Identification of Sulfur-Containing Chlorinated Paraffin Structural Analogues in Human Serum: Origination from Biotransformation or Bioaccumulation?

Chlorinated paraffins (CPs) are manufactured and used in high quantities and have diverse structural analogues. It is generally recognized that sulfur-containing structural analogues of CPs are mainly derived from sulfate-conjugated phase II metabolism. In this study, we non-targeted identified three classes of sulfur-containing CP structural analogues (CPs-S) in human serum, including 44 CP sulfates (CPs-SO4H/CPs-SO4H-OH), 14 chlorinated benzene sulfates (CBs-SO4H), and 19 CP sulfite esters (CPs-SO3/CPs-S2O6), which were generated during the production of commercial mixtures of CPs and, thus, bioaccumulated via environmental exposures. We first wrote a program to screen CPs-S, which were baseline-separated from CPs according to their polar functional groups. Then, mass spectral analyses of alkalization-acidification liquid-liquid extracts of serum samples and Orbitrap mass spectrometry analyses in the presence and absence of tetraphenylphosphonium chloride (Ph4PCl), respectively, were performed to determine the ionization forms ([M + Cl]- or [M - H]-) of CPs-S. The presence of fragment ions (SO4H-, SO3-, SO2Cl-, and HSO3-) revealed the structures of CPs-S, which were validated by their detections in commercial mixtures of CPs. The estimated total concentrations of CPs-S in the human serum samples were higher than the concentrations of medium- and long-chain CPs. The profiles of CPs-S in human serum were similar to those detected in CP commercial mixtures and rats exposed to the commercial mixtures, but CPs-S were not detected in human liver S9 fractions or rat tissues after exposure to CP standards. These results, together with the knowledge of the processes used to chemically synthesize CPs, demonstrate that CPs-S in humans originates from environmental bioaccumulation.

Association between urinary polycyclic aromatic hydrocarbons and unexplained recurrent spontaneous abortion from a case-control study.

Polycyclic aromatic hydrocarbons (PAHs) have been reported to be associated with adverse pregnancy outcomes. However, there is limited knowledge regarding the effects of single or mixed PAHs exposure on unexplained recurrent spontaneous abortion (URSA). This study aimed to investigate the association between monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and URSA in a case-control study. The results showed that 1-NAP, 2-NAP, 9-FLU, and 1-PYR were detected in 100% of the subjects among measured all sixteen OH-PAHs. Compared with those in the lowest quartiles, participants in the highest quartiles of 3-BAA were associated with a higher risk of URSA (OR (95%CI) = 3.56(1.28-9.85)). With each one-unit increase of ln-transformed 3-BAA, the odds of URSA increased by 41% (OR (95%CI) = 1.41(1.05-1.89)). Other OH-PAHs showed negative or non-significant associations with URSA. Weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and quantile-based g-computation (qgcomp) analyses consistently identified 3-BAA as the major contributor to the mixture effect of OH-PAHs on URSA. Our findings suggest that exposure to 3-BAA may be a potential risk factor for URSA. However, further prospective studies are needed to validate our findings in the future.

Recurrent Neural Network Methods for Extracting Dynamic Balance Variables during Gait from a Single Inertial Measurement Unit.

Monitoring dynamic balance during gait is critical for fall prevention in the elderly. The current study aimed to develop recurrent neural network models for extracting balance variables from a single inertial measurement unit (IMU) placed on the sacrum during walking. Thirteen healthy young and thirteen healthy older adults wore the IMU during walking and the ground truth of the inclination angles (IA) of the center of pressure to the center of mass vector and their rates of changes (RCIA) were measured simultaneously. The IA, RCIA, and IMU data were used to train four models (uni-LSTM, bi-LSTM, uni-GRU, and bi-GRU), with 10% of the data reserved to evaluate the model errors in terms of the root-mean-squared errors (RMSEs) and percentage relative RMSEs (rRMSEs). Independent t-tests were used for between-group comparisons. The sensitivity, specificity, and Pearson's r for the effect sizes between the model-predicted data and experimental ground truth were also obtained. The bi-GRU with the weighted MSE model was found to have the highest prediction accuracy, computational efficiency, and the best ability in identifying statistical between-group differences when compared with the ground truth, which would be the best choice for the prolonged real-life monitoring of gait balance for fall risk management in the elderly.

[Determination of sixteen antibiotics and four ß-agonists in human urine samples using ultra-performance liquid chromatography-tandem mass spectrometry based on high-throughput automatic solid-phase extraction].

