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简介：Toestablishasensitiveandspecificmethodforseroepidermiologicaldetectionofhumanher-pesvirus8(HHV-8)infection,threepotentantigenicproteinsencodedbyopenreadingframes(ORFs)K8.1,65and73CingenomeofHHV-8wereproducedasglutathioneS-transferasefusionproteinintheprokaryoticexpressionsystemandwasusedasantigenfortesting.Therecombinantfusionproteinex-pressedintheprokaryoticexpressionvectorE.coliBL21waspurifiedbyglutathioneSepharose4Baffin-itychromatographyandwasquantitatedwithSDS-PAGE.Allthese3fusionproteinsproducedinthepro-karyoticexpressionsystemshowedgoodimmunogenicityasdemonstratedbyWesternblottingandcouldberecognizedbymixedseraofpatientswithKaposi′ssarcoma(KS).Theimmuno-reactivitiesofthesingleorcompoundfusionproteinweredeterminedbymeansofELISAandcomparedwiththetraditionalimmu-nofluorescenceassay(IFA)todeterminetheirsensitivityandspecificityofthetest.Itwasdemonstratedthatthesensitivityofmixed-antigenELISAmethodwassignificantlyhigherthanthatofIFA(81.8%vs34.4%),whilethespecificityoftheformerwasdemonstratedtobe97.9%.Thecoincidenceofthede-tectionratebetweenthesetwomethodswasconsiderablyhigh,approachingupto90.0%.TheseresultssuggestthatthemixedantigenELISAassayappearstobeasensitiveandspecificmethodforsero-epide-miologicaldetectionofhumanherpesvirus8infection.

简介：AbstractBackground:Mycobacterium leprae and Toxoplasma gondii infections are both neglected tropical diseases highly prevalent in Brazil. Infection with certain parasite species can significantly alter susceptibility to other important pathogens, and/or influence the development of pathology. Here we investigated the possible influence of M. leprae/T. gondii co-parasitism on the manifestation of leprosy and its clinical forms.Methods:Participants (n = 291) were recruited in Campos dos Goytacazes city, Rio de Janeiro state, southeast Brazil, from August 2015 to December 2019 and clinically diagnosed for leprosy. Participants were selected based on the presence (patients) or absence (healthy controls) of the leprosy disease. Contacts of patients were also recruited for this study. Serum samples from patients (n = 199) with leprosy, contacts (n = 40) and healthy controls (n = 52) were investigated for levels of IgM and IgG anti-phenolic glycolipid-1 (PGL-1) by ELISA. Additionally, IgG antibody against soluble Toxoplasma antigen (STAg) was measured in sera samples from leprosy patients, contacts and healthy controls for Toxoplasma gondii serology by ELISA. Anti-PGL-1 IgG and IgM levels were compared using one-way ANOVA Kruskal-Wallis or Mann-Whitney, while Spearman test was used to correlate levels of IgG anti-STAg and IgM/IgG anti-PGL-1 from seropositive and seronegative individuals for T. gondii infection. The risk of T. gondii infection for leprosy disease was assessed using Fisher's test.Results:Levels of IgM anti-PGL-1 antibodies were significantly higher in multibacillary (MB) patients compared to paucibacillary (PB) patients (P = 0.0068). Higher IgM and IgG levels anti-PGL-1 were detected in patients with the lepromatous forms. The serologic prevalence for T. gondii infection was 74.9%. We detected increased anti-STAg antibody levels in leprosy patients (79.4%), reaching 88.8% within those with lepromatous form of this disease. The leprosy risk increase in T. gondii seropositive individuals was two-fold (odds ratio [OR]= 2.055; 95% confidence intervals [95% CI]: 1.18-3.51) higher than those seronegative, and considering the lepromatous leprosy risk this increase was even dramatic (OR = 4.33; 95% CI: 1.76-9.69) in T. gondii seropositive individuals. Moreover the leprosy risk in T. gondii seropositive individuals was weakly correlated to the levels of IgG anti-STAg and IgM/IgG anti-PGL-1.Conclusions:Altogether, our results suggest that T. gondii infection may exert immunomodulatory properties that influence to the susceptibility of leprosy, mainly on its more severe clinical form. A better understanding of parasite immunomodulation can ultimately contribute to the development of medical applications.

