Search

What are the potential clinical benefits of embryo culture and assessment in a time-lapse incubator compared with a standard incubator using static assessment?This large multicentre, single-blinded, randomized controlled study included 1224 participants randomly assigned (1:1) to the time-lapse or standard incubator group. In all patients one or two embryos were transferred on day 3. The primary outcome was the implantation rate in the first embryo transfer cycle. Secondary outcomes included the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate.Among 1224 participants recruited, 1182 underwent embryo transfer. The number of successfully implanted embryos in the first transfer cycle was significantly higher in the time-lapse incubator group (time-lapse group: 52.35%, standard incubator group: 47.11%, P = 0.014). The implantation rate in the first embryo transfer cycle was still significantly higher in the time-lapse group than the standard incubator group after adjusting for age, body mass index, medical centre and embryo status (relative risk 1.11, 95% confidence interval 1.02-1.20, P = 0.020). However, the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate were not statistically different between the groups.The implantation rate in the first embryo transfer cycle was significantly improved in the time-lapse group, but the effect of the time-lapse system on the cumulative implantation rate or cumulative live birth rate was not significant. The embryo assessment method offered by time-lapse systems rather than an undisturbed environment may play an important role in improving the implantation rate in the first embryo transfer cycle. These results are only applicable to young patients.

Ochratoxin A (OTA), a secondary fungal metabolite with nephrotoxicity, is widespread in numerous kinds of feeds and foodstuffs. Ursolic acid (UA), a water-insoluble pentacyclic triterpene acid, exists in a wide range of food materials and medicinal plants. Our earlier researches provided preliminary evidence that mitochondria- and mitochondria-associated endoplasmic reticulum membranes (MAMs)-located stress-responsive Lon protease 1 (Lonp1) had a protective function in OTA-induced nephrotoxicity, and the renoprotective function of UA against OTA partially due to Lonp1. However, whether other MAMs-located protiens, such as endoplasmic reticulum stress (ERS)-responsive Sigma 1-type opioid receptor (Sig-1R), contribute to the protection of UA against OTA-induced nephrotoxicity together with Lonp1 needs further investigation. In this study, the cell viability, reactive oxygen species, and protein expressions of human proximal tubule epithelial-originated kidney-2 (HK-2) cells varied with OTA and/or UA/CDDO-me/AVex-73/Sig-1R siRNA treatments were determined. Results indicated that a 24 h-treatment of 5 μM OTA could significantly induce mitochondrial-mediated apoptosis via repressing Lonp1 and Sig-1R, thereby enhancing the protein expressions of GRP78, p-PERK, p-eIF2α, CHOP, IRE1α, and Bax, and inhibiting the protein expression of Bcl-2 in HK-2 cells, which could be remarkably relieved by a 2 h-pre-treatment of 4 μM UA (P 0.05). In conclusion, through mutual promotion between Lonp1 and Sig-1R, UA could effectively relieve OTA-induced apoptosis in vitro and break the vicious cycle between oxidative stress and ERS, which activated the mitochondrial apoptosis pathway.

In this study, a distinct inoculum was investigated as an isolated variable within sequencing batch reactors via a comparison of the 4-fluoroaniline (4-FA) or 2,4-difluoroaniline (2,4-DFA) removal amounts. The inocula were derived from a treatment plant for treating pharmaceutical wastewater plus a small amount of municipal sewage (PMS), a treatment plant for treating fluoridated hydrocarbon wastewater (FHS), and a treatment plant for treating the comprehensive wastewater in an industrial park (CIS). There were slight differences among the degradation patterns of the 4-FA for the three inocula, whether during the enrichment period or the high concentration shock period. In contrast, it was observed that the degradation efficiency of 2,4-DFA initially varied with the inocula. The FHS-derived inoculum was determined to be optimal, exhibiting the earliest degradation reaction only after an acclimation of 7 days had the highest degradation rate constant of 0.519 h−1, and had the fastest recovery time of three weeks after high concentration shock. Additionally, compared with the PMS-derived inoculum, the CIS-derived inoculum exhibited an earlier degradation reaction within three weeks, and a higher microbial diversity, but a lower shock resistance and degradation rate constant of 0.257 h−1. High-throughput sequencing demonstrated that each final consortium was different in composition, and the microbial consortia developed well on the inoculum and substrate. In comparison of the similarity among the three 2,4-DFA enrichment cultures, the higher similarity (63.9–70.0%) among three final consortia enriching with 4-FA was observed. The results indicated that the inoculum played an important role in the degradation of FAs and the microbial bacterial communities of final consortia, and the effect extent might well depend on the fluorinated level of FAs.

Ochratoxin A (OTA) is a mycotoxin ubiquitous in feeds and foodstuffs. The water-insoluble pentacyclic triterpene bioactive compound, ursolic acid (UA), is widespread in various cuticular waxes of edible fruits, food materials, and medicinal plants. Although studies have reported that oxidative stress was involved in both the nephrotoxicity of OTA and the renoprotective function of UA, the role of stress-responsive Lon protease 1 (Lonp1) in the renoprotection of UA against OTA is still unknown. In this study, cell viability, reactive oxygen species (ROS) production, and several proteins' expressions of human embryonic kidney 293T (HEK293T) cells in response to UA, OTA, and/or Lonp1 inhibitor CDDO-me treatment were detected to reveal the protective mechanism of UA against OTA-induced renal cytotoxicity. Results indicated that a 2 h-treatment of 1 μM UA could significantly alleviate the ROS production and cell death induced by a 24 h-treatment of 8 μM OTA in HEK293T cells (P 0.05). Compared with the control, the protein expressions of Lonp1, Aco2 and Hsp75 were significantly inhibited after 8 μM OTA treating for 24 h (P 0.05), which could be notably reversed by the pre-treatment and post-treatment of 1 μM UA (P 0.05). The protein expressions of Lonp1, Aco2 and Hsp75 were inhibited by the addition of CDDO-me. The three protein expression trends were similar before and after the addition of CDDO-me. In conclusion, OTA could inhibit the expression of Lonp1, suppressing Aco2 and Hsp75 as a result, thereby activating ROS and inducing cell death in HEK293T cells, which could be alleviated by UA pre-treatment.

