Enzymatic properties and degradation characterization of a bis(2-hydroxyethyl) terephthalate hydrolase from Saccharothrix sp / 生物工程学报

The discovery of new enzymes for poly(ethylene terephthalate) (PET) degradation has been a hot topic of research globally. Bis-(2-hydroxyethyl) terephthalate (BHET) is an intermediate compound in the degradation of PET and competes with PET for the substrate binding site of the PET-degrading enzyme, thereby inhibiting further degradation of PET. Discovery of new BHET degradation enzymes may contribute to improving the degradation efficiency of PET. In this paper, we discovered a hydrolase gene sle (ID: CP064192.1, 5085270-5086049) from Saccharothrix luteola, which can hydrolyze BHET into mono-(2-hydroxyethyl) terephthalate (MHET) and terephthalic acid (TPA). BHET hydrolase (Sle) was heterologously expressed in Escherichia coli using a recombinant plasmid, and the highest protein expression was achieved at a final concentration of 0.4 mmol/L of isopropyl-β-d-thiogalactoside (IPTG), an induction duration of 12 h and an induction temperature of 20 ℃. The recombinant Sle was purified by nickel affinity chromatography, anion exchange chromatography, and gel filtration chromatography, and its enzymatic properties were also characterized. The optimum temperature and pH of Sle were 35 ℃ and 8.0, and more than 80% of the enzyme activity could be maintained in the range of 25-35 ℃ and pH 7.0-9.0 and Co2+ could improve the enzyme activity. Sle belongs to the dienelactone hydrolase (DLH) superfamily and possesses the typical catalytic triad of the family, and the predicted catalytic sites are S129, D175, and H207. Finally, the enzyme was identified as a BHET degrading enzyme by high performance liquid chromatography (HPLC). This study provides a new enzyme resource for the efficient enzymatic degradation of PET plastics.

Effects of Shoutai pills on immune function and oxidative stress in pregnant rats with di(2-ethylhexyl) phthalate exposure / 南方医科大学学报

OBJECTIVE@#To investigate the effects of Shoutai pills (a traditional Chinese medicinal preparation) on immune functions and oxidative stress in pregnant rats exposed to di(2-ethylhexyl) phthalate (DEHP).@*METHODS@#Thirty-six mature female SD rats were randomly divided into 3 groups (=12). After pregnancy was confirmed, the rats were given 10 mL/kg corn oil +10 mL/kg saline (control group), 500 mg/kg DEHP+10 mL/kg saline (model group), and 500 mg/kg DEHP+10 mL/kg Shoutai pills (treatment group). At 19 days of gestation, the rats were sacrificed and the fetal rats were weighed and the numbers of live and stillborn fetal rats were recorded. Serum levels of interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor-ɑ (TNF-ɑ), estradiol (E2) and progesterone (P) levels were detected. The appearance, color and quality of the placenta in each group were recorded, and the placental tissues were examined pathologically. The total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH- Px), catalase (CAT), reactive oxygen species (ROS) and malondialdehyde (MDA) in the placental tissues were measured.@*RESULTS@#Compared with the control group, the rats with DEHP exposure showed slow weight gain in the middle and late gestation period and significantly lower fetal weight ( < 0.05) with lowered serum levels of IL-2, IL-6 and TNF-ɑ, increased estradiol level ( < 0.05), decreased placental T-AOC, GSH-Px, SOD and CAT levels, and increased ROS and MDA levels ( < 0.01). Compared with the model group, the rats treated with Shoutai pills had significantly increased weight gain in mid and late pregnancy and greater fetal weight ( < 0.05) with significantly increased serum IL-2 and IL-6 levels, decreased estradiol level ( < 0.05), slightly increased TNF-ɑ expression (> 0.05), increased placenta T-AOC, GSH- Px and CAT levels, decreased MDA level ( < 0.05), and slightly increased SOD and decreased ROS levels (>0.05). No significant difference was found in progesterone levels among the groups (>0.05). HE staining showed that the trophoblast in the placental tissue sponge in the model group was loose and irregular with numerous vacuoles. In the treatment group, the structure of the placenta remained intact with clearly visible labyrinth zone, sponge trophoblast and giant cell trophoblast, and the cell distribution in each layer was better than that in the model group.@*CONCLUSIONS@#Shoutai pills can regulate the immune function of DEHP-exposed pregnant rats possibly by antagonizing the estrogenlike effect of DEHP and regulating serum immune factors; Shoutai pills can also reduce placental tissue damage and improve pregnancy outcome by correcting DEHP-induced imbalance of oxidative stress in the placental tissues.

