A total of 198 agricultural soil samples were collected from Zhangjiagang and Changshu in Southern Jiangsu for analysis of 13 polychlorinated biphenyls （PCBs） in order to assess the levels of pollution, sources, are...A total of 198 agricultural soil samples were collected from Zhangjiagang and Changshu in Southern Jiangsu for analysis of 13 polychlorinated biphenyls （PCBs） in order to assess the levels of pollution, sources, area distribution, and potential risk for the environment. All methods were rigorously tested and an adequate quality control was ensured. Only one site had no PCBs residues, and the highest total PCBs concentration in the surface soils was 32.83 ng/g. The average concentration in all the soil samples was 4.13 ng/g, signaling low-level pollution. Tetra-, penta-, and hexa-chlorinated biphenyls were dominant species in soil samples, accounting for more than 75% of ∑PCBs in the soil samples. PCB118 was the most abundant congener in all the samples. The PCB118 was about 20% of ∑PCBs. The soil organic matter content showed only a weak correlation with the levels of all PCB congeners, in which a better correlation was noted for the more volatile lighter PCB congeners than for the heavier homologues. To a certain extent, the sources and land use seemed to influence the levels of PCBs.展开更多
The exploration and identification of antiproliferative phytochemicals have received increased attention in medicinal chemistry. In particular, research focused on the toxicology of marine natural products has increas...The exploration and identification of antiproliferative phytochemicals have received increased attention in medicinal chemistry. In particular, research focused on the toxicology of marine natural products has increased in recent years. Terpenoids, among many secondary metabolites, have been demonstrated to act as effective anticancer agents. Soft corals, a group of marine invertebrates, produce a variety of terpenoids with biofunctional properties. The current study presents the extraction, purification, and identification of sterol congeners from the soft coral Dendronephthya putteri. The method involves 50% chloroform-methanol extraction, polar column fractionation, and analysis through GC-MSn. Dose-dependent antiproliferative activity was observed within the sterol-rich fraction (DPCMH 2-4), which consisted of 3β-hydroxy-Δ5-steroidal congeners. This fraction inhibited the growth of HL-60 and MCF-7 cells with IC50 values of 25.27±1.43 and 22.81±0.15 μg/mL, respectively. Apoptotic body formation, DNA damage, cell cycle arrest, and apoptotic cell signaling pathway activation were also observed, reinforcing the dose-dependent antiproliferative and apoptosis-inducing activity of 3β-hydroxy-Δ5-steroidal congeners. To our knowledge, this is the first report of anticancer agent identification from the soft coral D. putteri. Based on the observations, these steroidal congeners are promising candidates for the development of anticancer drugs.展开更多
The aim of this work was to study the reactions of wheat （T. aestivum L.） and its wild congeners under salt stress. Physiological mechanisms that underlie traits for salt tolerance plantlets have been used to test s...The aim of this work was to study the reactions of wheat （T. aestivum L.） and its wild congeners under salt stress. Physiological mechanisms that underlie traits for salt tolerance plantlets have been used to test some wheat species and to identify sources of salty tolerance. Stress conditions were founded by means of exposure of the plantlets in NaCI water solution, 1.68% that demonstrably differentiates the samples by growth parameters. Under laboratory conditions the ability of seedlings to bear a significant shortage of water, their ability to accumulate biomass, changing the parameters of linear growth processes and changes in water content in leaves and roots of seedlings under stress was determined. Interest is also the rate of growth of root fibrils in saline conditions. These experiments allowed to provide a comprehensive diagnosis of studied forms of wheat and make an initial opinion on their salt tolerance. Different features of abiotic stress responses of some wheat species at the early stages of development were shown that testifies necessi~ of great number of approaches at selection of genetic material for improvement of modern wheat eultivars. This work is the first phase of research for practical breeding.展开更多
A stereoselective and regiospecific synthesis of procursors(2),(4),(6)and(7)of prostacyclin analogues from 2,3-epoxylbicyclo[3.2.0]hept-6-one(1)are described.
Purpose of this work was to study changes in the ion balance under salt stress in roots and leaves of seedlings of T. aestivum L. and its wild congeners with different genomic composition. Laboratory assessment of sal...Purpose of this work was to study changes in the ion balance under salt stress in roots and leaves of seedlings of T. aestivum L. and its wild congeners with different genomic composition. Laboratory assessment of salt tolerance in seedlings was carried out and contents of ions K^＋, Na^＋ and Ca^2＋ in roots and leaves were defined. Considerable change of ionic balance in roots and leaves of studied forms of wheat against salt stress is shown. It is noticed that the parity K^＋/Na^＋ decreases in process of strengthening of salt stress. Authentic negative correlation between a relative gain of a biomass of leaves and roots in the stress conditions and accumulation of ions Na^＋ and between a relative gain of a biomass of leaves in the stress conditions and a parity in them of ions K^＋/Na^＋ is revealed. The research results also show that the stability characteristics of indicators of changes in ionic composition or balance in the leaves of young plants are more informative than in the roots and allow to reveal the form, characterized by relatively high of K^＋/Na^＋ ratio and the relatively low accumulation of Ca2^＋ as the most resistant to salt stress.展开更多
Marine natural products represent an important class of biologically active compounds critical for drug discovery.To date,17 marine-derived drugs,including trabectedin and eribulin,have been approved by the US FDA for...Marine natural products represent an important class of biologically active compounds critical for drug discovery.To date,17 marine-derived drugs,including trabectedin and eribulin,have been approved by the US FDA for clinical use and 33 others are in clinical trials[1].However,their medicinal investigation and clinical trials are often hampered by the scarcity of natural sources and by the difficulties of their harvesting in the delicate marine environment.Therefore,efficient and scalable approaches for the synthesis of promising marine natural products are essential to overcome supply issues for drug development.展开更多
Polybrominated diphenyl ether congeners (PBDEs) might activate the AhR (aromatic hydrocarbon receptor) signal transduction, and thus might have an adverse effect on the health of humans and wildlife. Because of the li...Polybrominated diphenyl ether congeners (PBDEs) might activate the AhR (aromatic hydrocarbon receptor) signal transduction, and thus might have an adverse effect on the health of humans and wildlife. Because of the limited experimental data, it is important and necessary to develop structure-based models for prediction of the toxicity of the compounds. In this study, a new molecular structure representation, molecular hologram, was employed to investigate the quantitative relationship between toxicity and molecular structures for 18 PBDEs. The model with the significant correlation and robustness (r <sup>2</sup> = 0.991, q <sup>2</sup> <sub>LOO</sub> = 0.917) was developed. To verify the robustness and prediction capacity of the derived model, 14 PBDEs were randomly selected from the database as the training set, while the rest were used as the test set. The results generated under the same modeling conditions as the optimal model are as follows: r <sup>2</sup> = 0.988, q <sup>2</sup> <sub>LOO</sub> = 0.598, r <sup>2</sup> <sub>pred</sub> = 0.955, and RMSE (root-mean-square of errors) = 0.155, suggesting the excellent ability of the derived model to predict the toxicity of PBDEs. Furthermore, the structural features and molecular mechanism related to the toxicity of PBDEs were explored using HQSAR color coding.展开更多