简介：AbstractBird infections with highly pathogenic avian influenza A(H5N6) viruses have been identified since 2014. With very limited occasion, the virus could sporadically spilled over to infect humans. It has been recognized that all human infections were within southern region of Mainland China until the case reported here in Beijing in Aug. 2019. This was the first human case infected with highly pathogenic avian influenza A(H5N6) virus in northern China. The infection was confirmed by real-time RT-PCR assay. The whole genome sequences were obtained from clinical sample. Genetic characteristics of the virus were identified similar to those of previous avian influenza A(H5N6) viruses, retaining the main features of the avian influenza virus.

简介：Wehavepreviouslydemonstratedtheabilityofmalariaparasitestointerferewithspecificimmuneresponses.CD4Tcellsspecifictoparasiteantigens,butnotCD4Tcellsspecifictoanirrelevantantigen,ovalbumin(OVA),aredeletedviaapoptosisduringmalariainfection.Itisofinterest,therefore,toinvestigatetheimmuneresponsesthatdevelopedfollowingvaccinationwiththe19kDacarboxylterminusofthemerozoitesurfaceprotein1(MSP119)inmicethathadpreviouslyexperiencedmalariainfection.Inthisstudy,pre-exposureofmicetoPlasmodiumyoeliielicitednativeanti-MSP119antibodyresponses,whichcouldbeboostedbyvaccinationwithrecombinantMSP119，Likewise,infectionofMSP119-primedmicewithPlasmodiumyoelii(P.yoelii)ledtoanincreaseofanti-MSP119antibodies.MSP119vaccinationofmalariapreexposedmiceorimmunizationbyinfection/cureofMSP119-primedmiceenabledthemicetosurvivechallengeinfection,withtheformergrouphavingslightlylowerparasitaemia.Thedatasuggestthatexposuretomalariainfectionprimesanaturalimmuneresponsewhichcanbeboostedbyvaccination.Thisinformationisrelevanttothedevelopmentofavaccineforuseinindividualslivinginmalaria-endemicareas.

简介：瞄准：把在病人之间的标准肝炎B(HBV)种痘的反应与长期的丙肝作比较病毒(HCV)感染和健康个人。方法：这是未来的盒子控制研究。有长期的HCV感染和40健康控制的38个病人的一个总数被包括。种痘被20大杯recombinantHBsAg的注射在瞬间0，1和6点执行进三角肌肌肉。Anti-HBs集中是在最后剂量以后决定了3瞬间并且在二个组之间比较了。反应模式是被描绘(1)高反应当anti-HBs抗体效价是>时100IU/L，(2)低反应当效价是10-100IU/L时并且(3)没有反应当效价是<时10IU/L。结果：在耐心的组，有10/38(26.3%)非应答者，8/38(21.1%)低应答者并且20/38(52.6%)高应答者。在控制组的相应价值是2/40(5.0%)，7/40(17.5%)和31/40(77.5%)分别地。反应模式在二个组之间是统计上不同的。在里面多变量分析，吸烟是重要confounder，当HCV感染与更低的抗体反应失去了它的重要关联时。结论：有长期的HCV感染的病人趋于与健康个人相比对HBV种痘微弱地作出回应，尽管这关联不是独立的根据多变量分析。