Circular RNA (circRNA) has been demonstrated to play key roles in regulating glioma progression. Understanding the regulatory mechanism of circRNA in glioma is vital to reveal the pathogenesis of glioma and develop novel therapeutic strategies. Therefore, our study focuses on the role and underlying mechanism of Circ_CLIP2 in glioma.The expression of Circ_CLIP2, miR-195-5p and HMGB3 in glioma cells and tissues were analyzed using qRT-PCR. Cell proliferation was determined with colony formation and MTT assays. Cell cycle and apoptosis were examined by flow cytometry. Western blot was conducted for analyzing HMGB3, PCNA, Bax, Bcl-2, cleaved-caspase 3, Wnt-1 and β-catenin. Dual-luciferase reporter assay was measured to investigate the interaction among Circ_CLIP2, miR-195-5p and HMGB3.The expression of Circ_CLIP2 and HMGB3 were increased while miR-195-5p was down-regulated in glioma cells and patients. Silencing of Circ_CLIP2 inhibited cell proliferation, enhanced cell apoptosis and inhibited the Wnt/β-catenin signaling pathway. Circ_CLIP2 suppressed miR-195-5p expression by directly sponging miR-195-5p. MiR-195-5p inhibited HMGB3 expression via directly targeting HMGB3. Knockdown of miR-195-5p facilitated cell proliferation, inhibited cell apoptosis and activated Wnt/β-catenin signaling, which were reversed by silencing of HMGB3.Knockdown of Circ_CLIP2 suppresses glioma progression by targeting miR-195-5p/HMGB3 thus inhibiting Wnt/β-catenin signaling. This study may provide potential therapeutic targets against glioma.

Glioblastoma multiforme (GBM) is the most malignant glioma with a high death rate. N6-methyladenosine (m6A) RNA methylation plays an increasingly important role in tumors. The current study aimed to determine the function of the regulators of m6A RNA methylation in GBM. We evaluated the difference, interaction, and correlation of these regulators with TCGA database. HNRNPC, WTAP, YTHDF2 and, YTHDF1 were significantly upregulated in GBM. To explore the expression characteristics of regulators in GBM, we defined two subgroups through consensus cluster. HNRNPC, WTAP, and YTHDF2 were significantly upregulated in the cluster2 which had a good overall survival (OS). To investigate the prognostic value of regulators, we used lasso cox regression algorithm to screen an independent prognostic risk characteristic based on the expression of HNRNPC, ZC3H13, and YTHDF2. The prognostic feature between the low and high-risk groups was significantly different (P < 0.05), which could predict significance of prognosis (area under the curve (AUC) = 0.819). Moreover, we used western blot, RT-PCR, and immunohistochemical staining to verify the expression of HNRNPC was associated with malignancy and development of gliomas. Similarly, the high expression of HNRNPC had a good prognosis. In conclusion, HNRNPC is a vital participant in the malignant progression of GBM and might be valuable for prognosis.

In this paper, the effects and mechanisms of a novel two-step tomato peeling method, hot lye with a post-assistance of ultrasound, were investigated. The present work aims to improve the environmental friendliness of the conventional hot lye tomato peeling method (10% w/v, 97 °C, 45 s). The results showed that 4% (w/v) lye treatment at 97 °C for 30 s with a post-assistance of a 31.97 W/L ultrasound treatment at 70 °C for 50 s achieved a 100% peelability. In this scenario, the peeling yield and lycopene content in the peeled product were significantly higher than the peeling yield and lycopene content with the conventional hot lye peeling method. The present two-step peeling method was concluded with a mechanism of chemico-mechanical synergism, in which the hot lye functions mainly in a chemical way while the ultrasound is a mechanical process. Especially from the lye side, this work first demonstrated that the lye penetrated across the tomato skin via a pitting model rather than evenly. The findings reported in this paper not only provide a novel tomato peeling method with significant environmental benefits but also discover new clues to the peeling mechanism using hot lye.

The Yeba Formation volcanic rocks in the Gangdese arc recorded important information regarding the early history of the Neo-Tethyan subduction. To explore their magmatic evolution and tectonic significance, we performed a systematic petrological, geochronological and geochemical study on these volcanic rocks. Our data indicated that the Yeba Formation documents a transition from andesite-dominated volcanism (which started before 182 Ma and continued until ~176 Ma) to bimodal volcanism (~174–168 Ma) in the earliest Middle Jurassic. The early-stage andesite-dominated volcanics are characterized by various features of major and trace elements and are interpreted as the products of interactions between mantle-derived arc magmas and lower crustal melts. Their positive eNd(t) and eHf(t) values suggest a significant contribution of asthenosphere-like mantle. The late-stage bimodal volcanism is dominated by felsic rocks with subordinate basalts. Geochemical signatures of the basalts indicate a composite magma source that included a “subduction component”, an asthenosphere-like upper mantle domain and an ancient subcontinental lithospheric mantle component. The felsic rocks of the late stage were produced mainly by the melting of juvenile crust, with some ancient crustal materials also involved. We suggest that the occurrence and preservation of the Yeba Formation volcanic rocks were tied to a tectonic switch from contraction to extension in the Gangdese arc, which probably resulted from slab rollback of the subducting Neo-Tethyan oceanic slab during the Jurassic.

