Objective:To analyze the combined therapeutic effect of clopidogrel(CLO)and aspirin(ASP)on coronary heart disease(CHD)in community-dwelling elderly.Methods:Thirty elderly patients with CHD who were admitted to the Xin...Objective:To analyze the combined therapeutic effect of clopidogrel(CLO)and aspirin(ASP)on coronary heart disease(CHD)in community-dwelling elderly.Methods:Thirty elderly patients with CHD who were admitted to the Xinxin Community Health Service Station,Pangzhuang Street,Quanshan District,Xuzhou City,from November 2020 to November 2022 were selected and randomly grouped into an observation group and a control group,with 15 cases in each group.The observation group was given the combination of CLO and ASP and the reference group was given only ASP.The total effective rate and other treatment indicators between the two groups were compared.Results:The total effective rate of the observation group(93.33%)was higher than that of the reference group(60.00%)(P<0.05).The adverse drug reaction rate(13.33%)and long-term cardiovascular adverse event rate(6.67%)of the observation group were lower than those of the reference group at 46.67%and 40.00%respectively,(P<0.05).Before treatment,the two groups had no difference in the quality-of-life scores(P>0.05).After treatment,the quality-of-life scores of the observation group were higher than those of the reference group(P<0.05).Conclusion:CLO combined with ASP improved the therapeutic effect of community-dwelling elderly patients with CHD,reduced adverse reactions during medication,prevented adverse cardiovascular events,and comprehensively improved the patient’s quality of life.展开更多
Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of internatio...Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.展开更多
Tea plants(Camellia sinensis)are commercially cultivated in>60 countries,and their fresh leaves are processed into tea,which is the most widely consumed beverage in the world.Although several chromosome-level tea p...Tea plants(Camellia sinensis)are commercially cultivated in>60 countries,and their fresh leaves are processed into tea,which is the most widely consumed beverage in the world.Although several chromosome-level tea plant genomes have been published,they collapsed the two haplotypes and ignored a large number of allelic variations that may underlie important biological functions in this species.Here,we present a phased chromosome-scale assembly for an elite oolong tea cultivar,"Huangdan",that is well known for its high levels of aroma.Based on the two sets of haplotype genome data,we identi fi ed numerous genetic variations and a substantial proportion of allelic imbalance related to important traits,including aroma-and stress-related alleles.Comparative genomics revealed extensive structural variations as well as expansion of some gene families,such as terpene synthases(TPSs),that likely contribute to the high-aroma characteristics of the backbone parent,underlying the molecular basis for the biosynthesis of aroma-related chemicals in oolong tea.Our results uncovered the genetic basis of special features of this oolong tea cultivar,providing fundamental genomic resources to study evolution and domestication for the economically important tea crop.展开更多
The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary...The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem repeats.Here we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland.We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens.Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes.Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences.Besides,several intra-host single nucleotide variations were identified in the first imported mpox case.This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens.The findings of this study will significantly enhance the surveillance of MPXV.展开更多
Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently.Its leaves have been traditionally used to treat obesity and diabetes with the well-known a...Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently.Its leaves have been traditionally used to treat obesity and diabetes with the well-known active ingredient cyclocaric acid B.Here,we presented three C.paliurus genomes from two diploids with different flower morphs and one haplotype-resolved tetraploid assembly.Comparative genomic analysis revealed two rounds of recent whole-genome duplication events and identified 691 genes with dosage effects that likely contribute to adaptive evolution through enhanced photosynthesis and increased accumulation of triterpenoids.Resequencing analysis of 45 C.paliurus individuals uncovered two bottlenecks,consistent with the known events of environmental changes,and many selectively swept genes involved in critical biological functions,including plant defense and secondary metabolite biosynthesis.We also proposed the biosynthesis pathway of cyclocaric acid B based on multi-omics data and identified key genes,in particular gibberellinrelated genes,associated with the heterodichogamy in C.paliurus species.Our study sheds light on evolutionary history of C.paliurus and provides genomic resources to study the medicinal herbs.展开更多
