Metabolomic and Lipidomic Analysis of Manganese-Associated Parkinsonism: a Case-Control Study in Brescia, Italy.

Background and Objectives: Excessive Manganese (Mn) exposure is neurotoxic and can cause Mn-Induced Parkinsonism (MnIP), marked by cognitive and motor dysfunction. Although metabolomic and lipidomic research in Parkinsonism (PD) patients exists, it remains limited. This study hypothesizes distinct metabolomic and lipidomic profiles based on exposure status, disease diagnosis, and their interaction. Methods: We used a case-control design with a 2×2 factorial framework to investigate the metabolomic and lipidomic alterations associated with Mn exposure and their link to PD. The study population of 97 individuals was divided into four groups: non-exposed controls (n=23), exposed controls (n=25), non-exposed with PD (n=26) and exposed with PD (n=23). Cases, defined by at least two cardinal PD features (excluding vascular, iatrogenic, and traumatic origins), were recruited from movement disorder clinics in four hospitals in Brescia, Northern Italy. Controls, free from neurological or psychiatric conditions, were selected from the same hospitals. Exposed subjects resided in metallurgic regions (Val Camonica and Bagnolo Mella) for at least 8 continuous years, while non-exposed subjects lived in low-exposure areas around Lake Garda and Brescia city. We conducted untargeted analyses of metabolites and lipids in whole blood samples using ultra-high-performance liquid chromatography (UHPLC) and mass spectrometry (MS), followed by statistical analyses including Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA), and Two-Way Analysis of Covariance (ANCOVA). Results: Metabolomic analysis revealed modulation of alanine, aspartate, and glutamate metabolism (Impact=0.05, p=0.001) associated with disease effect; butanoate metabolism (Impact=0.03, p=0.004) with the exposure effect; and vitamin B6 metabolism (Impact=0.08, p=0.03) with the interaction effect. Differential relative abundances in 3-sulfoxy-L-Tyrosine (ß=1.12, FDR p<0.001), glycocholic acid (ß=0.48, FDR p=0.03), and palmitelaidic acid (ß=0.30, FDR p<0.001) were linked to disease, exposure, and interaction effects, respectively. In the lipidome, ferroptosis (Pathway Lipids=11, FDR p=0.03) associated with the disease effect and sphingolipid signaling (Pathway Lipids=9, FDR p=0.04) associated with the interaction effect were significantly altered. Lipid classes triacylglycerols, ceramides, and phosphatidylethanolamines showed differential relative abundances associated with disease, exposure, and interaction effects, respectively. Discussion: These findings suggest that PD and Mn exposure induce unique metabolomic and lipidomic changes, potentially serving as biomarkers for MnIP and warranting further study.

Warming decreased plant litter decomposition by modulating soil fauna interactions in a Tibetan alpine meadow.

Litter decomposition is a vital process for maintaining ecosystem carbon cycling. It is affected by soil fauna which are predators and decomposers of litter. However, how the interactions of soil fauna communities affect litter decomposition remains unclear under warming. Here, we conducted a five-year in-situ manipulative warming experiment by Open-Top Chamber (OTC) in an alpine meadow on the Tibetan Plateau to reveal how warming affects litter decomposition. The results demonstrated that warming decreased the litter decomposition rate by 29 %, the soil collembola abundance by 25 %, and the nematode abundance by 27 %. Nematode ecological indices remain stable but a shift in the decomposition of litter to the fungivores pathway under warming. The piecewise structural equation modelling result revealed that the combined reduction in soil collembola and nematodes synergistically leads to a massive decline in litter decomposition rate under warming. Our results highlight that the interactions of soil fauna can regulate litter decomposition under warming, and collembola abundance as the "speed-limiter" of litter decomposition. Therefore, the response of changes in soil fauna relationships to warming should be completely considered in future climate change modelling of the grassland carbon cycle.

Changes in soil properties and microbial activity unveil the distinct impact of polyethylene and biodegradable microplastics on chromium uptake by peanuts.

