Tidal flats are soil resources of great significance.Nitrification plays a central role in the nitrogen cycle and is often a critical first step in nitrogen removal from estuarine and coastal environments.We determine...Tidal flats are soil resources of great significance.Nitrification plays a central role in the nitrogen cycle and is often a critical first step in nitrogen removal from estuarine and coastal environments.We determined the abundance as well as composition of ammonia-oxidizing bacteria(AOB) and ammonia-oxidizing archaea(AOA) in different soils during land reclamation process.The abundance of AOA was higher than that of AOB in farm land and wild land while AOA was not detected in tidal flats using real-time polymerase chain reaction(PCR).The different abundances of AOB and AOA were negatively correlated with the salinity.The diversities of AOB and AOA were also investigated using clone libraries by amplification of amoA gene.Among AOB,nearly all sequences belonged to the Nitrosomonas lineage in the initial land reclamation process,i.e.,tidal flats,while both Nitrosomonas and Nitrosospira lineages were detected in later and transition phases of land reclamation process,farm land and wild land.The ratio of the numbers of sequences of Nitrosomonas and Nitrosospira lineages was positively correlated with the salinity and the net nitrification rate.As for AOA,there was no obvious correlation with the changes in the physicochemical properties of the soil.This study suggests that AOB may be more import than AOA with respect to influencing the different land reclamation process stages.展开更多
Objective To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid(BDSF) and fluconazole(FLU) or itraconazole(ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in...Objective To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid(BDSF) and fluconazole(FLU) or itraconazole(ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. Methods Minimum inhibitory concentrations(MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction(qR T-PCR). Results BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ≤ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qR T-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mR NA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. Conclusion The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.展开更多
Hepatocellular carcinoma(HCC)is the most common primary liver cancer and accounts for 80%-90% of this class of malignancy.So far,understanding of its pathogenesis and effective therapeutic methods are rather limited.I...Hepatocellular carcinoma(HCC)is the most common primary liver cancer and accounts for 80%-90% of this class of malignancy.So far,understanding of its pathogenesis and effective therapeutic methods are rather limited.In this issue,11 invited review articles are published to address current advance of underlying molecular mechanisms for the deve-lopment of HCC, and novel therapeutic approaches for HCC.This series of review articles provide an in-depth unders-tanding of HCC that has led to or may lead to the development of novel therapies for HCC.展开更多
Background:Bacterial diarrhea is one of the most common causes for medical consultations,mortality and morbidity in the world.Diarrheagenic Escherichia coli(DEC)and non-typhoidal Salmonella(NTS)are major intestinal pa...Background:Bacterial diarrhea is one of the most common causes for medical consultations,mortality and morbidity in the world.Diarrheagenic Escherichia coli(DEC)and non-typhoidal Salmonella(NTS)are major intestinal pathogens in developing countries,and the indiscriminate use of antibiotics has greatly contributed to resistant strains.Hence,the aim of the present study is to identify the antimicrobial resistance patterns and the molecular characteristics of DEC and NTS in southwest,China.Methods:1121 diarrheal patients and 319 non-diarrheal subjects across all age groups were recruited from four sentinel hospitals from June 2014 to July 2015 in Kunming City,Yunnan Province.Each stool specimen was collected to detect DEC and NTS with standard microbiological and molecular methods.Antimicrobial resistance testing was performed with the Kirby-Bauer disk diffusion method,and the standards for antimicrobial susceptibility testing complied with the Clinical and Laboratory Standards Institute(CLSI).Molecular characterization of strains was carried out using pulsed-field gel electrophoresis(PFGE).A structured questionnaire was used to record basic epidemiological data(e.g.sex,age,residence,season,etc.).Data were analyzed using Chi-square