Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

DesTrans: A medical image fusion method based on Transformer and improved DenseNet.

Medical image fusion can provide doctors with more detailed data and thus improve the accuracy of disease diagnosis. In recent years, deep learning has been widely used in the field of medical image fusion. The traditional method of medical image fusion is to operate by superimposing and other methods of pixels. The introduction of deep learning methods has improved the effectiveness of medical image fusion. However, these methods still have problems such as edge blurring and information redundancy. In this paper, we propose a deep learning network model based on Transformer and an improved DenseNet network module integration that can be applied to medical images and solve the above problems. At the same time, the method can be moved to natural images. The use of Transformer and dense concatenation enhances the feature extraction capability of the method by limiting the feature loss which reduces the risk of edge blurring. We compared several representative traditional methods and more advanced deep learning methods with this method. The experimental results show that the Transformer and the improved DenseNet network module have a strong capability of feature extraction. The method yields good results both in terms of visual quality and objective image evaluation metrics.

The role and mechanism of miR-425-3p regulating neuronal pyroptosis -mediated inorganic arsenic-induced generalized anxiety disorder.

Pyroptosis plays a critical role in the pathogenesis of mental disorders. However, its specific role and mechanism in arsenic (As)-induced generalized anxiety disorder (GAD) remain elusive. We utilized the data from CtdBbase, Phenopedia and DisGeNet to analyze genes that interact with arsenic poisoning and GAD. Subsequently KEGG and GO enrichment analysis were conducted to preliminatively predict the mechanism of inorganic arsenic-induced GAD. Male Wistar rats were administered water containing NaAsO2 (50, 100 µg/L) to evaluate GAD-like behavior through open field test and elevated plus maze. The expression of differential miRNAs including miR-425-3p, and pyroptosis in the prefrontal cortex of rats were detected. Furthermore, SKNSH cells were stimulated with NaAsO2 to examine the molecular changes, and then miR-425-3p mimic was transfected into SKNSH cells to detect pyroptosis in order to verify the function of miR-425-3p. Inorganic arsenic was confirmed to induce GAD-like behavior in rats, characterized by decreased locomotor activity and exploratory activities. Rats with inorganic arsenic-induced GAD exhibited reduced miR-425-3p expression levels in the prefrontal cortex and increased expression of pyroptosis-related proteins, including NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Treating with different concentrations of NaAsO2 showed that inorganic arsenic exposure downregulates miR-425-3p expression in SKNSH cells and upregulates the expression levels of pyroptosis-related proteins. Dual-luciferase reporter gene experiments demonstrated that miR-425-3p targets the NFKB1. Overexpressing miR-425-3p reversed the inorganic arsenic-induced pyroptosis in SKNSH cells by inhibiting the expression of NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Our findings suggest that inorganic arsenic exposure may induce GAD-like behavior in rats by downregulating miR-425-3p in prefrontal cortex, which targets NF-κB and regulates pyroptosis in neuronal cells.

Discovery of 4-aminophenylacetamide derivatives as intestine-specific farnesoid X receptor antagonists for the potential treatment of nonalcoholic steatohepatitis.

Farnesoid X receptor (FXR) plays a key role in bile acid homeostasis, inflammation, fibrosis, lipid and glucose metabolism and is emerging as a promising therapeutic target for nonalcoholic steatohepatitis (NASH). Emerging evidence suggested that intestine-specific FXR antagonists exhibited remarkable metabolic improvements and slowed NASH progression. In this study, we discovered several potent FXR antagonists using a multistage ligand- and structure-based virtual screening approach. Notably, compound V023-9340, which possesses a 4-aminophenylacetamide scaffold, emerged as the most potent FXR antagonist with an IC50 value of 4.27 µM. In vivo, V023-9340 demonstrated selective accumulation in the intestine, substantially ameliorating high-fat diet (HFD)-induced NASH in mice by mitigating hepatic steatosis and inflammation. Mechanistic studies revealed that V023-9340 strongly inhibited intestinal FXR while concurrently feedback-activated hepatic FXR. Further structure-activity relationship optimization employing V023-9340 has resulted in the synthesis of a more efficacious compound V02-8 with an IC50 value of 0.89 µM, which exhibited a 4.8-fold increase in FXR antagonistic activity compared to V023-9340. In summary, 4-aminophenylacetamide derivative V023-9340 represented a novel intestine-specific FXR antagonist and showed improved effects against HFD-induced NASH in mice, which may serve as a promising lead in discovering potential therapeutic drugs for NASH treatment.