Di (2-ethylhexyl) phthalate-induced hypospadias in SD rats is related with Mafb expression: a transcriptome profiling-based study / 南方医科大学学报

OBJECTIVE@#To investigate the transcriptome profile of genital tubercles (GTs) in male SD rats and explore the mechanism of hypospadias induced by Di (2-ethylhexyl) phthalate (DEHP).@*METHODS@#Forty time-pregnant SD rats were randomly divided into 4 equal groups, namely GD16 group and GD19 group (in which the male GTs were collected on gestation day[GD]16 and GD19 for RNA-seq, respectively), control group and DEHP exposure group (with administration of oil and 750 mg/kg DEHP by gavage from GD12 to GD19, respectively).In the control and DEHP exposure groups, the GTs were collected from the male fetuses on GD19.5, and scanning electron microscopy and HE staining were used to observe the morphological changes.The differentially expressed genes (DEGs) in the GTs were screened using lllumina HiSeq 2000 followed by GO and KEGG enrichment analyses to characterize the transcriptome profile.Immunofluorescence assay was performed to verify the DEGs (Mafb) identified by RNA-seq results.Immunofluorescence assay and Western blotting were used to examine the expression levels of Mafb in the penile tissue.@*RESULTS@#A total of 1360 DEGs were detected in the GTs between GD16 group and GD19 group by RNA-seq.Among these genes, 797 were up-regulated and 563 were down-regulated.These DEGs were mainly enriched in the cell adhesion plaque signaling pathway, axon guidance signaling pathway, and extracellular matrix receptor signaling pathway.Compared with that in GD16 group, Mafb was significantly up-regulated in GD19 group, which was consistent with the sequencing results.Mafb and β-catenin were significantly down-regulated in DEHP-exposed group compared with the control group ( < 0.01).@*CONCLUSIONS@#Mafb expression increases progressively with the development of GTs in male SD rats.DEHP exposure causes significant down-regulation of Mafb and β-catenin, suggesting that β-catenin signaling pathway that affects Mafb is related to DEHP-induced hypospadias in SD rats.

Phthalate contamination of some plants and herbal products / Contaminación de algunas plantas y productos herbales con ftalatos

Phthalate derivatives cause a number of risks to human health and the environment. Essential oil and volatile fractions of some vegetables and herbal products were extracted by hydrodistillation and percolation methods to analyze using gas chromatography and mass spectrometry (GC-MS) for evaluation of phthalate contaminations. The results revealed that four vegetables and all aromatic waters were contaminated by phthalate derivatives including di-n-butyl phthalate (DBP), diisobutyl phthalate and di-(2-ethylhexyl) phthalate (DEHP) (0.1-7.95%). Butylated hydroxytoluene (BHT), a widely used synthetic antioxidant, was also found in the most of the aromatic waters in the range of 3.15-61.3%. In addition, three vegetable samples contained diazinon (0.36-4.61%), an organophosphorus insecticide. Plants and herbal preparations may be contaminated by the absorption of phthalates from contaminated water or soil or by the migration of phthalates from inexpensive recycled plastic. Regarding the widespread use and associated health risks of phthalates, effective quality and safety regulations for herbal products should be implemented with respect to their phthalate content.