Polychlorinated biphenyl (PCBs) congeners were measured in (unwashed) whole-body field (deer) mice (Peromyscus maniculaltus) collected directly upgradient from a sediment retention structure (weir) within Los Alamos C...Polychlorinated biphenyl (PCBs) congeners were measured in (unwashed) whole-body field (deer) mice (Peromyscus maniculaltus) collected directly upgradient from a sediment retention structure (weir) within Los Alamos Canyon (LAC), Los Alamos National Laboratory (LANL), New Mexico, USA, from 2007 through 2013. Samples were also collected approximately 8 km downgradient of the retention structure in 2009 and 2013. LAC, a major drainage that crosses LANL lands, contains legacy waste, including PCBs, and occasionally discharges storm water and snowmelt flows to the Rio Grande approximately 8.8 km away from the weir. The Rio Grande is the major waterway that flows southward across the state. The weir was constructed across the channel on the northeastern boundary of LANL in late 2000 to help contain sediments mobilized by floodwaters as a result of a large wildfire in early 2000 that burned forest lands west and adjacent to LANL. Total PCBs in field mice directly upgradient of the sediment retention structure from 2007 through 2012 were significantly greater (p 0.05) than in field mice collected from background locations but decreased in concentration over time;by 2013 the levels were statistically similar (p > 0.05) to background. The highest mean total PCB concentration in field mice was below the levels that may negatively impact field mice population attributes. Total PCBs in field mice collected 8 km below the sediment retention structure in 2009 were lower than field mice collected from behind the weir and decreased over time;also by 2013, the amount of PCBs in field mice 8 km below the sediment retention structure were not significantly different (p > 0.05) from background. The rank order of concentrations of ICES 7 PCB congeners in upgradient and downgradient field mice were: No. 153 > 180 > 138 > 118 > 28 > 101 > 52 and No. 153 > 180 > 138 > 52 > 101 > 118 > 28, respectively. Based on the PCB homolog distribution, the major formulation detected in field mice was Aroclor-1260. Overall, the reduction of PCBs in whole-body field mice from both sites over time was attributed, in part, to sediment control practices.展开更多
In the current study, the alopecia areata gene was introduced into the C57BL/6 （B6） mouse through repeated backcrossing/intercrossing, and the allelic homozygosity of congenic AAtJmice （named B6.KM-AA） was verifie...In the current study, the alopecia areata gene was introduced into the C57BL/6 （B6） mouse through repeated backcrossing/intercrossing, and the allelic homozygosity of congenic AAtJmice （named B6.KM-AA） was verified using microsatellites. The gross appearance, growth characteristics, pathological changes in skin, and major organs of B6.KM-AA mice were observed. Counts and proportions of CD4＋ and CD8＋ T lymphocytes in peripheral blood were determined by flow cytometry. Results show that congenic B6.KM-AA mice were obtained after 10 generations of backcrossing/intercrossing. B6.KM-AA mice grew slower than B6 control mice and AA skin lesions were developed by four weeks of age. The number of hair follicles was reduced, but hair structures were normal. Loss of hair during disease progression was associated with CD4＋ and CD8＋ T lymphocytes infiltration peri- and intrahair follicles. No pathological changes were found in other organs except for the skin. In the peripheral blood of B6.KM-AA mice, the percentage of CD4＋ T cells was lower and percentage of CD8＋ T cells higher than in control mice. These findings indicate that B6.KM-AA mice are characterized by a dysfunctional immune system, retarded development and T-cell infiltration mediated hair loss, making them a promising new animal model for human alopecia areata.展开更多
We measured 39 polybrominated diphenyl ethers （PBDEs） in the muscle tissue of three species of fish （Sciaenops ocellatus,Sparus macrocephalus,and Lateolabrax japonicus） and four species of shellfish （Tegillarca g...We measured 39 polybrominated diphenyl ethers （PBDEs） in the muscle tissue of three species of fish （Sciaenops ocellatus,Sparus macrocephalus,and Lateolabrax japonicus） and four species of shellfish （Tegillarca granosa,Cyclina sinensis,Sinonovacula constricta,and Ostrea cucullata） that were collected downstream of electronic-waste recycling plants in Taizhou,China.A total of 24 PBDE congeners （PBDE 24） in the samples were detected.The PBDE 24 （total PBDE） ranged from 545.4 to 1688.7 ng/kg ww （wet weight）.The mean PBDE 24 concentration was 1382.6 ng/kg ww in fish and 858.1 ng/kg ww in shellfish.The lower brominated congeners were detected at relatively high concentrations in all species.The penta-products,produced from e-waste,were found at relatively low levels.A principal component analysis suggested a significant correlation among di-,tri-,tetra-,and hepta-BDEs for the three species of fish.Similarly,we found a significant correlation between mono-and tri-BDEs in the shellfish.Our results suggested that the processes of PBDE metabolism and elimination were similar in both fish and shellfish.In addition,the primary source of PBDEs appeared to be from the debromination of high brominated PBDEs.展开更多
Autoimmune hepatitis(AIH),primary sclerosing cholangitis(PSC) and primary biliary cirrhosis(PBC) are considered as putative autoimmune diseases of the liver.Whereas strong evidence that bacterial infection may trigger...Autoimmune hepatitis(AIH),primary sclerosing cholangitis(PSC) and primary biliary cirrhosis(PBC) are considered as putative autoimmune diseases of the liver.Whereas strong evidence that bacterial infection may trigger PBC exists,the etiologies for PSC and AIH remain unknown.Although there have been significant discoveries of genetic polymorphisms that may underlie the susceptibility to these liver diseases,their associations with environmental triggers and the subsequent implications have been difficult to elucidate.While single nucleotide polymorphisms within the negative costimulatory molecule cytotoxic T lymphocyte antigen 4(CTLA-4) have been suggested as genetic susceptibility factors for all three disorders,we discuss the implications of CTLA-4 susceptibility alleles mainly in the context of PBC,where Novosphingobium aromaticivorans,an ubiquitous alphaproteobacterium,has recently been specifically associated with the pathogenesis of this devastating liver disease.Ultimately,the discovery of infectious triggers of PBC may expand the concept of genetic susceptibility in immune-mediated liver diseases from the concept of aberrant immune responses against self-antigens to insufficient and/or inappropriate immunological defense mechanisms allowing microbes to cross natural barriers,establish infection and damage respective target organs.展开更多
The activated carbon injection-circulating fluidized bed（ACI-CFB）-bag filter coupling technique was studied in an iron ore sintering plant. For comparison, the removal efficiencies under the conditions without or wi...The activated carbon injection-circulating fluidized bed（ACI-CFB）-bag filter coupling technique was studied in an iron ore sintering plant. For comparison, the removal efficiencies under the conditions without or with ACI technology were both evaluated. It was found that the polychlorinated dibenzo-p-dioxins and dibenzofuran（PCDD/F） removal efficiency for total international toxic equivalence quantity（I-TEQ） concentration was improved from 91.61% to 97.36% when ACI was employed, revealing that ACI was very conducive to further controlling the PCDD/F emissions. Detailed congener distributions of PCDD/Fs in the gas-phase and particle-phase of the Inlet and Outlet samples were determined. Additionally, the PCDD/F distribution for the Fly ash-with ACI sample of was also studied.展开更多
