A comprehensive comparison of residue-level methylation levels with the regression-based gene-level methylation estimations by ReGear.

MOTIVATION: DNA methylation is a biological process impacting the gene functions without changing the underlying DNA sequence. The DNA methylation machinery usually attaches methyl groups to some specific cytosine residues, which modify the chromatin architectures. Such modifications in the promoter regions will inactivate some tumor-suppressor genes. DNA methylation within the coding region may significantly reduce the transcription elongation efficiency. The gene function may be tuned through some cytosines are methylated. METHODS: This study hypothesizes that the overall methylation level across a gene may have a better association with the sample labels like diseases than the methylations of individual cytosines. The gene methylation level is formulated as a regression model using the methylation levels of all the cytosines within this gene. A comprehensive evaluation of various feature selection algorithms and classification algorithms is carried out between the gene-level and residue-level methylation levels. RESULTS: A comprehensive evaluation was conducted to compare the gene and cytosine methylation levels for their associations with the sample labels and classification performances. The unsupervised clustering was also improved using the gene methylation levels. Some genes demonstrated statistically significant associations with the class label, even when no residue-level methylation features have statistically significant associations with the class label. So in summary, the trained gene methylation levels improved various methylome-based machine learning models. Both methodology development of regression algorithms and experimental validation of the gene-level methylation biomarkers are worth of further investigations in the future studies. The source code, example data files and manual are available at http://www.healthinformaticslab.org/supp/.

A catalyst-free four-component domino reaction for the synthesis of functionalized 3-acyl-1,5-benzodiazepines.

Various functional 3-acyl-1,5-benzodiazepines containing carboxyl, ester and acyl groups at the 2-position were synthesized via an efficient, sustainable and catalyst-free domino reaction. During the synthesis process, one new cycle and four new bonds (one C-C, two C-N and one C[double bond, length as m-dash]C) were constructed by the nucleophilic substitution, nucleophilic addition, dehydration and cyclization reaction by the H+ shift. Furthermore, a total of 26 examples were examined by reacting inexpensive starting materials of N,N-dimethylformamide dimethyl acetal, aromatic ketones, 1,2-phenylenediamine compounds and aldehyde derivatives. Therefore, it displayed a broad substrate scope, good functional group tolerance, high yields (77-97%) and the ease of obtaining target compounds without the involvement of toxic solvents and column chromatography, which provided a novel method for the synthesis of a wide variety of biologically relevant 1,5-benzodiazepines.

Pollution characteristics and light-driven evolution of environmentally persistent free radicals in PM2.5 in two typical northern cities of China.

Environmentally persistent free radicals (EPFRs) in PM2.5 can pose significant health risks by generating reactive oxygen species (ROS). In this study, Beijing and Yuncheng were chosen as two representative northern cities of China that mainly relied on natural gas and coal respectively as the energy source for domestic heating in winter. The pollution characteristics and exposure risks of EPFRs in PM2.5 around the heating season of 2020 were investigated and compared between the two cities. Through laboratory simulation experiments, the decay kinetics and secondary formation of EPFRs in PM2.5 collected in both cities were also studied. EPFRs in PM2.5 collected in Yuncheng in the heating period showed longer lifetime and lower reactivity, suggesting that EPFRs originated from coal combustion were more stable in the atmosphere. However, the generation rate of hydroxyl radical (·OH) by the newly formed EPFRs in PM2.5 in Beijing under ambient conditions was 4.4 times of that in Yuncheng, suggesting higher oxidative potential of EPFRs from the atmospheric secondary processes. Accordingly, the control strategies of EPFRs and their health risks were raised for the two cities, which would also have direct implication for the control of EPFRs in other areas of similar atmospheric emission and reaction patterns.

Oxidative potential associated with water-soluble components of PM2.5 in Beijing: The important role of anthropogenic organic aerosols.

