Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods ...Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.展开更多
Objective This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase(DGC)in Vibrio cholerae and how its transcription is regulated by Fur and Hap R.Methods The roles of VCA0560 was ...Objective This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase(DGC)in Vibrio cholerae and how its transcription is regulated by Fur and Hap R.Methods The roles of VCA0560 was investigated by utilizing various phenotypic assays,including colony morphological characterization,crystal violet staining,Cyclic di-GMP(c-di-GMP)quantification,and swimming motility assay.The regulation of the VCA0560 gene by Fur and Hap R was analyzed by luminescence assay,electrophoretic mobility shift assay,and DNase I footprinting.Results VCA0560 gene mutation did not affect biofilm formation,motility,and c-di-GMP synthesis in V.cholerae,and its overexpression remarkably enhanced biofilm formation and intracellular c-di-GMP level but reduced motility capacity.The transcription of the VCA0560 gene was directly repressed by Fur and the master quorum sensing regulator Hap R.Conclusion Overexpressed VCA0560 functions as an active DGC in V.cholerae,and its transcription is repressed by Fur and Hap R.展开更多
West Nile virus(WNV)causes West Nile fever and West Nile encephalitis.Because infection by WNV creates serious public health problems,its simple,rapid,and visual detection is very important in clinical practice,especi...West Nile virus(WNV)causes West Nile fever and West Nile encephalitis.Because infection by WNV creates serious public health problems,its simple,rapid,and visual detection is very important in clinical practice,especially in resource-limited laboratories.We have developed a rapid,specific,and highly sensitive internally controlled reverse transcription recombinase-aided amplification(RTRAA)assay to detect WNV,using both real-timefluoresce nee and the lateral flow dipstick(LFD)at39.0°C for 30 min.The analytical sensitivity of theRT-RAA assay was 10 plasmid copies and 1.6 pfu perreacti on with real-time fluoresce nee,and 1,000plasmid copies per reaction with the LFD.No crossreactionwith other control viruses was observed.Compared with the RT-qPCR assay,the RT-RAA assaydemonstrated 100%sensitivity and 100%specificityfor WNV.展开更多
Objective We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases.Meth...Objective We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases.Methods We performed a descriptive study of notifiable infectious diseases among foreigners reported from 2004 to 2017 in China using data from the Chinese National Notifiable Infectious Disease Reporting System(NNIDRIS). Demographic, temporal-spatial distribution were described and analyzed.Results A total of 67,939 cases of 33 different infectious diseases were reported among foreigners.These diseases were seen in 31 provinces of China and originated from 146 countries of the world. The infectious diseases with the highest incidence number were human immunodeficiency virus(HIV) of18,713 cases, hepatitis B(6,461 cases), hand, foot, and mouth disease(6,327 cases). Yunnan province had the highest number of notifiable infectious diseases in foreigners. There were different trends of the major infectious diseases among foreign cases seen in China and varied among provinces.Conclusions This is the first description of the epidemiological characteristic of notifiable infectious diseases among foreigners in China from 2004 to 2017. These data can be used to better inform policymakers about national health priorities for future research and control strategies.展开更多
Objective To investigate genetic and antibiotic resistance characteristics of Campylobacter jejuni(C. jejuni) isolated from Shenzhen. Methods Multilocs sequence typing and agar dilution methods were used to define the...Objective To investigate genetic and antibiotic resistance characteristics of Campylobacter jejuni(C. jejuni) isolated from Shenzhen. Methods Multilocs sequence typing and agar dilution methods were used to define the genotype and antibiotic resistance of C. jejuni, respectively. Results In total, 126 C. jejuni strains were isolated. The prevalence of C. jejuni was 5.3% in diarrheal patients. The prevalence in poultry meat(36.5%) was higher than that in cattle meat(1.1%). However, the prevalence in poultry cloacal swabs(27.0%) was lower than that in cattle stool(57.3%). Sixty-two sequence types were obtained, among which 27 of the STs and 10 alleles were previously unreported. The most frequently observed clonal complexes were ST-21(11.9%), ST-22(10.3%), and ST-403(7.1%). ST-21, ST-45, ST-354, ST-403, and ST-443 complexes overlapped between isolates from patients and cattle, whereas ST-45 and ST-574 complexes overlapped between isolates from patients and poultry. All C. jejuni were resistant to at least one antibiotic. The highest resistance rate was toward ciprofloxacin(89.7%), followed by tetracycline(74.6%), and nalidixic acid(69.0%). Conclusion This is the first report of the genotypes and antibiotic resistance of C. jejuni in Shenzhen. Overlapping clonal complexes were found between isolates from patients and cattle, and between patients and poultry.展开更多
In an effort to end the HIV epidemic by 2030, the Joint United Nations Program on HIV/AIDS(UNAIDS)set the ‘90-90-90’ target and aimed to expand the timely use of ART worldwide. By the end of 2017,21.7 million people...In an effort to end the HIV epidemic by 2030, the Joint United Nations Program on HIV/AIDS(UNAIDS)set the ‘90-90-90’ target and aimed to expand the timely use of ART worldwide. By the end of 2017,21.7 million people living with HIV, amounting to59% of HIV patients worldwide, were receiving antiretroviral therapy(ART)[1]. In China, the National Free Antiretroviral Treatment Program(NFATP),which was initiated in 2002, continued to progress.展开更多
Objective This study aimed to evaluate the genetic diversity,virulence,and antimicrobial resistance of Aeromonas isolates from clinical patients,tap water systems,and food.Methods Ninety Aeromonas isolates were obtain...Objective This study aimed to evaluate the genetic diversity,virulence,and antimicrobial resistance of Aeromonas isolates from clinical patients,tap water systems,and food.Methods Ninety Aeromonas isolates were obtained from Ma’anshan,Anhui province,China,and subjected to multi-locus sequence typing(MLST)with six housekeeping genes.Their taxonomy was investigated using concatenated gyr B-cpn60 sequences,while their resistance to 12 antibiotics was evaluated.Ten putative virulence factors and several resistance genes were identified by PCR and sequencing.Results The 90 Aeromonas isolates were divided into 84 sequence types,80 of which were novel,indicating high genetic diversity.The Aeromonas isolates were classified into eight different species.PCR assays identified virulence genes in the isolates,with the enterotoxin and hemolysin genes act,aer A,alt,and ast found in 47(52.2%),13(14.4%),22(24.4%),and 12(13.3%)of the isolates,respectively.The majority of the isolates(≥90%)were susceptible to aztreonam,imipenem,cefepime,chloramphenicol,gentamicin,tetracycline,and ciprofloxacin.However,several resistance genes were detected in the isolates,as well as a new mcr-3 variant.Conclusions Sequence type,virulence properties,and antibiotic resistance vary in Aeromonas isolates from clinical patients,tap water systems,and food.展开更多