Bulk（wet and dry） deposition samples were collected in Saitama Prefecture, Japan throughout a year（February 8, 2012 to February 7, 2013） to estimate the influence of dioxins emitting from waste incinerators on riv...Bulk（wet and dry） deposition samples were collected in Saitama Prefecture, Japan throughout a year（February 8, 2012 to February 7, 2013） to estimate the influence of dioxins emitting from waste incinerators on river water quality. The annual deposition flux of dioxins was 3.3 ng-toxic equivalent（TEQ）/m^2/year. Source identification using indicative congeners estimated that 82% of dioxin TEQ in the bulk deposition（2.7 ng-TEQ/m^2/year）was combustion-originated, indicating that most of the dioxins in the deposition were derived from waste incinerators. In Saitama prefecture the annual flux of combustionoriginated dioxins in depositions was apparently consistent with that of dioxin emission into the air from waste incinerators. The TEQ of combustion-originated dioxins in the deposition per rainfall was 2.4 pg-TEQ/L on annual average, exceeding the environmental quality standard（EQS） for water in Japan of 1 pg-TEQ/L. This suggests there is a possibility that dioxins in atmospheric deposition have a significant influence on the water quality of urban rivers which rainwater directly flows into because of many paved areas in the basins.The influence of combustion-originated dioxin in the deposition on the water quality of Ayase River, an urban river heavily polluted with dioxins, was estimated at 0.29 pg-TEQ/L on annual average in 2015. It seems that dioxins in atmospheric deposition from waste incinerators have a significant influence on water quality of some urban rivers via rainwater though the dioxins in the ambient air have achieved the EQS for atmosphere at all monitoring sites in Japan.展开更多
The identification of contamination sources within the food chain with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs), (“dioxins”), and PCBs is difficult and complex. PCDD/PCDF ...The identification of contamination sources within the food chain with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs), (“dioxins”), and PCBs is difficult and complex. PCDD/PCDF can be formed as unintentional compounds in a number of chemical processes as well as in almost every combustion process. PCBs were intentionally produced chemicals that were manufactured for decades before the ban in marketing and use in many countries around 1985. The pattern of occurrence can change from the original source in particular via feedingstuffs to food of animal origin as result of bioaccumulation. A number of examples illustrate the challenging detective work and key scientific aspects for identification of the sources, for support of the risk management and for performance of monitoring programs. The contamination of milk and milk products in European countries with dioxins was caused by compound feeds containing citrus pulp pellets from Brazil which had high dioxin levels as a result of the use of heavily contaminated lime used for neutralization. The Belgian dioxin crisis was caused by a feed additive heavily contaminated with PCBs which were discharged into a recycled fat used in the production of animal feed. Guar gum from India was contaminated with sodium pentachlorophenate and dioxins. Clay was found to be possibly highly contaminated with dioxins possibly formed by geothermal processes over time;use of such clay as feed additive or for human intake led to elevated dioxin levels in food and humans. Bioanalytical screening in combination with comprehensive physicochemical investigations led to the detection of brominated flame retardants and brominated dioxins in a feed additive. Buffalo milk was contaminated in Italy presumably caused by illegal deposition of waste. High PCB levels in fuel oil for drying of breadcrumb used as a feed ingredient caused a major dioxin crisis with pork meat in Ireland. Fatty acids for technical purposes originating from a biodiesel company were used for production of feed fat which contaminated parts of the food chain in Germany. In addition to effects on human and animal health these incidents also have serious economic consequences which could be mitigated by more frequent control on food and feed. Addressing both these issues, the European Community has developed a strategy to reduce the presence of dioxins and PCBs in the environment and in feed and food comprising the establishment of maximum and action levels.展开更多
In this paper, a feasible scheme is reported for the detection and identification of trace alcohol congeners that have identical elemental composition using laser-induced breakdown spectroscopy （LIBS）. In the scheme...In this paper, a feasible scheme is reported for the detection and identification of trace alcohol congeners that have identical elemental composition using laser-induced breakdown spectroscopy （LIBS）. In the scheme, an intensive pulsed laser is used to break down trace alcohol samples and the optical emission spectra of the induced plasma are collected for the detection and identifq ication of alcohol molecules. In order to prepare trace alcohol samples, pure ethanol or methanol is bubbled by argon carrier gas and then mixed into matrix gases. The key issue for the scheme is to constitute indices from the LIBS data of the alcohol samples. Two indices are found to be suitable for alcohol detection and identification. One is the emission intensity ratio （denoted as H/C） of the hydrogen line （653.3 nm） to the carbon line （247.9 nm） for identification and the other is the ratio of the carbon line （as C/Ar） or the hydrogen line （as H/Ar） to the argon lines （866.7 nm） for quantitative detection. The calibration experiment result shows that the index H/C is specific for alcohol congeners while almost being independent of alcohol concentration. In detail, the H/C keeps a specific constant of 34 and 23 respectively for ethanol and methanol. In the meanwhile, the C/Ar and H/Ar indices respond almost linearly to the alcohol concentration below 1300 ppm, and are therefore competent for concentration measurement. With the indices, trace alcohol concentration measurement achieves a limit of 140 ppm using a laser pulse energy of 300 mJ.展开更多
Reproduction performance of 21 inbred experimental lines of White Leghorns was evaluated based on samples of reproduction records over a period of eight consecutive years. Two lines (63 and 72) have been extensively u...Reproduction performance of 21 inbred experimental lines of White Leghorns was evaluated based on samples of reproduction records over a period of eight consecutive years. Two lines (63 and 72) have been extensively used in studies, especially in research seeking for genetic and epigenetic factors underlying resistance to avian tumor virus-induced diseases in chickens. The other 19 lines are recombinant congenic strains (RCS), which were generated by crossing lines 63 and 72 followed by two consecutive backcrosses to the line 63 and then full-sib mating. In theory, each RCS processes 7/8 of progenitor background line 63 genome and a random sample (1/8) of the progenitor donor line 72 genome. All 21 inbred lines share a common major histocompatibility complex haplotype, B*2. The estimated average fertility of the 21 inbred lines ranged from 72.9% (RCS-J) up to 96.8% (RCS-P). Both progenitor lines 63 and 72 were observed with lower average fertility (82.4% and 81.6%, respectively) in comparison with the RCS except the RCS-J, suggesting a substantial polygenic component underlying the fertility phenotype. The average embryo mortality rate ranged from 14.5% (RCS-P) up to 47.0% (RCS-M). The background line 63 fell at about the middle of the range (28.3%) significantly higher than the donor line 72 (15.7%), which was among the group with the lowest embryo mortality. By definition, hatchability of fertile eggs is reversely correlated with embryo mortality. The average hatchability ranged from 26.5% (RCS-M) up to 66.8% (line 72) while the background line 63 remained (46.6%) at about the middle of the range. The variability of the average embryo mortality and hatchability observed among the 21 inbred lines indicated the two correlated traits also follow polygenic models of inheritance. Findings from this study paves the way for further investigation on genetic and environmental influence over reproductive performance of inbred lines of chickens, and particularly in understanding and improving the reproduction fitness of invaluable genetic resources like these inbred lines.展开更多