Microplastics (MPs) are emerging persistent pollutants, and heavy metals are typical environmental pollutants, with their coexistence potentially compounding pollution and ecological risks. However, the interactive impacts and the relevant mechanisms of heavy metal and different types of MPs in plant-soil systems are still unclear. This study investigated the differential impacts of polyethylene MPs (PE MPs) and biodegradable polybutylene adipate MPs (PBAT MPs) on chromium (Cr) uptake in peanuts, focusing on plant performance and rhizosphere soil microenvironment. Compared with nondegradable PE-MPs, biodegradable PBAT MPs produced less significant influences on plant phytotoxicity, soil Cr bioavailability, and soil properties such as pH, CEC, DOC, and MBC, with the exception of MBN in Cr-contaminated soils. Compared to the control, soil pH and cation exchange capacity (CEC) decreased by MPs, while soil-soluble carbon (DOC), microbial biomass carbon, and nitrogen (MBC and MBN) increased by MPs. Compared to the control, soil-bioavailable Cr increased by 11.8-177.8% under PE MPs treatments, while increased by 5.1-156.9% under PBAT MPs treatments. The highest Cr content in shoots and roots was observed at 500.0 mg·kg-1 Cr level, which increased by 53.1% and 79.2% under 5% PE MPs treatments, respectively, as well as increased by 38.3% and 60.4% under 5% PBAT MPs treatments, respectively, compared with the control. The regression path analysis indicated that pH, MBC, MBN, and soil-bioavailable Cr played a vital role in the changes of soil properties and Cr uptake by peanuts induced by MPs. Soil bacterial community analysis revealed that Nocardioides, Proteobacteria, and Sphingomonas were reduced by the inhibition of MPs, which affected Cr uptake by peanuts. These results indicated that the peanut soil microenvironment was affected by PBAT and PE MPs, altering the Cr bioavailability and plant Cr uptake in Cr-contaminated soil.

Effects of polyurethane microplastics combined with cadmium on maize growth and cadmium accumulation under different long-term fertilisation histories.

Agricultural production uses different types of fertilisation treatments, typically employing the combined application of organic fertiliser (OF) or organic-inorganic fertiliser (OIF) to improve soil quality. When coupled with cadmium (Cd), microplastics (MPs) affect plant growth and Cd accumulation in soils treated with different fertilisers. This study systematically examined the effects of polyurethane (PU) MPs coupled with Cd on the growth characteristics, root metabolite characteristics, rhizosphere bacterial community structure, and Cd bioavailability of maize under different long-term fertilisation treatments and soil types (red/cinnamon soil). The combined effects of PU MPs and Cd on maize growth differed across fertilisation treatments. Under OF, maize plants accumulated more Cd than under OIF. The accumulation of Cd in maize plants in red soil was twice that in cinnamon soil. Under OF, PU MPs promoted Cd activation by decreasing the soil pH, while root metabolites promoted Cd adsorption sites by synthesising specific amino acids, degrading aromatic compounds, and synthesising pantothenic acid and coenzyme A. Under OF, PU MPs can lower the soil pH to promote the activation of cadmium, while root metabolites promote root growth and increase cadmium adsorption sites by synthesizing specific amino acids, degrading aromatic compounds, and synthesizing pantothenic acid and coenzyme A, hereby promoting root Cd absorption. Under OIF, PU MPs act by influencing the biosynthesis of amino acids in root metabolites, enriching energy metabolism pathways, promoting the transport and translocation of mineral nutrients, thereby amplifying the "toxic effects" of Cd. This study provides new insights into the risk assessment of PU MPs and Cd coupling under different fertilisation treatments, and suggests that the prevention and control of combined PU MPs and Cd pollution in red soil under OF treatment should receive more attention in the future.

Effects of Long-Term Controlled-Release Urea on Soil Greenhouse Gas Emissions in an Open-Field Lettuce System.

Controlled-release urea (CRU) fertilizers are widely used in agricultural production to reduce conventional nitrogen (N) fertilization-induced agricultural greenhouse gas emissions (GHGs) and improve N use efficiency (NUE). However, the long-term effects of different CRU fertilizers on GHGs and crop yields in vegetable fields remain relatively unexplored. This study investigated the variations in GHG emissions at four growth stages of lettuce in the spring and autumn seasons based on a five-year field experiment in the North China Plain. Four treatments were setup: CK (without N application), U (conventional urea-N application), ON (20% reduction in urea-N application), CRU (20% reduction in polyurethane-coated urea without topdressing), and DCRU (20% reduction in polyurethane-coated urea containing dicyandiamide [DCD] without topdressing). The results show that N application treatments significantly increased the GHG emissions and the lettuce yield and net yield, and DCRU exhibited the lowest N2O and CO2 emissions, the highest lettuce yield and net yield, and the highest lettuce N content of the N application treatments. When compared to U, the N2O emission peak under CRU and DCRU treatments was notably decreased and delayed, and their average N2O emission fluxes were significantly reduced by 10.20-20.72% and 17.51-29.35%, respectively, leading to a significant reduction in mean cumulative N2O emissions during the 2017-2021 period. When compared to U, the CO2 fluxes of DCRU significantly decreased by 8.0-16.54% in the seedling period, and mean cumulative CO2 emission decreased by 9.28%. Moreover, compared to U, the global warming potential (GWP) and greenhouse gas intensity (GHGI) of the DCRU treatment was significantly alleviated by 9.02-17.13% and 16.68-20.36%, respectively. Compared to U, the N content of lettuce under DCRU was significantly increased by 6.48-17.25%, and the lettuce net yield was also significantly increased by 5.41-7.71%. These observations indicated that the simple and efficient N management strategy to strike a balance between enhancing lettuce yields and reduce GHG emissions in open-field lettuce fields could be obtained by applying controlled-release urea containing DCD without topdressing.