Introduction:The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has generated 2,431 variants over the course of its global transmission over the past 3 years.To better evaluate the genomic variation of SAR...Introduction:The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has generated 2,431 variants over the course of its global transmission over the past 3 years.To better evaluate the genomic variation of SARS-CoV-2 before and after the optimization of coronavirus disease 2019(COVID-19)prevention and control strategies,we analyzed the genetic evolution branch composition and genomic variation of SARS-CoV-2 in both domestic and imported cases in China(the data from Hong Kong and Macao Special Administrative Regions and Taiwan,China were not included)from September 26,2022 to January 29,2023.Methods:Analysis of the number of genome sequences,sampling time,dynamic changes of evolutionary branches,origin,and clinical typing of SARS-CoV-2 variants submitted by 31 provincial-level administrative divisions(PLADs)and Xinjiang Production and Construction Corps(XPCC)was conducted to assess the accuracy and timeliness of SARS-CoV-2 variant surveillance.Results:From September 26,2022 to January 29,2023,20,013 valid genome sequences of domestic cases were reported in China,with 72 evolutionary branches.Additionally,1,978 valid genome sequences of imported cases were reported,with 169 evolutionary branches.The prevalence of the Omicron variants of SARS-CoV-2 in both domestic and imported cases was consistent with that of international epidemic variants.Conclusions:This study provides an overview of the prevalence of Omicron variants of SARS-CoV-2 in China.After optimizing COVID-19 prevention and control strategies,no novel Omicron variants of SARSCoV-2 with altered biological characteristics or public health significance have been identified since December 1,2022.展开更多
Metagenomic next-generation sequencing(mNGs)has been widely applied to identify pathogens associated with infectious diseases.However,limited studies have explored the use of mNGs-based dynamic pathogen monitoring in ...Metagenomic next-generation sequencing(mNGs)has been widely applied to identify pathogens associated with infectious diseases.However,limited studies have explored the use of mNGs-based dynamic pathogen monitoring in intensive care unit patients with severe pneumonia.Here,we present a clinical case of an 86-year-old male patient with severe pneumonia caused by a fungal infection.During the clinical treatment,four mNGS analyses were performed within two consecutive weeks.Various respiratory fungal pathogens,including Candida orthopsilosis,Candida albicans,and Aspergillus fumigatus were detected by mNGS of bronchoalveolar lavage fluid(BALF).Based on conventional pathogen identification and clinical symptoms,the patient was diagnosed with severe pneumonia caused by a fungal infection.The abundance of fungal species decreased gradually in response to antifungal and empirical therapies,and the fungal infections were effectively con-trolled.In summary,our results demonstrated that mNGS could effectively identify pathogens in patients with severe pneumonia.Additionally,dynamic pathogen monitoring based on mNGS could assist in the precise diag-nosis of complex infections and may facilitate rapid induction of the most appropriate therapy.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a single-stranded positive RNA virus,exhibits a high rate of genome mutation and recombination(1–2).Recombinant strains of this virus could potentially affe...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a single-stranded positive RNA virus,exhibits a high rate of genome mutation and recombination(1–2).Recombinant strains of this virus could potentially affect their binding ability to the ACE2 receptor,which may in turn diminish the protection offered by vaccines and neutralizing antibodies.Notably,the Delta and Omicron recombinations have been collectively referred to as Deltacron(3).Furthermore,XBB.1.5,a recombinant strain resulting from the combination of the BA.2 sublineages BA.2.10.1 and BA.2.75,has demonstrated enhanced transmissibility(4).As such,it is imperative to monitor the genome recombination of SARS-CoV-2 in order to provide valuable insights regarding epidemic and transmission trends.展开更多
Introduction:Since 2019,numerous variants of concern for severe acute respiratory syndrome virus 2(SARS-CoV-2)have emerged,leading to significant outbreaks.The development of novel,highly accurate,and rapid detection ...Introduction:Since 2019,numerous variants of concern for severe acute respiratory syndrome virus 2(SARS-CoV-2)have emerged,leading to significant outbreaks.The development of novel,highly accurate,and rapid detection techniques for these new SARSCoV-2 variants remains a primary focus in the ongoing efforts to control and prevent the coronavirus disease 2019(COVID-19)pandemic.Methods:Reverse transcription-recombinase polymerase amplification combined with the clustered regularly interspaced short palindromic repeatsassociated protein 12a(CRISPR/Cas12a)system was used to validate the detection of the Omicron BA.2,BA.4,and BA.5 variants of SARS-CoV-2.Results:Our results demonstrate that the CRISPR/Cas12a assay is capable of effectively detecting the SARS-CoV-2 BA.2,BA.4,and BA.5 variants with a limit of detection of 10,1,and 10 copies/μL,respectively.Importantly,our assay successfully differentiated the three SARS-CoV-2 Omicron strains from one another.Additionally,we evaluated 46 SARS-CoV-2 positive clinical samples consisting of BA.2(n=20),BA.4(n=6),and BA.5(n=20)variants,and the sensitivity of our assay ranged from 90%to 100%,while the specificity was 100%.Discussion:This research presents a swift and reliable CRISPR-based method that may be employed to track the emergence of novel SARS-CoV-2 variants.展开更多
Dear Editor,Since September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been reported in more than 27 countries, and more than 2,000 cases have been confirmed in the laboratory (http:/...Dear Editor,Since September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been reported in more than 27 countries, and more than 2,000 cases have been confirmed in the laboratory (http://www.who.int/emergencies/mers-cov/en/). MERS-CoV causes an acute and severe respiratory illness with a high mortality rate(~35%) in humans (Shi et al., 2017, Zaki et al., 2012).Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease (Agrawal et al., 2016, Ying et al., 2014).展开更多
