Effects of Dufulin on Oxidative Stress and Metabolomic Profile of Tubifex.

Dufulin is a highly effective antiviral pesticide used in plants. In this study, a seven-day experiment was conducted to evaluate the effects of Dufulin at five different concentrations (1 × 10-4, 1 × 10-3, 1 × 10-2, 0.1, and 1 mg/L) on Tubifex. LC-MS-based metabolome analysis detected a total of 5356 features in positive and 9110 features in negative, of which 41 showed significant changes and were identified as differential metabolites. Four metabolic pathways were selected for further study. Detailed analysis revealed that Dufulin exposure affected the urea cycle of Tubifex, probably via argininosuccinate lyase (ASL) inhibition. It also affected the fatty acid metabolism, leading to changes in the concentration of free fatty acids in Tubifex. Furthermore, the changes in metabolites after exposure to Dufulin at 1 × 10-2 mg/L were different from those at the other concentrations.

Joint effects of microplastic and dufulin on bioaccumulation, oxidative stress and metabolic profile of the earthworm (Eisenia fetida).

Microplastics and pesticides are identified as two environmental pollutants that have an adverse impact on the environment. The knowledge about the combined exposure of pesticides and microplastics may facilitate further assessment of their ecotoxicity. In this study, we investigated joint effects of microplastic and dufulin on bioaccumulation, oxidative stress and metabolic profile of the earthworm. Bioaccumulation analysis showed that the bio-soil accumulation factor of dufulin in earthworms reached its maximum value on the 14th day, and microplastics could significantly increase the bioaccumulation of dufulin in earthworms. Biochemical analysis showed that the oxidative damage of earthworms could be observed on the 14th day of the exposure to dufulin, while the oxidative damage of earthworms could be observed on the 7th day of the combined exposure to microplastics and dufulin, and it could still be observed on the 14th day. 1H-NMR-based metabolomics revealed that the exposure of dufulin significantly altered the relative abundances of 14 metabolites and two metabolic pathways, but the combined exposure of dufulin and microplastics significantly changed the relative abundances of 21 metabolites and three metabolic pathways. It could be seen that microplastics could aggravate the oxidative damage and the interference with the metabolic profile caused by dufulin to earthworms. The results of this study could provide effective information for the risk assessment of dufulin and microplastic in environmental safety.

Evaluating the effects of the tebuconazole on the earthworm, Eisenia fetida by H-1 NMR-Based untargeted metabolomics and mRNA assay.

Tebuconazole, a widely used fungicide, can severely disrupt the reproductive process of various organisms. In this study, we investigated the subacute effects of tebuconazole on the earthworm to fully understand its toxic implications. Herein, untargeted metabolomics, mRNA assay and biochemical approaches were adopted to evaluate the subacute effects of Eisenia fetida earthworms, when exposed to tebuconazole at three different concentrations (0.5, 5 and 50 mg/kg) for seven days. SOD enzyme activity test displayed that tebuconazole exposure interfered with the earthworms' ROS. ANN mRNA expression was down-regulated after tebuconazole exposure. 1H nuclear magnetic resonance (1H-NMR)-based untargeted metabolomics study showed that 5 mg/kg tebuconazole exposure interfered with earthworms' metabolism. Twelve significantly changed metabolites were identified. The pathway analyses indicate that tebuconazole can disrupt the earthworm's metabolism, particularly in the AMP pathway, which impact the reproduction. This may explain the tebuconazole's mechanism of action behind the down-regulation of the expression of ANN mRNA, which is related to the earthworm's reproductive process. We comprehensively evaluated the mRNA expression, enzyme activity, and metabolomics, and acquired sufficient information for evaluating the toxicity of tebuconazole.

Effects of the Chiral Fungicides Metalaxyl and Metalaxyl-M on the Earthworm Eisenia fetida as Determined by ¹H-NMR-Based Untargeted Metabolomics.

Although metalaxyl and metalaxyl-M are widely used fungicides, very little is known about their subacute and enantiospecific effects on the earthworm metabolome. In this study, Eisenia fetida were exposed to metalaxyl and metalaxyl-M at three concentrations (0.5, 5 and 50 mg/kg) for seven days. ¹H nuclear magnetic resonance (¹H-NMR)-based untargeted metabolomics showed that metalaxyl and metalaxyl-M exposure disturbed earthworms' metabolism at all three concentrations. Endogenous metabolites, such as succinate, arginine, aspartate, urea, asparagine, alanine, trimethylamine, taurine, cysteine, serine, threonine, histidine, lysine, glucose, choline, carnitine, citric acid, alpha-ketoisovaleric acid, fumaric acid and so on, were significantly changed. These results indicate that metalaxyl and metalaxyl-M produce different, enantiospecific disturbances in the earthworm metabolism, particularly in the tricarboxylic acid (TCA) and urea cycles. The application of untargeted metabolomics thus provides more information for evaluating the toxic risks of metalaxyl and metalaxyl-M.

Effects of perinatal exposure to BPA, BPF and BPAF on liver function in male mouse offspring involving in oxidative damage and metabolic disorder.

