Dynamic Behavior and Interaction Mechanism of Soil Organic Matter in Water Systems: A Coarse-Grained Molecular Dynamics Study.

Investigating soil organic matter's (SOM) microscale assembly and functionality is challenging due to its complexity. This study constructs comparatively realistic SOM models, including diverse components such as Leonardite humic acid (LHA), lipids, peptides, carbohydrates, and lignin, to unveil their spontaneous self-assembly behavior at the mesoscopic scale through microsecond coarse-grained molecular dynamics simulations. We discovered an ordered SOM aggregation creating a layered phase from its hydrophobic core to the aqueous phase, resulting in an increasing O/C ratio and declining structural amphiphilicity. Notably, the amphiphilic lipids formed a bilayer membrane, partnering with lignin to constitute SOM's hydrophobic core. LHA, despite forming a layer, was embedded within this structure. The formation of such complex architectures was driven by nonbonded interactions between components. Our analysis revealed component-dependent diffusion effects within the SOM system. Lipids, peptides, and lignin showed inhibitory effects on self-diffusion, while carbohydrates facilitated diffusion. This study offers novel insights into the dynamic behavior and assembly of SOM components, introducing an effective approach for studying dynamic SOM mechanisms in aquatic environments.

New Mechanism for the Apoptosis of Human Neuroblastoma Cells by the Interaction between Fluorene-9-Bisphenol and the G Protein-Coupled Estrogen Receptor 1.

Fluorene-9-bisphenol (BHPF) is an emerging contaminant. Presently, there is no report on its interaction with G protein-coupled estrogen receptor 1 (GPER). By using an integrated toxicity research scenario that combined theoretical study with experimental methods, BHPF was found to inhibit the GPER-mediated effect via direct receptor binding. Molecular dynamics simulations found that Trp2726.48 and Glu2756.51 be the key amino acids of BHPF binding with GPER. Moreover, the calculation indicated that BHPF was a suspected GPER inhibitor, which neither can activate GPER nor is able to form water channels of GPER. The role of two residues was successfully verified by following gene knockout and site-directed mutagenesis assays. Further in vitro assays showed that BHPF could attenuate the increase in intracellular concentration of free Ca2+ induced by G1-activated GPER. Besides, BHPF showed an enhanced cytotoxicity compared with G15, indicating that BHPF might be a more potent GPER inhibitor than G15. In addition, a statistically significant effect on the mRNA level of GPER was observed for BHPF. In brief, the present study proposes that BHPF be a GPER inhibitor, and its GPER molecular recognition mechanism has been revealed, which is of great significance for the health risk and assessment of BHPF.

Precisely Identifying the Sources of Magnetic Particles by Hierarchical Classification-Aided Isotopic Fingerprinting.

Magnetic particles (MPs), with magnetite (Fe3O4) and maghemite (γ-Fe2O3) as the most abundant species, are ubiquitously present in the natural environment. MPs are among the most applied engineered particles and can be produced incidentally by various human activities. Identification of the sources of MPs is crucial for their risk assessment and regulation, which, however, is still an unsolved problem. Here, we report a novel approach, hierarchical classification-aided stable isotopic fingerprinting, to address this problem. We found that naturally occurring, incidental, and engineered MPs have distinct Fe and O isotopic fingerprints due to significant Fe/O isotope fractionation during their generation processes, which enables the establishment of an Fe-O isotopic library covering complex sources. Furthermore, we developed a three-level machine learning model that not only can distinguish the sources of MPs with a high precision (94.3%) but also can identify the multiple species (Fe3O4 or γ-Fe2O3) and synthetic routes of engineered MPs with a precision of 81.6%. This work represents the first reliable strategy for the precise source tracing of particles with multiple species and complex sources.

Remarkable Contamination of Short- and Medium-Chain Chlorinated Paraffins in Free-Range Chicken Eggs from Rural Tibetan Plateau.