or Fisher’s exact test.Results:DEC was detected in 127(11.33%)diarrhea cases and 9(2.82%)non-diarrheal cases(χ^(2)=20.69,P<0.001,OR=4.36,95%CI:2.19-8.65),and the prevalence of NTS isolated from diarrhea cases was higher than that of non-diarrheal cases across all age groups(n=42,3.75%,n=1,0.31%,χ^(2)=10.10,P=0.002,OR=12.38,95%CI:1.70-90.29).The rates of resistance to ten antibiotics of DEC and NTS showed significant differences(χ^(2)=386.77,P<0.001;χ^(2)=191.16,P<0.001).The rates of resistance to Amoxicillin and Clavulafiate(AMC),Cephalothin(CEP),Gentamicin(GEN)and Sulfamethoxazole-Trimethoprim(SXT)of DEC isolated from diarrhea cases were higher than those of NTS isolated from diarrhea patients(37.01%vs 14.29%,χ^(2)=7.57,P=0.006;29.92%vs 11.90%,χ^(2)=5.40,P=0.02;37.01%vs 11.90%,χ^(2)=5.80,P=0.016;62.20%vs 26.19%,χ^(2)=16.44,P<0.001;respectively).Ciprofloxacin(CIP)was the most sensitive antibiotic for DEC and NTS strains isolated from diarrhea cases.Resistance rates of DEC isolates from cases and controls to more than three kinds antimicrobials(multidrug resistance,MDR)showed no significant differences(81.10%vs 88.89%,P=0.33).Pulsotype patterns of DEC strains were highly diverse;however,the pulsotype pattern of NTS strains was closely related to the serotype.The pattern of S.enteritidis was highly similar,but the S.enterica Typhimurium strain was discrete.Conclusions:Antibiotic resistance of Enterobacteriaceae is of great concern.The societal effects of antibiotic use justify strict monitoring to combat increases in antimicrobial resistance.Molecular epidemiology and systematic epidemiological investigation can provide accurate evidence for tracking the infection source.展开更多
Background:Interventions are currently being used against‘infectious diseases of poverty’,which remain highly debilitating and deadly in most endemic countries,especially malaria,schistosomiasis,echinococcosis and A...Background:Interventions are currently being used against‘infectious diseases of poverty’,which remain highly debilitating and deadly in most endemic countries,especially malaria,schistosomiasis,echinococcosis and African sleeping sickness.However,major limitations of current‘traditional’methods for diagnosis are neither simple nor convenient for population surveillance,and showed low sensitivity and specificity.Access to novel technologies for the development of adequate and reliable tools are expressly needed.A collaborative project between African Network for Drugs and Diagnostics Innovation and partner institutions in Africa and China aims to screen suitable serological biomarkers for diagnostic pipelines against these‘diseases of the poor’.Methods:Parasite-specific exposed versus unexposed individuals were screened and sera or urine/stools were collected through case-control studies in China and African countries.Target genes/open reading frames were selected,then will be cloned and cell-free expressed,quantified and immuno-detected.Target antigens/epitopes will be probed and screened with sera from exposed or unexposed individuals using a high-throughput antigen screening platform as the study progresses.The specificity and sensitivity of highly immunoreactive biomarkers will be evaluated as well,using enzyme-linked immunosorbent assays or dipsticks.Discussion:This roadmap explicitly unfolds the integrated operating procedures with focus on malaria and schistosomiasis,for the identification of suitable biomarkers that will aid the prioritization of diagnostics for population use.However,there is need to further validate any new diagnostic through comparison with standard methods in field deployable tests for each region.Our expectations for the future are to seek regulatory approval and promote the use of diagnostics in endemic areas.展开更多
Non-pharmaceutical interventions(NPIs)have been proven effective in reducing the spread of the coronavirus disease 2019(COVID-19),but their broader impact on gastrointestinal disorders remains poorly studied.Here,we r...Non-pharmaceutical interventions(NPIs)have been proven effective in reducing the spread of the coronavirus disease 2019(COVID-19),but their broader impact on gastrointestinal disorders remains poorly studied.Here,we report an observational analysis and retrospective study that compares the incidence of acute diarrheal diseases in Hangzhou,Zhejiang,China,between 2019 and 2020,with an examination of the antimicrobial resistance and genetic spectrum of non-typhoidal Salmonella(NTS)from 2015 to 2022,before and during the COVID-19 pandemic.Our findings underscore that NPIs related to COVID-19 