As a vital member of AAA+ (ATPase associated with diverse cellular activities) protein superfamily, Lon, a homo-hexameric ring-shaped protein complex with a serine-lysine catalytic dyad, is highly conserved throughout almost all prokaryotic and eukaryotic organisms. Lon protease (LONP) plays an important role in maintaining mitoproteostasis through selectively recognizing and degrading oxidatively modified mitoproteins within mitochondrial matrix, such as oxidized aconitase, phosphorylated mitochondrial transcription factor A, etc. Furthermore, the up-regulated LONP increased mitochondrial ROS generation to promote cell survival, cell proliferation, epithelial-mesenchymal transition, and cell migration, which was attributed to the up-regulation of NADH:ubiquinone oxidoreductase core subunit S8 via interaction with chaperone Lon under hypoxic or oxidative stress in tumorigenesis. In addition, Lon also participated in protein kinase RNA (PKR)-like endoplasmic reticulum kinase signaling pathway under endoplasmic reticulum (ER) stress. In short, Lon, as a pivotal stress-responsive protein that involved in the crosstalks among mitochondria, ER and nucleus, participated in multifarious important cellular processes crucial for cell survival, such as the mitochondrial protein quality control system, the mitochondrial unfolded protein response, the mtDNA maintenance, and the ER unfolded protein response.

Diabetic nephropathy is one of the various complications of diabetes mellitus, affecting patients for lifetime. Earlier studies have revealed that genipin can not only improve diabetes, but also induce cytotoxicity. Therefore, it is not clear which effect of genipin on kidneys occurs, when it is used in the treatment of diabetes. In the present study, we performed nuclear magnetic resonance (NMR)-based metabolomics analysis of urine and kidney tissue samples obtained from diabetic rats to explore the change of endogenous metabolites associated with diabetes and concomitant kidney disease. Nine significant differential metabolites that were closely related to renal function were screened. They were mainly related to three metabolic pathways: synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, and butanoate metabolism, which are involved in methylamine metabolism, energy metabolism and amino acid metabolism. In addition, after the intervention of genipin, the metabolic levels of all the metabolites tended to be normal, indicating a protective effect of genipin on kidneys. Our results may be helpful for understanding the antidiabetic effect of genipin.

Background Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Methods Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. Results We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Conclusions Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society

Contamination with fluoroaromatics (FAs), particularly polyfluorinated aniline, is becoming a serious environmental problem worldwide. To shorten the start-up time, and increase the stability of treatment systems, this work focused on the effects of three seeding sources on treatment performances of 2,3,4-trifluoroaniline (2,3,4-TFA) during start-up and shock, as well as the acclimated strategy. After 246–323 days of acclimation in a stepwise feeding according to the inhibition degree, three sequencing batch reactors (SBRs) successfully achieved efficient removal, i.e., 300.00 mg/L of 2,3,4-TFA, with over 95.00% of degradation efficiency and 60.00–80.00% of defluorination rates. The sludge obtained from the fluorizated hydrocarbon wastewater treatment plant(FHS) without prior exposure to fluoroaniline was determined to be optimal, based on the observed shortest start-up time of 246 days, the highest defluorination rate of 70.00–80.00%, the fastest recovery time of 7 days after shock, and the highest microbial diversity with nine dominant bacterial groups. Furthermore, compared with the sludge obtained from pharmaceutical wastewater containing part of municipal wastewater treatment plant(PMS), the seeding source used in treating the comprehensive wastewater in industrial park (CIS) exhibited earlier defluorination reaction, higher defluorination rate and microbial diversity, but lower shock resistance. High-throughput sequencing demonstrated that microbial diversity was dependent on the origin of the inoculum after acclimation. We identified two predominant phyla in PMS, namely, Deinococcus-Thermus (24.43%) and Bacteroidetes (18.44%), whereas these were Acidobacteria and Chloroflexi in FHS and CIS. During the shock of 400 mg/L 2,3,4-TFA, the predominant bacteria norank_f_Blastocatellaceae and norank_f_Methylobacteriaceae disappeared, and the defluorination reaction hardly occurred, indicating that the bacterial genera could contribute to the defluorination reaction.

Among three monofluoroanilines, 2-fluoroaniline (2-FA) and 3-fluoroaniline (3-FA) exhibit relatively poor biodegradability. This work examined their degradation characteristics in a mixed culture system and also analyzed the microorganism community. After acclimation for 58 d and 43 d, the high removal efficiency of 100% of 2-FA and 95.3% of 3-FA was obtained by adding 25 mg L

The interest of fluoroanilines in the environment is due to their extensive applications in industry and their low natural biodegradability. A pure bacterial strain capable of degrading 3-fluoroaniline (3-FA) as the sole source of carbon and energy was isolated from a sequencing batch reactor operating for the treatment of 3-FA. The strain (designated as JF-3) was identified by 16S rRNA gene analysis as a member of the genus Rhizobium. When grown in 3-FA medium at concentrations of 100–700 mg/L, strain JF-3 almost completely removed 3-FA within 72 h. However, the obvious cell growth inhibition was observed in cultures treated with 3-FA concentrations greater than 500 mg/L. The degradation kinetics of 3-FA were consistent with Haldane’s model with the maximum degradation rate as 67.66 mg/(g dry cell h). The growth kinetics of strain JF-3 followed Andrew’s model with the maximum growth rate as 30.87 h−1. Also, strain JF-3 was able to degrade 4-fluoroaniline, aniline, and catechol, but hardly grew on 2-fluoroaniline, 2,4-dfluoroaniline, 2,3,4-trifluoroaniline, 3-fluorocatechol, and 4-fluorocatechol. Additionally, it was able to grow over a wide pH range (pH 6–10), and also showed tolerance to salinity with lower than 1.0%. This result, in combination with the enzyme assays and analysis of metabolite intermediates, indicated an unconventional pathway for 3-fluoroaniline metabolism that involved conversion to 3-aminophenol and resorcinol by monooxygenase, and which was subsequently metabolized via the ortho-cleavage pathway. To our knowledge, this is the first report on the utilization of 3-FA as a growth substrate by Rhizobium sp.