Bisphenols (BPs) are common environmental pollutants that are ubiquitous in the natural environment and can affect human health. In this study, we explored the effects of perinatal exposure to BPA, BPF and BPAF on liver function involving in oxidative damage and metabolic disorders in male mouse offspring. We found that BPA exposure impairs the antioxidant defense system, increases lipid peroxidation, and causes oxidative damage in the liver. Furthermore, the levels of 13 metabolites were significantly altered following BPA exposure. We found that BPF exposure significantly increased the expression and activity of CAT, suggesting disturbances in the antioxidant defense system. Moreover, BPF exposure led to metabolic disorders in the liver due to changes in the levels of 8 key metabolites. Exposure to BPAF caused no negative effects on oxidative damage, but altered the levels of ß-glucose and glycogen. In summary, perinatal exposure to BPA, BPF and BPAF differentially influence oxidative damage and metabolic disorders in the livers of male mouse offspring. The impact of early life exposure to BPs now warrants future investigations.

Perinatal exposure to low-dose decabromodiphenyl ethane increased the risk of obesity in male mice offspring.

Decabromodiphenyl Ethane (DBDPE), a kind of new brominated flame retardants (NBFRs) used to replace DecaBDE, has been frequently detected in the environment and human samples. In this study, we explored its toxic effects on male mouse offspring after perinatal exposure to DBDPE. During the perinatal period, pregnant ICR mice were exposed to DBDPE (100 µg/kg body weight) via oral gavage. After weaning, male offspring were fed on a low-fat diet and a high-fat diet, respectively. We measured and recorded body weight, liver weight, and epididymis fat mass, blood biochemical markers, metabolites changes in liver, and gene expression involved in lipid and glucose homeostasis. The results showed that perinatal exposure to DBDPE increased the risk of obesity in mouse offspring and affected triglyceride synthesis, bile secretion, purine synthesis, mitochondrial function and glucose metabolism, furthermore, the use of HFD feeding may further exacerbate these effects. All of these results show that early-life exposure to low doses of DBDPE can promote the development of metabolic dysfunction, which in turn induces obesity.

Multiplatform Metabolomics Investigation of Antiadipogenic Effects on 3T3-L1 Adipocytes by a Potent Diarylheptanoid.

Obesity is fast becoming a serious health problem worldwide. Of the many possible antiobesity strategies, one interesting approach focuses on blocking adipocyte differentiation and lipid accumulation to counteract the rise in fat storage. However, there is currently no drug available for the treatment of obesity that works by inhibiting adipocyte differentiation. Here we use a broad-based metabolomics approach to interrogate and better understand metabolic changes that occur during adipocyte differentiation. In particular, we focus on changes induced by the antiadipogenic diarylheptanoid, which was isolated from a traditional Chinese medicine Dioscorea zingiberensis and identified as (3 R,5 R)-3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane (1). Targeted aqueous metabolic profiling indicated that a total of 14 metabolites involved in the TCA cycle, glycolysis, amino acid metabolism, and purine catabolism participate in regulating energy metabolism, lipogenesis, and lipolysis in adipocyte differentiation and can be modulated by diarylheptanoid 1. As indicated by lipidomics analysis, diarylheptanoid 1 restored the quantity and degree of unsaturation of long-chain free fatty acids and restored the levels of 171 lipids mainly from 10 lipid classes in adipocytes. In addition, carbohydrate metabolism in diarylheptanoid-1-treated adipocytes further demonstrated the delayed differentiation process by flux analysis. Our results provide valuable information for further understanding the metabolic adjustment in adipocytes subjected to diarylheptanoid 1 treatment. Moreover, this study offers new insight into developing antiadipogenic leading compounds based on metabolomics.

The fate of technical-grade chlordane in mice fed a high-fat diet and its roles as a candidate obesogen.

Epidemiological studies indicate that exposure to persistent organic pollutants is positively associated with the prevalence of obesity. To delineate the potential role of technical-grade chlordane in obesity development, chlordane metabolism and chlordane-induced metabolic changes were investigated in mice fed high-fat diet (HFD) over a 6-week period. Gas chromatography-electron capture detector analysis showed that HFD induced more accumulation of technical chlordane in the liver, muscle and adipose tissue. The enantioselectivities of oxychlordane in selected tissues were also influenced by HFD. 1H NMR-based liver metabolome indicated that technical chlordane can enhance the metabolic alterations induced by HFD. Compared with the low-fat diet (LFD) group, no differences were observed in the LFD + chlordane group. However, as many as 16 metabolites were significantly different between the HFD group and HFD + chlordane group. Moreover, compared to the LFD + chlordane group, the abundances of 24 metabolites significantly increased or decreased in the HFD + chlordane group. Twenty metabolites were altered in the HFD group compared to the LFD group. Tryptophan profiling suggested that both chlordane and HFD can disturb tryptophan catabolism. These interactions between technical chlordane and HFD suggest that technical chlordane is a candidate obesogen.

Enantiomeric Separation of Chiral Pesticides by Permethylated ß-Cyclodextrin Stationary Phase in Reversed Phase Liquid Chromatography.