effectively reduced the incidence of acute diarrhea,with a substantial decrease in most enteric pathogens.Notably,NTS exhibited an unexpected surge.Further genomic investigations of NTS isolates revealed an overall reduction in antimicrobial-resistant(AMR),disinfection-tolerant,and virulent capabilities,but with marked variations detected between human and animal isolates.Additional genome-based analysis confirmed a decrease in the scale of zoonotic transmission in response to NPIs,suggesting particular NTS types may contribute to human infections via alternative pathways.The collective findings manifested that COVID-19-related NPIs had a mixed impact on NTS infections,which may inform AMR NTS mitigation policy.展开更多
This study investigated the therapeutic effects of interleukin （IL）-2 and granulocyte-macrophage colony-stimulating factor （GM-CSF） co-administrated with antibacterial agents isoniazid （INH） and rifampin （RIF）...This study investigated the therapeutic effects of interleukin （IL）-2 and granulocyte-macrophage colony-stimulating factor （GM-CSF） co-administrated with antibacterial agents isoniazid （INH） and rifampin （RIF） to treat a mouse model of tuberculo- sis （TB） infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 （P〈0.01） and 0.58 （P〈0.05） lg colony-forming units （CFU）, respectively, and in the spleens by 1.42 （P〈0.01） and 1.22 （P〈0.01） lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens （1.02 and 1.34 lg CFU） compared with antibacterial therapy alone （P〈0.01）. This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis （MDR-TB）.展开更多
Background:Babesiosis is an emerging health risk in several parts of the world.However,little is known about the prevalence of Babesia in malaria-endemic countries.The area along the China-Myanmar border in Yunnan is ...Background:Babesiosis is an emerging health risk in several parts of the world.However,little is known about the prevalence of Babesia in malaria-endemic countries.The area along the China-Myanmar border in Yunnan is a main endemic area of malaria in P.R.China,however,human infection with Babesia microti(B.microti)is not recognized in this region,and its profile of co-infection is not yet clear.Methods:To understand its profile of co-infections with B.microti,our investigation was undertaken in the malaria-endemic area along the China-Myanmar border in Yunnan between April 2012 and June 2013.Four parasite species,including B.microti,Plasmodium falciparum(P.falciparum),P.vivax,and P.malariae,were identified among 449 suspected febrile persons detected by nested polymerase chain reaction(PCR)assay based on small subunit ribosomal ribonucleic acid(RNA)genes of B.microti and Plasmodium spp.Results:Of all the collected samples from febrile patients,mono-infection with B.microti,P.vivax,P.falciparum,and P.malariae accounted for 1.8%(8/449),9.8%(44/449),2.9%(13/449),and 0.2%(1/449),respectively.The rate of mixed infections of B.microti with P.falciparum or P.vivax are both 0.2%(1/449),and mixed infections of P.falciparum and P.vivax accounted for 1.1%(5/449).Conclusions:This report supports the hypothesis that babesiosis caused by B.microti is emerging along the China-Myanmar border in the Yunnan province,P.R.China,but it was ignored because of low parasitemia or mixed infection with Plasmodium spp.More sensitive and specific diagnosis methods are needed to find the rapid response mechanism of emergency for babesiosis and malaria co-prevalence areas.展开更多
Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species （ROS） in infected cell...Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species （ROS） in infected cells, which may be closely related with their pathogenicity. In this report, chaetocin, a fimgal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent Epstein-Barr virus （EBV） in B95-8 cells. We found that chaetocin remarkably up-regulated EBV lytic transcription and DNA replication at a low concentration （50 nmol L-l）. The activation of latent EBV was accompanied by an increased cellular ROS level. N-acetyl-L-cysteine （NAC）, an ROS inhibitor, suppressed chaetocin-induced EBV activation. Chaetocin had little effect on histone H3K9 methylation, while NAC also significantly reduced H3K9 methylation. These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.展开更多