Theoretical Prediction of Electrocatalytic Reduction of CO2 Using a 2D Catalyst Composed of 3 d Transition Metal and Hexaamine Dipyrazino Quinoxaline.

Transition metals and organic ligands combine to form metal-organic frameworks (MOFs), which possess distinct active sites, large specific surface areas and stable porous structures, giving them considerable promise for CO2 reduction electrocatalysis. In the present study, using spin polarisation density-functional theory, a series of 2D MOFs constructed from 3d transition metal and hexamethylene dipyrazoline quinoxaline(HADQ) were investigated. The calculated binding energies between HADQ and metal atoms for the ten TM-HADQ monolayers were strong sufficient to stably disperse the metal atoms in the HADQ monolayers. Of the ten catalysts tested, seven (Sc, Ni, Cu, Zn, Ti, V and Cr) exhibited high CO2 reduction selectivity, while Mn, Fe and Co required pH values above 2.350, 6.461 and 6.363, respectively, to exhibit CO2 reduction selectivity. HCOOH was the most important producer for Sc, Zn, Ni and Mn, while CH4 was the main producer for Ti, Cr, Fe and V. Cu and Co were less selective, producing HCHO, CH3 OH, and CH4 simultaneously at the same rate-determining step and limiting potential. The Cu-HADQ catalyst had a high overpotential for the HCHO product (1.022 V), while the other catalysts had lower overpotentials between 0.016 V and 0.792 V. Thus, these results predict TM-HADQ to show excellent activity in CO2 electrocatalytic reduction and to become a promising electrocatalyst for CO2 reduction.

The Effect of Guisangyou Tea on Abnormal Lipid Metabolism in Mice Induced by High-Fat Diet.

This study was aimed to investigate the effect of Guisangyou tea (GSY tea) in improving abnormal lipid metabolism in mice with obesity induced by a high-fat diet (HFD). The results showed that intervention of the water extract of GSY tea (WE) decreased serum levels of lipids, and positively regulated the related antioxidant enzyme activities and the inflammatory factors in the serum and liver. In the liver, the mRNA and protein expression levels of sterol regulatory element-binding proteins-1 (SREBP-1), stearoyl-CoA desaturase-1 (SCD-1), fatty acid synthase (FASN), and acetyl CoA carboxylase (ACC) related to lipid synthesis were downregulated, and the mRNA and protein expression levels of the farnesoid X receptor (FXR) and small heterodimer partner (SHP) related to bile acid production were upregulated. The results demonstrate that GSY tea can improve abnormal lipid metabolism in obese mice by improving the body's antioxidant capacity, regulating the inflammatory state, and reducing the synthesis of lipids and increasing the production of bile acids. GSY tea can be processed and utilized as a safe and effective resource for improving abnormal lipid metabolism.

Leaching characteristics and potential risk of heavy metals from drip irrigation pipes and mulch substrate in agricultural ecosystems.

Drip irrigation is a valuable method for optimising water and fertiliser usage, motivating its increasing use. However, the ecological effects of drip irrigation fertilisation have not been sufficiently evaluated, limiting its effective and widespread use. Within this context, we aimed to determine the effects and potential ecological risks of using polyethylene irrigation pipes and mulch substrate under various drip irrigation conditions as well as burning of waste pipes and mulch substrate. Laboratory simulations of field conditions were used to determine the distribution, leaching, and migration pattern of heavy metals (Cd, Cr, Cu, Pb, and Zn) from plastic drip irrigation pipes and agricultural mulch substrate into various solutions. Maize samples obtained from drip-irrigated fields were analysed to determine the presence of heavy metal residues and assess the risk of heavy metal contamination. Heavy metal leaching from pipes and mulch substrate was high under acidic conditions, while the migration of heavy metals from plastic products was low in alkaline water-soluble fertiliser solutions. After combustion, heavy metal leaching from pipes and mulch residues increased considerably, with the migration capacity of Cd, Cr, and Cu increasing by >10-fold. Heavy metals in plastic pipes migrated primarily to the residue (bottom ash), whereas those from mulch substrate migrated to the fly ash component. Under experimental conditions, the migration of heavy metals from plastic pipes and mulch substrate had a negligible effect on the heavy metal content in aqueous environments. Although heavy metal leaching increased, the effect on water quality under actual irrigation conditions was relatively minor (in the order of 10-9). Thus, the use of plastic irrigation pipes and mulch substrate did not result in significant heavy metal contamination and potential risk to the agriculture ecosystem. Our study findings provide evidence for the effective application and widespread promotion of drip irrigation and fertiliser technology.

