FRMC: a fast and robust method for the imputation of scRNA-seq data.

The high-resolution feature of single-cell transcriptome sequencing technology allows researchers to observe cellular gene expression profiles at the single-cell level, offering numerous possibilities for subsequent biomedical investigation. However, the unavoidable technical impact of high missing values in the gene-cell expression matrices generated by insufficient RNA input severely hampers the accuracy of downstream analysis. To address this problem, it is essential to develop a more rapid and stable imputation method with greater accuracy, which should not only be able to recover the missing data, but also effectively facilitate the following biological mechanism analysis. The existing imputation methods all have their drawbacks and limitations, some require pre-assumed data distribution, some cannot distinguish between technical and biological zeros, and some have poor computational performance. In this paper, we presented a novel imputation software FRMC for single-cell RNA-Seq data, which innovates a fast and accurate singular value thresholding approximation method. The experiments demonstrated that FRMC can not only precisely distinguish 'true zeros' from dropout events and correctly impute missing values attributed to technical noises, but also effectively enhance intracellular and intergenic connections and achieve accurate clustering of cells in biological applications. In summary, FRMC can be a powerful tool for analysing single-cell data because it ensures biological significance, accuracy, and rapidity simultaneously. FRMC is implemented in Python and is freely accessible to non-commercial users on GitHub: https://github.com/HUST-DataMan/FRMC.

Associations of forest negative air ions exposure with cardiac autonomic nervous function and the related metabolic linkages: A repeated-measure panel study.

Forest environment has many health benefits, and negative air ions (NAI) is one of the major forest environmental factors. Many studies have explored the effect of forest environment on cardiac autonomic nervous function, while forest NAI in the among function and the underlying mechanism still remain unclear. To explore the associations and molecular linkages between short-term exposure to forest NAI and heart rate variability (HRV), a repeated-measure panel study was conducted among 31 healthy adults. Participants were randomly selected to stay in a forest park for 3 days and 2 nights. Individual exposures including NAI were monitored simultaneously and HRV indices were measured repeatedly at the follow-up period. Urine samples were collected for non-targeted metabolomics analysis. Mixed-effect models were adopted to evaluate associations among NAI, HRV indices and metabolites. The median of NAI concentration was 68.11 (138.20) cm-3 during the study period. Short-term exposure to forest NAI was associated with the ameliorative HRV indices, especially the excitatory parasympathetic nerve. For instance, per interquartile range increase of 5-min moving average of NAI was associated with 9.99 % (95%CI: 8.95 %, 11.03 %) increase of power in high frequency. Eight metabolites were associated with NAI exposure. The down-regulated tyrosine metabolism was firstly observed, followed by other amino acid metabolic alterations. The NAI-related metabolic changes reflect the reduction of inflammation and oxidative stress. HRV indices were associated with 25 metabolites, mainly including arginine, proline and histidine metabolism. Short-term exposure to forest NAI is beneficial to HRV, especially to the parasympathetic nerve activity, by successively disturbing different metabolic pathways which mainly reflect the increased anti-inflammation and the reduced inflammation. The results will provide epidemiological evidences for developing forest therapy and improving cardiac autonomic nervous function.

HCMB: A stable and efficient algorithm for processing the normalization of highly sparse Hi-C contact data.

The high-throughput genome-wide chromosome conformation capture (Hi-C) method has recently become an important tool to study chromosomal interactions where one can extract meaningful biological information including P(s) curve, topologically associated domains, A/B compartments, and other biologically relevant signals. Normalization is a critical pre-processing step of downstream analyses for the elimination of systematic and technical biases from chromatin contact matrices due to different mappability, GC content, and restriction fragment lengths. Especially, the problem of high sparsity puts forward a huge challenge on the correction, indicating the urgent need for a stable and efficient method for Hi-C data normalization. Recently, some matrix balancing methods have been developed to normalize Hi-C data, such as the Knight-Ruiz (KR) algorithm, but it failed to normalize contact matrices with high sparsity. Here, we presented an algorithm, Hi-C Matrix Balancing (HCMB), based on an iterative solution of equations, combining with linear search and projection strategy to normalize the Hi-C original interaction data. Both the simulated and experimental data demonstrated that HCMB is robust and efficient in normalizing Hi-C data and preserving the biologically relevant Hi-C features even facing very high sparsity. HCMB is implemented in Python and is freely accessible to non-commercial users at GitHub: https://github.com/HUST-DataMan/HCMB.