Rapid social-economic development introduces modern lifestyles into rural areas, not only bringing numerous modern products but also new pollutants, such as chlorinated paraffins (CPs). The rural Tibetan Plateau has limited industrial activities and is a unique place to investigate this issue. Herein we collected 90 free-range chicken egg pool samples across the rural Tibetan Plateau to evaluate the pollution status of CPs. Meanwhile, CPs in related soils, free-range chicken eggs from Jiangxi, and farmed eggs from markets were also analyzed. The median concentrations of SCCPs (159 ng g-1 wet weight (ww)) and MCCPs (1390 ng g-1 ww) in Tibetan free-range chicken eggs were comparable to those from Jiangxi (259 and 938 ng g-1 ww) and significantly higher than those in farmed eggs (22.0 and 81.7 ng g-1 ww). In the rural Tibetan Plateau, the median EDI of CPs via egg consumption by adults and children were estimated to be 81.6 and 220.2 ng kg-1 bw day-1 for SCCPs and 483.4 and 1291 ng kg-1 bw day-1 for MCCPs, respectively. MCCPs might pose potential health risks for both adults and children in the worst scenario. Our study demonstrates that new pollutants should not be ignored and need further attention in remote rural areas.

Novel heterozygous mutation of CACNA2D1 gene in a Chinese family with arrhythmia.

BACKGROUND: Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED. METHODS: We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family. RESULTS: A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband's parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation. CONCLUSIONS: WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.

First-principles study on the heterogeneous formation of environmentally persistent free radicals (EPFRs) over α-Fe2O3(0001) surface: Effect of oxygen vacancy.

Metal oxides with oxygen vacancies have a significant impact on catalytic activity for the transformation of organic pollutants in waste-to-energy (WtE) incineration processes. This study aims to investigate the influence of hematite surface oxygen point defects on the formation of environmentally persistent free radicals (EPFRs) from phenolic compounds based on the first-principles calculations. Two oxygen-deficient conditions were considered: oxygen vacancies at the top surface and on the subsurface. Our simulations indicate that the adsorption strength of phenol on the α-Fe2O3(0001) surface is enhanced by the presence of oxygen vacancies. However, the presence of oxygen vacancies has a negative impact on the dissociation of the phenol molecule, particularly for the surface with a defective point at the top layer. Thermo-kinetic parameters were established over a temperature range of 300-1000 K, and lower reaction rate constants were observed for the scission of phenolic O-H bonds over the oxygen-deficient surfaces compared to the pristine surface. The negative effects caused by the oxygen-deficient conditions could be attributed to the local reduction of FeIII to FeII, which lower the oxidizing ability of surface reaction sites. The findings of this study provide us a promising approach to regulate the formation of EPFRs.

Exogenous Chemicals Impact Virus Receptor Gene Transcription: Insights from Deep Learning.

Despite the fact that coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been disrupting human life and health worldwide since the outbreak in late 2019, the impact of exogenous substance exposure on the viral infection remains unclear. It is well-known that, during viral infection, organism receptors play a significant role in mediating the entry of viruses to enter host cells. A major receptor of SARS-CoV-2 is the angiotensin-converting enzyme 2 (ACE2). This study proposes a deep learning model based on the graph convolutional network (GCN) that enables, for the first time, the prediction of exogenous substances that affect the transcriptional expression of the ACE2 gene. It outperforms other machine learning models, achieving an area under receiver operating characteristic curve (AUROC) of 0.712 and 0.703 on the validation and internal test set, respectively. In addition, quantitative polymerase chain reaction (qPCR) experiments provided additional supporting evidence for indoor air pollutants identified by the GCN model. More broadly, the proposed methodology can be applied to predict the effect of environmental chemicals on the gene transcription of other virus receptors as well. In contrast to typical deep learning models that are of black box nature, we further highlight the interpretability of the proposed GCN model and how it facilitates deeper understanding of gene change at the structural level.

Source Identification of Organophosphate Esters through the Profiles in Proglacial and Ocean Sediments from Ny-Ålesund, the Arctic.

