Detection of Human Bocavirus in Children with Acute Respiratory Tract Infections in Lanzhou and Nanjing,China

Objective The aim of this study was to explore the prevalent characteristics of HBoV1 and its co-infection.Methods PCR was used to detect HBoV1-DNA（HBoV1） and other viruses.A multivariate logistic regression model was used to explore possibility of co-detected for related viruses.Results The positivity rates in Nanjing and Lanzhou were 9.38%（74/789） and 11.62%（161/1386）,respectively（P〉0.05）.The HBoV1 positive group was younger than negative group（P〈0.05）.Seasonal differences were noted,with a higher frequency of infection in December and July.HBoV1-positive children [72.34%（169/235）] were co-infected with other respiratory viruses.Multifactorial analysis showed no correlations between HBoV1 and the clinical classification,region,gender,age,or treatment as an outpatient or in a hospital.Correlations were identified between HBoV1 infections with ADV（OR=1.53,95% CI 1.03-2.28）,RSV（OR=0.71,95% CI 0.52-0.98）,and IFVA（OR=1.77,95% CI 1.00-3.13）.Conclusions Presence of HBoV1 in nasopharyngeal aspirates did not correlate with region or gender,although the prevalence of HBoV1 was higher in younger children.There were no correlations between HBoV1 and other variables,except for the season and ADV,RSV,or IFVA infections.

In vitro study on the antiviral activity of 9 extracts of traditional Chinese herbal medicine against the human respiratory syncytial virus

Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea officinalis and Elaeagnus gonyanthes,the alcohol extracts of Nauclea officinalis,Elaeagnus gonyanthes and Zanthoxylumarmatum)on human respiratory syncytial virus(HRSV).Methods:The cytotoxic effect of the extracts on cells was evaluated by a cell viability assay using the CCK-8 method,a concentration of the extracts with cell viability greater than 50%was selected for the follow-up anti-HRSV effect assay,the 50%effective concentration(EC50)was assessed by an in vitro cell infection model.Results:The EC50s of the water extract from Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes were 0.05 mg/mL,0.03 mg/mL and 0.05 mg/mL,and the therapeutic index(TI)of them were 18.60,21.67 and 56.80 respectively.Conclusion:The water extracts of Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes possess the activity of anti-HRSV virus.

Genetic Characterization of Fusion Protein of Human Respiratory Syncytial Virus: Beijing

Objective Fusion protein is a subunit of the human respiratory syncytial virus(HRSV)and a potential vaccine candidate.Thus,a study on the genetic characteristics of F protein was considered important for further investigations in this field.The aim of this study was to determine the prevalence and genetic diversity of the F gene of HRSV infections in hospitalized pediatric patients in Beijing with acute lower respiratory tract infections and to compare the circulating genotypes that are currently found worldwide.Methods HRSV particles were amplified by RT-PCR and the PCR products were purified for sequencing.Further analysis was carried out by Bioedit and MEGA 3.0 biological software programs.Results Seventy-six samples(23.1%)were positive for HRSV.The percentage of cases in patients younger than 1year was 84.21%.Among the six Beijing isolates,four belonged to subgroup A,whose respective F genes shared97.0%-97.4%nucleotide sequence identity and 92.1%-93.0%amino acid sequence identity.The other two isolates belonged to subgroup B.Here,97.3%and 98.2%sequence identity were found at nucleotide and amino acid levels,respectively.Conclusions Phylogenetic analysis of nucleotide sequences revealed that those four isolates within subgroup A were monophyletic and closely related to each other,but those two within subgroup B distributed in two distinct clusters.Subgroup A and B strains co-circulated,indicating that two different transmission chains occurred in Beijing from 2003-2004.

HEAT TRANSPORT IN HUMAN RESPIRATORY TRACT: A MATHEMATICAL MEDOL AND ITS ANALYTICAL SOLUTION

In this paper a mathematical model of heat transport in human respiratory tract was developed and solved analytically. By means of computer, the mean intra-temperature was calculated. It was consistent with the experimenatal data.

Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates

Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice.The constructed recombinant plasmids harbored(5′to 3′)a T7 promoter,hammerhead ribozyme,RSV Long strain antigenomic cDNA with cold-passaged(cp)mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain(A2cpts)or further combined with SH gene deletion(A2cptsΔSH),HDV ribozyme(δ),and a T7 terminator.These vectors were subsequently co-transfected with four helper plasmids encoding N,P,L,and M2-1 viral proteins into BHK/T7-9 cells,and the recovered viruses were then passaged in Vero cells.The rescued recombinant RSVs(rRSVs)were named rRSV-Long/A2cp,rRSV-Long/A2cpts,and rRSV-Long/A2cptsΔSH,respectively,and stably passaged in vitro,without reversion to wild type(wt)at sites containing introduced mutations or deletion.Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed temperature-sensitive(ts)phenotype in vitro and in vivo,all rRSVs were significantly attenuated in vivo.Furthermore,BALB/c mice immunized with rRSVs produced Th1-biased immune response,resisted wtRSV infection,and were free from enhanced respiratory disease.We showed that the combination ofΔSH with attenuation(att)mutations of cpts contributed to improving att phenotype,efficacy,and gene stability of rRSV.By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains,we have laid an important foundation for the development of RSV live attenuated vaccines.

