Three hundred and three children at age of seven were included in the current study. Urinary carbofuranphenol concentrations were measured using gas chromatography-tandem mass spectrometry. Verbal, performance and full-scale intelligence quotients (IQV, IQP, and IQFS) were assessed using Wechsler Intelligence Scale for Children-Chinese Revised. Generalized linear models were used to explore the associations between carbofuranphenol levels and IQs. Generalized estimating equations were used to explore long-term health effect and sensitive time window. Results: Carbofuranphenol was detected in 96.6% of the seven-year-old urinary samples, the geometric mean, median, and inter quartile range of the carbofuranphenol concentrations were 0.67 μg/L, 0.30 μg/L, and 0.09–3.72 μg/L, respectively, which were similar with the level of three-year-old children from the SMBCS cohort. Seven-year-old carbofuranphenol level was negatively associated with IQP [β = −0.044; 95% confidence interval (CI): −0.087, −0.001; p = 0.045]. Three-year-old carbofuranphenol level was negatively associated with IQP (β = −0.100; 95% CI: −0.186, −0.014; p = 0.022) and IQFS (β = −0.087; 95% CI: −0.173, −0.001; p = 0.047). Carbamate exposure of maternal and children at both three and seven years old had negative associations with IQP (β = −0.089; 95% CI: −0.171, −0.007; p = 0.034), and IQFS (β = −0.064; 95% CI: −0.127, −0.000; p = 0.049) of children at age of seven. Conclusion: Results of the present study verify that children in an agricultural region of China were widely exposed to carbamate pesticides. Carbamate exposure in utero and at three and seven years may adversely impact children’s neurodevelopment.

Objective: Prenatal exposure to heavy metals, pesticides and phenols has been suggested to interfere with neurodevelopment, but the neurotoxicity of their mixtures is still unclear. We aimed to elucidate the associations of maternal urinary concentrations of selected chemical mixtures with intelligence quotient (IQ) in children. Methods: Maternal urinary concentrations of selected heavy metals, pesticide metabolites, and phenols were quantified in pregnant women who participated in the Sheyang Mini Birth Cohort Study (SMBCS) from June 2009 to January 2010. At age 7 years, child’s IQ score was assessed using the Chinese version of Wechsler Intelligence Scale for Children (C-WISC) by trained pediatricians. Generalized linear regression models (GLM), Bayesian kernel machine regression (BKMR) models and elastic net regression (ENR) models were used to assess the associations of urinary concentrations individual chemicals and their mixtures with IQ scores of the 7-year-old children. Results: Of 326 mother-child pairs, single-chemical models indicated that prenatal urinary concentrations of lead (Pb) and bisphenol A (BPA) were significantly negatively associated with full intelligence quotient (FIQ) among children aged 7 years [β = −2.31, 95% confidence interval (CI): −4.13, −0.48; p = 0.013, sex interaction p-value = 0.076; β = −1.18, 95% CI: −2.21, −0.15; p = 0.025; sex interaction p-value = 0.296, for Pb and BPA, respectively]. Stratified analysis by sex indicated that the associations were only statistically significant in boys. In multi-chemical BKMR and ENR models, statistically significant inverse association was found between prenatal urinary Pb level and boy’s FIQ scores at 7 years. Furthermore, BKMR analysis indicated that the overall mixture was associated with decreases in boy’s IQ when all the chemicals’ concentrations were at their 75th percentiles or higher, compared to at their 50th percentiles. ENR models revealed that maternal urinary Pb levels were statistically significantly associated with lower FIQ scores (β = −2.20, 95% CI: −4.20, −0.20; p = 0.031). Conclusions: Prenatal exposure to selected chemical mixtures may affect intellectual performance at 7 years of age, particularly in boys. Pb and BPA were suspected as primary chemicals associated with child neurodevelopment.

Background/Aims: To investigate the impact of renal denervation (RDN) on myocardial fibrosis and ventricular arrhythmias (VAs) in rats with ischemic cardiomyopathy. Methods: An ischemic cardiomyopathy model was reproduced with myocardial infarction (MI) in adult Sprague–Dawley male rats. The RDN/Sham-RDN procedure was performed at 2 weeks after MI. Sham-MI and sham-RDN rats served as the control group. At 4 weeks after RDN, programmed electrical stimulation (PES) was used to induce VAs, including ventricular tachycardia and ventricular fibrillation, in all 3 groups (MI+RDN, MI, and control groups). At the end of PES, heart and kidney samples were harvested. Immunofluorescence labeling was used to investigate the distribution of connexin 43 (Cx43) in the infarcted border zone. Masson’s trichrome stain was adopted to determine the degree of cardiac fibrosis. Western blotting was performed to identify the expression of transforming growth factor beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and Cx43. An enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of B-type natriuretic peptide (BNP) and the amino-terminal pro-peptides of type I and III collagen (PINP and PIIINP, respectively) and the expression level of renal norepinephrine. Results: Compared with the MI group, RDN significantly decreased the inducibility of VAs (MI+RDN 3/8 rats vs. MI 8/9 rats, P < 0.05; control 1/8 rats) with PES, reduced myocardial fibrosis estimated by collagen volume fraction (MI+RDN 31.10 ± 3.97% vs. MI 54.80 ± 16.39%, P < 0.001; control 4.41 ± 0.92% ), suppressed TGF-β1 (P < 0.01) and α-SMA (P < 0.001) levels, and attenuated both PINP (MI+RDN 41.44 ± 10.10 ng/mL vs. MI 95.49 ± 24.83 ng/mL, P < 0.001; control 11.90 ± 4.96 ng/mL) and PIIINP (MI+RDN 82.12 ± 30.79 ng/mL vs. MI 124.60 ± 26.64 ng/mL, P < 0.05; control 64.69 ± 23.84 ng/mL) levels. Moreover, RDN reversed the abnormal myocardial distribution of Cx43 and its reduction by MI damage (P < 0.01). Conclusions: RDN reduced myocardial fibrosis and suppressed VAs in a rat model of ischemic cardiomyopathy.

