The intestinal microbiota plays an important role in inflammatory bowel disease(IBD).The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbi...The intestinal microbiota plays an important role in inflammatory bowel disease(IBD).The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals.However,there are still no definitive microbial pathogens linked to the onset of IBD.The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients.The special alterations of gut microbiota associated with IBD remain to be evaluated.The microbial interactions and hostmicrobe immune interactions are still not clarified.Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy,few available strains and no standardized administration.Fecal microbiota transplantation(FMT)may restore intestinal microbial ho-meostasis,and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection.Additionally,synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD.However,FMT-related barriers,including the mechanism of restoring gut microbiota,standardized donor screening,fecal material preparation and administration,and long-term safety should be resolved.The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germfree/human flora-associated animals and chemostat gut models.展开更多
Objective Knowledge of an enterovirus genome sequence is very important in epidemiological investigation to identify transmission patterns and ascertain the extent of an outbreak.The MinION sequencer is increasingly u...Objective Knowledge of an enterovirus genome sequence is very important in epidemiological investigation to identify transmission patterns and ascertain the extent of an outbreak.The MinION sequencer is increasingly used to sequence various viral pathogens in many clinical situations because of its long reads,portability,real-time accessibility of sequenced data,and very low initial costs.However,information is lacking on MinION sequencing of enterovirus genomes.Methods In this proof-of-concept study using Enterovirus 71(EV71) and Coxsackievirus A16(CA16) strains as examples,we established an amplicon-based whole genome sequencing method using MinION.We explored the accuracy,minimum sequencing time,discrimination and high-throughput sequencing ability of MinION,and compared its performance with Sanger sequencing.Results Within the first minute(min) of sequencing,the accuracy of MinION was 98.5% for the single EV71 strain and 94.12%-97.33% for 10 genetically-related CA16 strains.In as little as 14 min,99% identity was reached for the single EV71 strain,and in 17 min(on average),99% identity was achieved for 10 CA16 strains in a single run.Conclusion MinION is suitable for whole genome sequencing of enteroviruses with sufficient accuracy and fine discrimination and has the potential as a fast,reliable and convenient method for routine use.展开更多
Information regarding decabromodiphenyl ethane(DBDPE)effects on hepatotoxicity and metabolism is limited.In the present study,Wistar rats were given oral DBDPE at different doses.DBDPE induced oxidative stress,elevate...Information regarding decabromodiphenyl ethane(DBDPE)effects on hepatotoxicity and metabolism is limited.In the present study,Wistar rats were given oral DBDPE at different doses.DBDPE induced oxidative stress,elevated blood glucose levels,increased CYP2B2 mRNA,CYP2B1/2protein,7-pentoxyresorufin O-depentylase(PROD)activity,and induced CYP3A2 mRNA,CYP3A2protein,and luciferin benzylether debenzylase(LBD)activity.UDPGT activity increased with its increasing exposure levels,suggesting that oral DBDPE exposure induces drug-metabolizing enzymes in rats via the CAR/PXR signaling pathway.The induction of CYPs and co-regulated enzymes of phase II biotransformation may affect the homeostasis of endogenous substrates,including thyroid hormones,which may,in turn,alter glucose metabolism.展开更多
AIM:To clarify the specific roles and mechanisms of long interspersed nuclear element-1 ORF-1 protein [human long interspersed nuclear element-1(LINE-1),ORF-1p] in chemotherapeutic drug resistance and cell proliferati...AIM:To clarify the specific roles and mechanisms of long interspersed nuclear element-1 ORF-1 protein [human long interspersed nuclear element-1(LINE-1),ORF-1p] in chemotherapeutic drug resistance and cell proliferation regulation in hepatocellular carcinoma(HCC) cells.METHODS:MTT assays were performed to identify the effect of the chemotherapeutic drug toxicity on HepG2 cells.Cell proliferation inhibition and the IC 50 were calculated by the Origin 8.0 software.Western blotting assays were performed to investigate whether LINE-1 ORF-1p modulates the expression of some important genes,including p53,p27,p15,Bcl-2,mdr,and p-gp.To corroborate the proliferation and anchor-independent growth results,the HepG2 cells were analyzed by flow cytometry to investigate the effect of LINE-1 ORF1p on the apoptosis regulation.RESULTS:LINE-1 ORF-1p contributed to the resistance to several chemotherapeutic drugs(cisplatin and epirubicin) in HepG2 cells.The IC 50 of the epirubicin and cisplatin increased from 36.04 nmol/L to 59.11 nmol/L or from 37.94 nmol/L to 119.32 nmol/L.Repression of LINE-1 ORF-1p expression by the siRNA could markedly enhance the response of HepG2 cells to the epirubicin and cisplatin.The IC 50 correspondingly decreased from 28.06 nmol/L to 3.83 nmol/L or from 32.04 nmol/L to 2.89 nmol/L.Interestingly,down-regulation of LINE-1 ORF-1p level by siRNA could promote the response of HepG2 cells to the paclitaxel.The IC 50 decreased from 35.90 nmol/L to 7.36 nmol/L.However,overexpression of LINE-1 ORF-1p did not modulate the paclitaxel toxicity in HepG2 cells.Further Western blotting revealed that LINE-1 ORF-1p enhanced mdr and p-gp gene expression.As a protein arrested in the nucleus,LINE-1 ORF-1p may function through modulating transcriptional activity of some important transcription factors.Indeed,LINE-1 ORF-1p promoted HepG2 cell proliferation,anchor-independent growth and protected the cells against apoptosis through modulating the expression of p15,p21,p53,and Bcl-2 genes.CONCLUSION:LINE-1 ORF-1p promotes HepG2 cell proliferation and plays an important role in the resistance of chemotherapeutic drugs.By establishing novel roles and defining the mechanisms of LINE-1 ORF1p in HCC chemotherapeutic drug resistance and cell proliferation regulation,this study indicates that LINE-1 ORF-1p is a potential target for overcoming HCC chemotherapeutic resistance.展开更多
Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level(NOAEL),which is a critical factor in the establishment of an acceptable...Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level(NOAEL),which is a critical factor in the establishment of an acceptable dietary intake(ADI).Methods In accordance with the Organization for Economic Co-operation and Development(OECD) testing guidelines,lanthanum nitrate was administered once daily by gavage to Sprague-Dawley(SD) rats at dose levels of 0,1.5,6.0,24.0,and 144.0 mg/kg body weight(BW) per day for 90 days,followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups.Outcome parameters were mortality,clinical symptoms,body and organ weights,serum chemistry,and food consumption,as well as ophthalmic,urinary,hematologic,and histopathologic indicators.The benchmark dose(BMD) approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.Results Significant decreases were found in the 144.0 mg/kg BW group in the growth index,including body weight,organ weights,and food consumption.This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day.Importantly,the 95% lower confidence value of the benchmark dose(BMDL) was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.Conclusion The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements(REEs).展开更多