Emerging and re-emerging pathogens are great challenges to the public health(1).A cluster of pneumonia cases with an unknown cause occurred in Wuhan starting on December 21,2019.As of January 20,2020,a total of 201 ca...Emerging and re-emerging pathogens are great challenges to the public health(1).A cluster of pneumonia cases with an unknown cause occurred in Wuhan starting on December 21,2019.As of January 20,2020,a total of 201 cases of pneumonia in China have been confirmed.A team of professionals from the National Health Commission and China CDC conducted epidemiological and etiological investigations.On January 3,2020,the first complete genome of the novelβgenus coronaviruses(2019-nCoVs)was identified in samples of bronchoalveolar lavage fluid(BALF)from a patient from Wuhan by scientists of the National Institute of Viral Disease Control and Prevention(IVDC)through a combination of Sanger sequencing,Illumina sequencing,and nanopore sequencing.Three distinct strains have been identified,the virus has been designated as 2019-nCoV,and the disease has been subsequently named novel coronavirus-infected pneumonia(NCIP).展开更多
Monkeypox is a zoonotic viral disease caused by the monkeypox virus(MPXV),and historically,all outbreaks have been linked to Africa;however,monkeypox has been posing an alarming challenge to the world in 2022(1)as app...Monkeypox is a zoonotic viral disease caused by the monkeypox virus(MPXV),and historically,all outbreaks have been linked to Africa;however,monkeypox has been posing an alarming challenge to the world in 2022(1)as approximately 60,000 cases have been reported in more than 100 nations and regions worldwide(2).Currently,many cases of monkeypox were identified in many nonendemic countries outside of Central and West Africa,and human-to-human transmission has occurred frequently,especially among men who have sex with men(MSM)presenting new clinical symptoms similar to syphilis and other sexually transmitted infections(3).展开更多
The on-going global pandemic of coronavirus disease 2019(COVID-19)caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has been underway for about 11 months.Through November ...The on-going global pandemic of coronavirus disease 2019(COVID-19)caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has been underway for about 11 months.Through November 20,2020,51 detection kits for SARS-CoV-2 nucleic acids(24 kits),antibodies(25 kits),or antigens(2 kits)have been approved by the National Medical Products Administration of China(NMPA).Convenient and reliable SARS-CoV-2 detection assays are urgently needed worldwide for strategic control of the pandemic.In this review,the detection kits approved in China are summarised and the three types of tests,namely nucleic acid,serological and antigen detection,which are available for the detection of COVID-19 are discussed in detail.The development of novel detection kits will lay the foundation for the control and prevention of the COVID-19 pandemic globally.展开更多
With the development of the COVID-19 epidemic,there is an urgent need to establish a system for determining the effectiveness and neutralizing activity of vaccine candidates in biosafety level 2(BSL-2)facilities.Previ...With the development of the COVID-19 epidemic,there is an urgent need to establish a system for determining the effectiveness and neutralizing activity of vaccine candidates in biosafety level 2(BSL-2)facilities.Previously,researchers had developed a pseudotyped virus systemfor SARS-CoV andMERS-CoV,based onHIV-1 core,bearing virus spike protein.During the development of a pseudotyped SARS-CoV-2 system,a eukaryotic expression plasmid expressing SARSCoV-2 spike(S)protein was constructed and then co-transfectedwith HIV-1 based plasmid which containing the firefly luciferase reporter gene,into HEK293T cells to prepare the pseudotyped SARS-CoV-2 virus(ppSARS-2).We have successfully established the pseudotyped SARS-CoV-2 system for neutralization and entry inhibition assays.Huh7.5 cell line was found to be the most susceptible to our pseudotyped virus model.Different levels of neutralizing antibodies were detected in convalescent serum samples of COVID-19 patients using ppSARS-2.The recombinant,soluble,angiotensin-converting enzyme 2 protein was found to inhibit the entry of ppSARS-2 in Huh7.5 cells effectively.Furthermore,the neutralization results for ppSARS-2 were consistent with those of live SARS-CoV-2 and determined using the serum samples fromconvalescent patients.In conclusion,we have developed an easily accessible and reliable tool for studying the neutralizing efficiency of antibodies against SARS-CoV-2 and the entry process of the virus in a BSL-2 laboratory.展开更多
Although inoculation of COVID-19 vaccines has rolled out globally,there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries.Here,we report on the development ...Although inoculation of COVID-19 vaccines has rolled out globally,there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries.Here,we report on the development of a highly efficacious mRNA vaccine,SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex(LPP)nanoparticles.SWOT 23 is easy to produce using a large-scale microfluidics-based apparatus.The unique core-shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability,and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration.Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123,represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2,but also a panel of variants including D614G and N501Y variants.In addition,SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge.Taken together,SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.展开更多
What is already known on this topic?A novel human coronavirus,known as SARS-CoV-2 or 2019-nCoV,is the causative agent of the coronavirus disease 2019(COVID-19).We have released the primers and probes of real-time reve...What is already known on this topic?A novel human coronavirus,known as SARS-CoV-2 or 2019-nCoV,is the causative agent of the coronavirus disease 2019(COVID-19).We have released the primers and probes of real-time reverse transcription polymerase chain reaction(rRT-PCR)assays for the laboratory detection of COVID-19 infection.What is added by this report?Here we provide detailed technical data and evaluate the performance of three novel rRT-PCR assays targeting the ORF1ab,N,and E genes for detection of COVID-19 infection.The application of rRT-PCR assays among four types of specimens(alveolar lavage,sputum,throat swabs,and stool)from patients with COVID-19 indicated that the mean viral loads detected in sputum were higher than other specimens.What are the implications for public health practice?These rRT-PCR assays reported here could be used for laboratory diagnosis of COVID-19 infection with high sensitivity,specificity,and applicability.Sputum rather than throat swabs and stool should be a priority for specimen collection for laboratory detection of COVID-19.展开更多