In recent years, optically trapped luminescent particles have emerged as a reliable probe for contactless thermal sensing because of the dependence of their luminescence on environmental conditions. Although the temperature effect in the optical trapping stability has not always been the object of study, the optical trapping of micro/nanoparticles above room temperature is hindered by disturbances caused by temperature increments of even a few degrees in the Brownian motion that may lead to the release of the particle from the trap. In this report, we summarize recent experimental results on thermal sensing experiments in which micro/nanoparticles are used as probes with the aim of providing the contemporary state of the art about temperature effects in the stability of potential trapping processes.

Background/Aims: To investigate the effects of renal denervation (RDN) on multi-organ fibrosis and vascular remodeling in cardiomyopathy. Methods: Thirty-six male Sprague-Dawley rats underwent transverse aortic constriction (TAC). Five weeks later, 28 surviving TAC rats were randomly assigned to three groups: (1) RDN, (2) Sham, (3) Carvedilol. Six male Sham TAC rats served as the Control. Ten weeks after TAC, samples were collected. Results: TAC rats showed an increased diastolic interventricular septal thickness at week 5. At 10 weeks, Masson staining showed that left ventricular and renal glomerular fibrosis were significantly reduced in RDN compared with Sham group. In comparison to Sham group, hepatic perivascular fibrosis was attenuated in both RDN and Carvedilol group, so were the media thickness and the media/lumen of aorta. The plasma levels of B-type natriuretic peptide (BNP), Cystatin C (Cys-C), Alanine Transaminase, angiotensin II (Ang II), transforming growth factor beta 1 (TGF-β1), and malondialdehyde increased, and total superoxide dismutase (T-SOD) decreased in Sham but not in RDN group, compared with Control group. Both RDN and Carvedilol reduced the Cys-C and TGF-β1 levels, and restored T-SOD concentration, compared with Sham group. While only RDN lowered the plasma levels of BNP and Ang II. No significant effects of RDN on blood pressure (BP) and heart rate (HR) were oberved. Conclusions: RDN can attenuate multi-organ fibrosis and improve vascular remodeling independent of BP and HR change in TAC-induced cardiomyopathy. These effects of RDN may be associated with the direct inhibition of renin-angiotensin-aldosterone system and oxidative stress.

Perfluorooctanoic acid (PFOA) exposure level in human is negatively correlated with bone density according to the epidemiological research. Our study is aim to investigate the effects and mechanisms of PFOA on osteoblastic bone formation and osteoclastic bone resorption. Primary osteoblasts were isolated from the calvaria of newborn rats, and the cell proliferation, alkaline phosphatase (ALP) activity, and bone nodule formation were detected after 1,10, and 100 μmol/L PFOA treateatment for 24 h.The osteoclasts model were differentiation from bone marrow monocyte, which induced by Macrophage colony-stimulating factor (M-CSF) and Nuclear factor κB receptor-activating factor ligand (RANKL), and the effects on cell viability, anti-tartaric acid phosphatase (TRAP) activity, and bone resorption pit formation were investigated. The expression of OPG and RANKL proteins in osteoblasts were conducted by Western blot. The results show that PFOA at the concentration of 1 μmol/L and 10 μmol/L can promote osteoblast proliferation, but has no effect on ALP activity and bone nodule formation. 100 μmol/L PFOA can significantly inhibit cell proliferation, ALP activity, and bone nodule formation, as well as the proportion of OPG/RANKL protein expression. PFOA has no effect on osteoclast viability, and 10 μmol/L and 100 μmol/L PFOA can significantly inhibit the TRAP activity and the area of bone resorption pits. The conclusion can be draw that high concentration of PFOA can inhibit the bone formation of osteoblasts by suppressing WNT pathway and promote osteoclast bone resorption by inhibiting the OPG/RANKL/RANK pathway. [ABSTRACT FROM AUTHOR]