Los derivados de ftalato causan una serie de riesgos para la salud humana y el medio ambiente. El aceite esencial y las fracciones volátiles de algunos vegetales y productos a base de hierbas fueron extraídos mediante hidrodestilación y métodos de percolación y luego fueron analizados mediante cromatografía de gases y espectrometría de masas (GC-MS) con el propósito de identificar contaminación con ftalatos. Los resultados revelaron que cuatro productos herbales y todas las aguas aromáticas analizadas estaban contaminadas con derivados de ftalato, incluyendo el ftalato de dibutulo (DBP), ftalato de diisobutilo y ftalato de bis(2-etilhexilo) (DEHP) (0.1-7.95%). El butilhidroxitolueno (BHT), un antioxidante sintético ampliamente utilizado, también se encontró en aguas aromáticas en el rango de 3.15- 61.3%. Además, tres muestras vegetales contenían diazinón (0.36-4.61%), un insecticida organofosforado. Las plantas y las preparaciones herbales pueden ser contaminadas a partir de absorción de ftalatos del agua o el suelo contaminados o por la migración de ftalatos desde plástico reciclado de bajo costo. Con respecto al uso generalizado y los riesgos asociados a la salud de los ftalatos, deben implementarse normas efectivas de calidad y seguridad para los productos a base de hierbas con respecto a su contenido de ftalato.

Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children's Health

BACKGROUND@#Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates; however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age.@*METHODS@#The Strengths and Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5 years of age. BPA and phthalate metabolite levels in the first trimester maternal serum was determined by LC-MS/MS for 458 children. Variables used for adjustment were parental ages, maternal cotinine levels, family income during pregnancy, child sex, birth order, and age at SDQ completed.@*RESULTS@#The median concentrations of BPA, MnBP, MiBP, MEHP, and MECPP, primary and secondary metabolites of phthalates, were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml, respectively. MECPP level was associated with increase conduct problem risk (OR = 2.78, 95% CI 1.36-5.68) overall and the association remained after child sex stratification, and odds ratios were increased with wider confidence interval (OR = 2.85, 95% CI 1.07-7.57 for boys, OR = 4.04, 95% CI 1.31-12.5 for girls, respectively). BPA, ∑DBP (MnBP + MiBP), and ∑DEHP (MEHP+MECPP) levels were not associated with any of the child behavioral problems.@*CONCLUSIONS@#Our analyses found no significant association between BPA or summation of phthalate metabolite levels and any of the behavioral problems at 5 years of age but suggested possible association between MECPP levels and increased risk of conduct problems.

Effects of cysteinyl leukotriene receptors on phagocytosis of mouse microglial cells / 浙江大学学报·医学版

OBJECTIVE@#: To determine the effects of cysteinyl leukotriene receptors (CysLTR and CysLTR) on phagocytosis of mouse BV2 microglial cells.@*METHODS@#: BV2 cells were stimulated with microglial activators lipopolysaccharide (LPS) or CysLT receptor agonists LTD. The phagocytosis of BV2 cells was observed by immunofluorescence analysis and flow cytometry. The intracellular distributions of CysLTR and CysLTR in BV2 cells were examined with immunofluorescence staining.@*RESULTS@#: Both LPS and LTD could significantly enhance the phagocytosis of BV2 cells, and such effect could be inhibited by CysLTR selective antagonist Montelukast and CysLTR selective antagonist HAMI 3379. The activation of BV2 cells induced by LTD or LPS resulted in changes in intracellular distributions of CysLTR and CysLTR. CysLTR and CysLTR was co-localization with a similar distribution.@*CONCLUSIONS@#: CysLTR and CysLTR regulate the phagocytosis of mouse BV2 microglial cells with a synergistic effect.

Complete genome sequence of a phthalic acid esters degrading Mycobacterium sp. YC-RL4

ABSTRACT Mycobacterium sp. YC-RL4 is capable of utilizing a broad range of phthalic acid esters (PAEs) as sole source of carbon and energy for growth. The preliminary studies demonstrated its high degrading efficiency and good performance during the bioprocess with environmental samples. Here, we present the complete genome of Mycobacterium sp. YC-RL4, which consists of one circular chromosome (5,801,417 bp) and one plasmid (252,568 bp). The genomic analysis and gene annotation were performed and many potential genes responsible for the biodegradation of PAEs were identified from the genome. These results may advance the investigation of bioremediation of PAEs-contaminated environments by strain YC-RL4.