[Effects of Controlled-release Blended Fertilizer on Crop Yield and Greenhouse Gas Emissions in Wheat-maize Rotation System].

The increasing use of nitrogen fertilizers exerts extreme pressure on the environment (e.g., greenhouse gas emissions, GHGs) for winter wheat-summer maize rotation systems in the North China Plain. The application of controlled-release fertilizers is considered as an effective measure to improve crop yield and nitrogen fertilizer utilization efficiency. To explore the impact of one-time fertilization of controlled-release blended fertilizer on crop yield and GHGs of a wheat-maize rotation system, field experiments were carried out in Dezhou Modern Agricultural Science and Technology Park from 2020 to 2022. Five treatments were established for both winter wheat and summer maize, including no nitrogen control (CK), farmers' conventional nitrogen application (FFP), optimized nitrogen application (OPT), CRU1 (the blending ratio of coated urea and traditional urea on winter wheat and summer maize was 5:5 and 3:7, respectively), and CRU2 (the blending ratio of coated urea and traditional urea on winter wheat and summer maize was 7:3 and 5:5, respectively). The differences in yield, nitrogen fertilizer utilization efficiency, fertilization economic benefits, and GHGs among different treatments were compared and analyzed. The results showed that nitrogen application significantly increased the single season and annual crop yields of the wheat-maize rotation system (P < 0.05). Compared with those of FFP, the CRU1 and CRU2 treatments increased the yields of summer maize by 0.4% to 5.6%, winter wheat by -5.4% to 4.1%, and annual yields by -1.1% to 3.9% (P > 0.05). N recovery efficiency (NRE), N agronomic efficiency (NAE), and N partial factor productivity (NPFP) were increased by -8.6%-43.4%, 2.05-6.24 kg·kg-1, and 4.24-10.13 kg·kg-1, respectively. Annual net income increased by 0.2% to 6.3%. Nitrogen application significantly increased the annual emissions of soil N2O and CO2 in the rotation system (P < 0.05) but had no effect on the annual emissions of CH4 (except for in the FFP treatment in the first year). The annual total N2O emissions under the CRU1 and CRU2 treatments were significantly reduced by 23.4% to 30.2% compared to those under the FFP treatment (P < 0.05). Additionally, nitrogen application significantly increased the annual global warming potential (GWP) of the rotation system (P < 0.05), but the intensity of greenhouse gas emissions was reduced due to the increase in crop yields. Compared with that under FFP, the annual GWP under the CRU1 and CRU2 treatments decreased by 9.6% to 11.5% (P < 0.05), and the annual GHGs decreased by 11.2% to 13.8% (P > 0.05). In summary, the one-time application of controlled-release blended fertilizer had a positive role in improving crop yield and economic benefits, reducing nitrogen fertilizer input and labor costs, and GHGs, which is an effective nitrogen fertilizer management measure to promote cleaner production of food crops in the North China Plain.

[Effect of Film Mulching Age and Organic Fertilizer Application on the Distribution Characteristics of Microplastics in the Soil of a Peanut Field].

The large input of mulch film and organic fertilizer have led to increasingly serious microplastic pollution in farmland soil of China. In this study, the microplastic pollution of peanut farmland in Dezhou City, Shandong Province was investigated. The effects of different mulching years (0, 3, 5, and 8 years) and organic fertilizer application on the abundance, particle size, color, and shape of microplastics in farmland soil were analyzed. The results showed that the average abundances of microplastics in peanut soil were 65.33, 316.00, 1 098.67, and 1 346.34 n·kg-1, respectively, after 0, 3, 5, and 8 years of film mulching. The abundance of microplastics decreased with the increase in soil depth. The abundance of microplastics in 0-10, 10-20, and 20-30 cm topsoil was 1 076.00, 603.5, and 440.25 n·kg-1, respectively, and the abundance of microplastics increased significantly with increasing years of film mulching and organic fertilizer application (P<0.05). The particle size of microplastics in the sample plot <1 mm accounted for 77.30% of the total content, and with the increase in film mulching age, the proportion of microplastics with small particle size (<1 mm) increased significantly (P < 0.05). With the increase in soil depth, the proportion of microplastics with small particle size also gradually increased, whereas the application of organic fertilizer had no significant effect on the particle size of microplastics. The color of microplastics in the plot was mainly transparent (49.77%), followed by black (16.35%) and white (16.27%). The planting age and organic fertilizer application had no significant effect on the color of microplastics in the soil (P > 0.05), but the mulching age significantly increased the proportion of transparent microplastics. The abundance proportion of the five types of microplastics were 49.77%, 25.41%, 19.15%, 3.26%, and 2.41%, respectively. These field soil microplastics were mainly composed of polyethylene (PE), polypropylene (PP), and polystyrene (PS) polymers, accounting for 21.37%, 18.57%, and 19.77% of the total, respectively. Therefore, microplastics were widely present in the soil of the peanut field cultivated layer in Dezhou, Shandong, and the applications of mulch film and organic fertilizer were the main source. This study provides an important basis for the prevention and control of soil microplastic pollution in peanut fields.