An analytical method combining high-throughput automatic solid-phase extraction with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed to determine 16 antibiotics (macrolides, tetracyclines, quinolones, and sulfonamides) and 4 ß-agonists (terbutaline, salbutamol, ractopamine, and clenbuterol) in human urine samples. After thawing at room temperature, 1 mL of urine was sampled and the internal standard was added, followed by the addition of 200 µL ammonium acetate buffer and 20 µL ß-glucuronidase, and the mixture was incubated at 37 ℃ overnight. Automatic solid-phase extraction was used to extract the target compounds from the urine samples, and the recoveries were compared using different solid-phase extraction 96-well plates (PRiME MCX, Sep-Pak C18, PRiME HLB), types and volumes of rinse solutions and eluents. Satisfactory recoveries of the 20 target compounds were obtained using the Oasis PRiME HLB 96-well plate, with 1.5 mL 10% (v/v) methanol aqueous solution and 2.0 mL methanol as the rinse solution and eluent, respectively. The eluent was concentrated under nitrogen gas at 45 ℃, and the recoveries of the target compounds were compared under different conditions (completely or almost dry, drying to 1 mL, and adding water as a protective agent), and the recovery rate was optimal when water was added as a protective agent. In this study, two types of analytical columns (ACQUITY BEH C18 and ACQUITY HSS T3) and different gradient elution procedures and mobile phases were compared. The optimal chromatographic effect was realized using an HSS T3 column (100 mm×3.0 mm, 1.8 µm) and 0.1% (v/v) formic acid aqueous solution-0.1% (v/v) formic acid in acetonitrile as the mobile phase in gradient elution at a flow rate of 0.3 mL/min. Comparing the peaks observed using different proportions of methanol aqueous solution and the initial mobile phase as the injection solvent revealed that 30% (v/v) methanol aqueous solution was the optimal solution in terms of peak shape and signal-to-noise ratio. MS was conducted using positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, and the MS parameters were optimized, including the curtain (CUR) and collision gases (CAD). The standard curve obtained using this method exhibited a good linearity (correlation coefficient>0.997), and the respective limits of detection and quantification were 0.02-0.12 ng/mL and 0.06-0.41 ng/mL. At spiked levels of 0.25, 2.5, and 12.5 ng/mL, the recoveries were in the range of 81.7%-120.0% (except that of tetracycline), the intra- and inter-day RSDs (n=6) were 1.1%-11.0% and 1.2%-13.0%, respectively. Azithromycin, trimethoprim, terbutaline, salbutamol, ractopamine, and clenbuterol displayed moderate matrix effects, but all targets exhibited weak matrix effects after correction using the isotope internal standard. To evaluate the accuracy of this method, BCR-503 (containing salbutamol and clenbuterol) and internal quality control samples were used and the concentrations of salbutamol and clenbuterol were within the reference ranges. Additionally, the mean concentrations of the 20 target compounds of two different internal quality control samples after 7 measurements were in the ranges of 0.44-0.59 ng/mL (0.5 ng/mL) and 1.72-2.16 ng/mL (2.0 ng/mL), respectively, which were satisfactory. In this study, the analytical method employed automatic sample pretreatment with a 96-well solid-phase extraction plate, and the detection efficiency was considerably improved. This method displays the advantages of simple operation, ideal recovery, a high sensitivity and weak matrix effect, which satisfies the requirements for the simultaneous determination of 16 antibiotics and 4 ß-agonists in human urine samples. This study provides a crucial method for use in monitoring antibiotics and ß-agonists in human urine and studying their exposure characteristics and health risks.

Dexmedetomidine improves acute lung injury by activating autophagy in a rat hemorrhagic shock and resuscitation model.

Dexmedetomidine (DEX) can reduce lung injury in a hemorrhagic shock (HS) resuscitation (HSR) model in rats by inhibiting inflammation. Here, we aimed to investigate if these effects of DEX are due to autophagy activation. Therefore, we established HSR rat models and divided them into four groups. HS was induced using a blood draw. The rats were then resuscitated by reinjecting the drawn blood and saline. The rats were sacrificed 24 h after resuscitation. Lung tissues were harvested for histopathological examination, determination of wet/dry lung weight ratio, and detection of the levels of autophagy-related marker proteins LC3, P62, Beclin-1, and the ATG12-ATG5 conjugate. The morphological findings of hematoxylin and eosin staining in lung tissues and the pulmonary wet/dry weight ratio showed that lung injury improved in HSR + DEX rats. However, chloroquine (CQ), an autophagy inhibitor, abolished this effect. Detecting the concentration of autophagy-related proteins showed that DEX administration increased LC3, ATG12-ATG5, and Beclin-1 expression and decreased P62 expression. The expression levels of these proteins were similar to those in the HSR group after CQ + DEX administration. In summary, DEX induced autophagic activation in an HSR model. These findings suggest that DEX administration partially ameliorates HSR-induced lung injury via autophagic activation.