Association between Phthalate Exposure and the Use of Plastic Containers in Shanghai Adults / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Consuming phthalates may be due to the presence of food contact materials, such as plastic containers. In this study, we investigated the association between plastic container use and phthalate exposure in 2,140 Shanghai adults.</p><p><b>METHODS</b>Participants completed a questionnaire on the frequency of using plastic containers in different scenarios in the previous year (e.g., daily, weekly) and on the consumption of plastic-packaged foods in the previous three days (yes or no). Urinary phthalate metabolites were used to assess the association between phthalate exposure and the use of plastic containers.</p><p><b>RESULTS</b>The metabolites of di-(2-ethylhexyl) phthalate (DEHP) were the most frequently detected in urine. The results revealed that phthalate exposure was associated with consumption of plastic-packaged breakfast or processed food items in the previous three days. The consumption of these two food items had strong synergistic effects on increasing urinary concentrations of most phthalate metabolites.</p><p><b>CONCLUSION</b>Our results of plastic-packaged breakfast and processed food may be explained by the use of flexible plastic containers, indicating the importance of risk assessment for the application of flexible plastic containers.</p>

Effect of Mono-2-ethyhexyl Phthalate on DNA Methylation in Human Prostate Cancer LNCaP Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate whether mono (2-ethylhexyl) phthalate (MEHP) affects genomic DNA methylation and the methylation status of some specific genes such as patched gene (PTCH) and smoothened gene (SMO) in LNCaP cells.</p><p><b>METHODS</b>LNCaP cells were treated with MEHP (0, 1, 5, 10, and 25 μmol/L) for 3 days. An ELISA assay was preformed to detect genomic methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) content. A pyrosequencing assay was applied to assess DNA methylation in PTCH and SMO gene promoters. The correlation between DNA methylation and gene expression was assessed.</p><p><b>RESULTS</b>The proportion of cytosines with 5-mC methylation in LNCaP cells was significantly decreased by MEHP (1, 5, 10, and 25 μmol/L) in a dose-dependent manner (P < 0.01). For genes in the Hedgehog pathway, there was no significant MEHP concentration-dependent difference in the DNA methylation of PTCH and SMO.</p><p><b>CONCLUSION</b>MEHP might affect the progression of prostate cancer through its effect on global DNA methylation.</p>

Dietary Exposure to Benzyl Butyl Phthalate in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Benzyl butyl phthalate (BBP) is a plasticizer used in food contact materials. Dietary exposure to BBP might lead to reproduction and developmental damages to human. The present paper was aimed to assess the health risk of BBP dietary exposure in Chinese population.</p><p><b>METHODS</b>The BBP contents were detected in 7409 food samples from 25 food categories by gas chromatography-mass spectrometry operated in selected ion monitoring (SIM) mode. The dietary exposures of BBP in different age and sex groups were estimated by combining the content data with food consumption data derived from 2002 China National Nutrient and Health Survey, and evaluated according to the tolerable daily intake (TDI) of BBP established by European Food safety Agency.</p><p><b>RESULTS</b>It was found that BBP was undetectable in most samples and the highest level was 1.69 mg/kg detected in a vegetable oil sample. The average dietary exposure of BBP in people aged ⋝2 years was 1.03 μg/kg bw per day and the highest average exposure was found in 2-6 years old children (1.98 μg/kg bw per day). The BBP exposure in 7-12 months old children excessed 10% of tolerable daily intake (TDI) in worst scenario. .</p><p><b>CONCLUSION</b>The health risk of BBP dietary exposure in Chinese population is low and, considering BBP alone, there is no safety concern.</p>

Current status of bio-based materials industry in China / 生物工程学报

In recent years, bio-based materials are becoming a new dominant industry leading the scientific and technological innovation, and economic development of the world. We reviewed the new development of bio-based materials industry in China, analyzed the entire market of bio-based materials products comprehensively, and also stated the industry status of bio-based chemicals, such as lactic acid, 1,3-propanediol, and succinic acid; biodegradable bio-based polymers, such as co-polyester of diacid and diol, polylactic acid, carbon dioxide based copolymer, polyhydroxyalknoates, polycaprolactone, and thermoplastic bio-based plastics; non-biodegradable bio-based polymers, such as bio-based polyamide, polytrimethylene terephthalate, bio-based polyurethane, and bio-based fibers.

