Oral S2-Ag85 DNA Vaccine Activated Intestinal Cell dsDNA and RNA Sensors to Promote the Presentation of Intestinal Antigen.

Objective: To explore the molecular mechanism by which oral S2-Ag85DNA vaccines present intestinal antigens. The oral S2-Ag85 vaccine has been shown to protect the human body and effectively improve the titration of the vaccine by acting on intestinal mucosa cells and enhancing their immunogenicity. Method: Mice were immunized with the recombinant S2-Ag85 vaccine, and antibody secretion was then detected in the intestinal tissue. The molecular mechanisms of in vitro detection sensor molecules RIG-1, Pol III, and related conductor transductor molecules DAI, STING, AIM2, IRF3, and IRF7 were determined by separating intestinal IEC, DC, and IELC cells. Results: The S2-Ag85A vaccine was effective in activating dsDNA and RNA transduction pathways in intestinal cells and improving intestinal antigen presentation in mice.

Transcriptome sequencing revealed the inhibitory mechanism of ketoconazole on clinical Microsporum canis

Background@#Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. @*Objectives@#In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood.The antifungal mechanism of KTZ needs to be studied in detail. @*Methods@#In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis.The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. @*Results@#At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. @*Conclusions@#The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

Long-Term Persistence of IgG Antibodies in SARS-CoV Infected Healthcare Workers

BACKGROUNDThe ongoing worldwide outbreak of the 2019-nCoV is markedly similar to the severe acute respiratory syndrome (SARS) outbreak 17 years ago. During the 2002-2003 SARS outbreak, healthcare workers formed a special population of patients. Although virus-specific IgG play important roles in virus neutralization and prevention against future infection, limited information is available regarding the long term persistence of IgG after infection with SARS-like coronavirus. METHODSA long-term prospective cohort study followed 34 SARS-CoV-infected healthcare workers from a hospital with clustered infected cases during the 2002-2003 SARS outbreak in Guangzhou, China, with a 13-year follow-up. Serum samples were collected annually from 2003-2015. Twenty SARS-CoV-infected and 40 non-infected healthcare workers were enrolled in 2015, and their serum samples were collected. All sera were tested for IgG antibodies with ELISA using whole virus and a recombinant nucleocapsid protein of SARS-CoV, as a diagnostic antigen. RESULTSAnti SARS-CoV IgG was found to persist for up to 12 years. IgG titers typically peaked in 2004, declining rapidly from 2004-2006, and then continued to decline at a slower rate. IgG titers in SARS-CoV-infected healthcare workers remained at a significantly high level until 2015. Patients treated with corticosteroids at the time of infection were found to have lower IgG titers than those without. CONCLUSIONSIgG antibodies against SARS-CoV can persist for at least 12 years. The presence of SARS-CoV IgG might provide protection against SARS-CoV and other betacoronavirus. This study provides valuable information regarding humoral immune responses against SARS-CoV and the 2019-nCoV.

Distribution of the 2019-nCoV Epidemic and Correlation with Population Emigration from Wuhan, China

BACKGROUNDSThe ongoing new coronavirus (2019-nCoV) pneumonia outbreak is spreading in China and has not reached its peak. Five millions of people had emigrated from Wuhan before the city lockdown, which potentially represent a source of virus spreaders. Case distribution and its correlation with population emigration from Wuhan in early epidemic are of great importance for early warning and prevention of future outbreak. METHODSThe officially reported cases of 2019-nCoV pneumonia were collected as of January 30, 2020. Time and location information of these cases were extracted analyzed with ArcGIS and WinBUGS. Population migration data of Wuhan City and Hubei province were extracted from Baidu Qianxi and analyzed for their correlation with case number. FINDINGSThe 2019-nCoV pneumonia cases were predominantly distributed in Hubei and other provinces of South China. Hot spot provinces included Sichuan and Yunnan provinces that are adjacent to Hubei. While Wuhan city has the highest number of cases, the time risk is relatively stable. Numbers of cases in some cities are relatively low, but the time risks are continuously rising. The case numbers of different provinces and cities of Hubei province were highly correlated with the emigrated populations from Wuhan. Lockdown of 19 cities of Hubei province, and implementation of nationwide control measures efficiently prevented the exponential growth of case number. INTERPRETATIONPopulation emigrated from Wuhan was the main infection source for other cities and provinces. Some cities with low case number but were in rapid increase. Due to the upcoming Spring Festival return transport wave, understanding of the trends of risks in different regions is of great significance for preparedness for both individuals and institutions. FUNDINGSNational Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, State Key Program of National Natural Science of China.