Serum samples were tested for Bartonella henselae Ig G antibodies using indirect immunofluorescence assays.We then analyzed associated risk factors.Serum samples were considered positive when reactive at a dilution of...Serum samples were tested for Bartonella henselae Ig G antibodies using indirect immunofluorescence assays.We then analyzed associated risk factors.Serum samples were considered positive when reactive at a dilution of more than 1:320.展开更多
Arcobacter is an emerging foodborne pathogen worldwide.In this study,the prevalence,antimicrobial susceptibility and genetic characteristics of Arcobacter from different sources were investigated.Eighteen A.butzleri i...Arcobacter is an emerging foodborne pathogen worldwide.In this study,the prevalence,antimicrobial susceptibility and genetic characteristics of Arcobacter from different sources were investigated.Eighteen A.butzleri isolates were obtained from 60 raw chicken meat samples(16/60,27%)and 150 patients with diarrhea(2/150,1.3%).The resistance ratios to nalidixic acid,ciprofloxacin,clindamycin,chloramphenicol,and florfenicol were 83.33%(15/18),38.89%(7/18),38.89%(7/18),33.33%(6/18)and 33.33%(6/18),respectively.We performed whole genome sequencing of the 18 isolates,and we predicted antibiotic resistance genes and virulence factors by using assembled genomes through blastx analysis.Two resistance genes,blaOXA-464 and tet(H),and the C254T mutation in gyrA,were identified in the genomes of some resistant isolates.Furthermore,virulence genes,such as flgG,flhA,flhB,fliI,fliP,motA,cadF,cjl349,ciaB,mviN,pldA and tlyA,were found in all strains,whereas hecA,hecB and iroE were found in only some strains.Phylogenetic tree analysis of A.butzleri isolates on the basis of the core-genome single nucleotide polymorphisms showed that two isolates from patients with diarrhea clustered together,separately from the isolates from raw chicken and the chicken strains.This study is the first comprehensive analysis of Arcobacter isolated in Beijing.展开更多
Objective To investigate distinctive features in drug-resistant mutations （DRMs） and interpretations for reverse transcriptase inhibitors （RTIs） between proviral DNA and paired viral RNA in HIV-l-infected patients...Objective To investigate distinctive features in drug-resistant mutations （DRMs） and interpretations for reverse transcriptase inhibitors （RTIs） between proviral DNA and paired viral RNA in HIV-l-infected patients. Methods Forty-three HIV-l-infected individuals receiving first-line antiretroviral therapy were recruited to participate in a multicenter AIDS Cohort Study in Anhui and Henan Provinces in China in 2004. Drug resistance genotyping was performed by bulk sequencing and deep sequencing on the plasma and whole blood of 77 samples, respectively. Drug-resistance interpretation was compared between viral RNA and paired proviral DNA. Results Compared with bulk sequencing, deep sequencing could detect more DRMs and samples with DRMs in both viral RNA and proviral DNA. The mutations M1841 and M2301 were more prevalent in proviral DNA than in viral RNA （Fisher＇s exact test, P〈0.05）. Considering ＇majority resistant variants＇, 15 samples （19.48%） showed differences in drug resistance interpretation between viral RNA and proviral DNA, and 5 of these samples with different DRMs between proviral DNA and paired viral RNA showed a higher level of drug resistance to the first-line drugs. Considering ＇minority resistant variants＇, 22 samples （28.57%） were associated with a higher level of drug resistance to the tested RTIs for proviral DNA when compared with paired viral RNA. Conclusion Compared with viral RNA, the distinctive information of DRMs and drug resistance interpretations for proviral DNA could be obtained by deep sequencing, which could provide more detailed and precise information for drug resistance monitoring and the rational design of optimal antiretroviral therapy regimens.展开更多
Objective This study was performed to compare the genetic diversity,virulence,and antimicrobial resistance of Aeromonas strains isolated from patients and healthy individuals.Methods A total of 38 clinical strains and...Objective This study was performed to compare the genetic diversity,virulence,and antimicrobial resistance of Aeromonas strains isolated from patients and healthy individuals.Methods A total of 38 clinical strains and 19 strains from healthy individuals were isolated from the samples collected in Ma’anshan City,Anhui Province.Their taxonomy was investigated using concatenated gyrB-cpn60 sequences,and their resistance to 12 antibiotics was evaluated.The pathogenicity of these strains was examined through beta-hemolysis,protease activity,and virulence gene assays.Results The 57 Aeromonas strains were divided into 55 sequence types.Of these types,21 were novel,suggesting that their genetic diversity was high.These Aeromonas isolates could be divided into 7 species,and the positive rates of beta-hemolysis and protease activity were 49.1%and 73.7%,respectively.The detection rate of clinical patients in terms of beta-hemolysis and protease activity was higher than that of healthy individuals.Among the four most common Aeromonas strains,A.dhakensis had the highest detection rate of virulence genes.The multidrug resistance rate of the clinical isolates was much higher than that of the strains isolated from healthy individuals.Conclusions The taxonomy,virulence properties,and antibiotic resistance of Aeromonas isolates from patients differ from those of the isolates from healthy individuals.展开更多
Objective To explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine...Objective To explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer. Methods PCR was used to screen HPV16 and HPV18 oncogenes E6 and E7 in the SKBR3 cell line and in 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18 E6 and E7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined. Results HPV18 oncogenes E6 and E7 were amplified and sequenced from the SKBR3 cells. Of the patient samples, 6.58% and 23.68% were tested to be positive for HPV18 E6 and HPV18 E7. In the cell culture models, the knockdown of HPV18 E6 and E7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins. Conclusion HPV was a contributor to virus caused human breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer.展开更多
