Rice straw biochar and lime regulate the availability of heavy metals by managing colloid-associated- but dissolved-heavy metals.

Heavy metal (HM) pollution has extensively spread in agricultural soils, posing potential threats to food safety and human health. Biochar and lime are two amendments used to remediate the soils contaminated with HMs. However, colloids have been shown to increase the mobility of HMs in paddy soils. Nevertheless, limited investigations have been made into the impact of biochar and lime on the formation of colloid-associated (colloidal) HMs in paddy soils. In this study, column and microcosm incubation experiments were conducted to examine how biochar and lime affected the availability of HMs (arsenic, cadmium, copper, iron, manganese, lead, and zinc) in different layers of paddy soils. The results revealed that biochar significantly inhibited the formation of colloidal HMs in the soil flooding phase, whereas the lime increased the colloidal HMs. These colloids containing HMs were identified as poorly dissolved metal sulfides. When the soil was drained, colloidal HMs transformed into dissolved forms, thereby improving the availability of HMs. Biochar decreased HM availability by reducing colloidal- but dissolved- HMs, whereas lime had the opposite effect. Hence, biochar demonstrated a stable and reliable remediation ability to decrease HM availability in paddy soil during flooding and drainage processes. In conclusion, this study highlighted that biochar efficiently reduced HM availability by mitigating the formation of colloidal HMs during flooding and their transformation into dissolved HMs during drainage in paddy soils.

Direct inhibition of dioxygenases TET1 by the rheumatoid arthritis drug auranofin selectively induces cancer cell death in T-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) is a type of hematologic tumor with malignant proliferation of hematopoietic progenitor cells. However, traditional clinical treatment of T-ALL included chemotherapy and stem cell transplantation always lead to recurrence and poor prognosis, thus new therapeutic targets and drugs are urgently needed for T-ALL treatment. In this study, we showed that TET1 (ten-eleven translocation 1), a key participant of DNA epigenetic control, which catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to modulate gene expression, was highly upregulated in human T-ALL and negatively correlated with the prognosis of patients. Knockdown of TET1 suppressed T-ALL growth and progression, suggesting that TET1 inhibition maybe an effective way to fight T-ALL via DNA epigenetic modulation. Combining structure-guided virtual screening and cell-based high-throughput screening of FDA-approved drug library, we discovered that auranofin, a gold-containing compound, is a potent TET1 inhibitor. Auranofin inhibited the catalytic activity of TET1 through competitive binding to its substrates binding pocket and thus downregulated the genomic level of 5hmC marks and particularly epigenetically reprogramed the expression of oncogene c-Myc in T-ALL in TET1-dependent manner and resulted in suppression of T-ALL in vitro and in vivo. These results revealed that TET1 is a potential therapeutic target in human T-ALL and elucidated the mechanism that TET1 inhibitor auranofin suppressed T-ALL through the TET1/5hmC/c-Myc signaling pathway. Our work thus not only provided mechanism insights for T-ALL treatment, but also discovered potential small molecule therapeutics for T-ALL.

5-Hydroxymethylcytosine profiles in plasma cell-free DNA reflect molecular characteristics of diabetic kidney disease.