Objective To investigate the toxic effects of decabromodiphenyl ethane (DBDPE), used as an alternative to decabromodiphenyl ether in vitro. Methods HepG2 cells were cultured in the presence of DBDPE at various concent...Objective To investigate the toxic effects of decabromodiphenyl ethane (DBDPE), used as an alternative to decabromodiphenyl ether in vitro. Methods HepG2 cells were cultured in the presence of DBDPE at various concentrations (3.125-100.0 mg/L) for 24, 48, and 72 h respectively and the toxic effect of DBDPE was studied. Results As evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays and nuclear morphological changes, DBDPE inhibited HepG2 viability in a time- and dose-dependent manner within a range of 12.5 mg/L to 100 mg/L and for 48 h and 72 h. Induction of apoptosis was detected at 12.5-100 mg/L at 48 h and 72 h by propidium iodide staining, accompanied with overproduction of reactive oxygen species (ROS). Furthermore, N-acetyl-L-cysteine, a widely used ROS scavenger, significantly reduced DBDPE-induced ROS levels and increased HepG2 cells viability. Conclusion DBDPE has cytotoxic and anti-proliferation effect and can induce apoptosis in which ROS plays an important展开更多
We used a proteomic approach to identify Ibp A in Cronobacter sakazakii(C. sakazaki), which is related to heat tolerance in this strain. The abundance of Ibp A in C. sakazakii strains strongly increased after heat sho...We used a proteomic approach to identify Ibp A in Cronobacter sakazakii(C. sakazaki), which is related to heat tolerance in this strain. The abundance of Ibp A in C. sakazakii strains strongly increased after heat shock. C. sakazakii CMCC45402 ibpA deletion mutants were successfully constructed. The C. sakazakii CMCC 45402 ΔibpA and wild-type strains could not be distinguished based on colony morphology on LB agar plates or biochemical assays. The growth of the C. sakazaki CMCC 45402 ΔibpA mutant in heat shock conditions was indistinguishable from that of the isogenic wild-type, but showed greater heat resistance than E. coli O157:H7 strain CMCC 44828. This study suggests that the absence of a single ibpA gene has no obvious effect on the phenotype or heat resistance of the strain C. sakazakii CMCC 45402.展开更多
Objective To investigate the potential involvement of DMT1(IRE) protein in the brain vascular system in vivo during Pb exposure. Methods Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, a...Objective To investigate the potential involvement of DMT1(IRE) protein in the brain vascular system in vivo during Pb exposure. Methods Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the m RNA. Results Pb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1(IRE) protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1(IRE) m RNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1(IRE). Conclusion These results suggest that Pb is transported into the brain through DMT1(IRE), and the ERK MAPK pathway is involved in DMT1(IRE)-mediated transport regulation in brain vascular system in vivo.展开更多
This study was conducted to do exposure assessment of the possible migration of antimony trioxide(Sb2O3)from Polyethylene terephthalate(PET)food contact materials(FCM).Consumption Factor(CF)and Food-type Distribution ...This study was conducted to do exposure assessment of the possible migration of antimony trioxide(Sb2O3)from Polyethylene terephthalate(PET)food contact materials(FCM).Consumption Factor(CF)and Food-type Distribution Factor(fT)were calculated from survey data with reference to the US FDA method.The most展开更多
Objective: The study aimed to investigate the correlation between concentration of inhaled arsenic trioxide and dynamic changes in hematotoxicity in rats. Method: Wistar rats were randomly divided into four study grou...Objective: The study aimed to investigate the correlation between concentration of inhaled arsenic trioxide and dynamic changes in hematotoxicity in rats. Method: Wistar rats were randomly divided into four study groups that were treated with saline(control) or arsenic trioxide at a low(0.1 mg/mL), medium(1 mg/mL), or high(10 mg/mL) dose by intratracheal instillation. Blood samples were collected for analysis at 6, 12, 24, 48, and 72 h after exposure. Results: Compared with the control group, the red blood cell distribution width decreased significantly in each exposure group and then gradually recovered. The red blood cell count only increased in the high-dose group, and the hemoglobin levels did not differ significantly between the groups. Significant decreases in the platelet count and mean platelet volume were observed in each arsenic-exposed group. White blood cell countsalso decreased significantly and then gradually recovered; this was associated with an increased percentage of lymphocytes and a decreased percentage of neutrophils. The blood cell parameter changes were related to the arsenic trioxide concentration and the observation time. Conclusion: Intratracheal instillation of arsenic trioxide affected hematopoietic differentiation in rats, leading to blood cell changes that were related to observation time and concentration.展开更多
Objective: To evaluate Chinese medicine(CM) formula Bazheng Powder(八正散) as an alternative therapeutic option for female patients with recurrent urinary tract infection(RUTI). Methods: A randomized double-blinded tr...Objective: To evaluate Chinese medicine(CM) formula Bazheng Powder(八正散) as an alternative therapeutic option for female patients with recurrent urinary tract infection(RUTI). Methods: A randomized double-blinded trial was performed. Eligible female patients with RUTI were recruited from one hospital and two community health centers. By using a blocked randomization scheme, participants were randomized to receive a CM formula(10 herbs) and antibiotics placebo for 4 weeks, or antibiotics for 1 week followed by 3 weeks of placebo and CM formula placebo. Clinical cure rate and microbiological cure and recurrence after treatment were evaluated. Results: A total 122 eligible patients were enrolled, with 61 cases in each group. The clinical cure rate by the intent-to-treatment approach was 90.2% for the CM group and 82.0% for the antibiotics group(P>0.05). Bacteria were cleared from 88.5%(54/61) of patients in the CM group and 82.0%(50/61) in the antibiotics group. The recurrence rate in recovered patients at the 6-month follow-up was 9.1%(5/61) and 14.0(7/61) in the CM and antibiotics groups, respectively(P>0.05). Conclusion: CM formula Bazheng Powder is a good alternative option for RUTI treatment.(Registration No. NCT01745328)展开更多