Pathogens like bacteria and protozoa,which affect human and animal health worldwide,can be transmitted by vectors like ticks.To investigate the epidemiology and genetic diversity of bacteria and protozoans carried by ...Pathogens like bacteria and protozoa,which affect human and animal health worldwide,can be transmitted by vectors like ticks.To investigate the epidemiology and genetic diversity of bacteria and protozoans carried by ticks in Chengmai county of Hainan province,China,285 adult hard ticks belonging to two species[Rhipicephalus sanguineus(sensu lato):183,64.21%and Rhipicephalus microplus:102,35.79%]from dogs,cattle,and goats were collected.Microbial families were identified in these ticks by amplifying the 18 S r RNA,16 S r RNA(rrs),citrate synthase(glt A),and heat shock protein(gro EL)genes.Our data revealed the presence of four recognized species and two Candidatus spp.of Anaplasmataceae and Coxiellaceae.In sum,these data reveal an extensive diversity of Anaplasmataceae bacteria,Coxiellaceae bacteria,Babesiidae,and Hepatozoidae in ticks from Hainan Island,highlighting the need to understand the tickborne pathogen infection in local animals and humans.展开更多
Objective The Guanzhong Plain of Shaanxi Province is a severely afflicted hemorrhagic fever with renal syndrome(HFRS)epidemic area,while HFRS prevalence has decreased in most epidemic areas in China.Little information...Objective The Guanzhong Plain of Shaanxi Province is a severely afflicted hemorrhagic fever with renal syndrome(HFRS)epidemic area,while HFRS prevalence has decreased in most epidemic areas in China.Little information is available regarding the leading fine-scale influencing factors in this highly HFRSconcentrated area and the roles of natural environmental and socioeconomic factors.To investigate this,two regions in the Guanzhong Plain,that is,the Chang’an District and Hu County,with similar geographical environments,different levels of economic development,and high epidemic prevalence,were chosen as representative areas of the HFRS epidemic.Methods Maximum entropy models were constructed based on HFRS cases and fine-scale influencing factors,including meteorological,natural environmental,and socioeconomic factors,from 2014 to 2016.Results More than 95% of the HFRS cases in the study area were located in the northern plains,which has an altitude of less than 800 m,with topography contributed 84.1% of the impact on the spatial differentiation of the HFRS epidemic.In the northern plains,precipitation and population density jointly affected the spatial differentiation of the HFRS epidemic,with contribution rates of 60.7% and 28.0%,respectively.By comparing the influencing factors of the northern plains of Chang’an District and Hu County,we found that precipitation and the normalized difference vegetation index(NDVI)dominated the HFRS epidemic in the relatively developed Chang’an District,while land-use type,temperature,precipitation and population density dominated the HFRS epidemic in the relatively undeveloped Hu County.Conclusion Topography was the primary key factor for HFRS prevalence in the Chang’an District and Hu County,and the spatial differentiation of HFRS was dominated by precipitation and population density in the northern plains.Compared with the influencing factors of the relatively developed Chang’an District,the developing Hu County was more affected by socioeconomic factors.When formulating targeted HFRS epidemic prevention and control strategies in the targeted areas,it is crucial to consider the local economic development state and combine natural environmental factors,including the meteorological environment and vegetation coverage.展开更多
Objective In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were al...Objective In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were also discussed in this study. Methods Milk was preprocessed with 4% NaOH. Then, mycobacteria were isolated from the milk sample on L-J medium. The isolate was identified using multiple loci Polymerase Chain Reaction （PCR） and multi-locus sequence analysis with 16S rRNA, sodA, hsp65, and ITS genes. The drug sensitivity of the isolate to 27 antibiotics was tested through alamar blue assay. Results Smooth, moist, pale yellow colonies appeared on the L-J medium within a week after inoculation. Based on the results of multiple loci PCR analysis, the isolate was preliminarily identified as non-tuberculous mycobacteria. The 16S rRNA, SodA, hsp65, and ITS gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities, respectively, with those of the published reference strains of Mycobacteriurn elephantis （M. elephantis）. The drug sensitivity results showed that the strain is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin, levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin, ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline. Conclusion To the best of our knowledge, this study is initially to report the isolation of M. elephantis from the milk of a cow with mastitis in China.展开更多
Objective To establish a domestic database of Enterobacteria cloacae （E. cloacae）, and improve the identification efficiency using peptide mass fingerprinting. Methods Peptide mass fingerprinting was used for the id...Objective To establish a domestic database of Enterobacteria cloacae （E. cloacae）, and improve the identification efficiency using peptide mass fingerprinting. Methods Peptide mass fingerprinting was used for the identification and subtyping of E. cloacae. Eighty-seven strains, identified based on hsp60 genotyping, were used to construct and evaluate a new reference database. Results Compared with the original reference database, the identification efficiency and accuracy of the new reference database was greatly improved at the species level. The first super reference database for E. cloacae identification was also constructed and evaluated. Based on the super reference database and the main spectra projection dendrogram, E. cloacae strains were divided into two clades. Conclusion Peptide mass fingerprinting is a powerful method to identify and subtype E. cloacae, and the use of this method will allow us to obtain more information to understand the heterogeneous organism E. cloacae.展开更多