Conventional influenza vaccines need to be designed and manufactured yearly.However,they occasionally provide poor protection owing to antigenic mismatch.Hence,there is an urgent need to develop universal vaccines aga...Conventional influenza vaccines need to be designed and manufactured yearly.However,they occasionally provide poor protection owing to antigenic mismatch.Hence,there is an urgent need to develop universal vaccines against influenza virus.Using nucleoprotein(NP)and extracellular domain of matrix protein 2(M2e)genes from the influenza A virus A/Beijing/30/95(H3N2),we constructed four recombinant vaccinia virus-based influenza vaccines carrying NP fused with one or four copies of M2e genes in different orders.The recombinant vaccinia viruses were used to immunize BALB/C mice.Humoral and cellular responses were measured,and then the immunized mice were challenged with the influenza A virus A/Puerto Rico/8/34(PR8).NP-specific humoral response was elicited in mice immunized with recombinant vaccinia viruses carrying full-length NP,while robust M2e-specific humoral response was elicited only in the mice immunized with recombinant vaccinia viruses carrying multiple copies of M2e.All recombinant viruses elicited NP-and M2e-specific cellular immune responses in mice.Only immunization with RVJ-4M2eNP induced remarkably higher levels of IL-2 and IL-10 cytokines specific to M2e.Furthermore,RVJ-4M2eNP immunization provided the highest cross-protection in mice challenged with 20 MLD5〇of PR8.Therefore,the cross-protection potentially correlates with both NP and M2e-specific humoral and cellular immune responses induced by RVJ-4M2eNP,which expresses a fusion antigen of full-length NP preceded by four M2e repeats.These results suggest that the rational fusion of NP and multiple M2e antigens is critical toward inducing protective immune responses,and the 4M2eNP fusion antigen may be employed to develop a universal influenza vaccine.展开更多
Monkey B virus(BV),initially isolated in 1932,is currently designated as Macacine alphaherpesvirus 1 by the International Committee on Taxonomy of Viruses(1).BV is an alphaherpesvirus enzootic in macaques of the genus...Monkey B virus(BV),initially isolated in 1932,is currently designated as Macacine alphaherpesvirus 1 by the International Committee on Taxonomy of Viruses(1).BV is an alphaherpesvirus enzootic in macaques of the genus Macaca,normally transmitted horizontally via direct contact and exchange of bodily secretions,just like herpes simplex virus(HSV)in humans.展开更多
Introduction:The first imported case of monkeypox(MPX)from the mainland of China was reported in September 2022.Herein,the study reports the isolation and characterization of MPX virus(MPXV)in this case.Methods:Clinic...Introduction:The first imported case of monkeypox(MPX)from the mainland of China was reported in September 2022.Herein,the study reports the isolation and characterization of MPX virus(MPXV)in this case.Methods:Clinical specimens including skin blister fluid,oropharyngeal and nasopharyngeal swabs,and blood were collected and inoculated onto Vero cells.The isolated virus was identified as MPXV using quantitative polymerase chain reaction(qPCR),cytopathic effects(CPEs),immunofluorescence assay(IFA)and transmission electron microscopy(TEM).Plaque assays were employed to quantify infectious plaque-forming units(PFUs).The plaque reduction neutralization test(PRNT)was developed to determine the neutralizing antibody(nAb)against MPXV.Results:MPXV replication was confirmed with qPCR.Typical CPEs were observed 48 h postincubation.The isolated virus was named MPXV-B.1-China-C-Tan-CQ01.IFA showed that MPXV reacted with serum of MPX case.Orthopoxvirus morphology was observed using TEM.The virus titer increased to>106 PFU/mL after three passages.The serum PRNT 50%neutralization titer(NT50)was 35 for the MPX patient 6 days after symptom onset.Discussion:The study successfully isolated the first MPXV strain in the mainland of China,MPXV-B.1-China-C-Tan-CQ01.Infectious titration and PRNT methods have been developed.The study provides key resources and technical platforms for further research as well as anti-viral drug and vaccine development against MPX.展开更多
文摘Objective:To analyze the combined therapeutic effect of clopidogrel(CLO)and aspirin(ASP)on coronary heart disease(CHD)in community-dwelling elderly.Methods:Thirty elderly patients with CHD who were admitted to the Xinxin Community Health Service Station,Pangzhuang Street,Quanshan District,Xuzhou City,from November 2020 to November 2022 were selected and randomly grouped into an observation group and a control group,with 15 cases in each group.The observation group was given the combination of CLO and ASP and the reference group was given only ASP.The total effective rate and other treatment indicators between the two groups were compared.Results:The total effective rate of the observation group(93.33%)was higher than that of the reference group(60.00%)(P<0.05).The adverse drug reaction rate(13.33%)and long-term cardiovascular adverse event rate(6.67%)of the observation group were lower than those of the reference group at 46.67%and 40.00%respectively,(P<0.05).Before treatment,the two groups had no difference in the quality-of-life scores(P>0.05).After treatment,the quality-of-life scores of the observation group were higher than those of the reference group(P<0.05).Conclusion:CLO combined with ASP improved the therapeutic effect of community-dwelling elderly patients with CHD,reduced adverse reactions during medication,prevented adverse cardiovascular events,and comprehensively improved the patient’s quality of life.