Topological identification and interpretation for single-cell gene regulation elucidation across multiple platforms using scMGCA.

Single-cell RNA sequencing provides high-throughput gene expression information to explore cellular heterogeneity at the individual cell level. A major challenge in characterizing high-throughput gene expression data arises from challenges related to dimensionality, and the prevalence of dropout events. To address these concerns, we develop a deep graph learning method, scMGCA, for single-cell data analysis. scMGCA is based on a graph-embedding autoencoder that simultaneously learns cell-cell topology representation and cluster assignments. We show that scMGCA is accurate and effective for cell segregation and batch effect correction, outperforming other state-of-the-art models across multiple platforms. In addition, we perform genomic interpretation on the key compressed transcriptomic space of the graph-embedding autoencoder to demonstrate the underlying gene regulation mechanism. We demonstrate that in a pancreatic ductal adenocarcinoma dataset, scMGCA successfully provides annotations on the specific cell types and reveals differential gene expression levels across multiple tumor-associated and cell signalling pathways.

Exposure to fine particulate matter constituents and cognitive function performance, potential mediation by sleep quality: A multicenter study among Chinese adults aged 40-89 years.

Although exposure to fine particulate matter (PM2.5) has been associated with cognitive decline, little is known about which PM2.5 constituents are more harmful. Recent study on the association between PM2.5 and sleep quality prompted us to propose that sleep quality may mediate the adverse effects of PM2.5 components on cognitive decline. Understanding the association between PM2.5 constituents and cognitive function, as well as the mediating role of sleep quality provides a future intervention target for improving cognitive function. Using data involving 1834 participants from a multicenter cross-sectional study in nine cities of the Beijing-Tianjin-Hebei (BTH) region in China, we undertook multivariable linear regression analyses to quantify the association of annual moving-average PM2.5 and its chemical constituents with cognitive function and to assess the modifying role of exposure characteristic in this association. Besides, we examined the extent to which this association of PM2.5 constituents with cognitive function was mediated via sleep quality by a mediation analysis. We observed significantly negative associations between an increase of one interquartile range increase in PM2.5 [-0.876 (95 % CI: -1.205, -0.548)], organic carbon [-0.481 (95 % CI: -0.744, -0.219)], potassium [-0.344 (95 % CI: -0.530, -0.157)], iron [-0.468 (95 % CI: -0.646, -0.291)], and ammonium ion [-0.125 (95 % CI: -0.197, -0.052)] and cognitive decline. However, we didn't find any individual components more harmful than PM2.5. Poor sleep quality partially mediated the estimated associations, which were explained ranging from 2.28 % to 11.99 %. Stratification analyses showed that people living in areas with lower greenspace were more susceptible to specific PM2.5 components. Our study suggests that the adverse effect of suffering from PM2.5 components is more pronounced among individuals with poor sleep quality, amplifying environmental inequalities in health. Besides reducing environmental pollution, improving sleep quality may be another measure worth considering to improve cognition if our research is confirmed in the future.

Mercury may reduce the protective effect of sea fish consumption on serum triglycerides levels in Chinese adults: Evidence from China National Human Biomonitoring.

