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The excessive dosage of pesticides required for agronomic reality results in growing contamination of pesticide residues in environment, thus bringing high risks to crop production and human health.This study aims to unveil a novel mechanism for catabolism of two pesticides MTR and FSA facilitated by an uncharacterized Phase II reaction enzyme termed acetyltransferase-1 (ACE1) in rice and to make assessment of its potential for bioremediation to minimize the risks to crop production and food safety.We developed genetically improved cultivars overexpressing OsACE1 (OE) and knockout mutant lines by CRISPR-Cas9 technology to identify the MTR and FSA detoxic and metabolic functions and characterized their metabolites and conjugates by HPLC-LTQ-MS/MS.OsACE1 overexpression conferred rice resistance to toxicity of MTR/FSA compared to wild-type, manifested by improved plant elongation and biomass, attenuated cellular injury, and increased chlorophyll accumulation. The OE plants accumulated significantly less parent MTR/FSA and more degradative metabolites, and removed MTR/FSA from their growth medium by 1.38 and 1.61 folds over the wild-type. In contrast, knocking out OsACE1 led to compromised growth fitness and intensified toxic symptoms under MTR/FSA stress and accumulation of more toxic MTR and FSA in rice. The reduced metabolites of MTR and FSA detected in the Cas9 plants suggest the impaired capability of OsACE1 function.These results signified that OsACE1 expression is required for detoxifying the two poisoning chemicals in rice and plays a critical role in accelerating breakdown of the pesticides mainly through Phase II reaction mechanism pathways.

Background The human endometrium in premenopausal women is an active site of physiological angiogenesis, with regenerative cells present, suggesting that the endometrium contains adult angiogenic stem cells. In the context of cardiac repair after ischemic injury, angiogenesis is a crucial process to rescue cardiomyocytes. We therefore investigated whether human endometrium-derived stem cells (hEMSCs) can be used for cardiac repair after ischemic injury and their possible underlying mechanisms. Methods Comparisons were made between hEMSCs successfully isolated from 22 premenopausal women and human bone marrow mesenchymal stem cells (hBMSCs) derived from 25 age-matched patients. Cell proliferation, migration, differentiation, and angiogenesis were evaluated through in vitro experiments, while the ability of hEMSCs to restore cardiac function was examined by in vivo cell transplantation into the infarcted nude rat hearts. Results In vitro data showed that hEMSCs had greater proliferative and migratory capacities, whereas hBMSCs had better adipogenic differentiation ability. Human umbilical cord vein endothelial cells, treated with conditioned medium from hEMSCs, had significantly higher tube formation than that from hBMSCs or control medium, indicating greater angiogenic potentials for hEMSCs. In vivo, hEMSC transplantation preserved cardiac function, decreased infarct size, and improved tissue repair post-injury. Cardiac metabolism, assessed by 18F-FDG uptake, showed that 18F-FDG uptake at the infarction area was significantly higher in both hBMSC and hEMSC groups, compared to the PBS control group, with hEMSCs having the highest uptake, suggesting hEMSC treatment improves cardiomyocyte metabolism and survival after injury. Mechanistic assessment of the angiogenic potential for hEMSCS revealed that angiogenesis-related factors angiopoietin 2, Fms-like tyrosine kinase 1, and FGF9 were significantly upregulated in hEMSC-implanted infarcted hearts, compared to the PBS control group. Conclusion hEMSCs, compared to hBMSCs, have greater capacity to induce angiogenesis, and improved cardiac function after ischemic injury.

Developing a biotechnical system with rapid degradation of pesticide is critical for reducing environmental, food security and health risks. Here, we investigated a novel epigenetic mechanism responsible for the degradation of the pesticide atrazine (ATZ) in rice crops mediated by the key component CORONATINE INSENSITIVE 1a (OsCOI1a) in the jasmonate-signaling pathway. OsCOI1a protein was localized to the nucleus and strongly induced by ATZ exposure. Overexpression of OsCOI1a (OE) significantly conferred resistance to ATZ toxicity, leading to the improved growth and reduced ATZ accumulation (particularly in grains) in rice crops. HPLC/Q-TOF-MS/MS analysis revealed increased ATZ-degraded products in the OE plants, suggesting the occurrence of vigorous ATZ catabolism. Bisulfite-sequencing and chromatin immunoprecipitation assays showed that ATZ exposure drastically reduced DNA methylation at CpG context and histone H3K9me2 marks in the upstream of OsCOI1a. The causal relationships between the DNA demethylation (hypomethylatioin), OsCOI1a expression and subsequent detoxification and degradation of ATZ in rice and environment were well established by several lines of biological, genetic and chemical evidence. Our work uncovered a novel regulatory mechanism implicated in the defense linked to the epigenetic modification and jasmonate signaling pathway. It also provided a modus operandi that can be used for metabolic engineering of rice to minimize amounts of ATZ in the crop and environment.