Enhanced production of dimethyl phthalate-degrading strain Bacillus sp. QD14 by optimizing fermentation medium

Background Integrated statistical experimental designs were applied to optimize the medium constituents for the production of a dimethyl phthalate (DMP)-degrading strain Bacillus sp. QD14 in shake-flask cultures. A Plackett-Burman design (PBD) was applied to screen for significant factors, followed by the Steepest Ascent Method (SAM) to find the nearest region of maximum response. A Box-Behnken design (BBD) of the Response Surface Methodology (RSM) was conducted to optimize the final levels of the medium components. Results After the regression equation and response surface contour plots were analyzed, the concentrations of glucose, corn meal and NaCl were found to significantly influence the biomass of DMP-degrading bacteria. A combination of 22.88 g/L of glucose, 11.74 g/L of corn meal, and 10.34 g/L of NaCl was optimum for maximum biomass production of Bacillus sp. QD14. A 57.11% enhancement of the biomass production was gained after optimization in shake-flask cultivation. The biomass production of Bacillus sp. QD14 reached 9.13 ± 0.29 × 10(8) CFU/mL, which was an excellent match for the predicted value, and the mean value of the match degree was as high as 99.30%. Conclusion In this work, the key factors affected by the fermentation of DMP-degrading strain Bacillus sp. QD14 were optimized by PBD, SAM and BBD (RSM); the yield was increased by 57,11% in the conditions in our study. We propose that the conditions optimized in the study can be applied to the fermentation for commercialization production.

Bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials

There has been concern regarding the use of controversial paradigms for repetitive transcranial magnetic stimulation (rTMS) to manage treatment-resistant depression (TRD). This meta-analysis assessed the efficacy of bilateral rTMS compared with unilateral and sham rTMS in patients with TRD. PubMed, Embase, CENTRAL, PsycINFO, Web of Science, EAGLE and NTIS databases were searched to identify relevant studies, and randomized controlled trials (RCTs) on bilateral rTMS for TRD patients were included. The response was defined as the primary outcome, and remission was the secondary outcome. Ten RCTs that included 634 patients met the eligibility criteria. The risk ratio (RRs) of both the primary and secondary outcomes of bilateral rTMS showed non-significant increases compared to unilateral rTMS (RR=1.01, P=0.93; odds ratio [OR]=0.77, P=0.22). Notably, the RR of the primary bilateral rTMS outcome was significantly increased compared to that for sham rTMS (RR=3.43, P=0.0004). The results of our analysis demonstrated that bilateral rTMS was significantly more effective than sham rTMS but not unilateral rTMS in patients with TRD. Thus, bilateral rTMS may not be a useful paradigm for patients with TRD.

Maternal Disononyl Phthalate Exposure Activates Allergic Airway Inflammation via Stimulating the Phosphoinositide 3-kinase/Akt Pathway in Rat Pups / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the effect of diisononyl phthalate (DINP) exposure during gestation and lacta- tion on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it.</p><p><b>METHODS</b>Female Wistar rats were treated with DINP at different dosages (0, 5, 50, and 500 mg/kg of body weight per day). The pups were sensitized and challenged by ovalbumin (OVA). The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin (HE) staining; and the relative cytokines in phosphoinositide 3-kinase (PI3K)/Akt pathway were measured by enzyme-linked immunosorbent assay (ELISA) and western blot analysis.</p><p><b>RESULTS</b>There was no significant difference in DINP's effect on airway hyperresponsiveness (AHR) between male pups and female pups. In the 50 mg/(kg·d) DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance (RI) compared with those from controls (P<0.05). Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/(kg·d) DINP-treated group. However, in the 5 and 500 mg/(kg·d) DINP-treated pups, no significant effects were observed.</p><p><b>CONCLUSION</b>There was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.</p>