Objective Aeromonas has recently been recognized as an emerging human pathogen.Aeromonasassociated diarrhea is a phenomenon occurring worldwide.This study was designed to determine the prevalence,genetic diversity,ant...Objective Aeromonas has recently been recognized as an emerging human pathogen.Aeromonasassociated diarrhea is a phenomenon occurring worldwide.This study was designed to determine the prevalence,genetic diversity,antibiotic resistance,and pathogenicity of Aeromonas strains isolated from food products in Shanghai.Methods Aeromonas isolates(n=79)collected from food samples were analyzed using concatenated gyrB-cpn60 sequencing.The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing.Pathogenicity was assessed usingβ-hemolytic,extracellular protease,virulence gene detection,C.elegans liquid toxicity(LT),and cytotoxicity assays.Results Eight different species were identified among the 79 isolates.The most prevalent Aeromonas species were A.veronii[62(78.5%)],A.caviae[6(7.6%)],A.dhakensis[3(3.8%)],and A.salmonicida[3(3.8%)].The Aeromonas isolates were divided into 73 sequence types(STs),of which 65 were novel.The isolates were hemolytic(45.6%)and protease-positive(81.0%).The most prevalent virulence genes were act(73.4%),fla(69.6%),aexT(36.7%),and ascV(30.4%).The results of C.elegans LT and cytotoxicity assays revealed that A.dhakensis and A.hydrophila were more virulent than A.veronii,A.caviae,and A.bivalvium.Antibiotic resistance genes[tetE,blaTEM,tetA,qnrS,aac(6)-Ib,mcr-1,and mcr-3]were detected in the isolates.The multidrug-resistance rate of the Aeromonas isolates was 11.4%,and 93.7%of the Aeromonas isolates were resistant to cefazolin.Conclusion The taxonomy,antibiotic resistance,and pathogenicity of different Aeromonas species varied.The Aeromonas isolates A.dhakensis and A.hydrophila were highly pathogenic,indicating that food-derived Aeromonas isolates are potential risks for public health and food safety.The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.展开更多
Objective To describe the global profiles of acetylated proteins in the brains of scrapie agents 139Aand ME7-infected mice collected at mid-early,mid-late,and terminal stages.Methods The acetylated proteins from the c...Objective To describe the global profiles of acetylated proteins in the brains of scrapie agents 139Aand ME7-infected mice collected at mid-early,mid-late,and terminal stages.Methods The acetylated proteins from the cortex regions of scrapie agent(139A-and ME7)-infected mice collected at mid-early(80 days postinfection,dpi),mid-late(120 dpi),and terminal(180 dpi) stages were extracted,and the global profiles of brain acetylated proteins were assayed with proteomic mass spectrometry.The proteins in the infected mice showing 1.5-fold higher or lower levels than that of agematched normal controls were considered as differentially expressed acetylated peptides(DEAPs).Results A total of 118,42,and 51 DEAPs were found in the brains of 139A-80,139A-120,and 139A-180dpi mice,respectively.Meanwhile,390,227,and 75 DEAPs were detected in the brains of ME7-80,ME7-120,and ME7-180 dpi mice,respectively.The overwhelming majority of DEAPs in the mid-early stage were down-regulated,and more portions of DEAPs in the mid-late and late stages were up-regulated.Approximately 22.1%(328/1,485) of acetylated peptides mapped to 74 different proteins were mitochondrial associated.Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 39(80dpi),13(120 dpi),and 10(180 dpi) significantly changed pathways in 139A-infected mice.Meanwhile,55,25,and 18 significantly changed pathways were observed in the 80,120,and 180 dpi samples of139A-and ME7-infected mice(P < 0.05),respectively.Six pathways were commonly involved in all tested samples.Moreover,many steps in the citrate cycle(tricarboxylic acid cycle) were affected,represented by down-regulated acetylation for relevant enzymes in the mid-early stage and upregulated acetylation in the mid-late and late stages.Conclusion Our data here illustrated the changes in the global profiles for brain acetylated proteins during prion infection,showing remarkably inhibited acetylation in the early stage and relatively enhanced acetylation in the late stage.展开更多
Objective To develop a multiple-locus variable-number tandem-repeat(VNTR)analysis(MLVA)assay for Acinetobacter pittii typing.Methods Polymorphic VNTRs were searched by Tandem Repeats Finder.The distribution and polymo...Objective To develop a multiple-locus variable-number tandem-repeat(VNTR)analysis(MLVA)assay for Acinetobacter pittii typing.Methods Polymorphic VNTRs were searched by Tandem Repeats Finder.The distribution and polymorphism of each VNTR locus were analyzed in all the A.pittii genomes deposited in the NCBI genome database by BLAST and were evaluated with a collection of 20 well-characterized clinical A.pittii strains and one reference strain.The MLVA assay was compared with pulsed-field gel electrophoresis(PFGE)for discriminating A.pittii isolates.Results Ten VNTR loci were identified upon bioinformatic screening of A.pittii genomes,but only five of them showed full amplifiability and good polymorphism.Therefore,an MLVA assay composed of five VNTR loci was developed.The typeability,reproducibility,stability,discriminatory power,and epidemiological concordance were excellent.Compared with PFGE,the new optimized MLVA typing scheme provided the same and even greater discrimination.Conclusion Compared with PFGE,MLVA typing is a faster and more standardized alternative for studying the genetic relatedness of A.pittii isolates in disease surveillance and outbreak investigation.展开更多
Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,le...Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.展开更多
基金supported by Natural Science Foundation of Shandong ProvinceChina[ZR2022MH115]the National Natural Science Foundation of China[81301479,82202593]。
文摘Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.
基金supported by grants from the National Natural Science Foundation of China[Grant No.81471917]the National Basic Research Priorities Program[Grant 2015CB554201]the Science Foundation for the State Key Laboratory for Infectious Disease Prevention and Control of China[Grant No.2015SKLID509]
文摘Objective This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase(DGC)in Vibrio cholerae and how its transcription is regulated by Fur and Hap R.Methods The roles of VCA0560 was investigated by utilizing various phenotypic assays,including colony morphological characterization,crystal violet staining,Cyclic di-GMP(c-di-GMP)quantification,and swimming motility assay.The regulation of the VCA0560 gene by Fur and Hap R was analyzed by luminescence assay,electrophoretic mobility shift assay,and DNase I footprinting.Results VCA0560 gene mutation did not affect biofilm formation,motility,and c-di-GMP synthesis in V.cholerae,and its overexpression remarkably enhanced biofilm formation and intracellular c-di-GMP level but reduced motility capacity.The transcription of the VCA0560 gene was directly repressed by Fur and the master quorum sensing regulator Hap R.Conclusion Overexpressed VCA0560 functions as an active DGC in V.cholerae,and its transcription is repressed by Fur and Hap R.