Oxidative stress is the mainstream toxicological mechanism for the adverse health outcomes of ambient aerosols. However, our understanding of the crucial redox-active species affecting the oxidative potential of water-soluble aerosols (OPWS) remains limited. In this study, the OPWS of PM2.5 in Beijing was measured using dithiothreitol (DTT) assay, including DTT consumption rate and ·OH formation rate. OPWS was more closely related to water-soluble organic compounds (WSOC) rather than transition metals. Laboratory simulations were conducted to investigate the effects of individual target species in the context of complex metal-organic interactions. The results showed that reducing WSOC can effectively decrease OPWS, while reducing Cu2+ increased OPWS. Parallel factor analysis demonstrated that OPWS was the most significantly correlated with the highly oxidized humic-like or quinone-like substances. Multiple linear regression showed that aromatic secondary organic carbon (SOC) (34.4%), other primary combustion sources of WSOC (20.0%), primary biomass burning WSOC (19.8%), transition metal ions (12.9%) and biomass burning SOC (12.8%) made significant contributions to DTTV. In addition to the anthropogenic sources of WSOC, the aged biogenic SOC also contributed to OHV, particularly in summer. Reducing anthropogenic WSOC was the key to the effective control of OPWS of PM2.5 in Beijing.

Gas-PM2.5 partitioning, health risks, and sources of atmospheric PAHs in a northern China city: Impact of domestic heating.

The diurnal variation, gas-particle partitioning, health risks, and sources of polycyclic aromatic hydrocarbons (PAHs) were investigated in a northern basin city of China in winter, 2020. The mean concentrations of particulate and gaseous PAHs were 87.90 ng m-3 and 69.65 ng m-3, respectively, and their concentrations were considerably enhanced during the domestic heating period. The relationship between the gas-particle partitioning coefficient of PAHs (KP) and subcooled liquid vapor pressure of PAHs (PL0) indicated organic absorption as the mechanism for this partitioning. However, the dual sorption model confirmed adsorption onto elemental carbon (EC). The health risks indicated by several equivalent parameters showed an important health effect of PAHs, especially of particulate PAHs bound onto PM2.5 during the heating period. Environmentally persistent free radicals (EPFRs) were also studied as an auxiliary parameter to evaluate the health impact of PAHs. According to the diagnostic ratios of PAHs and PMF model results, petroleum volatilization and coal combustion were the dominant sources of particulate PAHs during the non-heating and heating periods, respectively. The source apportionment results can help efficiently control PAHs and their health risks.

Seasonal variation of dicarboxylic acids in PM2.5 in Beijing: Implications for the formation and aging processes of secondary organic aerosols.

Dicarboxylic acids are a group of highly oxidized components, which can provide insights into the formation mechanism and aging process of secondary organic aerosols (SOA). Based on the 12-h day and night PM2.5 samples collected in downtown Beijing in January, April, July and October of 2017, dicarboxylic acids and relevant components were measured to investigate their seasonal variation pattern and sources. High concentrations of the identified organic acids were observed, following the decreasing order of July > January > October > April. The high fractions of phthalic acid and maleic acid in January indicated severe aromatic SOA pollution during the sampling period in winter, and the high malonic acid to succinic acid and malic acid to succinic acid ratios in July suggested strong photochemical formation over the sampling period in summer. Based on the calculation of principle component analysis and multiple linear regression, water-soluble organic acids were mainly formed from the aerosol aging process during the sampling periods except for January, while water-soluble organic carbon (WSOC) mostly originated from combustion sources. Correlation analysis was conducted between the CO-normalized concentrations of organic acids and PM2.5, O3, as well as the meteorological parameters. The results suggested that gas-phase photooxidation contributed significantly to the formation of these organic acids during the entire sampling period, and the aqueous-phase process played an important role over the severe haze event in January. Our results also suggested that the intensity of photooxidation and the aging degree of SOA were enhanced along with the reduction of PM2.5 in Beijing in recent years.

Photocatalytic reduction of Cr (VI) on nano-sized red phosphorus under visible light irradiation.

Red phosphorus as a novel visible-light-responsive and metal-free photocatalyst has attracted extensive attention in the area of energy conversion and environmental remediation. Herein, nano-sized red phosphorus photocatalyst was synthesized via a hydrothermal and ultrasonic method and used for reduction of Cr (VI) for the first time. The as-prepared photocatalysts were characterized by XRD, UV-Vis-DRS, XPS, SEM, TEM and photoelectrochemical measurements. Compared to bulk red phosphorus, nano-sized red phosphorus exhibit a significantly enhanced photocatalytic activity for reduction of Cr (VI) due to the greatly reduced charge transfer resistance and enhanced adsorption capability of Cr (VI).