Ochratoxin A (OTA) is a nephrotoxic mycotoxin that is widely distributed in foodstuffs and feeds, meanwhile oleanolic acid (OA) is ubiquitous in various fruit skins, food materials, and medicinal herbs. Due to that OA has a nephroprotective effect, it has the poteintial to counteract OTA-induced nephrotoxicity by nutritional intervention of OA. Furthermore, tumor necrosis factor receptor-associated protein 1 (TRAP1) acts as the core of endoplasmic reticulum (ER)-mitochondria crosstalk, becoming our focus in the mechanism investigation. In this study, the cell viability, apoptosis rate, and protein expressions of human proximal tubule epithelial-originated kidney-2 (HK-2) cells in response to OTA and/or OA were determined. Results indicated that a 24 h-treatment of 1-5 μM OTA could notably induce mitochondrial-mediated and ER stress (ERS)-excitated apoptosis via inhibiting TRAP1, thereby activating CypD, Bax, Cyt-C, Cleaved Caspase-9, Cleaved Caspase-3, GRP78, p-PERK, p-eIF2α, ATF4, and CHOP and inhibiting Bcl-2 (P < 0.05). Results of the RNA interference of TRAP1 further ascertained its anti-apoptotic function via inhibiting CypD, Bax, GRP78, and CHOP and enhancing Bcl-2 (P < 0.05). The pre-treatment of 2 μM OA for 2 h could remarkably relieve OTA-induced suppression of TRAP1 (P < 0.05). In conclusion, TRAP1 played a central role in the ameliorative effect of OA on the mitochondrial-mediated and ERS-excitated apoptosis induced by OTA.

Ochratoxin A (OTA) is a widespread mycotoxin that naturally takes place in various human foodstuffs, such as cereals, cereal products, fruits, vegetables, meat, eggs, dairy products, dried products, wine and even the infant formula. Thus, the generation of serious harm to human health is inevitable. Among a variety of toxicological effects of OTA, nephrotoxicity is the most prominent. Until present, the review focusing on the nephrotoxicity of OTA was absent. Therefore, the advances in research of nephrotoxicity, nephrotoxicity mechanisms and toxic antagonism of OTA were reviewed in the present paper.

Diabetes mellitus is a typical heterogeneous metabolic disorder characterized by abnormal metabolism of carbohydrates, lipids and proteins. Genipin possesses a wide spectrum of biological activities including ameliorating effects on diabetes, but the definite mechanism of this effect remains unknown. To investigate the antidiabetic activities of genipin and explore the biochemical changes of serum endogenous metabolites on diabetic rats induced by alloxan, 1H NMR spectroscopy coupled with multivariate data analysis was used to. All rats were randomly divided into six groups including negative control (NC) group, diabetic mellitus (DM) group, metformin hydrochloride group, high dose group of genipin, middle dose group of genipin and low dose group of genipin. Diabetes was induced by a single intraperitoneal injection of 120 mg/kg body weight of alloxan. Serum samples were collected for the 1H NMR-based metabolomics and clinical biochemical analysis. Daily oral administration of genipin (25, 50 and 100 mg/kg body weight) and metformin hydrochloride (125 mg/kg) for two weeks showed beneficial effects on blood glucose level (P

We aimed to determine the effects of the inhibition of enhancer of zeste homolog 2 (EZH2) gene expression on the cisplatin resistance of the human ovarian cancer cell line, SKOV3/DDP, and to identify the underlying mechanisms. SKOV3/DDP cells were stably transfected with pSUPER-EZH2 (EZH2 RNA interference plasmid) or pcDNA3.1-EZH2 (EZH2 gene overexpression plasmid) using the lipofection method. Real-time fluorescence quantitative reverse transcription polymerase chain reaction and western blotting confirmed that EZH2 expression was downregulated in pSUPER-EZH2-transfected cells. Flow cytometry revealed that EZH2 inhibition did not induce apoptosis, but significantly inhibited autophagy. In addition, it significantly increased the expression of the cellular senescence-signaling proteins p14(ARF), p16(INK4a), p53, pRb, and p21, and significantly decreased the expression of cyclin-dependent kinase (CDK)1, CDK2, and H3K27me3. Cellular senescence was characterized by a significant increase in the G0/G1 ratio and the restoration of sensitivity to cisplatin in the drug-resistant cells. These findings suggest that interfering with EZH2 expression can inhibit SKOV3/DDP cell autophagy and reverse resistance to cisplatin. The underlying mechanisms could be associated with the regulation of the cellular senescence-signaling pathway.

Objective To investigate the change rules of endogenous metabolites in pancreas of the diabetic rats, and to explore the mechanism of genipin treatment for diabetes rats. Methods Metabolomic method based on 1H-NMR was applied, the diabetic rat model was prepared by ip injecting alloxan, and the high-, mid-, and low-dose genipin or metformin hydrochloride was ig injected as well as the rats in control and model groups were given the same volume of normal saline for 2 weeks. The pancreases of rats were collected and 1H-NMR test was conducted, the metabolomic technology was adopted to analyze the endogenous metabolite changes in pancreas. Results The high-dose genipin possessed a better hypoglycemic effect, which could increase the contents of isoleucine, phosphatidylcholine, and phosphatidylethanolamine, and significantly reduce the contents of lactic acid, alanine, glutamine, aspartic acid, and creatine in pancreas of diabetic rats. Conclusion This study provided a theoretical basis for further exploration on the pathogenesis of diabetes and the mechanism of genipin for treatment of diabetes.