Oropharyngeal Stenosis Caused by Significant Scar Hyperplasia Following Tonsillectomy: A Case Report.

Oropharyngeal stenosis (OPS) is a relatively rare long-term complication of tonsillectomy in children, resulting from the narrowing of the upper aerodigestive tract between the soft palate, pharyngeal sidewalls, and base of the tongue. This is the first reported case of OPS due to significant scar hyperplasia; however, whether it is as prone to recurrence as skin scar hypertrophy remains unknown. In this article, we present the case of a 5-year-old girl who presented to our otolaryngology clinic with sleep snoring and suffocation. Her medical history included tonsillectomy and adenoidectomy, performed 3 years prior to presentation. The patient underwent a combination of surgery and administration of triamcinolone injections, resulting in significant symptomatic improvement. To date, no signs of recurrence have been reported.

Alpha-1 antitrypsin deficiency and pregnancy complications and birth outcomes: A population-based cohort study in Denmark.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is related to developing lung and liver disease, but no large-scale studies examine its association with birth outcomes. OBJECTIVE: We investigated the risk of pregnancy complications and adverse birth outcomes in mothers and children with AATD. METHODS: Using a large cohort data of Danish mothers and children with AATD from 1973 to 2013 (n = 2,027,229), with 559 cases (305 mothers and 254 children). We conducted Poisson regression to examine associations between alpha-1 antitrypsin deficiency, adverse birth outcomes, and pregnancy complications in mothers and children. RESULTS: AATD was related to term low birth weight [<2500g; Risk Ratio(RR) = 2.04, 95% confidence interval (CI): 1.50-2.79], lowest quartile of abdominal circumference at birth in children of non-smoking mothers (RR = 1.55, 95% CI: 1.14-2.11), delivery via Cesarean-section (RR = 1.59, 95% CI: 1.05-2.40), preterm birth (RR = 1.54, 95% CI: 1.19-2.00) and preeclampsia (RR = 2.64, 95% CI: 1.76-3.94). CONCLUSIONS: This emphasizes the need for mothers with AATD to be monitored closely during pregnancy to reduce the risk of adverse birth outcomes. Routine screening for alpha-1 antitrypsin in pregnancy may be considered among mothers with a pulmonary and liver disease history.

Neonatal per- and polyfluoroalkyl substance exposure in relation to retinoblastoma.

BACKGROUND: Neonatal per- and polyfluoroalkyl substance (PFAS) exposure can disrupt hormonal homeostasis and induce neuro- and immunotoxicity in children. In this exploratory study, we investigated associations between PFAS levels in neonatal dried blood spots and retinoblastoma risk. MATERIALS AND METHODS: This study included 501 retinoblastoma cases born from 1983 to 2011 and 899 controls frequency-matched by birth year (20:1 matching ratio), born to 755 US-born and 366 Mexico-born mothers in California. Perfluorooctanesulfonic acid (PFOS), perflurooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) feature intensities were identified from neonatal blood spots from California newborn Genetic Disease Screening Program. Using logistic regression, we assessed whether an interquartile range (IQR) increase of PFAS levels or having above-mean levels of PFAS in blood affects retinoblastoma risk overall or its subtypes (i.e., unilateral, bilateral). We assessed children of US-born and Mexico-born mothers, separately. RESULTS AND DISCUSSION: Among all children, above-mean PFOS levels at birth increased the odds of retinoblastoma overall by 29% (95% Confidence Interval (CI): 1.00, 1.67) and unilateral retinoblastoma by 42% (95% CI: 1.03, 1.97). For children of Mexico-born mothers, we estimated the highest odds of retinoblastoma overall (adjusted odds ratio (aOR): 1.67; 95% CI: 1.06, 2.66) and bilateral retinoblastoma (aOR: 2.06; 95% CI: 1.12, 3.92) with above-mean PFOS levels. Among children of US-born mothers, higher PFOS levels increased the odds of unilateral retinoblastoma by 15% (95% CI: 0.99, 1.35) for each IQR increase and by 71% among children with above-mean PFOS levels (95% CI: 1.04, 2.90). In addition, for children of US-born mothers, PFOA increased the odds of retinoblastoma overall (aOR: 1.41; 95% CI: 1.00, 2.02 for above-mean levels, aOR: 1.06; 95% CI: 0.98, 1.16 per IQR increase). PFNA was not associated with retinoblastoma risk. CONCLUSIONS: Our results suggested that PFOS and PFOA might contribute to retinoblastoma risk in children born in California.