基金supported by grants from the China Mega-Projects for Infectious Disease [2017ZX10302301-004-002,2018ZX10711001,2017ZX10104001,2018ZX10713-002]IVDC [2019HYDQNJJ03]
文摘West Nile virus(WNV)causes West Nile fever and West Nile encephalitis.Because infection by WNV creates serious public health problems,its simple,rapid,and visual detection is very important in clinical practice,especially in resource-limited laboratories.We have developed a rapid,specific,and highly sensitive internally controlled reverse transcription recombinase-aided amplification(RTRAA)assay to detect WNV,using both real-timefluoresce nee and the lateral flow dipstick(LFD)at39.0°C for 30 min.The analytical sensitivity of theRT-RAA assay was 10 plasmid copies and 1.6 pfu perreacti on with real-time fluoresce nee,and 1,000plasmid copies per reaction with the LFD.No crossreactionwith other control viruses was observed.Compared with the RT-qPCR assay,the RT-RAA assaydemonstrated 100%sensitivity and 100%specificityfor WNV.
基金sponsored by National Science and Technology Major Project No. 2016ZX10004222-001。
文摘Objective We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases.Methods We performed a descriptive study of notifiable infectious diseases among foreigners reported from 2004 to 2017 in China using data from the Chinese National Notifiable Infectious Disease Reporting System(NNIDRIS). Demographic, temporal-spatial distribution were described and analyzed.Results A total of 67,939 cases of 33 different infectious diseases were reported among foreigners.These diseases were seen in 31 provinces of China and originated from 146 countries of the world. The infectious diseases with the highest incidence number were human immunodeficiency virus(HIV) of18,713 cases, hepatitis B(6,461 cases), hand, foot, and mouth disease(6,327 cases). Yunnan province had the highest number of notifiable infectious diseases in foreigners. There were different trends of the major infectious diseases among foreign cases seen in China and varied among provinces.Conclusions This is the first description of the epidemiological characteristic of notifiable infectious diseases among foreigners in China from 2004 to 2017. These data can be used to better inform policymakers about national health priorities for future research and control strategies.
基金supported by Sanming Project of Medicine in Shenzhen[SZSM201803081]Shenzhen Technology and Innovation Plan,China[JCYJ 20140416095154399]Nanshan District Technology and Innovation Plan,Shenzhen,China[2016064]
文摘Objective To investigate genetic and antibiotic resistance characteristics of Campylobacter jejuni(C. jejuni) isolated from Shenzhen. Methods Multilocs sequence typing and agar dilution methods were used to define the genotype and antibiotic resistance of C. jejuni, respectively. Results In total, 126 C. jejuni strains were isolated. The prevalence of C. jejuni was 5.3% in diarrheal patients. The prevalence in poultry meat(36.5%) was higher than that in cattle meat(1.1%). However, the prevalence in poultry cloacal swabs(27.0%) was lower than that in cattle stool(57.3%). Sixty-two sequence types were obtained, among which 27 of the STs and 10 alleles were previously unreported. The most frequently observed clonal complexes were ST-21(11.9%), ST-22(10.3%), and ST-403(7.1%). ST-21, ST-45, ST-354, ST-403, and ST-443 complexes overlapped between isolates from patients and cattle, whereas ST-45 and ST-574 complexes overlapped between isolates from patients and poultry. All C. jejuni were resistant to at least one antibiotic. The highest resistance rate was toward ciprofloxacin(89.7%), followed by tetracycline(74.6%), and nalidixic acid(69.0%). Conclusion This is the first report of the genotypes and antibiotic resistance of C. jejuni in Shenzhen. Overlapping clonal complexes were found between isolates from patients and cattle, and between patients and poultry.
基金supported by the Research Project of Chongqing Municipal Science and Technology Bureau[cstc2019jscx-msxm X0225]Medical Research Project of Chongqing Municipal Health Commission [2017ZDXM001,2019ZDXM005]。
文摘In an effort to end the HIV epidemic by 2030, the Joint United Nations Program on HIV/AIDS(UNAIDS)set the ‘90-90-90’ target and aimed to expand the timely use of ART worldwide. By the end of 2017,21.7 million people living with HIV, amounting to59% of HIV patients worldwide, were receiving antiretroviral therapy(ART)[1]. In China, the National Free Antiretroviral Treatment Program(NFATP),which was initiated in 2002, continued to progress.
基金supported by the National Natural Science Foundation of China grant numbers NSFC 81861138053 and NSFC 31761133004。
文摘Objective This study aimed to evaluate the genetic diversity,virulence,and antimicrobial resistance of Aeromonas isolates from clinical patients,tap water systems,and food.Methods Ninety Aeromonas isolates were obtained from Ma’anshan,Anhui province,China,and subjected to multi-locus sequence typing(MLST)with six housekeeping genes.Their taxonomy was investigated using concatenated gyr B-cpn60 sequences,while their resistance to 12 antibiotics was evaluated.Ten putative virulence factors and several resistance genes were identified by PCR and sequencing.Results The 90 Aeromonas isolates were divided into 84 sequence types,80 of which were novel,indicating high genetic diversity.The Aeromonas isolates were classified into eight different species.PCR assays identified virulence genes in the isolates,with the enterotoxin and hemolysin genes act,aer A,alt,and ast found in 47(52.2%),13(14.4%),22(24.4%),and 12(13.3%)of the isolates,respectively.The majority of the isolates(≥90%)were susceptible to aztreonam,imipenem,cefepime,chloramphenicol,gentamicin,tetracycline,and ciprofloxacin.However,several resistance genes were detected in the isolates,as well as a new mcr-3 variant.Conclusions Sequence type,virulence properties,and antibiotic resistance vary in Aeromonas isolates from clinical patients,tap water systems,and food.