Background: Marek’s disease(MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-resi...Background: Marek’s disease(MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-resistant line 63and MD-susceptible line 72are two highly inbred progenitor lines of White Leghorn. Recombinant Congenic Strains(RCS) were developed from these two lines, which show varied susceptibility to MD.Results: We investigated genetic structure and genomic signatures across the genome, including the line 63and line72, six RCSs, and two reciprocally crossed flocks between the lines 63and 72(F1 63× 72and F1 72× 63) using Affymetrix~? Axiom~? HD 600 K genotyping array. We observed 18 chickens from RCS lines were specifically clustered into resistance sub-groups distributed around line 63. Additionally, homozygosity analysis was employed to explore potential genetic components related to MD resistance, while runs of homozygosity(ROH) are regions of the genome where the identical haplotypes are inherited from each parent. We found several genes including SIK, SOX1, LIG4, SIK1 and TNFSF13B were contained in ROH region identified in resistant group(line 63and RCS), and these genes have been reported that are contribute to immunology and survival. Based on FSTbased population differential analysis, we also identified important genes related to cell death and anti-apoptosis, including AKT1, API5, CDH13, CFDP and USP15,which could be involved in divergent selection during inbreeding process.Conclusions: Our findings offer valuable insights for understanding the genetic mechanism of resistance to MD and the identified genes could be considered as candidate biomarkers in further evaluation.展开更多
Prepulse inhibition （PPI） of the startle response is a psychophysiological measure of sensorimotor gating believed to be cross-modal between different sensory systems. We analyzed the tactile startle response （TSR...Prepulse inhibition （PPI） of the startle response is a psychophysiological measure of sensorimotor gating believed to be cross-modal between different sensory systems. We analyzed the tactile startle response （TSR） and PPI of TSR （tPPI）, using light as a prepulse stimulus, in the mouse strains A/J and C57BL/6J and 36 recombinant congenic strains derived from them. Parental strains were significantly different for TSR, but were comparable for tPPI. Among the congenic strains, variation for TSR was significant in both genetic backgrounds, but that of tPPI was significant only for the C57BL/6J background. Provisional mapping for loci modulating TSR and tPPI was carried out. Using mapping data from our previous study on acoustic startle responses （ASR） and PPI of ASR （aPPI）, no common markers for aPPI and tPPI were identified. However, some markers were significantly associated with both ASR and TSR, at least in one genetic background. These results indicate cross-modal genetic regulation for the startle response but not for PPI, in these mouse strains.展开更多
AIM: To investigate a novel pharmacological intervention to mitigate cisplatin ototoxicity using a selective adenosine A1 receptor agonist adenosine amine congener(ADAC).METHODS: Male Wistar rats(8-10 wk) were exposed...AIM: To investigate a novel pharmacological intervention to mitigate cisplatin ototoxicity using a selective adenosine A1 receptor agonist adenosine amine congener(ADAC).METHODS: Male Wistar rats(8-10 wk) were exposed to a two-cycle cisplatin treatment similar to clinical course of cancer chemotherapy. Each cycle comprised 4 d of intraperitoneal cisplatin injections(1 mg/kg twice daily) separated by 10 d of rest. ADAC(100 μg/kg) or drug vehicle solution(control) was administered intraperitoneally for 5 d at 24 h intervals during the second cisplatin cycle(Regime 1), or upon completion of the cisplatin treatment(Regime 2). Hearing thresholds were measured using auditory brainstem responses(ABR) before cisplatin administration(baseline) and 7 d after the end of cisplatin treatment. Histological analysis of cochlear tissues included hair cell counting and qualitative assessment of apoptosis using terminal deoxynucleotidyl transferase mediated d UTP nick end labelling(TUNEL) staining.RESULTS: ABR threshold shifts in cisplatin-treated Wistar rats ranged from 5-29 d B across the frequency range used in the study(4-24 k Hz). Higher frequencies(16-24 k Hz) were mostly affected by cisplatin ototoxicity(mean threshold shift 25-29 d B). ADAC treatment during the second cisplatin cycle reduced cisplatininduced threshold shifts by 12-16 d B(P < 0.01) at higher frequencies compared to control vehicle-treated rats. However, the treatment was ineffective if ADAC administration was delayed until after the completion of the cisplatin regime. Functional recovery was supported by increased survival of hair cells in the cochlea. Qualitative analysis using TUNEL staining demonstrated reduced apoptosis of the outer hair cells and marginal cells in the stria vascularis in animals treated with ADAC during the second cisplatin cycle.CONCLUSION: A1 adenosine receptor agonist ADAC mitigates cisplatin-induced cochlear injury and hearing loss, however its potential interference with antineoplastic effects of cisplatin needs to be established.展开更多
Reproductive isolation is a fundamental require- ment for speciation and includes several sequential stages. Few studies have determined the relative contributions of pre- and post-zygotic reproductive isolation in pl...Reproductive isolation is a fundamental require- ment for speciation and includes several sequential stages. Few studies have determined the relative contributions of pre- and post-zygotic reproductive isolation in plants, especially between relative species with clear differentiation in flower form. To investigate the mechanisms responsible for repro- ductive isolation in sympatric A4ussaenda pubescens var. alba and Mussaenda shikokiana （Rubiaceae） in Guangxi Province, China, we made observations of flowering phenology, patterns of insect visitation, and conducted pollination experiments, including artificial hybridization. The two species had over- lapping flowering times and were pollinated by overlapping pollinators; however, their relative importance differed significantly with M. pubescens visited more commonly by bees and M. shikokiana more frequently by butterflies. Using vegetative and floral characters and molecular evidence based on nuclear ribosomal internal and external transcribed spacer regions we detected seven naturally occurring hybrids among a sample of approximately 125 individuals. Hybrids were characterized by morphologies that most closely resembled their maternal parents based on chloroplast evidence. Studies of artificially synthesized and natural hybrids demonstrated that hybrid seed had very low germination rates and naturally occurring hybrids exhibited pollen sterility. Post-zygotic reproductive isolating mechanisms play a primary role in limiting gene exchange between co-occurring species and maintaining species integrity in areas of sympatry.展开更多
基金Project supported by the National Basic Research Program (973) of China(No. 2002CB410810).