[Effect of miR-125b on T Cell Activation in Aplastic Anemia by Targetting B7-H4].

OBJECTIVE: To investigate the effect of miR-125b on T cell activation in patients with aplastic anemia (AA) and its molecular mechanism. METHODS: A total of 30 AA patients were enrolled in department of hematology, Binzhou Medical University Hospital from January 2018 to October 2021, as well as 15 healthy individuals as healthy control (HC) group. Peripheral blood mononuclear cells (PBMCs) were isolated, in which the levels of miR-125b and B7-H4 mRNA were detected by RT-qPCR. Immunomagnetic beads were used to separate naive T cells and non-naive T cells from AA patients and healthy people to detect the levels of miR-125b and B7-H4 mRNA. Lentivirus LV-NC inhibitor and LV-miR-125b inhibitor were transfected into cells, and T cell activation was detected by flow cytometry. The dual-luciferase reporter gene assay was used to detect the targetting relationship between miR-125b and B7-H4. RT-qPCR and Western blot were used to detect the levels of miR-125b, CD40L, ICOS, IL-10 mRNA and B7-H4 protein. RESULTS: Compared with HC group, the expression of miR-125b was up-regulated but B7-H4 mRNA was down-regulated in PBMCs of AA patients (P <0.05), and the proportions of CD4+CD69+ T cells and CD8+CD69+ T cells in PBMCs of AA patients were higher (P <0.05). The expression of miR-125b was significantly up-regulated but B7-H4 mRNA was down-regulated in both naive T cells and non-naive T cells of AA patients (P <0.05), and non-naive T cells was more significant than naive T cells (P <0.05). Compared with NC inhibitor group, the expression of miR-125b was significantly decreased, the expression level of CD69 on CD4+ and CD8+ T cells in PBMCs was also significantly decreased, while the luciferase activity was significantly increased after co-transfection of miR-125b inhibitor and B7-H4-3'UTR-WT in the miR-125b inhibitor group (P <0.05). Compared with NC inhibitor group, the mRNA and protein levels of B7-H4 were significantly increased in the miR-125b inhibitor group (P <0.05). Compared with miR-125b inhibitor+shRNA group, the expression levels of CD69 on CD4+ and CD8+ T cells were significantly increased, and the levels of CD40L, ICOS and IL-10 mRNA were also significantly increased in the miR-125b inhibitor+sh-B7-H4 group (P <0.05). CONCLUSION: MiR-125b may promote T cell activation by targetting B7-H4 in AA patients.

The neonatal blood spot metabolome in retinoblastoma.

Background: Retinoblastoma is rare but nevertheless the most common pediatric eye cancer that occurs in children under age 5. High-resolution metabolomics (HRM) is a powerful analytical approach to profile metabolic features and pathways or identify metabolite biomarkers. To date, no studies have used pre-diagnosis blood samples from retinoblastoma cases and compared them to healthy controls to elucidate early perturbations in tumor pathways. Objectives: Here, we report on metabolic profiles of neonatal blood comparing cases later in childhood diagnosed with retinoblastoma and controls. Methods: We employed untargeted metabolomics analysis using neonatal dried blood spots for 1327 children (474 retinoblastoma cases and 853 healthy controls) born in California from 1983 to 2011. Cases were selected from the California Cancer Registry and controls, frequency matched to cases by birth year, from California birth rolls. We performed high-resolution metabolomics to extract metabolic features, partial least squares discriminant analysis (PLS-DA) and logistic regression to identify features associated with disease, and Mummichog pathway analysis to characterize enriched biological pathways. Results: PLS-DA identified 1917 discriminative features associated with retinoblastoma and Mummichog identified 14 retinoblastoma-related enriched pathways including linoleate metabolism, pentose phosphate pathway, pyrimidine metabolism, fructose and mannose metabolism, vitamin A metabolism, as well as fatty acid and lipid metabolism. Interpretation: Our findings linked a retinoblastoma diagnosis in early life to newborn blood metabolome perturbations indicating alterations in inflammatory pathways and energy metabolism. Neonatal blood spots may provide a venue for early detection for this or potentially other childhood cancers.

Kaolinite reduced Cd accumulation in peanut and remediate soil contaminated with both microplastics and cadmium.