From SARS-CoV to Wuhan 2019-nCoV: Will History Repeat Itself?

This manuscript has been withdrawn as it was submitted without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Distribution of the COVID-19 Epidemic and Correlation with Population Emigration from Wuhan, China / 中华医学杂志(英文版)

Background The ongoing new coronavirus pneumonia (Corona Virus Disease 2019,COVID-19) outbreak is spreading in China, but it has not yet reached its peak. Five million people emigrated from Wuhan before lockdown, potentially representing a source of virus infection. Determining case distribution and its correlation with population emigration from Wuhan in the early stage of the epidemic is of great importance for early warning and for the prevention of future outbreaks. Methods The official case report on the COVID-19 epidemic was collected as of January 30, 2020. Time and location information on COVID-19 cases was extracted and analyzed using ArcGIS and WinBUGS software. Data on population migration from Wuhan City and Hubei province were extracted from Baidu Qianxi, and their correlation with the number of cases was analyzed. Results The COVID-19 confirmed and death cases in Hubei province accounted for 59.91% (5806/9692) and 95.77% (204/213) of the total cases in China respectively. Hot spot provinces included Sichuan and Yunnan, which are adjacent to Hubei. The time risk of Hubei province on the following day was 1.960 times that on the previous day. The number of cases in some cities was relatively low, but the time risk appeared to be continuously rising. The correlation coefficient between the provincial number of cases and emigration from Wuhan was up to 0.943. The lockdown of 17 cities in Hubei province and the implementation of nationwide control measures efficiently prevented an exponential growth in the number of cases. Conclusion The population that emigrated from Wuhan was the main infection source in other cities and provinces. Some cities with a low number of cases showed a rapid increase in case load. Owing to the upcoming Spring Festival return wave, understanding the risk trends in different regions is crucial to ensure preparedness at both the individual and organization levels and to prevent new outbreaks.

Expression pattern of MiR-146a and its correlation with antibody titers in human brucellosis / 中国免疫学杂志

Objective:To investigate the expression pattern of microRNA-146a in Brucella patients and its correlation with antibody titers.Methods: By using real time PCR assay, expression levels of microRNA-146a in sera samples from 20 brucellosis patients and 20 healthy volunteers were analyzed.The correlation between expression level of microRNA-146a and serum antibody titers were analyzed with SPSS17.0.Results: A quantification curve of microRNA-146a was constructed with synthesized standard.Expression levels of microRNA-146a among brucellosis patients were significantly lower than those in 20 healthy volunteers (P<0.001).For brucellosis patients,the expression level of microRNA-146a was negatively related with antibody titers (P<0.05). Conclusion:Expression of miRNA-146a in brucellosis patients was significantly inhibited and negatively related with antibody titer.

Luciferase expression is driven by the promoter of fibroblast activation protein-α in murine pulmonary fibrosis.

OBJECTIVES: We used optical imaging of live animals and transgenic technology to develop a pulmonary fibrosis model in mice that can non-invasively and in real-time trace the pulmonary fibrosis process. RESULTS: Fibroblast activation protein-α (FAPα) is selectively expressed in fibrotic foci of human pulmonary fibrosis. It is not expressed in normal tissue. We confirmed that FAPα is upregulated in fibroblasts of murine pulmonary fibrosis. Moreover, TGF-ß1, a central pathological mediator of fibrotic diseases, could promote FAPα expression in mouse embryonic fibroblasts. Luciferase reporter assays showed that 5.4 kb FAPα promoter response activities to TGF-ß1 was stronger than of the 2.1 kb promoter. We generated a transgenic mouse line expressing firefly luciferase under the control of the 5.4 kb FAPα gene promoter (FAPα-p-luc). After experimentally inducing murine pulmonary fibrosis, there luminescence appeared in the chests and excised lungs of FAPα-p-luc mice. The intensity of luminescence became stronger with the exacerbation of pulmonary fibrosis. CONCLUSION: Fluorescence intensity reflects the degree of pulmonary fibrosis in FAPα-p-luc mice. and this mouse model may be used to investigate molecular mechanisms and drug screening of pulmonary fibrosis.