Treatment capacity of a novel flexible fibre biofilm bioreactor treating high-strength milk processing wastewater.

This study was focused on the capacity investigation of a novel multistage flexible fibre biofilm reactor (MS-FFBR) to treat milk processing wastewater (MPW) with high organic loading (OLR). The MS-FFBR performance was evaluated at four intermediate stages separately, and also the final effluent quality of the overall system with an influent chemical oxygen demand (CODin) ranged from 1500 ± 20 to 6000 ± 50 mg/L and hydraulic retention times (HRTs) of 8, 12, and 16 h. By comparting the bioreactors into the four stages effectively enhanced the bioreactor's performance. The maximum TCOD removal efficiency was achieved at the first stage, which was about 89 ± 20, 82 ± 20, and 78 ± 20% at HRTs of 16, 12, 8 h, and low CODin of 1600 ± 20, 1590 ± 20, and 1673 ± 20 mg/L, respectively. However, the first stage had less contribution to TCOD removal at high CODin concentrations, reported to be about 42 ± 4%, 46 ± 4%, and 25 ± 4% at CODin of 5960 ± 40, 5830 ± 40, and 5870 ± 40 mg/L, respectively. Furthermore, the MS-FFBR was effective in removing total suspended solids (TSS) and turbidity. The bioreactor has reduced the effluent turbidity to 9.0 ± 0.2, 20.0 ± 0.6, and 16.1 ± 0.5 NTU at low CODin concentrations of 1600 ± 20, 1590 ± 20, and 1670 ± 20 mg/L and HRTs of 16, 12, and 8 h, respectively. The bioreactor revealed a high COD removal rate increased from 2.3 ± 0.1 to 12.2 ± 0.4 kg TCOD/m3d by increasing the OLR from 2.4 ± 0.1 to 17.6 ± 0.4 kg TCOD/m3d, confirming high reactor capacity for treatment of high-strength wastewater. Kinetic studies confirmed that the biomass yield was low at various HRTs ranging from 0.1 to 0.2 gVSS/gCOD.

Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica.

BACKGROUND: Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. METHODS: We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. RESULTS: Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. CONCLUSIONS: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.

Distribution Characteristics and Influencing Factors of Bio-elements in the Human Hair of Uyghur Communities in an Oasis Area of Xinjiang, China.

Located in central Asia, Xinjiang is characterized as a diverse environment in China, consisting of vast deserts, dotted oases, and high mountains. Due to the combined effect of climate conditions under such a diverse environment, there are large differences in human activities, living styles, and eating habits in farmland and grazing pastures between Xinjiang and other regions of China. This study aimed to investigate the variations and mechanisms of elemental distribution in the hair of Uyghur communities among different ages and genders and under different land use backgrounds in an oasis region in Xinjiang. Hair samples from 524 residents from four traditional farmland areas and two grazing pasture areas in Bai Cheng County in Xinjiang were collected, and the levels of thirteen elements were analyzed. The results indicated that the average levels of Cu, Mg, Mn, Zn, Ni, Co, Pb, Fe, Ca, Cd, Cr, As, and Se in the hair of Uyghur communities were within the background levels of Chinese and global residents' hair. Overall, the levels of elements in the hair of women residents were higher than those of men residents. The levels of elements in the human hair of the middle-aged group were higher than those of child and older-aged groups. Elements Cr and Se in the hair of grazing pastures were higher than those of farmland areas. The levels of Cd, Pb, As, and Zn in the hair of farmland areas were higher than those of grazing pasture areas. The levels of Ca, Mg, Cu, and Fe in the hair of Uyghur communities were higher than those of other ethnic groups, while the toxic elements in the hair of residents in Bai Cheng were lower than those in other regions of China. Middle-aged people were exposed to higher levels of toxic elements in their daily activities compared to elderly and child groups. Also, adult groups need much more nutrients for their growth and intellectual development compared to child and elderly groups. The change in land use from grazing pastures to farmland increased the toxic trace element concentration levels in human hair. The significant differences in the overall concentration levels of elements in human hair among the different ethnic groups and regions can be attributed to the differences in lifestyles, cultural customs, dietary habits, and internal and external exposure routes.