基金This work was supported by the National Research and Development Project of China(Grant No.2020YFC0841100)Fundamental Research Funds for CAMS of China(Grant No.2020HY320001)+3 种基金National Key Research and Development Project of China(Grant No.2016YFD0500304)CAMS initiative for Innovative Medicine of China(Grant No.2016-I2M-2-006)National Mega projects of China for Major Infectious Diseases(Grant No.2017ZX10304402)and National Key Research and Development Programme of China(2016YFD0500301,2020YFC0840800,2020YFC0840900).
文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.
基金This research was funded by the Fujian Province"2011 Collaborative Innovation Center",the Chinese Oolong Tea Industry Innovation Center special project(J 2015-75)the National Natural Science Foundation of China(31701874)+3 种基金the Major Special Project of Scientific and Technological Innovation on Anxi Tea(AX2021001)the Earmarked Fund for the China Agriculture Research System(CARS-19)the Scientific Research Foundation of the Graduate School of Fujian Agriculture and Forestry University(324-1122yb060)the Scientific Research Foundation of Horticulture College of Fujian Agriculture and Forestry University(2018B02).
文摘Tea plants(Camellia sinensis)are commercially cultivated in>60 countries,and their fresh leaves are processed into tea,which is the most widely consumed beverage in the world.Although several chromosome-level tea plant genomes have been published,they collapsed the two haplotypes and ignored a large number of allelic variations that may underlie important biological functions in this species.Here,we present a phased chromosome-scale assembly for an elite oolong tea cultivar,"Huangdan",that is well known for its high levels of aroma.Based on the two sets of haplotype genome data,we identi fi ed numerous genetic variations and a substantial proportion of allelic imbalance related to important traits,including aroma-and stress-related alleles.Comparative genomics revealed extensive structural variations as well as expansion of some gene families,such as terpene synthases(TPSs),that likely contribute to the high-aroma characteristics of the backbone parent,underlying the molecular basis for the biosynthesis of aroma-related chemicals in oolong tea.Our results uncovered the genetic basis of special features of this oolong tea cultivar,providing fundamental genomic resources to study evolution and domestication for the economically important tea crop.
基金supported by the National Key Research and Development Program of China(2022YFC2303401,2022YFC2304100,2016YFD0500301,2021YFC0863300)the Beijing Science and Technology Plan(Z211100002521017)the National Natural Science Foundation of China(82241080)。
文摘The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem repeats.Here we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland.We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens.Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes.Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences.Besides,several intra-host single nucleotide variations were identified in the first imported mpox case.This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens.The findings of this study will significantly enhance the surveillance of MPXV.
基金funded by the National Natural Science Foundation of China(Grant Nos.31971642,32271859,32071750,31470637,and 32222019)This work was also supported by the Key R&D Program of Jiangsu Province(Grant No.BE2019388)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China.
文摘Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently.Its leaves have been traditionally used to treat obesity and diabetes with the well-known active ingredient cyclocaric acid B.Here,we presented three C.paliurus genomes from two diploids with different flower morphs and one haplotype-resolved tetraploid assembly.Comparative genomic analysis revealed two rounds of recent whole-genome duplication events and identified 691 genes with dosage effects that likely contribute to adaptive evolution through enhanced photosynthesis and increased accumulation of triterpenoids.Resequencing analysis of 45 C.paliurus individuals uncovered two bottlenecks,consistent with the known events of environmental changes,and many selectively swept genes involved in critical biological functions,including plant defense and secondary metabolite biosynthesis.We also proposed the biosynthesis pathway of cyclocaric acid B based on multi-omics data and identified key genes,in particular gibberellinrelated genes,associated with the heterodichogamy in C.paliurus species.Our study sheds light on evolutionary history of C.paliurus and provides genomic resources to study the medicinal herbs.