Background:Schistosoma mansoni,causing intestinal schistosomiasis,is widely distributed in Ethiopia and new transmission foci are continually reported.Here we report new transmission sites and prevalence ofS.mansoni i...Background:Schistosoma mansoni,causing intestinal schistosomiasis,is widely distributed in Ethiopia and new transmission foci are continually reported.Here we report new transmission sites and prevalence ofS.mansoni infection among school children in Yachi areas,southwestern Ethiopia.Methods:A cross-sectional survey was conducted among school children of Yachi Yisa and Yachi Efo elementary schools,southwestern Ethiopia,from April 2017 to June 2017.Three hundred seventeen school children aged six to 15 years were randomly selected to provide stool specimens for helminth infection examination by Kato-Katz and formol-ether concentration techniques.Snail survey was carried out to assess schistosome infection inBiomphalaria pfeifferi.Laboratory bred mice were also exposed to schistosome cercariae shed byB.pfeifferi en masse for definite identification ofSchistosoma species.Results:From the 317 stool specimens examined using double Kato-Katz thick smear and single formol-ether concentration techniques,224(70.7%)were found positive for at least one intestinal helminth species.The most prevalent parasite wasS.mansoni(42.9%)followed byTrichuris trichiura(34.1%)andAscaris lumbricoides(14.2%).The prevalence ofS.mansoni infection was significantly higher among the children attending Yachi Yisa School(49.4%)than those in Yachi Efo School(35.6%)(P=0.002).The study also revealed that there was a significantly higher prevalence ofS.mansoni infection among males(51.2%)than females(33.1%)(P<0.001).However,the prevalence ofS.mansoni infection was not significantly associated with age categories(P=0.839).B.pfeifferi snails infected with schistosomes were collected from the water bodies found in the study area.After six weeks post exposure,adultS.mansoni worms were harvested from the mesenteric veins of laboratory bred mice.Conclusions:The study revealed establishment of newS.mansoni transmission foci and moderate prevalence of schistosomiasis in Yachi areas.Hence,treatment of all school-age children once every two years is recommended.Snail control and non-specific control approaches including provision of clean water supply and health education should also complement mass drug administration of praziquantel.展开更多
MicroRNAs （miRNAs） are short, endogenously expressed RNAs （-21-22 nt） processed from stem-loop regions of longer RNA precursors by a Dicer-like enzyme （Jones- Rhoades et al., 2006）. In plants, microRNAs play an ...MicroRNAs （miRNAs） are short, endogenously expressed RNAs （-21-22 nt） processed from stem-loop regions of longer RNA precursors by a Dicer-like enzyme （Jones- Rhoades et al., 2006）. In plants, microRNAs play an essential role in regulating many fundamental molecular in- teractions, including plant growth, development and re- sponse to environmental stress （Rogers and Chen, 2013）. In comparison with the roles of microRNAs in animals, bio- genesis and function of microRNAs in plants appears to be drastically different （Llave et al., 2002; Zhang et al., 2007）.展开更多
基金Project supported by the National Natural Science Foundation of China (Nos. 31070097 and 31011140339)the National Key Technologies R & D Program of China (Nos. 2006BAJ05A11 and2010BAK69B14)the Major Program of Science and Technology Department of Shanghai (No. 10DZ1200700),China
文摘Tidal flats are soil resources of great significance.Nitrification plays a central role in the nitrogen cycle and is often a critical first step in nitrogen removal from estuarine and coastal environments.We determined the abundance as well as composition of ammonia-oxidizing bacteria(AOB) and ammonia-oxidizing archaea(AOA) in different soils during land reclamation process.The abundance of AOA was higher than that of AOB in farm land and wild land while AOA was not detected in tidal flats using real-time polymerase chain reaction(PCR).The different abundances of AOB and AOA were negatively correlated with the salinity.The diversities of AOB and AOA were also investigated using clone libraries by amplification of amoA gene.Among AOB,nearly all sequences belonged to the Nitrosomonas lineage in the initial land reclamation process,i.e.,tidal flats,while both Nitrosomonas and Nitrosospira lineages were detected in later and transition phases of land reclamation process,farm land and wild land.The ratio of the numbers of sequences of Nitrosomonas and Nitrosospira lineages was positively correlated with the salinity and the net nitrification rate.As for AOA,there was no obvious correlation with the changes in the physicochemical properties of the soil.This study suggests that AOB may be more import than AOA with respect to influencing the different land reclamation process stages.