In the pilot-scale study, a kind of pretreated wastewater from the pickling process in a steel wire rope manufacturer was reused by a novel integrated membrane process (Reverse osmosis and R-HCO3 anion-exchange resin combined in series), and the operating parameters for the system had been optimized. After the pretreatment process through neutralization, coagulation, clarification sand filtration, and ultra-filtration in sequence, the wastewater was treated with the integrated membrane process. The integrated membrane process can remove most of inorganic and organic ions and realize the micro-alikalization for product water, which can facilitate the zero liquid discharge for cooling water system. Furthermore, the operating parameters of this process were optimized as well: when the pH of inlet water was 8.57, the dosage of scale inhibitor agent was 2.5 mg/L, the optimized operating trans-membrane pressure was 1.32 MPa, the flux was 39.87 L/(m2 h), and water recovery rate was 55%. The filtering flo...

Ochratoxin A (OTA) is one of the most common and dangerous mycotoxins in the world. Previous work indicated that OTA could elicit spontaneous HR-like lesions formation Arabidopsis thaliana, reactive oxygen species (ROS) play an important role in OTA toxicity, and their major endogenous source is mitochondria. However, there has been no evidence as to whether OTA induces directly PCD in plants until now. In this study, the presence of OTA in Arabidopsis thaliana leaves triggered accelerated respiration, increased production of mitochondrial ROS, the opening of ROS-dependent mitochondrial permeability transition pores and a decrease in mitochondrial membrane potential as well as the release of cytochrome c into the cytosol. There were 42 and 43 significantly differentially expressed proteins identified in response to exposure to OTA for 8 and 24 h, respectively, according to iTRAQ analysis. These proteins were mainly involved in perturbation of the mitochondrial electron transport chain, interfering with ATP synthesis and inducing PCD. Digital gene expression data at transcriptional level was consistent with the cell death induced by OTA being PCD. These results indicated that mitochondrial dysfunction was a prerequisite for OTA-induced PCD and the initiation and execution of PCD via a mitochondrial-mediated pathway.

The present case study aims to elucidate the correlation between the human 8-hydroxyguanineglycosylase (hOGG1), APE1 and X-ray repair cross-complementing gene 1 (XRCC1) gene polymorphisms to the susceptibility and clinicopathological features of primary angle closure glaucoma (PACG) in a Chinese Han population. Blood samples were obtained from 258 PACG patients (case group) and 272 healthy volunteers (control group). PCR with sequence-specific primer (PCR-SSP) was used to determine the allele frequencies and genotype distributions of the hOGG1, APE1 and XRCC1 genes. The risk factors of PACG were determined using logistic regression analysis. The results indicated that hOGG1 Ser326Cys, APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms were correlated with the risk of PACG. Furthermore, there were thicker corneas, higher intraocular pressure (IOP) and a shorter axial length in patients carrying the mutant genotypes of hOGG1 Ser326Cys (Ser/Cys + Cys/Cys), APE1 Asp148Glu (Asp/Glu + Glu/Glu) and XRCC1 Arg399Gln (Arg/Gln + Glu/Glu) than those carrying the corresponding wild-type genotypes. According to the logistic regression analysis, Asp148Glu and Arg399Gln polymorphisms, a short axial length and high IOP are major risk factors for PACG. These findings reveal that hOGG1 Ser326Cys, APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms are correlated with the risk and clinicopathological features of PACG in a Chinese Han population.

Zearalenone (ZEA), a Fusarium mycotoxin that contaminates cereal crops worldwide, has been shown to affect the male reproductive system and trigger reactive oxygen species (ROS) generation. However, the mechanisms of its toxicity have not been fully understood. Because mitochondrion is a key organelle involved in producing ROS and generating metabolic intermediates for biosynthesis, an iTRAQ-based mitoproteomics approach was employed to identify the molecular mechanism of zearalenone toxicity using mitochondria of mouse Leydig tumor cells (MLTC-1). A total of 2014 nonredundant proteins were identified, among which 1401 proteins (69.56%) were overlapped. There were 52 differentially expressed proteins in response to ZEA, and they were primarily involved in energy metabolism, molecular transport and endocrine-related functions. Consistent with mitochondrial proteomic analysis, the ATP and intracellular Ca2+ levels increased after ZEA treatment. The results suggest that lipid metabolism changed significantly after low-dose ZEA exposure, resulting in two alterations. One is the increase in energy production through promoted fatty acid uptake and β-oxidation, along with excessive oxidative stress; the other is an inhibition of steroidogenesis and esterification, possibly resulting in reduced hormone secretion. A hypothetical model of ZEA-induced mitochondrial damage is proposed to provide a framework for the mechanism of ZEA toxicity.

Nephrotoxicity is the most prominent toxicological effects of ochratoxin A (OTA). We have previously shown that autophagy might be involved in OTA-induced early renal cytotoxicity, but the mechanisms of action are unknown. Since OTA is known to induce mitochondrial damage and Nix is a selective autophagy receptor for mitochondrial clearance, the objective of this study was to investigate whether Nix mediates autophagic response to OTA-induced renal cytotoxicity. Our results showed that OTA induced autophagic and mitophagic activitits. Nix shRNA HEK 293 cells were more sensitive than scrambled shRNA cells to OTA-induced cell death, and differentially affect the mRNA expression of SDHA, AIFM1, and Bad and protein expression of AIF, VDAC, SDHA and LONP1 after OTA treatment. In particular, up-regulation of the pro-apoptotic Bad and AIF after OTA treatment was prominent only in Nix shRNA cells, which might explain the higher ratio of cell death. These results might indicate that Nix plays a critical role in the cellular protection against OTA toxicity through autophagy and mitochondria.