Natural killer (NK) cells are a major component of the host innate immune defense against various pathogens. Several viruses, including hepatitis C virus (HCV), have developed strategies to evade the NK-cell response....Natural killer (NK) cells are a major component of the host innate immune defense against various pathogens. Several viruses, including hepatitis C virus (HCV), have developed strategies to evade the NK-cell response. In our study, we found HCV infection could trigger DNA damage response by both ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) pathways. Recent reports had revealed that NKG2D ligands (NK cell-activating ligands) were upregulated when a major DNA damage checkpoint pathway was activated. However, here we found that DNA damage response was activated but NKG2D ligands were downregulated upon HCV infection. Further studies showed that the protease NS3/4A of HCV which had been shown relation with immune invasion contributed to the reduced expression of NKG2D ligands. These findings provide a novel insight into the mechanisms evolved by HCV to escape from the NK cell response.展开更多
Dear Editors,Ebola virus disease(EVD)is an acute,serious and fatal illness caused by the Ebola virus.EVD was first identified in 1976 during two simultaneous outbreaks,one in Nzara,Sudan,and the other in Yambuku,Democ...Dear Editors,Ebola virus disease(EVD)is an acute,serious and fatal illness caused by the Ebola virus.EVD was first identified in 1976 during two simultaneous outbreaks,one in Nzara,Sudan,and the other in Yambuku,Democratic Republic of Congo[1].The latter o ccurred in a village near the Ebola River,from which the disease takes its name.Since展开更多
Background: Particulate matter(PM), which has adverse effects on citizen health, is a major air pollutant in Beijing city. PM_(2.5) is an indicator of PM in urban areas and can cause serious damage to human health. Ma...Background: Particulate matter(PM), which has adverse effects on citizen health, is a major air pollutant in Beijing city. PM_(2.5) is an indicator of PM in urban areas and can cause serious damage to human health. Many epidemiological studies have shown that nuclear factor-kappa B(NF-κB) is involved in PM_(2.5)-induced cell injury, but the exact mechanisms are not well understood.Methods: The cytotoxic effects of PM_(2.5) at 25–1600μg/ml for 24 h were determined by MTT assay in Chinese hamster ovary cells(CHO) cells. Flow cytometry was used to determine the apoptosis rate induced by PM_(2.5). The destabilized enhanced green fluorescent protein(d2 EGFP) green fluorescent protein reporter system was used to determine the NF-κB activity induced by PM_(2.5). The expression of pro-apoptotic Bcl-2-associated death promoter(BAD) proteins induced by PM_(2.5) was determined by Western blotting to explore the relationship between PM_(2.5) and the NF-κB signaling pathway and to determine the toxicological mechanisms of PM_(2.5).Results: PM_(2.5) collected in Beijing urban districts induces cytotoxic effects in CHO cells according to MTT assay with 72.28% cell viability rates even at 200μg/ml PM_(2.5) and flow cytometry assays with 26.97% apoptosis rates at 200μg/ml PM_(2.5). PM_(2.5) increases the activation levels of NF-κB, which have maintained for 24 h. 200μg/ml PM_(2.5) cause activation of NF-κB after exposure for 4 h, the activation peak appears after 13.5 h with a peak value of 25.41%. The average percentage of NF-κB activation in whole 24 h is up to 12.90% by 200μg/ml PM_(2.5). In addition, PM_(2.5) decreases the expression level of the pro-apoptotic protein BAD in a concentration-dependent manner.Conclusion: PM_(2.5) induces NF-κB activation, which persists for 24 h. The expression of pro-apoptotic protein BAD decreased with increased concentrations of PM_(2.5). These findings suggest that PM_(2.5) plays a major role in apoptosis by activating the NF-κB signaling pathway and reducing BAD protein expression.展开更多
Background:Leptospirosis morbidity and mortality rates in China have decreased since the 2000s.Further analyses of the spatiotemporal and demographic changes occurring in the last decade and its implication on estimat...Background:Leptospirosis morbidity and mortality rates in China have decreased since the 2000s.Further analyses of the spatiotemporal and demographic changes occurring in the last decade and its implication on estimates of disease burden are required to inform intervention strategies.In this study,we quantified the epidemiological shift and geographical heterogeneity in the burden of leptospirosis during 2005-2015 in China.Methods:We used reported leptospirosis case data from 1st January 2005 to 31st of December 2015 that routinely collected by the China Information System for Disease Control and Prevention(CISDCP)to analyze the epidemiological trend and estimate the burden in terms of disability-adjusted life-years(DALYs)over space,time,and demographical groups.Results:A total of 7763 cases were reported during 2005-2015.Of which,2403(31%)cases were the laboratoryconfirmed case.Since 2005,the notified incidence rate was gradually decreased(P<0.05)and it was relatively stable during 2011-2015(P>0.05).During 2005-2015,we estimated a total of 10313 DALYs were lost due to leptospirosis comprising a total of 1804 years-lived with disability(YLDs)and 8509 years-life lost(YLLs).Males had the highest burden of disease(7149 DALYs)compared to females(3164 DALYs).The highest burden estimate was attributed to younger individuals aged 10-19 years who lived in southern provinces of China.During 2005-2015,this age group contributed to approximately 3078 DALYs corresponding to 30%of the total DALYs lost in China.Yet,our analysis indicated a declining trend in burden estimates(P<0.001)since 2005 and remained relatively low during 2011-2015.Low burden estimates have been identified in the endemic regions where infections principally distributed.Most of the changes in DALY estimates were driven by changes in YLLs.Conclusions:In the last 11-years,the burden estimates of leptospirosis have shown a declining trend across the country;however,leptospirosis should not be neglected as it remains an important zoonotic disease and potentially affecting the young and productive population in economically less-developed provinces in southern of China.In addition,while in the last five years the incidence has been reported at very low-level,this might not reflect the true incidence of leptospirosis.Strengthened surveillance in the endemic regions is,hence,substantially required to capture the actual prevalence to better control leptospirosis in China.展开更多
Background:Visceral leishmaniasis(VL)was one of the most important parasitic diseases in China,caused by Leishmania protozoans and transmitted by sand flies.Recently VL cases have reappeared in China,including the ext...Background:Visceral leishmaniasis(VL)was one of the most important parasitic diseases in China,caused by Leishmania protozoans and transmitted by sand flies.Recently VL cases have reappeared in China,including the extension region of the Loess Plateau.The purpose of this study was to collect fundamental data on the host-vector VL system in the Loess Plateau to assist in the development of prevention and control measures.Methods:Sand flies were collected by light traps from rural areas in Shanxian,Henan,China in 2015,as well as in Wuxiang and Yangquan,Shanxi,China in 2017.The blood sources of sand flies were analyzed by PCR detecting the host-specific mitochondrial cytochrome b(mtDNA cyt b)gene fragments.Leishmania infection in sand flies was detected by amplifying and sequencing ribosomal DNA internal transcribed spacer 1(ITS1).The Leishmania specific antibodies in the sera of local dogs were detected by ELISA kit.Results:Blood sources showed diversity in the extension region of the Loess Plateau,including human,chicken,dog,cattle,pig and goat.Multiple blood sources within a sand fly were observed in samples from Yangquan(17/118,14.4%)and Wuxiang(12/108,11.1%).Leishmania DNA was detected in sand flies collected from Yangquan with minimum infection rate of 1.00%.The ITS1 sequences were conserved with the Leishmania donowni complex.The positive rate of Leishmania specific antibodies in dogs was 5.97%.Conclusions:This study detected the blood sources and Leishmania parasites infection of sand flies by molecular methods in the extension region of Loess Plateau,China.A high epidemic risk of leishmaniasis is currently indicated by the results as the infection of Leishmania in sand flies,the extensive blood sources of sand flies including humans,and positive antibody of Leishmania in local dog sera.Given the recent increase of VL cases,asymptomatic patients,dogs and other potential infected animals should be screened and treated.Furthermore,the density of sand flies needs to be controlled and personal protection should be strengthened.展开更多