基金financially supported by the National Natural Science Foundation of China [81273409]the Program for Changjiang Scholars and Innovative Research Team in University [IRT_15R37]the Ministry of Science and Technology of China [2017YFA0205301]
文摘Objective To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid(BDSF) and fluconazole(FLU) or itraconazole(ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. Methods Minimum inhibitory concentrations(MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction(qR T-PCR). Results BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ≤ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qR T-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mR NA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. Conclusion The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.
文摘Hepatocellular carcinoma(HCC)is the most common primary liver cancer and accounts for 80%-90% of this class of malignancy.So far,understanding of its pathogenesis and effective therapeutic methods are rather limited.In this issue,11 invited review articles are published to address current advance of underlying molecular mechanisms for the deve-lopment of HCC, and novel therapeutic approaches for HCC.This series of review articles provide an in-depth unders-tanding of HCC that has led to or may lead to the development of novel therapies for HCC.
基金Pathogens identified were supported by the postdoctoral research funding of SX-Z from Guangzhou Women and Children’s Medical Center(5001–3001075)The field epidemiological investigation was supported from National Natural Science Foundation of China(Grant number:81473022)+2 种基金The antibiotic resistance testing and the experiment of molecular characterization of pathogens were supported by National Key Research and Development Project(No.2016YFC1202000)The data analysis was conducted by E.Serrano who was funded by the Spanish Ministerio de Economia y Competitividad(MINECO)through a Ramon y Cajal agreement(RYC-2016-21120)R.Tinoco-Torres was supported by a post-doctoral grant by the Portuguese Fundacao para a Ciencia e a Tecnologia FCT(SFRH/BPD/112482/2015).
文摘Background:Bacterial diarrhea is one of the most common causes for medical consultations,mortality and morbidity in the world.Diarrheagenic Escherichia coli(DEC)and non-typhoidal Salmonella(NTS)are major intestinal pathogens in developing countries,and the indiscriminate use of antibiotics has greatly contributed to resistant strains.Hence,the aim of the present study is to identify the antimicrobial resistance patterns and the molecular characteristics of DEC and NTS in southwest,China.Methods:1121 diarrheal patients and 319 non-diarrheal subjects across all age groups were recruited from four sentinel hospitals from June 2014 to July 2015 in Kunming City,Yunnan Province.Each stool specimen was collected to detect DEC and NTS with standard microbiological and molecular methods.Antimicrobial resistance testing was performed with the Kirby-Bauer disk diffusion method,and the standards for antimicrobial susceptibility testing complied with the Clinical and Laboratory Standards Institute(CLSI).Molecular characterization of strains was carried out using pulsed-field gel electrophoresis(PFGE).A structured questionnaire was used to record basic epidemiological data(e.g.sex,age,residence,season,etc.).Data were analyzed using Chi-square or Fisher’s exact test.Results:DEC was detected in 127(11.33%)diarrhea cases and 9(2.82%)non-diarrheal cases(χ^(2)=20.69,P<0.001,OR=4.36,95%CI:2.19-8.65),and the prevalence of NTS isolated from diarrhea cases was higher than that of non-diarrheal cases across all age groups(n=42,3.75%,n=1,0.31%,χ^(2)=10.10,P=0.002,OR=12.38,95%CI:1.70-90.29).The rates of resistance to ten antibiotics of DEC and NTS showed significant differences(χ^(2)=386.77,P<0.001;χ^(2)=191.16,P<0.001).The rates of resistance to Amoxicillin and Clavulafiate(AMC),Cephalothin(CEP),Gentamicin(GEN)and Sulfamethoxazole-Trimethoprim(SXT)of DEC isolated from diarrhea cases were higher than