基金supported by the National Science and Technology Major Projects[No.2018ZX10712001 and2017ZX10303404]Major Infectious Diseases Such as AIDS and Viral Hepatitis Prevention and Control Technology Major Projects[No.2018ZX10712-001].
文摘Serum samples were tested for Bartonella henselae Ig G antibodies using indirect immunofluorescence assays.We then analyzed associated risk factors.Serum samples were considered positive when reactive at a dilution of more than 1:320.
基金supported by National Key Research and Development Program of China [grant No.:2021YFC2301000]the Academic Commission of Shunyi District Center for Disease Control and Prevention,Beijing,China。
文摘Arcobacter is an emerging foodborne pathogen worldwide.In this study,the prevalence,antimicrobial susceptibility and genetic characteristics of Arcobacter from different sources were investigated.Eighteen A.butzleri isolates were obtained from 60 raw chicken meat samples(16/60,27%)and 150 patients with diarrhea(2/150,1.3%).The resistance ratios to nalidixic acid,ciprofloxacin,clindamycin,chloramphenicol,and florfenicol were 83.33%(15/18),38.89%(7/18),38.89%(7/18),33.33%(6/18)and 33.33%(6/18),respectively.We performed whole genome sequencing of the 18 isolates,and we predicted antibiotic resistance genes and virulence factors by using assembled genomes through blastx analysis.Two resistance genes,blaOXA-464 and tet(H),and the C254T mutation in gyrA,were identified in the genomes of some resistant isolates.Furthermore,virulence genes,such as flgG,flhA,flhB,fliI,fliP,motA,cadF,cjl349,ciaB,mviN,pldA and tlyA,were found in all strains,whereas hecA,hecB and iroE were found in only some strains.Phylogenetic tree analysis of A.butzleri isolates on the basis of the core-genome single nucleotide polymorphisms showed that two isolates from patients with diarrhea clustered together,separately from the isolates from raw chicken and the chicken strains.This study is the first comprehensive analysis of Arcobacter isolated in Beijing.
基金supported by grants from the State Key Laboratory of Infectious Disease Prevention and Control(2011SKLID102)the National Nature Science Foundation of China(81172733 and 81561128006)the 12th Five-Year National Science and Technology Major Project(2013ZX10001-006)
文摘Objective To investigate distinctive features in drug-resistant mutations （DRMs） and interpretations for reverse transcriptase inhibitors （RTIs） between proviral DNA and paired viral RNA in HIV-l-infected patients. Methods Forty-three HIV-l-infected individuals receiving first-line antiretroviral therapy were recruited to participate in a multicenter AIDS Cohort Study in Anhui and Henan Provinces in China in 2004. Drug resistance genotyping was performed by bulk sequencing and deep sequencing on the plasma and whole blood of 77 samples, respectively. Drug-resistance interpretation was compared between viral RNA and paired proviral DNA. Results Compared with bulk sequencing, deep sequencing could detect more DRMs and samples with DRMs in both viral RNA and proviral DNA. The mutations M1841 and M2301 were more prevalent in proviral DNA than in viral RNA （Fisher＇s exact test, P〈0.05）. Considering ＇majority resistant variants＇, 15 samples （19.48%） showed differences in drug resistance interpretation between viral RNA and proviral DNA, and 5 of these samples with different DRMs between proviral DNA and paired viral RNA showed a higher level of drug resistance to the first-line drugs. Considering ＇minority resistant variants＇, 22 samples （28.57%） were associated with a higher level of drug resistance to the tested RTIs for proviral DNA when compared with paired viral RNA. Conclusion Compared with viral RNA, the distinctive information of DRMs and drug resistance interpretations for proviral DNA could be obtained by deep sequencing, which could provide more detailed and precise information for drug resistance monitoring and the rational design of optimal antiretroviral therapy regimens.
基金supported by Major Project of the thirteenth Five Year Special for infectious diseases of China[2018ZX10101002]。
文摘Objective This study was performed to compare the genetic diversity,virulence,and antimicrobial resistance of Aeromonas strains isolated from patients and healthy individuals.Methods A total of 38 clinical strains and 19 strains from healthy individuals were isolated from the samples collected in Ma’anshan City,Anhui Province.Their taxonomy was investigated using concatenated gyrB-cpn60 sequences,and their resistance to 12 antibiotics was evaluated.The pathogenicity of these strains was examined through beta-hemolysis,protease activity,and virulence gene assays.Results The 57 Aeromonas strains were divided into 55 sequence types.Of these types,21 were novel,suggesting that their genetic diversity was high.These Aeromonas isolates could be divided into 7 species,and the positive rates of beta-hemolysis and protease activity were 49.1%and 73.7%,respectively.The detection rate of clinical patients in terms of beta-hemolysis and protease activity was higher than that of healthy individuals.Among the four most common Aeromonas strains,A.dhakensis had the highest detection rate of virulence genes.The multidrug resistance rate of the clinical isolates was much higher than that of the strains isolated from healthy individuals.Conclusions The taxonomy,virulence properties,and antibiotic resistance of Aeromonas isolates from patients differ from those of the isolates from healthy individuals.
文摘Objective To explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer. Methods PCR was used to screen HPV16 and HPV18 oncogenes E6 and E7 in the SKBR3 cell line and in 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18 E6 and E7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined. Results HPV18 oncogenes E6 and E7 were amplified and sequenced from the SKBR3 cells. Of the patient samples, 6.58% and 23.68% were tested to be positive for HPV18 E6 and HPV18 E7. In the cell culture models, the knockdown of HPV18 E6 and E7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins. Conclusion HPV was a contributor to virus caused human breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer.