Brucellosis is a worldwide zoonosis.Vaccination is the most efficient means to prevent and control brucellosis.The current licensed attenuated vaccines for animal use were developed by sequential passage in nonnatural...Brucellosis is a worldwide zoonosis.Vaccination is the most efficient means to prevent and control brucellosis.The current licensed attenuated vaccines for animal use were developed by sequential passage in nonnatural hosts that decreased virulence in its original hosts.The attenuation mechanism of these strains remains largely unknown.In the present study,we sequenced the genome of Brucella melitensis vaccine strain M5-10.Sequence analysis showed that a large number of genetic changes occurred in the vaccine strains.A total of 2854 genetic polymorphic sites,including 2548 SNP,241 INDEL and 65 MNV were identified.Of the 2074 SNPs in coding regions,1310(63.2%)were non-synonymous SNPs.Gene number,percent and N/S ratios were disproportionally distributed among the cog categories.Genetic polymorphic sites were identified in genes of the virB operon,flagella synthesis,and virulence regulating systems.These data indicate that changes in some cog categories and virulence genes might result in the attenuation.These attenuation mechanisms also have implications for screening and development of new vaccine strains.The genetic changes in the genome represent candidate sites for differential diagnosis between these vaccine strains and other virulence ones.Transcription analysis of virulence genes showed that expression of dnaK,vjbR were reduced in M5-10 strain when compared with that in 16M.A duplex PCR targeting virB6 and dnaK was successfully used to differentiate between M5-10 and the virulent 16M strain.The genome re-sequencing technique represents a strong strategy not only for evaluation of vaccines,but also for development of new vaccines.展开更多
T-2 toxin is one of the most important trichothecene mycotoxins occurring in various agriculture products. The developmental toxicity of T-2 toxin and the exact mechanism of action at early life stages are not underst...T-2 toxin is one of the most important trichothecene mycotoxins occurring in various agriculture products. The developmental toxicity of T-2 toxin and the exact mechanism of action at early life stages are not understood precisely. Zebrafish embryos were exposed to different concentrations of the toxin at 4–6 hours post fertilization(hpf) stage of development, and were observed for different developmental toxic effects at 24, 48, 72, and 144 hpf. Exposure to 0.20 μmol/L or higher concentrations of T-2 toxin significantly increased the mortality and malformation rate such as tail deformities, cardiovascular defects and behavioral changes in early developmental stages of zebrafish. T-2 toxin exposure resulted in significant increases in reactive oxygen species(ROS) production and cell apoptosis, mainly in the tail areas, as revealed by Acridine Orange staining at 24 hpf. In addition, T-2 toxin-induced severe tail deformities could be attenuated by co-exposure to reduced glutathione(GSH). T-2 toxin and GSH co-exposure induced a significant decrease of ROS production in the embryos. The overall results demonstrate that T-2 toxin is able to produce oxidative stress and induce apoptosis, which are involved in the developmental toxicity of T-2 toxin in zebrafish embryos.展开更多
Background:Arboviral disease transmitted by Aedes albopictus such as dengue fever is an important threat to human health.Pyrethroid resistance raises a great challenge for mosquito control.A systematic assessment of A...Background:Arboviral disease transmitted by Aedes albopictus such as dengue fever is an important threat to human health.Pyrethroid resistance raises a great challenge for mosquito control.A systematic assessment of Ae.albopictus resistance status in China is urgently needed,and the study of correlation between pyrethroid resistance and knockdown resistance(kdr)mutations would provide information to guide the control of the Ae.albopictus vector.Methods:Five field populations of Ae.albopictus were collected from Jinan(JN),Hangzhou(HZ),Baoshan(BS),Yangpu(YP)and Haikou(HK),China in 2017.Insecticide-impregnated papers were prepared with four pyrethroid chemicals,deltamethrin,permethrin,beta-cypermethrin and lambda-cyhalothrin.The susceptibility of Ae.albopictus to pyrethroids was tested by the WHO tube assay.Kdr mutations were identified by PCR and sequencing.Moreover,the correlation analysis between kdr alleles and pyrethroid resistance was performed.Results:All five populations of Ae.albopictus showed resistance to four pyrethroid insecticides.One kdr mutant allele at codon 1532 and three at 1534 were detected with frequency of 5.33%(I1532T),44.20%(F1534S),1.83%(F1534 L)and 0.87%(F1534C),respectively.Both 1532 and 1534 mutation mosquitoes were found in the BS and YP populations.Allele I1532T was negatively correlated with deltamethrin resistance phenotype(OR<1),while F1534S mutation was positively correlated with deltamethrin and permethrin resistance(OR>1).Conclusions:The five field populations of Ae.albopictus adults were all resistant to deltamethrin,permethrin,betacypermethrin and lambda-cyhalothrin.Mutant F1534S was clearly associated with pyrethroid resistance phenotype in Ae.albopictus and this could be developed as a molecular marker to monitor the pyrethroid resistance problem in China.展开更多
文摘The intestinal microbiota plays an important role in inflammatory bowel disease(IBD).The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals.However,there are still no definitive microbial pathogens linked to the onset of IBD.The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients.The special alterations of gut microbiota associated with IBD remain to be evaluated.The microbial interactions and hostmicrobe immune interactions are still not clarified.Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy,few available strains and no standardized administration.Fecal microbiota transplantation(FMT)may restore intestinal microbial ho-meostasis,and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection.Additionally,synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD.However,FMT-related barriers,including the mechanism of restoring gut microbiota,standardized donor screening,fecal material preparation and administration,and long-term safety should be resolved.The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germfree/human flora-associated animals and chemostat gut models.