Sea fish contain omega-3 polyunsaturated fatty acids (omega-3 PUFAs) which have been found to reduce triglyceride (TG) levels. However, sea fish may contain pollutants such as mercury which cause oxidative stress and increase TG levels. Therefore, the relationship between sea fish and TG remains unclear. We aimed to explore whether blood mercury (BHg) can affect the effect of sea fish consumption frequency on TG level among Chinese adults. A total of 10,780 participants were included in this study. BHg levels were measured using inductively coupled plasma mass spectrometry (ICP-MS). The associations of sea fish consumption frequency with BHg and TG levels as well as the association of BHg with TG levels were evaluated using multiple linear regression. Causal mediation analysis was used to evaluate the mediation effect of BHg levels on the association of sea fish consumption frequency with TG levels. The frequency of sea fish consumption showed a negative association with TG level. Compared with the participants who never ate sea fish, the TG level decreased by 0.193 mmol/L in those who ate sea fish once a week or more [ß (95%CI): -0.193 (-0.370, -0.015)]. Significant positive associations were observed of BHg with TG levels. With one unit increase of log2-transformed BHg, the change of TG level was 0.030 mmol/L [0.030 (0.009, 0.051)]. The association between sea fish consumption and TG was mediated by log2-transformed BHg [total effect = -0.037 (-0.074, -0.001); indirect effect = 0.009 (0.004, 0.015)], and the proportion mediated by log2-transformed BHg was 24.25%. BHg may reduce the beneficial effect of sea fish consumption frequency on TG levels among Chinese adults. Overall, sea fish consumption has more benefits than harms to TG.

Associations of Fine Particulate Matter Constituents with Metabolic Syndrome and the Mediating Role of Apolipoprotein B: A Multicenter Study in Middle-Aged and Elderly Chinese Adults.

Fine particulate matter (PM2.5) was reported to be associated with metabolic syndrome (MetS), but how PM2.5 constituents affect MetS and the underlying mediators remains unclear. We aimed to investigate the associations of long-term exposure to 24 kinds of PM2.5 constituents with MetS (defined by five indicators) in middle-aged and elderly adults and to further explore the potential mediating role of apolipoprotein B (ApoB). A multicenter study was conducted by recruiting subjects (n = 2045) in the Beijing-Tianjin-Hebei region from the cohort of Sub-Clinical Outcomes of Polluted Air in China (SCOPA-China Cohort). Relationships among PM2.5 constituents, serum ApoB levels, and MetS were estimated by multiple logistic/linear regression models. Mediation analysis quantified the role of ApoB in "PM2.5 constituents-MetS" associations. Results indicated PM2.5 was significantly related to elevated MetS prevalence. The MetS odds increased after exposure to sulfate (SO42-), calcium ion (Ca2+), magnesium ion (Mg2+), Si, Zn, Ca, Mn, Ba, Cu, As, Cr, Ni, or Se (odds ratios ranged from 1.103 to 3.025 per interquartile range increase in each constituent). PM2.5 and some constituents (SO42-, Ca2+, Mg2+, Ca, and As) were positively related to serum ApoB levels. ApoB mediated 22.10% of the association between PM2.5 and MetS. Besides, ApoB mediated 24.59%, 50.17%, 12.70%, and 9.63% of the associations of SO42-, Ca2+, Ca, and As with MetS, respectively. Our findings suggest that ApoB partially mediates relationships between PM2.5 constituents and MetS risk in China.

Using an Exposome-Wide Approach to Explore the Impact of Urban Environments on Blood Pressure among Adults in Beijing-Tianjin-Hebei and Surrounding Areas of China.

Existing studies mostly explored the association between urban environmental exposures and blood pressure (BP) in isolation, ignoring correlations across exposures. This study aimed to systematically evaluate the impact of a wide range of urban exposures on BP using an exposome-wide approach. A multicenter cross-sectional study was conducted in ten cities of China. For each enrolled participant, we estimated their urban exposures, including air pollution, built environment, surrounding natural space, and road traffic indicator. On the whole, this study comprised three statistical analysis steps, that is, single exposure analysis, multiple exposure analysis and a cluster analysis. We also used deletion-substitution-addition algorithm to conduct variable selection. After considering multiple exposures, for hypertension risk, most significant associations in single exposure model disappeared, with only neighborhood walkability remaining negatively statistically significant. Besides, it was observed that SBP (systolic BP) raised gradually with the increase in PM2.5, but such rising pattern slowed down when PM2.5 concentration reached a relatively high level. For surrounding natural spaces, significant protective associations between green and blue spaces with BP were found. This study also found that high population density and public transport accessibility have beneficially significant association with BP. Additionally, with the increase in the distance to the nearest major road, DBP (diastolic BP) decreased rapidly. When the distance was beyond around 200 m, however, there was no obvious change to DBP anymore. By cluster analysis, six clusters of urban exposures were identified. These findings reinforce the importance of improving urban design, which help promote healthy urban environments to optimize human BP health.

Comparison of Pb and Cd in wheat grains under air-soil-wheat system near lead-zinc smelters and total suspended particulate introduced modeling attempt.