Identification of novel inhibitors of S-adenosyl-L-homocysteine hydrolase via structure-based virtual screening and molecular dynamics simulations.

S-adenosyl-L-homocysteine hydrolase (SAHase) is an important regulator in the methylation reactions in many organisms and thus is crucial for numerous cellular functions. In recent years, SAHase has become one of the popular targets for drug design, and SAHase inhibitors have exhibited potent antiviral activity. In this study, we established the complex-based pharmacophore models based on the known crystal complex of SAHase (PDB ID: 1A7A) to screen the drug-likeness compounds of ChEMBL database. Then, three molecular docking programs were used to validate the reliability of compounds, involving Libdock, CDOCKER, and AutoDock Vina programs. The four promising hit compounds (CHEMBL420751, CHEMBL346387, CHEMBL1569958, and CHEMBL4206648) were performed molecular dynamics simulations and MM-PBSA calculations to evaluate their stability and binding-free energy in the binding site of SAHase. After screening and analyzing, the hit compounds CHEMBL420751 and CHEMBL346387 were suggested to further research to obtain novel potential SAHase inhibitors. A series of computer-aided drug design methods, including pharmacophore, molecular docking, molecular dynamics simulation and MM-PBSA calculations, were employed in this study to identity novel inhibitors of S-adenosyl-L-homocysteine hydrolase (SAHase). Some compounds from virtual screening could form various interactions with key residues of SAHase. Among them, compounds CHEMBL346387 and CHEMBL420751 exhibited potent binding affinity from molecular docking and MM-PBSA, and maintained good stability at the binding site during molecular dynamics simulations as well. All these results indicated that the selected compounds might have the potential to be novel SAHase inhibitors.

The bs-YHEDA peptide protects the brains of senile mice and thus recovers intelligence by reducing iron and free radicals.

Iron accumulates in the brain with age and catalyzes free radical damage to neurons, thus playing a pathogenic role in Alzheimer's disease (AD). To decrease the incidence of AD, we synthesized the iron-affinitive peptide 5YHEDA to scavenge the excess iron in the senile brain. However, the blood-brain barrier (BBB) blocks the entrance of macromolecules into the brain, thus decreasing the therapeutic effects. To facilitate the entrance of the 5YHEDA peptide, we linked the low-density lipoprotein receptor (LDLR)-binding segment of ApoB-100 to 5YHEDA (named "bs-YHEDA"). The results of intravenous injections of bs-5YHEDA into senescent mice demonstrated that bs-YHEDA entered the brain, increased ferriportin levels, reduced iron and free radical levels, decreased the consequences of neuronal necrosis and ameliorated cognitive disfunction without kidney or liver damage. bs-5YHEDA is a safe iron and free radical remover that potentially alleviates aging and Alzheimer's disease.

Comprehensive efficiency evaluation of wastewater treatment plants in northeast Qinghai-Tibet Plateau using slack-based data envelopment analysis.

Comprehensive efficiency analysis of wastewater treatment plants (WWPTs) in the alpine region with harsh environment and poor techniques as well as managing experience could provide targeted and effective improvement evidences for local wastewater treatment industry and help to improve the water quality of downstream reaches. In this paper, slack-based data envelopment analysis (SBM-DEA) was adopted to assess the operating efficiencies of WWPTs in northeast Qinghai-Tibet Plateau (QTP). Results showed that the average efficiency score for all WWPTs was 0.608, and 32.5% of WWPTs were efficient. Some WWPTs had large improvement potentials in operating costs and pollutant removal rates. Lowering expenditures and promoting facility construction for WWPTs to overcome the climate difficulties and improve management level was necessary according to their improvement potentials. In addition, the relative importance of the quantitative influential factors to efficiencies scores calculated by random forest regression (RFR) indicated that design capacity and temperature were important quantitative factors affecting the performance of WWPTs. Furthermore, geographical location and design capacity also had significant influence on the comprehensive efficiency of WWPTs verified by Kruskal-Wallis test. Our results highlight the importance of facilities upgrading, scientific management for WWPTs. And the relative improvement suggestions on overcoming the high and cold environment should also be considered for the efficient operations of WWTPs as well as the protection the aquatic environment.

Synthesis and biological evaluation of novel pentanediamide derivatives as S-adenosyl-l-homocysteine hydrolase inhibitors.