文摘Introduction:The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has generated 2,431 variants over the course of its global transmission over the past 3 years.To better evaluate the genomic variation of SARS-CoV-2 before and after the optimization of coronavirus disease 2019(COVID-19)prevention and control strategies,we analyzed the genetic evolution branch composition and genomic variation of SARS-CoV-2 in both domestic and imported cases in China(the data from Hong Kong and Macao Special Administrative Regions and Taiwan,China were not included)from September 26,2022 to January 29,2023.Methods:Analysis of the number of genome sequences,sampling time,dynamic changes of evolutionary branches,origin,and clinical typing of SARS-CoV-2 variants submitted by 31 provincial-level administrative divisions(PLADs)and Xinjiang Production and Construction Corps(XPCC)was conducted to assess the accuracy and timeliness of SARS-CoV-2 variant surveillance.Results:From September 26,2022 to January 29,2023,20,013 valid genome sequences of domestic cases were reported in China,with 72 evolutionary branches.Additionally,1,978 valid genome sequences of imported cases were reported,with 169 evolutionary branches.The prevalence of the Omicron variants of SARS-CoV-2 in both domestic and imported cases was consistent with that of international epidemic variants.Conclusions:This study provides an overview of the prevalence of Omicron variants of SARS-CoV-2 in China.After optimizing COVID-19 prevention and control strategies,no novel Omicron variants of SARSCoV-2 with altered biological characteristics or public health significance have been identified since December 1,2022.
基金supported by the National Key R&D Program of China(2022YFE0210300,2022YFC2303401,2016YFD0500300,2021YFC0863300,and 2021YFC2300101)the National Natural Science Foundation of China(32070407)the special fund for Science and Technology Innovation Teams of Shanxi Province(202204051001022)。
基金supported by the National Key Research and Development Program of China(2021YFC2300101).
文摘Metagenomic next-generation sequencing(mNGs)has been widely applied to identify pathogens associated with infectious diseases.However,limited studies have explored the use of mNGs-based dynamic pathogen monitoring in intensive care unit patients with severe pneumonia.Here,we present a clinical case of an 86-year-old male patient with severe pneumonia caused by a fungal infection.During the clinical treatment,four mNGS analyses were performed within two consecutive weeks.Various respiratory fungal pathogens,including Candida orthopsilosis,Candida albicans,and Aspergillus fumigatus were detected by mNGS of bronchoalveolar lavage fluid(BALF).Based on conventional pathogen identification and clinical symptoms,the patient was diagnosed with severe pneumonia caused by a fungal infection.The abundance of fungal species decreased gradually in response to antifungal and empirical therapies,and the fungal infections were effectively con-trolled.In summary,our results demonstrated that mNGS could effectively identify pathogens in patients with severe pneumonia.Additionally,dynamic pathogen monitoring based on mNGS could assist in the precise diag-nosis of complex infections and may facilitate rapid induction of the most appropriate therapy.
基金Supported by National Key R&D Program of China(2022YFC230410,2022 YFC2303401,2021YFC2300101 and 2021YFA 1201003).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a single-stranded positive RNA virus,exhibits a high rate of genome mutation and recombination(1–2).Recombinant strains of this virus could potentially affect their binding ability to the ACE2 receptor,which may in turn diminish the protection offered by vaccines and neutralizing antibodies.Notably,the Delta and Omicron recombinations have been collectively referred to as Deltacron(3).Furthermore,XBB.1.5,a recombinant strain resulting from the combination of the BA.2 sublineages BA.2.10.1 and BA.2.75,has demonstrated enhanced transmissibility(4).As such,it is imperative to monitor the genome recombination of SARS-CoV-2 in order to provide valuable insights regarding epidemic and transmission trends.
基金Supported by the National Key Research and Development Program of China(2021YFC2300101,2021YFC0863300,2022YFC 2304101,2022YFC2303401).
文摘Introduction:Since 2019,numerous variants of concern for severe acute respiratory syndrome virus 2(SARS-CoV-2)have emerged,leading to significant outbreaks.The development of novel,highly accurate,and rapid detection techniques for these new SARSCoV-2 variants remains a primary focus in the ongoing efforts to control and prevent the coronavirus disease 2019(COVID-19)pandemic.Methods:Reverse transcription-recombinase polymerase amplification combined with the clustered regularly interspaced short palindromic repeatsassociated protein 12a(CRISPR/Cas12a)system was used to validate the detection of the Omicron BA.2,BA.4,and BA.5 variants of SARS-CoV-2.Results:Our results demonstrate that the CRISPR/Cas12a assay is capable of effectively detecting the SARS-CoV-2 BA.2,BA.4,and BA.5 variants with a limit of detection of 10,1,and 10 copies/μL,respectively.Importantly,our assay successfully differentiated the three SARS-CoV-2 Omicron strains from one another.Additionally,we evaluated 46 SARS-CoV-2 positive clinical samples consisting of BA.2(n=20),BA.4(n=6),and BA.5(n=20)variants,and the sensitivity of our assay ranged from 90%to 100%,while the specificity was 100%.Discussion:This research presents a swift and reliable CRISPR-based method that may be employed to track the emergence of novel SARS-CoV-2 variants.