The excessive accumulation of wheat grain metals and metalloids caused by ambient air contamination has drawn an increasing concern. However, at present, the differences in the pathways of cadmium and lead accumulation in wheat grains in an air-soil-wheat system are not clear. In this study, wheat was grown around a lead­zinc smelting area and exposed to different soil Pb and Cd levels and different ambient air Pb and Cd levels. Lead and Cd accumulation in wheat grains was examined in this study. Two models of wheat grain Pb and Cd concentrations were established based on the 3 variables including soil Pb and Cd concentration, ambient air Pb and Cd concentration, and soil pH. The results showed that total suspended particulate (TSP), soil, and wheat grains exhibited different degrees of Pb and Cd contamination in the study area, and the contamination of Cd is more serious than Pb contamination. The Pb in wheat grains was more likely to derive from ambient air than from soil, whereas the impact of ambient air on the accumulation of Cd in wheat grains might be very limited. This speculation was confirmed by the results of the predictor variable relative weight method based on the multiple regression analysis. Introduction of ambient air factor (TSP Pb and Cd) greatly improved the modeling effect of wheat grains Pb, while the modeling of grain Cd was more dependent on soil pH and total soil Cd. This research suggests that the reduction in wheat grain Pb is likely to be achieved by the control over ambient air Pb, whereas the reduction in the wheat grain Cd by the remediation of soil pollutants.

Insights into site-specific influences of emission sources on accumulation of heavy metal(loid)s in soils by wheat grains.

Excessive accumulation of heavy metal(loid)s in agricultural environment usually originates from anthropogenic activities. Both large diversities of emission sources and complexity of plant accumulation challenge the understanding of the site-specific effects of emission sources on heavy metal(loid)s in wheat grains. Herein, both soil samples and wheat grain samples (n = 80) were collected from the farmland of Jiyuan City, China. Soil and grain burdens of heavy metal(loid)s were determined by inductively coupled plasma mass spectrometry (ICP-MS) and/or X-ray fluorescence spectrometry (XRF). The quotients (Q) were developed to indicate relative impacts of industrial plants and traffic to soil sites. Principal component analysis-absolute principal component scores-multivariate linear regression (PCA-APCS-MLR) analysis was conducted to reveal the source contributions to heavy metal(loid)s in grains, considering Q values, soil, and wheat grain data. Results showed that contributions of main sources and factors drastically varied with soil sites, and usually overlapped to different extents. For grain Cd and grain Pb, natural soil silicate (0.066/0.104 mg/kg) and iron-bearing minerals (- 0.044/ - 0.174 mg/kg) contributed to high extents, while metal smelting activities (0.018/0.019 mg/kg) and agronomic activities (- 0.017/ - 0.019 mg/kg) unexpectedly posed low or moderate contributions. The pH-mediated availability of soil Cd (0.035 mg/kg) and the sand-dust weather (0.028 mg/kg) also made considerable contributions to grain Cd. For grain As, both natural soil iron-bearing (- 0.048 mg/kg) and silicate minerals (- 0.013 mg/kg) made negative contributions. The results benefit to the decision-making of pollution remediation of farmland soils in the regional scales.

[Determination of polybrominated diphenyl ethers in serum using isotope internal standard-gas chromatography-high resolution dual-focus magnetic mass spectrometry].