基金supported by the National key research and development plan(2016TFC1202700,2016YFC1200900)Beijing Municipal Science&Technology Commission project(grant numbers D151100002115003)Guangzhou Municipal Science&Technology Commission project(grant numbers 2015B2150820)
文摘Objective Knowledge of an enterovirus genome sequence is very important in epidemiological investigation to identify transmission patterns and ascertain the extent of an outbreak.The MinION sequencer is increasingly used to sequence various viral pathogens in many clinical situations because of its long reads,portability,real-time accessibility of sequenced data,and very low initial costs.However,information is lacking on MinION sequencing of enterovirus genomes.Methods In this proof-of-concept study using Enterovirus 71(EV71) and Coxsackievirus A16(CA16) strains as examples,we established an amplicon-based whole genome sequencing method using MinION.We explored the accuracy,minimum sequencing time,discrimination and high-throughput sequencing ability of MinION,and compared its performance with Sanger sequencing.Results Within the first minute(min) of sequencing,the accuracy of MinION was 98.5% for the single EV71 strain and 94.12%-97.33% for 10 genetically-related CA16 strains.In as little as 14 min,99% identity was reached for the single EV71 strain,and in 17 min(on average),99% identity was achieved for 10 CA16 strains in a single run.Conclusion MinION is suitable for whole genome sequencing of enteroviruses with sufficient accuracy and fine discrimination and has the potential as a fast,reliable and convenient method for routine use.
基金financial support from the National Science and Technology Programme"Research&Development on Suitable Key Technologies of the Village Environmental Monitoring(2012BAJ24B02)"
文摘Information regarding decabromodiphenyl ethane(DBDPE)effects on hepatotoxicity and metabolism is limited.In the present study,Wistar rats were given oral DBDPE at different doses.DBDPE induced oxidative stress,elevated blood glucose levels,increased CYP2B2 mRNA,CYP2B1/2protein,7-pentoxyresorufin O-depentylase(PROD)activity,and induced CYP3A2 mRNA,CYP3A2protein,and luciferin benzylether debenzylase(LBD)activity.UDPGT activity increased with its increasing exposure levels,suggesting that oral DBDPE exposure induces drug-metabolizing enzymes in rats via the CAR/PXR signaling pathway.The induction of CYPs and co-regulated enzymes of phase II biotransformation may affect the homeostasis of endogenous substrates,including thyroid hormones,which may,in turn,alter glucose metabolism.
基金Supported by The Key Scientific and Technological Research Foundation of the National Special Purpose Program,No.2008ZX10002-018
文摘AIM:To clarify the specific roles and mechanisms of long interspersed nuclear element-1 ORF-1 protein [human long interspersed nuclear element-1(LINE-1),ORF-1p] in chemotherapeutic drug resistance and cell proliferation regulation in hepatocellular carcinoma(HCC) cells.METHODS:MTT assays were performed to identify the effect of the chemotherapeutic drug toxicity on HepG2 cells.Cell proliferation inhibition and the IC 50 were calculated by the Origin 8.0 software.Western blotting assays were performed to investigate whether LINE-1 ORF-1p modulates the expression of some important genes,including p53,p27,p15,Bcl-2,mdr,and p-gp.To corroborate the proliferation and anchor-independent growth results,the HepG2 cells were analyzed by flow cytometry to investigate the effect of LINE-1 ORF1p on the apoptosis regulation.RESULTS:LINE-1 ORF-1p contributed to the resistance to several chemotherapeutic drugs(cisplatin and epirubicin) in HepG2 cells.The IC 50 of the epirubicin and cisplatin increased from 36.04 nmol/L to 59.11 nmol/L or from 37.94 nmol/L to 119.32 nmol/L.Repression of LINE-1 ORF-1p expression by the siRNA could markedly enhance the response of HepG2 cells to the epirubicin and cisplatin.The IC 50 correspondingly decreased from 28.06 nmol/L to 3.83 nmol/L or from 32.04 nmol/L to 2.89 nmol/L.Interestingly,down-regulation of LINE-1 ORF-1p level by siRNA could promote the response of HepG2 cells to the paclitaxel.The IC 50 decreased from 35.90 nmol/L to 7.36 nmol/L.However,overexpression of LINE-1 ORF-1p did not modulate the paclitaxel toxicity in HepG2 cells.Further Western blotting revealed that LINE-1 ORF-1p enhanced mdr and p-gp gene expression.As a protein arrested in the nucleus,LINE-1 ORF-1p may function through modulating transcriptional activity of some important transcription factors.Indeed,LINE-1 ORF-1p promoted HepG2 cell proliferation,anchor-independent growth and protected the cells against apoptosis through modulating the expression of p15,p21,p53,and Bcl-2 genes.CONCLUSION:LINE-1 ORF-1p promotes HepG2 cell proliferation and plays an important role in the resistance of chemotherapeutic drugs.By establishing novel roles and defining the mechanisms of LINE-1 ORF1p in HCC chemotherapeutic drug resistance and cell proliferation regulation,this study indicates that LINE-1 ORF-1p is a potential target for overcoming HCC chemotherapeutic resistance.