基金The National Science and Technology Major Project of China[No.2018ZX10101002-002]the National Natural Science Foundation of China[grants 81702016]the National Science and Technology Major Project of China[2018ZX10712001-006-002 and 2018ZX10305409-003-005]。
文摘Pathogens like bacteria and protozoa,which affect human and animal health worldwide,can be transmitted by vectors like ticks.To investigate the epidemiology and genetic diversity of bacteria and protozoans carried by ticks in Chengmai county of Hainan province,China,285 adult hard ticks belonging to two species[Rhipicephalus sanguineus(sensu lato):183,64.21%and Rhipicephalus microplus:102,35.79%]from dogs,cattle,and goats were collected.Microbial families were identified in these ticks by amplifying the 18 S r RNA,16 S r RNA(rrs),citrate synthase(glt A),and heat shock protein(gro EL)genes.Our data revealed the presence of four recognized species and two Candidatus spp.of Anaplasmataceae and Coxiellaceae.In sum,these data reveal an extensive diversity of Anaplasmataceae bacteria,Coxiellaceae bacteria,Babesiidae,and Hepatozoidae in ticks from Hainan Island,highlighting the need to understand the tickborne pathogen infection in local animals and humans.
基金funded by the National Natural Science Foundation of China[grant number 41901337 and 42071136]。
文摘Objective The Guanzhong Plain of Shaanxi Province is a severely afflicted hemorrhagic fever with renal syndrome(HFRS)epidemic area,while HFRS prevalence has decreased in most epidemic areas in China.Little information is available regarding the leading fine-scale influencing factors in this highly HFRSconcentrated area and the roles of natural environmental and socioeconomic factors.To investigate this,two regions in the Guanzhong Plain,that is,the Chang’an District and Hu County,with similar geographical environments,different levels of economic development,and high epidemic prevalence,were chosen as representative areas of the HFRS epidemic.Methods Maximum entropy models were constructed based on HFRS cases and fine-scale influencing factors,including meteorological,natural environmental,and socioeconomic factors,from 2014 to 2016.Results More than 95% of the HFRS cases in the study area were located in the northern plains,which has an altitude of less than 800 m,with topography contributed 84.1% of the impact on the spatial differentiation of the HFRS epidemic.In the northern plains,precipitation and population density jointly affected the spatial differentiation of the HFRS epidemic,with contribution rates of 60.7% and 28.0%,respectively.By comparing the influencing factors of the northern plains of Chang’an District and Hu County,we found that precipitation and the normalized difference vegetation index(NDVI)dominated the HFRS epidemic in the relatively developed Chang’an District,while land-use type,temperature,precipitation and population density dominated the HFRS epidemic in the relatively undeveloped Hu County.Conclusion Topography was the primary key factor for HFRS prevalence in the Chang’an District and Hu County,and the spatial differentiation of HFRS was dominated by precipitation and population density in the northern plains.Compared with the influencing factors of the relatively developed Chang’an District,the developing Hu County was more affected by socioeconomic factors.When formulating targeted HFRS epidemic prevention and control strategies in the targeted areas,it is crucial to consider the local economic development state and combine natural environmental factors,including the meteorological environment and vegetation coverage.
基金supported by the project 81401647 of Natural Science Foundation of ChinaProject 2014SKLID104 of State Key Laboratory for Infectious Diseases Prevention and Controlprojects 16411967900 of Science and Technology Commission of Shanghai Municipality
文摘Objective In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were also discussed in this study. Methods Milk was preprocessed with 4% NaOH. Then, mycobacteria were isolated from the milk sample on L-J medium. The isolate was identified using multiple loci Polymerase Chain Reaction （PCR） and multi-locus sequence analysis with 16S rRNA, sodA, hsp65, and ITS genes. The drug sensitivity of the isolate to 27 antibiotics was tested through alamar blue assay. Results Smooth, moist, pale yellow colonies appeared on the L-J medium within a week after inoculation. Based on the results of multiple loci PCR analysis, the isolate was preliminarily identified as non-tuberculous mycobacteria. The 16S rRNA, SodA, hsp65, and ITS gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities, respectively, with those of the published reference strains of Mycobacteriurn elephantis （M. elephantis）. The drug sensitivity results showed that the strain is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin, levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin, ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline. Conclusion To the best of our knowledge, this study is initially to report the isolation of M. elephantis from the milk of a cow with mastitis in China.
基金supported by the Mega Project of Research on the Prevention and Control of HIV/AIDS,Viral Hepatitis Infectious Diseases 2011ZX10004-001,2013ZX10004-101 to YE Chang Yun
文摘Objective To establish a domestic database of Enterobacteria cloacae （E. cloacae）, and improve the identification efficiency using peptide mass fingerprinting. Methods Peptide mass fingerprinting was used for the identification and subtyping of E. cloacae. Eighty-seven strains, identified based on hsp60 genotyping, were used to construct and evaluate a new reference database. Results Compared with the original reference database, the identification efficiency and accuracy of the new reference database was greatly improved at the species level. The first super reference database for E. cloacae identification was also constructed and evaluated. Based on the super reference database and the main spectra projection dendrogram, E. cloacae strains were divided into two clades. Conclusion Peptide mass fingerprinting is a powerful method to identify and subtype E. cloacae, and the use of this method will allow us to obtain more information to understand the heterogeneous organism E. cloacae.