简介：Multiprotein桥因素2(MBF2)基因首先作为涉及Fushitarazu基因的BmFTZ-F1-mediated激活的激活剂被识别。此处，MBF2基因的九相应基因被识别。进化分析显示出那这个基因家庭是昆虫特定的并且家庭成员是仔细与对病原体(REPAT)的反应有关基因。织物分发分析表明这些基因能以一种织物特定的方式被表示。发展侧面分析证明MBF2基因家庭成员高度在不同阶段被表示。九MBF2家庭基因的表示模式的分析证明杆菌bombysepticus处理导致了几MBF2家庭基因的起来规定，包括MBF2-4，-7,-9,-8。而且，我们发现MBF2家庭基因被饥饿和在重新喂之上恢复的这些基因的表示调制，除了MBF2-5，-9。这些调查结果对病原体和滋养的新陈代谢在昆虫防卫为这些蛋白质建议了角色，它为设计害虫控制策略有重要指导意义。

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简介：AIM:TodeterminetheassociationbetweenchlamydialconjunctivitisandgenitalinfectionbyChlamydiatrachomatis,MycoplasmagenitaliumandCandidaalbicans,inadditiontothepossiblerelationshipbetweenculturedbacterialpathogensandoculogenitalchlamydialinfection.METHODS:Thisstudywasperformedon100(50symptomaticand50asymptomatic)womenattendingtheGynecologicalandObstetricoutpatientclinicofAlzahrahospital,AlazharUniversity.Simultaneouslyaconjunctivalswabwastakenfromthesepatients.Polymerasechainreaction(PCR)wasdoneonDNAextractedfrombothvaginalandconjunctivalswabsamples.Cultureforbothvaginalandconjunctivalswabswasalsodone.RESULTS:Candidaalbicanswasthepredominantorganismisolatedbyculturein20%and40%ofconjunctivalandvaginalswabsrespectively.BythePCRmethod,ocularChlamydiatrachomatiswaspresentin60%ofsymptomaticwomen,whilegenitalChlamydiatrachomatisinfectionwaspresentin30%ofsymptomaticwomen.Theresultsofthismethodalsoindicatedthat25/50(50%)vaginalswabswerepositivewithPCRforCandidaalbicansversus15/50(30%)werePCRpositiveinconjunctivalswab.Mycoplasmagenitaliumwaspresentinonly10%ofvaginalswabs.ConcomitantoculogenitalPCRpositiveresultsforChlamydiatrachomatisandCandidaalbicanswere30%and28%respectively.CONCLUSION:OcularChlamydiatrachomatiswasassociatedwithgenitalChlamydiatrachomatisinahighpercentageofwomenfollowedbyCandidaalbicans.CulturedbacterialorganismsdonotplayaroleinenhancementofChlamydiatrachomatisinfection.

简介：Interactionsbetweenecologicalcommunitiesofherbivoresandmicrobesarecommonlymediatedbyasharedplant.Atripartiteinteractionbetweenapathogenicfungus-hostplant-herbivorousinsectisanexampleofsuchmutualinfluences.Insuchasystemafungalpathogencommonlyhasanegativeinfluenceonthemorphologyandbiochemistryofthehostplant,withconsequencesforinsectherbivoreperformance.HerewestudiedwhetherthebiotrophicfbngusPodosphaeraferruginea,attackingthegreatburnetSanguisorbaofficinalis,affectscaterpillarperformanceoftheendangeredscarcelargebluebutterflyPhengaristeleius.Ourresultsshowedthatthepathogenicftmgusaffectedthenumberandsizeofinflorescencesproducedbyfood-plantsand,moreimportantly,hadindirect,plant-mediatedeffectsontheabundance,bodymassandimmuneresponseofcaterpillars.Specifically,wefoundtherelationshipbetweencaterpillarabundanceandvariabilityininflorescencesizeonaplanttobepositiveamonghealthyfood-plants,andnegativeamonginfectedfood-plants.Caterpillarsthatfedonhealthyfood-plantsweresmallerthanthosethatfedoninfectedfood-plantsinonestudiedseason,whiletherewasnosuchdifferenceintheotherseason.Weobservedtherelationshipbetweencaterpillarimmuneresponseandtheproportionofinfectedgreatburnetswithinahabitatpatchtobepositivewhencaterpillarsfedonhealthyfood-plants,andnegativewhencaterpillarsfedoninfectedfood-plants.OurresultssuggestthatthisbiotrophicfungalinfectionofthegreatburnetmayimposeasignificantindirectinfluenceonP.teleiuscaterpillarperformancewithpotentialconsequencesforthepopulationdynamicsandstructureofthisendangeredbutterfly.