Visual Abstract, Highlights • The benefits of cell transplantation for cardiac repair are diminished in older individuals and effective methods to rejuvenate aged stem cells are needed to treat the increasing number of older patients with heart failure. • Over-expressing NDNF in old hBM-MSCs rejuvenated the cells, increasing their proliferative capacity and reducing cellular apoptosis. • In vivo engraftment of NDNF-overexpressing old hBM-MSCs into the ischemic area of mouse hearts improved cardiac function after myocardial infarction, while promoting engrafted stem cell survival and proliferation and decreasing cell senescence. • NDNF rejuvenated aged human stem cells, improving their capability to repair the aged heart after ischemic injury through Activation of Akt singling., Summary Reduced regenerative capacity of aged stem cells hampers the benefits of autologous cell therapy for cardiac regeneration. This study investigated whether neuron-derived neurotrophic factor (NDNF) could rejuvenate aged human bone marrow (hBM)- multipotent mesenchymal stromal cells (MSCs) and whether the rejuvenated hBM-MSCs could improve cardiac repair after ischemic injury. Over-expression of NDNF in old hBM-MSCs decreased cell senescence and apoptosis. Engraftment of NDNF over-expressing old hBM-MSCs into the ischemic area of mouse hearts resulted in improved cardiac function after myocardial infarction, while promoting implanted stem cell survival. Our findings suggest NDNF could be a new factor to rejuvenate aged stem cells and improve their capability to repair the aged heart after injury.

There is a rising public concern on accumulation of harmful pesticides in environment and crops. Epigenetic alteration caused by environmental contaminants is one of the key factors in the etiology of environmentally-associated diseases. Growing evidence shows that harmful pesticide atrazine (ATZ) has a profound effect on DNA methylation in human genome, however, little is known about the epigenetic mechanism underlying ATZ accumulation and degradation in plants, particularly in edible plants growing in the ATZ-contaminated areas. This study investigated the atrazine elimination that was mediated by DNA methylation and histone modification in the food crop rice. Studies with two mutant Osmet1-1/2 defective in the genomic CG DNA methylation show significantly lower accumulation of atrazine than its wild-types. Profiling methylome and transcriptome of ATZ-exposed Osmet1 and wild-type identified many differentially methylated loci (≥2 fold change, p

The decline of cell function caused by ageing directly impacts the therapeutic effects of autologous stem cell transplantation for heart repair. The aim of this study was to investigate whether overexpression of neuron‐derived neurotrophic factor (NDNF) can rejuvenate the adipose‐derived stem cells in the elderly and such rejuvenated stem cells can be used for cardiac repair. Human adipose‐derived stem cells (hADSCs) were obtained from donors age ranged from 17 to 92 years old. The effects of age on the biological characteristics of hADSCs and the expression of ageing‐related genes were investigated. The effects of transplantation of NDNF over‐expression stem cells on heart repair after myocardial infarction (MI) in adult mice were investigated. The proliferation, migration, adipogenic and osteogenic differentiation of hADSCs inversely correlated with age. The mRNA and protein levels of NDNF were significantly decreased in old (>60 years old) compared to young hADSCs (

Neovascularization drives tumor development, and angiogenic factors are important neovascularization initiators. We recently identified the secreted angiogenic factor CNPY2 , but its involvement in cancer has not been explored. Herein, we investigate CNPY2 's role in human colorectal cancer (CRC) development. Tumor samples were obtained from CRC patients undergoing surgery. Canopy 2 (CNPY2) expression was analyzed in tumor and adjacent normal tissue. Stable lines of human HCT116 cells expressing CNPY2 shRNA or control shRNA were established. To determine CNPY2 's effects on tumor xenografts in vivo , human CNPY2 shRNA HCT116 cells and controls were injected into nude mice, separately. Cellular apoptosis, growth, and angiogenesis in the xenografts were evaluated. CNPY2 expression was significantly higher in CRC tissues. CNPY2 knockdown in HCT116 cells inhibited growth and migration and promoted apoptosis. In xenografts, CNPY2 knockdown prevented tumor growth and angiogenesis and promoted apoptosis. Knockdown of CNPY2 in the HCT116 CRC cell line reversibly increased p53 activity. The p53 activation increased cyclin-dependent kinase inhibitor p21 and decreased cyclin-dependent kinase 2, thereby inhibiting tumor cell growth, inducing cell apoptosis, and reducing angiogenesis both in vitro and in vivo . CNPY2 may play a critical role in CRC development by enhancing cell proliferation, migration, and angiogenesis and by inhibiting apoptosis through negative regulation of the p53 pathway. Therefore, CNPY2 may represent a novel CRC therapeutic target and prognostic indicator.