基金supported by the National Key Research and Development Program of China[grant number 2018YFC1603804]。
文摘Objective Aeromonas has recently been recognized as an emerging human pathogen.Aeromonasassociated diarrhea is a phenomenon occurring worldwide.This study was designed to determine the prevalence,genetic diversity,antibiotic resistance,and pathogenicity of Aeromonas strains isolated from food products in Shanghai.Methods Aeromonas isolates(n=79)collected from food samples were analyzed using concatenated gyrB-cpn60 sequencing.The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing.Pathogenicity was assessed usingβ-hemolytic,extracellular protease,virulence gene detection,C.elegans liquid toxicity(LT),and cytotoxicity assays.Results Eight different species were identified among the 79 isolates.The most prevalent Aeromonas species were A.veronii[62(78.5%)],A.caviae[6(7.6%)],A.dhakensis[3(3.8%)],and A.salmonicida[3(3.8%)].The Aeromonas isolates were divided into 73 sequence types(STs),of which 65 were novel.The isolates were hemolytic(45.6%)and protease-positive(81.0%).The most prevalent virulence genes were act(73.4%),fla(69.6%),aexT(36.7%),and ascV(30.4%).The results of C.elegans LT and cytotoxicity assays revealed that A.dhakensis and A.hydrophila were more virulent than A.veronii,A.caviae,and A.bivalvium.Antibiotic resistance genes[tetE,blaTEM,tetA,qnrS,aac(6)-Ib,mcr-1,and mcr-3]were detected in the isolates.The multidrug-resistance rate of the Aeromonas isolates was 11.4%,and 93.7%of the Aeromonas isolates were resistant to cefazolin.Conclusion The taxonomy,antibiotic resistance,and pathogenicity of different Aeromonas species varied.The Aeromonas isolates A.dhakensis and A.hydrophila were highly pathogenic,indicating that food-derived Aeromonas isolates are potential risks for public health and food safety.The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.
基金supported by National Key R&D Program of China [2020YFE0205700]Chinese National Natural Science Foundation Grants [81630062]grants from the State Key Laboratory for Infectious Disease Prevention and Control(China CDC)[Grant Nos.2019SKLID501,2019SKLID603,and 2019SKLID307]
文摘Objective To describe the global profiles of acetylated proteins in the brains of scrapie agents 139Aand ME7-infected mice collected at mid-early,mid-late,and terminal stages.Methods The acetylated proteins from the cortex regions of scrapie agent(139A-and ME7)-infected mice collected at mid-early(80 days postinfection,dpi),mid-late(120 dpi),and terminal(180 dpi) stages were extracted,and the global profiles of brain acetylated proteins were assayed with proteomic mass spectrometry.The proteins in the infected mice showing 1.5-fold higher or lower levels than that of agematched normal controls were considered as differentially expressed acetylated peptides(DEAPs).Results A total of 118,42,and 51 DEAPs were found in the brains of 139A-80,139A-120,and 139A-180dpi mice,respectively.Meanwhile,390,227,and 75 DEAPs were detected in the brains of ME7-80,ME7-120,and ME7-180 dpi mice,respectively.The overwhelming majority of DEAPs in the mid-early stage were down-regulated,and more portions of DEAPs in the mid-late and late stages were up-regulated.Approximately 22.1%(328/1,485) of acetylated peptides mapped to 74 different proteins were mitochondrial associated.Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 39(80dpi),13(120 dpi),and 10(180 dpi) significantly changed pathways in 139A-infected mice.Meanwhile,55,25,and 18 significantly changed pathways were observed in the 80,120,and 180 dpi samples of139A-and ME7-infected mice(P < 0.05),respectively.Six pathways were commonly involved in all tested samples.Moreover,many steps in the citrate cycle(tricarboxylic acid cycle) were affected,represented by down-regulated acetylation for relevant enzymes in the mid-early stage and upregulated acetylation in the mid-late and late stages.Conclusion Our data here illustrated the changes in the global profiles for brain acetylated proteins during prion infection,showing remarkably inhibited acetylation in the early stage and relatively enhanced acetylation in the late stage.
基金supported by the Major Infectious Diseases Such as AIDS and Viral Hepatitis Prevention and Control technology major projects(grants 2013ZX-100040101,2013ZX10004805-005)the key projects of state key laboratory of infectious disease prevention and control(grants 2014SKLID102)
文摘Objective To develop a multiple-locus variable-number tandem-repeat(VNTR)analysis(MLVA)assay for Acinetobacter pittii typing.Methods Polymorphic VNTRs were searched by Tandem Repeats Finder.The distribution and polymorphism of each VNTR locus were analyzed in all the A.pittii genomes deposited in the NCBI genome database by BLAST and were evaluated with a collection of 20 well-characterized clinical A.pittii strains and one reference strain.The MLVA assay was compared with pulsed-field gel electrophoresis(PFGE)for discriminating A.pittii isolates.Results Ten VNTR loci were identified upon bioinformatic screening of A.pittii genomes,but only five of them showed full amplifiability and good polymorphism.Therefore,an MLVA assay composed of five VNTR loci was developed.The typeability,reproducibility,stability,discriminatory power,and epidemiological concordance were excellent.Compared with PFGE,the new optimized MLVA typing scheme provided the same and even greater discrimination.Conclusion Compared with PFGE,MLVA typing is a faster and more standardized alternative for studying the genetic relatedness of A.pittii isolates in disease surveillance and outbreak investigation.
基金supported by the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600)the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(Grant No.:2020YFE0205100)+13 种基金the National Natural Science Foundation of China(Grant Nos.:82104480,82004248,82141001,82274182,82074098,82173914)the Fundamental Research Funds for the Central public welfare research institutes(Grant Nos.:ZZ14-YQ-055,ZZ14-YQ-059,ZZ14-YQ-060,ZXKT19018,ZXKT19021,ZXKT19022,ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010,ZZ15-ND-10,ZZ16-ND-10-19)the Beijing Municipal Natural Science Foundation(Grant No.:7214287)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-C-202002)the Young Elite Scientists Sponsorship Program by CACM(Grant No.:2021QNRC2B29)the CACMS Innovation Fund(Grant Nos.:CI2021A05101,CI2021A05104)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Grant No.:CI2021B014)the Science and Technology Foundation of Shenzhen(Grant No.:JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases)Shenzhen Governmental Sustainable Development Fund(Grant No.:KCXFZ20201221173612034)Shenzhen key Laboratory of Kidney Diseases(Grant No.:ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(Grant No.:SZGSP001)the Distinguished Expert Project of Sichuan Province Tianfu Scholar(Grant No.:CW202002)the State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process Open Fund(Grant No.:SKL2020Z0302).
文摘Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.