A series of novel pentanediamide derivatives were designed, synthesized and evaluated as S-adenosyl-l-homocysteine hydrolase (SAHase) inhibitors in this study. Some compounds showed good inhibitory activity against SAHase. The optimal compound 7i showed good inhibitory activity against SAHase with IC50 value of 3.58 ± 0.19 µM, cytotoxicity with IC50 values ranging from 13.16 ± 1.44 to 21.23 ± 0.73 µM against four tumor cell lines (MCF-7, A549, MGC-803, Hela) and very weak cytotoxicity (IC50 = 84.22 ± 1.89 µM) on normal LO2 cells. In addition, compound 7i showed potency against respiratory syncytial virus with EC50 value of 27.4 µM and selectivity index of 6.84. Further molecular simulation study suggested that compound 7i had good ADMET properties, and strongly binds to the active site of SAHase. In summary, compound 7i could serve as a new lead compound for further screening novel non-adenosine SAHase inhibitors.

Exposure Routes and Health Risks Associated with Pesticide Application.

Pesticides play an important role in agricultural development. However, pesticide application can result in both acute and chronic human toxicities, and the adverse effects of pesticides on the environment and human health remain a serious problem. There is therefore a need to discuss the application methods for pesticides, the routes of pesticide exposure, and the health risks posed by pesticide application. The health problems related to pesticide application and exposure in developing countries are of particular concern. The purpose of this paper is to provide scientific information for policymakers in order to allow the development of proper pesticide application technics and methods to minimize pesticide exposure and the adverse health effects on both applicators and communities. Studies indicate that there are four main pesticide application methods, including hydraulic spraying, backpack spraying, basal trunk spraying, and aerial spraying. Pesticide application methods are mainly selected by considering the habits of target pests, the characteristics of target sites, and the properties of pesticides. Humans are directly exposed to pesticides in occupational, agricultural, and household activities and are indirectly exposed to pesticides via environmental media, including air, water, soil, and food. Human exposure to pesticides occurs mainly through dermal, oral, and respiratory routes. People who are directly and/or indirectly exposed to pesticides may contract acute toxicity effects and chronic diseases. Although no segment of the general population is completely protected against exposure to pesticides and their potentially serious health effects, a disproportionate burden is shouldered by people in developing countries. Both deterministic and probabilistic human health risk assessments have their advantages and disadvantages and both types of methods should be comprehensively implemented in research on exposure and human health risk assessment. Equipment for appropriate pesticide application is important for application efficiency to minimize the loss of spray solution as well as reduce pesticide residuals in the environment and adverse human health effects due to over-spraying and residues. Policymakers should implement various useful measures, such as integrated pest management (IPM) laws that prohibit the use of pesticides with high risks and the development of a national implementation plan (NIP) to reduce the adverse effects of pesticides on the environment and on human health.

Environmental monitoring and potential health risk assessment from Pymetrozine exposure among communities in typical rice-growing areas of China.

Pymetrozine is one of the most commonly used insecticides in China. This study was conducted to analyse Pymetrozine's potential exposures through various environmental routes beyond the treatment areas. The aim was to estimate the potential health risk for communities due to non-dietary exposures to Pymetrozine in soil and paddy water. Data on registration of pesticides in China, government reports, questionnaires, interviews and literature reviews as well as toxicological health investigations were evaluated to determine the hazard and dose-response characteristics of Pymetrozine. These were based on the US EPA exposure and human health risk assessment methods and exposure data from soil and paddy water samples collected between 10 and 20 m around the resident's location. The exposure doses from dermal contact through soil and paddy water were estimated. The potential cancer risk from the following exposure routes was evaluated: ingestion through soil; dermal contact exposure through soil; dermal contact exposure through paddy water. The potential total cancer risk for residents was estimated to be less than 1 × 10-6. These were relatively low and within the acceptable risk levels. The potential hazard quotient (HQ) from acute and lifetime exposure by dermal contact through paddy water and soil and acute and lifetime exposure by soil ingestion for residents was less than 1, indicating an acceptable risk level. This study suggested that there were negligible cancer risk and non-cancer risks based on ingestion and dermal contact routes of exposure to residents.

Natural dynamics and residues of pymetrozine for typical rice-growing areas of China.