Obestatin is an endogenous peptide sharing a precursor with ghrelin. This study aims to investigate whether and how obestatin protects MES23.5 dopaminergic cells against 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity. MES23.5 cells were pretreated with obestatin (10(-13)-10(-6) mol/L) for 20 min prior to incubation with 200 μmol/L MPP(+) for 12 or 24 h, or treated with obestatin alone (10(-13) to 10(-6) mol/L) for 0, 6, 12, and 24 h. The methyl thiazolyl tetrazolium (MTT) assay was used to measure cell viability. Flow cytometry was used to measure the caspase-3 activity and the mitochondrial transmembrane potential. Proliferating cell nuclear antigen (PCNA) protein levels were determined by Western blotting. Obestatin (10(-13) to 10(-7) mol/L) pretreatment blocked or even reversed the MPP(+)-induced reduction of viability in MES23.5 cells, but had no effect on MPP(+)-induced mitochondrial transmembrane potential collapse and caspase-3 activation. When applied alone, obestatin increased viability. Elevated PCNA levels occurred with 10(-7), 10(-9), 10(-11) and 10(-13) mol/L obestatin treatment for 12 h. The results suggest that the protective effects of obestatin against MPP(+) in MES23.5 cells are due to its proliferation-promoting rather than anti-apoptotic effects.

The present case study aims to elucidate the correlation between the human 8-hydroxyguanineglycosylase (hOGG1), APE1 and X-ray repair cross-complementing gene 1 (XRCC1) gene polymorphisms to the susceptibility and clinicopathological features of primary angle closure glaucoma (PACG) in a Chinese Han population. Blood samples were obtained from 258 PACG patients (case group) and 272 healthy volunteers (control group). PCR with sequence-specific primer (PCR-SSP) was used to determine the allele frequencies and genotype distributions of the hOGG1, APE1 and XRCC1 genes. The risk factors of PACG were determined using logistic regression analysis. The results indicated that hOGG1 Ser326Cys, APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms were correlated with the risk of PACG. Furthermore, there were thicker corneas, higher intraocular pressure (IOP) and a shorter axial length in patients carrying the mutant genotypes of hOGG1 Ser326Cys (Ser/Cys + Cys/Cys), APE1 Asp148Glu (Asp/Glu + Glu/Glu) and XRCC1 Arg399Gln (Arg/Gln + Glu/Glu) than those carrying the corresponding wild-type genotypes. According to the logistic regression analysis, Asp148Glu and Arg399Gln polymorphisms, a short axial length and high IOP are major risk factors for PACG. These findings reveal that hOGG1 Ser326Cys, APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms are correlated with the risk and clinicopathological features of PACG in a Chinese Han population.

// Kun Zeng 1, * , Bo Zhong 2, * , Xiao-Li Shen 1 , Min Fang 1 , Bao-Tao Lin 1 and Da-Hui Ma 1 1 Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Ophthalmology College of Shenzhen University, Shenzhen 518000, P.R. China 2 Department of Stomatology, Shenzhen Second People’s Hospital, Shenzhen 518000, P.R. China * Considered to be the first author Correspondence to: Kun Zeng, email: kunz1215@163.com Keywords: Nogo receptor, RNA interference, proliferation, apoptosis, mouse retinal ganglion cells Received: December 15, 2016 Accepted: March 24, 2017 Published: April 21, 2017 ABSTRACT We investigated the effects of lentivirus-mediated RNAi targeting of Nogo Receptor ( NgR ) on the proliferation and survival of murine retinal ganglion cells (mRGCs) in vitro and in vivo . Cultured mRGCs and C57BL/6 male mice were divided into 4 experimental groups: blank, model [100 μM N-methyl-D-aspartate (NMDA)], nscRNA (100 μM NMDA+ nscRNA vectors) and siNgR (100 μM NMDA+ siNgR vectors). CCK-8 and flow cytometry analyses revealed that silencing NgR enhanced proliferation, cell cycling and survival of NMDA-treated mRGCs. H&E staining showed that NgR silencing enhanced mRGC cell density and reduced angiogenesis in NMDA-treated retinal tissues. TUNEL assays showed that mRGC apoptosis was significantly diminished by NgR silencing in NMDA-treated retinal tissues. Western blotting and qRT-PCR analysis in NMDA-treated mRGCs and murine retinal tissues revealed that NgR silencing resulted in downregulation of RhoA signaling (RhoA and ROCK2). Western blotting showed that levels of activated Bax and cleaved caspase 3 were decreased, while Bcl-2 and pro-caspase 3 were increased in NMDA-treated mRGCs and murine retinal tissues, which corroborated the decreased apoptosis. These findings indicate that NgR gene silencing increases proliferation and survival of mRGCs in NMDA-treated murine retinas, which suggests a potential for therapeutic application to preventing optic nerve damage.