基金supported by China Food Safety Talent Competency Development Initiative:CFSA 523 Programthe National Natural Science Foundation of China[No.81402683]
文摘Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level(NOAEL),which is a critical factor in the establishment of an acceptable dietary intake(ADI).Methods In accordance with the Organization for Economic Co-operation and Development(OECD) testing guidelines,lanthanum nitrate was administered once daily by gavage to Sprague-Dawley(SD) rats at dose levels of 0,1.5,6.0,24.0,and 144.0 mg/kg body weight(BW) per day for 90 days,followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups.Outcome parameters were mortality,clinical symptoms,body and organ weights,serum chemistry,and food consumption,as well as ophthalmic,urinary,hematologic,and histopathologic indicators.The benchmark dose(BMD) approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.Results Significant decreases were found in the 144.0 mg/kg BW group in the growth index,including body weight,organ weights,and food consumption.This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day.Importantly,the 95% lower confidence value of the benchmark dose(BMDL) was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.Conclusion The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements(REEs).
基金supported by the NSFC(No.20877102)"973"project(No.2010CB933904)
文摘Objective To investigate the toxic effects of decabromodiphenyl ethane (DBDPE), used as an alternative to decabromodiphenyl ether in vitro. Methods HepG2 cells were cultured in the presence of DBDPE at various concentrations (3.125-100.0 mg/L) for 24, 48, and 72 h respectively and the toxic effect of DBDPE was studied. Results As evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays and nuclear morphological changes, DBDPE inhibited HepG2 viability in a time- and dose-dependent manner within a range of 12.5 mg/L to 100 mg/L and for 48 h and 72 h. Induction of apoptosis was detected at 12.5-100 mg/L at 48 h and 72 h by propidium iodide staining, accompanied with overproduction of reactive oxygen species (ROS). Furthermore, N-acetyl-L-cysteine, a widely used ROS scavenger, significantly reduced DBDPE-induced ROS levels and increased HepG2 cells viability. Conclusion DBDPE has cytotoxic and anti-proliferation effect and can induce apoptosis in which ROS plays an important
基金funded by National Science and Technology Major Project of the Ministry of Science and Technology of China(2013ZX09304101)
文摘We used a proteomic approach to identify Ibp A in Cronobacter sakazakii(C. sakazaki), which is related to heat tolerance in this strain. The abundance of Ibp A in C. sakazakii strains strongly increased after heat shock. C. sakazakii CMCC45402 ibpA deletion mutants were successfully constructed. The C. sakazakii CMCC 45402 ΔibpA and wild-type strains could not be distinguished based on colony morphology on LB agar plates or biochemical assays. The growth of the C. sakazaki CMCC 45402 ΔibpA mutant in heat shock conditions was indistinguishable from that of the isogenic wild-type, but showed greater heat resistance than E. coli O157:H7 strain CMCC 44828. This study suggests that the absence of a single ibpA gene has no obvious effect on the phenotype or heat resistance of the strain C. sakazakii CMCC 45402.
基金supported by National Natural Science Foundation of China(No.81472478)Medical Science Youth Breeding Project of PLA(13QNP161)
文摘Objective To investigate the potential involvement of DMT1(IRE) protein in the brain vascular system in vivo during Pb exposure. Methods Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the m RNA. Results Pb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1(IRE) protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1(IRE) m RNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1(IRE). Conclusion These results suggest that Pb is transported into the brain through DMT1(IRE), and the ERK MAPK pathway is involved in DMT1(IRE)-mediated transport regulation in brain vascular system in vivo.
基金financially supported by the Beijing Natural Science Foundation-Sanyuan Joint FundingNo.15S00033
文摘This study was conducted to do exposure assessment of the possible migration of antimony trioxide(Sb2O3)from Polyethylene terephthalate(PET)food contact materials(FCM).Consumption Factor(CF)and Food-type Distribution Factor(fT)were calculated from survey data with reference to the US FDA method.The most
基金supported by a grant from the Army Logistics Research Plan of China (AEP14C001)National Natural Science Foundation of China (81472478)Public Science and Technology Research Funds Projects of Quality Inspection (201510024)
文摘Objective: The study aimed to investigate the correlation between concentration of inhaled arsenic trioxide and dynamic changes in hematotoxicity in rats. Method: Wistar rats were randomly divided into four study groups that were treated with saline(control) or arsenic trioxide at a low(0.1 mg/mL), medium(1 mg/mL), or high(10 mg/mL) dose by intratracheal instillation. Blood samples were collected for analysis at 6, 12, 24, 48, and 72 h after exposure. Results: Compared with the control group, the red blood cell distribution width decreased significantly in each exposure group and then gradually recovered. The red blood cell count only increased in the high-dose group, and the hemoglobin levels did not differ significantly between the groups. Significant decreases in the platelet count and mean platelet volume were observed in each arsenic-exposed group. White blood cell countsalso decreased significantly and then gradually recovered; this was associated with an increased percentage of lymphocytes and a decreased percentage of neutrophils. The blood cell parameter changes were related to the arsenic trioxide concentration and the observation time. Conclusion: Intratracheal instillation of arsenic trioxide affected hematopoietic differentiation in rats, leading to blood cell changes that were related to observation time and concentration.
基金Supported by Chinese Academy of Traditional Chinese Medicine Joint Innovation Research Project(No.ZZ070808)Traditional Chinese Medicine Dominant Disease Clinical Research Project(No.CACMS08Y0016)Capital Featured Clinical Application and Promotion Project(No.Z151100004015132),China
文摘Objective: To evaluate Chinese medicine(CM) formula Bazheng Powder(八正散) as an alternative therapeutic option for female patients with recurrent urinary tract infection(RUTI). Methods: A randomized double-blinded trial was performed. Eligible female patients with RUTI were recruited from one hospital and two community health centers. By using a blocked randomization scheme, participants were randomized to receive a CM formula(10 herbs) and antibiotics placebo for 4 weeks, or antibiotics for 1 week followed by 3 weeks of placebo and CM formula placebo. Clinical cure rate and microbiological cure and recurrence after treatment were evaluated. Results: A total 122 eligible patients were enrolled, with 61 cases in each group. The clinical cure rate by the intent-to-treatment approach was 90.2% for the CM group and 82.0% for the antibiotics group(P>0.05). Bacteria were cleared from 88.5%(54/61) of patients in the CM group and 82.0%(50/61) in the antibiotics group. The recurrence rate in recovered patients at the 6-month follow-up was 9.1%(5/61) and 14.0(7/61) in the CM and antibiotics groups, respectively(P>0.05). Conclusion: CM formula Bazheng Powder is a good alternative option for RUTI treatment.(Registration No. NCT01745328)
文摘Natural killer (NK) cells are a major component of the host innate immune defense against various pathogens. Several viruses, including hepatitis C virus (HCV), have developed strategies to evade the NK-cell response. In our study, we found HCV infection could trigger DNA damage response by both ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) pathways. Recent reports had revealed that NKG2D ligands (NK cell-activating ligands) were upregulated when a major DNA damage checkpoint pathway was activated. However, here we found that DNA damage response was activated but NKG2D ligands were downregulated upon HCV infection. Further studies showed that the protease NS3/4A of HCV which had been shown relation with immune invasion contributed to the reduced expression of NKG2D ligands. These findings provide a novel insight into the mechanisms evolved by HCV to escape from the NK cell response.