Increasing cardiopulmonary effects of ultrafine particles at relatively low fine particle concentrations.

Ultrafine particles (UFPs) are of concern because of their high pulmonary deposition efficiency. However, present control measures are generally targeted at fine particles (PM2.5), with little effect on UFPs. The health effects of UFPs at different PM2.5 concentrations may provide a basic for controlling UFPs but remain unclear in polluted areas. School children spend the majority of their time in the classrooms. This study investigated the different short-term effects of indoor UFPs on school children in Beijing, China when indoor PM2.5 concentrations exceeded or satisfied the recently published Chinese standard for indoor PM2.5. Cardiopulmonary functions of 48 school children, of whom 46 completed, were measured three times. Indoor PM2.5 and UFPs were monitored in classrooms on weekdays. Measurements were separated into two groups according to the abovementioned standard. Mixed-effect models were used to explore the health effects of the air pollutants. Generally, UFP-associated effects on children's cardiopulmonary function persisted even at relatively low PM2.5 concentrations, especially on heart rate variability indices. The risks associated with high PM2.5 concentrations are well-known, but the effects of UFPs on children's cardiopulmonary function deserve more attention even when PM2.5 has been controlled. UFP control and standard setting should therefore be considered.

Metabolic linkages between indoor negative air ions, particulate matter and cardiorespiratory function: A randomized, double-blind crossover study among children.

BACKGROUND: Ionization air purifiers, which purify particulate matter (PM) by producing vast number of negative air ions (NAI), are widely used. Recent study implied that ionization air purification could bring respiratory benefits but deterioration of heart rate variability (HRV). However, its underlying molecular mechanisms remain unclear. OBJECTIVES: To explore the molecular linkages between indoor NAI, decreased PM and the cardiorespiratory effect after purification. METHODS: Urine samples were collected from 44 healthy children three times of each study period (real and sham purification) in an existing randomized, double-blind crossover study. Ultra-high performance liquid chromatography/mass spectrometry was conducted in metabolomics analysis, the associations between indoor NAI, decreased PM and the cardiorespiratory function were investigated via the meet-in-metabolite approach (MIMA) based on statistical and metabolic pathway analysis. Mixed-effect models were used to establish associations between exposure, health parameters and metabolites. RESULTS: Twenty-eight and fourteen metabolites were identified with significant correlations to NAI and PM, respectively. Besides, eight and eighteen metabolites were separately associated with respiratory function and HRV. The increased NAI and decreased PM improved respiratory function mainly with eight pathways, promoting energy production, anti-inflammation and anti-oxidation capacity. Decreased PM ameliorated HRV with six main pathways, increasing energy production and anti-inflammation capacity while increased NAI deteriorated HRV with five main pathways, lowering energy generation and anti-oxidation capacity. CONCLUSIONS: Increased NAI and decreased PM ameliorated respiratory function by increasing energy production, improving anti-inflammation and anti-oxidation capacity. Decreased PM improved cardiac autonomic function by increasing energy production and anti-inflammation capacity, while these benefits were overcast by massive NAI via lowering energy generation and anti-oxidation capacity with different metabolic pathways.

Urine metabolites associated with cardiovascular effects from exposure of size-fractioned particulate matter in a subway environment: A randomized crossover study.