Background: Diabetic kidney disease (DKD), one of the main complications of diabetes mellitus (DM), has become a frequent cause of end-stage renal disease. A clinically convenient, non-invasive approach for monitoring the development of DKD would benefit the overall life quality of patients with DM and contribute to lower medical burdens through promoting preventive interventions. Methods: We utilized 5hmC-Seal to profile genome-wide 5-hydroxymethylcytosines in plasma cell-free DNA (cfDNA). Candidate genes were identified by intersecting the differentially hydroxymethylated genes and differentially expressed genes from the GSE30528 and GSE30529. Then, a protein interaction network was constructed for the candidate genes, and the hub genes were identified by the MCODE and cytoHubba algorithm. The correlation analysis between the hydroxymethylation level of the hub genes and estimated glomerular filtration rate (eGFR) was carried out. Finally, we demonstrated differences in expression levels of the protein was verified by constructing a mouse model of DKD. In addition, we constructed a network of interactions between drugs and hub genes using the Comparative Toxicogenomics Database. Results: This study found that there were significant differences in the overall distribution of 5hmC in plasma of patients with DKD, and an alteration of hydroxymethylation levels in genomic regions involved in inflammatory pathways which participate in the immune response. The final 5 hub genes, including (CTNNB1, MYD88, CD28, VCAM1, CD44) were confirmed. Further analysis indicated that this 5-gene signature showed a good capacity to distinguish between DKD and DM, and was found that protein levels were increased in renal tissue of DKD mice. Correlation analysis indicated that the hydroxymethylation level of 5 hub genes were nagatively correlated with eGFR. Toxicogenomics analysis showed that a variety of drugs for the treatment of DKD can reduce the expression levels of 4 hub genes (CD44, MYD88, VCAM1, CTNNB1). Conclusions: The 5hmC-Seal assay was successfully applied to the plasma cfDNA samples from a cohort of DM patients with or without DKD. Altered 5hmC signatures indicate that 5hmC-Seal has the potential to be a non-invasive epigenetic tool for monitoring the development of DKD and it provides new insight for the future molecularly targeted anti-inflammation therapeutic strategies of DKD.

Epilepsy Detection Based on Variational Mode Decomposition and Improved Sample Entropy.

Epilepsy detection based on electroencephalogram (EEG) signal is of great significance to diagnosis and treatment of epilepsy. The denoised EEG signal is adopted by most traditional epilepsy detection methods. But due to nonideal denoising ability, the loss of local information and residual noise will occur, resulting in detection performance degradation. To solve the problem, the paper proposed an epilepsy detection method in noisy environment. Although epileptic signals and nonepileptic signals have some discrimination, they need to overcome the interference of noise. Hence, the improved sample entropy and phase synchronization indexes of corresponding 2 intrinsic mode functions (IMFs) caused by variational mode decomposition (VMD) are proposed as features, which can reduce the impact of noise on detection performance. The experimental results show that the accuracy, sensitivity, and specificity are 91.78%, 91.27%, and 93.61%, respectively. It can be used as an auxiliary method for clinical treatment of epilepsy.

5-Hydroxymethylcytosine profiles of cfDNA are highly predictive of R-CHOP treatment response in diffuse large B cell lymphoma patients.

BACKGROUND: Although R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard chemotherapy regimen for diffuse large B cell lymphoma (DLBCL) patients, not all patients are responsive to the scheme, and there is no effective method to predict treatment response. METHODS: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 86 DLBCL patients before they received R-CHOP chemotherapy. To investigate the correlation between 5hmC modifications and curative effectiveness, we separated patients into training (n = 56) and validation (n = 30) cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict the treatment response in the validation cohort. RESULTS: In this study, we identified thirteen 5hmC markers associated with treatment response. The prediction performance of the logistic regression model, achieving 0.82 sensitivity and 0.75 specificity (AUC = 0.78), was superior to existing clinical indicators, such as LDH and stage. CONCLUSIONS: Our findings suggest that the 5hmC modifications in cfDNA at the time before R-CHOP treatment are associated with treatment response and that 5hmC-Seal may potentially serve as a clinical-applicable, minimally invasive approach to predict R-CHOP treatment response for DLBCL patients.

5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Early Warning Biomarkers for COVID-19 Progression and Myocardial Injury.