A method for the determination of 14 polybrominated diphenyl ethers (PBDEs) in human serum using isotope internal standard-gas chromatography-high resolution dual-focus magnetic mass spectrometry (GC-HRMS) was developed. After thawed to room temperature, 0.5 mL serum samples were mixed with 13C-labeled isotopic internal standard. Subsequently, methanol was added to precipitate the proteins in the samples. The effects of three kinds of acids on the removal of cellulite from the serum samples and the corresponding recoveries were compared, and the results revealed that sulfuric acid was the most optimal. The target compounds were extracted by liquid-liquid extraction (LLE), and the effects of different extraction solvents on recoveries were compared. The results indicated that n-hexane (6 mL)-methyl tert-butyl ether (6 mL) was the best extraction solvent. The extracts were cleaned and eluted using solid phase extraction cartridges. Furthermore, the factors that influenced the cleanup effects and recoveries, including the solid phase extraction columns and elution solvents, were investigated in detail. The results indicated that the optimal conditions were cleanup with a silica gel column and elution with hexane-dichloromethane (1∶1, v/v). The eluate was re-dissolved in hexane after being blown to near dryness using nitrogen. The detection of PBDEs was performed using GC-HRMS. The instrument conditions were optimized, and the capillary column used was an Rtx-1614 column (30 m×0.25 mm×0.1 µm). Helium was used as the carrier gas at a flow rate of 1.0 mL/min. The injector temperature was 290 ℃, and the oven temperature was programmed as follows: 150 ℃ for 2 min, 150 ℃ to 250 ℃ at 15 ℃/min, held for 1 min, 250 ℃ to 290 ℃ at 25 ℃/min, held for 3 min, and 290 ℃ to 320 ℃ at 25 ℃/min, held for 12.5 min. The injection volume was 1 µL in splitless mode. The samples were ionized in the positive electron ionization (EI) mode at 35 eV. Precursor ions and the production of each compound were identified using a voltage-selective ion detection (VSIR) program with a resolution of 10000. The ionization temperature was set at 280 ℃, and the transmission line temperature was set at 320 ℃. To ensure the integrity of the separation of low-brominated components, the column separation time was shortened, the response of high-boiling components was improved (BDE-190 and BDE-209), the decomposition of BDE-209 on the chromatographic column was effectively prevented, and the requirement of the simultaneous determination of multiple PBDEs was met. The method demonstrated good linearity in the range of 0.40 to 25 µg/L for BDE-209, and 0.08 to 5 µg/L for the other 13 PBDEs, with correlation coefficients greater than 0.995. The method detection limits (MDLs) were in the range of 0.01 to 0.51 µg/L, and the limits of quantification (LOQs) ranged from 0.04 to 1.70 µg/L. The recoveries of the 14 compounds ranged from 75.5% to 120.7%. The intra-day relative standard deviations (RSDs) were within 3.8%-10.9% (n=6) and the inter-day RSDs were within 4.2% to 12.4% (n=6). This method was successfully applied to the determination of 14 PBDEs in 15 serum samples from an adolescent population in an area. Notably, 1.86 to 4.66 ng/g lipid BDE-47 was detected in the serum samples with a detection frequency of 100%, and the other compounds were not detected. The results imply that the adolescent population in this region was exposed to some PBDE. Compared with the existing methods reported, this method has less sample demand and higher sensitivity and accuracy, can simultaneously determine 14 PBDEs, including BDE-209 in human serum, and effectively improve the efficiency of detection. This study offers a new method for studying the impact of polybrominated diphenyl ethers on population health in China.

GMHCC: high-throughput analysis of biomolecular data using graph-based multiple hierarchical consensus clustering.

MOTIVATION: Thanks to the development of high-throughput sequencing technologies, massive amounts of various biomolecular data have been accumulated to revolutionize the study of genomics and molecular biology. One of the main challenges in analyzing this biomolecular data is to cluster their subtypes into subpopulations to facilitate subsequent downstream analysis. Recently, many clustering methods have been developed to address the biomolecular data. However, the computational methods often suffer from many limitations such as high dimensionality, data heterogeneity and noise. RESULTS: In our study, we develop a novel Graph-based Multiple Hierarchical Consensus Clustering (GMHCC) method with an unsupervised graph-based feature ranking (FR) and a graph-based linking method to explore the multiple hierarchical information of the underlying partitions of the consensus clustering for multiple types of biomolecular data. Indeed, we first propose to use a graph-based unsupervised FR model to measure each feature by building a graph over pairwise features and then providing each feature with a rank. Subsequently, to maintain the diversity and robustness of basic partitions (BPs), we propose multiple diverse feature subsets to generate several BPs and then explore the hierarchical structures of the multiple BPs by refining the global consensus function. Finally, we develop a new graph-based linking method, which explicitly considers the relationships between clusters to generate the final partition. Experiments on multiple types of biomolecular data including 35 cancer gene expression datasets and eight single-cell RNA-seq datasets validate the effectiveness of our method over several state-of-the-art consensus clustering approaches. Furthermore, differential gene analysis, gene ontology enrichment analysis and KEGG pathway analysis are conducted, providing novel insights into cell developmental lineages and characterization mechanisms. AVAILABILITY AND IMPLEMENTATION: The source code is available at GitHub: https://github.com/yifuLu/GMHCC. The software and the supporting data can be downloaded from: https://figshare.com/articles/software/GMHCC/17111291. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effect of exposures to mixtures of lead and various metals on hypertension, pre-hypertension, and blood pressure: A cross-sectional study from the China National Human Biomonitoring.