基金supported by the National Key Program for Infectious Diseases of China(2013ZX10004-203,2013ZX10004805-006)
文摘Dear Editors,Ebola virus disease(EVD)is an acute,serious and fatal illness caused by the Ebola virus.EVD was first identified in 1976 during two simultaneous outbreaks,one in Nzara,Sudan,and the other in Yambuku,Democratic Republic of Congo[1].The latter o ccurred in a village near the Ebola River,from which the disease takes its name.Since
基金the Education Committee of Beijing Science and Technology Plan Key Project(No.KZ201211417041)
文摘Background: Particulate matter(PM), which has adverse effects on citizen health, is a major air pollutant in Beijing city. PM_(2.5) is an indicator of PM in urban areas and can cause serious damage to human health. Many epidemiological studies have shown that nuclear factor-kappa B(NF-κB) is involved in PM_(2.5)-induced cell injury, but the exact mechanisms are not well understood.Methods: The cytotoxic effects of PM_(2.5) at 25–1600μg/ml for 24 h were determined by MTT assay in Chinese hamster ovary cells(CHO) cells. Flow cytometry was used to determine the apoptosis rate induced by PM_(2.5). The destabilized enhanced green fluorescent protein(d2 EGFP) green fluorescent protein reporter system was used to determine the NF-κB activity induced by PM_(2.5). The expression of pro-apoptotic Bcl-2-associated death promoter(BAD) proteins induced by PM_(2.5) was determined by Western blotting to explore the relationship between PM_(2.5) and the NF-κB signaling pathway and to determine the toxicological mechanisms of PM_(2.5).Results: PM_(2.5) collected in Beijing urban districts induces cytotoxic effects in CHO cells according to MTT assay with 72.28% cell viability rates even at 200μg/ml PM_(2.5) and flow cytometry assays with 26.97% apoptosis rates at 200μg/ml PM_(2.5). PM_(2.5) increases the activation levels of NF-κB, which have maintained for 24 h. 200μg/ml PM_(2.5) cause activation of NF-κB after exposure for 4 h, the activation peak appears after 13.5 h with a peak value of 25.41%. The average percentage of NF-κB activation in whole 24 h is up to 12.90% by 200μg/ml PM_(2.5). In addition, PM_(2.5) decreases the expression level of the pro-apoptotic protein BAD in a concentration-dependent manner.Conclusion: PM_(2.5) induces NF-κB activation, which persists for 24 h. The expression of pro-apoptotic protein BAD decreased with increased concentrations of PM_(2.5). These findings suggest that PM_(2.5) plays a major role in apoptosis by activating the NF-κB signaling pathway and reducing BAD protein expression.
基金PWD received support from Australia Awards Scholarships–Department of Foreign Affairs and Trade.WYZ received support from National Natural Science Foundation of China(No.11501339)The funder had no role in the study design,data collection or analysis,the decision to publish,and the preparation of this manuscriptThe findings and conclusions of this study are those of the authors and do not necessarily represent the views of the funding agency。
文摘Background:Leptospirosis morbidity and mortality rates in China have decreased since the 2000s.Further analyses of the spatiotemporal and demographic changes occurring in the last decade and its implication on estimates of disease burden are required to inform intervention strategies.In this study,we quantified the epidemiological shift and geographical heterogeneity in the burden of leptospirosis during 2005-2015 in China.Methods:We used reported leptospirosis case data from 1st January 2005 to 31st of December 2015 that routinely collected by the China Information System for Disease Control and Prevention(CISDCP)to analyze the epidemiological trend and estimate the burden in terms of disability-adjusted life-years(DALYs)over space,time,and demographical groups.Results:A total of 7763 cases were reported during 2005-2015.Of which,2403(31%)cases were the laboratoryconfirmed case.Since 2005,the notified incidence rate was gradually decreased(P<0.05)and it was relatively stable during 2011-2015(P>0.05).During 2005-2015,we estimated a total of 10313 DALYs were lost due to leptospirosis comprising a total of 1804 years-lived with disability(YLDs)and 8509 years-life lost(YLLs).Males had the highest burden of disease(7149 DALYs)compared to females(3164 DALYs).The highest burden estimate was attributed to younger individuals aged 10-19 years who lived in southern provinces of China.During 2005-2015,this age group contributed to approximately 3078 DALYs corresponding to 30%of the total DALYs lost in China.Yet,our analysis indicated a declining trend in burden estimates(P<0.001)since 2005 and remained relatively low during 2011-2015.Low burden estimates have been identified in the endemic regions where infections principally distributed.Most of the changes in DALY estimates were driven by changes in YLLs.Conclusions:In the last 11-years,the burden estimates of leptospirosis have shown a declining trend across the country;however,leptospirosis should not be neglected as it remains an important zoonotic disease and potentially affecting the young and productive population in economically less-developed provinces in southern of China.In addition,while in the last five years the incidence has been reported at very low-level,this might not reflect the true incidence of leptospirosis.Strengthened surveillance in the endemic regions is,hence,substantially required to capture the actual prevalence to better control leptospirosis in China.
基金This work was supported by National Natural Sciences Foundation of China(No.31970445&81371848)Shanxi Province Science and Technology Department(201803D31205).