简介：AbstractPurpose:COVID-19 is also referred to as a typical viral septic pulmonary infection by 2019-nCoV. However, little is known regarding its characteristics in terms of systemic inflammation and organ injury, especially compared with classical bacterial sepsis. This article aims to investigate the clinical characteristics and prognosis between COVID-19-associated sepsis and classic bacterial-induced sepsis.Methods:In this retrospective cohort study, septic patients with COVID-19 in the intensive care unit (ICU) of a government-designed therapy center in Shenzhen, China between January 14, 2020 and March 10, 2020, and septic patients induced by carbapenem-resistant klebsiella pneumonia (CrKP) admitted to the ICU of the Second People's Hospital of Shenzhen, China between January 1, 2014 and October 30, 2019 were enrolled. Demographic and clinical parameters including comorbidities, critical illness scores, treatment, and laboratory data, as well as prognosis were compared between the two groups. Risk factors for mortality and survival rate were analyzed using multivariable logistic regression and survival curve, respectively.Results:A total of 107 patients with COVID-19 and 63 patients with CrKP were enrolled. A direct comparison between the two groups demonstrated more serious degrees of primary lung injury following 2019-nCoV infection (indicated by lower PaO2/FiO2), but milder systemic inflammatory response, lower sequential organ failure assessment score and better functions of the organs like heart, liver, kidney, coagulation, and circulation. However, the acquired immunosuppression presented in COVID-19 patients was more severe, which presented as lower lymphocyte counts (0.8×109/L vs. 0.9×109/L). Moreover, the proportion of COVID-19 patients treated with corticosteroid therapy and extracorporeal membrane oxygenation was larger compared with CrKP patients (78.5% vs. 38.1% and 6.5% vs. 0, respectively) who required less invasive mechanical ventilation (31.6% vs. 54.0%). The incidence of hospitalized mortality and length of ICU stay and total hospital stay were also lower or shorter in viral sepsis (12.1% vs. 39.7%, 6.5 days vs. 23.0 days and 21.0 days vs. 33.0 days, respectively) (all p < 0.001). Similar results were obtained after being adjusted by age, gender, comorbidity and PaO2/FiO2. Lymphocytopenia and high acute physiology and chronic health evaluation II scores were common risk factors for in-hospital death. While the death cases of COVID-19 sepsis mostly occurred at the later stages of patients’ hospital stay.Conclusion:Critical COVID-19 shares clinical characteristics with classical bacterial sepsis, but the degree of systemic inflammatory response, secondary organ damage and mortality rate are less severe. However, following 2019-nCoV infection, the level of immunosuppression may be increased and thus induce in more death at the later stage of patients’ hospitalstay.