Background: The symptoms of coronavirus disease 2019 (COVID-19) range from moderate to critical conditions, leading to death in some patients, and the early warning indicators of the COVID-19 progression and the occurrence of its serious complications such as myocardial injury are limited. Methods: We carried out a multi-center, prospective cohort study in three hospitals in Wuhan. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles in plasma cell-free DNA (cfDNA) was used to identify risk factors for COVID-19 pneumonia and develop a machine learning model using samples from 53 healthy volunteers, 66 patients with moderate COVID-19, 99 patients with severe COVID-19, and 38 patients with critical COVID-19. Results: Our warning model demonstrated that an area under the curve (AUC) for 5hmC warning moderate patients developed into severe status was 0.81 (95% CI 0.77-0.85) and for severe patients developed into critical status was 0.92 (95% CI 0.89-0.96). We further built a warning model on patients with and without myocardial injury with the AUC of 0.89 (95% CI 0.84-0.95). Conclusion: This is the first study showing the utility of 5hmC as an accurate early warning marker for disease progression and myocardial injury in patients with COVID-19. Our results show that phosphodiesterase 4D and ten-eleven translocation 2 may be important markers in the progression of COVID-19 disease.

5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic and predictive biomarkers for coronary artery disease.

BACKGROUND: The 5-hydroxymethylcytosine (5hmC) DNA modification is an epigenetic marker involved in a range of biological processes. Its function has been studied extensively in tumors, neurodegenerative diseases, and atherosclerosis. Studies have reported that 5hmC modification is closely related to the phenotype transformation of vascular smooth muscle cells and endothelial dysfunction. However, its role in coronary artery disease (CAD) has not been fully studied. RESULTS: To investigate whether 5hmC modification correlates with CAD pathogenesis and whether 5hmC can be used as a biomarker, we used a low-input whole-genome sequencing technology based on selective chemical capture (hmC-Seal) to firstly generate the 5hmC profiles in the circulating cell-free DNA(cfDNA) of CAD patients, including stable coronary artery disease (sCAD) patients and acute myocardial infarction (AMI) patients. We detected a significant difference of 5hmC enrichment in gene bodies from CAD patients compared with normal coronary artery (NCA) individuals. Our results showed that CAD patients can be well separated from NCA individuals by 5hmC markers. The prediction performance of the model established by differentially regulated 5hmc modified genes were superior to common clinical indicators for the diagnosis of CAD (AUC = 0.93) and sCAD (AUC = 0.93). Specially, we found that 5hmC markers in cfDNA showed prediction potential for AMI (AUC = 0.95), which was superior to that of cardiac troponin I, muscle/brain creatine kinase, and myoglobin. CONCLUSIONS: Our results suggest that 5hmC markers derived from cfDNA can serve as effective epigenetic biomarkers for minimally noninvasive diagnosis and prediction of CAD.

Characterization of lead-containing aerosol particles in Xiamen during and after Spring Festival by single-particle aerosol mass spectrometry.

To comparatively analyze lead (Pb)-containing particles during and after the Chinese Spring Festival (SF), real-time single-particle aerosol mass spectrometry (SPAMS) was conducted in Xiamen during February 9-19 and March 4-14, 2013. Pb-containing particles were found in 2.4% and 5.3% of the total particle numbers during and after SF, respectively. Based on the SPAMS mass spectral results, the Pb-containing particles were classified into three major types and 11 subtypes: Pb-rich particles comprising Pb-nitrate, Pb-sulfate and Pb-chloride; K-rich particles comprising K-nitrate, K-sulfate, K-metal, K-carbonaceous, K-phosphate, and K-chloride; and metal particles including Fe-rich and Mn-nitrate particles. During SF, lower contributions of Pb-containing particles were due to the effect of the SF holiday. Firework emissions contributed little to the Pb-containing particles. K-rich particles were a major contribution to Pb-containing particles during SF, accounting for approximately 70% of the total number of Pb-containing particles. After SF, significantly increased Pb-containing particles were observed, coincided with NO2 and SO2, due to increased industrial activities and other anthropogenic activities, and Pb-rich particles increased to approximately 50.3% of the total number of Pb-containing particles. Local industrial emissions and the stagnant meteorological conditions resulted in the higher concentrations of Pb-containing particles in the early morning after SF, especially Pb-nitrate particles. This study provides data on the in-situ monitoring of Pb emissions during and after SF and could be helpful for the mitigation of Pb pollution.