Enantiomeric separation of six chiral pesticides by high-performance liquid chromatography with permethylated ß-cyclodextrin (ß-PM) chiral stationary phase were tested under reversed phase conditions. The influences of water composition from 10% to 45% in the mobile phase and column temperatures from 0°C to 40°C on the separation were investigated. Baseline separation was obtained for diclofop-methyl, fenoxaprop-ethyl, tebuconazole and triticonazole, and Rs of these pesticides were greater than 1.5. However, etoxazole and lactofen were partially separated in all experiments.

Enantioselective bioaccumulation of hexaconazole and its toxic effects in adult zebrafish (Danio rerio).

Little is known about the bioaccumulation and toxicity of hexaconazole (HEX) in spite of the fact that they are indispensable parts for a comprehensive assessment of its environmental behavior and toxic effects in organisms of freshwater ecosystems. In this study, adult zebrafish were used to study the enantioselective bioaccumulation of HEX and its effect endpoints in liver, including oxidative stress and the regulation of apoptosis-related gene expression. Significant enantioselective bioaccumulation was demonstrated when exposed to HEX of 100 and 200 µg L(-)(1), finding that the (-)-enantiomer tended to accumulate in zebrafish more easily than (+)-enantiomer. Activities of antioxidant enzymes (SOD, CAT and GPx) and GSH content were all significantly decreased when zebrafish were exposed to 50 and 200 µg L(-1) HEX for 21 d. A series of genes of the apoptosis pathway were examined in groups treated with 50 and 200 µg L(-)(1) HEX for 21 d using real-time PCR. Significant up-regulation of p53, Puma, Apaf-1, caspase-3 and caspase-9 expression and down-regulation of Bcl-2/Bax expression ratio were proved. The overall results indicated that waterborne HEX was able to produce oxidative stress and induce apoptosis through the involvement of caspases in adult zebrafish. The above information will play a vital role in the integrated environmental risk assessment of HEX and make its toxic mechanism in fish clear.

[Transurethral prostatectomy with the bipolar plasma kinetic technique for benign prostate hyperplasia: a report of 297 cases].

OBJECTIVE: To evaluate the effect and safety of transurethral prostatectomy with the bipolar plasma kinetic technique (PKRP) in the treatment of benign prostate hyperplasia(BPH). METHODS: Two hundred and ninty-seven BPH patients underwent transurethral prostatectomy with the bipolar plasma kinetic technique. The preoperative estimated weight of the prostate ranged from 35 g to 102 g, averaging 52 g. RESULTS: The operation lasted 40 approximately 65 min, averaging 51 min. The resected tissues weighed 40 approximately 80 g, averaging 46 g. During the operation no transurethral resection (TUR) syndrome occurred. The catheter was removed 4 approximately 5 days after the operation, all with fluent urination. The patients were followed up for 2 approximately 33 months. IPSS decreased from average 31.5 preoperatively to average 6.8 postoperatively (P < 0.001). Average maximum flow-rate (Q(max)) decreased from 6.3 ml/s preoperatively to 18.6 ml/ s postoperatively (P < 0.001). Preoperative average residual urine was 97 ml and reduced to average 9 ml after the operation. Temporary incontinence occurred in 4 cases, perioperative hemorrhage in 2, and urethral stricture in 1. CONCLUSION: Transurethral prostatectomy with the bipolar plasma kinetic technique is a safe and effective means for the treatment of BPH.

[Management and investigation of testicular torsion].

OBJECTIVE: To improve the diagnosis and treatment of testicular torsion. METHODS: The clinical data of 9 cases of suspected testicular torsion were restrospectively analyzed to summarize the diagnostic experiences. RESULTS: The 9 patients were 12-27 (mean 15) years old, 8 treated by surgery and 1 by spontaneous detorsion under anesthesia. Among them, 7 cases were proved to be testicular torsion and 1 case was acute epididymitis. Of the 7 cases of testicular torsion, 6 were found to have 180-720-degree torsion around the spermatic cord and 1 case 180-degree around the verticality of the spermatic cord. The accuracy rate of color ultrasonic examination was 87.5%. CONCLUSION: Patients with acute scrotum pain should have color ultrasonic examination. Not all cases of the disease had testicular torsion around the spermatic cord. Emergency operation should be performed on any suspected case of testicular torsion.

[The combined therapy of intervention, operation and biology in patients with middle-advanced renal cell carcinoma].

OBJECTIVE: To observe the effect of the combined therapy of intervention, operation and biology in patients with middle-advanced renal cell carcinoma. METHODS: Combined therapy was used in 52 cases as combined care groups and the single operational therapy was used in 50 cases as control group. Compare their resection rates, surgical risks and 3, 5 years survival rates. RESULTS: In the combined care group, the excision rate was 100%, the average amount of blood transfusion during the operation was 280 ml, the average operation time was 100 minutes, and the 3, 5 years survival rates were 73% and 50%; While in the control group, the results were 90%, 396 ml, 130 minutes, 55% and 27% respectively. There were significant differences between 2 groups (P < 0.05). CONCLUSION: Combined therapy could elevate resection rates and 3, 5 years survival rates and decrease surgical risks.