文摘Background:Visceral leishmaniasis(VL)was one of the most important parasitic diseases in China,caused by Leishmania protozoans and transmitted by sand flies.Recently VL cases have reappeared in China,including the extension region of the Loess Plateau.The purpose of this study was to collect fundamental data on the host-vector VL system in the Loess Plateau to assist in the development of prevention and control measures.Methods:Sand flies were collected by light traps from rural areas in Shanxian,Henan,China in 2015,as well as in Wuxiang and Yangquan,Shanxi,China in 2017.The blood sources of sand flies were analyzed by PCR detecting the host-specific mitochondrial cytochrome b(mtDNA cyt b)gene fragments.Leishmania infection in sand flies was detected by amplifying and sequencing ribosomal DNA internal transcribed spacer 1(ITS1).The Leishmania specific antibodies in the sera of local dogs were detected by ELISA kit.Results:Blood sources showed diversity in the extension region of the Loess Plateau,including human,chicken,dog,cattle,pig and goat.Multiple blood sources within a sand fly were observed in samples from Yangquan(17/118,14.4%)and Wuxiang(12/108,11.1%).Leishmania DNA was detected in sand flies collected from Yangquan with minimum infection rate of 1.00%.The ITS1 sequences were conserved with the Leishmania donowni complex.The positive rate of Leishmania specific antibodies in dogs was 5.97%.Conclusions:This study detected the blood sources and Leishmania parasites infection of sand flies by molecular methods in the extension region of Loess Plateau,China.A high epidemic risk of leishmaniasis is currently indicated by the results as the infection of Leishmania in sand flies,the extensive blood sources of sand flies including humans,and positive antibody of Leishmania in local dog sera.Given the recent increase of VL cases,asymptomatic patients,dogs and other potential infected animals should be screened and treated.Furthermore,the density of sand flies needs to be controlled and personal protection should be strengthened.
基金supported by grants from National Twelfth Five-Year Plan for Science&Technology Support of China(2014BAI13B03)National Natural Science Foundation of China(81460248,81260457,81271899,31272592,81071320)+3 种基金Inner Mongolia Natural Science Funds(2013MS1138,2012MS1121,2011MS1110)Beijing Natural Science Foundation(6122030,7132153)Inner Mongolia Science&Technology Plan(20120101,20120402,20110502)the National Key Program for Infectious Diseases of China(2013ZX10004-203,2013ZX10004-217-002,2013ZX10004805-006).
文摘Brucellosis is a worldwide zoonosis.Vaccination is the most efficient means to prevent and control brucellosis.The current licensed attenuated vaccines for animal use were developed by sequential passage in nonnatural hosts that decreased virulence in its original hosts.The attenuation mechanism of these strains remains largely unknown.In the present study,we sequenced the genome of Brucella melitensis vaccine strain M5-10.Sequence analysis showed that a large number of genetic changes occurred in the vaccine strains.A total of 2854 genetic polymorphic sites,including 2548 SNP,241 INDEL and 65 MNV were identified.Of the 2074 SNPs in coding regions,1310(63.2%)were non-synonymous SNPs.Gene number,percent and N/S ratios were disproportionally distributed among the cog categories.Genetic polymorphic sites were identified in genes of the virB operon,flagella synthesis,and virulence regulating systems.These data indicate that changes in some cog categories and virulence genes might result in the attenuation.These attenuation mechanisms also have implications for screening and development of new vaccine strains.The genetic changes in the genome represent candidate sites for differential diagnosis between these vaccine strains and other virulence ones.Transcription analysis of virulence genes showed that expression of dnaK,vjbR were reduced in M5-10 strain when compared with that in 16M.A duplex PCR targeting virB6 and dnaK was successfully used to differentiate between M5-10 and the virulent 16M strain.The genome re-sequencing technique represents a strong strategy not only for evaluation of vaccines,but also for development of new vaccines.
基金supported by the National Basic Re-search Program(973)of China(No.2011CB503803)the National Key Project on Drug Development from the Ministry of Science and Technology of China(No.2009ZX09501-034)China Postdoctoral Science Foundation(No.20110491865)
文摘T-2 toxin is one of the most important trichothecene mycotoxins occurring in various agriculture products. The developmental toxicity of T-2 toxin and the exact mechanism of action at early life stages are not understood precisely. Zebrafish embryos were exposed to different concentrations of the toxin at 4–6 hours post fertilization(hpf) stage of development, and were observed for different developmental toxic effects at 24, 48, 72, and 144 hpf. Exposure to 0.20 μmol/L or higher concentrations of T-2 toxin significantly increased the mortality and malformation rate such as tail deformities, cardiovascular defects and behavioral changes in early developmental stages of zebrafish. T-2 toxin exposure resulted in significant increases in reactive oxygen species(ROS) production and cell apoptosis, mainly in the tail areas, as revealed by Acridine Orange staining at 24 hpf. In addition, T-2 toxin-induced severe tail deformities could be attenuated by co-exposure to reduced glutathione(GSH). T-2 toxin and GSH co-exposure induced a significant decrease of ROS production in the embryos. The overall results demonstrate that T-2 toxin is able to produce oxidative stress and induce apoptosis, which are involved in the developmental toxicity of T-2 toxin in zebrafish embryos.
基金This work was supported by National Natural Sciences Foundation of China(No.81371848)the Infective Diseases Prevention and Cure Project of China(No.2017ZX10303404–002).
文摘Background:Arboviral disease transmitted by Aedes albopictus such as dengue fever is an important threat to human health.Pyrethroid resistance raises a great challenge for mosquito control.A systematic assessment of Ae.albopictus resistance status in China is urgently needed,and the study of correlation between pyrethroid resistance and knockdown resistance(kdr)mutations would provide information to guide the control of the Ae.albopictus vector.Methods:Five field populations of Ae.albopictus were collected from Jinan(JN),Hangzhou(HZ),Baoshan(BS),Yangpu(YP)and Haikou(HK),China in 2017.Insecticide-impregnated papers were prepared with four pyrethroid chemicals,deltamethrin,permethrin,beta-cypermethrin and lambda-cyhalothrin.The susceptibility of Ae.albopictus to pyrethroids was tested by the WHO tube assay.Kdr mutations were identified by PCR and sequencing.Moreover,the correlation analysis between kdr alleles and pyrethroid resistance was performed.Results:All five populations of Ae.albopictus showed resistance to four pyrethroid insecticides.One kdr mutant allele at codon 1532 and three at 1534 were detected with frequency of 5.33%(I1532T),44.20%(F1534S),1.83%(F1534 L)and 0.87%(F1534C),respectively.Both 1532 and 1534 mutation mosquitoes were found in the BS and YP populations.Allele I1532T was negatively correlated with deltamethrin resistance phenotype(OR<1),while F1534S mutation was positively correlated with deltamethrin and permethrin resistance(OR>1).Conclusions:The five field populations of Ae.albopictus adults were all resistant to deltamethrin,permethrin,betacypermethrin and lambda-cyhalothrin.Mutant F1534S was clearly associated with pyrethroid resistance phenotype in Ae.albopictus and this could be developed as a molecular marker to monitor the pyrethroid resistance problem in China.