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简介：ToinvestigatethephenotypicknockoutofHIV-1chemokinecoreceptorCXCR4andCCR5byintrakinesanditsinhibitoryeffectonHIV-1infection.PrimaryhumanPBLsweretransducedwiththerecombinantvectorpLNCX-R-K-S-K(△NGFR),followedbyanti-NGFR/anti-IgG-magneticbeadmethodselectionandFCMdetection.ThetransducedPBLswereinfectedwithDP1HIV-1virusthereafterenvelope-mediatedsyncytiumformationandp24detectionwerecarriedouttostudytheblockageofHIV-1infectionbyco-inactivationofCCR5andCXCR4.pLNCX-R-K-S-K(△NGFR)-transducedPBILswereisolatedwithananti-NGFR/anti-IgG-magneticbeadmethod.Afterisolation,about70%ofthePBLswerepositivefortheNGFRmarker.WhenthetransducedPBLswereinfectedwithDP1HIV-1virus,envelop-mediatedsyncytiumformationwasalmostcompletelyinhibitedbypLNCX-R-K-S-K(△NGFR)transfection.Also,p24antigenwasverylowintheculturesofpLNCX-R-K-S-K(△NGFR)transducedPBLs.pLNCX-R-K-S-K(△NGFR)transductioninhibitedtheproductionofDP1p24antigenby15%,43%and19%ondays4,7and10respectively.ThelymphocyteswiththephenotypicknockoutofCCR5andCXCR4couldprotectprimaryhumanPBLsfromDP1HIV-1virusinfection.

简介：瞄准：为了学习流行和风险因素，与人的免疫不全与三倍的感染联系了在一张城市的诊所人口的病毒(HIV)/hepatitisB(HBV)/hepatitisC病毒(HCV)。方法：5639个病人的回顾的图表评论在纽约城市里在圣卢凯斯鲁塞韦尔特医院HIV诊所(全面照顾的中心)列在后面，从1999年1月的美国到2007年5月。下列人口统计的特征被分析：年龄，性别，种族和HIV冒因素的风险。多重逻辑回归分析被执行在这些病毒的获得上评估人口统计的因素的影响。结果：HIV/HBV，HIV/HCV和HIV/HBV/HCV感染在252/5639(4.47%)被检测，1411/5639(25.02%)和89/5639(1.58%)病人分别地。HIV/HBV合作感染与男性被联系(或1.711；P=0.005)，黑色跑(或2.091；P<0.001)，人与\O性交人(MSM)(或1.747；P=0.001)，静脉内的药使用(IDU)(或0.114；P<0.001)，IDU和异性爱的活动(或0.247；P=0.018)，或未知(或1.984；P=0.004)。HIV/HCV合作感染与男性被联系(或1.241；P=0.011)，黑色跑(或0.788；P=0.036)，MSM(或0.565；P<0.001)，IDU(或8.956；P<0.001)，IDU和异性爱的活动(或9.106；P<0.001)，IDU和MSM(或9.179；P<0.001)，或输送(或3.224；P<0.001)。HIV/HBV/HCV合作感染与男性被联系(或2.156；P=0.015)，IDU(或6.345；P<0.001)，IDU和异性爱的活动(或9.731；P<0.001)，IDU和MSM(或9.228；P<0.001)，或未知(或4.219；P=0.007)。结论：我们的学习证明有HBV/HCV/HIV的合作感染显著地与IDU被联系。这些结果加亮需要加强教育和综合照顾的最佳的模型，特别地为有IDU的人口，到减少病毒的传播的风险。

简介：AbstractThe coronavirus disease 2019 (COVID-19) pandemic was triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a previously unknown strain of coronavirus. To fully understand the consequences and complications of SARS-CoV-2 infections, we have reviewed current literature on coagulation dysfunctions that are related to the disease and vaccination. While COVID-19 is more commonly considered as a respiratory illness, studies indicate that, in addition to respiratory illness, a coagulation dysfunction may develop in individuals after the initial infection, placing them at the risk of developing thrombotic events. Patients who died of COVID-19 had higher levels of D-dimer, a biomarker for blood clot formation and breakdown. Effective treatments for coagulation dysfunctions are critically needed to improve patient survival. On the other hand, antibodies against platelet factor 4 (PF4)/heparin may be found in patients with rare instances of vaccine-induced immunological thrombotic thrombocytopenia (VITT) following vaccination with adenovirus-based vaccines. VITT is characterized by atypical thrombosis and thrombocytopenia, similar to immune-mediated heparin-induced thrombocytopenia (HIT), but with no need for heparin to trigger the immune response. Although both adenovirus-based and mRNA-based vaccines express the Spike protein of SARS-CoV-2, VITT is exclusively related to adenovirus-based vaccines. Due to the resemblance with HIT, the use of heparin is highly discouraged against treating patients with thrombotic thrombocytopenia after SARS-CoV-2 infection or with VITT after vaccination. Intravenous immunoglobulin therapy coupled with anticoagulation is recommended instead. The well-studied anti-PF4 monoclonal antibody RTO, which does not induce pathologic immune complexes in the presence of heparin and has been humanized for a potential treatment modality for HIT, may provide a nonanticoagulant HIT-specific solution to the problem of increased blood coagulation after SARS-CoV-2 infection or the VITT after immunization.