We aimed to explore the effects of mixtures of lead and various metals on blood pressure (BP) and the odds of pre-hypertension (systolic blood pressure (SBP) 120-139 mmHg, and/or diastolic blood pressure (DBP) 80-89 mmHg) and hypertension (SBP/DBP ≥140/90 mmHg) among Chinese adults in a cross-sectional study. This study included 11,037 adults aged 18 years or older from the 2017-2018 China National Human Biomonitoring. Average BP and 13 metals (lead, antimony, arsenic, cadmium, mercury, thallium, chromium, cobalt, molybdenum, manganese, nickel, selenium, and tin) in blood and urine were measured and lifestyle and demographic data were collected. Weighted multiple linear regressions were used to estimate associations of metals with BP in both single and multiple metal models. Weighted quantile sum (WQS) regression was performed to assess the relationship between metal mixture levels and BP. In the single metal model, after adjusting for potential confounding factors, the blood lead levels in the highest quartile were associated with the greater odds of both pre-hypertension (odds ratio (OR): 1.56, 95% CI: 1.22-1.99) and hypertension (OR:1.75, 95% CI: 1.28-2.40) when compared with the lowest quartile. We also found that blood arsenic levels were associated with increased odds of pre-hypertension (OR:1.31, 95% CI:1.00-1.74), while urinary molybdenum levels were associated with lower odds of hypertension (OR:0.68, 95% CI:0.50-0.93). No significant associations were found for the other 10 metals. WQS regression analysis showed that metal mixture levels in blood were significantly associated with higher SBP (ß = 1.56, P < 0.05) and DBP (ß = 1.56, P < 0.05), with the largest contributor being lead (49.9% and 66.8%, respectively). The finding suggests that exposure to mixtures of metals as measured in blood were positively associated with BP, and that lead exposure may play a critical role in hypertension development.

Declines in Blood Lead Levels Among General Population - China, 2000-2018.

What is already known about this topic?: Environmental and occupational lead exposure has generally declined in the past two decades. However, there is no large-scale monitoring of blood lead levels (BLLs) in the Chinese general population. What is added by this report?: This nationally representative study showed declines of BLLs in all ages of participants; for children aged 3-5 years, down from 78.1 µg/L to 16.9 µg/L, corresponding to 78.4% decrease in the past two decades (2000-2018). What are the implications for public health practice?: Recommendations for elevated BLLs on screening children at high risk now need to be revisited and updated from 100 µg/L to 50 µg/L in guidelines to conform with the substantial declines in China.

Changeable effects of coexisting heavy metals on transfer of cadmium from soils to wheat grains.

Cadmium (Cd) and other heavy metals usually coexist in soils. Effects of coexisting heavy metals on the accumulation and transfer of Cd in field soils by wheat remain poorly understood. Here we revealed changeable effects of coexisting Pb, Zn and Cu on the Cd transfer from soils to wheat grains. Soil burdens of Cd were found to exhibit positive correlations (r = 0.459-0.946) with those of coexisting Pb, Zn and Cu (particularly Pb). Effects of three coexisting metals on to the uptake of Cd by wheat varied in the directions and/or extents with types of metals and transfer processes of Cd. Coexisting Zn inhibited the uptake of Cd by wheat grains to higher extent than Pb and Cu. Soil Zn, along with soil Cd, soil pH and soil Ca, was used to construct the predictive model of grain Cd (R2 = 0.868). External verifications of the model on 572 datasets of large representation performed well. The predictive accuracy was about 54%, 73% and 89% for a factor of 1, 2 and 5 above and below the ideal fit, respectively. This finding has practical interest in risk assessments and remediation measures of Cd-contaminated soil sites in regional scales.

Cohort profile: China National Human Biomonitoring (CNHBM)-A nationally representative, prospective cohort in Chinese population.