those of NTS isolated from diarrhea patients(37.01%vs 14.29%,χ^(2)=7.57,P=0.006;29.92%vs 11.90%,χ^(2)=5.40,P=0.02;37.01%vs 11.90%,χ^(2)=5.80,P=0.016;62.20%vs 26.19%,χ^(2)=16.44,P<0.001;respectively).Ciprofloxacin(CIP)was the most sensitive antibiotic for DEC and NTS strains isolated from diarrhea cases.Resistance rates of DEC isolates from cases and controls to more than three kinds antimicrobials(multidrug resistance,MDR)showed no significant differences(81.10%vs 88.89%,P=0.33).Pulsotype patterns of DEC strains were highly diverse;however,the pulsotype pattern of NTS strains was closely related to the serotype.The pattern of S.enteritidis was highly similar,but the S.enterica Typhimurium strain was discrete.Conclusions:Antibiotic resistance of Enterobacteriaceae is of great concern.The societal effects of antibiotic use justify strict monitoring to combat increases in antimicrobial resistance.Molecular epidemiology and systematic epidemiological investigation can provide accurate evidence for tracking the infection source.
基金On behalf of the WHA-WHO Demonstration Project,this work was granted by the United Nations Office for Project Services(UNOPS),in the context of the implementation of‘Development for Easy to Use and Affordable Biomarkers as Diagnostics for Types II and III Diseases’(Grant No.UNOPS/ANDI/G/2016/01)It has also received the support of the National Key Research and Development Program of China(Grant No.2016YFC1202000,2016YFC1202003 and 2016YFC1200500)+1 种基金the National Natural Science Foundation of China(Grant No.81101266)the Fourth Round of Three-Year Public Health Action Plan(2015-2017)in Shanghai(Grant No.GWIV-29 and 15GWZK0101).
文摘Background:Interventions are currently being used against‘infectious diseases of poverty’,which remain highly debilitating and deadly in most endemic countries,especially malaria,schistosomiasis,echinococcosis and African sleeping sickness.However,major limitations of current‘traditional’methods for diagnosis are neither simple nor convenient for population surveillance,and showed low sensitivity and specificity.Access to novel technologies for the development of adequate and reliable tools are expressly needed.A collaborative project between African Network for Drugs and Diagnostics Innovation and partner institutions in Africa and China aims to screen suitable serological biomarkers for diagnostic pipelines against these‘diseases of the poor’.Methods:Parasite-specific exposed versus unexposed individuals were screened and sera or urine/stools were collected through case-control studies in China and African countries.Target genes/open reading frames were selected,then will be cloned and cell-free expressed,quantified and immuno-detected.Target antigens/epitopes will be probed and screened with sera from exposed or unexposed individuals using a high-throughput antigen screening platform as the study progresses.The specificity and sensitivity of highly immunoreactive biomarkers will be evaluated as well,using enzyme-linked immunosorbent assays or dipsticks.Discussion:This roadmap explicitly unfolds the integrated operating procedures with focus on malaria and schistosomiasis,for the identification of suitable biomarkers that will aid the prioritization of diagnostics for population use.However,there is need to further validate any new diagnostic through comparison with standard methods in field deployable tests for each region.Our expectations for the future are to seek regulatory approval and promote the use of diagnostics in endemic areas.
基金supported by the National Program on Key Research Project of China(2019YFE0103900)as well as the European Union's Horizon 2020 Research and Innovation Program(861917-SAFFI)Zhejiang Provincial Key R&D Program of China(2023C03045)+3 种基金Ningbo Public Service Technology Foundation,China(2021S155)the Medical Scientific Research Foundationof Zhejang Province,China(2022KY1158 and 2024KY1557)Ningbo Natural Science Foundation,China(2023J203)Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(2021JJLH0083).