BACKGROUND: Ambient particulate matter (PM) is closely associated with morbidity and mortality from cardiovascular disease. Urine metabolites can be used as a non-invasive means to explore biological mechanisms for such associations, yet has not been performed in relation to different sizes of PM. In this randomized crossover study, we used metabolomics approach to explore the urine biomarkers linked with cardiovascular effects after PM exposure in a subway environment. METHODS AND RESULTS: Thirty-nine subjects were exposed to PM for 4 h in subway system, with either a respirator intervention phase (RIP) with facemask and no intervention phase (NIP) in random order with a 2-week washout period. Electrocardiogram (ECG) parameters and ambulatory blood pressure (BP) were monitored during the whole riding period and urine samples were collected for metabolomics analysis. After exposure to PM for 4 h in subway system, 4 urine metabolites in male and 7 urine metabolites in female were screened out by UPLC/Q-TOF MS/MS-based metabolomics approach. Cardiovascular parameters (HRV and HR) predominantly decreased in response to all size-fractions of PM and were more sensitive in response to different size-fractioned PM in males than females. Besides LF/HF, most of the HRV indices decrease induced by the increase of all size-fractioned PM while PM1.0 was found as the most influential one on indicators of cardiovascular effects and urine metabolites both genders. Prolyl-arginine and 8-OHdG were found to have opposing role regards to HRV and HR in male. CONCLUSION: Our data indicated that short-term exposure to PM in a subway environment may increase the risk of cardiovascular disease as well as affect urine metabolites in a size dependent manner (besides PM0.5), and male were more prone to trigger the cardiovascular events than female after exposure to PM; whereas wearing facemask could effectively reduce the adverse effects caused by PM.

Different cardiorespiratory effects of indoor air pollution intervention with ionization air purifier: Findings from a randomized, double-blind crossover study among school children in Beijing.

Indoor air pollution is associated with numerous adverse health outcomes. Air purifiers are widely used to reduce indoor air pollutants. Ionization air purifiers are becoming increasingly popular for their low power consumption and noise, yet its health effects remain unclear. This randomized, double-blind crossover study is conducted to explore the cardiorespiratory effects of ionization air purification among 44 children in Beijing. Real or sham purification was performed in classrooms for 5 weekdays. Size-fractionated particulate matter (PM), black carbon (BC), ozone (O3), and negative air ions (NAI) were monitored, and cardiorespiratory functions were measured. Mixed-effect models were used to establish associations between exposures and health parameters. Real purification significantly decreased PM and BC, e.g. PM0.5, PM2.5, PM10 and BC were decreased by 48%, 44%, 34% and 50%, respectively. O3 levels were unchanged, while NAI was increased from 12 cm-3 to 12,997 cm-3. Real purification was associated with a 4.4% increase in forced exhaled volume in 1 s (FEV1) and a 14.7% decrease in fractional exhaled nitrogen oxide (FeNO). However, heart rate variability (HRV) was altered negatively. Interaction effects of NAI and PM were observed only on HRV, and alterations in HRV were greater with high NAI. Ionization air purifier could bring substantial respiratory benefits, however, the potential negative effects on HRV need further investigation.

Cardiorespiratory responses to low-level ozone exposure: The inDoor Ozone Study in childrEn (DOSE).

BACKGROUND: Indoor air pollution has emerged as a significant environmental and public health concern in recent years. However, evidence regarding the cardiorespiratory effects of indoor ozone is limited, and the underlying biological mechanisms are unclear, especially in children. Our study aimed to assess the cardiorespiratory responses to indoor ozone exposure in children. METHODS: A repeated-measure study was conducted in 46 middle-school children in Beijing, China. Real-time concentrations of ozone, along with co-pollutants including particulate matter (PM) and black carbon (BC), were monitored in classrooms from Monday to Friday. Three repeated health measurements of cardiorespiratory functions, including ambulatory electrocardiogram (ECG), blood pressure, fractional exhaled nitric oxide (FeNO) and lung function, were performed on each participant. Mixed-effect models were used to evaluate the effects of indoor ozone exposure. RESULTS: The mean (SD) indoor ozone concentration was 8.7 (6.6) ppb during the study period, which was largely below the current guideline and standards. However, even this low-level ozone exposure was associated with reduced cardiac autonomic function and increased heart rate (HR) in children. For instance, per interquartile range (IQR) increase in ozone at 2-hour moving average was associated with -7.8% (95% CI: -9.9%, -5.6%) reduction in standard deviation of all normal-to-normal intervals (SDNN), and 2.6% (95% CI: 1.6%, 3.6%) increment in HR. In addition, the associations were stronger at high BC levels (BC ≥ 3.7 µg/m3). No significant associations were found for airway inflammation and pulmonary function. CONCLUSIONS: Exposure to low-level indoor ozone that is not associated with respiratory effects was significantly related to disturbed cardiac autonomic function and increased HR in children, which suggested a possible mechanism through which ozone may affect cardiovascular health in children, and indicated more protective measures should be taken to alleviate the acute adverse effects of indoor ozone in this susceptible population.