Levels of phthalate internal exposure levels in pregnant women and influencing factors / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the levels and influencing factors of phthalate internal exposure in pregnant women (gestation age ≤ 16 weeks).</p><p><b>METHODS</b>During April to June in 2013, 1 020 pregnant women (gestation age ≤ 16 weeks) who had established the maternal care manual were recruited in maternal and child health hospital of Siming District, Xiamen city. Participators were asked to complete a questionnaire to obtain information on socio-demographic characteristics, lifestyle behaviors, and antenatal examination and to provide a urine sample. Finally, 998 pregnant women who provided a urine sample and completed the questionnaire were enrolled. Adopting systematic sampling method, 100 ones were selected randomly among 998 pregnant women. High performance liquid chromatography-electrospray ionization-tandern mass was used to determine the concentration of five phthalate monoesters in each urine, including mono-n-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-ethylhexyl phthalate (MEHP). Based on the measurements and questionnaire data, multivariate logistic regression was used to analyze the association between the phthalate monoester levels and potential influential factors.</p><p><b>RESULTS</b>The detection rates of MMP, MEP, MBP, MBzP and MEHP in 100 pregnant urine samples were 94%, 93%, 87%, 83%, 99%, respectively. And the urinary median uncorrected concentrations of MMP, MEP, MBP, MBzP and MEHP in 100 urine samples were 20.56, 17.62, 10.15, 2.03, and 5.12 ng/ml, respectively. Specific gravity-corrected concentration were 20.81, 20.36, 12.88, 2.58, 5.00 ng/ml, respectively. The results of multivariate logistic regression analysis indicated that: education degree was negatively associated with urinary concentration of MMP, MEP, MBP, MBzP and MEHP, OR (95% CI) were 0.495 (0.253-0.966), 0.380 (0.191-0.755), 0.379 (0.186-0.774), 0.401 (0.196-0.819), 0.373(0.183-0.762), respectively. Participants who had hair permed and dyed during pregnancy had higher urinary level of MBP and MBzP, OR (95% CI) were 12.867 (1.240-133.525), 15.982 (1.367-186.911), respectively; Participants who use cosmetics during pregnancy had higher urinary level of MEP and MBP, OR (95% CI) were 2.977 (1.012-8.757), 4.440 (1.485-13.272), respectively; plastic bottled water consumption was positively associated with urinary concentrations of MEP and MEHP, OR (95% CI) were 3.780 (1.417-10.083), 2.699 (1.039-7.010), respectively; annual household income was negatively associated with urinary concentration of MMP, OR (95% CI) was 0.597 (0.372-0.959); individuals who took medications during pregnancy had higher urinary level of MEHP than non-takers, OR (95% CI) was 4.853 (1.084-21.732).</p><p><b>CONCLUSION</b>Pregnant women whose gestation age was less than 16 weeks are generally exposed to phthalate. Phthalate internal exposure levels are significantly associated with most measured factors and the influencing factors with different phthalates internal exposure levels are different.</p>

Synthesis of 13-β-elemene ester derivatives and evaluation of their antioxidant activity in human umbilical vein endothelial cells / 中国天然药物

In the present study, a series of 13-β-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells (HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase (SOD), malonyldialdehyde (MDA), nitric oxide (NO), and lactic dehydrogenase (LDH), which were superior to that of the positive control vitamin E. Further more, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.

Design, synthesis of novel N, N'-bis-(halogenophenyl)-4- methoxybenzene-1, 3-disulfonamides and evaluation of their anti-platelet aggregation activity / 药学学报

Combining the structural features of picotamide and linotroban, a series of N,N'-bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides were designed and synthesized on the basic principles of drug design. The structures of target compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet aggregation activity was evaluated by Born turbidimetric method with adenosine diphosphate (ADP) as the platelet aggregation inducers. The assay results showed that twelve compounds (4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n) were found to have superior anti-platelet aggregation activities than the positive drug picotamide. The preliminary structure-activity relationship (SAR) has been explored.

Impairment of renal structure and function following heterogeneous chemical mixture exposure in rats.