Microplastics (MPs) increase the effective state of heavy metals (HMs) in soil and seriously threaten the yield and quality of peanuts (Arachis Hypogea L.). Kaolinite (KL) has the potential to ameliorate MP- and HM- contaminated soils, but the mechanism of action between them is not well understood. Therefore, 60-day experiments were conducted, where KL (1 %, 2 %) and MPs (0.1 %, 1 %) were individually or jointly mixed into soils with different cadmium (Cd) concentrations (0.5, 2.5, and 5.0 mg·kg-1) to cultivate peanuts in a greenhouse. Finally, soil-bioavailable Cd, peanut dry weight, peanut Cd concentrations, the pH, cation exchange capacity (CEC), dissolved organic carbon (DOC), microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) were determined. It was shown that MPs negatively affected the peanut dry weight and increased the content of soil-bioavailable Cd and Cd concentration in peanut. In the MP- and Cd-contaminated soils, KL mitigated the negative influence of MPs by increasing the dry weight of peanuts by 8.40 %-40.59 %, decreasing the soil-bioavailable Cd by 23.70-35.74 %, and significantly decreasing peanut Cd concentrations by 9.65-30.86 %. The presence of MPs decreased soil pH (7.69-7.87) and the CEC (20.96-23.95 cmol·L-1) and increased the soil DOC (1.84-2.26 mg·kg-1). KL significantly increased soil pH (7.79-8.03) and the CEC (24.96-28.28 cmol·L-1) and mitigated the adverse influence of MPs on the pH and CEC of Cd-contaminated soils. A regression path analysis (RPA) evidenced that KL decreased Cd accumulation in plants by changing the properties of soil contaminated with MPs and Cd. The research results revealed the mechanism of KL on peanut growth and Cd absorption in MP- and Cd-contaminated soil. The results of this study provide a foundation to improve the quality of MP- and HM-contaminated soils and realize safe peanut production.

Altered Peripheral Blood Gene Expression in Childhood Cancer Survivors With Anthracycline-Induced Cardiomyopathy - A COG-ALTE03N1 Report.

Background Anthracycline-induced cardiomyopathy is a leading cause of premature death in childhood cancer survivors, presenting a need to understand the underlying pathogenesis. We sought to examine differential blood-based mRNA expression profiles in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Methods and Results We designed a matched case-control study (Children's Oncology Group-ALTE03N1) with mRNA sequencing on total RNA from peripheral blood in 40 anthracycline-exposed survivors with cardiomyopathy (cases) and 64 matched survivors without (controls). DESeq2 identified differentially expressed genes. Ingenuity Pathway Analyses (IPA) and Gene Set Enrichment Analyses determined the potential roles of altered genes in biological pathways. Functional validation was performed by gene knockout in human-induced pluripotent stem cell-derived cardiomyocytes using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) technology. Median age at primary cancer diagnosis for cases and controls was 8.2 and 9.7 years, respectively. Thirty-six differentially expressed genes with fold change ≥±2 were identified; 35 were upregulated. IPA identified "hepatic fibrosis" and "iron homeostasis" pathways to be significantly modulated by differentially expressed genes, including toxicology functions of myocardial infarction, cardiac damage, and cardiac dilation. Leading edge analysis from Gene Set Enrichment Analyses identified lactate dehydrogenase A (LDHA) and cluster of differentiation 36 (CD36) genes to be significantly upregulated in cases. Interleukin 1 receptor type 1, 2 (IL1R1, IL1R2), and matrix metalloproteinase 8, 9 (MMP8, MMP9) appeared in multiple canonical pathways. LDHA-knockout human-induced pluripotent stem cell-derived cardiomyocytes showed increased sensitivity to doxorubicin. Conclusions We identified differential mRNA expression profiles in peripheral blood of anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Upregulation of LDHA and CD36 genes suggests metabolic perturbations in a failing heart. Dysregulation of proinflammatory cytokine receptors IL1R1 and IL1R2 and matrix metalloproteinases, MMP8 and MMP9 indicates structural remodeling that accompanies the clinical manifestation of symptomatic cardiotoxicity.

Identification of novel hypermethylated or hypomethylated CpG sites and genes associated with anthracycline-induced cardiomyopathy.