基金We would like to thank Annemieke van den Dool(Duke Kunshan University)for the critical reading of the manuscriptThis study was supported by the National Program on the Key Research Project of China(2022YFC2604201)+4 种基金the European Union’s Horizon 2020 Research and Innovation Programme(861917-SAFFI)Zhejiang Provincial Key R&D Program of China(2023C030452022C02024)Zhejiang Provincial Naturaal Science Foundation of China(LZ24C180002)Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Techonology City(2021JJLH0083).
文摘Non-pharmaceutical interventions(NPIs)have been proven effective in reducing the spread of the coronavirus disease 2019(COVID-19),but their broader impact on gastrointestinal disorders remains poorly studied.Here,we report an observational analysis and retrospective study that compares the incidence of acute diarrheal diseases in Hangzhou,Zhejiang,China,between 2019 and 2020,with an examination of the antimicrobial resistance and genetic spectrum of non-typhoidal Salmonella(NTS)from 2015 to 2022,before and during the COVID-19 pandemic.Our findings underscore that NPIs related to COVID-19 effectively reduced the incidence of acute diarrhea,with a substantial decrease in most enteric pathogens.Notably,NTS exhibited an unexpected surge.Further genomic investigations of NTS isolates revealed an overall reduction in antimicrobial-resistant(AMR),disinfection-tolerant,and virulent capabilities,but with marked variations detected between human and animal isolates.Additional genome-based analysis confirmed a decrease in the scale of zoonotic transmission in response to NPIs,suggesting particular NTS types may contribute to human infections via alternative pathways.The collective findings manifested that COVID-19-related NPIs had a mixed impact on NTS infections,which may inform AMR NTS mitigation policy.
基金supported in part by the Key Technologies Research and Development Program for Infectious Diseases of China (Grant No. 2012ZX10003001)the Key Project of Science and Technology of Shanghai (Grant No.10411955000)the Shanghai Science and Technology Development Funds (Grant No. 10XD1400900)
文摘This study investigated the therapeutic effects of interleukin （IL）-2 and granulocyte-macrophage colony-stimulating factor （GM-CSF） co-administrated with antibacterial agents isoniazid （INH） and rifampin （RIF） to treat a mouse model of tuberculo- sis （TB） infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 （P〈0.01） and 0.58 （P〈0.05） lg colony-forming units （CFU）, respectively, and in the spleens by 1.42 （P〈0.01） and 1.22 （P〈0.01） lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens （1.02 and 1.34 lg CFU） compared with antibacterial therapy alone （P〈0.01）. This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis （MDR-TB）.
基金The research has been partially supported by the Special Fund for Health Research in the Public Interest China(No.201202019)Strengthen Action Plan for Shanghai Public Health System Construction 2011–2013(GW-11)by the National S&T Major Program(No.2012ZX10004-220).
文摘Background:Babesiosis is an emerging health risk in several parts of the world.However,little is known about the prevalence of Babesia in malaria-endemic countries.The area along the China-Myanmar border in Yunnan is a main endemic area of malaria in P.R.China,however,human infection with Babesia microti(B.microti)is not recognized in this region,and its profile of co-infection is not yet clear.Methods:To understand its profile of co-infections with B.microti,our investigation was undertaken in the malaria-endemic area along the China-Myanmar border in Yunnan between April 2012 and June 2013.Four parasite species,including B.microti,Plasmodium falciparum(P.falciparum),P.vivax,and P.malariae,were identified among 449 suspected febrile persons detected by nested polymerase chain reaction(PCR)assay based on small subunit ribosomal ribonucleic acid(RNA)genes of B.microti and Plasmodium spp.Results:Of all the collected samples from febrile patients,mono-infection with B.microti,P.vivax,P.falciparum,and P.malariae accounted for 1.8%(8/449),9.8%(44/449),2.9%(13/449),and 0.2%(1/449),respectively.The rate of mixed infections of B.microti with P.falciparum or P.vivax are both 0.2%(1/449),and mixed infections of P.falciparum and P.vivax accounted for 1.1%(5/449).Conclusions:This report supports the hypothesis that babesiosis caused by B.microti is emerging along the China-Myanmar border in the Yunnan province,P.R.China,but it was ignored because of low parasitemia or mixed infection with Plasmodium spp.More sensitive and specific diagnosis methods are needed to find the rapid response mechanism of emergency for babesiosis and malaria co-prevalence areas.