文摘A total of 198 agricultural soil samples were collected from Zhangjiagang and Changshu in Southern Jiangsu for analysis of 13 polychlorinated biphenyls （PCBs） in order to assess the levels of pollution, sources, area distribution, and potential risk for the environment. All methods were rigorously tested and an adequate quality control was ensured. Only one site had no PCBs residues, and the highest total PCBs concentration in the surface soils was 32.83 ng/g. The average concentration in all the soil samples was 4.13 ng/g, signaling low-level pollution. Tetra-, penta-, and hexa-chlorinated biphenyls were dominant species in soil samples, accounting for more than 75% of ∑PCBs in the soil samples. PCB118 was the most abundant congener in all the samples. The PCB118 was about 20% of ∑PCBs. The soil organic matter content showed only a weak correlation with the levels of all PCB congeners, in which a better correlation was noted for the more volatile lighter PCB congeners than for the heavier homologues. To a certain extent, the sources and land use seemed to influence the levels of PCBs.
基金Supported by the "Regional Specialized Industry Development Program",Ministry of Trade,Industry,and Energy(MOTIE),Koreasupervised by the Korea Institute for Advancement of Technology(KIAT)
文摘The exploration and identification of antiproliferative phytochemicals have received increased attention in medicinal chemistry. In particular, research focused on the toxicology of marine natural products has increased in recent years. Terpenoids, among many secondary metabolites, have been demonstrated to act as effective anticancer agents. Soft corals, a group of marine invertebrates, produce a variety of terpenoids with biofunctional properties. The current study presents the extraction, purification, and identification of sterol congeners from the soft coral Dendronephthya putteri. The method involves 50% chloroform-methanol extraction, polar column fractionation, and analysis through GC-MSn. Dose-dependent antiproliferative activity was observed within the sterol-rich fraction (DPCMH 2-4), which consisted of 3β-hydroxy-Δ5-steroidal congeners. This fraction inhibited the growth of HL-60 and MCF-7 cells with IC50 values of 25.27±1.43 and 22.81±0.15 μg/mL, respectively. Apoptotic body formation, DNA damage, cell cycle arrest, and apoptotic cell signaling pathway activation were also observed, reinforcing the dose-dependent antiproliferative and apoptosis-inducing activity of 3β-hydroxy-Δ5-steroidal congeners. To our knowledge, this is the first report of anticancer agent identification from the soft coral D. putteri. Based on the observations, these steroidal congeners are promising candidates for the development of anticancer drugs.
文摘The aim of this work was to study the reactions of wheat （T. aestivum L.） and its wild congeners under salt stress. Physiological mechanisms that underlie traits for salt tolerance plantlets have been used to test some wheat species and to identify sources of salty tolerance. Stress conditions were founded by means of exposure of the plantlets in NaCI water solution, 1.68% that demonstrably differentiates the samples by growth parameters. Under laboratory conditions the ability of seedlings to bear a significant shortage of water, their ability to accumulate biomass, changing the parameters of linear growth processes and changes in water content in leaves and roots of seedlings under stress was determined. Interest is also the rate of growth of root fibrils in saline conditions. These experiments allowed to provide a comprehensive diagnosis of studied forms of wheat and make an initial opinion on their salt tolerance. Different features of abiotic stress responses of some wheat species at the early stages of development were shown that testifies necessi~ of great number of approaches at selection of genetic material for improvement of modern wheat eultivars. This work is the first phase of research for practical breeding.
文摘A stereoselective and regiospecific synthesis of procursors(2),(4),(6)and(7)of prostacyclin analogues from 2,3-epoxylbicyclo[3.2.0]hept-6-one(1)are described.
文摘Purpose of this work was to study changes in the ion balance under salt stress in roots and leaves of seedlings of T. aestivum L. and its wild congeners with different genomic composition. Laboratory assessment of salt tolerance in seedlings was carried out and contents of ions K^＋, Na^＋ and Ca^2＋ in roots and leaves were defined. Considerable change of ionic balance in roots and leaves of studied forms of wheat against salt stress is shown. It is noticed that the parity K^＋/Na^＋ decreases in process of strengthening of salt stress. Authentic negative correlation between a relative gain of a biomass of leaves and roots in the stress conditions and accumulation of ions Na^＋ and between a relative gain of a biomass of leaves in the stress conditions and a parity in them of ions K^＋/Na^＋ is revealed. The research results also show that the stability characteristics of indicators of changes in ionic composition or balance in the leaves of young plants are more informative than in the roots and allow to reveal the form, characterized by relatively high of K^＋/Na^＋ ratio and the relatively low accumulation of Ca2^＋ as the most resistant to salt stress.
文摘Marine natural products represent an important class of biologically active compounds critical for drug discovery.To date,17 marine-derived drugs,including trabectedin and eribulin,have been approved by the US FDA for clinical use and 33 others are in clinical trials[1].However,their medicinal investigation and clinical trials are often hampered by the scarcity of natural sources and by the difficulties of their harvesting in the delicate marine environment.Therefore,efficient and scalable approaches for the synthesis of promising marine natural products are essential to overcome supply issues for drug development.