Anthracycline-induced cardiomyopathy is a leading cause of late morbidity in childhood cancer survivors. Aberrant DNA methylation plays a role in de novo cardiovascular disease. Epigenetic processes could play a role in anthracycline-induced cardiomyopathy but remain unstudied. We sought to examine if genome-wide differential methylation at 'CpG' sites in peripheral blood DNA is associated with anthracycline-induced cardiomyopathy. This report used participants from a matched case-control study; 52 non-Hispanic White, anthracycline-exposed childhood cancer survivors with cardiomyopathy were matched 1:1 with 52 survivors with no cardiomyopathy. Paired ChAMP (Chip Analysis Methylation Pipeline) with integrated reference-based deconvolution of adult peripheral blood DNA methylation was used to analyze data from Illumina HumanMethylation EPIC BeadChip arrays. An epigenome-wide association study (EWAS) was performed, and the model was adjusted for GrimAge, sex, interaction terms of age at enrollment, chest radiation, age at diagnosis squared, and cardiovascular risk factors (CVRFs: diabetes, hypertension, dyslipidemia). Prioritized genes were functionally validated by gene knockout in human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) using CRISPR/Cas9 technology. DNA-methylation EPIC array analyses identified 32 differentially methylated probes (DMP: 15 hyper-methylated and 17 hypo-methylated probes) that overlap with 23 genes and 9 intergenic regions. Three hundred and fifty-four differential methylated regions (DMRs) were also identified. Several of these genes are associated with cardiac dysfunction. Knockout of genes EXO6CB, FCHSD2, NIPAL2, and SYNPO2 in hiPSC-CMs increased sensitivity to doxorubicin. In addition, EWAS analysis identified hypo-methylation of probe 'cg15939386' in gene RORA to be significantly associated with anthracycline-induced cardiomyopathy. In this genome-wide DNA methylation profile study, we observed significant differences in DNA methylation at the CpG level between anthracycline-exposed childhood cancer survivors with and without cardiomyopathy, implicating differential DNA methylation of certain genes could play a role in pathogenesis of anthracycline-induced cardiomyopathy.

Under flooding conditions, controlled-release fertiliser coated microplastics affect the growth and accumulation of cadmium in rice by increasing the fluidity of cadmium and interfering with metabolic pathways.

The combined pollution of microplastics (MPs) and Cd can affect plant growth and development and Cd accumulation, with most studies focusing on dryland soil. However, the effects of polyurethane (PU) controlled-release fertiliser coated MPs (PU MPs), which widely exist in rice systems, coupled with Cd on plant growth and Cd accumulation under flooding conditions are still unknown. Therefore, in the present study, in situ techniques were used to systematically study the effects of PU MPs and Cd coupling on the physiological and biochemical performance, metabolomics characteristics, rhizosphere bacterial community, and Cd bioavailability of rice in different soil types (red soil/cinnamon soil). The results showed that the effects of PU MPs on rice growth and Cd accumulation were concentration-dependent, especially in red soil. High PU concentration (1 %) inhibited rice root growth significantly (44 %). The addition of PU MPs inhibited photosynthetically active radiation, net photosynthesis, and transpiration rate of rice, mainly with low concentration (0.1 %) in red soil and high concentration (1 %) in cinnamon soil. PU MPs can enhance the expression of Cd resistance genes (cadC and copA) in soil, enhance the mobility of Cd, and affect the metabolic pathways of metabolites in the rhizosphere soil (red soil: fatty acid metabolism; cinnamon soil: amino acid degradation, heterobiodegradation, and nucleotide metabolism) to promote Cd absorption in rice. Especially in red soil, Cd accumulation in the root and aboveground parts of rice after the addition of high concentration PU (1 %) was 1.7 times and 1.3 times, respectively, that of the control (p < 0.05). Simultaneously, microorganisms can affect rice growth and Cd bioavailability by affecting functional bacteria related to carbon, iron, sulfur, and manganese. The results of the present study provide novel insights into the potential effects of PU MPs coupled with Cd on plants, rhizosphere bacterial communities, and Cd bioavailability.

Haptoglobin Gene Expression and Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A COG-ALTE03N1 Report.

Background: Anthracycline-related cardiomyopathy is a leading cause of premature death in childhood cancer survivors. The high interindividual variability in risk suggests the need to understand the underlying pathogenesis. Objectives: The authors interrogated differentially expressed genes (DEGs) to identify genetic variants serving regulatory functions or genetic variants not easily identified when using genomewide array platforms. Using leads from DEGs, candidate copy number variants (CNVs) and single-nucleotide variants (SNVs) were genotyped. Methods: Messenger RNA sequencing was performed on total RNA from peripheral blood of 40 survivors with cardiomyopathy (cases) and 64 matched survivors without cardiomyopathy (control subjects). Conditional logistic regression analysis adjusting for sex, age at cancer diagnosis, anthracycline dose, and chest radiation was used to assess the associations between gene expression and cardiomyopathy and between CNVs and SNVs and cardiomyopathy. Results: Haptoglobin (HP) was identified as the top DEG. Participants with higher HP gene expression had 6-fold greater odds of developing cardiomyopathy (OR: 6.4; 95% CI: 1.4-28.6). The HP2-specific allele among the HP genotypes (HP1-1, HP1-2, and HP2-2) had higher transcript levels, as did the G allele among SNVs previously reported to be associated with HP gene expression (rs35283911 and rs2000999). The HP1-2 and HP2-2 genotypes combined with the G/G genotype for rs35283911 and/or rs2000999 placed the survivors at 4-fold greater risk (OR: 3.9; 95% CI: 1.0-14.5) for developing cardiomyopathy. Conclusions: These findings provide evidence of a novel association between HP2 allele and cardiomyopathy. HP binds to free hemoglobin to form an HP-hemoglobin complex, thereby preventing oxidative damage from free heme iron, thus providing biological plausibility to the mechanistic basis of the present observation.