基金supported by the National Key Research and Development Program of China (2016YFD0500300 to Wenjie Tan)
文摘Dear Editor,Since September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been reported in more than 27 countries, and more than 2,000 cases have been confirmed in the laboratory (http://www.who.int/emergencies/mers-cov/en/). MERS-CoV causes an acute and severe respiratory illness with a high mortality rate(~35%) in humans (Shi et al., 2017, Zaki et al., 2012).Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease (Agrawal et al., 2016, Ying et al., 2014).
文摘Emerging and re-emerging pathogens are great challenges to the public health(1).A cluster of pneumonia cases with an unknown cause occurred in Wuhan starting on December 21,2019.As of January 20,2020,a total of 201 cases of pneumonia in China have been confirmed.A team of professionals from the National Health Commission and China CDC conducted epidemiological and etiological investigations.On January 3,2020,the first complete genome of the novelβgenus coronaviruses(2019-nCoVs)was identified in samples of bronchoalveolar lavage fluid(BALF)from a patient from Wuhan by scientists of the National Institute of Viral Disease Control and Prevention(IVDC)through a combination of Sanger sequencing,Illumina sequencing,and nanopore sequencing.Three distinct strains have been identified,the virus has been designated as 2019-nCoV,and the disease has been subsequently named novel coronavirus-infected pneumonia(NCIP).
文摘Monkeypox is a zoonotic viral disease caused by the monkeypox virus(MPXV),and historically,all outbreaks have been linked to Africa;however,monkeypox has been posing an alarming challenge to the world in 2022(1)as approximately 60,000 cases have been reported in more than 100 nations and regions worldwide(2).Currently,many cases of monkeypox were identified in many nonendemic countries outside of Central and West Africa,and human-to-human transmission has occurred frequently,especially among men who have sex with men(MSM)presenting new clinical symptoms similar to syphilis and other sexually transmitted infections(3).
基金supported by the National Key Program for Infectious Disease of China(2018ZX10101002)the National Key Research and Development Program of China(2016YFD0500301,2020YFC0840900)。
文摘The on-going global pandemic of coronavirus disease 2019(COVID-19)caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has been underway for about 11 months.Through November 20,2020,51 detection kits for SARS-CoV-2 nucleic acids(24 kits),antibodies(25 kits),or antigens(2 kits)have been approved by the National Medical Products Administration of China(NMPA).Convenient and reliable SARS-CoV-2 detection assays are urgently needed worldwide for strategic control of the pandemic.In this review,the detection kits approved in China are summarised and the three types of tests,namely nucleic acid,serological and antigen detection,which are available for the detection of COVID-19 are discussed in detail.The development of novel detection kits will lay the foundation for the control and prevention of the COVID-19 pandemic globally.
基金support this work:The National Key Research and Development Program of China(No.2016YFD0500301,No.2020YFC0842100)the National Major Project for Control and Pre-vention of Infectious Disease in China(No.2018ZX10101002).
文摘With the development of the COVID-19 epidemic,there is an urgent need to establish a system for determining the effectiveness and neutralizing activity of vaccine candidates in biosafety level 2(BSL-2)facilities.Previously,researchers had developed a pseudotyped virus systemfor SARS-CoV andMERS-CoV,based onHIV-1 core,bearing virus spike protein.During the development of a pseudotyped SARS-CoV-2 system,a eukaryotic expression plasmid expressing SARSCoV-2 spike(S)protein was constructed and then co-transfectedwith HIV-1 based plasmid which containing the firefly luciferase reporter gene,into HEK293T cells to prepare the pseudotyped SARS-CoV-2 virus(ppSARS-2).We have successfully established the pseudotyped SARS-CoV-2 system for neutralization and entry inhibition assays.Huh7.5 cell line was found to be the most susceptible to our pseudotyped virus model.Different levels of neutralizing antibodies were detected in convalescent serum samples of COVID-19 patients using ppSARS-2.The recombinant,soluble,angiotensin-converting enzyme 2 protein was found to inhibit the entry of ppSARS-2 in Huh7.5 cells effectively.Furthermore,the neutralization results for ppSARS-2 were consistent with those of live SARS-CoV-2 and determined using the serum samples fromconvalescent patients.In conclusion,we have developed an easily accessible and reliable tool for studying the neutralizing efficiency of antibodies against SARS-CoV-2 and the entry process of the virus in a BSL-2 laboratory.
基金supported by the National Key Research and Development Program of China(2016YFD0500301,2020YFC0840900,and 2020YFC0842200)the National Natural Science Foundation of China(82041041,82061138008)+1 种基金Shanghai Pujiang Talent Program(2020PJD068,to A.L.)internal funds from Stemirna Therapeutics.
文摘Although inoculation of COVID-19 vaccines has rolled out globally,there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries.Here,we report on the development of a highly efficacious mRNA vaccine,SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex(LPP)nanoparticles.SWOT 23 is easy to produce using a large-scale microfluidics-based apparatus.The unique core-shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability,and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration.Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123,represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2,but also a panel of variants including D614G and N501Y variants.In addition,SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge.Taken together,SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.