基金Supported by the Key Project of the National Natural Science Foundation of China (Grant No. 20737001)the National Natural Science Foundation Key Project of China (Grant No. 20737001)the Science and Technology Development Founda-tion Project of Nanjing Medical University (Grant No. 06NMUM021)
文摘Polybrominated diphenyl ether congeners (PBDEs) might activate the AhR (aromatic hydrocarbon receptor) signal transduction, and thus might have an adverse effect on the health of humans and wildlife. Because of the limited experimental data, it is important and necessary to develop structure-based models for prediction of the toxicity of the compounds. In this study, a new molecular structure representation, molecular hologram, was employed to investigate the quantitative relationship between toxicity and molecular structures for 18 PBDEs. The model with the significant correlation and robustness (r <sup>2</sup> = 0.991, q <sup>2</sup> <sub>LOO</sub> = 0.917) was developed. To verify the robustness and prediction capacity of the derived model, 14 PBDEs were randomly selected from the database as the training set, while the rest were used as the test set. The results generated under the same modeling conditions as the optimal model are as follows: r <sup>2</sup> = 0.988, q <sup>2</sup> <sub>LOO</sub> = 0.598, r <sup>2</sup> <sub>pred</sub> = 0.955, and RMSE (root-mean-square of errors) = 0.155, suggesting the excellent ability of the derived model to predict the toxicity of PBDEs. Furthermore, the structural features and molecular mechanism related to the toxicity of PBDEs were explored using HQSAR color coding.
文摘Polychlorinated biphenyl (PCBs) congeners were measured in (unwashed) whole-body field (deer) mice (Peromyscus maniculaltus) collected directly upgradient from a sediment retention structure (weir) within Los Alamos Canyon (LAC), Los Alamos National Laboratory (LANL), New Mexico, USA, from 2007 through 2013. Samples were also collected approximately 8 km downgradient of the retention structure in 2009 and 2013. LAC, a major drainage that crosses LANL lands, contains legacy waste, including PCBs, and occasionally discharges storm water and snowmelt flows to the Rio Grande approximately 8.8 km away from the weir. The Rio Grande is the major waterway that flows southward across the state. The weir was constructed across the channel on the northeastern boundary of LANL in late 2000 to help contain sediments mobilized by floodwaters as a result of a large wildfire in early 2000 that burned forest lands west and adjacent to LANL. Total PCBs in field mice directly upgradient of the sediment retention structure from 2007 through 2012 were significantly greater (p 0.05) than in field mice collected from background locations but decreased in concentration over time;by 2013 the levels were statistically similar (p > 0.05) to background. The highest mean total PCB concentration in field mice was below the levels that may negatively impact field mice population attributes. Total PCBs in field mice collected 8 km below the sediment retention structure in 2009 were lower than field mice collected from behind the weir and decreased over time;also by 2013, the amount of PCBs in field mice 8 km below the sediment retention structure were not significantly different (p > 0.05) from background. The rank order of concentrations of ICES 7 PCB congeners in upgradient and downgradient field mice were: No. 153 > 180 > 138 > 118 > 28 > 101 > 52 and No. 153 > 180 > 138 > 52 > 101 > 118 > 28, respectively. Based on the PCB homolog distribution, the major formulation detected in field mice was Aroclor-1260. Overall, the reduction of PCBs in whole-body field mice from both sites over time was attributed, in part, to sediment control practices.
基金supported by the Public Program of the Science Technology Department,Zhejiang(2011C37077)the National Natural Science Foundation of China(31071092)
文摘In the current study, the alopecia areata gene was introduced into the C57BL/6 （B6） mouse through repeated backcrossing/intercrossing, and the allelic homozygosity of congenic AAtJmice （named B6.KM-AA） was verified using microsatellites. The gross appearance, growth characteristics, pathological changes in skin, and major organs of B6.KM-AA mice were observed. Counts and proportions of CD4＋ and CD8＋ T lymphocytes in peripheral blood were determined by flow cytometry. Results show that congenic B6.KM-AA mice were obtained after 10 generations of backcrossing/intercrossing. B6.KM-AA mice grew slower than B6 control mice and AA skin lesions were developed by four weeks of age. The number of hair follicles was reduced, but hair structures were normal. Loss of hair during disease progression was associated with CD4＋ and CD8＋ T lymphocytes infiltration peri- and intrahair follicles. No pathological changes were found in other organs except for the skin. In the peripheral blood of B6.KM-AA mice, the percentage of CD4＋ T cells was lower and percentage of CD8＋ T cells higher than in control mice. These findings indicate that B6.KM-AA mice are characterized by a dysfunctional immune system, retarded development and T-cell infiltration mediated hair loss, making them a promising new animal model for human alopecia areata.
基金supported by the Wenling Science and Technology Bureau of Zhejiang Province (No. 2007-35)
文摘We measured 39 polybrominated diphenyl ethers （PBDEs） in the muscle tissue of three species of fish （Sciaenops ocellatus,Sparus macrocephalus,and Lateolabrax japonicus） and four species of shellfish （Tegillarca granosa,Cyclina sinensis,Sinonovacula constricta,and Ostrea cucullata） that were collected downstream of electronic-waste recycling plants in Taizhou,China.A total of 24 PBDE congeners （PBDE 24） in the samples were detected.The PBDE 24 （total PBDE） ranged from 545.4 to 1688.7 ng/kg ww （wet weight）.The mean PBDE 24 concentration was 1382.6 ng/kg ww in fish and 858.1 ng/kg ww in shellfish.The lower brominated congeners were detected at relatively high concentrations in all species.The penta-products,produced from e-waste,were found at relatively low levels.A principal component analysis suggested a significant correlation among di-,tri-,tetra-,and hepta-BDEs for the three species of fish.Similarly,we found a significant correlation between mono-and tri-BDEs in the shellfish.Our results suggested that the processes of PBDE metabolism and elimination were similar in both fish and shellfish.In addition,the primary source of PBDEs appeared to be from the debromination of high brominated PBDEs.
基金Supported by a Grant from the Deutsche Forschungsgemein-schaft(MA 2621/2-1)the Lupus Research Institute and by Award Number R01DK084054 from the National Institute of Diabetes and Digestive and Kidney Diseases
文摘Autoimmune hepatitis(AIH),primary sclerosing cholangitis(PSC) and primary biliary cirrhosis(PBC) are considered as putative autoimmune diseases of the liver.Whereas strong evidence that bacterial infection may trigger PBC exists,the etiologies for PSC and AIH remain unknown.Although there have been significant discoveries of genetic polymorphisms that may underlie the susceptibility to these liver diseases,their associations with environmental triggers and the subsequent implications have been difficult to elucidate.While single nucleotide polymorphisms within the negative costimulatory molecule cytotoxic T lymphocyte antigen 4(CTLA-4) have been suggested as genetic susceptibility factors for all three disorders,we discuss the implications of CTLA-4 susceptibility alleles mainly in the context of PBC,where Novosphingobium aromaticivorans,an ubiquitous alphaproteobacterium,has recently been specifically associated with the pathogenesis of this devastating liver disease.Ultimately,the discovery of infectious triggers of PBC may expand the concept of genetic susceptibility in immune-mediated liver diseases from the concept of aberrant immune responses against self-antigens to insufficient and/or inappropriate immunological defense mechanisms allowing microbes to cross natural barriers,establish infection and damage respective target organs.