Identification of novel transcripts and sRNA of Brucella melitensis by RNA-Seq / 中国人兽共患病学报

To identify novel transcripts and sRNA in genome of B .melitensis by transcriptome sequencing ,total RNA were extracted from B .melitensis culture and rRNA were removed .After the addition of adaptor ,RNA was reversely transcribed into cDNA ,which were then subjected to PCR amplification and sequencing .The generated reads were mapped to genome se‐quence of B .melitensis strain 16M .With the mapping results ,novel transcripts and sRNA were identified by bioinformatics methods .Sequencing results analysis showed that genome sequence was covered with the reads with good quality .A total of 773 genes were extended in their 5′and/or 3′ends of their original locations .Sixteen novel transcripts and 241 sRNAs candi‐dates were identified .RT‐PCR showed that some of the sRNAs were differentially expressed under stress conditions .In B . melitensis genome ,there is novel transcript which is not predicted .The sRNA does exist in B .melitensis and were expressed under different conditions .

Western area surge for controlling Ebola hemorrhagic fever outbreak in Sierra Leone and evaluation of its effect / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the Western Area Surge (WAS) program in the Ebola outbreak of Sierra Leone, and to analyze its implementing effect.</p><p><b>METHODS</b>The subject of this study was 3,813 laboratory confirmed Ebola hemorrhagic fever (EHF) cases reported in Sierra Leone from November 19, 2014 through January 27, 2015, a period before and after the implementation of the WAS program. To analyze and make conclusions according to the working experience of China Mobile Laboratory Reponses Team in the fight of Ebola outbreak, using WHO published EHF case definition to make diagnosis and compare the number of bed numbers, confirmed EHF cases, samples tested, and positive rates before and after implementation of WAS program.</p><p><b>RESULTS</b>From the implementation of WAS program on 17th December 2014 to half a month later, the total numbers of Ebola holding and treatment centers increased from 640 to 960, six additional laboratories were established. On January, 2015, another two laboratories from America and The Netherlands were established. The numbers of samples tested one month before and after WAS program were 7,891 and 9,783, respectively, with an increase of 24.0 percent, while the positive rate of Ebola virus decreased from 22.2% (1,752/7,891) to 11.0% (1,077/9,783). The positive rate of blood samples decreased from 39.6% (248/626) in the month before WAS program to 27.4% (131/478) (χ2=17.93, P<0.001) in the mother after WAS program, the positive rate of blood samples 22.7% (103/454) to 10% (62/609) (χ2=31.03, P<0.001), accordingly. After 3 weeks of WAS program, in addition to Western Area, another four hotspots in Sierra Leone had also reported a significant decrease of the numbers of confirmed EVD cases. Forty-two days after implementation of WAS program, the daily number of laboratory confirmed EHF cases decreased from 63 to 10.</p><p><b>CONCLUSION</b>WAS program played a vital role in controlling the EHF outbreak rapidly in Sierra Leone. It could also provide guidance for the control similar large infectious diseases outbreak in the future.</p>

Transcriptional analysis of Brucella virulence regulation genes under stress conditions and during cell infection / 中华微生物学和免疫学杂志

Objective To study the important virulence regulation genes of Brucella,and to understand their function.Methods Quantitative RT-PCR was used to quantify their relative transcription profiles under stress conditions and during macrophage cell infection.Results These genes were activated at different levels under these conditions and during cell infection,indicating their roles in pathogenesis at different srage of infection.Conclusion The transcription profiles of these genes have different effects about their functions.