A multi-center study on Molecular Epidemiology of Human Respiratory Syncytial Virus from Children with Acute Lower Respiratory Tract Infections in the Mainland of China between 2015 and 2019

Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.

Numerical simulation of micro-particle deposition in a realistic human upper respiratory tract model during transient breathing cycle

An more reliable human upper respiratory tract model that consisted of an oropharynx and four generations of asymmetric tracheo-bronchial （TB） airways has been constructed to investigate the micro-particle deposition pattern and mass distribution in five lobes under steady inspiratory condition in former work by Huang and Zhang （2011 ）. In the present work, transient airflow patterns and particle deposition during both inspiratory and expiratory processes were numerically simulated in the realistic human upper respiratory tract model with 14 cartilaginous rings （CRs） in the tracheal tube. The present model was validated under steady inspiratory flow rates by comparing current results with the theoretical models and pub- lished experimental data. The transient deposition fraction was found to strongly depend on breathing flow rate and particle diameter but slightly on turbulence intensity. Particles were mainly distributed in the high axial speed zones and traveled basically following the secondary flow. ＂Hot spots＂ of deposition were found in the lower portion of mouth cavity and posterior wall of pharynx/larynx during inspiration, but transferred to upper portion of mouth and interior wall of pharynx/larynx during expiration. The deposition fraction in the trachea during expiration was found to be much higher than that during inspiration because of the stronger secondary flow.

An RNA polymerase I-driven human respiratory syncytial virus minigenome as a tool for quantifying virus titers and screening antiviral drug

Human respiratory syncytial virus（RSV） is an important pediatric pathogen of lower respiratory tract worldwide. No vaccines and antiviral drugs are available. Herein the use of an RNA polymerase I-driven RSV minigenome for analyzing RSV replication and screening anti-RSV drugs was investigated. The RNA polymerase I（Pol I） was used to transcribe RSV minigenome from the constructed plasmid, designated p HM-RSV-Gluc, of minigenome c DNA which comprised trailer region, gene start sequence（GS）, reverse complementary copy of Gaussia luciferase（Gluc） gene, gene end sequence（GE）, and leader region in the direction of 5＇–3＇end and was flanked by promoter and terminator of Pol I. The expression of Gluc was confirmed in p HM-RSV-Gluc transfected HEp-2 cells following RSV infection and had the characteristics of dose-dependent, which provided a rapid, sensitive, and quantitative method for quantifying virus titers and screening antiviral drugs.

Cryo-EM structure of human respiratory megacomplex

With the support by the National Natural Science Foundation of China,the group of Yang Maojun（杨茂君）firstly solved the medium resolution structure of human respiratory megacomplex Ⅰ2Ⅲ2Ⅳ2 and the atomic structure of the supercomplex Ⅰ1Ⅲ2Ⅳ1in the world.The results were published in Cell(2017,

Fast-response,high-sensitivity multi-modal tactile sensors based on PPy/Ti_(3)C_(2)T_(x) films for multifunctional applications

In recent years,multi-modal flexible tactile sensors have become an important direction in the development of electronic skin because of their excellent sensitivity,flexibility and wearable properties.In this work,a humidity-pressure multi-modal flexible sensor based on polypyrrole(PPy)/Ti_(3)C_(2)T_(x) sensitive film packaged with porous polydimethylsiloxane(PDMS)is investigated by combining the sensitive structure generation mechanism of in situ polymerization to achieve the simultaneous detection of humidity and pressure,which has a sensitivity of 89,113.4Ω/%RH in a large humidity range of 0%-97%RH,and response/recovery time of 2.5/1.9 s.The tactile pressure sensing has a high sensitivity,a fast response of 67/52 ms,and a wide detection limit.The device also has excellent performance in terms of stability and repeatability,making it promising for respiratory pattern and motion detection.This work provides a new solution to address the construction of multi-modal tactile sensors with potential applications in the fields of medical health,epidemic prevention.

Recent progress of diversiform humidity sensors based on versatile nanomaterials and their prospective applications

Humidity sensors are of significance in various fields,such as environmental and food quality monitoring,industrial processing,wearable and flexible electronics,and human health care.High-performance humidity sensors with high sensitivity,rapid response time,and good stability are of paramount importance in humidity sensing.In this paper,diversiform humidity sensors with different sensing mechanisms are summarized,including resistive,impedance,capacitive,quartz crystal microbalance(QCM),surface acoustic wave(SAW),field-effect transistor(FET),and optical fiber humidity sensors.Versatile nanomaterials such as graphene,transition-metal chalcogenide,MXenes,black phosphorus(BP),boron nitride(BN),polymers,and nanofibers were promising building-blocks for constructing humidity sensors.The latest progress in the wearable and flexible humidity sensors,and self-powered humidity sensors was summarized.The diversiform applications of the humidity sensors with great prospects were demonstrated in various fields in terms of human respiratory monitoring,skin dryness diagnosing,fingertip approaching,and non-contact switch.Moreover,the challenges and prospects of nanomaterials-based humidity sensors were discussed.