基金supported by the State 863 Project(No.2013AA065102,2012AA062501)the National Natural Science Foundation of China(No.21207132)
文摘The activated carbon injection-circulating fluidized bed（ACI-CFB）-bag filter coupling technique was studied in an iron ore sintering plant. For comparison, the removal efficiencies under the conditions without or with ACI technology were both evaluated. It was found that the polychlorinated dibenzo-p-dioxins and dibenzofuran（PCDD/F） removal efficiency for total international toxic equivalence quantity（I-TEQ） concentration was improved from 91.61% to 97.36% when ACI was employed, revealing that ACI was very conducive to further controlling the PCDD/F emissions. Detailed congener distributions of PCDD/Fs in the gas-phase and particle-phase of the Inlet and Outlet samples were determined. Additionally, the PCDD/F distribution for the Fly ash-with ACI sample of was also studied.
文摘Bulk（wet and dry） deposition samples were collected in Saitama Prefecture, Japan throughout a year（February 8, 2012 to February 7, 2013） to estimate the influence of dioxins emitting from waste incinerators on river water quality. The annual deposition flux of dioxins was 3.3 ng-toxic equivalent（TEQ）/m^2/year. Source identification using indicative congeners estimated that 82% of dioxin TEQ in the bulk deposition（2.7 ng-TEQ/m^2/year）was combustion-originated, indicating that most of the dioxins in the deposition were derived from waste incinerators. In Saitama prefecture the annual flux of combustionoriginated dioxins in depositions was apparently consistent with that of dioxin emission into the air from waste incinerators. The TEQ of combustion-originated dioxins in the deposition per rainfall was 2.4 pg-TEQ/L on annual average, exceeding the environmental quality standard（EQS） for water in Japan of 1 pg-TEQ/L. This suggests there is a possibility that dioxins in atmospheric deposition have a significant influence on the water quality of urban rivers which rainwater directly flows into because of many paved areas in the basins.The influence of combustion-originated dioxin in the deposition on the water quality of Ayase River, an urban river heavily polluted with dioxins, was estimated at 0.29 pg-TEQ/L on annual average in 2015. It seems that dioxins in atmospheric deposition from waste incinerators have a significant influence on water quality of some urban rivers via rainwater though the dioxins in the ambient air have achieved the EQS for atmosphere at all monitoring sites in Japan.
文摘The identification of contamination sources within the food chain with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs), (“dioxins”), and PCBs is difficult and complex. PCDD/PCDF can be formed as unintentional compounds in a number of chemical processes as well as in almost every combustion process. PCBs were intentionally produced chemicals that were manufactured for decades before the ban in marketing and use in many countries around 1985. The pattern of occurrence can change from the original source in particular via feedingstuffs to food of animal origin as result of bioaccumulation. A number of examples illustrate the challenging detective work and key scientific aspects for identification of the sources, for support of the risk management and for performance of monitoring programs. The contamination of milk and milk products in European countries with dioxins was caused by compound feeds containing citrus pulp pellets from Brazil which had high dioxin levels as a result of the use of heavily contaminated lime used for neutralization. The Belgian dioxin crisis was caused by a feed additive heavily contaminated with PCBs which were discharged into a recycled fat used in the production of animal feed. Guar gum from India was contaminated with sodium pentachlorophenate and dioxins. Clay was found to be possibly highly contaminated with dioxins possibly formed by geothermal processes over time;use of such clay as feed additive or for human intake led to elevated dioxin levels in food and humans. Bioanalytical screening in combination with comprehensive physicochemical investigations led to the detection of brominated flame retardants and brominated dioxins in a feed additive. Buffalo milk was contaminated in Italy presumably caused by illegal deposition of waste. High PCB levels in fuel oil for drying of breadcrumb used as a feed ingredient caused a major dioxin crisis with pork meat in Ireland. Fatty acids for technical purposes originating from a biodiesel company were used for production of feed fat which contaminated parts of the food chain in Germany. In addition to effects on human and animal health these incidents also have serious economic consequences which could be mitigated by more frequent control on food and feed. Addressing both these issues, the European Community has developed a strategy to reduce the presence of dioxins and PCBs in the environment and in feed and food comprising the establishment of maximum and action levels.
基金supported by National Natural Science Foundation of China(Nos.11375041,10675028)the Fundamental Research Funds for the Central Universities(No.DUT11ZD(G)06)the Fund of the Key Laboratory of Chemical Laser,CAS(No.20131008)
文摘In this paper, a feasible scheme is reported for the detection and identification of trace alcohol congeners that have identical elemental composition using laser-induced breakdown spectroscopy （LIBS）. In the scheme, an intensive pulsed laser is used to break down trace alcohol samples and the optical emission spectra of the induced plasma are collected for the detection and identifq ication of alcohol molecules. In order to prepare trace alcohol samples, pure ethanol or methanol is bubbled by argon carrier gas and then mixed into matrix gases. The key issue for the scheme is to constitute indices from the LIBS data of the alcohol samples. Two indices are found to be suitable for alcohol detection and identification. One is the emission intensity ratio （denoted as H/C） of the hydrogen line （653.3 nm） to the carbon line （247.9 nm） for identification and the other is the ratio of the carbon line （as C/Ar） or the hydrogen line （as H/Ar） to the argon lines （866.7 nm） for quantitative detection. The calibration experiment result shows that the index H/C is specific for alcohol congeners while almost being independent of alcohol concentration. In detail, the H/C keeps a specific constant of 34 and 23 respectively for ethanol and methanol. In the meanwhile, the C/Ar and H/Ar indices respond almost linearly to the alcohol concentration below 1300 ppm, and are therefore competent for concentration measurement. With the indices, trace alcohol concentration measurement achieves a limit of 140 ppm using a laser pulse energy of 300 mJ.
文摘Reproduction performance of 21 inbred experimental lines of White Leghorns was evaluated based on samples of reproduction records over a period of eight consecutive years. Two lines (63 and 72) have been extensively used in studies, especially in research seeking for genetic and epigenetic factors underlying resistance to avian tumor virus-induced diseases in chickens. The other 19 lines are recombinant congenic strains (RCS), which were generated by crossing lines 63 and 72 followed by two consecutive backcrosses to the line 63 and then full-sib mating. In theory, each RCS processes 7/8 of progenitor background line 63 genome and a random sample (1/8) of the progenitor donor line 72 genome. All 21 inbred lines share a common major histocompatibility complex haplotype, B*2. The estimated average fertility of the 21 inbred lines ranged from 72.9% (RCS-J) up to 96.8% (RCS-P). Both progenitor lines 63 and 72 were observed with lower average fertility (82.4% and 81.6%, respectively) in comparison with the RCS except the RCS-J, suggesting a substantial polygenic component underlying the fertility phenotype. The average embryo mortality rate ranged from 14.5% (RCS-P) up to 47.0% (RCS-M). The background line 63 fell at about the middle of the range (28.3%) significantly higher than the donor line 72 (15.7%), which was among the group with the lowest embryo mortality. By definition, hatchability of fertile eggs is reversely correlated with embryo mortality. The average hatchability ranged from 26.5% (RCS-M) up to 66.8% (line 72) while the background line 63 remained (46.6%) at about the middle of the range. The variability of the average embryo mortality and hatchability observed among the 21 inbred lines indicated the two correlated traits also follow polygenic models of inheritance. Findings from this study paves the way for further investigation on genetic and environmental influence over reproductive performance of inbred lines of chickens, and particularly in understanding and improving the reproduction fitness of invaluable genetic resources like these inbred lines.