AIM: To evaluate the diagnostic capability of Heidelberg retinal tomography-Ⅲ(HRT-Ⅲ)for primary openangle glaucoma(POAG)at different stages.METHODS: Sixty-five patients(116 eyes)with POAG and 60 normal persons(114 eyes)were tested by HRT-Ⅲ with optic disk tomography to observe their optic disk structure parameters. The optic disk parameters of normal persons, patients with POAG, and patients of POAG at different stages were compared and analyzed. The correlation between optic disk parameters and mean defect of the visual field of patients were analyzed. RESULTS: There were statistical differences in cup area, rim area, cup volume, rim volume, cup/disk area ratio, rim/disk area ratio, linear cup/disk ratio, mean cup depth, maximun cup depth, mean retinal nerve fiber layer(RNFL)thickness between normal persons and patients and among patients of the three stages(early, developing and late). A positive correlation was found between cup area, cup volume, cup/disk area ratio, linear cup/disk ratio, mean cup depth and mean defect of the visual field in POAG patients, while, a negative correlation was found between rim area, rim volume, rim/disk area ratio, mean RNFL thickness and mean deviation in POAG patients. CONCLUSION: HRT-Ⅲ can effectively reflect changes of optic disc in each stage of POAG. It shows a good correlation with visual field and provides basis for the diagnosis of POAG.

PURPOSE The aim of this study was to evaluate the outcome of surgical resection and amniotic membrane transplantation (AMT) for treatment of refractory symptomatic giant papillae in vernal keratoconjunctivitis (VKC). METHODS This is a retrospective study of 13 eyes of 9 patients with refractory giant papillae associated with corneal shield ulcer and/or punctate epithelial erosions who underwent surgical resection of the papillae combined with AMT to cover the tarsal conjunctival defect. RESULTS During 14.2 ± 4.2 months of postoperative follow-up, smooth tarsal conjunctival surface was achieved in all cases, with no recurrence of the giant papillae in any eye. Corneal shield ulcers and punctate epithelial erosions healed within 2 weeks after surgery and did not recur during the follow-up. Best-corrected visual acuity improved from 0.26 ± 0.21 logarithm of the minimum angle of resolution preoperatively to 0.02 ± 0.04 logarithm of the minimum angle of resolution postoperatively (P = 0.01). Three patients experienced recurrence of VKC symptoms, but without giant papillae, which could be well controlled by topical medications. CONCLUSIONS Surgical resection combined with AMT is an effective procedure for treatment of refractory giant papillae in patients with VKC.

Nephrotoxicity is the most prominent of ochratoxin A (OTA) among the diverse range of toxicological effects. Previous work indicated that reactive oxygen species (ROS) play an important role in the pathogenesis of a variety of renal diseases, and its major endogenous source is mitochondria. No research has used global protein expression profiling to investigate potential toxicity mechanisms of OTA at the mitochondria level. An iTRAQ-based mitoproteomics approach was used to explore possible toxicity mechanisms of OTA and potential protective mechanisms of N-acetyl-L-cysteine (NAC) using the mitochondria of Human Embryonic Kidney 293 (HEK 293) cells. Our results showed that OTA induced a decrease in ΔΨm, and an increase in ROS and cell death. We identified a total of 1973 nonredundant proteins, among which 1398 proteins (70.86%) were overlapped. There were 66 significantly different proteins expressed in response to OTA, which were mainly involved in the perturbation of the mitochondrial electron transport chain (mETC), inhibition of protein synthesis, and induction of stress response and cell death. In addition, NAC could almost completely reverse the adverse effects of OTA at the protein level. Finally, a hypothetical model of OTA-induced mitochondria damage is proposed to provide a framework for the toxicity mechanism of OTA.

This research is to establish TLC and UPLC methods for simultaneous determination of 3 atractylenolides in Atractylodes macrocephala. Silica gel GF254 plate was used for identification of A. macrocephala, and UPLC-PDA gradient elution method was used to simultaneously determine atractylenolide Ⅰ, Ⅱ and Ⅲ. The Waters BEH C₁₈ column（2.1 mm×100 mm,1.7 μm）with acetonitrile-water as mobile phase and the wavelength of UV detector of 235 nm were performed. The quality control study showed that the characteristic for identification by TLC was distinct and highly specific. The method of content determination was in accordance with the regulations. The quantitative evaluation of atractylenolide Ⅰ,Ⅱ and Ⅲ was in good linear range（r0.999 9）, and the average recovery was 93.48%（RSD 1.4%）,94.97%（RSD 1.6%）,92.71%（RSD 1.2%）,respectively. TLC identification was in good specificity and repeatability, and the UPLC-PDA method for the simultaneous determination of 3 atractylenolides was simple and reliable for the quality control of A.macrocephala.

Several brain-gut peptides have been reported to have a close relationship with the central dopaminergic system; one such brain-gut peptide is nesfatin-1. Nesfatin-1 is a satiety peptide that is predominantly secreted by X/A-like endocrine cells in the gastric glands, where ghrelin is also secreted. We previously reported that ghrelin exerted neuroprotective effects on nigral dopaminergic neurons, which implied a role for ghrelin in Parkinson’s disease (PD). In the present study, we aim to clarify whether nesfatin-1 has similar effects on dopaminergic neurons both in vivo and in vitro. We show that nesfatin-1 attenuates the loss of nigral dopaminergic neurons in the 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. In addition, nesfatin-1 antagonized 1-methyl-4-phenylpyridillium ion (MPP+)-induced toxicity by restoring mitochondrial function, inhibiting cytochrome C release and preventing caspase-3 activation in MPP+-treated MES23.5 dopaminergic cells. These neuroprotective effects could be abolished by selective inhibition of C-Raf and the extracellular signal-regulated protein kinase 1/2 (ERK1/2). Our data suggest that C-Raf-ERK1/2, which is involved in an anti-apoptotic pathway, is responsible for the neuroprotective effects of nesfatin-1 in the context of MPTP-induced toxicity. These results imply that nesfatin-1 might have therapeutic potential for PD.