Little is known about the sources and environmental behavior of organophosphate esters (OPEs) in the Arctic, especially their transformation products. The present study unprecedentedly investigated both 16 tri-OPEs and 8 di-OPEs in proglacial and ocean sediments from Ny-Ålesund, the Arctic. Mean concentrations of tri-OPEs and di-OPEs in proglacial sediments were 487 and 341 pg/g dry weight (dw), respectively, which were significantly lower than those in ocean sediments (1692 and 525 pg/g dw). Ocean sediments might be simultaneously influenced by long-range atmospheric transport (LRAT), oceanic transport, and human activities, whereas proglacial sediments, since they are isolated from human settlements, may be dominantly affected by LRAT. Such source difference was evidenced by the contamination profile of OPEs: chlorinated tri-OPEs with high environmental persistence and high LRAT were dominant in proglacial sediments (66%); however, weakly environmentally persistent and highly hydrophobic aryl tri-OPEs were dominant in ocean sediments (47%), which were plausibly from local emission sources due to their low LRAT potential. Di-OPEs in proglacial and ocean sediments were dominated by groups of parent tri-OPEs with strong photodegradability, such as alkyl (75%) and aryl (58%). A higher mean molar ratio of di-OPE/tri-OPE in the proglacial sediment (14) than that in the ocean sediment (2.2) may be related to its higher photodegradation than that of the ocean sediment.

Linking Transthyretin-Binding Chemicals and Free Thyroid Hormones: In Vitro to In Vivo Extrapolation Based on a Competitive Binding Model.

Large numbers of pollutants competitively inhibit the binding between thyroid hormones and transthyretin (TTR) in vitro. However, the impact of this unintended binding on free thyroid hormones in vivo has not yet been characterized. Herein, we established a quantitative in vitro to in vivo extrapolation (QIVIVE) method based on a competitive binding model to quantify the effect of TTR-binding chemicals on free thyroid hormones in human blood. Twenty-five TTR-binding chemicals including 6 hydroxyl polybromodiphenyl ethers (OH-PDBEs), 6 hydroxyl polychlorobiphenyls (OH-PCBs), 4 halogenphenols, 5 per- and polyfluorinated substances (PFASs), and 4 phenols were selected for investigation. Incorporating the in vitro binding parameters and human exposure data, the QIVIVE model could well predict the in vivo effect on free thyroid hormones. Co-exposure to twenty-five typical TTR-binding chemicals resulted in median increases of 0.080 and 0.060% in circulating levels of free thyroxine (FT4) and free triiodothyronine (FT3) in the general population. Individuals with occupational exposure to TTR-binding chemicals suffered 1.88-32.2% increases in free thyroid hormone levels. This study provides a quantitative tool to evaluate the thyroid-disrupting risks of TTR-binding chemicals and proposes a new framework for assessing the in vivo effects of chemical exposures on endogenous molecules.

RNA adenosine modifications related to prognosis and immune infiltration in osteosarcoma.

BACKGROUND: RNA adenosine modifications, which are primarily mediated by "writer" enzymes (RMWs), play a key role in epigenetic regulation in various biological processes, including tumorigenesis. However, the expression and prognostic role of these genes in osteosarcoma (OS) remain unclear. METHODS: Univariate and multivariate Cox analyses were used to construct the RMW signature for OS using Target datasets. RMW expression in OS tissue was detected by qPCR analysis. Xcell and GSVA were used to determine the relationship between RMWs and immune infiltration. The DGIdb and CMap databases were used for drug prediction. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS. RESULTS: A 3-RMW (CSTF2, ADAR and WTAP) prognostic signature in OS was constructed using the Target dataset and verified using GEO datasets and 63 independent OS tissues via qPCR analysis. High-risk OS patients had poor overall survival, and the prognostic signature was an independent prognostic factor for OS. Functional studies showed that tumour-, metabolism-, cell cycle- and immune-related pathways were related to high risk. Next, we found that RMW-derived high-risk patients exhibited increased infiltration of M2 macrophages and cDCs. Furthermore, we predicted the potential drugs for OS using the DGIdb and CMap databases. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS by repressing cell growth and inducing cell cycle arrest at the G1 phase. CONCLUSION: The 3-RWM-based prognostic signature established in this study is a novel gene signature associated with immune infiltration, and strophanthidin was identified as a candidate therapy for OS by repressing OS cell growth and the cell cycle.