Search

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.

Agricultural chemical residues in farmland and crops is one of the serious public issues that constantly threatens crop production, food security, and human health. Understanding their decay mechanism in crops for accelerating their degradative metabolism is important. In this study, a rice uncharacterized cytochrome P450 gene encoding

Mesotrione (MTR) is a highly effective pesticide widely used for weeding in farmland. Overload of MTR in agricultural soils may result in environmental problems. To evaluate the potential contamination of MTR in environments, a better understanding of the MTR degradation process and mechanisms in crops is required. This study investigated the impact of MTR on growth and toxicological responses in rice (Oryza sativa). The growth of rice tissues was significantly compromised with increasing MTR concentrations. RNA-sequencing combined with HRLC-Q-TOF-MS/MS analysis identified many transcriptional components responsible for MTR degradation. Four libraries composed of root and shoot tissues exposed to MTR were RNA-sequenced in biological triplicate. Compared to -MTR, treatment with environmentally realistic MTR concentration upregulated 1995 genes in roots and 326 genes in shoots. Gene enrichment revealed many MTR-degradative enzymes functioning in resistance to environmental stress and molecular metabolism of xenobiotics. Specifically, many differentially expressed genes are critical enzymes like cytochrome P450, glycosyltransferases, methyltransferase, glutathione S-transferases and acetyltransferase involved in the process. To evidence MTR degradative metabolisms, HRLC-Q-TOF-MS/MS was used to characterize eight metabolites and five conjugates in the pathways involving hydrolysis, reduction, glycosylation, methylation or acetylation. The precise association between the specific MTR-degraded products and enhanced activities of its corresponding enzymes was established. This study advanced our understanding of the detailed MTR degradative mechanisms and pathways, which may help engineer genotypes to facilitate MTR degradation in the paddy crop.

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.

Autologous bone marrow mesenchymal stem cell (BM-MSC) transplantation is a novel strategy for treating ischemic heart disease. However, limited benefits have been reported in aging patients. Rejuvenation of aged human BM-MSCs (hBM-MSCs) could be a means to improve the efficacy of stem cell transplantation in older patients. While it has been shown that sirtuin 6 (SIRT6) is an important antiaging factor in various cells, the role of SIRT6 in hBM-MSCs remains unknown. The hBM-MSCs from different ages were cultured for quantifying SIRT6 expression by mRNA and Western blotting. The cell proliferative and migration abilities were evaluated by BrdU staining, cell growth curves, and scratch assay. Senescence-associated β-galactosidase (SA-β-Gal) activity and aging-associated p16 (cyclin-dependent kinase inhibitor 2A) expression were also quantified. The knockdown of SIRT6 in hBM-MSCs was used to investigate its impact on aging. SIRT6 expression increased with age, while the proliferative and migration abilities of aged hBM-MSCs were decreased compared with young cells. Knockdown of SIRT6 impaired the proliferative, migration, and oxidative stress resistance potentials of BM-MSCs. SA-β-Gal activity and p16 expression were increased in aged cells compared with young ones and in siRNA SIRT6 knockdown cells compared with their controls. Aging results in compensatory overexpression of SIRT6 in hBM-MSCs. Downregulation of SIRT6 in these cells resulted in less cell proliferation and migration but increased SA-β-Gal activity and p16 expression. These results suggest that SIRT6 regulates the aging process in hBM-MSCs and could serve as a target for their rejuvenation.

In a complex evaluation system, not only it is often necessary to deal with multiple attributes decision problems, but also it is unavoidable to deal with the uncertainness and fuzziness of people’s judgment. This paper considers the multiple attributes and uncertainness decision problems in the complex decision systems, a fuzzy multiple attributes evaluation and selection model is built, a new method is developed for ranking fuzzy priorities from the model, and calculation formulae for fuzzy priorities are derived. Finally, an applied example on suppliers’ selection is given for demonstrating the method.

From the viewpoint of production efficiency, a general cargo wharf system optimization analysis is discussed in this paper. Wharf of Huangpu Port is taken as an example. A simulation model of the general cargo handling system is built by applying Flexsim simulation technology, which simulates the real operation process of wharf once being run. Then the analyses on the system bottlenecks, problems and causes are carried out by figuring out the system output index such as throughput, equipment occupying rate, average stay time of truck etc., on the basis of which, a series of optimization approaches to solve the problems are proposed.

In this paper, the problem of ranking fuzzy number is discussed. An improved ranking method is proposed for finding the correct order of fuzzy numbers. Firstly, Based on the distance in fuzzy number space, an index for characterizing uncertain degree is defined and its properties are discussed. Then, by this index the ordering rules are given. Finally, three numerical examples are presented to illustrate the efficiency of the proposed model.

The aim of this paper is to develop a portfolio selection model with fuzzy return rate. Fuzzy number is used to model the anticipative return rate of security, and an index is defined to measure the variability of the portfolio return. By taking the possibilistic mean as the portfolio return and the variability as the portfolio risk, a portfolio selection model is constructed. It is shown that there exists an optimal solution in the model, and the solution can be obtained by solving a convex quadratic programming problem.

In the complex control or decision process, it is not evitable to deal with the fuzziness of people's thinking, judgment and uncertainness of the information in the systems. This paper considers the fuzziness in the complex systems, discusses the problem about extracting the fuzzy weights of the projects from the fuzzy judgment matrix, and proposes a ranking approach of fuzzy additive inverse on the column, which is a valid and simple ranking method in the analytic hierarchy process. Finally, an example to apply our approach is presented.