文摘Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species （ROS） in infected cells, which may be closely related with their pathogenicity. In this report, chaetocin, a fimgal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent Epstein-Barr virus （EBV） in B95-8 cells. We found that chaetocin remarkably up-regulated EBV lytic transcription and DNA replication at a low concentration （50 nmol L-l）. The activation of latent EBV was accompanied by an increased cellular ROS level. N-acetyl-L-cysteine （NAC）, an ROS inhibitor, suppressed chaetocin-induced EBV activation. Chaetocin had little effect on histone H3K9 methylation, while NAC also significantly reduced H3K9 methylation. These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.
基金We sincerely thank the School of Graduate Studies,Addis Ababa University for financial support.
文摘Background:Schistosoma mansoni,causing intestinal schistosomiasis,is widely distributed in Ethiopia and new transmission foci are continually reported.Here we report new transmission sites and prevalence ofS.mansoni infection among school children in Yachi areas,southwestern Ethiopia.Methods:A cross-sectional survey was conducted among school children of Yachi Yisa and Yachi Efo elementary schools,southwestern Ethiopia,from April 2017 to June 2017.Three hundred seventeen school children aged six to 15 years were randomly selected to provide stool specimens for helminth infection examination by Kato-Katz and formol-ether concentration techniques.Snail survey was carried out to assess schistosome infection inBiomphalaria pfeifferi.Laboratory bred mice were also exposed to schistosome cercariae shed byB.pfeifferi en masse for definite identification ofSchistosoma species.Results:From the 317 stool specimens examined using double Kato-Katz thick smear and single formol-ether concentration techniques,224(70.7%)were found positive for at least one intestinal helminth species.The most prevalent parasite wasS.mansoni(42.9%)followed byTrichuris trichiura(34.1%)andAscaris lumbricoides(14.2%).The prevalence ofS.mansoni infection was significantly higher among the children attending Yachi Yisa School(49.4%)than those in Yachi Efo School(35.6%)(P=0.002).The study also revealed that there was a significantly higher prevalence ofS.mansoni infection among males(51.2%)than females(33.1%)(P<0.001).However,the prevalence ofS.mansoni infection was not significantly associated with age categories(P=0.839).B.pfeifferi snails infected with schistosomes were collected from the water bodies found in the study area.After six weeks post exposure,adultS.mansoni worms were harvested from the mesenteric veins of laboratory bred mice.Conclusions:The study revealed establishment of newS.mansoni transmission foci and moderate prevalence of schistosomiasis in Yachi areas.Hence,treatment of all school-age children once every two years is recommended.Snail control and non-specific control approaches including provision of clean water supply and health education should also complement mass drug administration of praziquantel.
基金This work was supported by National Basic Research Program （973 Program） （No. 2012CB721102）, National Natural Science Founda- tion of China （Grant No. 30830002） and the China Postdoctoral Science Foundation funded project （2012T50444 and 2012M 520947）.
文摘MicroRNAs （miRNAs） are short, endogenously expressed RNAs （-21-22 nt） processed from stem-loop regions of longer RNA precursors by a Dicer-like enzyme （Jones- Rhoades et al., 2006）. In plants, microRNAs play an essential role in regulating many fundamental molecular in- teractions, including plant growth, development and re- sponse to environmental stress （Rogers and Chen, 2013）. In comparison with the roles of microRNAs in animals, bio- genesis and function of microRNAs in plants appears to be drastically different （Llave et al., 2002; Zhang et al., 2007）.