基金supported in part by U.S.Department of Agriculture(USDA)-Nation Research Initiative/National Institute of Food and Agriculture(NRI/NIFA)2008–35204-04660,2010–65205-20588 and 2011–67015-30183
文摘Background: Marek’s disease(MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-resistant line 63and MD-susceptible line 72are two highly inbred progenitor lines of White Leghorn. Recombinant Congenic Strains(RCS) were developed from these two lines, which show varied susceptibility to MD.Results: We investigated genetic structure and genomic signatures across the genome, including the line 63and line72, six RCSs, and two reciprocally crossed flocks between the lines 63and 72(F1 63× 72and F1 72× 63) using Affymetrix~? Axiom~? HD 600 K genotyping array. We observed 18 chickens from RCS lines were specifically clustered into resistance sub-groups distributed around line 63. Additionally, homozygosity analysis was employed to explore potential genetic components related to MD resistance, while runs of homozygosity(ROH) are regions of the genome where the identical haplotypes are inherited from each parent. We found several genes including SIK, SOX1, LIG4, SIK1 and TNFSF13B were contained in ROH region identified in resistant group(line 63and RCS), and these genes have been reported that are contribute to immunology and survival. Based on FSTbased population differential analysis, we also identified important genes related to cell death and anti-apoptosis, including AKT1, API5, CDH13, CFDP and USP15,which could be involved in divergent selection during inbreeding process.Conclusions: Our findings offer valuable insights for understanding the genetic mechanism of resistance to MD and the identified genes could be considered as candidate biomarkers in further evaluation.
文摘Prepulse inhibition （PPI） of the startle response is a psychophysiological measure of sensorimotor gating believed to be cross-modal between different sensory systems. We analyzed the tactile startle response （TSR） and PPI of TSR （tPPI）, using light as a prepulse stimulus, in the mouse strains A/J and C57BL/6J and 36 recombinant congenic strains derived from them. Parental strains were significantly different for TSR, but were comparable for tPPI. Among the congenic strains, variation for TSR was significant in both genetic backgrounds, but that of tPPI was significant only for the C57BL/6J background. Provisional mapping for loci modulating TSR and tPPI was carried out. Using mapping data from our previous study on acoustic startle responses （ASR） and PPI of ASR （aPPI）, no common markers for aPPI and tPPI were identified. However, some markers were significantly associated with both ASR and TSR, at least in one genetic background. These results indicate cross-modal genetic regulation for the startle response but not for PPI, in these mouse strains.
基金Supported by Action on Hearing Loss(United Kingdom)
文摘AIM: To investigate a novel pharmacological intervention to mitigate cisplatin ototoxicity using a selective adenosine A1 receptor agonist adenosine amine congener(ADAC).METHODS: Male Wistar rats(8-10 wk) were exposed to a two-cycle cisplatin treatment similar to clinical course of cancer chemotherapy. Each cycle comprised 4 d of intraperitoneal cisplatin injections(1 mg/kg twice daily) separated by 10 d of rest. ADAC(100 μg/kg) or drug vehicle solution(control) was administered intraperitoneally for 5 d at 24 h intervals during the second cisplatin cycle(Regime 1), or upon completion of the cisplatin treatment(Regime 2). Hearing thresholds were measured using auditory brainstem responses(ABR) before cisplatin administration(baseline) and 7 d after the end of cisplatin treatment. Histological analysis of cochlear tissues included hair cell counting and qualitative assessment of apoptosis using terminal deoxynucleotidyl transferase mediated d UTP nick end labelling(TUNEL) staining.RESULTS: ABR threshold shifts in cisplatin-treated Wistar rats ranged from 5-29 d B across the frequency range used in the study(4-24 k Hz). Higher frequencies(16-24 k Hz) were mostly affected by cisplatin ototoxicity(mean threshold shift 25-29 d B). ADAC treatment during the second cisplatin cycle reduced cisplatininduced threshold shifts by 12-16 d B(P < 0.01) at higher frequencies compared to control vehicle-treated rats. However, the treatment was ineffective if ADAC administration was delayed until after the completion of the cisplatin regime. Functional recovery was supported by increased survival of hair cells in the cochlea. Qualitative analysis using TUNEL staining demonstrated reduced apoptosis of the outer hair cells and marginal cells in the stria vascularis in animals treated with ADAC during the second cisplatin cycle.CONCLUSION: A1 adenosine receptor agonist ADAC mitigates cisplatin-induced cochlear injury and hearing loss, however its potential interference with antineoplastic effects of cisplatin needs to be established.
基金supported by the National Natural Science Foundation of China (31170184, U1202261, 31000109)the China Scholarship Council (for C. S.’s study in Canada)
文摘Reproductive isolation is a fundamental require- ment for speciation and includes several sequential stages. Few studies have determined the relative contributions of pre- and post-zygotic reproductive isolation in plants, especially between relative species with clear differentiation in flower form. To investigate the mechanisms responsible for repro- ductive isolation in sympatric A4ussaenda pubescens var. alba and Mussaenda shikokiana （Rubiaceae） in Guangxi Province, China, we made observations of flowering phenology, patterns of insect visitation, and conducted pollination experiments, including artificial hybridization. The two species had over- lapping flowering times and were pollinated by overlapping pollinators; however, their relative importance differed significantly with M. pubescens visited more commonly by bees and M. shikokiana more frequently by butterflies. Using vegetative and floral characters and molecular evidence based on nuclear ribosomal internal and external transcribed spacer regions we detected seven naturally occurring hybrids among a sample of approximately 125 individuals. Hybrids were characterized by morphologies that most closely resembled their maternal parents based on chloroplast evidence. Studies of artificially synthesized and natural hybrids demonstrated that hybrid seed had very low germination rates and naturally occurring hybrids exhibited pollen sterility. Post-zygotic reproductive isolating mechanisms play a primary role in limiting gene exchange between co-occurring species and maintaining species integrity in areas of sympatry.