An oil dielectric helical pulse line to demonstrate the principles of a Pulse Line Ion Accelerator (PLIA) has been designed and fabricated. The simulation of the axial electric field of an accelerator with CST code has been completed and the simulation results show complete agreement with the theoretical calculations. To fully understand the real value of the electric field excited from the helical line in PLIA, an optical electric integrated electric field measurement system was adopted. The measurement result shows that the real magnitude of axial electric field is smaller than that calculated, probably due to the actual pitch of the resister column which is much less than that of helix.

We have performed a detailed study on the synthesis, the characterization of structural phases and superconductivity of the binary FeSex system from the Fe-rich phase into the Se-rich phase with 0.80≤ x≤1.20. The results indicate that by long-time low- temperature annealing, single phase sample could be obtained near the composition of FeSe 0.95 with the tetragonal PbO-type structure, while impurities of Fe or Fe 7 Se 8 would appear if Fe enriched or Se enriched in the starting composition respectively. Bulk super- conductivity was found to exist in highly Se deficient phase, but not the single phase, and superconductivity is very sensitive to the Se vacancy content. The anomalous downturn of resistivity around 100 K was eliminated in Se-rich phase, along with the suppression of the main superconducting phase.

BACKGROUND: The commercial use of organofluorine compounds has dramatically increased over the past few years. However, little information has been reported on the potential toxicity of organofluorine compounds to anaerobic digestion processes. In this work, the effects of 4-fluorophenol (p-FP), 4-fluorobenzoic acid (p-FB) and 4-fluoroaniline (p-FA) on methanogenesis and biodegradability were evaluated using sucrose-fed systems. RESULTS: The anaerobic biodegradation of three test compounds was not observed in the study. Adsorption of p-FP, p-FB and p-FA to the sludge fitted the linear model well (r2 > 0.94). The partition coefficient Kd was 25 L kg−1 for p-FP, 16 L kg−1 for p-FB and 26 L kg−1 for p-FA. Both methanogensis and hydrolysis acidification were inhibited in the presence of three test compounds. The half maximal inhibitory concentrations (IC50s) of methanogenic activity were 339, 1390 and 1907 mg L−1 for p-FP, p-FB and p-FA, respectively. A significant linear correlation (R2 = 0.99, P < 0.05) was obtained between the half maximal inhibitory concentrations and the most negative atomic charges of molecules (q−) of the three F-substituent aromatics. CONCLUSIONS: Three F-substituent aromatics had specific effects on methanogensis, hydrolysis acidification and syntrophic cooperation in anaerobic systems. Copyright © 2012 Society of Chemical Industry

To investigate the trichostain A (TSA)-induced expression of costinmulatory molecules CD80 and CD86 in HL-60, K562 and mononuclear cells (MNC) of bone marrow in AML patients and its clinical significance.The TSA-induced expression of costimulatory molecules CD80, CD86 in HL-60, K562 and BMMNC, and the cell viability were detected by flow cytometry; the mRNA expression of CD80 and CD86 was detected by RT-PCR; after the TSA-induced HL-60 cells and K562 cells were irradiated with 75 Gy, the effect of these cells on proliferation of PBMNC from healthy volunteers was determined with CCK-8 method.The HL-60 cells and BMMNC in AML patients expressed CD86, not expressed CD80, while the K562 cells not expressed CD86 and CD80. TSA could up-regulate the expression of CD86 in HL-60 cells and BMMNC of AML patients. The TSA-induced HL-60 cells expressing costimulatory molecule CD86 showed the proliferative effect on BMMNC from healthy volunteers.The TSA can induce the expression of costimulatory molecule CD86 in HL-60 cells and BMMNC in AML patients, and can improve the proliferation of PBMNC in healthy volunteers.

Antimicrobial biodegradable films have been prepared with sweet potato starch by incorporating potassium sorbate or chitosan. Films incorporated with potassium sorbate ≥ 15% or chitosan ≥ 5% were found to have an anti-Escherichia coli effect. Staphylococcus aureus could be effectively suppressed by incorporation of chitosan at ≥10%. Whereas potassium sorbate lowers the tensile strength and elongation at break, and raises the oxygen permeability, water vapor permeability and water solubility, chitosan has the opposite effect. Fourier Transform Infrared (FT-IR) spectra analysis revealed that starch crystallinity was retarded by potassium sorbate incorporation and that hydrogen bonds were formed between chitosan and starch. This explained the modification of the mechanical and physical properties of the films by the incorporation of these two antimicrobial agents.

To investigate the association between CHI3L1 single nucleotide polymorphisms (SNPs) and the susceptibility to childhood asthma.A total of 316 children diagnosed with asthma between January 2011 and October 2013 and 297 healthy children were selected as asthma group and control group respectively. Peripheral blood samples were collected from all subjects. Chemiluminescence and flow cytometry were applied to measure total IgE level and the percentage of eosinophils. ELISA was used to measure YKL-40 level. Genomic DNA was extracted from peripheral blood hemocytes, and the genotype and allele frequencies at CHI3L1 SNPs rs4950928, rs10399805, and rs883125 were determined by MALDI-TOP mass spectrometry.The total IgE and YKL-40 levels were significantly higher in the asthma group than in the control group (P0.05), while the percentage of eosinophils showed no significant difference between the two groups (P0.05). The frequency of GG genotype at rs883125 in the asthma group was significantly higher than that in the control group (P0.05). For rs4950928, the asthma group had a significantly lower frequency of CC genotype (P0.05) but a significantly higher frequency of CG genotype (P0.05) compared with the control group. In the asthma group, the patients with GG and CG genotypes at rs4950928 had significantly increased total IgE and YKL-40 levels compared with those with CC genotype at this locus (P0.05).YKL-40 is a potential molecular biomarker for the primary diagnosis of childhood asthma. CHI3L1 SNPs rs4950928 and rs883125 may be associated with childhood asthma. G allele at rs4950928 may increase the risk of childhood asthma.