简介：AbstractBackground:Differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) has been a challenge for clinicians in high TB burden countries. The purpose of this study was to improve the accuracy of differential diagnosis of ATB and LTBI by using fluorescent immunospot (FluoroSpot) assay to detect specific Th1 cell immune responses. The novel mycobacterium tuberculosis (MTB) latency-associated antigens Rv1733c and synthetic long peptides derived from Rv1733c (Rv1733c SLP) were used based on virulence factors early secreting antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10).Methods:Fifty-seven ATB cases, including 20 pathogen-confirmed ATB and 37 clinically diagnosed ATB, and 36 LTBI cases, were enrolled between January and December 2017. FluoroSpot assay was used to detect the interferon γ (IFN-γ) and interleukin 2 (IL-2) secreted by the specific T cells after being stimulated with MTB virulence factors ESAT-6 and CFP-10, MTB latency-associated antigens Rv1733c and Rv1733c SLP. The receiver operating characteristic (ROC) curve was used to define the best cutoff value of latency-associated antigens in the use of differentiating ATB and LTBI. The sensitivity, specificity, predictive value, and likelihood ratio of ESAT-6 and CFP-10-FluoroSpot combined with latency-associated antigen in the differential diagnosis of ATB and LTBI were also calculated.Results:Following the stimulation with Rv1733c and Rv1733c SLP, the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP had the largest area under the ROC curve, which was 0.766. With a cutoff value of 1 (spot-forming cells [SFCs]/2.5 × 105 peripheral blood mononuclear cells) for frequency, the sensitivity and specificity of distinguishing ATB from LTBI were 72.2% and 73.7%, respectively. ESAT-6 and CFP-10-FluoroSpot detected the frequency and proportion of single IFN-γ-secreting T cells; the sensitivity and specificity of distinguishing ATB from LTBI were 82.5% and 66.7%, respectively. Combined with the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP on the basis of ESAT-6 and CFP-10-FluoroSpot, the sensitivity and specificity increased to 84.2% and 83.3%, respectively.Conclusion:Rv1733c SLP, combined with ESAT-6 and CFP-10, might be used as a candidate antigen for T cell-based tuberculosis diagnostic tests to differentiate ATB from LTBI.

简介：AbstractBackground:Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.Methods:We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.Results:Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression.Conclusion:This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

简介：流行性感冒A病毒(IAV)感染是一个主要全球公共的健康问题。然而，因素在调停包含了煽动性的反应到这感染和他们糟糕理解的关系遗体。这里，我们证明IAV感染刺激可溶的IL-6受体(sIL-6R)的表示，涉及IL-6发信号的多功能的蛋白质。有趣地，sIL-6R表示upregulated它的自己的ligand，支持inflammatorycytokineIL-32的IL-6和那些的层次。调停shRNAsIL-6R击倒压制的IL-6和IL-32，显示这条规定在IAV感染期间依赖于sIL-6R。而且，我们的结果证明IL-32参予禁止sIL-6R的一个否定反馈环当时upregulatingIL-6表示在IAV感染期间。因此，我们证明sIL-6R是涉及对病毒的感染的尖锐煽动性的反应的一个关键细胞的因素。