基金This work was supported by the National Key Research and Development Program of China(2016YFD0500301,2020YFC0840900).
文摘What is already known on this topic?A novel human coronavirus,known as SARS-CoV-2 or 2019-nCoV,is the causative agent of the coronavirus disease 2019(COVID-19).We have released the primers and probes of real-time reverse transcription polymerase chain reaction(rRT-PCR)assays for the laboratory detection of COVID-19 infection.What is added by this report?Here we provide detailed technical data and evaluate the performance of three novel rRT-PCR assays targeting the ORF1ab,N,and E genes for detection of COVID-19 infection.The application of rRT-PCR assays among four types of specimens(alveolar lavage,sputum,throat swabs,and stool)from patients with COVID-19 indicated that the mean viral loads detected in sputum were higher than other specimens.What are the implications for public health practice?These rRT-PCR assays reported here could be used for laboratory diagnosis of COVID-19 infection with high sensitivity,specificity,and applicability.Sputum rather than throat swabs and stool should be a priority for specimen collection for laboratory detection of COVID-19.
基金supported by grant from the National Key Plan for Scientific Research and Development of China (2016YFC1200200)
文摘Conventional influenza vaccines need to be designed and manufactured yearly.However,they occasionally provide poor protection owing to antigenic mismatch.Hence,there is an urgent need to develop universal vaccines against influenza virus.Using nucleoprotein(NP)and extracellular domain of matrix protein 2(M2e)genes from the influenza A virus A/Beijing/30/95(H3N2),we constructed four recombinant vaccinia virus-based influenza vaccines carrying NP fused with one or four copies of M2e genes in different orders.The recombinant vaccinia viruses were used to immunize BALB/C mice.Humoral and cellular responses were measured,and then the immunized mice were challenged with the influenza A virus A/Puerto Rico/8/34(PR8).NP-specific humoral response was elicited in mice immunized with recombinant vaccinia viruses carrying full-length NP,while robust M2e-specific humoral response was elicited only in the mice immunized with recombinant vaccinia viruses carrying multiple copies of M2e.All recombinant viruses elicited NP-and M2e-specific cellular immune responses in mice.Only immunization with RVJ-4M2eNP induced remarkably higher levels of IL-2 and IL-10 cytokines specific to M2e.Furthermore,RVJ-4M2eNP immunization provided the highest cross-protection in mice challenged with 20 MLD5〇of PR8.Therefore,the cross-protection potentially correlates with both NP and M2e-specific humoral and cellular immune responses induced by RVJ-4M2eNP,which expresses a fusion antigen of full-length NP preceded by four M2e repeats.These results suggest that the rational fusion of NP and multiple M2e antigens is critical toward inducing protective immune responses,and the 4M2eNP fusion antigen may be employed to develop a universal influenza vaccine.
基金The National Key Research and Development Program of China(2016YFD0500301)and Viral Center of National Pathogen Resource Center,China CDC(NPRC-32).
文摘Monkey B virus(BV),initially isolated in 1932,is currently designated as Macacine alphaherpesvirus 1 by the International Committee on Taxonomy of Viruses(1).BV is an alphaherpesvirus enzootic in macaques of the genus Macaca,normally transmitted horizontally via direct contact and exchange of bodily secretions,just like herpes simplex virus(HSV)in humans.
基金Supported by the National Key Research and Development Program of China(2022YFC 2304100,2022YFC2303401,2021YFA1201003,2016YFD0500301,2020YFC0840900,2021YFC 0863300)the Beijing Science and Technology Plan(Z211100002521017,Z211100002521015).
文摘Introduction:The first imported case of monkeypox(MPX)from the mainland of China was reported in September 2022.Herein,the study reports the isolation and characterization of MPX virus(MPXV)in this case.Methods:Clinical specimens including skin blister fluid,oropharyngeal and nasopharyngeal swabs,and blood were collected and inoculated onto Vero cells.The isolated virus was identified as MPXV using quantitative polymerase chain reaction(qPCR),cytopathic effects(CPEs),immunofluorescence assay(IFA)and transmission electron microscopy(TEM).Plaque assays were employed to quantify infectious plaque-forming units(PFUs).The plaque reduction neutralization test(PRNT)was developed to determine the neutralizing antibody(nAb)against MPXV.Results:MPXV replication was confirmed with qPCR.Typical CPEs were observed 48 h postincubation.The isolated virus was named MPXV-B.1-China-C-Tan-CQ01.IFA showed that MPXV reacted with serum of MPX case.Orthopoxvirus morphology was observed using TEM.The virus titer increased to>106 PFU/mL after three passages.The serum PRNT 50%neutralization titer(NT50)was 35 for the MPX patient 6 days after symptom onset.Discussion:The study successfully isolated the first MPXV strain in the mainland of China,MPXV-B.1-China-C-Tan-CQ01.Infectious titration and PRNT methods have been developed.The study provides key resources and technical platforms for further research as well as anti-viral drug and vaccine development against MPX.