OBJECTIVE: Globally, developed countries such as the United States, Canada, Germany, Korea, have carried out long-term and systematic biomonitoring programs for environmental chemicals in their populations. The China National Human Biomonitoring (CNHBM) was to document the extent of human exposure to a wide array of environmental chemicals, to understand exposure profiles, magnitude and ongoing trends in exposure in the general Chinese population, and to establish a national biorepository. METHODS: CNHBM adopted three-stage sampling method to obtain a nationally representative sample of the population. A total of 21,888 participants who were permanent residents in 31 provinces were designed to interviewed in this national biomonitoring (152 monitoring sites × 3 survey units × 2 sexes × 6 age groups × 4 persons = 21,888 persons) in 2017-2018. Unlike the US National Health and Nutrition Examination Survey, the CNHBM will follow the same participants in subsequent cycles allowing for dynamic, longitudinal data sets for epidemiologic follow-up. Each survey cycle of CNHBM will last 2 years and each subsequent cycle will occur 3 years after the prior cycle's completion. RESULTS: In 2017-2018, the CNHBM created a large cohort of Chinese citizens that included districts/counties questionnaire, community questionnaire collecting information on villages/communities, individual questionnaire, household questionnaire, comprehensive medical examination, and collection of blood and urine samples for measurement of clinical and exposure biomarkers. A total of 21,746 participants were finally included in CNHBM, accounting for 99.4% of the designed sample size; and 152 PSUs questionnaires, 454 community questionnaires, 21,619 family questionnaires, 21,712 cases of medical examinations, 21,700 individual questionnaires, 21,701 blood samples and 21,704 urine samples were collected, respectively. Planned analyses of blood and urine samples were to measure both inorganic and organic chemicals, including 13 heavy metals and metalloids, 18 poly- and per-fluorinated alkyl substances, 12 phthalate metabolites, 9 polycyclic aromatic hydrocarbons metabolites, 4 environmental alkylated phenols, and 2 benzene metabolites. CONCLUSIONS: CNHBM established the first nationally representative, prospective cohort in the Chinese population to understand the baseline and trend of internal exposure of environmental chemicals in general population, and to understand environmental toxicity.

[Spatial-temporal Variation and Source Change of Heavy Metals in the Cropland Soil in the Industrial City].

Environmental policy regulation affects the accumulation of heavy metals in soil. Two soil surveys were conducted in farmland in industrial cities. Classical statistical and geostatistical methods were applied to examine the content changes and spatial-temporal distribution characteristics of Cd, Pb, Cu, and Zn in soil. The pollution sources and their contribution rates were further analyzed by a principal component analysis/absolute principal component scores (PCA/APCS) model. The results indicated that the concentrations of Cd, Pb, Cu, and Zn increased during the two periods. The content of Cd and Pb in the spatial distribution decreased from northwest to southeast in both periods. The content of Cu and Zn decreased from north to south in 2011, and gradually decreased from northwest to southeast in 2017. Compared with 2011, the contribution rate of industrial activities increased by 5.58%, 10.4%, and 20.4% for Cd, Cu, and Zn, respectively, but decreased by 19.7% for Pb. The contribution rates of the other factors to Cd and Pb increased by 3.76% and 24.83%, respectively, and decreased by 9.27% and 4.31% for Cu and Zn, respectively. Relevant measures have reduced the accumulation of Pb in regional soil caused by industrial activities, but not Cd, Cu, or Zn. In addition, new Cd and Pb pollution sources need to be paid attention to.

Investigation of phthalate metabolites in urine and daily phthalate intakes among three age groups in Beijing, China.

Phthalates are widely used as binders and plasticizers in industrial and consumer products but show diverse toxicity. We investigated the level of human exposure to phthalates in Beijing, one of the most densely populated cities in the world. In this study, 12 metabolites of phthalates were measured in 70 spot urine samples collected from Beijing residents from August 2017 to April 2018 using ultra high-performance liquid chromatography tandem mass spectrometry. We found that metabolites of phthalates were ubiquitous in all urine samples. Total concentrations of phthalate metabolites ranged from 39.6 to 1931 ng mL-1, with median concentrations were in decreasing order of children (371 ng mL-1)> younger adults (332 ng mL-1)> older adults (276 ng mL-1). Mono-n-butyl phthalate (MnBP) was the predominant compound, and occurred at concentrations greater than those reported for people in other countries. The mean values of estimated daily intakes (EDIs) of ∑phthalate were 35.2, 10.3 and 10.9 ng (kg-bm)-1 d-1 for children, younger adults and older adults, respectively. EDIs of di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP) and di-(2-ethylhexyl) phthalate (DEHP) exceeded reference values suggested by the US Environmental Protection Agency and the European Food Safety Authority. When concentrations were normalized to volume or creatinine-adjusted, hazard quotients (HQs) for 40 of 70 participants exhibited larger HQs >1 for individual phthalates, which was indicative of potential for adverse effects. Thus, exposure to phthalates might be a critical factor contributing to adverse health effects in Beijing residents. To the best of our knowledge, this is the first study to establish a pre-baseline level of urinary phthalate metabolites among residents in Beijing.