Renal structural and functional alterations following an exposure to a heterogeneous chemical mixture (HCM) of phthalic acid di butyl ester, 1, 2–dichlorobenzene, cadmium chloride and chromium trioxide, administered through oral gavage in low doses (1/100 and 1/1000 of LD50 value of individual chemical) for 60 days, followed by withdrawal till 120 days resulted in significant rise in kidney lipid peroxidation and fall in the activities of enzymatic antioxidants. However, withdrawal of HCM treatment restored most of these altered parameters. Degenerative changes in the kidney included proximal convoluted tubules devoid of brush boarder with cytoplasmic blebbing, dissolution and sloughing of nuclei. Cortical glomeruli were also affected with epithelial disintegration, pyknosis of podocyte nuclei and mesengial cell hyperplasia. The morphological alterations recovered fully in the low dose compared to the high dose treatment group.

Phthalates in Commercial Chinese Rice Wines: Concentrations and the Cumulative Risk Assessment to Adult Males in Shanghai / 生物医学与环境科学（英文）

The concentrations of 16 phthalates in 164 commercial Chinese rice wines (CRW) were detected by GC-MS, and consumption data on CRW in different packaging types was investigated from 634 adult males in Shanghai using a food frequency questionnaire. Based on the principles of probabilistic modelling and cumulative risk assessment, the exposure and health risk of phthalates from CRW to adult males in Shanghai was evaluated. DMP, DEP, DIBP, DnBP, BBP, and DEHP were detected in the samples, the range of detection frequency of individual phthalates varied from 6.10% for BBP to 15.24% for DIBP, and the detected concentrations were 51.06-200.34 ng/mL. All the respondents consumed CRW, 90.69% of them consumed CRW 0.01-49.9 mL/d, the minimum value of the average daily intake of CRW was 6.25 mL/d, the median was 13.72 mL/d and the maximum was 300 mL/d. The median exposure level of the 6 detected Phthalates to adult males in Shanghai were 6.58-7.10 ng/(d•kg), and the maximum exposure level were 137.38-540.47 ng/(d•kg). The cumulative exposure health risk index (HI) based on the median and maximum exposure level of the 6 Phthalates (DMP, DEP, DIBP, DnBP, BBP, and DEHP) were 0.001147 and 0.063396, both were far less than 1. In conclusion, CRW were generally consumed by the adult males in Shanghai, although multiple phthalates were detected in commercial CRW, health risk of such exposure levels from commercial CRW to the target adult males in Shanghai was very low.

Study on the association between maternal urinary phthalate metabolites and testicular steroid hormones in the cord blood in a Chinese population / 中华预防医学杂志

<p><b>OBJECTIVE</b>The purposes of our study were to investigate the association between maternal urinary phthalate metabolites and the levels of inhibin B (INHB) and insulin-like factor 3 (INSL3) in the cord blood in a Chinese pregnant population.</p><p><b>METHODS</b>Maternal urine samples in the third trimester of pregnancy of 69 participants were collected and stored, and the samples of cord blood (10 ml) were collected at delivery between June 2011 and September 2012 in a comprehensive hospital of gynecology and obstetrics in Tianjin, China.Four phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), and mono-2-ethylhexyl phthalate (MEHP) were measured in the urine samples using liquid chromatography-tandem mass spectrometry. The levels of INHB, INSL3 in the cord blood were tested by ELISA. Associations of phthalate exposure with INHB and INSL3 levels were determined by spearman correlation and multiple regression model analysis.</p><p><b>RESULTS</b>The median concentrations of observed metabolites in descending order were 49.74 µg/L for MMP, 24.96 µg/L for MEHP, 19.52 µg/L for MEP and 17.73 µg/L for MBP. The median concentrations of INHB and INSL3 were 89.09 and 106.21 ng/L.Significant negative associations between INHB and MMP(β' = -0.252), MEP(β' = -0.363) or the sum value (∑PAEs) (β' = -0.346) were found by the multiple regression model analysis. For INSL3, only the sum value (β' = -0.313) was inversely significantly associated with the levels of INSL3 in the cord blood.</p><p><b>CONCLUSIONS</b>Maternal urinary phthalate metabolites were associated with INHB and INSL3 in the cord blood in a Chinese population.</p>