Organic fertilizer and irrigation water are the primary sources of microplastics in the facility soil, Beijing.

The large-scale utilization of plastic products in agricultural facility production has resulted in considerable accumulation of microplastics in the soil. However, there is a lack of systematic research on the accumulation and distribution of microplastics in facility agriculture. This study examined the presence of microplastics in the 15 representatives of Beijing facility agriculture soil in five districts with different planting years, and assessed the potential pollution risks. The abundance of microplastics in soil layers at a depth of 0-10, 10-20, and 20-30 cm was 896.5 ± 80.0 (range, 160-2120), 630.6 ± 47.0 (180-1340), and 445.3 ± 47.0 (80-1480) items/kg, respectively. Overall, the microplastics were primarily fiber-shaped (72.2 %), white (75.9 %), 1-2 mm in size (37.9 %), and composed of polypropylene and polyethene. The risk assessment indices of the microplastics in the 0-10, 10-20, and 20-30 cm soil layers were 272.1, 289.5, and 291.6, respectively, representing a risk level of 4 in each case. Using the conditional fragmentation model, we found that the microplastics in facility soil featured low stability and small sizes, and their primary sources were organic fertilizer and irrigation water. The number of mulching years, irrigation method, and the amount of organic fertilizer applied, influenced the accumulation of microplastics in the facility soil. This study provides scientific evidence supporting the pollution levels and need for risk control related to microplastics in facility soils.

Microplastic pollution and the related ecological risks of organic composts from different raw materials.

Organic composts are considered emerging contributors to microplastics (MPs) accumulation in agricultural soils. However, MPs pollution in organic compost from different raw materials is unknown. This study investigated MPs occurrence and characteristics in 124 organic compost samples, including single feedstock (livestock manure, poultry manure, crop straw, and solid waste) and compound organic composts, and quantitatively assessed related ecological risks of MPs pollution. The highest and lowest MPs abundances were observed in solid waste (6615 items kg-1) and crop straw (1500 items kg-1) composts, respectively. Compost MPs were mainly 0.5-1 mm (39.5%), colorful polypropylene and polyethylene fragments and films, and polyethylene terephthalate fibers, and the input to farmland soils was 6.96 × 107 to 1.88 × 108 items ha-1 yr-1. Regardless of feedstock, compost-based MPs of different shapes exhibited complicated weathering morphologies and adhered to some mineral colloids. The highest and lowest MPs-induced risk indices in solid waste (H = 134.3) and crop straw (H = 8.9) composts yielded hazard levels IV (high risk) and II (low risk), respectively, due to the different abundance of polymers with diverse hazard scores. These findings provide insights into MPs pollution in organic composts and a theoretical basis for the safe production and application of compost.

Global Research Activities on Micro(nano)plastic Toxicity to Earthworms.

Micro(nano)plastics are emerging contaminants that have been shown to cause various ecotoxicological effects on soil biota. Earthworms, as engineers of the ecosystem, play a fundamental role in soil ecosystem processes and have been used as model species in ecotoxicological studies. Research that evaluates micro(nano)plastic toxicity to earthworms has increased greatly over the last decade; however, only few studies have been conducted to highlight the current knowledge and evolving trends of this topic. This study aims to visualize the research status and knowledge structure of the relevant literature. Bibliometrics and visualization analyses were conducted using co-citations, cooperation networks and cluster analysis. The results showed that micro(nano)plastic toxicity to earthworms is an emerging and increasingly popular topic, with 78 articles published from 2013 to 2022, the majority of which were published in the last two years. The most prolific publications and journals involved in this topic were also identified. In addition, the diversity of cooperative relationships among different countries and institutions confirmed the evolution of this research field, in which China contributed substantially. The high-frequency keywords were then determined using co-occurrence analysis, and were identified as exposure, bioaccumulation, soil, pollution, toxicity, oxidative stress, heavy metal, microplastic, Eisenia foetida and community. Moreover, a total of eight clusters were obtained based on topic knowledge clustering, and these included the following themes: plastic pollution, ingestion, combined effects and the biological endpoints of earthworms and toxic mechanisms. This study provides an overview and knowledge structure of micro(nano)plastic toxicity to earthworms so that future researchers can identify their research topics and potential collaborators.