Pymetrozine has replaced toxic organophosphate pesticides previously used for controlling pests of rice crops in China. Existing data on its environmental behavior are usually related to studies on artificial plots that do not adequately address the natural dynamics and residues in actual field conditions. Therefore, studies under field conditions were carried out to investigate the natural dynamics and residues of pymetrozine in two typical rice-growing areas in China - Hunan and Guangxi provinces. Samples of paddy soil and water were collected in relation to spraying events in the study areas. The quick, easy, cheap, effective, rugged and safe (QuEChERS) method was used to extract pymetrozine residues from the samples by a Waters ACQUITY UPLC (Milford, MA, USA) system interfaced with a triple-quadrupole mass spectrometer (Xevo TQ-D, Waters Corp., USA). The initial deposition of pymetrozine in paddy soils was higher than in paddy waters in both areas. The decay of pymetrozine followed an exponential trend consistent with the first order kinetics. The half-life of pymetrozine in paddy water was determined to be 3.0 and 3.8 days, whereas the half-life in soil was 3.8 and 3.5 days in the Guangxi and Hunan samples, respectively. The decline rates of pymetrozine in paddy soil and paddy water in this field study were faster than those conducted under non-field conditions reported in previous studies. Compared to other pesticides used in China as reported in previous studies, the environmental persistence of pymetrozine in both paddy water and soils in Guangxi and Hunan provinces is very low. This has important implications for the use of pymetrozine in agricultural systems globally.

Toxicological effects of hypoxanthine on Heterosigmaakashiwo: Mechanism of growth inhibition and change in hemolytic toxin content.

Heterosigmaakashiwo is an algal species that causes harmful algal blooms (HABs) with strong hemolytic toxicity on coastal aquatic organisms. This study investigated the mechanism of growth inhibition and changes in hemolytic toxin contents in algal culture after exposure to hypoxanthine, a compound secreted by algicidal bacterium Bacillus sp.strain B1. An algal inhibition rate of 86% was observed with 1.0 mM hypoxanthine treatment on day 15. The levels of superoxide dismutase and catalase in algal cell culture increased while that of glutathione decreased during the treatment. In addition,the level of hemolytic toxin contents increased on day 3 under hypoxanthine treatment, and significantly decreased on days 6, 9, 12, and 15. Twelve fatty acids in H.akashiwo were detected by GC-MS, and the changes in the contents of C16, C18, C18:4ω3, and C20:5ω3 in the treatment group were consistent with the change in hemolytic toxin content. The four fatty acids were tested for hemolysis and it was observed that the hemolysis rate of 25 µg/mL C18:4ω3 and 5 µg/mL C20:5ω3 reached more than 80%, but C16 and C18 exhibited no hemolytic capability.Therefore, our results showed that hypoxanthine inhibited the growth of H. akashiwo through the changes of levels of antioxidants and hemolytic toxin content in the cultures, and fatty acids C18:4ω3 and C20:5ω3 were contributors to hemolytic toxins. The results confirmed that hypoxanthine is a potential algal inhibitor to prevent HABs.

Circulating methylated THBS1 DNAs as a novel marker for predicting peritoneal dissemination in gastric cancer.

OBJECTIVES: Thrombospondin 1 (THBS1) is known to play a key role in tumor metastasis, and aberrant DNA methylation is one of the mechanisms regulating THBS1. The present study investigated whether methylated THBS1 in circulating cell-free DNA from preoperative peritoneal lavage fluid (PPLF) and peripheral blood could be used as a potential biomarker for predicting peritoneal dissemination in gastric cancer (GC) patients. METHODS: The status of THBS1 methylation was detected by quantitative methylation-specific PCR (MSP) in tumor tissues, paired PPLF, and serum from 92 GC patients. The correlation between methylated THBS1 levels and peritoneal dissemination of GC was studied, and its diagnostic value for predicting peritoneal dissemination was clarified by the receiver operating characteristic (ROC) curve. RESULTS: Aberrant THBS1 methylation in tumor tissues was significantly higher than that in paracancerous normal tissues (p < 0.0001). No THBS1 methylation was found in 40 healthy controls, and partial methylation was detected in 3 of 48 patients with chronic non-atrophic gastritis. The frequency of THBS1 methylation in pairing PPLF and serum from 92 GC patients was 52.2% (48/92) and 58.7% (54/92), respectively. The results of methylated THBS1 in pairing PPLF and serum were similar to those of tumor tissues. Aberrant THBS1 methylation in tumor tissues and pairing PPLF or serum was closely related to peritoneal dissemination, tumor progression, and poor prognosis (all p < 0.0001). CONCLUSION: Circulating methylated THBS1 DNAs in PPLF/serum may predict peritoneal dissemination, a potential poor prognostic factor for GC patients.